Publications by authors named "Segar J"

Background: The importance of the brain renin-angiotensin system in cardiovascular function is well accepted. However, not knowing the precise source of renin in the brain has been a limitation toward a complete understanding of how the brain renin-angiotensin system operates.

Methods: Highly sensitive in situ hybridization techniques and conditional knockout mice were used to address the location and function of renin in the brainstem.

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Preterm birth increases the risk of cardiometabolic disease in adulthood. Infants born during the second trimester of pregnancy, a critical period of hypothalamic development, are at risk of sodium (Na) depletion due to renal immaturity and large urine Na losses. We previously demonstrated in male mice that Na restriction during the equivalent mouse hypothalamic development period [postnatal day (PD)21-PD42] programs long-term changes in energy balance via increased thermogenic sympathetic nervous activity.

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  • * It analyzed data from two groups of infants before and after the protocol's implementation, showing significant growth improvements (body weight and head circumference) in those born at 26-29 weeks.
  • * Results indicated that the protocol reduced the need for mechanical ventilation but did not increase the risk of health issues like hypertension or infections in extremely preterm infants.
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The American Heart Association has identified obesity as a primary impediment to ongoing improvements in cardiovascular diseases, including hypertension. Although drugs, exercise, diets, and surgeries can each cause weight loss, few subjects maintain a reduced weight over the long term. Dysfunctional integrative control (ie, adaptation) of resting metabolic rate (RMR) appears to underlie this failed weight maintenance, yet the neurobiology of physiological and pathophysiological RMR control is poorly understood.

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Importance: Kidney disease is common in infants admitted to the neonatal intensive care unit (NICU). Despite the risk of chronic kidney disease (CKD) in infants discharged from the NICU, neither evidence- nor expert-based recommendations exist to guide clinical care after discharge.

Objective: To develop recommendations for risk stratification and kidney health monitoring among infants after discharge from the NICU.

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Background: While intermittent fasting leads to weight loss and improved glucose metabolism, food insecurity, the insufficient access to food for a healthy life, is associated with obesity and adverse cardiometabolic health, especially in women. We aimed to characterize the effects of intermittently restricted feeding on energy balance and glucose tolerance in female mice.

Methods: Female C57BL/6J mice were fed a high-fat, high-sucrose diet and intermittently food restricted to 60% of control littermates' ad libitum intake, starting at weaning and until week 19.

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Aim: Breast cancer is commonest cancer among Malaysian women and screening is essential for the early detection. Therefore our study aimed at measuring the levels of knowledge, attitude and perception towards personalized risk stratified breast cancer screening in Malaysia.

Methods: A cross-sectional study was carried out in Malaysia to assess the knowledge, perception and attitudes of the women in Malaysia.

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Objective: Evaluate the impact of a sodium (Na) supplementation protocol based upon urine Na concentration on growth parameters and morbidities.

Study Design: Retrospective cohort study of infants 26-33 weeks gestational age (GA) cared for before (2012-15, n = 225) and after (2016-20, n = 157) implementation of the protocol. Within- and between-group changes over time were assessed using repeated measures generalized linear models.

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  • The study examines the incidence and outcomes of recurrent acute kidney injury (rAKI) in critically ill neonates, highlighting a gap in current knowledge.
  • Conducted as a secondary analysis of a larger international study, the research focused on neonates under 14 days old who received intravenous fluids and excluded those with severe congenital issues.
  • Findings revealed that 22% of neonates with acute kidney injury developed rAKI, associated with younger gestational ages, lower birthweights, and more severe initial AKI; these infants had longer hospital stays compared to those without AKI.
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The estrous cycle is known to modify food, fluid, and electrolyte intake behaviors and energy homeostasis in various species, in part through fluctuations in estrogen levels. Simultaneously, commonly commercially available rodent dietary formulations greatly vary in soy protein content, and thereby the delivery of biologically active phytoestrogens. To explore the interactions among the estrous cycle, sodium, fluid, and caloric seeking behaviors, and energy homeostasis, young adult C57BL/6J female mice were maintained on a soy protein-free 2920x diet and provided water, or a choice between water and 0.

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Background: Checkpoint inhibitors are standard adjuvant treatment for stage IIB-IV resected melanoma, but many patients recur. Our study aimed to evaluate whether mRNA-4157 (V940), a novel mRNA-based individualised neoantigen therapy, combined with pembrolizumab, improved recurrence-free survival and distant metastasis-free survival versus pembrolizumab monotherapy in resected high-risk melanoma.

Methods: We did an open-label, randomised, phase 2b, adjuvant study of mRNA-4157 plus pembrolizumab versus pembrolizumab monotherapy in patients, enrolled from sites in the USA and Australia, with completely resected high-risk cutaneous melanoma.

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The recommends mice be pair or group housed and provided with nesting materials. These provisions support social interactions and are also critical for thermoregulatory behaviors such as huddling and burrowing. However, studies of fluid and electrolyte balance and digestive function may involve use of metabolic caging (MC) systems in which mice are housed individually on wire-mesh floors that permit quantitative collection of urine and feces.

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Purpose Of Review: This review highlights recent advances in understanding fluid and electrolyte homeostasis during the newborn period, including heightened recognition of fluid overload and acute kidney injury contributing to poor clinical outcomes. Particular attention is given towards the care of extremely preterm infants.

Recent Findings: Emerging data demonstrate (i) disproportionally large transepidermal water loss in the extremely preterm population, (ii) the relationship between postnatal weight loss (negative fluid balance) and improved outcomes, (iii) the frequency and negative effects of dysnatremias early in life, (iv) the role of sodium homeostasis in optimizing postnatal growth, and (v) the deleterious effects of fluid overload and acute kidney injury.

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Postnatal growth failure remains a significant problem for infants born prematurely, despite aggressive efforts to improve perinatal nutrition. Though often dysregulated in early life when children are born preterm, sodium (Na) homeostasis is vital to achieve optimal growth. We hypothesize that insufficient Na supply in this critical period contributes to growth restriction and programmed risks for cardiometabolic disease in later adulthood.

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Article Synopsis
  • Conservation gardening (CG) is a new approach aimed at reversing the decline of native plant species while transforming gardening practices into effective conservation tools, though there is limited information about suitable plants for gardening and their availability.
  • The study used Germany as a case study to create a user-friendly app that offers localized lists of plants suitable for conservation gardening, noting that a significant number of red-listed species can be integrated into gardens.
  • The findings suggest that many of these plants are drought-tolerant and low-fertilizer users, indicating CG's potential for urban planning and climate adaptation while also serving as vital refuges for biodiversity.
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Aim: This article is intended to review the relationship between sodium homeostasis and growth, outline reasons why preterm infants may become sodium deficient, and share data from our group and others regarding the potential benefits of dietary sodium supplementation.

Background: Despite tremendous efforts over the past 20 years to optimize neonatal nutrition, postnatal growth failure in preterm infants remains a significant problem. Compelling associations have been identified between in-hospital growth failure and cardiometabolic and neurodevelopmental disorders, heightening the need to further identify the optimal nutritional needs of preterm infants.

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Non-enzymatic activation of renin via its interaction with prorenin receptor (PRR) has been proposed as a key mechanism of local renin-angiotensin system (RAS) activation. The presence of renin and angiotensinogen has been reported in the rostral ventrolateral medulla (RVLM). Overactivation of bulbospinal neurons in the RVLM is linked to hypertension (HTN).

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  • Premature neonates commonly experience acute kidney injury (AKI) and fluid balance issues, making it difficult to accurately diagnose AKI based on serum creatinine levels alone.
  • The study investigates whether adjusting serum creatinine for fluid balance can reveal additional cases of AKI in extremely premature neonates and affect their short-term and long-term health outcomes.
  • Conducted as part of a larger clinical trial across multiple centers, the analysis focused on how fluid-corrected AKI impacts factors like the need for mechanical ventilation and overall hospital stay length.
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Introduction And Hypothesis: The Variation in Surgical Technique study (VaST), demonstrated the large variation in surgical techniques used in native tissue (NT) anterior pelvic organ prolapse (POP) repairs. However, there are few comparative studies of different surgical techniques. This study was aimed at exploring whether surgical technique influenced the outcomes of NT anterior POP repairs.

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Background: Mice prefer warmer environments than humans. For this reason, behavioral and physiological thermoregulatory responses are engaged by mice in response to a standard room temperature of 22 to 24 °C. Autonomic mechanisms mediating thermoregulatory responses overlap with mechanisms activated in hypertension, and, therefore, we hypothesized that housing at thermoneutral temperatures (TNs; 30 °C) would modify the cardiometabolic effects of deoxycorticosterone acetate (DOCA)-salt in mice.

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Aromatase inhibitor-induced arthralgia (AIA) presents a major problem for patients with breast cancer but is poorly understood. This prospective study explored the inflammatory metabolomic changes in the development of AIA. This single-arm, prospective clinical trial enrolled 28 postmenopausal women with early-stage (0-3) ER+ breast cancer starting adjuvant anastrozole.

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Importance: Extremely low gestational age neonates are at risk of disorders of fluid balance (FB), defined as change in fluid weight over a specific period. Few data exist on the association between FB and respiratory outcomes in this population.

Objective: To describe FB patterns and evaluate the association of FB with respiratory outcomes in a cohort of extremely low gestational age neonates.

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Ungulate populations are increasing across Europe with important implications for forest plant communities. Concurrently, atmospheric nitrogen (N) deposition continues to eutrophicate forests, threatening many rare, often more nutrient-efficient, plant species. These pressures may critically interact to shape biodiversity as in grassland and tundra systems, yet any potential interactions in forests remain poorly understood.

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Background: GPCRs (G protein-coupled receptors) are implicated in blood pressure (BP) and fluid intake regulation. There is a developing concept that these effects are mediated by both canonical G protein signaling and noncanonical β-arrestin mediated signaling, but the contributions of each remain largely unexplored. Here, we hypothesized that β-arrestin contributes to fluid homeostasis and blood pressure (BP) regulation in deoxycorticosterone acetate (DOCA) salt hypertension, a prototypical model of salt-sensitive hypertension.

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