Annals of the New York Academy of Sciences最新文献

Studies of the human microbiome are progressing rapidly but have largely focused on populations living in high-income countries. With increasing evidence that the microbiome contributes to the pathogenesis of diseases that affect infants, children, and adults in low- and middle-income countries (LMICs), and with profound and rapid ongoing changes occurring in our lifestyles and biosphere, understanding the origins of and developing microbiome-directed therapeutics for treating a number of global health challenges requires the development of programs for studying human microbial ecology in LMICs. Here, we discuss how the establishment of long-term human microbial observatory programs in selected LMICs could provide one timely approach.

We examined whether math anxiety is related to a response inhibition deficit and, if so, whether it is a domain-specific inhibition deficit in numerical tasks or a general inhibition deficit. Behavioral performance and electroencephalogram activity were recorded while 28 highly math–anxious (HMA) and 28 low math–anxious (LMA) individuals performed both a numerical and a non-numerical Go/Nogo task. In the numerical task, single-digit numbers were presented, and participants were asked to press a button if the number was even. In the non-numerical task, letters were presented, and the button had to be pressed if the letter was a vowel. Nogo trials were answered less accurately and elicited larger Nogo-N2 and Nogo-P3 than Go trials in both tasks and both groups. Importantly, behavioral and brain response differences between tasks were only found in the HMA group. First, they were more error-prone in numerical Nogo than in non-numerical Nogo trials; and second, their Nogo-N2 and N2d (Nogo–Go difference) were smaller in the numerical task than in the non-numerical task. No differences were found in the LMA group. These results suggest that HMA individuals’ response inhibition is impaired specifically when dealing with numbers, which could contribute to their low achievement in math tasks.

Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea, resulting in anovulation and infertility, and is a low estrogen state that increases the risk of cardiovascular disease and impairs bone health. FHA is characterized by acquired suppression of physiological pulsatile gonadotropin-releasing hormone (GnRH) release by the hypothalamus in the absence of an identifiable structural cause, resulting in a functional hypogonadotropic hypogonadism. FHA results from either decreased energy intake and/or excessive exercise, leading to low energy availability and weight loss—often in combination with psychological stress on top of a background of genetic susceptibility. The hypothalamic neuropeptide kisspeptin is a key component of the GnRH pulse generator, tightly regulating pulsatile GnRH secretion and the downstream reproductive axis. Here, we review the physiological regulation of pulsatile GnRH secretion by hypothalamic kisspeptin neurons and how their activity is modulated by signals of energy status to affect reproductive function. We explore endocrine factors contributing to the suppression of GnRH pulsatility in the pathophysiology of FHA and how hypothalamic kisspeptin neurons likely represent a final common pathway through which these factors affect GnRH pulse generation. Finally, we discuss the therapeutic potential of kisspeptin as a novel treatment for women with FHA.

Increasing dietary calcium intakes of Ethiopian women of reproductive age (WRA) is a public health priority for reducing pre-eclampsia in pregnancy. Using linear programming, we determined whether locally available foods consumed by WRA in nine regions (urban and rural) and two administrative cities of Ethiopia could provide 1000 mg/day of dietary calcium, and we identified food-based recommendations (FBRs) to improve dietary calcium adequacy in each region. Results showed that diets providing 1000 mg/day of calcium were feasible in eight regions (40%) of the target populations examined. It would, however, require marked changes for most populations (90%), increasing the number of servings per week of several food groups to levels close to those of high consumers in each population. The selected calcium-specific FBRs integrate well into the 2022 Ethiopian Dietary Guidelines, requiring additional messages to consume green leafy vegetables, milk, root crops, or teff (Eragrostis tef) or to consume a higher number of servings of vegetables than currently recommended, depending on the population. In conclusion, these analyses show that a food-based approach can be used to achieve dietary calcium adequacy among WRA in 40% of the populations examined. For the other populations, food-based interventions alone may be inadequate and other interventions are likely needed.

The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host–microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities.

School feeding programs can support children's nutrition, health, and education in emergencies. This study assessed the feasibility, trade-offs, cost efficiency, and perceived benefits of school feeding modalities operating in urban Yemen. It draws on primary data from a qualitative evaluation with 21 school feeding implementers and 88 beneficiaries conducted in Feb–Mar 2023, and secondary data from a desk review of published and program literature on school feeding operations. Results showed that school feeding provided students with on average 18%, 40%, and 66% of daily energy, protein, and micronutrient requirements, respectively. Models including fortified snacks were 3–11 times more cost-efficient in terms of nutrient delivery. The most prominent strength of the models examined were the perceived benefits on child, family, and financial outcomes. Among the main weaknesses was the poor nutritional quality of the meal, which in turn emerged as a primary opportunity to improve school feeding through hybrid models providing a combination of fortified snacks and healthy meals. Other weaknesses such as poor water, sanitation, and hygiene infrastructure, and desired improvements such as the school kitchen and canteen, require considerable investments. Hybrid models are cost-efficient, acceptable, and feasible in Yemen and can serve the diet and nutrition needs of school-aged children.

Ameliorating the deleterious impact of systemic or tissue-level hypoxia or ischemia is key to preventing or treating many human diseases and pathologies. Usefully, environmental hypoxia is also a common challenge in many natural habitats; animals that are native to such hypoxic niches often exhibit strategies that enable them to thrive with limited O₂ availability. Studying how such species have evolved to tolerate systemic hypoxia offers a promising avenue of discovery for novel strategies to mitigate the deleterious effects of hypoxia in human diseases and pathologies. Of particular interest are naked mole-rats, which are among the most hypoxia-tolerant mammals. Naked mole-rats that tolerate severe hypoxia in a laboratory setting are also protected against clinically relevant mimics of heart attack and stroke. The mechanisms that support this tolerance are currently being elucidated but results to date suggest that metabolic rate suppression, reprogramming of metabolic pathways, and mechanisms that defend against deleterious perturbations of cellular signaling pathways all provide layers of protection. Herein, we synthesize and discuss what is known regarding adaptations to hypoxia in the naked mole-rat cardiopulmonary system and brain, as these systems comprise both the primary means of delivering O₂ to tissues and the most hypoxia-sensitive organs in mammals.

Previous studies have implicated epithelial–mesenchymal transition (EMT) in salamander limb regeneration. In this review, we describe putative roles for EMT during each stage of limb regeneration in axolotls and other salamanders. We hypothesize that EMT and EMT-like gene expression programs may regulate three main cellular processes during limb regeneration: (1) keratinocyte migration during wound closure; (2) transient invasion of the stump by epithelial cells undergoing EMT; and (3) use of EMT-like programs by non-epithelial blastemal progenitor cells to escape the confines of their niches. Finally, we propose nontraditional roles for EMT during limb regeneration that warrant further investigation, including alternative EMT regulators, stem cell activation, and fibrosis induced by aberrant EMT.

The neuropeptide kisspeptin and its cognate receptor have been extensively studied in reproductive physiology, with diverse and well-established functions, including as an upstream regulator of pubertal onset, reproductive hormone secretion, and sexual behavior. Besides classical reproduction, both kisspeptin and its receptor are extensively expressed in bone-resorbing osteoclasts and bone-forming osteoblasts, which putatively permits direct bone effects. Accordingly, this sets the scene for recent compelling findings derived from in vitro experiments through to in vivo and clinical studies revealing prominent regulatory interactions for kisspeptin signaling in bone metabolism, as well as certain oncological aspects of bone metabolism. Herein, we comprehensively examine the experimental evidence obtained to date supporting the interaction between kisspeptin and bone. A comprehensive understanding of this emerging facet of kisspeptin biology is fundamental to exploiting the future therapeutic potential of kisspeptin-based medicines as a novel strategy for treating bone-related disorders.

Bouillon is a widely consumed condiment in many West African countries, including Nigeria. Although Nigeria has mandatory fortification standards for multiple food vehicles, bouillon fortification could help address remaining gaps in micronutrient intake. Using household food consumption data, we used the nutrient density method to model the additional contribution of bouillon fortified with vitamin A (40–250 µg/g bouillon), folic acid (20–120 µg/g), vitamin B12 (0.2–2 µg/g), iron (0.6–5 mg/g), and zinc (0.6–5 mg/g) for meeting micronutrient requirements of women of reproductive age (WRA) and children aged 6–59 months. Accounting for existing fortification programs, our results showed that, except for iron, the prevalence of inadequacy was substantially higher among WRA and children living in poorer and rural households. Given the ubiquity of bouillon consumption, bouillon fortification has the potential to virtually eliminate vitamin A, folate, and vitamin B12 inadequacy, reduce the prevalence of zinc inadequacy by over 20 percentage points, and improve equity in the micronutrient adequacy of diets across socioeconomic strata and urban and rural residence. Our results also suggested that designing a bouillon fortification program would require careful planning to balance reductions in inadequacy with the risk of high intakes. This evidence provides important input into decisions around bouillon fortification in Nigeria.