X-chromosomal short tandem repeats (X-STRs) are informative genetic markers in kinship testing and specific forensic contexts, particularly when standard autosomal approaches are less informative. This study aimed to provide preliminary allele frequency, haplotype diversity, and linkage disequilibrium (LD) data for 12 X-STR loci in a sample from Türkiye. A total of 136 unrelated individuals from Türkiye were genotyped for 12 X-STR loci. Inferential analyses of X-linked loci require diploid genotypes; therefore, allele frequencies, Hardy-Weinberg equilibrium (HWE), LD, and regional comparisons were based primarily on female samples (n = 115), whereas male haplotypes (n = 21) were summarized descriptively only. Female regional subgroup sizes were uneven (southeast Anatolia, n = 39; Marmara, n = 22; Central Anatolia, n = 14; Mediterranean, n = 13; Black Sea, n = 10; Aegean, n = 9; eastern Anatolia, n = 8). Forensic parameters, HWE exact tests, and pooled and region-stratified LD analyses were calculated using Bonferroni-adjusted thresholds; findings were interpreted cautiously given the modest overall sample size and subgroup imbalance. All loci were polymorphic, and locus-level forensic efficiency measures were generally high, with DXS10135 showing the highest informativeness in this dataset. In the female sample, five loci deviated from HWE after Bonferroni correction. In pooled LD analysis, only two of 66 locus pairs remained significant after correction (DXS10146-DXS10134 and DXS8378-DXS10103), whereas no region-specific LD signal remained significant after multiple-testing adjustment. Male haplotype diversity estimates were high across linkage groups, but these estimates were based on a small male subset and should be considered exploratory. This study provides a preliminary X-STR dataset for a sample from Türkiye and suggests that the analyzed panel is informative at the locus level. However, the modest sample size, very limited male subset, uneven regional distribution, and genotype-handling assumptions restrict population-level inference and generalizability. The data may be useful as an initial local reference resource, but broader and more balanced sampling is required before making strong conclusions about national allele distributions, regional structure, or routine forensic implementation.
This case series aims to report preliminary clinical experience in treating plantar heel pain with stromal vascular fraction (SVF) derived from adipose tissue. Four representative cases are presented. The patients were treated with a single injection of stromal vascular fraction obtained through mechanical processing of each patient's adipose tissue. Each patient was followed up for up to 360 days after treatment. Pain was evaluated with the visual analog scale (VAS), and ultrasound (US) examination was performed at baseline and six months after treatment. A significant improvement in the VAS scale was observed in all patients within seven days. This improvement was maintained for up to 360 days. This is the first report on the treatment of plantar heel pain with SVF. These initial cases showed promising results in terms of fast and durable pain resolution. A larger clinical series is currently underway to confirm these preliminary data.
Regional anaesthesia in the emergency department requires reliable techniques with minimal complications. We describe a subdeltoid ultrasound-guided brachial plexus approach targeting a potential "nerve funnel" at the surgical neck of the humerus, bridging infraclavicular and axillary approaches. Cadaveric dissection explored its anatomical basis and correlated it with clinical sonographic findings. This retrospective case series included six adult patients with traumatic upper-limb injuries. Cadaveric observations suggested terminal nerve clustering and proximity of the musculocutaneous and intercostobrachial nerves at the subdeltoid level. All patients achieved adequate anaesthesia with a single 15 mL injection of 0.5% bupivacaine with 4 mg dexamethasone. The mean pain-free duration was 17.3 hours, with consistent tourniquet tolerance and no procedural complications. The subdeltoid approach appears feasible as a single-injection technique for upper-limb procedures. Using a superficial acoustic window and favourable anatomical clustering, it may provide effective coverage with technical simplicity. These preliminary findings require validation in larger prospective studies.
Dental hypersensitivity (DH) is a common clinical condition characterized by brief, intense pain. This condition is treated with fluoride-containing specialized dental gels. The effect of calcium ions present in saliva and pH of the oral cavity are indicated as factors affecting their clinical performance. In the presented study, two dental desensitizing gels were evaluated. Fourier Transform Infrared Spectroscopy (FTIR) spectra of the gels were registered and analyzed. Measurement of concentration of measurable free fluoride ions and pH in vitro assessment was performed using selective electrodes. Measurement with addition of TISAB witch CDTA was performed to evaluate the amount of fluoride bound within the gel matrix. Univariate and multifactorial ANOVA tests were used to analyze acquired results of measurable free fluoride in twelve distinct incubation solutions. The highest values of free, measurable fluoride were obtained after addition of TISAB with CDTA. However, in physiological study without ionic strength adjuster and chelator, the highest free, measurable fluoride observed in the artificial saliva solutions was 1,043 ppm for the SensiKIN desensitizing gel at pH 4.5 in the solution without calcium ion addition. The lowest value (658 ppm) was denoted for the Teeth Desensitiser TD gel at pH 7.0 with calcium ion addition. The presented amounts of fluoride pertain to measurable free fluoride in solution. It has been shown that the presence of calcium in saliva reduces the concentration of measurable free fluoride in solution (by as much as 137 ppm). Although the effect of presence of Ca2+ is pronounced, the initial pH remains the most significant variable. Observed levels of measurable free fluoride in solution might reflect initial and preliminary bioavailability under static in vitro conditions. Measurable free fluoride may serve as an indirect analytical proxy for potentially available fluoride under the tested in vitro conditions. However, it does not represent direct biological or clinical bioavailability. The evaluated desensitizing gels showed maximal free, measurable fluoride concentration under acidic conditions. For studies incorporating TISAB/CDTA, the most profound effect on F- concentration was gel composition. Future formulation studies could investigate whether calcium- complexing or buffering components influence measurable solution-phase free fluoride under standardized in vitro conditions.
This pilot study aims to evaluate the preliminary effects and feasibility of the Vestibular Infant Screening - Rehabilitation (VIS-REHAB) protocol, a structured Vestibular Rehabilitation Therapy (VRT) program combining postural and gaze stability exercises, in children with peripheral vestibular dysfunction. Four children (aged 4-14 years) with peripheral vestibular dysfunction were recruited from the Ghent University Hospital and enrolled in a two-parallel-group randomized controlled crossover trial comparing the VIS-REHAB protocol with a no-therapy control. The VIS-REHAB protocol consisted of structured exercises targeting postural (20 min) and gaze stability (10 min), delivered in 30-min sessions twice weekly over nine weeks. Primary and secondary outcome measures included postural stability, gaze stability, motor performance, and quality of life. Descriptive analyses were conducted for each participant. All participants demonstrated improvements in the postural (Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) Balance Subtest) and gaze stability (Gaze Stabilization Test) during therapy, while changes during the no-therapy period were more variable and generally less pronounced. Among the secondary outcomes, improvements were observed in the Pediatric Modified Dynamic Gait Index, BOT-2 Bilateral Coordination Subtest, and Dynamic Visual Acuity Test. Children and caregivers reported better balance, a perceived reduction in falls, and increased participation in daily life. The protocol was feasible and well-tolerated, though some age-related limitations were noted. The protocol is feasible and may improve postural and gaze stability in children with peripheral vestibular dysfunction. A larger trial is planned to confirm these findings. This research presents an important first step towards developing evidence-based guidelines for pediatric VRT.
Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors, which restricts targeted therapies and contributes to poor survival. Conventional chemotherapeutics such as doxorubicin and cisplatin show limited efficacy, significant toxicity, and resistance, underscoring the need for alternative strategies. Nerium oleander, a traditional medicinal plant, has demonstrated anticancer activity through leaf extracts; however, the role of exosome-like nanoparticles derived from its flowers (NELNs) remains unexplored. The therapeutic efficacy of NELNs was evaluated in the MDA-MB-231 TNBC cell line using in vitro and in silico approaches. Cytotoxicity was assessed by the MTT assay, while AO/EtBr and DCFDA staining examined apoptosis and ROS generation through fluorescence microscopy. Flow cytometry was employed for apoptosis confirmation and cell cycle analysis. Network pharmacology integrating target prediction, PPI network construction, and functional enrichment analysis was performed, followed by molecular docking of NELN-encapsulated metabolites against predicted targets. NELNs induced significant cytotoxicity, promoted apoptosis, and increased intracellular ROS levels in MDA-MB-231 cells. Flow cytometry confirmed apoptotic induction and revealed alterations in cell cycle progression. Pathway enrichment analysis of previously identified NELN-associated metabolites computationally highlighted arachidonic acid and linoleic acid metabolism, with cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP3A4) emerging as putative targets. Molecular docking predicted favorable binding interactions of NELN metabolites to these targets. This study provides preliminary evidence that flower-derived NELNs exerted antiproliferative and pro-apoptotic activity against MDA-MB-231 cells under the tested experimental conditions. Furthermore, network pharmacology analyses generated putative mechanistic insights into pathways relevant to TNBC.
Surgery for colorectal cancer (CRC) entails significant physical and psychological stress. This clinical trial evaluated whether a trimodal prehabilitation program combining exercise, nutritional support, and psychological counseling could reduce anxiety and depression while improving health-related quality of life (HRQoL) within an Enhanced Recovery After Surgery (ERAS) pathway. In this single-blind randomized controlled trial, an interim analysis was conducted on 45 patients undergoing elective CRC surgery, assigned to trimodal prehabilitation (n = 20) or standard ERAS care (n = 25). The primary outcome was the longitudinal change in perioperative anxiety severity from baseline (T-4 weeks) to long-term follow-up (T + 52 weeks post-surgery) assessed via the GAD-7 scale. Secondary outcomes included depressive symptoms (PHQ-9) across five time points (T-4 to T + 52 weeks), HRQoL (SF-36, EORTC QLQ-C30/CR29), and exploratory correlations between baseline physical performance (6MWT and CPET) and longitudinal psychological trajectories. GAD-7 scores decreased from 6.2 ± 5.1 to 2.2 ± 3.1 in the intervention group and from 4.7 ± 4.8 to 2.9 ± 2.8 in controls (between-group p < 0.001). Perceived health improvement (SF-36 "Health Change") at 52 weeks was 76.6 ± 26.6 in the intervention group vs. 74.8 ± 29.2 in controls (p < 0.00001). No significant between-group differences were observed in PHQ-9 scores over time (p = 0.437). Significant improvements were observed in emotional functioning and cancer-related fatigue domains of the EORTC QLQ-C30 (p < 0.05). Correlations between physical performance and psychological outcomes were not statistically significant. Trimodal prehabilitation within an ERAS pathway reduces anxiety and improves perceived health status in patients undergoing CRC surgery. Larger multicenter studies are warranted to confirm its effects on depression and long-term outcomes. https://clinicaltrials.gov/study/NCT06443203, identifier NCT06443203.
Rare earth elements (REEs) are commonly found in minerals such as monazite and xenotime and often occur in association with tin deposits. These minerals also contain significant amounts of natural radionuclides, uranium (U) and thorium (Th). Mining residues and their weathering can contaminate ecosystems. This study aimed to evaluate the natural background levels, fractionation, distribution, possible sources, and ecological risk of REEs in soils from different locations on Phuket Island, southern Thailand, which was once the main center of tin mining. The correlations between REEs, U, and Th and radiological hazard were also investigated. The results showed that the REEs content ranged from 0.14 to 1287.13 mg/kg, with an average of 344.85 mg/kg. The chondrite-normalized REEs patterns showed enrichment in light rare earth elements (LREEs) and depletion in heavy rare earth elements (HREEs). Most of the soils showed negative Ce and Eu anomalies, indicating weathering of granitic rock. The enrichment factor (EF), geoaccumulation index (Igeo), and potential ecological risk (PERI) of REEs in most soils were classified as moderate enrichment, moderately contaminated, and low ecological risk, respectively. The mean activity concentration of 226Ra (149.3 Bq/kg), 232Th (104.7 Bq/kg), and 40K (825.2 Bq/kg), and the radiological hazard indices were slightly higher than the recommended safe limits of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR 2008 and 2000). The results of this study can be used as a background for tracking environmental changes and developing safety strategies.
This study investigated the effectiveness of a German version of the Active Communication Education (ACE) program. An exploratory cohort study was conducted with pre-post measures of communication strategy use, acceptance, activity and participation, health-related quality of life, anxiety, and depression. Post-program measures also included the International Outcome Inventory - Alternative Interventions (IOI-AI), a modified version of the Client Oriented Scale of Improvement (M-COSI), and open-ended questions. Thirty older adults with acquired hearing loss (M age = 70.27, SD = 5.77) attended three or more ACE sessions. The ACE program consisted of five, weekly 2 h group sessions with 6 to 10 participants. Pre-post self-report measures were completed pre-program, after two weeks, and 6 months post-program. Within-group changes and effect sizes were calculated. The IOI-AI results were descriptively analysed. Categories for the M-COSI and open-ended data were analysed using the qualitative method of summarizing-content analysis. Statistically significant within-group improvements were found for communication strategy use and acceptance of hearing loss. The IOI-AI showed a positive impact of ACE on activity and participation. The majority of participants (83.3%) reported improvement in their primary communication goal. The German version of the ACE program showed positive benefits for adults with hearing loss and can be recommended as a rehabilitative intervention for the target population.
Palliative and end-of-life care (PEoLC) systems are expanding across services, settings, and stakeholders, increasing their complexity and the need for systemic understanding to support patient outcomes and service delivery. Hospice care is central to the future of PEoLC, as hospices provide holistic services and engage diverse stakeholders. Participatory system mapping offers a way to collectively understand and visualize complex dynamics with those who live and work within these systems. This study aims to capture hospice system dynamics and preliminary leverage points via participatory causal loop diagram (CLD) mapping while evaluating method suitability through 3 research questions: (RQ1) What key variables and causal interrelationships do stakeholders identify in a hospice through participatory system mapping workshops? (RQ2) What preliminary leverage points emerge from the system map? and (RQ3) How effective are participatory system mapping workshops for capturing hospice dynamics? We developed and iteratively refined an innovative hybrid, asynchronous, multimodal design workshop series in a hospice in North West England. Stakeholders were introduced to core concepts in technology, design, systems thinking, and CLDs before engaging in participatory system mapping focused on the hospice experience quality. CLDs generated in workshops and through asynchronous participation were consolidated into a composite hospice system map. Twenty-seven participants, including patients, health care professionals, volunteers, managers, maintenance staff, and chaplaincy, contributed to the mapping process. The resulting map was analyzed using quantitative network analysis (in-degree, out-degree, betweenness, and closeness centrality) alongside qualitative interpretation of key system dynamics. The participatory hospice system map contained 84 variables connected by 175 causal links. Network analysis highlighted patient experience (highest in-degree, 20), advanced care planning (highest out-degree, 8), fundraising (highest betweenness centrality, 0.19), and relationships with community organizations and external stakeholders (highest closeness centrality, 0.23) as central elements in the map. Qualitative analysis illuminated important dynamics, including the impact of hospital admissions and hospice stereotypes, as well as uncertainties around how advanced care planning is shaped and enacted in practice. Participatory system mapping with hospice stakeholders was feasible in a time-pressured setting and generated a nuanced, stakeholder-led representation of hospice system dynamics. The hybrid, multimodal workshop model enhanced access and flexibility, supporting diverse engagement. Network analysis of the CLD suggested preliminary structural and conceptual leverage points and revealed gaps in shared understanding, indicating candidate areas for service development, policy attention, and further research. Future work should examine the replicability of this approach across PEoLC settings and integrate context-specific processes to validate and act on candidate leverage points.
This study aimed to preliminarily construct a screening and evaluation index system for dysphagia in the elderly based on expert consensus, so as to provide a preliminary theoretical reference for subsequent clinical verification and optimized screening and assessment of elderly dysphagia patients. A systematic literature review was conducted to extract core items, and the preliminary framework was developed via team and expert discussion. A standardized dispute resolution mechanism was adopted during expert correspondence consultation. Reasons for retention, revision, or elimination of indicators were determined based on screening criteria and expert suggestions. The analytic hierarchy process (AHP) was used to verify the index weight system, and a consistency test (i.e., the consistency ratio [CR] value is <0.1) was applied to guarantee rationality. This study established a preliminary, expert consensus-based theoretical framework for elderly dysphagia screening and assessment. The expert panel demonstrated high enthusiasm and authority. However, the present framework has inherent limitations, including single-region expert sampling, moderate expert consensus consistency, and lack of prospective clinical validation. Three rounds of expert consultations were conducted among 19 specialists recruited from tertiary hospitals in a single regional area. The questionnaire response rates were 94.7%, 100%, and 100%, respectively. 17 (89.5%), 14 (73.7%), and 5 (26.3%) experts put forward revision suggestions in each round. The expert authority coefficient was 0.920, and Kendall coordination coefficients were 0.219, 0.261 and 0.306 (all P<.001), indicating statistically significant but only moderate expert agreement. The final index system consisted of 3 primary indicators, 10 secondary indicators, and 26 tertiary indicators.
Introduction Human rickettsiosis is an emerging and reemerging disease caused by bacteria of the genus Rickettsia, transmitted through bites from infected ticks and other arthropods. This pathogen induces a potentially lethal acute febrile syndrome in human beings. While cases have been documented in Colombia, the absence of accessible diagnostic services highlights an urgent need to develop rapid, economical, and reliable strategies to enable timely detection and identification of the most pathogenic species. The objective of this study was to standardize and analytically validate a nested PCR followed by RFLP as a preliminary assay for the genotyping and differentiation of Rickettsia species reported in Colombia. Methods For preliminary validation, key analytical parameters were assessed, including the limit of detection, repeatability, reproducibility, robustness, and digestion profiles used for the identification of each Rickettsia species. Results The limit of detection was established at a single copy of the ompB gene, and the assay demonstrated a reproducibility of 96.7%. The technique proved robust against variations in reagent concentrations, except for the amount of Taq DNA polymerase, which significantly affected the results. Digestion profiles were determined for most circulating Rickettsia species, and these profiles were consistent with in silico analyses. Conclusions The analytically validated nested PCR-RFLP assay is a reliable technique for the diagnosis of Rickettsia. Species identification using a single restriction enzyme represents a cost-effective strategy for screening patient and tick samples, which could strengthen the diagnosis and surveillance of rickettsioses in Colombia.
Contingency management (CM) is effective for stimulant use disorder (STUD) in community settings. This pilot study assessed the feasibility, acceptability, and preliminary effectiveness of a CM intervention for STUD in a Vancouver, Canada hospital that supports patients to complete medical treatment despite ongoing substance use. Medical inpatients with STUD received a CM intervention involving twice-weekly gift card rewards for stimulant-negative urine drug tests and/or achieving SMART health care goals. Feasibility was defined by recruitment, retention, engagement until discharge, and lack of interference with medical care. Acceptability was assessed through weekly and exit surveys; preliminary effectiveness was determined through self-reported stimulant use via Timeline Followback and survey data on substance use and hospital experience. Forty-two participants enrolled; 21 (50%) had severe STUD and 34 (81%) had concurrent opioid use disorder. Thirty-five participants engaged with CM; 33 (79%) participated until discharge, contributing 227 encounters (median 5 per participant, interquartile range 3.5-8). Weekly surveys indicated high acceptability, including improved hospital experience (90%, 86/96 responses) and desire to continue CM postdischarge (97%, 93/96 responses). Twenty (57%) reported decreased stimulant use compared with baseline Timeline Followback. Exit interviews highlighted CM as motivating behavioral change. Staff (n=6) reported improved patient engagement and no negative impact on care delivery. CM for STUD appears feasible and acceptable in hospital settings and may improve patient experience and engagement. Further research is needed to examine the effectiveness of hospital-based CM on patient outcomes during admission and postdischarge.
Self-management is a key component of effective chronic obstructive pulmonary disease (COPD) management and is mainly promoted through pulmonary rehabilitation (PR) programmes. However, less than 2% of patients participate in PR programmes. Among those who do, approximately 40% fail to complete the programme. The reasons for this are multifactorial and include dyspnoea, reduced exercise tolerance, lack of motivation and inadequate transportation and infrastructure to access PR centres. In this context, self-management digital health interventions emerge as a promising approach to support the development of self-management competencies, contribute to changing and maintaining behaviours and prevent a downward spiral of deconditioning in this population. The aim of this study is to evaluate the feasibility, acceptability and preliminary effects of a theory-based self-management digital intervention (Respir'air BPCO) designed to promote physical activity in patients with COPD. This pilot randomised controlled trial will enrol 20 patients with COPD who are being followed at a Swiss pulmonary centre. Participants will be randomised using Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage stratification (1:1) at the end of the in-person PR programme into either an experimental group receiving a mobile app-based self-management intervention aimed at promoting physical activity or a control group receiving only usual care. Data will be collected at three time points: immediately after completion of the PR programme (T0), 3 months post-PR (T1) and 6 months post-PR (T2). The study will assess trial methodological feasibility, including recruitment duration, consent rate, retention rate, acceptance of the allocated group and data completeness. Intervention feasibility will be evaluated through intervention fidelity, the number and type of technical problems reported by patients, and patients' and/or researchers' observations regarding the intervention design, content and use to inform future refinements. Intervention acceptability will be assessed using mobile app usage data and the Treatment Acceptability and Preferences questionnaire. In addition, preliminary effects will be evaluated through daily step count (pedometer), self-management (Self-Care in Chronic Obstructive Pulmonary Disease Inventory), motivational regulation of physical activity (Behavioural Regulation in Exercise Questionnaire-3), quality of life (St. George's Respiratory Questionnaire and EuroQol 5-Dimensions-5 Levels), severity of dyspnea (Modified Medical Research Council Dyspnea Scale) and the number of exacerbations and hospitalisations. Analyses will include descriptive statistics and estimation-based comparative analyses using generalised linear mixed-effects models under the intention-to-treat principle, which accommodate missing data under standard assumptions, with reporting of effect sizes and CIs. The study protocol has been approved by the Ethics Commission of the Canton of Vaud (registration no.: 2025-01697). Results will be published in international peer-reviewed journals and presented at national and international conferences. NCT07262229.
Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) is a common otological emergency driven by intertwined microcirculatory disorders, immune-inflammatory activation and metabolic dysregulation.This narrative overview collates representative published evidence to summarize research advances on hematological, immunological and metabolomic biomarkers, with a focus on their investigational-not yet clinically validated- diagnostic and prognostic potential. Key observational findings from existing cohorts are outlined as follows: (i) inflammatory and coagulation markers display promising discriminatory performance in single-center exploratory analyses, yet consistent cut-off values across populations remain absent; (ii) multi-indicator combined nomograms yield favorable predictive metrics within isolated research groups, though external multi-center validation is still required; (iii) exosomal molecules, complement C3, and other novel metabolic markers provide new analytical angles to interpret disease mechanisms and guide tentative individualized intervention research. Despite these preliminary observational results, widespread clinical translation is hindered by limited sample scales, non-uniform detection protocols and confounding comorbidities. Future multi-omics combined modeling aided by artificial intelligence may only serve as auxiliary stratification tools after rigorous prospective verification, rather than supporting definitive clinical classification at the current stage.This narrative collation merely offers preliminary analytical references for auxiliary clinical assessment and personalized research design of ISSNHL, without claiming validated diagnostic utility for routine practice.
To evaluate the efficiency and reliability of a large language model (LLM) as a decision-support tool in hospital compounding pharmacy for pediatric extemporaneous preparations requiring assessment of drug crushability, regulatory compliance, and formulation feasibility. A proof-of-concept study compared a structured LLM-assisted workflow with the traditional manual information retrieval process in a hospital pharmacy setting. The LLM (Claude Sonnet 4.6) was configured with a standardized prompt to extract and consolidate data from multiple authoritative sources: the Friuli Venezia Giulia "Do Not Crush" list, the Italian Medicines Agency (AIFA) database for Summary of Product Characteristics (SmPC), AIFA Law 648/96 off-label use lists, and the Stabilis database for oral liquid formulation stability. Two representative drugs, propranolol hydrochloride and imatinib mesylate, were analyzed. For each drug, the model generated a structured output including crushability, regulatory information, off-label status, and extemporaneous formulation data. The same queries were manually performed by an experienced hospital pharmacist. Primary outcome was information retrieval time; secondary outcomes included completeness and accuracy. The LLM-assisted workflow reduced retrieval time to less than 2 minutes per drug (mean 1 minute 45 seconds), compared with a mean of 20 minutes (range 15-25 minutes) for the manual process, plus an additional 5 to 10 minutes for transcription. Output completeness was 100%, with all predefined fields correctly populated. The model accurately classified drug crushability and correctly identified Law 648/96 regulatory status. For propranolol, the system identified crushability, pediatric off-label authorization, and SyrSpend-based formulations with stability data of up to 146 days at room temperature. For imatinib, the model highlighted cytotoxic handling precautions, identified the absence of SyrSpend formulations, and retrieved alternative formulation stability data (30 days refrigerated). A properly configured LLM can function as an effective decision-support tool in hospital compounding pharmacy, improving efficiency while maintaining high standards of completeness, accuracy, and regulatory compliance. These preliminary results support further investigation into the integration of the LLM system into routine pediatric galenical preparation practice.
The flare-horned markhor (Capra falconeri), a near-threatened mountain ungulate endemic to the Western Himalayas, remains vulnerable to habitat fragmentation, human disturbance, and environmental change. Although localized conservation efforts have stabilized some populations, genomic resources for this species remain limited. Here, we report nuclear and mitochondrial genome assemblies for C. falconeri, including a nuclear genome assembly (GCA_038502695.1) and a complete mitochondrial genome (OR799853.1), and place these data within an ecological context derived from field surveys. A structured winter survey conducted between 2020 and 2022 documented 225 individuals across 14 sites, indicating a demographically stable population with marked spatial heterogeneity. Genome-completeness assessment with BUSCO indicated that the short-read nuclear assembly is a fragmented draft (49.4% complete), and should be regarded as a preliminary genomic resource rather than a reference-quality genome. The complete mitochondrial genome is 16,639 bp in length and exhibits conserved gene organization and pronounced AT bias; comparison with the reference mitogenome identified high-confidence coding-region substitutions, exclusively transitions, distributed across the major mitochondrial protein-coding gene groups. Codon usage analyses revealed moderate bias, whereas Ka/Ks ratios across the mitochondrial protein-coding genes were consistently below one, indicating pervasive purifying selection. Comparative phylogenetic analyses based on mitochondrial and nuclear data resolved the evolutionary placement of C. falconeri within the genus Capra. Together, these results provide genomic assemblies supported by ecological context and establish a foundation for future comparative, population, and conservation genomics studies of this species.
An increase in wrinkles, laxity, and dyschromia characterizes facial-skin aging. The skin is a natural barrier that prevents or limits the entry of external therapeutic compounds to the body. Enhancing the efficacy of transdermal delivery of anti-aging compounds is a key therapeutic strategy. The study aimed to evaluate the efficacy and safety of a combined therapy that included a topical anti-aging serum and a multi-technology facial device designed to improve transdermal absorption. A 41-year-old woman with moderate facial aging was treated using a split-face design for 12 weeks. Every day, the left hemiface received a hyaluronic acid-niacinamide-Matrixyl serum. In contrast, the right hemiface received the same serum plus application of a multi-therapy device that delivered red light (630 nm), galvanic current, micro-vibration, and controlled heat. Skin changes were assessed using the VISIA Skin Analysis System (Canfield Scientific, Parsippany, New Jersey) at baseline, 6, and 12 weeks. Both hemifaces showed improvement in skin quality parameters (wrinkles, texture, and UV spots). TruSkin age decreased by five years on the treated side with the device + serum and by one year on the serum-only side. Greater improvement in wrinkle reduction was observed on the device-treated side. No adverse events were reported. As a preliminary observation, combined therapy using a topical serum and a multimodal device appears safe and attenuates aging effects, particularly in reducing wrinkles. Further studies are needed to confirm these findings.
Perimortem traumatic dental injuries (PTDIs) can provide critical forensic information for reconstructing events occurring around the time of death. Accurate assessment and differentiation of traumatic dental injuries (TDIs) may contribute to the interpretation of injury patterns, the evaluation of possible causes and manners of death, and forensic investigations. However, accurately determining the timing of dental trauma, particularly distinguishing PTDIs from antemortem dental injuries (ADIs) and postmortem (PM) alterations, remains a significant forensic challenge. To provide a structured forensic framework for interpretation, a comprehensive literature search was conducted across three major electronic databases, PubMed, Scopus, and Web of Science. In accordance with structured narrative review recommendations (SANRA criteria), experimental, clinical, and observational studies published between 1965 and 2025 (including early electronic records from 2026) in English addressing morphological, biomechanical, taphonomic, and imaging characteristics of dental trauma were eligible for inclusion. Screening was performed in four distinct stages, incorporating a preliminary calibration exercise where two independent reviewers assessed a 20% sample of titles to ensure consistent application of eligibility criteria. Following full-text assessment, a total of 34 studies were finally selected. Evidence indicates that injury patterns result from the interaction between the impact characteristics and the biomechanical properties of dental and supporting tissues. PM alterations, particularly weathering-related changes and non-traumatic fractures, may mimic traumatic lesions and complicate diagnosis. Accurate differentiation relies on fracture morphology, surface characteristics, staining patterns, and evidence of bone biological response. Future research on advanced imaging, including cone-beam computed tomography (CBCT) and micro-computed tomography (micro-CT), could enhance non-destructive documentation. Integrating biomechanical and imaging data may improve diagnostic reliability in forensic contexts and supports robust medico-legal interpretation.
For children with complicated choledochal cyst (CDC), the decision between primary radical surgery (PRS) and preoperative drainage (PD) remains subjective. We aimed to develop an objective preoperative risk framework to inform this choice. A retrospective, single-center review of 454 children with CDCs was conducted. The primary outcome was disease-related severe complications (Clavien-Dindo ≥II). A prediction model for severe complications was built using logistic regression. A sensitivity analysis used a composite outcome that also included extreme surgical difficulty (prolonged operative time plus prolonged hospital stay). A point score was derived from the composite-outcome analysis. Severe complications occurred in 24 of 380 PRS patients (6.3%). Intrahepatic duct dilatation (OR 3.58, P=0.005) and inflammation score ≥2 (OR 2.35, P=0.058) were the main predictors. In the composite-outcome analysis (50 events), a simplified 11-point score (inflammation score, intrahepatic dilatation, hemoglobin) stratified patients into low- (0 points, 5.5%), medium- (1-3 points, 13.6%) and high-risk (≥4 points, 18.3%) groups. PD patients (n=74) had a higher predicted risk of suboptimal outcome if they had undergone PRS (19.2% vs. observed 13.2% in PRS, P<0.001). A preliminary risk score using three preoperative variables can help identify children at higher risk of poor outcome after PRS. The tool requires external validation and should support, not replace, clinical judgment. Level III TYPE OF STUDY: Diagnostic/Prognostic.