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Reproductive Intentions and Fertility Preservation Among Transgender and Nonbinary Individuals: A Cross-Sectional Study in Brazil.

PURPOSE: This study evaluated reproductive intentions, fertility-related knowledge, prior fertility counseling, and factors associated with reproductive intentions among transgender and nonbinary individuals receiving care at a Brazilian public reference center. METHODS: This cross-sectional study with a qualitative component was conducted between July and November 2025 in a specialized gender-affirming care clinic in Brazil. Quantitative data included sociodemographic characteristics, reproductive history, gender-affirming hormone therapy (GAHT), and fertility-related variables. Logistic regression was used to assess factors associated with desire for future parenthood. Responses to a single open-ended question regarding perceived effects of GAHT on fertility were analyzed using thematic content analysis. RESULTS: Eighty-two participants were included (mean age 27.5 ± 7.4 years). Most identified as transgender men (65.9%), followed by transgender women (26.8%) and nonbinary individuals (7.3%); 79.3% were receiving GAHT. Although 63.4% expressed a desire for future parenthood, only 7.3% had children. Current interest in fertility preservation was reported by 20.8% (15/72). Having children (adjusted odds ratio [aOR] = 0.03; 95% confidence interval [CI]: 0.001-0.62; p = 0.023) and each additional year of GAHT duration (aOR = 0.83; 95% CI: 0.70-0.99; p = 0.038) were associated with lower odds of desiring future parenthood. Sex assigned at birth was not independently associated with reproductive intentions. Qualitative analysis revealed misconceptions, uncertainty, and conditional beliefs regarding fertility. CONCLUSIONS: Desire for future parenthood was common among transgender and nonbinary individuals, whereas engagement with fertility preservation remained limited. These findings highlight the need for longitudinal, patient-centered reproductive counseling integrated into gender-affirming care.

fertility preservation

Care Experience Disparities in Individuals With Lower Urinary Tract Symptoms: Systematic Review and Content Analysis.

OBJECTIVES: In this study, we aimed to characterize the landscape of the literature and describe lower urinary tract symptom (LUTS) care experiences using the Agency for Healthcare Research and Quality's (AHRQ's) patient experience framework, describe the characteristics of the studies, and identify critical knowledge gaps. METHODS: We performed a systematic search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus of peer-reviewed publications from 1995 to 2024. The search terms were related to LUTSs, drivers of healthcare inequities, and the domains of the AHRQ. We then performed a content analysis of the included studies. RESULTS: Of the 4597 articles reviewed, we included 11 studies in the analysis. The most studied LUTS was urinary incontinence (10/11, 91%). Of the included studies, six were comparative, and most (4/6, 66.7%) found worse care experience in patients with limited English proficiency and low socioeconomic status. When examining the studies using the care experience framework of the AHRQ, the most frequently evaluated domains of care experience were communication with clinicians (8/11, 73%) and access to care (8/11, 73%). For communication with clinicians, language barriers (3/11, 27%) and symptom minimization by clinicians (3/11, 27%) were common, especially among patients with limited English proficiency and of older age, respectively. In regard to access to care, concerns about healthcare costs (5/11, 45%) and patients' fear or embarrassment about accessing LUTS care (4/11, 36%) were commonly occurring themes, especially among racially minoritized groups. CONCLUSIONS: The findings of this systematic review demonstrated that patients with limited English proficiency, older age, low socioeconomic status, and racially minoritized backgrounds have poor LUTS care experiences.

Humans

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I² statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R²=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans

Failure modes and effects analysis for clinical implementation of online adaptive radiotherapy: A systematic review.

BACKGROUND: The accuracy of radiotherapy is limited by anatomical variations occurring over time scales ranging from sub-seconds to days. Online Adaptive Radiotherapy (OART) addresses this by enabling daily plan adaptation based on real-time imaging. While OART offers improved dose conformity, its dynamic, time-constrained workflow introduces novel failure modes that challenge traditional quality assurance protocols. PURPOSE: This study aims to synthesize the existing literature on Failure Modes and Effects Analysis (FMEA) for OART to systematically catalog risks and identify mitigation strategies. METHODS: A systematic literature search was conducted to identify studies applying FMEA to OART workflows. Eleven studies were included, covering MR-guided (ViewRay MRIdian, Elekta Unity), CBCT-guided (Varian Ethos), and MR-enhanced C-arm linac systems. To address heterogeneity in risk scoring methodologies (e.g., TG-100 10-point scales vs. 5-point rankings), extracted failure modes were harmonized into a standardized three-tier risk classification system (Class I: Low, Class II: Intermediate, Class III: High). RESULTS: A total of 300 unique failure modes were identified, with 49.6 percent classified as high-risk (Class III). Analysis revealed that the majority of high-risk failures were concentrated in the online treatment delivery phase, specifically within human-computer interactions and anatomical contouring steps. CONCLUSIONS: This study supports the development of tailored, robust QA frameworks that prioritize human factors and process consistency to guide safe implementation in diverse clinical settings.

Humans

Evaluating the Efficacy of Electronic Screening, Brief Intervention, and Referral to Treatment (e-SBIRT) for Gambling: An Online Pilot Randomised Trial.

OBJECTIVES: To investigate the efficacy of electronic screening, brief intervention, and referral to treatment (e-SBIRT) at improving gambling outcomes and increasing help-seeking. METHODS: We conducted a two-arm, randomised online pilot trial (n = 83) comparing an e-SBIRT intervention with an active control over 12 weeks. The brief intervention was informed by motivational interviewing and incorporated personalised normative feedback, information provision, and relapse-prevention components. Eligible participants were aged 18 or older, resided in the UK and had scores indicating at least moderate severity gambling. RESULTS: Participants (54 [65.1%] male; mean [SD] age = 40.58 [12.75] years, mean [SD] PGSI = 7.16 [5.58]) in the e-SBIRT and control conditions showed improvements in gambling harms (p = 0.033) and perceived ability to control gambling (p = 0.029). No significant effects of condition assignment or condition x time interactions were observed. However, exploratory analyses of individual model coefficients suggested greater improvement in perceived ability to control gambling among participants receiving e-SBIRT at 12 weeks (p = 0.043). Exploratory analyses also suggested higher rates of help-seeking at 12-week follow-up among participants receiving e-SBIRT. CONCLUSION: Overall, e-SBIRT did not demonstrate clear advantages over assessment and information provision alone. Further research should prioritise refining intervention components and evaluating SBIRT approaches in settings that better reflect its opportunistic delivery model.

Humans

Perceptions of Pharmacogenomic Testing Among People With Treatment Resistant Depression: Legitimization as a Facilitator of Acceptance.

Pharmacogenomic testing for psychiatric medications has been proposed as both an early intervention to optimize treatment response, and for use among patients who have tried multiple medications without symptom remission. Therefore, this testing may be particularly salient to the subset of individuals with major depressive disorder for whom depression has been labeled as "treatment resistant". Understanding the impact of this diagnostic label on illness identity and attitudes towards new therapies is important as genomic technology expands and rates of depression increase. We sought to explore perceptions and attitudes towards pharmacogenomic testing among individuals who had received a diagnosis of treatment resistant depression. We conducted a qualitative study with a constructivist orientation. Participants were recruited from a larger genomic research study and interviewed by phone or video call. We took an inductive approach to coding guided by reflexive thematic analysis. Themes were then organized into a relational framework following principles of interpretive description. Twelve individuals were interviewed. Key themes included internalized acceptance/hopelessness, and external validation/frustration, which were cyclically interconnected. These themes were situated within a larger framework illustrating the ways that illness identity and modifying factors such as relief of guilt, social support, pharmacogenomic testing and depressive symptoms can either facilitate acceptance and validation or contribute to feelings of hopelessness and frustration. Though participants expressed some skepticism around its effectiveness, pharmacogenomic testing may contribute to the shift towards acceptance and validation by legitimizing individuals' experiences with lack of treatment response. Genetic counselors and other healthcare providers should be aware of the complex balance between hope and frustration underlying conversations around pharmacogenomic testing, and factors that are more likely to foster self-acceptance.

Humans

Psychological Capital and Perceived Stress in Nurses: The Mediating Role of Need for Recovery and Recovery Experiences.

AIM: To examine whether recovery experiences and need for recovery mediate the association between psychological capital and perceived stress in nurses. DESIGN: Cross-sectional online survey. METHODS: A total of 184 nurses currently practicing in France completed an anonymous online questionnaire administered in January 2023. Participants completed the French versions of the Psychological Capital Questionnaire, the Recovery Experience Scale, the Need for Recovery Scale, and the Perceived Stress Scale. Two mediation models were estimated using ordinary least squares regression with percentile bootstrap inference for the indirect effects. RESULTS: Psychological capital was positively associated with recovery experiences and negatively associated with need for recovery. Need for recovery was strongly and positively associated with perceived stress, while psychological capital showed no direct association with perceived stress. The indirect effect of psychological capital on perceived stress through need for recovery was statistically detectable, whereas a complementary indirect effect through recovery experiences was in the expected direction but did not meet the bootstrap criterion for statistical significance. CONCLUSION: In this cross-sectional sample, psychological capital was associated with lower perceived stress primarily through its association with reduced need for recovery rather than through a direct association with stress. Interventions intended to protect nurse well-being should therefore be conceived as combining individual resource-building with organizational architectures that enable effective recovery. IMPLICATION FOR NURSING PRACTICE: Psychological capital should be seen as one element in integrated interventions rather than a stand-alone solution to nursing stress. Brief recovery-focused interventions for nurses need to be combined with scheduling practices and organizational policies that protect rest and make recovery feasible, a configuration that appears more promising than psychological capital training alone. REPORTING METHOD: The study followed the STROBE Statement for the reporting of cross-sectional studies. NO PATIENT OR PUBLIC CONTRIBUTION: This study focused on nurses as study participants. No patient or public stakeholder was involved in the design, conduct, or interpretation of the research, since the research question concerns occupational psychological resources rather than clinical practice or care delivery.

Humans

Exploring Professional Experiences in Caring for Vulnerable Migrants in an Italian Rural Reception Centre: A Qualitative Study Using Multidimensional Textual Analysis-Professional Experiences in Rural Migrant Care.

AIM: This study aims to explore the experiences, strengths, challenges, and potential improvements for professionals in managing the complex needs of vulnerable migrants (VM) in an Italian rural reception centre. METHODS: A qualitative study using semi-structured interviews was conducted in April 2024. Data were analysed using the Automatic Analysis of Textual Data, based on Fraire's seven-step model for Exploratory Multidimensional Data Analysis. DATA SOURCES: Data were collected from 16 professionals working in a rural reception centre in southern Italy. Interviews were conducted and analysed using AATD in April 2024. FINDINGS: The analysis identified two main dimensions of professionals' roles: balancing systemic responsibilities with personal engagement and managing immediate needs versus long-term integration goals. Professionals face significant challenges, such as resource scarcity, bureaucratic inefficiencies, and emotional fatigue, which impact their well-being and the quality of care provided to migrants. Resilience, adaptability, and multidisciplinary collaboration were identified as key strengths. CONCLUSION: The study highlights the dual nature of professionals' work in reception centres, requiring them to balance operational tasks with emotional involvement in migrant care. Targeted interventions and systemic reforms are necessary to support professionals and enhance the quality of care for vulnerable migrants, particularly in resource-constrained rural settings. IMPLICATIONS FOR PRACTICE AND/OR PATIENT CARE: This study underscores the importance of providing targeted support to professionals working in reception centres, including training in intercultural competence, stress management, and coping strategies. Policies should address systemic challenges and provide resources to enhance healthcare delivery and social integration programs. REPORTING METHOD: This study adhered to the EQUATOR guidelines for reporting qualitative research (COREQ). The findings were reported in compliance with these guidelines, ensuring methodological rigour and transparency. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study highlights the critical need for targeted support and training for professionals working in reception centres, particularly in rural settings. To improve care for vulnerable migrants, professionals should receive training in intercultural competence, stress management, and coping strategies to better navigate the complex challenges they face. Furthermore, systemic changes are necessary to alleviate the pressures on reception centres, such as streamlining bureaucratic processes and enhancing healthcare infrastructure, particularly in rural areas where resources are limited. By addressing these needs, we can improve the well-being of both the professionals and the migrants they serve, fostering more effective support systems and better care outcomes. Additionally, fostering multidisciplinary collaboration and community engagement can contribute to more comprehensive and sustainable care models. PROTOCOL REGISTRATION: The Ethics Committee of the University of Rome Tor Vergata approved this study on 07/07/2021 (protocol registration number 160.21).

Humans

Clinical and Psychosocial Characteristics of Adult Primary Care IBS Patients: A Post hoc Analysis of the DOMINO Study.

BACKGROUND: The majority of irritable bowel syndrome (IBS) patients are diagnosed and managed in primary care, but this setting is underinvestigated to date. OBJECTIVE: The present study aimed to improve our understanding of IBS in primary care by evaluating the clinical and psychosocial characteristics of affected patients. METHODS: We performed a cross-sectional post hoc analysis of the DOMINO study, which enrolled 483 adult IBS patients newly diagnosed by primary care physicians. We investigated baseline demographics and questionnaires assessing Rome IV criteria and stool pattern subtype, symptom severity (IBS-SSS), quality of life (IBS-QoL), somatic symptom disorder (PHQ-12), depression (PHQ-9) and anxiety (GAD-7). RESULTS: 70% of the primary care diagnosed IBS patients fulfilled the Rome IV criteria (Rome+). The stool pattern subtype distribution according to the Rome IV diagnostic questionnaire was: 20% constipation (IBS-C), 33% diarrhea (IBS-D), 31% mixed (IBS-M) and 16% unclassified (IBS-U). Mean IBS-SSS was 268 ± 98, with 46% and 36% of cases reporting moderate and severe IBS-SSS, respectively. Rome + patients had, compared to Rome-, a significantly higher IBS-SSS, lower quality of life and higher psychosocial comorbidity. IBS-M, IBS-D and IBS-C participants scored significantly higher on IBS-SSS and IBS-QoL than IBS-U. Furthermore, IBS-M had significantly higher somatic symptom disorder and depression and anxiety levels compared with IBS-U. CONCLUSION: The majority of primary care IBS patients fulfilled the Rome IV criteria, were subtyped as IBS-D or IBS-M and were characterised by moderate or severe IBS-SSS. Rome+ and IBS-M participants had higher symptom severity, lower quality of life and higher psychosocial comorbidity. CLINICALTRIALS: gov, Number NCT04270487.

Adult

Ictal electroencephalography and heart rate as treatment criteria in electroconvulsive therapy: a systematic review of the literature.

BACKGROUND: Decades before the emergence of precision medicine, psychiatrists raised the question of whether specific seizure characteristics could help optimize electroconvulsive therapy (ECT), as relationships between some of these characteristics and better outcomes were found. From 1990 onward, researchers focused on electroencephalography (EEG) and cardiovascular markers, which were broadly adopted by guidelines worldwide. However, the prognostic value of these markers is still controversial. Here, we provide a systematic summary of the studies on this topic. METHODS: We conducted a literature review on the use of ictal EEG and heart rate as outcome predictors in ECT using the PubMed, EMBASE, Cochrane and PsycINFO databases. RESULTS: Thirty-seven studies addressing more than 100 quality markers fulfilled our inclusion criteria. Single EEG markers were assigned to five categories (postictal inhibition, amplitude, coherence, regularity, and seizure duration). Heart rate and composite markers were considered separately. In contrast to single EEG markers, heart rate and composite markers could be consistently linked to better outcomes in patients with depression. Only a few studies on schizophrenia could be retrieved. CONCLUSION: Multiparametric markers outperformed single markers. Furthermore, changes in heart rate during seizures were related to better outcomes. Although clinical assessment remains the cornerstone of treatment guidance decisions, EEG and cardiac monitoring could help prevent insufficient seizures during the period preceding clinical improvement. Evidence on schizophrenia remains limited. More randomized trials are needed to analyze the role of composite markers as prognostic tools.

Humans

Effects of an internet-based combined exercise and cognitive-behavioral therapy intervention on endocannabinoid system biomarkers and physical fitness in adults with mild-to-moderate depression: a SONRIE randomized controlled trial.

BACKGROUND: This SONRIE randomized controlled trial (NCT05849792) examined the effects of a 12-week combined physical exercise and internet-based cognitive-behavioral therapy (iCBT) intervention on endocannabinoid system (ES) biomarkers and physical fitness in adults with mild-to-moderate depression. METHODS: Eighty adults were randomly assigned 1:1 to an intervention (IG) or control (CG) group. Outcomes included nine ES biomarkers (2-arachidonoylglycerol, 2-AG; anandamide, AEA; seven analogues) and physical fitness, including cardiorespiratory fitness (CRF; 6-minute walking test) and muscular strength. Measurements were taken at baseline, post-intervention and 8-week follow-up. Primary analysis performed 2 × 3 repeated-measures ANOVA on completers; mixed-effects intention-to-treat model as sensitivity analysis. RESULTS: No significant time × group interaction was detected for any ES biomarker, including 2-AG (F(2,88) = 0.17, p = 0.844) and AEA (F(2,88) = 1.20, p = 0.306); both groups showed comparable within-group decreases in 2-AG, 2-LG and 2-OG. The intervention significantly improved CRF [between-group difference + 81.6 m at 12 weeks (F(2,78) = 7.88, p = 0.001)], exceeding the established minimal clinically important difference. None of the exploratory muscular fitness outcomes reached statistical significance; the arm curl test showed a borderline non-significant interaction (F(2,78) = 2.83, p = 0.065). CONCLUSION: A 12-week internet-based combined exercise and iCBT intervention significantly improved CRF in adults with mild-to-moderate depression. We did not find evidence of an intervention-specific effect on plasma ES biomarkers. These findings support the inclusion of internet-delivered exercise and psychological interventions in comprehensive treatment strategies for depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT05849792 (registered 6 May 2023).

Humans

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as ≥ 50% reduction in MADRS score, and remission as MADRS ≤ 10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p&#x2009;<&#x2009;0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62&#xa0;min, 95% CI 0.18-7.06; p&#x2009;<&#x2009;0.05) and reduced mean power output (mean difference&#x2009;-&#x2009;19.97 W, 95% CI&#x2009;-&#x2009;36.87 to&#x2009;-&#x2009;3.06; p&#x2009;<&#x2009;0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health

Optimizing smoking cessation pharmacotherapy and counseling for adult primary care patients: a factorial randomized controlled trial.

BACKGROUND: Even with the most effective smoking cessation pharmacotherapies (i.e., varenicline or combination nicotine replacement [C-NRT]), the majority of people ultimately return to smoking. This research explored how to optimize the use of varenicline and C-NRT to promote smoking cessation. METHODS: Primary care patients participated in a 2x2x2x2 factorial experiment that evaluated 4 factors: 1) Medication Type (Varenicline vs. C-NRT [patch&#xa0;+&#xa0;mini-lozenge]), 2) Preparation (pre-quit) Medication (4 Weeks vs. Standard); 3) Medication Duration (Extended [24&#xa0;weeks] vs. Standard [12&#xa0;weeks]); and 4) Counseling Type (Cessation Counseling [4 sessions] vs. Referral Support [2 sessions focused on use of referral resources]). This study was discontinued prior to reaching the proposed sample size (N&#xa0;=&#xa0;608) due to pandemic-related budgetary constraints. RESULTS: Participants (N&#xa0;=&#xa0;496) were 55% women and 45.6% Black individuals. There were no statistically significant main effects of the 4 factors on abstinence at 12, 26 or 52&#xa0;weeks. There was a 3-way interaction between Medication Type, Preparation Medication, and Counseling Type (p&#xa0;=&#xa0;0.04) predicting the primary outcome of biochemically confirmed abstinence at 52&#xa0;weeks; cessation counseling vs. referral support improved varenicline quit rates when 4&#xa0;weeks versus 1&#xa0;week of pre-quit medication was offered. For C-NRT, counseling type did not significantly improve quit rates regardless of the use of preparation medication. CONCLUSIONS: There was no robust evidence that enhanced pre-quit or extended duration of varenicline or C-NRT increased abstinence rates. More intensive counseling may support cessation for different pharmacotherapy regimens. Given the lack of consistent findings, this research should be viewed as exploratory to guide future research.

Humans

Physical therapy for urinary incontinence in older women: A systematic review.

BACKGROUND: Urinary incontinence is highly prevalent among older women, affecting more than one-third of this population and significantly impairing quality of life, independence, and healthcare utilization. Older women often present with complex needs that may require broader rehabilitation strategies. METHODS: This systematic review evaluated randomized controlled trials of physical therapy interventions for urinary incontinence in older women. PubMed, Embase, and Scopus were searched to October 2025. Eligible studies included women &#x2265;60 years and assessed interventions such as Pelvic floor muscle training (PFMT), bladder training, Yoga, Pilates, general resistance training, electrical stimulation, or multimodal programs. Methodological quality was appraised using the PEDro scale, and random-effects meta-analysis was performed where appropriate. RESULTS: Twenty studies involving 2002 women across 13 countries were included. Eleven trials were rated as good quality and nine as fair. Meta-analysis demonstrated that PFMT significantly reduced urinary incontinence severity compared with usual care (SMD = -1.27, 95% CI: -2.18 to -0.36, p = 0.006). Multimodal programs combining PFMT with mobility, strength, or fall-prevention training also showed significant benefits (SMD = -0.98, 95% CI: -1.60 to -0.36, p = 0.002). Comparative studies indicated that PFMT was similarly effective to Yoga and Pilates, while adjuncts such as general resistance training or tibial nerve stimulation provided additional improvements. CONCLUSION: Physical therapy interventions, particularly PFMT and multimodal programs, are effective in reducing urinary incontinence severity and improving functional outcomes among older women. These findings support prioritizing physical therapy as an important management strategy, with multimodal approaches offering added value for enhancing functional independence and fall prevention.

Humans

Effectiveness of psychosocial and lifestyle interventions in promoting behaviour change and improving cognitive outcomes in older people with memory concerns: A systematic review.

BACKGROUND: Older adults with mild cognitive impairment or subjective cognitive decline have a greater dementia risk, particularly those from minority ethnic and socioeconomically disadvantaged backgrounds. Psychosocial and lifestyle interventions targeting modifiable risk factors offer hope for reducing risk, yet behavioural mechanisms remain unclear. This systematic review examines these mechanisms and associated outcomes. METHOD: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Web of Science, and Scopus for randomised control trials testing interventions that aimed to improve lifestyle and cognition in older adults with memory concerns. We explored behavioural mechanisms using the COM-B model and synthesised intervention effectiveness, overall and within underserved groups. We prioritised lower risk of bias studies. RESULTS: 26 studies described 23 randomised controlled trials (14 multidomain, 9 single domain interventions). Certainty of evidence that behaviour change was associated with cognition was low. Moderate-certainty evidence indicated that interventions providing a socially supportive environment and combining nutritional education and counselling for 6&#x202f;+&#x202f;months improved diet. Physical activity improved primarily in interventions incorporating education, structured training, and enablement strategies (e.g., tailored programmes, providing tools). Interventions simultaneously targeting capability, opportunity and motivation showed greater overall effectiveness. Few studies recorded ethnicity (13%) or sociodemographic status (9%), and none explored their impact. CONCLUSIONS: Non-pharmacological interventions can help this population improve their lifestyles if they feel capable, equipped and motivated, highlighting the value of careful design and implementation. There is scarce evidence on how these interventions work for underserved populations. Future research should explore this to inform tailored interventions and develop equitable dementia prevention strategies.

Humans

Policy pathways and historical insights: Canada's evolving approach to psychedelic access for end-of-life distress.

Canada's evolving attitudes toward psychedelic interventions in palliative and end-of-life care reflect a departure from historically prohibitionist policies and an emerging recognition of their therapeutic potential for individuals facing end-of-life distress. This shift parallels international regulatory developments in jurisdictions such as the United States, Australia and parts of Europe, where cautious policy liberalization has signaled growing acceptance of psychedelics within clinical contexts. Canada is also a relevant case because of its formative role in the development of modern palliative care, its contemporary frameworks emphasizing holistic approaches to suffering at the end of life, and its experience with medical assistance in dying, all of which have shaped national conversations about suffering, autonomy, and end-of-life care. Additionally, Canada's distinctive historical approach to drug regulation-marked by federal flexibility, mechanisms for compassionate access, and responsiveness to patient advocacy-combined with rising public demand and incremental provincial changes, may uniquely position the country along a transitional pathway toward clinical integration of psychedelics in palliative care. At the same time, Canadian drug policy remains heterogeneous across substances and provinces, underscoring the political contingency of reform. Within this dynamic landscape, Canada's psychedelic drug policy trajectory aligns with broader international trends toward cautious medicalization and regulated access to psychedelic therapies, while also offering an instructive case for how end-of-life frameworks and federal-provincial governance shape policy development.

Humans