Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.

Blood vessels in the central nervous system (CNS) develop unique features, but the contribution of CNS neurons to regulating those features is not fully understood. We report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevents invasion of endothelial cells into the deep layers of the retina and causes blood-retinal-barrier (BRB) dysfunction in mice. Vascular endothelial growth factor (VEGF), which drives angiogenesis, and Norrin, a Wnt ligand that induces BRB properties, are decreased after activity blockade. Exogenous VEGF restores vessel growth but not BRB function, whereas stabilizing beta-catenin in endothelial cells rescues BRB dysfunction but not vessel formation. We further identify that inhibiting cholinergic activity reduces angiogenesis during oxygen-induced retinopathy. Our findings demonstrate that neural activity lies upstream of VEGF and Norrin, coordinating angiogenesis and BRB formation. Neural activity originating from specific neural circuits may be a general mechanism for driving regional angiogenesis and barrier formation across CNS development

Celiac Disease and Pediatric Type 1 Diabetes: Diagnostic and Treatment Dilemmas

Despite the advent of sensitive and specific serologic testing, routine screening for celiac disease (CD) in diabetic populations may not be universal practice, and many clinicians struggle to find the optimal approach to managing CD in pediatric Type 1 diabetes (T1D) patients. While some clinicians advocate screening for CD in all patients with T1D, others are unsure whether this is warranted. The diagnosis of patients who present with symptomatic CD, including malabsorption and obvious pathology upon biopsy, remains straightforward, with improvements noted on a gluten-free diet. Many patients identified by screening, however, tend to be asymptomatic. Evidence is inconclusive as to whether the benefits of screening and potentially treating asymptomatic individuals outweigh the harms of managing a population already burdened with a serious illness. This review focuses on current knowledge of CD in children and youth with T1D, highlighting important elements of the disease's pathophysiology, epidemiology, clinical presentation, and diagnostic challenges

Zika virus impairs the development of blood vessels in a mouse model of congenital infection

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly

Investigating the burden of antibiotic resistance in ethnic minority groups in high-income countries: protocol for a systematic review and meta-analysis.

BACKGROUND: Antibiotic resistance (ABR) is an urgent problem globally, with overuse and misuse of antibiotics being one of the main drivers of antibiotic-resistant infections. There is increasing evidence that the burden of community-acquired infections such as urinary tract infections and bloodstream infections (both susceptible and resistant) may differ by ethnicity, although the reasons behind this relationship are not well defined. It has been demonstrated that socioeconomic status and ethnicity are often highly correlated with each other; however, it is not yet known whether accounting for deprivation completely explains any discrepancy seen in infection risk. There have currently been no systematic reviews summarising the evidence for the relationship between ethnicity and antibiotic resistance or prescribing. METHODS: This protocol will outline how we will conduct this systematic literature review and meta-analysis investigating whether there is an association between patient ethnicity and (1) risk of antibiotic-resistant infections or (2) levels of antibiotic prescribing in high-income countries. We will search PubMed/MEDLINE, EMBASE, Global Health, Scopus and CINAHL using MESH terms where applicable. Two reviewers will conduct title/abstract screening, data extraction and quality assessment independently. The Critical Appraisal Skills Programme (CASP) checklist will be used for cohort and case-control studies, and the Cochrane collaboration's risk of bias tool will be used for randomised control trials, if they are included. Meta-analyses will be performed by calculating the minority ethnic group to majority ethnic group odds ratios or risk ratios for each study and presenting an overall pooled odds ratio for the two outcomes. The Grading of Recommendations, Assessments, Development and Evaluation (GRADE) approach will be used to assess the overall quality of the body of evidence. DISCUSSION: In this systematic review and meta-analysis, we will aim to collate the available evidence of whether there is a difference in rates of AMR and/or antibiotic prescribing in minority vs. majority ethnic groups in high-income countries. Additionally, this review will highlight areas where more research needs to be conducted and may provide insight into what may cause differences in this relationship, should they be seen. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( CRD42016051533 )

Understanding Young Children's Health Beliefs and Diabetes Regimen Adherence

Previous studies of chronic illness management in children have focused mainly on parents' health beliefs. However, children's health beliefs also can be an important factor in predicting adherence. Indeed, children 6 to 10 years old spend most waking hours away from home, are under less parental supervision, and are becoming more responsible for their own care. The purpose of this study was to develop a pictorial, multi-item instrument to measure dimensions of the Health Belief Model (HBM) and self-efficacy (SE), designed specifically for children with diabetes, thus making it possible to examine both the parent's and child's health beliefs; to explore the relationship between their beliefs; and to examine the extent to which these beliefs are predictors of adherence and metabolic control.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68551/2/10.1177_014572179301900508.pd

Monocoque structure for the SKITTER three-legged walker

The SKITTER 2 design is a monocoque version of the proposed lunar three-legged walker. By the definition of monocoque, the body and legs are a shell with no internal ribbing or supports added for absorbing stresses. The purpose of the monocoque is to encase the elements used for power transmission, power supply, and control of the motion. The material for the structure is a vinyl ester resin, Derakane 8084. This material is easily formable and locally obtainable. The body consists of a hexagonally shaped cylinder with truncated hexagonal pyramids on the top and botton. The legs are eight inch diameter cylinders. The legs are comprised of a tibia section and a femur section. The SKITTER 2 is powered by six actuators which provide linear forces that are transformed into rotary torques by a series of chains and sprockets. The joints connect the femur to the body and the tibia to the femur. Surrounding the joints are flexible rubber hoses that fully encase the chains and sprockets. The SKITTER 2 is capable of walking upside down, righting itself after being overturned, and has the ability to perform in many environments. Applications for this walker include lunar transport or drilling, undersea exploration, and operation in severe surroundings such as arctic temperatures or high radiation

The urinary cytokine/chemokine signature of renal hyperfiltration in adolescents with type 1 diabetes.

OBJECTIVE: Urinary cytokine/chemokine levels are elevated in adults with type 1 diabetes (T1D) exhibiting renal hyperfiltration. Whether this observation extends to adolescents with T1D remains unknown. Our first objective was to determine the relationship between hyperfiltration and urinary cytokines/chemokines in normotensive, normoalbuminuric adolescents with T1D using GFR(cystatin). Our second aim was to determine the relationship between urine and plasma levels of inflammatory biomarkers, to clarify the origin of these factors. METHODS: Urine and serum cytokines/chemokines (Luminex platform) and GFR(cystatin) were measured in normofiltering (n = 111, T1D-N, GFR<135 ml/min/1.73 m(2)) and hyperfiltering (n = 31, T1D-H, GFR ≥ 135 ml/min/1.73 m(2)) adolescents with T1D (ages 10-16), and in age and sex matched healthy control subjects (HC, n = 59). RESULTS: We noted significant step-wise increases in urinary cytokine/chemokine excretion according to filtration status with highest levels in T1D-H, with parallel trends in serum analyte concentrations. After adjusting for serum glucose at the time of sampling, differences in urinary cytokine excretion were not statistically significant. Only serum IL-2 significantly differed between HC and T1D (p = 0.0076). CONCLUSIONS: Hyperfiltration is associated with increased urinary cytokine/chemokine excretion in T1D adolescents, and parallel trends in serum cytokine concentration. The GFR-associated trends in cytokine excretion may be driven by the effects of ambient hyperglycemia. The relationship between hyperfiltration, glycemia, and variations in serum and urine cytokine expression and their impact on future renal and systemic vascular complications requires further study