Medical Journal Club with Dr. Takuji Shirasawa

 The aim of the study was to explore the clinical significance of school refusal behavior, its negative impact on psychological well-being of children and adolescents and its relationship with the most common psychopathological conditions during childhood and adolescence (e.g. neurodevelopmental disorders, psychiatric disorders). School refusal behavior refers to a distressing condition experienced by children and adolescents that compromise regular school attendance and determine negative consequences on mental health and adaptive functioning. A narrative review of the literature published between January 2019 and March 2023 was conducted. Ten studies (n = 10) were included from a literature search of the electronic databases PubMed, CINAHL, PsycInfo, MedLine, and Cochrane Library. The results indicate that school refusal is highly present in neurodevelopmental disorders such as autism and attention-deficit/hyperactivity disorder due to the presence of behavioral problems and deficits in communication skills. As for psychiatric disorders, school refusal appears to be highly common in anxiety disorders, depressive disorders, and somatic symptoms. We also found that school refusal behavior may be associated with various emotional and behavioral conditions that act as risk factors. Especially, but are not limited to, it may be associated with a diminished self-concept, exposure to cyberbullying, specific affective profiles and excessive technology usage. Our results indicate that school refusal is a condition with many clinical facets. It can be attributed to both vulnerability factors, both temperamental and relational, and to various psychopathological conditions that differ significantly from each other, such as neurodevelopmental disorders and psychiatric disorders. Recognizing these aspects can improve the implementation of patient-tailored therapeutic interventions that are consequently more likely to produce effective outcomes. The therapeutic intervention should facilitate the recognition of cognitive biases regarding school as a threatening environment, while regulating negative emotions associated with school attendance. Additionally, therapeutic intervention programs linked to social skill training and problem-solving training, conducted directly within the school setting, can enhance children’s abilities to cope with academic performance and social relationships, ultimately preventing school refusal. Keywords School phobia, Neurodevelopmental disorder, Psychiatric disorder, Bullying, School-based interventions

Glial cell line–derived neurotrophic factor (GDNF) is a potent trophic factoressential for neuronal survival and function. Encoded by the GDNF gene,its mature protein arises from specific post-translational modifications andis secreted through distinct isoform-dependent pathways. Once released,GDNF binds to its receptors, GFRα1 and RET, activating downstream signalingcascades that regulate cell growth, differentiation, and survival. In thecentral nervous system, GDNF exerts protective effects on dopaminergicneurons—highlighted in Parkinson’s disease research—and shows promise formodulating schizophrenia, depression, and addiction. Beyond dopaminergicpathways, GDNF influences synaptic plasticity in hippocampal neuronsand supports GABAergic function. Glial cells also produce and respondto GDNF: astrocyte-derived GDNF can promote neuroprotection but alsomodulate microglial state and neuroinflammation. Other cell sources, suchas pericytes and endothelial cells, contribute to GDNF levels, impactingblood-brain and blood-nerve barrier permeability. Peripherally, GDNF is criticalfor sympathetic and parasympathetic neuron development, somatic sensoryneuron maintenance, and motor neuron reinnervation at the neuromuscularjunction. Finally, GDNF has been recently implicated in tumour biology,underscoring its multifaceted role at the interface between beneficial anddetrimental effects. Clinically, its therapeutic potential is being explored indifferent diseases, including neurodegenerative disorders and epilepsy. Inthis review, we will explore various aspects of GDNF biology and thenfocus our attention to the physiological mechanisms of GDNF-regulatedprocesses in the central and peripheral nervous system, concluding witha brief perspective related to its therapeutic potential for central nervoussystem disorders. A deeper knowledge of the mechanisms regulatingGDNF secretion and signaling, particularly the cellular source and thespecificity of the GDNF-engaged intracellular signaling pathways, couldFrontiers in Physiology 01 frontiersin.orgPorcari et al. 10.3389/fphys.2025.1618330be helpful to develop more precise therapeutic strategies for differentCNS diseases.

Background: the diagnosis of Parkinson’s disease (PD) can be challenging, especially in the early stages, albeit its updated and validated clinical criteria. Recent developments on neuroimaging in PD, altogether with its consolidated role of excluding secondary and other neurodegenerative causes of parkinsonism, provide more confidence in the diagnosis across the different stages of the disease. This review highlights current knowledge and major recent advances in magnetic resonance and dopamine transporter imaging in aiding PD diagnosis.

Objective: This study aims to review current knowledge about the role of magnetic resonance imaging and neuroimaging of the dopamine transporter in diagnosing Parkinson’s disease. Methods: We performed a non-systematic literature review through the PubMed database, using the keywords “Parkinson”, “magnetic resonance imaging”, “diffusion tensor”, “diffusion-weighted”, “neuromelanin”, “nigrosome-1”, “single-photon emission computed tomography”, “dopamine transporter imaging”. The search was restricted to articles written in English, published between January 2010 and February 2022. Results: The diagnosis of Parkinson’s disease remains a clinical diagnosis. However, new neuroimaging biomarkers hold promise for increased diagnostic accuracy, especially in earlier stages of the disease. Conclusion: Futurevalidation of new imaging biomarkers bring the expectation of an increased neuroimaging role in the diagnosis of PD in the following years.

Keywords: Parkinson Disease; Parkinsonian Disorders; Diffusion Tensor Imaging; Single Photon Emission Computed Tomography ComputedTomography; Melanins; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging.

Background: 

Parkinson’s disease (PD) is a multifactorial, progressive neurodegenerative disorder that primarily affects dopaminergic neurons in the substantia nigra. In addition to hallmark motor symptoms, it manifests a wide range of nonmotor complications, including cognitive decline, neuropsychiatric symptoms, autonomic dysfunction, and comorbid metabolic and infectious diseases.

Objectives: 

This review aims to elucidate the molecular and cellular mechanisms underlying PD, explore the influence of genetic and environmental factors, evaluate current treatment limitations, and assess the clinical and socioeconomic burden globally. Emphasis is placed on emerging therapeutic avenues and innovative research directions.

Methods: 

A structured literature review was conducted using PubMed, Scopus, and Web of Science databases. The search included articles published between 2010 and 2025, using keywords: “Parkinson’s disease,” “α-synuclein,” “dopaminergic degeneration,” “ferroptosis,” “deep brain stimulation,” “stem cell therapy,” and “AI in PD diagnosis.”

Results: 

The review highlights a multifactorial etiology involving α-synuclein pathology, oxidative stress, mitochondrial dysfunction, genetic mutations (SNCA, LRRK2, VPS35), environmental toxins, and gut dysbiosis. Comorbidities such as HIV, diabetes, and cardiovascular disorders exacerbate disease burden. While Levodopa remains the gold standard, its limitations necessitate combination therapy and adjunct modalities such as deep brain stimulation and nanocarrier-based drug delivery. Emerging approaches—stem cell therapy, CRISPR-Cas9, and AI-enhanced diagnostics—show promise.

Conclusion: 

PD management requires a paradigm shift toward precision medicine. Advancing research into biomarkers, immunotherapy, and systems biology, coupled with equitable access to care and early diagnosis tools, is critical to mitigating the global impact of PD.

Sjogren syndrome is traditionally considered an autoimmune disease characterized by

lymphocytic infiltration of the salivary and lacrimal glands, autoantibody production,

progressive glandular dysfunction, and systemic immune activation. Current therapies are

primarily directed toward symptom control and immunosuppression. Although these

approaches may reduce inflammatory activity, they generally do not restore normal

glandular architecture or biological function

 Sjögren’s syndrome (SS) is a systemic autoimmune disorder predominantly affecting middle-aged and elderly women, characterized by lymphocytic infiltration of exocrine glands—particularly the salivary and lacrimal glands—resulting in xerophthalmia and xerostomia. Osteoporosis (OP), sharing similar age of onset and gender predilection, is a skeletal disorder defined by reduced bone mineral density and heightened fracture risk. The comorbidity of SS and OP represents a prevalent clinical phenomenon, with studies reporting an incidence rate of 33.1% to 51.6% among SS patients, significantly higher than that observed in healthy elderly populations. Vitamin D metabolism, widespread abnormal immune responses, hormonal imbalances, metabolic acidosis, and the RANKL/RANK/OPG axis exert significant contributory roles in the pathogenesis of both conditions. Treatment regimens for SS and OP may present certain overlaps yet potential contradictions. In this narrative review, we summarize the bidirectional relationship between these two diseases, thoroughly discuss the existing challenges in their management, and emphasize that recommending a comprehensive management strategy for SS patients with concurrent OP is crucial for enhancing patients’ quality of life. 

 Sj¨ogren’s syndrome (SS) is a systemic autoimmune disease characterized by immune-mediated injury of exocrine glands. Extensive lymphocytic infiltrates may contribute to the destruction and loss of secretory function of glands. B-cell hyperactivity is a key feature of the disease resulting in the production of a diverse array of autoantibodies in these patients. Although not specific for SS, anti-Ro/SSA and anti-La/SSB antibodies have been useful biomarkers for disease classification and diagnosis. During recent years, novel autoantibodies have been discovered in SS. In this review, we summarize the historical role and clinical relevance that autoantibodies have played in the classification criteria of Sj¨ogren’s syndrome, discuss laboratory aspects in antibody detection and review the role of novel autoantibodies in predicting particular stages of the disease, clinical phenotypes and long-term complications. 

 Alcohol-related liver disease (ALD) is a prevalent global health issue, contributing to significant mortality and encompassing a spectrum of liver damage from steatosis to decompensated cirrhosis and hepatocellular carcinoma. This review summarizes the current state of ALD, emphasizing both early and advanced stages, including alcohol-related hepatitis (AH). The epidemiology, diagnostic tools, natural history, and key progression factors of ALD are discussed, highlighting the role of diagnostic tools and pathways in early and advanced stages of ALD. The review also addresses the importance and particularities of the treatment of alcohol use disorder in patients with ALD, covering both psychological and pharmaceutical interventions. Finally, treatments for ALD-related fibrosis and AH are discussed, presenting both the currently available and future treatment options. The conclusions of this review underscore the need for comprehensive strategies to improve diagnosis, prognostic stratification, and treatment strategies at all stages of ALD. 

Sjögren’s syndrome (SS) is an autoimmune disease with glandular and extraglandular manifestations. Pleural

and pericardial effusions in association with SS are rare. Similarly, ascites is rare and it can occur in SS when

combined with primary biliary cirrhosis (PBC). Inflammatory Abdominal Aortic Aneurysm together with SS has been

described only in one case. We report herein the case of a 70-year-old man with SS presenting with polyserositis

(pleural and pericardial effusion and ascites) and gastrointestinal manifestations (atrophic gastritis and candida

esophagitis) and ascending aorta aneurysm. SS was diagnosed based on xerophthalmia, xerostomia,

extraglandular manifestations, positive results for the Schirmer test, ocular surface staining score, histopathologic

examination of labial buccal mucosa revealing focal lymphocytic sialadenitis and unstimulated salivary flow rate. The

only positive autoantibody was against smooth muscle cells (ASMA). We thought that pleural, pericardial effusions,

ascites, gastrointestinal findings and ascending aortic aneurysm may be related with autoimmunological

inflammation of SS. To evaluate the extent of aortic vasculitis, we performed a whole body 18-Fluorodeoxyglucosepositron

emission tomography (FDG-PET) and showed increased uptake of FDG in aneurysmal section of the

ascending aorta. Treatment with high dose corticosteroid was proved to be successful in both clinically and

laboratory.

Interstitial lung disease (ILD) is the most common lung manifestation in patients with Sjögren

syndrome (SJS) and is associated with poor outcomes. This study aimed to investigate the longterm

clinical course and prognostic factors in patients with SJS-ILD. Clinical data and high-resolution

computed tomography (HRCT) images of 62 patients with primary SJS-ILD were retrospectively

analyzed (biopsy-proven cases, n = 16). The mean patient age was 59.8 years; 83.9% of the patients

were females, and 38.7% showed a usual interstitial pneumonia (UIP) pattern on HRCT. The median

follow-up period was 61.5 months. During follow-up, 15 patients (24.2%) died, 7 (11.3%) experienced

acute exacerbation (AE), and 27 (43.5%) progressed. The 1-, 3- and 5-year survival rates were 93.5%,

85.8%, and 81.1%, respectively. Age (hazard ratio [HR]: 1.158, P = 0.003), C-reactive protein (CRP)

level (HR: 1.212, P = 0.045), FVC (HR: 0.902, P = 0.005), and a UIP pattern on HRCT (HR: 4.580,

P = 0.029) were significant prognostic factors in multivariable Cox analysis. In conclusion, death, AE,

and ILD progression occurred in 25%, 10%, and 50% of the patients with SJS-ILD, respectively. Older

age, higher CRP level, lower FVC, and a UIP pattern on HRCT indicated poor prognosis.

Primary Sj.gren syndrome (SJS) is a chronic systemic inflammatory disorder characterized by impaired