Bronchiolitis: an update on management and prophylaxis.

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children less than 2 years of age in the UK. Respiratory syncytial virus is the most common virus associated with bronchiolitis and has the highest disease severity, mortality and cost. Bronchiolitis is generally a self-limiting condition, but can have serious consequences in infants who are very young, premature, or have underlying comorbidities. Management of bronchiolitis in the UK is guided by the National Institute for Health and Care Excellence (2015) guidance. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Pharmacological interventions including nebulized bronchodilators, steroids and antibiotics generally have limited or no evidence of efficacy and are not advised by National Institute of Health and Care Excellence. Antiviral therapeutics remain in development. As treatments are limited, there have been extensive efforts to develop vaccines, mainly targeting respiratory syncytial virus. At present, the only licensed product is a monoclonal antibody for passive immunisation. Its cost restricts its use to those at highest risk. Vaccines for active immunisation of pregnant women and young infants are also being developed

Development of an in vitro three dimensional loading-measurement system for long bone fixation under multiple loading conditions: a technical description

The purpose of this investigation was to design and verify the capabilities of an in vitro loading-measurement system that mimics in vivo unconstrained three dimensional (3D) relative motion between long bone ends, applies uniform load components over the entire length of a test specimen, and measures 3D relative motion between test segment ends to directly determine test segment construct stiffness free of errors due to potting-fixture-test machine finite stiffness

Human dispersal and plant processing in the Pacific 55 000–50 000 years ago

The dynamics of our species’ dispersal into the Pacific remains intensely debated. The authors present archaeological investigations in the Raja Ampat Islands, north-west of New Guinea, that provide the earliest known evidence for humans arriving in the Pacific more than 55 000–50 000 years ago. Seafaring simulations demonstrate that a northern equatorial route into New Guinea via the Raja Ampat Islands was a viable dispersal corridor to Sahul at this time. Analysis of faunal remains and a resin artefact further indicates that exploitation of both rainforest and marine resources, rather than a purely maritime specialisation, was important for the adaptive success of Pacific peoples

What is the Role of Community Capabilities for Maternal Health? An Exploration of Community Capabilities as Determinants to Institutional Deliveries in Bangladesh, India, and Uganda

Background: While community capabilities are recognized as important factors in developing resilient health systems and communities, appropriate metrics for these have not yet been developed. Furthermore, the role of community capabilities on access to maternal health services has been underexplored. In this paper, we summarize the development of a community capability score based on the Future Health System (FHS) project’s experience in Bangladesh, India, and Uganda, and, examine the role of community capabilities as determinants of institutional delivery in these three contexts. Methods: We developed a community capability score using a pooled dataset containing cross-sectional household survey data from Bangladesh, India, and Uganda. Our main outcome of interest was whether the woman delivered in an institution. Our predictor variables included the community capability score, as well as a series of previously identified determinants of maternal health. We calculate both population-averaged effects (using GEE logistic regression), as well as sub-national level effects (using a mixed effects model). Results: Our final sample for analysis included 2775 women, of which 1238 were from Bangladesh, 1199 from India, and 338 from Uganda. We found that individual-level determinants of institutional deliveries, such as maternal education, parity, and ante-natal care access were significant in our analysis and had a strong impact on a woman’s odds of delivering in an institution. We also found that, in addition to individual-level determinants, greater community capability was significantly associated with higher odds of institutional delivery. For every additional capability, the odds of institutional delivery would increase by up to almost 6 %. Conclusion: Individual-level characteristics are strong determinants of whether a woman delivered in an institution. However, we found that community capability also plays an important role, and should be taken into account when designing programs and interventions to support institutional deliveries. Consideration of individual factors and the capabilities of the communities in which people live would contribute to the vision of supporting people-centered approaches to health

Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder

BACKGROUND: Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD). Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4) have been shown to modulate amygdala and prefrontal cortex (PFC) activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined. METHODS: We investigated whether SLC6A4 promoter polymorphisms (5-HTTLPR, rs25531) and several downstream single nucleotide polymorphisms (SNPs) modulated activity of brain regions involved in the cognitive control of emotion in post-9/11 veterans with PTSD. We used functional MRI to examine neural activity in a PTSD group (n = 22) and a trauma-exposed control group (n = 20) in response to trauma-related images presented as task-irrelevant distractors during the active maintenance period of a delayed-response working memory task. Regions of interest were derived by contrasting activation for the most distracting and least distracting conditions across participants. RESULTS: In patients with PTSD, when compared to trauma-exposed controls, rs16965628 (associated with serotonin transporter gene expression) modulated task-related ventrolateral PFC activation and 5-HTTLPR tended to modulate left amygdala activation. Subsequent to combat-related trauma, these SLC6A4 polymorphisms may bias serotonin signaling and the neural circuitry mediating cognitive control of emotion in patients with PTSD. CONCLUSIONS: The SLC6A4 SNP rs16965628 and 5-HTTLPR are associated with a bias in neural responses to traumatic reminders and cognitive control of emotions in patients with PTSD. Functional MRI may help identify intermediate phenotypes and dimensions of PTSD that clarify the functional link between genes and disease phenotype, and also highlight features of PTSD that show more proximal influence of susceptibility genes compared to current clinical categorizations

Single-Molecule Force Spectroscopy: Experiments, Analysis, and Simulations

International audienceThe mechanical properties of cells and of subcellular components are important to obtain a mechanistic molecular understanding of biological processes. The quantification of mechanical resistance of cells and biomolecules using biophysical methods matured thanks to the development of nanotechnologies such as optical and magnetic tweezers, the biomembrane force probe and atomic force microscopy (AFM). The quantitative nature of force spectroscopy measurements has converted AFM into a valuable tool in biophysics. Force spectroscopy allows the determination of the forces required to unfold protein domains and to disrupt individual receptor/ligand bonds. Molecular simulation as a computational microscope allows investigation of similar biological processes with an atomistic detail. In this chapter, we first provide a step-by-step protocol of force spectroscopy including sample preparation, measurement and analysis of force spectroscopy using AFM and its interpretation in terms of available theories. Next, we present the background for molecular dynamics (MD) simulations focusing on steered molecular dynamics (SMD) and the importance of bridging of computational tools with experimental technique