Summary
Background
Research on the association between alcohol consumption and hepatic steatosis revealed conflictive results.
Aim
To investigate the associations between average daily alcohol ...consumption and binge drinking with hepatic steatosis, and to analyse combined effects of average daily alcohol consumption and binge drinking with body mass index (BMI) on hepatic steatosis.
Methods
Data from the population‐based Study of Health in Pomerania (SHIP) conducted in north‐east Germany comprising 4009 adults were used. Alcohol consumption was assessed by self‐report. Serum carbohydrate‐deficient transferrin (CDT) was analysed as biomarker for alcohol consumption. Hepatic steatosis was diagnosed by ultrasonography.
Results
Analyses revealed a dose–response relationship between average daily alcohol consumption and hepatic steatosis in men starting with a consumption of 20 g of alcohol per day adjusted odds ratio (OR) compared to abstainers 1.53; 95% confidence interval (CI) 1.15–2.05. Using CDT as alternative exposure variable confirmed these results. Binge drinking was associated with hepatic steatosis in men (adjusted OR of binge drinkers compared to nonbinge drinkers 1.36, 95% CI 1.06–1.74). The likelihood of having hepatic steatosis increased in men and women with increasing levels of average daily alcohol consumption in combination with overweight or obesity. Similarly, binge drinking in combination with overweight or obesity enhanced the likelihood of having hepatic steatosis.
Conclusions
Overweight or obesity substantially enhanced the effect of high levels of average daily alcohol consumption and binge drinking on hepatic steatosis in the present study population. This finding underlines the necessity to screen for multiple risk factors in the prevention of hepatic steatosis.
Summary
Background
The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin–microbiome interactions are still insufficiently characterized. This contrasts ...with the broader knowledge about factors influencing gut microbiota.
Objectives
We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two German populations.
Methods
This is a cross‐sectional study with 647 participants from two population‐based German cohorts, PopGen (n = 294) and KORA FF4 (n = 353), totalling 1794 skin samples. The V1–V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs).
Results
We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus.
Conclusions
We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria. Finally, we hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.
What is already known about this topic?
The skin microbiome is essential for maintaining skin health.
Skin bacteria abundances are associated with skin physiology patterns (microenvironments), host traits, such as age and sex, and domestic environmental factors, such as pets.
Evaluation and translation of these associations are difficult because most studies have a limited number of candidate factors.
What does this study add?
We expand the current knowledge of factors associated with skin microbiota by revealing new factors associated with skin bacteria, including diet.
We provide a comprehensive view of the factors associated with skin microbiota, which suggests that skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.
What is the translational message?
Future clinical research involving skin microbiota should acknowledge the associations found as potential confounders.
Host factors (age, body mass index and sex) and skin microenvironments should be particularly considered because they were associated with skin bacteria at the community level.
Linked Comment: A.M. Schneider and A.M. Nelson. Br J Dermatol 2021; 185:481–483.
Periodontitis has low-prevalence, highly severe disease manifestations with an early onset and rapid progression. The diagnosis is based on severe destruction of the alveolar bone in adolescents and ...young adults. Genetic susceptibility variants and smoking are well-established risk factors, but their interactions in modifying disease susceptibility have not been studied. We aimed to identify genetic risk variants of early-onset periodontitis that unmask their effects on tobacco smoke exposure. To this end, we analyzed 79,780,573 common variants in 741 northwest Europeans diagnosed to have >30% bone loss at >2 teeth before 35 y of age, using imputed genotypes of the OmniExpress BeadChip. Never versus ever smokers were compared in a logistic regression analysis via a case-only approach. To explore the effect of tobacco smoke on the expression of the G×S-associated genes, cultures of primary gingival fibroblasts (n = 9) were exposed to cigarette smoke extract, and transcripts were quantified by reverse transcription polymerase chain reaction. We identified 16 loci for which our analysis suggested an association with G×S increased disease risk (P < 5 × 10−5). Nine loci had previously been reported to be associated with spirometric measures of pulmonary function by an earlier G×S genome-wide association study. Genome-wide significant cis expression quantitative trait loci were reported for G×S-associated single-nucleotide polymorphisms at ST8SIA1 and SOST, indicating a causal role of these genes in tobacco-related etiopathology. Notably, SOST is a negative regulator of bone growth, and ST8SIA1 has a role in tissue remodeling. Cigarette smoke extract significantly altered the expression of 2 associated genes: SSH1 (P = 5 × 10−07), which is required for NF-κB activation and innate immune responses to bacterial invasion, and ST8SIA1 (P = 0.0048). We conclude that the genetic predisposition to early-onset periodontitis is in part triggered by smoking and that tobacco smoke directly affects the expression of genes involved in bone homeostasis, tissue repair, and immune response.
Objectives
Low copy numbers and deletion of complement C4 genes are potent risk factors for systemic lupus erythematosus (SLE). However, it is not known whether this genetic association affects the ...clinical outcome. We investigated C4 copy number variation and its relationship to clinical and serological features in a Northern European lupus cohort.
Methods
We genotyped the C4 gene locus using polymerase chain reaction (PCR)-based TaqMan assays in 169 patients with SLE classified according to the 1997 revised American College of Rheumatology (ACR) criteria and in 520 matched controls. In the patient group the mean C4 serum protein concentrations nephelometrically measured during a 12-month period prior to genetic analysis were compared to C4 gene copy numbers. Severity of disease was classified according to the intensity of the immunosuppressive regimens applied and compared to C4 gene copy numbers, too. In addition, we performed a TaqMan based analysis of three lupus-associated single-nucleotide polymorphisms (SNPs) located inside the major histocompatibility complex (MHC) to investigate the independence of complement C4 in association with SLE.
Results
Homozygous deficiency of the C4A isotype was identified as the strongest risk factor for SLE (odds ratio (OR) = 5.329; p = 7.7 × 10−3) in the case-control comparison. Moreover, two copies of total C4 were associated with SLE (OR = 3.699; p = 6.8 × 10−3). C4 serum levels were strongly related to C4 gene copy numbers in patients, the mean concentration ranging from 0.110 g/l (two copies) to 0.256 g/l (five to six copies; p = 4.9 × 10−6). Two copies of total C4 and homozygous deletion of C4A were associated with a disease course requiring cyclophosphamide therapy (OR = 4.044; p = 0.040 and OR = 5.798; p = 0.034, respectively). Homozygous deletion of C4A was associated with earlier onset of SLE (median 24 vs. 34 years; p = 0.019) but not significant after correction for multiple testing. SNP analysis revealed a significant association of HLA-DRB1*0301 with SLE (OR = 2.231; p = 1.33 × 10−5).
Conclusions
Our findings confirm the important role of complement C4 genes in the development of SLE. Beyond the impact on the susceptibility for lupus, C4 copy numbers may be related to earlier onset and a more severe course of the disease. The association of homozygous deletion of C4A and SLE is accompanied by the presence of HLA-DRB1*0301 without a proven pathophysiological mechanism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
How does xenon produce anaesthesia? Franks, N. P; Dickinson, R; de Sousa, S. L. M ...
Nature (London),
11/1998, Letnik:
396, Številka:
6709
Journal Article
Recenzirano
Odprti dostop
Since the discovery that the gas xenon can produce general anaesthesia without causing undesirable side effects, we have remained surprisingly ignorant of the molecular mechanisms underlying this ...clinical activity of an 'inert' gas. Although most general anaesthetics enhance the activity of inhibitory GABAA (γ-aminobutyric acid type-A) receptors,, we find that the effects of xenon on these receptors are negligible. Instead, xenon potently inhibits the excitatory NMDA (N-methyl-D-aspartate) receptor channels, which may account for many of xenon's attractive pharmacological properties.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood ...and risk of CRC remains unresolved. We quantified this association in a meta‐analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between‐study heterogeneity was assessed using I² statistics. Overall, the summary RR (95% CI) was 1.22 (1.14–1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I² = 21.2%). In a dose‐response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%–5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.
General anaesthetics are much more selective than is usually appreciated and may act by binding to only a small number of targets in the central nervous system. At surgical concentrations their ...principal effects are on ligand-gated (rather than voltage-gated) ion channels, with potentiation of postsynaptic inhibitory channel activity best fitting the pharmacological profile observed in general anaesthesia. Although the role of second messengers remains uncertain, it is now clear that anaesthetics act directly on proteins rather than on lipids.
Periodontitis is a common dysbiotic inflammatory disease with an estimated heritability of 50%. Due to the limited sample size of available periodontitis cohorts and the underlying trait ...heterogeneity, genome-wide association studies (GWAS) of chronic periodontitis (CP) have been unsuccessful in discovering susceptibility factors. A strategy that combines agnostic GWAS with a well-powered candidate-gene approach has the potential to discover novel loci. We combined RNA-seq data from gingival tissues with quantitative trait loci (QTLs) that were identified in a F2-cross of mice resistant and susceptible to infection with oral bacterial pathogens. Four genes, which were located within the mapped QTLs, showed differential expression. The chromosomal regions across the human orthologous were interrogated for putative periodontitis-associated variants using existing GWAS data from a German case-control sample of aggressive periodontitis (AgP; 651 cases, 4,001 controls), the most severe and early onset form of periodontitis. Two haplotype blocks, one upstream to the coding region of UGT2A1 (rs146712414, P = 9.1 × 10−5; odds ratio OR, 1.34; 95% confidence interval CI, 1.16–1.56) and one downstream of the genes PF4/PPBP/CXCL5 (rs1595009, P = 1.3 × 10−4; OR, 1.32; 95% CI, 1.15–1.52), were associated with AgP. The association of rs1595009 was validated in an independent cohort of CP of European Americans (1,961 cases and 1,864 controls; P = 0.03; OR, 1.45; 95% CI, 1.01–1.29). This association was further replicated in another sample of 399 German CP cases (disease onset <60 y of age) and 1,633 controls (P = 0.03; OR, 1.75; 95% CI, 1.06–2.90). The combined estimates of association from all samples were P = 2.9 × 10−5 (OR, 1.2; 95% CI, 1.1–1.3). This study shows the strength of combining QTL mapping and RNA-Seq data from a mouse model with association studies in human case-control samples to identify genetic risk variants of periodontitis.
Chronic inflammatory diseases (CID) are associated with a profound increase in cardiovascular (CV) risk resulting in reduced life expectancy. However, LDL-cholesterol is reported to be low in CID ...patients which is referred to as the “LDL paradoxon”. The aim of the present study was to investigate whether LDL-particles in CID exhibit an increased content of the highly atherogenic small-dense LDL subfraction (sdLDL).
In this prospective, single center, observational study we enrolled 141 patients with CID (RA n = 59, inflammatory bowel disease (IBD) n = 35, ankylosing spondylitis (SpA) n = 25, Psoriasis n = 22) in 2011 through 2013 to evaluate sdLDL levels before as well as 6 and 26 weeks after initiation of different anti-cytokine therapies (anti-TNFα, anti-IL-6R antibodies). sdLDL levels were compared to 141 healthy individuals in a case control design. Compared to healthy controls, all CID patients displayed a significantly higher sdLDL content within the LDL cholesterol fraction: RA 35.0 ± 9.2% (p < 0.001), SpA 42.5 ± 10.5% (p < 0.001), IBD 37.5 ± 7.1% (p < 0.001), Psoriasis 33.6 ± 4.6% (p < 0.01). Furthermore, the sdLDL/LDL ratio was significantly higher in male compared to female RA subjects (p < 0.05). Neither anti-TNFα nor anti-IL6R medication altered sdLDL levels despite a significant improvement of disease activity.
In several different chronic inflammatory disease entities, LDL-cholesterol is shifted toward a pro-atherogenic phenotype due to an increased sdLDL content which might in part explain the LDL paradoxon. Since premature CV disease is a major burden of affected patients, specifically targeting lipid metabolism should be considered routinely in clinical patient care.
Registration at German Clinical Trial Register (DRKS): DRKS00005285.
•SdLDL/LDL ratio is increased in various chronic inflammatory diseases.•Gender difference in sdLDL/LDL ratio in rheumatoid arthritis.•SdLDL is not influenced by anti-cytokine therapy.
Purpose
Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with ...non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany.
Methods
The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained.
Results
As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once.
Conclusion
NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity.
Trial registration
Registered at the German registry for clinical studies (DRKS00023742).
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