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Walking Together: A Cross-Cultural Study of the Relationship Between Religiosity and Substance Use Disorder.

The literature suggests that religiosity is a protective factor for substance use. However, individuals with substance use disorder (SUD) may actively cultivate their religiosity during substance use. This qualitative study analyzed the perceptions and meanings homeless people attribute to their substance use trajectories and religiosity, as well as the potential connections between these two themes. The analysis was conducted based on the content analysis technique proposed by Bardin. A total of 40 semi-structured interviews were conducted with 20 Brazilian and 20 Portuguese participants. The present study found that religiosity can play a role in the substance use trajectory and the development of SUD by offering a subjective sense of protection, serving as a marker for the need for change, or providing relief from the suffering associated with SUD. We discuss how homeless people with SUD experience religiosity and how religious aspects traditionally seen as protective in the literature, such as church attendance, may paradoxically become risk factors for these socially vulnerable populations.

Humans

Relationships Between Risky Substance Use and Irritable Bowel Syndrome (IBS) Severity, Mental Health, and Smoking-Related Processes in Adults with IBS Who Smoke.

Objective: Irritable Bowel Syndrome (IBS) is a debilitating chronic pain condition that presents a major and growing public health burden. Combustible cigarette smoking plays a role in the maintenance of IBS, and the co-occurrence of these conditions warrants greater focus. Moreover, given that smoking co-occurs with other substance use behaviors, the impact of these comorbid behaviors on physical and mental health-related outcomes among individuals with IBS who smoke is warranted. The goal of the present cross-sectional study was to assess relationships of risky alcohol, cannabis, and opioid use with IBS severity, anxiety and depression, and smoking-related processes among adults with IBS who smoke. Methods: In total, 263 adults who met Rome IV criteria for IBS and who smoked combustible cigarettes were included in the study. Hierarchical regression analyses were conducted to examine the influence of risky substance uses on IBS symptom severity, IBS-related quality of life, anxiety, depression, perceived barriers for smoking cessation, and cigarette dependence. Results: Results indicated that opioid use was statistically related to all criterion variables, whereas alcohol use was specifically associated with depression and anxiety. Cannabis use showed a statistically significant association only with anxiety symptoms. Conclusions: The present investigation is among the first to explore the role of risky substance use in terms of a wide array of IBS, mental health, and smoking processes among adults with IBS who smoke. The findings suggest that substance use should be a focal point of screening and intervention for the IBS population to optimize outcomes beyond the reach of medical therapies.

Irritable bowel syndrome

Causal Relationship of Polyunsaturated Fatty Acids With Mental Disorders: A Systematic Review and Meta-analysis.

CONTEXT: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options. OBJECTIVE: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs. DATA SOURCES: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs. DATA EXTRACTION: Two-sample MR technology was used to assess the role of PUFAs in MDs. DATA ANALYSIS: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders. CONCLUSION: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for further research into the complex interactions between omega-3 and omega-6. The study provides a scientific foundation for future clinical trials and dietary intervention strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42024598472.

Humans

Integrated miRNA-mRNA profiling reveals candidate regulatory relationships associated with high-fat diet-induced muscle lipid deposition in black seabream (Acanthopagrus schlegelii).

High-fat diets are increasingly used in aquaculture due to their protein-sparing effects; however, the post-transcriptional regulatory mechanisms of fish muscle in response to high-fat diets (HFD) remain unclear. In this study, juvenile black seabream were fed either a normal-fat diet (NFD) or a HFD to investigate the miRNA-mRNA regulatory network associated with diet-induced muscle lipid deposition. Oil Red O staining and biochemical analysis showed that high-fat diet feeding markedly increased lipid droplet accumulation and crude lipid content in muscle, indicating significant induction of muscle lipid deposition. Integrated mRNA and miRNA expression profiling revealed substantial transcriptomic and post-transcriptional responses to high-fat diet challenge. A total of 271 differentially expressed genes were identified, including 120 upregulated and 151 downregulated genes. Through combined target prediction and expression correlation analysis, thirteen candidate inverse miRNA-mRNA relationships were subsequently identified, and RT-qPCR supported the expression patterns of selected miRNAs and mRNAs. These pairs included miR-499-x-dmgdh, miR-499-y-gatm, miR-727-y-ass1, miR-4649-x-foxo4, miR-9129-z-myl7, and several novel miRNA-mediated interactions involving adk, chst11, lypla2, frem2, kcnc4, wars1, bag2, and capn2. Functional analysis suggested that these regulatory pairs were mainly associated with metabolic adaptation, structural remodeling, and cellular stress responses. In particular, gatm, dmgdh, ass1, and adk were associated with energy metabolism-related processes, including pathways previously linked to Ampk regulation, whereas myl7, frem2, and kcnc4 may contribute to muscle structural maintenance and excitability regulation. Overall, this study provides candidate miRNA-mRNA regulatory relationships potentially involved in high-fat diet-induced muscle lipid deposition and adaptive remodeling in black seabream, offering a basis for future functional studies on muscle metabolism and quality regulation in marine fish.

Animals

Analysis of the Relationship between Early Clinical Factors and Glasgow Outcome Scale in Patients With Traumatic Brain Injury.

OBJECTIVE: This study aimed to evaluate the association between early clinical factors and the Glasgow outcome scale (GOS) in patients with traumatic brain injury (TBI). METHODS: We conducted a retrospective analysis of 98 TBI patients who underwent emergency surgery between January 2021 and January 2024. Based on GOS scores at 6 months post-surgery, patients were classified into a favorable outcome group (GOS&#xa0;&#x2265;&#xa0;4, defined as moderate disability or good recovery,&#xa0;n = 58) and an unfavorable outcome group (GOS < 4, i.e., death, persistent vegetative state, or severe disability,&#xa0;n = 40). Baseline and early clinical parameters were compared between groups. Statistically significant variables from univariate analysis were entered into a multivariate logistic regression model to identify independent prognostic factors. RESULTS: Significant intergroup differences were observed in age, time from injury to surgery, bleeding site, midline shift, Glasgow coma scale (GCS) score at admission, blood glucose level, and D-dimer level (all p < 0.05). Multivariate analysis confirmed that age, time from injury to surgery, GCS score, blood glucose, and D-dimer level were independent predictors of GOS (all p < 0.05). CONCLUSION: Early clinical factors, including age, time to surgery, GCS score, blood glucose, and D-dimer level, independently influence GOS in TBI patients. Time from injury to surgery&#xa0;emerged as a potentially modifiable factor in this cohort, suggesting that minimizing delays may improve outcomes.

Humans

Exploring the dose-response relationship between prenatal exercise and postpartum depression: A systematic review and meta-analysis of randomized controlled trials.

IMPORTANCE: Postpartum depression (PPD) is a hidden and widespread global public health crisis affecting millions of mothers and infants annually. Prenatal exercise is a potentially accessible nonpharmacological strategy for PPD prevention, but its optimal dose remains uncertain. OBJECTIVE: To explore the dose-response relationship between prenatal exercise and the incidence of PPD through meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library using MeSH terms and keywords related to "pregnant women," "prenatal exercise," and "postpartum depression," up to June 23, 2025. STUDY SELECTION: RCTs included examined prenatal exercise interventions in pregnant women without a history of depression, with PPD incidence reported using validated depression scales (such as EPDS, CES-D). Non-RCT studies, duplicate publications, and studies with insufficient data were excluded. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted data according to the PRISMA guidelines. A random-effects model was used to pool odds ratios (OR) and their 95% confidence intervals (CI). Linear and nonlinear dose-response models were employed to analyze and evaluate the relationship between exercise dose (measured in METs-min/week) and the incidence of PPD. MAIN OUTCOME(S) AND MEASURE(S): The primary outcome is the incidence of PPD, analyzing its relationship with prenatal exercise dose. RESULTS: Eight RCTs involving 2231 pregnant women were included. The pooled analysis showed that prenatal exercise was associated with a potential reduction in PPD incidence, although the overall effect did not reach statistical significance (OR=0.58, 95% CI [0.33, 1.02]). In dose-stratified analysis, exercise doses &#x2265;500 METs-min/week were associated with significantly lower PPD incidence (OR=0.44, 95% CI [0.24, 0.78]). Subgroup analyses suggested trends toward greater benefits among women aged &#x2265;30 years and those initiating exercise between 14 and 28 weeks of gestation; however, subgroup differences did not reach statistical significance. The linear dose-response trend did not reach statistical significance (p = 0.0533), and neither the overall spline association (p = 0.1704) nor the test for nonlinearity (p = 0.6361) was statistically significant. CONCLUSIONS AND RELEVANCE: Prenatal exercise may be associated with a lower risk of PPD, but the overall pooled effect did not reach statistical significance. Findings concerning &#x2265;500 METs-min/week and the apparent flattening of the dose-response curve should be considered exploratory and require confirmation in larger trials.

Humans

Targeting SIRT6: the design and therapeutic implications of activators and inhibitors.

Sirtuin 6 (SIRT6) is an NAD+-dependent deacylase that maintains genomic stability, regulates metabolism, and influences aging, making it an attractive but challenging therapeutic target. Pharmacological modulation of SIRT6 holds promise for cancer and metabolic disorders, yet its context-dependent functions demand precise intervention strategies. Potent, selective, and drug-like chemical probes are therefore essential to dissect SIRT6 biology and to validate its therapeutic potential. This review critically evaluates recent medicinal chemistry advances in SIRT6 modulation. We focus on structure-guided design strategies and structure-activity relationships (SAR) that have transformed initial hits into optimized leads for both activators and inhibitors, highlighting the remaining challenges in achieving isoform selectivity and drug-like properties.

Sirtuins

Neighborhood Hostility is Associated With the Relationship Between Park Proximity and Physical Activity Among Youth: National Evidence From Chile.

PURPOSE: Physical inactivity among youth is highly prevalent worldwide. Although proximity to parks and recreational facilities is generally associated with higher physical activity (PA), unsafe or hostile neighborhood environments may limit their use. This study examined whether neighborhood hostility moderates the association between access to recreational facilities and adherence to World Health Organization PA guidelines among Chilean youth. METHODS: This cross-sectional study analyzed data from the 2024 National Physical Activity and Sport Survey of Chile, including 3,477 urban participants stratified into childhood (5-10 years), early adolescence (11-13 years), and late adolescence (14-17 years). Built environment exposures included perceived access to recreational facilities, a cumulative neighborhood hostility score (0-5). Logistic regression models were stratified by age group and adjusted for covariates. Interaction terms assessed moderation by neighborhood hostility, and causal mediation analyses were performed. RESULTS: Adherence to World Health Organization guidelines was low (41.9% in childhood, 43.8% in early adolescence, and 43.9% in late adolescence). Greater distance to recreational facilities was associated with lower odds of meeting activity guidelines. Higher neighborhood hostility was independently associated with lower PA levels. Among adolescents, neighborhood hostility substantially attenuated the association between proximity and activity. Mediation analyses indicated partial mediation, with effective park utilization emerging as the strongest mechanism, accounting for 21.8% of the association (p < .001), followed by psychological motivation (11.9%). DISCUSSION: Proximity to recreational infrastructure alone is insufficient to promote PA in hostile neighborhoods. Policy approaches should integrate infrastructure provision with strategies addressing neighborhood safety and promoting active engagement.

Humans

Relationship between menopausal hormone therapy and incidence risk of breast cancer: systematic review and meta-analysis.

BACKGROUND: Menopausal hormone therapy (MHT) is widely prescribed for alleviating menopausal symptoms. Prior studies have mainly focused on individual hormone therapy formulations. This meta-analysis comprehensively synthesized evidence across various regimens to systematically evaluate the association between MHT and breast cancer risk. MATERIALS AND METHODS: We systematically searched CNKI, Wanfang, PubMed, and Web of Science from inception through August 2024. Eligible studies examining breast cancer risk following MHT were independently screened and assessed by two reviewers. The review and meta-analysis followed PRISMA guidelines. RESULTS: Thirty-four studies were included. The random-effects model showed a significant but heterogeneous overall association (OR = 1.15, 95% CI: 1.09-1.22; I&#xb2; = 92.4%). Subgroup analysis identified hormone type, use status, and region as key determinants (P for interaction < 0.001). Stratification by hormone type resolved much of the heterogeneity, revealing risk confined to estrogen-progestin therapy (EPT; OR = 1.44, 95% CI: 1.26-1.64), while estrogen-only therapy (ET) showed no overall association (OR = 1.00, 95% CI: 0.91-1.10). Study type, region, and sample size were significant effect modifiers. For ET, randomized controlled trials demonstrated a protective effect (OR = 0.78, 95% CI: 0.70-0.87), contrasting with neutral findings from observational studies. CONCLUSIONS: MHT is associated with a modest but significant increase in breast cancer risk, primarily driven by EPT. This risk was not observed with ET in observational studies, though trials suggested a protective effect. Crucially, the association shows marked geographical heterogeneity, indicating risk is modified by regimen and regional factors.

Humans

"It was good because they have a relationship with us": A qualitative study on low-threshold buprenorphine treatment at syringe services programs.

INTRODUCTION: Syringe service programs (SSPs) reach people who inject drugs with opioid use disorder (OUD) and are novel "low-threshold" venues to initiate buprenorphine treatment. The study investigated patients' experiences with SSP-initiated buprenorphine treatment, which could aid in improving buprenorphine treatment delivery at SSPs. METHODS: The study included 12 participants who completed qualitative exit interviews after a randomized controlled trial of buprenorphine treatment at SSPs. In the parent study, participants received buprenorphine treatment through an onsite model at an SSP or enhanced referral to a community health center based on the randomization sequence. Most participants started taking buprenorphine at home. Exit interviews included participants from both study arms, and the semi-structured interview guide focused on their experiences with clinicians, experiences initiating buprenorphine, prior experiences with OUD treatment, and perceptions about continuing buprenorphine treatment. Four researchers iteratively read, coded, and discussed each transcript, then they derived recurring themes using thematic analysis. RESULTS: Participants were mostly male, middle-aged, and 50% identified as Latino. Four main themes related to buprenorphine treatment initiation: 1) Onsite treatment facilitated buprenorphine prescription, but some participants also expressed a need for additional support; 2) Precipitated withdrawal complicated participants' buprenorphine initiation in both arms; 3) Participants largely experienced the SSPs as affirming and welcoming; and 4) Developing strong relationships with healthcare providers was critical to successful buprenorphine treatment initiation. CONCLUSIONS: The SSP-based model provided rapid access to buprenorphine prescriptions, but precipitated withdrawal was a common complication. Some participants desired additional support and guidance when they started taking buprenorphine at home. The findings point to a "low-threshold, high-touch" approach where participants receive expedited access to buprenorphine providers at SSPs but also additional support throughout the initiation process to avoid and/or manage precipitated withdrawal. Despite some challenges, SSP-based buprenorphine treatment was highly valued by study participants.

Humans

Genetic evidence for a causal relationship between melatonin metabolism and depression.

To investigate the causal relevance of melatonin metabolism, which provides the biological basis for circulating melatonin levels, to specific depression symptom subtypes, we performed a targeted systematic review of melatonin metabolism pathways in the human brain and liver. Using two-sample Mendelian randomization (MR), we assessed the causal effects of metabolism pathways and/or individual genes on major depressive disorder (MDD) and nine symptom subtypes derived from Patient Health Questionnaire-9 (PHQ-9). Instrumental variables (IVs) were expression quantitative trait loci (eQTL) for eight individual genes, one synthesis route, and three degradation routes. Results were assessed using Bayesian colocalization and phenome-wide association analyses. At the pathway-level, the genetically proxied synthesis-route signal was associated with PHQ-9 Assessment 5 (PHQ9A5, OR: 0.89, 95% CI: 0.85-0.93), but sensitivity analyses suggested this association was primarily driven by TPH1 and may reflect serotonin-related biology. In contrast, higher brain melatonin degradation raised the risk of both PHQ9A1 (OR: 1.03, 95% CI: 1.02-1.04) and PHQ9A7 (OR: 1.03, 95% CI: 1.02-1.03). Within degradation, up-regulation of the kynurenine sub-pathway increased the odds of PHQ9A3 (OR: 1.05, 95% CI: 1.02-1.07), PHQ9A4 (OR&#xa0;=&#xa0;1.04, 95% CI: 1.02-1.06) and PHQ9A7 (OR: 1.05, 95% CI: 1.02-1.07). Gene-level analyses were largely concordant, except for SULT1A1, whose higher expression was genetically protective for PHQ9A3 but risk-increased for PHQ9A1 and PHQ9A4. Overall, these results demonstrate that melatonin metabolism exerts symptom-specific and pathway-specific causal effects on depression. A stratified view of melatonin's role may help optimize the application of exogenous melatonin supplementation.

Melatonin

Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.

OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66&#xa0;years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.

Humans

Nipocalimab Phase 3 Dose Selection for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab, a neonatal Fc receptor (FcRn) blocker, is under evaluation for severe hemolytic disease of the fetus and newborn (HDFN). In the Phase 2 UNITY trial, weekly intravenous antenatal treatment with nipocalimab at dose regimens of 30 and 45 mg/kg prevented fetal anemia requiring intrauterine transfusion (IUT) in 54% of high-risk pregnancies and delayed the need for IUTs versus their previous pregnancies in the remaining 46% of pregnancies. This analysis aimed to select a weekly dose regimen of nipocalimab for the Phase 3 study in severe HDFN (NCT05912517) that maintains FcRn blockade throughout antenatal treatment, including with an unplanned dosing delay of up to 3 days. Observed pharmacokinetic/pharmacodynamic (PK/PD) data from UNITY (i.e., nipocalimab concentrations, FcRn occupancy, and serum IgG) were analyzed using a model-based approach. A PK/PD model originally developed in nonpregnant participants was updated to incorporate gestational weight gain. Nipocalimab PK and FcRn occupancy were described by a two-compartment model with nonlinear, dose-dependent PK, which captured longitudinal PK, FcRn occupancy, and IgG profiles during dosing and return toward baseline postpartum after discontinuation. Both 30 and 45 mg/kg achieved &#x223c;80%-85% reductions in maternal IgG; however, 30 mg/kg showed greater variability in predose trough concentrations, increasing the risk of falling below concentrations required for full FcRn occupancy across antenatal treatment. Simulations incorporating PK/PD variability indicated that 45 mg/kg weekly per current weight maintained full FcRn occupancy in >95% of pregnant individuals, even with dosing delays up to 3 days. Exploratory exposure-response analyses supported 45 mg/kg for the Phase 3 HDFN study.

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 &#x2265;&#x2009;50% reduction in MADRS score, and remission as MADRS&#x2009;&#x2264;&#x2009;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

Efficacy, tolerability, and threshold effect of atropine eye drops for myopia control: A systematic review and dose-response meta-analysis.

Atropine is an emerging therapy for myopia, yet the optimal concentration for prescription remains uncertain. We searched PubMed, Embase, Web of Science, Cochrane Library, World Health Organization International Clinical Trials, and ClinicalTrials.gov registry platforms. We included the randomized clinical trials (RCTs) that compared any dose of atropine against a placebo in myopic children. Among 3566 studies assessed, we identified 33 eligible RCTs involving 6301 children aged 4-18 years, with 10 different concentrations and a mean follow-up time of 19.5&#x202f;&#xb1;&#x202f;12.3 months. A nonlinear relationship was observed between atropine dosage and treatment efficacy (P&#x202f;<&#x202f;0.001). Compared to placebo groups, the mean differences in reducing annual spherical equivalent refraction progression for atropine concentrations of 0.01%, 0.02%, 0.03%, 0.04%, and 0.05% were 0.21 diopters (D) (95% CI, 0.13-0.28), 0.35 D (95% CI, 0.23-0.46), 0.42 D (95% CI, 0.28-0.56), 0.45 D (95% CI, 0.30-0.60), and 0.46 D (95% CI, 0.32-0.61) respectively For higher concentrations, the estimates were 0.49 D (95% CI, 0.34-0.63) for 0.1% and 0.99 D (95% CI, 0.66-1.31) for 1%, although these were based on fewer and smaller trials. Higher doses of atropine were associated with decreased amplitude of accommodation (P&#x202f;=&#x202f;0.02), increased pupil diameters (P&#x202f;=&#x202f;0.01) and a higher frequency of photophobia (P&#x202f;=&#x202f;0.02). Our findings suggest that the increase in treatment efficacy with higher concentrations may plateau beyond a certain range, and that the current practice of increasing atropine concentrations for children who show inadequate responses to lower doses should be confined to a specific concentration range. This analysis is limited by the number, design heterogeneity, and sample sizes of available trials for higher concentrations, and by the frequent lack of pre-intervention refractive history in included studies. Therefore, estimates-particularly for doses exceeding 0.1%-should be interpreted with caution.

Humans

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n&#xa0;=&#xa0;15,765) consisted of UK Biobank participants (MDD only n&#xa0;=&#xa0;1230; T2DM only n&#xa0;=&#xa0;3644; comorbid T2DM&#xa0;+&#xa0;MDD n&#xa0;=&#xa0;721). Individuals with T2DM&#xa0;+&#xa0;MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR&#xa0;=&#xa0;4.44, 95% CI&#xa0;=&#xa0;[3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM&#xa0;+&#xa0;MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM&#xa0;+&#xa0;MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM&#xa0;+&#xa0;MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans

Relationship Between Number of Acute Pancreatitis Episodes and Risk of New-onset Diabetes in the U.S.: A Real-world Data Analysis.

INTRODUCTION: Acute pancreatitis (AP) is a common inflammatory disorder that is associated with increased risk for diabetes mellitus (DM). It remains unclear whether recurrent acute pancreatitis (RAP) is associated with further increased risk of incident DM. This study aims to investigate the association between RAP and incident DM using real-world data. METHODS: We conducted a retrospective cohort study using the MerativeTM MarketScan&#xae; claims database (2016-2023), identifying patients with AP and no prior history of DM at baseline. The primary exposure of interest, RAP, was defined as one or more episodes of AP occurring &#x2265;90 days after the index AP diagnosis, whereas one episode of AP referred to a single episode of AP (SAP) with no subsequent recurrence within 90 days following the index event. A multivariable stratified Cox proportional hazards regression models were used to determine the association between RAP and incident DM, identified using ICD-10 codes. RESULTS: In total, 16,184 individuals with AP (mean [SD] age: 45.8 [12.3]) contributed 40,712 person-years of follow-up, during which 1,477 incident cases of DM were documented. Individuals with RAP had an increased risk of incident DM compared with those with a SAP(adjusted HR, 1.92; 95% CI, 1.61-2.29). The risk increased significantly with the frequency of RAP. In comparing the modifying effect of patient demographics and comorbidities, a stronger association between RAP and incident DM was observed in females (adjusted HR, 2.44; 95% CI, 1.87-3.19) than in males (adjusted HR, 1.64; 95% CI, 1.30-2.07; Pinteraction=0.03). Also, stronger associations were observed among younger patients (18-46&#xa0;y) (adjusted HR=2.56; 95% CI, 1.97-3.31) and among non-tobacco abuse (adjusted HR=2.19; 95% CI, 1.81-2.65), with significant interactions for all comparisons (Pinteraction<0.05. CONCLUSIONS: In this real-world study, RAP was associated with an increased risk of incident DM. Our findings highlight an opportunity for glycemic monitoring and proactive management of patients with RAP to mitigate their risk of developing DM.

AP

Communication crossroads: Exploring generational dynamics in nursing from the bedside to the boardroom.

Nurses have up to four times more patient contact than physicians, positioning them as central drivers of communication in health care. Effective communication directly influences patient outcomes, teamwork, staff engagement, and the overall care experience. Today's nurses operate within a highly diverse environment that includes four generations in the workforce and up to eight generations of patients, each with distinct values, expectations, and communication preferences. This article examines how generational differences shape communication across three key relational domains: peer-to-peer, nurse-to-patient, and nurse-to-leader interactions, and offers insights to strengthen collaboration, engagement, and quality of care.

Humans