Search

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.

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.

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.