Twelve tips to leverage AI for efficient and effective medical question generation: A guide for educators using Chat GPT.

BACKGROUND: Crafting quality assessment questions in medical education is a crucial yet time-consuming, expertise-driven undertaking that calls for innovative solutions. Large language models (LLMs), such as ChatGPT (Chat Generative Pre-Trained Transformer), present a promising yet underexplored avenue for such innovations. AIMS: This study explores the utility of ChatGPT to generate diverse, high-quality medical questions, focusing on multiple-choice questions (MCQs) as an illustrative example, to increase educator's productivity and enable self-directed learning for students. DESCRIPTION: Leveraging 12 strategies, we demonstrate how ChatGPT can be effectively used to generate assessment questions aligned with Bloom's taxonomy and core knowledge domains while promoting best practices in assessment design. CONCLUSION: Integrating LLM tools like ChatGPT into generating medical assessment questions like MCQs augments but does not replace human expertise. With continual instruction refinement, AI can produce high-standard questions. Yet, the onus of ensuring ultimate quality and accuracy remains with subject matter experts, affirming the irreplaceable value of human involvement in the artificial intelligence-driven education paradigm.

Diagnosis and management of polycystic ovary syndrome: Perspectives of clinicians in Singapore.

INTRODUCTION: To harmonise the diagnostic processes of polycystic ovary syndrome (PCOS) and enable clinicians to provide better patient care, it is critical to understand the knowledge gaps in PCOS diagnosis. We evaluated how clinicians in endocrinology, family medicine, general practice and gynaecology diagnose PCOS. METHODS: This cross-sectional survey involved 208 clinicians from specific subspecialties across various healthcare settings in Singapore. RESULTS: A total of 160 responses were included in the final analysis. Among all the diagnostic criteria, the Rotterdam 2003 criteria was most frequently used (66.3%). More than half of the gynaecologists reported having a standardised workplace protocol while the majority from other specialties reported otherwise. A large percentage of respondents (60.5%) were unable to identify the correct PCOS clinical features, which is concerning. Only 8.8% of respondents used clinical and biochemical hyperandrogenism, menstrual disturbances and pelvic ultrasound to diagnose PCOS without performing unnecessary and incorrect investigations. Most clinicians recognised insulin resistance/type 2 diabetes mellitus and fertility problems as complications while only a few recognised psychological complications. Many clinicians (37.3%) sought standardisation of PCOS diagnosis and management guidelines for improvement in PCOS care and 81.9% of respondents would appreciate standardised educational materials. CONCLUSION: This is the first study to the best of our knowledge that gives an insight into the diagnostic and management processes of PCOS among various healthcare institutions in Singapore. This study calls for greater harmonisation of diagnostic processes and holistic evidence-based management of patients with PCOS through standardised workplace protocols and patient education resources.

Disruptive behavior in a high-power distance culture and a three-dimensional framework for curbing it.

BACKGROUND: Disruptive behavior can harm high-quality care and is prevalent in many Western public health systems despite increasing spotlight on it. Comparatively less knowledge about it is available in Asia, a region commonly associated with high-power distance, which may limit its effectiveness in addressing disruptive behavior. PURPOSE: The aim of this study was to develop a comprehensive framework for tackling disruptive behavior among health care professionals in a public health system. METHODOLOGY: A nationwide cross-sectional study relying on the Nurse-Physician Relationship Survey was conducted in Singapore. Four hundred eighty-six public health care professionals responded. RESULTS: Two hundred ninety-eight doctors (95.5%) and 163 nurses (93.7%) had witnessed a form of disruptive behavior. Doctors observed disruptive behavior committed by other doctors and nurses much more frequently than did nurses. Doctors made stronger associations between disruptive behavior and negative employee outcomes and between disruptive behavior and negative patient outcomes. Qualitative analyses of participants' open-ended answers produced a multipronged three-dimensional approach for tackling disruptive behavior: (a) deterrent measures, (b) development of knowledge and skills, and (c) demonstration of organizational commitment through proper norms, empathizing with staff, and structural reforms. PRACTICE IMPLICATIONS: Disruptive behavior is a multifaceted problem requiring a multipronged approach. Our three-dimensional framework is a comprehensive approach for giving health care professionals the capability, opportunity, and motivation to address disruptive behavior effectively.

TRAF6 Mediates Suppression of Osteoclastogenesis and Prevention of Ovariectomy-Induced Bone Loss by a Novel Prenylflavonoid.

Given the limitations of current therapeutic options for postmenopausal osteoporosis, there is a need for alternatives with minimal adverse effects. In this study, we evaluated the effects of icaritin (ICT), a natural prenylflavonoid, on osteoclastogenesis both in vitro and in an ovariectomized (OVX) rat model and investigated its underlying molecular mechanism(s) of action. ICT inhibited osteoclast formation in two osteoclast precursor models, RAW 264.7 mouse monocyte cell line and human PBMC. ICT also inhibited sealing zone and resorption pit formation in a dose-dependent manner. Mechanistically, ICT inhibited RANKL-induced NF-κB and MAPK/AP-1 pathways to suppress gene expression of nuclear factor of activated T cells (NFAT)c1, the master transcription regulator of osteoclast differentiation. ICT, by inhibiting the TRAF6/c-Src/PI3K pathway, suppressed NADPH oxidase-1 activation to attenuate intracellular ROS production and downregulate calcineurin phosphatase activity. As a result, NFATc1 nuclear translocation and activity was suppressed. Crucially, ICT promoted proteasomal degradation of TRAF6, the critical adaptor protein that transduces RANKL/RANK signaling, and the inhibitory effect of ICT on osteoclastogenesis was reversed by the proteasomal inhibitor MG 132. ICT administration inhibited OVX-induced bone loss and resorption by suppressing osteoclast formation and activity. Consistent with cellular studies, ICT downregulated TRAF6 and NFATc1 protein expression in CD11b+ /Gr-1-/low osteoclast precursors isolated from OVX rats. Put together, we present novel findings that ICT, by downregulating TRAF6, coordinates inhibition of NF-κB, MAPK/AP-1, and ROS signaling pathways to reduce expression and activity of NFATc1. These results demonstrate the potential of ICT for treatment of postmenopausal osteoporosis and point to TRAF6 as a promising target for novel anti-osteoporotic drugs. © 2017 American Society for Bone and Mineral Research.

Cellular and Animal Studies: Insights into Pathophysiology and Therapy of PCOS.

Basic science studies have advanced our understanding of the role of key enzymes in the steroidogenesis pathway and those that affect the pathophysiology of PCOS. Studies with ovarian theca cells taken from women with PCOS have demonstrated increased androgen production due to increased CYP17A1 and HSD3B2 enzyme activities. Furthermore, overexpression of DENND1A variant 2 in normal theca cells resulted in a PCOS phenotype with increased androgen production. Notably, cellular steroidogenesis models have facilitated the understanding of the mechanistic effects of pharmacotherapies, including insulin sensitizers (e.g., pioglitazone and metformin) used for the treatment of insulin resistance in PCOS, on androgen production. In addition, animal models of PCOS have provided a critical platform to study the effects of therapeutic agents in a manner closer to the physiological state. Indeed, recent breakthroughs have demonstrated that natural derivatives such as the dietary medium-chain fatty acid decanoic acid (DA) can restore estrous cyclicity and lower androgen levels in an animal model of PCOS, thus laying the platform for novel therapeutic developments in PCOS. This chapter reviews the current understanding on the pathways modulating androgen biosynthesis, and the cellular and animal models that form the basis for preclinical research in PCOS, and sets the stage for clinical research.

Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health.

The morbidity and mortality associated with fractures due to osteoporosis or "porous bone" contributes significantly to global healthcare costs and will increase exponentially with ageing populations. In menopausal women, the onset of menopause and rapid estrogen withdrawal leads to osteoporotic fractures. Healthy bone requires the coordinated remodeling function of osteoclasts, osteoblasts, and osteocytes in the basic bone multicellular unit, regulated by estrogen, RANKL/OPG, ROS, growth factors, and other kinase signaling pathways. Anti-osteoporotic drugs in current use such as hormone replacement therapy, selective estrogen receptor modulators, and bisphosphonates are designed to target these pathways, but all have their limitations. Extracts of the dried aerial parts of the traditional Chinese medicinal plant Epimedium (Berberidaceae) has long been used for bone health. Some nine Epimedium prenylflavonoid compounds have been reported to target estrogen signaling and other bone morphogenesis pathways in mesenchymal stem cell, osteoblast, and osteoclast cell lineages. Epimedium prenylflavonoids and enriched extracts can exert beneficial effects on bone health in estrogen-deficient and other osteoporosis animal models. The development of sensitive and rapid mass chromatographic techniques to quantify compounds extracted from Epimedium, including icariin and icaritin, has been used to standardize production and to study the pharmacokinetics and metabolism of Epimedium in animal models and humans. Recent clinical trials have reported positive effects on bone health, suggesting that compounds or extracts of Epimedium have the potential to be developed as agents, alone or in combination with other drugs, to prevent or delay the onset of osteoporosis and reduce the risk of hip fractures.

Polymorphisms of anti-Müllerian hormone signaling pathway in healthy Singapore women: population differences, endocrine effects and reproductive outcomes.

In order to study the association of genetic polymorphisms of anti-Müllerian hormone (AMH) signaling pathway with endocrine changes and pregnancy outcomes, a total of 213 women of reproductive ages were recruited according to our inclusion and exclusion criteria between November 2011 and September 2014 in Singapore. Genotyping studies were performed using a minor groove binder primer/probe Taqman assay. The allele frequencies of the AMH Ile(49)Ser and AMHR2 -482A > G polymorphisms were analyzed in relation to female reproductive hormone levels, ovarian parameters, menstrual cycle lengths and pregnancy outcomes. AMH Ser allele frequency and AMHR2 G allele frequency of our Singapore population were compared with those of other populations reported in HapMap. The genotype distributions and allele frequencies for the AMH Ile(49)Ser and AMHR2 -482A > G polymorphisms were not associated with estradiol (E2) levels, ovarian parameters, menstrual cycle length, or pregnancy outcomes in our cohort. Our findings suggest that genetic variants in the AMH signal transduction pathway have population differences but do not appear to have significant effects on ovarian, endocrine, metabolic parameters and reproductive outcomes.

A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome.

Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%-70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3ß-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMP-stimulated pathway. Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS.

Antimüllerian hormone, antral follicle count and ovarian volume predict menstrual cycle length in healthy women.

OBJECTIVE: Although menstrual cycle length is one of the main concerns of women and may have important health consequences, little is known about its predictors. The aim of this study was to identify predictors of menstrual cycle length variability in healthy women. DESIGN: Prospective cross-sectional study. PATIENTS: Two hundred healthy women aged 21-45. MEASUREMENTS: A questionnaire was administered to determine lifestyle factors. Ovarian parameters, metabolic parameters, pituitary hormones, sex steroids and antimüllerian hormone (AMH) were measured. RESULTS: Women with long (≥35 days) and normal (25-34 days) menstrual cycles had >5-fold and >2-fold higher serum AMH levels, respectively, compared to those with short cycles (<25 days). Menstrual cycle length was associated with age but not lifestyle factors. Only one factor group (AMH, antral follicle count [AFC], ovarian volume, testosterone and LH) was significantly associated with menstrual cycle length. Within this factor group, only the ovarian parameters (AMH, AFC, ovarian volume) predicted menstrual cycle length. Each SD increase in AMH (32·9 pmol/l) and ovarian volume (2·29 cm(3) ) was associated with 2·80-fold (95% CI: 1·67-4·69) and 1·62-fold (95% CI: 1·08-2·43) increased risks, respectively, for longer menstrual cycles. CONCLUSIONS: AMH, AFC and ovarian volume are positively associated with menstrual cycle length in healthy women. Our identification of AMH as an independent predictor of menstrual cycle length puts forth a new notion of utilizing menstrual cycle length to predict possible AMH-dependent/-associated outcomes. In addition, this novel relationship may facilitate the interpretation of AMH levels and its clinico-pathological significance across different centres.

Phytoplankton blooms: an overlooked marine source of natural endocrine disrupting chemicals.

BACKGROUND: We had previously reported high androgenic and estrogenic activities in seawaters in confined clusters close to Singapore. Further investigations revealed a hitherto unsuspected link between estrogenic/androgenic activity and net phytoplankton count. OBJECTIVE: The primary objective of this study was to investigate the cause of a correlation between net phytoplankton and endocrine activity, and corroborate this observation, and rule out other possible confounding factors. Our secondary objective was to study if these estrogenic secretions can impact human health. METHODS: Five species of phytoplankton, Gymnodinium catenatum, Prorocentrum minimum, Alexandrium leei, Chattonella marina, and Fibrocapsa japonica, were isolated from Singapore waters and mass cultured and the cells and culture media screened for estrogenic and androgenic activity using human cell-based bioassays. RESULTS: The raphidophytes C. marina and F. japonica displayed significant estrogenic activity whilst the dinoflagellates G. catenatum and P. minimum displayed significant androgenic activity in both the cell extracts and the cell culture media extract. CONCLUSIONS: Our data shows that selected phytoplankton isolates are potent secretors of estrogenic and androgenic substances, which are potential endocrine disrupting chemicals (EDCs). As the harmful nature of EDCs is largely due to their bioaccumulation in the aquatic food chain our findings imply that the impact of these phytoplankton secretions needs to be investigated especially for seafoods, which are only a single trophic level away from phytoplankton. Alternatively, should these phytoplankton-origin EDCs not accumulate through marine food chains to significantly impact humans or marine mammals, our results indicate that functional assays could greatly over-estimate the risk from naturally occurring EDCs produced by marine phytoplankton. It remains to be determined if these EDCs affect zooplankton and other organisms that directly feed on marine phytoplankton, or if the secreted EDCs can directly impact other marine fauna.

Selective estrogen receptor modulator effects of epimedium extracts on breast cancer and uterine growth in nude mice.

Epimedium is popularly used in traditional Chinese medicine to treat sexual dysfunction, menstrual irregularity, and osteoporosis. The estrogenic effects of the prenylated flavonoids of Epimedium make it an attractive alternative for hormone replacement therapy. Here, we examined the therapeutic potential of the estrogenic herb extract of Epimedium brevicornum as an alternative to hormone replacement therapy in a breast cancer mouse model. To that end, athymic and ovariectomized female nude mice were subcutaneously injected into the mammary fat pads with MCF-7 breast cancer cells, randomly grouped and fed with soy-free feeds, alone or in combination with ethinyl estradiol or different doses of the estrogenic herb extract of E. brevicornum. Our findings demonstrate that unlike ethinyl estradiol, it did not promote the growth of breast cancer xenograft volume and weight, with the highest dose showing a significant reduction in growth and ERα protein content. Moreover, the extract increased uterine weight at the lowest dose, while higher doses had no effects. Put together, our data shows for the first time that despite the estrogenic activity of E. brevicornum, its action is largely tissue specific and dose-dependent. Our data on E. brevicornum presents in vivo evidence for its selective estrogen receptor modulator effect and warrants exploration of its use as an alternative to hormone replacement therapy in menopausal women.

A shark liver gene-derived active peptide expressed in the silkworm, Bombyx mori: preliminary studies for oral administration of the recombinant protein.

Active peptide from shark liver (APSL) is a cytokine from Chiloscyllium plagiosum that can stimulate liver regeneration and protects the pancreas. To study the effect of orally administered recombinant APSL (rAPSL) on an animal model of type 2 diabetes mellitus, the APSL gene was cloned, and APSL was expressed in Bombyx mori N cells (BmN cells), silkworm larvae and silkworm pupae using the silkworm baculovirus expression vector system (BEVS). It was demonstrated that rAPSL was able to significantly reduce the blood glucose level in mice with type 2 diabetes induced by streptozotocin. The analysis of paraffin sections of mouse pancreatic tissues revealed that rAPSL could effectively protect mouse islets from streptozotocin-induced lesions. Compared with the powder prepared from normal silkworm pupae, the powder prepared from pupae expressing rAPSL exhibited greater protective effects, and these results suggest that rAPSL has potential uses as an oral drug for the treatment of diabetes mellitus in the future.

Tumor cell redox state and mitochondria at the center of the non-canonical activity of telomerase reverse transcriptase.

Telomerase (hTERT) activation in cancer cells is an invariable finding resulting in the maintenance of telomere lengths and enhanced replicative capacity. Therefore a variety of therapeutic approaches are being investigated to target hTERT, such as hTERT-promoter driven expression of apoptosis inducing genes, inhibiting telomeric RNA (hTR), and anti-sense or siRNA mediated gene silencing. Whereas, the conventional oncogenic role of hTERT has been linked to its ability to induce replicative senescence and immortalization, evidence is accumulating to support non-canonical activity of hTERT in cancer cells. To that end, hTERT has been implicated in redox-mediated events and its expression has been shown to impact cellular redox status via the recruitment of the mitochondria, a critical intracellular source of reactive oxygen species (ROS). Further evidence in support of the role of mitochondria in hTERT biology comes from findings demonstrating localization of hTERT to the mitochondria, and the ability of hTERT inhibitors to induce mitochondrial-dependent apoptosis in target cells. Here we review the emerging evidence to support the involvement of the mitochondria and intracellular ROS as critical mediators of the non-canonical functions/activity of hTERT with potential implications for its therapeutic targeting in cancer cells.