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In silico proteomic and phylogenetic analysis of the outer membrane protein repertoire of gastric Helicobacter species

Helicobacter (H.) pylori is an important risk factor for gastric malignancies worldwide. Its outer membrane proteome takes an important role in colonization of the human gastric mucosa. However, in zoonotic non-H. pylori helicobacters (NHPHs) also associated with human gastric disease, the composition of the outer membrane (OM) proteome and its relative contribution to disease remain largely unknown. By means of a comprehensive survey of the diversity and distribution of predicted outer membrane proteins (OMPs) identified in all known gastric Helicobacter species with fully annotated genome sequences, we found genus- and species-specific families known or thought to be implicated in virulence. Hop adhesins, part of the Helicobacter-specific family 13 (Hop, Hor and Horn) were restricted to the gastric species H. pylori, H. cetorum and H. acinonychis. Hof proteins (family 33) were putative adhesins with predicted Occ- or MOMP-family like 18-stranded beta-barrels. They were found to be widespread amongst all gastric Helicobacter species only sporadically detected in enterohepatic Helicobacter species. These latter are other members within the genus Helicobacter, although ecologically and genetically distinct. LpxR, a lipopolysaccharide remodeling factor, was also detected in all gastric Helicobacter species but lacking as well from the enterohepatic species H. cinaedi, H. equorum and H. hepaticus. In conclusion, our systemic survey of Helicobacter OMPs points to species and infection-site specific members that are interesting candidates for future virulence and colonization studies.Peer reviewe

Numeracy and COVID-19: Examining interrelationships between numeracy, health numeracy and behaviour

During the COVID-19 pandemic, people across the globe have been exposed to large amounts of statistical data. Previous studies have shown that individuals mathematical understanding of health-related information affects their attitudes and behaviours. Here, we investigate the relation between (i) basic numeracy, (ii) COVID-19 health numeracy, and (iii) COVID-19 health-related attitudes and behaviours. An online survey measuring these three variables was distributed in Canada, the United States (US) and the United Kingdom (UK) (n = 2032). In line with predictions, basic numeracy was positively related to COVID-19 health numeracy. However, predictions, neither basic numeracy nor COVID-19 health numeracy was related to COVID-19 healthrelated attitudes and behaviours (e.g. follow experts recommendations on social distancing, wearing masks etc.). Multi-group analysis was used to investigate mean differences and differences in the strength of the correlation across countries. Results indicate there were no between-country differences in the correlations between the main constructs but there were between-country differences in latent means. Overall, results suggest that while basic numeracy is related to one s understanding of data about COVID-19, better numeracy alone is not enough to influence a population s health-related attitudes about disease severity and to increase the likelihood of following public health advice

Numeracy and COVID-19: examining interrelationships between numeracy, health numeracy and behaviour

During the COVID-19 pandemic, people across the globe have been exposed to large amounts of statistical data. Previous studies have shown that individuals' mathematical understanding of health-related information affects their attitudes and behaviours. Here, we investigate the relation between (i) basic numeracy, (ii) COVID-19 health numeracy, and (iii) COVID-19 health-related attitudes and behaviours. An online survey measuring these three variables was distributed in Canada, the United States (US) and the United Kingdom (UK) (n = 2032). In line with predictions, basic numeracy was positively related to COVID-19 health numeracy. However, predictions, neither basic numeracy nor COVID-19 health numeracy was related to COVID-19 health-related attitudes and behaviours (e.g. follow experts’ recommendations on social distancing, wearing masks etc.). Multi-group analysis was used to investigate mean differences and differences in the strength of the correlation across countries. Results indicate there were no between-country differences in the correlations between the main constructs but there were between-country differences in latent means. Overall, results suggest that while basic numeracy is related to one's understanding of data about COVID-19, better numeracy alone is not enough to influence a population's health-related attitudes about disease severity and to increase the likelihood of following public health advice

Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries

BackgroundAs management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.MethodsIn a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.FindingsThe study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 10(9) cells/L, p=0.0098).ConclusionAnti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2

Timing of eating across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study

Objective To examine timing of eating across ten European countries. Design Cross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 h diet recalls collected during 1995-2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00-14.00 and 15.00-24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake. Setting Ten Western European countries. Subjects In total, 22 985 women and 13 035 men aged 35-74 years (n 36 020). Results A south-north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0 center dot 68 (France) to 1 center dot 39 (Norway) among women, and from 0 center dot 71 (Greece) to 1 center dot 35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all PPeer reviewe

Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy

Background Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recru

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging : a multi-cohort analysis

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions