Robust markers and sample sizes for multi‐centre trials of Huntington's disease

Objective: The identification of sensitive biomarkers is essential to validate therapeutics for Huntington disease (HD). We directly compare structural imaging markers across the largest collective imaging HD dataset to identify a set of imaging markers robust to multicenter variation and to derive upper estimates on sample sizes for clinical trials in HD. Methods: We used 1 postprocessing pipeline to retrospectively analyze T1-weighted magnetic resonance imaging (MRI) scans from 624 participants at 3 time points, from the PREDICT-HD, TRACK-HD, and IMAGE-HD studies. We used mixed effects models to adjust regional brain volumes for covariates, calculate effect sizes, and simulate possible treatment effects in disease-affected anatomical regions. We used our model to estimate the statistical power of possible treatment effects for anatomical regions and clinical markers. Results: We identified a set of common anatomical regions that have similarly large standardized effect sizes (>0.5) between healthy control and premanifest HD (PreHD) groups. These included subcortical, white matter, and cortical regions and nonventricular cerebrospinal fluid (CSF). We also observed a consistent spatial distribution of effect size by region across the whole brain. We found that multicenter studies were necessary to capture treatment effect variance; for a 20% treatment effect, power of >80% was achieved for the caudate (n = 661), pallidum (n = 687), and nonventricular CSF (n = 939), and, crucially, these imaging markers provided greater power than standard clinical markers. Interpretation: Our findings provide the first cross-study validation of structural imaging markers in HD, supporting the use of these measurements as endpoints for both observational studies and clinical trial

Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in C. elegans

Reduced protein homeostasis leading to increased protein instability is a common molecular feature of aging, but it remains unclear whether this is a cause or consequence of the aging process. In neurodegenerative diseases and other amyloidoses, specific proteins self-assemble into amyloid fibrils and accumulate as pathological aggregates in different tissues. More recently, widespread protein aggregation has been described during normal aging. Until now, an extensive characterization of the nature of age-dependent protein aggregation has been lacking. Here, we show that age-dependent aggregates are rapidly formed by newly synthesized proteins and have an amyloid-like structure resembling that of protein aggregates observed in disease. We then demonstrate that age-dependent protein aggregation accelerates the functional decline of different tissues in C. elegans. Together, these findings imply that amyloid-like aggregates contribute to the aging process and therefore could be important targets for strategies designed to maintain physiological functions in the late stages of life

State-of-the-art microscopy to understand islets of Langerhans:what to expect next?

The discovery of Langerhans and microscopic description of islets in the pancreas were crucial steps in the discovery of insulin. Over the past 150 years, many discoveries in islet biology and type 1 diabetes have been made using powerful microscopic techniques. In the past decade, combination of new probes, animal and tissue models, application of new biosensors and automation of light and electron microscopic methods and other (sub)cellular imaging modalities have proven their potential in understanding the beta cell under (patho)physiological conditions. The imaging evolution, from fluorescent jellyfish to real-time intravital functional imaging, the revolution in automation and data handling and the increased resolving power of analytical imaging techniques are now converging. Here, we review innovative approaches that address islet biology from new angles by studying cells and molecules at high spatiotemporal resolution and in live models. Broad implementation of these cellular imaging techniques will shed new light on cause/consequence of (mal)function in islets of Langerhans in the years to come

Status and risk factors of unintentional injuries among Chinese undergraduates: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Injuries affect all age groups but have a particular impact on young people. To evaluate the incidence of non-fatal, unintentional, injuries among undergraduates in Wenzhou, China, assess the burden caused by these injuries, and explore the associated risk factors for unintentional injuries among these undergraduates, we conducted a college-based cross-sectional study.</p> <p>Methods</p> <p>Participants were selected by a multi-stage random sampling method, and 2,287 students were asked whether they had had an injury in the last 12 months; the location, cause, and consequences of the event. The questionnaire included demographic and socioeconomic characteristics, lifestyle habits, and the scale of type A behaviour pattern (TABP). Multivariate logistic regression models were used; crude odds ratios (ORs), adjusted ORs and their 95% confidence intervals (CIs) were estimated, with students having no injuries as the reference group.</p> <p>Results</p> <p>The incidence of injuries among undergraduates in Wenzhou was 18.71 injuries per 100 person-years (95%CI: 17.12~20.31 injuries per 100 person-years). Falls were the leading cause of injury, followed by traffic injuries, and animal/insect bites. Male students were more likely to be injured than female students. Risk factors associated with unintentional injuries among undergraduates were: students majoring in non-medicine (adjusted OR: 1.53; 95% CI: 1.19-1.96); type A behaviour pattern (adjusted OR: 2.99; 95% CI: 1.45-6.14); liking sports (adjusted OR: 1.86; 95% CI: 1.41-2.45).</p> <p>Conclusions</p> <p>Injuries have become a public health problem among undergraduates. Falls were the major cause of non-fatal injury. Therefore, individuals, families, schools and governments should promptly adopt preventive measures aimed at preventing and controlling morbidity due to non-fatal injury, especially among students identified to be at high-risk; such as male students with type A behaviour pattern who like sports.</p