COVID-19 in multiple sclerosis patients and risk factors for severe infection

Multiple sclerosis (MS) patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, there is little data identifying clinical characteristics of MS associated with worse COVID-19 outcomes. Therefore, we conducted a multicenter prospective cohort study looking at the outcomes of 40 MS patients with confirmed COVID-19. Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor, and most severe was defined as requiring intensive care unit admission and/or death. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P = 0.0121, P = 0.0373). There was differing prevalence of progressive MS phenotype in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P = 0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P = 0.00435) of moderate course-patients and 2/6(33.3%, P = 0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P = 0.123). MS patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive phenotype, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses

Rise in carriage of group W meningococci in university students in United Kingdom

MenACWY conjugate vaccination was recently introduced in the UK for adolescents and 24 young adults to reduce disease due to Neisseria meningitidis group W (MenW). We 25 conducted a cross-sectional carriage study in first year university students. Despite 71% 26 MenACWY vaccine coverage, carriage of MenW, but not MenY, rose significantly in 27 students

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

Congenital Hypothyroidism Long‐Term Follow‐up Project: Navigating the Rough Waters of a Multi‐Center, Multi‐State Public Health Project

The Region 4 Midwest Genetics Collaborative, made up of seven regional states (Illinois, Indiana, Kentucky, Michigan, Minnesota, Ohio, and Wisconsin), brought together pediatric endocrinologists, state laboratory experts, public health follow‐up specialists, and parents of children with congenital hypothyroidism (CH) to identify the three‐year follow‐up management and education patterns of primary care clinicians and pediatric endocrinologists in the care of children diagnosed with CH by state newborn screening (NBS) programs. Among a number of challenges, each state had different NBS methods, data systems, public health laws, and institutional review board (IRB) requirements. Furthermore, the diagnosis of CH was complicated by the timing of the NBS sample, the gestational age, weight, and co‐morbidities at delivery. There were 409 children with CH identified through NBS in 2007 in the seven state region. The clinician of record and the parents of these children were invited to participate in a voluntary survey. Approximately 64 % of clinician surveys were collected with responses to questions relating to treatment, monitoring practices, educational resources, genetic counseling, and services provided to children with confirmed CH and their families. Nearly one‐quarter (24 %) of parents surveyed responded to questions relating to treatment, education, genetic counseling, resources, and services they received or would like to receive. De‐identified data from six of the seven states were compiled for analysis, with one state being unable to obtain IRB approval within the study timeline. The data from this collaborative effort will improve state follow‐up programs and aid in developing three‐year follow‐up guidelines for children diagnosed with CH. To aid in the facilitation of similar public health studies, this manuscript highlights the challenges faced, and focuses on the pathway to a successful multi‐state public health endeavor.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147153/1/jgc40464.pd

Discontinuation of thyroid hormone treatment among children in the United States with congenital hypothyroidism: findings from health insurance claims data

<p>Abstract</p> <p>Background</p> <p>Thyroid hormone treatment in children with congenital hypothyroidism can prevent intellectual disability. Guidelines recommend that children diagnosed with congenital hypothyroidism through newborn screening remain on treatment to at least 3 years of age, after which a trial off therapy can determine which children have transient hypothyroidism. The purpose of this study was to describe the rate at which children with congenital hypothyroidism in the United States discontinue thyroid hormone treatment in early childhood.</p> <p>Methods</p> <p>Retrospective analysis of the 2002-2006 MarketScan^®Commercial Claims and Encounters research databases and the 2001-2005 MarketScan Multi-State Medicaid databases. Children were classified as having congenital hypothyroidism based on billing codes and having filled a prescription for thyroid hormone treatment. Kaplan-Meier curve analysis was used to determine discontinuation rates.</p> <p>Results</p> <p>There were a total of 412 Medicaid-enrolled children and 292 privately-insured children with presumed congenital hypothyroidism included in this study. The overall birth prevalence of congenital hypothyroidism across both datasets was about 1 per 2,300. By 36 months, the percentage who had discontinued thyroid replacement treatment was 38% (95% Confidence Interval: 32%-44%). Medicaid-enrolled children had a more rapid decline in the first 24 months of treatment compared to those with private insurance (<it>P </it>= 0.02).</p> <p>Conclusions</p> <p>More than one-third of children treated for congenital hypothyroidism discontinued treatment within 36 months, which is inconsistent with current guidelines. It is not known how many of these children required continued treatment or experience adverse effects from discontinuation. These findings emphasize the critical need for follow-up systems to monitor the outcome of newborn screening.</p

Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson's disease on chromosome 7p15.3

Genome wide association studies (GWAS) for Parkinson's disease (PD) have previously revealed a significant association with a locus on chromosome 7p15.3, initially designated as the glycoprotein non-metastatic melanoma protein B (GPNMB) locus. In this study, the functional consequences of this association on expression were explored in depth by integrating different expression quantitative trait locus (eQTL) datasets (Braineac, CAGEseq, GTEx, and Phenotype-Genotype Integrator (PheGenI)). Top risk SNP rs199347 eQTLs demonstrated increased expressions of GPNMB, KLHL7, and NUPL2 with the major allele (AA) in brain, with most significant eQTLs in cortical regions, followed by putamen. In addition, decreased expression of the antisense RNA KLHL7-AS1 was observed in GTEx. Furthermore, rs199347 is an eQTL with long non-coding RNA (AC005082.12) in human tissues other than brain. Interestingly, transcript-specific eQTLs in immune-related tissues (spleen and lymphoblastoid cells) for NUPL2 and KLHL7-AS1 were observed, which suggests a complex functional role of this eQTL in specific tissues, cell types at specific time points. Significantly increased expression of GPNMB linked to rs199347 was consistent across all datasets, and taken in combination with the risk SNP being located within the GPNMB gene, these results suggest that increased expression of GPNMB is the causative link explaining the association of this locus with PD. However, other transcript eQTLs and subsequent functional roles cannot be excluded. This highlights the importance of further investigations to understand the functional interactions between the coding genes, antisense, and non-coding RNA species considering the tissue and cell-type specificity to understand the underlying biological mechanisms in PD

Modelling Blood Flow and Metabolism in the Preclinical Neonatal Brain during and Following Hypoxic-Ischaemia

Hypoxia-ischaemia (HI) is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS), and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue. Copyright

A Model of Brain Circulation and Metabolism: NIRS Signal Changes during Physiological Challenges

We construct a model of brain circulation and energy metabolism. The model is designed to explain experimental data and predict the response of the circulation and metabolism to a variety of stimuli, in particular, changes in arterial blood pressure, CO2 levels, O2 levels, and functional activation. Significant model outputs are predictions about blood flow, metabolic rate, and quantities measurable noninvasively using near-infrared spectroscopy (NIRS), including cerebral blood volume and oxygenation and the redox state of the CuA centre in cytochrome c oxidase. These quantities are now frequently measured in clinical settings; however the relationship between the measurements and the underlying physiological events is in general complex. We anticipate that the model will play an important role in helping to understand the NIRS signals, in particular, the cytochrome signal, which has been hard to interpret. A range of model simulations are presented, and model outputs are compared to published data obtained from both in vivo and in vitro settings. The comparisons are encouraging, showing that the model is able to reproduce observed behaviour in response to various stimuli