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BackgroundNon-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, affecting 25-30% of the general population globally. The condition is even more prevalent in individuals with obesity and is frequently linked to the metabolic syndrome. Given the known associations between the metabolic syndrome and common mental health issues, it is likely that such a relationship also exists between NAFLD and mental health problems. However, studies in this field remain limited. Accordingly, the aim of this systematic review and meta-analysis was to explore the prevalence of one or more common mental health conditions (i.e., depression, anxiety, and/or stress) in adults with NAFLD.MethodsPubMed, EBSCOhost, ProQuest, Ovid, Web of Science, and Scopus were searched in order to identify studies reporting the prevalence of depression, anxiety, and/or stress among adults with NAFLD. A random-effects model was utilized to calculate the pooled prevalence and confidence intervals for depression, anxiety and stress.ResultsIn total, 31 studies were eligible for inclusion, involving 2,126,593 adults with NAFLD. Meta-analyses yielded a pooled prevalence of 26.3% (95% CI: 19.2 to 34) for depression, 37.2% (95% CI: 21.6 to 54.3%) for anxiety, and 51.4% (95% CI: 5.5 to 95.8%) for stress among adults with NAFLD.ConclusionThe present findings suggest a high prevalence of mental health morbidity among adults with NAFLD. Given the related public health impact, this finding should prompt further research to investigate such associations and elucidate potential associations between NAFLD and mental health morbidity, exploring potential shared underlying pathophysiologic mechanisms.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021288934.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder impacting women’s health and quality of life. This scoping review explores the use of the Internet of Things (IoT) in PCOS management. Results were grouped into six domains of the IoT: mobile apps, social media, wearables, machine learning, websites, and phone-based. A further domain was created to capture participants’ perspectives on using the IoT in PCOS management. Mobile apps appear to be useful for menstrual cycle tracking, symptom recording, and education. Despite concerns regarding the quality and reliability of social media content, these platforms may play an important role in disseminating PCOS-related information. Wearables facilitate detailed symptom monitoring and improve communication with healthcare providers. Machine learning algorithms show promising results in PCOS diagnosis accuracy, risk prediction, and app development. Although abundant, PCOS-related content on websites may lack quality and cultural considerations. While patients express concerns about online misinformation, they consider online forums valuable for peer connection. Using text messages and phone calls to provide feedback and support to PCOS patients may help them improve lifestyle behaviors and self-management skills. Advancing evidence-based, culturally sensitive, and accessible IoT solutions can enhance their potential to transform PCOS care, address misinformation, and empower women to better manage their symptoms.

BackgroundGestational diabetes mellitus (GDM) is a prevalent condition where diabetes is diagnosed during pregnancy, affecting both maternal and fetal outcomes. Retinol-binding protein 4 (RBP4) is a circulating adipokine which belongs to the lipocalin family and acts as a specific carrier protein that delivers retinol (vitamin A) from the liver to the peripheral tissues. Growing data indicate that circulating RBP4 levels may positively correlate with GDM. Thus, this systematic review and meta-analysis aimed to investigate the potential relationship between circulating RBP4 levels and GDM when measured at various stages of pregnancy.MethodsMEDLINE, CINAHL, EMCARE, EMBASE, Scopus, and Web of Science databases were searched to identify studies comparing pregnant women with and without GDM, whose circulating RBP4 levels were measured in at least one pregnancy trimester. Findings were reported using standardized mean difference (SMD) and random-effects models were used to account for variability among studies. Furthermore, the risk of bias was assessed using the RoBANS tool.ResultsOut of the 34 studies identified, 32 were included in the meta-analysis (seven with circulating RBP4 levels measured in the first trimester, 19 at 24–28 weeks, and 14 at >28 weeks of pregnancy). RBP4 levels were statistically higher in the GDM group than in controls when measured during all these pregnancy stages, with the noted RBP4 SMD being 0.322 in the first trimester (95% CI: 0.126–0.517; p 28 weeks of gestation (95% CI: 0.252–1.498; p = 0.006; 870 GDM cases vs. 1942 non-GDM controls). Significant study heterogeneity was noted for all three pregnancy timepoints.ConclusionThe present findings indicate consistently higher circulating RBP4 levels in GDM cases compared to non-GDM controls, suggesting the potential relevance of RBP4 as a biomarker for GDM. However, the documented substantial study heterogeneity, alongside imprecision in effect estimates, underscores the need for further research and standardization of measurement methods to elucidate whether RBP4 can be utilized in clinical practice as a potential GDM biomarker.Systematic review registrationPROSPERO (CRD42022340097: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022340097).

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.

Representing a growing ‘silent epidemic’, non-alcoholic fatty liver disease (NAFLD) affects around 25–30% of the general population. Alarmingly, NAFLD increases the risk of cardiovascular disease, both independently and through its strong associations with obesity, type 2 diabetes, and metabolic syndrome, whilst posing a substantial burden from an economic and health-related quality of life perspective. Moreover, growing evidence links NAFLD to common mental health disorders including depression, anxiety, and stress. In this context, recent clinical and research attention further focuses on potential additional problems faced by patients with NAFLD, such as perceived stigma, lack of awareness regarding the condition, and possible feelings of loneliness and isolation that might emerge from unmet support needs. To date, despite a wealth of literature on NAFLD, management of the condition remains challenging and not straightforward, with most cases in primary care being treated with lifestyle modification on top of any other comorbidity treatment. However, for many patients with NAFLD, weight loss is hard to accomplish and/or sustain (e.g., patients may lack the skills, confidence, and motivation required to adhere to dietary changes, and/or may have problems limiting opportunities for increased physical activity). Therefore, tailored interventions which are manageable from the perspective of the individual patient with NAFLD could glean greater results. Accordingly, although there is a lack of research exploring the potential benefits of person-centered and compassion-based approaches to the management of NAFLD, in the present review, we draw on evidence from methods utilized in the treatment of other chronic conditions in postulating the view that such approaches might prove beneficial in the future management of NAFLD.

Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR dysregulation in endometriosis and EAOCs, investigating cancer driver gene mutations and their potential interaction with the mTOR pathway. Additionally, we explore the complex pathogenesis of transformation, considering environmental, hormonal, and epigenetic factors. We then discuss postmenopausal endometriosis pathogenesis and propensity for malignant transformation. Finally, we summarize the current advancements in mTOR-targeted therapeutics for endometriosis and EAOCs.

Abstract Background Dysfunctional adipose tissue (AT) is known to contribute to the pathophysiology of metabolic disease, including type 2 diabetes mellitus (T2DM). This dysfunction may occur, in part, as a consequence of gut-derived endotoxaemia inducing changes in adipocyte mitochondrial function and reducing the proportion of BRITE (brown-in-white) adipocytes. Therefore, the present study investigated whether endotoxin (lipopolysaccharide; LPS) directly contributes to impaired human adipocyte mitochondrial function and browning in human adipocytes, and the relevant impact of obesity status pre and post bariatric surgery. Methods Human differentiated abdominal subcutaneous (AbdSc) adipocytes from participants with obesity and normal-weight participants were treated with endotoxin to assess in vitro changes in mitochondrial function and BRITE phenotype. Ex vivo human AbdSc AT from different groups of participants (normal-weight, obesity, pre- and 6 months post-bariatric surgery) were assessed for similar analyses including circulating endotoxin levels. Results Ex vivo AT analysis (lean & obese, weight loss post-bariatric surgery) identified that systemic endotoxin negatively correlated with BAT gene expression (p

Background: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). Methods: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. Results: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. Conclusions: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer.

Non-alcoholic fatty liver disease (NAFLD) is the most frequently occurring chronic liver disease, affecting approximately 25–30% of the adult general population worldwide. NAFLD reflects excess hepatic accumulation of fat in the absence of increased alcohol intake, and, due to its close association with obesity, is frequently referred to as the ‘hepatic manifestation’ of metabolic syndrome. Indeed, a high percentage of individuals with NAFLD present with a combination of the cardio-metabolic comorbidities that are associated with the metabolic syndrome. In addition to its well-established link with the metabolic syndrome and increased risk for cardiovascular disease, NAFLD has also been associated with certain mental health issues (e.g., depression and stress). Although this link is now being increasingly recognized, there are still unmet needs regarding the holistic management of patients with NAFLD, which could further contribute to feelings of social isolation and loneliness. The latter conditions are also increasingly reported to pose a substantial risk to overall health and quality of life. To date, there is limited research that has explored these issues among patients with NAFLD, despite existing data which indicate that perceived loneliness and isolation may pose an additional health risk. Notably, many features associated with NAFLD have been related to these concepts, such as perceived stigma, fatigue, stress, and confusion regarding this diagnosis. As such, this review aimed to assess such potential problems faced by patients with NAFLD, and to explore the possibility of unmet support needs which could lead to perceived social isolation. Moreover, the importance of a compassionate approach towards such patients is discussed, together with potential coping strategies. Future research directions and the need for a multidisciplinary approach are also highlighted.

Background Long-term adherence to exercise is often poor for people with coronary heart disease (CHD) who have completed supervised, centre-based cardiac rehabilitation. The aim of this study is to assess the feasibility of a remotely prescribed, delivered and monitored cardiac rehabilitation intervention using a wearable device to support long-term adherence to exercise and physical activity during maintenance of cardiac rehabilitation. Methods After completing cardiac rehabilitation, 30 participants with CHD, will be randomised (1:1) to an intervention ( n = 15) or a usual care group ( n = 15) in a 12-month feasibility randomised controlled trial (RCT). The intervention will comprise of an exercise consultation, personalised exercise prescription delivered via a wearable activity monitor using biometric feedback, regular monitoring via check-ins, and feedback text-messages for 6-months. Participants will be assessed at baseline (following completion of cardiac rehabilitation) and at three-, six-, and 12-months post-randomisation. The primary outcome will be feasibility, including assessment of eligibility, recruitment, adherence, and acceptability. Secondary outcomes will include exercise capacity, physical activity behaviours, cardiovascular disease risk and quality of life. Semi-structured interviews will be conducted at three-, six-, and 12-months post-randomisation (and with those who drop-out) to explore the acceptability of the study intervention and procedures. A questionnaire will be offered to those who decline participation. Discussion The MAINTAIN study will evaluate the feasibility of conducting a future definitive multi-centre RCT testing a remotely prescribed and monitored long-term mHealth maintenance exercise programme, versus usual care, for people with CHD who have completed cardiac rehabilitation. Trial registration number ClinicalTrials.gov, NCT05292287. Registered on 22/03/2022

Abstract Background Team-based learning (TBL) combines active and collaborative learning, while incorporating aspects of the flipped classroom approach and problem-based learning. The COVID-19 pandemic presented certain challenges in the delivery of TBL in class. In this study, we investigated the impact of TBL on the academic performance of final year Biomedical Sciences’ undergraduate students in the context of an “Endocrine Disorders” study block. We did so by comparing the classical in-person approach and online delivery due to the COVID-19 pandemic. Methods A non-compulsory TBL session was introduced to the curriculum of this block, which followed the traditional 2-h lecture delivery. Comparative analysis was performed for the exam and coursework performance of students who attended the TBL sessions (online and in-person) and those that did not. Results Both cohorts of students who attended either in-person (n = 66) or online TBL sessions (n = 109) performed significantly better in their exams (p

Abstract Background Double Diabetes (DD), type 1 diabetes (T1DM) + insulin resistance (IR), is associated with increased risk of micro/macro-vascular complications and mortality. Obesity can contribute to the development of DD. This study explored the prevalence of overweight/obesity and their association with DD in adults with T1DM. Methods Cross-sectional study of consecutive adults with T1DM attending diabetes clinics in a secondary care hospital (January-November 2019). Estimated glucose disposal rate (eGDR) was used as a marker of IR, and an eGDR

Three-dimensional (3D) cancer models are revolutionising research, allowing for the recapitulation of an in vivo-like response through the use of an in vitro system, which is more complex and physiologically relevant than traditional monolayer cultures. Cancers such as ovarian (OvCa) are prone to developing resistance, are often lethal, and stand to benefit greatly from the enhanced modelling emulated by 3D cultures. However, the current models often fall short of the predicted response, where reproducibility is limited owing to the lack of standardised methodology and established protocols. This meta-analysis aims to assess the current scope of 3D OvCa models and the differences in the genetic profiles presented by a vast array of 3D cultures. An analysis of the literature (Pubmed.gov) spanning 2012–2022 was used to identify studies with paired data of 3D and 2D monolayer counterparts in addition to RNA sequencing and microarray data. From the data, 19 cell lines were found to show differential regulation in their gene expression profiles depending on the bio-scaffold (i.e., agarose, collagen, or Matrigel) compared to 2D cell cultures. The top genes differentially expressed in 2D vs. 3D included C3, CXCL1, 2, and 8, IL1B, SLP1, FN1, IL6, DDIT4, PI3, LAMC2, CCL20, MMP1, IFI27, CFB, and ANGPTL4. The top enriched gene sets for 2D vs. 3D included IFN-α and IFN-γ response, TNF-α signalling, IL-6-JAK-STAT3 signalling, angiogenesis, hedgehog signalling, apoptosis, epithelial–mesenchymal transition, hypoxia, and inflammatory response. Our transversal comparison of numerous scaffolds allowed us to highlight the variability that can be induced by these scaffolds in the transcriptional landscape and identify key genes and biological processes that are hallmarks of cancer cells grown in 3D cultures. Future studies are needed to identify which is the most appropriate in vitro/preclinical model to study tumour microenvironments.

Cardiovascular diseases (CVDs) still remain the major cause of death worldwide; however, CVD-related mortality has been reduced due to lifestyle modification interventions, as well as novel pharmacological therapies and advances in cardiovascular surgery [...]

Background COVID-19 placed significant challenges on healthcare systems. People with diabetes are at high risk of severe COVID-19 with poor outcomes. We describe the first reported use of inpatient digital flash glucose monitoring devices in a UK NHS hospital to support management of people with diabetes hospitalized for COVID-19. Methods Inpatients at University Hospitals Coventry & Warwickshire (UHCW) NHS Trust with COVID-19 and diabetes were considered for digitally enabled flash glucose monitoring during their hospitalization. Glucose monitoring data were analysed, and potential associations were explored between relevant parameters, including time in hypoglycaemia, hyperglycaemia, and in range, glycated haemoglobin (HbA1c), average glucose, body mass index (BMI), and length of stay. Results During this pilot, digital flash glucose monitoring devices were offered to 25 inpatients, of whom 20 (type 2/type 1: 19/1; mean age: 70.6 years; mean HbA1c: 68.2 mmol/mol; mean BMI: 28.2 kg/m 2 ) accepted and used these (80% uptake). In total, over 2788 h of flash glucose monitoring were recorded for these inpatients with COVID-19 and diabetes. Length of stay was not associated with any of the studied variables (all p-values >0.05). Percentage of time in hyperglycaemia exhibited significant associations with both percentage of time in hypoglycaemia and percentage of time in range, as well as with HbA1c (all p-values

Abstract Background In women of reproductive age, polycystic ovary syndrome (PCOS) constitutes the most frequent endocrine disorder. Women with PCOS are considered to typically belong to an age and sex group which is at lower risk for severe COVID-19. Main body Emerging data link the risk of severe COVID-19 with certain factors such as hyper-inflammation, ethnicity predisposition, low vitamin D levels, and hyperandrogenism, all of which have known direct associations with PCOS. Moreover, in this common female patient population, there is markedly high prevalence of multiple cardio-metabolic conditions, such as type 2 diabetes, obesity, and hypertension, which may significantly increase the risk for adverse COVID-19-related outcomes. This strong overlap of risk factors for both worse PCOS cardio-metabolic manifestations and severe COVID-19 should be highlighted for the clinical practice, particularly since women with PCOS often receive fragmented care from multiple healthcare services. Comprehensively informing women with PCOS regarding the potential risks from COVID-19 and how this may affect their management is also essential. Conclusion Despite the immense challenges posed by the COVID-19 outbreak to the healthcare systems in affected countries, attention should be directed to maintain a high standard of care for complex patients such as many women with PCOS and provide relevant practical recommendations for optimal management in the setting of this fast moving pandemic.

Abstract Background Type 2 diabetes mellitus (T2DM) comprises the vast majority of all diabetes cases in adults, with alarmingly increasing prevalence over the past few decades worldwide. A particularly heavy healthcare burden of diabetes is noted in Europe, where 8.8% of the population aged 20–79 years is estimated to have diabetes according to the International Diabetes Federation. Multiple risk factors are implicated in the pathogenesis of T2DM with complex underlying interplay and intricate gene-environment interactions. Thus, intense research has been focused on studying the role of T2DM risk factors and on identifying vulnerable groups for T2DM in the general population which can then be targeted for prevention interventions. Methods For this narrative review, we conducted a comprehensive search of the existing literature on T2DM risk factors, focusing on studies in adult cohorts from European countries which were published in English after January 2000. Results Multiple lifestyle-related and sociodemographic factors were identified as related to high T2DM risk, including age, ethnicity, family history, low socioeconomic status, obesity, metabolic syndrome and each of its components, as well as certain unhealthy lifestyle behaviors. As Europe has an increasingly aging population, multiple migrant and ethnic minority groups and significant socioeconomic diversity both within and across different countries, this review focuses not only on modifiable T2DM risk factors, but also on the impact of pertinent demographic and socioeconomic factors. Conclusion In addition to other T2DM risk factors, low socioeconomic status can significantly increase the risk for prediabetes and T2DM, but is often overlooked. In multinational and multicultural regions such as Europe, a holistic approach, which will take into account both traditional and socioeconomic/socioecological factors, is becoming increasingly crucial in order to implement multidimensional public health programs and integrated community-based interventions for effective T2DM prevention.

A rapidly increasing incidence of non-alcoholic fatty liver disease (NAFLD) is noted worldwide due to the adoption of western-type lifestyles and eating habits. This makes the understanding of the molecular mechanisms that drive the pathogenesis of this chronic disease and the development of newly approved treatments of utmost necessity. Animal models are indispensable tools for achieving these ends. Although the ideal mouse model for human NAFLD does not exist yet, several models have arisen with the combination of dietary interventions, genetic manipulations and/or administration of chemical substances. Herein, we present the most common mouse models used in the research of NAFLD, either for the whole disease spectrum or for a particular disease stage (e.g., non-alcoholic steatohepatitis). We also discuss the advantages and disadvantages of each model, along with the challenges facing the researchers who aim to develop and use animal models for translational research in NAFLD. Based on these characteristics and the specific study aims/needs, researchers should select the most appropriate model with caution when translating results from animal to human.

Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. Asprosin is a recently described adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes. In vitro studies have reported pro-inflammatory effects of asprosin in a variety of tissues. The present study aimed to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages. THP-1 monocytes were differentiated to macrophages by 48 h treatment with dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL lipopolysaccharide (LPS), and 10 μM caffeic acid phenethyl ester (CAPE; an inhibitor of NFκB activation) or 1 µM TAK-242 (a Toll-like receptor 4, TLR4, inhibitor). The expression and secretion of pertinent pro-inflammatory mediators were measured by qPCR, Western blot, ELISA and Bioplex. Asprosin stimulation significantly upregulated the expression and secretion of the pro-inflammatory cytokines: tumour necrosis factor α (TNFα), interleukin-1β (IL-1β), IL-8 and IL-12 in vitro. This pro-inflammatory response in THP-1 macrophages was partly attenuated by the treatments with CAPE and was significantly inhibited by TAK-242 treatment. Asprosin-induced inflammation is significantly counteracted by TLR4 inhibition in THP-1 macrophages, suggesting that asprosin exerts its pro-inflammatory effects, at least in part, via the TLR4 signalling pathway.

Background: Augmented glycolysis in cancer cells is a process required for growth and development. The Warburg effect provides evidence of increased glycolysis and lactic acid fermentation in cancer cells. The lactate end-product of glycolysis is receiving growing traction for its role as a cell signalling molecule. Ovarian cancer (OvCa) is also characterised by altered glucose metabolism. We aim to explore circulating lactate levels in patients with high-grade serous OvCa (HGSOC) and to elucidate the expression of the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1) in OvCa. Methods: HCAR1 expression was detected in patient biopsy cores using immunohistochemistry, while lactate was measured from whole blood with a Biosen-C line clinic measuring system. Results: We noted significantly elevated lactate levels in OvCa patients (4.3 ± 1.9 mmol/L) compared with healthy controls (1.4 ± 0.6 mmol/L; p < 0.0001), with an AUC of 0.96. The HCAR1 gene is overexpressed in OvCa compared to healthy controls (p < 0.001). Using an OvCa tissue microarray (>75% expression in 100 patients), high protein expression was also recorded across all epithelial OvCa subtypes and ovarian normal adjacent tissue (NAT). Conclusions: Lactate monitoring is a simple, cost-efficient test that can offer point-of-care results. Our data suggest that the potential of circulating lactate as a screening biomarker in OvCa merits further research attention.

Background: Ovarian cancer (OvCa) is one of the most lethal forms of gynaecological malignancy. Altered energy metabolism and increased aerobic glycolysis in OvCa are hallmarks that demand attention. The glucogenic hormone asprosin is often dysregulated in metabolic disorders such as insulin resistance, diabetes (type 2 and gestational), and preeclampsia. Despite association with metabolic disorders, its role in energy metabolism within the tumour microenvironment is yet to be explored. Here, we study the role of asprosin in OvCa using transcriptomics and expand on functional studies with clinical samples. Methods: RNA sequencing, functional gene enrichment analysis, Western blotting and ImageStream. Results: Following treatment with 100 nM of asprosin, the serous OvCa cell line, SKOV-3, displayed 160 and 173 gene regulatory changes, at 4 and 12 h respectively, when compared with control samples (p < 0.05 and Log2FC > 1). In addition to energy metabolism and glucose-related pathways, asprosin was shown to alter pathways associated with cell communication, TGF-β signalling, and cell proliferation. Moreover, asprosin was shown to induce phosphorylation of ERK1/2 in the same in vitro model. Using liquid biopsies, we also report for novel expression of asprosin’s predicted receptors OR4M1 and TLR4 in cancer-associated circulating cells; with significant reduction seen between pre-chemotherapy and end of first line chemotherapy, in addition to patients under maintenance with bevacizumab +/− olaparib for OR4M1. Conclusions: In relation to OvCa, asprosin appears to regulate numerous signalling pathways in-vitro. The prognostic potential of OR4M1 in liquid biopsies should also be explored further.

Summary: Objectives: To capture perceptions regarding personal protective equipment (PPE) among healthcare professionals during the COVID-19 pandemic, including staff subgroups at high risk for severe COVID-19, such as black and minority ethnic (BAME) groups. Design: Electronically distributed survey with semi-quantitative analysis. Survey distributed at a major academic NHS tertiary referral centre in the West Midlands with a diverse medical workforce to medically qualified staff who completed COVID-19 redeployment training. (N=121; 47% female; 49% of BAME background; 26% international medical graduates). Results: All demographic groups reported overall good awareness of when and how to use PPE during COVID-19 pandemic. Statistically significant differences in the perceptions regarding PPE use during COVID-19 were noted between BAME vs non-BAME staff, international vs UK medical graduates, and male vs female participants, as well as between professionals at different stages of their career. The differences related to perceptions around availability, degree of protection provided, perceived inconvenience, ability to raise concerns about availability, confidence in sharing underlying health conditions with managers and the impact of full PPE in emergency situations causing delay patient care. Conclusions: Amongst medically qualified staff, significant differences exist in the perceptions relating to the, availability and effectiveness of PPE during the COVID-19 pandemic depending on country of training, ethnic background and sex. GAFREC Study Approval: Study ID GF0392.

Background: Guidelines for the management of polycystic ovary syndrome (PCOS) focus on lifestyle changes, incorporating exercise. Whilst evidence suggests that aerobic exercise may be beneficial, less is known about the effectiveness of resistance training (RT), which may be more feasible for those that have low fitness levels and/or are unable to tolerate/participate in aerobic exercise. Objectives: To identify the available evidence on RT in women with PCOS and to summarise findings in the context of a scoping review. Eligibility criteria: Studies utilising pre-post designs to assess the effectiveness of RT in PCOS; all outcomes were included. Sources of evidence: Four databases (PubMed, CENTRAL, CINAHL and SportDiscus) were searched and supplemented by hand searching of relevant papers/reference lists. Charting methods: Extracted data were presented in tables and qualitatively synthesised. Results: Searches returned 42 papers; of those, 12 papers were included, relating to six studies/trials. Statistical changes were reported for multiple pertinent outcomes relating to metabolic (i.e., glycaemia and fat-free mass) and hormonal (i.e., testosterone and sex hormone-binding globulin) profiles. Conclusions: There is a striking lack of studies in this field and, despite the reported statistical significance for many outcomes, the documented magnitude of changes are small and the quality of the evidence questionable. This highlights an unmet need for rigorously designed/reported and sufficiently powered trials.

In the presence of established atherosclerosis, estrogens are potentially harmful. MMP-2 and MMP-9, their inhibitors (TIMP-2 and TIMP-1), RANK, RANKL, OPG, MCP-1, lysyl oxidase (LOX), PDGF-β, and ADAMTS-4 play critical roles in plaque instability/rupture. We aimed to investigate (i) the effect of estradiol on the expression of the abovementioned molecules in endothelial cells, (ii) which type(s) of estrogen receptors mediate these effects, and (iii) the role of p21 in the estrogen-mediated regulation of the aforementioned factors. Human aortic endothelial cells (HAECs) were cultured with estradiol in the presence or absence of TNF-α. The expression of the aforementioned molecules was assessed by qRT-PCR and ELISA. Zymography was also performed. The experiments were repeated in either ERα- or ERβ-transfected HAECs and after silencing p21. HAECs expressed only the GPR-30 estrogen receptor. Estradiol, at low concentrations, decreased MMP-2 activity by 15-fold, increased LOX expression by 2-fold via GPR-30, and reduced MCP-1 expression by 3.5-fold via ERβ. The overexpression of ERα increased MCP-1 mRNA expression by 2.5-fold. In a low-grade inflammation state, lower concentrations of estradiol induced the mRNA expression of MCP-1 (3.4-fold) and MMP-9 (7.5-fold) and increased the activity of MMP-2 (1.7-fold) via GPR-30. Moreover, p21 silencing resulted in equivocal effects on the expression of the abovementioned molecules. Estradiol induced different effects regarding atherogenic plaque instability through different ERs. The balance of the expression of the various ER subtypes may play an important role in the paradoxical characterization of estrogens as both beneficial and harmful.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. It is strongly associated with obesity, type 2 diabetes (T2DM), and other metabolic syndrome features. Reflecting the underlying pathogenesis and the cardiometabolic disorders associated with NAFLD, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has recently been proposed. Indeed, over the past few years, growing evidence supports a strong correlation between NAFLD and increased cardiovascular disease (CVD) risk, independent of the presence of diabetes, hypertension, and obesity. This implies that NAFLD may also be directly involved in the pathogenesis of CVD. Notably, liver sinusoidal endothelial cell (LSEC) dysfunction appears to be implicated in the progression of NAFLD via numerous mechanisms, including the regulation of the inflammatory process, hepatic stellate activation, augmented vascular resistance, and the distortion of microcirculation, resulting in the progression of NAFLD. Vice versa, the liver secretes inflammatory molecules that are considered pro-atherogenic and may contribute to vascular endothelial dysfunction, resulting in atherosclerosis and CVD. In this review, we provide current evidence supporting the role of endothelial cell dysfunction in the pathogenesis of NAFLD and NAFLD-associated atherosclerosis. Endothelial cells could thus represent a “golden target” for the development of new treatment strategies for NAFLD and its comorbid CVD.

Background: Lockdown measures have been enforced globally in response to the COVID-19 pandemic. Given the comorbidity burden in women with polycystic ovary syndrome (PCOS), these lockdown measures may have a particularly negative impact on sleep health, quality of life (QoL), and depression/stress levels in this population. The aim of this study was to explore whether such potential problems were present in women with PCOS during the COVID-19 lockdown in the UK.Methods: UK women with PCOS were recruited through social media into a cross-sectional study during the COVID-19 lockdown. The study survey was delivered online, and included demographic and COVID-19 relevant questions, as well as validated questionnaires/scales, namely the Insomnia Severity Index (ISI), Depression Anxiety and Stress Scale (DASS-21), and PCOSQOL questionnaire.Results: Three hundred and thirty-three women with PCOS [median age: 30.0 (9.0) years] were recruited. Participants were dichotomized based on responses regarding the impact of COVID-19 restrictions on their sleep [negative (N = 242) vs. no/positive (N = 91) impact]. No differences were noted between groups regarding age, time since PCOS diagnosis, body mass index, or number of comorbidities. Based on the ISI, 44.2% of participants reporting a negative impact on sleep exhibited at least moderately severe clinical insomnia. Compared to those who reported no/positive effect on sleep, the participants reporting a negative impact on sleep also reported poorer QoL, based on the total PCOSQOL score, with a greater impact of PCOS and poorer mood in the corresponding PCOSQOL domains. Based on the DASS-21, the latter also had statistically higher depression and stress levels compared to the former. Finally, for this cohort significant inverse correlations were noted between the ISI and PCOSQOL scores (total and domain scores), whilst the DASS-21 and ISI scores were positively correlated (all p-values

Abstract Background Typically, management of PCOS focuses on lifestyle changes (exercise and diet), aiming to alleviate symptoms, and lower the associated risk of type 2 diabetes and cardiovascular disease. Our objective was to analyse evidence on the effectiveness of exercise in the management of PCOS, when compared to (i) usual care, (ii) diet alone, and (iii) exercise combined with diet, and also exercise combined with diet, compared to (i) control or usual care and (ii) diet alone. Methods Relevant databases were searched (June 2017) with no time limit for trial inclusion. Eligible trials employed a randomised or quasi-randomised design to measure the chronic effects of exercise, or exercise and diet in women with PCOS. Results Searches returned 2390 articles; of those, 27 papers from 18 trials were included. Results are presented as mean difference (MD) and 95% confidence intervals (95% CI). Compared with control, exercise had a statistical effect on change from baseline fasting insulin (MD − 2.44 μIU/mL, 95% CIs − 4.24 to − 0.64; very low-quality evidence), HOMA-IR (− 0.57, − 0.99 to − 0.14; very low-quality evidence), total cholesterol (− 5.88 mg/dL, − 9.92 to − 1.83; low-quality evidence), LDL cholesterol (− 7.39 mg/dL, − 9.83 to − 4.95; low-quality evidence), and triglycerides (− 4.78 mg/dL, − 7.52 to − 2.05; low-quality evidence). Exercise also improved VO2 max (3.84 ml/kg/min, 2.87 to 4.81), waist circumference (− 2.62 cm, − 4.13 to − 1.11), and body fat percentage (− 1.39%, − 2.61 to − 0.18) when compared with usual care. No effect was found for change value systolic/diastolic blood pressure, fasting glucose, HDL cholesterol (all low-quality evidence), or waist-to-hip ratio. Many favourable change score findings were supported by post-intervention value analyses: fasting insulin (− 2.11 μIU/mL, − 3.49 to − 0.73), total cholesterol (− 6.66 mg/dL, − 11.14 to − 2.17), LDL cholesterol (− 6.91 mg/dL, − 12.02 to − 1.80), and VO2 max (5.01 ml/kg/min, 3.48 to 6.54). Statistically lower BMI (− 1.02 kg/m2, − 1.81 to − 0.23) and resting heart rate (− 3.26 beats/min − 4.93 to − 1.59) were also revealed in post-intervention analysis. Subgroup analyses revealed the greatest improvements in overweight/obese participants, and more outcomes improved when interventions were supervised, aerobic in nature, or of a shorter duration. Based on limited data, we found no differences for any outcome between the effects of exercise and diet combined, and diet alone. It was not possible to compare exercise vs diet or exercise and diet combined vs diet. Conclusion Statistically beneficial effects of exercise were found for a range of metabolic, anthropometric, and cardiorespiratory fitness-related outcomes. However, caution should be adopted when interpreting these findings since many outcomes present modest effects and wide CIs, and statistical effects in many analyses are sensitive to the addition/removal of individual trials. Future work should focus on rigorously designed, well-reported trials that make comparisons involving both exercise and diet. Systematic review registration This systematic review was prospectively registered on the Prospero International Prospective Register of Systematic Reviews (CRD42017062576)

Cardiovascular diseases (CVDs) are a major healthcare burden on the population worldwide. Early detection of this disease is important in prevention and treatment to minimise morbidity and mortality. Biomarkers are a critical tool to either diagnose, screen, or provide prognostic information for pathological conditions. This review discusses the historical cardiac biomarkers used to detect these conditions, discussing their application and their limitations. Identification of new biomarkers have since replaced these and are now in use in routine clinical practice, but still do not detect all disease. Future cardiac biomarkers are showing promise in early studies, but further studies are required to show their value in improving detection of CVD above the current biomarkers. Additionally, the analytical platforms that would allow them to be adopted in healthcare are yet to be established. There is also the need to identify whether these biomarkers can be used for diagnostic, prognostic, or screening purposes, which will impact their implementation in routine clinical practice.

Endocrine-disrupting chemicals (EDCs), including the xenoestrogen Bisphenol A (BPA), can interfere with hormonal signalling. Despite increasing reports of adverse health effects associated with exposure to EDCs, there are limited data on the effect of BPA in normal human ovaries. In this paper, we present a detailed analysis of the transcriptomic landscape in normal Human Epithelial Ovarian Cells (HOSEpiC) treated with BPA (10 and 100 nM). Gene expression profiles were determined using high-throughput RNA sequencing, followed by functional analyses using bioinformatics tools. In total, 272 and 454 differentially expressed genes (DEGs) were identified in 10 and 100 nM BPA-treated HOSEpiCs, respectively, compared to untreated controls. Biological pathways included mRNA surveillance pathways, oocyte meiosis, cellular senescence, and transcriptional misregulation in cancer. BPA exposure has a considerable impact on 10 genes: ANAPC2, AURKA, CDK1, CCNA2, CCNB1, PLK1, BUB1, KIF22, PDE3B, and CCNB3, which are also associated with progesterone-mediated oocyte maturation pathways. Future studies should further explore the effects of BPA and its metabolites in the ovaries in health and disease, making use of validated in vitro and in vivo models to generate data that will address existing knowledge gaps in basic biology, hazard characterisation, and risk assessment associated with the use of xenoestrogens such as BPA.

Background: Liver fibrosis is a consequence of chronic inflammation and is associated with protein changes within the hepatocytes structure. In this study, we aimed to investigate if this is reflected by the urinary proteome and can be explored to diagnose liver fibrosis in patients with chronic liver disease. Methods: In a multicentre combined cross-sectional and prospective diagnostic test validation study, 129 patients with varying degrees of liver fibrosis and 223 controls without liver fibrosis were recruited. Additionally, 41 patients with no liver, but kidney fibrosis were included to evaluate interference with expressions of kidney fibrosis. Urinary low molecular weight proteome was analysed by capillary electrophoresis coupled to mass spectrometry (CE-MS) and a support vector machine marker model was established by integration of peptide markers for liver fibrosis. Findings: CE-MS enabled identification of 50 urinary peptides associated with liver fibrosis. When combined into a classifier, LivFib-50, it separated patients with liver fibrosis (N = 31) from non-liver disease controls (N = 123) in cross-sectional diagnostic phase II evaluation with an area under the curve (AUC) of 0.94 (95% confidence intervals (CI): 0.89–0.97, p

Non-alcoholic fatty liver disease (NAFLD) is an ‘umbrella’ term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment.

Background: Excess adipose tissue accumulation and obesity are characterised by chronic, low-grade, systemic inflammation. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. The present study aimed to investigate the effects of an obesogenic diet (OD; high-fat, high-sugar) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 preadipocytes. Methods: Subcutaneous white adipose tissue (Sc-WAT) samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND), or the OD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were treated with 100 nM nesfatin-1 during differentiation and stimulated with 1 µg/mL LPS for measuring the expression and secretion of pro-inflammatory mediators by qPCR, western blotting, immunofluorescence, Bioplex, and ELISA. Results: Following the OD, the mRNA, protein and cellular expression of pro-inflammatory mediators (Tnfα, Il-6, Il-1β, Adgre1, Mcp1, TLR4, Hmbgb1 and NF-kB) significantly increased in the ScWAT of NUCB2 KO mice compared to ND controls. Adiponectin and Nrf2 expression significantly decreased in the ScWAT of OD-fed NUCB2 KO, without changes in the OD-fed WT mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression and secretion of pro-inflammatory cytokines (Tnfα, Il-6, Il-1β, Mcp1) and hmgb1. Conclusion: An obesogenic diet can induce significant inflammation in the ScWAT of NUCB2 KO mice, involving the HMGB1, NRF2 and NF-kB pathways, while nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells. These findings provide a novel insight into the metabolic regulation of inflammation in WAT.

Background: DNA double strand breaks can affect genome integrity potentially leading to cancer. RAD51-associated protein 1 (RAD51AP1), an accessory protein to RAD51, is critical for homologous recombination, a key DNA damage response pathway. Emerging studies indicate a novel role for RAD51AP1 in carcinogenesis. Here we provide additional insight into the role of RAD51AP1 in ovarian cancer (OvCa). Methods: Gene expression and patient phenotype data were obtained from TCGA and GTEX project consortia for bioinformatics analysis. Immunohistochemistry of OvCa tissue microarray was undertaken. Functional analyses were performed in a SKOV3 OvCa cell line with down-regulation of RAD51AP1 using siRNA. Results: RAD51AP1 is overexpressed at gene level in primary and recurrent OvCa compared to controls. At protein level, RAD51AP1 was up-regulated in low grade serous tumors compared to high grade OvCa. There was higher expression of RAD51AP1 in OvCa metastatic to lymph nodes compared to primary cancer samples. Gene enrichment analyses identified 12 differentially expressed genes (DEGs) related to OvCa, eight of which are also common in tissue from patients with type 2 diabetes mellitus (T2DM). Conclusions: RAD51AP1 is overexpressed in OvCa, Given the link between OvCa and T2DM, the eight-gene signature shows potential for predictive value.

Background: Obstructive sleep apnoea (OSA) and polycystic ovary syndrome (PCOS) are associated with significant comorbidities and commonly coexist. The primary aim of this study was to examine the relationship between OSA and quality of life (QoL) in women with PCOS. Methods: We conducted an observational cross-sectional study. PCOS was diagnosed according to the Rotterdam criteria. Women with increased risk of OSA, based on the Berlin questionnaire or the Epworth Sleepiness Scale (ESS), had home-based polysomnography performed (ALICE PDx). Participants were divided into two groups: (a) PCOS only: women with normal ESS and low-risk Berlin questionnaire (no sleep studies performed), or women with normal sleep studies [oxygen desaturation index (ODI)

Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease worldwide, and is frequently linked to the metabolic syndrome. The latter represents a clustering of related cardio-metabolic components, which are often observed in patients with NAFLD and increase the risk of cardiovascular disease. Furthermore, growing evidence suggests a positive association between metabolic syndrome and certain mental health problems (e.g., depression, anxiety, and chronic stress). Given the strong overlap between metabolic syndrome and NAFLD, and the common underlying mechanisms that link the two conditions, it is probable that potentially bidirectional associations are also present between NAFLD and mental health comorbidity. The identification of such links is worthy of further investigation, as this can inform more targeted interventions for patients with NAFLD. Therefore, the present review discusses published evidence in relation to associations of depression, anxiety, stress, and impaired health-related quality of life with NAFLD and metabolic syndrome. Attention is also drawn to the complex nature of affective disorders and potential overlapping symptoms between such conditions and NAFLD, while a focus is also placed on the postulated mechanisms mediating associations between mental health and both NAFLD and metabolic syndrome. Relevant gaps/weaknesses of the available literature are also highlighted, together with future research directions that need to be further explored.

Background and Objectives: Hyperbaric oxygen is a recognised treatment for a range of medical conditions, including treatment of diabetic foot disease. A number of studies have reported an impact of hyperbaric oxygen treatment on glycaemic control in patients undergoing treatment for diabetic foot disease. There has been no systematic review considering the impact of hyperbaric oxygen on glycaemia in people with diabetes. Materials and Methods: A prospectively PROSPERO-registered (PROSPERO registration: CRD42021255528) systematic review of eligible studies published in English in the PUBMED, MEDLINE, and EMBASE databases, based on the following search terms: hyperbaric oxygen therapy, HBO2, hyperbaric oxygenation, glycaemic control, diabetes, diabetes Mellitus, diabetic, HbA1c. Data extraction to pre-determined piloted data collection form, with individual assessment of bias. Results: In total, 10 eligible publications were identified after screening. Of these, six articles reported a statistically significant reduction in blood glucose from hyperbaric oxygen treatment, while two articles reported a statistically significant increase in peripheral insulin sensitivity. Two articles also identified a statistically significant reduction in HbA1c following hyperbaric oxygen treatment. Conclusions: There is emerging evidence suggesting a reduction in glycaemia following hyperbaric oxygen treatment in patients with diabetes mellitus, but the existing studies are in relatively small cohorts and potentially underpowered. Additional large prospective clinical trials are required to understand the precise impact of hyperbaric oxygen treatment on glycaemia for people with diabetes mellitus.

Abstract Background Irisin is a hormone released mainly from skeletal muscle after exercise which increases adipose tissue energy expenditure. Adipocytes can also release irisin after exercise, acting as a local adipokine to induce white adipose tissue to take on a brown adipose tissue-like phenotype, suggesting that irisin and its receptor may represent a novel molecular target for the treatment of obesity and obesity-related diabetes. Previous reports provide conflicting evidence regarding circulating irisin levels in patients with type 2 diabetes (T2DM). Methods This study investigated plasma irisin concentrations in 79 T2DM individuals, assessing potential associations with measures of segmental body composition, markers of endothelial dysfunction and peripheral blood mononuclear cell telomere length (TL). Results Resting, overnight-fasted plasma irisin levels were significantly higher in this group of T2DM patients compared with levels we previously reported in healthy volunteers (p

Background: The COVID-19 pandemic and the related lockdown measures presented a significant risk to physical and mental wellbeing in affected populations. Women with polycystic ovary syndrome (PCOS) are predisposed to several cardio-metabolic risk factors which increase the susceptibility to severe COVID-19 and also exhibit increased likelihood of impaired mental health wellbeing. Therefore, these women who usually receive care from multiple primary and specialist healthcare services may be disproportionately impacted by this pandemic and the related restrictions. This study aimed to explore the lived experience of the first UK national lockdown as a woman with PCOS. Methods: As part of a larger cross-sectional study, 12 women with PCOS living in the UK during the first national COVID-19 lockdown were recruited to a qualitative study. Telephone interviews were conducted in June/July of 2020, and data collected were subjected to thematic analysis. Results: Five themes were identified. “My PCOS Journey” describes participants’ experiences of diagnosis, treatment and ongoing management of their PCOS. “Living Through Lockdown” describes the overall experience and impact of the lockdown on all aspects of participants’ lives. “Self-care and Managing Symptoms” describe multiple challenges to living well with PCOS during the lockdown, including lack of access to supplies and services, and disruption to weight management. “Healthcare on Hold” describes the uncertainty and anxiety associated with delays in accessing specialised healthcare for a range of PCOS aspects, including fertility treatment. “Exacerbating Existing Issues” captures the worsening of pre-existing mental health issues, and an increase in health anxiety and feelings of isolation. Conclusion: For the women with PCOS in this study, the COVID-19 pandemic and the first national lockdown was mostly experienced as adding to the pre-existing challenges of living with their condition. The mental health impact experienced by the study participants was increased due to lack of access to their normal support strategies, limitations on healthcare services and uncertainty about their risk of COVID-19.

Reproductive function depends upon an operational hypothalamo–pituitary–gonadal (HPG) axis. Due to its role in determining survival versus reproductive strategies, the HPG axis is vulnerable to a diverse plethora of signals that ultimately manifest with Central Hypogonadism (CH) in all its many guises. Acquired CH can result from any pituitary or hypothalamic lesion, including its treatment (such as surgical resection and/or radiotherapy). The HPG axis is particularly sensitive to the suppressive effects of hyperprolactinaemia that can occur for many reasons, including prolactinomas, and as a side effect of certain drug therapies. Physiologically, prolactin (combined with the suppressive effects of autonomic neural signals from suckling) plays a key role in suppressing the gonadal axis and establishing temporary CH during lactation. Leptin is a further key endocrine regulator of the HPG axis. During starvation, hypoleptinaemia (from diminished fat stores) results in activation of hypothalamic agouti-related peptide neurons that have a dual purpose to enhance appetite (important for survival) and concomitantly suppresses GnRH neurons via effects on neural kisspeptin release. Obesity is associated with hyperleptinaemia and leptin resistance that may also suppress the HPG axis. The suppressibility of the HPG axis also leaves it vulnerable to the effects of external signals that include morphine, anabolic-androgenic steroids, physical trauma and stress, all of which are relatively common causes of CH. Finally, the HPG axis is susceptible to congenital malformations, with reports of mutations within >50 genes that manifest with congenital CH, including Kallmann Syndrome associated with hyposmia or anosmia (reduction or loss of the sense of smell due to the closely associated migration of GnRH with olfactory neurons during embryogenesis). Analogous to the HPG axis itself, patients with CH are often vulnerable, and their clinical management requires both sensitivity and empathy.

Objective: To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). Methods: A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. Results: Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. Conclusion: We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity.