Investigation of serum monomeric C-reactive protein and associated auto-antibodies in rheumatoid arthritis

The research described here considers molecular variations of the acute phase response protein, C reactive protein (CRP), and the presence of CRP and anti CRP autoantibodies in rheumatoid arthritis (RA) patient serum. Monomeric CRP (mCRP) was generated in vitro by 2M urea induced dissociation of native pentameric CRP (pCRP), over a 10 week period in the absence of calcium. The subunit size (23kDa) and identity were confirmed by size exclusion chromatography, and western blotting with mCRP specific antibodies. Once dissociated, it was not possible to induce re-association. Human RA (n=30) and healthy control samples (n=30) were tested for the presence of serum mCRP. RA patients had higher mean mCRP levels than non RA (0.092mg/l, 0.069mg/l), however no samples were elevated above the calculated normal threshold for mCRP (≥ mean + 2SD, 30 control samples). There was no correlation between serum levels of mCRP and pCRP, suggesting physiological dissociation of pCRP may not be solely responsible for the presence of mCRP. Auto-antibody detection by competitive ELISA confirmed the presence of antimCRP and pCRP auto-antibodies of the classes IgG, IgA and IgM in both RA and control groups. Anti-mCRP and pCRP auto-antibodies in RA samples were significantly higher than controls in the female cohort in all but anti-mCRP IgM, with only anti-m/pCRP IgA significantly higher for the males (P<0.01). Both mCRP and pCRP were found to interact directly with anti-IgG at high concentrations of both. A greater proportion of RA samples contained all three auto-antibody classes, anti pCRP - RA 66.6%, control 50%; antimCRP- RA 50%, control 13%. Auto-antibody profile varied between RA and control groups, elevated anti-mCRP IgA antibodies being a key predictor of RA risk P<0.0001, more so when combined with advancing age although no correlation between CRP and auto-antibody concentrations was found. This may prove useful diagnostically

Utilization of Wellness Practices For Burnout and Stress During COVID-19 Among an Interdisciplinary Cohort of Emergency Healthcare Workers

Introduction: The Coronavirus Disease (COVID-19) introduced additional stress to the baseline occupational stressors of emergency care workers. The objectives of this study were to evaluate perceived stress and burnout and the utilization and perceived benefit of wellness practices among emergency healthcare workers (EHCWs), including: emergency physicians, advanced practice providers (APPs), nurses, and departmental administrative staff during the COVID-19 pandemic. Methods: A cross-sectional 28-item electronic survey of EHCWs at three hospitals in a major United States city was used to measure participants’ utilization and perceived benefit of wellness practices, burnout (2-item measure), overall stress (perceived stress scale), and stress related to COVID-19. Results: The sample consisted of 260 respondents (response rate 44.6%, 583 eligible). Over one-half (56.5%) reported burnout from their job and a majority (58.5%) reported moderate to high stress. Wellness activities including regular exercise and engaging in hobbies were associated with lower reports of burnout. Higher stress levels were reported by participants who had tested positive for COVID-19. Nurses reported the highest rates of burnout overall (80.6%). Females reported higher rates of burnout than males across the cohort (64.5 vs 41.9%, p = 0.001), and female APPs reported significantly higher burnout than did male APPs (69.2 vs 38.5%, p = 0.048). Participants reported donated personal protective equipment (PPE) and meals on shift were extremely helpful. Conclusion: The COVID-19 pandemic was a significant contributor to the stress of EHCWs. Regular engagement in wellness activities was associated with lower rates of burnout. The benefit of engagement in wellness practices, both individual practices and organizational interventions are paramount to mitigate stress and burnout in EHCWs

Rapid development of interprofessional in situ simulation-based training in response to the COVID-19 outbreak in a tertiary-level hospital in Ireland:Initial response and lessons for future disaster preparation.

INTRODUCTION: The first case of COVID-19 in Ireland was diagnosed on 29 February 2020. Within the same week, our Department of Anaesthesia and Critical Care at University Hospital Galway began to tackle the educational challenge by developing an  in situ interprofessional simulation programme to prepare staff for the impending outbreak. PRINCIPLES AND APPROACHES USED FOR SIMULATION-BASED TRAINING: We describe principles applied to identify core educational and system engineering objectives to prepare healthcare workers (HCWs) for infection control, personal and psychological safety, technical and crisis resource management skills. We discuss application of educational theories, rationale for simulation modes and debriefing techniques. DEVELOPMENT OF THE SIMULATION PROGRAMME: 3 anaesthesia (general, obstetric, paediatric) and 1 critical care silo were created. 13 simulated scenarios were developed for teaching as well as for testing workflows specific to the outbreak. To support HCWs and ensure safety, management guidelines, cognitive aids and checklists were developed using simulation. The cumulative number of HCWs trained in simulation was 750 over a 4-week period. CHALLENGES AND FUTURE DIRECTIONS: Due to the protracted nature of the pandemic, simulation educators should address questions related to sustainability, infection control while delivering simulation, establishment of hybrid programmes and support for psychological preparedness

The Diverse Bacterial Community in Intertidal, Anaerobic Sediments at Sapelo Island, Georgia

The phylogenetic diversity and composition of the bacterial community in anaerobic sediments from Sapelo Island, GA, USA were examined using 16S rRNA gene libraries. The diversity of this community was comparable to that of soil, and 1,186 clones formed 817 OTUs at 99% sequence similarity. Chao1 estimators for the total richness were also high, at 3,290 OTUs at 99% sequence similarity. The program RDPquery was developed to assign clones to taxonomic groups based upon comparisons to the RDP database. While most clones could be assigned to describe phyla, fewer than 30% of the clones could be assigned to a described order. Similarly, nearly 25% of the clones were only distantly related (<90% sequence similarity) to other environmental clones, illustrating the unique composition of this community. One quarter of the clones were related to one or more undescribed orders within the γ-Proteobacteria. Other abundant groups included the δ-Proteobacteria, Bacteroidetes, and Cyanobacteria. While these phyla were abundant in other estuarine sediments, the specific members at Sapelo Island appeared to be different from those previously described in other locations, suggesting that great diversity exists between as well as within estuarine intertidal sediments. In spite of the large differences in pore water chemistry with season and depth, differences in the bacterial community were modest over the temporal and spatial scales examined and generally restricted to only certain taxa

Study protocol for WHO and UNICEF estimates of global, regional, and national preterm birth rates for 2010 to 2019.

BACKGROUND: Preterm birth is a leading cause of death among children under five years. Previous estimates indicated global preterm birth rate of 10.6% (14.8 million neonates) in 2014. We aim to update preterm birth estimates at global, regional, and national levels for the period 2010 to 2019. METHODS: Preterm birth is defined as a live birth occurring before 37 completed gestational weeks, or <259 days since a woman's last menstrual period. National administrative data sources for WHO Member States with facility birth rates of ≥80% in the most recent year for which data is available will be searched. Administrative data identified for these countries will be considered if ≥80% of UN estimated live births include gestational age information to define preterm birth. For countries without eligible administrative data, a systematic review of studies will be conducted. Research studies will be eligible if the reported outcome is derived from an observational or intervention study conducted at national or sub-national level in population- or facility-based settings. Risk of bias assessments will focus on gestational age measurement method and coverage, and inclusion of special subgroups in published estimates. Covariates for inclusion will be selected a priori based on a conceptual framework of plausible associations with preterm birth, data availability, and quality of covariate data across many countries and years. Global, regional and national preterm birth rates will be estimated using a Bayesian multilevel-mixed regression model. DISCUSSION: Accurate measurement of preterm birth is challenging in many countries given incomplete or unavailable data from national administrative sources, compounded by limited gestational age assessment during pregnancy to define preterm birth. Up-to-date modelled estimates will be an important resource to measure the global burden of preterm birth and to inform policies and programs especially in settings with a high burden of neonatal mortality. TRIAL REGISTRATION: PROSPERO registration: CRD42021237861

A rapid systematic review and evidence synthesis of effective coverage measures and cascades for childbirth, newborn and child health in low- and middle-income countries.

BACKGROUND: Effective coverage measures aim to estimate the proportion of a population in need of a service that received a positive health outcome. In 2020, the Effective Coverage Think Tank Group recommended using a 'coverage cascade' for maternal, newborn, child and adolescent health and nutrition (MNCAHN), which organises components of effective coverage in a stepwise fashion, with each step accounting for different aspects of quality of care (QoC), applied at the population level. The cascade outlines six steps that increase the likelihood that the population in need experience the intended health benefit: 1) the population in need (target population) who contact a health service; 2) that has the inputs available to deliver the service; 3) who receive the health service; 4) according to quality standards; 5) and adhere to prescribed medication(s) or health workers instructions; and 6) experience the expected health outcome. We examined how effective coverage of life-saving interventions from childbirth to children aged nine has been defined and assessed which steps of the cascade are captured by existing measures. METHODS: We undertook a rapid systematic review. Seven scientific literature databases were searched covering the period from May 1, 2017 to July, 8 2021. Reference lists from reviews published in 2018 and 2019 were examined to identify studies published prior to May 2017. Eligible studies reported population-level contact coverage measures adjusted for at least one dimension of QoC. RESULTS: Based on these two search approaches this review includes literature published from 2010 to 2021. From 16 662 records reviewed, 33 studies were included, reporting 64 effective coverage measures. The most frequently examined measures were for childbirth and immediate newborn care (n = 24). No studies examined measures among children aged five to nine years. Definitions of effective coverage varied across studies. Key sources of variability included (i) whether a single effective coverage measure was reported for a package of interventions or separate measures were calculated for each intervention; (ii) the number and type of coverage cascade steps applied to adjust for QoC; and (iii) the individual items included in the effective coverage definition and the methods used to generate a composite quality measure. CONCLUSION: In the MNCAHN literature there is substantial heterogeneity in both definitions and construction of effective coverage, limiting the comparability of measures over time and place. Current measurement approaches are not closely aligned with the proposed cascade. For widespread adoption, there is a need for greater standardisation of indicator definitions and transparency in reporting, so governments can use these measures to improve investments in MNACHN and implement life-saving health policies and programs

The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing

International audienceCurrent sampling of genomic sequence data from eukaryotes is relatively poor, biased, and inadequate to address important questions about their biology, evolution, and ecology; this Community Page describes a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans

Genome-wide Association Analysis Identifies 14 New Risk Loci for Schizophrenia

Schizophrenia is a heritable disorder with substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases, 6,243 controls) followed by meta-analysis with prior schizophrenia GWAS (8,832 cases, 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls, and 581 trios). In total, 22 regions met genome-wide significance (14 novel and one previously implicated in bipolar disorder). The results strongly implicate calcium signaling in the etiology of schizophrenia, and include genome-wide significant results for CACNA1C and CACNB2 whose protein products interact. We estimate that ∼8,300 independent and predominantly common SNPs contribute to risk for schizophrenia and that these collectively account for most of its heritability. Common genetic variation plays an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this devastating disorder

A Rare Functional Noncoding Variant at the GWAS-Implicated MIR137/MIR2682 Locus Might Confer Risk to Schizophrenia and Bipolar Disorder

Schizophrenia (SZ) genome-wide association studies (GWASs) have identified common risk variants in >100 susceptibility loci; however, the contribution of rare variants at these loci remains largely unexplored. One of the strongly associated loci spans MIR137 (miR137) and MIR2682 (miR2682), two microRNA genes important for neuronal function. We sequenced ∼6.9 kb MIR137/MIR2682 and upstream regulatory sequences in 2,610 SZ cases and 2,611 controls of European ancestry. We identified 133 rare variants with minor allele frequency (MAF) <0.5%. The rare variant burden in promoters and enhancers, but not insulators, was associated with SZ (p = 0.021 for MAF < 0.5%, p = 0.003 for MAF < 0.1%). A rare enhancer SNP, 1:g.98515539A>T, presented exclusively in 11 SZ cases (nominal p = 4.8 × 10−4). We further identified its risk allele T in 2 of 2,434 additional SZ cases, 11 of 4,339 bipolar (BP) cases, and 3 of 3,572 SZ/BP study controls and 1,688 population controls; yielding combined p values of 0.0007, 0.0013, and 0.0001 for SZ, BP, and SZ/BP, respectively. The risk allele T of 1:g.98515539A>T reduced enhancer activity of its flanking sequence by >50% in human neuroblastoma cells, predicting lower expression of MIR137/MIR2682. Both empirical and computational analyses showed weaker transcription factor (YY1) binding by the risk allele. Chromatin conformation capture (3C) assay further indicated that 1:g.98515539A>T influenced MIR137/MIR2682, but not the nearby DPYD or LOC729987. Our results suggest that rare noncoding risk variants are associated with SZ and BP at MIR137/MIR2682 locus, with risk alleles decreasing MIR137/MIR2682 expression