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Probiotic supplementation improves body composition, lipid profiles, and fatty acid metabolism in combat sports athletes during the weight reduction phase.

PURPOSE: Pre-competition weight control for combat sports athletes may alter body composition and fatty acid metabolism. Probiotics have shown potential to regulate overall metabolism; however, their specific effects on fatty acid metabolism during weight control in athletes remain unclear. METHODS: Thirty-two combat sports athletes participating in the 4-week weight reduction period were assigned to either the probiotic group (Group E) or the placebo group (Group C). Body composition, lipid profiles, and fatty acid metabolism were measured before and after the 4-week weight reduction phase. RESULTS: All the athletes experienced a decrease in body weight, body mass index (BMI), body fat percentage, and muscle mass following the 4-week weight loss intervention. Notably, a more significant reduction in body fat percentage (p&#x2009;<&#x2009;0.05) was observed, along with lower levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), specifically in Group E. Weight loss intervention resulted in increased levels of short-chain fatty acids (SCFAs), specifically acetic acid, propionic acid, and butyric acid. Notably, Group E exhibited higher mean values for SCFAs compared to Group C (p&#x2009;<&#x2009;0.05). Additionally, the serum levels of &#x3b3;-linolenic acid and 8,11,14-eicosatrienoic acid were significantly reduced in Group E (p&#x2009;<&#x2009;0.05). In contrast, the majority of free fatty acids (FFAs) showed significant increases, with greater magnitudes of change observed in Group C (p&#x2009;<&#x2009;0.05). CONCLUSION: Probiotic supplementation can improve body composition, enhance SCFAs levels, and decrease circulating FFAs in combat sports athletes, suggesting that probiotics may have a beneficial impact on pre-competition weight management. TRIAL REGISTRATION NUMBER: chiCTR2400079908 (Reg Date:2024-01-16).

Humans

Efficacy and Safety of Anti-Obesity Medications for Weight Loss Maintenance in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

AIMS: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of anti-obesity medications (AOMs) for long-term weight maintenance following initial weight loss in adults with overweight or obesity. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library from inception to 31 October 2025. Eligible studies were randomised controlled trials (RCTs) comparing AOMs with placebo during the weight-maintenance phase in adults with overweight or obesity after initial weight loss achieved through lifestyle, dietary, surgical or pharmacological interventions. Outcomes included anthropometric indices, cardiometabolic measures, safety endpoints, quality of life and neuropsychiatric adverse events. Weighted mean differences (WMDs) and odds ratios (ORs), each with 95% confidence intervals (CIs), were pooled for continuous and categorical outcomes, respectively, using fixed-effect or random-effects models as appropriate. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE framework. The protocol was registered with PROSPERO (CRD420261293040). RESULTS: A total of 12 RCTs comprising 4915 participants met the inclusion criteria. Compared with placebo, AOM therapy during the weight-maintenance phase was associated with prevention of weight regain and additional improvements in anthropometric and cardiometabolic outcomes. AOMs led to further reductions in body weight (BW, WMD: -8.68&#x2009;kg, 95% CI: -13.25 to -4.11), waist circumference (WC, WMD: -7.16&#x2009;cm, 95% CI: -10.34 to -3.98) and body mass index (BMI, WMD: -3.58&#x2009;kg/m2, 95% CI: -5.69 to -1.46). Additional benefits were observed for triglycerides, total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure and diastolic blood pressure. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Neuropsychiatric adverse events were generally comparable between groups, and available quality-of-life measures favoured AOM treatment. CONCLUSIONS: AOM therapy during the weight-maintenance phase can help prevent weight regain, provide further reductions in body weight and improve cardiometabolic risk factors in adults with overweight or obesity. Gastrointestinal adverse events were more common with AOMs, whereas serious adverse events were not significantly increased. Further long-term trials are needed to clarify optimal treatment strategies and safety.

Humans

Relationships between cannabis and cocaine use in a randomized trial of combined buprenorphine and naltrexone for DSM-IV cocaine dependence.

BACKGROUND: Cannabis is the most commonly used drug in the United States, and among people who use cannabis, polysubstance use is common and understudied. We aimed to examine the association of tetrahydrocannabinol (THC) positive urine drug screen (+UDS) with the odds of submitting a cocaine&#xa0;+&#xa0;UDS during cocaine use disorder treatment. METHODS: We conducted a secondary data analysis of a previously reported double-blind, placebo-controlled clinical trial, CTN0048. Participants meeting criteria for opioid abuse/dependence were assigned to receive extended-release naltrexone and one of three conditions of buprenorphine (placebo, 4&#xa0;mg/day, 16&#xa0;mg/day) for 8&#xa0;weeks. Generalized estimating equations (GEE) were used to analyze urine samples (Liu et al., 2018) collected over time, examining the association between THC&#xa0;+&#xa0;UDS and cocaine&#xa0;+&#xa0;UDS during treatment. RESULTS: Participants (n&#xa0;=&#xa0;301) averaged 46 (SD&#xa0;=&#xa0;8.64) years of age, were majority male (78.41&#xa0;%), non-Hispanic (89.70&#xa0;%), and African American (66.45&#xa0;%). GEE results indicated that patients who submitted THC&#xa0;+&#xa0;UDS had significantly higher odds of submitting cocaine&#xa0;+&#xa0;UDS compared to participants who submitted THC-negative UDS across the 25 time points examined (OR&#xa0;=&#xa0;1.47, 95&#xa0;% CI&#xa0;=&#xa0;1.21-1.79, p&#xa0;=&#xa0;0.00). Time (OR&#xa0;=&#xa0;0.9998, 95&#xa0;% CI: 0.9997, 0.9999, p&#xa0;=&#xa0;0.018) and the covariate of sex assigned at birth (OR&#xa0;=&#xa0;1.77, 95&#xa0;% CI&#xa0;=&#xa0;1.13-2.77, p&#xa0;=&#xa0;0.013) were also significant in the model, indicating very small decreases in the odds of submitting a cocaine&#xa0;+&#xa0;UDS over time for all patients and 77&#xa0;% higher odds of submitting cocaine&#xa0;+&#xa0;UDS for females. CONCLUSION: THC&#xa0;+&#xa0;UDS was associated with increased odds of submitting a cocaine&#xa0;+&#xa0;UDS during treatment. Further investigation is needed to discern whether decreasing THC use will result in reduced cocaine use; however, these results suggest that it may be beneficial to counsel patients on cannabis use cessation both before and during treatment for cocaine use, as it is related to cocaine use treatment outcomes. TRIAL REGISTRATION: Secondary data analysis of ClinicalTrials.gov, TRN: NCT01402492 ("A randomized study to test the safety and effectiveness of buprenorphine in the presence of naltrexone for the treatment of cocaine dependence"; National Drug Abuse Treatment Clinical Trials Network (CTN) clinical trial: CTN0048), Registration date: 27 July 2011.

Humans

Meta-analysis of prostacyclin therapy for persistent pulmonary hypertension with congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the efficacy and safety of prostacyclin in the treatment of persistent pulmonary hypertension in congenital diaphragmatic hernia. METHODS: A systematic literature search was conducted in four main databases (PubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The protocol was registered in advance in the International Prospective of Systematic Reviews (CRD420261325458). RESULTS: A total of nine studies were included involving a total of 7009 infants in this systematic review and meta-analysis. GRADE assessment revealed substantial heterogeneity in the quality of evidence across outcomes, with most outcomes rated very low quality and only one rated moderate quality. Studies were performed meta-analysis, which showed the use of prostacylin resulted a statistically significant decrease in the OI compared to the control group (Mean Difference (MD), 9.34; I2 0%; p < 0.00001), no statistically significant in mortality (OR, 0.83; I2 84%; p = 0.70), ECMO (OR = 4.9; I2 98%; p = 0.27), BNP (std MD, 6.98; I2 98%; p = 0.31), FiO2 (SMD = 8.0;, I2 64%; p = 0.11), Systolic orientation of IVS curvature (SMD = 0.69; I2 97%; p = 0.32), Diastolic orientation of IVS differences (MD = 0.62; I2 93% p = 0.26). After applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. CONCLUSION: In conclusion, this meta-analysis has confirmed that prostacyclin may temporarily improve oxygenation. However, after applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. Further validation through high-quality studies are still needed. TRIAL REGISTRATION: PROSPERO: CRD420261325458.

Humans

Safety and Immunogenicity of Varicella Vaccination in Children and Adolescents Living With HIV: A Systematic Review.

INTRODUCTION: Preventing varicella-zoster virus infection is important in the management of human immunodeficiency virus (HIV)-positive persons. Varicella remains endemic worldwide, and HIV-positive persons can experience greater morbidity than the general population. We summarized the global literature on the safety and immunogenicity of the varicella vaccine in HIV-positive children. METHODS: Systematic review of original reports on varicella vaccination of HIV-positive children, published through December 31, 2024, including assessment of safety, immunologic responses and effectiveness after vaccination. RESULTS: Eighteen articles were analyzed. Local reactions were the most common adverse events, albeit infrequent (<21% and <10% of vaccinees after dose 1 and 2, respectively). Systemic reactions were also infrequent, consisting mostly of low-grade fever. A vaccine-related rash, reported in <5% of vaccinees, had fewer lesions and a shorter duration than typical varicella. Serious adverse events were reported only when the vaccine was inadvertently administered to children with severe HIV immunosuppression. Varicella vaccination had no clinically significant impact on plasma HIV RNA or CD4+ T-cell count after either dose. An antibody response was reported in 60%-79% of HIV-positive vaccinees after dose 2 and often declined more rapidly than in uninfected children. Cell-mediated immunity was detected in 67%-83% after dose 2. No significant differences in adverse events or short-term immune response after vaccination correlated with past or current CD4+ T-cell status. CONCLUSIONS: The varicella vaccine had a favorable safety profile and induced specific immune responses in most nonseverely immunocompromised HIV-positive children. The vaccine remains contraindicated for persons with severe HIV infection. Robust data on the durability of immune response and long-term effectiveness are needed.

Humans

Ruling out pediatric bacterial epididymo-orchitis with urinalysis - The case for minimizing unnecessary antibiotic prescription.

INTRODUCTION: Epididymo-orchitis in pediatric patients is predominantly non-bacterial, often stemming from viral or reactive etiologies. Despite guidelines recommending conservative management for non-bacterial cases, antibiotic overtreatment remains prevalent in the outpatient setting. We evaluated the diagnostic accuracy of urinalysis in ruling out bacterial infection to support antibiotic stewardship in this population. METHODS: We conducted a cross-sectional diagnostic accuracy study using electronic health records from a large health maintenance organization in Israel. The cohort included patients younger than 18 years with a diagnosis of epididymo-orchitis or clinically overlapping entities (acute scrotum, appendage torsion) who had paired urinalysis and urine culture results within one week of diagnosis. Logistic regression and ROC curve analysis were performed to assess the ability of urinalysis parameters to predict positive urine cultures. RESULTS: Of 682 eligible cases, confirmed bacterial infection was rare, occurring in only 17 patients (2.5%). Nitrite positivity was the strongest independent predictor of infection (OR 43.98; p < 0.001). A prediction model incorporating all urinalysis parameters yielded an area under the curve (AUC) of 0.825 and achieved a 97.7% classification accuracy for correctly predicting negative cultures. Despite the low prevalence of infection, antibiotics were prescribed in 237 cases (34.7%). Urinary anatomic abnormalities were significantly associated with culture positivity. CONCLUSIONS: Bacterial coinfection in pediatric epididymo-orchitis is uncommon. Urinalysis serves as a highly accurate screening tool to rule out bacterial etiology. A negative urinalysis supports withholding antibiotics in this setting, reserving treatment for children with positive markers or known anatomic abnormalities. This evidence-based approach This evidence-based approach has the potential to reduce unnecessary antibiotic exposure, however prospective studies are needed to validate these findings before broad implementation.

Humans

Weight-bearing locomotion mitigates the progression of post-traumatic knee osteoarthritis in male rodents: A systematic review and meta-analysis.

OBJECTIVE: Although knee post-traumatic osteoarthritis (PTOA) has been associated with altered loading, how weight-bearing (WB) activities should be modulated post-injury to preserve knee health remains unknown. This systematic review and meta-analysis examined the effects of WB locomotion on knee PTOA in rodents to provide insight into potential clinical implications. DESIGN: Studies published in PubMed, Cochrane Library, Embase, and CINAHL through 02/2025 and meeting the following criteria were included: 1) rodents with knee PTOA, 2) compared locomotor exercises (treadmill/wheel) to no exercise, 3) outcome measures of PTOA (OARSI/Mankin OA scores, bone quality, osteophyte condition, cartilage quality/morphology). If significant heterogeneity across studies was observed, locomotion speed, time/number of intervention sessions, frequency and duration of intervention, exercise initiation, follow-up time, animal species, PTOA model were analyzed as potential moderator variables that may influence findings. RESULTS: Twenty-two studies met the criteria, resulting in a total of 156 effect sizes (ESs) for meta-analysis (all males). A positive ES denotes less PTOA. Based on the CAMARADES checklist, 5 studies were ranked low risk of bias and 14 studies were ranked moderate risk of bias. Locomotion significantly reduced PTOA severity evaluated using OARSI/Mankin scores (ES=0.927, 95% CI: [0.590, 1.264]) and improved bone quality (ES=0.379, 95% CI: [-0.023, 0.780]) with substantial heterogeneity across studies. Follow-up analyses indicated that greater ESs for reducing OA scores were associated with a shorter duration of each training session, more training sessions, longer intervention duration, and longer follow-up time (all P&#x2264;0.004). Greater ESs for improving bone quality were associated with a longer follow-up time and later exercise initiation post-injury (both P&#x2264;0.014). Locomotion resulted in small to moderate but non-significant positive effects for isolated measures assessing osteophyte condition (ES=0.379, 95% CI: [-0.023, 0.780]), cartilage quality (ES=0.430, 95% CI: [-0.034, 0.893]), and cartilage morphology (ES=0.464, 95% CI: [-0.006, 0.934]). CONCLUSION: WB locomotion reduced the overall degree of knee PTOA in male rodents. Composite knee OA scores may be more responsive to exercise interventions than isolated cartilage/osteophyte measures. The benefits of locomotion may be more prominent with a longer follow-up time or with exercise protocols consisting of shorter but more individual sessions and longer overall intervention durations.

Animals

Factors Impacting Overall Survival Post-Relapse in High-Risk Neuroblastoma: Children's Oncology Group Outcomes From 2000 to 2019.

PURPOSE: Prior studies of features impacting post-relapse survival in high-risk neuroblastoma (HRNB) evaluated patient cohorts that did not receive contemporary high-risk or relapse therapies. We describe overall survival (OS) after first progression or first relapse of HRNB in a modern cohort. METHODS: Patients with HRNB enrolled on COG ANBL00B1(NCT00904241) between 2000 and 2019, who had relapsed or progressive disease were eligible. Clinical and molecular risk factors at diagnosis, therapy era, clinical trial enrollment, and clinical features at relapse, including site of and time to relapse, were evaluated. OS post-relapse was compared between groups using log-rank tests and Cox models. RESULTS: Among 4253 eligible HRNB patients, 1616 had relapse or progression as a first event. Five-year OS post-relapse was 19.1&#xa0;&#xb1;&#xa0;1.1%. The risk group with the lowest post-relapse survival was observed in patients with INSS Stage 4 or 4S disease <&#xa0;18 months of age at diagnosis with MYCN amplified (MYCN-A) tumors. The other significant most unfavorable factors at diagnosis included diagnosis 2000-2004, tumor MYCN-A, 1p loss of heterozygosity (LOH), and elevated LDH or ferritin. Unfavorable factors at relapse included the time to relapse <&#xa0;36 months from diagnosis, and combined local and metastatic disease at relapse. Multivariable analysis indicated that those with tumors harboring 1p LOH, age &#x2264;&#xa0;5 years at diagnosis, or earlier treatment therapy era (2000-2004) had a higher risk of post-relapse death. CONCLUSIONS: While the 5-year OS rate was low in this cohort, there are subsets of patients with relapsed HRNB who demonstrate long-term survival. TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00904241.

Humans

Extended Venous Thromboembolism Prophylaxis After One-Anastomosis Gastric Bypass: A Three-Arm Randomized Trial of Enoxaparin Duration and Rivaroxaban.

BACKGROUND: Venous thromboembolism (VTE) is a serious but preventable complication after bariatric surgery, most of them after hospital discharge. The optimal regimen and duration of post-discharge prophylaxis, particularly the role of direct oral anticoagulants, remain uncertain. OBJECTIVES: To estimate 30-day VTE and bleeding event rates in high-risk patients undergoing one-anastomosis gastric bypass who received 15-day enoxaparin, 30-day enoxaparin, or 30-day rivaroxaban prophylaxis, and to perform exploratory comparisons among the regimens. METHODS: In this randomized, open-label, three-arm clinical trial, high-risk adults undergoing laparoscopic OAGB were randomized before discharge (1:1:1) to enoxaparin 40&#xa0;mg subcutaneously twice daily for 15 days, enoxaparin 40&#xa0;mg twice daily for 30 days, or rivaroxaban 10&#xa0;mg orally once daily for 30 days, after standardized in-hospital enoxaparin and early ambulation. Participants underwent clinical assessment and duplex ultrasonography of the lower-limb and porto-mesenteric veins on postoperative days 15 and 30. The primary outcome was objectively confirmed VTE within 30 days. Bleeding was classified as International Society on Thrombosis and Haemostasis (ISTH) major bleeding or clinically relevant non-major bleeding (CRNMB). Because the expected event rate was low and no non-inferiority or equivalence margin was prespecified, comparisons were interpreted as exploratory. RESULTS: A total of 288 patients were randomized to 15-day enoxaparin (n&#x2009;=&#x2009;97), 30-day enoxaparin (n&#x2009;=&#x2009;97), or 30-day rivaroxaban (n&#x2009;=&#x2009;94). One symptomatic lower-limb deep vein thrombosis occurred in the 15-day enoxaparin group (1.0%; 95% CI, 0.03%-5.6%); no VTE events occurred in the 30-day enoxaparin group (0%; 95% CI, 0%-3.7%) or the rivaroxaban group (0%; 95% CI, 0%-3.8%). Total bleeding occurred in 4/97 patients (4.1%) in each enoxaparin group and 8/94 patients (8.5%) in the rivaroxaban group. The absolute difference in total bleeding between rivaroxaban and 30-day enoxaparin was 4.4% points (95% CI, -&#x2009;2.9 to 12.2), indicating substantial imprecision. No porto-mesenteric venous thrombosis was detected. CONCLUSION: Only one VTE event occurred, precluding reliable conclusions regarding comparative efficacy or prophylaxis duration. Bleeding estimates were also imprecise and do not establish comparative safety or equivalence between rivaroxaban and enoxaparin. The trial adds descriptive event-rate data from a standardized OAGB pathway, but larger multicenter studies with prespecified comparative hypotheses and assessment of adherence, oral tolerance, and drug exposure are required. The study was approved by the Research Ethics Committee and registered at ClinicalTrials.gov.

Humans

Effectiveness of Caregiver-Mediated Spoken Language Interventions for Children Under Five at Risk of Developmental Language Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Caregiver-mediated interventions are commonly used by Speech and Language Therapists to support early language development. Developmental Language Disorder (DLD) is associated with reduced quality of life throughout the lifespan. Understanding factors that predict intervention success is essential for developing appropriate, cost-effective therapy provision for the approximately 12% of preschool children who present with early markers for Developmental Language Disorder (DLD). This systematic review and meta-analysis examined the effectiveness of caregiver-mediated spoken language interventions for under-fives at risk of DLD, and factors influencing intervention effectiveness. METHODS: A systematic review following PRISMA guidelines was conducted. Five electronic databases were searched to identify experimental studies comparing caregiver-mediated spoken language interventions to control conditions in under-fives presenting with risk factors for DLD. Risk factors included prematurity, socioeconomic factors, caregiver language development concerns, and formal or informal language screening or assessment scores. Twenty-six experimental studies with 1407 child participants were included in qualitative synthesis. Meta-analysis was performed on nine Randomised Controlled Trials involving 947 children. RESULTS: Effectiveness was examined for outcomes including child language gains, child wellbeing, inclusion and attainment. Meta-analysis indicated a significant effect of caregiver-mediated spoken language interventions on language outcomes compared to treatment-as-usual, non-language intervention or waitlist control conditions. Non-language outcomes were evaluated via qualitative synthesis. Interventions significantly improved language development trajectories for under-fives presenting with risk factors or early markers for DLD. CONCLUSION AND IMPLICATIONS: This review contributes to the growing evidence base demonstrating that caregiver-mediated interventions can positively impact language development and wellbeing outcomes for children under five at risk of DLD. These findings support the implementation of caregiver-mediated environmental language interventions in clinical practice to maximise accessibility and cost-effectiveness while delivering optimal outcomes for vulnerable populations. WHAT THIS PAPER ADDS: What is already known on this subject Previous research on caregiver-mediated spoken language interventions has highlighted gaps in the evidence regarding the impact of risk factors, demographic characteristics, dosage and intervention components on child language outcomes. Developmental Language Disorder has relatively high population prevalence, estimated at 7%. Prevalence is associated with risk factors including low household socioeconomic status (SES), prematurity and late language emergence. In contrast to its prevalence, there is low public and professional awareness of DLD and a low diagnostic rate. Therefore, a strengthened evidence base and additional insights into the factors affecting success of family-based interventions is important in order to increase the effectiveness of service provision and care planning for this underserved population. Timely and effective intervention with young children presenting with early markers for DLD has the potential to offer lifelong improvement to their wellbeing, inclusion and attainment outcomes. Recent systematic reviews of the effectiveness of caregiver-mediated language interventions had differences in population age range and diagnostic inclusion criteria. What this paper adds to existing knowledge Our review examines the effectiveness of caregiver-mediated early spoken language interventions on child language, attainment and wellbeing, and on caregiver self-efficacy and adherence to language support strategies. Our population was children under five presenting with risk factors for Developmental Language Disorder, in the absence of other neurodevelopmental or genetic conditions such as intellectual disability or autism. This review adds depth and detail to the evidence base supporting the effectiveness of caregiver-mediated spoken language interventions in improving outcomes for this population of young children, and factors that influence their success. What are the potential or actual clinical implications of this work? The high prevalence of Developmental Language Disorder, estimated at around 7% of the population, and the strong association with risk factors including low SES, prematurity and late language emergence, coupled with the low awareness of DLD and low diagnostic rate, mean that a strengthened evidence base and additional insights into the factors affecting success of family-based interventions can increase the effectiveness of service provision and care planning for this population. Timely and effective intervention in this group of young children has the potential to improve wellbeing and attainment outcomes across the lifespan. This review contributes to our understanding of how to implement cost-effective, socially valid and maximally engaging partnership working with families of young children at risk for DLD.

Humans

Weight and metabolic changes in patients with schizophrenia treated with paliperidone palmitate 6-month formulation versus paliperidone palmitate 3-month formulation: a post-hoc analysis.

OBJECTIVE: To determine the effect that paliperidone palmitate 6-month long-acting injectable formulation (PP6M) had on metabolic parameters including body weight (BW), and blood lipid profiles, a post-hoc analysis was conducted to assess changes in BW from baseline to the end of study based on age, body mass index (BMI), and changes in blood lipid profiles during a 12-month, phase 3, double-blind (DB) clinical study. Long term effects of PP6M on BW and BMI were further explored during a 24-month extension study in which participants were treated exclusively with PP6M. METHOD: In the 12-month DB phase, participants were randomized to receive PP6M or paliperidone palmitate 3-month long-acting injectable formulation (PP3M). The mean change in BW and abnormal weight percent change from baseline were calculated at endpoint by age, gender, and BMI. Additionally, treatment-emergent shifts from baseline for the four key lipid parameters (fasting low density lipoprotein [LDL], fasting triglycerides [TG], fasting total cholesterol [TC], and fasting high density lipoprotein [HDL]) during DB were assessed. Following this study, participants were given the opportunity to transition to a 24-month extension study and be treated with PP6M. The mean change and percent change in BW, and the mean change in BMI from DB baseline to the end of the extension study (36&#xa0;months total) were calculated. RESULTS: Participants who were treated with PP6M showed numerically less weight gain, BMI, waist circumference, and more weight decrease compared to PP3M group during 12-month DB phase, though the proportion of participants reporting an abnormal change (&#x2265;7% change) in BW did not significantly differ between PP3M and PP6M. The weight differences were more pronounced in the younger age group (18-25&#xa0;years) and those who were overweight (BMI: 25 to <30&#xa0;kg/m2. Numerical differences in favor of PP6M were found in fasting blood lipids (HDL, LDL, TG, and TC). The changes in BW and BMI over time remained consistent throughout the 24-month extension, favoring PP6M in each instance. CONCLUSIONS: This post-hoc analysis demonstrated that PP6M was comparable to PP3M in terms of metabolic parameters; however, it may have a beneficial effect on weight gain, especially in young patients. TRIAL REGISTRATION: Post-Hoc Analysis of Studies NCT03345342 and NCT04072575 (ClinicalTrials.gov). Significant outcomes The findings from this study have highlighted that participants who were treated with the 6-month long-acting injectable formulation of paliperidone exhibited less weight gain during treatment overall, and significantly less weight gain in adolescents and young adults. Importantly, this trend continued over the course of long-term treatment, regardless of age. Participants treated with the 6-month formulation also had fewer shifts in blood lipids outside of the normal range and had more favorable changes in body mass index and waist circumference. These results suggest that when considering metabolic dysregulation as a factor in choosing a long-acting injectable antipsychotic, the 6-month formulation is a viable alternative to the 3-month formulation, particularly in younger patients with schizophrenia. Limitations Because this is a post hoc analysis and the study was not powered to test weight and metabolic changes, most endpoints were summarized descriptively and the statistical test was limited to the main endpoint (abnormal percent weight gain and loss).

Adult

User Engagement and Feature Preferences in an AI-Powered mHealth Intervention for Diabetes Prevention: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Prediabetes is highly prevalent and increasing globally, yet lifestyle interventions remain underused. AI-driven mobile health (mHealth) tools can help scale diabetes prevention efforts, but the key factors driving their success are not well understood. OBJECTIVE: This post hoc secondary analysis of a randomized controlled trial (RCT) aimed to characterize the most valued features and the role of user engagement in outcomes of a fully automated mHealth intervention for diabetes prevention. METHODS: Data from 151 participants with prediabetes and overweight or obesity who were assigned to an AI-based diabetes prevention program (Sweetch) in a parent RCT (NCT05056376) were analyzed. Engagement (defined as the total number of days the app was used) was categorized into tertiles (low, medium, and high). Baseline characteristics were compared across engagement groups using ANOVA, Kruskal-Wallis, and chi-square tests, and regression models assessed the association between engagement and achievement of diabetes risk reduction outcomes (&#x2265;5% weight loss, &#x2265;4% weight loss with &#x2265;150 min/week of physical activity, or &#x2265;0.2 percentage point reduction in hemoglobin A1c [HbA1c] at 12 months). Perceived usefulness of intervention features was surveyed at 12 months. RESULTS: Median engagement was 98 (IQR 34-232) days. Older age (P<.001) and lower baseline BMI (P=.04) were significantly associated with higher engagement. Compared with low engagement, high engagement was associated with greater odds of achieving the composite diabetes risk reduction outcome (odds ratio [OR] 2.59, 95% CI 1.11-6.01; P=.03), &#x2265;5% weight loss (OR 3.31, 95% CI 1.16-9.42; P=.03), and &#x2265;0.2 percentage point reduction in HbA1c (OR 3.57, 95% CI 1.19-10.75; P=.02). Participants most frequently rated weight tracking, physical activity tracking, and the digital body weight scale as the features that were most helpful for achieving their health goals. CONCLUSIONS: Higher engagement with an AI-driven intervention requiring no human intervention was associated with improved diabetes risk reduction. Contrary to concerns about lower digital literacy, older adults engaged with the intervention more than younger adults. Features related to weight and physical activity tracking were most valued by patients in the program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05056376; https://clinicaltrials.gov/study/NCT05056376.

Humans

Flavoromics-based profiling reveals taste and aroma differences between infant formula and breast milk.

Flavor differences between infant formula (IF) and breast milk (BM) are considered a potential factor affecting infants' acceptance of IF. This experiment employs flavoromics combined with multivariate statistical analysis to systematically compare the flavor profiles of IF and BM. Electronic tongue analysis and amino acid correlation revealed that IF was characterised by pronounced saltiness and umami richness, whereas BM exhibited greater bitterness and astringency. Volatile compound profiling identified five key flavor constituents in IF, predominantly aldehydes such as hexanal and pentanal. In contrast, BM contained a broader array of compounds-including acids, aldehydes, and esters-resulting in a more complex flavor profile. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based metabolic pathway annotation, together with fatty acid profiling, suggested that some volatiles may be associated with lipid oxidation, Maillard reaction and sulfur-containing amino acid degradation pathways, offering a theoretical basis for the targeted optimisation of IF flavor.

Humans

Exploring precision risk in pediatric vesicoureteral reflux: Innate immune gene variations and reflux outcomes in the RIVUR cohort.

INTRODUCTION: Children with vesicoureteral reflux (VUR) are at increased risk for morbidity from recurrent urinary tract infections (UTIs), yet the factors influencing spontaneous VUR resolution remain poorly defined. This study evaluates whether genetic variations in key urinary innate immune effectors (DEFA1A3, DMBT1, and RNASE7) influences VUR resolution and interacts with prophylaxis to alter clinical response. METHODS: We conducted a secondary analysis of 303 RIVUR participants with available DEFA1A3 and DMBT1 copy number variation (CNV) data and RNASE7 rs1263872 genotype. Primary outcomes were (1) VUR improvement (decrease in grade) and (2) VUR resolution at study exit. Multivariable logistic regression models included genotype, treatment, and their interactions, adjusting for age, sex, baseline grade (high vs low), laterality, bowel/bladder dysfunction, and any UTI. Internal validation used 2000-sample bootstrap with bias-corrected and accelerated confidence intervals and influence diagnostics. RESULTS: Clinical covariates did not significantly predict VUR improvement. Children with DEFA1A3 CNV >5 had higher odds of improvement (OR 2.36, 95% CI 1.12-4.96, p = 0.023), an effect that remained significant in bootstrap analyses. High-grade VUR was associated with lower odds of resolution (OR 0.34, 95% CI 0.12-0.94, p = 0.038). A significant interaction was observed between prophylaxis and high DMBT1 copy number for VUR resolution (interaction OR 2.99, 95% CI 1.11-8.04, p = 0.031); no interaction was seen for improvement. RNASE7 rs1263872 was not associated with either outcome. CONCLUSION: Innate immune gene variation may contribute to heterogeneity in VUR outcomes. High DEFA1A3 copy number was associated with reflux improvement and a DMBT1-prophylaxis interaction was associated with reflux resolution. The results of this study is hypothesis-generating and prompt further evaluation to assess whether a subset of children may experience structural benefit from prophylaxis or have a more favorable natural history based on their innate immune genotype.

Humans

Advances in cereal protein applications for infant and Young child nutrition.

BACKGROUND: The increasing use of plant-derived proteins in infant and young child nutrition necessitates tailored amino acid profiles, high digestibility and strict safety controls. Cereal proteins, such as rice, oat, maize, millet, barley, and wheat, are widely used in complementary foods but face intrinsic limitations, notably lysine and tryptophan deficits, antinutritional factors that reduce bioavailability, gluten immunogenicity in wheat/barley, and inorganic arsenic risks in rice. SCOPE AND APPROACH: This review synthesizes recent advances in processing and formulation strategies, including enzymatic hydrolysis, fermentation, germination, extrusion, cereal-legume complementation, and micronutrient fortification. Their impacts on digestibility, techno-functionality, iron and zinc bioavailability, and protein quality, including Protein Digestibility-Corrected Amino Acid Score (PDCAAS) and Digestible Indispensable Amino Acid Score (DIAAS) are critically reviewed using data from in vitro assays, product development, and clinical trials. KEY FINDINGS AND CONCLUSIONS: Processing and blending approaches can substantially improve protein digestibility, amino acid balance and micronutrient availability, and hydrolyzed rice protein holds clinical promise for cow's milk protein allergy (CMPA). However, most evidence is preclinical, reporting of protein quality is inconsistent, and industrial translation is constrained by sensory, shelf-life, contaminant and cost issues. We recommend standardized DIAAS-based reporting, large-scale feeding trials, sensory /stability optimization, and targeted exploration of underutilized grains (e.g., oat, millet) with active allergen monitoring. Prioritizing amino acid-focused formulation coupled with strategies to enhance micronutrient bioavailability will accelerate safe adoption of cereal proteins in early-life nutrition.

Humans

Prevalence of Breastfeeding in Infants With Down Syndrome: A Systematic Review and Meta-Analysis.

AIM: To estimate the prevalence of breastfeeding-overall, exclusive, partial and depending on infants' age-in infants with Down syndrome, and to investigate associated factors. METHODS: A systematic literature search was conducted in Medline, Cochrane Library, Web of Science, Embase, CINAHL and SciELO up to 1 August 2024. Original articles that estimated the prevalence of breastfeeding in infants with Down syndrome, written in French, English or Spanish, were included. Study quality was assessed using the Joanna Briggs Institute (JBI) scale. Meta-analyses were performed for breastfeeding outcomes and meta-regression explored heterogeneity. The review was registered in PROSPERO (CRD42021278019). RESULTS: Twenty-six studies (3463 infants) were included. The estimated prevalence of overall breastfeeding regardless of duration was 71.6% (95% CI [60.3; 80.7]; 25 studies, 3351 infants) with high heterogeneity, I2&#x2009;=&#x2009;94%. The estimated prevalence of exclusive breastfeeding was 38.4% (95% CI [22.4; 57.3]; 10 studies, 1099 infants). No factor assessed in meta-regression was significantly associated with overall breastfeeding. CONCLUSION: The estimated breastfeeding prevalence in infants with Down syndrome is similar to that reported in the general population, despite high heterogeneity. Further studies using standardised methodology to assess breastfeeding barriers and facilitators in the context of Down syndrome would allow us to improve support for breastfeeding.

Humans

Congenital Laryngomalacia: Pathophysiology, Clinical Spectrum, and Holistic Management.

Congenital laryngomalacia is the most common cause of infant stridor and arises from interacting structural, neuromuscular, and inflammatory mechanisms that produce dynamic supraglottic collapse. Disease severity spans mild stridor to significant obstruction, aspiration, and failure to thrive, often influenced by comorbid medical conditions. Diagnosis relies on flexible laryngoscopy supported by instrumental swallowing studies and microdirect laryngoscopy and bronchoscopy when indicated. Most infants respond to conservative management, particularly targeted feeding modifications, while acid suppression offers benefit in selective cases. Supraglottoplasty provides effective, durable improvement for severe disease and significantly enhances infant outcomes and family quality of life.

Humans