Successful Cessation Programs that Reduce Comorbidity May Explain Surprisingly Low Smoking Rates Among Hospitalized COVID-19 Patients

A recent, non-peer-reviewed meta-analysis suggests that smoking may reduce the risk of hospitalization with COVID-19 because the prevalence of smoking among hospitalized COVID-19 is less than that of the general population. However, there are alternative explanations for this phenomena based on (1) the failure to report, or accurately record, smoking history during emergency hospital admissions and (2) a pre-disposition to avoid smoking among COVID-19 patients with tobacco-related comorbidities (a type of “reverse” causation). For example, urine testing of hospitalized patients in Australia for cotinine showed that smokers were under-counted by 37% because incoming patients failed to inform staff about their smoking behavior. Face-to-face interviews can introduce bias into the responses to attitudinal and behavioral questions not present in the self-completion interviews typically used to measure smoking prevalence in the general population. Subjects in face-to-face interviews may be unwilling to admit socially undesirable behavior and attitudes under direct questioning. Reverse causation may also contribute to the difference between smoking prevalence in the COVID-19 and general population. Patients hospitalized with COVID-19 may be simply less prone to use tobacco than the general population. A potentially robust “reverse causation” hypothesis for reduced prevalence of smokers in the COVID-19 population is the enrichment of patients in that population with serious comorbidities that motivates them to quit smoking. We judge that this “smoking cessation” mechanism may account for a significant fraction of the reduced prevalence of smokers in the COVID-19 population. Testing this hypothesis will require a focused research program

Successful Cessation Programs that Reduce Comorbidity May Explain Surprisingly Low Smoking Rates Among Hospitalized COVID-19 Patients

A recent, non-peer-reviewed meta-analysis suggests that smoking may reduce the risk of hospitalization with COVID-19 because the prevalence of smoking among hospitalized COVID-19 is less than that of the general population. However, there are alternative explanations for this phenomena based on (1) the failure to report, or accurately record, smoking history during emergency hospital admissions and (2) a pre-disposition to avoid smoking among COVID-19 patients with tobacco-related comorbidities (a type of “reverse” causation). For example, urine testing of hospitalized patients in Australia for cotinine showed that smokers were under-counted by 37% because incoming patients failed to inform staff about their smoking behavior. Face-to-face interviews can introduce bias into the responses to attitudinal and behavioral questions not present in the self-completion interviews typically used to measure smoking prevalence in the general population. Subjects in face-to-face interviews may be unwilling to admit socially undesirable behavior and attitudes under direct questioning. Reverse causation may also contribute to the difference between smoking prevalence in the COVID-19 and general population. Patients hospitalized with COVID-19 may be simply less prone to use tobacco than the general population. A potentially robust “reverse causation” hypothesis for reduced prevalence of smokers in the COVID-19 population is the enrichment of patients in that population with serious comorbidities that motivates them to quit smoking. We judge that this “smoking cessation” mechanism may account for a significant fraction of the reduced prevalence of smokers in the COVID-19 population. Testing this hypothesis will require a focused research program

Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease

BackgroundResearch suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson's disease (PD) risk.MaterialsMethodsIn 324 incident PD patients and 334 population controls from our rural California case-control study, we genotyped rs2652510, rs2550956 (for the DAT 5' clades), and the 3' variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele-pesticide interactions.ResultsPD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08-2.57] and 3' VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96-3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88-10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70-12.1). We obtained similar results for occupational pesticide measures.DiscussionUsing two independent pesticide measures, we a) replicated previously reported gene-environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure.ConclusionOur results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk

Veterans and Agent Orange: Update 11 (2018) (2018)

Contents ACRONYMS AND ABBREVIATIONS xvii SUMMARY 1 1 INTRODUCTION 17 Previous Veterans and Agent Orange Reports, 18 Charge to the Committee, 19 Information Gathering, 20 Organization of the Report, 21 2 BACKGROUND 25 The Current Population of Vietnam Veterans,25 Military Use of Herbicides in Vietnam, 27 Exposure of Different Groups of Vietnam Veterans, 30 Characterizing Exposure, 38 Determining Increased Risk in Vietnam Veterans, 4

α-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease

Currently, there are no reported genetic predictors of motor symptom progression in Parkinson’s disease (PD). In familial PD, disease severity is associated with higher α-synuclein (SNCA) expression levels, and in postmortem studies expression varies with SNCA genetic variants. Furthermore, SNCA is a well-known risk factor for PD occurrence. We recruited Parkinson’s patients from the communities of three central California counties to investigate the influence of SNCA genetic variants on motor symptom progression in idiopathic PD. We repeatedly assessed this cohort of patients over an average of 5.1 years for motor symptom changes employing the Unified Parkinson’s Disease Rating Scale (UPDRS). Of 363 population-based incident PD cases diagnosed less than 3 years from baseline assessment, 242 cases were successfully re-contacted and 233 were re-examined at least once. Of subjects lost to follow-up, 69% were due to death. Adjusting for covariates, risk of faster decline of motor function as measured by annual increase in motor UPDRS exam score was increased 4-fold in carriers of the REP1 263bp promoter variant (OR 4.03, 95%CI:1.57–10.4). Our data also suggest a contribution to increased risk by the G-allele for rs356165 (OR 1.66; 95%CI:0.96–2.88), and we observed a strong trend across categories when both genetic variants were considered (p for trend  = 0.002). Our population-based study has demonstrated that SNCA variants are strong predictors of faster motor decline in idiopathic PD. SNCA may be a promising target for therapies and may help identify patients who will benefit most from early interventions. This is the first study to link SNCA to motor symptom decline in a longitudinal progression study

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe

Vaccine responses in newborns.

Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants. Innate immunity also shows functional deficiency in antigen-presenting cells: the expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Nevertheless, the effectiveness of BCG, hepatitis B and oral polio vaccines, the only immunisations currently in use in the neonatal period, is proof of concept that vaccines can be successfully administered to the newborn via different routes of delivery to induce a range of protective mechanisms for three different diseases. In this review paper, we discuss the rationale for and challenges to neonatal immunisation, summarising progress made in the field, including lessons learnt from newborn vaccines in the pipeline. Furthermore, we explore important maternal, infant and environmental co-factors that may impede the success of current and future neonatal immunisation strategies. A variety of approaches have been proposed to overcome the inherent regulatory constraints of the newborn innate and adaptive immune system, including alternative routes of delivery, novel vaccine configurations, improved innate receptor agonists and optimised antigen-adjuvant combinations. Crucially, a dual strategy may be employed whereby immunisation at birth is used to prime the immune system in order to improve immunogenicity to subsequent homologous or heterologous boosters in later infancy. Similarly, potent non-specific immunomodulatory effects may be elicited when challenged with unrelated antigens, with the potential to reduce the overall risk of infection and allergic disease in early life

Evidence for Novel Hepaciviruses in Rodents

Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 roden