Diagnostic yield from symptomatic gastroscopy in the UK: British Society of Gastroenterology analysis using data from the National Endoscopy Database.

OBJECTIVE: This national analysis aimed to calculate the diagnostic yield from gastroscopy for common symptoms, guiding improved resource utilisation. DESIGN: A cross-sectional study was conducted of diagnostic gastroscopies between 1 March 2019 and 29 February 2020 using the UK National Endoscopy Database. Mixed-effect logistic regression models were used, incorporating random (endoscopist) and fixed (symptoms, age and sex) effects on two dependent variables (endoscopic cancer; Barrett's oesophagus (BO) diagnosis). Adjusted positive predictive values (aPPVs) were calculated. RESULTS: 382 370 diagnostic gastroscopies were analysed; 30.4% were performed in patients aged <50 and 57.7% on female patients. The overall unadjusted PPV for cancer was 1.0% (males 1.7%; females 0.6%, p<0.01). Other major pathology was found in 9.1% of procedures, whereas 89.9% reported only normal findings or minor pathology (92.5% in females; 94.6% in patients <50).Highest cancer aPPVs were reached in the over 50s (1.3%), in those with dysphagia (3.0%) or weight loss plus another symptom (1.4%). Cancer aPPVs for all other symptoms were below 1%, and for those under 50, remained below 1% regardless of symptom. Overall, 73.7% of gastroscopies were carried out in patient groups where aPPV cancer was <1%.The overall unadjusted PPV for BO was 4.1% (males 6.1%; females 2.7%, p<0.01). The aPPV for BO for reflux was 5.8% and ranged from 3.2% to 4.0% for other symptoms. CONCLUSIONS: Cancer yield was highest in elderly male patients, and those over 50 with dysphagia. Three-quarters of all gastroscopies were performed on patients whose cancer risk was <1%, suggesting inefficient resource utilisation.

Extensive heterogeneity in the expression of steroid receptors in superficial peritoneal endometriotic lesions.

RESEARCH QUESTION: Is the expression of steroid hormone receptors (oestrogen receptor-α and progesterone receptor A/B) and proliferative markers (Bcl-2 and Ki67) uniform among superficial peritoneal endometriotic lesions? DESIGN: A retrospective cohort study of 24 patients with surgically and histologically confirmed endometriosis. Immunofluorescence was used to determine the proportion of oestrogen receptor-α (ERα), progesterone receptor A/B, Bcl-2 and Ki67 positive cells in 271 endometriotic lesions (defined as endometriotic gland profile/s within an individual region of CD10 stromal immunostaining from a single biopsy) from 67 endometriotic biopsies from 24 patients. Data were analysed to examine associations related to menstrual cycle stage, lesion location and gland morphology. RESULTS: Oestrogen receptor-α and progesterone receptor A/B expression in superficial peritoneal endometriotic lesions was extremely heterogeneous. Bcl-2 immunostaining in endometriotic lesions was also variable, whereas Ki67 immunostaining was minimal. Menstrual cycle stage associations were limited in steroid hormone receptor and Bcl-2 expression in lesions. Patterns in progesterone receptor A/B and Bcl-2 immunostaining were associated with lesion location. Bcl-2 was differentially expressed, based on lesion gland morphology. CONCLUSIONS: These data demonstrate considerable diversity in the expression of steroid hormone receptors and Bcl-2 between lesions, even within an individual patient.

Distribution of smooth muscle actin and collagen in superficial peritoneal endometriotic lesions varies from the surrounding microenvironment.

RESEARCH QUESTION: Do different subtypes of superficial peritoneal endometriotic lesions exist, based on the presence and morphology of smooth muscle, collagen fibres and immune cell populations? DESIGN: A retrospective cohort study of 24 patients, from across the menstrual cycle, with surgically and histologically confirmed endometriosis. Immunofluorescence was used to delineate the CD10 stromal area of lesions (n = 271 lesions from 67 endometriotic biopsies), and then smooth muscle actin (SMA) positive tissue and immune cell populations (CD45+ and CD68+) were quantified within and adjacent to these lesions. Second harmonic generation microscopy was used to evaluate the presence and morphology of type-1 collagen fibres within and surrounding lesions. RESULTS: Overall, immune cell numbers and the area of SMA and collagen within endometriotic lesions tended to be low, but a spectrum of presentations significantly varied, particularly in the adjacent tissue microenvironment, based on lesion locations, the morphology of endometriotic gland profiles, or both. Lesions in which collagen fibres formed well aligned capsules around the CD10+ stromal border were identified compared with lesions in which collagen fibre distribution was random. Considerable inter- and intra-patient variability in the morphology of SMA and collagen was observed within and surrounding lesions. CONCLUSION: These data demonstrate considerable diversity in the presence of immune cells and morphology of SMA and collagen within, but even more so, surrounding endometriotic lesions, even within individual patients. This heterogeneity, especially within individual patients, presents a challenge to incorporating these cell and tissue types into any new endometriosis classification systems or prognostic approaches.

Splenic flexure mobilization in left-sided colonic and rectal resections: A meta-analysis and meta-regression of factors associated with anastomotic leak and complications.

AIM: Splenic flexure mobilization (SFM) is commonly performed during left-sided colon and rectal resections. The aim of the present systematic review was to assess the outcomes of SFM in left-sided colon and rectal resections and the risk factors for complications and anastomotic leak (AL). METHOD: This study was a PRISMA-compliant systematic review. PubMed, Scopus and Web of Science were searched for studies that assessed the outcomes of sigmoid and rectal resections with or without SFM. The primary outcomes were AL and total complications, and the secondary outcomes were individual complications, operating time, conversion to open surgery, length of hospital stay (LOS) and pathological and oncological outcomes. RESULTS: Nineteen studies including data on 81 116 patients (49.1% male) were reviewed. SFM was undertaken in 40.7% of patients. SFM was associated with a longer operating time (weighted mean difference 24.50, 95% CI 14.47-34.52, p < 0.0001) and higher odds of AL (OR 1.19, 95% CI 1.06-1.33, p = 0.002). Both groups had similar odds of total complications, splenic injury, anastomotic stricture, conversion to open surgery, (LOS), local recurrence, and overall survival. A secondary analysis of rectal cancer cases only showed similar outcomes for SFM and the control group. CONCLUSIONS: SFM was associated with a longer operating time and higher odds of AL, yet a similar likelihood of total complications, splenic injury, anastomotic stricture, conversion to open surgery, LOS, local recurrence, and overall survival. These conclusions must be cautiously interpreted considering the numerous study limitations. SFM may have only been selectively undertaken in cases in which anastomotic tension was suspected. Therefore, the suboptimal anastomoses may have been the reason for SFM rather than the SFM being causative of the anastomotic insufficiencies.

Ostomy continence devices: a systematic review of the literature and meta-analysis.

AIM: Colostomy complication rates range widely from 10% to 70%. The psychological burden on patients, leading to lifestyle changes and decreased quality of life (QoL), is one of the largest factors. The aim of this work was to assess the history and efficacy of ostomy continence devices in improving continence and QoL. METHOD: In this PRISMA-compliant systematic review and meta-analysis, we searched PubMed, Scopus, Google Scholar and clinicaltrials.gov for studies on continence devices for all ostomies up to April 2023. Primary outcomes were continence and improvement in QoL. Secondary outcomes were leakage, patient's device preference and complications. Risk of Bias 2 and the revised tool to assess risk of bias in non-randomized studies of interventions (ROBINS-1) were used to assess risk of bias. Certainty of evidence was graded using GRADE. RESULTS: Twenty-two studies assessed devices from 1978 to 2022. The two main types identified were ball-valve devices and plug systems. Conseal and Vitala were the two main devices with significant evidence allowing for pooled analyses. Conseal, the only currently marketed device, had a pooled rate of continence of 67.4%, QoL improvement was 74.9%, patient preference over a traditional appliance was 69.1%, leakage was 10.1% and complications was 13.7%. Since 2011, five studies have investigated experimental devices on both human and animal models. CONCLUSION: Ostomy continence has been a long-standing goal without a consistently reliable solution. We propose that selective and short-term usage of continence devices may lead to improved continence and QoL in ostomy patients. Further research is needed to develop a reliable daily device for ostomy continence. Future investigation should include the needs of ileostomates.

Nutrient clustering, NOVA classification, and nutrient profiling: How do they overlap, and what do they predict about food palatability?

We compared the performance of three food categorisation metrics in predicting palatability (taste pleasantness) using a dataset of 52 foods, each rated virtually (online) by 72 to 224 participants familiar with the foods in question, as described in Appetite 193 (2024) 107124. The metrics were nutrient clustering, NOVA, and nutrient profiling. The first two of these metrics were developed to identify, respectively: 'hyper-palatable' foods (HPFs); and ultra-processed foods (UPFs), which are claimed to be 'made to be hyper-palatable'. The third metric categorises foods as high fat, sugar, salt (HFSS) foods versus non-HFSS foods. There were overlaps, but also significant differences, in categorisation of the foods by the three metrics: of the 52 foods, 35 (67%) were categorised as HPF, and/or UPF, and/or HFSS, and 17 (33%) were categorised as none of these. There was no significant difference in measured palatability between HPFs and non-HPFs, nor between UPFs and non-UPFs (p ≥ 0.412). HFSS foods were significantly more palatable than non-HFSS foods (p < 0.049). None of the metrics significantly predicted food reward (desire to eat). These results do not support the use of hypothetical combinations of food ingredients as proxies for palatability, as done explicitly by the nutrient clustering and NOVA metrics. To discover what aspects of food composition predict palatability requires measuring the palatability of a wide range of foods that differ in composition, as we do here.

Evidence that carbohydrate-to-fat ratio and taste, but not energy density or NOVA level of processing, are determinants of food liking and food reward.

This virtual (online) study tested the common but largely untested assumptions that food energy density, level of processing (NOVA categories), and carbohydrate-to-fat (CF) ratio are key determinants of food reward. Individual participants (224 women and men, mean age 35 y, 53% with healthy weight, 43% with overweight or obesity) were randomised to one of three, within-subjects, study arms: energy density (32 foods), or level of processing (24 foods), or CF ratio (24 foods). They rated the foods for taste pleasantness (liking), desire to eat (food reward), and sweetness, saltiness, and flavour intensity (for analysis averaged as taste intensity). Against our hypotheses, there was not a positive relationship between liking or food reward and either energy density or level of processing. As hypothesised, foods combining more equal energy amounts of carbohydrate and fat (combo foods), and foods tasting more intense, scored higher on both liking and food reward. Further results were that CF ratio, taste intensity, and food fibre content (negatively), independent of energy density, accounted for 56% and 43% of the variance in liking and food reward, respectively. We interpret the results for CF ratio and fibre in terms of food energy-to-satiety ratio (ESR), where ESR for combo foods is high, and ESR for high-fibre foods is low. We suggest that the metric of ESR should be considered when designing future studies of effects of food composition on food reward, preference, and intake.

Restricting sugar or carbohydrate intake does not impact physical activity level or energy intake over 24 h despite changes in substrate use: a randomised crossover study in healthy men and women.

PURPOSE: To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h. METHODS: In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning. RESULTS: The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d-1; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d-1; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations (P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG (p < 0.01). CONCLUSION: When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes. CLINICAL TRIALS REGISTRATION ID: NCT03509610, https://clinicaltrials.gov/show/NCT03509610.

It tastes OK, but I don't want to eat it: New insights into food disgust.

To better understand food-disgust, we investigated the long-standing theory that disgust towards a food causes it to taste 'bad'. To induce disgust, participants were served cookies labelled as containing crickets (Study 1); or served whole crickets versus novel (leblebi) and familiar (peanuts) control foods (Study 2). Participants (Study 1: N = 80; Study 2: N = 90) tasted the foods and rated taste pleasantness, desire to eat, disgust and, in Study 1, 16 taste attributes (e.g., nuttiness). Latency to eat and food intake were included as behavioural indicators of disgust. In both studies disgusting foods were presumed to taste bad, but this was disconfirmed after tasting - disgust did not cause the food to taste bad. Nonetheless, the taste attribute results suggested increased attention towards cricket flavours/textures. Furthermore, desire to eat and intake results suggested that disgust, but not novelty, was associated with reduced food wanting. Even if a disgust-inducing food tastes OK, people do not 'want' to consume it. By offering novel insights into our understanding of disgust, these results may stimulate progress in new avenues of emotion research, as well as informing the development of methods to reduce disgust and increase the acceptance of novel, sustainable, foods. For example, interventions should encourage tasting to overcome negative expectations of taste pleasantness and should tackle low levels of wanting, e.g., by normalising consumption of the target food.

A social norm intervention increases liking and intake of whole crickets, and what this tells us about food disgust.

Edible insects are healthy and sustainable but are rejected as food in Western populations due to disgust. We tested the effectiveness of written interventions to reduce disgust and increase intake of whole crickets. Cricket acceptance after reading a descriptive social norm or food preparation intervention passage was compared with a control passage, and an unfamiliar but non-disgusting food ('leblebi' - roasted chickpeas). Participants (N = 120) were randomised to one of four conditions (control + crickets, food preparation + crickets, social norm + crickets and control + leblebi). Outcome measures included taste pleasantness, desire to eat, food intake and, to measure disgust, self-report disgust, tactile sensitivity and latency to eat. In the control condition, crickets were rejected due to disgust and low desire to eat. In comparison, in the social norm condition, crickets were rated as tasting more pleasant, more desirable, and less disgusting, and intake was greater. The food preparation passage had a small but positive effect on cricket intake. For the first time, this study shows that a descriptive social norm can affect eating behaviour even when a food is disgusting; however, a food preparation intervention cannot overcome high disgust. The pattern of results suggested that expected and perceived taste pleasantness affects disgust. Therefore, taste quality and normalising consumption are targets for promoting acceptance of insects, and probably other novel, sustainable foods.

Consumers' attitudes towards alternatives to conventional meat products: Expectations about taste and satisfaction, and the role of disgust.

The livestock sector has environmental, health, and animal welfare impacts. This UK-based, quantitative study aimed to elucidate consumers' valuation of alternatives to conventional meat products. In an online study, 151 meat eaters and 44 non-meat eaters were shown pictures of meat, dairy, and bakery products, including beef burger, cheese sandwich and blueberry muffin. Each product was evaluated with three different labels (e.g., 'conventional', 'plant-based' and 'cultured' for beef burger). Participants rated expected taste pleasantness, fullness, satisfaction, healthiness, disgust and willingness-to-pay for each product/label combination. The results obtained demonstrate that alternatives to conventional meat products overall are acceptable to both meat and non-meat eaters. Although meat eaters' expected plant-based meat alternatives to be less satisfying, due to lower expected taste pleasantness and fillingness (Cohen's d = 0.14 to 0.63), they perceived the plant-based alternatives to be more healthy (d ≥ 1.18). Cultured meat products were perceived by meat eaters to be equally or more healthy, but more disgusting (d ≥ 0.41), than conventional meat products. These results suggest there is an opportunity to promote (motivate) acceptance of alternatives to conventional meat products based on their perceived healthiness, to at least partly balance reduced expected taste pleasantness and other negative attributes (i.e., barriers).

Serum progesterone concentration on the day of embryo transfer in stimulated cycles does not correlate with reproductive outcomes.

RESEARCH QUESTION: Is the live birth rate (LBR) in fresh embryo transfer IVF cycles affected by serum progesterone concentration on the day of embryo transfer? DESIGN: A single-centre retrospective analysis of prospectively collected data from women who underwent IVF or intracytoplasmic sperm injection between July 2019 and July 2020, and had a fresh day 5 single embryo transfer. Overall, 825 first and second stimulation cycles were included. Patients underwent a gonadotrophin-releasing hormone antagonist protocol with human chorionic gonadotrophin (HCG) trigger, and received vaginal-only luteal phase support. The study population was an everyday patient cohort, treated with the unit's usual stimulation protocols. The correlation between serum progesterone concentrations on the day of embryo transfer and the incidence of positive HCG, clinical pregnancy and live birth were examined. Patients were divided into four groups based on serum progesterone concentrations (<150, 150-250, 251-400 and >400 nmol/l). The data were further interrogated using additional progesterone cut-offs. RESULTS: There was no concentration of progesterone below or above which the chance of pregnancy was reduced. The chance of live birth following a blastocyst transfer was no different across the four groups (29.8, 26.6, 32.7 and 31.5%, respectively, P = 0.55). There was no negative association between progesterone and chance of pregnancy when other progesterone thresholds were applied. Estimates were adjusted for confounding factors such as maternal age. CONCLUSION: Serum progesterone concentration on the day of fresh embryo transfer does not correlate with the LBR.

Timing of progesterone luteal support in natural cryopreserved embryo transfer cycles: back to basics.

Moderate quality evidence suggests that the administration of progesterone luteal phase support (LPS) is beneficial in natural and modified (HCG-triggered) natural frozen embryo transfer (FET) cycles. No comparative studies examining the optimal timing of progesterone LPS administration in natural FET cycles have been conducted, and the common practice differs greatly between clinics worldwide. In the absence of clinical trials, we aimed to provide a scheme for progesterone supplementation in an attempt to mimic its natural secretion by the corpus luteum. On the basis of early studies of ovulation physiology, we suggest that progesterone luteal support administration in natural FET cycles should start 36 h after the onset of the LH surge when measured in a morning serum test, or 36 h after the administration of HCG for triggering final follicular maturation. Blastocyst transfer should be carried out after 5 full days of progesterone supplementation. Randomized clinical trials are required to confirm these recommendations.

Stress, caffeine and psychosis-like experiences-A double-blind, placebo-controlled experiment.

OBJECTIVE: Psychosis-like perceptual distortions can occur in the general population, and both stress and caffeine can enhance the proneness to psychosis-like experiences, such as hallucinations. The current study aims to explore the effects of acute caffeine intake and acute stress on perceptual distortions in a double-blind, placebo-controlled experiment. METHODS: Regular caffeine consumers (n = 92) and non/low consumers (n = 89) were assigned to 100 mg caffeine/placebo and stress/no stress conditions. The White Christmas Paradigm (WCP) was used to measure hallucination-like symptoms, and bias towards threat-related words was used as an indicator of persecutory ideation. Participants reported their daily caffeine intake, and completed the State-Trait Anxiety Inventory, the Launay-Slade Hallucination Scale, the Persecutory Ideation Questionnaire and the Marlow-Crowne Social Desirability Scale. RESULTS: Acute stress slightly increased hallucination-like experiences, but not recall bias, while the small amount of caffeine had a time-dependent effect on recall bias. Proneness to persecutory ideation was positively and social desirability was negatively correlated with recall bias towards threat-related words, while proneness to hallucinations positively correlated with hallucination-like experiences. CONCLUSIONS: Our results indicate that psychosocial stress-in line with the diathesis-stress model-can lead to the enhancement of hallucination-like experiences.

Consumption of low-calorie sweetened drinks is associated with 'sweet satiation', but not with 'sweet-taste confusion': A virtual study.

Originating from studies on rats, the 'taste confusion' hypothesis predicts that exposure to low-calorie sweeteners (LCS) will impair compensatory responses to sugar intake, resulting in increased overall calorie intake. We conducted a virtual study in which young adult human participants (n = 332), who differed in their history of exposure to sweet drinks (e.g., drank 'diet' (LCS) soft drinks or 'regular' (sugar-sweetened) soft drinks), imagined consuming a cheese sandwich and two-thirds of a 500 ml drink (still water, sparkling water, diet Coca Cola, regular Coca Cola, or semi-skimmed milk), or no drink, as a hypothetical lunch-time meal. They then used a screen-based tool to select the amount of a sweet snack (chocolate M&M's) or savoury snack (salted peanuts) that they would eat immediately with the remaining third of their drink (i.e., a total of 12 drink and snack combinations per participant). The results were inconsistent with the predictions of the taste confusion hypothesis; specifically, the extent to which consumption of sugar cola compared with water (still or sparkling) reduced snack intake did not differ between habitual diet (LCS) and habitual sugar soft-drink consumers. Other results showed a 'sweet satiation' effect (i.e., lower sweet versus savoury snack intake when the drink accompanying the meal was sweet compared with when it was water), and negligible compensation in snack food intake for the difference in the energy content of diet versus sugar cola.

Impact of the COVID-19 pandemic on UK endoscopic activity and cancer detection: a National Endoscopy Database Analysis.

OBJECTIVE: The COVID-19 pandemic has had a major global impact on endoscopic services. This reduced capacity, along with public reluctance to undergo endoscopy during the pandemic, might result in excess mortality from delayed cancer diagnosis. Using the UK's National Endoscopy Database (NED), we performed the first national analysis of the impact of the pandemic on endoscopy services and endoscopic cancer diagnosis. DESIGN: We developed a NED COVID-19 module incorporating procedure-level data on all endoscopic procedures. Three periods were designated: pre-COVID (6 January 2020 to 15 March), transition (16-22 March) and COVID-impacted (23 March-31 May). National, regional and procedure-specific analyses were performed. The average weekly number of cancers, proportion of missing cancers and cancer detection rates were calculated. RESULTS: A weekly average of 35 478 endoscopy procedures were performed in the pre-COVID period. Activity in the COVID-impacted period reduced to 12% of pre-COVID levels; at its low point, activity was only 5%, recovering to 20% of pre-COVID activity by study end. Although more selective vetting significantly increased the per-procedure cancer detection rate (pre-COVID 1.91%; COVID-impacted 6.61%; p<0.001), the weekly number of cancers detected decreased by 58%. The proportion of missing cancers ranged from 19% (pancreatobiliary) to 72% (colorectal). CONCLUSION: This national analysis demonstrates the remarkable impact that the pandemic has had on endoscopic services, which has resulted in a substantial and concerning reduction in cancer detection. Major, urgent efforts are required to restore endoscopy capacity to prevent an impending cancer healthcare crisis.

Genetic analyses of gynecological disease identify genetic relationships between uterine fibroids and endometrial cancer, and a novel endometrial cancer genetic risk region at the WNT4 1p36.12 locus.

Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-cancerous gynecological diseases and endometrial cancer risk by assessing genetic correlation, causal relationships and shared risk loci. We found significant genetic correlation between endometrial cancer and PCOS, and uterine fibroids. Adjustment for genetically predicted body mass index (a risk factor for PCOS, uterine fibroids and endometrial cancer) substantially attenuated the genetic correlation between endometrial cancer and PCOS but did not affect the correlation with uterine fibroids. Mendelian randomization analyses suggested a causal relationship between only uterine fibroids and endometrial cancer. Gene-based analyses revealed risk regions shared between endometrial cancer and endometriosis, and uterine fibroids. Multi-trait GWAS analysis of endometrial cancer and the genetically correlated gynecological diseases identified a novel genome-wide significant endometrial cancer risk locus at 1p36.12, which replicated in an independent endometrial cancer dataset. Interrogation of functional genomic data at 1p36.12 revealed biologically relevant genes, including WNT4 which is necessary for the development of the female reproductive system. In summary, our study provides genetic evidence for a causal relationship between uterine fibroids and endometrial cancer. It further provides evidence that the comorbidity of endometrial cancer, PCOS and uterine fibroids may partly be due to shared genetic architecture. Notably, this shared architecture has revealed a novel genome-wide risk locus for endometrial cancer.

The effects of low-calorie sweeteners on energy intake and body weight: a systematic review and meta-analyses of sustained intervention studies.

Previous meta-analyses of intervention studies have come to different conclusions about effects of consumption of low-calorie sweeteners (LCS) on body weight. The present review included 60 articles reporting 88 parallel-groups and cross-over studies ≥1 week in duration that reported either body weight (BW), BMI and/or energy intake (EI) outcomes. Studies were analysed according to whether they compared (1) LCS with sugar, (2) LCS with water or nothing, or (3) LCS capsules with placebo capsules. Results showed an effect in favour of LCS vs sugar for BW (29 parallel-groups studies, 2267 participants: BW change, -1.06 kg, 95% CI -1.50 to -0.62, I2 = 51%), BMI and EI. Effect on BW change increased with 'dose' of sugar replaced by LCS, whereas there were no differences in study outcome as a function of duration of the intervention or participant blinding. Overall, results showed no difference in effects of LCS vs water/nothing for BW (11 parallel-groups studies, 1068 participants: BW change, 0.10 kg, 95% CI -0.87 to 1.07, I2 = 82%), BMI and EI; and inconsistent effects for LCS consumed in capsules (BW change: -0.28 kg, 95% CI -0.80 to 0.25, I2 = 0%; BMI change: 0.20 kg/m2, 95% CI 0.04 to 0.36, I2 = 0%). Occurrence of adverse events was not affected by the consumption of LCS. The studies available did not permit robust analysis of effects by LCS type. In summary, outcomes were not clearly affected when the treatments differed in sweetness, nor when LCS were consumed in capsules without tasting; however, when treatments differed in energy value (LCS vs sugar), there were consistent effects in favour of LCS. The evidence from human intervention studies supports the use of LCS in weight management, constrained primarily by the amount of added sugar that LCS can displace in the diet.

Elucidating the role of long intergenic non-coding RNA 339 in human endometrium and endometriosis.

Endometriosis is a complex disease, influenced by genetic factors. Genetic markers associated with endometriosis exist at chromosome 1p36.12 and lead to altered expression of the long intergenic non-coding RNA 339 (LINC00339), however, the role of LINC00339 in endometriosis pathophysiology remains unknown. The aim of this work was to characterize the expression patterns of LINC00339 mRNA in endometrium and endometriotic lesions in situ and to determine the functional role of LINC00339 in human endometrium. We employed RNA-sequencing (RNA-seq), quantitative RT-PCR and in situ hybridization to investigate the abundance of LINC00339 transcripts in endometrium and endometrial cell lines and to describe the pattern and localization of LINC00339 expression in endometrium and endometriotic lesions. LINC00339 mRNA expression was manipulated (overexpressed and silenced) in endometrial stromal cell lines and RNA-seq data from overexpression models were analysed using online bioinformatics platforms (STRING and Ingenuity Pathway Analysis) to determine functional processes. We demonstrated the expression of LINC00339 in endometriotic lesions for the first time; we found LINC00339 expression was restricted to the lesion foci and absent in surrounding non-lesion tissue. Furthermore, manipulation of LINC00339 expression in endometrial stromal cell lines significantly impacted the expression of genes involved in immune defence pathways. These studies identify a novel mechanism for LINC00339 activity in endometrium and endometriosis, paving the way for future work, which is essential for understanding the pathogenesis of endometriosis.

An algorithm to personalise the diagnosis of recurrent implantation failure based on theoretical cumulative implantation rate.

Recurrent implantation failure (RIF) is an imprecisely defined disorder lacking a robust scientific basis. The incomplete understanding of RIF provides significant diagnostic and therapeutic challenges, and a better understanding of the underlying issues is necessary to improve outcomes. We propose a novel concept termed 'Theoretical Cumulative Implantation Rate', the calculation of which is based on objective data, to define whether a patient should be diagnosed with RIF. An updated definition to assist with patient counselling and planning research studies, which is more precise and standardised, is well overdue.