Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity.

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e. neuroticism) and promising biomarker (i.e. amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression

When Less is More: Mindfulness Predicts Adaptive Affective Responding to Rejection Via Reduced Prefrontal Recruitment

Social rejection is a distressing and painful event that many people must cope with on a frequent basis. Mindfulness—defined here as a mental state of receptive attentiveness to internal and external stimuli as they arise, moment-to-moment—may buffer such social distress. However, little research indicates whether mindful individuals adaptively regulate the distress of rejection—or the neural mechanisms underlying this potential capacity. To fill these gaps in the literature, participants reported their trait mindfulness and then completed a social rejection paradigm (Cyberball) while undergoing functional magnetic resonance imaging. Approximately 1 hour after the rejection incident, participants reported their level of distress during rejection (i.e. social distress). Mindfulness was associated with less distress during rejection. This relation was mediated by lower activation in the left ventrolateral prefrontal cortex during the rejection incident, a brain region reliably associated with the inhibition of negative affect. Mindfulness was also correlated with less functional connectivity between the left ventrolateral prefrontal cortex and the bilateral amygdala and the dorsal anterior cingulate cortex, which play a critical role in the generation of social distress. Mindfulness may relate to effective coping with rejection by not over-activating top-down regulatory mechanisms, potentially resulting in more effective long-term emotion-regulation

Scapular Performance in Women with Breast Cancer Compared to Healthy Controls

The Scapular Flip Test is designed to recognize abnormal scapular position defined by winging/tipping of the scapula on resisted external rotation. Originally created to detect scapular dysfunction with spinal accessory nerve damage, the Scapular Flip Test may be a simple screening tool for any scapular dysfunction that results from breast cancer surgery and treatment to the shoulder and axillary region.https://ecommons.udayton.edu/dpt_symposium/1020/thumbnail.jp

Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study

Abstract Background Despite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 (IL-21), a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor. Methods In this phase 1/2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 (10–50 mcg/kg) on days 1–5 and 15–19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were evaluated. Results In phase 1 (n = 19), the maximum tolerated dose for IL-21 with the standard dose of sorafenib was determined to be 30 mcg/kg/day; grade 3 skin rash was the only dose-limiting toxicity. In phase 2, 33 previously-treated patients tolerated the combination therapy well with appropriate dose reductions; toxicities were mostly grade 1 or 2. The objective response rate was 21% and disease control rate was 82%. Two patients have durable responses that are ongoing, despite cessation of both IL-21 and sorafenib, at 41+ and 30+ months, respectively. The median progression-free survival in phase 2 was 5.6 months. The pharmacokinetic and pharmacodynamic properties of IL-21 appeared to be preserved in the presence of sorafenib. Conclusion IL-21 plus sorafenib has antitumor activity and acceptable safety in previously treated mRCC patients. IL-21 may represent a suitable immunotherapy in further exploration of combination strategies in mRCC. Trial registration ClinicalTrials.gov Identifier: NCT0038928

Complex Faraday depth structure of active galactic nuclei as revealed by broad-band radio polarimetry

We present a detailed study of the Faraday depth structure of four bright (>1 Jy), strongly polarized, unresolved radio-loud quasars. The Australia Telescope Compact Array (ATCA) was used to observe these sources with 2 GHz of instantaneous bandwidth from 1.1 to 3.1 GHz. This allowed us to spectrally resolve the polarization structure of spatially unresolved radio sources, and by fitting various Faraday rotation models to the data, we conclusively demonstrate that two of the sources cannot be described by a simple rotation measure (RM) component modified by depolarization from a foreground Faraday screen. Our results have important implications for using background extragalactic radio sources as probes of the Galactic and intergalactic magneto-ionic media as we show how RM estimations from narrow-bandwidth observations can give erroneous results in the presence of multiple interfering Faraday components. We postulate that the additional RM components arise from polarized structure in the compact inner regions of the radio source itself and not from polarized emission from galactic or intergalactic foreground regions. We further suggest that this may contribute significantly to any RM time variability seen in RM studies on these angular scales. Follow-up, high-sensitivity very long baseline interferometry (VLBI) observations of these sources will directly test our predictions

Diabetes in sub-Saharan Africa: from clinical care to health policy.

Rapid demographic, sociocultural, and economic transitions are driving increases in the risk and prevalence of diabetes and other non-communicable diseases (NCDs) in sub-Saharan Africa. The impacts of these transitions and their health and economic consequences are evident. Whereas, in 1990, the leading causes of death in sub-Saharan Africa were HIV/AIDS, lower respiratory infections, diarrhoeal diseases, malaria, and vaccine-preventable diseases in children, in more recent years, cardiovascular diseases and their risk factors are replacing infectious diseases as the leading causes of death in this region, and rates of increase of cardiovascular risk factors are predicted to be greater in sub-Saharan Africa than in other parts of the world. Thus, sub-Saharan Africa—which contains a high proportion of the world\u27s least developed countries—will face the multifaceted challenge of dealing with a high burden of infectious diseases and diseases of poverty, while also addressing the increasing burden of cardiovascular disease and its risk factors. At present, many of the health systems in sub-Saharan Africa struggle to cope with infectious diseases. Meeting the goals of the UN high-level meeting on NCDs (to reduce premature mortality from NCDs by 25% by 2025) and Sustainable Development Goals (SDGs; to reduce premature mortality from NCDs by a third by 2030) requires a coordinated approach within countries, which starts with a firm consideration of disease burden, needs, and priorities

Characterisation of insulin analogues therapeutically available to patients

The structure and function of clinical dosage insulin and its analogues were assessed. This included ‘native insulins’ (human recombinant, bovine, porcine), ‘fast-acting analogues’ (aspart, glulisine, lispro) and ‘slow-acting analogues’ (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein

The benefits of a 5-day dysphagia intensive placement

Finding practical dysphagia opportunities for students pre-qualification is challenging. Discussions with clinicians led to the development of a new placement model. The placement was just five days and had an accompanying workbook. The current study aimed to evaluate the benefits of the placement. Data were analysed from 40 students who attended an adult dysphagia placement and 13 who attended a paediatric dysphagia placement. Measures included a pre and post self-rating questionnaire, qualitative feedback from clinical educators and students and a pre and post measure of knowledge using concept maps. Student self-rating data indicated gains in experience, awareness, knowledge, clinical skills, competence, confidence and interest in dysphagia. Clinical educators and students also reported a range of benefits from this placement. Students who undertook a placement that focused on adult dysphagia significantly increased their knowledge of adult dysphagia, but this did not generalize to paediatric dysphagia. Despite reporting that they felt they had gained in knowledge of dysphagia, the students who did a paediatric dysphagia placement did not significantly increase their knowledge of dysphagia. The study raises a number of important considerations when designing placements including length, timing, intensity, how best to encourage generalization of knowledge, and how best to measure learning