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e detailed pathophysiological components acting at onset and during disease progression in late-onset autoimmune diabetes.

The objective of this study is to evaluate the effect of policy change disallowing body checking in adolescent ice hockey leagues (ages 15-17) on reducing rates of injury and concussion.

This is a prospective cohort study. Players 15-17 years-old were recruited from teams in non-elite divisions of play (lower 40%-70% by division of play depending on year and city of play in leagues where policy permits or prohibit body checking in Alberta and British Columbia, Canada (2015-18). A validated injury surveillance methodology supported baseline, exposure-hours and injury data collection. Any player with a suspected concussion was referred to a study physician. Primary outcomes include game-related injuries, game-related injuries (>7 days time loss), game-related concussions and game-related concussions (>10 days time loss).

44 teams (453 player-seasons) from non-body checking and 52 teams (674 player-seasons) from body checking leagues participated. In body checking leagues there were 213 injuries (69 ey players.Voices are arguably among the most relevant sounds in humans' everyday life, and several studies have suggested the existence of voice-selective regions in the human brain. Despite two decades of research, defining the human brain regions supporting voice recognition remains challenging. Moreover, whether neural selectivity to voices is merely driven by acoustic properties specific to human voices (e.g., spectrogram, harmonicity), or whether it also reflects a higher-level categorization response is still under debate. Here, we objectively measured rapid automatic categorization responses to human voices with fast periodic auditory stimulation (FPAS) combined with electroencephalography (EEG). Participants were tested with stimulation sequences containing heterogeneous non-vocal sounds from different categories presented at 4 Hz (i.e., four stimuli/s), with vocal sounds appearing every three stimuli (1.333 Hz). A few minutes of stimulation are sufficient to elicit robust 1.333 Hz voice-selective focal brain responses over superior temporal regions of individual participants. This response is virtually absent for sequences using frequency-scrambled sounds, but is clearly observed when voices are presented among sounds from musical instruments matched for pitch and harmonicity-to-noise ratio (HNR). Overall, our FPAS paradigm demonstrates that the human brain seamlessly categorizes human voices when compared with other sounds including musical instruments' sounds matched for low level acoustic features and that voice-selective responses are at least partially independent from low-level acoustic features, making it a powerful and versatile tool to understand human auditory categorization in general.Insulin-producing pancreatic β-cells are central to glucose homeostasis, and their failure is a principal driver of diabetes development. To preserve optimal health β-cells must withstand both intrinsic and extrinsic stressors, ranging from inflammation to increased peripheral insulin demand, in addition to maintaining insulin biosynthesis and secretory machinery. Autophagy is increasingly being appreciated as a critical β-cell quality control system vital for glycemic control. Here we focus on the underappreciated, yet crucial, roles for selective and organelle-specific forms of autophagy as mediators of β-cell health. We examine the unique molecular players underlying each distinct form of autophagy in β-cells, including selective autophagy of mitochondria, insulin granules, lipid, intracellular amyloid aggregates, endoplasmic reticulum, and peroxisomes. We also describe how defects in selective autophagy pathways contribute to the development of diabetes. As all forms of autophagy are not the same, a refined view of β-cell selective autophagy may inform new approaches to defend against the various insults leading to β-cell failure in diabetes.Critical insights into the etiology of type 1 diabetes (T1D) came from genome-wide association studies that unequivocally connected genetic susceptibility to immune cell function. At the top of the susceptibility are genes involved in regulatory T-cell (Treg) function and development. The advances in epigenetic and transcriptional analyses have provided increasing evidence for Treg dysfunction in T1D. These are well supported by functional studies in mouse models and analysis of peripheral blood during T1D. For these reasons, Treg-based therapies are at the forefront of research and development and have a tangible probability to deliver a long-sought-after successful immune-targeted treatment for T1D. The current challenge in the field is whether we can directly assess Treg function at the tissue site or make informative interpretations based on peripheral data. Future studies focused on Treg function in pancreatic lymph nodes and pancreas could provide key insight into the ultimate mechanisms underlying Treg failure in T1D. In this Perspective we will provide an overview of current literature regarding Treg development and function in T1D and how this knowledge has been applied to Treg therapies.TCF7L2 is the most potent locus for type 2 diabetes (T2D) risk and the first locus to have been robustly reported by genomic linkage studies. TCF7L2 is a transcription factor that forms a basic part of the Wnt signaling pathway. This gene has highly conserved sequence regions that correspond to functional domains. The association of TCF7L2 with T2D is one of the most powerful genetically discovered in studies of complex diseases, as it has been consistently replicated in multiple populations with diverse genetic origins. The mechanisms over which TCF7L2 exerts its effect on T2D are still not well understood. In this article, we describe the main molecular mechanisms of how TCF7L2 is related to T2D. TCF7L2 variants associated with T2D risk exert an influence on the initial therapeutic success of the hypoglycemic oral agent sulfonylurea. Thus, it is important to know whether there are other TCF7L2 variants associated with T2D that can influence treatment with oral hypoglycemic agents. Resequencing of the TCF7L2 gene in diverse ethnic groups is required to reveal common and rare variations and their role in different pathologies and in adverse reactions to drugs. Identification of TCF7L2-susceptibility disease variants will permit, at a given moment, offering of therapies to patients according to their genotype.

To identify risk factors for asthma attacks and poor asthma control in children aged 5-16 years.

Prospective observational cohort study of 460 children with asthma or suspected asthma from 10 UK general practices.Gender, age, ethnicity, body mass index, practice deprivation decile, spirometry and fraction of exhaled nitric oxide (FeNO) were recorded at baseline. Asthma control scores, asthma medication ratio (AMR) and the number of asthma attacks were recorded at baseline and at 6 months.The above independent variables were included in binary multiple logistic regression analyses for the dependent variables of (1) poor symptom control and (2) asthma attacks during follow-up.

Poor symptom control at baseline predicted poor symptom control at 6 months (OR 4.4, p=0.001), while an increase in deprivation decile (less deprived) was negatively associated with poor symptom control at 6 months (OR 0.79, p=0.003). Higher FeNO levels (OR 1.02, p<0.001) and a recent history of asthma attacks (OR 2.03, p=0.02) predicted asthma attacks during follow-up. Asian ethnicity was associated with a lower OR for a future attack (OR 0.32, p=0.02).A decrease in AMR was also associated with an increased OR for future asthma attacks (OR 2.99, p=0.003) when included as an independent variable.

We identified risk factors for poor symptom control and asthma attacks in children. Routine assessment of these factors should form part of the asthma review to identify children at an increased risk of adverse asthma-related events.

We identified risk factors for poor symptom control and asthma attacks in children. Routine assessment of these factors should form part of the asthma review to identify children at an increased risk of adverse asthma-related events.

The aim of this study was to investigate whether being on dialysis at the time of renal transplantation affected renal allograft survival in paediatric renal transplant recipients (pRTRs).

Retrospective study of UK Transplant Registry (National Health Service Blood and Transplant) data on all children (aged <18 years) receiving a kidney-only transplant from 1 January 2000 to 31 December 2015. Kaplan-Meier estimates of patient and renal allograft survival calculated and Cox regression modelling accounting for donor type. The relationship between time on dialysis and renal allograft survival was examined.

2038 pRTRs were analysed 607 (30%) were pre-emptively transplanted, 789 (39%) and 642 (32%) on peritoneal dialysis and haemodialysis, respectively, at the time of transplantation. Five-year renal allograft survival was significantly better in the pre-emptively transplanted group (90.6%) compared with those on peritoneal dialysis and haemodialysis (86.4% and 85.7%, respectively; p=0.02). After accountift survival, there was no evidence that short periods of dialysis pre-transplant affected renal allograft survival.

Adult patients with ischemic Moyamoya disease are advised to undergo selective revascularization surgery based on cerebral hemodynamics. The purpose of this study was to determine the diagnostic accuracy of arterial spin-labeling MR imaging using Hadamard-encoded multiple postlabeling delays for the detection of reduced CBF in such patients.

Thirty-seven patients underwent brain perfusion SPECT and pseudocontinuous arterial spin-labeling MR imaging using standard postlabeling delay (1525 ms) and Hadamard-encoded multiple postlabeling delays. For Hadamard-encoded multiple postlabeling delays, based on data obtained from the 7 sub-boluses with combinations of different labeling durations and postlabeling delays, CBF corrected by the arterial transit time was calculated on a voxel-by-voxel basis. Using a 3D stereotaxic template, we automatically placed ROIs in the ipsilateral cerebellar hemisphere and 5 MCA territories in the symptomatic cerebral hemisphere; then, the ratio of the MCA to cerebellar ROI was cect reduced CBF on brain perfusion SPECT with 100% sensitivity and a 100% negative predictive value in adult patients with ischemic Moyamoya disease.Hyperactivation of the colliculi has been observed in some patients with coronavirus disease 2019.Medically unexplained symptoms (MUS) are those with no identified organic aetiology. Our emergency department (ED) perceived an increase in MUS frequency during COVID-19. The primary aim was to compare MUS incidence in frequent attenders (FAs) during COVID-19 and a control period.A retrospective list of FA-MUS presenting to our ED from March to June 2019 (control) and March to June 2020 (during COVID-19) was compared. Fisher's exact test was used to compare binomial proportions; this presented as relative risk (RR) with 95% confidence intervals (95%CI).During COVID-19, ED attendances reduced by 32.7%, with a significant increase in the incidence of FA-MUS and FA-MUS ED visits compared to control; RR 1.5 (95%CI 1.1-1.8) p=0.0006, and RR 1.8 (95%CI 1.6-2.0), p less then 0.0001, respectively.Despite reduced ED attendances during COVID-19, there was a significant increase in the incidence of FA-MUS patients and corresponding ED visits by this cohort. This presents a challenge to ED clinicians who may feel underprepared to manage these patients effectively.