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Paediatric penile length: a systematic review and meta-analysis.

OBJECTIVE: To assess geographical variation in stretched penile length among prepubertal boys and evaluate temporal trends over the past two decades, as defining reference values for genital organ size remains crucial for early identification of development disorders. METHODS: The PubMed, Cochrane and Scopus databases (no deadlines for publishing were imposed) were searched according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Five authors independently extracted individual participant data and assessed the risk of bias. Studies with quantitative penile lengths were included; those involving congenital malformations were excluded. The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (registration number CRD42022335643). RESULTS: A total of 55 studies from 2000 to 2024 were evaluated, including data from 31&#x2009;915 boys. Pooled mean stretched penile length estimates were 3.07&#x2009;cm (95% confidence interval [CI] 2.88-3.26&#x2009;cm) for the 1-week-old boys, 3.73&#x2009;cm (95% CI 3.53-3.93&#x2009;cm) for the 1-year-old boys, 4.69&#x2009;cm (95% CI 4.49-4.88&#x2009;cm) for the 2-5&#x2009;year-old boys, and 5.43&#x2009;cm (95% CI 5.20-5.66&#x2009;cm) for the 5-10&#x2009;year- old boys. When comparing data from the 2000s to the 2020s, stretched penile length decreased by 16.2% (from 3.46 to 2.90&#x2009;cm), 16.3% (from 4.17 to 3.49&#x2009;cm), 21.5% (from 5.31 to 4.17) and 26.2% (from 6.46 to 4.77&#x2009;cm) in the 1-week-old, 1-year-old, 2-5-year-old and 5-10-year-old boys, respectively. Subgroup analysis for those aged >2&#x2009;years showed significant variations by geographical region (P&#x2009;<&#x2009;0.001). CONCLUSIONS: The present study observed large variations in penile length across geographical regions and among prepubescent boys of different ages, while also suggesting a possible decline over the past two decades.

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Triggering modalities to synchronise non-invasive respiratory support in preterm infants: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence suggests that synchronised nasal intermittent positive pressure ventilation (sNIPPV) may be the optimal mode of non-invasive respiratory support. However, no comprehensive review of sNIPPV modes is available. This review aims to describe different synchronisation methods for sNIPPV and compare their effectiveness in clinical, physiological and technical outcomes with other modes of non-invasive respiratory support. METHODS: This review identified all clinical studies in preterm infants that compared sNIPPV to other non-invasive respiratory support modes or compared different trigger modalities between 1990 and 2026. A search was carried out in MEDLINE, Embase and the Cochrane Library. Main outcomes were categorised as clinical (eg, extubation failure (EF)), physiological (eg, breathing effort) and technical (eg, synchronisation rate). RESULTS: 49 studies (2864 infants) were included, with a low to moderate risk of bias. Meta-analysis showed a reduction in EF (risk ratio=0.38; 95%&#x2009;CI 0.17 to 0.85; p=0.03) in favour of sNIPPV compared with nasal continuous positive airway pressure (nCPAP). Physiological outcomes were significantly improved during sNIPPV compared with nCPAP and nasal intermittent positive pressure ventilation (NIPPV), especially breathing effort. When reviewing technical outcomes, non-invasive neurally adjusted ventilatory assist showed lower patient-ventilator asynchrony (PVA) (index ranging from 7% to 50%), a higher synchronisation rate (80%-99%) and a shorter trigger delay (35 ms) compared with other sNIPPV modes. CONCLUSIONS: This review shows that synchronising NIPPV results in consistent physiological (reduced patient effort) and technical benefits (reduced PVA). However, evidence on positive effects on (long-term) major clinical outcomes remains limited and requires further studies. PROSPERO REGISTRATION NUMBER: CRD420251022479.

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Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n&#xa0;=&#xa0;75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p&#xa0;=&#xa0;0.02 to p&#xa0;<&#xa0;0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

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Bipolar circumcision with mucocutaneous plane separation: A safe, precise, blood-sparing, dressing-free approach.

Conventional circumcision techniques may result in bleeding, limited control of the mucosal collar, and the need for dressings. We describe a modified bipolar technique enabling near-bloodless dissection with precise mucosal trimming. Following bipolar division of the preputial skin, the inner mucosa is separated using two forceps and retracted proximally, creating a protective plane for safe skin adjustment. The mucosal collar is trimmed with scissors. The wound is closed with sutures and 2-octyl cyanoacrylate, avoiding dressings. This technique has been performed in 55 consecutive cases (median age: 2 years and 2 months; range: 0 days-17 years and 5 months) with no reported complications over a median follow-up of 2 years and 7 months (range: 3 months-4 years and 1 month).

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Orthoplastic management of open calcaneal fractures: A systematic review of flap selection and complications.

BACKGROUND: Open calcaneal fractures are rare, high-energy injuries involving extensive soft-tissue loss and comminuted bone disruption. Successful management depends on coordinated orthoplastic reconstruction to achieve stable fixation and durable coverage. Multiple flap types have been described, yet comparative outcomes remain poorly defined. METHODS: A systematic review was performed in accordance with PRISMA guidelines (PROSPERO: CRD420251138394). MEDLINE, Embase, Cochrane CENTRAL, and Scopus were searched from January 2000 to July 2025. Studies reporting flap-based reconstruction for open calcaneal fractures in adults were included. Extracted data included flap type, fixation method, follow-up duration, and complications such as infection, necrosis, vascular crises, flap loss, and amputation. RESULTS: Thirteen studies comprising 88 major flap reconstructions were analysed. Overall flap survival was 97.7%, with two failures (both muscle/myocutaneous). Fasciocutaneous flaps showed the lowest complication rates (8.3%) with no reported cases of infection, while muscle/myocutaneous flaps demonstrated cases of infection (20%) and accounted for both flap failures and the only reported amputation. Chimeric flaps were increasingly used in recent series (n&#x202f;=&#x202f;32), achieving reliable survival but higher vascular compromise (6.3%). Osteocutaneous flaps were rare (n&#x202f;=&#x202f;4) and primarily used for defects with bone loss, showing infection in 50% of cases. Meta-analysis was not possible due to heterogeneity and small sample sizes. CONCLUSIONS: Fasciocutaneous flaps provide reliable, low-complication coverage for clean wounds, while muscle flaps remain valuable for contamination or complex cases with extensive tissue loss. Chimeric, and osteocutaneous flaps show promise, but larger, standardised studies are needed to clarify their roles in hindfoot reconstruction.

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

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

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The neuroendoscopic factors affecting outcome of endoscopic third ventriculostomy in pediatric patients with post infectious hydrocephalus.

BACKGROUND: The role of endoscopic third ventriculostomy(ETV) in infective hydrocephalus remains uncertain. Infection alters cerebrospinal-fluid composition, flow-dynamics, absorptive capacity, undermining the effectiveness of ETV. AIMS AND OBJECTIVES: This study aims to describe the intraventricular morphological findings and its correlation with ETV outcomes in a cohort of paediatric infective hydrocephalus. METHODOLOGY: Total 98 cases of infective HCP underwent ETV, were studied for intraventricular findings. Thin transparent third ventricular floor were considered as type-1, transluscent as type-2, floor with granuloma as type-3 and unidentifiable anatomy as type-4. Infective deposits were sent for histopathology. RESULT: Overall ETV was successful in 46 patients (46.93%). Success rate of ETV in type 1 (72.7%) was better than type-2 (50%) and type-3 (33.3%). The difference between type-1 and type-3 was statistically significant, p&#xa0;=&#xa0;0.01. The success rate in presence of pre-pontine adhesions (46 cases) was 34.7%, significantly lower than the 66.6% observed in their absence (p&#xa0;=&#xa0;0.005). ETV was not successful in all the 7 cases withy type-4 floor. Tissue biopsy confirmed microbiological diagnosis in 13 cases and helped in modifying pharmacological treatment as per culture (two with tuberculosis and three with fungal infection). CONCLUSION: ETV offers a meaningful therapeutic option in post-infectious HCP. Endoscopic appearance of the third ventricular floor and the pre-pontine space may predict its outcome. A thin, transparent floor in the absence of cisternal adhesions is associated with best outcomes, while progressive floor thickening, granuloma formation, and pre pontine fibrosis each correlate with declining success rates. The culture from exudates often helps in achieving organism oriented pharmaco-therapy that improves ETV success rate.

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Obstructive sleep apnea and idiopathic intracranial hypertension: a systematic review and meta-analysis.

OBJECTIVE: To determine the pooled prevalence of obstructive sleep apnea (OSA) among adults with idiopathic intracranial hypertension (IIH) using polysomnography (PSG) and the Berlin Questionnaire screening. NATURE: IIH is a vision-threatening disorder characterized by elevated intracranial pressure. OSA shares overlapping risk factors and pathophysiological mechanisms with IIH, including nocturnal hypoxia and hypercapnia. Clarifying OSA prevalence in IIH is clinically important for diagnosis and management. METHODS: For this prospectively registered systematic review and meta-analysis (PROSPERO: CRD420251132794), we searched MEDLINE, Embase, and CENTRAL from inception to August 23, 2025, for studies reporting PSG-confirmed OSA or Berlin Questionnaire positivity in adults with IIH. Risk of bias was assessed using ROBINS-I and RoB-2, and certainty of evidence was checked using the Grading of Recommendations, Assessment, Development and Evaluation tool. Random-effects meta-analyses of proportions generated pooled prevalence estimates. Subgroup analyses excluded high-risk studies, leave-one-out analyses assessed robustness, and funnel plots evaluated publication bias. RESULTS: Eleven studies met the inclusion criteria. Across 9 PSG-based studies (n&#x202f;=&#x202f;299), the pooled prevalence of OSA in IIH was 0.44 (95% CI: 0.26-0.63; I&#xb2;&#x202f;=&#x202f;90.5%). Leave-one-out analyses showed stable results (39%-50%). Excluding high-risk studies (4 studies; n&#x202f;=&#x202f;132) yielded a pooled prevalence of 0.53 (95% CI: 0.32-0.74). Four Berlin Questionnaire studies (n&#x202f;=&#x202f;154) showed a pooled prevalence of 0.65 (95% CI: 0.54-0.74; I&#xb2;&#x202f;=&#x202f;0%). Funnel plot asymmetry suggested publication bias, and certainty of evidence was very low. CONCLUSIONS: OSA is common among patients with IIH, supporting routine objective sleep evaluation. Prospective studies are needed to clarify this association.

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Evaluating the persistence of semen under controlled environmental conditions.

When semen is deposited at a crime scene, it may be exposed to harmful environmental conditions. It is important to understand to what extent the different components of semen, specifically acid phosphatase (AP), prostate specific antigens (PSA), sperm and DNA, may become less detectable after exposure to high temperatures and varying levels of humidity. In this study, semen (50&#xa0;&#x3bc;L) was deposited onto squares of black cotton and exposed to 45&#xa0;&#xb0;C and a relative humidity (RH) of 10 or 80% for 0, 7, 14, 21 or 28&#xa0;days (n&#xa0;=&#xa0;5 per day, per climate condition). Source testing included AP test reagent, ABAcard&#xae; p30 immunoassay kits, and hematoxylin and eosin staining. DNA was extracted using the DNA IQ&#x2122; System (Promega, Australia) and quantified using Quantfiler Trio&#x2122; (Thermo Fisher Scientific, Australia). Over the 28-day period under both RH conditions, the time taken for a positive AP test to develop increased significantly (p&#xa0;<&#xa0;0.01) and the number of sperm observed decreased significantly (p&#xa0;<&#xa0;0.01). All ABAcard&#xae; p30 tests were positive regardless of exposure time or conditions. No impact on the quantity of DNA recovered was observed when semen was exposed to 45&#xa0;&#xb0;C and 10% RH, with a higher median quantity of DNA recovered at day 28 compared to day 0. In contrast, when the RH was raised to 80%, the median quantity of DNA recovered was substantially less at day 28 (81.5&#xa0;ng, IQR: 87.5&#xa0;ng) compared to day 0 (181.5&#xa0;ng, IQR: 1172.4&#xa0;ng). This study highlights the impact that temperature and RH may have on the persistence of AP, PSA, sperm and DNA over time.

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Donor Human Milk Utilization in a Level 1 Newborn Unit of a High-Volume Delivery Hospital: A Cautionary Tale.

INTRODUCTION: Donor human milk (DHM) is an alternative to formula for supplementation of breastfed newborns and has been associated with higher in-hospital exclusive breast milk feeding rates. Its use has increased substantially, most recently among term newborns, yet there is scarce data to describe patient characteristics and volumes administered. We aimed to characterize DHM utilization in our level 1 nursery. METHODS: We conducted a retrospective cross-sectional study of newborns discharged in 2022 from the level 1 nursery. Variables included sex, gestational age, birth weight, delivery type, hypoglycemia diagnosis, DHM volume, and length of stay. DHM use was compared across preferred language, race, ethnicity, and payer type using chi-square testing. RESULTS: A total of 10,432 discharges were reviewed-those transferred to Neonatal Intensive Care Unit (NICU) or another unit were excluded. Of 9,074 newborns receiving level 1 care, 1,094 (12.1%) received DHM. Newborns born between 35 and 37 weeks gestation, delivered by cesarean section, or diagnosed with hypoglycemia or small for gestational age were more likely to receive DHM (p < 0.05). DHM was also more common among newborns whose birth parent preferred the English language, identified as White or non-Hispanic, or had non-Medicaid insurance (p < 0.05). 6,552.6 ounces were consumed, with a total median of 3.9 ounces per newborn (dose range 2-50 mL). CONCLUSIONS: DHM use in the level 1 nursery varied by clinical and sociodemographic factors, revealing inequities. In addition, some doses exceeded recommended supplemental volumes. Future efforts should focus on ensuring equitable access to DHM, standardized dosing and discontinuation guidelines, and evaluation of impacts on exclusive breastfeeding rates.

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Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 &#xd7; 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

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Meniscal preservation in the age of biologics: toward a quantitative decision algorithm for personalized repair.

BACKGROUND: Despite advances in arthroscopic repair and biologic augmentation, surgical indication for meniscal tears remains heterogeneous. No standardized framework currently integrates biomechanical, clinical, and biological determinants to guide repair versus resection. PURPOSE: To develop a quantitative decision model-the Meniscal Preservation Score (MPS)-that unifies biomechanical and biological evidence to stratify reparability potential and standardize treatment selection in meniscal surgery. METHODS: A systematic evidence synthesis conducted in accordance with PRISMA 2020 reporting standards of studies published from 2000 to 2025 in PubMed, Embase, and Scopus identified key determinants of meniscal healing. Five consistent predictors-patient age, vascularity, tear morphology, associated pathology, and activity profile-were weighted through a two-round modified Delphi consensus among ten experienced knee surgeons. The resulting 0-9-point MPS was incorporated into a stepwise decision tree linking lesion morphology, biological context, and surgical strategy. Conceptual validation used 50 simulated cases and a retrospective cohort of 45 patients to test agreement between algorithm recommendations and expert surgical decisions. RESULTS: The MPS achieved 86% concordance with expert judgment in simulation and 84% agreement in clinical validation. In this retrospective exploratory cohort, cases in which surgical management was concordant with MPS recommendations demonstrated higher mean IKDC scores at 24&#xa0;months and lower observed reoperation rates. These findings should be interpreted as associative rather than causal, as treatment allocation was not controlled and discordant cases may have represented inherently more complex pathology. CONCLUSION: The MPS represents an evidence-informed decision-support framework designed to systematize reparability assessment. While exploratory analyses suggest structural coherence with expert reasoning, prospective implementation and external validation are required before clinical adoption as a predictive tool. LEVEL OF EVIDENCE: conceptual model with exploratory validation.

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Outcomes of patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications.

OBJECTIVE: This post hoc analysis of the phase 3b JUMP trial evaluated addition of anemia-supporting medications to ruxolitinib in patients with myelofibrosis and anemia. METHODS: 101 patients with baseline hemoglobin <12.0&#x2009;g/dL initiated an erythropoiesis-stimulating agent (ESA) or danazol <3&#x2009;months post-enrollment and maintained ESA/danazol &#x2265;3&#x2009;months; 97% initiated ESAs. Patients enrolled in JUMP who had hemoglobin <12.0&#x2009;g/dL but did not initiate ESAs/danazol within 3 months were evaluated as an unmatched comparator. Total JUMP population data were also analyzed for spleen length (&#x2265;50% reduction from baseline) and symptom response (&#x2265;6.5-point improvement in FACT-Lym score). RESULTS: Baseline characteristics were similar to comparator JUMP patients (no ESAs/danazol within 3&#x2009;months, n&#x2009;=&#x2009;1242). Mean total daily ruxolitinib dose remained >25&#x2009;mg. Week 24 spleen length response was achieved by 37% of patients; 26% achieved symptom response, similar to the comparator population (28% and 26%, respectively) and comparable to the total JUMP population (N&#x2009;=&#x2009;2233). Outcomes were similar between the hemoglobin <12.0&#x2009;g/dL analysis population and patients with baseline hemoglobin <10.0&#x2009;g/dL (n&#x2009;=&#x2009;52). In all groups, hemoglobin levels increased after Week 4 following an expected initial decrease. DISCUSSION: This analysis suggests that patients treated with ruxolitinib and anemia-supporting care continued to receive optimal ruxolitinib dosing; spleen-length and symptom response rates in these patients were comparable to the overall JUMP population, the majority of whom did not have anemia. CONCLUSION: Results support use of anemia-supporting medications with ruxolitinib and may allow maintenance of ruxolitinib dose intensity in patients with myelofibrosis and anemia.

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Culturally adapted post-diagnostic dementia support for South Asian people living with dementia and caregivers: a rapid review.

BACKGROUND: The number of minority ethnic people living with dementia (PLWD) in the UK is predicted to rise to 50 000 by 2026 and 172 000 by 2051. As the global population ages, there is a greater need to develop culturally appropriate post-diagnostic support for PLWD from minority ethnic backgrounds. METHODS: A rapid review was conducted of culturally adapted post-diagnostic dementia support for South Asian people with dementia and carers. Eight electronic databases were searched from inception until 16 September 2025. Databases included Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, MEDical Literature Analysis and Retrieval System Online, Psychological Information, Turning Research Into Practice, Allied and Complementary Medicine Database, Social Policy and Practice and the Cochrane Database of Systematic Reviews. Two reviewers independently screened the studies. Consistent with rapid review methods, no formal quality assessment of included studies was undertaken. The rapid review adhered to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. RESULTS: Twelve studies were included. These included seven carer support programmes focusing on raising awareness and education on dementia and care. These interventions increased carers' knowledge of dementia and confidence in caregiving. Four studies reported on psychosocial interventions: Cognitive Stimulation Therapy, Cognitive Behaviour Therapy and Meditation Therapy, demonstrating benefits for caregiver burden and mental health. One study reported on service-level innovations through a South Asian link nurse, which improved access to services and facilitated the development of culturally appropriate information materials. CONCLUSION: The findings of this rapid review demonstrate the feasibility and perceived value of culturally sensitive psychoeducation, carer training and psychosocial interventions. However, research remains small-scale, methodologically limited, with little focus given to interventions directly supporting PLWD.

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Lower-limb electromyographic responses across four recumbent cycling configurations in healthy young men.

Recumbent cycling provides an adjustable configuration in which backrest angle and crank-axis height can alter lower-limb loading. Backrest angle changes the orientation of the active musculature relative to gravity, whereas crank-axis height modifies the foot-pedal interface and the ankle lever arm. Whether such positioning is associated with differences in lower-limb electromyographic (EMG) activation across both factors together has not been examined. Using a randomized crossover design, fifty-nine healthy young men cycled at 100&#xa0;W and 50&#xa0;rpm under four conditions combining two backrest angles (30&#xb0;, 75&#xb0;) and two crank-axis heights (Rh, high, 77&#xa0;cm; Rl, low, 45&#xa0;cm). Surface EMG from the rectus femoris (RF), biceps femoris (BF), and gastrocnemius medialis (GAS) was analyzed for root mean square (RMS) amplitude, absolute onset sequence, and relative recruitment timing (%Sequence, derived using Telescan software and referenced to RF). RMS amplitude did not differ across conditions for any muscle (all p&#xa0;&#x2265;&#xa0;0.356), and absolute onset sequence showed no condition effect (all p&#xa0;&#x2265;&#xa0;0.197). For GAS %Sequence, the Greenhouse-Geisser-corrected omnibus test was significant (F(1.32, 76.56)&#xa0;=&#xa0;28.45, p&#xa0;<&#xa0;0.001), driven by a within-30&#xb0; contrast in which %Sequence was lower under Rl than Rh (paired t(58)&#xa0;=&#xa0;10.39, Holm-adjusted p&#xa0;<&#xa0;0.0001; mean difference 22.0 percentage points, 95&#xa0;% CI [17.8, 26.3]; dz&#xa0;=&#xa0;1.35). Because %Sequence is referenced to RF, this exploratory shift should be interpreted cautiously. Lower-limb activation may be constrained by the closed-chain nature of pedaling, whereas distal recruitment timing may be sensitive to crank-axis height and the foot-pedal interface.

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A retrospective population-based cohort study to assess outcomes, time to complications and cost of follow-up care following pediatric pyeloplasty in Ontario, Canada (2002-2016).

PURPOSE: Pediatric dismembered pyeloplasty (PP) is the gold standard surgery for uretero-pelvic junction obstruction (UPJO) in children. However, there is no consensus regarding the duration and methods of providing follow-up care after PP. This study aims to assess the rate of redo-interventions following PP and to define the ideal follow-up care following PP. MATERIALS AND METHODS: This is a retrospective population-based cohort study including all PP patients in Ontario between April 2002 and March 2016 using routinely collected data, with a minimum 5-year follow-up. Baseline variables included demographics, surgical approach, laterality and surgeon experience. The primary outcome was time to secondary surgical intervention, including redo PP. Secondary outcomes included costs of follow-up care and rates of early ER visits. Regression analyses were preformed to predict need for secondary intervention 2-years post PP, including independent variables: age, sex, surgical approach and early complication. RESULTS: The study included 1049 patients with a median age of 2 (IQR 0-7) years. Of the 13.6% of patients who had at least one secondary intervention following PP (including 3.8% who underwent a redo PP), 90.2% occurred within 3-years of PP. The median cost/patient of follow up care was $1472 CAD (IQR $292-$31,133). Regression analysis did not reveal any predictors of delayed secondary intervention. CONCLUSIONS: This study demonstrates that over 86% of PP are completed successfully, with a 3.8% rate of redo-PP. The majority of secondary interventions for post-PP complications occur within 3 years post-PP. Variability in duration and cost of follow-up care post- PP should be addressed to minimize costs, and a minimum 3-years follow-up after PP is recommended.

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The burden of male breast cancer (MBC) in the GBD Central, Eastern, and Western Europe Regions from 1990 to 2023: Results from the Global Burden of Disease Study 2023.

PURPOSE: Male breast cancer (MBC) is underrepresented in cancer statistics: this study aimed to assess the burden of MBC in Central, Eastern, and Western Europe from 1990 to 2023, using data from the Global Burden of Disease (GBD) Study 2023. METHODS: Estimates from GBD 2023 were analyzed to determine the MBC incidence, mortality, and disability-adjusted life years, their all-ages and age-standardized rates, and the 1990 through 2023 annual percent change. These estimates were compared to those for the GBD Super Regions and the Socio-Demographic Index quintile countries. RESULTS: In Central Europe, age-standardized incidence rates (ASIR) increased from 0.54 (0.40-0.76) to 1.05 (0.70-1.52), age-standardized mortality rates (ASMR) from 0.29 (0.25-0.34) to 0.40 (0.36-0.45), and age-standardized disability life-year rates (ASDR) from 7.19 (6.15-8.41) to 9.63 (8.52-11.07). In Eastern Europe, ASIR remained relatively stable, changing from 0.81 (0.56-1.19) to 0.60 (0.38-0.92), whereas ASMR decreased from 0.40 (0.33-0.49) to 0.21 (0.16-0.25) and ASDR from 10.54 (8.69-12.89) to 5.55 (4.52-6.85). In Western Europe, ASIR increased from 0.47 (0.33-0.67) to 0.88 (0.59-1.24), whereas ASMR (0.22 [0.19-0.25] vs. 0.24 [0.21-0.27]) and ASDR (5.20 [4.49-5.97] vs. 5.75 [4.96-6.66]) remained stable. CONCLUSIONS: The burden of MBC is increasing across Europe, particularly in the Central region, with huge regional differences. Population growth and variations over time impacted on the metrics. Even with a composite European scenario, the mortality-to-incidence ratio markedly declined in the three areas.

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Genome-Wide Impact of Human DBR1 Depletion on RNA Processing Networks Reveal a Connection Between Pre-mRNA Splicing, mRNA Surveillance and Stress Granule Dynamics.

The RNA lariat debranching enzyme DBR1 is essential for intron turnover and RNA metabolism, yet its broader impact on transcriptome regulation remains incompletely defined. To elucidate the consequences of DBR1 depletion, we performed transcriptome-wide RNA sequencing of DBR1-knockdown and wild-type HEK293 cells. Differential expression analysis revealed widespread perturbations in pathways linked to RNA splicing, mRNA surveillance, translational control, and stress-granule biology. Many of the most significantly altered transcripts encode splicing factors and RNA quality-control components, underscoring DBR1's influence on post-transcriptional regulation. Alternative splicing analysis showed changes across multiple event types, with exon skipping accounting for >50% of events, followed by mutually exclusive exons, alternative 5' and 3' splice sites, and retained introns, indicating that DBR1 depletion induces pervasive splicing defects. Direct spliceosome inhibition using isoginkgetin (blocks tri-snRNP recruitment) and pladienolide B (targets SF3B1) reproduced the DBR1-KD mis-splicing patterns of cell signaling genes and factors involved in RNA metabolism, supporting a functional link between DBR1 activity and alternative splicing. Notably, DBR1 knockdown revealed a subset of transcripts that are both NMD-sensitive and enriched within stress granules. Consistent with this observation, G3BP1 immunopurification and confocal microscopy further support a role for DBR1 and UPF1 in stress-granule dynamics, suggesting that these factors may participate at distinct stages to influence mRNA fate under stress conditions. Together, these findings indicate that DBR1 functions beyond lariat RNA turnover as a common regulator of RNA processing, transcriptome stability, and stress granule homeostasis, revealing intricate crosstalk between RNA splicing and RNA quality control pathways in human cells.

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