The month of July: an early experience with pandemic influenza A (H1N1) in adults with cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Pandemic Influenza A (H1N1) 2009 is a novel viral infection that emerged in March 2009. This is the first report addressing the clinical course of patients with cystic fibrosis (CF) and H1N1 infection.</p> <p>Methods</p> <p>All patients with an influenza-like illness (ILI) attending our adult centre during July 2009 were identified. Baseline respiratory function, nutritional status, approach to management and short-term clinical course were recorded.</p> <p>Results</p> <p>Most patients experienced a mild course and were able to be managed with antiviral agents as an outpatient. Robust infection control policies were implemented to limit transmission of H1N1 infection within our CF centre. Patients with severe lung disease, poor baseline nutritional reserve and presenting with more than 48 hours of ILI experienced a more severe course. Prompt antiviral therapy within the first 48 hours of illness may have been important in improving outcomes.</p> <p>Conclusions</p> <p>This observational study demonstrates that most adults with CF with H1N1 infection had mild clinical courses and recovered rapidly.</p

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Determining physiological and psychological predictors of time to task failure on a virtual reality sørensen test in participants with and without recurrent low back pain: Exploratory study

© Megan E Applegate, Christopher R France, David W Russ, Samuel T Leitkam, James S Thomas. Originally published in JMIR Serious Games (http://games.jmir.org), 10.09.2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License. Background: Sørensen trunk extension endurance test performance predicts the development of low back pain and is a strong discriminator of those with and without low back pain. Performance may greatly depend on psychological factors, such as kinesiophobia, self-efficacy, and motivation. Virtual reality video games have been used in people with low back pain to encourage physical activity that would otherwise be avoided out of fear of pain or harm. Accordingly, we developed a virtual reality video game to assess the influence of immersive gaming on the Sørensen test performance. Objective: The objective of our study was to determine the physiological and psychological predictors of time to task failure (TTF) on a virtual reality Sørensen test in participants with and without a history of recurrent low back pain. Methods: We recruited 24 individuals with a history of recurrent low back pain and 24 sex-, age-, and body mass index-matched individuals without a history of low back pain. Participants completed a series of psychological measures, including the Center for Epidemiological Studies-Depression Scale, Pain Resilience Scale, Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, and a self-efficacy measure. The maximal isometric strength of trunk and hip extensors and TTF on a virtual reality Sørensen test were measured. Electromyography of the erector spinae, gluteus maximus, and biceps femoris was recorded during the strength and endurance trials. Results: A two-way analysis of variance revealed no significant difference in TTF between groups (P=.99), but there was a trend for longer TTF in females on the virtual reality Sørensen test (P=.06). Linear regression analyses were performed to determine predictors of TTF in each group. In healthy participants, the normalized median power frequency slope of erector spinae (beta=.450, P=.01), biceps femoris (beta=.400, P=.01), and trunk mass (beta=−.32, P=.02) predicted TTF. In participants with recurrent low back pain, trunk mass (beta=−.67, P\u3c.001), Tampa Scale for Kinesiophobia (beta=−.43, P=.01), and self-efficacy (beta=.35, P=.03) predicted TTF. Conclusions: Trunk mass appears to be a consistent predictor of performance. Kinesiophobia appears to negatively influence TTF for those with a history of recurrent low back pain, but does not influence healthy individuals. Self-efficacy is associated with better performance in individuals with a history of recurrent low back pain, whereas a less steep median power frequency slope of the trunk and hip extensors is associated with better performance in individuals without a history of low back pain

Ivacaftor in severe cystic fibrosis lung disease and a G551D mutation

Ivacaftor is gene-specific oral therapy for patients with cystic fibrosis who have a cystic fibrosis transmembrane conductance regulator mutation, G551D. To date, limited information is available about the benefit in patients with severe CF related lung disease, as such patients were excluded from the phase III trials. We report the early results on clinical outcomes, sweat electrolytes and C-reactive protein in three adults with a G551D mutation and advanced lung disease. A mean increase of 6% in FEV1 was observed at 2 weeks and a mean reduction in sweat chloride of -48.9 mmol/L. While improvements in spirometry, weight gain and reduction in sweat electrolytes are similar with those reported in the phase III trials, a formal comparison was not performed