Thyroid Function at Age Fifty After Prenatal Famine Exposure in the Dutch Famine Birth Cohort.

Background: Early-life exposures during gestation may permanently alter thyroid physiology and health in adulthood. We investigated whether exposure to the Dutch Famine (1944-1945) in late, mid, or early gestation influences thyroid function (i.e., incidence of thyroid disease, thyroid autoantibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) levels) in adulthood. We specifically assessed whether potential effects of famine differed for men and women. Methods: This study includes 910 men and women born as term singletons in the Wilhelmina Gasthuis in Amsterdam, the Netherlands, shortly before, during, or after the Dutch Famine. We evaluated medical histories for previous diagnosis or current treatment for thyroid dysfunction. At age 50 blood samples were drawn from 728 individuals for tests of thyroid function. We studied the prevalence of overt hypo- and hyperthyroidism and thyroid autoimmunity using medical histories, and measurements of TSH, FT4, anti-TPO and anti-TG, comparing participants exposed to famine at different pregnancy trimesters or born before or conceived after the famine. Additionally, we studied associations of TSH and FT4 levels with in utero famine exposure in a subsample of men and women free of thyroid disease that were exposed in late, mid, or early gestation. Results: There were no differences in thyroid dysfunction diagnosis or current treatment between participants at age 50 years who been exposed to famine during different periods of gestation and those born before or conceived after. There was no association between famine exposure and overt hypo- or hyperthyroidism or thyroid autoantibody positivity. Women who had been exposed to famine in mid gestation had slightly lower TSH levels than women who had not been exposed to famine prenatally (b=-0.06; 95%; CI=[-0.11,-0.02]; p<0.01). No differences in TSH levels were observed in men, and no differences in FT4 levels were observed in men or women. Conclusions: There are no differences in adult thyroid disease at age 50 years according to prenatal famine exposure. However, the lower TSH levels in women exposed to famine in the second trimester suggest that there may be sex-specific effects of famine exposure during a critical period of thyroid development on hypothalamic-pituitary-thyroid axis regulation in adulthood.

Public Risk-Taking and Rewards During the COVID-19 Pandemic - A Case Study of Remdesivir in the Context of Global Health Equity.

Public investment, through both research grants and university funding, plays a crucial role in the research and development (R&D) of novel health technologies, including diagnostics, therapies, and vaccines, to address the coronavirus disease 2019 (COVID-19) pandemic. Using the example of remdesivir, one of the most promising COVID-19 treatments, this paper traces back public contributions to different stages of the innovation process. Applying the Risk-Reward Nexus framework to the R&D of remdesivir, we analyse the role of the public in risk-taking and reward and address inequities in the biomedical innovation system. We discuss the collective, cumulative and uncertain characteristics of innovation, highlighting the lack of transparency in the biomedical R&D system, the need for public investment in the innovation process, and the "time-lag" between risk-taking and reward. Despite the significant public transnational contributions to the R&D of remdesivir, the rewards are extracted by few actors and the return to the public in the form of equitable access and affordable pricing is limited. Beyond the necessity to treat remdesivir as a global public good, we argue that biomedical innovation needs to be viewed in the broader concept of public value to prevent the same equity issues currently seen in the COVID-19 pandemic. This requires the state to take a market-shaping rather than market-fixing role, thereby steering innovation, ensuring that patents do not hinder global equitable access and affordable pricing and safeguarding a global medicines supply.

Quantifying patterns of alcohol consumption and its effects on health and wellbeing among BaYaka hunter-gatherers: A mixed-methods cross-sectional study.

Ethnographers frequently allude to alcoholism and related harms in Indigenous hunter-gatherer communities, but very few studies have quantified patterns of alcohol consumption or its health and social impacts. We present a case study of the Mbendjele BaYaka, a Congolese population undergoing socioeconomic transition. 83 adults answered questions about their frequency and quantity of alcohol consumption, underwent biometric measurements and reported whether they were currently experiencing a cough or diarrhoea; 56 participated in structured interviews about their experiences with alcohol. Based on WHO standards, we found 44.3% of the full sample, and 51.5% of drinkers (excluding abstainers), had a hazardous volume of alcohol consumption; and 35.1% of the full sample, and 40.9% of drinkers, engaged in heavy episodic drinking; consumption habits varied with sex and age. Total weekly consumption was a positive predictor of blood pressure and the likelihood of experiencing diarrhoea; associations with other biometric variables were not statistically significant. Interview responses indicated numerous other economic, mental and physical health harms of alcohol use, the prevalence of which demonstrate some variability between forest camps and permanent village settlements. These include high rates of drinking during pregnancy and breastfeeding (~40%); frequent alcohol-induced violence; and considerable exchange of foraged foods and engagement in exploitative labour activities to acquire alcohol or repay associated debts. Our findings demonstrate the prevalence of hazardous alcohol consumption among transitioning hunter-gatherers is higher than other segments of the Congolese population and indicate negative impacts on health and wellbeing, highlighting an urgent need for targeted public health interventions.

Out of balance: the role of evolutionary mismatches in the sex disparity in autoimmune disease.

Over the past century autoimmune disease incidence has increased rapidly in (post-) industrialised, affluent societies, suggesting that changes in ecology and lifestyle are driving this development. Epidemiological studies show that (i) 80% of autoimmune disease patients are female, (ii) autoimmune diseases co-occur more often in women, and (iii) the incidence of some autoimmune diseases is increasing faster in women than in men. The female preponderance in autoimmunity is most pronounced between puberty and menopause, suggesting that diverging sex hormone levels during the reproductive years are implicated in autoimmune disease development. Using an evolutionary perspective, we build on the hypotheses that female immunity is cyclical in menstruating species and that natural selection shaped the female immune system to optimise the implantation and gestation of a semi-allogeneic foetus. We propose that cyclical immunomodulation and female immune tolerance mechanisms are currently out of balance because of a mismatch between the conditions under which they evolved and (post-)industrialised, affluent lifestyles. We suggest that current changes in autoimmune disease prevalence may be caused by increases in lifetime exposure to cyclical immunomodulation and ovarian hormone exposure, reduced immune challenges, increased reproductive lifespan, changed reproductive patterns, and enhanced positive energy balance associated with (post-)industrialised, affluent lifestyles. We discuss proximate mechanisms by which oestrogen and progesterone influence tolerance induction and immunomodulation, and review the effect of the menstrual cycle, pregnancy, and contraceptive use on autoimmune disease incidence and symptoms.

The timing of adrenarche in Maya girls, Merida, Mexico.

BACKGROUND: Adrenarche involves maturation of the hypothalamic-pituitary-adrenal axis and increased production of dehydroepiandrosterone and its sulfate ester, dehydroepiandrosterone-sulfate (DHEA-S). It occurs at ages 6 to 8 in industrialized populations, marking the transition from childhood to juvenility and cognitive development at middle childhood. Studies in subsistence level populations indicate a later age (8-9) for adrenarche, but only two such studies currently exist for comparison. AIMS: To investigate adrenarcheal age among Maya girls and its association with body composition and dietary variables. We hypothesized adrenarche would occur earlier given the current dual burden of nutrition in Mexico. MATERIALS AND METHODS: 25 Maya girls aged 7 to 9 from Merida, Mexico using ELISAs to measure salivary DHEA-S, standard anthropometry for height, weight, and skinfolds, bioelectrical impedance for body composition variables, as well as a food frequency questionnaire for dietary information. RESULTS: Our hypothesis was rejected-adrenarche occurred close to 9 years. While no measures of body composition were significantly associated with adrenarcheal status, girls eating meat and dairy products more frequently had significantly higher DHEA-S levels. DISCUSSION: Like other populations living in ecologically challenging environments, adrenarche occurred relatively late among Maya girls. Adrenarche has been linked to measures of body composition, particularly, the adiposity or body mass index rebound, but no relevant anthropometric measures were associated, possibly because of the small sample. CONCLUSION: Further studies are required to illuminate how adrenarcheal variation relates to developmental plasticity, body composition, pubertal progression, and animal product consumption in other transitional populations.

Global WEIRDing: transitions in wild plant knowledge and treatment preferences in Congo hunter-gatherers.

Cultures around the world are converging as populations become more connected. On the one hand this increased connectedness can promote the recombination of existing cultural practices to generate new ones, but on the other it may lead to the replacement of traditional practices and global WEIRDing. Here we examine the process and causes of changes in cultural traits concerning wild plant knowledge in Mbendjele BaYaka hunter-gatherers from Congo. Our results show that the BaYaka who were born in town reported knowing and using fewer plants than the BaYaka who were born in forest camps. Plant uses lost in the town-born BaYaka related to medicine. Unlike the forest-born participants, the town-born BaYaka preferred Western medicine over traditional practices, suggesting that the observed decline of plant knowledge and use is the result of replacement of cultural practices with the new products of cumulative culture.