Using Gene Ontology to describe the role of the neurexin-neuroligin-SHANK complex in human, mouse and rat and its relevance to autism

People with an autistic spectrum disorder (ASD) display a variety of characteristic behavioral traits, including impaired social interaction, communication difficulties and repetitive behavior. This complex neurodevelopment disorder is known to be associated with a combination of genetic and environmental factors. Neurexins and neuroligins play a key role in synaptogenesis and neurexin-neuroligin adhesion is one of several processes that have been implicated in autism spectrum disorders

Structure-function Specialisation of the Interfascicular Matrix in the Human Achilles Tendon

Tendon consists of highly aligned collagen-rich fascicles surrounded by interfascicular matrix (IFM). Some tendons act as energy stores to improve locomotion efficiency, but such tendons commonly obtain debilitating injuries. In equine tendons, energy storing is achieved primarily through specialisation of the IFM. However, no studies have investigated IFM structure-function specialisation in human tendons. Here, we compare the human positional anterior tibial tendon and energy storing Achilles tendons, testing the hypothesis that the Achilles tendon IFM has specialised composition and mechanical properties, which are lost with ageing. Data demonstrate IFM specialisation in the energy storing Achilles, with greater elasticity and fatigue resistance than in the positional anterior tibial tendon. With ageing, alterations occur predominantly to the proteome of the Achilles IFM, which are likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of these key energy storing specialisations and their changes with ageing offers crucial insight towards developing treatments for tendinopathy. STATEMENT OF SIGNIFICANCE: Developing effective therapeutics or preventative measures for tendon injury necessitates the understanding of healthy tendon function and mechanics. By establishing structure-function relationships in human tendon and determining how these are affected by ageing, potential targets for therapeutics can be identified. In this study, we have used a combination of mechanical testing, immunolabelling and proteomics analysis to study structure-function specialisations in human tendon. We demonstrate that the interfascicular matrix is specialised for energy storing in the Achilles tendon, and that its proteome is altered with ageing, which is likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of these key energy storing specialisations and their changes with ageing offers crucial insight towards developing treatments and preventative approaches for tendinopathy

Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153088/1/feb213699.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153088/2/feb213699_am.pd

Prevalence and Correlates of Common Mental Disorders among Mothers of Young Children in Kilimanjaro Region of Tanzania.

Although poor maternal mental health is a major public health problem, with detrimental effects on the individual, her children and society, information on its correlates in low-income countries is sparse. This study investigates the prevalence of common mental disorders (CMD) among at-risk mothers, and explores its associations with sociodemographic factors. This population-based survey of mothers of children aged 0-36 months used the 14-item Shona Symptom Questionnaire (SSQ). Mothers whose response was "yes" to 8 or more items on the scale were defined as "at risk of CMD." Of the 1,922 mothers (15-48 years), 28.8% were at risk of CMD. Risk of CMD was associated with verbal abuse, physical abuse, a partner who did not help with the care of the child, being in a polygamous relationship, a partner with low levels of education, and a partner who smoked cigarettes. Cohabiting appeared to be protective. Taken together, our results indicate the significance of the quality of relations with one's partner in shaping maternal mental health. The high proportion of mothers who are at risk of CMD emphasizes the importance of developing evidence-based mental health programmes as part of the care package aimed at improving maternal well-being in Tanzania and other similar settings

Prevalence and age-of-onset distributions of DSM IV mental disorders and their severity among school going Omani adolescents and youths: WMH-CIDI findings

<p>Abstract</p> <p>Background</p> <p>There is a dearth of studies exploring the magnitude of mental disorders amongst adolescents and youths in the Arab world. To our knowledge, this phase 2 survey in Oman is the first nationally representative school-based study to determine the prevalence of DSM-IV mental disorders (lifetime and over the preceding 12 months), their age-of-onset distributions and determine their severity over the past 12 months using the World Mental Health-Composite International Diagnostic Interview, the WMH-CIDI, used for international comparison.</p> <p>Methods</p> <p>A total of 1,682 (91.61%) students out of 1836 students who formed the phase 2 random sub-sample of a multi-stage, stratified, random sampling design (phase 1), participated in the face-to-face structured interview using the Arabic-version of WMH-CIDI 3.0.</p> <p>Results</p> <p>The phase 1 results using the General Health Questionnaire (GHQ-12) and Child Depression Inventory (CDI) showed depressive symptoms to be 17% prevalent in the larger sample of 5409 adolescents and youths. Amongst the phase 2 respondents from this sample, 13.9% had at least one DSM IV diagnostic label. The lifetime prevalence of Major Depressive Disorder (MDD) was 3.0%; Bipolar Mood Disorder (BMD) was 1%, Specific phobia 5.8% and Social phobia 1.6%. The female gender was a strong predictor of a lifetime risk of MDD (OR 3.3, 95% CI 1.7-6.3, <it>p </it>= 0.000); Any Mood Disorders (OR 2.5, 95% CI 1.4-4.3, p = 0.002) and Specific Phobia (OR 1.5, 95% CI 1.0-2.4, p = 0.047). The severity of illness for cases diagnosed with 12 month DSM IV disorders was found to be 80% lower in females (OR 0.2, 95%CI 0.0-0.8). The estimates over the previous 12 month period when compared with the lifetime prevalence showed a 25% to 40% lower prevalence for MDD, Specific phobia, Social phobia, Any Anxiety Disorders (AAD) and Any Mood disorders (AMD) while the rate was 80% lower for Separation Anxiety Disorder/Adult Separation Anxiety (SAD/ASA). Mood disorders were significantly lower in the 14-16 age groups (70% lower) in comparison to the older age groups and AMD showed a linear increase in prevalence across increasing age groups (<it>p </it>= 0.035).</p> <p>Conclusion</p> <p>The implications of the present findings are not clear cut, however this study endorses the adult CIDI studies findings that mental disorders do begin earlier in life. The relatively lower prevalence of DSM IV depressive disorders cautions against any conclusive interpretation of the inflated results based on the exclusive study of the depressive symptoms alone in the same sample in the same time period. The female gender proved to be a strong predictor of lifetime risk of MDD, any mood disorder and specific phobia. Under-reporting by males or some other gender-specific factors may have contributed to such a discrepancy. The odds of the severity of illness for cases with 12 month DSM IV disorders were significantly lower in females.</p

A patient on RIPE therapy presenting with recurrent isoniazid-associated pleural effusions: a case report

<p>Abstract</p> <p>Introduction</p> <p>The clinical scenario of a new or worsening pleural effusion following the initiation of antituberculous therapy has been classically referred to as a 'paradoxical' pleural response, presumably explained by an immunological rebound phenomenon. Emerging evidence suggests that there also may be a role for a lupus-related reaction in the pathophysiology of this disorder.</p> <p>Case presentation</p> <p>An 84-year-old Asian man treated with isoniazid, along with rifampin, pyrazinamide and ethambutol for suspected extrapulmonary tuberculosis, presented with a recurrent pleural effusion, his third episode since the initiation of this therapy. The first effusion occurred one month after the start of treatment, without any prior evidence of pulmonary tuberculosis involvement. Follow-up testing, including thoracoscopic pleural biopsies, never confirmed tuberculosis infection. Further evaluation yielded serological evidence suggesting drug-induced lupus. No effusions recurred following the discontinuation of isoniazid, although other antituberculosis medications were continued.</p> <p>Conclusion</p> <p>The immunological rebound construct is inconsistent with the evolution of this case, which indicates rather that drug-induced lupus may explain at least some cases of new pleural effusions following the initiation of isoniazid.</p

Olanzapine and pulmonary embolism, a rare association: a case report

Venous thromboembolism is a very common pathological process for which there are many well known (and less well-known) predisposing factors. Likewise, olanzapine is a commonly used anti-psychotic medication