Consensus Competencies for Postgraduate Fellowship Training in Global Neurology.

Background And Objectives: Use a modified Delphi approach to develop competencies for neurologists completing ≥1 year of advanced global neurology training.

Methods: An expert panel of 19 United States-based neurologists involved in global health was recruited from the American Academy of Neurology Global Health Section and the American Neurological Association International Outreach Committee. An extensive list of global health competencies was generated from review of global health curricula and adapted for global neurology training.

Deleterious, protein-altering variants in the transcriptional coregulator ZMYM3 in 27 individuals with a neurodevelopmental delay phenotype.

Neurodevelopmental disorders (NDDs) result from highly penetrant variation in hundreds of different genes, some of which have not yet been identified. Using the MatchMaker Exchange, we assembled a cohort of 27 individuals with rare, protein-altering variation in the transcriptional coregulator ZMYM3, located on the X chromosome. Most (n = 24) individuals were males, 17 of which have a maternally inherited variant; six individuals (4 male, 2 female) harbor de novo variants.

Efficacy of Prednisolone for Bell Palsy in Children: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

Background And Objectives: Corticosteroids are used to treat the early stages of idiopathic facial paralysis (Bell palsy) in children, but their effectiveness is uncertain. We set out to determine whether prednisolone improves the proportion of children with Bell palsy with complete recovery at 1 month.

Methods: We conducted a double-blind, placebo-controlled, randomized trial of prednisolone in children presenting to emergency departments with Bell palsy.

Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria.

Background: New approaches for the prevention and elimination of malaria, a leading cause of illness and death among infants and young children globally, are needed.

Methods: We conducted a phase 1 clinical trial to assess the safety and pharmacokinetics of L9LS, a next-generation antimalarial monoclonal antibody, and its protective efficacy against controlled human malaria infection in healthy adults who had never had malaria or received a vaccine for malaria. The participants received L9LS either intravenously or subcutaneously at a dose of 1 mg, 5 mg, or 20 mg per kilogram of body weight.

Prevention of arterial and venous thrombotic events in symptomatic peripheral arterial disease patients after lower extremity revascularization in the VOYAGER PAD trial: Dual anticoagulant/antiplatelet regimen vs antiplatelet therapy alone.

Background: Vascular disease burden after lower extremity revascularization (LER) comprises more than the first event, more vascular beds than the local arteries, and more than one clinical event type.

Objectives: Assess total arterial and venous thrombotic burden after LER for symptomatic peripheral artery disease (PAD) and effect of low-dose anticoagulation added to low-dose antiplatelet therapy.

Patients/methods: VOYAGER PAD randomized 6564 symptomatic PAD patients undergoing LER to rivaroxaban 2.

Inpatient Management of Acute Stroke of Unknown Type in Resource-Limited Settings.

Stroke is the second leading cause of death and disability worldwide, with a disproportionate burden on low- and middle-income countries. Critical elements of guideline-based stroke care developed in high-income countries are not applicable to resource-limited settings, where lack of access to neuroimaging prevents clinicians from distinguishing between ischemic stroke and intracranial hemorrhage, requiring challenging clinical decision-making, particularly in the acute setting. We discuss strategies for acute inpatient management of stroke of unknown type with a focus on blood pressure management and antiplatelet therapy when neuroimaging is unavailable, and review some of the challenges and strategies for successfully implementing stroke unit care in resource-limited health care settings.

A Monoclonal Antibody for Malaria Prevention.

Background: Additional interventions are needed to reduce the morbidity and mortality caused by malaria.

Methods: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with . Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria.

"More Guts Than Brains?"-The Role of Gut Microbiota in Idiopathic Intracranial Hypertension.

Background: Idiopathic intracranial hypertension syndrome (IIH) is most common among obese women. Weight loss is an important factor in improving papilledema. Over the last decade, growing evidence has identified gut microbiota as a potential factor in the pathophysiology of obesity.

Acetate, a Short-Chain Fatty Acid, Acutely Lowers Heart Rate and Cardiac Contractility Along with Blood Pressure.

Short-chain fatty acids (SCFAs) are metabolites produced almost exclusively by the gut microbiota and are an essential mechanism by which gut microbes influence host physiology. Given that SCFAs induce vasodilation, we hypothesized that they might have additional cardiovascular effects. In this study, novel mechanisms of SCFA action were uncovered by examining the acute effects of SCFAs on cardiovascular physiology in vivo and ex vivo.

Is zeaxanthin needed for desiccation tolerance? Sustained forms of thermal dissipation in tolerant versus sensitive bryophytes.

Desiccation tolerant (DT) plants engage and disengage sustained forms of energy dissipation in response to desiccation and rehydration. This project sought to characterize the role of zeaxanthin and thylakoid protein phosphorylation status in sustained energy dissipation during desiccation in bryophytes with varying DT. Tolerant (Polytrichum piliferum, Dicranum species, Calliergon stramineum) and sensitive (Grimmia species, Schistidium rivulare, Sphagnum species) moss were desiccated in darkness or natural light conditions for up to three weeks.

Safety and efficacy of anticoagulant therapy in pediatric catheter-related venous thrombosis (EINSTEIN-Jr CVC-VTE).

Anticoagulant treatment of pediatric central venous catheter-related venous thromboembolism (CVC-VTE) has not been specifically evaluated. In EINSTEIN-Jr, 500 children with any VTE received rivaroxaban or standard anticoagulants. A predefined analysis of the CVC-VTE cohort was performed.

Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline: The COMPASS MRI Substudy.

Background And Purpose: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.

Rivaroxaban in Peripheral Artery Disease after Revascularization.

Background: Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain.

Methods: In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.

Bleeding and New Cancer Diagnosis in Patients With Atherosclerosis.

Background: Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer.

Methods: We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites.

A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry.

Enhancing the Quality of Rivaroxaban Exposure Estimates Using Prothrombin Time in the Absence of Pharmacokinetic Sampling.

Prothrombin time (PT) is a measure of coagulation status and was assessed in the majority of patients in the rivaroxaban phase II and III clinical trials as a pharmacodynamic marker. In the absence of sufficient phase III pharmacokinetic (PK) data to provide individual exposure measures for input into rivaroxaban exposure-response analyses, the aim of the present study was to investigate the use of PT-adjustment approaches (i.e.

Impact Of Physicians, Nurse Practitioners, And Physician Assistants On Utilization And Costs For Complex Patients.

Because of workforce needs and demographic and chronic disease trends, nurse practitioners (NPs) and physician assistants (PAs) are taking a larger role in the primary care of medically complex patients with chronic conditions. Research shows good quality outcomes, but concerns persist that NPs' and PAs' care of vulnerable populations could increase care costs compared to the traditional physician-dominated system. We used 2012-13 Veterans Affairs data on a cohort of medically complex patients with diabetes to compare health services use and costs depending on whether the primary care provider was a physician, NP, or PA.

Heterotopic Pregnancy Including Intrauterine Normal Gestation and Tubal Complete Hydatidiform Mole: A Case Report and Review of the Literature.

We report a rare case of heterotopic pregnancy with intrauterine normal gestation alongside tubal complete hydatidiform mole (CHM) that resulted in a viable pregnancy after removal of molar tissue. Because of their rarity and inherent complexity, such cases represent a significant challenge in diagnosis and management. A 34-year-old female in her 10th week of gestation presented with nausea, vomiting, and intermittent abdominal pain that progressively worsened.

Caregiver-Reported Quality of Life in Youth with Down Syndrome.

Objectives: To describe caregiver-reported quality of life (QOL) in youth with Down syndrome (DS) and to examine the role of obesity on QOL.

Study Design: Caregivers of youth with and without DS aged 10 through 20 years completed questionnaires examining QOL (Pediatric Quality of Life Questionnaire) and weight-related QOL (Impact of Weight on Quality of Life - Kids). Age- and sex-specific z scores were generated for body mass index.

Observed parent-child feeding dynamics in relation to child body mass index and adiposity.

Background: Restrictive feeding is associated with child overweight; however, the majority of studies used parent-report questionnaires.

Objectives: The relationship between child adiposity measures and directly observed parent and child behaviours were tested using a novel behavioural coding system (BCS).

Methods: Data from 109 children, participants in a twin study and their mothers, were analyzed.

The Transcription Factor MYB29 Is a Regulator of .

Plants sense and integrate a variety of signals from the environment through different interacting signal transduction pathways that involve hormones and signaling molecules. Using () gene expression as a model system of retrograde or stress signaling between mitochondria and the nucleus, MYB DOMAIN PROTEIN29 (MYB29) was identified as a negative regulator ( [] mutant) in a genetic screen of Arabidopsis (). mutants have increased levels of AOX1a transcript and protein compared to wild type after induction with antimycin A.

A useful methoxyvinyl cation equivalent: α-t-butyldimethylsilyl-α-methoxyacetaldehyde.

Described are the synthesis and application of α-t-butyldimethylsilyl-α-methoxyacetaldehyde as a formal methoxyvinyl cation equivalent. Addition of Grignard reagents to the title aldehyde, followed by treatment of the intermediate β-hydroxysilanes with KH, gives good yields of large -methoxyvinylated products. Assuming a Peterson-like elimination mechanism, one can infer that the Grignard addition proceeds with high selectivity.

Soluble guanylate cyclase is required for systemic vasodilation but not positive inotropy induced by nitroxyl in the mouse.

Nitroxyl (HNO), the reduced and protonated form of nitric oxide (NO·), confers unique physiological effects including vasorelaxation and enhanced cardiac contractility. These features have spawned current pharmaceutical development of HNO donors as heart failure therapeutics. HNO interacts with selective redox sensitive cysteines to effect signaling but is also proposed to activate soluble guanylate cyclase (sGC) in vitro to induce vasodilation and potentially enhance contractility.