Infection

Background: Radiographic detection of caries lesions adjacent to restorations is challenging due to limitations of two-dimensional imaging and difficulties distinguishing true lesions from restorative or anatomical radiolucencies. Artificial intelligence (AI)-based clinical decision support systems (CDSSs) have been introduced to assist radiographic interpretation; however, different AI tools may yield variable diagnostic outputs, and their comparative performance remains unclear. Objective: To compare the diagnostic performance of commercial and experimental AI algorithms for detecting secondary caries lesions on bitewings. Methods: This cross-sectional diagnostic accuracy study included 200 anonymized bitewings comprising 885 restored tooth surfaces. A consensus group reference standard identified all surfaces with a caries lesion and classified each lesion by type (primary/secondary) and depth (enamel-only/dentin-involved). Five commercial (Second Opinion, CranioCatch, Diagnocat, DIO Inteligencia, and Align X-ray Insights) and three experimental (Mask R-CNN-based and Mask DINO-based) systems were tested. Diagnostic performance was expressed through sensitivity, specificity, and overall accuracy (95% CI). Comparisons used generalized estimating equations, adjusted for clustered data. Results: Specificity was high across all systems (0.957-0.986), confirming accurate recognition of non-carious surfaces, whereas sensitivity was moderate (0.327-0.487), reflecting frequent missed detections of enamel and dentin lesions. Accuracy ranged from 0.882 to 0.917, with no significant differences among models (p >= 0.05). Confounding factors, such as radiographic overlapping, marginal restoration defects, and cervical artifacts, were the main sources of misclassification. Conclusions: AI algorithms, regardless of architecture or commercial status, showed similar diagnostic capabilities and a conservative detection profile, favoring specificity over sensitivity. Improvements in dataset diversity, labeling precision, and explainability may further enhance reliability for secondary caries detection. Clinical Significance: AI-based CDSSs assist clinicians by providing consistent detection. Their high specificity is particularly valuable in minimizing unnecessary invasive treatments (overtreatment), though they should be used as adjuncts rather than a replacement for expert judgment.

A multiplex diagnostic test is evaluated for self-reported long COVID associated persistent symptoms and a poor recovery from a SARS-CoV-2 infection. A mass-standardised concentration of total antibodies (AC), high-quality (HQ) antibodies and percentage of HQ antibodies (HQ%) is assessed against a spectrum of spike proteins to the SARS-CoV-2 variants: Wuhan, , {delta}, and the Omicron variants BA.1, BA.2, BA.2.12.1, BA.2.75, BA.5, CH.1.1, BQ.1.1 and XBB.1.5 in three cohorts. A cohort of control patients (n = 46) recovered (CC) and a cohort of self-declared long COVID patients (n = 113) (LCC). A nested Receiver Operating Characteristic (ROC) analysis, performed for the variant with lowest HQ concentration in the spectrum, produced an area under the curve and AUC = 0.61 (0.53-0.70) for the CC vs LCC cohorts. For the LCC cohort, the cut-off thresholds for AC = 0.8 mg/L, HQ = 1.5 mg/L and HQ% of 34% were determined, leading to a 71% sensitivity and 66% specificity derived by the Youden metric. The cohorts may be fully classified based on ROC and outlier analysis to give an incidence of persistent virus 62% (95% CI 52% - 71%), hyperimmune 12% (95% CI 7% - 20%) and unclassified, 26% (95% CI 18% - 35%). The overall diagnostic accuracy for both the hyper and hypo immune is 69%. All clinical interventions can now be tailored for the heterogenous long COVID patient cohort.

Gingival inflammation is associated with dysbiotic oral biofilms characterized by reduced nitrate-reducing capacity and diminished nitric oxide (NO) bioavailability. While dietary nitrate has been shown to influence oral microbial activity, the effects of sustained, localized nitrate delivery on oral biofilm ecology and gingival inflammation remain incompletely defined. In this randomized, double-blind, placebo-controlled trial, 30 adults with gingival bleeding were assigned to receive localized prebiotic nitrate (~0.989 mmol per dose) or placebo for 21 days. The primary outcome was mean bleeding on probing (mBOP). Secondary outcomes included modified Gingival Index (mGI), Quigley-Hein plaque index (QHPI), salivary nitrite (as a proxy for NO bioavailability), oral pH, and microbiome composition assessed by 16S rRNA gene sequencing. Prebiotic nitrate supplementation formulation delivered in a slow-release chewing gum significantly reduced mBOP (25.7% to 15.3%; p = 0.0002) compared to placebo chewing gum. Salivary nitrite levels and oral pH increased, indicating enhanced nitrate metabolism. Microbiome analysis demonstrated enrichment of nitrate-reducing taxa, including Rothia mucilaginosa and Neisseria spp., and a relative reduction in inflammation-associated genera such as Prevotella and Porphyromonas. Localized prebiotic nitrate formula delivered in a functional chewing gum was associated with reduced gingival inflammation and shifts in oral microbiome composition consistent with enhanced nitrate-reducing capacity critical in nitric oxide formation. These findings support a role for biofilm-directed nutritional modulation as a non-antimicrobial approach for managing gingival inflammation and improving nitric oxide bioavailability.

Background: Impacted maxillary incisors present significant clinical challenges requiring interdisciplinary management. To date, no meta-analysis has quantitatively synthesized success rates specifically for impacted maxillary incisors. This systematic review and meta-analysis aimed to determine the pooled success rate of orthodontic traction for impacted maxillary incisors and identify factors influencing outcomes. Methods: A systematic review and meta-analysis of observational studies was conducted following PRISMA 2020 guidelines. A systematic search was performed in PubMed, Epistemonikos, Cochrane Library, and Google Scholar (January 2011 - March 5, 2026). Primary studies reporting success rates of orthodontic traction for impacted maxillary incisors were included. The primary outcome was successful eruption and alignment into the dental arch. Although the protocol was not registered in PROSPERO, the methodology was predefined, documented, and strictly followed to minimize risk of bias. Pooled success rates were calculated using a random-effects model (DerSimonian-Laird method) with R software (meta package). Heterogeneity was assessed using I2 statistics. Publication bias was evaluated using funnel plots and Egger's test. Quality assessment employed ROBINS-I. Results: Eleven studies with 2,847 patients were included in the systematic review; 2,149 patients from 11 studies provided sufficient data for quantitative synthesis. The pooled success rate was 82.3% (95% CI: 78.6-86.0%), with a prediction interval ranging from 70% to 91%. Considerable heterogeneity was observed (I2 = 78%, p < 0.001). Subgroup analysis showed that younger age (<14 years) was associated with significantly higher success rates (88.4% vs. 78.2%, p = 0.01). Mild impaction depth (<5mm) was associated with higher success rates (89.2% vs. 76.5%, p = 0.02). No significant publication bias was detected (Egger's test, p = 0.18); however, the power to detect publication bias is limited with fewer than 15 studies. Certainty of evidence was moderate due to heterogeneity and observational study designs. Conclusions: Orthodontic traction is an effective, though not universally successful, treatment modality, with a pooled success rate of 82.3% for impacted maxillary incisors, and success significantly associated with patient age and impaction severity. Early intervention and favorable impaction characteristics are associated with better outcomes

Ambulatory Care Sensitive Conditions (ACSCs) are conditions for which effective and timely primary health care (PHC) can prevent hospitalizations. They are widely used as a proxy indicator of access to and quality of PHC. Despite their relevance, evidence from Central America remains scarce. This study aimed to quantify the burden, describe the epidemiological profile, and assess temporal trends of ACSCs hospitalizations in Honduras from 2014 to 2024. We conducted a retrospective observational study using national administrative hospital discharge data from all Ministry of Health hospitals. ACSCs were defined using a standardized list of 20 diagnostic groups based on ICD-10 codes. We estimated percentages and sex-age-standardized hospitalization rates per 10,000 inhabitants. Clinical indicators included length of stay (LOS) and in-hospital fatality rates. Temporal trends were evaluated using joinpoint regression models to estimate annual percent changes (APC). Analyses included stratification by age, sex, and disease category. A total of 4,023,944 hospitalizations were analyzed, of which 547,486 (13.6%) were classified as ACSCs. The overall sex-age-standardized rate was 54.1 per 10,000 inhabitants. ACSCs' standardized rates increased between 2014 and 2018 (APC: 2.7%; 95% CI: -2.4; 15.2), declined sharply between 2018 and 2021 (APC: -17.8%; 95% CI: -30.6; -10.3), and increased again between 2021 and 2024 (APC: 15.9%; 95% CI: 4.6; 37.6). Despite this rebound, rates remained below pre-pandemic levels. ACSCs were concentrated among children under 5 years (27.7%) and adults aged 60 years and older (29.9%). Noncommunicable diseases accounted for 56.8% of cases, with diabetes mellitus as the leading cause. Compared with non-ACSCs hospitalizations, ACSCs were associated with longer LOS (4.9 vs. 3.9 days; p <0.001) and higher in-hospital fatality rates (2.4% vs. 1.7%; p <0.001). ACSCs hospitalizations constitute a substantial burden in Honduras and reflect persistent gaps in PHC performance. Strengthening PHC resilience and capacity, particularly for chronic disease management and vulnerable populations, is essential to reduce avoidable hospitalizations and improve health system efficiency and equity.

Aim: To comprehensively characterize the salivary proteome in periodontitis using Orbitrap Astral data-independent acquisition mass spectrometry (DIA-MS), identify an atlas of differentially expressed proteins (DEPs), and develop a machine learning-derived multi-protein biomarker panel for non-invasive diagnosis of stage III/IV periodontitis. Materials and Methods: Unstimulated saliva samples from 199 participants (periodontal health/gingivitis, n=120; stage III/IV periodontitis, n=79) were analyzed by Orbitrap Astral DIA-MS. DEPs were identified, and pathway enrichment analysis was performed. A two-tier machine learning pipeline, integrating pathway-based feature selection with cross-validated evaluation, was applied to identify the optimal diagnostic panel. Results: Orbitrap Astral DIA-MS quantified 5,597 salivary proteins and 1,966 DEPs (|log2FC|>0.5, FDR<0.05). Pathway analysis identified 14 periodontitis-relevant KEGG pathways, including Th17 cell differentiation, IL-17 signaling, neutrophil extracellular trap formation, and complement and coagulation cascades. A four-protein panel (TEC, RAC1, MAPK14, KRT17) achieved an area under the curve (AUC) of 0.985 plus-or-minus sign 0.010, with 83% sensitivity and 100% specificity. The panel was corroborated using public datasets. Conclusions: To our knowledge, this study represents the first application of Orbitrap Astral DIA mass spectrometry in periodontitis research, establishing a disease-specific DEPs atlas and a salivary biomarker panel with high diagnostic accuracy for stage III/IV periodontitis, providing a foundation for future external validation studies.

Objectives: Accurate assessment of orthognathic surgical accuracy is essential in the evaluation of operative techniques. Surgical accuracy is often reported as rotational and translational deviations from planned positions. This results in 6 separate values, translation in three planes, anterior-posterior (AP), superior-inferior (SI) and medial-lateral (ML) and rotations about three axes, pitch, roll and yaw. However, rotations will influence 3-dimensional positions and translational discrepancies. Methods: We have derived a mathematical formula using Euclidean geometry and quadratic functions that quantifies the impact of rotations on translational discrepancies. This allows for the calculation of a total discrepancy value that incorporates the three translations and rotations. Furthermore, we developed an interactive web-based application using the open-source shiny R package. Results: We have successfully reduced equations from Euclidean geometry into a quadratic form. The equation is as follows, [4(sin{theta}/2)2-2]x2 + [8d(sin{theta}/2)2-2d]x + 4d2(sin{theta}/2)2 = 0, where {theta} represents the rotational discrepancy in radians and d represents the translation discrepancy. This allows us to solve for the correction needed to be made to translational discrepancies to account for the influence of rotational discrepancies. We successfully developed a web application with a user-friendly graphical user interface. Clinicians upload their own data in the excel (.xlsx) file format and the application automatically performs the necessary calculations over many patients, returning a downloadable table of results. Conclusion: We present a mathematical formula incorporated into a web-application to combine translational and rotational discrepancies for deeper insight when evaluating orthognathic surgical accuracy. Clinical Relevance: This allows surgeons to account for rotational influence on 3-dimensional translational discrepancies.

Background: Potassium is involved in multiple physiological processes in the body, and hyperkalemia is a common, potentially life-threatening condition. Objective: The aim of our study was to examine the association between plasma potassium levels, and 30-day mortality in patients presenting to an emergency department with normo- or hyperkalemia. Design: Retrospective Cohort study. Setting: Emergency Departments in the Capital region of Denmark Participants: Persons attending Emergency Departments in the Capital Region of Denmark from 2017--2021 with a plasma potassium level of at least 3.5 mM measured within 4 hours after arrival. Measurements: The study was based on data from Danish National Registries and electronic patient records. We performed Kaplan-Meier survival analyses and unadjusted and adjusted cox regression analyses utilizing plasma [K+] 3.5--4.4 mM as the reference group for 30-day mortality hazard ratios (HRs). Results: A total of 248,453 patients were included with a median age of 60 years (Q1;Q3 42;75), and 6,959 (2.8%) died within 30 days. Mortality was 2.2% for potassium level 3.5--4.4 mM, 6.9% for 4.5--4.9 mM, 17.1% for 5.0--5.9 mM, and 26.9% for [&ge;] 6.0 mM. Unadjusted 30-day HRs were 3.2 (95%CI: 3.0--3.4) for [K+] 4.5--4.9 mM, 8.6 (95%CI: 7.9--9.3) for [K+] 5.0--5.9 mM, and 14.7 (95%CI: 12.5--17.0) for [K+] [&ge;]6.0 mM. Adjusted HRs were 1.4 (1.3--1.5), 2.10 (1.9--2.3), and 2.4 (2.0--2.8), respectively. Limitations: Risk of residual confounding. Missing data. No access to data regarding in-hospital treatment. Conclusion: Plasma potassium levels above 4.4 mM were associated with increased 30-day mortality among patients presenting to emergency departments. Primary funding source: Department of Emergency Medicine, Copenhagen University hospital, Bispebjerg and Frederiksberg Hospital.

To make effective antimicrobial toothpastes, you need to optimize many parts that work together. Creating new formulations the old-fashioned way takes a lot of time and money. This research formulates and substantiates a methodological framework that combines systematic antimicrobial susceptibility testing with Particle Swarm Optimization (PSO) to enhance toothpaste formulations against clinically significant oral pathogens. Using a D-optimal mixture design, we made 24 different toothpaste formulations by changing the type of fluoride (NaF, MFP, SnF2), the concentration of fluoride (1000-1500 ppm), the concentration of SLS (0.5-2.5%), the type of abrasive (silica, calcium carbonate, dicalcium phosphate), and the concentration of abrasive (10-30%). We used agar well diffusion and minimum inhibitory concentration (MIC) tests to see how well the drugs worked against Streptococcus mutans ATCC 25175, Porphyromonas gingivalis ATCC 33277, and Lactobacillus acidophilus ATCC 4356. A Random Forest surrogate model was trained on 120 experimental data points (24 formulations x 5 concentrations) and validated through 10-fold cross-validation. Multi-objective PSO was used to improve the effectiveness of antimicrobials, the availability of fluoride, and the cost of the formulation. Chosen PSO-predicted formulations underwent experimental validation. The antimicrobial activity changed a lot (p < 0.001) depending on the formulation parameters. The optimized formulation (sodium fluoride 1120 ppm, SLS 2.3%, hydrated silica 18%, pH 7.2) showed 28.4 {+/-} 1.2 mm of inhibition against S. mutans, 26.8 {+/-} 1.4 mm against P. gingivalis, and 24.2 {+/-} 1.1 mm against L. acidophilus. These were improvements of 18.5%, 22.3%, and 19.8%, respectively, over the best commercial comparator. Experimental validation corroborated PSO predictions with a mean absolute error of 5.2%. Multi-objective Optimization found Pareto-optimal formulations that let you choose based on trade-offs between effectiveness, safety, and cost. Combining systematic experimental design with PSO gives a tested framework for making rational toothpaste formulations. This method significantly lowers the amount of work needed for experiments while also allowing for the Optimization of multiple competing formulation goals.

Objectives: To assess the availability of key clinical trial registration data and compliance with legal reporting requirements for all Phase 2-4 drug trials registered on the new European Clinical Trial Information System (CTIS) registry. This study is the first ever assessment of data quality and legal compliance with reporting requirements on CTIS. Design: Cross-sectional observational study of CTIS registry data combined with manual review of results documents. Setting: Cohort of all 7,547 Phase II-IV clinical trials registered on CTIS as of November 2025. Main outcome measures: Number and proportion of missing data points in CTIS registration data. Proportion of completed clinical trials that are compliant with regulatory reporting requirements. Results: Trial registration data quality was high overall with more than 99% of expected data present. Of 234 clinical trials legally required to report results, fewer than half (49.6%) fully reported results within the required timeframe, 20 trials (8.5%) fully reported results late, and 98 trials (41.9%) failed to fully report results. Legal compliance was similar for adult trials (79/158) and paediatric trials (37/76). Conclusions: Sponsor compliance with legal reporting requirements is weak. Current efforts by European regulators to monitor and enforce compliance appear to be insufficient. New results reporting functions currently being set up by trial registries worldwide will require quality assurance processes. Trial registration: Study protocol prospectively registered on OSF: https://osf.io/sn4j2/overview

Background: Peak height velocity (PHV) is a critical indicator of pubertal growth timing and is widely used in orthodontics to determine optimal timing for growth modification interventions. Secular trends toward earlier maturation have been reported, but a quantitative synthesis of PHV age reduction across generations is lacking. Objective: To systematically review and quantitatively synthesize evidence for secular trends in age at PHV and to estimate the pooled mean difference in PHV age between historical and contemporary cohorts. Methods: A systematic search was conducted in PubMed and Google Scholar from January 1990 to December 2021. The Directory of Open Access Journals (DOAJ) was also searched but yielded no eligible studies due to the specificity of the search string. Studies were included if they reported age at PHV in two or more birth cohorts separated by at least 20 years, used objective methods to determine PHV (longitudinal growth data with curve fitting), and reported means with standard deviations or standard errors. Risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects quantitative synthesis (meta-analytic approach) was performed to calculate the pooled mean difference in PHV age between historical and contemporary cohorts. Between-study variance (tau-squared) was estimated using the restricted maximum likelihood (REML) method. Heterogeneity was assessed using I-squared statistics. Given the limited number of eligible studies, findings should be interpreted as preliminary. Results: Two high-quality longitudinal studies met inclusion criteria, comprising 171 participants from historical cohorts (1969-1973) and 71 participants from contemporary cohorts (1996-2000). The pooled mean difference in PHV age was -0.48 years (95% CI: -0.72 to -0.24, P < 0.001), indicating that contemporary children reach PHV approximately 0.5 years earlier than their historical counterparts. PHV velocity showed a pooled increase of 0.71 cm/year (95% CI: 0.48 to 0.94, P < 0.001). Heterogeneity was low (I-squared = 0% for both analyses). Both studies were rated as low risk of bias. These findings are based on a limited number of studies and should be interpreted as preliminary. Conclusions: This preliminary quantitative synthesis provides evidence of a secular decline in age at peak height velocity of approximately 0.5 years in contemporary children compared to historical cohorts, accompanied by an increase in growth velocity. These findings suggest that orthodontic growth modification strategies may need to be initiated earlier than traditionally recommended. However, given the limited evidence base, results should be interpreted with caution and require confirmation in large-scale longitudinal studies.

ObjectivesTo evaluate the effect of surgical hubs on the volume of surgeries, patient waiting times, and length of hospital stay for elective hip and knee replacements in the English NHS. DesignA retrospective longitudinal study using a difference-in-differences approach to compare changes in outcomes at NHS trusts that opened surgical hubs with those that did not. SettingThe study was set in the English NHS, using administrative data from NHS acute trusts providing elective hip and knee replacements between April 2014 and September 2024. ParticipantsThe study included 76 NHS trusts. The treatment group consisted of 29 trusts that opened a surgical hub for trauma and orthopaedic surgery during the study period. The control group consisted of 47 trusts that did not. 48 trusts that performed fewer than 1,000 relevant procedures over the ten-year period or that reported data for fewer than 41 of the 42 quarters in the sample period were excluded. InterventionThe phased introduction of surgical hubs dedicated to elective procedures at 29 NHS trusts between Q1 2020 and Q3 2024. Main outcome measuresThe three main outcomes were, measured at the trust-quarter level: the total number of elective primary hip and knee replacements (surgical volume), the average length of stay in hospital, and the average waiting time from being added to the waiting list to hospital admission. ResultsThe opening of a surgical hub was associated with an increase of 43.75 hip and knee replacement surgeries per quarter (95% CI: 22.22 to 65.28), which represents a 19.1% increase compared to the pre-hub mean. Length of stay was reduced by 0.32 days (95% CI: - 0.48 to -0.16), a 7.8% reduction. There was no statistically significant effect on average waiting times (-14.96 days, 95% CI: -33.11 to 3.19). ConclusionsSurgical hubs appear to be effective at increasing the number of hip and knee replacements and reducing the time patients spend in hospital. However, in this study, they did not lead to a statistically significant reduction in waiting times overall.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem disease characterized by profound fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Its pathophysiology is incompletely understood and likely involves complex interactions between immune, autonomic, and metabolic dysregulation. Despite features with potential relevance for anesthesia and perioperative care, evidence to guide anesthetic management in individuals with ME/CFS remains limited. We therefore performed a retrospective matched-pair analysis to generate clinical data on perioperative responses and identify areas for future research. Methods: We conducted a retrospective matched-pair analysis at a single tertiary center. All patients with ME/CFS undergoing general anesthesia from 2015 to 2026 were identified using ICD-10 codes (G93.3 and U09.9) with additional manual verification and matched 1:1 to controls for comparison. Patients with confounding diagnoses or American Society of Anesthesiologists physical status above III were excluded. The analysis focused on intraoperative hemodynamic parameters, including baseline, post-induction, median, and lowest recorded systolic blood pressure and heart rate, as well as early postoperative outcomes in the post-anesthesia care unit (PACU), including maximum pain scores and requirement for rescue analgesia. Results: Out of 189 individuals identified through ICD-10 codes, 15 matched pairs were included after application of exclusion criteria. ME/CFS patients exhibited lower lowest recorded intraoperative systolic blood pressure (90 [82.5-95.0] mmHg in ME/CFS vs 100 [90.0-110.0] mmHg in controls, p = 0.044) as well as lower lowest heart rate (50 [40.0-57.5] bpm in ME/CFS vs 60 [50.0-65.0] bpm in controls, p = 0.012). Vasopressor use and fluid administration did not differ, and no episodes of severe hypotension or perioperative adverse events were observed. Postoperative pain was higher in ME/CFS, with higher maximum pain scores (NRS 5.0 [4.0-6.0] in ME/CFS vs 1.0 [0.0-4.0] in controls, p = 0.008) and more frequent opioid rescue analgesia (80% in ME/CFS vs 33% in controls, p = 0.039). Postoperative nausea or vomiting, oxygen supplementation, and PACU length of stay were similar between groups. Conclusions: General anesthesia appears hemodynamically well tolerated in individuals with ME/CFS. In contrast, postoperative pain burden is increased and may require tailored analgesic strategies. Post-exertional malaise, a key disease feature with potentially delayed onset and significant impact, was not captured in this study and remains an important target for future research. These hypothesis-generating findings highlight the need for prospective studies to optimize perioperative management and evaluate patient-relevant outcomes in ME/CFS.

BackgroundPleuroparenchymal fibroelastosis (PPFE) is a rare, fibrotic lung disease with poor prognosis, usually affecting adults which most commonly occurs idiopathically. Biallelic pathogenic variants in DGUOK cause mitochondrial DNA (mtDNA) depletion syndrome, predominantly affecting infants with severe hepatic and neurological symptoms. Detailed description of pulmonary manifestations with late-onset presentation have not been reported. MethodsWe describe nine patients with PPFE and DGUOK-associated mitochondriopathy. Clinical, radiological, histopathological, and genetic data were systematically collected from all patients. Functional studies, single nucleus RNA sequencing (snRNAseq), immunofluorescence staining, transmission electron microscopy and respiratory chain enzyme activity assays were conducted on patient-derived fibroblasts, muscle or lung tissues. mtDNA content quantification was performed on whole genome sequencing (WGS) data. ResultsAll patients (ages 5-36) presented with progressive dyspnea, weight loss and some with spontaneous pneumothoraces. Chest computed tomography and lung biopsies showed features of PPFE. Biallelic pathogenic DGUOK variants were identified in all patients, seven of them carry an unreported intronic variant leading to mtDNA depletion. snRNAseq of lung tissue from four pediatric patients identified Aberrant Basaloid cells and intermediate cells as their precursor localized at the fibrotic edge. Mitochondrial alterations were identified by electron microscopy. ConclusionPPFE in children and young adults is associated with DGUOK-related mitochondriopathy. For the first time, we demonstrate Aberrant Basaloid cells in pediatric fibrotic lung tissue. Since pulmonary involvement may be underrecognized or misinterpreted and the clinical presentation may not always be typical of a mitochondriopathy, we recommend genetic testing in all patients with PPFE of unknown origin.

Care workers are central to health systems and the broader care economy, but they often lack the legal protections afforded to other workers. Furthermore, there currently exists no single legal definition of "care worker" under any binding or non-binding international legal instrument. Drawing on the WHO Global Health and Care Worker Compact, we analyzed whether national laws and policies in 10 countries protect care workers. Using comparative legal methods and primary source legal and policy documents, we evaluated both care worker coverage and alignment with four indicators: guaranteed access to protective equipment, protection against discrimination on internationally recognized grounds, unemployment insurance, and the right to join independent unions. We reviewed 43 laws and policies and found that 56% fully or partially met the relevant indicator criteria. The United Kingdom was the only country meeting all four indicators. Overall, we found while many countries recognize these protections in law, care workers are often left outside their coverage, underscoring the need for clearer legal recognition and more inclusive worker protections.

Background: In sub-Saharan Africa where both tuberculosis (TB) and HIV are prevalent, empiric TB treatment in people living with HIV (PLHIV) persists due to limited sensitivity of sputum-based TB tests. We evaluated mortality among molecular test-negative presumptive TB adult PLHIV in a population where the majority are or have been on antiretroviral therapy (ART), comparing mortality between those who received empiric TB treatment and those who did not. Materials and Methods: From November 2017 to December 2020, Xpert-negative presumptive TB adult PLHIV were recruited at Mulago Referral Hospital and Kisenyi Health Centre-IV in Kampala, Uganda. Clinical data including TB symptoms, chest X-ray, and empiric TB treatment decision were collected. Laboratory investigations included CD4 cell count, serum cryptococcal antigen (CrAg), urine TB-lipoarabinomannan (TB-LAM), microbiological blood cultures, and sputum mycobacterial growth indicator tube (MGIT) cultures. Participants were followed monthly for 12 months to ascertain vital status. Results: Overall, 300 participants were enrolled; 61.3% inpatients, 55.7% female, median age 37 (IQR 29-45) years, 82.3% on ART, median CD4 206 cells/mm3 (IQR 36-507). Of the 300 participants, 68 (22.7%) received empiric TB treatment, of which 53 (77.9%) were inpatients. 12-month mortality was 31.0% (93/300); 91.4% among inpatients, 72% within three months post-enrolment. Mortality was higher among those who received empiric TB treatment (51.5 vs. 30.2 per 1,000 person-months; p=0.013) compared to those who did not. TB cultures were positive in 5.0% (15/300), of whom seven (46.7%) were also TB-LAM positive. CrAg was positive in 12.3% and 3.7% had positive blood culture. Conclusion: We found high mortality among Xpert-negative PLHIV, particularly those who received empiric TB treatment, despite high ART coverage. Cryptococcal antigenemia and bacteremia were not uncommon. In presence of negative Xpert results in PLHIV, clinicians should perform extensive laboratory evaluations to identify possible comorbidities or alternative non-TB diagnosis.

Functional dairy products are increasingly recognized for their ability to provide both essential nutrition and additional health benefits. This study aimed to develop and evaluate a synbiotic yogurt enriched with Lactobacillus plantarum as a probiotic and Stevia rebaudiana extract (1% w/v) as a prebiotic source. Thirteen lactic acid bacteria (LAB) strains were isolated from fermented dairy and vegetable samples and evaluated for probiotic potential through tests for acid and bile tolerance, hydrophobicity, aggregation abilities, and pathogen co-aggregation. Isolate PG1 (Lactobacillus plantarum) demonstrated the highest prebiotic growth stimulation index (49%) in the presence of stevia extract and was selected for yogurt formulation. Yogurt samples were prepared and stored at 4{degrees}C for 10 days. Physicochemical properties (pH, titratable acidity, and protein content), microbiological viability, total phenolic and flavonoid content, antioxidant activity (DPPH assay), and sensory attributes were monitored. The synbiotic yogurt (St-Y) showed enhanced functional properties, with a total phenolic content of 16.67 {micro}g GAE/g, a flavonoid content of 6.28 {micro}g QE/g, and 57.84% antioxidant activity. Additionally, it showed improved protein content and superior sensory scores compared to control samples. These findings suggest that S. rebaudiana fortified probiotic yogurt can serve as a nutritious, antioxidant-rich, and sensory-acceptable functional dairy product.

BackgroundThere is a close correlation between neuroendocrine regulation and pulpitis progression. This study aims to identify key neuroendocrine regulation-related genes in pulpitis, providing insights for its treatment. MethodsGSE77459 and GSE92681 datasets were used to validate experimental findings. Key neuroendocrine regulation-related genes were identified via Cytoscape plugin cytoHubba and expression validation. Gene set enrichment analysis, RNA-binding protein regulatory networks, post-translational modifications, molecular regulatory networks, and drug prediction were performed. Key gene expression was experimentally verified in clinical samples. ResultsTop 10 genes were obtained via cytoHubba; 4 (IL6R, OSM, IL1RN, CCL4) with significant differences between pulpitis and control samples and consistent trends in both datasets were identified as key genes. Gene set enrichment analysis showed key genes participate in pathways like cytokine-cytokine receptor interaction. Related RNA-binding proteins were ELAVL1 and HNRNPA1, with phosphorylation as the main post-translational modification. Core regulatory microRNAs included miR-519, miR-765, miR-23, and regulatory factors included FOXC1, PRRX2. Targeted drugs (e.g., sarilumab, haloperidol decanoate, cyclosporine) were predicted, and clinical sample verification confirmed consistent expression trends. Conclusion4 key neuroendocrine regulation-related genes were identified, which may have clinical significance for the diagnosis and treatment of pulpitis.

Background: How post-COVID-19 condition (PCC) differs from post-acute infection syndromes (PAIS) caused by other respiratory viruses remains uncertain. Comparing these conditions may clarify whether post-acute symptoms reflect specific consequences of SARS-CoV-2 infection or broader post-viral mechanisms. Methods: We conducted a systematic review and meta-analysis of cohort studies comparing persistent symptoms or conditions in adults after SARS-CoV-2 infection with those following other acute respiratory viral infections. PubMed, Embase, and Scopus were searched. Random-effects models were used to estimate pooled risks. Results: Among 9,371 records screened, 22 studies were included and 14 contributed to the meta-analysis. Increased risk after SARS-CoV-2 infection was observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations; heart rate abnormalities showed borderline significance. For most other outcomes pooled estimates were inconclusive. Conclusions: Only a subset of outcomes appears more frequent after SARS-CoV-2 infection, suggesting many symptoms attributed to PCC may reflect broader post-viral syndromes.

BackgroundAn upsurge in Streptococcus pyogenes infections 2022-2023 highlighted potential benefits of point-of-care tests (POCT) to support clinical pathways, prevent outbreaks, and optimise antibiotic use. ObjectivesWe conducted a pilot research study in a west London paediatric emergency department (ED) to determine whether a molecular POCT had potential to alter management in children who were also having a conventional throat swab taken for culture. MethodsChildren <16 years presenting to ED who had a throat swab requested by a clinician were invited to have a second swab taken for research purposes only. Clinical management was unaffected by the research swab result, which was processed using a molecular POCT that was not approved for use in the host NHS Trust. ResultsPrevalence of streptococcal infection was low during the study (May 2023-June 2025); swab positivity in symptomatic children was 12.8% (6/47). Overall, 38/49 (77.6%) participants who had throat swabs received antibiotics. Of those children recommended to receive antibiotics, 29/38 (76.3%) had a negative POCT. Mean time to reporting of positive throat swab culture results was 3.67 days (range 3-5 days) leading to occasional delay in treatment, although POCT identified positive results within minutes. ConclusionAntibiotic use was frequent and could be avoided or stopped by use of a rule out POCT in over three-quarters of children in the ED, if suspicion of S. pyogenes is the main driver for prescribing. POCT were easy to process and produced immediate results compared with culture, in theory enabling timely decision-making and avoiding treatment delay.