Complex regional pain syndrome 1 – the Swiss cohort study

BACKGROUND: Little is known about the course of Complex Regional Pain Syndrome 1 and potential factors influencing the course of this disorder over time. The goal of this study is a) to set up a database with patients suffering from suspected CRPS 1 in an initial stadium, b) to perform investigations on epidemiology, diagnosis, prognosis, and socioeconomics within the database and c) to develop a prognostic risk assessment tool for patients with CRPS 1 taking into account symptomatology and specific therapies. METHODS/DESIGN: Prospective cohort study. Patients suffering from a painful swelling of the hand or foot which appeared within 8 weeks after a trauma or a surgery and which cannot be explained by conditions that would otherwise account for the degree of pain and dysfunction will be included. In accordance with the recommendations of International Classification of Functioning, Disability and Health (ICF model), standardised and validated questionnaires will be used. Patients will be monitored over a period of 2 years at 6 scheduled visits (0 and 6 weeks, 3, 6, 12, and 24 months). Each visit involves a physical examination, registration of therapeutic interventions, and completion of the various study questionnaires. Outcomes involve changes in health status, quality of life and costs/utility. DISCUSSION: This paper describes the rationale and design of patients with CRPS 1. Ideally, potential risk factors may be identified at an early stage in order to initiate an early and adequate treatment in patients with increased risk for delayed recovery

Segregation of myoblast fusion and muscle-specific gene expression by distinct ligand-dependent inactivation of GSK-3β

Myogenic differentiation involves myoblast fusion and induction of muscle-specific gene expression, which are both stimulated by pharmacological (LiCl), genetic, or IGF-I-mediated GSK-3β inactivation. To assess whether stimulation of myogenic differentiation is common to ligand-mediated GSK-3β inactivation, myoblast fusion and muscle-specific gene expression were investigated in response to Wnt-3a. Moreover, crosstalk between IGF-I/GSK-3β/NFATc3 and Wnt/GSK-3β/β-catenin signaling was assessed. While both Wnt-3a and LiCl promoted myoblast fusion, muscle-specific gene expression was increased by LiCl, but not by Wnt-3a or β-catenin over-expression. Furthermore, LiCl and IGF-I, but not Wnt-3a, increased NFATc3 transcriptional activity. In contrast, β-catenin-dependent transcriptional activity was increased by Wnt-3a and LiCl, but not IGF-I. These results for the first time reveal a segregated regulation of myoblast fusion and muscle-specific gene expression following stimulation of myogenic differentiation in response to distinct ligand-specific signaling routes of GSK-3β inactivation

Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains

Ruiz JC, D'Afonseca V, Silva A, et al. Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains. PLoS ONE. 2011;6(4): e18551.Background: Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity. Methodology and Findings: We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer. Conclusions: These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers CP001809 and CP001829

Shared and Disorder-Specific Event-Related Brain Oscillatory Markers of Attentional Dysfunction in ADHD and Bipolar Disorder.

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) often present with overlapping symptoms and cognitive impairments, such as increased fluctuations in attentional performance measured by increased reaction-time variability (RTV). We previously provided initial evidence of shared and distinct event-related potential (ERP) impairments in ADHD and BD in a direct electrophysiological comparison, but no study to date has compared neural mechanisms underlying attentional impairments with finer-grained brain oscillatory markers. Here, we aimed to compare the neural underpinnings of impaired attentional processes in ADHD and BD, by examining event-related brain oscillations during a reaction-time task under slow-unrewarded baseline and fast-incentive conditions. We measured cognitive performance, ERPs and brain-oscillatory modulations of power and phase variability in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. Compared to controls, both ADHD and BD groups showed increased RTV in the baseline condition and increased RTV, theta phase variability and lower contingent negative variation in the fast-incentive condition. Unlike controls, neither clinical group showed an improvement from the slow-unrewarded baseline to the fast-incentive condition in attentional P3 amplitude or alpha power suppression. Most impairments did not differ between the disorders, as only an adjustment in beta suppression between conditions (lower in the ADHD group) distinguished between the clinical groups. These findings suggest shared impairments in women with ADHD and BD in cognitive and neural variability, preparatory activity and inability to adjust attention allocation and activation. These overlapping impairments may represent shared neurobiological mechanisms of attentional dysfunction in ADHD and BD, and potentially underlie common symptoms in both disorders.We thank all who made this research possible: The National Adult ADHD Clinic at the South London and Maudsley Hospital, Dr Helen Costello, Prof Sophia Frangou, Prof Anne Farmer, Jessica Deadman, Hannah Collyer, Sarah-Jane Gregori, and all participants who contributed their time to the study. Dr Giorgia Michelini was supported by a 1+3 PhD studentship awarded by the MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London (G9817803). This project was supported by an Economic and Social Research Council studentship to Dr Viryanaga Kitsune (ES/100971X/1). Dr Giorgia Michelini and Prof Philip Asherson are supported by generous grants from the National Institute for Health Research Biomedical Research Centre for Mental Health at King’s College London, Institute of Psychiatry, Psychology and Neuroscience and South London and Maudsley National Health Service (NHS) Foundation Trust. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

Behavioural and educational outcomes following extremely preterm birth : current controversies and future directions

As a consequence of improved survival rates for extremely preterm (EP; <28 weeks of gestation) births, there is a growing body of evidence detailing the impact of extreme prematurity on outcomes throughout childhood and adolescence. Historically, attention first focused on documenting rates of sensory impairments and severe neurodevelopmental disabilities. However, over recent years, there has been growing interest in the impact of EP birth on long term mental health and educational outcomes. In this chapter we review literature relating to the impact of EP birth on attention, social and emotional problems, psychiatric disorders and educational outcomes. We also outline current controversies in the field. In particular, we present emergent research exploring developmental trajectories to determine whether the sequelae associated with EP birth represent a developmental delay or persistent deficit, and we consider what approaches to intervention may be most fruitful in improving behavioural and educational outcomes in this population

The burden of injury in Central, Eastern, and Western European sub-region: a systematic analysis from the Global Burden of Disease 2019 Study.

Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries

The effect of SARS-CoV-2 infection and vaccination on Th17 and regulatory T cells in a pregnancy cohort in NYC

Disturbances in T-cells, specifically the Th17/Treg balance, have been implicated in adverse pregnancy outcomes. We investigated these two T-cell populations following pre-pregnancy and pregnancy SARS-CoV-2 infection and COVID-19 vaccination in 351 participants from a pregnancy cohort in New York City (Generation C; 2020-2022). SARS-CoV-2 infection status was determined via laboratory or medical diagnosis and COVID-19 vaccination status via survey and electronic medical records data. Peripheral blood mononuclear cells (PBMCs) were collected at routine prenatal visits throughout gestation (median 108 days; IQR 67-191 days) with repeated measures for 104 participants (29.6%). T-cell populations CD4+/CD3+, Th17/CD4+, Treg/CD4+ and the Th17/Treg ratio were quantified using flow cytometry. Results showed that inter-individual differences are a main influencing factor in Th17 and Treg variance, however total variance explained remained small (R2 = 15-39%). Overall, Th17 and Treg populations were not significantly affected by SARS-CoV-2 infection during pregnancy in adjusted linear mixed models (p&gt;0.05), however comparison of repeated measures among SARS-CoV-2 infected participants and non-infected controls suggests a relative increase of the Th17/Treg ratio following infection. In addition, the Th17/Treg ratio was significantly higher after SARS-CoV-2 infection prior to pregnancy (10-138 weeks) compared to controls (β=0.48, p=0.003). COVID-19 vaccination was not associated with Th17 and Treg cells. Our findings suggest an impact of SARS-CoV-2 infection on the Th17/Treg ratio, likely depending on severity of infection, yet the observed trends and their potential consequences for pregnancy outcomes require further investigation. Our study contributes to growing evidence that COVID-19 vaccination during pregnancy does not lead to an exacerbated immune response.</p