High-quality pharmacoepidemiological research is essential for credible real-world evidence (RWE). This expert consensus-based review explores how pharmaceutical Quality Management Systems (QMS) developed for studies using primary data collection (e.g., clinical trials, registries) can be adapted to support studies utilising secondary data to generate RWE, in line with regulatory expectations. The aim was to identify fit-for-purpose considerations for proportional oversight, data integrity, and regulatory-grade evidence generation. An international working group (WG) comprising RWE experts from industry, academia, and independent consultancy (including QMS specialist) assessed which elements of QMS frameworks developed for primary data collection are applicable to RWE studies utilising secondary data sources and those elements where adaptation would be required. Using the Nominal Group Technique, the WG identified and prioritised relevant quality systems and adaptation needs. In parallel, a targeted literature review of guidance and reports from International Coalition of Medicines Regulatory Authorities (ICMRA) member sites (focusing on the EU, USA and UK) assessed guidance against prioritized quality systems. Of 21 quality systems identified, 12 were considered most relevant to RWE studies utilising secondary data, with ten requiring contextual adaptations. The literature review identified 26 publications referencing one or more of these systems; quality manuals (69.2% (n = 18)) and quality control (34.6% (n = 9)) were most frequently addressed, whilst other systems were inconsistently covered; vendor management was not explicitly addressed. Overall, this review highlights the need for fit-for-purpose adaptation of existing QMS frameworks to support regulatory-relevant, scientifically robust RWE generated from secondary use of existing data sources.
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays essential roles in nervous system development, neuronal maintenance, and neurogenesis. Aberrant BDNF concentrations, observed both peripherally and within the central nervous system (CNS), have been consistently implicated in the pathogenesis of a spectrum of neurodegenerative disorders (NDDs), including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and Multiple sclerosis. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), regulate gene expression and are critical factors in cellular processes relevant to neurodegenerative disease pathobiology. Consequently, ncRNAs are posited as promising biomarkers and potential therapeutic modalities for CNS-related pathologies. However, robust empirical evidence substantiating ncRNA-mediated, post-transcriptional regulation of BDNF expression in the context of neurodegeneration remains relatively scarce. The objective of this systematic review is to provide a critical synthesis of the current literature on the diagnostic and prognostic utility of ncRNAs that modulate BDNF expression, specifically within the scope of neurodegenerative disorders. Furthermore, we will explore innovative therapeutic strategies centered on targeting BDNF-associated miRNAs for the treatment of these disorders.
To summarize current evidence regarding vision-threatening ocular complications associated with midface trauma and to propose a practical systems-oriented framework for their early recognition, evaluation, and management. A narrative review of the literature was conducted focusing on ocular injuries associated with midface trauma, including orbital compartment syndrome, open-globe injury, extraocular muscle entrapment, hyphema, posterior segment trauma, and traumatic optic neuropathy. Evidence was synthesized to develop a clinically applicable framework for multidisciplinary trauma care. Vision-threatening ocular injuries following midface trauma require rapid identification and timely escalation. Key components include bedside ocular screening, recognition of red-flag findings, appropriate imaging, early ophthalmology consultation, and coordinated communication between emergency, maxillofacial, ophthalmology, and trauma teams. Evidence strongly supports urgent intervention for orbital compartment syndrome and does not support routine high-dose corticosteroid therapy for traumatic optic neuropathy. Additional recommendations include standardized checklists, structured handover processes, and local quality-improvement measures. A systems-based approach may improve the early detection and management of vision-threatening ocular injuries in patients with midface trauma. The proposed framework aims to reduce preventable visual loss, standardize multidisciplinary care pathways, and support future prospective evaluation of clinical outcomes.
Water temperature variability in river systems is a significant environmental concern. This study aimed to assess the effects of thermal regime variability on adult Oncorhynchus mykiss mortality in Afromontane river systems; using time series data spanning from 1994 to 2024. The objectives of the study were to analyze temporal and seasonal trends in water temperature (1994-2024) in Nyanga National Park, Zimbabwe, evaluate how temperature variability relates to adult O. mykiss mortality, and identify critical thermal thresholds that increase mortality. The research used both secondary and primary data. Time series approach with a 5-year moving average analyzed temperature trends, while correlation and regression assessed the relationship between water temperature and rainbow trout mortality, and threshold analysis identified critical temperature limits increasing adult O. mykiss mortality. Seasonal comparisons revealed marked differences in both water temperature and mortality of O. mykiss. Mean water temperature was significantly higher in summer (20.13 ± 0.10 °C) than in winter (13.30 ± 0.13 °C; Welch's t-test, t = 17.91, p < 0.01; n = 93 per season). Similarly, mean mortality was substantially greater during summer (1272 ± 44) compared to winter (229 ± 27), with this difference also highly significant (Welch's t-test, t = 13.17, p < 0.001). Correlation and regression analyses revealed a strong positive association between temperature anomalies and mortality anomalies (ρ = 0.713; R2 = 0.453) indicating that nearly half of the variability in mortality anomalies is explained by temperature. The positive regression slope (134.1 fish per 1 °C anomaly) highlights the biological sensitivity of the population to even modest warming departures from baseline conditions. A critical thermal threshold of 15.20 °C was identified where O. mykiss mortality increased disproportionately above this threshold. Although mean temperatures have not shifted significantly, intra-seasonal variability acts as a primary driver of mortality. Implementing strategies that mitigate the effect of water temperature changes on rainbow trout mortality is imperative to support economic growth and food security.
Under the DRG payment system, the choice of enteral nutrition for stroke patients requires balancing clinical efficacy and economic costs. Nasogastric (NG) and nasojejunal (NJ) feeding are widely used, but comprehensive comparisons of nutritional outcomes, complications, and DRG‑related economic indicators remain limited. To compare the clinical effects and economic burden of NG versus NJ enteral nutrition in stroke patients under DRG, and to provide evidence for individualized clinical decision‑making. A retrospective study was conducted in stroke patients receiving enteral nutrition at a tertiary hospital in central China from January 2021 to December 2024. A total of 322 patients were initially enrolled (193 in NG group, 129 in NJ group), and 149 patients were eligible for final DRG economic analysis (83 in NG group, 66 in NJ group). To confirm model robustness, 1:1 propensity score matching (PSM) was performed (n = 66 pairs). Nutritional indicators, complications, length of stay, hospitalization costs, nutritional costs, and DRG cost overrun rates were compared. The NJ group had lower pretreatment hemoglobin, but showed significantly greater improvements in hemoglobin and albumin than the NG group (both P < 0.001). The incidence of malnutrition and inflammatory burden index were significantly lower in the NJ group (both P < 0.05). In DRG analysis, total hospitalization costs and nutritional costs were significantly higher in the NJ group (both P < 0.001), with a higher DRG overrun rate (77.3% vs. 62.7%, P = 0.055). Length of stay was similar between groups (P > 0.05). NJ is superior to NG in improving nutritional status and reducing malnutrition and inflammatory burden in stroke patients, but is associated with higher short‑term costs and greater DRG overrun risk. A risk‑stratified strategy is recommended under DRG to balance clinical benefits and economic sustainability.
Flavonoids comprise an exclusive class of biomolecules with extensive therapeutic features. Rutin is one of the flavonoids that has antioxidant, anticancer, and other pharmacological actions, but its clinical use is deterred by poor solubility, poor bioavailability, and incomplete absorption. Development of nanotechnology-based delivery platforms is a promising solution to counter these issues. We evaluated the antioxidant and anticancer properties of nanocrystals and spanlastic nanoparticles of rutin against the human breast adenocarcinoma cell line MCF-7 to establish effective delivery methods with improved therapeutic efficacy. The physicochemical characteristics of the nano-formulations were investigated through particle size and zeta potential measurement, Fourier Transform Infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), electronic bandgap energy, and dissolution behavior. Antioxidant activity was investigated through DPPH and ABTS radical scavenger assays. Anticancer potential was established through a viability assay, cell cycle analysis, dual labeling with annexin-V/propidium iodide (PI) (using fluorescence-activated flow cytometric methods), and Caspase 3 activity. Rutin spanlastic nanoparticles showed a considerably smaller particle size, homogeneous dispersion, and negative zeta potential, indicating stability. Rutin spanlastic nanoparticles exhibited greater antioxidant activity compared with free rutin and rutin nanocrystals, as manifested through stronger inhibition of the viability of MCF-7 cells, stronger induction of apoptosis (annexin-V/PI double staining and Caspase 3 activity), and significant G1/0 phase cell cycle arrest. These observations imply an increased solubilization and elastovesicular behaviour of spanlastic nanoparticles with enhanced bioactivity of rutin. In conclusion, rutin spanlastic nanoparticles are an efficient delivery vehicle compared to rutin nanocrystals or free rutin in amplifying both antioxidant and anticancer activity, hence warranting further in vivo experiments to treat breast carcinoma.
Spinal cord stimulation (SCS) has become increasingly widespread in recent years for the management of refractory chronic pain, primarily owing to the development of novel waveform technology allowing variable spinal cord modulation, and indication expansion. The existing literature suggests that despite having favorable initial responses, the efficacy of SCS sometimes is reduced over time. To restore analgesic efficacy, a strategy of altering stimulation waveforms known as salvage therapy has been used. Here, we consolidate the existing evidence and describe the efficacy of salvage therapy. A literature search using relevant keywords was conducted on PubMed, Web of Sciences, and Cochrane Library data bases, yielding a total of 809 articles. After a full text review and screening for consistency with eligibility criteria were conducted, 22 studies with a collective sample size of 1591 patients were included in the final analysis. Data extraction was performed by six reviewers, with a secondary reviewer verifying each entry. Of the 1591 patients included in our review, the most frequent indication for salvage therapy was loss of waveform efficacy and paresthesia coverage. In most studies, patients received salvage therapy after experiencing loss of efficacy with a single waveform. Most studies also did not strictly control the phase in which salvage therapy was implemented, with only eight of 22 studies reporting exclusively trial phase interventions. The efficacy of salvage therapy was found to be favorable, with 685 of 879 salvage therapy trials (77.9%) being reported as successful. New waveform technologies in SCS have expanded therapeutic options for patients with refractory chronic pain. Available evidence suggests that waveform switching may restore analgesic benefit in a subset of patients who experience loss of efficacy after an initial favorable response. However, many salvage strategies involve device revision or generator replacement, and the long-term durability of these interventions remains uncertain. Further prospective studies are needed to better define patient selection, timing of intervention, and long-term outcomes after waveform-based salvage strategies.
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The systematic integration of heterogeneous host-pathogen interaction data with disease modules and pharmacological knowledge remains a major challenge in translational biomedical informatics. Network medicine offers a promising strategy for identifying conserved regulatory vulnerabilities and therapeutic repositioning opportunities across distinct mucosal ecosystems. We developed a scalable multilayer network integration framework that unifies pathogen-host protein interactions, disease-risk gene modules, and drug-target associations into a consolidated human interactome. The integrated network comprised 7,262 human proteins, 17,016 high-confidence protein-protein interactions, nine bacterial pathogens, four respiratory viruses, and 514 FDA-approved drugs. Network topology was quantitatively characterized using complementary centrality metrics (degree, betweenness, closeness, clustering coefficient, and topological coefficient) to identify high-influence host regulators. Drug prioritization employed a multi-criteria ranking pipeline integrating functional network scoring (CoDReS), structural similarity clustering (Tanimoto-based hierarchical modeling), and pharmacokinetic constraint filtering (ADMET profiling). Pathway enrichment analysis was performed to identify convergent biological mechanisms. The integrative framework identified conserved cross-ecosystem regulatory hubs, including PPARG, CDC42, JUN, RHOA, and CAV1, which link microbial perturbations to cardiometabolic and inflammatory disease pathways. Centrality-weighted drug prioritization consistently ranked indomethacin, ibuprofen, dexibuprofen, mesalazine, and cannabidiol as high-confidence repositioning candidates for densely connected host networks. Enrichment analyses demonstrated convergence on immune signaling pathways, cytoskeletal remodeling, PPAR signaling, and focal adhesion networks. This study presents a reproducible and generalizable network medicine workflow that formalizes interactome construction, multi-metric centrality assessment, and composite drug ranking in a unified analytical framework. The proposed strategy enables the systematic identification of conserved host regulatory vulnerabilities and repositionable therapeutics across infectious and chronic inflammatory diseases, thereby advancing host-directed therapeutic discovery in translational biomedical informatics.
This study aimed to comprehensively assess the implications of long COVID on the health-related quality-of-life (HRQoL) among Japanese adults and to identify its associated factors. This study used prospective cohort data from the CARE Japan Study between January 2022 and January 2023. The outcome of this study was HRQoL, which was measured using SF-12 questionnaire. Self-reported long COVID was the primary independent variable. We fitted adjusted beta regression models to calculate beta regression coefficients with 95% confidence intervals (CI) and average marginal effects (AME) to explore the determinants of HRQoL. We also performed latent class analysis (LCA) to identify unobserved patterns of long COVID symptoms. Final sample size was 1,285. Compared to the participants with no long COVID, the HRQoL among long COVID patients (β: -0.25; 95% CI: -0.36 to -0.14; AME: -0.036) was significantly lower. The effect of long COVID on HRQoL was the most pronounced among the respondents with pre-existing lung diseases (β: -0.72; 95% CI: -1.29 to -0.16; AME: -0.114). LCA identified three subgroups of long COVID patients - class 1, 2, and 3. Compared to the participants with no long COVID, participants belonged to class 1 (β: -0.47; 95% CI: -0.57 to -0.36; AME: -0.065), class 2 (β: -0.48; 95% CI: -0.60 to -0.35; AME: -0.066), and class 3 (β: -0.93; 95% CI: -1.06 to -0.79; AME: -0.148) had poorer HRQoL. Long COVID patients had reduced HRQoL. Female gender, young-age, thin BMI or pre-existing psychological disorders were associated with lower HRQoL. Now, after five years of COVID-19 pandemic about 779 million of COVID-19 cases were reported, as of October 2025. Survivors of COVID − 19 often report complex, multisystemic, persistent or relapsing symptoms for weeks, months, or even years after the initial infection of COVID-19. When the symptoms are persistent or relapsing even after 12 weeks of initial acute infection, it is termed as long COVID. Due to high prevalence, heterogeneous nature, lack of clear diagnostic markers, prolonged, and obscure recovery process, long COVD is posing challenges on individuals’ lives, public healthcare systems, and workforce. Increasing evidence is suggesting that long COVID is impairing functional and cognitive capacity of the patients resulting poor health-related quality-of-life. Longitudinal studies on health-related quality-of-life among COVID-19 survivors with long follow up period is scarce in Japan. Therefore, in our study we measured the impact of COVID-19 infection on the health-related quality-of-life among Japanese adults with follow up period of 1 year. We found that, long COVID patients had lower health-related quality-of-life compared to the COVID-19 survivors without long COVID. The presence of minimal long COVID symptoms lowered the health-related quality-of-life. For COVID-19 cases with lung disease as a comorbid condition, the risk of reduced quality of life remains high even after recovery. Findings of this research will enhance the understanding of the implications of long COVD on individual’s lives and will underscore the need of coordinated approach for long-term treatment, care, and prevention of long COVID through policies, interventions, and integrated health care system.
Spinal cord injury (SCI) disrupts the integrated neuroendocrine network linking the hypothalamic-pituitary-adrenal (HPA) axis, renin-angiotensin-aldosterone system, and sympathetic nervous system, resulting in endocrine and immune dysfunction. However, the effects of SCI on angiotensin II receptor signaling remain unclear. This study investigated temporal and lesion-dependent changes in angiotensin II type 1 (AT1) and type 2 (AT2) receptor expression following SCI in rats. Low-thoracic SCI (Th9 compression, 40 g/15 min) was evaluated over 28 days, while acute responses to partial (Th9) versus near-complete (Th1) sympathoadrenal denervation were compared. Receptor expression was assessed in the hypothalamic paraventricular nucleus, pituitary, adrenal gland, and spleen, and correlated with hormonal and morphological alterations. Surgical stress alone activated systemic angiotensin II signaling. Low-thoracic SCI induced time- and tissue-specific changes in angiotensin receptor expression independent of circulating angiotensin II levels, indicating adaptive remodeling of HPA axis sensitivity. SCI caused transient adrenal enlargement, zona fasciculata hypertrophy, dysregulated HPA axis activity, angiotensin II-independent aldosterone production, and altered catecholamine secretion. Splenic AT1 receptor expression showed early upregulation followed by compensatory downregulation, consistent with dynamic neuroimmune modulation. In contrast, high-thoracic SCI markedly reduced receptor expression across central and peripheral HPA axis components and the spleen, accompanied by decreased corticotropin-releasing hormone, aldosterone, and norepinephrine, stable adrenocorticotropic hormone, and elevated corticosterone and epinephrine. These findings demonstrate that the extent of sympathetic disruption critically determines neuroendocrine-immune responses after SCI and identify sympathetic innervation as a key regulator of angiotensin receptor balance and stress-axis homeostasis following spinal cord trauma.
The most prevalent malignant tumor of the urinary system, bladder cancer, exhibits a rising global incidence rate. However, recent diagnostic and therapeutic techniques, such as ostomy surgery, can effectively prolong patient survival. The majority of patients require support from family carers, presenting considerable challenges to these caregivers. Although existing research has primarily focused on patients' physiological adaptation, quality of life, and the burden on family carers, the moral dilemmas faced by these caregivers have not been explored yet. This study aimed to explore the psychological and moral dilemmas of family caregivers in a specific care situation. Using a descriptive research design, we conducted one-on-one qualitative interviews with 23 patients who had undergone urostomy. The interview time for each patient lasted over 60 min. All the interviewees emphasized that urostomy had significantly influenced their sexual experience. Moreover, we used thematic analysis to analyze the data. All the interviewees emphasized that a urostomy had significantly influenced their sexual experience. Our analysis yielded three primary themes: (1) the tearing of care responsibility and self-life, (2) reconstruction of family roles and relationships, and (3) the contradiction between the best care and practical limitations, and eight subthemes: guilt of giving up, social alienation, sacrifice of physical and mental health, the challenge of intimacy, balance of multiple responsibilities, great economic pressure, limited knowledge and skills, and emotional collapse. This study reveals that family carers of Chinese urostomy patients perceive caregiving as a moral obligation rather than a mere action, viewing self-sacrifice as evidence of virtue within a Confucian ethical framework. Hence, providers must develop culturally sensitive assessment tools, redesign supportive interventions respecting diverse moral perspectives, and establish ethical support systems to bridge understanding between differing moral contexts. This might foster a healthcare system that genuinely honors the carers' moral dignity.
Supragastric belching (SGB) is a behavioral disorder involving rapid air influx into the esophagus through a transiently relaxed upper esophageal sphincter, followed by immediate expulsion. Unlike gastric belching, it is not related to lower esophageal sphincter (LES) dysfunction or gastroesophageal reflux disease (GERD). Often associated with psychological stress, SGB can significantly impair quality of life and some patients remain refractory to conventional therapies. In this retrospective study, clinical records of patients diagnosed with refractory supragastric belching were systematically analyzed. Extracted data included detailed clinical history and upper gastrointestinal endoscopy findings; high-resolution esophageal manometry (HREM) was performed using Herbert's 16-channel water perfusion system, with interpretation of esophageal motility patterns based on the Chicago Classification version 3.0 and perceived stress levels assessed using the PSS-10 questionnaire. All patients underwent a standardized intervention protocol consisting of nasogastric tube insertion followed by structured diaphragmatic breathing training (Yellapu Technique), aimed at behavioral modulation of belching. Follow-up evaluations included symptom assessment and perceived stress scores over a three-month period to determine therapeutic response. Total 56 patients were analyzed (40 females and 16 males, mean age of 45.6 ± 10.0 years). Upper gastrointestinal endoscopy and HREM findings were within normal limits in all patients. Endoscopy showed normal mucosal findings. HREM demonstrated normal esophageal motility and sphincter function, with a baseline esophagogastric junction (EGJ) pressure of 33.75 ± 6.45 mmHg and an integrated relaxation pressure (IRP) of 10.90 ± 2.8 mmHg, both within physiological limits. Complete resolution of supragastric belching was observed in 55 patients. The paired mean Perceived Stress Scale (PSS) score showed a statistically significant reduction, decreasing from 33 ± 3.65 at baseline to 22.92 ± 2.34 at one month (p < 0.001). No recurrence of symptoms was reported during the follow-up period. In conclusion, the Yellapu Technique appears to offer a practical and innovative therapeutic approach for the management of refractory supragastric belching. By combining mechanical interruption with behavioral modification, it was associated with immediate symptom relief as well as sustained improvement. These findings suggest that this technique may represent a promising adjunct or alternative to existing therapies, warranting further validation through well-designed prospective controlled studies.
The presence of estrogenic compounds in aqueous environments has raised significant environmental and public health concerns due to their endocrine-disrupting effects. These compounds, both natural (estrone: E1, 17β-estradiol: E2, and estriol: E3) and synthetic (17α-ethinylestradiol: EE2), are frequently detected in wastewater and surface waters, where conventional treatment processes often fail to remove them successfully. Adsorption has been regarded as a promising, low-cost solution for removing these compounds, especially when coupled with activated carbon made from agro-industrial waste. This is considered an environmentally friendly solution, as it reuses waste materials and adds value to them. This review presents a comprehensive analysis of 28 studies published from 2011 to 2026 on the use of activated carbon for the removal of estrogens. It discusses the properties of estrogens, their environmental impact, and the health risks of long-term exposure. It also explains the physicochemical mechanisms behind estrogen adsorption and highlights the main adsorption and kinetic models used, with a reflective discussion on the results. Although results are promising, most studies only performed their assays under ideal matrices or monocomponent systems. Future research should include multicomponent systems, simulated wastewater matrices, and initial estrogen concentrations closer to those found in nature. Challenges remain in improving adsorbent efficiency, regeneration, and overall sustainability.
Patient-reported outcome measures (PROMs), when used at the point-of-care, provide a mechanism to systematically integrate patients' voices into shared decision-making. We examined clinicians' perspectives on the acceptability and preferred timing of PROM completion in routine clinical care for respiratory, musculoskeletal, cardiac, kidney and diabetic condition management. Semi-structured interviews were conducted over videoconference between October 2024 and May 2025. Participants worked at various New South Wales Health clinics, providing care for patients with chronic conditions, and were eligible to collect and review PROMs digitally using the Health Outcomes Patient Experience platform (NSW PRMs-HOPE program). Reflexive thematic analysis was undertaken. Twenty-two physiotherapists and nurses were interviewed. Acceptability themes included: (1) purpose of PROMs; (2) broader ethical considerations for PROMs collection and use; (3) practical aspects of PROM administration. Findings highlighted the elusiveness of an "ideal" timing for PROMs. Timing themes included: (1) (mis)alignment in timing of PROM administration; (2) preferences for fixed or customised timing and frequency of administration; (3) temporal fit and workflow alignment. PROMs were reported as most acceptable when their selection, content, and timing aligned with clinical purpose, scope of practice, and existing workflows. Flexibility in PROM administration was perceived to enhance relevance at the point-of-care and support timely, condition-specific clinical conversations and interventions. However, clinicians also recognised that increased flexibility may reduce the comparability of aggregated PROM data across cohorts, highlighting an inherent acceptability trade-off between meeting individual clinical needs and supporting system-level performance monitoring and benchmarking. People with long‑term health conditions can fill out health surveys called patient‑reported outcome measures (PROMs). These health surveys help patients share how they are coping day to day and how their health condition or treatment is affecting their quality of life. PROMs are used more in healthcare now, but we do not know enough about how clinicians feel about using them or when they should be given to patients to improve their care.In this study, we spoke with physiotherapists and nurses who use PROMs. They told us what they think about PROMs and when these should be completed by patients.Physiotherapists and nurses said PROMs can help them better understand their patients, find changes in their patients' health, and support conversations about care. But they also said they needed extra time to help patients fill in PROMs, some of the questions were unclear for patients, there were language and cultural barriers for some patients, and they did not always know how to use the results.Overall, physiotherapists and nurses wanted more choice in which PROMs they use and when patients complete them. They felt this would make PROMs more useful for patient care. But, too much choice could make it harder to compare results across clinics and to see how well services are looking after people.
This work aims to develop and validate a hybrid electromagnetic(EM)-ArUco tracking framework integrated into a laparoscopic ultrasound augmentation system, aiming to improve accuracy, stability, and robustness in intraoperative visualization. A novel hybrid tracking method was developed that combines continuous hardware-based EM tracking with accurate but intermittent computer vision-based ArUco marker tracking, utilizing dynamically computed correction matrices to optimize the real-time spatial alignment of ultrasound and laparoscopic images. Validation involved three experiments: image-based analysis measuring pixel error between projected and ground-truth needle tips, target registration error analysis quantifying the distance between an EM- tracked stylus tip and the inverse projection from the ultrasound, and an ex vivo tissue experiment to assess distortions in a simulated clinical environment. Hybrid tracking demonstrated a significant reduction in tracking error compared to EM tracking alone. Hybrid tracking reduced projection error from 116 ± 49 px to 49 ± 18 px and decreased registration error from 2.1 ± 0.9 mm to 1.1 ± 0.6 mm. Under the influence of externally applied distortion, hybrid tracking improved tracking accuracy by approximately 62.3%. The system also exhibited robustness to camera rotation and zoom changes during periodic ArUco marker detection. The hybrid tracking framework significantly improved accuracy, stability, and robustness compared to EM tracking. This integration has the potential to enhance intraoperative visualization, thereby contributing to safer and more effective minimally invasive surgeries.
Extracellular vesicles (EVs), including exosomes (EXOs) and microvesicles, are small particles surrounded by lipid bilayers that almost all cell types produce. They are essential for cell signaling because they transport bioactive molecules, including DNA, RNA, proteins, and lipids. The amount and make-up of EXOs are linked to several illnesses, including inflammatory diseases, cancer, metabolic diseases, and the one we're communicating about here, female infertility. Bacteria, fungi, viruses, and parasites are just a few of the organisms known to affect the reproductive system in both men and women. EVs are very important for reproductive health, and they can be a cause of infections that make women unable to have children. EVs play a significant role in cell communication and can influence both healthy and pathological processes in the female reproductive system. We looked into the use of EVs as an alternative way to treat vaginal infections (VIs), like bacterial vaginosis, viral vaginitis, and vaginal yeast infections, because traditional treatments for these diseases have some problems. In this study, we also examined the role of EVs in infertility associated with VI. Then, the pros and cons of this method for treating this sickness in the future are discussed.
In June 2023, the US Food and Drug Administration (FDA) approved ritlecitinib (50 mg once daily) for treatment of severe alopecia areata (AA) in patients ≥ 12 years. This study aimed to assess the characteristics of patients prescribed ritlecitinib within the first 10 months following approval. This retrospective study analyzed data from the Komodo Healthcare Map® (Komodo) and OMNY Health Foundation databases. Patients were aged ≥ 12 years with ≥ 1 ritlecitinib prescription on or after June 23, 2023, ≥ 1 AA diagnoses on or before index date (first prescription date), and ≥ 12 months of continuous enrollment before study entry. Two cohorts were assessed: patients with Komodo data (cohort 1) and linked Komodo and OMNY data (cohort 2). Clinical characteristics and AA treatment history were assessed over the 12-month pre-index period and stratified by age (12-17 and ≥ 18 years). Cohort 1 included 2562 patients; of these, 61.8% were prescribed ritlecitinib by a dermatologist, 58.9% were female, and 35.2% were adolescents. Approximately 24% had alopecia totalis/alopecia universalis as the closest diagnosis prior to index, 12.4% had ≥ 1 other autoimmune disorder, 23.9% had ≥ 1 atopic disorder, and 23.7% had ≥ 1 diagnosis of a mental health condition captured. In cohort 1 during the 12 months before index date, 26.6% of patients received no AA treatments, 31.9% received systemic immunomodulators, and 31.3% received injectable corticosteroids. Cohort 2 included 381 patients; of those in cohort 2 with reported disease location, hair loss primarily occurred on the scalp (90.5%) and face (43.2%). In cohort 2, 77.2% of patients with a scalp hair loss (SHL) assessment had ≥ 50% SHL. In the first 10 months following US approval, ritlecitinib was prescribed to a broad range of patients, including those with and without prior treatments and comorbidities. This suggests that ritlecitinib may provide new opportunities to engage or re-engage patients in AA-directed care. Ritlecitinib is an oral medicine used to treat severe alopecia areata (AA) in adults and adolescents ≥12 years of age. Ritlecitinib was approved by the US Food and Drug Administration in June 2023, and studies have shown ritlecitinib to be safe and effective. However, less is known about how ritlecitinib is used in everyday clinical practice. This study describes the characteristics of patients with AA (aged ≥12 years) who were prescribed ritlecitinib during the first 10 months after approval. Most patients (62%) were prescribed ritlecitinib by a dermatologist, 59% were female, and 35% were adolescents (12–17 years old). About one in four patients (24%) had severe forms of AA, identified by a recorded diagnosis of either alopecia totalis (complete scalp hair loss) or alopecia universalis (complete scalp and body hair loss), around the time of their first ritlecitinib prescription. Twelve percent of patients had at least one other autoimmune condition, 24% had at least one allergy-related condition, and 24% had at least one diagnosed mental health condition. In the year before the first ritlecitinib prescription, 27% of patients received no AA treatments, while about one-third received immune-system-targeting medications (32%) and/or steroid injections (31%). In the subset of patients with linked electronic health records and scalp hair loss measurements, about three-quarters (77%) had hair loss on ≥50% of their scalp. Overall, during the first 10 months after approval, ritlecitinib was prescribed to patients with a wide range of treatment histories and health conditions, supporting its role as a treatment option for AA.
The degree to which motor and psychosocial functions may recover following hand and upper-extremity transplantation (HUET) remains unclear. This study quantifies HUET outcome changes in the first 10 years post-transplantation to provide insight into this question. A systematic review of PubMed, Embase, Cochrane, and Medline yielded 2104 records; 118 articles were included in the final review. HUETs above the proximal third of the forearm were designated as proximal and the remaining distal. Semmes-Weinstein Monofilament (SWMF) test, grip strength, Kapandji, finger and thumb total active range of motions (TAROMs), Carroll, Short Form 36 (SF-36), Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH), and Hand Transplantation Score System (HTSS) were recorded according to patient and postoperative year (POY). Ninety-seven patients were identified between 1998 and 2025. Distal HUETs' SWMF improved from POY1 (4 [4-4]) to POY2 (5 [4-6]). Power grip remained constant for distal and proximal HUETs, but proximal HUETs recovered less than distal HUETs (4.51 ± 1.49 kg vs 7.33 ± 0.71 kg). Lateral pinch strengths did not differ between groups. Proximal HUETs' lateral grips demonstrated sustained improvement after POY3. Bilateral HUETs demonstrated higher SF-36 scores than unilateral HUETs across POY1-10. HTSS measured significant improvements in distal HUETs increasing from 65 (57-79.5) (POY1) to 76 (71-85) by POY3, while proximal HUET only improved from POY1 (61 [45-70.5]) at POY8-10 (82.5 [72-91.5]). Finger TAROMs remained largely unchanged after POY1 while distal and proximal Kapandji thumb opposition scores improved at POY3-6 and POY8-10, respectively. Transplant level influenced recovery of power grip and HTSS. HUET power grip strength and finger TAROM stabilized after POY1 while lateral grip, Kapandji scores, HTSS, and SWMF showed improvements in the decade following transplantation, mostly for distal HUETs. Bilateral HUETs had better psychosocial (SF-36) outcomes than unilateral HUETs, but no difference in DASH scores. Therapeutic IV.
Artificial intelligence (AI) technologies such as machine learning (ML), deep learning (DL), predictive analytics and other tools are rapidly changing pediatric health care, using large amounts of health data. AI tools aid in triage, real-time monitoring and risk stratification in acute care settings, towards improving overall outcomes and fewer complications. During newborn resuscitation, AI analyses real-time data, can guide decisions and enhance training. Computer vision systems with AI tools can generate reliable neonatal bilirubin estimates without the need for blood sampling. AI technology is also being used in the management of necrotising enterocolitis, respiratory distress syndrome, and screening and early diagnosis of retinopathy of prematurity. ML models assist in detecting brain injuries on MRI for conditions such as hypoxic-ischemic encephalopathy, intraventricular hemorrhage; MRI biomarkers can be analyzed using AI to predict neurodevelopmental outcomes. AI-based clinical decision support systems have been deployed to enhance workflows and outcomes by early detection of disease, reducing medication errors and help clinicians improve decision-making. However, there remain ethical and practical challenges in the use of AI including data privacy, the need for high-quality pediatric datasets, rigorous clinical validation and transparency, to ensure that AI strengthens clinical judgement and is trustworthy.