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PubMed2026

The cold case of state transition 7 (stt7) mutants of Chlamydomonas reinhardtii, solved by whole-genome sequencing.

The process of State Transitions (ST) corresponds to an STT7 kinase-driven redistribution of the transmembrane LHCII antenna proteins between Photosystem II (PSII) and Photosystem I (PSI), which results from changes in their phosphorylation state. For the past two decades, two LHCII-kinase mutants, stt7-1 and stt7-9, have been instrumental in the study of STs in Chlamydomonas reinhardtii, the former being a null mutant for the kinase but quasi-sterile in crosses, while the latter, although fertile, has a leaky phenotype. Using long-read sequencing, this study further characterized the genetic lesions of the stt7 mutant strains through whole-genome reconstruction and de novo chromosome assembly. In addition, two new stt7 null mutants were generated, one derived by crosses from the original stt7-1 and one obtained by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9) technology. This work provides a comprehensive genomic characterization of the original stt7-1 null mutant, revealing extensive chromosomal rearrangements and high levels of aneuploidy, associated with increased cell size and meiotic dysfunction. Reassessment of their physiology and genetic backgrounds highlights the need for caution in interpreting genetic information. We thus produced more reliable null mutants for the LHCII-kinase, amenable to genetic crosses for the study of STs in a variety of genetic backgrounds.

Chlamydomonas reinhardtii↗

PubMed2026

Maternal transfer of nonylphenol drives oxidative, immune, and epigenetic dysregulation in zebrafish offspring.

Nonylphenol (NP), a widespread surfactant and endocrine-disrupting pollutant, poses significant ecological and public health risks globally; however, its transgenerational effects remain poorly understood. Using zebrafish (Danio rerio), we compared chronic maternal NP exposure (50 and 100 µg/L, 28 days) with acute embryonic exposure (0.22 µmol/L) during 0-3 days post-fertilization (dpf) to delineate mechanistic differences in toxicity. Maternal NP exposure produced severe developmental defects in offspring, including edema, axial curvature, impaired swim bladder inflation, reduced growth, cardiac dysfunction, and decreased viability. These phenotypes were accompanied by systemic molecular disruptions including oxidative stress, altered estrogen receptor (ER) expression, dysregulated mitogen-activated protein kinase (MAPK) signaling, and suppressed innate immune response characterized by attenuated neutrophil/macrophage density, reduced CD68 and complement protein C3 expression, diminished nitrite load, and downregulation of pro-inflammatory mediators at both transcript and protein levels. Maternal exposure further induced apoptosis and persistent epigenetic reprogramming (alterations in DNA methylation and histone-modifying enzymes), hallmarks of transgenerational toxicity. In contrast, direct embryonic NP exposure elicited morphological abnormalities without significant lethality, accompanied by induction of pro-inflammatory cytokines, nitric oxide (NO) synthesis, and MAPK activation, reflecting an augmented inflammatory response. These mechanistic contrasts reveal that maternal NP exposure is a potent driver of systemic, heritable molecular reprogramming, whereas embryonic exposure triggers acute inflammatory pathways. Together, our findings underscore the global relevance of NP as a transgenerational toxicant, advocating for its urgent inclusion in ecotoxicological risk assessments and regulatory frameworks.

Animals↗

PubMed2026

Male accessory gland proteins in Grapholita molesta: Identification and reproductive functional validation of four accessory gland-specific lipases.

Accessory gland proteins (Acps), synthesized in the male accessory glands (AGs), are transferred to females via spermatophores during mating and elicit diverse post-mating physiological and behavioral responses. However, Acps have not been comprehensively characterized in Grapholita molesta, a cosmopolitan orchard pest. Here, using data-independent acquisition mass spectrometry, we describe an integrated proteomic approach combining comparative AG analyses (virgin vs. newly mated) with spermatophore profiling to identify Acps in G. molesta. According to the established screening criteria, we identified 83 confirmed Acps, which were classified into nine categories. Tissue-specific expression patterns of 20 randomly selected Acp genes were evaluated, revealing that these genes were specifically or highly expressed in male AGs. Among the 83 confirmed Acps, four Acps harbored the PLN02872 superfamily domain and were classified into the canonical lipase family. Notably, their transcripts were all highly expressed in the AGs during the pre-maturation stage. These four Acps were selected for preliminary validation of their male reproductive functions. RNAi-mediated knockdown of three out of four lipase genes in G. molesta males significantly decreased the fertility of mated females, with phenotypes including a significant reduction in egg production and egg hatching rate. This study provides a comprehensive catalog of high-confidence Acps, lays a foundation for subsequent in-depth functional characterization of these reproductive proteins, and offers promising molecular targets for the development of novel genetic regulation-based integrated pest management strategies.

Animals↗

PubMed2026

Age-related differences in semen quality in Holstein-Friesian bulls: a paired within-bull comparison of early and mature reproductive stages.

Genomic selection has changed dairy cattle breeding by increasing the use of young bulls for artificial insemination and shortening the reproductive lifespan of sires. Under these conditions, semen quality at the beginning of commercial use has become an important practical issue. Semen samples from 39 fertile Holstein-Friesian bulls used for commercial AI were collected between 2013 and 2016, during the introduction of genomic selection in Poland. This paired within-bull study compared semen collected from the same bulls at an early reproductive stage (13-20 months; young bulls, YB) and at full maturity (5-6 years; mature bulls, MB). The evaluation included conventional ejaculate traits, CASA-derived motility and kinematic descriptors, mtDNA copy number, and mitochondrial content per sperm cell. Importantly, all ejaculates met the quality requirements for commercial insemination. Ejaculate volume, sperm concentration, mitochondrial DNA copy number, and mitochondrial content did not differ significantly between age groups. The CASA-derived sperm movement profile, in contrast, differed with age. Semen from young bulls showed a higher proportion of progressively motile spermatozoa, whereas semen from mature bulls showed higher velocity-related parameters, including VSL, VCL, and STR. These findings indicate that bull age mainly affected sperm movement characteristics rather than semen output or mitochondrial content. Overall, the results support the use of young bulls in artificial insemination programs and show that age-related differences in semen quality are expressed mainly through changes in the post-thaw sperm motility and kinematic profile.

Animals↗

PubMed2026

An allograft inflammatory factor enhances sperm viability by modulating intracellular calcium in oyster Crassostrea gigas.

As an important aquaculture bivalve, the Pacific oyster Crassostrea gigas faces severe constraints in artificial reproduction, where low sperm motility often leads to fertilization failure and limits the sustainable development of the oyster aquaculture industry. In the present study, the variation of sperm from different oyster individuals was observed, and high-quality sperm possessed intact, elongated flagella with no structural abnormalities, while low-quality sperm showed shortened flagella with frequent tangling or coiling defects. Transcriptomic analysis comparing high- and low-quality sperm revealed significantly reduced expression of genes associated with sperm motility and release (CgAIF1, CgAchR, CgSEX), sperm quality and development (CgEP4, CgIFi2b), and cryoprotection (CgISPs) in low-quality sperm. Notably, an allograft inflammatory factor (designed as CgAIF1) encoding EF-hand domain, known as Ca2+ binding activity, was among the most significantly downregulated in low-motility sperm. CgAIF1 is highly expressed in haemocytes, ganglia, and gonads of oysters. Incubation with the recombinant AIF1 protein (rCgAIF1) significantly improved sperm curvilinear velocity, thereby enhancing the overall motility of C. gigas sperm. Furthermore, rCgAIF1 incubation increased intracellular Ca2+ levels (2.13-fold at 30 min, 2.71-fold at 60 min) and superoxide dismutase (SOD) activity (1.44-fold at 30 min, 1.24-fold at 60 min) in sperm, suggesting potential roles in calcium homeostasis regulation and antioxidant defense. In conclusion, this study demonstrates that CgAIF1 significantly enhances motility of oyster sperm, providing a scientific basis for artificial breeding and seed production in oyster aquaculture.

Animals↗

PubMed2026

First evaluation of a novel recombinant eCG molecule in ewes reveals a discrepancy between ovulatory response and pregnancy outcome.

This study evaluated the reproductive performance and clinical safety of a novel recombinant eCG (r-eCG) in ewes. Two weeks prior to study onset (Day 0: intravaginal progesterone device insertion), 45 ewes were randomly assigned to negative control (NC; no eCG; n = 10), positive control (PC; 400IU commercial non-recombinant eCG; n = 20), or treatment group (T; 400IU r-eCG; n = 15). Ewes were inseminated with fresh-diluted semen (200 × 106 sperm). Ultrasonography assessed follicle count/diameter (days 11, 13), ovulation (day 13), corpus luteum (CL) number/characteristics (day 20), and pregnancy (day 44). Serum progesterone was measured on day 20; Group T underwent clinical/hematological evaluations (days 0, 20, and 44). Estrus signs were more frequent (P < 0.01) in T (100%) than NC (50%), while PC (85%) did not differ. Ovulation rates were similar between T (93%) and PC (95%), but higher than NC (50%; P < 0.05). On day 13, largest follicle diameter did not differ (P > 0.05) among groups; however, fewer follicles > 2 mm occurred in PC than NC and T (P < 0.05). CL number was higher in T than PC (2.0 ± 0.3 vs. 1.0 ± 0.0, P < 0.01), while NC did not differ (1.0 ± 0.25). Conversely, pregnancy rate was higher (P < 0.05) in PC (70%) than T (28.6%) and NC (20%). Among ovulated ewes, progesterone concentration and progesterone/CL ratio did not differ among groups (P = 0.92 and P = 0.08, respectively). No relevant r-eCG-related clinical or hematological alterations occurred. In conclusion, 400IU r-eCG effectively induces estrus and ovulation without adverse effects; however, the discrepancy between ovulatory response and pregnancy rate underscores the need for further study refinement to improve fertility.

Animals↗

PubMed2026

The effects of cold temperature on the development, microbiome, and transcriptome of the sea anemone Nematostella vectensis.

Thermal conditions impact essentially all aspects of the physiology for ectotherms. While the effects of high temperatures have been widely studied, cold temperature effects on aquatic invertebrates and their microbial communities have been poorly characterized. To determine the diverse effects of exposure to cold temperatures, we assessed acute and long-term impacts of ecologically relevant low temperatures on the development, microbiome, and gene expression of the sea anemone Nematostella vectensis. Two hours post fertilization, embryos were exposed to temperatures from 4°C to 35°C and development rate to the juvenile stage was quantified. We found temperature impacts the development rate of embryos, where lower temperatures extended development time and resulted in mortality below 10°C. For both microbiome and host transcriptomic responses, anemones were held at 20°C, 10°C, and 0°C and compared at 24 hours and 7 days. Extended exposures to colder temperatures caused restructuring of the host-associated microbiome, with the loss of common taxonomic groups from the class Bacteroidia and Bacilli. Lastly, cold stress induced significant changes in gene expression, which were more pronounced at the 10°C than 0°C but showed little change over time in each temperature. Interestingly, expression of genes associated with innate immunity were among the most differentially expressed genes including heat shock proteins and innate immune genes providing a potential host-imposed mechanism to explain the shift in the microbiome. Overall, cold temperatures have broad effects on many facets of this sea anemone and its microbial community and indicate the importance of cold temperature events when characterizing how ectotherms acclimate to thermal variation.

Animals↗

PubMed2026

Dynamics of soil fungal communities restored with biochar from a quarry site.

Quarrying activities have intensified due to population expansion, leading to landscape degradation and ecological destruction. Quarry restoration is usually mandatory in Hong Kong, China. Although biochar is used for sustainable soil amendment, its effectiveness in restoring quarry soil with poor properties has rarely been investigated. A 24-month field study was conducted to evaluate the ecological feasibility of restoring a quarry site by using native species (that is, Castanopsis fissa and Cyclobalanopsis edithiae) and biochar amendment. The results revealed that after 24 months, the application of biochar increased the organic carbon, phosphorus and potassium of the vegetated soil by at least 120 %, 31 % and 12 %, respectively, due to higher cation exchange capacity and better plant growth. The relative abundance of Ascomycota and Basidiomycota increased by 24 % and 47 % with biochar application when C. fissa was planted, which was likely associated with the improved nutrient cycling and soil fertility. Even though adding biochar to bare soil was found to increase the complexity of fungal co-occurrence networks, biochar application only increased fungal diversity in vegetated quarry soil but usually reduced its fungal richness. Moreover, fungal co-occurrence networks in vegetated soil became less complex, suggesting that biochar potentially helped plants to assemble specific, beneficial fungal communities. This effect is most pronounced in the soil planted with C. edithiae, where the structure of fungal communities after 24 months was significantly different from that at other restoration times. This study identifies key fungal phyla enhanced by biochar in quarry soil and provides an effective strategy for facilitating the restoration and management of degraded lands, especially quarry sites.

Charcoal↗

PubMed2026

Mineral-driven molecular signatures of energy metabolism underpin sperm motility in buffalo.

The success of spermatogenesis depends on the interplay of various biomolecules that ultimately determine sperm quality. In this study, RNA-seq analysis of frozen-thawed buffalo sperm (n = 8) revealed the presence of 263 mineral-associated genes (>1 FPKM) in high (n = 4) and 181 in low motile (n = 4) sperm groups. Among these, 177 mineral-associated genes were commonly expressed between them, and the majority were upregulated (>1 fold), LOC102391588 (ncRNA; 37-fold), ZNF699 (26.5-fold), MYZAP (13-fold), etc., in the high motile group. The expression of selected mineral-associated genes was validated. The top enriched functions in commonly expressed genes were regulation of transcription by RNA polymerase II (FDR: 4.7 × 10⁻2; ZNF331, ZNF692, ZNF180, etc.), followed by spermatogenesis (FDR: 2.9 × 10⁻2; CALR3, ADAM18, ADAM29, etc.), proton transmembrane transport (FDR: 4.0 × 10⁻2; ATP6V0E1, ATP1A4, ATP6V1B2, etc.) and flagellated sperm motility (FDR: 2.3 × 10⁻1; CATSPERD, EFCAB6, CABS1, etc.). Additionally, the chromatin remodeling pathway (FDR: 3 × 10⁻2; PTP4A1, PPM1A, DUSP1, etc.) emerged as the most significant and may suggest that these minerals influence genome packaging and sperm functionality. Mineral-associated genes were predominantly associated with zinc (49%), followed by calcium (20%), phosphorus (10%), iron (5%), sodium (2%), potassium (2%), copper (1%) and other trace elements (11%). Although the current study uses frozen-thawed sperm, the findings indicate that mineral-associated genes are crucial for promoting membrane stability, energy production, motility and chromatin integrity, which may contribute to the superior fertilizing ability of sperm.

Animals↗

PubMed2026

Expression profiles of miRNAs in ruminant intermediate hosts with cystic echinococcosis.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a parasitic zoonotic disease recognized by the World Health Organization as a neglected tropical disease of significant public health concern. Despite ongoing control programs, CE remains endemic, underlining the need for integrated control strategies that involve new diagnostic and therapeutic tools. Recent investigations have spotlighted microRNAs (miRNAs) as key regulators in parasite development, immunomodulation, and as potential diagnostic and therapeutic targets. In the present research, a molecular study was conducted to investigate hydatid cyst samples (protoscoleces and germinal membranes) collected in southern Italy from different ruminant species (sheep, cattle, and water buffaloes), naturally infected with CE, with the ultimate goal of establishing a more comprehensive picture of miRNA expression patterns in these intermediate hosts. The bioinformatic analysis of hydatid cyst samples revealed 168 mature miRNAs. Among these, egr-miR-10-5p, egr-let-7-5p, and egr-miR-71-5p were the most abundant, with egr-miR-10-5p showing particularly high expression levels. No significant differences in miRNA abundance between host species were found. In contrast, when focusing on the comparison between protoscoleces and sterile germinal membranes, 24 miRNAs were found to be differentially expressed. Targeted qPCR of four selected miRNAs (egr-miR-71-5p, egr-let-7-5p, egr-miR-125-5p, and egr-miR-10-5p) showed clear overexpression in protoscoleces and in fertile germinal membranes compared with sterile ones. The differential miRNA expression patterns provide insight into the molecular mechanisms controlling the parasite's lifecycle and may guide the development of novel intervention methods to enhance CE control in endemic areas.

Animals↗

PubMed2026

Effects of cinnamon supplementation combined with exercise training on anthropometric indices and reproductive hormones in overweight and obese women.

BACKGROUND: The prevalence of obesity and increased fat in the chest and abdomen in women and hormonal changes, can affect female fertility. The present study aims to investigate the effect of exercise training combined with cinnamon supplementation on chest and abdominal circumference, as well as sex hormones, in overweight and obese women. METHODS: Twenty-six inactive overweight and obese women were randomly allocated to an exercise (E; n = 13) and exercise plus cinnamon supplementation (E+S; n = 13) group. Both groups completed a 4-week exercise program three times weekly, while the E+S group additionally received cinnamon supplementation three times weekly. Chest and abdominal circumferences and serum concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed before and after the intervention. RESULTS: Significant pre-to-post reductions in chest and abdominal circumference were observed in both groups (all p ≤ 0.005). Estradiol, progesterone, and FSH concentrations increased, whereas LH concentrations decreased significantly in both groups (all p ≤ 0.005). However, between-group comparisons revealed a significant difference only for chest circumference (p = 0.003), with no significant group differences in abdominal circumference or any reproductive hormone concentration (all p > 0.05). CONCLUSION: Both groups showed favorable changes in anthropometric and reproductive hormone measures following the 4-week study period. However, the significant between-group difference was limited to chest circumference, providing no clear evidence that cinnamon supplementation conferred additional benefits for abdominal circumference or reproductive hormone profiles beyond those observed with exercise. These findings highlight the potential relevance of exercise-based interventions while warranting confirmation in larger, adequately powered trials.

Humans↗

PubMed2026

Effect of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Male Sexual Function: A Systematic Review and Meta-Analysis.

BACKGROUND: Obesity negatively impacts male sexual function and fertility through hormonal imbalances, endothelial dysfunction, and psychosocial factors. Metabolic and bariatric surgery (MBS) constitutes an effective intervention; however, procedure-stratified changes in male reproductive parameters after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remain incompletely synthesized. METHODOLOGY: A systematic search of PubMed, Embase, Cochrane Library, Scopus, and Web of Science was conducted in November 2024. Sexual function, testosterone levels, and semen quality were included. Risk of bias was assessed using MINORS criteria. Random-effects meta-analyses were performed separately for each surgical modality, with heterogeneity quantified via I2 statistics. RESULTS: Twenty-one studies comprising 848 patients were included. Meta-analysis of pre-post data demonstrated that both RYGB and SG were independently associated with improvements in sex hormone-binding globulin and testosterone levels. In studies examining SG, significant improvements were observed in erectile function (SMD: 1.38, 95% CI: 0.66-2.10, p = 0.0002) and sperm concentration (SMD: 0.91, 95% CI: 0.56-1.26, p < 0.00001). Studies evaluating RYGB did not demonstrate statistically significant changes in erectile function (SMD: 0.62, 95% CI: -0.06 to 1.30, p = 0.07) or sperm concentration (SMD: -0.01, 95% CI: -0.45 to 0.42, p = 0.95). CONCLUSION: The meta-analytical findings suggest beneficial effects of both RYGB and SG on male hormonal parameters. Studies of SG demonstrated significant improvements in erectile function and sperm concentration. However, direct comparative analyses between the two procedures were not performed, precluding definitive conclusions regarding their relative efficacy. Future research necessitates head-to-head comparisons with standardized reproductive endpoints and extended follow-up periods.

Humans↗

PubMed2026

Norgestrel drives mitochondrial collapse and plasma membrane impairment in Pacific oyster (Crassostrea gigas) sperm by triggering premature acrosome reaction.

The toxic mechanisms of norgestrel (NGT), an emerging marine pollutant, on the sperm from externally fertilized invertebrates remain elusive. This study employed an integrated physiological and multi-omics framework to elucidate how NGT (10 and 1000 ng/L) disrupts acrosome reaction (AR) signaling machinery, thereby impairing the functional integrity of Pacific oyster (Crassostrea gigas, also known as Magallana gigas) sperm. Exposure to NGT triggered a significant, dose-dependent premature AR, characterized by elevated acrosin activity and a loss of acrosomal integrity. Multi-omics integration supports a model in which this premature exocytosis is linked to signaling disturbances, including disruption of calcium signaling and reduced transcript abundance of calmodulin (CaM) and the primary recognition protein zonadhesin (Zan). This signaling interference induced an premature AR, subsequently driving a cascade of bioenergetic and structural failures. At the mitochondrial level, NGT induced abnormal mitochondrial permeability transition pore (mPTP) opening and elevated the transcript levels of antioxidant defense genes (e.g., peroxiredoxin-5, PRDX5). These alterations indicate the occurrence of mitochondrial collapse. Concurrently, scanning electron microscopy verified localized plasma membrane wrinkling and pore formation in sperm. In addition, NGT exposure decreased the transcript abundance of cytoskeleton-related genes, including solute carrier family 26 member 6 (SLC26A6), actin (ACT), and tubulin polymerization promoting protein family member 3 (TPPP3). These molecular changes further disrupted membrane phospholipid homeostasis, as represented by altered glycerophospholipid metabolism. At the same time, cumulative cellular stress was associated with decreased transcript abundance of cytoprotective factors (e.g., baculoviral IAP repeat-containing proteins, birc2) and changes in apoptosis-related genes consistent with activation of a caspase-8-mediated apoptotic programme. In conclusion, NGT, as a representative synthetic progestin, exerts reproductive toxicity by interfering with signaling mediators to induce premature AR, which subsequently exhausts metabolic energy and triggers plasma membrane impairment. These findings provide a critical mechanistic basis for the aquatic ecological risk assessment of synthetic progestins.

Animals↗

PubMed2026

Transcriptomic insights into thermal stress reveal physiological trade-off between thermal stress adaptation and reproductive investment in Spodoptera litura.

Spodoptera litura, a highly polyphagous lepidopteran pest, poses a major threat to agricultural productivity due to its remarkable adaptability to diverse environmental conditions. Although heat stress is known to trigger transcriptional reprogramming in insects, the molecular mechanisms underlying thermal stress responses in S. litura remain poorly understood. In the present study, fourth-instar larvae were exposed to acute heat stress (44 °C) and compared with control conditions (27 ± 1 °C) to investigate heat-induced transcriptional alterations affecting physiology and reproduction. High-quality RNA-Seq data achieved more than 80% mapping efficiency, with a total of 15,782 transcripts were identified. Transcriptome analysis of S. litura larvae showed 323 differentially expressed genes (DEGs), of which 262 genes were significantly upregulated and 61 were downregulated in heat-stressed larvae compared to the control group. The DEGs were associated with stress response, reproduction, signalling, proteostasis, detoxification, oxidative stress, metabolism, development, and chromatin regulation. Heat shock proteins genes, including HSP70, HSP90, and HSP27, together with co-chaperones such as TRET-1, STIP1, and Starvin, were strongly upregulated, indicating enhanced cellular protection against protein damage and oxidative stress under heat stress. Conversely, key reproductive and cell cycle-related genes, including BARR, CAPD2, FEO, CDK2 and MORULA, were significantly downregulated, suggesting reproductive impairment and developmental arrest. RT-qPCR validation corroborated the RNA-Seq findings, demonstrating a heat-induced physiological trade-off that prioritizes survival over reproduction. Consistent with these molecular responses, heat-stressed insects exhibited marked reproductive impairment, including significant reductions in gonadosomatic index, eupyrene sperm bundle count, mating frequency, mating success, female calling behaviour, copulation duration, fecundity, and egg fertility. Collectively, these findings provide comprehensive insights into the molecular basis of thermal adaptation in S. litura and demonstrate that acute heat stress compromises reproductive fitness while activating conserved stress-response pathways that promote short-term survival.

Animals↗

PubMed2026

Long-term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy is widely provided to control menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess the long-term effects of prolonged use (at least one year) of hormone therapy on mortality, cardiovascular outcomes, cancer, gallbladder disease, fractures and cognition in perimenopausal and postmenopausal women. SEARCH METHODS: We used the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, three other databases and two trial registers, together with reference checking, citation searching and contact with study authors to identify the studies included in the review. The latest search date was 26 September 2024. SELECTION CRITERIA: We included randomised, double-blind trials in which peri- or postmenopausal women took hormone therapy or placebo for at least one year. We included various oestrogen formulations, with or without progestogens. We focused on studies assessing hormone therapy's effects on long-term clinical outcomes, including death, coronary events and cancer. Hormone therapy's efficacy in managing menopausal symptoms was beyond the scope of this review, and is assessed in other Cochrane reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 24 studies - with two newly added in this update - involving 45,660 participants. We derived nearly 70% of the data from two well-conducted studies: the Heart and Estrogen/progestin Replacement Study (HERS 1998) and the large, multi-component Women's Health Initiative research programme, which included two hormone therapy arms (WHI 1998). Across all the studies, most participants were postmenopausal American women with one or more comorbidities. The mean participant age in most studies was over 60 years. Only one included study focused on perimenopausal women. We present full results for all included studies with available data in the main review. The results presented below are drawn from WHI 1998, in which the combined hormone therapy arm and the oestrogen-only arm were run concurrently, with women assigned to the appropriate trial based on their uterus status. One study with 16,608 postmenopausal women with an intact uterus compared combined continuous hormone therapy (conjugated equine oestrogen and medroxyprogesterone acetate) to placebo, and measured outcomes at an average of 5.6 years of follow-up. Based on this study, combined continuous hormone therapy probably makes little to no difference to the risk of a coronary event (RR 1.17, 95% CI 0.95 to 1.44; moderate-certainty evidence). It may increase the risk of stroke (RR 1.39, 95% CI 1.09 to 2.09; low-certainty evidence) and venous thromboembolism (RR 2.03, 95% CI 1.55 to 6.64; low-certainty evidence). Compared to placebo, combined continuous hormone therapy probably increases the risk of breast cancer (RR 1.27, 95% CI 1.03 to 1.56; moderate-certainty evidence) and probably makes little to no difference to the risk of lung cancer (RR 1.06, 95% CI 0.77 to 1.46; moderate-certainty evidence). It may increase gallbladder disease requiring surgery (RR 1.64, 95% CI 1.30 to 2.06; 14,203 participants; low-certainty evidence), and probably reduces the risk of all clinical fractures (RR 0.78, 95% CI 0.71 to 0.86; moderate-certainty evidence). One study including 10,739 postmenopausal women who had undergone a hysterectomy compared oestrogen-only (conjugated equine oestrogen) hormone therapy to placebo, and measured outcomes at an average of seven years' follow-up. Based on this study, oestrogen-only hormone therapy probably makes little to no difference to the risk of coronary events (RR 0.94, 95% CI 0.78 to 1.13), venous thromboembolism (RR 1.32, 95% CI 1.00 to 1.74) and breast cancer (RR 0.79, 95% CI 0.61 to 1.01), all with moderate-certainty evidence. It may make little to no difference to the risk of lung cancer (RR 1.04, 95% CI 0.73 to 1.48; low-certainty evidence). Oestrogen-only hormone therapy probably increases the risk of stroke (RR 1.33, 95% CI 1.06 to 1.67) and gallbladder disease requiring surgery (RR 1.78, 95% CI 1.42 to 2.24), and probably reduces the risk of all clinical fractures (RR 0.73, 95% CI 0.65 to 0.80), all with moderate-certainty evidence. We judged most included studies to have a low risk of bias for most domains. The overall certainty of evidence for the main comparisons was moderate. The main limitation was that only about 30% of women were 50 to 59 years old at baseline, the age group most likely to consider hormone therapy for vasomotor symptoms. AUTHORS' CONCLUSIONS: Long-term follow-up of women using hormone therapy suggests that the risk profiles vary between combined hormone therapy and oestrogen-only therapy. Oestrogen-only hormone therapy probably makes little to no difference to coronary events, and probably increases the risk of stroke and gallbladder disease. It probably makes little to no difference in the risk of breast cancer, and probably reduces the risk of all fractures. Combined hormone therapy may increase the risk of thromboembolism and probably increases the risk of breast cancer. These results should be interpreted with caution as they are based on one study using oral hormone therapy, which may not represent the risks of the hormone therapy currently used in clinical practice.

Humans↗

PubMed2026

Patient-reported outcomes in pediatric regional anesthesia trials: current use and limitations.

PURPOSE OF REVIEW: This review examines the current use and limitations of patient-reported outcome measures (PROMs) in pediatric regional anesthesia research. Despite the increasing emphasis on patient-centered outcomes, existing pediatric outcome assessment frameworks may inadequately capture the pain experience and interference with daily living. RECENT FINDINGS: Across 17 identified randomized controlled trials and 15 ongoing studies, PROM use remains highly variable, with consistent reliance on observational pain scales such as the Face, Legs, Activity, Cry, and Consolability scale and limited incorporation of standardized, longitudinal health-related quality-of-life measures. SUMMARY: Current pediatric PROM frameworks remain fragmented, limiting comprehensive evaluation of recovery. Greater standardization and incorporation of developmentally appropriate, longitudinal outcome measures are needed to better align clinical research with meaningful patient-centered endpoints and to improve assessment of functional and psychosocial recovery.

Humans↗

PubMed2025

Selective Neurectomy Outcomes in Synkinesis Patients: The First 56 Consecutive Primary Cases with Minimum 1-Year Follow-Up.

INTRODUCTION: Evaluation of 1-year follow-up outcomes after selective neurectomy (SN) is essential to confirm sustained improvements in patient-reported, clinician-graded, and objective results. OBJECTIVE: To assess outcomes of SN in synkinesis, using patient-reported outcomes (VAS), clinician-graded assessments (eFACE), and objective evaluations. METHODS: Synkinesis patients who underwent SN were included in the study. Patients with less than 12 months of follow-up were excluded. Visual analog scale (VAS) was assessed as patient-reported outcomes. The Electronic Clinician-Graded Facial Function Scale (eFACE) was also assessed. Objective evaluations were carried out via Emotrics Software. RESULTS: Fifty-six primary cases were included, with a mean patient age at surgery of 33.8 ± 11.0 years. Of these, 45 patients (80.3%) were female. The average duration between paralysis and surgery was 124.3 ± 103.3 months. The mean duration between surgery and evaluation was 19.7 ± 7.5 months (mean/SD). Preoperative and postoperative mean aggregate VAS scores were 35.5 ± 19.8 and 67.7 ± 16.5, respectively (p < 0.001). However, two patients (3.7%) reported worsening in moving food around in the mouth, and four patients (7.5%) reported worsening in drooling. All postoperative eFACE subscores except periocular demonstrated significant improvement (p < 0.001). Emotrics analysis demonstrated improvement in all postoperative symmetry parameters, except in the periocular region. CONCLUSIONS: SN improves patient-reported outcomes, clinician-graded assessments, and objective measurements. However, periocular outcomes remain suboptimal, and functional deficits should be carefully considered.

Humans↗

PubMed2026

Long-term outcomes of surgical correction of ventral penile curvature in children: Patient-reported measures, surgical results, and decisional regret.

INTRODUCTION: There is a dearth of data on long-term outcomes, including patient-reported outcomes (PROMs), decisional regret, and complication rates for surgical correction of isolated ventral penile curvature in childhood. PATIENTS AND METHODS: Twenty-six children treated for ventral curvature between 1993 and 2008 were identified; 24 met inclusion criteria (isolated ventral curvature without hypospadias or need for urethral reconstruction). Surgical correction consisted of degloving alone or degloving with Nesbit-like dorsal plication when residual curvature >20° persisted after degloving. PROMs were collected via pre-mailed validated questionnaires after puberty: Danish Prostatic Symptom Score (DAN-PSS) for LUTS, Erection Hardness Score (EHS) for erectile function, Penile Perception Score (PPS) for cosmetic perception, and items assessing decisional regret and perceived appropriateness of surgical timing. RESULTS: Curvature was corrected intraoperatively in all 24 patients. Twelve underwent degloving alone and 12 required additional dorsal plication. During long-term follow-up (median 14.2 years), one patient (4%) underwent re-operation for residual curvature, and three (13%) underwent cosmetic revisions; two (8%) underwent cystoscopy for flow concerns. 71% returned PROMs at a median age of 16.2 years. LUTS were uncommon, with low bother scores. Erectile function was favorable: 87% (13/15) reported EHS 4 and 93% (14/15) reported ejaculation. Cosmetic outcomes were favorable, with PPS dissatisfaction rates comparable to controls. Two patients reported dissatisfaction with overall appearance, and one with residual subjective curvature. No patient expressed decisional regret, and 88% felt timing of surgery was appropriate. CONCLUSION: Early surgical correction of isolated ventral penile curvature using degloving with or without dorsal plication provided durable anatomical correction and favorable long-term functional and cosmetic outcomes. These findings support early intervention as an effective approach with sustained patient-perceived benefits.

Humans↗