The vomeronasal system (VNS) mediates pheromonal communication in mammals. From the vomeronasal organ, two populations of sensory neurons, expressing either Galphai2 or Galphao proteins, send projections that end in glomeruli distributed either at the rostral or caudal half of the accessory olfactory bulb (AOB), respectively. Neurons at the AOB contact glomeruli of a single subpopulation. The dichotomic segregation of AOB glomeruli has been described in opossums, rodents and rabbits, while Primates and Laurasiatheres present the Galphai2-pathway only, or none at all (such as apes, some bats and aquatic species). We studied the AOB of the Madagascan lesser tenrec Echinops telfairi (Afrotheria: Afrosoricida) and found that Galphai2 and Galphao proteins are expressed in rostral and caudal glomeruli, respectively. However, the segregation of vomeronasal glomeruli at the AOB is not exclusive, as both pathways contained some glomeruli transposed into the adjoining subdomain. Moreover, some glomeruli seem to contain intermingled afferences from both pathways. Both the transposition and heterogeneity of vomeronasal afferences are features, to our knowledge, never reported before. The organization of AOB glomeruli suggests that synaptic integration might occur at the glomerular layer. Whether intrinsic AOB neurons may make synaptic contact with axon terminals of both subpopulations is an interesting possibility that would expand our understanding about the integration of vomeronasal pathways.

Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05). Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.

Objective: To systematically evaluate the feasibility and methodology to carry out wireless capsule endoscopy (WCE) in children <8 years to define small intestinal pathology.

Design: Prospective European multicentre study with negative prior investigation.

Patients and interventions: 83 children aged 1.5–7.9 years were recruited. Initially, all were offered “swallowing” (Group 1) for capsule introduction. If this failed endoscopic placement (Group 2) was used and the Roth net, Advance or custom-made introducers were compared.

Outcome measures: Primary endpoint: to determine pathology; secondary endpoint: comparison of capsule introduction methods.

Results: Capsule introduction: 20 (24%) children aged 4.0–7.9 years (mean, 6.9 years; 14 male) comprising Group 1 were older (p<0.025) than 63 (76%) aged 1.5–7.9 years (mean, 5.25 years; 30 male) forming Group 2. Complications: Roth net mucosal trauma in 50%; no others occurred. The available recording apparatus was inappropriate for those <3 years. Indications: gastrointestinal bleeding: n = 30 (16 positive findings: four ulcerative jejunitis, four polyps, two angiodysplasia, two blue rubber blebs, two Meckel’s diverticula, one anastomotic ulcer, one reduplication); suspected Crohn’s disease: n = 20 (11 had Crohn’s disease); abdominal pain: n = 12 (six positive findings: three Crohn’s disease, two lymphonodular hyperplasia, one blue rubber bleb); protein loss: n = 9 (four lymphangectasia); malabsorption: n = 12 (seven positive findings: six enteropathy, one ascaris). No abnormalities overall: 45%.

Conclusion: WCE is feasible and safe down to the age of 1.5 years. 20 children >4 years swallowed the capsule. The Advance introducer proved superior for endoscopic placement. The pathologies encountered showed age specificity and, unlike in adolescents, obscure gastrointestinal bleeding was the commonest indication.

Background: Almost half of global child deaths due to acute lower respiratory infections (ALRIs) occur in sub-Saharan Africa, where three-quarters of the population cook with solid fuels. This study aims to quantify the impact of fuel type and cooking practices on childhood ALRI mortality in Africa, and to explore implications for public health interventions.

Methods: Early-release World Health Survey data for the year 2003 were pooled for 16 African countries. Among 32 620 children born during the last 10 years, 1455 (4.46%) were reported to have died prior to their fifth birthday. Survival analysis was used to examine the impact of different cooking-related parameters on ALRI mortality, defined as cough accompanied by rapid breathing or chest indrawing based on maternal recall of symptoms prior to death.

Results: Solid fuel use increases the risk of ALRI mortality with an adjusted hazard ratio of 2.35 (95% CI 1.22 to 4.52); this association grows stronger with increasing outcome specificity. Differences between households burning solid fuels on a well-ventilated stove and households relying on cleaner fuels are limited. In contrast, cooking with solid fuels in the absence of a chimney or hood is associated with an adjusted hazard ratio of 2.68 (1.38 to 5.23). Outdoor cooking is less harmful than indoor cooking but, overall, stove ventilation emerges as a more significant determinant of ALRI mortality.

Conclusions: This study shows substantial differences in ALRI mortality risk among African children in relation to cooking practices, and suggests that stove ventilation may be an important means of reducing indoor air pollution.

Background: Clinical subtypes of mild cognitive impairment

(MCI) may represent different underlying aetiologies.

Methods: This European, multicentre, memory clinic

based study (DESCRIPA) of non-demented subjects

investigated whether MCI subtypes have different brain

correlates on MRI and whether the relation between

subtypes and brain pathology is modified by age. Using

visual rating scales, medial temporal lobe atrophy (MTA)

(0–4) and white matter hyperintensities (WMH) (0–30)

were assessed.

Results: Severity of MTA differed between MCI subtypes

(p,0.001), increasing from a mean of 0.8 (SD 0.7) in

subjective complaints (n=77) to 1.3 (0.8) in nonamnestic

MCI (n=93), and from 1.4 (0.9) in single

domain amnestic MCI (n=70) to 1.7 (0.9) in multiple

domain amnestic MCI (n=89). The association between

MCI subtype and MTA was modified by age and mainly

present in subjects .70 years of age. Severity of WMH

did not differ between MCI subtypes (p=0.21).

However, the combination of MTA and WMH differed

between MCI subtypes (p=0.02)

Conclusion: We conclude that MCI subtypes may have

different brain substrates, especially in older subjects.

Isolated MTA was mainly associated with amnestic MCI

subtypes, suggesting AD as the underlying cause. In nonamnestic

MCI, the relatively higher prevalence of MTA in

combination with WMH may suggest a different

pathophysiological origin.

Objective: The aim of the current prospective study was

to analyse the validity of MRI based diagnosis of

brainstem gliomas which was verified by stereotactic

biopsy and follow-up evaluation as well as to assess

prognostic factors and risk profile.

Methods: Between 1998 and 2007, all consecutive adult

patients with radiologically suspected brainstem glioma

were included. The MRI based diagnosis of the lesions

was made independently by an experienced neuroradiologist.

Histopathological evaluation was performed in all

patients from paraffin embedded specimens obtained by

multimodal image guided stereotactic serial biopsy

technique. Histopathological results were compared with

prior radiological assessment. Length of survival was

estimated with the Kaplan–Meier method and prognostic

factors were calculated using the Cox model.

Results: 46 adult patients were included. Histological

evaluation revealed pilocytic astrocytoma (n=2), WHO

grade II glioma (n=14), malignant glioma (n=12),

metastasis (n=7), lymphoma (n=5), cavernoma

(n=1), inflammatory disease (n=2) or no tumour/

gliosis (n=3). Perioperative morbidity was 2.5% (n=1).

There was no permanent morbidity and no mortality. All

patients with ‘‘no tumour’’ or ‘‘inflammatory disease’’

survived. Patients with low grade glioma and malignant

glioma showed a 1 year survival rate of 75% and 25%,

respectively; the 1 year survival rate for patients with

lymphoma or metastasis was 30%. In the subgroup with a

verified brainstem glioma, negative predictors for length of

survival were higher tumour grade (p=0.002) and

Karnofsky performance score (70 (p=0.004).

Conclusion: Intra-axial brainstem lesions with a radiological

pattern of glioma represent a very heterogeneous

tumour group with completely different outcomes.

Radiological features alone are not reliable for diagnostic

classification. Stereotactic biopsy is a safe method to

obtain a valid tissue diagnosis, which is indispensible for

treatment decision.

Objective: To measure functional gait improvements of

robotic-assisted locomotion training in children with

cerebral palsy (CP).

Design: Single-case experimental A-B design.

Settings: Rehabilitation Centre Affoltern am Albis,

Children’s University Hospital Zurich, Switzerland (inpatient

group) and Neurology Department of the Dr von

Haunersches Children’s Hospital Munich, Germany (outpatient

group).

Participants: 22 children (mean age 8.6 years, range

4.6–11.7) with CP and a Gross Motor Function

Classification System level II to IV.

Interventions: 3 to 5 sessions of 45–60 minutes/week

during a 3–5-week period of driven gait orthosis training.

Main outcome measures: 10-metre walk test

(10MWT), 6-minute walk test (6MinWT), Gross Motor

Function Measure (GMFM-66) dimension D (standing) and

dimension E (walking), and Functional Ambulation

Categories (FAC).

Results: The mean (SD) maximum gait speed (0.78

(0.57) to 0.91 (0.61) m/s; p,0.01) as well as the mean

(SD) dimension D of the GMFM-66 (40.3% (31.3%) to

46.6% (28.7%); p,0.05) improved significantly after the

intervention period. The mean (SD) 6MinWT (176.3

(141.8) to 199.5 (157.7) m), the mean FAC (2.6 (1.7) to

3.0 (1.6)) and the mean (SD) dimension E of the GMFM-

66 (29.5% (30.3%) to 31.6% (29.2%)) also showed an

increase, but did not reach a statistically significant level.

Conclusion: These results suggest that children with CP

benefit from robotic-assisted gait training in improving

functional gait parameters.

Background: The comprehensive International

Classification of Functioning, Disability and Health (ICF)

Core Set for rheumatoid arthritis (RA) is a selection of 96

categories from the ICF, representing relevant aspects in

the functioning of patients with RA.

Objectives: To study the responsiveness of the ICF Core

Set for RA in rheumatological practice.

Methods: A total of 46 patients with RA (72% women,

mean (SD) age 53.6 (12.6) years, disease duration 6.3

(8.0) years) were interviewed at baseline and again after

6 months treatment with a disease-modifying antirheumatic

drug (DMARD), applying the ICF Core Set for RA

with qualifiers for problems on a modified three-point

scale (no problem, mild/moderate, severe/complete).

Patient-reported outcomes included Modified Health

Assessment Questionnaire (MHAQ) and Short-Form 36

(SF-36) health survey, and disease activity was calculated.

Responsiveness was measured as change in

qualifiers in ICF categories, and was also compared with

change in patient-reported outcomes.

Results: After 6 months of DMARD treatment,

improvement by at least one qualifier was seen in 20% of

patients (averaged across all ICF categories), 71%

experienced no change and 9% experienced worsening

symptoms. Findings were similar across the different

aspects of functioning. Mainly moderate effect sizes were

seen for 6-month changes in the ICF Core Set for RA,

especially in patients with improved health status, with

similar effect size for disease activity. The components in

the ICF Core Set for RA were only weakly associated with

patient-reported outcomes and disease activity.

Conclusions: The ICF Core Set for RA demonstrated

moderate responsiveness in this real-life setting of

patients where minor changes occurred during treatment

with DMARDs.

Background: Recent evidence suggests that distinction

of subsets of rheumatoid arthritis (RA) depending on anticyclic

citrullinated peptide antibody (anti-CCP) status may

be helpful in distinguishing distinct aetiopathologies and in

predicting the course of disease. HLA-DRB1 shared

epitope (SE) and peptidylarginine deiminase type 4

(PADI4) genotype, both of which have been implicated in

anti-CCP generation, are assumed to be associated with

RA.

Objectives: To elucidate whether PADI4 affects the

clinical characteristics of RA, and whether it would

modulate the effect of anti-CCPs on clinical course. The

combined effect of SE and PADI4 on autoantibody profile

was also analysed.

Methods: 373 patients with RA were studied. SE,

padi4_94C.T, rheumatoid factor, anti-CCPs and antinuclear

antibodies (ANAs) were determined. Disease

severity was characterised by cumulative therapy

intensity classified into ordinal categories (CTI-1 to CTI-3)

and by Steinbrocker score.

Results: CTI was significantly associated with disease

duration, erosive disease, disease activity score (DAS) 28

and anti-CCPs. The association of anti-CCPs with CTI was

considerably influenced by padi4_94C.T genotype (C/C:

ORadj=0.93, padj=0.92; C/T: ORadj=2.92,

padj=0.093; T/T: ORadj=15.3, padj=0.002). Carriage of

padi4_94T exhibited a significant trend towards higher

Steinbrocker scores in univariate and multivariate

analyses. An association of padi4_94C.T with ANAs

was observed, with noteworthy differences depending on

SE status (SE2: ORadj=6.20, padj,0.04; SE+:

ORadj=0.36, padj=0.02) and significant heterogeneity

between the two SE strata (p=0.006).

Conclusions: PADI4 genotype in combination with anti-

CCPs and SE modulates clinical and serological characteristics

of RA.