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First identification and molecular subtyping of Blastocystis spp. in donkeys in Aksaray province, Türkiye.

Blastocystis is a common intestinal protist worldwide that can infect humans and animals. Although its molecular epidemiology in Türkiye is mostly focused primarily on humans and livestock, equids have received limited attention despite their traditional roles and frequent contact with humans and other animals in rural environments. This study aimed to determine the molecular prevalence and subtype (ST) distribution of Blastocystis spp. in donkeys in Aksaray Province, providing the first molecular data on donkeys in Türkiye. A total of 182 fresh fecal samples were collected from donkeys in nine villages within Aksaray province. Genomic DNA was extracted, and the small subunit ribosomal RNA (SSU rRNA) gene fragment of Blastocystis spp. was amplified via PCR analysis. Positive isolates were sequenced bidirectionally for identification and subsequent phylogenetic analysis of Blastocystis in donkeys. The overall molecular prevalence of Blastocystis spp. in donkeys was 4.4% (8/182). The infection rate was higher in young donkeys (under 3 years old; 8.33%) than in adults (3 years or older; 2.46%). However, this difference was not statistically significant. Sequence analysis of the positive PCR products revealed the presence of one known livestock-specific subtype, ST10. Phylogenetic analysis showed that the ST10 isolates characterized in this study clustered with isolates identified from different hosts. This study provides the first molecular data on Blastocystis presence in donkeys in Türkiye. The exclusive detection of ST10 suggests potential cross-species transmission, likely facilitated by the traditional practice of co-housing donkeys with other animals in confined barns. These findings indicate that donkeys may contribute to Blastocystis transmission, underscoring the importance of a "One Health" approach in future epidemiological surveillance.

Animals

Sociodemographic and clinical characteristics associated with nocturnal enuresis among children in a tertiary care center in Cairo, Egypt: A cross-sectional study.

BACKGROUND: Nocturnal enuresis (NE) is a significant pediatric health concern that warrants increased attention from healthcare providers, educators, and society. This study aimed to determine the frequency of NE among children attending a tertiary care center in Cairo, Egypt, and to explore their sociodemographic characteristics and associated factors. METHODS: A cross-sectional study was conducted among 1587 children aged 6-16 years attending a tertiary care center in Cairo from December 2022 to February 2024. Data were obtained from parents via a structured questionnaire covering sociodemographic characteristics. Sleep problems were assessed via the Children's Sleep Habits Questionnaire. The multivariate logistic regression analysis was conducted to estimate the odds ratio and identify factors associated with NE. RESULTS: The total prevalence of NE among children attending a tertiary care center was 333 (21%). Our results indicated that being female and being older were associated with a lower likelihood of NE. Low socioeconomic status (OR = 5.559; 95% CI = 1.24-24.88), stressful events (OR = 3.697; 95% CI = 1.73-7.88), a family history of NE (OR = 26.231; 95% CI = 8.617-79.85), and sleep problems (OR = 13.233; 95% CI = 6.082-28.793) were associated with increased odds of NE. Furthermore, consuming caffeinated drinks before sleep, the presence of urinary tract infections, and intestinal infestations were also associated with NE. CONCLUSION: The findings of the present study confirm the multifactorial etiology of NE and identify several associated factors. Integrating these factors into screening and management programs may improve early identification and lead to more effective, tertiary care-specific preventive and therapeutic interventions.

Humans

Epidemiological status of bovine viral diarrhea virus in water buffalo (Bubalus bubalis): A global systematic review and meta-analysis.

Bovine viral diarrhea virus (BVDV) remains a neglected viral disease in water buffalo despite its significant economic impact in production systems. Although limited epidemiological studies have been reported worldwide, the serostatus and active infection in buffalo have not been systematically reviewed. A systematic review and meta-analysis were conducted to estimate BVDV prevalence in water buffalo and identify associated epidemiological factors. Relevant studies published up to January 31, 2026, were retrieved from five electronic databases. A total of 49 studies were identified from 15 different countries were found for inclusion. A random-effects model was used to estimate pooled-prevalence and assess heterogeneity among studies. A meta-analysis of 37 studies (9270 buffalo) estimated a pooled BVDV seroprevalence of 30.5%, while analysis of 16 studies (7189 animals) indicated an antigen prevalence of 16.5%. Continent-wise analysis revealed the highest BVDV seroprevalence in South-America (44.0%), while antigen prevalence was highest in Africa (21.2%) followed by Asia at 12.2%, and no BVDV data reported from North-America. Among the different countries, the highest BVDV seroprevalence was detected in Turkey (61.6%) and Argentina (59.0%), while antigen prevalence was highest in Egypt (21.2%), with lower estimates in Brazil (11.8%) and Iraq (11.3%). Notably, high heterogeneity (I2 > 90%) was observed in the all-pooled estimates, indicating variations in sampling period, age, sex, sample source and types, diagnostic methods, production-system, and study quality. These findings demonstrate the widespread presence of BVDV in water buffalo populations and indicate the need for targeted control strategies to mitigate its impact on health and productivity.

Animals

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans

Anabolic androgen therapy in critically ill adults: A systematic review and meta-analysis.

Critical illness is characterized by a catabolic, proinflammatory state. Anabolic agents, such as testosterone, have therefore been proposed as therapeutic targets. Our objectives were to assess the effects of testosterone in critically ill populations on patient-important outcomes and identify design limitations to inform future studies. We searched for randomized control trials (RCTs) through Medline, Embase, and EBM Reviews databases from inception through February 24, 2026, including English language articles enrolling adults (≥18 years) admitted to ICU where anabolic androgen therapies (AAT) were compared with placebo or standard of care. Studies had to report at least one of: mortality, ICU and hospital lengths of stay, or duration of mechanical ventilation. We extracted data independently using a standardized data extraction tool, and feedback was received from all co-authors to ensure agreement. For each outcome, we performed meta-analyses using a random-effects model with inverse variance weighting in RevMan. We used the GRADE approach to assess certainty in pooled estimates of effect. Of 1325 screened articles, we found 4 that fit our inclusion criteria. Together, we judged risk of bias as 'some concerns' in 3 trials and 'high' in the final trial, and ultimately found that the effects of anabolic-androgen therapy on patient-important outcomes uncertain. With the uncertainty of current evidence for the effects of anabolic-androgen therapy in critically ill adults, there is insufficient support for its routine use. Future randomized evidence is needed to determine whether anabolic-androgen therapy improves clinically-important outcomes and better define its safety profile in critically ill adults.

Humans

Evidence-based insights into medial pedicle reduction mammaplasty: A systematic review and meta-analysis.

BACKGROUND: Breast reduction relieves the physical and psychosocial burden of macromastia. Medial pedicle reduction mammaplasty may enhance vascular reliability, preserve nipple-areola complex (NAC) sensation, and sustain upper pole fullness, even in large-volume reductions. The purpose of this study was to assess the outcomes of medial pedicle breast reduction. METHODS: A search across ScienceDirect, Cochrane, and PubMed was conducted. Included studies reported on perioperative outcomes and complications of medial pedicle breast reduction. Data on demographics, surgical variables, complications, sensory recovery, volumetric changes, and patient satisfaction were extracted. Proportion meta-analysis was performed, and odds ratios were calculated for comparison with inferior pedicle breast reduction. RESULTS: Twenty-five studies comprising 1033 patients met the inclusion criteria. Mean BMI ranged from 27 to 42 kg/m2, with mean resection weights between 412 and 3828 g. Mean surgical times ranged from 104 to 204 min. Pooled complication rates were low: infection 1%, seroma 1%, hematoma 1%, fat necrosis 2%, NAC necrosis 1%, dehiscence 8%, and reintervention 5%. Odds of complications did not differ significantly from inferior pedicle reductions. NAC sensation typically recovered by 6-12 months, with no long-term deficits. Volumetric analyses demonstrated stable breast shape after the first postoperative year, with superior upper pole tissue maintained. Patient satisfaction ranged 75-100%, with higher ratings for scar appearance and overall aesthetics in medial pedicle reductions. CONCLUSION: Medial pedicle breast reduction is a well-established and reproducible technique, preserving NAC sensation, achieving stable long-term shape, and enhancing upper pole fullness. It offers satisfactory aesthetic outcomes compared to other traditional methods, even in large-volume reductions.

Humans

Does future-oriented imagery rescripting increase willingness to carry out a social anxiety-related behavioral experiment? An extended replication.

BACKGROUND AND OBJECTIVES: Mental images of threat are common in social anxiety disorder and could impede exposure to fear-relevant situations. Landkroon et al. (2022) found that imagery rescripting of anticipated future threat, compared to no-task, increases willingness of non-clinical individuals to conduct a social anxiety-related behavioral experiment. The aim of this two-day preregistered extended replication study was to examine whether the effects persist beyond the intervention session by scheduling the behavioral experiment 1-7 days after the intervention. METHODS: On Day 1, 60 pre-screened participants were asked to design a behavioral experiment to test an idiosyncratic negative belief about a feared social situation. They were then randomly assigned to imagery rescripting (focused on their worst feared outcome of the behavioral experiment) or no-task. Participants' willingness to do the behavioral experiment and their threat beliefs was measured. On Day 2, they were asked to carry out the behavioral experiment. RESULTS: The imagery rescripting group, compared to the control group, did not show increased willingness or compliance to do the behavioral experiment on Day 1 or 2. Furthermore, the imagery rescripting did not lead to greater reductions in threat beliefs on either day. LIMITATIONS: The quality of the imagery rescripting intervention was not assessed, and given the brief nature of the intervention, any effects may have dissipated before participants decided whether to carry out the behavioral experiment. CONCLUSIONS: There was no evidence that imagery rescripting leads to changes in willingness or compliance to do a fear-relevant behavioral experiment. More research is needed to examine interventions that can enhance exposure in socially anxious people.

Humans

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8 Da), and herbicolin B (1138 Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5 mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5 mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea

Exploring hormonal influences on nicotine craving and use across the perinatal period: A prospective longitudinal study.

INTRODUCTION: Perinatal nicotine use is common despite well-documented adverse consequences. We examined associations between reproductive-related hormones with nicotine craving and use during the perinatal period to identify potential novel intervention points. METHODS: All participants reported use of nicotine during the perinatal period. Participants were enrolled at gestational week ≥ 36 and followed to postpartum week 12 via daily surveys (i.e., nicotine craving via 100-point scale, dichotomous use) and weekly hormone measurement in saliva (cortisol, oxytocin) or dried blood spots (progesterone, estradiol, testosterone, dehydroepiandrosterone sulfate). Bayesian mixed-effects models accounted for within-person correlation while estimating hormone effects. RESULTS: Participants (n = 46) were 28.9 ± 4.9 years old. During follow-up, exclusive combustible cigarettes (n = 20), electronic nicotine delivery systems (ENDS; n = 13), or dual (n = 2) use was observed, with variability in use and craving across participants and over time. During pregnancy, higher oxytocin was linked to greater craving (β=16.31, 95% CI: 3.71, 28.83). Greater peripartum declines in oxytocin were associated with more craving (β=8.71, 95% CI: 0.75, 16.93) and use (β=1.13, 95% CI: 0.05, 2.43). During postpartum, lower estradiol was linked to more craving (β=-1.17, 95% CI: -2.15, -0.18) and use (β=-0.40, 95% CI: -0.76, -0.03). In models simultaneously evaluating all postpartum hormones, the lone meaningful association was between estradiol and craving (β=-1.66, 95% CI: -2.84, -0.48). CONCLUSIONS: The results of this study suggest that oxytocin and estradiol may contribute to the risk of perinatal nicotine use. Additional research is needed to replicate our observations in more diverse study samples and explore implications for clinical intervention.

Bayesian

MET expression by immunohistochemistry as a biomarker in pancreatic neuroendocrine tumours.

INTRODUCTION: MET (c-MET) is a receptor tyrosine kinase implicated in numerous cancers, including pancreatic neuroendocrine tumours (pNETs), by promoting cell proliferation, survival, invasion and angiogenesis. Recognizing its oncogenic potential, there is significant interest in MET-targeted therapies for malignancies like pNETs, which often develop treatment resistance. Immunohistochemistry (IHC) has become a practical method for detecting MET overexpression in cancers. This study evaluates MET expression in pNETs by IHC and assesses its correlation with prognostic variables and survival outcomes. METHODS AND RESULTS: Tissue microarrays containing well-differentiated neuroendocrine tumours from the gastrointestinal tract were analysed. The study included 125 pNET cores from 112 patients after application of inclusion criteria. MET expression was determined using the H-score system. Different variables were assessed for H-score distribution and cross-tables. Survival analyses were conducted based on progression-free survival and overall survival. Positive MET expression was found in 83.5% of cases. Higher MET H-scores were seen in patients with lymphovascular invasion (LVI), distant metastases and higher tumour grade (P&#x2009;<&#x2009;0.05). When assessing different variables for higher MET H-scores, a significant association emerged at the 150-cut-off-point for LVI, perineural invasion, radiological evidence of progression and overall survival. For survival analysis, at a MET H-score threshold of 200, high MET expression was significantly associated with shorter progression-free survival (mean 8.7 versus 13.4&#x2009;years, P&#x2009;<&#x2009;0.05) and overall survival (mean 3.6 versus 7.7&#x2009;years, P&#x2009;<&#x2009;0.05). CONCLUSION: Elevated MET expression is linked to adverse histopathological features and worse clinical outcomes in pNET. Standardizing MET IHC evaluation is critical as anti-MET therapies develop, and identifying patients likely to benefit from these treatments remains essential.

MET protein

A therapeutic atlas of monogenic inflammatory bowel disease.

BACKGROUND AND AIMS: Evidence-based, mechanism-guided therapies are urgently needed for treating monogenic inflammatory bowel disease (mIBD). For such rare diseases, mechanistic insight is essential to guide treatment when conventional clinical trials are often not feasible. We aimed to summarize literature-based evidence and to identify knowledge gaps. METHODS: We conducted a systematic review of published manuscripts evaluating the therapeutic efficacy in mIBD. We quantified and compared the global therapeutic response score across treatments and conditions. In a subset of conditions, biomarkers of longitudinal therapeutic response were evaluated in comparison to non-monogenic pediatric IBD cohorts. RESULTS: Responses to 35 therapeutics across the 102 known genetic causes of mIBD were evaluated in 241 articles and 669 patients, summarizing 302 gene-drug responses. The efficacy of at least one pharmacological intervention was identified in 61% (n&#x2009;=&#x2009;62/102) of the mIBD conditions, highlighting a major unmet need for effective medications in many others. Gene- and pathway-specific responses were demonstrated for several therapies, including allogeneic hematopoietic stem cell transplantation, gene therapy, and advanced therapies such as anti-TNF agents, IL-1 inhibitors, mTOR inhibitors, as well as eculizumab in CD55 deficiency, abatacept in CTLA4 deficiency, and the immunometabolic agent empagliflozin in glycogen storage disease type 1b. CONCLUSIONS: This study highlights the potential of precision medicine approaches tailored to genetic and pathway-specific mechanisms, while underscoring the urgent need for effective therapies in many monogenic conditions that remain without established treatment options.

Humans

The Efficacy of Pharmacotherapy Intervention on Anthropometric Outcomes in Survivors of Childhood Brain Tumors: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Many survivors of childhood brain tumors face long-term adverse health outcomes like obesity. Uncertainties surround the effect of interventions to manage obesity-related outcomes in survivors of childhood brain tumors. The goal of this updated systematic review and meta-analysis was to provide the best estimate of the treatment efficacy of pharmacotherapy intervention on anthropometric outcomes in this pediatric population. METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, and ProQuest for articles published from January 1, 2015, to January 31, 2025. A meta-analysis was performed using the generic inverse-variance method in RevMan 5.4. Heterogeneity was assessed using the Cochrane Q test and the I2 statistic. We used the GRADE approach to determine the certainty of evidence. RESULTS: A total of six studies met the inclusion criteria: four newly identified studies published after January 1, 2015 (125 participants), and two from the previously published review (23 participants). The pooled estimate showed no significant change in body mass index z-score after intervention (mean difference&#x2009;=&#x2009;-0.02; 95% CI: -0.06 to 0.02, I2&#x2009;=&#x2009;0%; 4 studies, 94 participants; low certainty of evidence). Similar pooled effects were observed across other outcomes; however, individual studies reported significant changes in some outcomes within the treatment groups after the intervention. CONCLUSION: Pharmacological agents showed no significant change in anthropometric outcomes for survivors of childhood brain tumors. Further trials are needed to assess the efficacy of pharmacological agents and to identify subgroups most likely to benefit.

Humans

Reported exposure to news portrayals about mental health problems and their impact: Findings from the 2025 National Survey of Stigma and Discrimination.

OBJECTIVE: Media portrayals of people with mental illness have the power to mitigate or perpetuate stigma related to mental health. This study aimed to investigate reported real-world exposure to news media portrayals about people with mental health problems in the past 12&#x2009;months and the impact of these. METHODS: Data were from a nationally representative survey of 6032 Australians exploring attitudes towards people with mental health problems. Participants were asked about their exposure to positive news stories about a person with a mental health problem, as well as negative portrayals, in which someone was harmed by a person with a mental health problem. Further questions covered the sources (traditional or social media) and impact of these exposures. RESULTS: Regression models were used to explore sociodemographic predictors of impact. Most participants reported exposure to negative news portrayals (68.4%, 95% confidence interval = [66.9, 69.8]), while fewer reported exposure to positive news stories (33.7%, 95% confidence interval = [32.3, 35.2]). Most people exposed to the negative news stories reported a negative impact (69.0%, 95% confidence interval = [67.2, 70.7]), and most exposed to positive news stories reported a positive impact (80.2%, 95% confidence interval = [77.6, 82.5]). Age and gender were associated with reported impact but not lived experience of mental illness. CONCLUSIONS: Exposure to negative news stories about mental health problems was prevalent. Given their impact on news audiences broadly, negative news stories need to be accurate and responsible to mitigate negative impacts. A renewed focus on generating and promoting positive and stigma-challenging news stories is needed to increase subsequent positive impacts.

Humans

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals

Assessing the Concurrent Validity of the Australian Treatment Outcomes Profile in a Methamphetamine Dependent Treatment-Seeking Population.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool assessing substance use, health and well-being used in Australian alcohol and other drug treatment services. It is validated for use with clients using alcohol, opioids and cannabis, but not yet for clients who primarily use methamphetamine. METHODS: An embedded validation study was undertaken in treatment-seeking adults enrolled in a randomised double-blind placebo-controlled trial of lisdexamfetamine for methamphetamine dependence with sites in New South Wales, South Australia and Victoria. Participant demographics were collected during study screening. The ATOP and comparators (Time Line Follow Back, Opiate Treatment Index, Depression Anxiety Stress Scale, WHOQOL-BREF and Personal Wellbeing Index) were collected at baseline. Continuous ATOP items were analysed using Pearson's correlation coefficient, and dichotomous items were analysed using Fleiss's &#x3ba;. Agreement was rated as strong where measures were &#x2265;&#x2009;0.50, moderate where agreement was 0.30-0.49, and weak where <&#x2009;0.30. RESULTS: One hundred and eighteen study participants (2018-2020) had data for concurrent validity analysis. Strong validity was demonstrated for physical health, psychological health, quality of life, injecting drug use and crime items, and for days of use for amphetamines, alcohol, cannabis and cocaine. There was weak validity for days of use for benzodiazepines. Heroin use days and other opioid use days were endorsed by fewer than five participants and were therefore unable to be assessed. DISCUSSION AND CONCLUSIONS: The ATOP is valid for use in a treatment-seeking methamphetamine-dependent population, expanding the range of tools for assessment and standardised outcome monitoring across different settings and services.

Humans

Sex differences in sleep and alcohol consumption outcomes following a digital insomnia intervention.

BACKGROUND: Poor sleep is a well-established risk factor for heavy drinking, and evidence suggests that sleep could serve as a potential treatment target for reducing alcohol consumption. The relationship between poor sleep and problematic drinking appears to be stronger among females, but no studies to date have assessed sex differences in alcohol consumption following insomnia treatment. Here, we combine the samples from two clinical trials to investigate sex differences in the effects of a digital cognitive behavioral therapy for insomnia (Sleep Healthy Using the Internet; SHUTi) on sleep and alcohol outcomes. METHODS: 184 heavy drinking individuals with insomnia (weekly binge episodes: 4/5&#x2009;+ drinks in one sitting for females/males; AUDIT score >7; ISI score >14) were randomly assigned to either the SHUTi program (n&#x2009;=&#x2009;102) or an active control program (n&#x2009;=&#x2009;82). Participants completed self-report assessments at baseline, immediately following the 9-week intervention period, and at 3 and 6-months post-intervention. RESULTS: Linear mixed effects models showed that SHUTi effects over time were stronger among females than males for improved sleep outcomes and reduced frequency of total and heavy drinking days (ps &#x2264; 0.038). Follow-up comparisons of within-group effect sizes revealed consistently larger reductions in alcohol consumption among SHUTi females (Cohen's d range = 0.92-2.23) than SHUTi males (Cohen's d range = 0.65-1.95). CONCLUSIONS: Findings suggest that SHUTi may be more efficacious in improving sleep and reducing drinking among females with insomnia compared to males. These results could have important implications for sex-specific prevention and treatment efforts for heavy drinking individuals with insomnia.

Humans

Changes in ACL T2* Metrics Over the Course of the Female Menstrual Cycle: A New Biomarker for the ACL Injury Risk?

BACKGROUND: Sex-based disparities in the anterior cruciate ligament (ACL) injury risk may be partly explained by cyclic variations in sex hormones that drive systemic shifts in tissue osmoregulation. Ultrashort echo time (UTE) T2* magnetic resonance imaging provides a noninvasive, quantitative means of evaluating the water content and collagen orientation in tissue. HYPOTHESIS: Eumenorrheic female participants will exhibit significant ACL T2* changes across the cycle, while anovulatory control participants will demonstrate no significant changes over time. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 25 women with no prior knee injuries were enrolled: 10 premenopausal, eumenorrheic participants and 15 anovulatory control participants (6 postmenopausal and 9 premenopausal using oral contraceptives). Bilateral knee magnetic resonance imaging was performed at 4 time points evenly spaced over 1 month, with the first visit within 24 hours of menses onset. Ovulation status was confirmed using commercially available ovulation predictor kits. Three-dimensional UTE sequences (11 echoes; 0.03-25 ms) were acquired to evaluate bicomponent ACL T2* metrics. Linear mixed-effects models assessed temporal differences in long and short T2* values, and the Cohen d quantified effect size. RESULTS: Eumenorrheic participants demonstrated significantly shorter preovulatory long T2* values compared with postovulatory values (mean difference, 1.0 ms [95% CI, 0.2-1.9 ms]; P = .015; Cohen d = 0.51). No significant temporal differences were observed for any T2* metric in anovulatory controls. CONCLUSION: Eumenorrheic female participants exhibited significant preovulatory to postovulatory changes in ACL T2* metrics, while anovulatory controls demonstrated no significant changes over time. These findings suggest that ACL T2* metrics are sensitive to cyclic fluctuations in female sex hormones across the menstrual cycle.

Humans

Fatty acids and breast cancer: Epidemiology, subtype-specific metabolism, immune regulation, and clinical translation.

Fatty acids (FAs) are bioactive dietary and metabolic molecules that participate in membrane architecture, energy homeostasis, inflammatory signaling, gene regulation and immune function, all of which intersect with breast cancer (BC) risk, progression and treatment response. In this narrative review we integrate epidemiological, clinical, translational and mechanistic evidence on the role of FAs in BC. Saturated, monounsaturated, trans- and polyunsaturated FAs (PUFAs) are treated as distinct biological exposures rather than interchangeable measures of total fat intake. Similarly, evidence from dietary assessment, circulating biomarkers, erythrocyte membrane composition, adipose tissue stores and tumor lipid signatures is interpreted separately, because each captures exposure and biology at a different level. BC subtypes differ in FA synthesis, uptake, oxidation, storage and remodeling: luminal tumors are frequently linked to hormone-regulated lipogenesis, human epidermal growth factor receptor 2 (HER2)-positive tumors to growth-factor-driven lipid metabolism, and triple-negative tumors to exogenous FA uptake, inflammatory lipid mediators and ferroptosis-related vulnerabilities. FA-derived mediators also shape immune-cell polarization, cytokine signaling and the tumor microenvironment, and dietary FAs may reshape the gut microbiota; the fiber-derived short-chain FAs it produces, distinct from dietary FAs, likewise help regulate immune and inflammatory tone. Clinical data suggest possible roles for fat-quality modification and selected n-3 PUFA interventions, but findings are heterogeneous and not yet sufficient to support routine biomarker-guided precision onco-nutrition. Candidate biomarkers, such as erythrocyte n-6:n-3 composition, require prospective validation before clinical implementation. FA biology thus represents a modifiable but complex axis in BC prevention, tumor biology and supportive care.

Humans