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Purpose: Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility, often requiring ovarian stimulation in affected women attempting to conceive. Male partner semen quality and shared lifestyle factors can significantly impact reproductive outcomes. However, current international guidelines lack evidence-based recommendations on the necessity and timing of semen analysis for the fertility management of anovulatory PCOS women., Methods: In a retrospective case-control study, semen analysis results of male partners of 187 anovulatory PCOS women scheduled for ovarian stimulation were analyzed and compared to a control group of 76 male partners of women with bilateral tubal occlusion., Results: The prevalence of semen analysis results with at least one parameter classified as "borderline" and "pathological" among male partners of women with PCOS eligible to undergo ovarian stimulation was 51.3% and 22.5%, compared to 44.7% and 13.2% in the control group, respectively (p = 0.027). In the PCOS group, male body mass index (odds ratio, OR 1.478, p < 0.001), and smoking status (OR 6.228, p < 0.001) were significant predictors of pathological sperm test results, while no association was observed with any female characteristics (p > 0.05)., Conclusion: The high frequency of pathological sperm analysis results provides lacking epidemiological data on semen quality in this population, emphasizing the critical need for early male fertility evaluation prior to ovarian stimulation in PCOS women. Moreover, our findings indicate that the risk prediction for abnormal semen quality cannot be based on the female's data., (© 2024. The Author(s).)

Background and Objectives : Fallopian tubal pathology is a primary risk factor for female infertility, with simple proximal disease and proximal disease extending more distally being more common than pure distal occlusion. Proximal tubal occlusion is often attributed to ascending events, such as pelvic inflammatory disease. Conversely, while distal occlusion can also be attributable to ascending pelvic inflammatory disease, it can also have a pelvic origin, such as through endometriosis and ruptured appendicitis. The aim of this study was to identify certain causes of infertility and their association with tubal occlusion. The focus was on the location of tubal occlusion, uni- versus bilateral occlusion, and other causes of infertility, including male factors. Methods : In a retrospective study cohort study, 373 women aged between 18 and 40 years, treated from 1 January 2017 to 31 December 2022, were included. Fallopian tube patency was tested using either hysterosalpingography, hysterosalpingo-contrast sonography, or laparoscopic chromopertubation. Results : In total, 95 of 373 women (25.5%) revealed at least one occluded tube, with unilateral occlusion being more common than bilateral occlusion (60/95, 63.2% vs. 35/95, 36.8%). The majority of tubal occlusions occurred proximally (86.2%). According to the adjusted multivariate regression models, the presence of hydrosalpinx (odds ratio, OR, 13.323, 95% confidence interval, CI: 2.679-66.253, p = 0.002), myomas (OR 2.108, 95%CI: 1.008-4.409; p = 0.048), and an abnormal sperm test result of the male partner (OR 2.105, 95%CI: 1.156-3.833; p = 0.015) were statistically significant associated factors for tubal occlusion. Conclusions : Fallopian tube patency testing is still of major relevance in fertility evaluation. The presence of uterine myomas, hydrosalpinges, and a male factor significantly increase the risk.

Purpose: Functional hypothalamic amenorrhea (FHA) is due to hypothalamic dysregulation. Literature lacks data about prolactin in FHA women, although both prolactin levels and FHA are associated with stress. Moreover, polycystic ovarian morphology is common in FHA and there is an association between FHA and polycystic ovary syndrome. Thus, the aim of this study was to assess prolactin levels in FHA patients and controls with a special focus on factors influencing prolactin levels, that could be considered as "sensors" of the hypothalamic-pituitary dysregulation., Methods: In a retrospective cohort study, 140 women with clearly defined FHA were compared to 70 healthy, normally ovulating women matched for age. The main outcome parameter was prolactin. Factors associated with prolactin levels > 12 µg/L were tested using a multivariable binary logistic regression model., Results: The median prolactin level was 11.5 µg/L (interquartile range, IQR 7.5-14.4), which was similar to the control group (median 10.7, IQR 8.3-14.5; p = 0.065). Only two women had hyperprolactinemia (prolactin > 25 µg/L; 1.4%). In a multivariable binary logistic regression model eating disorder (odds ratio, OR 0.206; p = 0.040), excessive exercise (OR 0.280; p = 0.031) and TSH (OR 1.923; p = 0.020) were significantly associated with prolactin levels > 12 µg/L., Conclusion: Women with FHA have similar prolactin levels to healthy age-matched individuals. Eating disorders and excessive exercise where associated with prolactin levels < 12 µg/L, in contrast to TSH., (© 2023. The Author(s).)

There are limited data on how non-infectious risk factors influence tubal patency in women with subfertility. With hormonal shifts influencing tubal secretions, it has been argued that subfertile women with polycystic ovary syndrome (PCOS) have lower tubal patency. In a retrospective study, 216 women, who underwent diagnostic evaluation for PCOS and infertility, were included. Fallopian tube patency was tested using HSG, HyCoSy, and laparoscopic chromopertubation in 171 (79.2%), 28 (13.0%), and 17 (7.9%), respectively. Bilateral patency was found in 193 women (89.4%), unilateral patency in 13 (6.0%) and bilateral occlusion in 10 (4.6%) patients. Women with PCOS phenotypes C (odds ratio, OR 0.179, 95% CI: 0.039-0.828) and D (OR 0.256, 95% CI: 0.069-0.947) demonstrated lower risks for Fallopian tube occlusion. In conclusion, our data suggest that about 5% of infertile women with PCOS also have bilateral tubal occlusion, which seems similar to the rate in non-subfertile women. With 11% of participants having unilateral or bilateral tubal occlusion, this should reassure women with PCOS that their hormonal challenges do not seem to increase their risk for tubal factor subfertility., Competing Interests: Ott reports personal fees from Lenus Pharma GesmbH (Vienna, Austria), outside the submitted work. All other authors declare that there is no conflict of interest.

STAT3 is constitutively activated in many cancers and regulates gene expression to promote cancer cell survival, proliferation, invasion, and migration. In diffuse large B cell lymphoma (DLBCL), activation of STAT3 and its kinase JAK1 is caused by autocrine production of IL-6 and IL-10 in the activated B cell-like subtype (ABC). However, the gene regulatory mechanisms underlying the pathogenesis of this aggressive lymphoma by STAT3 are not well characterized. Here we performed genome-wide analysis and identified 2,251 STAT3 direct target genes, which involve B cell activation, survival, proliferation, differentiation, and migration. Whole-transcriptome profiling revealed that STAT3 acts as both a transcriptional activator and a suppressor, with a comparable number of up- and down-regulated genes. STAT3 regulates multiple oncogenic signaling pathways, including NF-κB, a cell-cycle checkpoint, PI3K/AKT/mTORC1, and STAT3 itself. In addition, STAT3 negatively regulates the lethal type I IFN signaling pathway by inhibiting expression of IRF7 , IRF9 , STAT1 , and STAT2 Inhibition of STAT3 activity by ruxolitinib synergizes with the type I IFN inducer lenalidomide in growth inhibition of ABC DLBCL cells in vitro and in a xenograft mouse model. Therefore, this study provides a mechanistic rationale for clinical trials to evaluate ruxolitinib or a specific JAK1 inhibitor combined with lenalidomide in ABC DLBCL., Competing Interests: The authors declare no conflict of interest.

Diatom biosilica may offer an interesting perspective in the search for sustainable solutions meeting the high demand for heterogeneous catalysts. Diatomaceous earth (diatomite), i.e., fossilized diatoms, is already used as adsorbent and carrier material. While diatomite is abundant and inexpensive, freshly harvested and cleaned diatom cell walls have other advantages, with respect to purity and uniformity. The present paper demonstrates an approach to modify diatoms both in vivo and in vitro to produce a porous aluminosilicate that is serving as a potential source for sustainable catalyst production. The obtained material was characterized at various processing stages with respect to morphology, elemental composition, surface area, and acidity. The cell walls appeared normal without morphological changes, while their aluminum content was raised from the molar ratio n (Al): n (Si) 1:600 up to 1:50. A specific surface area of 55 m²/g was measured. The acidity of the material increased from 149 to 320 µmol NH₃/g by ion exchange, as determined by NH₃ TPD. Finally, the biosilica was examined by an acid catalyzed test reaction, the alkylation of benzene. While the cleaned cell walls did not catalyze the reaction at all, and the ion exchanged material was catalytically active. This demonstrates that modified biosilica does indeed has potential as a basis for future catalytically active materials., Competing Interests: The authors declare no conflict of interest.

Background: Since the introduction of pandemic influenza A (H1N1) to the USA in 2009, the Influenza Incidence Surveillance Project has monitored the burden of influenza in the outpatient setting through population-based surveillance., Methods: From Oct 1, 2009, to July 31, 2013, outpatient clinics representing 13 health jurisdictions in the USA reported counts of influenza-like illness (fever including cough or sore throat) and all patient visits by age. During four years, staff at 104 unique clinics (range 35-64 per year) with a combined median population of 368,559 (IQR 352,595-428,286) attended 35,663 patients with influenza-like illness and collected 13,925 respiratory specimens. Clinical data and a respiratory specimen for influenza testing by RT-PCR were collected from the first ten patients presenting with influenza-like illness each week. We calculated the incidence of visits for influenza-like illness using the size of the patient population, and the incidence attributable to influenza was extrapolated from the proportion of patients with positive tests each week., Findings: The site-median peak percentage of specimens positive for influenza ranged from 58.3% to 77.8%. Children aged 2 to 17 years had the highest incidence of influenza-associated visits (range 4.2-28.0 per 1000 people by year), and adults older than 65 years had the lowest (range 0.5-3.5 per 1000 population). Influenza A H3N2, pandemic H1N1, and influenza B equally co-circulated in the first post-pandemic season, whereas H3N2 predominated for the next two seasons. Of patients for whom data was available, influenza vaccination was reported in 3289 (28.7%) of 11,459 patients with influenza-like illness, and antivirals were prescribed to 1644 (13.8%) of 11,953 patients., Interpretation: Influenza incidence varied with age groups and by season after the pandemic of 2009 influenza A H1N1. High levels of influenza virus circulation, especially in young children, emphasise the need for additional efforts to increase the uptake of influenza vaccines and antivirals., Funding: US Centers for Disease Control and Prevention., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We studied the role of the mineralocorticoid receptor (MR) in the signaling that promotes atrial fibrosis. Left atrial myocardium of patients with atrial fibrillation (AF) exhibited 4-fold increased hydroxyproline content compared with patients in sinus rhythm. Expression of MR was similar, as was 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which also increased. 11β-HSD2 converts cortisol to receptor-inactive metabolites allowing aldosterone occupancy of MR. 11β-HSD2 was up-regulated by arrhythmic pacing in cultured cardiomyocytes and in a mouse model of spontaneous AF (RacET). In cardiomyocytes, aldosterone induced connective tissue growth factor (CTGF) in the absence but not in the presence of cortisol. Hydroxyproline expression was increased in cardiac fibroblasts exposed to conditioned medium from aldosterone-treated cardiomyocytes but not from cardiomyocytes treated with both cortisol and aldosterone. Aldosterone increased connective tissue growth factor and hydroxyproline expression in cardiac fibroblasts, which were prevented by BR-4628, a dihydropyridine-derived selective MR antagonist, and by spironolactone. Aldosterone activated RhoA GTPase. Rho kinase inhibition by Y-27632 prevented CTGF and hydroxyproline, whereas the RhoA activator CN03 increased CTGF expression. Aldosterone and CTGF increased lysyl oxidase, and aldosterone enhanced miR-21 expression. MR antagonists reduced the aldosterone but not the CTGF effect. In conclusion, MR signaling promoted fibrotic remodeling. Increased expression of 11β-HSD2 during AF leads to up-regulation of collagen and pro-fibrotic mediators by aldosterone, specifically RhoA activity as well as CTGF, lysyl oxidase, and microRNA-21 expression. The MR antagonists BR-4628 and spironolactone prevent these alterations. MR inhibition may, therefore, represent a potential pharmacologic target for the prevention of fibrotic remodeling of the atrial myocardium.

The present study examined the utility of daily naltrexone for decreasing alcohol drinking in hazardous drinkers. Forty-one participants participated in a 10-week trial and received 30 min of brief counseling on the first and second week of treatment, as well as a daily dose of 50 mg of naltrexone throughout the trial. Overall, naltrexone-treated participants did not show the same degree of improvement on drinking outcomes as placebo-treated participants. The placebo group drank fewer drinks per drinking day and achieved more abstinence days than the naltrexone group. Craving was also lower for the placebo group. The groups were not balanced on gender or family history of alcoholism and this may explain the lack of effect of naltrexone on the drinking outcomes.

The innervation of the canine hip joint has become increasingly important in the treatment of hip dysplasia and hip arthrosis, since investigations proved that simple removal of periosteum around attachment of hip joint capsule, called denervation results in an instant analgesia and allows the dog to regain joyful freedom of movement. A macroscopic-anatomic examination of 16 canine hips furnished new findings and knowledge in the field of veterinary medicine on the sensitive innervation of the canine hip joint capsule. Accordingly, the craniolateral area of hip joint capsule is innervated by rami articulares of N. glutaeus cranialis, the caudolateral area by rami articulares of N. ischiadicus and the medial area by rami articulares of N. femoralis.