Aims/hypothesis
Increasing evidence suggests that environmental factors changing the normal colonisation pattern in the gut strongly influence the risk of developing autoimmune diabetes. The aim of ...this study was to investigate, both during infancy and adulthood, whether treatment with vancomycin, a glycopeptide antibiotic specifically directed against Gram-positive bacteria, could influence immune homeostasis and the development of diabetic symptoms in the NOD mouse model for diabetes.
Methods
Accordingly, one group of mice received vancomycin from birth until weaning (day 28), while another group received vancomycin from 8 weeks of age until onset of diabetes. Pyrosequencing of the gut microbiota and flow cytometry of intestinal immune cells was used to investigate the effect of vancomycin treatment.
Results
At the end of the study, the cumulative diabetes incidence was found to be significantly lower for the neonatally treated group compared with the untreated group, whereas the insulitis score and blood glucose levels were significantly lower for the mice treated as adults compared with the other groups. Mucosal inflammation was investigated by intracellular cytokine staining of the small intestinal lymphocytes, which displayed an increase in cluster of differentiation (CD)4
+
T cells producing pro-inflammatory cytokines in the neonatally treated mice. Furthermore, bacteriological examination of the gut microbiota composition by pyrosequencing revealed that vancomycin depleted many major genera of Gram-positive and Gram-negative microbes while, interestingly, one single species,
Akkermansia muciniphila
, became dominant.
Conclusions/interpretation
The early postnatal period is a critical time for microbial protection from type 1 diabetes and it is suggested that the mucolytic bacterium
A. muciniphila
plays a protective role in autoimmune diabetes development, particularly during infancy.
. Ahlehoff O, Gislason GH, Charlot M, Jørgensen CH, Lindhardsen J, Olesen JB, Abildstrøm SZ, Skov L, Torp‐Pedersen C, Hansen PR. (Copenhagen University Hospital Gentofte, Hellerup; Copenhagen ...University Hospital Bispebjerg, Copenhagen; National Institute of Public Health, University of Southern Denmark, Copenhagen; Copenhagen University Hospital Gentofte, Hellerup; University of Copenhagen, Copenhagen, Denmark) Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J Intern Med2011; 270: 147–157.
Objective. The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis‐related risk of adverse cardiovascular events and mortality.
Design, setting and subjects. We conducted a cohort study of the entire Danish population aged ≥18 years followed from 1997 to 2006 by individual‐level linkage of nationwide registers. Psoriasis was defined by prescription claims and classified as severe if patients received hospital‐based treatment. Time‐dependent Poisson regression models were applied to assess cardiovascular risk in patients with psoriasis and psoriatic arthritis.
Main outcome measures. All‐cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded.
Results. A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all‐cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate ratio increased with disease severity and decreased with age of onset. The overall RRs for the composite endpoint were 1.20 (95% confidence interval CI 1.14–1.25) and 1.58 (95% CI 1.36–1.82) for mild and severe psoriasis, respectively. The corresponding RRs for cardiovascular death were 1.14 (95% CI 1.06–1.22) and 1.57 (95% CI1.27–1.94). The risk was similar in patients with severe skin affection alone and those with psoriatic arthritis.
Conclusions. Psoriasis is associated with increased risk of adverse cardiovascular events and all‐cause mortality. Young age, severe skin affection and/or psoriatic arthritis carry the most risk. Patients with psoriasis may be candidates for early cardiovascular risk factor modification.
BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to ...update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.
We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two ...independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.
Gut microbiota have been implicated as a relevant factor in the development of type 2 diabetes mellitus (T2DM), and its diversity might be a cause of variation in animal models of T2DM. In this ...study, we aimed to characterise the gut microbiota of a T2DM mouse model with a long term vision of being able to target the gut microbiota to reduce the number of animals used in experiments. Male B6.V-Lepob/J mice were characterized according to a number of characteristics related to T2DM, inflammation and gut microbiota. All findings were thereafter correlated to one another in a linear regression model. The total gut microbiota profile correlated to glycated haemoglobin, and high proportions of Prevotellaceae and Lachnospiraceae correlated to impaired or improved glucose intolerance, respectively. In addition, Akkermansia muciniphila disappeared with age as glucose intolerance worsened. A high proportion of regulatory T cells correlated to the gut microbiota and improved glucose tolerance. Furthermore, high levels of IL-10, IL-12 and TNF-α correlated to impaired glucose tolerance, blood glucose or glycated haemoglobin. The findings indicate that gut microbiota may contribute to variation in various disease read-outs in the B6.V-Lepob/J model and considering them in both quality assurance and data evaluation for the B6.V-Lepob/J model may have a reducing impact on the inter-individual variation.
Post‐operative pain affects millions of patients worldwide and the post‐operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of ...this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non‐opioid analgesics: paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta‐analyses of analgesic efficacy and/or adverse effects of perioperative non‐opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post‐operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single‐dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non‐opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.
BACKGROUND Recent studies indicate that not only women's but also men's obesity has adverse effects on fecundity and since fecundity is a couple concept, we examined fecundity in relation to ...overweight and obesity of the couple. We also examined the association between weight changes and fecundity over time. METHODS Between 1996 and 2002, 64 167 pregnant women enrolled in the Danish National Birth Cohort were interviewed during and 18 months after pregnancy. Information on body mass index (BMI) and waiting time to pregnancy (TTP) was available for 47 835 couples. RESULTS Among men and women with a BMI of 18.5 kg/m2 or more, we found a dose-response relationship between increasing BMI group and subfecundity (a TTP of more than 12 months): Odds ratio (OR) = 1.32 (95% CI: 1.26–1.37) for women and OR = 1.19 (95% CI: 1.14–1.24) for men. Among 2374 women with an initial BMI of 18.5 kg/m2 or more, who participated more than once in the Danish National Birth Cohort, each kilogram increment in weight between the two pregnancies was associated with a 2.84 (95% CI: 1.33–4.35) days longer TTP. CONCLUSIONS Couples have a high risk of being subfecund if they are both obese.
BACKGROUND Concurrent alcohol exposure has been associated with reduced fecundity, but no studies have estimated the effect of prenatal alcohol exposure on male fecundity. The aim of this study was ...to investigate the association between maternal alcohol consumption during pregnancy, semen quality and levels of reproductive hormones in young, adult men. METHODS From a Danish pregnancy cohort established in 1984–1987, 347 sons were selected for a follow-up study conducted in 2005–2006. Semen and blood samples were analyzed for conventional semen characteristics and reproductive hormones, respectively, and results were related to prospectively self-reported information on maternal alcohol consumption during pregnancy. RESULTS The sperm concentration decreased with increasing prenatal alcohol exposure. The adjusted mean sperm concentration among sons of mothers drinking ≥4.5 drinks per week during pregnancy was 40 (95% CI: 25–60) millions/ml. This concentration was ∼32% lower compared with men exposed to <1.0 drink per week, who had a sperm concentration of 59 (95% CI: 44–77) millions/ml. The semen volume and the total sperm count were also associated with prenatal alcohol exposure; sons prenatally exposed to 1.0–1.5 drinks per week had the highest values. No associations were found for sperm motility, sperm morphology or any of the reproductive hormones, including testosterone. CONCLUSIONS These results indicate that prenatal exposure to alcohol may have a persisting adverse effect on Sertoli cells, and thereby sperm concentration. If these associations are causal they could explain some of the reported differences between populations and long-term changes in semen quality.
Summary
Background
Despite extensive research, the aetiology of atopic dermatitis remains largely unknown, but reduced intestinal microbiota diversity in neonates has been linked to subsequent atopic ...dermatitis. Consequently, postnatal antibiotics have been proposed as a risk factor, but a potential association between prenatal antibiotics and atopic dermatitis is not well studied. Overall, the current evidence suggests a positive association between exposure to prenatal antibiotics and atopic dermatitis.
Objective
To investigate the association between prenatal antibiotics and atopic dermatitis among 18‐month‐old children.
Methods
This study conducted within the Danish National Birth Cohort included 62 560 mother‐child pairs. Data on maternal prenatal antibiotics were collected in the 30th gestation week and 6 months post‐partum, and offspring atopic dermatitis 18 months post‐partum through telephone interviews. Antibiotic use was categorized by the timing of exposure as 1st‐2nd trimester (gestation week 0‐29), 3rd trimester (gestation week 30‐birth), all three trimesters or none. Data were analysed by logistic regression analyses adjusting for potential confounders.
Results
Exposure to antibiotics prenatally was associated with increased odds of atopic dermatitis among children born by atopic mothers but only when used in both 1st‐2nd and 3rd trimester (ORadj 1.45, 95% CI: 1.19‐1.76). The findings were consistent using different definitions of atopic dermatitis.
Conclusions and Clinical Relevance
Prenatal exposure to antibiotics throughout pregnancy was associated with an increased risk of atopic dermatitis but only within the first 18 months of life among children born by atopic mothers. The clinical usefulness of this finding must rest on corroboration in independent data sources.
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