Deriving and validating a risk prediction model for long COVID: a population-based, retrospective cohort study in Scotland.

Objectives: Using electronic health records, we derived and internally validated a prediction model to estimate risk factors for long COVID and predict individual risk of developing long COVID.

Design: Population-based, retrospective cohort study.

Setting: Scotland.

SID-2 is a conserved extracellular vesicle protein that is not associated with environmental RNAi in parasitic nematodes.

In the free-living nematode the transmembrane protein SID-2 imports double-stranded RNA into intestinal cells to trigger systemic RNA interference (RNAi), allowing organisms to sense and respond to environmental cues such as the presence of pathogens. This process, known as environmental RNAi, has not been observed in the most closely related parasites that are also within clade V. Previous sequence-based searches failed to identify orthologues in available clade V parasite genomes.

mRNA-delivery of IDO1 suppresses T cell-mediated autoimmunity.

Indoleamine-2,3-dioxygenase (IDO)1 degrades tryptophan, obtained through dietary intake, into immunoregulatory metabolites of the kynurenine pathway. Deficiency or blockade of IDO1 results in the enhancement of autoimmune severity in rodent models and increased susceptibility to developing autoimmunity in humans. Despite this, therapeutic modalities that leverage IDO1 for the treatment of autoimmunity remain limited.

Inflammation and bacteriophages affect DNA inversion states and functionality of the gut microbiota.

Reversible genomic DNA inversions control the expression of numerous gut bacterial molecules, but how this impacts disease remains uncertain. By analyzing metagenomic samples from inflammatory bowel disease (IBD) cohorts, we identified multiple invertible regions where a particular orientation correlated with disease. These include the promoter of polysaccharide A (PSA) of Bacteroides fragilis, which induces regulatory T cells (Tregs) and ameliorates experimental colitis.

An engineered immunomodulatory IgG1 Fc suppresses autoimmune inflammation through pathways shared with i.v. immunoglobulin.

Immunoglobulin G (IgG) antibodies in the form of high-dose intravenous immunoglobulin (IVIG) exert immunomodulatory activity and are used in this capacity to treat inflammatory and autoimmune diseases. Reductionist approaches have revealed that terminal sialylation of the single asparagine-linked (N-linked) glycan at position 297 of the IgG1 Fc bestows antiinflammatory activity, which can be recapitulated by introduction of an F241A point mutation in the IgG1 Fc (FcF241A). Here, we examined the antiinflammatory activity of CHO-K1 cell-produced FcF241A in vivo in models of autoimmune inflammation and found it to be independent of sialylation.

Risk of winter hospitalisation and death from acute respiratory infections in Scotland: national retrospective cohort study.

Objectives: We undertook a national analysis to characterise and identify risk factors for acute respiratory infections (ARIs) resulting in hospitalisation during the winter period in Scotland.

Design: A population-based retrospective cohort analysis.

Setting: Scotland.

External validation of the QCovid 2 and 3 risk prediction algorithms for risk of COVID-19 hospitalisation and mortality in adults: a national cohort study in Scotland.

Objective: The QCovid 2 and 3 algorithms are risk prediction tools developed during the second wave of the COVID-19 pandemic that can be used to predict the risk of COVID-19 hospitalisation and mortality, taking vaccination status into account. In this study, we assess their performance in Scotland.

Methods: We used the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 national data platform consisting of individual-level data for the population of Scotland (5.

Quality of ethnicity data within Scottish health records and implications of misclassification for ethnic inequalities in severe COVID-19: a national linked data study.

Background: We compared the quality of ethnicity coding within the Public Health Scotland Ethnicity Look-up (PHS-EL) dataset, and other National Health Service datasets, with the 2011 Scottish Census.

Methods: Measures of quality included the level of missingness and misclassification. We examined the impact of misclassification using Cox proportional hazards to compare the risk of severe coronavirus disease (COVID-19) (hospitalization & death) by ethnic group.

Understanding and reporting odds ratios as rate-ratio estimates in case-control studies.

Background: We noted that there remains some confusion in the health-science literature on reporting sample odds ratios as estimated rate ratios in case-control studies.

Methods: We recap historical literature that definitively answered the question of when sample odds ratios (ORs) from a case-control study are consistent estimators for population rate ratios. We use numerical examples to illustrate the magnitude of the disparity between sample ORs in a case-control study and population rate ratios when sufficient conditions for them to be equal are not satisfied.

Predictors of incomplete COVID-19 vaccine schedule among adults in Scotland: Two retrospective cohort analyses of the primary schedule and third dose.

Background: Vaccination continues to be the key public health measure for preventing severe COVID-19 outcomes. Certain groups may be at higher risk of incomplete vaccine schedule, which may leave them vulnerable to COVID-19 hospitalisation and death.

Aim: To identify the sociodemographic and clinical predictors for not receiving a scheduled COVID-19 vaccine after previously receiving one.

Laparoscopic transversus abdominis plane block reduces postoperative opioid requirements after laparoscopic cholecystectomy.

Background: Surgeons directly contribute to the over-prescription of opioids. Alternative postoperative pain management strategies are necessary to reduce opioid dispensation and combat the opioid epidemic. We set out to examine the effectiveness of a laparoscopic transversus abdominis plane block on reducing opioid requirements after laparoscopic cholecystectomy.

Immune chromatin reader SP140 regulates microbiota and risk for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is driven by host genetics and environmental factors, including commensal microorganisms. Speckled Protein 140 (SP140) is an immune-restricted chromatin "reader" that is associated with Crohn's disease (CD), multiple sclerosis (MS), and chronic lymphocytic leukemia (CLL). However, the disease-causing mechanisms of SP140 remain undefined.

Sleep exerts lasting effects on hematopoietic stem cell function and diversity.

A sleepless night may feel awful in its aftermath, but sleep's revitalizing powers are substantial, perpetuating the idea that convalescent sleep is a consequence-free physiological reset. Although recent studies have shown that catch-up sleep insufficiently neutralizes the negative effects of sleep debt, the mechanisms that control prolonged effects of sleep disruption are not understood. Here, we show that sleep interruption restructures the epigenome of hematopoietic stem and progenitor cells (HSPCs) and increases their proliferation, thus reducing hematopoietic clonal diversity through accelerated genetic drift.

Epigenetic reader SP140 loss of function drives Crohn's disease due to uncontrolled macrophage topoisomerases.

How mis-regulated chromatin directly impacts human immune disorders is poorly understood. Speckled Protein 140 (SP140) is an immune-restricted PHD and bromodomain-containing epigenetic "reader," and SP140 loss-of-function mutations associate with Crohn's disease (CD), multiple sclerosis (MS), and chronic lymphocytic leukemia (CLL). However, the relevance of these mutations and mechanisms underlying SP140-driven pathogenicity remains unexplored.

One genome, many cell states: epigenetic control of innate immunity.

A hallmark of the innate immune system is its ability to rapidly initiate short-lived or sustained transcriptional programs in a cell-specific and pathogen-specific manner that is dependent on dynamic chromatin states. Much of the epigenetic landscape is set during cellular differentiation; however, pathogens and other environmental cues also induce changes in chromatin that can either promote tolerance or 'train' innate immune cells for amplified secondary responses. We review chromatin processes that enable innate immune cell differentiation and functional transcriptional responses in naive or experienced cells, in concert with signal transduction and cellular metabolic shifts.

Human enteric viruses autonomously shape inflammatory bowel disease phenotype through divergent innate immunomodulation.

Altered enteric microorganisms in concert with host genetics shape inflammatory bowel disease (IBD) phenotypes. However, insight is limited to bacteria and fungi. We found that eukaryotic viruses and bacteriophages (collectively, the virome), enriched from non-IBD, noninflamed human colon resections, actively elicited atypical anti-inflammatory innate immune programs.

"You're a 'high-risk' customer": A qualitative study of women's experiences of receiving information from health professionals regarding health problems or complications in pregnancy.

Background: Experiencing complications in pregnancy is stressful for women and can impact on fetal and maternal outcomes. Supportive encounters with health professionals can reduce the worry women experience. Further research is needed to understand women's perspectives on communicating with their healthcare providers about their concerns.

Upping the ante on mammalian antiviral RNA interference.

SARS-CoV-2 has mutually illuminated our collective knowledge and knowledge gaps, particularly in antiviral defense and therapeutic strategies. A recent study in Science (Poirier et al., 2021) uncovers an ancient antiviral mechanism that mammals utilize to suppress viruses, including SARS-CoV-2 and Zika virus, that could have broad implications for therapeutic strategies.

The continued need for animals to advance brain research.

Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised.