Objectives. We aimed to assess if Caesarean section is a risk factor for overnutrition in early- and late-childhood, and to assess the magnitude of the effect of child- versus family-related variables in these risk estimates. Methods. Longitudinal data from Peruvian children from the Young Lives Study was used. Outcomes assessed were overweight, obesity, overnutrition (overweight plus obesity), and central obesity (waist circumference) at the age 5 (first follow-up) and 7 (second follow-up) years. The exposure of interests was delivery by Caesarean section. Relative risks (RR) and 95% confidence intervals (95% CI) were calculated using multivariable models adjusted for child-related (e.g., birth weight) and familyrelated (e.g., maternal nutritional status) variables. Results. At baseline, mean age was 11.7 (± 3.5) months and 50.1% were boys. Children born by Caesarean section were 15.6%. The 10.5% of the children were overweight and 2.4% were obese. For the obesity outcome, data from 6,038 and 9,625 children-years was included from baseline to the first and second follow-up, respectively. Compared to those who did not experience Caesarean delivery, the risk of having obesity was higher in the group born by Caesarean: RRs were higher at early-childhood (first follow-up: 2.25; 95% CI [1.36–3.74]) than later in life (second follow-up: 1.57; 95% CI [1.02–2.41]). Family-related variables had a greater effect in attenuating the risk estimates for obesity at the first, than at the second follow-up. Conclusion. Our results suggest a higher probability of developing obesity, but not overweight, among children born by Caesarean section delivery. The magnitude of risk estimates decreased over time, and family-related variables had a stronger effect on the risk estimates at early-childhood. / RMC-L, JJM, AB-O, and the CRONICAS Center of Excellence in Chronic Diseases were supported by the National Heart, Lung, and Blood Institute Global Health Initiative under the contract Global Health Activities in Developing Countries to Combat Non-Communicable Chronic Diseases (Project Number 268200900033C-1-0-1). AB-O is currently supported by a Wellcome Trust Research Training Fellowship in Public Health and Tropical Medicine (Grant 103994/Z/14/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. / Revisión por pares

Folliculogenesis is a complex process which describes the maturation of the ovarian follicle, from the primordial stage all the way to the ovulation of the antral follicle, and its sequela, the formation of the corpus luteum (CL). Imitation switch (ISWI) proteins are a class of ATP-dependent chromatin remodelers which mobilize nucleosomes to regulate a number of cellular processes including transcription, replication, and DNA repair. The pattern of expression of the mammalian ISWI proteins SNF2H and SNF2L in the mouse ovary suggests a role in the coordination of the proliferation and differentiation of granulosa cells during folliculogenesis. Here, we report that SNF2H is associated with proliferating granulosa cells, while SNF2L expression is induced following the LH surge which triggers their terminal differentiation into luteal cells. Knockdown of Snf2l by siRNA is sufficient to downregulate the expression of StAR, an important steroidogenic enzyme, and marker of the CL. Furthermore, SNF2L is thought to directly regulate StAR expression by physically binding to its promoter as indicated by chromatin immunoprecipitation (ChIP). In order to identify additional targets regulated by SNF2L, an unbiased microarray screen was developed to look for genes induced by LH in a SNF2L-dependent manner. One of the candidates, Fgl2 is strongly induced at 8h post hCG only in granulosa cells with intact SNF2L activity. Furthermore overexpression of SNF2L is sufficient to induce FGL2, and SNF2L is present on its promoter in the SIGC rat granulosa cell line. Some of the SNF2L binding partners that may be important in this regulation are PR-A and FLI-I, which have been found to interact with SNF2L by IP. Finally we describe here the phenotype of a Snf2l KO mouse which includes multiple reproductive defects, including resistance to superovulation, low secondary follicle counts, and a high incidence of abnormal antral follicles. Taken together these data suggest an important role of ISWI proteins in folliculogenesis, particularly SNF2L, which may regulate multiple genes important for the terminal differentiation of granulosa cells into luteal cells following the LH surge.

Nearly 20% of U.S. children are reported to have neurobehavioral deficits in part linked to environmental exposure to industrial chemicals like polychlorinated biphenyls (PCBs). PCB exposure is associated with neurotoxicity including both reduced IQ and response inhibition. PCBs may affect normal brain development by acting on the thyroid hormone (TH) system, either by reducing serum TH levels and/or by interfering with TH receptors (TRs). A critical endpoint, dependent upon sufficient TH, is maturation of oligodendrocytes during development and therefore subject to disruption by PCBs. Due to the complexity of the brain we used both in vitro and in vivo approaches to understand the mechanism of PCBs interfering with TH action. Previous work in our lab has demonstrated that metabolism of PCB congeners is necessary for them to act on the TR in vitro. In neonatal rat livers, we evaluated the TR-agonistic properties of PCBs on TR-dependent gene expression in the presence and absence of metabolism. We found that expression of TH target genes in PCB-exposed livers varied between different congener combinations and was independent of the PCB-induced reduction in circulating T4 levels. Further evaluation of global changes in gene expression between a commercial PCB mixture A1254 and hypothyroidism revealed that only 25% of TH-responsive genes also respond to PCB exposure. Individual congeners accounted for only half of the A1254 effects on TH-regulated genes, suggesting that unidentified congeners or metabolites are affecting TH action. In the neonatal brain, we evaluated the congener-specific effects on a TH- sensitive endpoint during development, the white matter cell numbers in the corpus callosum (CC). In the CC, hypothyroidism decreased oligodendrocytes by about 80%. A1254 achieved a 35% reduction in oligodendrocytes; an effect mediated by a mixture of individual congeners. Hypothyroidism and A1254 exposure increased astrocyte numbers by 30%, but the effect of A1254 seems to be mediated by yet another subset of PCB congeners independent of the TH serum levels. PCB exposure has a differential effect on glial cell differentiation in the CC compared to hypothyroidism that is congener-specific as well as region-specific. Both changes in glia cells during development are not observed in adulthood. The disruption of glia cell ratio in the CC by PCBs could lead to diminished CNS functionality during a critical window of neonatal development.

No description available.

No description available.

This dissertation research contained three studies. The first two studies were conducted to investigate the ability of ewes to rebreed while lactating during seasonal anestrus. Breeds studied included the Virginia Tech Out-of-season (OOS) Line, which is a wool line genetically selected to lamb in the fall, and the St. Croix, a hair breed of tropical origin thought to be lowly seasonal. When January-lambing ewes were exposed to rams while lactating in April, significantly more OOS than St. Croix ewes were marked by rams in the first 21 d and total 39 d of ram exposure (58.3 vs. 8.7%, P = 0.0003 and 95.8 vs. 43.5%, P < 0.0001). Percentages of ewes diagnosed pregnant (53.2%) and percentages of ewes lambing (41.3%) were not different between breeds. When March-lambing OOS ewes were exposed to rams while lactating in May, 52.9% of ewes were marked though only 20% of ewes exposed to rams gave birth to viable lambs. Both OOS and St. Croix ewes appear to be well suited to accelerated production systems involving 7 to 8 mo lambing intervals. However, reduction of lambing intervals to 6 to 7 mo appeared to have detrimental effects on fetal survival in OOS ewes. In a third study, alterations in endocrine profiles associated with differing degrees of hypothalamic sensitivity to estradiol-negative feedback and changing daylength in OOS, St. Croix, and Suffolk ewes in the absence of rams were investigated for 1 yr. The results show for the first time that based on progesterone profiles from intact ewes, St. Croix ewes do not have shorter anestrous periods than ewes of wool breeds, as previously thought. Based on luteinizing hormone profiles from ovariectomized ewes treated with estradiol implants, the duration of luteinizing hormone inhibition was shorter in OOS than Suffolk ewes (68 vs. 170.2 d, P = 0.02), but was not different from that found in St. Croix ewes (124.8 d). Specific roles for thyroxine and prolactin in timing the breeding season could not be assigned. This study was the first known use of the ovariectomized, estradiol-implanted ewe model to compare degree of reproductive seasonality in different breeds. / Ph. D.

Free-ranging banded mongooses (Mungos mungo) in northeastern Botswana are infected by a novel Mycobacterium tuberculosis complex pathogen, M. mungi, which putatively infects mongooses through lesions in the skin (often the planum nasale) from an environmental reservoir. To understand the epidemiology of the yearly and highly seasonal outbreaks of M. mungi in this population of banded mongooses, researchers need to understand what factors influence banded mongoose exposure to M. mungi and banded mongoose susceptibility to M. mungi infection. Researchers have no baseline data on the behavioral ecology of this population of banded mongooses - such as home range dynamics, denning ecology, movement ecology, and foraging ecology, all of which may play a role in banded mongoose exposure to M. mungi. Further, researchers have highlighted the potential role of prolonged elevations of glucocorticoids in impairing cell-mediated immunity, which would play a significant role in determining susceptibility to a mycobacterium such as M. mungi, however, researchers have no data on the endocrinology of banded mongooses. Finally, researchers have not detected M. mungi infection in any other population of banded mongooses. Our study population has a gradient of troops (social groups) that vary from troops with extremely close association with humans in a town, to troops associated with humans at tourist lodges within the Chobe National Park, to troops with no discernible association with humans within the national park and surrounding forest reserve. Researchers have few data on how synanthropy (living with humans) affects banded mongoose behavioral ecology and no data on how synanthropy affects banded mongoose endocrinology. Researchers do not know whether or how the high level of synanthropy in this population of banded mongooses plays a role in the epidemiology of M. mungi outbreaks. Thus, we document here some aspects of banded mongoose home range dynamics, movement metrics, denning ecology and foraging behavior for our study population in northeastern Botswana. We present a novel method for screening data from global positioning system (GPS) collars for large measurement error and we present a detailed home range study. We also document the spatio-temporal dynamics of glucocorticoid production among several banded mongoose study troops across our study site, using a non-invasive assay for fecal glucocorticoid metabolites, which we validated and also present here.  We tested to see which factors, including nutritional limitation, predation risk, and reproduction (and associated competition, agonistic encounters, and predation), best explained the variation in glucocorticoid production among our study troops over several years. We found that the metrics traditionally used to screen data from GPS collars, horizontal dilution of precision (HDOP) or fix dimension (2-D or 3-D), performed poorly relative to a new screening metric that we propose, the estimated elevation error (EEE). We propose that researchers use our screening method, which combines test data and a model-averaging information-theoretic framework that uses a priori candidate models of telemetry measurement error. Although we recommend including EEE in a priori candidate models, it may not describe telemetry error in other systems as well as it did in our own. Banded mongooses in our study population formed troops of a median of 13 adults (IQR: 11 to 21 adults) and these troops used home ranges of a median of 68 ha (IQR: 39 to 134 ha) with core areas of a median of 15 ha (IQR: 9 to 28 ha). These cores (statistically-clumped space use) occurred at a median volume contour of 66 % (IQR: 58 to 71 %). Synanthropic troops showed more clumped area use than apoanthropic troops (those living away from humans). Synanthropic troops also used man-made structures for den sites in SI{81}{percent} of nights, fed from refuse sites in 13 % of foraging observations, and drank from anthropogenic water sources in 78 % of drinking observations. From our conducted adrenocorticotropic hormone challenge, we detected valid increases in fecal glucocorticoid metabolite concentrations in mongoose feces using our four tested enzyme-immunoassays. An 11-oxoetiocholanolone assay detecting 11,17-dioxoandrostanes (11,17-DOA) performed best. Using this assay, we detected expected decreases in fecal glucocorticoid metabolite concentrations 48 h after administering dexamethasone sodium phosphate. We also validated this assay using biological events as challenges, in which captive mongooses showed higher fecal glucocorticoid metabolite concentrations during reproductive activity, agonistic encounters, and depredation events. The time delay of fecal glucocorticoid metabolite excretion approximately corresponded with food transit time, at a minimum of approximately 24 h. Fecal glucocorticoid metabolite metabolism was minimal up to 8 h post-defecation. Reproduction and its associated challenges dramatically increased glucocorticoid production, which otherwise remained low and stable in a captive troop with a constant food supply and lowered predation risk. Variation in glucocorticoid production in free-ranging banded mongooses was best explained by food limitation as described by current nutritional limitation (proportion of fecal organic matter), recent rainfall (which increases soil macrofauna availability), and access to concentrated anthropogenic food resources. Habitat differences in soil macrofauna density and reproductive events also explained variation in glucocorticoid production in free-ranging mongooses, but to a much lower degree. Predation risk, as measured by canopy cover (escape from aerial predators) and group size (decreased per capita vigilance) explained very little of the variation in glucocorticoid production. In the late dry season, banded mongooses in our population may face a "perfect storm" of nutritional limitation, agonistic encounters at concentrated food resources, aggressive evictions, estrus, competition for mates, parturition, and predation pressure on pups. We suspect that this prefect storm may push glucocorticoid responses into homeostatic overload and may impair cell-mediated immunity in banded mongooses. / Ph. D.

<p>Sex steroids are critical for the post-natal development of the female reproductive system, and are involved in ovulatory cycling and pregnancy. In mice, <em>Mus musculus</em>, female development, cycling, and pregnancy can be affected by the urine of conspecifics, which is known to contain active steroids. Specifically, puberty can be accelerated (the Vandenbergh effect), estrous cycling can be prolonged (the Lee-Boot effect) or synchronized (the Whitten effect), and blastocyst implantation can be disrupted (the Bruce effect). Since steroids alone can affect females in ways that are indistinguishable from these social reproductive effects, I hypothesized that urinary steroids of conspecifics may be absorbed by females, arrive in the reproductive system, and thereby affect females through known mechanisms. First I showed that tritium-labelled 17β-estradiol (³H-E₂) injected into males is excreted in their urine, and that application of urine from these males to the nose of an inseminated female results in detectable levels in her uterus. When I paired inseminated females with non-sire males injected with ³H-E₂, radioactivity was detected in the brain and reproductive tissues of the females. This was the first demonstration of steroids from one animal directly entering the body of another. Similar results were found when I exposed juvenile females to adult males injected with ³H-E₂, and when I exposed nulliparous adult females to same-strain ³H‑E₂- or ³H-progesterone- (³H-P₄) treated adult males or females. Taken with the existing literature, these results suggest that steroid transfer may underlie various social reproductive phenomena in mice, with potential implications for many other species.</p> / Doctor of Philosophy (PhD)

<p> Type 2 Diabetes Mellitus (T2DM) is the seventh leading cause of death in the United States with a projected increase of 552 million people worldwide who will be affected with this illness by 2030. The need to address this issue is vital to prevent complications and reduce healthcare spending. The DNP project is aimed at planning and designing a nutritional education program tailored toward specific ethnic groups in order to increase knowledge in making healthy food choices. This project is intended to educate Registered Nurses (RNs) on nutrition so that they can offer dietary knowledge to T2DM patients. Additional patients can be reached by educating the RNs rather than patients being limited to consultations with a Certified Diabetes Educator or Registered Dietician. This project focused on whether healthy nutrition tailored toward the individual&rsquo;s own ethnic foods helps to stabilize glycemic values for patients with Type 2 diabetes. A toolkit was utilized to aid with the RNs&rsquo; learning on healthy nutrition and its impact on the management of blood glucose. It addressed areas such as food groups and calories, grocery shopping, preparation methods, and portion control. The framework for design utilized the basic concepts associated with the systems theory with an intended goal to prevent further complications and improve patients&rsquo; glycemic value through consuming nutritious foods. The logic model will be used to evaluate the impact of healthy nutrition on blood glucose through pre- and post-program tests of the RNs&rsquo; nutritional knowledge on healthy eating. The continuation of this program will promote positive social change by helping patients to achieve a healthier lifestyle and reduce healthcare expenditures.. </p>

<p> Type 1 diabetes is an autoimmune condition which has seen numbers increase in recent years. Being a diabetic is neither easy for the diabetic themselves nor the parents raising the diabetic child. In looking over the literature, very little research was found on the lived experiences of fathers raising a child with type 1 diabetes. Therefore, a qualitative design with a phenomenological approach was used in order to discover and describe the phenomenon. This study was based on 12 male respondents (fathers) who shared their experiences on parenting a child with type 1 diabetes. The responses of the 12 participants revealed four major themes discovered via the hermeneutic method of textual description, and sought to present the essence of their lived experience. The four major themes were diabetes is forever, dealing with it, increased pressure, and the &ldquo;new normal.&rdquo; The lived experiences of fathers who participated in this study disclosed a sense of resiliency, while learning a lot of information, quickly to better understand type 1 diabetes. The interviewees wanted to share their stories and help others, interested in this topic, gain a better understanding of what life is like parenting and raising a child with type 1 diabetes.</p>