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Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans

The future of pediatric vesicoureteral reflux management.

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is a common condition in pediatric urology, yet important uncertainties persist regarding risk stratification, imaging strategies, and prevention of long-term renal damage. Emerging technologies may help address these challenges. This review provides a forward-looking overview of recent advances in artificial intelligence (AI) and immunomodulation that may influence future management of pediatric VUR. METHODS: A forward-looking literature review was performed using the PubMed database (January 2000-March 2025), focusing on studies addressing AI, immunomodulation, or vaccination in the context of VUR and urinary tract infections. Criteria of inclusion were the relevance to pediatric VUR, the novelty of the proposed concept, the potential clinical implications and, for the AI literature, the existence of a clinical evaluation of the algorithm on a dataset from patients. KEY FINDINGS AND LIMITATIONS: AI-based models show promising performance in supporting clinical decision-making, including prediction of the need for voiding cystourethrography, automated grading of VUR, estimation of recurrent urinary tract infection risk and prediction of chemoprophylaxis. These tools may facilitate more individualized diagnostic and therapeutic strategies, although current evidence is largely retrospective and requires prospective validation. Immunization and immunomodulatory approaches aim to reduce infection burden and modulate inflammatory pathways associated with renal scarring. While early experimental and adult clinical data are encouraging, pediatric-specific evidence remains limited, and clinical applicability in children with VUR is not yet established. CONCLUSION: Artificial intelligence and immunologically targeted strategies represent complementary, emerging approaches that may contribute to more personalized management of pediatric VUR. At present, both should be regarded as exploratory tools whose clinical impact will depend on further validation and appropriately designed pediatric studies.

Humans

Axial Length Adjustment and AL/R Ratio Optimization of IOL Power Calculation in Extremely Long Eyes.

PURPOSE: To evaluate the accuracy of modern intraocular lens (IOL) power calculation formulas and axial length (AL) adjustment methods in eyes with AL ≥ 30.0 mm. DESIGN: Retrospective consecutive cross-sectional study. PARTICIPANTS AND CONTROLS: A total of 308 eyes (308 patients) with AL ≥ 30.00 mm were included. METHODS: Accuracy of modern online formulas, alone or with established AL adjustments methods, was analyzed. Subgroup analyses were performed based on AL, keratometry (K), anterior chamber depth (ACD), lens thickness (LT), and AL-to-corneal radius (AL/R) ratio. MAIN OUTCOME MEASURES: Predictive accuracy was evaluated using the formula performance index (FPI), root mean square absolute prediction error (RMSAE), standard deviation (SD) of prediction error (PE), and percentage of eyes within ±0.25 and ±0.50 diopters (D). RESULTS: Overall, Holladay 1 combined with the nonlinear polynomial Wang-Koch axial length adjustment (H1-PWK) demonstrated the best overall performance, achieving the lowest SD (0.40), RMSAE (0.40), and highest FPI (0.494). A tendency toward hyperopic error was observed in eyes with AL ≥ 32.0 mm, K ≥ 46.0 D. The AL/R ratio showed a significant positive correlation with PE in the Ladas Super formula, Barrett Universal II, EVO, PEARL-DGS, and Hoffer QST formulas. Spline-based regression analysis indicated that the transition point of AL/R from myopic to hyperopic PE varied across different formulas. CONCLUSIONS: H1-PWK provides robust refractive accuracy in extremely long eyes. The AL/R ratio may provide a useful composite biometric stratification parameter compared to AL alone.

Humans

Modulation of heart rate and heart rate variability during animal-assisted treatment of patients in a minimally conscious state: A randomized controlled crossover study.

BACKGROUND: Animal-assisted treatment (AATx) is a promising and increasingly used approach in neurorehabilitation, yet its psychophysiological effects remain largely unexplored. Patients in a minimally conscious state (MCS) show severely altered consciousness with minimal but definite behavioral signs of awareness. Because behavioral assessment in this population is limited, psychophysiological measures such as heart rate (HR) and heart rate variability (HRV) may offer valuable insights into autonomic regulation during therapy. AIM: The present study investigated whether AATx influences HR and HRV compared to treatment as usual (TAU). METHODS: A randomized controlled crossover design with repeated measures was conducted. HR and HRV data were recorded using an Empatica E4 wristband, and linear mixed-effects models were fitted for each outcome variable. The analytic sample included twenty-one patients with MCS who completed at least one of the four sessions. RESULTS: We found a significant decrease in mean HR (estimate = -12.75, p = .041) and a significant increase in the standard deviation of normal-to-normal intervals (SDNN) (estimate = 15.76, p = .020) during AATx compared to TAU from the pretreatment to the posttreatment phase, indicating enhanced parasympathetic activation and greater autonomic flexibility. Other HRV parameters revealed no significant effects of AATx, though trends were consistent with the hypotheses. CONCLUSIONS: These findings provide preliminary physiological evidence that AATx can modulate autonomic activity in MCS patients. Despite limitations related to sample size and recording quality, the results highlight the potential of AATx as an emotionally engaging intervention in early neurorehabilitation.

Humans

De-escalation of radiotherapy in HPV-negative non-nasopharyngeal head and neck squamous cell carcinoma: a systematic review.

BACKGROUND: Definitive and postoperative radiotherapy are central components of treatment for head and neck squamous cell carcinoma (HNSCC) but are associated with significant toxicities that can impair long-term function and quality of life. De-escalation strategies, aiming to reduce treatment-related morbidity while maintaining tumor control, have attracted increasing interest. However, most research has focused on HPV-positive oropharyngeal carcinoma. Systematic evidence for HPV-negative disease remains limited. METHODS: PubMed and EMBASE were searched for prospective studies investigating radio(chemo)therapy de-escalation in HPV-negative, HPV-unspecified, or mixed non-nasopharyngeal HNSCC populations. CLINICALTRIALS: gov was searched for ongoing prospective trials. Data extraction and verification were performed independently by three investigators. RESULTS: Screening of 3156 records identified 14 published prospective studies, 10 in the definitive and four in the postoperative setting. Strategies included reduction or omission of elective nodal volumes, dose reduction, and combined approaches. Additionally, 23 ongoing prospective trials were identified. Across studies, elective nodal failure rates were consistently low (0-4.6%), with most recurrences occurring within high-dose volumes rather than de-escalated elective regions. Randomized evidence for elective nodal dose reduction is mixed: two trials maintained regional control and reduced acute toxicity, whereas another was stopped for futility. CONCLUSION: Available evidence on de-escalation in HPV-negative HNSCC is limited, derived primarily from small, heterogeneous phase II studies with mixed HPV populations. Although data are promising in selected settings, notably for elective nodal control, the randomized evidence for elective nodal dose reduction is conflicting, and further adequately designed prospective randomized trials are required.

Humans

Multiplexed CRISPR/Cas9 mediated knockdown of BCH gene in potato enhances beta-carotene to combat vitamin A deficiency.

The inadequate amounts of provitamin A carotenoids in crops contribute to the widespread vitamin A deficiency, leading to malnutrition and blindness in humans. Suppression of the β-carotene hydroxylase (BCH) increases β-carotene levels. In the current study, we utilized the multiplexed CRISPR/Cas9 approach by designing three targets against the BCH gene in a local potato cultivar. Transformation efficiency was recorded as 15%, the successful integration of the CRISPR/Cas9-BCH multiplex construct in potatoes was confirmed through PCR. When analysed using TIDE software, Sanger sequencing revealed the highest indel efficacy of 92.1% in plant 7 and 26.6% in plant 1. qRT-PCR (quantitative real-time PCR) analysis indicated a significant 89-fold reduction in BCH transcript levels in genome-edited potato lines compared to control plants. Spectrophotometry demonstrated a notable increase in beta-carotene levels in genome-edited potato plants, ranging from 0.831 µg/mL FW to 4.236 µg/mL FW, compared to the control plant with the lowest beta-carotene concentration (0.344 µg/mL FW). HPLC analysis further confirmed increased beta-carotene levels in genome-edited potato plants, ranging from 0.11 mg/mL FW to 0.36 mg/mL FW, compared to the unmodified control plant with a minimum beta-carotene value of 0.09 mg/mL. Our results revealed that the multiplexed CRISPR-Cas9 approach targeting the BCH gene results in enhanced beta-carotene contents in potato tubers.

Solanum tuberosum

Specialized pro-resolving mediators in obesity and overweight conditions: A systematic review of human and animal evidence on comparative differences and associations.

Obesity and overweight are characterized by persistent low-grade inflammation. Specialized pro-resolving mediators (SPMs), polyunsaturated fatty acid-derived metabolites, actively promote inflammatory resolution, and their dysregulation has been linked to unresolved inflammation and metabolic disturbances in obesity. This systematic review synthesized human and animal evidence on adiposity-related differences and associations in SPMs and SPM precursors. The protocol was prospectively registered in PROSPERO (CRD420251067464). PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched up to 22 May 2026. Eligible studies included human and animal research comparing SPMs and/or SPM precursors between overweight/obese and normal-weight/lean groups or assessing their associations with adiposity indices. Due to heterogeneity across matrices and analytical platforms, findings were synthesized narratively. Twenty-seven unique studies were included, providing 28 experimental datasets (14 animal and 14 human). The most consistent alterations were observed in adipose tissue and circulation, where overweight/obesity was frequently associated with lower concentrations of SPMs and/or SPM precursors. In humans, circulating Resolvin E1 showed reproducible reductions and was inversely associated with adiposity measures in several cohorts. In contrast, selected metabolites, including SPM Lipoxin A4 and the SPM precursors 15-HETE and 18-HEPE, exhibited mixed directionality across studies. Evidence for hepatic and central nervous system compartments was limited and heterogeneous. Overall, available evidence suggests that excess adiposity is associated with altered SPM and precursor profiles, most consistently in adipose tissue and circulation, whereas hepatic and central nervous system findings remain inconsistent. Future studies using standardized quantification and tissue-specific designs are needed to clarify whether targeting pro-resolving pathways has translational potential in obesity-related metabolic dysfunction.

Animals

Ciliochoroidal Effusion and Regional Scleral Thickening in Peripapillary Pachychoroid Syndrome.

PURPOSE: To assess anterior scleral thickness and the presence of ciliochoroidal effusion (CE) in eyes with peripapillary pachychoroid syndrome (PPS), and to compare the results with a cohort of healthy age-matched controls. DESIGN: Retrospective cross-sectional study METHODS: A total of 20 eyes from 12 patients diagnosed with PPS and 30 eyes from 15 healthy control subjects. All participants underwent a comprehensive ophthalmic examination, including spectral-domain optical coherence tomography with enhanced depth imaging (EDI-OCT) and anterior segment OCT (AS-OCT). Choroidal thickness was measured at predefined macular and peripapillary locations, while anterior scleral thickness was assessed 6 mm posterior to the scleral spur in 4 quadrants. Ciliochoroidal effusion was evaluated qualitatively using AS-OCT. Comparisons between groups were performed using linear mixed models with Bonferroni correction (scleral thickness corrected P < .010) RESULTS: The mean age of PPS patients was 75.6 &#xb1; 9.8 years, and 16% were females. Anterior scleral thickness was significantly greater in the temporal quadrant in PPS eyes compared to controls (396.85 &#xb1; 74.97 &#xb5;m vs 331.13 &#xb1; 62.65 &#xb5;m: P = .007). Ciliochoroidal effusion was detected in 60% of PPS eyes, predominantly in the superior and temporal sectors, whereas no effusion was observed in healthy controls (P < .001). Eyes with CE exhibited a thicker mean scleral thickness and a thicker subfoveal choroidal thickness compared to eyes without effusion (P < .05). CONCLUSION: Eyes with PPS demonstrated increased temporal scleral thickness and a high prevalence of CE. These findings suggest that scleral characteristics may represent a predisposing anatomical factor in PPS, although the precise pathophysiological mechanisms remain to be elucidated.

Humans

Impact of kangaroo care on circadian rhythm, growth, physiological stability in premature infants, and cortisol and melatonin levels in maternal breast milk: A randomized controlled trial.

PURPOSE: This study aimed to examine the effects of regular kangaroo care (KC) on sleep-wake cycles, growth, physiological stability, and maternal breast milk cortisol and melatonin levels in premature infants. DESIGN: This study was a parallel group, single-blind, pre-test-post-test, randomised controlled trial (RCT). METHODS: This randomized controlled study was conducted in a neonatal intensive care unit (NICU) in T&#xfc;rkiye between September 2024 and September 2025 Thirty-six premature infants were randomized to intervention (n = 28) or control (n = 28). Infants in the intervention group received KC for three consecutive days, twice daily (10:00 a.m. and 10:00 p.m.) for 60 min per session. Data were collected using the Infant Information Form, Physiological Parameters Monitoring Chart, and Premature Infant Sleep-Wake Cycles Tracking Chart. Sleep-wake cycles were monitored using a Bispectral Index device. Breast milk cortisol and melatonin levels were measured at baseline and on day three using the competitive ELISA method. The study was registered at ClinicalTrials.gov (NCT06589349). RESULTS: Regular KC had a statistically significant effect on BIS values, heart rate, respiratory rate, oxygen saturation, and body temperature (p < 0.05). No statistically significant effects were observed on infant body weight or on maternal breast milk cortisol and melatonin levels (p > 0.05). CONCLUSION: The findings indicate that regular KC is associated with improved regulation of the sleep-wake cycle and enhanced physiological stability in premature infants. No significant changes were observed in maternal breast milk cortisol or melatonin levels following KC.

Humans

The influence of organizational culture on medication safety practices and associated risk factors in the community setting: A systematic review.

BACKGROUND: Increasing attention has been given to the role of organizational culture in influencing medication safety practices across healthcare settings. The lack of widely accepted standardized instrumentation makes operational measurement of organizational culture and medication safety challenging. The purpose of this systematic review was to examine the impact of organizational culture on medication safety within community healthcare settings. METHODS: MEDLINE, CINAHL, Scopus, and Nursing & Allied Health were searched in August 2025 using keywords, subject terms, field codes, and Boolean operators to identify papers relevant to the review question; bibliographies of included studies were also reviewed. Screening and full-text review were completed independently by two reviewers with a third to adjudicate conflicts. The Critical Appraisal Skills Programme was used for quality assessment. The PRISMA statement guided the development and implementation of the review. RESULTS: Thirteen articles were included representing various community settings. Most studies reported on untoward medication events, but few measured systematically collected safety data before and after an intervention. Organizational culture was seldom defined or operationalized. Most studies were methodologically sound, but the overall level of evidence was weak to moderate. CONCLUSION: Organizational culture influences medication safety through aspects such as communication channels, teamwork, training, and an environment that allows error and near-miss reporting. Few studies explicitly evaluate the causal impact of culture interventions on measurable medication safety outcomes in community healthcare settings. Further research should incorporate standardized measurement tools and intervention-based, pre-post designs to better understand how organizational culture influences medication safety in community healthcare settings.

Organizational Culture

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

Effects of umbilical cord mesenchymal stem cell-derived exosomes on periodontal ligament stem cells: An exploratory study.

OBJECTIVE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) at two osteogenic induction stages (undifferentiated and late-stage) differentially affect periodontal ligament stem cells (PDLSCs), and to explore the potential molecular basis. DESIGN: UCMSCs and PDLSCs were isolated and cultured. Exosomes were harvested from undifferentiated UCMSCs (Exo-D0) and UCMSCs after 14 days of osteogenic induction (Exo-D14). PDLSCs were treated with both exosome types. Proliferation and migration were analyzed using EdU and scratch assays, the latter under serum-free conditions. Early osteogenic differentiation was assessed by alkaline phosphatase staining and quantitative reverse transcription PCR (qRT-PCR). Differentially expressed miRNAs were identified by high-throughput sequencing and further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: Both exosome types promoted PDLSC migration. Exo-D0 enhanced early osteogenic differentiation, whereas Exo-D14 enhanced proliferation but reduced early osteogenic marker expression. Sequencing identified 21 differentially expressed miRNAs (13 upregulated, 8 downregulated). Bioinformatic prediction suggested that the putative target genes were enriched in Ras signal transduction, regulation of kinase activity, and focal adhesion, and further predicted significant enrichment in the MAPK, Ras, and PI3K-Akt signaling pathways, which are central to cell proliferation and osteogenic differentiation. CONCLUSIONS: Exosomes from undifferentiated and osteogenically induced UCMSCs exerted distinct effects on PDLSCs, potentially associated with differentially packaged miRNAs. These findings offer a basis for hypotheses about exosome-mediated mechanisms and support matching exosome sources to the intended therapeutic outcome as potential cell-free strategies for periodontal tissue regeneration and alveolar bone repair.

Humans

Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p&#x2009;<&#x2009;0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2&#x2009;=&#x2009;50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

Humans

Risk prediction models for blood transfusion in patients undergoing total hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA). METHODS: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0. RESULTS: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear. CONCLUSION: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Humans

Financial incentives and social messaging for repeat SARS-CoV-2 antibody testing among the underserved: A randomized trial.

Financial incentives may influence health behavior beyond their expected monetary value, and their effectiveness may depend on how the behavior is framed. Behavioral theories of decision making suggest that individuals may value protection against small-stakes losses more than expected utility predicts, while theories of family-centered health behavior suggest that messages emphasizing benefits to family members may strengthen participation in preventive health activities. We tested these ideas in a 2&#xd7;2 factorial randomized trial involving 625 households recruited from a Federally Qualified Health Center serving low-income Latino/Hispanic communities. Participants completed repeat SARS-CoV-2 antibody testing. The trial crossed two messaging strategies (Family vs. Personal) with two incentive structures (Loss Protection vs. Lottery) that offered equivalent expected monetary value. Family Messaging emphasized protecting one's family from COVID-19, whereas Personal Messaging emphasized protecting oneself. Loss Protection allowed participants to secure an at-risk reward through repeat testing, whereas the Lottery condition offered a chance of a large reward. Repeat testing was approximately 8 percentage points higher under Family Messaging and 7 percentage points higher under Loss Protection. Baseline trust in medical providers, financial barriers to vaccination, and risk aversion were associated with initial testing, whereas household characteristics were not associated with repeat testing. Incentive design may matter beyond expected monetary value and that framing health behaviors in terms of family welfare may increase participation in repeated healthy activities. Broadly, the results support behavioral theories emphasizing loss aversion, anticipated regret, and family-centered motivations, and suggest practical approaches for improving engagement in repeat health behaviors. CLINICALTRIALS.GOV REGISTRATION NUMBER:: NCT01901624.

Adult

Impact of Contact Lens Use on Clinical Profile and Outcomes of Fungal Keratitis: An 8-Year Retrospective Study.

PURPOSE: To compare clinical characteristics, microbiological profiles, treatment strategies, and outcomes between contact lens-associated (CL) and noncontact lens-associated (non-CL) fungal keratitis. DESIGN: Retrospective, comparative clinical cohort study. METHODS: A review of culture-proven fungal keratitis treated at a tertiary referral center between 2018 and 2025 was conducted. Cases were categorized as CL or non-CL-associated. Demographic, clinical, microbiological, treatment, and outcome data were analyzed and compared between groups. RESULTS: Thirty-seven eyes were included, comprising 16 CL and 21 non-CL cases. CL users presented earlier than non-CL patients (median 7 vs 14 days, P = .007) and had fewer associated ocular risk factors (31% vs 81%, P = .001). Baseline visual acuity and infiltrate size did not differ significantly between groups. Candida species were isolated in 21% cases, Fusarium in 16% and Aspergillus in 8%. Fusarium (19% vs 13%) and Candida (24% vs 19%) infections were slightly more frequent in non-CL cases. Overall, filamentous fungi were the predominant organism group. Topical voriconazole was the most frequently used antifungal agent (78%). All CL-associated cases resolved with medical therapy alone, with a median time to resolution of 38 days (IQR 22-58). In contrast, 76% of non-CL cases resolved medically (median 42 days, IQR 32-76), while 23% required therapeutic keratoplasty (P = .04). Final visual acuity was comparable between groups (logMAR 0.2 vs 0.5, P = .56). CONCLUSION: Contact lens-associated fungal keratitis is characterized by earlier presentation and fewer underlying ocular comorbidities, with favorable outcomes achieved through medical therapy alone. Despite similar microbiological profiles and treatment approaches, noncontact lens-associated fungal keratitis more frequently follows a complicated course requiring surgical intervention.

Humans

Effects of phytosterols supplementation on hepatic lipid metabolism and metabolic outcomes in obese rodent models: a systematic review and meta-analysis.

This study aimed to synthesize and quantitatively assess the available evidence on the effects of phytosterol supplementation on hepatic lipid metabolism and obesity-related metabolic outcomes in obese rodent models, integrating biochemical, histological, and molecular evidence. A systematic search was conducted in electronic databases (PubMed, EMBASE, and Web of Science). Data on study design, population, intervention, outcomes, and risk of bias were extracted and analyzed. A quantitative meta-analysis was performed. Meta-analysis showed reductions in body weight, serum triglycerides, total cholesterol, LDL-C, VLDL-C, glucose, liver weight, hepatic cholesterol, hepatic triglycerides, and nonalcoholic fatty liver disease activity score. No significant changes were observed for adiposity index, HDL-C, insulin, or hepatic expression of PPAR&#x3b1;, FAS, and SREBP1c. Conversely, CPT1A expression was significantly increased following PS supplementation. Subgroup analyses indicated that the beneficial effects on lipid and hepatic outcomes were generally consistent across rodent species (mice, rats, and hamsters), obesity induction models, and routes of administration, although the magnitude of responses varied between strains, with C57BL/6 mice showing more pronounced metabolic improvements. Additional analyses suggested that treatment duration and phytosterol composition may modulate specific outcomes, whereas dose-response meta-regression identified dose-dependent associations for serum and hepatic cholesterol, and PPAR&#x3b1; expression in dietary supplementation studies. Overall, the available preclinical evidence suggests that phytosterol supplementation may improve several metabolic and hepatic outcomes in rodent models of obesity. However, the substantial heterogeneity across studies highlights the need for standardized experimental protocols and future clinical studies before these findings can be translated to human health.

Animals

Timeliness of publication of randomized controlled trials in rheumatology: A systematic review.

OBJECTIVE: To systematically review the (1) timeliness of publication of randomized controlled trials (RCTs) in rheumatology, (2) impact of the COVID-19 pandemic on time to publication, and (3) factors associated with publication delays. METHODS: We searched Medline, Embase, EBM Reviews, Cochrane Central Register of Controlled Trials, and Scopus from January 1, 2018, to June 30, 2023 for Phase 3, superiority, parallel-design RCTs that evaluated any treatment for a rheumatologic illness or a rheumatologic treatment for COVID-19 and reported clinical primary efficacy outcome. Outcomes of interest were time to publication after trial completion and publication delay of >2 years after trial completion. RESULTS: 448 RCTs were included in this systematic review. Median time from completion to publication was 549 days and 65.9 % RCTs were published within 2 years of completion. Compared with RCTs on rheumatologic diseases, RCTs on COVID-19 were published sooner (253 vs. 549 days; p < 0.001) and were more likely to be published within 2 years (adjusted OR 9.49, 95 % CI 2.07 to 43.61). Compared with RCTs completed before March 1, 2020, RCTs completed after March 1, 2020, were published sooner (327 vs. 724 days; p < 0.001) and were more likely to be published within 2 years (adjusted OR 9.40, 95 % CI 5.14 to 17.21). Time from RCT completion to submission accounted for most (67 %) of the time to publication. CONCLUSIONS: Publication delay continues to be an important concern in dissemination of clinical research. Most of the delays in publication were attributable to delays in submission to journals after trial completion.

Humans