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Glucocorticoid (GC) hormones are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and insufficient GC associated with adverse effects on health. Current assessment of GC status is primarily clinical, often in conjunction with serum cortisol values, which may be stimulated or suppressed depending on the GC disturbance being assessed. In the setting of extreme perturbations in cortisol levels ie, markedly low or high levels, symptoms and signs of GC dysfunction may be overt. However, when disturbances in cortisol GC status values are less extreme, such as when assessing optimization of a GC replacement regimen, signs and symptoms can be more subtle or nonspecific. Current tools for assessing GC status are best suited to identifying profound disturbances but may lack sensitivity for confirming optimal GC status. Moreover, single cortisol values do not necessarily reflect an individual's GC status, as they are subject to inter- and intraindividual variation and do not take into account the pulsatile nature of cortisol secretion, variation in binding proteins, or local tissue concentrations as dictated by 11beta-hydroxysteroid dehydrogenase activity, as well as GC receptor sensitivity. In the present review, we evaluate possible alternative methods for the assessment of GC status that do not solely rely on the measurement of circulating cortisol levels. We discuss the potential of changes in metabolomic profiles, micro RNA, gene expression, and epigenetic and other novel biomarkers such as growth differentiating factor 15 and osteocalcin, which could in the future aid in the objective classification of GC status. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic ovarian syndrome (PCOS) is the commonest endocrine condition affecting reproductive age women. Many biomarkers may aid assessment and management, however evidence is limited on their utility in clinical practice. We conducted a review of systematic reviews to identify the most useful biomarkers in the clinical management of PCOS. Methods: We searched MEDLINE, EMBASE, CENTRAL and HTA until August 2023 for reviews evaluating biomarkers in PCOS women compared to healthy controls. Methodological quality was assessed using the AMSTAR2 tool. We reported pooled evidence for each biomarker with 95% confidence intervals from the most recent, up‐to‐date, and best quality review. Results: From 3360 citations, we included 75 systematic reviews (88 biomarkers, 191,792 women). Most reviews (50/75, 67%) were moderate quality, but reported high heterogeneity (66/75, 88%). We identified 63 abnormal biomarkers in women with PCOS versus healthy controls. Of these, 22 core biomarkers could help evaluate the multisystemic impact of PCOS and inform patient management and surveillance: dehydroepiandrosterone, prolactin, sex hormone‐binding globulin, total and free testosterone, anti‐Mullerian hormone, systolic and diastolic blood pressure, c‐reactive protein, fibrinogen, oral glucose tolerance test, homoeostatic model assessment‐insulin resistance index, fasting insulin, total cholesterol, triglycerides, lipoprotein(a), HDL, LDL, non‐HDL‐cholesterol, ferritin, iron, and 25‐hydroxy‐vitamin D. Conclusion: We identified 22 core biomarkers assessing the multisystemic impact of PCOS and inform its clinical management. Future research is required to establish validated healthcare pathways. [ABSTRACT FROM AUTHOR]

Virtual reality (VR) holds unmeasured potential as a multicomponent tool for managing chronic pain by adapting conventional in-person biopsychosocial pain management strategies into one virtual space. We review recent evidence showcasing the successful integration of cognitive behavioural therapy, mindfulness-based stress reduction, embodiment techniques, and physical therapy into VR environments, demonstrating positive outcomes in patients with chronic pain. We propose that future clinical and basic research build on this by integrating pain neuroscience techniques to help better understand pathophysiological pain mechanisms and treatment response. This could help facilitate early assessment and personalised treatment of chronic pain using a VR-based biopsychosocial approach. [ABSTRACT FROM AUTHOR]

Introduction Kisspeptin is recognized to play a pivotal role in the regulation of reproductive hormone secretion following 2 landmark reports in 2003, demonstrating that decreased signaling of its G protein-coupled [...], BACKGROUND. Kisspeptin is a key regulator of hypothalamic gonadotropin-releasing hormone (GnRH) neurons and is essential for reproductive health. A specific kisspeptin receptor (KISS1R) agonist could significantly expand the potential clinical utility of therapeutics targeting the kisspeptin pathway. Herein, we investigate the effects of a KISS1R agonist, MVT-602, in healthy women and in women with reproductive disorders. METHODS. We conducted in vivo and in vitro studies to characterize the action of MVT-602 in comparison with native kisspeptin-54 (KP54). We determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n = 9), and in women with polycystic ovary syndrome (PCOS; n = 6) or hypothalamic amenorrhea (HA; n = 6). Further, we investigated their effects on KISS1R-mediated inositol monophosphate ([IP.sub.1]) and [Ca.sup.2+] signaling in cell lines and on action potential firing of GnRH neurons in brain slices. RESULTS. In healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs. 4.7 hours; P = 0.0002), with correspondingly increased AUC of LH exposure (169.0 vs. 38.5 IU-h/L; P = 0.0058). LH increases following MVT-602 were similar in PCOS and healthy women, but advanced in HA (P = 0.004). In keeping with the clinical data, MVT-602 induced more potent signaling of KISS1R-mediated [IP.sub.1] accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs. 55 minutes; P = 0.0012). CONCLUSION. Taken together, these clinical and mechanistic data identify MVT-602 as having considerable therapeutic potential for the treatment of female reproductive disorders. TRIAL REGISTRATION. International Standard Randomised Controlled Trial Number (ISRCTN) Registry, ISRCTN21681316. FUNDING. National Institute for Health Research and NIH.

There has been a wealth of investigation into the use of online multiple-choice questions as a means of summative assessment, however the research into the use of formative MCQs by the same mode of delivery still remains patchy. Similarly, research and implementation has been largely concentrated within the Sciences and Medicine rather than the more discursive subjects within the Humanities and Social Sciences. The INQUIRE (Interactive Questions Reinforcing Education) Evaluation Project was jointly conducted by two groups at the University of Oxford--the Said Business School and the Academic Computing Development Team to evaluate the use of online MCQs as a mechanism to reinforce and extend student learning. This initial study used a small set of highly focused MCQ tests that were designed to complement an introductory series of first-year undergraduate management lectures. MCQ is a simple and well-established technology, and hence the emphasis was very much on situating the tests within the student experience. The paper will cover how the online MCQs are intended to fit into the Oxford Undergraduate study agenda, and how a simple evaluation was executed and planned to investigate their usage and impact. The chosen method of evaluation was to combine focus groups with automated online methods of tracking, and the paper discusses the findings of both of these. (Contains 1 note.)

Introduction Unraveling the intrinsic links among sex, emotion, and reproduction relies on a focused exploration of putative factors. Identifying a factor that unites these fundamental components of human behavior has [...], BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).