Tag: pubmed

Rev Int Androl. 2022 Oct 20:S1698-031X(22)00076-0. doi: 10.1016/j.androl.2021.02.011. Online ahead of print.

ABSTRACT

INTRODUCTION: Depression is not uncommon among infertile couples. The objective of the study is to analyze factors that predict depression in these couples, when they are in Assisted Reproduction Techniques programs.

MATERIALS AND METHOD: We analyze the level of depression in couples referred from the Human Reproduction Unit to study the male factor using the Beck Depression Inventory and the clinical information contained in the SARAplus program.

RESULTS: Depressive ranges appear in approximately half of the participants. The degree of depression correlates in a statistically significant way between both members of the couple. Among the analyzed clinical factors, we observed relational tendency between depression and obesity and depression and smoking.

CONCLUSIONS: Depression in infertile couples is a fact. ART specialists should be on the lookout for symptoms of depression in order to provide patients psychological and psychiatric care and treatments, as part of the overall therapeutic framework for infertility.

PMID:36273995 | DOI:10.1016/j.androl.2021.02.011

Rev Int Androl. 2022 Oct 20:S1698-031X(22)00083-8. doi: 10.1016/j.androl.2021.11.004. Online ahead of print.

ABSTRACT

INTRODUCTION: Sexual attitudes are related to the norms and customs that are considered appropriate according to the era in which one lives, usually showing themselves more restrictive for women.

OBJECTIVE: The aim of this study is to analyze how sexual attitudes (erotophilia-erotophobia and sexual double standards) may predispose to sexual violence (attitudes in favor of rape).

MATERIAL AND METHODS: The sample consisted of 868 students from the University of Huelva (723 women and 145 men), aged between 17 and 57 years. The Double Moral Scale, the Rape Favorable Attitude Scale and the Revised Sexual Opinion Survey were used.

RESULTS: People who are more erotophilic are bisexuals (x̄=99.10) and people who consider themselves left-wing in politics (x̄=96.91). The highest double standards scores are obtained by men (x̄=18.50), master’s students (x̄=18.58), asexuals (x̄=20.50) and people who consider themselves centrist (x̄=18.24). In terms of pro-rape attitudes, men (x̄=37.72), heterosexuals (x̄=33.29) and people who consider themselves right-wing (x̄=37.35) stand out. The differences found between the groups are statistically significant.

CONCLUSIONS: It is confirmed that sexual attitudes can predispose to sexual violence, which shows the need to continue working in this line in order to promote pleasurable sexual experiences.

PMID:36273994 | DOI:10.1016/j.androl.2021.11.004

Hematol Transfus Cell Ther. 2022 Oct 17:S2531-1379(22)01426-2. doi: 10.1016/j.htct.2022.09.1275. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of romiplostim (thrombopoietin-receptor agonist) in the treatment of pediatric immune thrombocytopenia (ITP).

METHODS: Searches were conducted in MEDLINE, EMBASE, LILACS, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov (from January 2011 to August 2021). Randomized controlled trials (RCTs), double-blind, comparing romiplostim with a placebo in pediatric persistent or chronic ITP were included. The primary outcome was the overall response rate (platelets ≥ 50 × 10⁹/L) in the absence of rescue therapy for at least two consecutive weeks. The secondary endpoints were the minimization of clinically significant bleeding and the necessity for rescue treatments and the maximization of safety (incidence of overall adverse events) and durable response (maintaining platelet counts for at least twelve weeks).

RESULTS: Two double-blind randomized placebo-controlled trials (84 participants) were included in this systematic review. Our data showed that, compared to the placebo group, the proportion of patients achieving durable platelet response was significantly higher in the romiplostim group (p = 0.003, RR = 6.34, 95%CI = 1.89 – 21.23), as was the overall response in the romiplostim group (p = 0.002, RR = 3.62, 95%CI = 1.63 – 8.03). Significant bleeding incidents (p = 0.49), overall adverse events (p = 0.71) and the need for rescue treatment (p = 0.13) were not statistically different between the romiplostim and placebo groups.

CONCLUSIONS: Romiplostim might improve both durable and overall platelet response in children and adolescents with ITP, compared to a placebo. More clinical trials are needed to evaluate the efficacy and safety of romiplostim and to compare it with other second-line treatments that are being used in pediatric ITP.

PMID:36273985 | DOI:10.1016/j.htct.2022.09.1275

Surgery. 2022 Oct 20:S0039-6060(22)00711-5. doi: 10.1016/j.surg.2022.08.042. Online ahead of print.

ABSTRACT

BACKGROUND: Studies evaluating endoscopic resection for early-stage (cT1N0M0) esophageal adenocarcinoma include small numbers of patients with T1b tumors. The role of endoscopic resection in esophageal adenocarcinoma remains incompletely defined.

METHODS: We queried the National Cancer Database to identify patients presenting with esophageal adenocarcinoma between 2010 and 2017. Those treated with neoadjuvant chemoradiotherapy and endoscopic ablation were excluded. Patients undergoing endoscopic resection for cT1a and cT1b tumors were separately 1:1 propensity matched for relevant demographic and tumor factors to those undergoing esophagectomy for disease of like clinical stage. The Kaplan-Meier method was used to compare 5-year overall survival for matched cohorts.

RESULTS: A total of 3,157 patients met the inclusion criteria. Of these patients, 2,024 (64.1%) had cT1a and 1133 (35.9%) had cT1b disease. Among those with cT1a tumors, 461 (22.8%) underwent esophagectomy, 1,357 (67.0%) endoscopic resection, and 206 (10.2%) treatment with chemoradiotherapy alone. Among those with cT1b tumors, 649 (57.3%) underwent esophagectomy, 293 (25.9%) endoscopic resection, and 191 (16.8%) chemoradiotherapy. On unadjusted comparison, patients treated for esophageal adenocarcinoma with chemoradiotherapy had a lower rate of overall survival than those treated with endoscopic resection or esophagectomy (26.1% vs 73.1% vs 75.5%, P < .001). On comparison of matched cohorts, patients undergoing endoscopic resection for cT1b tumors demonstrated lower rates of overall survival than those undergoing esophagectomy (60.6% vs 74.1%, P = .0013), whereas those undergoing endoscopic resection for cT1a tumors demonstrated rates of overall survival statistically similar to those undergoing esophagectomy (77.8% vs 80.2%, P = .75).

CONCLUSION: Esophagectomy is associated with improved overall survival relative to endoscopic resection in patients presenting with cT1bN0M0 but not in those with cT1a esophageal adenocarcinoma.

PMID:36273971 | DOI:10.1016/j.surg.2022.08.042

Eur Urol. 2022 Oct 20:S0302-2838(22)02707-5. doi: 10.1016/j.eururo.2022.09.030. Online ahead of print.

ABSTRACT

BACKGROUND: Bladder cancer (BCa) is more common in men and presents differences in molecular subtypes based on sex. Fibroblast growth factor receptor 3 (FGFR3) mutations are enriched in the luminal papillary muscle-invasive BCa (MIBC) and non-MIBC subtypes.

OBJECTIVE: To determine whether FGFR3 mutations initiate BCa and impact BCa male sex bias.

DESIGN, SETTING, AND PARTICIPANTS: We developed a transgenic mouse model expressing the most frequent FGFR3 mutation, FGFR3-S249C, in urothelial cells. Bladder tumorigenesis was monitored in transgenic mice, with and without carcinogen exposure. Mouse and human BCa transcriptomic data were compared.

INTERVENTION: Mutant FGFR3 overexpression in mouse urothelium and siRNA knockdown in cell lines, and N-butyl-N(4-hydroxybutyl)-nitrosamine (BBN) exposure.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Impact of transgene dosage on tumor frequency, synergy with BBN treatment, and FGFR3 pathway activation were analyzed. The sex-specific incidence of FGFR3-mutated tumors was evaluated in mice and humans. FGFR3 expression in FGFR3-S249C mouse urothelium and in various human epithelia was measured. Mutant FGFR3 regulation of androgen (AR) and estrogen (ESR1) receptor activity was evaluated, through target gene expression (regulon) and reporter assays.

RESULTS AND LIMITATIONS: FGFR3-S249C expression in mice induced low-grade papillary BCa resembling human luminal counterpart at histological, genomic, and transcriptomic levels, and promoted BBN-induced basal BCa formation. Mutant FGFR3 expression levels impacted tumor incidence in mice, and mutant FGFR3-driven human tumors were restricted to epithelia presenting high normal FGFR3 expression levels. BCa male sex bias, also found in our model, was even higher in human FGFR3-mutated tumors compared with wild-type tumors and was associated with higher AR and lower ESR1 regulon activity. Mutant FGFR3 expression inhibited both ESR1 and AR activity in mouse tumors and human cell lines, demonstrating causation only between FGFR3 activation and low ESR1 activity in tumors.

CONCLUSIONS: Mutant FGFR3 initiates luminal papillary BCa formation and favors BCa male sex bias, potentially through FGFR3-dependent ESR1 downregulation. Patients with premalignant lesions or early-stage BCa could thus potentially benefit from FGFR3 targeting. FGFR3 expression level in epithelia could account for FGFR3-driven carcinoma tissue specificity.

PATIENT SUMMARY: By developing a transgenic mouse model, we showed that gain-of-function mutations of FGFR3 receptor, among the most frequent genetic alterations in bladder cancer (BCa), initiate BCa formation. Our results could support noninvasive detection of FGFR3 mutations and FGFR3 targeting in early-stage bladder lesions.

PMID:36273937 | DOI:10.1016/j.eururo.2022.09.030

J Atheroscler Thromb. 2022 Oct 21. doi: 10.5551/jat.63798. Online ahead of print.

ABSTRACT

AIMS: Whether the multi-dimensional data of serially measured blood pressure contains information for predicting the future risk of death in elderly individuals in nursing homes is unclear.

METHODS: Of the elderly individuals staying in a nursing home, 19,740 and 40,055 individuals with serially measured blood pressure from day 1 to 365 (for AI-long) and 1 to 90 (for AI-short) along with the death information at day 366 to 730 and 91-365 were included. The neural network-based artificial intelligence (AI) was applied to find the relationship between BP time-series and the future risks of death in both populations.

RESULTS: AI-long found a significant relationship between the serially measured BP from day 1 to day 365 days and the risk of death occurring 366-730 days with c-statistics of 0.57 (95% CI: 0.51-0.63). AI-short also found a significant relationship between the serially measured BP from day 1 to day 90 and the rate of death occurring 91-365 days with c-statistics of 0.58 (95%CI: 0.52-0.63).

CONCLUSION: Our results suggest that neural network-based AI could find the hidden subtle relationship between multi-dimensional data of serially measured BP and the future risk of death in apparently healthy elderly Japanese individuals under nursing care.

PMID:36273901 | DOI:10.5551/jat.63798

J Matern Fetal Neonatal Med. 2022 Oct 23:1-7. doi: 10.1080/14767058.2022.2139175. Online ahead of print.

ABSTRACT

BACKGROUND: Gestational diabetes mellitus (GDM) prevalence has risen in the U.S. and worldwide over the past decade. Minority groups, especially Asian and Hispanic women, are often disproportionately affected by GDM. Identifying modifiable risk factors such as sleep-disordered breathing and smoking and their interaction with race/ethnicity could play a pivotal role in preventing GDM.

METHODS: Data from the 2017-2018 National Health and Nutrition Examination Surveys (NHANES) were used to run a survey-weighted multivariable logistic regression assessing the association between sleep-disordered breathing and smoking with GDM among women aged 15-60 (n = 1326). The interaction term of the two predictors and race/ethnicity was introduced to the model to assess the interaction effect. The analyses were adjusted for age, marital status, education level, and BMI.

RESULTS: Approximately 13% of the participants reported having GDM. The lowest prevalence was observed among Non-Hispanic Blacks (7.8%) and the highest was among Other (15.5%). Sleep-disordered breathing was significantly associated with GDM (OR = 1.69, 95% CI 1.05, 2.73). No statistically significant association was observed between smoking and GDM (OR = 1.03, 95% CI 0.47, 2.27), and neither was the association between race/ethnicity and GDM. Furthermore, none of the interaction effects were statistically significant.

CONCLUSION: Preventive strategies targeting GDM should focus on improving modifiable risk factors, such as sleep-disordered breathing. It is important to screen women with sleep-disordered breathing and monitor their blood sugar before becoming pregnant to prevent the development of GDM. Future studies are recommended to understand the lower prevalence of GDM among Black women and the higher prevalence among “Other” race group which mostly includes Asian women.

PMID:36273849 | DOI:10.1080/14767058.2022.2139175

Am J Obstet Gynecol MFM. 2022 Oct 20:100776. doi: 10.1016/j.ajogmf.2022.100776. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with a hypertensive disorder of pregnancy are more likely to have underlying cardiovascular risk factors and are at increased risk of future cardiovascular disease. These patients are more likely to be diagnosed with new onset chronic hypertension and meet the criteria for Metabolic Syndrome postpartum. High-sensitivity C-reactive protein is a marker of general inflammation and may be used to identify increased risk for cardiovascular disease.

OBJECTIVE: This collaborative data sharing study between Yale University, United States (Yale Heart Moms study) and Queen’s University, Canada (Maternal Health Clinic) is to better study the utility of high-sensitivity C-reactive protein in postpartum cardiovascular risk screening, as determined by 30-year risk (Framingham) and Metabolic Syndrome 6-12 months postpartum.

STUDY DESIGN: Patients with a hypertensive disorder of pregnancy (n=478) or an uncomplicated, term pregnancy (n=90) had cardiovascular risk screening and risk scoring performed at 6-12 months postpartum. Patients were excluded if they had a multiple gestation or chronic hypertension, diabetes or cardiovascular disease diagnosed before pregnancy. Patients were categorized according to high-sensitivity C-reactive protein (mg/L) into Normal (<3.0), High (3.1 to <10.0), and Acute (≥10.0) groups. The primary outcome of the study is risk for future cardiovascular events, calculated through surrogate measures such as hypertension and cholesterol. Kruskal Wallis and Chi Square tests were used to compare groups, with post-hoc tests corrected using the Bonferroni method. Multivariable logistic regression was used to assess the association between high-sensitivity C-reactive protein and cardiovascular risk, adjusting for relevant medical and sociodemographic variables. Analysis was completed with IBM SPSS Statistics v27.

RESULTS: Patients in the High and Acute hsCRP groups were more likely to have a BMI≥30, have experienced a hypertensive disorder of pregnancy, have a lower household income, and to have not breastfed or breastfed <6 month, when compared to the Normal hsCRP group (all p<0.05). Patients in the High and Acute hsCRP groups had higher 30-year cardiovascular risk scores and were more likely to have Metabolic Syndrome, when compared to the Normal hsCRP group (all p<0.05). Patients with High hsCRP had a 2-fold odds of Metabolic Syndrome 6-12 months after delivery, compared to those in the Normal hsCRP group (aOR 2.85 (95% CI 1.66, 4.91)), adjusting for hypertensive disorder of pregnancy, body mass index, clinic site, breastfeeding, income, and family history of cardiovascular disease. Those with Acute hsCRP also appeared to have elevated odds of Metabolic Syndrome compared to the Normal hsCRP group (aOR 2.52 (95% CI 1.24, 5.12)). The odds of chronic hypertension were significantly higher (p<0.05) in the High hsCRP group [aOR 1.72 [95% CI 1.12, 2.65]] compared to the Normal group.

CONCLUSIONS: Individuals with elevated postpartum high-sensitivity C-reactive protein are at an increased risk of cardiovascular disease 6-12 months postpartum after a pregnancy complicated by a hypertensive disorder of pregnancy. Future research is critical to determine the most comprehensive and accurate method and timing of postpartum cardiovascular risk screening in order to decrease the incidence of preventable cardiovascular mortality among women.

PMID:36273813 | DOI:10.1016/j.ajogmf.2022.100776

Genet Epidemiol. 2022 Oct 23. doi: 10.1002/gepi.22506. Online ahead of print.

ABSTRACT

Mendelian randomization (MR) is the use of genetic variants to assess the existence of a causal relationship between a risk factor and an outcome of interest. Here, we focus on two-sample summary-data MR analyses with many correlated variants from a single gene region, particularly on cis-MR studies which use protein expression as a risk factor. Such studies must rely on a small, curated set of variants from the studied region; using all variants in the region requires inverting an ill-conditioned genetic correlation matrix and results in numerically unstable causal effect estimates. We review methods for variable selection and estimation in cis-MR with summary-level data, ranging from stepwise pruning and conditional analysis to principal components analysis, factor analysis, and Bayesian variable selection. In a simulation study, we show that the various methods have comparable performance in analyses with large sample sizes and strong genetic instruments. However, when weak instrument bias is suspected, factor analysis and Bayesian variable selection produce more reliable inferences than simple pruning approaches, which are often used in practice. We conclude by examining two case studies, assessing the effects of low-density lipoprotein-cholesterol and serum testosterone on coronary heart disease risk using variants in the HMGCR and SHBG gene regions, respectively.

PMID:36273411 | DOI:10.1002/gepi.22506

Bull Math Biol. 2022 Oct 23;84(12):137. doi: 10.1007/s11538-022-01088-2.

ABSTRACT

The MEK/ERK signalling pathway is involved in cell division, cell specialisation, survival and cell death (Shaul and Seger in Biochim Biophys Acta (BBA)-Mol Cell Res 1773(8):1213-1226, 2007). Here we study a polynomial dynamical system describing the dynamics of MEK/ERK proposed by Yeung et al. (Curr Biol 2019, https://doi.org/10.1016/j.cub.2019.12.052 ) with their experimental setup, data and known biological information. The experimental dataset is a time-course of ERK measurements in different phosphorylation states following activation of either wild-type MEK or MEK mutations associated with cancer or developmental defects. We demonstrate how methods from computational algebraic geometry, differential algebra, Bayesian statistics and computational algebraic topology can inform the model reduction, identification and parameter inference of MEK variants, respectively. Throughout, we show how this algebraic viewpoint offers a rigorous and systematic analysis of such models.

PMID:36273372 | DOI:10.1007/s11538-022-01088-2