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The differences - and similarities - in self-immolation patterns around the globe. In response to: "Drivers and consequences of self-immolation in parts of Iran, Iraq and Uzbekistan: A systematic review of qualitative evidence" Cleary et al. 2021.
No full textMyelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis-A Review.
No full textABSTRACT
Our understanding of demyelinating optic neuritis has substantially evolved over the past 2 decades. With advancements in serological testing, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been recently discovered in a distinct subset of demyelinating neuroinflammatory disease. Although MOG-immunoglobulin G (IgG)-associated disorder (MOGAD) has previously been seen as a component of neuromyelitis optica spectrum disorder (NMOSD), evidence increasingly suggests that it should be distinguished as a separate condition. The distinction of MOGAD from aquaporin-4 IgG NMOSD is imperative as treatment plans need to be tailored to its unique disease course and prognosis. The purpose of this review is to explore the nature and outcomes of MOGAD optic neuritis to help guide acute and long-term immunosuppressive treatment decisions
BronchUK: protocol for an observational cohort study and biobank in bronchiectasis.
No full textBronchiectasis has been a largely overlooked disease area in respiratory medicine. This is reflected by a shortage of large-scale studies and lack of approved therapies, in turn leading to a variation of treatment across centres. BronchUK (Bronchiectasis Observational Cohort and Biobank UK) is a multicentre, prospective, observational cohort study working collaboratively with the European Multicentre Bronchiectasis Audit and Research Collaboration project. The inclusion criteria for patients entering the study are a clinical history consistent with bronchiectasis and computed tomography demonstrating bronchiectasis. Main exclusion criteria are 1) patients unable to provide informed consent, 2) bronchiectasis due to known cystic fibrosis or where bronchiectasis is not the main or co-dominant respiratory disease, 3) age <18 years, and 4) prior lung transplantation for bronchiectasis. The study is aligned to standard UK National Health Service (NHS) practice with an aim to recruit a minimum of 1500 patients from across at least nine secondary care centres. Patient data collected at baseline includes demographics, aetiology testing, comorbidities, lung function, radiology, treatments, microbiology and quality of life. Patients are followed up annually for a maximum of 5 years and, where able, blood and/or sputa samples are collected and stored in a central biobank. BronchUK aims to collect robust longitudinal data that can be used for analysis into current NHS practice and patient outcomes, and to become an integral resource to better inform future interventional studies in bronchiectasis
Development of a high sensitivity ELISA detecting IgG, A & M antibodies to the SARS-CoV-2 spike glycoprotein in serum and saliva.
No full textDetecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA assay, optimizing different antigens and amplification steps, in serum and saliva from non-hospitalised SARS-CoV-2-infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti-spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT-PCR confirmed, non-hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti-spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS-CoV-2 infection
Sinusoidal endothelial cells as orchestrators of the gut liver immune axis.
No full textThe paper by Gola and colleagues published recently in Nature uses an array of state-of-the-art techniques to demonstrate how commensal organisms shape protective immunity in the liver by organising immune cells into anatomical zones that are closely related to blood flow into the liver from the gut via the portal venous system. Sophisticated confocal imaging is used to map leukocyte distribution within the liver, targeted disruption of critical signalling pathways and RNA sequencing of specific cell types to determine molecular and cellular mechanisms and murine models of bacterial and malarial infection to demonstrate functional relevance
Lifestyle changes associated with COVID-19 quarantine among young Saudi women: A prospective study.
No full textBACKGROUND
Negative lifestyle behaviors are associated with an increased risk of adverse outcomes from coronavirus disease (COVID-19). This study aimed to assess lifestyle changes affecting weight, sleep, mental health, physical activity, and dietary habits prospectively from before COVID-19 to during lockdown.
METHODS
A total of 297 Saudi women, aged 19-30 years (mean age, 20.7 ± 1.4 years), were interviewed at two time points, before and during the quarantine. The data collected included anthropometrics, sociodemographic data, clinical history, food frequency questionnaire responses, Pittsburgh Sleep Quality Index scores, Global Physical Activity Questionnaire (GPAQ) responses, and Perceived Stress Scale measures. In addition, during quarantine, COVID-19 and nutrition-related information and Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 scores were collected. Multivariate multinomial logistic regression analysis was used to examine the indicators of weight gain and loss from before COVID-19 (baseline) until during lockdown.
RESULTS
Although approximately half of the participants did not report a weight change, 30% revealed weight loss and 18%, weight gain. The variables associated with increased weight gain were self-quarantine since COVID-19 started (OR: 5.17, 95% CI: 1.57-17.01, p = 0.007), age (OR: 1.53, 1.03-2.28, p = 0.04), and stress at baseline and during lockdown (OR: 1.15, 1.03-1.29, p = 0.01; OR: 1.10, 1.01-1.19, p = 0.03, respectively). The variables associated with a reduced risk of weight gain were the GPAQ score during lockdown (OR: 0.16, 0.04-0.66, p = 0.01), coffee consumption (OR: 0.36, 0.19-0.67, p = 0.01), and total sleep time (OR: 0.70, 0.51-0.97, p = 0.03).
CONCLUSION
While most young Saudi women experienced no weight change during the COVID-19 lockdown, one-third lost weight and a significant proportion gained weight. Factors associated with weight, such as stress, sleep hours, physical activity, and coffee consumption, highlight the need to carefully consider those at risk during future circumstances that may require lockdowns. These factors could also aid in implementing policies for future lockdowns and support those most at risk of gaining weight
Is spurious penicillin allergy a major public health concern only in high-income countries?
No full textWFS1 protein expression correlates with clinical progression of optic atrophy in patients with Wolfram syndrome.
No full textBACKGROUND
Wolfram syndrome (WFS) is a rare disorder characterised by childhood-onset diabetes mellitus and progressive optic atrophy. Most patients have variants in the gene. We undertook functional studies of variants and correlated these with WFS1 protein expression and phenotype.
METHODS
9 patients with a clinical diagnosis of WFS were studied with quantitative PCR for markers of endoplasmic reticulum (ER) stress and immunoblotting of fibroblast protein extracts for WFS1 protein expression. Luciferase reporter assay was used to assess ATF-6 dependent unfolded protein response (UPR) activation.
RESULTS
6 patients with compound heterozygous nonsense mutations in had no detectable WFS1 protein expression; 3 patients with missense variants had 4%, 45% and 48% WFS1 protein expression. One of these also had an mutation and was reclassified as autosomal dominant optic atrophy-plus syndrome. There were no correlations between ER stress marker mRNA and WFS1 protein expression. ERSE-luciferase reporter indicated activation of the ATF6 branch of UPR in two patients tested. Patients with partial WFS1 expression showed milder visual acuity impairment (asymptomatic or colour blind only), compared with those with absent expression (registered severe vision impaired) (p=0.04). These differences remained after adjusting for duration of optic atrophy.
CONCLUSIONS
Patients with WFS who have partial WFS1 protein expression present with milder visual impairment. This suggests a protective effect of partial WFS1 protein expression on the severity and perhaps progression of vision impairment and that therapies to increase residual WFS1 protein expression may be beneficial
