Search Results (1,745)

Chemotherapy-induced cognitive impairment (CICI), often referred to as “chemobrain,” is a common and sometimes persistent consequence of cancer treatment, characterized by deficits in memory, attention, executive function, and processing speed; it disproportionately affects older adults and women, suggesting a role for aging- and sex-related biological factors, including estrogen depletion. This work examines the potential of dietary phenolic compounds as multi-target modulators of mechanisms underlying CICI. A narrative synthesis of preclinical and clinical evidence was conducted, focusing on major phenolic subclasses (flavonoids, phenolic acids, stilbenes, lignans, and secoiridoids) and their effects on pathways implicated in chemotherapy-related neurotoxicity. The reviewed data indicate that phenolic compounds can influence redox balance, neuroinflammatory responses, mitochondrial function, synaptic plasticity, and estrogen-related signaling, with effects that appear to be structure-dependent; however, evidence remains heterogeneous and largely derived from experimental models rather than studies in humans. Overall, the current findings suggest that selected phenolic compounds could mitigate vulnerability to CICI, particularly in higher risk groups such as older individuals and women with low estrogen levels. These compounds represent promising and safe adjunctive strategies, although further well-designed clinical studies are needed to confirm their efficacy and clarify the underlying mechanisms. Full article

Background: Primary glomerular diseases (PGDs) are a leading cause of end-stage kidney disease (ESKD). While sex differences in chronic kidney disease progression have been reported, their role in PGDs remains unclear. Methods: We analyzed 2081 patients with biopsy-proven PGDs from the Turkish Society of Nephrology Glomerular Diseases Working Group (TSN-GOLD) registry. Baseline demographic, clinical, biochemical, and histopathological characteristics were compared between women and men. Outcomes were assessed as a composite of ESKD or death. Logistic and Cox regression models were applied to identify independent risk factors. Kaplan–Meier analyses evaluated survival differences. Results: At baseline, women and men had similar rates of hypertension (36.8% vs. 34.7%, p = 0.322). Women more frequently presented with leukocyturia (31.7% vs. 17.2%, p < 0.001) and hematuria (57.8% vs. 52.3%, p = 0.016), whereas men had higher proteinuria (5011 ± 4925 vs. 4388 ± 4529 mg/day, p = 0.003) and were more likely to be active smokers (20.7% vs. 7.4%, p < 0.001). Serum albumin (3.3 ± 0.8 vs. 3.2 ± 0.9 g/dL) and eGFR (79.7 ± 44.3 vs. 78.7 ± 45.5 mL/min/1.73 m²) were comparable between sexes (both NS). During a median follow-up of 24 months (IQR 7-60), 431 patients (20.7%) reached the composite outcome of ESKD or death (137 deaths [6.6%], 294 ESKD [14.1%]). In the multivariable Cox regression model, lower baseline eGFR (HR 0.98, 95% CI 0.98–0.98, p < 0.001), lower serum albumin (HR 0.65, 95% CI 0.55–0.77, p < 0.001), higher proteinuria (HR 1.03, 95% CI 1.00–1.05, p = 0.043), and biopsy diagnosis of RPGN (HR 3.78, 95% CI 1.37–10.45, p = 0.010) were independent predictors of poor prognosis. Sex was not an independent predictor of outcome (p = 0.48). Kaplan–Meier analysis demonstrated no significant survival difference between women and men (log-rank p = 0.052). Conclusions: In this nationwide PGD cohort, women and men differed significantly in baseline biochemical and clinical parameters, yet sex was not independently associated with progression to ESKD or death. Instead, disease severity at baseline and histopathological features were the main drivers of prognosis. Full article

This concept paper advances stigma power as a central analytical mechanism for understanding how patriarchy, capitalism, white supremacy, and cis-heteronormativity operate with particular intensity against sex workers. Integrating Link and Phelan’s stigma power with Bourdieu’s symbolic violence and Foucauldian productive power, the framework theorises stigma as a mechanism institutionalised through law and enforced by institutions, which produces measurable consequences that include violence, exclusion, and health harms. Analysing the intersecting axes of gender, sexuality, race, migration, and class across three qualitative studies (SWMH, SEXHUM, VICSW), the article demonstrates why labour-rights reforms, including decriminalisation, are necessary but insufficient. Dismantling stigma requires not only removing sanctions but actively contesting the actors exercising stigma power and interrupting the stabilising mechanisms that reproduce it. This requires policy that acknowledges stigma’s existence whilst working to dismantle it, rather than eliding its reality through liberal mainstreaming or strengthening it through criminalisation or rescue frameworks. The framework explains why decriminalisation is associated with better access to rights and health; why all criminalisation including the so-called Swedish model correlates with increased violence; why stigma persists under optimal legal conditions; and how intersecting marginalisations produce differential vulnerability. Policy implications emphasise pairing decriminalisation with peer-led anti-stigma work, institutional reform, migrant rights, and funded support for sex worker self-organisation. Full article

Cardiac safety assessment is an integral part of drug discovery and development. Drug candidates that adversely affect cardiac or hemodynamic function should be discontinued early unless a favorable benefit-risk ratio for patients can be justified. In this hypothesis-generating work, we aimed to develop a conceptual framework for informing early safety risk assessment based on in vitro drug affinities to pharmacological targets. For illustration, we used the drug-induced cardiotoxicity rank (DICTrank) data comprising 1318 drugs with cardiac safety concerns according to FDA labeling. The data was enriched with information on affinity to the most plausible mechanistic targets, clinical drug exposure, and human plasma protein binding. We descriptively identified 18 target classes potentially associated with elevated cardiovascular risk: potassium channels (accounting alone for 20% of the ‘most concern’ safety group); adrenergic, dopamine, serotonin, androgen, sex hormone, and opioid receptors; cyclooxygenase; sodium and calcium channels; muscarinic and glucocorticoid receptors; phosphodiesterase; topoisomerase; angiotensin-converting enzyme; angiotensin II type 1 receptor; monoamine transporters, and acetylcholinesterase. Overall, 80% of the ‘most concern’ drugs compared with only 12% of the ‘no concern’ drugs were associated with these targets in this exploratory descriptive analysis. Concentration–response analyses revealed differences in target potency and free drug exposure that appeared associated with variability in the severity of cardiotoxicity among drugs acting on the same target. This framework demonstrates how in vitro data can be used to benchmark new compounds early in development, enabling the timely discontinuation of candidates associated with substantial risk. Full article

Background/Objectives: During the first COVID-19 lockdown, the sudden disruption of formal care services substantially increased reliance on informal caregiving. Emerging evidence suggests that increased caregiving demands may have contributed to a higher burden of mental-health-related temporary work disability; however, population-based data from occupational health systems remain limited. This study aimed to quantify and characterise, descriptively, the sociodemographic, clinical, and territorial characteristics of mental-health-related temporary work disability among workers with informal caregiving responsibilities in Spain during the first COVID-19 lockdown, and to descriptively examine differences between episodes occurring among workers with and without caregiving responsibilities. Methods: A retrospective descriptive study was conducted using anonymised nationwide occupational health records from Mutua Asepeyo. All episodes of temporary work disability certified for mental and behavioural disorders (ICD-10 F00–F99) between 14 March and 21 June 2020 were analysed. Caregiver status was determined based on documented informal caregiving responsibilities recorded within the occupational disability records. Sociodemographic, occupational, clinical, and territorial variables were examined using descriptive statistics and non-parametric tests. Results: A total of 2857 caregiver-associated episodes were identified, representing 55.6% (95% CI: 54.2–57.0) of all mental-health-related temporary work disability episodes during the study period. The majority involved women (68.1%) and caregivers of older dependent adults (59.3%). Generalised anxiety disorder was the most frequent diagnosis, followed by adjustment disorders and acute stress reactions, with significant differences by sex and employment regime. Marked territorial variability was observed, as well as longer durations of temporary work disability in specific regions and among women. Conclusions: A substantial proportion of mental-health-related temporary work disability episodes during the lockdown occurred among workers with informal caregiving responsibilities, particularly women and those caring for older dependents. These findings suggest that informal caregiving may be a determinant of occupational mental health during crises. However, given the descriptive and unadjusted nature of the study, no causal inferences can be drawn. Further research is needed to understand these associations better and inform future occupational health strategies. Full article

(1) Background: Asymmetry in strength, movement, and neuromuscular control is common in youth sports, yet its role in anterior cruciate ligament (ACL) injury risk in pediatric athletes remains underexamined. (2) Methods: This narrative review synthesized studies that examined lower-limb asymmetry, biomechanics, ACL injury or reconstruction (ACLR), and rehabilitation in participants younger than 18 years, supplemented by key mechanistic and methodological work. (3) Results: Evidence indicates that asymmetry is multifactorial and sometimes functional, arising from limb dominance, sport-specific loading, growth-related morphological change, and neuromuscular variability. However, asymmetry becomes concerning when it coincides with high-risk landing or cutting mechanics, growth-related coordination deficits, or incomplete recovery after ACL reconstruction. Persistent strength and loading asymmetries are linked to secondary ACL injury and early structural joint changes, whereas neuromuscular training and technique-modification programs can improve symmetry and reduce high-risk mechanics. Major gaps include the absence of pediatric-specific asymmetry norms, limited longitudinal and sex-specific data, and heterogeneous measurement approaches. (4) Conclusions: Clarifying when asymmetry is adaptive versus maladaptive, and integrating this knowledge into screening, rehabilitation, and return-to-sport decision-making, will be essential for optimizing performance and promoting lifelong knee health in pediatric athletes. Full article

The work was performed to assess the relationship of single-nucleotide polymorphisms (SNPs), which determine the concentration of sex hormones (confirmed in previously performed genome-wide studies (GWASs)), with the risk of endometrial hyperplasia (EH). The objects of the study were 1493 women, of which 520 individuals had EH; the control group consisted of 973 women. Nine SNPs that were GWAS-associated with the level of sex hormones were investigated. The correlations of SNPs that determine the level of sex hormones with EH risk were found: minor polymorphic variants rs11031002 (allele A: OR = 0.45–0.50) and rs11031005 (allele C: OR = 0.05–0.53) of the FSHB gene were associated with a low risk of developing the disease, and the TT*rs11031002-rs11031005 FSHB haplotype, at a level of statistical significance (p = 1 × 10⁻¹¹) exceeding the GWAS “standard”, increases the EH risk by more than 2.5 times (OR = 2.84). The 16 multilevel SNP interaction exploratory models of nine considered loci were EH-associated (p_adj-perm < 0.001). Two loci, T>A rs11031002 and T>C rs11031005 FSHB, play a fundamental role in these models (100% and 75% of models, respectively), and two more loci, C>G rs112295236 SLC22A10 and C>A rs117585797 ANO2, are part of more than 30% of all models. Sex hormone-level genetic determinants are involved in numerous EH-significant hormone-mediated molecular pathways (regulation of gene transcription, processes of embryogenesis and development, regulation of metabolism, differentiation and maturation of the epithelium, TGFβ pathway, fat cell differentiation, etc.). In conclusion, for the first time, it was found that the genetic polymorphisms that determine an organism’s sex hormone levels are associated with EH. Full article

Background/Objectives: Sarcopenia, characterized by progressive loss of skeletal muscle mass and function, is a major public health concern among aging populations. While physical activity is recognized as protective, the comparative effectiveness of different exercise modalities remains understudied in Asian populations. This cross-sectional study investigated the association between exercise type and sarcopenia prevalence among Korean adults aged 40 years and older. Methods: This cross-sectional study analyzed data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2024. A total of 1688 adults aged ≥40 years were included. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia (AWGS) 2019 criteria, incorporating dual-energy X-ray absorptiometry (DXA)-based appendicular skeletal muscle mass index (ASMI) and handgrip strength. Due to the absence of physical performance measures in this survey cycle, the operational definition required both low ASMI and low handgrip strength. Exercise types were categorized into four groups: no exercise, aerobic only, resistance only, and combined exercise. Multivariable logistic regression, adjusting for age, sex, socioeconomic status, lifestyle factors, nutritional intake, and comorbidities, was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Sarcopenia prevalence was 13.2% (n = 223). In the fully adjusted model, resistance-only exercise was associated with 56% lower odds of sarcopenia (OR 0.44, 95% CI 0.23–0.82, p = 0.010), and combined exercise with 69% lower odds (OR 0.31, 95% CI 0.13–0.78, p = 0.012). Aerobic-only exercise showed no significant association (OR 0.88, 95% CI 0.54–1.42, p = 0.594). The protective association was statistically significant in the 60–69 age group (OR 0.28, 95% CI 0.11–0.74), with similar but non-significant trends in other age groups. Conclusions: Resistance exercise, either alone or combined with aerobic exercise, is associated with lower odds of sarcopenia in Korean adults aged 40 and older. These observational findings warrant further investigation through prospective and interventional studies before informing public health strategies. Interpretation should consider the limited sample size in the resistance-only subgroup (n = 18 with sarcopenia) and the cross-sectional design, which precludes causal inference. Full article

Working memory, the capacity to store information for near-immediate use, and visual attention, the ability to focus on task-relevant information, are integral skills for military personnel. In civilian populations, stress is associated with worse skills. However, little is known about the relationship between stress, working memory, and visual attention in military officers, who are trained to handle acute stress and operate in high-stress environments. Thirty-three military officers completed a working memory test, a Perceived Stress Questionnaire (PSQ), and an oculometric assessment of visual tracking. The oculometric test was a modified step-ramp test that produces 10 z-scored metrics. Working memory and executive function were assessed via the n-back task. Oculometric performance and self-reported stress levels were independently associated with n-back accuracy, explaining 67% of the variance (adjusted R², n = 30). The association between oculometric performance and n-back accuracy was driven by directional anisotropy, directional noise and proportion of smooth pursuit. The association between oculometric performance and stress was complicated by sex differences. Results have important implications for the assessment of cognitive readiness in military populations. The strong relationship between oculometric performance and working memory suggests that eye-tracking-based metrics may serve as candidate indicators of cognitive function under operational demands. Full article

Background/Objectives: Anabolic resistance is thought to underlie muscle loss in sarcopenia. Here, we investigated the adjuvant role of beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, on the acute muscle anabolic response to oral protein supplementation in older adults. Methods: A total of 24 community-dwelling older adults (68.5 ± 0.6 years; 13 men, 11 women) were randomized in a cross-over double-blind design to 40 g whey protein (Control) or 40 g whey protein with 3 g calcium–HMB (HMB). Subjects received a primed constant infusion of ¹³C₆ phenylalanine to assess muscle protein synthesis (MPS, by tracer incorporation in myofibrils) and muscle protein breakdown (MPB, via arterio-venous dilution) at baseline and post supplementation. Fasted and 3 h fed-state plasma HMB, aminoacidemia, rates of MPS, MPB, limb and muscle blood flow were measured. Results: In all subjects, both interventions displayed significant increases in MPS in response to feeding [fasted to 3 h-fed change (mean ± SEM, standard error of the mean). Males: control, +0.032 ± 0.006%.h⁻¹; HMB, +0.023 ± 0.004%.h⁻¹; females: control, +0.023 ± 0.006%.h⁻¹; HMB, +0.038 ± 0.006%.h⁻¹, p < 0.05]. In older women, the addition of HMB further enhanced the MPS response (fasted to 3 h-fed change, p = 0.0495) and area under the curve (p = 0.0364) versus protein alone. During the late-fed period, MPB significantly decreased in HMB versus control (p = 0.0298), and this was also observed when subjects were separated by sex (p = 0.0012). Conclusions: High-dose protein bolus feeding increased MPS in older adults. Surprisingly, 40 g whey did not maximize the anabolic response in older women, and HMB further increased the MPS feeding response to protein. HMB further suppressed the MPB feeding response over a longer period of time. Further work is needed to understand the apparent sexual dimorphic MPS response to high protein. Full article

Risk and loss aversion are key forms of behavioral decision-making describing how people weigh potential gains and losses. Although most of the literature on risk and loss aversion comes from the field of behavioral economics, these concepts are applicable to complex medical decision making, especially when those decisions are shaped by sociopolitical factors as in gender transitions. For clinicians providing gender-affirming care, discussions of risk and loss aversion can support the informed consent process by reducing “noise” that may obscure gender identity and embodiment goals and delay critical decisions. Using this framework and understanding the impact of oppositional sexism and the gender binary can help clinicians understand why their clients might be hesitant to transition and how they can help affirm their client’s gender identity while supporting their transition goals. This approach is especially helpful when working with individuals who undergo transition in later life who may be struggling to overcome tacit assumptions about sex and gender identity that stand in the way of pursuing gender-affirming care. Full article

Background/Objectives: Severe hemorrhagic shock progressing to clinical death remains a major cause of mortality and long-term neurological morbidity despite advances in trauma care. While current resuscitation strategies restore circulation, their ability to preserve brain structure and function following global ischemia–reperfusion injury remains limited. Hemorrhagic shock induces widespread neuronal vulnerability, particularly within the hippocampus and prefrontal cortex, contributing to persistent cognitive and behavioral deficits among survivors. Methods: Using a rat model of hemorrhagic shock-induced clinical death, we evaluated whether resuscitation with VBI-1, a phospholipid nanoparticle-based colloid, supports neurological recovery compared with whole blood-based resuscitation. Animals underwent controlled exsanguination to the point of clinical death, followed by rapid intra-arterial reanimation with either shed whole blood or VBI-1. Two phases of study were performed: histological evaluation of tissues 12 h after resuscitation and, in a separate cohort of animals, longitudinal behavioral recovery over 30 days. Histology focused on evaluating neuronal integrity in the hippocampal CA1 region and prefrontal cortex, neuronal functional status, and microglial responses. Sex was analyzed as a biological variable. Results: Resuscitation with VBI-1 is associated with sustained behavioral recovery, with pronounced sex-dependent effects favoring females during the subacute-to-chronic recovery phase. VBI-1 preserved neuronal density, laminar organization, and neuronal functional integrity in ischemia-vulnerable brain regions. This, and neuronal preservation, correlated with hippocampal-dependent working memory performance. Importantly, resuscitation with VBI-1 did not increase microglial density, coverage, or spatial organization, exacerbating the neuroinflammatory burden. Conclusions: These findings demonstrate that phospholipid nanoparticle-based resuscitation confers meaningful neurological recovery following profound circulatory collapse, highlighting the importance of evaluating resuscitation agents based on long-term brain outcomes. Full article

Nowadays, the application of insect sex pheromones in pest control technology has reached a relatively advanced technological maturity stage. However, the traditional research and development of sex pheromones requires a “one pest, one strategy” approach, which has drawbacks such as being time-consuming and focused on a single control target. The insect sex pheromone synthesis pathway involves multiple molecular components that work together to promote the synthesis and release of sex pheromone from the pheromone gland. Elucidating the mechanisms underlying pheromone biosynthesis offers the potential to uncover universal strategies for pheromone development, thereby improving the efficiency and effectiveness of pest management. This study arranged knowledge of the upstream regulatory pathways and summarized the structure and function of the molecular components involved. We also investigated the divergence of neuropeptides and their receptors that regulate pheromone biosynthesis among different insect species from an evolutionary perspective. Future research should integrate multi-omics, bioinformatics, structural biology, and artificial intelligence technologies to elucidate the synthesis and regulatory processes of insect semiochemicals, develop specific dsRNA and small molecule inhibitors, and accelerate the transformation and application of related molecular targets into highly effective and green pesticides. Full article

Background/Objectives: Breaking bad news is crucial for patient-centered care. This study aimed to assess physicians’ skills and investigate the possible factors affecting their ability to communicate bad news. Methods: This web-based cross-sectional survey of 633 Greek physicians included demographic and other breaking bad news related questions to evaluate their skills and practices in breaking bad news to patients with cancer. Results: Most physicians defined bad news (91.5%) and frequently used both verbal and non-verbal communication (82.6%). About three-quarters rated their ability to communicate bad news as good to very good (75%) and about half (50.4%) disclosed bad news in a private and comfortable setting. Emotional responses, like sadness (53.4%) and compassion (49.6%), were common, while fears mainly focused on diminishing patients’ hope (60.8%) or managing patients’ reactions (53.9%). Female physicians showed higher anxiety (15.9% vs. 4.3%, p < 0.0005) and sadness (53.4% vs. 43.5%, p = 0.018) and lower self-perceived competence (p = 0.001) compared to males. Specialists and physicians with formal training demonstrated greater competence (p < 0.0005) and were more likely to choose private and comfortable settings (p < 0.0005). Multivariable logistic regression identified increased age (OR = 1.03; p = 0.018), male sex (OR = 1.63; p = 0.015), formal training in breaking bad news (OR = 9.34; p < 0.0005), residence outside Athens (OR = 2.27; p = 0.002), working in oncology (OR = 1.90; p = 0.043), and employment in private hospitals (OR = 1.81; p = 0.014) as statistically significant predictors of good to very good ability to communicate bad news to cancer patients. Conclusions: These findings highlight the value of structured training, targeted practice and institutional support in fostering physicians’ communication skills and boosting patient-centered care. Full article

Once dismissed as “junk”, transposable elements (TEs) have recently gained recognition for their regulatory roles, notably in the brain and during development. The brain is hormone-responsive and the hippocampus in particular is sensitive to circulating gonadal hormones. While transcriptionally active, TE function remains poorly understood, especially in the brain. We and other researchers have shown that one particular TE RNA, B2 SINE ncRNA, is a regulator in the rodent hippocampus, especially after a psychologically stressful event like acute restraint stress. However, it is unknown if B2 SINE ncRNA is necessary for the proper development of hippocampal neurons, and, furthermore, if there are sex differences in this development. This work investigates the differences in the expression of B2 SINE RNA across sexes and its role in the development of primary hippocampal neurons. We utilized pooled locked nucleic acid (LNA) GapmeRs to knock down the expression of B2 SINE RNA, and we treated primary hippocampal neurons with dihydrotestosterone (DHT) to test if there is a difference in dendritic complexity. We used Sholl analysis to quantify branching, number of tips, and Sholl mean. We found a sex difference in both B2 SINE, higher in males compared to females, and ß-actin, lower in males compared to females. Additionally, knocking down B2 SINE RNA results in a reduction in dendritic complexity in male but not in female neurons. Taken together, this work suggests that B2 SINE RNA is expressed differentially and that it plays an important role in the proper development of hippocampal neurons in a sex-dependent manner. Our findings support the identification of a sex-specific biomarker that may enable individualized treatment of conditions influenced by sex. This is the first evidence of the role B2 SINE RNA may play in the regulation of the development of neuronal dendritic structure and the first to show differential regulation by sex. Full article