Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus.

BACKGROUND: Mountain areas of the North Caucasus host several large ethnic communities that have preserved their national identity over the centuries. METHODS: This study involved high-grade serous ovarian cancer (HGSOC) and breast cancer (BC) patients from Dagestan (HGSOC: 37; BC: 198), Kabardino-Balkaria (HGSOC: 68; BC: 155), North Ossetia (HGSOC: 51; BC: 104), Chechnya (HGSOC: 68; BC: 79), Ingushetia (HGSOC: 19; BC: 103), Karachay-Cherkessia (HGSOC: 13; BC: 47), and several Armenian settlements (HGSOC: 16; BC: 101). The group of BC patients was enriched by young-onset and/or family history-positive and/or bilateral and/or receptor triple-negative cases. The entire coding region of BRCA1, BRCA2, PALB2, and ATM genes was analyzed by next-generation sequencing. RESULTS: A significant contribution of BRCA1/2 pathogenic variants (PVs) to HGSOC and BC development was observed across all North Caucasus regions (HGSOC: 19-39%; BC: 6-13%). Founder alleles were identified in all ethnic groups studied, e.g., BRCA1 c.3629_3630delAG in Chechens, BRCA2 c.6341delC in North Ossetians, BRCA2 c.5351dupA in Ingush, and BRCA1 c.2907_2910delTAAA in Karachays. Some BRCA1/2 alleles, particularly BRCA2 c.9895C > T, were shared by several nationalities. ATM PVs were detected in 14 patients, with c.1673delG and c.8876_8879delACTG alleles occurring twice each. PALB2 heterozygosity was observed in 5 subjects, with one variant seen in 2 unrelated women. CONCLUSION: This study adds to the evidence for the global-wide contribution of BRCA1/2 genes to HGSOC and BC morbidity, although the spectrum of their PVs is a subject of ethnicity-specific variations. The data on founder BRCA1/2 alleles may be considered when adjusting the BRCA1/2 testing procedure to the ethnic origin of patients.

Higher testosterone is associated with higher HDL-cholesterol and lower triglyceride concentrations in older women: an observational study.

OBJECTIVE: This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women. METHODS: The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography-tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders. RESULTS: The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7-77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.002 and p < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol (p = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) (p = 0.024, p = 0.003 and p < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C (p = 0.024). CONCLUSIONS: In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.

Association between testosterone and cognitive performance in postmenopausal women: a systematic review of observational studies.

This review was conducted to explore the association between endogenous testosterone blood concentrations and cognitive performance among community dwelling postmenopausal women. We searched Ovid MEDLINE, EMBASE, PsycINFO and Web of Science databases for observational studies with at least 100 postmenopausal participants. The results were categorized by study design, reporting of total or free testosterone and risk of bias assessments, narratively. Ten of the 26 articles retrieved for full-text review met the inclusion criteria, six provided cross-sectional data, seven provided longitudinal data and one provided case-control data. Cognitive performance tests differed between studies. Eight studies measured testosterone by immunoassay, one by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and one did not specify their methodology. Eleven different cognitive domains were tested by 37 different instruments. Irrespective of the study design, the findings were inconsistent and inconclusive. Both positive and inverse associations were reported for each of global cognition and immediate and delayed verbal recall. The majority of studies reported no association between total or free testosterone and cognitive performance. Although this review did not demonstrate an association between testosterone and cognitive performance in postmenopausal women, the findings should be considered inconclusive due to the imprecision of testosterone measurement and the methodological heterogeneity of the included studies.

Menopause symptoms, sexual dysfunctions and pelvic floor disorders in refugee and asylum seeker women: a scoping review.

Refugee and asylum seeker women face a variety of health challenges. However, little is known globally about health problems in these women at midlife and beyond, including menopausal symptoms, sexual dysfunctions and pelvic floor disorders. This scoping review aimed to understand these neglected health issues with respect to prevalence and risk factors. Eight databases were searched in August 2022 without the limit of publication year. Data were analyzed narratively. A total of 10 reports from seven studies were included with 945 women living in Australia, Canada, the USA and Pakistan. Three reports were addressing menopause, seven addressed sexual dysfunctions and one addressed pelvic floor disorders. There were no data regarding menopause symptoms; however, perceptions of menopause varied widely across studies. Few studies reported a high prevalence of sexual dysfunctions and pelvic organ prolapses, but none of them used a validated questionnaire. Taboos and cultural factors, lack of knowledge and education, lack of family support, language insufficiency and financial problems were common barriers to not seeking care for these health issues. This review demonstrates lack of evidence of these neglected health issues in refugee and asylum seeker women at midlife, and further studies with validated questionnaires and larger samples are warranted.

Sex hormones, SHBG and cognitive performance among older Australian women: an observational study.

OBJECTIVE: This study aims to explore the associations between sex hormones and cognitive performance in older women. METHODS: Associations between sex hormones, sex hormone binding globulin (SHBG) and cognitive performance were examined in women aged at least 70 years, without dementia and not using medications that influence sex hormones. Linear and generalized linear regression models included age, body mass index, education, smoking, alcohol, living circumstances, diabetes, hypertension, depression and impaired renal function. RESULTS: The included 5511 women had a median (interquartile range) age of 73.9 (71.6-77.6) years. No associations were found for estrone, estradiol, testosterone or dehydroepiandrosterone and cognitive performance. SHBG concentrations above quartile 1 (Q1) were significantly inversely associated with processing speed (Q2, ß = -0.94, 95% confidence interval [CI] - 1.64 to -0.24, p = 0.009; Q3, ß = -0.82, 95% CI -1.53 to -0.10, p = 0.025; and Q4, ß = -0.95, 95% CI -1.70 to -0.20, p = 0.013). CONCLUSIONS: Sex hormones were not associated with cognitive performance. The finding that low SHBG is associated with better processing speed warrants further investigation. The null findings for the sex hormones establish a firm baseline to confidently explore the association between sex hormones and longitudinal cognitive performance in this population. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and ClinicalTrials.gov (NCT01038583).

The 2023 Practitioner's Toolkit for Managing Menopause.

OBJECTIVE: The Practitioner's Toolkit for Managing the Menopause, developed in 2014, provided an accessible desk-top tool for health-care practitioners caring for women at midlife. To ensure the Toolkit algorithms and supporting information reflect current best practice, the Toolkit has been revised in accordance with the published literature. METHODS: A systematic search for guidelines, position and consensus statements pertaining to the menopause and published after 2014 was undertaken, and key recommendations extracted from the Clinical Practice Guidelines determined to be the most robust by formal evaluation. The peer-reviewed literature was further searched for identified information gaps. RESULTS: The revised Toolkit provides algorithms that guide the clinical assessment and care of women relevant to menopause. Included are the reasons why women present, information that should be ascertained, issues that may influence shared decision-making and algorithms that assist with determination of menopausal status, menopause hormone therapy (MHT) and non-hormonal treatment options for symptom relief. As clear guidelines regarding when MHT might be indicated to prevent bone loss and subsequent osteoporosis in asymptomatic women were found to be lacking, the Toolkit has been expanded to support shared decision-making regarding bone health. CONCLUSIONS: The 2023 Toolkit and supporting document provide accessible desk-top information to support health-care providers caring for women at midlife.The Toolkit has been endorsed by the International Menopause Society, Australasian Menopause Society, British Menopause Society, Endocrine Society of Australia and Jean hailes for Women's Health.

Estrone, sex hormone binding globulin and lipid profiles in older women: an observational study.

OBJECTIVE: We investigated whether estrone and sex hormone binding globulin (SHBG) concentrations are associated with lipid concentrations in older postmenopausal women. METHODS: This was a cross-sectional study of 6358 Australian women, aged 70-95 years, recruited between 2010 and 2014. Associations between estrone and SHBG and lipid concentrations were examined in participants not using medications that influence estrogen concentrations or lipid-lowering therapy. Linear regression models included age, body mass index, smoking, alcohol consumption, renal function and diabetes, with the lowest quartile (Q1) as the reference for estrone and SHBG. RESULTS: The study included 3231 participants with median age of 74.0 (interquartile range 71.7-77.9) years. Estrone concentration Q3 and Q4 were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.017 and p = 0.046, respectively). Inverse associations were seen for estrone Q4 with total cholesterol (p = 0.018), Q2 and Q4 with non-HDL-C (p = 0.045 and p = 0.002, respectively) and Q3 and Q4 with triglycerides (p = 0.030 and p = 0.001, respectively). For SHBG, Q2, Q3 and Q4 were positively associated with HDL-C (all p < 0.001), and inversely with non-HDL-C (all p = 0.001) and triglycerides (all p < 0.001). CONCLUSIONS: Estrone and SHBG are associated with lipid concentrations in older women. SHBG, but not estrone, may provide additional clinical predictive utility for the assessment of cardiometabolic disease risk in older women.

Steric and Energetic Studies on the Synergetic Enhancement Effect of Integrated Polyaniline on the Adsorption Properties of Toxic Basic and Acidic Dyes by Polyaniline/Zeolite-A Composite.

The synergetic enhancement effect of the polyaniline (PANI) integration process on the adsorption properties of the PANI/zeolite-A composite (PANI/ZA) as an adsorbent for malachite green and Congo red synthetic dyes was evaluated based on classic equilibrium modelling in addition to the steric and energetic parameters of advanced isotherm studies. The PANI/ZA composite displays enhanced adsorption capacities for both methylene blue (270.9 mg/g) and Congo red (235.5 mg/g) as compared to ZA particles (methylene blue (179.6 mg/g) and Congo red (140.3 mg/g)). The reported enhancement was illustrated based on the steric parameters of active site density (Nm) and the number of adsorbed dyes per active site (n). The integration of PANI strongly induced the quantities of the existing active sites that have enhanced affinities towards both methylene blue (109.2 mg/g) and Congo red (92.9 mg/g) as compared to the present sites on the surface of ZA. Every site on the surface of PANI/ZA can adsorb about four methylene blue molecules and five Congo red molecules, signifying the vertical orientation of their adsorbed ions and their uptake by multi-molecular mechanisms. The energetic investigation of the methylene blue (-10.26 to -16.8 kJ/mol) and Congo red (-9.38 to -16.49 kJ/mol) adsorption reactions by PANI/ZA suggested the operation of physical mechanisms during their uptake by PANI/ZA. These mechanisms might involve van der Waals forces, dipole bonding forces, and hydrogen bonding (<30 kJ/mol). The evaluated thermodynamic functions, including enthalpy, internal energy, and entropy, validate the exothermic and spontaneous behaviours of the methylene blue and Congo red uptake processes by PANI/ZA.

Intracranial hemorrhage in primary immune thrombocytopenia (ITP): 20 years' experience in pediatrics.

Incidence of intracranial hemorrhage (ICH) among children with primary immune thrombocytopenia (ITP) varies among different studies. We published data during the period of 1997-2007 of ICH in children with primary ITP, addressing risk factors and outcome. The aim of this study is to assess changes in incidence, risk factors, and outcome of ICH in children with ITP from last decade and to report the overall 20 years' experience. We compared 2008-2018 with the decade before it. Data of children with ITP and ICH during study period and ITP control cases were analyzed. Neurosurgical intervention and outcome were also reported. A total of 4340 children with primary ITP were evaluated. Twenty-five (0.63%) ICH events were reported over 2 decades. Head trauma, hematuria, and platelet counts < 10 × 109/L were the risk factors mostly associated with ICH. Overall mortality was 24%, and a further 28% had neurologic sequelae. Neurosurgical intervention was done in 12% of cases with good outcome.Conclusion: Persistent platelet counts < 10 × 109/L were a significant risk factor for ICH in both time periods, while head trauma and hematuria were more reported in the period of 2008-2018 as significant risk factors for ICH. Outcome was comparable in both periods. What is Known: • ICH is a rare complication of ITP; however, early recognition of risk factors and aggressive treatment might lead to complete recovery without sequalae. Platelet counts less than < 10 × 109/L are the main risk factor for ICH. Few studies reported other significant risk factors. What is New: • Hematuria and head trauma are significant risk factors for ICH in ITP, in addition to having a persistently low platelet count < 10 × 109/L. (more than 90 days in chronic ITP, 45 days in persistent and 21 days in acute ITP) • Combined treatment with IVIG and HDMP followed by platelet transfusion was associated with complete recovery without sequelae in almost 50% of patients.

Precise Identification of Prostate Cancer from DWI Using Transfer Learning.

Background and Objective: The use of computer-aided detection (CAD) systems can help radiologists make objective decisions and reduce the dependence on invasive techniques. In this study, a CAD system that detects and identifies prostate cancer from diffusion-weighted imaging (DWI) is developed. Methods: The proposed system first uses non-negative matrix factorization (NMF) to integrate three different types of features for the accurate segmentation of prostate regions. Then, discriminatory features in the form of apparent diffusion coefficient (ADC) volumes are estimated from the segmented regions. The ADC maps that constitute these volumes are labeled by a radiologist to identify the ADC maps with malignant or benign tumors. Finally, transfer learning is used to fine-tune two different previously-trained convolutional neural network (CNN) models (AlexNet and VGGNet) for detecting and identifying prostate cancer. Results: Multiple experiments were conducted to evaluate the accuracy of different CNN models using DWI datasets acquired at nine distinct b-values that included both high and low b-values. The average accuracy of AlexNet at the nine b-values was 89.2±1.5% with average sensitivity and specificity of 87.5±2.3% and 90.9±1.9%. These results improved with the use of the deeper CNN model (VGGNet). The average accuracy of VGGNet was 91.2±1.3% with sensitivity and specificity of 91.7±1.7% and 90.1±2.8%. Conclusions: The results of the conducted experiments emphasize the feasibility and accuracy of the developed system and the improvement of this accuracy using the deeper CNN.

Genetic diversity and population structure in multiple Chinese goat populations using a SNP panel.

Information about genetic diversity and population structure among goat breeds is essential for genetic improvement, understanding of environmental adaptation as well as utilization and conservation of goat breeds. Here, we measured genetic diversity and population structure in multiple Chinese goat populations, namely, Nanjiang, Qinggeda, Arbas Cashmere, Jining Grey, Luoping Yellow and Guangfeng goats. A total of 193 individuals were genotyped for about 47 401 autosomal single nucleotide polymorphisms (SNPs). We found a high proportion of informative SNPs, ranging from 69.5% in the Luoping Yellow to 93.9% in the Jining Grey goat breeds with an average mean of 84.7%. Diversity, as measured by expected heterozygosity, ranged from 0.371 in Luoping Yellow to 0.405 in Jining Grey goat populations. The average estimated pair-wise genetic differentiation (FST ) among the populations was 8.6%, ranging from 0.2% to 16% and indicating low to moderate genetic differentiation. Principal component analysis, genetic structure and phylogenetic tree analysis revealed a clustering of six Chinese goat populations according to geographic distribution. The results from this study can contribute valuable genetic information and can properly assist with within-breed diversity, which provides a good opportunity for sustainable utilization of and maintenance of genetic resource improvements in the Chinese goat populations.

Clinical parameters of ovarian hyperstimulation syndrome following different hormonal triggers of oocyte maturation in IVF treatment.

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic condition, predominantly related to the hormone used to induce oocyte maturation during IVF treatment. Kisspeptin is a hypothalamic neuropeptide that has recently been demonstrated to safely trigger final oocyte maturation during IVF treatment even in women at high risk of OHSS. However, to date, the safety of kisspeptin has not been compared to current hormonal triggers of oocyte maturation. DESIGN: We conducted a retrospective single-centre cohort study investigating symptoms and clinical parameters of early OHSS in women at high risk of OHSS (antral follicle count or total number of follicles on day of trigger ≥23) triggered with human chorionic gonadotrophin (hCG) (n = 40), GnRH agonist (GnRHa; n = 99) or kisspeptin (n = 122) at Hammersmith Hospital IVF unit, London, UK (2013-2016). RESULTS: Clinical Parameters of OHSS: Median ovarian volume was larger following hCG (138 ml) than GnRHa (73 ml; P < .0001), and in turn kisspeptin (44 ml; P < .0001). Median ovarian volume remained enlarged 20-fold following hCG, 8-fold following GnRHa and 5-fold following kisspeptin compared to prestimulation ovarian volumes. Mean (±SD) ascitic volumes were lesser following GnRHa (9 ± 44 ml) and kisspeptin (5 ± 8 ml) than hCG (62 ± 84 ml; P < .0001). Symptoms of OHSS were most frequent following hCG and least frequent following kisspeptin. Diagnosis of OHSS: The odds ratio for OHSS diagnosis was 33.6 (CI 12.6-89.5) following hCG and 3.6 (CI 1.8-7.1) following GnRHa, when compared to kisspeptin. CONCLUSION: Triggering oocyte maturation by inducing endogenous gonadotrophin release is preferable to the use of exogenous hCG in women at high risk of OHSS.

The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function.

STUDY QUESTION: What are the in vivo and in vitro actions of kisspeptin-54 on the expression of genes involved in ovarian reproductive function, steroidogenesis and ovarian hyperstimulation syndrome (OHSS) in granulosa lutein (GL) cells when compared with traditional triggers of oocyte maturation? SUMMARY ANSWER: The use of kisspeptin-54 as an oocyte maturation trigger augmented expression of genes involved in ovarian steroidogenesis in human GL cells including, FSH receptor (FSHR), LH/hCG receptor (LHCGR), steroid acute regulatory protein (STAR), aromatase, estrogen receptors alpha and beta (ESR1, ESR2), 3-beta-hydroxysteroid dehydrogenase type 2 (3BHSD2) and inhibin A (INHBA), when compared to traditional maturation triggers, but did not alter markers of OHSS. WHAT IS KNOWN ALREADY: hCG is the most widely used trigger of oocyte maturation, but is associated with an increased risk of OHSS. The use of GnRH agonists to trigger oocyte maturation is a safer alternative to hCG. More recently, kisspeptin-54 has emerged as a novel therapeutic option that safely triggers oocyte maturation even in women at high risk of OHSS. Kisspeptin indirectly stimulates gonadotropin secretion by acting on hypothalamic GnRH neurons. Kisspeptin and its receptor are also expressed in the human ovary, but there is limited data on the direct action of kisspeptin on the ovary. STUDY DESIGN SIZE, DURATION: Forty-eight women undergoing IVF treatment for infertility consented to kisspeptin-54 triggering and/or granulosa cell collection and were included in the study. Twelve women received hCG, 12 received GnRH agonist and 24 received kisspeptin-54 to trigger oocyte maturation. In the kisspeptin-54 group, 12 received one injection of kisseptin-54 (9.6 nmol/kg) and 12 received two injections of kisspeptin-54 at a 10 h interval (9.6 nmol/kg × 2). PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicular fluid was aspirated and pooled from follicles during the retrieval of oocytes for IVF/ICSI. GL cells were isolated and either RNA extracted immediately or cultured in vitro ± kisspeptin or hCG. MAIN RESULTS AND THE ROLE OF CHANCE: GL cells from women who had received kisspeptin-54 had a 14-fold and 8-fold higher gene expression of FSHR and a 2-fold (ns) and 2.5-fold (P < 0.05) higher expression of LHCGR than GL cells from women who had received hCG or GnRH agonist, respectively. CYP19A1 expression was 3.6-fold (P < 0.05) and 4.5-fold (P < 0.05) higher, STAR expression was 3.4-fold (P < 0.01) and 1.8-fold (P < 0.05) higher, HSD3B2 expression was 7.5- (P < 0.01) and 2.5-fold higher (P < 0.05), INHBA was 2.5-fold (P < 0.01) and 2.5-fold (P < 0.01) higher in GL cells from women who had received kisspeptin-54 than hCG or GnRHa, respectively. ESR1 (P < 0.05) and ESR2 (P < 0.05) both showed 3-fold higher expression in cells from kisspeptin treated than GnRHa treated women. Markers of vascular permeability and oocyte growth factors were unchanged (VEGFA, SERPINF1, CDH5, amphiregulin, epiregulin). Gene expression of kisspeptin receptor was unchanged. Whereas treating GL cells in vitro with hCG induced steroidogenic gene expression, kisspeptin-54 had no significant direct effects on either OHSS genes or steroidogenic genes. LIMITATIONS REASONS FOR CAUTION: Most women in the study had PCOS, which may limit applicability to other patient groups. For the analysis of the in vitro effects of kisspeptin-54, it is important to note that GL cells had already been exposed in vivo to an alternate maturation trigger. WIDER IMPLICATIONS OF THE FINDINGS: The profile of serum gonadotropins seen with kisspeptin administration compared to other triggers more closely resemble that of the natural cycle as compared with hCG. Thus, kisspeptin could potentially permit an ovarian environment augmented for steroidogenesis, in particular progesterone synthesis, which is required for embryo implantation. STUDY FUNDING/COMPETING INTEREST(S): Dr Owens is supported by an Imperial College London PhD Scholarship. Dr Abbara is supported by an National Institute of Health Research Academic Clinical Lectureship. The authors do not have any conflict of interest to declare. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01667406.

A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels.

We investigated five methylation markers recently linked to body mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus and frontal gyri, some of which have been previously associated to food signaling, obesity or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity and genetic differences.

Fibroids that do not distort the uterine cavity and IVF success rates: an observational study using extensive matching criteria.

OBJECTIVE: To assess the impact of non-cavity-distorting fibroids on in vitro fertilisation (IVF) pregnancy outcomes. DESIGN: A retrospective, matched, single-centre, cohort study was performed. SETTING: The IVF unit of a tertiary, university hospital. POPULATION: We analysed all women with non-cavity-distorting uterine fibroids undergoing IVF/intracytoplasmic sperm injection (ICSI) cycles from 1 January 2011 to 1 May 2015. METHODS: Each woman was matched with two separate controls of the same age (±6 months), stimulation protocol (gonadotropin-releasing hormone agonist or antagonist), starting dose of follicle-stimulating hormone (FSH), number of embryos transferred (one or two), day of transfer (day 3 or day 5), and no uterine fibroids identified by transvaginal ultrasound. MAIN OUTCOME MEASURES: Clinical pregnancy and live birth rates. RESULTS: Our study demonstrates that the presence of non-cavity-distorting fibroids appears to negatively affect clinical pregnancy (odds ratio, OR 0.62; 95% confidence interval, 95% CI 0.41-0.94) and live birth rates (OR 0.58; 95% CI 0.48-0.78) in patients undergoing their first IVF/ICSI cycle, when matched with controls of the same age, starting dose of FSH, stimulation protocol, number of embryos, and day of embryo transfer. The deleterious effect of fibroids on live birth rates was significant in women with two or more fibroids (OR 0.47; 95% CI 0.26-0.83) and in women with fibroids of ≥30 mm in diameter (OR 0.41; 95% CI 0.19-0.89). The negative impact of non-cavity-distorting fibroids was also present in women with an embryo transfer on day 5 (OR 0.58; 95% CI 0.35-0.94). Conversely, in women with single fibroids of <30 mm in diameter, no difference in pregnancy outcomes was identified. CONCLUSIONS: A well-designed, adequately powered, randomised controlled trial is required to address the role of medical or surgical interventions in patients with intramural and subserosal fibroids before undergoing fertility treatment. TWEETABLE ABSTRACT: Non-cavity-distorting fibroids negatively affect pregnancy rates after IVF.

Quantum simulation of frustrated Ising spins with trapped ions.

A network is frustrated when competing interactions between nodes prevent each bond from being satisfied. This compromise is central to the behaviour of many complex systems, from social and neural networks to protein folding and magnetism. Frustrated networks have highly degenerate ground states, with excess entropy and disorder even at zero temperature. In the case of quantum networks, frustration can lead to massively entangled ground states, underpinning exotic materials such as quantum spin liquids and spin glasses. Here we realize a quantum simulation of frustrated Ising spins in a system of three trapped atomic ions, whose interactions are precisely controlled using optical forces. We study the ground state of this system as it adiabatically evolves from a transverse polarized state, and observe that frustration induces extra degeneracy. We also measure the entanglement in the system, finding a link between frustration and ground-state entanglement. This experimental system can be scaled to simulate larger numbers of spins, the ground states of which (for frustrated interactions) cannot be simulated on a classical computer.

The prevalence of symptomatic pelvic floor disorders in women in Bangladesh.

OBJECTIVE: To investigate the prevalence of, and risk factors for, pelvic floor disorders (PFDs) in women in Bangladesh. METHODS: A nationally representative sample of 1590 Bangladeshi women, aged 30-59 years, was recruited using a multistage cluster sampling technique, between September 2013 and March 2014. Urinary incontinence (UI), fecal incontinence (FI) and pelvic organ prolapse (POP) were assessed using validated questionnaires. The weighted prevalence and the factors associated with each PFD were investigated using multivariable weighted logistic regression. RESULTS: The weighted prevalence of UI was 23.7% (95% confidence interval (CI) 21.3-26.0%), FI 5.3% (95% CI 4.0-6.6%), POP 16.2% (95% CI 14.2-18.2%), and having at least one PFD 35.3% (95% CI 32.6-37.9%). Women were more likely to have at least one PFD if aged 40-49 years (adjusted odds ratio (AOR) 1.46, 95% CI 1.02-2.08; p = 0.040) or 50-59 years (AOR 2.39, 95% CI 1.59-3.58; p < 0.0001), compared with women aged 30-39 years. Having at least one PFD was positively associated with having three or more versus fewer children (AOR 1.61, 95% CI 1.14-2.27; p = 0.007), being in the middle (AOR 3.05, 95% CI 1.72-5.41; p < 0.0001), second lowest (AOR 2.49, 95% CI 1.39-4.47; p = 0.002) or lowest (AOR 3.13, 95% CI 1.68-5.86; p < 0.0001) wealth quintile compared with the highest, and self-reporting diabetes (AOR 2.55, 95% CI 1.54-4.23; p < 0.0001). CONCLUSIONS: One-third of Bangladeshi women aged 30-59 years had at least one symptomatic PFD. Risk factors included greater age, higher parity, lower wealth status and self-reported diabetes. The diagnosis, treatment, and prevention of PFDs in Bangladesh need greater attention, as the prevalence of these disabling conditions is likely to increase with the aging of the population.

Epidemiological Aspect and common Bacterial and Fungal isolates from Suppurative Corneal Ulcer in Mymensingh Region.

This prospective study was done to find out the epidemiological factors of suppurative corneal ulcer and the common causative bacterial and fungal isolates from the, patients with suppurative corneal ulcer in secondary and tertiary level hospital at Mymensingh region. A total 100 samples of corneal scrapings were collected purposively from clinically diagnosed suppurative corneal ulcer patients from March 18, 2012 to March 17, 2013. Out of the total 100 samples, bacterial species were 29(29%) cases and the fungal spacies were 71(71%) identified by the culture in blood agar, chocolate agar and sabouraud's agar media and also by microscopic examination. The bacterial species were streptococcus pneumonae 12 cases (12%), Staphylococcus aureus 9 cases (9%), pseudomonas in 6 cases (6%), and Streptococcus pyoganes 2 cases (2%). Fungal species were aspergillus fumigatus 61 cases (61%), aspergillus niger 10 cases (10%). Out of the study populations, most of the populations were from the age group of 41 to 60 years (39 %), followed 21 to 40 years (34%) age group. Considering the sex, male were 67%, female were 33%. The majority of patients came from the rural area of Mymensingh region; occupationally they were farmers (44%). Ocular trauma due to agricultural materials was the most common associated factor (71%). The etiological and epidemiological pattern of suppurative corneal ulcer varies significantly with geographical region, patient population and health of the cornea. The present study was carried out to explore the epidemiological pattern, causative bacterial and fungal specie by laboratory procedure from corneal scraping and to invent a prospective guide line for the management of corneal ulcer in the community.