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PubMed2026

Sex-dependent protective effects of microglial tumor necrosis factor on post-stroke inflammation and myelin injury.

Tumor necrosis factor (TNF) is rapidly induced after ischemic stroke, but its proposed cell-specific and sex-dependent functions during post-stroke inflammation remain insufficiently understood. Here, we investigated the role of microglia-derived TNF in the acute and subacute response to permanent middle cerebral artery occlusion (pMCAO). Tnf expression was transiently upregulated after stroke, becoming significant at 4 h, peaking at 12-24 h, and returning to baseline by 5 days. In situ hybridization confirmed strong Tnf expression in the infarct and peri-infarct regions. Whole-brain transcriptomic profiling showed that global TNF deficiency reshaped the early post-ischemic response, shifting it from microglia-associated phagocytic and wound-healing pathways toward an interferon-related inflammatory signature. To define the specific contribution of microglial TNF, we used inducible Cx3cr1CreER:Tnffl/fl mice. Microglial TNF deletion had no effect on infarct volume in males at 24 h or 5 days after pMCAO, but significantly increased infarct size in females at both time points. In both sexes, brain TNF levels peaked at 24 h and were significantly reduced in Cx3cr1CreER:Tnffl/fl mice, confirming microglia as a major source of early post-ischemic TNF. However, downstream consequences diverged by sex. At 5 days, male Cx3cr1CreER:Tnffl/fl mice showed reduced microglial reactivity and 18 kDa translocator protein (TSPO) signal, with no change in T-cell infiltration, and exhibited increased density of mature oligodendrocytes. In contrast, female Cx3cr1CreER:Tnffl/fl mice displayed enhanced microglial reactivity, increased TSPO binding, higher peri-infarct T-cell infiltration, and reduced oligodendrocyte density and myelin integrity. Together, these findings identify microglial TNF as a sex-dependent regulator of post-stroke inflammation and myelin injury.

Animals↗

PubMed2026

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans↗

PubMed2026

Role of External Vibratory Lithoclast (Lithecbole) in Improving Lower Pole Stone Clearance After Extracorporeal Shock Wave Lithotripsy (ESWL).

Background and Objective: Extracorporeal shock wave lithotripsy (ESWL) is a widely used non-invasive treatment for renal stones. However, its effectiveness in clearing stones located in the lower pole of the kidney is often limited due to the anatomical challenges that impede the spontaneous passage of fragmented stones. This study evaluate the efficacy and safety of External Physical Vibration Lithecbole (EPVL) when used as an adjunctive therapy following ESWL in patients with lower pole renal stones, with a focus on improving stone clearance rates. Materials and Methods: This prospective interventional study was conducted at Al Yarmouk Teaching Hospital over two years and included 100 patients with 10-15 mm lower pole renal stones. Patients were randomized into two groups: The ESWL alone and ESWL plus EPVL. All patients received two ESWL sessions (3000 shocks/session). The treatment group additionally received EPVL therapy using a flank-applied vibration device. Follow-up was performed using ultrasound and KUB radiography. Statistical analysis was conducted using appropriate tests with significance set at p<0.05. Results: Baseline characteristics, including age, gender, weight, stone size and location, were statistically comparable between groups. The mean stone size was 12.4±1.7 mm. A significantly higher stone-free rate was observed in the ESWL+EPVL group compared to the ESWL-only group (66% vs. 48%, p = 0.027). Although the residual stone size showed a numerical difference favoring EPVL, it was not statistically significant (p = 0.11). Complication rates were low, mild and similar in both groups (p = 0.3). Logistic regression analysis revealed that smaller stone size (p<0.001) and lower patient weight (p = 0.030) were significantly associated with successful stone clearance. Subgroup analysis further confirmed that patients with stones <11 mm or a weight <70 kg had the highest stone-free rates. Conclusion: In this initial evaluation, EPVL demonstrated a safe and effective adjunct to ESWL in enhancing stone clearance for lower-pole renal stones. Its application was associated with improved treatment outcomes without increasing complication rates. Further studies with extended EPVL sessions and longer follow-up are warranted.

Humans↗

PubMed2025

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1‑chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals↗

PubMed2026

Wildlife forensic DNA evidence links a suspected vehicle to a fatal lowland tapir (Tapirus terrestris) collision in Misiones, Argentina.

Vehicle collisions are recognized as a major driver of biodiversity loss, particularly in road-dense landscapes, exceeding the impact of invasive species and wildlife trafficking. For large-bodied, slow-reproducing, and low-abundance species, such as the lowland tapir (Tapirus terrestris), this threat can have major impacts. Here, we present a wildlife forensic investigation in Misiones, Argentina, involving a tapir, a species afforded the highest level of legal protection as a Provincial Natural Monument. The fatal hit-by-vehicle (HBV) incident occurred in northern Misiones on 31 March 2019 along Provincial Route 19, in a portion that bisects Parque Provincial Urugua-í, with the driver involved in the collision leaving the scene. The suspect was later located and claimed that the damage to the vehicle resulted from a collision with a horse (Equus caballus) rather than a tapir. To legally resolve the incident, DNA (hair and blood) recovered from the suspected vehicle's bumper (evidence) was compared with tissue samples from the tapir carcass (reference). Genetic confirmation of species identity used a 110-bp region of the mitochondrial cytochrome b gene, and individual identity was assessed using 12 species-specific microsatellite loci. These analyses confirmed that all evidence matched the tapir carcass at both species and individual levels, strongly supporting the association between the suspected vehicle and the HBV tapir, and refuting the alternative explanation proposed by the driver. This case demonstrates the value of using wildlife forensic genetics to reconstruct wildlife-vehicle collisions, supporting environmental law enforcement, and strengthening conservation efforts in the Atlantic Forest of Misiones, Argentina.

Animals↗

PubMed2026

Optimizing smoking cessation pharmacotherapy and counseling for adult primary care patients: a factorial randomized controlled trial.

BACKGROUND: Even with the most effective smoking cessation pharmacotherapies (i.e., varenicline or combination nicotine replacement [C-NRT]), the majority of people ultimately return to smoking. This research explored how to optimize the use of varenicline and C-NRT to promote smoking cessation. METHODS: Primary care patients participated in a 2x2x2x2 factorial experiment that evaluated 4 factors: 1) Medication Type (Varenicline vs. C-NRT [patch + mini-lozenge]), 2) Preparation (pre-quit) Medication (4 Weeks vs. Standard); 3) Medication Duration (Extended [24 weeks] vs. Standard [12 weeks]); and 4) Counseling Type (Cessation Counseling [4 sessions] vs. Referral Support [2 sessions focused on use of referral resources]). This study was discontinued prior to reaching the proposed sample size (N = 608) due to pandemic-related budgetary constraints. RESULTS: Participants (N = 496) were 55% women and 45.6% Black individuals. There were no statistically significant main effects of the 4 factors on abstinence at 12, 26 or 52 weeks. There was a 3-way interaction between Medication Type, Preparation Medication, and Counseling Type (p = 0.04) predicting the primary outcome of biochemically confirmed abstinence at 52 weeks; cessation counseling vs. referral support improved varenicline quit rates when 4 weeks versus 1 week of pre-quit medication was offered. For C-NRT, counseling type did not significantly improve quit rates regardless of the use of preparation medication. CONCLUSIONS: There was no robust evidence that enhanced pre-quit or extended duration of varenicline or C-NRT increased abstinence rates. More intensive counseling may support cessation for different pharmacotherapy regimens. Given the lack of consistent findings, this research should be viewed as exploratory to guide future research.

Humans↗

PubMed2026

Early infantile developmental and epileptic encephalopathy: clinical spectrum, diagnosis, outcomes, and evolving treatment strategies.

Early infantile developmental and epileptic encephalopathy (EIDEE) is among the most severe epilepsy syndromes, with onset before three months of age and an estimated incidence of approximately 10 per 100,000 live births. The 2022 International League Against Epilepsy classification unified the historically distinct Ohtahara syndrome and early myoclonic encephalopathy under a single diagnostic framework defined by frequent drug-resistant tonic and/or myoclonic seizures, an abnormal neurological examination, and an abnormal interictal electroencephalogram-most characteristically a burst-suppression pattern. This narrative review synthesizes the clinical, electrophysiological, neuroimaging, genetic, and therapeutic literature within the EIDEE framework. The clinical phenotype is characterized by central hypotonia, postnatal microcephaly, cortical visual impairment, and age-dependent syndromic evolution toward infantile epileptic spasms syndrome or Lennox-Gastaut syndrome in the majority of patients. Electroencephalography remains essential for syndromic classification, while systematic metabolic screening and early trio whole-exome or whole-genome sequencing are central to the etiologic workup, achieving diagnostic yields of 60-65%. The most commonly identified genetic causes include STXBP1, KCNQ2, and SCN2A variants. Outcomes are poor overall and strongly etiology-dependent: vitamin-responsive disorders carry a substantially more favorable prognosis, whereas mortality reaches 25% in genetic cohorts. Genotype-guided pharmacotherapy is now applicable to a clinically meaningful subset of patients, with sodium channel blockers, potassium channel openers, and emerging antisense oligonucleotide therapies representing important therapeutic advances. Gene therapy trials are underway but have encountered early safety signals, underscoring the vulnerability of this population. Critical unmet needs include earlier molecular diagnosis, precision therapies targeting developmental outcomes beyond seizure control, and prospective international registries to characterize the long-term natural history of EIDEE.

Humans↗

PubMed2026

Superficial Cervical Plexus Block and Quality of Recovery after Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Whether adding a bilateral superficial cervical plexus block to a thyroidectomy enhanced recovery pathway improves postoperative quality of recovery remains uncertain. METHODS: In a single-center prospective, randomized, double-blind, placebo-controlled trial in adults undergoing thyroidectomy with general anesthesia, participants were randomized to bilateral superficial cervical plexus blocks with 0.25% bupivacaine or saline. All participants received multimodal analgesia with dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, and incisional local anesthetic. The primary outcome was quality of recovery, measured by the QoR-40 survey, on postoperative day 1. Secondary outcomes included the need for rescue opioid, total opioid consumption, nausea, vomiting, antiemetic administration, length of stay in the postanesthesia care unit (PACU), and opioid use on postoperative day 1. RESULTS: A total of 160 participants were randomized to receive a superficial cervical plexus block with bupivacaine 0.25% (n = 78) or saline (n = 82). On postoperative day 1, mean QoR-40 scores were 174 (95% CI, 170 to 178) for bupivacaine and 173 (95% CI, 169 to 177) for saline. The adjusted mean difference between bupivacaine versus saline was 0.91 (95% CI, -3.57 to 5.40; P = 0.688). There were no significant between-group differences in the need for opioids in the PACU or on postoperative day 1, nausea, vomiting, or PACU length of stay. However, the total amount of opioid administered in the PACU was lower in the bupivacaine group (median [interquartile range], 0 [0 to 8]) compared with the saline group (2 [0 to 20]; Hodges-Lehmann location shift, 0 morphine milligram equivalents; 95% CI, -4 to 0; P = 0.017), and fewer participants in the bupivacaine group received rescue antiemetics (3 [3.8%] vs . 13 [16%]; difference, -12%; 95% CI, -22% to -1.8%; P = 0.011). CONCLUSIONS: Bilateral superficial cervical plexus blocks did not improve quality of recovery after thyroidectomy when added to a multimodal analgesic regimen including dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, and incisional local anesthetic but were associated with lower total PACU opioid consumption.

Humans↗

PubMed2026

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans↗

PubMed2026

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female↗

PubMed2026

Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy has not only significantly improved motor outcome and survival in patients with classic infantile Pompe disease, but also revealed previously unrecognized central nervous system (CNS) involvement. In this international study, involving patients from the Netherlands, Italy, Argentina, Germany, the United Kingdom, and Taiwan, we investigated whether epilepsy should be considered part of the CNS phenotype. METHODS: We included patients with classic infantile Pompe disease, defined by the presence of hypertrophic cardiomyopathy, symptom onset < 6 months of age, complete acid α-glucosidase (GAA) deficiency, and/or 2 severe variants in the GAA gene, who developed epilepsy. Data on epilepsy characteristics, electroencephalogram (EEG), cognitive testing, serum neurofilament light chain (NfL), and brain magnetic resonance imaging (MRI) were retrospectively collected. RESULTS: Seventeen patients from 10 centers were identified. The median follow-up duration was 13.7 years (range 3.3-19). Seven patients had deceased at the time of analysis. The median age at first seizure was 11.5 years (range 2.5-17.5). Seizure semiology was variable: six patients experienced generalized tonic-clonic seizures and 3 focal seizures with impaired consciousness only; 6 had multiple seizure types, and 7 experienced seizures during fever or infection. Seizure frequency varied considerably (in 9 occasionally, 5 monthly, 2 weekly, 1 daily). The most common EEG findings were a slowed background activity and focal epileptiform discharges, not substantially activated by sleep. Levetiracetam was most frequently used as antiseizure medication. Overall, 70% of patients became seizure-free. Serum NfL was elevated in all 6 patients in whom it was measured, and 8 of 10 patients had an intelligence quotient ≤66 at onset of epilepsy. Although brain MRI was not always performed at the age of first seizure, 14 of 15 patients showed white matter abnormalities, which were extensive in 11 of 14 (score ≥7/12). Brain atrophy was present in 9 cases and calcifications in 4. DISCUSSION: Our findings suggest a potential increased frequency of seizures in classic infantile Pompe disease in comparison with unaffected children, occurring predominantly after the age of 7, and that epilepsy is part of the CNS phenotype. The risk of seizures should be evaluated during follow-up in long-term survivors with classic infantile Pompe disease.

Journal Article↗

PubMed2026

Use of Wearable Sensors in Angelman Syndrome: A Systematic Review.

BACKGROUND: Wearable sensors are a promising method for collecting clinical trial outcome data for people with Angelman syndrome (AS). However, there has yet to be a systematic probe into the ways in which wearable sensors have been successfully used in AS. The current study aims to provide a quantitative summary of wearable sensors used in AS, including contexts of use and psychometric properties, and to present key narrative highlights. METHOD: Literature searches were performed in three electronic databases: APA PsycInfo, PubMed and Web of Science Core Collection. Data items were categorized into four categories: sample characteristics, study methodological details, wearable sensor characteristics and psychometric properties assessed. Sample characteristics included sample size, age, biological sex, race/ethnicity and cognitive/developmental functioning. Study methodological details were subdivided into study design and setting. Wearable sensor characteristics included sensor type, placement site, means of attachment, assessed construct and sensor-related data loss. Psychometric properties assessed included reliability and validity of sensor-derived data. RESULTS: We identified 16 articles through our systematic review. Wearable sensors were used to study sleep (n = 10, 62.5%), language (n = 2, 12.5%), gait (n = 2, 12.5%), caregiver proximity (n = 1, 6.3%), EEG power (n = 1, 6.3%), and arousal (n = 1, 6.3%) in AS through actigraphs, vocalization recorders, inertial sensors, radio-frequency identification watches, wireless EEG caps, and functional near-infrared spectroscopy caps, respectively. Findings from these studies broadly indicate that wearable sensors are feasible, reliable and valid for assessing a range of behaviours relevant to AS. CONCLUSIONS: Wearable sensors are a promising solution to enhance assessments in AS. However, with the small extant literature characterized by small sample sizes and restricted focus on a few relevant features in AS, there remains ample opportunities to explore the use of wearable sensors in people with AS. Additional studies will better inform clinical decision-making and ultimately improve the lives of people with AS and their families.

Humans↗

PubMed2026

A validated sensitive LC-MS/MS method and its application in elucidating the unique ocular pharmacokinetic profile of 0.01% atropine underpinning its clinical utility for myopia.

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify atropine in ten rabbit ocular tissues enabling systematic characterization of the ocular pharmacokinetic profile of 0.01% atropine sulfate eye drops after a single topical administration. The method demonstrated excellent linearity (coefficient of determination, R2 ≥ 0.9908) across all matrices, with lower limits of quantification (LLOQ) of 0.05 ng/mL for most tissues and 0.10 ng/mL for retina and lens; intra- and inter-day accuracy, precision, matrix effects, extraction recoveries, and stability all met the acceptance criteria. Following a single bilateral topical dose (50 μL/eye) in New Zealand White rabbits, atropine distributed rapidly into all 12 ocular compartments (the sclera further divided into three anatomical regions) with marked heterogeneity-the highest exposures were found in conjunctiva and cornea, a distinct anterior-to-posterior concentration gradient was observed in the sclera, sustained retention was noted in the retina (mean residence time from zero to the last measurable time point, MRT0-t 3.30 h), while aqueous and vitreous humor eliminated rapidly (elimination half-life, t₁/₂ < 0.7 h), and all tissues except aqueous humor followed a two-compartment model. This validated method and the comprehensive pharmacokinetic data reveal that topically applied 0.01% atropine achieves sustained exposure in key myopia-regulating tissues (retina, choroid, posterior sclera) with low exposure in side-effect target tissues (iris, ciliary body, lens).

Animals↗

PubMed2026

O'nyong-nyong virus adaptive mutations in non-structural protein 1 and 3 enhance RNA replication and overcome FHL1 requirement.

Arthritogenic alphaviruses, like o'nyong-nyong virus (ONNV), cause debilitating musculoskeletal diseases and are geographically expanding. To predict their emergence, we seek to better understand evolutionary mechanisms that enable changes in virus tropism. Here, we identify adaptive mutations in the ONNV non-structural proteins (nsPs) that arose during cellular serial passaging and enabled ONNV to infect non-permissive Lunet cells. Using shotgun proteomics, we show that this human hepatoma cell line lacks the four-and-a-half-LIM domain protein 1 (FHL1), an essential host factor in ONNV RNA replication. Individual single nucleotide mutations in the nsP1 ring-aperture membrane-binding and oligomerization domain, the nsP3 macrodomain, and the nsP3 opal stop codon overcome FHL1 deficiency in Lunet cells by enhanced RNA replication. These findings demonstrate how subtle genomic changes in nsPs can profoundly influence alphavirus replication and tropism.

LIM Domain Proteins↗

PubMed2026

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20 ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r = 0.926). PFOS was the only compound detected at concentrations ≥0.2 ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50 ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans↗

PubMed2026

Effect of Various Types of Remineralizing Agents on the Remineralization of Mild and Moderate Defects Caused by Molar-Incisor Hypomineralization in Mexican Schoolchildren: A 12-month Follow-up Randomized Clinical Trial.

PURPOSE: Using Laser-Induced Fluorescence (LIF), this study aimed to evaluate the effect of three remineralizing agents on permanent molars and incisors with both mild and moderate Molar-Incisor Hypomineralization (MIH) in 8-to-12-year-old Mexican schoolchildren. MATERIALS AND METHODS: In this randomized clinical trial, 104 children were selected to participate and then divided randomly into four groups: Group I: control, Oral-B kids (toothpaste); Group II: Fluor Protector (varnish); Group III: Clinpro White Varnish; and Group IV: MI Paste (CCP-ACP). Both varnishes were applied once every four weeks for twelve months for each group. Remineralization was evaluated by LIF at intervals of 1, 3, 6, 9, and 12 months. Paired-sample t-tests and repeated-measures ANOVA were performed, while the Greenhouse-Geisser correction was used to evaluate sphericity. RESULTS: The three test agents used increased the level of remineralization observed at the site of mild and moderate MIH defects over the course of twelve months (p0.001). A similar decrease in average LIF values was observed across the three treatment groups. CONCLUSIONS: The use of both fluoride varnishes and the CPP-ACP toothpaste was observed to promote the remineralization of both mild and moderate MIH defects.

Humans↗

PubMed2026

Effects of a situational interest-based rotational fitness training program on positive affect in university students: A randomized controlled trial.

BACKGROUND: To evaluate whether a 12-week situational interest-based rotational fitness program improved positive emotional states in university students, to compare module-specific effects, and to examine whether the intervention moderated the heart rate-emotion association. METHODS: In this 2-arm randomized controlled trial, 560 freshmen from 10 Chinese universities were assigned to an experimental (n = 280) or control group (n = 280). The experimental group completed weekly 90-minute sessions covering strength, endurance, speed, and agility modules; controls received regular physical education. Positive emotional states were assessed using the positive well-being subscale of the Subjective Exercise Experiences Scale through ecological momentary assessment at 3 points per session, yielding over 14,000 observations. Linear mixed-effects models tested group, time, group × time, heart rate, and heart rate × group effects. Assessors and analysts were blinded. Ethical approval for the trial was granted by the Institutional Review Board of Capital University of Physical Education and Sports (2025A055). RESULTS: Improvement was greater in the experimental group than in controls (EMM change: 1.843 vs 0.505; difference = 1.338, 95% confidence interval [CI]: 1.275-1.400, P < .001). At week 12, the raw between-group difference was 1.85 (d = 2.23), and all group × week interactions from weeks 2 to 12 were significant. Heart rate positively predicted emotional states in controls (B = 0.005, 95% CI: 0.003-0.007), but this association was attenuated in the experimental group (interaction B = -0.008, 95% CI: -0.011 to -0.005). Strength and agility showed significant improvements, while endurance produced consistently higher emotional states across assessment points. Heart rate moderation was significant for strength and endurance, but not speed or agility. CONCLUSION: The rotational program improved positive emotional states more than regular physical education, although effects varied by module. Strength showed the most robust benefit. The program also weakened, but did not eliminate, the heart rate-emotion association during more demanding activities.

Humans↗

PubMed2026

Fracture-related infection following open forefoot fractures caused by dropped objects.

INTRODUCTION: This study evaluated the rate of fracture-related infection (FRI) of open forefoot fractures caused by dropped objects, and examined associations of treatment characteristics, including intravenous and oral antibiotics and operative debridement, with FRI. METHODS: Patients aged 18-80 years who sustained an open metatarsal or phalanx fracture caused by a dropped object between January 2021 and June 2024 were retrospectively identified from two Level 1 trauma centers. The primary outcome was FRI, determined based on the FRI consensus criteria. FRI rates were compared between those who underwent irrigation and debridement (I&D) at bedside versus in the operating room, and between those who received oral versus intravenous (IV) antibiotics. Patient characteristics were also analyzed to determine host factors associated with FRI. RESULTS: A total of 86 patients (median age 41 years [IQR: 29-56], 58% male) were included. Eighty-five patients (99%) received antibiotics, 31 (36%) of whom received intravenous antibiotics. Sixty-six patients (77%) received an I&D at presentation, 57 (66%) at bedside and 9 (10%) in the operating room. Thirteen patients (15%, 95% CI: 8.3%-24%) developed FRI. No significant difference in FRI rate was found between patients who underwent I&D at bedside versus in the operating room (12% versus 11%, p > 0.99). Among patients who did not undergo I&D in the operating room, no significant difference in FRI rate was found between patients who received oral versus IV antibiotics (17% versus 13%, p = 0.74). Insulin-dependent diabetes was associated with an increased risk of FRI (60% versus 12%, p = 0.02). CONCLUSIONS: In this cohort, one in seven patients developed FRI. No statistically significant differences in FRI rates were observed by I&D setting (bedside versus operative) or antibiotic route (oral versus IV), including in a subgroup analysis excluding patients treated with operating room I&D. These findings are limited by sample size and potential treatment selection bias and should not be interpreted as evidence of equivalence. Management should be individualized based on clinical judgement, resource availability, and patient factors. These findings can help guide the management protocols for "dropped objects" open forefoot fractures presenting to urgent care and the emergency department. LEVEL OF EVIDENCE: Therapeutic Level III.

Humans↗