Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey

ObjectiveTo investigate the association between birth weight of offspring and mothers'' insulin resistance in late adulthood.DesignCross sectional survey.SettingGeneral practitioner''s surgeries in 23 towns in Great Britain.Participants4286 women aged 60-79 years.ResultsBirth weight of offspring was inversely related to maternal insulin resistance in late adulthood. For each 1 kg higher birth weight of offspring, women had a 15% reduction in the odds of being in the fourth with highest insulin resistance, compared to other fourths (odds ratio 0.85; 95% confidence interval 0.71 to 1.00). This increased to 27% (0.73; 0.60 to 0.90) after adjusting data for potential confounders. A U shaped relation between birth weight of offspring and diabetes in older age was found; women with the lightest and heaviest offspring had the highest prevalence of diabetes.ConclusionsBirth weight of offspring is inversely related to the mother''s insulin resistance in late adulthood, despite the association of glucose intolerance during pregnancy with heavier offspring at birth. Common genetic factors contribute to the relation between birth weight and risk of cardiovascular disease and diabetes in adults.

What is already known on this topic

Small birth weight is related to increased risk of cardiovascular disease and diabetes in adulthood; the underlying mechanisms are unclearSmall birth weight of offspring is related to parental cardiovascular disease, suggesting that common genetic factors affect birth weight and the risk of disease in adulthoodGenetic factors associated with the metabolism of insulin are plausible in linking birth weight and cardiovascular disease (the fetal insulin hypothesis)

What this study adds

Birth weight of offspring is inversely related to maternal insulin resistance in older ageGenetic factors related to both insulin resistance and birth weight explain at least part of the association between birth weight and risk of cardiovascular disease and diabetes in adulthood     

Newborns of Preeclamptic Women Show Evidence of Sex-Specific Disparity in Fetal Growth

BackgroundEvidence suggests that in response to in utero insults, male versus female infants have greater disadvantages in pregnancy outcome. In addition, there is a growing body of evidence suggesting that there is a sex-specific fetal response to maternal disease during pregnancy. We considered that a sex-specific relationship may exist between preeclampsia and reduced fetal growth.ObjectiveWe investigated if the relationship between preeclampsia and fetal growth was modified by fetal sex.MethodsWe limited the study population to singleton pregnancies of black and white normotensive and preeeclamptic women enrolled in the Collaborative Perinatal Project (1959–1965). The patients were offspring of 516 preeclamptic and 8801 normotensive women. After adjustment for confounders, interaction terms between preeclamptic status and fetal sex were evaluated to determine if the influence of preeclampsia on fetal growth varied with fetal sex. Separate linear and logistic regression models were then fitted for males and females to report the estimate of the relationship between preeclampsia and fetal growth by fetal sex. The results were stratified by preterm status (<37 vs ≥37 completed weeks of gestation). The mean head and chest circumferences, birthweight, ponderal index, and frequency of small for gestational age were examined. A 2-sided P value of <0.05 was considered statistically significant.ResultsThe results were stratified by preterm status. Male preterm offspring of preeclamptic mothers had greater reductions in chest circumference, head circumference, and birthweight than preterm female offspring of preeclamptic women (P = 0.01, P = 0.02, and P = 0.05, respectively, for interaction). Female versus male preterm offspring exposed to preeclampsia were less susceptible to being small for gestational age (synergy index 0.38; 95% CI, 0.00–0.84). The influence of preeclampsia on the growth of term offspring was more modest, and the influence of sex was opposite that in preterm infants. Compared with term offspring of normotensive women, the reduction in mean ponderal index was greater for female versus term male offspring of preeclamptic women (P = 0.02, interaction).ConclusionFetal growth was more impaired among male versus female preterm infants born to preeclamptic women. Our study underlined the importance of incorporating sex differences in the study of biological mechanisms for immediate- and long-term consequences of suboptimal fetal growth.     

Industrial Fermentation Ethanol Production in South America

Abstract

Alcohol production from biomass has been of great interest in several countries since the mid 70s due to its potential use as a fuel. This idea, together with internal combustion engines (Otto engines), was born towards the end of the last century. Well into this century several countries used ethanol for mixture with gasoline up to a ratio of 25%. When World War II was over, alcohol lost markets, fossil fuels such as petroleum being economically more viable.     

Individualism,self‐control,and the Finnish temperance movement*

This article analyzes the role of self‐control, moral and ethical doctrines in the rise of individualist world‐view in Finland. In the Finnish case, the formation of the modern individual was closely linked with the temperance movement, the ideology of which is therefore used as an illustrative example. The guiding line in the article is not to treat self‐control as a theoretical concept used in analyzing individual behavior, but as a legitimation of an increasing use of a utilitarian framework. The author discusses the developments in Finnish individualist world‐view by analyzing the main turning points in Finnish notions about drinking. First he discusses the end of the 19th century and the beginning of the 20th century, the era of the strength of Finnish temperance movement. Secondly he analyzes the way in which conceptions about drinking changed when the temperance movement lost its appeal to the masses.     

Towards improving tsetse fly paratransgenesis: stable colonization of Glossina morsitans morsitans with genetically modified Sodalis

Background

Tsetse flies (Glossina sp.) refractory to trypanosome infection are currently being explored as potential tools to contribute in the control of human and animal African trypanosomiasis. One approach to disrupt trypanosome transmission by the tsetse fly vector involves the use of paratransgenesis, a technique that aims to reduce vector competence of disease vectors via genetic modification of their microbiota. An important prerequisite for developing paratransgenic tsetse flies is the stable repopulation of tsetse flies and their progeny with its genetically modified Sodalis symbiont without interfering with host fitness.

Results

In this study, we assessed by qPCR analysis the ability of a chromosomally GFP-tagged Sodalis (recSodalis) strain to efficiently colonize various tsetse tissues and its transmission to the next generation of offspring using different introduction approaches. When introduced in the adult stage of the fly via thoracic microinjection, recSodalis is maintained at high densities for at least 21 days. However, no vertical transmission to the offspring was observed. Oral administration of recSodalis did not lead to the colonization of either adult flies or their offspring. Finally, introduction of recSodalis via microinjection of third-instar larvae resulted in stably colonized adult tsetse flies. Moreover, the subsequent generations of offspring were also efficiently colonized with recSodalis. We show that proper colonization of the female reproductive tissues by recSodalis is an important determinant for vertical transmission.

Conclusions

Intralarval microinjection of recSodalis proves to be essential to achieve optimal colonization of flies with genetically modified Sodalis and its subsequent dissemination into the following generations of progeny. This study provides the proof-of-concept that Sodalis can be used to drive expression of exogenous transgenes in Glossina morsitans morsitans colonies representing a valuable contribution to the development of a paratransgenic tsetse fly based control strategy.

     

Alcohol consumption and mortality from all causes,coronary heart disease,and stroke: results from a prospective cohort study of Scottish men with 21 years of follow up

ObjectivesTo relate alcohol consumption to mortality.DesignProspective cohort study.Setting27 workplaces in the west of Scotland.Participants5766 men aged 35-64 when screened in 1970-3 who answered questions on their usual weekly alcohol consumption.ResultsRisk for all cause mortality was similar for non-drinkers and men drinking up to 14 units a week. Mortality risk then showed a graded association with alcohol consumption (relative rate compared with non-drinkers 1.34 (95% confidence interval 1.14 to 1.58) for 15-21 units a week, 1.49 (1.27 to 1.75) for 22-34 units, 1.74 (1.47 to 2.06) for 35 or more units). Adjustment for risk factors attenuated the increased relative risks, but they remained significantly above 1 for men drinking 22 or more units a week. There was no strong relation between alcohol consumption and mortality from coronary heart disease after adjustment. A strong positive relation was seen between alcohol consumption and risk of mortality from stroke, with men drinking 35 or more units having double the risk of non-drinkers, even after adjustment.ConclusionsThe overall association between alcohol consumption and mortality is unfavourable for men drinking over 22 units a week, and there is no clear evidence of any protective effect for men drinking less than this.

Key messages

• Results from a large cohort study of employed Scottish men showed different relations between alcohol consumption and mortality than previous studies
• There was no relation between mortality from coronary heart disease and alcohol consumption once adjustments were made for potential confounding factors
• There was a strong relation with mortality from stroke; drinkers of over 35 units a week had double the risk of mortality compared with non-drinkers
• Some but not all of this could be accounted for by alcohol related increases in blood pressure
• Overall, risk of all cause mortality was higher in men drinking 22 or more units a week

     

Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood,adolescence, and young adulthood: A national population-based cohort study

BackgroundThe prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited.Methods and findingsWe conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare.ConclusionsOffspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.

Chen Huang and co-workers study associations between maternal hypertensive disorders and cardiovascular disease in offspring.     

Ferroptosis is involved in alcohol-induced cell death in vivo and in vitro

ABSTRACT

A critical pathogenic factor in the development of lethal liver failure is cell death induced by the accumulation of lipid reactive oxygen species. In this study, we discovered and illuminated a new mechanism that led to alcoholic liver disease via ferroptosis, an iron-dependent regulated cell death. Study in vitro showed that both necroptosis inhibitor and ferroptosis inhibitors performed significantly protective effect on alcohol-induced cell death, while apoptosis inhibitor and autophagy inhibitor had no such effect. Our data also indicated that alcohol caused the accumulation of lipid peroxides and the mRNA expression of prostaglandin-endoperoxide synthase 2, reduced the protein expression of the specific light-chain subunit of the cystine/glutamate antiporter and glutathione peroxidase 4. Importantly, ferrostatin-1 significantly ameliorated liver injury that was induced by overdosed alcohol both in vitro and in vivo. These findings highlight that targeting ferroptosis serves as a hepatoprotective strategy for alcoholic liver disease treatment.     

Parental death in childhood and pathways to increased mortality across the life course in Stockholm,Sweden: A cohort study

BackgroundPrevious studies have shown that the experience of parental death during childhood is associated with increased mortality risk. However, few studies have examined potential pathways that may explain these findings. The aim of this study is to examine whether familial and behavioural factors during adolescence and socioeconomic disadvantages in early adulthood mediate the association between loss of a parent at age 0 to 12 and all-cause mortality by the age of 63.Methods and findingsA cohort study was conducted using data from the Stockholm Birth Cohort Multigenerational Study for 12,615 children born in 1953, with information covering 1953 to 2016. Familial and behavioural factors at age 13 to 19 included psychiatric and alcohol problems in the surviving parent, receipt of social assistance, and delinquent behaviour in the offspring. Socioeconomic disadvantage in early adulthood included educational attainment, occupational social class, and income at age 27 to 37. We used Cox proportional hazard regression models, combined with a multimediator analysis, to separate direct and indirect effects of parental death on all-cause mortality.Among the 12,582 offspring in the study (men 51%; women 49%), about 3% experienced the death of a parent in childhood. During follow-up from the age of 38 to 63, there were 935 deaths among offspring. Parental death was associated with an elevated risk of mortality after adjusting for demographic and household socioeconomic characteristics at birth (hazard ratio [HR]: 1.52 [95% confidence interval: 1.10 to 2.08, p-value = 0.010]). Delinquent behaviour in adolescence and income during early adulthood were the most influential mediators, and the indirect associations through these variables were HR 1.03 (1.00 to 1.06, 0.029) and HR 1.04 (1.01 to 1.07, 0.029), respectively. After accounting for these indirect paths, the direct path was attenuated to HR 1.35 (0.98 to 1.85, 0.066). The limitations of the study include that the associations may be partly due to genetic, social, and behavioural residual confounding, that statistical power was low in some of the subgroup analyses, and that there might be other relevant paths that were not investigated in the present study.ConclusionsOur findings from this cohort study suggest that childhood parental death is associated with increased mortality and that the association was mediated through a chain of disadvantages over the life course including delinquency in adolescence and lower income during early adulthood. Professionals working with bereaved children should take the higher mortality risk in bereaved offspring into account and consider its lifelong consequences. When planning and providing support to bereaved children, it may be particularly important to be aware of their increased susceptibility to delinquency and socioeconomic vulnerability that eventually lead to higher mortality.

In this cohort study, Ayako Hiyoshi and colleagues show associations between parental death in a child’s life and mortality risk later in that child’s life.     

Advanced paternal age increased metabolic risks in mice offspring

ObjectivesThe Developmental Origins of Health and Disease Science indicate that chronic diseases in adulthood are associated with prenatal and early-life traits. Our study aimed to explore the metabolic phenotype of offspring from advanced paternal age (APA) and the inherited alterations in sperm.Methods3-month-old (Young father, YF-F0) and 21-month-old male (Old Father, OF-F0) C57BL/6J mice were used to study paternal aging's effect on offspring. Blood glucose testing, lipid analysis, indirect calorimetry and RNA sequencing were performed.ResultsThe characterized metabolic changes in OF-F1 male mice offspring were glucose intolerance, hepatic lipid accumulation, increased adipocytes and impaired energy balance that lasted until they were elderly. Gene expression in both 8-week-old and 52-week-old offspring livers significantly altered in lipid metabolism- and thermogenesis-related pathways. PPAR signaling pathway was activated in both young and elderly offspring livers as indicated by significant upregulation of Cyp7a1, Cyp8b1, Cyp4a10, Cyp4a31, Fabp2, and Scd1. These targeted genes were also confirmed to be increased in offspring adipocytes. Furthermore, when examined the differentially expressed genes in F0 and F1 sperm, upregulated pathways including cholesterol metabolism, type II diabetes mellitus and endocrine resistance were strongly related to the APA offspring phenotype. Importantly, approximately 46.7% of enriched pathways in the sperm of APA offspring were consistent with those of APA fathers.ConclusionsThese findings added evidence of the connection between paternal gametes and alterations in progeny genome and raised the possibility that inherited alterations in sperm contribute to the intergenerational effects of paternal aging offspring's chronic metabolic risks.     

邻苯二甲酸二丁酯降低雄激素浓度导致尿道下裂发生机制研究

目的:验证邻苯二甲酸二丁酯(DBP)是通过降低血清雄激素水平导致自噬异常激活,同时探讨DBP致子代大鼠尿道下裂发生的具体机制。方法:将孕鼠随机分为DBP染毒组与对照组,并于妊娠期14-18天通过灌胃的方式,分别用DBP(750 mg/kg/天)饲养DBP染毒,用等量花生油饲养对照组。依照此方法成功构建了子代新生大鼠尿道下裂模型。采集子鼠生殖结节(GT)用福尔马林保存,用免疫组织化学(IHC)染色观察生殖结节组织中自噬水平,即LC3B及Beclin1表达水平;在子鼠麻醉后采集血液标本,用放射免疫分析方法观测子鼠血清睾酮水平。在原代大鼠尿路上皮细胞(PUECs)基础上,用Western印迹方法检测有无双氢睾酮(DHT)对PUECs中LC3I、LC3II及Beclin1表达水平影响。结果:DBP染毒组尿道下裂发生率为42.3%,对照组子代无尿道下裂。DBP染毒组子代GT组织中自噬表达较对照组明显增加。DBP染毒组(n=10)较对照组中血清睾酮水平有明显差异(n=10)(P<0.05)。体外研究表明DHT缺乏组Beclin1及LC3蛋白转化率水平较对照组升高。结论:孕期暴露于DBP可以诱发子代尿道下裂发生,这可能是由于DBP降低子鼠雄激素水平促使自噬发生导致的,然而该疾病的机制仍需要进一步研究。     

Alcohol Consumption among HIV-Infected Persons in a Large Urban HIV Clinic in Kampala Uganda: A Constellation of Harmful Behaviors

IntroductionAlcohol use by persons living with HIV/AIDS (PLWHA) negatively impacts the public health benefits of antiretroviral therapy (ART). Using a standardized alcohol assessment tool, we estimate the prevalence of alcohol use, identify associated factors, and test the association of alcohol misuse with sexual risk behaviors among PLWHA in Uganda.MethodsA cross-section of PLWHA in Kampala were interviewed regarding their sexual behavior and self-reported alcohol consumption in the previous 6 months. Alcohol use was assessed using the alcohol use disorders identification test (AUDIT). Gender-stratified log binomial regression analyses were used to identify independent factors associated with alcohol misuse and to test whether alcohol misuse was associated with risky sexual behaviors.ResultsOf the 725 subjects enrolled, 235 (33%) reported any alcohol use and 135 (18.6%) reported alcohol misuse, while 38 (5.2%) drank hazardous levels of alcohol. Alcohol misuse was more likely among subjects not yet on ART (adjusted prevalence ratio [aPR] was 1.65 p=0.043 for males and 1.79, p=0.019 for females) and those with self-reported poor adherence (aPR for males=1.56, p=0.052, and for females=1.93, p=0.0189). Belonging to Pentecostal or Muslim religious denominations was protective against alcohol misuse compared to belonging to Anglican and Catholic denominations in both sexes (aPR=0.11 for men, p<0.001, and aPR=0.32 for women, p=0.003). Alcohol misuse was independently associated with reporting risky sexual behaviors (aPR=1.67; 95% CI: 1.07–2.60, p=0.023) among males, but not significant among females (aPR=1.29; 95% CI: 0.95–1.74, p=0.098). Non-disclosure of HIV positive status to sexual partner was significantly associated with risky sex in both males (aPR=1.69; p=0.014) and females (aPR 2.45; p<0.001).ConclusionAlcohol use among PLWHA was high, and was associated with self-reported medication non-adherence, non-disclosure of HIV positive status to sexual partner(s), and risky sexual behaviors among male subjects. Interventions targeting alcohol use and the associated negative behaviors should be tested in this setting.     

Alcohol abstinence and mortality in a general population sample of adults in Germany: A cohort study

BackgroundEvidence suggests that people who abstain from alcohol have a higher mortality rate than those who drink low to moderate amounts. However, little is known about factors that might be causal for this finding. The objective was to analyze former alcohol or drug use disorders, risky drinking, tobacco smoking, and fair to poor health among persons who reported abstinence from alcohol drinking in the last 12 months before baseline in relation to total, cardiovascular, and cancer mortality 20 years later.Methods and findingsA sample of residents aged 18 to 64 years had been drawn at random among the general population in northern Germany and a standardized interview conducted in the years 1996 to 1997. The baseline assessment included 4,093 persons (70.2% of those who had been eligible). Vital status and death certificate data were retrieved in the years 2017 and 2018.We found that among the alcohol-abstinent study participants at baseline (447), there were 405 (90.60%) former alcohol consumers. Of the abstainers, 322 (72.04%) had met one or more criteria for former alcohol or drug dependence or abuse, alcohol risky drinking, or had tried to cut down or to stop drinking, were daily smokers, or self-rated their health as fair to poor. Among the abstainers with one or more of these risk factors, 114 (35.40%) had an alcohol use disorder or risky alcohol consumption in their history. Another 161 (50.00%) did not have such an alcohol-related risk but were daily smokers. The 322 alcohol-abstinent study participants with one or more of the risk factors had a shorter time to death than those with low to moderate alcohol consumption. The Cox proportional hazard ratio (HR) was 2.44 (95% confidence interval (CI), 1.68 to 3.56) for persons who had one or more criteria for an alcohol or drug use disorder fulfilled in their history and after adjustment for age and sex. The 125 alcohol-abstinent persons without these risk factors (27.96% of the abstainers) did not show a statistically significant difference from low to moderate alcohol consumers in total, cardiovascular, and cancer mortality. Those who had stayed alcohol abstinent throughout their life before (42; 9.40% of the alcohol-abstinent study participants at baseline) had an HR 1.64 (CI 0.72 to 3.77) compared to low to moderate alcohol consumers after adjustment for age, sex, and tobacco smoking. Main limitations of this study include its reliance on self-reported data at baseline and the fact that only tobacco smoking was analyzed as a risky behavior alongside alcohol consumption.ConclusionsThe majority of the alcohol abstainers at baseline were former alcohol consumers and had risk factors that increased the likelihood of early death. Former alcohol use disorders, risky alcohol drinking, ever having smoked tobacco daily, and fair to poor health were associated with early death among alcohol abstainers. Those without an obvious history of these risk factors had a life expectancy similar to that of low to moderate alcohol consumers. The findings speak against recommendations to drink alcohol for health reasons.

In this cohort study conducted over 20 years, Ulrich John and colleagues examine the relationship between alcohol abstinence and mortality in a German adult population.     

The Epidemiology of Alcohol Use and Alcohol Use Disorders among Young People in Northern Tanzania

IntroductionAlcohol use is a global public health problem, including as a risk factor for HIV infection, but few data are available on the epidemiology of alcohol use and alcohol use disorders (AUD) among young people in sub-Saharan Africa.MethodsWe conducted a cross-sectional survey among 4 groups of young people aged 15–24 years old (secondary school students, college/university students, employees of local industries and casual labourers) in two regions (Kilimanjaro and Mwanza) of northern Tanzania. Using a multistage stratified random sampling strategy, we collected information on demographics, alcohol use, and behavioural factors. We screened severity of alcohol use using the Alcohol Use Disorder Identification Test (AUDIT) and estimated the quantity and frequency of alcohol consumption using the timeline-follow-back-calendar (TLFB) method.ResultsA total of 1954 young people were surveyed. The prevalence of reported alcohol use was higher among males (47–70% ever users and 20–45% current users) than females (24–54% ever users and 12–47% current users). Prevalence of use was substantially higher in Kilimanjaro than Mwanza region. In both regions, participants reported high exposure to alcohol advertisements, and wide alcohol availability. College students reported the highest prevalence of current alcohol use (45% among males; 26% among females) and of heavy episodic drinking (71% among males; 27% among females) followed by casual labourers. Males were more likely to have AUD (an AUDIT score ≥8) than females, with 11–28% of males screening positive for AUD. Alcohol use was associated with male gender, being in a relationship, greater disposable income, non-Muslim religion and a higher number of sexual partners.ConclusionsAlcohol use is a significant problem among young people in northern Tanzania. There is an urgent need to develop, pilot and deliver interventions to help young people delay initiation and reduce levels of harmful drinking, particularly among college students and casual labourers.     

Sexual selection theory meets disease vector control: Testing harmonic convergence as a “good genes” signal in Aedes aegypti mosquitoes

BackgroundThe mosquito Aedes aegypti is a medically important, globally distributed vector of the viruses that cause dengue, yellow fever, chikungunya, and Zika. Although reproduction and mate choice are key components of vector population dynamics and control, our understanding of the mechanisms of sexual selection in mosquitoes remains poor. In “good genes” models of sexual selection, females use male cues as an indicator of both mate and offspring genetic quality. Recent studies in Ae. aegypti provide evidence that male wingbeats may signal aspects of offspring quality and performance during mate selection in a process known as harmonic convergence. However, the extent to which harmonic convergence may signal overall inherent quality of mates and their offspring remains unknown.Methodology/Principal findingsTo examine this, we measured the relationship between acoustic signaling and a broad panel of parent and offspring fitness traits in two generations of field-derived Ae. aegypti originating from dengue-endemic field sites in Thailand. Our data show that in this population of mosquitoes, harmonic convergence does not signal male fertility, female fecundity, or male flight performance traits, which despite displaying robust variability in both parents and their offspring were only weakly heritable.Conclusions/SignificanceTogether, our findings suggest that vector reproductive control programs should treat harmonic convergence as an indicator of some, but not all aspects of inherent quality, and that sexual selection likely affects Ae. aegypti in a trait-, population-, and environment-dependent manner.     

Anticonvulsant use and fracture: a case-control study

Objectives:We aimed to investigate fracture risk associated with anticonvulsant use in a population-based sample of men and women.Methods:Data from 1,458 participants (51.8% women) with a radiologically confirmed incident fracture (cases) were compared to 1,796 participants (46.5% women) without fracture (controls). Lifestyle factors, medication use and medical history were self-reported. Associations between anticonvulsant use and fracture were explored using binary logistic regression following adjustment for confounders.Results:In men, fracture cases and controls differed in age, smoking history, education, alcohol use, and gonadal hormone supplementation. In women, fracture cases and controls differed by previous fracture history, alcohol use, physical activity levels and use of anti-fracture agents. After adjustment for age, pooled anticonvulsant use was associated with a 3.4-fold higher risk of fracture in men and a 1.8-fold higher risk in women. Following further adjustments for confounders these patterns persisted; a 2.8-fold higher fracture risk in men and a 1.8-fold higher fracture risk in women.Conclusions:Anticonvulsant use was associated with increased fracture risk, independent of demographic, lifestyle, medical and medication related factors. While further studies exploring potential underlying mechanisms are warranted, regular monitoring of bone health in anticonvulsant users with risk factors may be useful.     

Smoking and other health factors in patients with head and neck cancer

BackgroundInformation on smoking and other health factors in head and neck cancer (HNC) patients throughout treatment, follow-up and survivorship is limited. This study explores patterns of multiple health factors during radiotherapy (RT) and naturalistic long-term follow-up in a convenience sample of patients with HNC.MethodsSmoking, alcohol use and depression were measured at baseline, 4 and 12 weeks post RT for a sub-group of 99 patients who participated in a randomised controlled trial and completed long-term follow-up. These factors plus healthy eating, physical activity and fatigue are also reported from the long-term follow-up component. Smoking was measured by self-report and biochemically, whilst all other variables were by self-report. Where variables were assessed at multiple time points logistic mixed effects regression models determined within-person changes over time.ResultsThere were important discrepancies between self-reported (4–7%) and biochemically verified (13–29%) rates of smoking. Rates of smoking and hazardous alcohol intake were significantly increased at follow-up compared to baseline. Depression rates were observed to be higher at end of RT compared to baseline. At long-term follow-up, fatigue was common and co-occurred with suboptimal healthy eating and hazardous alcohol use.ConclusionClinically important levels of smoking and alcohol consumption post RT in this sample suggest possible targets for intervention beyond treatment into long-term follow-up of patients.     

Health of children born to childhood cancer survivors: Participant characteristics and methods of the Multicenter Offspring Study

IntroductionResearch on childhood cancer survivor offspring has been limited to genetic disease occurrence, malformations or non-hereditary cancers. However, previous surveys indicated that survivors harbor fears about their (prospective) children's overall health. Our Multicenter Offspring Study examined extensive health aspects in children born to survivors and their siblings providing comprehensive information to be used in patient counseling to elucidate and alleviate existing concerns.MethodsUsing a specifically designed questionnaire, childhood cancer survivors and their siblings were surveyed on their offspring’s health (Supplementary material). Recruitment strategies depended on local infrastructures and standards of participating centers, including registry-based and direct approaches. Group differences were tested non-parametrically and effect sizes were calculated.ResultsIn total, 1126 survivors reported on 1780 offspring and 271 siblings reported on 441 offspring. Response rates ranged from 32.1% (Czech Republic) to 85.0% (Austria). Respondents were more likely to be female (p = .007), older at time of survey (p < .001), diagnosed 1980–1999 (p < .001) and treated with chemotherapy (p < .001). Compared to siblings, survivors were younger at time of survey (35 years vs. 39 years, p < .001) and at first birth (29 years vs. 30 years, p < .001). Survivor and sibling offspring only differed in terms of age at survey (6.3 years vs. 8.9 years, p < .001).ConclusionThe Multicenter Offspring Study investigates a wide variety of health aspects in offspring born to survivors and their siblings in five European countries. Our study cohorts form a solid basis for future analyses; yet, certain limitations, due to differences in approach among participating centers, must be considered when interpreting findings.     

Attending a social event and consuming alcohol is associated with changes in serum microRNA: a before and after study in healthy adults

Abstract

Purpose: Circulating microRNAs represent a reservoir for biomarker discovery. Our objective was to profile the change in human circulating microRNA associated with recreational use of alcohol at a social event.

Material and methods: Blood was collected from healthy volunteers (N?=?16) before and after recreational consumption of alcohol (ethanol). Biochemistry, hematology and ethanol measurements were performed. The change in the serum small RNA fraction was quantified by RNA sequencing.

Results: Blood ethanol was undetectable at study entry in all subjects [<10?mg/dL]. After consuming alcohol the median concentration was 89?mg/dL [IQR: 71–138. Min–max 20–175]. There were no changes in biochemistry and hematology parameters. Serum RNA sequencing identified 1371 small RNA species (1305 microRNAs). There were significant increases [adjusted p-value <0.05, fold increase 2 or more] in 265 microRNAs, around a fifth of the total [median fold increase 2.3 [IQR: 2.1–2.5; Max: 3.7]]. miR-185-5p decreased following alcohol exposure [adjusted p-value <0.05, fold decrease 2 or more].

Conclusions: The microRNA composition of human serum is dynamic and environmental factors may have a significant impact. Within its context of use the fold change ‘signal’ of a microRNA must be large enough to negate the risk of false results due to background ‘noise’.     

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring

AimsThe goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin–angiotensin–aldosterone-system (RAAS) of the adult offspring.Main methodsFemale Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.16% NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study.Key findingsTcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA, ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff.SignificanceHigh maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring.