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Background: Rotavirus is a leading cause of severe pediatric gastroenteritis; 2 highly effective vaccines are used in the United States (US). We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort., Methods: Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) is a birth cohort of 245 mother-child pairs enrolled in 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as reverse-transcription polymerase chain reaction detection of rotavirus vaccine virus in stools collected 4-28 days after dose 1. Seroconversion was defined as a 3-fold rise in immunoglobulin A between the 6-week and 6-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression., Results: Prevaccination immunoglobulin G (IgG) (odds ratio [OR], 0.84 [95% confidence interval {CI}, .75-.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("nonsecretors") with nonsecretor mothers, versus all other combinations (OR, 0.37 [95% CI, .16-.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose 1. Prevaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product., Conclusions: In this US cohort, prevaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

A major challenge in integrative biology is understanding the mechanisms by which organisms regulate trade-offs among various functions competing for limiting resources. Key among these competing processes is the maintenance of health and the production of offspring. Optimizing both, given limited resources, can prove challenging. The physiological and behavioral changes that occur during reproduction have been shown to greatly influence an organism's immune system, which can have consequences for susceptibility to disease. Likewise, investing in costly immunological defenses can impair reproductive function. However, the precise nature of these physiological and behavioral interactions appears to be greatly dependent upon the environmental context in which they occur. Here we take a comparative look at interactions between the reproductive and immune systems, including current immunological approaches, and discuss how similar studies can reveal vastly disparate results. Specifically, we highlight results from the ornate tree lizard (Urosuarus ornatus) and the Siberian hamster (Phodopus sungorus) model systems, which provide an example of current research in the field. Collectively, these results emphasize the importance of resource availability and an individual's energy stores for the existence of life-history trade-offs and the efficiency of physiological processes in general. Akin to Dobzhansky's famous line, like other aspects of biology, nothing in ecoimmunology seems to make sense except in the context of an organism's environment.

The discovery by Schwabl that maternal steroid hormones are transferred to the egg yolk and have effects on the phenotype of offspring revealed a new pathway for non-genetic maternal effects. The initial model relied on passive transfer. The thinking was that steroids passively entered the lipophillic yolk during yolk deposition and then were deposited in the yolk until they were passively delivered to the embryo as the yolk was used. Subsequent studies revealed that the system is much more dynamic than that. Here, we explore questions about how dynamic the system really is and look at questions like: Is transfer of maternal steroids to the yolk passive or is it actively regulated? At what stages of the maternal reproductive cycle are steroids transferred? During reproduction, how dynamic are the levels of yolk steroids? Especially in the case of potentially deleterious steroids (e.g., androgens in female offspring; glucocorticoids), once deposited can they come out of the yolk over time? Can they be metabolized by the yolk or by the embryo? During incubation, how much do steroid levels in the yolk change? Can steroids diffuse from the yolk to the embryo prior to yolk utilization? Does the embryo contribute to yolk steroid levels as it develops? We believe that comprehensive answers to questions like these will eventually allow us to generate a much more accurate and complete model of the transfer and utilization of yolk steroids and that this model will be much more dynamic and active than the one initially proposed.

In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load. Therefore, we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers (5 men and 6 women). Each subject underwent an oral glucose tolerance test (OGTT) on 2 separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without 7.5 g fructose (OGTT+F or OGTT-F), in random order. Arterialized blood samples were obtained from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward. The area under the curve (AUC) of the change in plasma glucose was 19% less in OGTT+F vs. OGTT-F (P: < 0.05). Glucose tolerance was improved by fructose in 9 subjects and worsened in 2. All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F (31 +/- 5% decrease). The insulin AUC did not differ between the 2 studies. Of the 9 subjects with improved glucose tolerance during the OGTT+F, 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50% greater during the OGTT+F (P: < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTT. In conclusion, low dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.

In vitro evidence indicates that the liver responds directly to changes in circulating glucose concentrations with reciprocal changes in glucose production and that this autoregulation plays a role in maintenance of normoglycemia. Under in vivo conditions it is difficult to separate the effects of glucose on neural regulation mediated by the central nervous system from its direct effect on the liver. Nevertheless, it is clear that nonhormonal mechanisms can cause significant changes in net hepatic glucose balance. In response to hyperglycemia, net hepatic glucose output can be decreased by as much as 60-90% by nonhormonal mechanisms. Under conditions in which hepatic glycogen stores are high (i.e. the overnight-fasted state), a decrease in the glycogenolytic rate and an increase in the rate of glucose cycling within the liver appear to be the explanation for the decrease in hepatic glucose output seen in response to hyperglycemia. During more prolonged fasting, when glycogen levels are reduced, a decrease in gluconeogenesis may occur as a part of the nonhormonal response to hyperglycemia. A substantial role for hepatic autoregulation in the response to insulin-induced hypoglycemia is most clearly evident in severe hypoglycemia (< or = 2.8 mmol/l). The nonhormonal response to hypoglycemia apparently involves enhancement of both gluconeogenesis and glycogenolysis and is capable of supplying enough glucose to meet at least half of the requirement of the brain. The nonhormonal response can include neural signaling, as well as autoregulation. However, even in the absence of the ability to secrete counterregulatory hormones (glucocorticoids, catecholamines, and glucagon), dogs with denervated livers (to interrupt neural pathways between the liver and brain) were able to respond to hypoglycemia with increases in net hepatic glucose output. Thus, even though the endocrine system provides the primary response to changes in glycemia, autoregulation plays an important adjunctive role.