The Gary Null Show

Tokyo Metropolitan Institute of Medical Science, May 27, 2021

Schizophrenia is a heterogeneous psychiatric disorder characterized by positive symptoms such as hallucinations and delusions, negative symptoms such as apathy and lack of emotion, and cognitive impairment. We have reported that VB6 (pyridoxal) levels in peripheral blood of a subpopulation of patients with schizophrenia is significantly lower than that of healthy controls. More than 35% of patients with schizophrenia have low levels of VB6 (clinically defined as male: < 6 ng/ml, female: < 4 ng/ml). VB6 level is inversely proportional to severity score on the positive and negative symptom scale (PANSS), suggesting that VB6 deficiency might contribute to the development of schizophrenia symptoms. In fact, a recent review has shown the decreased VB6 in patients with schizophrenia as the most convincing evidence in peripheral biomarkers for major mental disorders. Additionally, we recently reported that high-dose VB6 (pyridoxamine) was effective in alleviating psychotic symptoms, particularly the PANSS negative and general subscales, in a subset of patients with schizophrenia. Although a link between lower VB6 level and schizophrenia is widely hypothesized, the mechanism behind this remains poorly understood.

VB6 is not synthesized de novo in humans, but is primarily obtained from foods. In the present study, to clarify the relationship between VB6 deficiency and schizophrenia, we generated VB6-deficient (VB6(-)) mice through feeding with a VB6-lacking diet as a mouse model for the subpopulation of schizophrenia patients with VB6 deficiency. After feeding for 4 weeks, plasma VB6 level in VB6(-) mice decreased to 3% of that in control mice. The VB6(-) mice showed social deficits and cognitive impairment. Furthermore, the VB6(-) mice showed a marked increase in 3-methoxy-4-hydroxyphenylglycol (MHPG) in the brain, suggesting enhanced NA metabolism in VB6(-) mice. We confirmed the increased NA release in the prefrontal cortex and the striatum of VB6(-) mice through in vivo microdialysis. These findings suggest that the activities of NAergic neuronal systems are enhanced in VB6(-) mice.

Furthermore, VB6 supplementation directly into the brain using an osmotic pump ameliorated the hyperactivation of the NAergic system and behavioral abnormalities. indicating that the enhanced NA turnover and the behavioral deficits shown in the VB6(-) mice are attributed to VB6 deficiency in the central nervous system. In addition, the ?2A adrenergic receptor agonist guanfacine also improved the hyperactivated NAergic system in the frontal cortex and behavioral disorders. These results show that the behavioral deficits in VB6(-) mice may be caused by an enhancement of NAergic signaling.

Schizophrenic patients with VB6 deficiency, who account for more than 35% of all patients, present with relatively severe clinical symptoms and treatment resistance. Our findings suggest that a new therapeutic strategy targeting the NAergic system might be effective for these patients. They will also provide evidence based on pathophysiology for a new therapeutic strategy called "VB6 treatment for schizophrenia," which we are currently conducting clinical research on.

Radboud University Medical Center (Netherlands), May 27, 2021

Children with ADHD are generally treated with medication and/or behavioral treatments. However, medication-alone is insufficient in a quarter to a third of the children. For that reason, the scientists investigated whether a mindfulness-based intervention (MBI) would have a positive effect on children who did not respond sufficiently to other ADHD treatments. MBIs can elicit positive effects on psychological symptoms and behavior of children and parents. 

In the study, two groups of children between the ages of eight and sixteen were compared. One group received only regular care (CAU, care-as-usual), and the other group also received MYmind, the mindfulness-based intervention (MBI) with at least one parent. They did this training for a period of eight weeks.

A striking result was that parents especially benefited from this training. There was an increase in mindful parenting, self-compassion and an improvement in mental health among the parents. These effects were still visible six months after the end of the training. In the children, there were some effects on ADHD symptoms, anxiety, and autistic traits, but effects were small. Yet, a subgroup appeared to benefit: One in three children reliably improved on self-control following MYmind, whereas only one in ten improved when following only regular care.

Professor of Environmental Sensitivity in Health and psychologist Corina Greven of Radboudumc, the Donders Institute and Karakter says that usual interventions for children with ADHD typically do not target mental health of parents, although they often struggle with parenting stress, anxiety or own ADHD symptoms. "While effects in children were small, we still found effects in the parents. Interviewing families , our team also discovered that many families reported important improvements in family relationships and insight in and acceptance of ADHD. We need to go broader than just looking at whether an intervention reduces symptoms, and include additional outcomes that families find important." The study was conducted in collaboration with the Radboud Center for Mindfulness.

Anthocyanins from sweet cherries may protect against diet-induced liver steatosis, or excessive amounts of fat in the liver’s tissue, says a new study with rats. 

The study , published in the journal Nutrition, built upon the abundant existing literature on the beneficial role anthocyanins have as an antioxidative, anti-inflammatory, and anti-hyperlipidemic component.

Specifically, the cyanidin-3-glucoside variant “[has] been reported to ameliorate hepatic steatosis and adipose inflammation,” the researchers wrote. The condition known as liver steatosis is a common non-alcoholic fatty liver disease usually treated with drugs, but according to the researchers, some drug used for treatment “are usually accompanied by some adverse effect.”

For 15 weeks, the researchers investigated the effects of sweet cherry anthocyanin supplementation have on alleviating high-fat diet-induced liver steatosis in rodents to explore the possibility of a none-drug treatment for the liver condition.

Preparing the mice and the sweet cherry anthocyanins

The sweet cherry anthocyanin was extracted and pulverized, with one mg of the anthocyanin measured to contain amounts of cyanidine-3-rutinoside and pelargonidin-3-rutinoside, among other things.

Thirty male rodents were used for the study. The animals were housed five per cage and randomly divided into three groups: 10 rodents fed a low-fat diet, 10 rodents fed a high-fat diet, and 10 rodents fed a high-fat diet supplemented with sweet cherry anthocyanins.

The supplementation was given in liquid form at 200 mg/kg orally at the same time daily for 15 weeks, and the body weights and food intakes were monitored weekly.

Observations

The mice were sacrificed at week 15 after a half-day fast. Blood samples were collected and livers collected, rinsed with cold saline, and then weighed.

An automatic biochemistry analyser was used to measure total cholesterol, triacylglycerol, alanine aminotransferase, aspartate aminotransferase, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol.

They found that at week 15, mice fed a high-fat diet supplemented with sweet cherry anthocyanins “displayed a significant reduction in body weight, liver weight, and liver index” compared to the mice that were only given a high-fat diet without supplementation.

They also found the serum levels for tricylglycerol, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in high-fat diet mice to be substantially higher than those fed a low-fat diet, but the group supplemented with the anthocyanin resulted in a significant reduction in these serum parameters.”

According to the researchers, the results demonstrated how sweet cherry anthocyanins may be developed into a supplement to “protect from high-fat diet-induced hepatic steatosis in mice,”leading to a suggested potential for the anthocyanin’s application in the “treatment of hepatic steatosis and other obesity related metabolic disorders.”

New study suggests importance of maintaining healthy lifestyle even after age 80

Duke University & Kunshan University (China), June 1, 2021

A new analysis of adults aged 80 years and older shows that a healthier lifestyle is associated with a lower risk of cognitive impairment, and that this link does not depend on whether a person carries a particular form of the gene APOE. Xurui Jin of Duke Kunshan University in Jiangsu, China, and colleagues present these findings in the open-access journal PLOS Medicine.

The APOE gene comes in several different forms, and people with a form known as APOE ε4 have an increased risk of cognitive impairment and Alzheimer's disease. Previous research has also linked cognitive function to lifestyle factors, such as smoking, exercise, and diet. However, it has been unclear whether the benefits of a healthy lifestyle are affected by APOE ε4, particularly for adults over 80 years of age.

To clarify the relationship between APOE ε4 and lifestyle, Jin and colleagues examined data from 6,160 adults aged 80 or older who had participated in a larger, ongoing study known as the Chinese Longitudinal Healthy Longevity Survey. The researchers statistically analyzed the data to investigate links between APOE ε4, lifestyle, and cognition. They also accounted for sociodemographics and other factors that could impact cognition.

The analysis confirmed that participants with healthy lifestyles or intermediately healthy lifestyles were significantly less likely to have cognitive impairment than those with an unhealthy lifestyle, by 55 and 28 percent, respectively. In addition, participants with APOE ε4 were 17 percent more likely to have cognitive impairment than those with other forms of APOE.

A previous study suggested that in individuals at low and intermediate genetic risk, favorable lifestyle profiles are related to a lower risk of dementia compared to unfavorable profiles. But these protective associations were not found in those at high genetic risk. However, the investigation showed the link between lifestyle and cognitive impairment did not vary significantly based on APOE ε4 status which represented the genetic dementia risk. This suggests that maintaining a healthier lifestyle could be important for maintaining cognitive function in adults over 80 years of age, regardless of genetic risk. 

This cross-sectional study emphasized the importance of a healthy lifestyle on cognitive health. While further research will be needed to validate these findings among different population, this study could help inform efforts to boost cognitive function for the oldest of adults.

In the next step, the team will explore this association using the AD polygenetic risk score (AD-PRS) and explore the interactive relationship between AD-PRS and lifestyle on cognition with the longitudinal data.

University of Calgary (Canada) June 1, 2021

BPA disrupts development of the mouse brain sleep centre (outlined), image on right. The change can impact behaviour. The control image on the left ("CON") shows sleep centre without BPA. Credit: Kurrasch lab, published in Science Advances

Humans are exposed to a bath of chemicals every day. They are in the beds where we sleep, the cars that we drive and the kitchens we use to feed our families. With thousands of chemicals floating around in our environment, exposure to any number is practically unavoidable. Through the work of researchers like Dr. Deborah Kurrasch, Ph.D., the implications of many of these chemicals are being thoroughly explored.

"Manufacturers follow standards set by regulatory bodies, it's not up to the manufacturers to prove the chemicals in consumer products are safe," says Kurrasch, a researcher in the University of Calgary's Hotchkiss Brain Institute (HBI) and Alberta Children's Research Institute at the Cumming School of Medicine. "Scientists play a critical role and do the meticulous work of determining where the risks lie."

Kurrasch's research over the past decade has focused on a chemical that is broadly recognizable: Bisphenol A, also known as BPA. This chemical is commonly found in plastics, canned food linings, and even thermal receipts. Studies from Kurrasch's lab contribute to the collective research that shows the harms of exposure to this industrial compound.

The latest study out of Kurrasch's lab, published in Science Advances, suggests that continued vigilance is needed. A postdoctoral researcher in her lab, Dr. Dinu Nesan, Ph.D., examined the impact of low levels of BPA exposure to pregnant mice and the brain development of their offspring.

"Our goal was to model BPA levels equivalent to what pregnant women and developing babies are typically exposed to," says Kurrasch. "We purposefully did not use a high dose. In fact, our doses were 11-times and nearly 25-times lower than those deemed safe by Health Canada and the FDA (U.S. Food and Drug Administration), respectively. Even at these low levels, we saw effects on prenatal brain development in the mice."

Using this BPA exposure model, Nesan found striking changes to the brain region responsible for driving circadian rhythms, the suprachiasmatic nucleus, located in the hypothalamus. When prenatally exposed to these low levels of BPA, the suprachiasmatic nucleus failed to develop properly. This change can have implications for sleep, activity levels, and other behaviors.

"Previously we showed embryonic exposure to low-dose BPA can affect the timing of when neurons develop in zebrafish, but it was unclear whether a similar effect would be observed in a mammalian model with more similarities to humans," says Nesan, first author on the study. When neurons develop, they rely on proper signals to guide them. If neurons develop too early, the cues they experience are different, which can lead to developmental errors such as migrating to the wrong location, becoming the wrong type of neuron, or forming inappropriate connections. These errors can lead to altered behaviors later in life.

"Our study shows that in pregnant mice, prenatal exposure to BPA affects the timing of neuron development in the fetal brain, which has lasting effects on behaviors. Offspring that are exposed to BPA during gestation are awake longer and exhibit hyperactivity. The prenatal BPA exposure seems to change the brain's circadian cues, causing the animals to have elevated energy levels and spend less time resting," says Nesan.

The researchers are hopeful their findings will add continued pressure on regulatory bodies to keep revisiting their determinations around safe levels of BPA.

"We think there's an incredible abundance of data showing BPA exposure guidelines are not yet at the appropriate level, which includes even the EU (European Union) who is leading on this front, but their 'safe' levels are still twice the dose we used in our study" says Kurrasch, "We hope our research serves as a reminder that low dose BPA is still capable of causing changes that are measurable and significant."

Her message of how to interpret this research is simple:

• Limit your exposure to BPA the best you can. 

This research was conducted in collaboration with Dr. Michael Antle, Ph.D., professor of psychology and member of the HBI.

Linköping University (Sweden), June 2, 2021

Findings from a randomized, double-blind, placebo-controlled trial, published on April 17, 2021 in the journal Nutrients,revealed a reduction in D-dimer levels among older Swedish men and women who received selenium and coenzyme Q10 (CoQ10), as well as a lower risk of mortality from cardiovascular disease in individuals having higher D-dimer levels at baseline. 

Coenzyme Q10 is an antioxidant involved in the mitochondria’s production of energy. It has been estimated that the body’s production of CoQ10 at the age of 80 years is approximately half that of someone who is 20 years old. 

Selenium is a trace element necessary for normal function of human cells. Dietary intake of this mineral may be insufficient in areas of the world that have low soil selenium levels. Selenium also is necessary for the function of many antioxidant enzymes, including one which recycles CoQ10, and has anti-inflammatory activity.

D-dimer is a fragment of degraded fibrin and is commonly used to assess for the presence or degradation of potentially dangerous blood clots (venous thromboembolism or pulmonary embolism). It also reflects the activity of peripheral artery disease and has been shown to be associated with endothelial dysfunction and inflammation even in the absence of thromboembolism.

The current investigation included 213 men and women aged 70 to 88 years who did not have conditions known to influence D-dimer concentrations (e.g., atrial fibrillation, malignancies). Participants received a placebo or 200 micrograms selenium plus 200 milligrams CoQ10 daily for four years. 

Blood samples collected from the subjects upon enrollment in the trial and at 48 months were analyzed for levels of D-dimer. Although D-dimer levels were not significantly different between groups at the beginning of the trial, it was noted to be significantly associated with age. At 48 months, a significantly lower level of D-dimer was found among those who received selenium and CoQ10 in comparison with the placebo, which was maintained after adjustment for co-variates that might influence D-dimer (such as C-reactive protein). 

When participants with D-dimer levels that were above the median of all participants at baseline were analyzed, an association was found between intake of selenium and CoQ10 and a lower risk of cardiovascular mortality. Among those whose D-dimer levels were higher than 0.21 mg/L at the beginning of the study, one person among 53 who received selenium and CoQ10 died during a median 4.9-year follow-up period compared to 8 of the 52 who received a placebo. Mortality from all causes was also lower in the selenium and CoQ10 group; however, the reduction failed to reach statistical significance.

This group also reported a larger study, which didn’t exclude individuals having conditions known to increase D-dimer, finding that in the older Swedish citizens the combination of selenium and CoQ10 significantly increased heart systolic function, lowered NT-proBNP (which is elevated during heart failure) and decreased risk of cardiovascular mortality, defined as death from myocardial infarctions, cerebrovascular lesions, cardiac arrythmias, heart failure or aortic aneurysms.1

“[Intake of] selenium and coenzyme Q10 in a group of elderly low in selenium and coenzyme Q10 prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group,” concluded first author Urban Alehagen and his colleagues. “The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.”

Seoul Medical Center  (Korea) June 1, 2021

Researchers detail new data in Neurodegenerative Diseases. According to news reporting originating in Seoul, South Korea  research stated, "Korean red ginseng (KRG) has a nootropic effect. This study assessed the efficacy of KRG on cognitive function and quantitative electroencephalography (EEG) in patients with Alzheimer's disease (AD)."

The news reporters obtained a quote from the research from Seoul Medical Center, "Fourteen patients with AD (mean age, 74.93 years; 11 women and 3 men) were recruited and treated with KRG (4.5 g per day) for 12 weeks. Cognitive function was assessed by the Korean Mini-Mental State Examination (K-MMSE) and the Frontal Assessment Battery (FAB). EEG performed before and after treatment were analyzed with quantitative spectral analysis. The FAB score improved significantly after 12 weeks of treatment. In the relative power spectrum analysis performed according to responsiveness, alpha power increased significantly in the right temporal area of the responders. The increments of relative alpha power in the right temporal, parietal, and occipital areas were significantly higher in the responders than the nonresponders."

According to the news reporters, the research concluded: "This study indicates the efficacy of KRG on frontal lobe function in AD, related to increasing relative alpha power."

Tsimane people are unique for their healthy brains that age more slowly

University of Southern California, May 27, 2021

A team of international researchers has found that the Tsimane indigenous people of the Bolivian Amazon experience less brain atrophy than their American and European peers. The decrease in their brain volumes with age is 70% slower than in Western populations. Accelerated brain volume loss can be a sign of dementia. 

The study was published May 26, 2021 in the Journal of Gerontology, Series A: Biological Sciences and Medical Sciences. 

Although people in industrialized nations have access to modern medical care, they are more sedentary and eat a diet high in saturated fats. In contrast, the Tsimane have little or no access to health care but are extremely physically active and consume a high-fiber diet that includes vegetables, fish and lean meat. 

"The Tsimane have provided us with an amazing natural experiment on the potentially detrimental effects of modern lifestyles on our health," said study author Andrei Irimia, an assistant professor of gerontology, neuroscience and biomedical engineering at the USC Leonard Davis School of Gerontology and the USC Viterbi School of Engineering. "These findings suggest that brain atrophy may be slowed substantially by the same lifestyle factors associated with very low risk of heart disease." 

The researchers enrolled 746 Tsimane adults, ages 40 to 94, in their study. To acquire brain scans, they provided transportation for the participants from their remote villages to Trinidad, Bolivia, the closest town with CT scanning equipment. That journey could last as long as two full days with travel by river and road. 

The team used the scans to calculate brain volumes and then examined their association with age for Tsimane. Next, they compared these results to those in three industrialized populations in the U.S. and Europe. 

The scientists found that the difference in brain volumes between middle age and old age is 70% smaller in Tsimane than in Western populations. This suggests that the Tsimane's brains likely experience far less brain atrophy than Westerners as they age; atrophy is correlated with risk of cognitive impairment, functional decline and dementia. 

The researchers note that the Tsimane have high levels of inflammation, which is typically associated with brain atrophy in Westerners. But their study suggests that high inflammation does not have a pronounced effect upon Tsimane brains. 

According to the study authors, the Tsimane's low cardiovascular risks may outweigh their infection-driven inflammatory risk, raising new questions about the causes of dementia. One possible reason is that, in Westerners, inflammation is associated with obesity and metabolic causes whereas, in the Tsimane, it is driven by respiratory, gastrointestinal, and parasitic infections. Infectious diseases are the most prominent cause of death among the Tsimane. 

"Our sedentary lifestyle and diet rich in sugars and fats may be accelerating the loss of brain tissue with age and making us more vulnerable to diseases such as Alzheimer's," said study author Hillard Kaplan, a professor of health economics and anthropology at Chapman University who has studied the Tsimane for nearly two decades. "The Tsimane can serve as a baseline for healthy brain aging." 

Healthier hearts and -- new research shows -- healthier brains 

The indigenous Tsimane people captured scientists' -- and the world's -- attention when an earlier study found them to have extraordinarily healthy hearts in older age. That prior study, published by the Lancet in 2017, showed that Tsimane have the lowest prevalence of coronary atherosclerosis of any population known to science and that they have few cardiovascular disease risk factors. The very low rate of heart disease among the roughly 16,000 Tsimane is very likely related to their pre-industrial subsistence lifestyle of hunting, gathering, fishing, and farming. 

"This study demonstrates that the Tsimane stand out not only in terms of heart health, but brain health as well," Kaplan said. "The findings suggest ample opportunities for interventions to improve brain health, even in populations with high levels of inflammation."

University of Hong Kong, May 31, 2021

A randomized controlled trial found that tai chi is about as effective as conventional exercise for reducing waist circumference in middle-aged and older adults with central obesity. Central obesity, or weight carried around the midsection, is a major manifestation of metabolic syndrome and a common health problem in this cohort. The findings are published in Annals of Internal Medicine. 

Tai chi is a form of mind-body exercise often described as "meditation in motion." It is practiced in many Asian communities and is becoming increasingly popular in Western countries, with more than 2 million people practicing it in the United States. While it is known to be a suitable activity for older people including those who are not active, there previously has been little evidence on tai chi's health benefits. 

Researchers from the University of Hong Kong randomly assigned more than 500 adults over 50 with central obesity to a regimen of tai chi, conventional exercise, or no exercise over 3 months. Participants in the tai chi and exercise groups met for instructor-led workouts for 1 hour 3 times a week for 12 weeks. The tai chi program consisted of the Yang style of tai chi, the most common style adopted in the literature, and the conventional exercise program consisted of brisk walking and strength training activities. Waist circumference and other indicators of metabolic health were measured at baseline, 12 weeks, and 38 weeks. The researchers found that both the tai chi intervention and conventional exercise intervention group had reductions in waist circumference, relative to control. The reduction in waist circumference had a favorable impact on HDL cholesterol, or so-called good cholesterol, but did not translate into detectable differences in fasting glucose or blood pressure. 

According to the study authors, their findings are good news for middle-aged and older adults who have central obesity but may be averse to conventional exercise due to preference or limited mobility.

Study of more than 70,000 European children bolsters the findings of previous research

Barcelona Institute for Global Health (Spain), May 31, 2021

An epidemiological study of more than 70,000 children in six European cohorts has linked symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum conditions (ASC) to the mothers' use of paracetamol (acetaminophen) during pregnancy. The study, published in the European Journal of Epidemiology, was led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation. 

In total, the researchers analysed 73,881 children for whom data were available on prenatal or postnatal exposure to paracetamol, at least one symptom of ASC or ADHD, and main covariates. Depending on the cohort, 14% to 56% of the mothers reported taking paracetamol while pregnant. 

The study found that children exposed to paracetamol before birth were 19% more likely to develop ASC symptoms and 21% more likely to develop ADHD symptoms than children who were not exposed. 

"Our findings are consistent with previous research," explained ISGlobal researcher Sílvia Alemany, lead author of the study. "We also found that prenatal exposure to paracetamol affects boys and girls in a similar way, as we observed practically no differences." 

"Our results address some of the weaknesses of previous meta-analyses," commented Jordi Sunyer, researcher at ISGlobal and last author of the study. "Considering all the evidence on the use of paracetamol and neurological development, we agree with previous recommendations indicating that while paracetamol should not be suppressed in pregnant women or children, it should be used only when necessary." 

At some point during pregnancy, an estimated 46%-56% of pregnant women in developed countries use paracetamol, which is considered the safest analgesic/antipyretic for pregnant women and children. However, mounting evidence has linked prenatal paracetamol exposure to poorer cognitive performance, more behavioural problems, and ASC and ADHD symptoms.

Those previous studies have been criticised for their heterogeneity. In the new study, therefore, "an effort was made to harmonise the assessment of ADHD and ASC symptoms and the definition of paracetamol exposure," explained Alemany. "The sample is large," she added, "and it includes cohorts from multiple European countries: the United Kingdom, Denmark, the Netherlands, Italy, Greece and Spain. We also used the same criteria for all of the cohorts, thereby reducing the heterogeneity of criteria that has hampered previous studies." 

The study also analysed postnatal exposure to paracetamol and found no association between paracetamol use during childhood and ASC symptoms. Nevertheless, the research team concluded that further studies are needed, given the heterogeneity of postnatal paracetamol exposure among the various cohorts, which ranged from 6% to 92.8%.

The six cohorts included the study were as follows:

2. Danish National Birth Cohort (DNBC) 

3. Gene and Environment: Prospective Study on Infancy in Italy (GASPII) 

4. Generation R Study

5. INMA (including four subcohorts)

6. Mother-Child Cohort in Crete (RHEA)

University of Colorado, May 28, 2021

Waking up just one hour earlier could reduce a person's risk of major depression by 23%, suggests a sweeping new genetic study published May 26 in the journal JAMA Psychiatry.

The study of 840,000 people, by researchers at University of Colorado Boulder and the Broad Institute of MIT and Harvard, represents some of the strongest evidence yet that chronotype--a person's propensity to sleep at a certain time --influences depression risk. 

It's also among the first studies to quantify just how much, or little, change is required to influence mental health. 

As people emerge, post-pandemic, from working and attending school remotely-- a trend that has led many to shift to a later sleep schedule--the findings could have important implications. 

"We have known for some time that there is a relationship between sleep timing and mood, but a question we often hear from clinicians is: How much earlier do we need to shift people to see a benefit?" said senior author Celine Vetter, assistant professor of integrative physiology at CU Boulder. "We found that even one-hour earlier sleep timing is associated with significantly lower risk of depression."

Previous observational studies have shown that night owls are as much as twice as likely to suffer from depression as early risers, regardless of how long they sleep. But because mood disorders themselves can disrupt sleep patterns, researchers have had a hard time deciphering what causes what.

Other studies have had small sample sizes, relied on questionnaires from a single time point, or didn't account for environmental factors which can influence both sleep timing and mood, potentially confounding results. 

In 2018, Vetter published a large, long term study of 32,000 nurses showing that "early risers" were up to 27% less likely to develop depression over the course of four years, but that begged the question: What does it mean to be an early riser?

To get a clearer sense of whether shifting sleep time earlier is truly protective, and how much shift is required, lead author Iyas Daghlas, M.D., turned to data from the DNA testing company 23 and Me and the biomedical database UK Biobank. Daghlas then used a method called "Mendelian randomization" that leverages genetic associations to help decipher cause and effect. 

"Our genetics are set at birth so some of the biases that affect other kinds of epidemiological research tend not to affect genetic studies," said Daghlas, who graduated in May from Harvard Medical School. 

More than 340 common genetic variants, including variants in the so-called "clock gene" PER2, are known to influence a person's chronotype, and genetics collectively explains 12-42% of our sleep timing preference. 

The researchers assessed deidentified genetic data on these variants from up to 850,000 individuals, including data from 85,000 who had worn wearable sleep trackers for 7 days and 250,000 who had filled out sleep-preference questionnaires. This gave them a more granular picture, down to the hour, of how variants in genes influence when we sleep and wake up. 

In the largest of these samples, about a third of surveyed subjects self-identified as morning larks, 9% were night owls and the rest were in the middle. Overall, the average sleep mid-point was 3 a.m., meaning they went to bed at 11 p.m. and got up at 6 a.m.

With this information in hand, the researchers turned to a different sample which included genetic information along with anonymized medical and prescription records and surveys about diagnoses of major depressive disorder. 

Using novel statistical techniques, they asked: Do those with genetic variants which predispose them to be early risers also have lower risk of depression?

The answer is a firm yes. 

Each one-hour earlier sleep midpoint (halfway between bedtime and wake time) corresponded with a 23% lower risk of major depressive disorder.

This suggests that if someone who normally goes to bed at 1 a.m. goes to bed at midnight instead and sleeps the same duration, they could cut their risk by 23%; if they go to bed at 11 p.m., they could cut it by about 40%.

It's unclear from the study whether those who are already early risers could benefit from getting up even earlier. But for those in the intermediate range or evening range, shifting to an earlier bedtime would likely be helpful.

What could explain this effect?

Some research suggests that getting greater light exposure during the day, which early-risers tend to get, results in a cascade of hormonal impacts that can influence mood.

Others note that having a biological clock, or circadian rhythm, that trends differently than most peoples' can in itself be depressing.

"We live in a society that is designed for morning people, and evening people often feel as if they are in a constant state of misalignment with that societal clock," said Daghlas.

He stresses that a large randomized clinical trial is necessary to determine definitively whether going to bed early can reduce depression. "But this study definitely shifts the weight of evidence toward supporting a causal effect of sleep timing on depression." 

For those wanting to shift themselves to an earlier sleep schedule, Vetter offers this advice:

"Keep your days bright and your nights dark," she says. "Have your morning coffee on the porch. Walk or ride your bike to work if you can, and dim those electronics in the evening."

A compound found in olive oil may help to prevent cancer developing in the brain, a study shows.

Research into oleic acid – the primary ingredient in olive oil – has shown how it can help prevent cancer-causing genes from functioning in cells.

The oily substance – one of a group of nutrients known as fatty acids – stimulates the production of a cell molecule whose function is to prevent cancer-causing proteins from forming.

The study team says it is too soon to say whether dietary consumption of olive oil may help prevent brain cancer.

Their findings, however, point towards possible therapies based on the oil to prevent brain cancer from occurring.

Scientists from the University analysed the effect of oleic acid on a cell molecule, known as miR-7, which is active in the brain and is known to suppress the formation of tumours.

They found that oleic acid prevents a cell protein, known as MSI2, from stopping production of miR-7.

In this way, the olive oil component supports the production of miR-7, which helps prevent tumours from forming.

Researchers made their discoveries in tests on human cell extracts and in living cells in the lab.

The study, published in the Journal of Molecular Biology, was funded by the Medical Research Council and the Wellcome Trust.

"While we cannot yet say that olive oil in the diet helps prevent brain cancer, our findings do suggest that oleic acid can support the production of tumour-suppressing molecules in cells grown in the lab. Further studies could help determine the role that olive oil might have in brain health," says Dr Gracjan Michlewski.

Central South University (China), May 29, 2021

Researchers from China have found that increased selenium intake may reduce a person’s risk for osteoporosis. In their report, experts from Central South University in Changsha recruited over 6,200 participants and measured the bone mineral density in the middle phalanges of the second to fourth fingers of their non-dominant hand. The team then assessed the participants’ dietary patterns, particularly their selenium intake, through a validated semi-quantitative food frequency questionnaire which the subjects answered twice within three weeks.

After analyzing the participants’ bone mineral density using a compact radiographic absorptiometry system, the team discovered that 9.6 percent of the subjects have osteoporosis. The majority of the cases were reported among women, with 19.7 percent having been diagnosed with the disease. Among men, only 2.3 percent were diagnosed with osteoporosis.

The researchers also compared the dietary data of those diagnosed with osteoporosis to those who were not. They found that there are significant differences between the participants in terms of age, gender, smoking and drinking habits, BMI, blood pressure levels, physical activity levels, nutrient supplementation, dietary calcium intake, dietary fiber intake and dietary energy intake. The factors above were measured as they are considered to be vital for the development and prevention of osteoporosis.

But most of all, the team observed a significant difference between the subjects with osteoporosis and those who don’t have the disease in terms of dietary selenium intake. The researchers found that those who have osteoporosis also have lower levels of dietary selenium consumption.

A person can increase his selenium intake by eating Brazil nuts, fish, shellfish, beef, turkey, chicken, fortified cereals, whole-wheat bread, beans, lentils and eggs. The recommended dietary allowance for selenium is 55 micrograms per day for adult men and women above 19 years old. For pregnant and lactating women, the recommended intake is between 60 to 70 micrograms per day.

However, in the study, which involved Chinese citizens, the participants’ selenium intake averaged only 43.5 micrograms per day. This is comparable to the average daily selenium intake of Europeans, which is 40 micrograms per day. The low selenium intake of both populations could be due to the low-selenium content of the soil in both areas.

Selenium primarily functions in the body as an essential component of selenoproteins, composed of various enzymes and proteins that help protect the cells from damage and infections. Selenoproteins are also needed in producing DNA and in the metabolism of thyroid hormones. The thyroid glands have the highest concentration of selenium in the body.

In connection to thyroid hormones, the researchers postulated that low selenium levels might have increased the level of thyroid hormones in the blood, which may have caused an accelerated bone loss and osteoporosis in the subjects with low dietary selenium intake. Thyroid problems have indirect correlations with osteoporosis and are considered as secondary causes. This means that elevated thyroid hormone levels don’t directly cause osteoporosis, but they can influence how the body maintains a healthy mineral bone density.

In addition, hyperthyroidism, a thyroid disorder characterized by too much production of a thyroid hormone thyroxine, is considered as having a close link to the development of osteoporosis. This is because elevated levels of thyroxine accelerate the process of bone degradation, which is conducted by the osteoclasts. Osteoclasts are the cells that dissolvethe bones, initiating new bone production, which is conducted by another cell — the osteoblasts. Excessive thyroxine levels make the osteoclasts work faster than the osteoblasts, causing the bones to be fragile or brittle.

However, the researchers in the study did not confirm a causal relationship between dietary selenium intake and osteoporosis, but future studies are underway to provide support to their findings.

According to news originating from Honolulu, Hawaii, by NewsRx correspondents, research stated, “Selenium (Se) is an essential micronutrient of critical importance to mammalian life.”

The news reporters obtained a quote from the research from University of Hawaii: “Its biological effects are primarily mediated via co-translational incorporation into selenoproteins, as the unique amino acid, selenocysteine. These proteins play fundamental roles in redox signaling and includes the glutathione peroxidases and thioredoxin reductases. Environmental distribution of Se varies considerably worldwide, with concomitant effects on Se status in humans and animals. Dietary Se intake within a narrow range optimizes the activity of Se-dependent antioxidant enzymes, whereas both Se-deficiency and Se-excess can adversely impact health. Se-deficiency affects a significant proportion of the world’s population, with hypothyroidism, cardiomyopathy, reduced immunity, and impaired cognition being common symptoms. Although relatively less prevalent, Se-excess can also have detrimental consequences and has been implicated in promoting both metabolic and neurodegenerative disease in humans.”

According to the news editors, the research concluded: “Herein, we sought to comprehensively assess the developmental effects of both Se-deficiency and Se-excess on a battery of neurobehavioral and metabolic tests in mice. Se-deficiency elicited deficits in cognition, altered sensorimotor gating, and increased adiposity, while Se-excess was surprisingly beneficial.”

NOVA Southeastern University of Florida, May 27, 2021

Aristotelia chilensis, also known as maqui berry, is a fruit-bearing shrub native to South America. 

According to a study published in the journal Phytochemical Analysis, maqui berries are rich in anthocyanins, which give the fruits their dark purple color. Anthocyanins are plant pigments that possess many remarkable biological properties, such as antioxidant, anti-inflammatory, anti-viral and anti-cancer activities.

In a recent study, researchers at NOVA Southeastern University in Florida discussed the potential of Chilean maqui berry for use as a nutritional supplement that can help treat hyperinsulinemia and related diseases. Hyperinsulinemia, or higher-than-normal insulin levels, is often caused by insulin resistance, which is said to be the precursor to diabetes. Chronic hyperinsulinemia also promotes cancer growth by allowing insulin to exert its oncogenic effects, which include enhancing growth factor-dependent cell proliferation, among others.

The researchers discussed how Chilean maqui berry can help with insulin resistance and reduce cancer risk in an article published in the journal Food Science and Human Wellness.

Researchers have long considered nutritional supplementation to be a possible alternative or adjunct treatment to conventional therapies for common ailments and diseases. According to recent studies, maqui berries can reduce postprandial insulin levels by as much as 50 percent and are just as effective as metformin at increasing insulin sensitivity and stabilizing blood glucose levels.

Maqui berries’ mechanism of action involves inhibiting sodium-dependent glucosetransporters in the small intestine and slowing the rate of entry of glucose in the bloodstream. Thanks to these actions, maqui berries can effectively reduce the likelihood of blood sugar spikes and prevent the corresponding rise in insulin levels that follows. 

At the same time, maqui berries contribute to cancer prevention since chronically high blood glucose levels — besides chronic hyperinsulinemia — are also linked to the development of cancer. In fact, numerous studies have shown that diabetics and prediabetics have an elevated risk of developing cancerous growths.

Based on the findings of previous studies, the researchers believe that consistent supplementation with Chilean maqui berries could indirectly reduce the risk of cancer and other diseases that are promoted by hyperglycemia (high blood sugar) and hyperinsulinemia.

University of Naples (Italy) and Teva Pharmaceuticals, May 30, 2021

Abstract 803: Impact of social isolation and quarantine on the course of diabetes mellitus and its complications during Covid 19 pandemic in Adjara Region Country of Georgia

Abstract 1337: Psychological distress in patients with hypocortisolism during mass quarantine for Covid-19 epidemic in Italy

Studies reveal that social isolation and quarantine throughout the COVID-19 pandemic may have a detrimental impact on people living with pre-existing conditions. 

Social isolation and quarantine can have a detrimental impact on physical and mental health of people living with pre-existing conditions, according to two studies being presented at the 23rd European Congress of Endocrinology (e-ECE 2021) 

The studies bring together research on the impact of social isolation and quarantine for people living with diabetes in the Adjara Region of Georgia, and on patients with hypocortisolism in Italy. Both studies reported that social isolation during the pandemic caused significant psychological and/or physical distress on the observed individuals. 

Data from the first study revealed that the impact of quarantine on people living with diabetes in the Adjara Region caused blood pressure (BP) levels to increase in 88.2% of patients with 50% of these cases resulting in high BP hospitalisation. In addition to these physical factors, increased feelings of anxiety and fear were observed on 82% of patients. In the second study, patients with hypocortisolism experienced increased anxiety and depression, associated with a dissatisfaction feeling of self and a reduced resiliency, when compared with Italian healthy controls. As these are all contributing factors to overall health deterioration, these findings suggest further research is required to allow patients with pre-existing conditions to remain fit and healthy during the current pandemic.

In the Adjara Region study, Dr Liana Jashi and the research team disseminated an online questionnaire and collected answers from 16 endocrinologists and 22 family and general practice doctors. The study confirmed the negative, indirect effects social isolation and quarantine had on people living with diabetes. It reported a list of negative effects such as the reduced access to medical care, weight gain and increased cigarette and alcohol consumption. Physical activity decreased by 29.8%, a vital preventative to further physical and psychological problems. 

"This study highlights that people living with diabetes require greater support during pandemics to maintain exercise and protect their physical and mental health. National health services should use these data and future studies to implement better social care around supporting people with pre-existing conditions," commented Dr Jashi.

In the second study, Dr Chiara Simeoli at the University of Naples reported data collected during the last three weeks of the mass quarantine lasted 2 months in Italy, in a web-survey-based, multicenter, case- control research involving 12 different Italian centres. The study confirmed that a large cohort of 478 patients with hypocortisolism, and particularly, 363 with adrenal insufficiency and 115 with congenital adrenal hyperplasia, adequately treated with glucocorticoids, showed higher anxiety and depression, associated with a dissatisfaction feeling of self and a reduced resiliency, when compared with Italian healthy controls, suggesting the detrimental impact of social isolation on mental health of these patients, particularly frail and vulnerable to infections and stress. Moreover, patients with adrenal insufficiency reported a worse quality of life than patients with congenital adrenal hyperplasia. 

"These findings confirmed that beyond the huge impact on physical health, COVID-19 epidemic, social isolation and mass quarantine represent significant psychological stressors, causing severe effects on mental health, even more on people with pre-existing conditions. An empowerment of psychological counselling for these vulnerable patients during COVID-19 should be considered by national health-care services," adds Dr Simeoli. 

Both studies indicate that additional larger studies over a longer period of time are needed for further investigation.

University of Seville (Spain), May 24, 2021

The study, published in the journal Nature Aging and led by the laboratories of Dr. Alberto Pascual (CSIC), from the Neuronal Maintenance Mechanisms Group, and Prof. Javier Vitorica (University of Seville/CIBERNED) of the Physiopathology of Alzheimer's Disease Group at IBiS, demonstrates for the first time that low oxygen levels in the so-called senile plaques in the brain reduces the immune system's defensive capacity against the disease.

The study also suggests that this lack of oxygen in the brain enhances the action of disorders associated with Alzheimer's disease that are characterized by low systemic oxygen levels, such as atherosclerosis and other cardiovascular diseases.

What happens in the brain?

A characteristic feature of Alzheimer's patients is the accumulation of highly toxic substances in their brains, known as senile plaques. The brain has an immune system whose main component are the microglial cells, which were first described and named 100 years ago by Pío del Río Hortega, a disciple of Ramón y Cajal. In the absence of damage, these cells facilitate the neurons' function. In response to Alzheimer's disease, microglia defend neurons by surrounding senile plaques, preventing their spread in the brain and decreasing damage.

Alzheimer's disease is aggravated by other pathologies, such as cardiovascular diseases, which cause a decrease in oxygen levels in the body. This study has revealed reduced oxygen levels around senile plaques, compromising microglial activity (Image, center). When this is compounded by reduced oxygen supply to the brain due to other systemic pathologies, the microglia are unable to provide protection and there is an increase in the pathology associated with the disease.

Relevance

Alzheimer's disease is the leading cause of dementia in Spain and around the world. In Spain, its incidence is increasing dramatically as the population ages. Unfortunately, the origin of the disease remains unknown.

The mechanism proposed in this study is mediated by the expression of the HIF1 molecule, whose discoverers received the Nobel Prize in Physiology or Medicine in 2019. Increased HIF1 levels compromise the mitochondrial activity of microglial cells and limit their protective capacity against disease.

This study opens new lines of research to improve the metabolic capacity of microglia, which would enable a sustained response over time against the disease. Indirectly, the study supports previous work highlighting the importance of maintaining good cardiovascular health for healthy aging.

Guilan University of Medical Sciences (Iran), May 21, 2021

According to news reporting out of Rasht, Iran, research stated, “Alzheimer Disease (AD) is an age-related neurodegenerative disorder with a progressive impairment of cognitive function. The pineal gland hormone melatonin (MEL) has been known as a protection agent against AD.”

Our news reporters obtained a quote from the research from Guilan University of Medical Sciences: “However, the effect of melatonin in various doses is inconsistent. In this study, we aimed to investigate two doses of MEL on learning and memory in the amyloid-beta (Ab)-induced AD in the rats. Forty-eight male Wistar rats were used in the experiment and randomly divided control, sham, vehicle, AD, AD+MEL10 mg/kg, and AD+MEL 20 mg/kg groups. Intracerebroventricular injection of Ab1-42 was used to develop the animal model of AD. Also, MEL-treated groups received an intraperitoneal injection of MEL for 4 next weeks. The Morris Water Maze (MWM) and Passive Avoidance Learning (PAL) tests were used to examine animals’ learning and memory. The brain of animals was removed for immunohistochemistry for anti- Amyloid Precursor Protein (APP). Intra-peritoneal injection of MEL significantly improve learning and memory in MWM (P=0.000) and PAL test (P=0.000), but there were no significant changes in the two groups that received the melatonin (P>0.05). Histopathological analysis revealed that the clearance of APP deposition in the AD+MEL20 group was considerable compared with the AD+MEL10 group (P=0.000).”

According to the news editors, the research concluded: “Our findings indicate that 10 and 20 mg/kg doses of melatonin have similar results on learning and memory in the AD model. But 20 mg/kg of melatonin has significantly more effect on the clearance of APP deposition.”

Lorestan University of Medical Sciences (Iran), May 25, 2021

Given the antioxidant properties of flaxseed and its biologically active ingredients, this study was conducted to determine the effects of flaxseed supplementation on body mass index (BMI), blood pressure, and total cholesterol levels in patients with hypertension.

In this triple-blind clinical trial, 112 patients, with an age range of 35 to 70 years, were randomized to 2 groups receiving 10 g (n=45) and 30 g (n=45) of flaxseed supplementation and 1 group receiving placebo (n=45) for 12 weeks by stratified block randomization. They were evaluated in terms of systolic (SBP) and diastolic blood pressure (DBP), BMI, and total serum cholesterol. Physical activity was measured using the International Physical Activity Questionnaire–Short Form (IPAQ–SF) and food intake was assessed using the Food Frequency Questionnaire (FFQ). The data were analyzed with SPSS, version 22, using the chi-square, Kruskal–Wallis, repeated measures analysis, ANOVA, and ANCOVA tests.

The interaction effects among the study groups and time on the mean SBP (p = 0.001), DBP (p = 0.001), total cholesterol level (p = 0.032), and BMI (p < 0.001) were significant. During the study, the 30-g group achieved the best results, so that a 13.38-unit decrease in SBP was observed compared to a 1.72 unit increase in the placebo group and a 5.6-unit decrease in DBP was measured compared to a 2.39 unit increase in the placebo group. BMI decreased by 0.86 units compared to 0.06 units in the placebo group. Total cholesterol also decreased by 20.4 units compared to 11.86 units in the placebo group.

The results of this study showed that flaxseed can be effective in reducing blood pressure, total cholesterol, and body mass index in hypertensive patients in a twelve-week period.

Michigan State University, May 27, 2021

Rough night of sleep? Relying on caffeine to get you through the day isn't always the answer, says a new study from Michigan State University.

Researchers from MSU's Sleep and Learning Lab, led by psychology associate professor Kimberly Fenn, assessed how effective caffeine was in counteracting the negative effects of sleep deprivation on cognition. As it turns out, caffeine can only get you so far.

The study -- published in the most recent edition of Journal of Experimental Psychology: Learning, Memory, & Cognition -- assessed the impact of caffeine after a night of sleep deprivation. More than 275 participants were asked to complete a simple attention task as well as a more challenging "placekeeping" task that required completion of tasks in a specific order without skipping or repeating steps.

Fenn's study is the first to investigate the effect of caffeine on placekeeping after a period of sleep deprivation.

"We found that sleep deprivation impaired performance on both types of tasks and that having caffeine helped people successfully achieve the easier task. However, it had little effect on performance on the placekeeping task for most participants," Fenn said.

She added: "Caffeine may improve the ability to stay awake and attend to a task, but it doesn't do much to prevent the sort of procedural errors that can cause things like medical mistakes and car accidents." 

Insufficient sleep is pervasive in the United States, a problem that has intensified during the pandemic, Fenn said. Consistently lacking adequate sleep not only affects cognition and alters mood, but can eventually take a toll on immunity. 

"Caffeine increases energy, reduces sleepiness and can even improve mood, but it absolutely does not replace a full night of sleep, Fenn said. "Although people may feel as if they can combat sleep deprivation with caffeine, their performance on higher-level tasks will likely still be impaired. This is one of the reasons why sleep deprivation can be so dangerous."

Fenn said that the study has the potential to inform both theory and practice. 

"If we had found that caffeine significantly reduced procedural errors under conditions of sleep deprivation, this would have broad implications for individuals who must perform high stakes procedures with insufficient sleep, like surgeons, pilots and police officers," Fenn said. "Instead, our findings underscore the importance of prioritizing sleep."

Parkinson's disease more likely in people with depression, study suggests

Umea University (Sweden), May 21 2021

People with depression may be more likely to develop the movement disorder Parkinson's disease, according to new research published in Neurology.

According to the authors of the study, depression is more common in people with Parkinson's disease than those without the movement disorder.

"We saw this link between depression and Parkinson's disease over a timespan of more than 2 decades, so depression may be a very early symptom of Parkinson's disease or a risk factor for the disease," says study co-author Prof. Peter Nordström, at Umeå University in Sweden.

Parkinson's disease is a progressive disorder of the nervous system that affects how a person moves, including how they speak and write. As well as problems with movement, Parkinson's disease can also cause cognitive problems, neurobehavioral problems and sensory difficulties.

The authors of the study state that depression is more common in patients with Parkinson's disease than in members of the general population. The mood disorder has a major influence on health-related quality of life and could also be involved in more rapid deterioration of cognitive and motor functions.

However, few studies have investigated this association for periods of longer than 10 years, with any long-term findings so far inconclusive.

For the study, the researchers used a cohort consisting of all Swedish citizens aged 50 years and above as of December 31st, 2005. From this group, they then took the 140,688 people diagnosed with depression .

These individuals were each matched with three control participants (a total of 421,718 controls) of the same age and sex who had not been diagnosed with depression.

The participants were then followed for up to 26 years. A total of 1,485 people with depression (1.1%) developed Parkinson's disease during this time, compared with 1,775 of those who did not have depression (0.4%).

On average, Parkinson's disease was diagnosed 4.5 years after the beginning of the study, with the likelihood of the disorder developing decreasing over time.

No sibling link found for depression and Parkinson's disease

The researchers calculated that participants with depression were 3.2 times more likely than those without depression to develop Parkinson's disease within a year of the study beginning. After 15-25 years, the researchers found participants with depression were almost 50% more likely to develop the condition.

If a participant's depression was severe, their likelihood of developing Parkinson's disease was also higher. For example, those who had been hospitalized for depression five or more times were 40% more likely to develop Parkinson's disease than participants who had been hospitalized for depression just once.

In addition to these observations, the researchers examined siblings. No link was found between one sibling having Parkinson's disease and the other having depression.

"This finding gives us more evidence that these two diseases are linked," says Prof. Nordström. "If the diseases were independent of each other but caused by the same genetic or early environmental factors, then we would expect to see the two diseases group together in siblings, but that didn't happen."

The authors suggest there are a number of mechanisms that could explain their findings. Depression or antidepressive treatment could increase the risk of Parkinson's disease, depression could be an early symptom of Parkinson's disease, or that the two conditions could share environmental causative factors.

In the paper, the authors acknowledge that they are unable to evaluate the potential role of substances used in antidepressive treatment as risk factors for Parkinson's disease. The study is an observational one and cannot determine causation.

"Our findings suggest a direct association between depression and subsequent [Parkinson's disease], supported by a time-dependent hazard ratio, a dose-response pattern for recurrent depression, and a lack of evidence for coaggregation among siblings," the authors conclude.

"Given that the association was significant over more than two decades of follow-up, depression may be a very early prodromal symptom of or a causal risk factor for [Parkinson's disease]."

Elsewhere, a study published in December previously suggested that users of methamphetamine are at three times more risk of getting Parkinson's disease than people who do not use illegal drugs.

Exposing the lies behind the Covid-19 pandemic and the motivations behind it

Ronnie Cummins is the co-founder and International Director of the Organic Consumers Association and its Mexican affiliate Via Organica, the largest non-profit organization serving over 2 million consumers to safeguard organic standards and promote healthy sustainable agriculture and commerce.  In the 1990s, he was a director of the Foundation for Economic Trends in Washington DC. With almost  a million members, the Association is a non profit public interest organization campaigning for sustainable health and justice on critical issues of food safety, industrial agriculture, genetic engineering, Fair Trade and environmental sustainability. Ronnie has been a life-long activist in the human rights, anti-nuclear, labor and agricultural movements. His writings appear on numerous alternative, independent news including Commondreams, Truthout, and Huffington Post.  He is the author of “Genetically Engineered Foods: A Self Defense Guide for Consumers” and has just released a new book co-authored with Dr. Joseph Mercola, "The Truth About Covid-19: Exposing the Great Reset, Lockdowns, Vaccine Passports and the New Normal" which exquisitely goes into each of these topics.   His organization’s website is www.OrganicConsumers.org

Have the Architects of the Covid-19 Pandemic Lost Touch with Reality?

Richard Gale & Gary Null PhD

Progressive Radio Network, May 28, 2021

As the pandemic wages into its second year, two diametrically opposing movements have consolidated in defiance against each other. The dominant contingent, represented by Biden, Congress, Anthony Fauci, Bill Gates and the mainstream media, has decided that any citizen who refuses a Covid-19 vaccine is a de facto enemy of the state. “Ultimately,” Joe Biden declared during another gaff remark about the status of the government’s vaccination campaign, “those who are not vaccinated will pay – end up paying the price.” Despite the dubious claims that the mRNA vaccines are approximately 95 percent effective, the unvaccinated therefore mysteriously pose a health risk to the vaccinated. Consequently, any punitive actions the federal and state governments undertake, including encouraging the social media to publicly shame and censor voices of caution and reason, are justified. 

In an effort to marginalize and socially victimize Israeli citizens who have postponed or refused vaccination, Netanyahu and his right-wing Knesset supporters passed a bill permitting personal information and data about unvaccinated citizens to be shared across government agencies and civil institutions.  Israel was named by Pfizer’s CEO Albert Bourla as the “world’s lab” for the company’s Covid-19 vaccine roll out. Contrary to the government’s response to criticisms, the unvaccinated are theoretically second-class citizens, branded with a “scarlet letter” depriving them of full engagement with Israeli society, including going to a restaurant, attending a movie, concert or athletic event. Many are unable to shop or go to work.  Even the staunch pro-Zionist New York Times indicated the government’s policies are “moving in the direction of a two-tier system for the vaccinated and unvaccinated.” 

An analysis comparing Israeli Covid-19 infection and vaccine-related deaths conducted by Dr. Herve Seligmann, an Israeli-national at Aix-Marseille University of Medicine’s Faculty of Emerging Infectious and Tropical Diseases, concluded that the Pfizer vaccine has caused “mortality hundreds of times greater in young people compare[d] to the mortality from coronavirus without the vaccine, and dozens of times more in the elderly, when the documented mortality from coronavirus is in the vicinity of the vaccine, thus adding greater mortality from heart attack, stroke, etc.”  Seligmann and his co-author Haim Yativ have referred to Netanyahu’s draconian policies with unsafe experimental vaccines as a “new Holocaust.”  A civilian organization, the Israeli People Committee, which includes many health professionals, released a devastating report on the number of injuries and deaths resulting from Pfizer’s vaccine.  It was during the peak of the government’s vaccination campaign that Israel experienced its highest mortality rate, especially among those between 20 and 29 years of age. The Committee reported, “26 percent of all cardiac events occurred in young people up to the age of 40, with the most common diagnosis in these cases being myositis and pericarditis.” Other adverse vaccine reactions included infarction, stroke, miscarriage, impaired blood circulation and pulmonary embolisms.

Nevertheless, Israel has become the poster child for far more than serving as Pfizer’s experimental laboratory for human ferrets. It also models a caste society of haves and have nots, the rewarded and the repressed, the vaccine-anointed and the untouchables, as strategized by the World Economic Forum’s future technological proposals in its Great Reset. Netanyahu is has seemingly fully bought into Schwab’s Fourth Industrial Revolution and it’s re-visioning of the very definition of the human species. Last October, during the WEF’s “Great Reset” virtual session, Netanyahu appeared with Colombia’s far-right president Ivan Dugue – polled as the least popular president during that nation’s history -- and Rwanda’s war criminal Paul Kagame, along with executives in the biotech and financial industries, to advocate on behalf of the Forum’s mantra that the pandemic is an “opportunity” to further mobilize global digital infrastructure systems, including Covid-19 vaccination verification via microchip technology.

Now we are witnessing Canada, the UK and the US aggressively mimicking Israel’s heavy-handed policies to establish full-spectrum social control and make efforts to implement a post-modern, technologically driven caste system. Although Biden stated he does not support a federal mandate on vaccination passports, it has been left to the individual states to decide. Democrat-controlled states, notably New York, are issuing vaccine passports as a ticket to allow the vaccinated to return to a new normal. Republican governors on the other hand have been quick to denounce them, and in the case of Arizona, Florida, Idaho, Montana and Texas to executively ban them altogether. Hopefully some of the bans will challenge many of the over one hundred private colleges and universities that decided to require students to be vaccinated before returning in Fall.

The mainstream corporate-Democrat media, led by the New York Times, Washington Post, the Daily Beast, US News & World Report, CNN, NPR and MSNBC spew volleys of baseless propaganda that the vaccines are effective and wholly safe. However, thousands of medical school professors, physicians and researchers worldwide are challenging this non-consensual assumption. They regularly point out that there is no reliable science to justify any such claims. This raises the question: what are the vaccines effective against? Surely not contracting SARS-CoV-2; thousands of fully-vaccinated people are testing positive with the infection. The CDC has reported “seven percent of those [vaccinated] who have been infected have been hospitalized and 74 have died.”

Government efforts to reach a fictitious herd immunity threshold will inevitably come at a great cost to human life. More recent studies suggest that an exceedingly large percentage of Americans should technically be exempt from Covid-19 vaccines.  The University of Michigan published a recent analysis in JAMA Network Open suggesting that three percent of vaccinated Americans taking immune-weakening drugs have an increased risk of hospitalization. The study is grossly conservative and undermines the breadth of the problem. The researchers only analyzed patients with private insurance, under the age of 65, and who were only prescribed immunosuppressive steroids, such as corticosteroids and prednisone. Other immunosuppressive drugs such “selective immunosuppressants” and calcineurin and interleukin inhibitors were seemingly excluded from the Michigan analysis. Thirty-three percent of the American population was therefore excluded from the study because, according to the CDC, only 66.8 percent of the population has private health insurance. New York University researchers reported in the British Medical Journal that a third of patients receiving methotrexate and TNF-inhibitors for immune-mediated inflammatory illnesses such as rheumatoid arthritis and psoriasis fail to achieve sufficient antibodies from the Pfizer vaccine. We are certain this will be found equally true for many other medications if or when studies are conducted. 

The CDC’s belief that only 4 percent of Americans are immune-compromised is a misleading under-estimation. The agency’s defining criteria is narrow and limited to HIV/AIDS and cancer patients, inherited genetic diseases, and patients who have undergone organ transplants and are prescribed immunosuppressive drugs. On the other hand, there are over 100 different autoimmune conditions, including type-1 diabetes, multiple sclerosis, blood cancers, lupus, fibromyalgia, rheumatoid and other types of arthritis, psoriasis, IgG4 disease, Hashimoto’s and Addison’s diseases, celiac disease, etc. These additional individuals, who account for over 50 million Americans, have malfunctioning immune systems that increase their susceptibility to both severe SARS-CoV-2 infections (if left untreated during its early stage) and a higher probability of vaccine adverse reactions. 

Consequently, a very conservative 17 percent of Americans are at greater risk from either viral infection or vaccine injury or death. This also excludes tens of millions of adults (30 percent) and children (40 percent) with chronic allergies and many of the over 89,000 cancer patients diagnosed annually and prescribed chemotherapeutic drugs. Every year, nearly two-thirds of all Americans require emergency medical care from allergic reactions alone.  Furthermore, those with certain immune weaknesses are less likely to generate sufficient vaccine-induced antibodies thereby making Covid-19 vaccination ineffective. 

Especially disturbing is that the clinical trials the FDA relied upon for Emergency Use Authorization for the past five months of the vaccination campaign were based upon enrollment of healthy participants. Only recently are clinical trials either underway or in recruitment to test the vaccines on participants with weakened immune systems, including small children and infants, and on pregnant women. In the meantime, millions of immunosuppressed people diagnosed with autoimmune conditions or pre-existing comorbidities, from young to old, are being indiscriminately injected. Given the CDC’s previous track record of reckless vaccination policies, upon these trials’ completion, we will surely see vaccination forced upon every infant carelessly. This has been a policy enacted so far on the elderly, the sickly, the immune-compromised, pregnant moms, and the rest of the nation. It is not irrational, therefore, to suspect that past and present Covid-19 trials have been conducted with malice of forethought and with the unconditional approval of our federal health officials. 

During the pandemic, the rapid ascent of our vaccine-addicted culture’s mantra of “vaccination at any cost” truly borders on medical malfeasance and criminal negligence. The overriding emphasis on vaccination and near total disregard for implementing very simple preventative measures to inhibit infections from progressing in severity. If our health policymakers were wise men and women, alternative treatments such as ivermectin, hydroxycholoroquine, and more recent inexpensive off-patent drugs, which have been shown to be highly effective for early stage treatment and being widely prescribed elsewhere in the world, would be permitted and encouraged without reservation. There would be no reason to wait for a novel drug costing thousands of dollars per patient to arrive.  And we still await that magic bullet drug because the previous one, remdesivir, was faulty blank. This is just another example of the institutionalized pathology that infects our health agencies. 

There is no convincing science to support our federal officials belief that a previously infected person requires a Covid-19 vaccine to acquire immunity. In fact, more recent research indicates the opposite and goes directly against the intellectually fetid arguments of the now disgraced financier Bill Gates that every person on the planet should be vaccinated without exception. Johns Hopkins University professor Dr. Marty Makary has put forth the evidence that “natural immunity works.” Makary notes that it is only the rare instance when a person is being re-infected. Washington University School of Medicine reported this month that even mild Covid-19 infections induce long lasting antibody protection. The study’s lead researcher Dr. Ali Ellebedy stated,

"Last fall, there were reports that antibodies wane quickly after infection with the virus that causes COVID-19, and mainstream media interpreted that to mean that immunity was not long-lived… But that's a misinterpretation of the data. It's normal for antibody levels to go down after acute infection, but they don't go down to zero; they plateau. Here, we found antibody-producing cells in people 11 months after first symptoms. These cells will live and produce antibodies for the rest of people's lives. That's strong evidence for long-lasting immunity."

The information we were fed to downplay natural immunity was wrong at best, and more likely a lie, in order to further persuade the public into the importance of the vaccines to return their lives to normal. Another study appearing in this month’s Journal of Infectious Diseases found that “SARS-CoV-2 specific immune memory response [following infection] persists in most patients nearly one year after infection.” The Covid-19 vaccines can’t make the same promise. In fact, more reports show that  fully vaccinated persons are becoming infected. 

But it gets worse.  

The pro-vaccine argument wrongly assumes that anyone who refuses the Covid-19 vaccines is therefore anti-vaxxer. We would argue it is rational caution in the face of a national healthcare system indebted to the pharmaceutical industry and that is rapidly losing public trust. Likewise, if a doctor is successfully treating hundreds of patients without a reported death with cheap, effective drugs, she or he is canceled and ridiculed as a quack. Instead of open dialogue and debate, those who challenge the Medical Church Scientific are censored by Google and from all social platforms, such as Facebook, Twitter and Wikipedia. This is despite the impeccable credentials of many medical professionals abiding by the precautionary principle and who dare to challenge Anthony Fauci and the global vaccine czar Bill Gates, whose faux philanthropy is nothing less than another profitmaking enterprise like Microsoft. 

Conflicts of interests, both financial and non-financial, are endemic in our medical system. Therefore it becomes increasingly more difficult to trust any clinical study or government policy that is based upon flawed evidence submitted by a drug maker that fails to undergo a thorough independent and impartial review by qualified medical experts. There is a clear psychological reason for this. Many psychologists have pointed out over the years that “cognitive bias,” “motivated reasoning” and the heuristics driving the evaluation of clinical trial data and the subsequent institutional regulatory review and decision-making are deeply contrary and undermine the entire evidence-based criteria that should oversee what drugs, vaccines, medical devices, therapeutic protocols should be recommended or approved for use upon the public.  

The late Scott Lilienfeld, a professor of psychology at Emory University, writes, “Clinicians are subject to the same errors in thinking that affect virtually all people. In particular, practitioners must be wary of (a) the misuse of certain heuristics (e.g., availability, representativeness) and (b) cognitive biases (e.g., confirmation bias, hindsight bias) in their everyday work.” Although Lilienfeld is singling out clinical physicians, it applies more rigorously and accurately to the pharmaceutical presidents, CEOs and chief science officers overseeing vaccine development who have stock prices to reach and shareholders to please.  Cognitive bias equally plagues the entire executive hierarchy at the CDC, NIAID, FDA and HHS who are beholden to the gaping revolving door between these agencies and private industry and their revenues. Writing about the deep ethical concerns behind bias in our medical institutions, Dr. Thomas Murray, President of the Hastings Center, states, “For scientists on a panel of the Food and Drug Administration, for example, it isn’t immediately clear to whom they owe their primary loyalty.”  Such biases, Murray believes, have completely destroyed the credibility of the World Health Organization.  

The fact that rates to reproduce medical clinical trials are so poor, according to behavioral economist Susann Fielder at the Max Planck Institute, is that “cognitive biases may be a reason for that.”  It also explains why Stanford University Medical School professor John Ioannidis argues, “most published research findings are false,” and “an estimated 85 percent of research resources are wasted.” Junk science based upon bias should also include every vaccine application submitted to the FDA for regulatory approval, since the vaccine companies are privileged to cherry-pick whichever trials they want to submit to create the most promising portfolio. 

One could review all of the official decisions made during the past 17 months – by Anthony Fauci, Trump and Biden and the naïve stances in both political parties – and should easily observe the frailties of cognitive bias and repeated contradictions throughout. None whatsoever are reliably truthful. And of course, cognitive bias leads to cognitive dissonance, such as denying that one has a bias or resorting to flagrant rejection and disparagement in order to avoid any scientific data that conflicts with one’s unfounded beliefs.

We now live in a nation of medicine by bureaucratic decree rather than by immunological science. This is postmodern cultism at its worst because it hides behind the veneer of being scientific. And it has the full support of a political technocracy that can ordain authoritarian laws. There is a dire need for a collective epiphany. All of us are experiencing the pandemic as a failed experiment orchestrated by institutions that have lost touch with reality. And it has been a very deadly experiment due to the extraordinary incompetence of our medical-degreed bureaucrats. Sadly the decades of institutional ineptitude has had to reach national and perhaps global awareness at this time when the powers that possess every technological tool at their disposal to conduct wide surveillance, pass undemocratic and draconian laws with full impunity, and control the fenced sheep within the mainstream media.

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The DisInformation Chronicle,

https://disinformationchronicle.substack.com/p/i-never-trusted-bill-gates-nor-should

The last year has not been kind to Bill Gates. 

For two decades, Gates has shoveled out buckets of cash through the Bill and Melinda Gates Foundation to transform himself from despised 1990’s software monopolist to a present-day public health intellectual—a miraculous, money-fueled metamorphosis. But that reputational makeover has stumbled, as a series of critical articles have tarnished Gates’ paid-for golden image and cast doubt on his credibility. However, long before these articles came to light, I already knew that Gates could not to be trusted. 

A decade ago, I led a Senate investigation into a multi-billion-dollar diabetes drug sold by GlaxoSmithKline (GSK) that government scientists found to have caused around 83,000 heart attacks. During this federal investigation, I uncovered multiple examples of GSK officials intimidating medical experts who decried the drug’s dangers. A leader in this campaign was GSK’s chairman of research and development, Dr. Tadataka (Tachi) Yamada. 

By the time our committee uncovered GSK’s coercion campaign, Yamada had left the company to run Gates’ global health program. And yet, as the media outlets reported on Yamada’s prior role bullying physicians who tried to warn about the drug’s dangers, the Gates Foundation ignored this public outcry and allowed Yamada to maintain his pulpit as global health protector.

Twenty years back, journalists scrutinized Gates’ foundation as a vehicle to enrich himself and polish his appearance. But over the years, reporters began to forget Gates’ past and provide him a platform to puff himself up as scientific expert, despite his having no medical or scientific credentials. Bill Gates’ sculpted persona as health policy guru began to wobble last summer, however, precisely because of revelations showing the tools he had used to improve his media cachet.

In August 2020, Tim Schwab published an article in the Columbia Journalism Review exposing around $250 million in grants that Gates was throwing at journalism outlets including the BBC, NBC, Al Jazeera, ProPublica, National Journal, The Guardian, Univision, Medium, the Financial Times, The Atlantic, the Texas Tribune, Gannett, Washington Monthly, Le Monde, and the Center for Investigative Reporting. 

A later article in The Nation spotlighted Gates’ potential to profit from investments in companies situated to reap a windfall from the COVID pandemic. And another report in The Nation found that Gates’ funding has stifled debate in public health—described as “the Bill chill”—as organizations are reluctant to bite the hand that feeds them.

These revelations came as little surprise to me. Back in 2007, I was working as an investigator for the Senate Finance Committee and learned first-hand that Bill Gates does not put the public first. That year, I wrote the Senate Finance Committee’s report showing that, shortly after the GSK diabetes drug Avandia came on the market in 1999, the company attacked and silenced several scientists including Dr. John Buse, a professor of medicine at the University of North Carolina. 

GSK began to bully Dr. Buse after he gave talks stating that Avandia might increase cardiovascular problems such as heart attacks. By the time we released the 2007 report, FDA scientists estimated that Avandia had caused approximately 83,000 heart attacks.

When Dr. Buse began warning physicians about the drug, Dr. Yamada was at GSK and contacted Dr. Buse’s department chairman to complain. In an email discussing Dr. Buse with GSK’s CEO and other executives, Dr. Yamada wrote: 

In any case, I plan to speak to Fred Sparling, his former chairman as soon as possible. I think there are two courses of action. One is to sue him for knowingly defaming our product even after we have set him straight as to the facts—the other is to launch a well planned offensive on behalf of Avandia....

In our report, we released a private email that Dr. Buse later sent a colleague detailing this encounter with GSK:

[T]he company’s leadership contact[ed] my chairman and a short and ugly set of interchanges occurred over a period of about a week ending in my having to sign some legal document in which I agreed not to discuss this issue further in public.

Dr. Buse ended the email, “I was certainly intimidated by them.... It makes me embarrassed to have caved in several years ago.”

Multiple media outlets covered Yamada’s actions, including The Guardian (GSK accused of trying to intimidate critic), NBC News (Diabetes drug probe leads to Gates Foundation), and even Bill Gates hometown newspaper, the Seattle Times (Senate committee turns attention to Gates Foundation official).

Months prior to the report’s release, The New York Times also detailed Dr. Yamada’s behavior (Doctor Says He Was Assailed for Challenging Drug’s Safety), as some initial evidence came to light during a hearing in the House. 

In response to all this outcry, Bill Gates did... nothing.

To put this matter directly under Bill Gates’ nose, I then wrote the Senate Committee’s letter demanding that Dr. Yamada come and brief Senate investigators. Just in case Gates was too distracted with saving the world and playing public health saviour to have noticed the bad press, I had the letter sent directly to the Gates Foundation.

When Dr. Yamada showed up for his appointment in Senate Hart, we started with some brief niceties and formalities—typical DC nonsense such as shaking hands, passing out business cards, asking how the plane flight was—before getting down to business. Dr. Yamada’s lawyer then pulled from his briefcase a marked-up copy of a Committee report I had written titled: The Intimidation of Dr. John Buse and the Diabetes Drug Avandia.  

We spent about twenty minutes going over the report, as the lawyer explained what Dr. Yamada had done. He then turned the matter over to Dr. Yamada to detail why, many years prior, he had called Dr. Buse's superiors at the University of North Carolina.

As Dr. Yamada explained, he wasn't trying to intimidate anyone. Ironically, he even offered up the idea that he had called Dr. Buse's dean at North Carolina, because he was concerned that Avandia might actually be harmful. And if the drug was harmful, Dr. Yamada said, he wanted to know.

I almost giggled when he said that.

I then asked, "So this is the only time that you can remember calling a university about one of their faculty?"

"Yes," he replied.

I let him drone on some more, explaining medical research, before I asked him again if he had ever called a university to complain about a professor. Again, he denied doing so, and then started explaining drug development and the regulatory process at the FDA. 

I then asked again, "So during all your time at GSK, this is the only incident you can remember where you placed a call to a university about a researcher who raised concerns about one of your products, correct?” I asked. “It was a singular incident in your time at the company?”

"Yes," he said.

This was the third time that Dr. Yamada had denied making calls to other universities to intimidate academics speaking up about Avandia. I then pulled out copies of GSK emails, showing that Dr. Yamada had called the University of Pennsylvania about physicians there who were worried about drug’s dangers.

“Would you like to explain to us about the call you made to the University of Pennsylvania?” I asked. “One of the physicians involved told me, 'It left a really bad taste in my mouth. After that happened, I said that I would never work for a drug company.’ Another physician who was involved told me, 'It’s the kind of thing you imagine happening on TV.'’’

I then slid the emails across the table to him. Dr. Yamada’s attorney jumped up and grabbed the emails saying, “These emails weren't in the report!”

“No shit, Counselor,” I thought. “I left these ones out, to see if your client might lie to us. Calm down. Everything's going to be A-O-K....”

We then exchanged some more niceties as Yamada “reexplained himself.” Oddly enough, it seems there may have been more than just that one incident at North Carolina, Dr. Yamada said. But I really wasn't interested in listening and started checking my Blackberry.

It took a couple more years to go through hundreds of thousands of GSK’s internal documents before we released our final 342-page report in 2010 titled: Staff Report on GlaxoSmithKline and the Diabetes Drug Avandia. But we redacted the names of the scientists at the University of Pennsylvania who Dr. Yamada had harassed for speaking up, because they were still scared about possible retaliation from the drug industry. 

After reading the report, Yale cardiologist Harlan Krumholz wrote that it "read like a spy novel.” Analysts at UBS predicted that GlaxoSmithKline could face legal liability of up to $6 billion. The New York Times covered the report on its front page and the CBS News put Yamada in its story’s headline: Meet Glaxo's Fixer -- The Man Who Scuttles Drug Critics With One Phone Call.

And still, Bill Gates did nothing.

Five months after the 2010 Senate Finance report, GSK agreed to a $460 million settlement with 10,000 Americans who sued the company for withholding Avandia’s heart attack risks. The New York Times editorialized that GSK and its leaders “can’t be trusted to report adverse clinical results fairly.” 

Nothing at all happened to Yamada. He remained in his role as global health expert at the Gates Foundation, until he left the following year, in June 2011. 

Keeping someone like Yamada to run a global health program has always made me doubt Bill Gates’ commitment to public health. How could anyone have faith in Gates’ judgement after watching him stand idly by as a stream of evidence proved that one of his top lieutenants had a history of corrupt behavior?

Since that time, I have never trusted Bill Gates. And neither should you.

Weizmann Institute of Science, May 24, 2021

A natural food supplement reduces anxiety in mice, according to a new Weizmann Institute of Science study. The plant-derived substance, beta-sitosterol, was found to produce this effect both on its own and in synergic combination with an antidepressant known under the brand name Prozac. If these findings, published today in Cell Reports Medicine, are confirmed in clinical trials, they could point the way toward the use of beta-sitosterol as a treatment for relieving anxiety in humans.

Anxiety is not always a bad thing. In fact, in evolutionary terms, feeling anxious about potential threats is critical for survival because it helps us mount an appropriate response. That's precisely why developing antianxiety drugs is so challenging. The circuits for anxiety in the brain are closely related to those responsible for memory, awareness and other functions vital for handling danger, so scientists are on the lookout for compounds that can selectively suppress anxiety without causing unwanted side effects.

The starting point for the present study was research conducted several years ago in the lab of Prof. Mike Fainzilber in Weizmann's Biomolecular Sciences Department. Dr. Nicolas Panayotis and other lab members studied the roles of proteins that shuttle cargoes into the nuclei of nerve cells, and they discovered that in stressful situations, mice lacking a shuttling protein known as importin alpha-five showed less anxiety than the control mice. The researchers then checked how these 'calmer' mice differed from regular ones in terms of gene expression, and they identified a genetic signature of their calmness: about 120 genes with a characteristic pattern of expression in the hippocampus, one of the brain regions that regulate anxiety.

In the new study, Panayotis, now a senior intern in Fainzilber's lab, together with colleagues, searched an international genomic database for existing drugs or other compounds that might mimic the same gene expression signature. He identified five candidates and tested their effects on behavior in mice. That was how the researchers zeroed in on beta-sitosterol, a plant substance sold as a dietary supplement intended mainly to reduce cholesterol levels.

In a series of behavioral experiments, mice given beta-sitosterol showed much less anxiety than the controls. They were, for example, less fearful than the controls when placed in an illuminated enclosure, daring to walk into its brightly lit center, whereas regular mice were careful to stay on the darker periphery, avoiding the stress of the bright light. Moreover, the mice receiving beta-sitosterol did not exhibit any of the side effects that might be expected from antianxiety medications—their locomotion was not impaired, and they did not refrain from exploring novel stimuli.

Next, the researchers tested the effects of beta-sitosterol on mice when given in combination with fluoxetine, a drug belonging to the class of selective serotonin reuptake inhibitors, or SSRIs, and sold under the brand name Prozac, among others. The combination had a synergistic effect: Both beta-sitosterol and fluoxetine reduced the anxiety of mice at lower doses when given together, compared with the doses needed to produce the same effect when they were administered separately.

"One of the major problems with existing antianxiety medications is that they produce side effects, so if beta-sitosterol could help cut down the dosage of such medications, it might potentially also reduce the unwanted side effects," Panayotis says.

A great advantage of beta-sitosterol is that it is naturally present in a variety of edible plants, and it is thought to be safe, as it has been marketed for years as a nutraceutical. It is found in particularly large concentrations in avocados, but also in pistachios, almonds and other nuts, in canola oil, in various grains and cereals and more.

However, this does not mean that eating avocado can induce a calming effect, since it doesn't contain enough beta-sitosterol. "You'd need to eat avocado day and night to get the right dose—and you would be more likely to develop digestive problems than relieve your anxiety," Panayotis says.

The precise mechanism of beta-sitosterol's effect on anxiety remains to be revealed, but the scientists did find that the expression of several genes known to be activated in stressful situations was reduced in mice given the supplement. They also found that these mice had changes in the levels of certain metabolites and neurotransmitters in brain areas involved in anxiety.

Since the study focused on brain regions and neural pathways that are involved in regulating anxiety in both mice and humans, it is likely that the findings will apply to humans as well. This will, however, require further clinical testing.

As Fainzilber points out: "There's a need for a clinical trial to test the use of beta-sitosterol for reducing anxiety in humans. Until then, we recommend that people consult their physicians before taking the supplement for this purpose."

Weil Cornell Medicine, May 20, 2021

A randomized phase II trial reported in 2020 in the Journal of Alzheimer’s Disease resulted in positive effects among individuals with amnestic mild cognitive impairment or mild Alzheimer’s dementia who were given capsules that contained benfotiamine, a derivative of thiamine (vitamin B1). 

The trial included 70 cognitively impaired men and women who received physical examinations and completed the Mini-Mental Status Exam (MMSE) prior to enrollment. Prospective candidates received positron emission tomography (PET)/CT scans of the brain to confirm the presence of amyloid plaques that are characteristic of Alzheimer disease) and other general blood tests, an electrocardiogram and neurological exam prior to enrollment. Screening tests commonly used to test for diabetes were also performed prior to enrollment, and participants were required to have a hemoglobin A1c (HbA1c) of less than 8% and/or a fasting glucose of less than 200 milligrams per deciliter to be enrolled in the trial.

APOE genotype was determined upon enrollment in the trial. The presence of one or two copies of the APOE4 variant of the APOE gene is associated with a greater risk of Alzheimer disease in comparison with APOE2 or APOE3.

Blood testing conducted at the beginning and end of the trial measured levels of vitamin B1 and advanced glycation end-products (AGEs), which are formed when fats or proteins react with sugar in the blood. (Research suggests that AGEs are predictive of long-term decline in cognition-related daily living performance in Alzheimer disease patients.) Participants also underwent fluorodeoxyglucose positron-emission tomography (FDG PET) at these time points to assess brain glucose utilization which, when reduced, is associated with cognitive decline. Cognitive tests, including the Alzheimer Disease Assessment Scale-Cognitive Subscale, Clinical Dementia Rating and others were administered at the beginning of the study and at varying time points thereafter. Participants received capsules containing 300 milligrams benfotiamine or a placebo twice daily for one year. 

At the end of the treatment period, thiamine levels were significantly elevated in the benfotiamine-intake group. The 12 month increase in Alzheimer Disease Assessment Scale-Cognitive Subscale scores (indicating increased cognitive dysfunction) was lower among those who received benfotiamine compared to the placebo group. Benfotiamine intake participants additionally experienced 77% less deterioration in Clinical Dementia Rating scores compared to the placebo group; however, the effect seen with benfotiamine was stronger among participants who did not have the APOE4 variant. Benfotiamine was also associated with a significant reduction in the increase in AGEs compared to the placebo, which again was stronger in noncarriers of APOE4. FDG PET data suggested that participants without APOE4 were more responsive to benfotiamine intake.

“Benfotiamine is safe and cost effective, and the results of this pilot study are encouraging, providing preliminary evidence of efficacy,” authors Gary E. Gibson of Weil Cornell Medicine and colleagues concluded. “Our next step is to propose a larger clinical trial appropriately powered to replicate our findings. We believe that further studies would be very valuable to determine whether benfotiamine may be helpful in delaying onset or treating Alzheimer disease.”

Dana Farber Cancer Institute, May 21, 2021

BOSTON - Prompted by a recent alarming rise in cases of colorectal cancer in people younger than 50, an independent expert panel has recommended that individuals of average risk for the disease begin screening exams at 45 years of age instead of the traditional 50. 

The guideline changes by the U.S. Preventive Services Task Force (USPSTF), published in the current issue of JAMA, updates its 2016 recommendations and aligns them with those of the American Cancer Society, which lowered the age for initiation of screening to 45 years in 2018.

Colorectal cancer (CRC) is one of the most preventable malignancies, owing to its long natural history of progression and the availability of screening tests that can intercept and detect the disease early. Overall incidence of CRC in individuals 50 years of age and older has declined steadily since the mid-1980s, largely because of increased screening and changing patterns of modifiable risk factors.

"A concerning increase in colorectal cancer incidence among younger individuals (ie, younger than 50 years; defined as young-onset colorectal cancer) has been documented since the mid-1990s, with 11% of colon cancers and 15% of rectal cancers in 2020 occurring among patients younger than 50 years, compared with 5% and 9%, respectively, in 2010," said Kimmie Ng, MD, MPH, first author of an editorial in JAMA accompanying the article about the guideline change of the USPSTF. Ng is the director of the Young-Onset Colorectal Cancer Center at Dana-Farber Cancer Institute. 

The causes of the increase in young-onset CRC aren't currently known. 

Lowering the recommended age to initiate screening "will make colorectal cancer screening, which is so important, available to millions more people in the United States, and hopefully many more lives will be saved by catching colorectal cancer earlier, as well as by preventing colorectal cancer," said Ng.

The USPSTF is an independent panel of experts funded by the U.S. Department of Health and Human Services. It systematically reviews the evidence of effectiveness of preventive services and develops recommendations. American health insurance groups are required to cover, at no charge to the patient, any service that the USPSTF recommends with a grade A or B level of evidence, regardless of how much it costs.

The task force recommendation means that insurers will be required to cover preventive procedures such as colonoscopies and stool tests designed to detect colon cancer in early stages.

The task force selected age 45 based on research showing that initiating screening at that age averted more early deaths than starting at age 50, with a relatively small increase in the number of colonoscopy complications. There is no change to the USPSTF 2016 recommendation to only selectively screen individuals aged 76 to 85, as research shows only small increases in life-years gained.

The accompanying JAMA editorial asked rhetorically whether the age of screening should be lowered even younger than age 45. While the majority of young-onset CRC diagnoses and deaths occurs in persons 45 to 49, the rate of increase in young-onset CRC is actually steepest in the very youngest patients. Colon cancer incidence is increasing by 2% per year in 20 to 29-year-olds, compared with 1.3% in 40 to 49-year-olds. Rectal cancer incidence is increasing by 3.2% per year in 20 to 29-year-olds and 30 to 39-year-olds, versus 2.3% in 40 to 49-year-olds.

"We are now seeing patients even younger than 45 - in their 20s and 30s - who are being diagnosed with this cancer and often at very late stages," said Ng. "Clearly the USPSTF recommendation to start screening at age 45 will not be enough to catch those young people who are being diagnosed."

Ultimately, optimal prevention and early detection of CRC in people younger than 45 will require further research into the underlying causes and risk factors of young-onset CRC, which have thus far remained elusive, said the editorial authors. 

The authors also called for "bold steps" to translate the lowered age of beginning screening into meaningful decreases in CRC incidence and mortality, noting that despite the preventive benefits of colorectal cancer screening, only 68.8 percent of eligible individuals in the United States undergo screening. The rate is lower among the uninsured and underinsured, those with low incomes, and racial and ethnic minorities. Barriers include lack of knowledge of the importance of screening, concerns about the invasive nature of colonoscopy, and lack of access to and provider recommendations for screening.

The editorial lists examples including public awareness campaigns, including those aimed at gaps in CRC incidence and mortality between Black and white Americans, and specific actions. Employers could provide 45-year-old employees with a paid "wellness day" to undergo CRC screening, or offer day care or transportation vouchers to overcome the logistical hurdles of colonoscopies. Health systems could offer weekend or after-hours appointments for colonoscopies.

The new recommendation "represents an important policy change," the authors wrote, "to drive progress toward reducing colorectal cancer incidence and mortality."

Study Finds New and Effective Treatment for Vitamin D Deficiency

Boston University School of Medicine, May 20, 2021

There are several million people worldwide with various fat malabsorption syndromes including those who have undergone gastric bypass surgery and those with obesity. These patients often have a difficult time absorbing vitamin D and both groups of patients are at an increased risk for vitamin D deficiency and therefore at higher risk for osteoporosis and osteomalacia (softening of the bones). Patients with obesity are also susceptible to vitamin D deficiency as vitamin D derived from intestinal absorption and cutaneous synthesis is diluted in a larger body pool of fat. Now a new study demonstrates 25-hydroxyvitamin D3 is an effective treatment for vitamin D deficiency for these specific patients.

According to the researchers, approximately one third of adults are obese and require much larger doses of vitamin D to satisfy their requirement. "This vitamin D metabolite is better absorbed in patients with fat malabsorption syndromes and since it is not as fat soluble, it does not gets diluted in the body fat and is effective in raising and maintaining blood levels of 25-hydroxyvitamin D in obese people," explained corresponding author Michael F. Holick, PhD, MD, professor of medicine, physiology and biophysics and molecular medicine at Boston University School of Medicine.

Healthy adults, adults with a fat malabsorption syndrome and obese adults were compared to evaluate if a more water-soluble form of vitamin D3 known as 25-hydroxyvitamin D3 was more effective than the same dose of vitamin D3 in improving their vitamin D status. The researchers observed that compared to healthy adults only about 36 percent of orally ingested vitamin D3 was found in the blood of patients with fat malabsorption syndromes including patients who had gastric bypass surgery. When the same adults ingested 25-hydroxyvitamin D3 the patients with fat malabsorption syndromes were able to absorb it as well as the healthy adults thereby raising their vitamin D status to the same degree. A similar observation was made in the obese subjects compared to the healthy controls. "Therefore using 25-hydroxyvitamin D3 could be a novel approach for treating vitamin D deficiency in patients with fat malabsorption syndromes and obese adults," added Holick.

Vitamin D deficiency not only results in bone loss increasing risk for fracture but causes the painful bone disease osteomalacia. Patients who are vitamin D deficient with osteomalacia have unrelenting achiness in their bones and muscles. Vitamin D deficiency has been associated with an increased risk of many chronic illnesses including multiple sclerosis, type 1 diabetes, heart disease, type 2 diabetes, depression, neurocognitive dysfunction and Alzheimer's disease as well as infectious diseases including COVID.

These findings appear online in the American Journal of Clinical Nutrition.

Rutgers University, May 24, 2021

Middle-school aged children who use the internet, social media or video games recreationally for more than an hour each day during the school week have significantly lower grades and test scores, according to a study from the Center for Gambling Studies at Rutgers University-New Brunswick.

The findings appear in the journal Computers in Human Behavior. 

Researchers say the findings give parents and children a moderate threshold for using entertainment-related technology -- no more than one hour daily on school days and four hours a day on weekends. 

"Interactive technology is widely used to promote children's educational access and achievement," said lead author Vivien (Wen Li) Anthony, an assistant professor at the School of Social Work and research associate at the Rutgers Center for Gambling Studies. "During the COVID-19 pandemic, technology has been essential to facilitating remote learning. At the same time, there is a growing concern that excessive technology use, particularly for entertainment, may adversely affect children's educational development by facilitating undesirable study habits and detracting from time spent on learning activities." 

The researchers, which include Professor Lia Nower of the Rutgers Center for Gambling Studies and a researcher from Renmin University of China, analyzed the China Education Panel Survey data, a national survey of educational needs and outcomes of children in China. Approximately 10,000 first-year middle school students were surveyed and followed. Their average age was 13.5 years.

The results showed that children who used the internet, social media or video games for entertainment four or more hours daily were four times more likely to skip school than those who did not. Boys used interactive technology for entertainment significantly more than girls. Boys also performed worse and showed lower school engagement levels than girls.

"Such findings are critical, particularly in light of the recent movement toward online learning in countries throughout the world," said Anthony. "In a learning environment that integrates the internet, it is easy for children to move across educational and entertainment platforms during learning without alerting teachers or adults to alternate activities."

Anthony said children in the study who used technology in moderation (i.e., less than one hour per day on weekends) experienced less boredom at school, potentially due to the positive effects of participation in social media, video games and video streaming such as peer bonding and relationship building. Using interactive technology for entertainment in moderation advanced children's cognitive development. 

The findings suggest that parents place time limits on their children's interactive technology use, and that parents and teachers should help children to develop effective time management and self-regulation skills to reduce their reliance on technology.

University of Bologna (Italy),  May 19, 2021

Researchers have found that people who live beyond 105 years tend to have a unique genetic background that makes their bodies more efficient at repairing DNA, according to a study published in eLife.

This is the first time that people with ‘extreme longevity’ have had their genomes decoded in such detail, providing clues as to why they live so long and manage to avoid age-related diseases.

“Aging is a common risk factor for several chronic diseases and conditions,” explains Paolo Garagnani, Associate Professor at the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy, and a first author of the study. “We chose to study the genetics of a group of people who lived beyond 105 years old and compare them with a group of younger adults from the same area in Italy, as people in this younger age group tend to avoid many age-related diseases and therefore represent the best example of healthy aging.”

Garagnani and colleagues, in collaboration with several research groups in Italy and a research team led by Patrick Descombes at Nestle Research in Lausanne, Switzerland, recruited 81 semi-supercentenarians (those aged 105 years or older) and supercentenarians (those aged 110 years or older) from across the Italian peninsula. They compared these with 36 healthy people matched from the same region who were an average age of 68 years old.

They took blood samples from all the participants and conducted whole-genome sequencing to look for differences in the genes between the older and younger group. They then cross-checked their new results with genetic data from another previously published study which analysed 333 Italian people aged over 100 years old and 358 people aged around 60 years old.

They identified five common genetic changes that were more frequent in the 105+/110+ age groups, between two genes called COA1 and STK17A. When they cross-checked this against the published data, they found the same variants in the people aged over 100. Data acquired from computational analyses predicted that this genetic variability likely modulates the expression of three different genes.

The most frequently seen genetic changes were linked to increased activity of the STK17A gene in some tissues. This gene is involved in three areas important to the health of cells: coordinating the cell’s response to DNA damage, encouraging damaged cells to undergo programmed cell death and managing the amount of dangerous reactive oxygen species within a cell. These are important processes involved in the initiation and growth of many diseases such as cancer.

The most frequent genetic changes are also linked to reduced activity of the COA1 gene in some tissues. This gene is known to be important for the proper crosstalk between the cell nucleus and mitochondria - the energy-production factories in our cells whose dysfunction is a key factor in aging.

Additionally, the same region of the genome is linked to an increased expression of BLVRA in some tissues - a gene that is important to the health of cells due to its role in eliminating dangerous reactive oxygen species.

“Previous studies showed that DNA repair is one of the mechanisms allowing an extended lifespan across species,” says Cristina Giuliani, Senior Assistant Professor at the Laboratory of Molecular Anthropology, Department of Biological, Geological and Environmental Sciences, University of Bologna, and a senior author of the study. “We showed that this is true also within humans, and data suggest that the natural diversity in people reaching the last decades of life are, in part, linked to genetic variability that gives semi-supercentenarians the peculiar capability of efficiently managing cellular damage during their life course.”

The team also measured the number of naturally occurring mutations that people in each age group had accumulated throughout their life. They found that people aged 105+ or 110+ had a much lower burden of mutations in six out of seven genes tested. These individuals appeared to avoid the age-related increase in disruptive mutations, and this may have contributed in protecting them against diseases such as heart disease.

“This study constitutes the first whole-genome sequencing of extreme longevity at high coverage that allowed us to look at both inherited and naturally occurring genetic changes in older people,” says Massimo Delledonne, Full Professor at the University of Verona and a first author of the study.

“Our results suggest that DNA repair mechanisms and a low burden of mutations in specific genes are two central mechanisms that have protected people who have reached extreme longevity from age-related diseases,” concludes senior author Claudio Franceschi, Professor Emeritus of Immunology at the University of Bologna.

University of Chicago, May 18, 2021

A new study has yielded a radically different picture of aging in America, finding that how old you are plays little or no role in determining differences in health and well-being.

The researchers say the results suggest the medical community is focusing on the wrong set of factors to determine risk of dying. Rather than rely on a checklist of infirmities—heart disease, cancer, diabetes, high blood pressure, and cholesterol levels—perhaps it’s time to consider a new “comprehensive model” that looks at factors such as psychological well-being, sensory function, and mobility.

“The new comprehensive model of health identifies constellations of health completely hidden by the medical model and reclassifies about half of the people seen as healthy as having significant vulnerabilities that affect the chances that they may die or become incapacitated within five years,” says Professor Martha McClintock, a biopsychologist and lead author of the study in the Proceedings of the National Academy of Sciences.

“At the same time, some people with chronic disease are revealed as having many strengths that lead to their reclassification as quite healthy, with low risks of death and incapacity,” adds Professor Linda Waite, a demographer and study coauthor.

The study is a major longitudinal survey of a representative sample of 3,000 people between the ages of 57 to 85 conducted by the independent research organization NORC at the University of Chicago.

• Cancer itself is not related to other conditions that undermine health.

The comprehensive model reflects a definition of health long advanced, but little studied, by the World Health Organization, which considers health to include psychological, social, and physical factors in addition to the diseases that are the basis for the current medical model of health.

Twenty-two percent of older Americans were in the model’s healthiest category. This group was typified by higher obesity and blood pressure, but had fewer organ system diseases, better mobility, sensory function, and psychological health. They had the lowest prevalence of dying or becoming incapacitated (six percent) five years into the study.

A second category had normal weight, low prevalence of cardiovascular disease and diabetes, but had one minor disease such as thyroid disease, peptic ulcers, or anemia. They were twice as likely to have died or become incapacitated within five years.

Two emerging vulnerable classes of health traits, completely overlooked by the medical model, included 28 percent of the older population. One group included people who had broken a bone after age 45. A second new class had mental health problems, in addition to poor sleep patterns, engaged in heavy drinking, had a poor sense of smell, and walked slowly, all of which correlate with depression.

The most vulnerable older people were in two classes—one characterized by immobility and uncontrolled diabetes and hypertension. A majority of people in each of these categories were women, who tend to outlive men.

“From a health system perspective, a shift of attention is needed from disease-focused management, such as medications for hypertension or high cholesterol, to overall well-being across many areas,” says William Dale, associate professor of medicine and a member of the research team.

“Instead of policies focused on reducing obesity as a much lamented health condition, greater support for reducing loneliness among isolated older adults or restoring sensory functions would be more effective in enhancing health and well-being in the older population,” says Edward Laumann, also a collaborator and sociology professor.

Diet rich in sugar, fat damages immune cells in digestive tracts of mice

Washington University School of Medicine in St. Louis and Cleveland Clinic

Eating a Western diet impairs the immune system in the gut in ways that could increase risk of infection and inflammatory bowel disease, according to a study from researchers at Washington University School of Medicine in St. Louis and Cleveland Clinic.

The study, in mice and people, showed that a diet high in sugar and fat causes damage to Paneth cells, immune cells in the gut that help keep inflammation in check. When Paneth cells aren't functioning properly, the gut immune system is excessively prone to inflammation, putting people at risk of inflammatory bowel disease and undermining effective control of disease-causing microbes. The findings, published May 18 in Cell Host & Microbe, open up new approaches to regulating gut immunity by restoring normal Paneth cell function.

"Inflammatory bowel disease has historically been a problem primarily in Western countries such as the U.S., but it's becoming more common globally as more and more people adopt Western lifestyles," said lead author Ta-Chiang Liu, MD, PhD, an associate professor of pathology & immunology at Washington University. "Our research showed that long-term consumption of a Western-style diet high in fat and sugar impairs the function of immune cells in the gut in ways that could promote inflammatory bowel disease or increase the risk of intestinal infections."

Paneth cell impairment is a key feature of inflammatory bowel disease. For example, people with Crohn's disease, a kind of inflammatory bowel disease characterized by abdominal pain, diarrhea, anemia and fatigue, often have Paneth cells that have stopped working.

Liu and senior author Thaddeus Stappenbeck, MD, PhD, chair of the Department of Inflammation and Immunity at Cleveland Clinic, set out to find the cause of Paneth cell dysfunction in people. They analyzed a database containing demographic and clinical data on 400 people, including an assessment of each person's Paneth cells. The researchers found that high body mass index (BMI) was associated with Paneth cells that looked abnormal and unhealthy under a microscope. The higher a person's BMI, the worse his or her Paneth cells looked. The association held for healthy adults and people with Crohn's disease.

To better understand this connection, the researchers studied two strains of mice that are genetically predisposed to obesity. Such mice chronically overeat because they carry mutations that prevent them from feeling full even when fed a regular diet. To the researchers' surprise, the obese mice had Paneth cells that looked normal.

In people, obesity is frequently the result of eating a diet rich in fat and sugar. So the scientists fed normal mice a diet in which 40% of the calories came from fat or sugar, similar to the typical Western diet. After two months on this chow, the mice had become obese and their Paneth cells looked decidedly abnormal.

"Obesity wasn't the problem per se," Liu said. "Eating too much of a healthy diet didn't affect the Paneth cells. It was the high-fat, high-sugar diet that was the problem."

The Paneth cells returned to normal when the mice were put back on a healthy mouse diet for four weeks. Whether people who habitually eat a Western diet can improve their gut immunity by changing their diet remains to be seen, Liu said.

"This was a short-term experiment, just eight weeks," Liu said. "In people, obesity doesn't occur overnight or even in eight weeks. People have a suboptimal lifestyle for 20, 30 years before they become obese. It's possible that if you have Western diet for so long, you cross a point of no return and your Paneth cells don't recover even if you change your diet. We'd need to do more research before we can say whether this process is reversible in people."

Further experiments showed that a molecule known as deoxycholic acid, a secondary bile acid formed as a byproduct of the metabolism of gut bacteria, forms the link between a Western diet and Paneth cell dysfunction. The bile acid increases the activity of two immune molecules -- farnesoid X receptor and type 1 interferon -- that inhibit Paneth cell function.

Liu and colleagues now are investigating whether fat or sugar plays the primary role in impairing Paneth cells. They also have begun studying ways to restore normal Paneth cell function and improve gut immunity by targeting the bile acid or the two immune molecules.

University of New South Wales(Australia), May 12, 2021

According to news originating from Sydney, Australia, research stated, “The accumulation of oxidative stress, neuroinflammation and abnormal aggregation of amyloid beta-peptide (A beta) have been shown to induce synaptic dysfunction and memory deficits in Alzheimer’s disease (AD). Cellular depletion of the major endogenous antioxidant Glutathione (GSH) has been linked to cognitive decline and the development of AD pathology.”

Our news journalists obtained a quote from the research from the University of New South Wales, “Supplementation with gamma-glutamylcysteine (gamma-GC), the immediate precursor and the limiting substrate for GSH biosynthesis, can transiently augment cellular GSH levels by bypassing the regulation of GSH homeostasis. In the present study, we investigated the effect of dietary supplementation of gamma-GC on oxidative stress and A beta pathology in the brains of APP/PS1 mice. The APP/PS1 mice were fed gamma-GC from 3 months of age with biomarkers of apoptosis and cell death, oxidative stress, neuroinflammation and A beta load being assessed at 6 months of age. Our data showed that supplementation with gamma-GC lowered the levels of brain lipid peroxidation, protein carbonyls and apoptosis, increased both total GSH and the glutathione/glutathione disulphide (GSH/GSSG) ratio and replenished ATP and the activities of the antioxidant enzymes (superoxide dismutase (SOD), catalase, glutamine synthetase and glutathione peroxidase (GPX)), the latter being a key regulator of ferroptosis. Brain A beta load was lower and acetylcholinesterase (AChE) activity was markedly improved compared to APP/PS1 mice fed a standard chow diet. Alteration in brain cytokine levels and matrix metalloproteinase enzymes MMP-2 and MMP-9 suggested that gamma-GC may lower inflammation and enhance A beta plaque clearance in vivo. Spatial memory was also improved by gamma-GC as determined using the Morris water maze.”

According to the news editors, the research concluded: “Our data collectively suggested that supplementation with gamma-GC may represent a novel strategy for the treatment and/or prevention of cognitive impairment and neurodegeneration.”

This research has been peer-reviewed.

Nanyang Technological University (Singapore) May 21, 201

Traditionally, an infection is thought to happen when microbes - bacteria, fungi, or viruses - enter and multiply in the body, and its severity is associated with how prevalent the microbes are in the body.

Now, an international research team led by Nanyang Technological University, Singapore (NTU Singapore) has proposed a new way of understanding infections. Their study of close to 400 respiratory samples from patients with bronchiectasis, a chronic lung condition, has shown that microbes in the body exist as a network, and that an infection's severity could be a result of interactions between these microbes.

Through statistical modelling of data from these respiratory samples, the scientists found that flare-ups of coughs and breathlessness (known as exacerbations) occurred more often when there were 'negative interactions' between communities of bacteria, viruses and fungi in the airways. A negative interaction occurs when the microbes compete rather than cooperate with one another.

These findings, published in one of the world's leading scientific journals Nature Medicine in April, bring the scientists one step closer to developing a new way of tackling infections, by targeting microbial interactions rather than the specific microbes.

Assistant Professor Sanjay Haresh Chotirmall from the NTU Lee Kong Chian School of Medicine, who led the study, said: "Our current understanding of infections is that they occur when harmful microbes enter our bodies. This model of understanding, however, fails to account for resident microbes or explain why some patients with infection respond to antibiotics to which the microbe is resistant in laboratory testing. We are therefore proposing that microbes exist as networks, where interactions happen and that the resistant antibiotic in this case targets another microbe with which the culprit is interacting. We therefore can potentially improve clinical outcomes by breaking such crosstalk. 

"The findings of our study are the first steps in providing a more holistic view of how infections occur. While our study looked at patients with bronchiectasis, we believe this concept applies to all forms of infection - whether skin, lung, or a gastrointestinal infection. This way of looking at infections potentially changes our understanding of infection and may offer fresh ways of treating them." 

Associate Professor John Abisheganaden, co-author of the study and Head of Department of Respiratory & Critical Care Medicine at Tan Tock Seng Hospital, said: "By applying an integrated and holistic method, this study provides a new and fresh approach to our understanding of respiratory infection. Applying this precision-medicine approach can help the managing physician better understand and choose the most appropriate antibiotic or other therapy to confer clinical benefit - in short, to guide us to the right treatment at the right time, and for the best outcome."

Microbial interactions and infection 

For their study, the scientists looked at patients with bronchiectasis, a disease of high Asian prevalence, where airways dilate irreversibly and, where infection promotes progression. Targeting bacteria with antibiotics reduces bacterial load and accompanying inflammation, which in turn alleviates symptoms and improves clinical outcomes.

To investigate interactions between microbes in the airways of patients with bronchiectasis, the team collected respiratory (sputum) samples from 383 patients from Singapore, Malaysia, Italy, and Scotland, including samples before, during and after bronchiectasis flare-ups.

After analysing the genetic material from bacteria, fungi and viruses in the samples, the scientists assessed for possible microbial interactions and found that patients with frequent flare-ups had more negative interactions, where microbes compete rather than cooperate, and that the number of such negative interactions increased even further during a flare-up. While changes to interactions between microbes during flare-ups was detected, there was surprisingly minimal change to the type and quantity of microbes present during a flare-up, and even after antibiotics were administered. 

New treatment possibilities

The scientists believe that these findings suggest that microbial interactions potentially drive frequent flare-ups in patients.

Using these findings, the scientists have developed an online tool to help other researchers and physicians analyse microbial interactions in their own patient samples through the microbes' genetic sequences. 

Asst Prof Chotirmall, who is also NTU Provost's Chair in Molecular Medicine, said: "We are proposing a fresh way to view infection, as networks rather than individual microbes. Targeting microbial interactions within an established network may promote more judicious antibiotic use and help curb rising antimicrobial resistance."

The team is currently exploring the use of probiotics to treat bronchiectasis by regulating microbiomes within the air passages.

Imperial College London, May 21, 201

Adding pea flour to foods for severely malnourished children helps them gain weight and restores the balance of microbes in their gut.

In a small study of severely malnourished children in Uganda, researchers found that providing them with a mix containing cowpea flour improved their ability to absorb nutrients and gain weight, while maintaining their gut microbiome comparable to healthy children.

According to the researchers, the findings, published today in the journal Cell Reports Medicine, lay the foundations for larger trials with cowpea-based supplements and highlight the critical role of gut health in restoring nutrition in children with severe acute malnutrition.

Acute malnutrition is a major contributor to child mortality around the world. It remains a leading cause of death in children under five years of age and increases their risk of life-threatening events such as pneumonia, diarrheal disease or infections. Children with severe acute malnutrition can be treated with nutrient-rich, milk-based formulas to restore weight and nutrition, but despite treatment many will later go on to die.

Professor Gary Frost, head of the Center for Translational Nutrition and Food Research at Imperial College London, said: "These are children who have been admitted to hospital and often have other disease, such as bacterial sepsis, which complicates the picture—so they are very fragile.

"High quality feeds are lifesaving for many thousands of children. But sadly, when children are severely malnourished they can struggle to absorb nutrients and despite initial improvements in hospital, many remain very weak and will later go on to die."

"We have been able to show that legume-enriched feeds are well tolerated by these very sick children, and they may also protect their 'good' gut microbes, compared to traditional feeds. Our hope is that this kind of intervention will help them to grow stronger by enabling their bodies to absorb more of the nutrients from the feed."

More than 'calories in'

Researchers at Imperial College London have been exploring the links between gut health and nutrition, with the aim of improving outcomes for severely malnourished children. Growing evidence suggests that gut microbes feed on carbohydrates from our diet, releasing nutrients which maintain the lining of the gut. Without this regular supply of nutrients, the gut lining deteriorates and becomes 'leaky," reducing our ability to absorb nutrients and increasing the risk of bugs entering the bloodstream where they can cause infection.

Previous research by the Imperial team has shown that increasing dietary fiber can help to overcome this 'leaky gut' syndrome and improve the absorption of nutrients, so they designed and tested a new feed fortified with cowpea—which contains a source of easily fermentable carbohydrates and fiber, both known to be key in maintaining gut health.

In a small proof of concept trial, researchers recruited 58 hospitalized children in Uganda with severe acute malnutrition to receive one of three feeds: a conventional feed; a feed containing the plant compound inulin; and a feed fortified with cowpea flour. Children in all three groups received antibiotics and other medical treatments, as needed, in addition to the feed.

Led by Ph.D. candidates Nuala Calder and Kevin Walsh, the team measured changes to weight after seven days of treatment, along with fecal sampling to look at changes to the makeup of their gut microbiome. The children were also followed up at 28 days.

The researchers found that overall, all feeds resulted in comparable weight gain after one week, and duration of hospital stay did not vary between groups. However, the cowpea feed limited the damage to gut microbes associated with antibiotic treatment—which can reduce the richness of the microbiome by killing off key groups of bugs. The same effect was not seen in conventional feeds or those enriched with inulin—a compound derived from plants—highlighting the role of fiber and other elements in the legume feed.

Following 28 days, there was limited difference in mortality between the groups, and sadly, despite treatment 12 children died (3, 6 and 3 from the respective groups). But analysis suggested that across the groups, children that died had higher levels of gut dysfunction and altered levels of short chain fatty acids, indicating reduced diversity of gut microbes.

Protecting gut bugs

Professor Frost said: "Our major finding was that the cowpea enriched feeds actually protect the gut bugs when these children are given antibiotics, so we know that the feed is actually helping the microbiota to survive some of the concurrent medical therapy these children are receiving.

"We also found that the children that died tended to have a worse gut problem than those who survived, so it has highlighted that the gut is very important in rescuing children from severe malnutrition. These legume enriched feeds may be a small step towards improving outcomes for those children."

Professor Kathryn Maitland, Professor of Tropical Pediatric Infectious Disease at Imperial and based in Kenya, said: "This is a very small study, but it's an important first step. The role the gut actively plays in the pathology of severe malnutrition has not been fully appreciated, and there are multiple parameters that need fixing. Fortifying feeds with legumes can go some way towards that. Many of these children may receive multiple antibiotics, which kills the microbiota, leaving only the microbes that are bad for human health, and these legume enriched feeds may actually help to resist that."

Future trials are now planned to test the legume-enriched feeds in larger numbers of children with severe acute malnutrition in more regions. The team believes that if the feeds could be produced regionally, using legumes such as cowpea which can be grown and milled in East Africa, it could help to reduce the dependency on internationally produced feeds which may be more expensive and less effective.

Professor Maitland added: "Many feeds which are imported to East Africa are based on cow's milk, or a dried form of it. They can contain a lot of sugars, such as sucrose and lactose, and these children can't absorb this. In fact, quite a lot of these malnourished children may develop severe diarrhea from these feeds as they are lacking the enzymes to properly digest and absorb them, so our next steps are to tackle that as well.

"We think that the next iterations of our feed will include legumes, but will also not include any aspect of cow's milk, replacing the sucrose with other carbohydrate sources. This also means that they can be produced locally."

Professor Frost added: "We know that we can reverse the malnutrition, but this isn't really fixing the whole problem. This approach is a radical change for these children. It's taking a very different view of feeding. It's not just about the nutrients flowing in, it's about how compounds in plants are metabolized, and underlying gut health."

Why blueberries are an effective weapon in the war against Alzheimer’s disease

University of Cincinnati,  May 21, 2021 

Could a plump, little blueberry really hold colossal promise in the fight against Alzheimer’s disease?  New research adds to the growing evidence that blueberries, bursting with antioxidants, could help diminish the devastating defects of dementia.

Blueberries are already known as a “super fruit,” thanks to their documented contribution to lowering the risk of heart disease and cancer. But now, newly released study findings show that certain flavonoids found in blueberries could also hold the key to lessening the effects of Alzheimer’s disease.

Over 5 million Americans suffer from Alzheimer’s disease, a number that is expected to continue to rise as the population ages. The Alzheimer’s Association estimates that as many as 7 million could fall prey to the disease by 2025, and that the number could triple by 2050.  In fact, Alzheimer’s has become the sixth leading cause of death in the United States, with one out of every three elderly persons dying of complications from Alzheimer’s or some other form of dementia.

But Alzheimer’s takes a toll on more than just human life. It is an extremely costly disease as well. Experts estimate that Alzheimer’s will cost the nation $236 million and that caregivers will spend more than $5,000 a year trying to care for their loved one.

Hope for Alzheimer’s disease patients: Blueberries found to improve cognition and memory

As scientists work to slow this alarming trend, researchers out of the University of Cincinnati Academic Health Center have released promising results of two human studies conducted in follow up to their earlier clinical trials. Lead author Robert Krikorian, Ph.D., stated that the new findings corroborate those from previous human and animal research.

The researchers, led by Krikorian, believe that blueberries’ beneficial effects against Alzheimer’s could be due to certain flavonoids found in the berries. Known as anthocyanins, they have been shown to improve cognition in tests with animals.

In one study, 47 adults, aged 68 and older, exhibiting mild cognitive impairment – a risk factor for Alzheimer’s disease – were given either freeze-dried blueberry powder or a placebo powder once a day for 16 weeks. The blueberry powder was equivalent to one cup of fresh blueberries.

Those receiving the blueberry powder were found to exhibit improved brain function and cognitive performance compared to those in the control group, with better memory and improved access to words and concepts.  In another study, 94 people, aged 62 to 80, were divided into four groups. The subjects did not have diagnosed early-onset Alzheimer’s, but did report feelings of having their memory decline.

In the trial, stated above (with 94 people), cognition was somewhat better for those consuming powder or fish oil only, but there was little improvement with memory. Also, researchers report that the MRI results were not as definitive for those receiving blueberry powder.

Even with somewhat less striking results from the second study, the scientists believe the two studies show that blueberries may be more effective in treating patients with cognitive impairments. Next up, the researchers want to conduct a study involving younger subjects, all with risk factors for Alzheimer’s.

Reaping the benefits of blueberries from your regular diet can be easy. Blueberries are an extremely popular berry and can be found in many stores (and farmers’ markets) throughout the world.  Naturally, to avoid excess consumption of chemicals, it’s best to eat organic varieties only.

As a matter of convenience and potency, the best way to incorporate blueberries into your diet is through a powder of pure (organic) blueberry extract or by eating whole, organic berries.  Baking or cooking blueberries will diminish the nutritional value of this powerful fruit.

Aga Khan University (Pakistan), May 21, 2021

Infertility is a known source of distress among couples worldwide. This agony significantly stems from the concern of not having an identifiable cause leading to infertility. With male factors accounting for 20-30% of the total causes of infertility (1), a thorough evaluation of both the partners is done.

Upon evaluation, Vitamin D deficiency was noticed significantly in males coming to infertility centres. However, its functions and how it impacted reproduction was not known until the research led to the discovery of Vitamin D Receptor (VDR) in many organs of the male reproductive tract. It is now known that vitamin D deficiency decreases male fertility by contributing to oxidative stress and gonadal insufficiency, disrupting spermatogenesis, affecting sperm morphology and normal calcium haemostasis. (2)

Oxidative stress, caused by an imbalance between oxidative and antioxidative mechanisms, is believed to be a well-known mechanism underlying idiopathic male infertility. Reproductive health professionals and researchers fittingly started searching for antioxidants to combat this imbalance. A study concluded that adding vitamin D to a cryopreserved semen sample reduced oxidative stress and resulted in better fertility outcomes (3). Animal trials have shown that Vitamin D supplementation reduced oxidative stress and improved semen DNA integrity (4).

As Vitamin D exerts its effects by binding to Vitamin D receptors, it was noted that vitamin D receptor null mutant mice had a significant reduction in successful reproductive outcomes due to gonadal insufficiencies. Reduced levels of oestrogen and testosterone were seen along with low sperm count, reduced motility, abnormal spermatogenesis and histological abnormalities in testes of mutant mice. These insufficiencies were attributed to a decreased CYP2R1, CYP27B1 and CYP24A1 expression, lower aromatase activity, secondary to suppression of CYP19 gene and calcium supplementation improved fertility in such cases. (5)

There is limited human data available on how Vitamin D deficiency causes gonadal insufficiency, which is important to maintain normal reproductive physiology. More studied are needed to clarify the role of vitamin D in gonadal physiology. Considering the importance of Vitamin D on reproductive functions, its role in causing Oxidative stress and gonadal dysfunction, we suggest randomized control trials in pre-pubertal phase.

Want to escape Alzheimer's disease? Run for your life and exercise

Tel Aviv Sourasky Medical Center (Israel), May 20, 2021



Exercise slows down aging of the brain and can reduce risks of Alzheimer's disease and other dementias by about half.







There is a growing amount of medical evidence that exercise slows down the aging of the brain and can reduce the risk of Alzheimer's disease and other dementias by about half, according to Prof. Nir Giladi, chief of neurology at Tel Aviv Sourasky Medical Center.


He said that the modern sedentary way of life reduces the amount of body movement. Long-term epidemiological and physical studies show that exercise can improve memory, concentration and mood and minimize pain, as well as reduce the risk of cognitive damage, stroke, Parkinson's disease and depression.


The connection between exercise and brain function was first disclosed from animal studies two decades ago, said Giladi. Brains of rats that ran on a wheel for three months at a time had many more neurons and synapses through which electric signals connect. Exercise causes these to multiply, said Giladi.


"These findings flew in the face of the belief that over the age of 30, the neurons decline irreversibly. Today we know that the adult brain has many stem cells that when stimulated can differentiate and turn into ripe neurons that know how to create synapses." The neurologist added that for some unknown reason, the best potential for differentiation exists in brain regions responsible for memory.


Exercise promotes the secretion of trophic factors -- including brain-derived neurotrophic factor that encourage the growth of stem cells that turn into adult nerve cells. he added. These factors activate genes responsible for the development of stem cells in the hippocampus and other brain regions involved in memory, storage and processing of data. They are available in large quantities during a baby's first years when the brain develops at a rapid pace, but the amounts decline during adolescence and aging.


The greater the amount, the more the brain grows and holds more nerve cells, especially in the hippocampus, he said. Exerting the muscles activates unique genes that encourage the muscle cells and apparently others to create proteins that increase the synthesis of trophic factors. "This is why those who exercise regularly look and have younger brain function -- and their cells are more protected from diseases, trauma and natural aging."


Giladi said it was best to do aerobic exercise (causing the heart and lungs to exert themselves) along with non-aerobic exercise (strengthening the muscles on the skeleton) at least three times a week. Even if you exercise just as an adult and the cognitive decline has begun, your physical activity will slow down the rate of decline.


A study published in the journal PNAS  using MRI to see the effect of regular exercise on the brain showed that the brains of healthy 75-year-olds who performed physical activity at least three times a week declined slower in the regions of memory, concentration, planning, initiative and management abilities. The same thing was noted in studies of teenagers, Giladi said. Exercise influences the brain cell in deciding which genes will function and contribute to this and which will be neutralized. This is thus epigenetics, in which the environment actually affects the genes, the neurologist said.


Exercise also increases the supply of blood to the organs, including the brain, he continued, and encourages the growth of alternate blood vessels to take over functions from clogged vessels.


He bemoaned the fact that many Israelis don't exercise regularly. An average of 150 to 300 minutes per week -- half aerobic and half non-aerobic -- can improve the abilities of the brain and protect it from disease, Giladi concluded.

Findings from a randomized, double-blind, cross-over trial reported on February 25, 2021 in the Chinese Journal of Physiology revealed an association between intake of vitamin C and a reduction in blood pressure before and after exercise among men and women with type 2 diabetes. “During exercise, mechanical stress on the arterial wall is increased, leading to an increased release of vasodilators by the endothelium (e.g., nitric oxide, bradykinin, etc.),” explained authors C. Boonthongkaew and colleagues at Khon Kaen University in Thailand. “This response can attenuate blood pressure (BP) after acute exercise at low, moderate, and high intensity in normotensive individuals. However, the magnitude of this effect seems to decline in type 2 diabetes patients because of endothelial dysfunction.”

The trial included 24 type 2 diabetics with poorly controlled disease who received 1,000 milligrams vitamin C or a placebo daily for six weeks, followed by a six-week washout period, followed by six weeks of the alternate intervention. For inclusion in the study, participants were required to have a blood pressure of ≤140/90 mmHg or less, maintained if necessary with antihypertensive treatment. 

Twenty-minute low-intensity exercise sessions were conducted on the day before and the last day of each treatment period. Blood pressure was measured before, immediately after and 60 minutes after the exercise sessions. Blood samples collected before and after exercise were analyzed for plasma vitamin C levels, markers of lipid peroxidation and nitric oxide concentration. 

Compared to pre-intake, participants who received vitamin C experienced an average 12.8 mmHg reduction in systolic BP and an 8.9 mmHg reduction in diastolic BP when at rest before exercise. Immediately after exercise, systolic and diastolic BP were lower by 11.4 mmHg and 6.8 mmHg, and an hour after exercise, systolic and diastolic BP were lower by 12.5 mmHg and 8.9 mmHg in the vitamin C group compared to baseline values. No significant differences between pre- and post-treatment measurements occurred in the placebo group. When compared to the placebo, participants who received vitamin C also had lower systolic and diastolic BP before and after the post-supplementation exercise sessions. 

Post-intake, plasma vitamin C and nitric oxide levels were higher, and markers of lipid peroxidation were lower among vitamin C patients before and immediately after exercise compared to baseline, while the placebo group experienced no significant changes. And when compared to the placebo, vitamin C and nitric oxide were higher and lipid peroxidation markers were lower before and after the exercise session among participants who had received the vitamin.

In their discussion of the findings, the authors remarked that vitamin C’s ability to decrease oxidative stress helps prevent nitric oxide from being degraded by free radicals, which results in higher nitric oxide levels that benefit endothelial function and BP. They announced that the study is the first to report the effect of vitamin C compared to a placebo on BP before and within an hour after exercise. “This study suggests that 6‑week vitamin C [intake] decreased pre-exercise and postexercise blood pressures, possibly due to improved oxidative stress and nitric oxide release,” they concluded.

Brown University, May 18, 2021

Mindfulness-based meditation programs have emerged as a promising treatment for conditions ranging from stress to sleeplessness to depression. In some cases, they're even offered to people—schoolkids or employees, for example—who aren't actively seeking help or who haven't been screened for suitability. Yet most research and discourse about these programs focuses only on their benefits, with little investigation of the risks or the potential for adverse effects.

A recent review of nearly 7,000 studies of meditation practices found that less than 1% of them measured adverse effects. Willoughby Britton, an associate professor of psychiatry and human behavior at Brown University, said that this is largely because assessing adverse effects (a process known as "harms monitoring") in non-pharmacological treatments like mindfulness-based meditation programs is difficult to do well.

To address that gap, Britton conducted a new study on adverse effects in mindfulness-based programs that identified common obstacles to harms monitoring and, importantly, showed how to address them. The study also found that the rates of adverse effects from mindfulness were similar to those found in other psychological treatments.

The study was published on May 18 in Clinical Psychological Science.

"Our ultimate goal is to maximize the efficacy of mindfulness-based meditation while minimizing harms," said Britton, who directs the Clinical and Affective Neuroscience Laboratory at Brown. "In order to address risks and modify treatment accordingly, you need thorough and detailed knowledge about potential harms. Our study, the most comprehensive of its kind, provides a blueprint for how to accurately assess the risks of mindfulness-based meditation programs."

Why no one wants to talk about meditation's adverse effects

The adverse effects of mindfulness-based meditation programs are often an unpleasant topic for providers and participants alike, Britton said. For the study, she and her colleagues reviewed the most current harms monitoring best practices from regulatory agencies like the World Health Organization, the National Institutes of Health and the U.S. Food and Drug Administration. In the paper, they outlined the key considerations around assessing adverse effects, including hesitancy of participants to report negative reactions to treatment because of feelings of shame or a desire to please the researcher or instructor.

Researchers and mindfulness teachers (Britton is both) are understandably more focused on the help they can provide than any harm they could cause. As a result, a lack of negative feedback from participants is often interpreted as evidence of absence of harm. "It's very easy for our enthusiasm and desire to help to become a kind of blindness," Britton explained.

Another complicating factor, she said, is the lack of knowledge of proper harms assessment.

"Often the mindfulness teacher will ask the class, 'Did anyone have any challenges with your meditation practice this week?'" Britton said. "But participants, in general, tend to avoid answering open-ended questions asked by the teacher in a public setting. Research has shown that having someone other than the teacher ask specific questions in a private setting will increase the likelihood of honest reporting."

Finally, she highlighted the fact that term "adverse" is a highly subjective judgment that can vary across people and even across the same person in different contexts.

"The re-living of a previous trauma may be healing for some and destabilizing for others, in the same way that the drowsiness caused by cold medicine—or meditation—may be undesirable or 'adverse' in the morning but highly desirable before bed," she said. What's more, Britton added, the literature shows that mental health treatment providers (like therapists or doctors) may dismiss patient complaints or reframe them as a sign that the therapy is working.

Designing a model assessment

Britton's research team followed 24 current harms monitoring guidelines to assess the nature and frequency of meditation-related adverse effects in mindfulness-based programs. The study participants were representative of typical meditators in the U.S.: predominantly middle-age women seeking methods to self-manage mild to severe levels of anxiety, depression and stress. After completing one of three versions of an eight-week mindfulness meditation program, participants were interviewed by a researcher unaffiliated with the treatment about their experiences, with 44 questions based on previous research of meditation-related challenges.

To more accurately and thoroughly capture patient perspectives, this study allowed each participant to evaluate the emotional tone or "valence" of each of 44 meditation-related experiences as well as the impact it had on their life and functioning. By asking participants specific questions about duration and impact, researchers were able to differentiate temporary distress, negative-impact side effects and "lasting bad effects." In this way, the researchers sought to clarify which effects were experienced as "adverse" on a case-by-case basis.

To accommodate the varying definitions of harm, results were reported in tiers of severity ranging from "transient distress during meditation" (i.e., temporary) to "enduring impairment in functioning"—or "lasting bad effects."

The "what" is as important as the "how"

The significance of the study, Britton said, has as much to do with what it found as how it found it.

"The fact that meditation can cause altered states, for example, isn't news: It's something that people have been talking about for centuries," Britton said. "What we haven't been very good about is measuring the impact and significance of these states on individual participants."

Of the 96 participants, 58% reported at least one meditation-related adverse effect, which ranged from perpetual hypersensitivity to nightmares to traumatic re-experiencing. Meditation-related adverse effects with negative impacts on functioning occurred in 37% of the sample. Six percent of the sample had "lasting bad effects," or impairments in functioning lasting more than one month. Notably, the researchers say, this rate is similar to those of other psychological treatments.

In the study, meditation-related effects with negative impacts tended to be associated with signs of what's called dysregulated arousal—for example, the participants reported feeling anxious, hyper-stimulated or emotionally flat or disconnected after meditating.

This is important for instructors and participants to note, Britton said, because unlike the experiences of anxiety or insomnia, a feeling of being dissociated or emotionally checked-out is not always experienced as unpleasant and can provide some relief, especially for a person suffering from intense anxiety. Yet in the study, this feeling of dissociation tended to predict more significant and lasting impairment in functioning.

"This is where the differentiation between valence and impact becomes important, because the valence, or emotional tone, of an experience might be not particularly distressing at the time," Britton said. "Meditators are often taught to reappraise their experience as not being problematic, and to accept it for what it is. Our results are basically saying that when it comes to dissociation, this approach isn't going to work."

Britton and colleagues also found that the open-ended question "Have you had any unexpected, unpleasant, adverse or challenging experiences as a result of mindfulness meditation practice during or following the program?" underestimated the true rate by 70%, confirming the inadequacy of open-ended questions compared to specific ones.

The study concludes that the active ingredient of these therapeutic programs, which is mindfulness meditation practice, can be associated with both transient distress and enduring negative impacts on life and functioning. Britton said that it is important to note that adverse effects and benefits are not mutually exclusive: many of the same participants who reported adverse effects also reported improvements in depression.

Britton noted that the intent of the study, as well as of her broader research, is not to discourage mindfulness-based meditation programs—rather, it is to generate findings on both the positive and negative effects so that providers and meditators can make informed decisions.

She compared mindfulness to aspirin, as an example. This medicine-cabinet staple can cause nausea, heartburn and stomach cramps—and taking a daily aspirin can cause gastrointestinal bleeding in some people. But these potential adverse effects do not take away from aspirin's many benefits. Instead, detailed knowledge about the benefits and risks allows practitioners to make educated, effective and safe recommendations to specific patients.

"That's where we need to get with mindfulness, too," Britton said. "Our study is an attempt to bring harms monitoring up to the standards of other treatments so that providers can identify events that require monitoring and intervention in order to maximize the safety and efficacy of mindfulness-based meditation."

Sandro Pertini Hospital (Italy), May 19, 2021

In an article whose title asks the question, “Uterine fibroids treatment: do we have new valid alternative?” findings from researchers from Sandro Pertini Hospital in Rome suggest the answer may be “yes.”

The article, published in the April 2021 issue of the European Review for Medical and Pharmacological Sciences reported a benefit for intake of vitamin B6, vitamin D and epigallocatechin gallate (EGCG, a flavonoid that occurs in green tea) in women with uterine fibroids (myomas), benign tumors of the uterus that affect a significant percentage of reproductive-aged women. Uterine fibroids adversely impact fertility, and unfortunately, there are few treatment options for women who desire to become pregnant.

The study included 95 women who had between one and five fibroids. Forty-one participants received 5 milligrams (mg) vitamin B6, 25 micrograms (1,000 international units) vitamin D and 150 mg EGCG twice daily for four months, while a control group of 54 women were monitored without receiving the vitamin B6, vitamin D and EGCG. The number and volume of fibroids was measured using ultrasound before and after the treatment period. Fibroid vascularization was measured by color flow Doppler ultrasound, which color codes blood flow to indicate the direction of flow and/or the presence of high blood turbulence. Other factors assessed at these time points included the presence of heavy bleeding, pelvic pain and health/quality of life. Overall improvement was assessed by a questionnaire, the Patient Global Impression of Improvement (PGI-I), administered to participants who completed the four-month study.

After four months, total fibroid volume significantly decreased by 37.9% among participants who received vitamins B6 and D, plus ECGC, while increasing by 5.5% among women who did not receive the nutrients. Similar results were observed in a subgroup of participants who were smokers – fibroid volume was significantly reduced with the supplement combination. 

Doppler visualization of blood flow to the myomas suggested reduced vascularization in the intervention group and increased vascularization in the control group. Pelvic pain and health, including the participants’ all-over impressions of improvement, significantly improved in comparison with pretreatment levels in the group that received the nutrients while no change occurred in the control group. Specifically, 85.4% of women taking the supplement reported improvements in their PGI-I score, with 73.2% reporting their symptoms were “very much better”.  No side effects were reported. 

Authors Donatella Miriello and colleagues concluded that the study’s findings “showed the effectiveness and safety of a 4-month oral [intake of] a combination of vitamin D, EGCG and vitamin B6 in reducing uterine fibroids’ volume and improving the quality of life of childbearing women. Thus, this…may represent a valid alternative to the classic ‘wait and see’ approach and, at the same time, an adjuvant treatment that could be administered along with pharmacological therapies, even before surgery to reduce the occurrence of possible complications.”

Background: Dietary nitrate is receiving increased attention due to its reported ergogenic and cardioprotective properties. The extent to which ingestion of various nitrate-rich vegetables increases postprandial plasma nitrate and nitrite concentrations and lowers blood pressure is currently unknown.

Objective: We aimed to assess the impact of ingesting different nitrate-rich vegetables on subsequent plasma nitrate and nitrite concentrations and resting blood pressure in healthy normotensive individuals.

Methods: With the use of a semirandomized crossover design, 11 men and 7 women [mean ± SEM age: 28 ± 1 y; mean ± SEM body mass index (BMI, in kg/m2): 23 ± 1; exercise: 1–10 h/wk] ingested 4 different beverages, each containing 800 mg (∼12.9 mmol) nitrate: sodium nitrate (NaNO3), concentrated beetroot juice, a rocket salad beverage, and a spinach beverage. Plasma nitrate and nitrite concentrations and blood pressure were determined before and up to 300 min after beverage ingestion. Data were analyzed using repeated-measures ANOVA.

Results: Plasma nitrate and nitrite concentrations increased after ingestion of all 4 beverages (P < 0.001). Peak plasma nitrate concentrations were similar for all treatments (all values presented as means ± SEMs: NaNO3: 583 ± 29 μmol/L; beetroot juice: 597 ± 23 μmol/L; rocket salad beverage: 584 ± 24 μmol/L; spinach beverage: 584 ± 23 μmol/L). Peak plasma nitrite concentrations were different between treatments (NaNO3: 580 ± 58 nmol/L; beetroot juice: 557 ± 57 nmol/L; rocket salad beverage: 643 ± 63 nmol/L; spinach beverage: 980 ± 160 nmol/L; P = 0.016). When compared with baseline, systolic blood pressure declined 150 min after ingestion of beetroot juice (from 118 ± 2 to 113 ± 2 mm Hg; P < 0.001) and rocket salad beverage (from 122 ± 3 to 116 ± 2 mm Hg; P = 0.007) and 300 min after ingestion of spinach beverage (from 118 ± 2 to 111 ± 3 mm Hg; P < 0.001), but did not change with NaNO3. Diastolic blood pressure declined 150 min after ingestion of all beverages (P < 0.05) and remained lower at 300 min after ingestion of rocket salad (P = 0.045) and spinach (P = 0.001) beverages.

Conclusions: Ingestion of nitrate-rich beetroot juice, rocket salad beverage, and spinach beverage effectively increases plasma nitrate and nitrite concentrations and lowers blood pressure to a greater extent than sodium nitrate. These findings show that nitrate-rich vegetables can be used as dietary nitrate supplements.

University of Tsukuba (Japan), May 17, 2021

Researchers at the University of Tsukuba have found that, despite only covering about one-third of the distance in HIIT compared with that covered in endurance training, similar improvements in exercise capacity and brain function were observed for both forms of exercise.

"We investigated how rats' muscles and brains—specifically, the region of the brain involved in spatial learning called the hippocampus—adapted to these types of exercise, and how the rats consequently learned and remembered navigating mazes," explains Professor Hideaki Soya, the principal investigator.

In the experiment, rats were assigned to one of three groups—resting, endurance running, or alternating intervals (short sprints and rest)—during training sessions on treadmills five days/week for four weeks.

Both endurance running and HIIT resulted in weight loss, greater muscle mass, and the ability to exercise longer compared with controls; however, increased cellular aerobic capacity was found in the soleus (a muscle with predominantly slow-twitch fibers that makes it functionally well suited to endurance) and in the plantaris (a muscle with predominantly fast-twitch fibers for meeting high-energy functional demands) in the endurance-running and HIIT groups, respectively.

Rats in both groups demonstrated better memory of spatial learning trials in searching for an escape platform in a water maze. In the hippocampus, increased cell development—neurogenesis—was also observed for both forms of exercise; however, levels of a signaling protein that promotes neurogenesis (BDNF) were increased by HIIT but not by endurance running, whereas the levels of its receptor (TrkB) were increased by both.

Given that BDNF expression is known to be affected by exercise, why didn't endurance running increase BDNF expression? The answer may lie in the mediating role of stress on BDNF expression; exercise is a type of stress. While stress indicators in both exercise groups were found to be similar, this line of enquiry may lead to future studies:

"In this study, we showed that an HIIT exercise regimen with a low exercise volume nevertheless improves spatial memory, and we demonstrated that these improvements are supported by changes in neuronal plasticity in the hippocampus. In a previous study, we found that continuous light-intensity training had a similar beneficial effect, whereas continuous high-intensity training did not," Professor Soya summarizes. "Thus, it seems that the benefits yielded by exercise may actually depend on optimization, that is, a trade-off between exercise time and intensity."

A future where exercise regimens can be tailored to improve both physical and cognitive features may be on the horizon.

Ruhr-University Bochum (Germany), May 21, 2021

The researchers found that the variants have a similar surface stability as the wild type virus under laboratory conditions, but can be effectively eliminated by disinfection and thorough hand washing, heat or alcohol treatment. They report their results in the Journal of Infectious Diseases from 16 May 2021.

For this study, the team from the Department for Molecular and Medical Virology and the Chair of Materials Discovery and Interfaces at Ruhr-Universität Bochum (RUB) cooperated with the European Virus Bioinformatics Center Jena, the University Hospital Duisburg-Essen and Paracelsus Medical University Nuremberg.

The fact that viruses change genetically over time is well known. Variants of concern are those that give the virus an advantage, for example by allowing it to replicate faster, become more infectious or enable it to evade the immune response. The British and South African variants have accumulated several mutations which result in an increased transmission and, in some cases, lead to more severe courses of disease. "Therefore, the question arose whether they also differ from the original variant in terms of their sensitivity to hygiene measures," explains Toni Meister from Ruhr-Universität Bochum.

Heat, soap, alcohol

For this reason, the team analysed how long the variants remain infectious on surfaces made of steel, silver, copper and on face masks and how they can be rendered harmless by means of soap, heat or alcohol.

It turned out that both variants, as well as the wild type virus, could be inactivated when treated with at least 30 percent alcohol for at least 30 seconds. "Common disinfectants are therefore effective against all these variants," says Stephanie Pfänder from RUB. Thorough hand washing with soap could also lower the risk of infection. Heat also works against the virus: after 30 minutes at 56 degrees Celsius, all variants were rendered harmless.

To find out whether the stability of the different mutant variants on surfaces differs from each other, they analyzed the amount of infectious virus particles on surfaces made of steel, copper, silver and on surgical and FFP2 masks over 48 hours. "The surface stability did not differ between the virus variants," points out Eike Steinmann from the Department for Molecular and Medical Virology at RUB. "As described several times before, copper in particular has a very strong antiviral effect". In conclusion, the team did not detect any differences between the different mutants in terms of their sensitivity to different hygiene measures.

University of Westminster, May 12, 2021

A new study led by the Centre for Nutraceuticals in the University of Westminster shows that pink drinks can help to make you run faster and further compared to clear drinks.

The researchers found that a pink drink can increase exercise performance by 4.4 per cent and can also increase a 'feel good' effect which can make exercise seem easier. 

The study, published in the journal Frontiers in Nutrition, is the first investigation to assess the effect of drink colour on exercise performance and provides the potential to open a new avenue of future research in the field of sports drinks and exercise.

During the study participants were asked to run on a treadmill for 30 minutes at a self-selected speed ensuring their rate of exertion remained consistent. Throughout the exercise they rinsed their mouths with either a pink artificially sweetened drink that was low in calories or a clear drink which was also artificially sweetened and low in calories.

Both drinks were exactly the same and only differed in appearance - the researchers added food dye to the pink drink to change the colour. 

The researchers chose pink as it is associated with perceived sweetness and therefore increases expectations of sugar and carbohydrate intake.

Previous studies have also shown that rinsing the mouth with carbohydrates can improve exercise performance by reducing the perceived intensity of the exercise, so the researchers wanted to assess whether rinsing with a pink drink that had no carbohydrate stimulus could elicit similar benefits through a potential placebo effect. 

The results show that the participants ran an average 212 metres further with the pink drink while their mean speed during the exercise test also increased by 4.4 per cent. Feelings of pleasure were also enhanced meaning participants found running more enjoyable.

Future exploratory research is necessary to find out whether the proposed placebo effect causes a similar activation to the reward areas of the brain that are commonly reported when rinsing the mouth with carbohydrates. 

Talking about the study, Dr Sanjoy Deb, corresponding author on the paper from the University of Westminster, said: "The influence of colour on athletic performance has received interest previously, from its effect on a sportsperson's kit to its impact on testosterone and muscular power. Similarly, the role of colour in gastronomy has received widespread interest, with research published on how visual cues or colour can affect subsequent flavour perception when eating and drinking. 

"The findings from our study combine the art of gastronomy with performance nutrition, as adding a pink colourant to an artificially sweetened solution not only enhanced the perception of sweetness, but also enhanced feelings of pleasure, self-selected running speed and distance covered during a run."