Search

An individual's nutritional status has a powerful effect on sexual maturation. Puberty onset is delayed in response to chronic energy insufficiency and is advanced under energy abundance. The consequences of altered pubertal timing for human health are profound. Late puberty increases the chances of cardiometabolic, musculoskeletal and neurocognitive disorders, whereas early puberty is associated with increased risks of adult obesity, type 2 diabetes mellitus, cardiovascular diseases and various cancers, such as breast, endometrial and prostate cancer. Kennedy and Mitra's trailblazing studies, published in 1963 and using experimental models, were the first to demonstrate that nutrition is a key factor in puberty onset. Building on this work, the field has advanced substantially in the past decade, which is largely due to the impressive development of molecular tools for experimentation and population genetics. In this Review, we discuss the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development, with a focus on perspectives and future directions. Key papers on the role of nutrition and metabolic cues in puberty timing were published in 1963, and there have been many advances in this field in the subsequent 60 years. This Review discusses the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development. Key points: In 1963, Kennedy and Mitra published a seminal study in rats demonstrating that body weight is a major determinant of pubertal timing. An increasing incidence of earlier ages at puberty has been documented; early pubertal timing favours the occurrence of type 2 diabetes mellitus, cardiovascular diseases and certain cancers in adulthood. Macronutrients and hormones that modulate growth and/or signal adipose tissue mass serve as metabolic cues conveying the nutritional status and stored energy available for sexual maturation, differentiation and growth. The effect of metabolic cues on puberty is mediated by neural targets upstream of GnRH neurons; considerable progress in defining the neuronal circuitry and glial components has been achieved. A number of molecular pathways and epigenetic mechanisms have been identified as primary components in the modulation of pubertal timing by hormones and nutritional cues. [ABSTRACT FROM AUTHOR]

Reproductive function is critical for species survival; however, it is energetically costly and physically demanding. Reproductive suppression is therefore a physiologically appropriate adaptation to certain ecological, environmental, and/or temporal conditions. This 'allostatic' suppression of fertility enables individuals to accommodate unfavorable reproductive circumstances and safeguard survival. The mechanisms underpinning this reproductive suppression are complex, yet culminate with the reduced secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which in turn suppresses gonadotropin release from the pituitary, thereby impairing gonadal function. The focus of this review will be on the role of RFamide-related peptide (RFRP) neurons in different examples of allostatic reproductive suppression. RFRP neurons release the RFRP-3 peptide, which negatively regulates GnRH neurons and thus appears to act as a 'brake' on the neuroendocrine reproductive axis. In a multitude of predictable (e.g., pre-puberty, reproductive senescence, and seasonal or lactational reproductive quiescence) and unpredictable (e.g., metabolic, immune and/or psychosocial stress) situations in which GnRH secretion is suppressed, the RFRP neurons have been suggested to act as modulators. This review examines evidence for and against these roles. [ABSTRACT FROM AUTHOR]

The article presents the results of the survey of the law of professional responsibility in Indiana from August 2021 to September 2022. Also cited are the per curiam rulings by the state's Supreme Court imposing sanctions for lawyer misconduct, the need for civility in both trials and disciplinary proceedings, and the application of the Rules of Professional Conduct to common ethical dilemmas.

In Fall 2020, all universities in Alberta went with remote delivery of classes due to COVID-19 restrictions. This provided not only teaching challenges, but also opportunities. Professors at three Canadian universities teaching similar undergraduate courses in international political economy decided to use the challenges/opportunities of COVID-19 restrictions to experiment with a World Trade Organization (WTO) simulation across three campuses through remote delivery. Simulations are frequently used for teaching in political science, but what was unusual was doing it through remote delivery. This paper assesses the effectiveness of the experiment. It traces the origins/evolution of the idea, learning objectives for the students, preparation by the professors to design the WTO simulation, and the experience of the actual simulation. It also addresses the challenges (technological, timing, assignments, grading, student anxiety, etc.). In addition, it identifies the steps that were taken to reduce and mitigate the challenges. It also acknowledges the mistakes that were made by the professors in designing and implementing the assignment. These observations and reflections are informed by the materials that the professors prepared, their thoughts on the experience, and the feedback from participating students (through official student evaluations as well as a special survey instrument). It provides lessons for future online simulations. [ABSTRACT FROM AUTHOR]

Orthopedic sports surgery of the knee and shoulder is generally considered to be safe and effective. Vascular complications can occur during or after arthroscopy of either joint. A thorough understanding of anatomy, particularly when placing portals in non-routine locations, is extremely important. Prompt recognition of any vascular complication is of significant importance. This review will discuss the potential vascular complications for both knee and shoulder sports surgery, review the relevant anatomy, and discuss the treatment and expected outcome of each. [ABSTRACT FROM AUTHOR]

Being truthful with patients is a critical foundation of the doctorpatient relationship and is fundamental to development of trust. A professional commitment to truth telling may sometimes contradict other principles of bioethics, which may challenge decision-making for the doctor and/or the treatment team. Practitioners may fail to address all ethical or legal aspects of a case and therefore make inappropriate decisions. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Approximately half of the diagnosed individuals also experience the metabolic syndrome. Central and peripheral resistance to the hormones insulin and leptin have been reported to contribute to both metabolic and reproductive dysregulation. In PCOS and preclinical PCOS animal models, circulating insulin and leptin levels are often increased in parallel with the development of hormone resistance; however, it remains uncertain whether these changes contribute to the PCOS state. In this study, we tested whether central actions of protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling 3 (SOCS3), negative regulators of insulin and leptin signaling pathways, respectively, play a role in the development of PCOS-like phenotype. A peripubertal dihydrotestosterone (DHT) excess PCOS-like mouse model was used, which exhibits both metabolic and reproductive dysfunction. Mice with knockout of the genes encoding PTP1B and SOCS3 from forebrain neurons were generated, and metabolic and reproductive functions were compared between knockout and control groups. DHT treatment induced mild insulin resistance but not leptin resistance, so the role of SOCS3 could not be tested. As expected, DHT excess abolished estrous cycles and corpora lutea presence and caused increased visceral adiposity and fasting glucose levels. Knockout mice did not show any rescue of reproductive dysfunction but did have reduced adiposity compared to the control DHT mice. These data suggest that negative regulation of central insulin signaling by PTP1B is not responsible for peripubertal DHT excess-induced reproductive impairments but may mediate its increased adiposity effects. [ABSTRACT FROM AUTHOR]

Excess levels of circulating androgens during prenatal or peripubertal development are an important cause of polycystic ovary syndrome (PCOS), with the brain being a key target. Approximately half of the women diagnosed with PCOS also experience metabolic syndrome; common features including obesity, insulin resistance and hyperinsulinemia. Although a large amount of clinical and preclinical evidence has confirmed this relationship between androgens and the reproductive and metabolic features of PCOS, the mechanisms by which androgens cause this dysregulation are unknown. Neuron‐specific androgen receptor knockout alleviates some PCOS‐like features in a peripubertal dihydrotestosterone (DHT) mouse model, but the specific neuronal populations mediating these effects are undefined. A candidate population is the agouti‐related peptide (AgRP)‐expressing neurons, which are important for both reproductive and metabolic function. We used a well‐characterised peripubertal androgenized mouse model and Cre‐loxP transgenics to investigate whether deleting androgen receptors specifically from AgRP neurons can alleviate the induced reproductive and metabolic dysregulation. Androgen receptors were co‐expressed in 66% of AgRP neurons in control mice, but only in <2% of AgRP neurons in knockout mice. The number of AgRP neurons was not altered by the treatments. Only 20% of androgen receptor knockout mice showed rescue of DHT‐induced androgen‐induced anovulation and acyclicity. Furthermore, androgen receptor knockout did not rescue metabolic dysfunction (body weight, adiposity or glucose and insulin tolerance). While we cannot rule out developmental compensation in our model, these results suggest peripubertal androgen excess does not markedly influence Agrp expression and does not dysregulate reproductive and metabolic function through direct actions of androgens onto AgRP neurons. [ABSTRACT FROM AUTHOR]

Lawrie and Margaret had five children, and he is survived by Elizabeth - herself a distinguished hepatologist, Mark, Martine and Christa. GLO:EUW/01nov22:jgh16031-gra-0001.jpg PHOTO (COLOR): . gl More than "Mr. Iron", Lawrie Powell was a Foundation Stone of Asia-Pacific Gastroenterology and Liver disease. Remembering Lawrie Powell 1934-2022. [Extracted from the article]

Reproductive function is tightly regulated by both environmental and physiological factors. The adipose-derived hormone leptin has been identified as one such critical factor that relays information about peripheral energy availability to the centrally-governed HPG axis to ensure there is sufficient energy availability to support the high energy demands of mammalian reproduction. In the absence of adequate central leptin signaling, reproductive function is suppressed. While leptin levels are predominantly regulated by adiposity, circulating leptin levels are also under the modulatory influence of other factors, such as stress system activation, circadian rhythmicity, and immune activation and the inflammatory response. Furthermore, changes in leptin sensitivity can affect the degree to which leptin exerts its influence on the neuroendocrine reproductive axis. This review will discuss the different mechanisms by which leptin serves to integrate and relay information about metabolic, psychological, environmental and immune conditions to the central neuronal network that governs reproductive function. [ABSTRACT FROM AUTHOR]

Agouti‐related peptide (AgRP) neurons are thought to indirectly regulate the activity of hypothalamic gonadotrophin‐releasing hormone neurons which control fertility. AgRP neurons also drive caloric intake and are modulated by metabolically‐relevant hormones, providing a link to the hypothalamic–pituitary‐gonadal axis. In mice expressing Cre‐dependant designer receptors (DREADDs) in AgRP neurons, we activated or silenced these neurons in vivo using the synthetic ligand clozapine‐N‐oxide (CNO) to observe the effect of AgRP neuron activity on timing of puberty. To validate these animals, we chronically treated both stimulatory (hM3Dq) and inhibitory (hM4Di) DREADD × AgRP‐Cre mice with CNO, observing a pronounced increase and decrease of food intake, respectively, consistent with the known orexigenic effects of these neurons. RNAscope was performed to visually confirm the activation of AgRP neurons. Puberty onset was assessed in males and females. There was no effect on preputial separation in males or vaginal opening and first oestrus in females after CNO treatment from day 26 to 30 to chronically modulate AgRP neurons. Next, to determine whether the delay in puberty onset occurring in response to neonatal underfeeding could be overcome by inhibiting AgRP neuronal activity, mice were raised in large (neonatally underfed) or normal litter sizes. The delay in puberty from underfeeding was completely reversed in CNO‐treated AgRP‐hM4Di male mice. These data highlight the inhibitory role of AgRP neurons to delay puberty onset when undernutrition occurs during the neonatal period, at least in male mice. Trail registration number: JNE‐22‐0081‐OA.R2 [ABSTRACT FROM AUTHOR]

Female anti-Müllerian hormone (AMH) overexpressing (Thy1.2-AMHTg/0) mice experience fetal resorption (miscarriage) by mid-gestation. This study examined whether the ovary, uterine implantation sites and hypothalamus are potential sites of AMH action, as AMH type-2 receptor (AMHR2) expression is reported in each tissue. Pregnancy in Thy1.2-AMHTg/0 mice was compared to wild-type (WT) mice via histological examination of implantation sites, hormone assays, embryo culture and embryo transfer. Uterine AMH and AMHR2 expression was examined by RT-qPCR and immunohistochemistry. The first signs of fetal resorption in the Thy1.2-AMHTg/0 dams occurred at embryonic day 9.5 (E9.5) with 100% of fetuses resorbing by E13.5. Cultured embryos from Thy1.2-AMHTg/0 dams had largely normal developmental rates but a small proportion experienced a minor developmental delay relative to embryos from WT dams. However, embryos transferred from WT donor females always failed to survive to term when transferred into Thy1.2-AMHTg/0 dams. Amh and Amhr2 mRNA was detected in the gravid uterus but at very low levels relative to expression in the ovaries. Progesterone and estradiol levels were not significantly different between WT and Thy1.2-AMHTg/0 dams during pregnancy but luteinizing hormone (LH) levels were significantly elevated in Thy1.2-AMHTg/0 dams at E9.5 and E13.5 relative to WT dams. Collectively, these experiments suggest that AMH overexpression does not cause fetal resorption through an effect on oocytes or preimplantation embryo development. The Thy1.2-AMHTg/0 fetal resorption phenotype is nearly identical to that of transgenic LH overexpression models, suggesting that neuroendocrine mechanisms may be involved in the cause of the miscarriage. [ABSTRACT FROM AUTHOR]

Background: Organizations of all types require the use of teams. Poor team member engagement costs billions of US dollars annually. Objective: This study aimed to explain how team building can be accomplished with team video gaming based on a team cohesion model enhanced by team flow theory. Methods: In this controlled experiment, teams were randomly assigned to a team video gaming treatment or a control treatment. Team productivity was measured during both pretreatment and posttreatment team tasks. After the pretest, teams who were involved in the team video gaming treatment competed against other teams by playing the Halo or Rock Band video game for 45 minutes. After the pretest, teams in the control treatment worked alone for 45 minutes. Then, all teams completed the posttest team activity. This same experimental protocol was conducted on 2 different team tasks. Results: For both tasks, teams in the team video gaming treatment increased their productivity significantly more (F1=8.760, P=.004) on the posttest task than teams in the control treatment. Our flow-based theoretical model explained team performance improvement more than twice as well (R²=40.6%) than prior related research (R²=18.5%). Conclusions: The focused immersion caused by team video gaming increased team performance while the enjoyment component of flow decreased team performance on the posttest. Both flow and team cohesion contributed to team performance, with flow contributing more than cohesion. Team video gaming did not increase team cohesion, so team video gaming effects are independent of cohesion. Team video gaming is a valid practical method for developing and improving newly formed teams. [ABSTRACT FROM AUTHOR]

The adipocyte-derived 'satiety promoting' hormone, leptin, has been identified as a key central regulator of body weight and fertility, such that its absence leads to obesity and infertility. Plasma leptin levels reflect body adiposity, and therefore act as an 'adipostat', whereby low leptin levels reflect a state of low body adiposity (under-nutrition/starvation) and elevated leptin levels reflect a state of high body adiposity (over-nutrition/obesity). While genetic leptin deficiency is rare, obesity-related leptin resistance is becoming increasingly common. In the absence of adequate leptin sensitivity, leptin is unable to exert its 'anti-obesity' effects, thereby exacerbating obesity. Furthermore, extreme leptin resistance and consequent low or absent leptin signalling resembles a state of starvation and can thus lead to infertility. However, leptin resistance occurs on a spectrum, and it is possible to be resistant to leptin's metabolic effects while retaining leptin's permissive effects on fertility. This may be because leptin exerts its modulatory effects on energy homeostasis and reproductive function through discrete intracellular signalling pathways, and these pathways are differentially affected by the molecules that promote leptin resistance. This review discusses the potential mechanisms that enable leptin to exert differential control over metabolic and reproductive function in the contexts of healthy leptin signalling and of diet-induced leptin resistance. [ABSTRACT FROM AUTHOR]