Δευτέρα, 15 Ιανουαρίου 2018

Clinical association of anti-glutathione S-transferase T1 antibodies and de novo immune hepatitis after hematopoietic cell transplantation



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The utility of motor unit number estimation methods versus quantitative motor unit potential analysis in diagnosis of ALS

Amyotrophic Lateral Sclerosis (ALS) is a fatal anterior horn cell disorder characterized by progressive degeneration of both upper and lower motor neurons (Brooks et al., 2000). Showing denervation activity by needle electromyography (EMG) and detection of chronic neurogenic changes are essential for ALS diagnosis. Motor unit potential (MUP) analysis is the most commonly used method to show chronic neurogenic changes. However, MUP analysis provides information about reinnervation rather than motor unit loss.

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Fetal growth: too little or just right?

Abstract

Fetal somatic growth rate is a controlled variable that is not completely understood. While we do not fully understand the mechanisms by which the growth rate is controlled (i.e. how or whether fetal body mass is sensed, what might constitute the "set-point" for the control mechanism, and how growth is accelerated or decelerated to match a "normal" growth rate), we do understand several variables that affect the rate of fetal somatic growth.

This article is protected by copyright. All rights reserved



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Content of First Prenatal Visits

Abstract

Objective The purpose of this study was to examine the content of the first prenatal visit within an academic medical center clinic and to compare the topics discussed to 2014 American College of Obstetrics and Gynecologists guidelines for the initial prenatal visit. Methods Clinical interactions were audio recorded and transcribed (n = 30). A content analysis was used to identify topics discussed during the initial prenatal visit. Topics discussed were then compared to the 2014 ACOG guidelines for adherence. Coded data was queried though the qualitative software and reviewed for accuracy and content. Results First prenatal visits included a physician, nurse practitioner, nurse midwife, medical assistant, medical students, or a combination of these providers. In general, topics that were covered in most visits and closely adhered to ACOG guidelines included vitamin supplementation, laboratory testing, flu vaccinations, and cervical cancer screening. Topics discussed less often included many components of the physical examination, education about pregnancy, and screening for an identification of psychosocial risk. Least number of topics covered included prenatal screening. Conclusions for Practice While the ACOG guidelines may include many components that are traditional in addition to those based on evidence, the guidelines were not closely followed in this study. Identifying new ways to disseminate information during the time constrained initial prenatal visit are needed to ensure improved patient outcomes.



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Thoracic aortic aneurysm in patients with loss of function Filamin A mutations: Clinical characterization, genetics, and recommendations

The frequency and gender distribution of thoracic aortic aneurysm as a cardiovascular manifestation of loss-of-function (LOF) X-linked FilaminA (FLNA) mutations are not known. Furthermore, there is very limited cardiovascular morbidity or mortality data in children and adults. We analyzed cardiac data on the largest series of 114 patients with LOF FLNA mutations, both children and adults, with periventricular nodular heterotopia (PVNH), including 48 study patients and 66 literature patients, median age of 22.0 years (88 F, 26 M, range: 0–71 years), with 75 FLNA mutations observed in 80 families. Most (64.9%) subjects had a cardiac anomaly or vascular abnormality (80.8% of males and 60.2% of females). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4% (n = 21), and were associated with other structural cardiac malformations in 57.1% of patients, most commonly patent ductus arteriosus (PDA) and valvular abnormalities. TAA most frequently involved the aortic root and ascending aorta, and sinus of Valsalva aneurysms were present in one third of TAA patients. Six TAA patients (28.5%) required surgery (median age 37 yrs, range 13–41 yrs). TAA with its associated complications was also the only recorded cause of premature, non-accidental mortality in adults (2 M, 2 F). Two adult patients (1 F, 1 M, median 38.5 yrs), died of spontaneous aortic rupture at aortic dimensions smaller than current recommendations for surgery for other aortopathies. Data from this largest series of LOF FLNA mutation patients underscore the importance of serial follow-up to identify and manage these potentially devastating cardiovascular complications.



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Table of Contents, Volume 176A, Number 2, February 2018



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In this issue



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GTEx project maps wide range of normal human genetic variation



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Reanalysis of clinical whole-exome sequence data yields multiple new diagnoses



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Publication schedule for 2018



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Cover Image, Volume 176A, Number 2, February 2018

Thumbnail image of graphical abstract

The cover image, by Ming Hui Chen et al., is based on the Original Article Thoracic Aortic Aneurysm in Patients with Loss of Function Filamin A Mutations: Clinical Characterization, Genetics, and Recommendations, DOI: 10.1002/ajmg.a.38580.



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Better diagnostic accuracy of neuropathy in obesity: A new challenge for neurologists



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Do you define the limits of normalcy from looking at the patient or the healthy subject?

In the practice of clinical neurophysiology, you are asked to differentiate between a normal and an abnormal function of the nervous system. The clinical question is often whether specific symptoms can be attributed to a disease process in the nervous system. This dichotomy between normal and abnormal is often posed by the patient, too. The wish is granted either to reassure him, that nothing is wrong, or to give him/her the reassurance of knowledge about a diagnosis and a prognosis.

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Reversal of Intestinal Failure in Children With Tufting Enteropathy Supported With Parenteral Nutrition at Home

ABSTRACTObjectives:To review long-term outcome of Intestinal Epithelial Dysplasia(IED)/tufting enteropathy(TE) patients treated with parenteral nutrition(PN) at home managed by an intestinal failure(IF) rehabilitation serviceMethods:Infants presenting from 1986–2010 with IF, and TE histology were retrospectively reviewed for up to 30 years. Data collected included: outcome, presentation, nutrition(parenteral/enteral), country of residence, race, EpCAM gene, growth, bone age, occupation.Results:13 patients (6 male) in Malta and the UK with TE histology were established on home PN. Survival was 100% for UK children and 92% overall (one death aged 13 months). Six patients (50% of the surviving 12) weaned off PN. Overall PN requirements reduced with increasing age and 25 years. Two/12 cases weaned from PN by 10 years, 1/8 by 15 years, 3/7 by 20 years and 3/4 or 75% >25 years. Six Maltese patients homozygous for the same EPCAM gene abnormality had a similar outcome to the other cases.Weight, height, bone mineralisation, bone age and IGF-1 levels were low, but improved with age. Patients achieved educational levels of parents and were employed.Conclusions:IED cases should have >92% chance of long-term survival and >50% chance of enteral autonomy by/in early adult life and 75% by 25 years. Even if PN dependent s/he can gain employment. Patients with IED managed on PN at home by an IF rehabilitation service should avoid intestinal transplant. Objectives: To review long-term outcome of Intestinal Epithelial Dysplasia(IED)/tufting enteropathy(TE) patients treated with parenteral nutrition(PN) at home managed by an intestinal failure(IF) rehabilitation service Methods: Infants presenting from 1986–2010 with IF, and TE histology were retrospectively reviewed for up to 30 years. Data collected included: outcome, presentation, nutrition(parenteral/enteral), country of residence, race, EpCAM gene, growth, bone age, occupation. Results: 13 patients (6 male) in Malta and the UK with TE histology were established on home PN. Survival was 100% for UK children and 92% overall (one death aged 13 months). Six patients (50% of the surviving 12) weaned off PN. Overall PN requirements reduced with increasing age and 25 years. Two/12 cases weaned from PN by 10 years, 1/8 by 15 years, 3/7 by 20 years and 3/4 or 75% >25 years. Six Maltese patients homozygous for the same EPCAM gene abnormality had a similar outcome to the other cases. Weight, height, bone mineralisation, bone age and IGF-1 levels were low, but improved with age. Patients achieved educational levels of parents and were employed. Conclusions: IED cases should have >92% chance of long-term survival and >50% chance of enteral autonomy by/in early adult life and 75% by 25 years. Even if PN dependent s/he can gain employment. Patients with IED managed on PN at home by an IF rehabilitation service should avoid intestinal transplant. Address correspondence and reprint requests to Dr Susan Hill, BM, MRCP, MRCPCH, DM, Gastroenterology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH UK (e-mail: susan.hill@gosh.nhs.uk). Received 1 August, 2017 Accepted 22 December, 2017 Conflicts of Interests: None declared © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Evaluation of recombinant factor VIIa, tranexamic acid and desmopressin to reduce prasugrel-related bleeding: A randomised, placebo-controlled study in a rabbit model

BACKGROUND Prasugrel is a thienopyridine that inhibits platelet aggregation more rapidly and effectively than clopidogrel, with an increased bleeding risk. OBJECTIVE The current study aimed to evaluate the efficacy of three nonspecific haemostatic drugs – recombinant activated factor VII (rFVIIa), tranexamic acid and desmopressin (DDAVP) – to limit blood loss after administration of prasugrel in a rabbit model of bleeding while also evaluating any prothrombotic effects. DESIGN Randomised, placebo-controlled study. SETTING Faculty of Medicine, University of Geneva, Switzerland, in 2013. ANIMALS Anaesthetised and artificially ventilated rabbits (n=56). INTERVENTIONS Animals were randomly allocated to one of five groups: control (placebo–placebo), prasugrel–placebo, rFVIIa (prasugrel–rFVIIa 150 μg kg−1), tranexamic acid (prasugrel–tranexamic acid 20 mg kg−1) or DDAVP (prasugrel–DDAVP 1 μg kg−1). Two hours after an oral prasugrel loading dose (4 mg kg−1), a stenosis and an injury were inflicted on the carotid artery to induce cyclic flow reductions (CFRs) due to thrombosis. Haemostatic drugs were administered during the ensuing observation period. MAIN OUTCOME MEASURES Standardised hepatosplenic sections were performed to evaluate the primary endpoint of blood loss, monitored for 15 min. Ear-immersion bleeding time and incidence of CFRs were secondary endpoints. RESULTS Prasugrel decreased ADP-induced platelet aggregation (light transmission method) from 66 ± 4% (mean ± SD) to 41 ± 7% (P 

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Comparing peri-operative complications of paediatric and adult anaesthesia: A retrospective cohort study of 81 267 cases

BACKGROUND Comparisons of peri-operative complications associated with paediatric (≤16 years) and adult anaesthesia are poorly available, especially in which cardiac surgery, organ transplantation and neurosurgery are involved. OBJECTIVE The aim of this study was to evaluate the nature and incidence of peri-operative complications that might be due to anaesthesia and to identify independent risk factors for complications in children and adults, including those undergoing cardiac surgery, organ transplantation and neurosurgery. DESIGN Retrospective cohort study. SETTING The study was performed at the University Medical Centre Groningen in the 4 years between 1 January 2010 and the 31 December 2013. MAIN OUTCOME MEASURES Complications and their severity were graded according to the standard complication score (20 items) of the Dutch Society of Anaesthesia. Univariate and multivariate regression analysis was used to identify independent risk factors for the reported complications. RESULTS A total of 81 267 anaesthetic cases were included. In the paediatric cohort, there were 410 (2.9%) complications and 1675 (2.5%) in the adults. In both cohorts age, American Society of Anaesthesiologists classification and emergency treatment were independent risk factors for complications. With respect to age, infants less than 1 year were at the highest risk, whereas in the adult cohort, increased age was related to a greater number of complications. The incidences of the specific complications were different between both cohorts. Upper airway obstruction was more frequently observed in paediatric patients (26%), whereas in the adults, complications with the highest incidence concerned conversion of regional-to-general anaesthesia (25%) and hypotension (17%). CONCLUSION Risk factors for all peri-operative complications were similar for paediatric and adult anaesthesia. However, the incidence of specific complications differed between both age categories. Correspondence to Andrie C. Westerkamp, MD, PhD, Department of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Box 30.001, 9700 RB Groningen, The Netherlands Tel: +31 50 3613155; fax: +31 50 3613763; e-mail: ac.westerkamp@umcg.nl © 2018 European Society of Anaesthesiology

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Genomic trade-offs: are autism and schizophrenia the steep price of the human brain?

Abstract

Evolution often deals in genomic trade-offs: changes in the genome that are beneficial overall persist even though they also produce disease in a subset of individuals. Here, we explore the possibility that such trade-offs have occurred as part of the evolution of the human brain. Specifically, we provide support for the possibility that the same key genes that have been major contributors to the rapid evolutionary expansion of the human brain and its exceptional cognitive capacity also, in different combinations, are significant contributors to autism and schizophrenia. Furthermore, the model proposes that one of the primary genes behind this trade-off may not technically be "a gene" or "genes" but rather are the highly duplicated sequences that encode the Olduvai protein domain family (formerly called DUF1220). This is not an entirely new idea. Others have proposed that the same genes involved in schizophrenia were also critical to the rapid expansion of the human brain, a view that has been expressed as "the same 'genes' that drive us mad have made us human". What is new is that a "gene", or more precisely a protein domain family, has been found that may satisfy these requirements.



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The ethics of interventional procedures for patients too ill for surgery

Purpose of review Minimally invasive interventional procedures are increasingly popular options for patients who are high-risk candidates for open surgical procedures. It is unclear how to proceed in the rare circumstance of a complication during an interventional procedure, where addressing the complication would require exposing the patient to the full risk that was being avoided with the minimally invasive technique. This review provides recommendations on how to approach this paradoxical scenario. Recent findings Risk stratification, communication frameworks, and advanced care planning can facilitate shared decision-making between physicians and patients. Risk stratification may include mortality predictive models, disability and frailty scores, and patient-centered outcome studies. In the event of procedural complication or failure, aggressive surgical treatment or limited repair should be guided by patient preferences to best ensure value concordant care. Summary Interventional procedures, and emergent open surgery, should be offered as long as patients are fully informed about the benefits and risks, including the implications of potential life-sustaining treatments, and whether their respective goals of treatment are consistent with the intervention. Implementing this framework will require a cultural shift in physician attitudes to recognize that in some cases, nonintervention or less aggressive treatment may be a reasonable alternative to surgical intervention. Correspondence to Michael Nurok, Cedars-Sinai Heart Institute, 127 S. San Vicente Blvd., A3100, Los Angeles, CA, 90048, USA. Tel: +1 310 248 7369; e-mail: michael.nurok@cshs.org Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Oxygen in the critically ill: friend or foe?

Purpose of review To examine the potential harmful effects of hyperoxia and summarize the results of most recent clinical studies evaluating oxygen therapy in critically ill patients. Recent findings Excessive oxygen supplementation may have detrimental pulmonary and systemic effects because of enhanced oxidative stress and inflammation. Hyperoxia-induced lung injury includes altered surfactant protein composition, reduced mucociliary clearance and histological damage, resulting in atelectasis, reduced lung compliance and increased risk of infections. Hyperoxemia causes vasoconstriction, reduction in coronary blood flow and cardiac output and may alter microvascular perfusion. Observational studies showed a close relationship between hyperoxemia and increased mortality in several subsets of critically ill patients. In absence of hypoxemia, the routine use of oxygen therapy in patients with myocardial infarction, stroke, traumatic brain injury, cardiac arrest and sepsis, showed no benefit but rather it seems to be harmful. In patients admitted to intensive care unit, a conservative oxygen therapy aimed to maintain arterial oxygenation within physiological range has been proved to be well tolerated and may improve outcome. Summary Liberal O2 use and unnecessary hyperoxia may be detrimental in critically ill patients. The current evidence supports the use of a conservative strategy in O2 therapy to avoid patient exposure to unnecessary hyperoxemia. Correspondence to Professor Massimo Girardis, Anesthesia and Intensive Care Unit, Department of Anaesthesia and Intensive Care, University Hospital of Modena, Via del Pozzo 71, 41124 Modena, Italy. E-mail: girardis.massimo@unimo.it Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Deep vein thrombosis and venous thromboembolism in trauma

Purpose of review Deep vein thrombosis (DVT) and pulmonary embolus are major causes of hospital-related morbidity and mortality, and are recognized as complications in patients with traumatic injury. Despite the significant morbidity and mortality associated with DVTs, prophylaxis and treatment are still not well understood and remain the subject of research and debate. Recent findings Elements of the patient's history and physical examination, along with thromboelastography, can be used to predict patients who are at greatest risk of DVT and venous thromboembolism (VTE). Novel assays and biomarkers hold promise for more accurate evaluation of coagulation status. Patients with traumatic injury are routinely treated with either mechanical or pharmacological treatments to prevent DVT, and a growing body of evidence suggests that DVT prophylaxis should be initiated as early as possible in a patient's hospital course. Summary In trauma patients with traumatic injury, early identification and targeted VTE prophylaxis in trauma patients may prevent this life-threatening complication. Correspondence to Keith J. Ruskin, MD, Department of Anesthesia and Critical Care, University of Chicago School of Medicine, 5841 S Maryland Avenue, MC4028, Chicago, IL 60637, USA. Tel: +1 773 834 2369; e-mail: ruskin@uchicago.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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A mitochondrial-targeted antioxidant improves myofilament Ca2+ sensitivity during prolonged low frequency force depression at low PO2

Abstract

Skeletal muscle can develop a prolonged low frequency-stimulation force depression (PLFFD) following fatigue-inducing contractions. Increased levels of reactive oxygen species (ROS) have been implicated in the development of PLFFD. During exercise the skeletal muscle intracellular PO2 decreases to relatively low levels, and can be further decreased when there is an impairment in O2 diffusion or availability, such as in certain chronic diseases and during exercise at high altitude. Since ROS generation by mitochondria is elevated at very low PO2 in cells, we tested the hypothesis that treatment of muscle fibres with a mitochondrial-targeted antioxidant at a very low, near hypoxic PO2, can attenuate PLFFD. We treated intact single fibres from mice with the mitochondrial-specific antioxidant SS31, and measured force development and intracellular [Ca2+] 30 min after fatigue at an extracellular PO2 of ∼5 Torr. After 30 min following the end of the fatiguing contractions, fibres treated with SS31 showed significantly less impairment in force development compared to untreated fibres at submaximal frequencies of stimulation. The intracellular peak [Ca2+] transients (peak [Ca2+]c) were equally decreased in both groups compared to pre-fatigue values. The combined force and peak [Ca2+]c data demonstrated that myofibrillar Ca2+ sensitivity was diminished in the untreated fibres 30 min after fatigue compared to pre-fatigue values, but Ca2+ sensitivity was unaltered in the SS31 treated fibres. These results demonstrate that at a very low PO2, treatment of skeletal muscle fibres with a mitochondrial antioxidant prevents a decrease in the myofibrillar Ca2+ sensitivity, which alleviates the fatigue induced PLFFD.

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Fla. hospital system implements telemedicine program

The NCH Healthcare System launched a "virtual visit" program, enabling patients to have a telemedicine visit any time of day or night for non-emergency issues

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The Health Behaviors of Ethnically Diverse Women at Increased Risk of Gestational Diabetes: The Behaviors Affecting Baby and You (B.A.B.Y.) Study

Abstract

Objectives Cigarette smoking, low physical activity, and sedentary behavior are modifiable risk factors for adverse pregnancy outcomes. However, only one study has evaluated predictors of these health risk behaviors among women at high risk for gestational diabetes mellitus (GDM). Therefore, our goal was to examine predictors of smoking, low physical activity, and sedentary behavior during pregnancy in an ethnically diverse high risk cohort. Methods This cross-sectional analysis utilized baseline data from the Behaviors Affecting Baby and You (B.A.B.Y.) study conducted among prenatal care patients at high risk for GDM (personal history of GDM or family history of diabetes and body mass index [BMI] ≥ 25 kg/m2). Smoking was assessed using questions from the Pregnancy Risk Assessment Monitoring System questionnaire and sedentary behavior (top vs. lower quartiles) and moderate/vigorous physical activity (bottom vs. upper quartile) via the Pregnancy Physical Activity Questionnaire. Results Participants (n = 400) enrolled at a mean of 12.4 (SD 3.6) weeks gestation. A total of 150 (44.1%) engaged in one, 37 (10.9%) in two, and 4 (1.2%) in three risk behaviors. Lower household income and not having children at home were each associated with a 2–6 fold increased odds of smoking, high sedentary behavior, and engaging in at least one risk behavior. Being married, Hispanic or of younger age was associated with a 2–6 fold reduced odds of smoking. BMI and personal history of GDM were not associated with risk behaviors. Conclusions for Practice Findings help characterize high risk groups and inform prenatal interventions targeting these health risk behaviors.



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Runs of homozygosity: windows into population history and trait architecture

Runs of homozygosity: windows into population history and trait architecture

Runs of homozygosity: windows into population history and trait architecture, Published online: 15 January 2018; doi:10.1038/nrg.2017.109

Runs of homozygosity (ROH) are genomic regions of homozygosity where the identical maternal and paternal haplotypes are descended from a shared common ancestor, and they are well known to occur as a result of inbreeding. This article discusses strategies for detecting ROH, their underappreciated prevalence across diverse outbred populations and implications for complex traits and human disease.

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Elevated sympathetic vasomotor outflow in response to increased inspiratory muscle activity during exercise is less in young women compared with men

Abstract

We compared changes in muscle sympathetic nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with increased inspiratory muscle resistance in men and women. We hypothesized that sympathetic vasomotor outflow during exercise with increased inspiratory resistance would be attenuated in young women compared with age-matched men. Eight women and seven men completed the study. The subjects performed two 10-min exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and voluntary hyperventilation with or without inspiratory resistive breathing for 5 min (breathing frequency: 50 breaths min−1 with a 50% duty cycle, inspiratory resistance: 30% of maximal inspiratory pressure)]. Mean arterial blood pressure (MAP) was acquired using finger photoplethysmography. MSNA was recorded via microneurography of the right median nerve at the cubital fossa. During leg cycle exercise with inspiratory resistive breathing, MSNA burst frequency (BF) was increased accompanied by an increase in MAP both in men and women. Women, compared with men, had less of an increase in MAP (Women: +22.8 ± 12.3 vs. Men: +32.2 ± 5.4 mmHg, P < 0.05) and MSNA BF (Women: +9.6 ± 2.9 vs. Men: +14.6 ± 6.4 bursts min−1, P < 0.05). These results suggest that the attenuated inspiratory muscle-induced metaboreflex during exercise in young women is partially attributed to a lesser sympathetic vasomotor outflow compared with men.

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Healthcare and Social Services Providers Who Serve Sexual and Gender Minorities in a U.S.-Mexico Border City

Abstract

Sexual and gender minorities, including lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals, experience barriers to healthcare as a result of stigma, discrimination, and poor cultural competence by healthcare and social services providers (HCSSP). The purpose of the study is to increase access to care and services for the LGBTQ community in a U.S.-Mexico border city by identifying LGBTQ-friendly HCSSP. A survey, developed based on concerns voiced in a predominantly Hispanic LGBTQ community, was administered to HCSSP and used to create a referral list, "The Purple Pages of El Paso" (PPoEP). Overall, 77 HCSSP have responded and 43 are included in the most recent version of the PPoEP. This model for developing a referral list of providers can be adapted in areas where LGBTQ communities face similar barriers to care and services. To be effective in reducing barriers to care, PPoEP must be updatable and sustainable.



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Runs of homozygosity: windows into population history and trait architecture



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Neurological prognosis of 6 cases after chest compression during general anesthesia

Abstract

Introduction

Data on the outcomes after chest compression (CC) of patients who are under general anesthesia (GA) are limited. The present study aimed to evaluate the neurological outcomes in patients who received CC while under GA.

Methods

The patients who received CC while under GA, between 2010 and 2015, in Kyoto Medical Center were surveyed retrospectively. The primary outcome was poor neurologic function or death, as defined by a cerebral performance category score (CPC) score of 3–5 on day 28.

Results

Six patients received CC while under GA, and four patients had poor neurological outcomes with a CPC score of 4 or 5 on day 28. All these patients required emergency operation because of their primary disease.

Conclusion

Even if the patients were monitored and immediately managed under GA, ineffective management of preoperative conditions tended to result in the poor neurological prognosis.



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Ether-à-go-go K+ channels: effective modulators of neuronal excitability

Abstract

Mammalian EAG (ether-à-go-go) channels are voltage-gated K+ channels. They are encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10), erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes are expressed in the brain where they effectively modulate neuronal excitability. This Topical Review describes the biophysical properties of each of the EAG channel subtypes, their function in neurons and the neurological diseases induced by EAG channel mutations. In contrast to the function of erg currents in the heart where they contribute to repolarization of the cardiac action potential, erg currents in neurons are involved in the maintenance of the resting potential, setting of action potential threshold and frequency accommodation. They can even support high frequency firing by preventing a depolarization-induced Na+ channel block. EAG channels are modulated differentially, e.g. eag channels by intracellular Ca2+, erg channels by extracellular K+ and GPCRs, and elk channels by changes in pH. So far, only currents mediated by erg channels have been recorded in neurons with the help of selective blockers. Neuronal eag and elk currents have not been isolated due to the lack of suitable channel blockers. However, findings in KO mice indicate a physiological role of eag1 currents in synaptic transmission and an involvement of elk2 currents in cognitive performance. Human eag1 and eag2 gain-of-function mutations underlie syndromes associated with epileptic seizures.

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Issue Information



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Corrigendum



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