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PubMed2026

Immunogenicity and safety of prophylactic HPV vaccines in people living with HIV: A systematic review and meta-analysis.

Human papillomavirus (HPV) is a major global public health concern, causing genital warts and cancers of the cervix, anus, oropharynx, vulva, and penis. People living with HIV (PLWH) face a disproportionately elevated burden of HPV infection and HPV-related malignancies due to chronic immunosuppression. We conducted a systematic review and meta-analysis searching six databases from January 2006 to June 2026 without language restrictions. Twenty-five studies were included in the systematic review; 12 independent studies (N = 1,493 for HPV16) were included in the quantitative meta-analysis. Using a DerSimonian-Laird random-effects model with logit transformation, pooled seroconversion rates were: HPV16 97.8% (95% CI: 94.9-99.1%; I2 = 89.6%; 15 datasets), HPV18 94.2% (95% CI: 86.1-97.7%; I2 = 95.8%; 13 datasets), HPV6 97.0% (95% CI: 93.7-98.6%; I2 = 66.1%; 10 studies), and HPV11 97.1% (95% CI: 90.5-99.1%; I2 = 95.5%; 10 studies). CD4 count was the most consistently reported modifier of immunogenic response: HPV16 seroconversion was 98.5% in PLWH with CD4 > 350 cells/μL vs. 71.1% in those with CD4 ≤ 200 cells/μL (ACTG A5240). All three vaccine generations demonstrated high immunogenicity. Two doses of the nonavalent vaccine were non-inferior to three doses in virologically suppressed women (Papillon RCT). No vaccine-related serious adverse events were reported. GRADE certainty of evidence was moderate for HPV16, HPV6, and HPV11, and low for HPV18. Prophylactic HPV vaccination achieves high seroconversion rates across all vaccine generations in PLWH. CD4 count significantly modifies vaccine response, underscoring the importance of vaccination before severe immunosuppression develops. These findings support current international recommendations advocating HPV vaccination for all PLWH.

Humans↗
PubMed2026

Distress Intolerance, Social Anxiety, and Depressive Symptoms in Adolescents: Evidence from Random-Intercept Cross-Lagged Panel and Cross-Lagged Panel Network Analyses.

Social anxiety and depressive symptoms frequently co-occur during adolescence, yet the mechanisms underlying their longitudinal associations remain insufficiently understood. Distress intolerance has been proposed as a transdiagnostic risk factor implicated across internalizing symptoms. However, it remains unclear whether distress intolerance is predicted by social anxiety and depressive symptoms, as well as the underlying mechanisms among these three constructs. The specific symptoms most centrally involved in these cross-domain associations remain poorly understood. The present study investigated the longitudinal associations among distress intolerance, social anxiety, and depressive symptoms using a dual-method framework combining random-intercept cross-lagged panel models (RI-CLPM) and cross-lagged panel network (CLPN) analyses. A total of 1,378 Chinese adolescents (Mage = 12.57, SDage = 0.63; 50.4% female) were assessed at three time points with six-month intervals between waves. The RI-CLPM analyses revealed that higher distress intolerance prospectively predicted subsequent increases in both social anxiety and depressive symptoms, whereas elevated social anxiety and depressive symptoms in turn predicted subsequent increases in distress intolerance. Moreover, distress intolerance mediated the longitudinal associations between social anxiety and depressive symptoms. Additionally, distress intolerance was also indirectly associated with its own subsequent levels through social anxiety and depressive symptoms. The CLPN analyses revealed that fear of negative evaluation and fatigue were the strongest predictors of other network nodes from T1 to T2 and from T2 to T3, respectively. In contrast, distress intolerance symptoms were predominantly predicted by other nodes in both cross-lagged networks. These findings extend prior views of distress intolerance as a unidirectional vulnerability by showing that distress intolerance is also predicted by social anxiety and depressive symptoms and accounts for part of their longitudinal associations across adolescence.

Humans↗
PubMed2026

Orange juice and hesperidin increase flavanone exposure without detectable short-term vascular benefits: a randomized crossover trial.

Orange juice is a major dietary source of hesperidin, a citrus flavanone with vascular protective effects in experimental models. However, whether nutritionally realistic intake levels induce measurable benefits in humans remains unclear. We investigated the effects of orange juice and hesperidin supplementation, at realistic dietary doses, on vascular function, flavanone bioavailability, and molecular responses. Thirty-seven centrally overweight men completed a randomized, double-blind, controlled, three-period crossover trial with three 6-week interventions separated by washout periods. Participants consumed daily 330 mL of 100% orange juice (OJ), an isoenergetic control beverage (CON), or a hesperidin-enriched control beverage (HESP, 210 mg day-1). Fasting vascular, metabolic and anthropometric parameters were assessed before and after each intervention, with flow-mediated dilation (FMD) as the primary endpoint. Postprandial FMD, circulating flavanone metabolites and oxylipin profiles were evaluated following a standardized high-fat meal challenge, and flavanone bioavailability was assessed by 24 h urinary excretion. Whole-blood transcriptomics were performed in a subset (n = 9). Plasma exposure to phase II hesperetin metabolites (AUC0-6 h) and 24 h urinary excretion were comparable after OJ and HESP, indicating effective hesperidin delivery and limited matrix effects on bioavailability. Neither intervention significantly affected fasting or postprandial FMD, vascular, metabolic or anthropometric parameters, or oxylipin profiles versus CON. Marked interindividual variability was observed in vascular responses and flavanone bioavailability, although treatment effects were unrelated to baseline endothelial function or flavanone exposure. Exploratory transcriptomic analyses suggested modulation of pathways involved in vascular biology following OJ and HESP. Under nutritionally realistic conditions, orange juice and hesperidin induced measurable biological engagement without detectable short-term vascular benefits, highlighting the complexity of linking flavanone exposure to functional vascular outcomes in humans.

Humans↗
PubMed2026

Identification and formation pathways of oxidation products of chlorinated paraffins during ozonation in municipal wastewater.

Chlorinated paraffins (CPs) cannot be efficiently removed by conventional water treatment processes and are continually discharged into the aqueous environment. Ozonation can effectively remove lipophilic and persistent pollutants. However, the degradation behaviors of short-chain CPs (SCCPs), medium-chain CPs (MCCPs), and long-chain CPs (LCCPs) in wastewater during the ozonation process remained unknown. In this study, ozonation treatment achieved removal efficiencies of 61 % for SCCPs, 66 % for MCCPs, and 51 % for LCCPs from wastewater within 30 min. Approximately 147 oxidative products of SCCPs, MCCPs, and LCCPs were non-targeted identified through Ph4PCl-enhanced ionization with ultra-high performance liquid chromatography-Orbitrap mass spectrometry. These oxidation products were structurally classified into three categories: carbon chain breakage (53 products), HCl-elimination (27 products), and hydroxylation (67 products). Twenty-three di-hydroxylated CPs were newly identified among the products. Hydroxylation was the predominant pathway for SCCPs, producing di-hydroxylated SCCPs ((OH)₂-SCCPs) with a higher generation rate constant (KG = 22.28 × 10⁻² min⁻¹) compared to other products. MCCPs and LCCPs mainly underwent carbon chain breakage and hydroxylation, generating shorter carbon chain congeners, (OH)2-SCCPs, and di-hydroxylated MCCPs ((OH)2-MCCPs). The KG values of (OH)2-SCCPs (10.56 × 10-2 min-1) and (OH)2-MCCPs (12.05 × 10-2 min-1) generated from the MCCPs were the highest, and the KG values of MCCPs (6.49 × 10-2 min-1), SCCPs (6.27 × 10-2 min-1), and (OH)2-SCCPs (4.74 × 10-2 min-1) generated from the LCCPs were higher than those of other products. These results comprehensively clarify the oxidation efficiencies and pathways of CPs during ozonation. Future studies must explore the potential risks associated with the oxidation products.

Water Pollutants, Chemical↗
PubMed2026

Online Social Anxiety in the Digital Age: Transitions, Predictors, and Mental Health Associations in Emerging Adulthood.

BACKGROUND: Online social anxiety (OSA), a multidimensional form of social evaluative anxiety in online social contexts, disproportionately affects emerging adults who constitute the largest active group of media users and face heightened psychological sensitivity due to growing pressures and immature sociocognitive regulation during the transition to adulthood. However, its heterogeneity, transitions, and longitudinal associations with mental health outcomes remain underexplored. METHODS: This study utilized data from two waves of a three-wave longitudinal survey, with 849 Chinese participants (Meanage = 21.6 years; 50.4 percent female) assessed at 4-month intervals. Individuals were classified using latent profile analysis and the stability and changes of profiles were assessed via latent transition analysis (LTA). Multinomial logistic regressions were conducted separately at baseline and follow-up to identify correlates of profile membership. Predictors of profile transitions were examined using manual three-step LTA models, and associations between latent transition patterns and follow-up mental health outcomes were examined using BCH-LTA distal outcome analyses controlling for the corresponding baseline symptom level. RESULTS: Four profiles of OSA were identified: low, privacy-sensitive, moderate-high, and high OSA. Extreme profiles (low/high OSA) showed high stability (80.4 percent and 79.1 percent), while privacy-sensitive OSA exhibited the lowest stability (55.1 percent). Profile memberships were influenced by social-cognitive biases and digital interaction, particularly fear of negative evaluation and online interpersonal trust, whereas profile transitions were mainly associated with anxiety. Transitions toward less severe OSA profiles were generally associated with better subsequent mental health, whereas transitions toward more severe profiles corresponded to poorer outcomes, particularly for offline social anxiety. CONCLUSION: OSA was heterogeneous in its manifestation, severity and transitions. Personalized and early interventions targeting profile-specific vulnerabilities are critical to prevent the worsening of OSA and mitigate its psychological burden.

Humans↗
PubMed2026

Comparative Effectiveness of Oral Ivermectin, 1% Permethrin Shampoo, and 4% Dimethicone Liquid Gel in Treatment of Pediculosis Capitis among School Children in Chachoengsao Province, Thailand.

Pediculosis capitis remains a persistent public health issue, especially in developing countries where resistance to standard neurotoxic pediculicides like permethrin is increasingly prevalent. This study aimed to compare the effectiveness of alternative treatment options against the standard care in a resource-limited setting. We conducted a single-blind randomized controlled trial involving three primary schools in Chachoengsao Province, Thailand (ClinicalTrials.gov: NCT06332872). Eighty-five female participants ages 6-13 years with active infestations were enrolled. Schools were randomly assigned to three treatment arms: 1) oral ivermectin (200 &#xb5;g/kg) on Days 0 and 7; 2) 1% permethrin shampoo on Days 0 and 7, or 3) 4% dimethicone liquid gel as a single dose on Day 0. The primary outcome was the cure rate, defined as the absence of live lice and viable nits upon clinical assessment on Day 9. Of the 66 participants included in the final per-protocol analysis, oral ivermectin achieved a cure rate of 95.5% (21/22), which was significantly higher than that of the 1% permethrin standard of care (37.0%; 10/27) and the 4% dimethicone physical suffocant (29.4%; 5/17) (P <0.001). Although dimethicone achieved high initial parasitic clearance on Day 0 (88.2%), a rapid reinfestation rate of 58.8% was observed by Day 9, indicating that a single-dose protocol may be clinically insufficient. Adverse events were mild and temporary across all groups. Oral ivermectin appears significantly more effective than both 1% permethrin and single-dose 4% dimethicone in this population. These findings suggest that permethrin resistance is clinically prevalent and relevant in this area.

Humans↗
PubMed2026

Stigma, discrimination-related events, and determinants among adult people living with systemic lupus erythematosus (SLE): Systematic review and indicator-level meta-analysis.

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease with 0.4&#xa0;million new cases diagnosed annually. With its wide variety of visible and invisible manifestations, people living with SLE report being exposed to stigmatization, which impacts their personal and professional lives. However, the current literature is unclear on whether healthcare management teams assess this concern during follow-up. This study aims to synthesize existing evidence on the prevalence and determinants of stigma among people living with SLE.MethodsThis systematic review and meta-analysis gathered evidence from observational studies identified from three databases on 16 July 2025. Dual independent screening, data extraction, and risk-of-bias assessment (using the Newcastle-Ottawa Scale) were performed. Results were synthesized using descriptive statistics, narrative synthesis, and indicator-level meta-analyses.ResultsWithin the past two decades, 11 studies comprising 2254 people living with SLE reported and measured stigma- and discrimination-related events using various scales. Stigma was found to be prevalent across its three constructs: interpersonal, perceived, and intrapersonal stigma. This review demonstrated that people living with SLE reported a moderate overall burden of stigma (34.71 [95% CI 26.15, 43.27]), with average stigma scores indicating psychological impact. Additionally, nearly one in two persons (46% [95% CI 28-66%]) experienced at least one form of stigma or discrimination, most commonly social isolation and unfair treatment. Mental health associations were correlated with higher stigma burden.ConclusionThis review demonstrates that stigma and discrimination are not just social challenges but also critical determinants of health. With cautious interpretation, pooled evidence reveals a consistent high prevalence of stigma and discrimination, which act as "toxic" stressors, creating a vicious cycle with psychological stress and psychiatric manifestations and disease activity. There is an urgent clinical need to move beyond a mere biological approach to disease assessment and management and to begin screening for the "invisible" burden of invalidation and discrimination.

Humans↗
PubMed2026

Long-term safety of oral orforglipron in Japanese participants with type 2 diabetes (ACHIEVE-J): a multicentre, randomised, open-label, parallel-group phase 3 trial.

BACKGROUND: Orforglipron, an oral GLP-1 receptor agonist, requires further evaluation in east Asian populations with type 2 diabetes, given this group's distinct pathophysiological characteristics. This study aimed to assess orforglipron as add-on treatment to diet and exercise alone or to oral antihyperglycaemic medications in Japanese participants with type 2 diabetes. METHODS: This multicentre, randomised, open-label phase 3 study was conducted in 40 medical research centres and hospitals in Japan. Adults with type 2 diabetes and elevated glucose levels managing their condition with diet and exercise alone or with one or two oral antihyperglycaemic medications were assigned (1:1:1) via computer-generated random sequence to receive once-daily oral orforglipron (3 mg, 12 mg, or 36 mg). Randomisation was stratified by background therapy, baseline HbA1c (&#x2264;8&#xb7;5% or >8&#xb7;5%), and metformin use (yes vs no; applied only to &#x3b1;-glucosidase inhibitors, thiazolidinedione, and glinides). Investigators, participants, and site staff were not masked to treatment. The primary endpoint was safety for 52 weeks, assessed in all randomly assigned participants who received at least one dose of orforglipron. This study is registered with ClinicalTrials.gov, NCT06010004 (ACHIEVE-J). FINDINGS: Between Sept 28, 2023, and June 5, 2025, 450 participants were screened and 401 were randomly assigned to three groups (3 mg, n=132; 12 mg, n=135; and 36 mg, n=134). 352 (88%) completed study treatment. 339 participants (85%, 95% CI 80&#xb7;7-87&#xb7;8) had at least one treatment-emergent adverse event (TEAE), more frequently in the 36-mg group (118 [88%, 95% CI 81&#xb7;5-92&#xb7;5]) than in the 3-mg (107 [81%, 73&#xb7;5-86&#xb7;8]) and 12-mg (114 [84%, 77&#xb7;4-89&#xb7;6]) groups. Most TEAEs were of mild (267 [67%, 61&#xb7;8-71&#xb7;0]) or moderate (63 [16%, 12&#xb7;5-19&#xb7;6]) severity. Discontinuations due to an adverse event occurred in 19 of 134 participants (14%, 95% CI 9&#xb7;3-21&#xb7;1) in the 36-mg group compared with seven of 132 (5%, 2&#xb7;6-10&#xb7;5) in the 3-mg group and 11 of 135 (8%, 4&#xb7;6-14&#xb7;0) in the 12-mg group. Across treatment groups, gastrointestinal symptoms were the most common TEAEs leading to study treatment discontinuation (3 mg: 5 [3&#xb7;8%, 1&#xb7;6-8&#xb7;6]; 12 mg: 8 [5&#xb7;9%, 3&#xb7;0-11&#xb7;3]; and 36 mg: 11 [8&#xb7;2%, 4&#xb7;7-14&#xb7;1]). Level 2 (blood glucose <54 mg/dL) hypoglycaemia events occurred in three of 135 participants in the 12-mg group (2%, 0&#xb7;8-6&#xb7;3) and in three of 134 in the 36-mg group (2%, 0&#xb7;8-6&#xb7;4) groups. No level 3 (severe) hypoglycaemia events occurred. Outcomes were generally similar across background therapies. INTERPRETATION: Treatment with orforglipron in combination with diet and exercise alone or one or two oral antihyperglycaemic medications for 52 weeks demonstrated an acceptable safety profile in Japanese adults with type 2 diabetes. FUNDING: Eli Lilly. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Aged↗
PubMed2026

Systematic Review on the Effectiveness of Photobiomodulation Therapy on Enhancing Musculoskeletal Rehabilitation Outcomes after Total Knee and Hip Arthroplasty.

BACKGROUND: Total knee and hip arthroplasty (TKA/THA) effectively alleviate chronic pain and improve joint function and quality of life. However, postoperative recovery is often hindered by pain, edema, restricted range of motion (ROM), and muscle weakness, necessitating structured physical rehabilitation. Photobiomodulation Therapy (PBMT) has been proposed as an adjunct modality to enhance rehabilitation outcomes. This systematic review evaluates the efficacy of PBMT in reducing postoperative pain and edema as well as improving ROM and functional performance compared with placebo or standard physical therapy in post-arthroplasty patients. METHODS: A systematic search of PubMed, ProQuest, ScienceDirect, and Google Scholar was conducted from inception to May 31, 2025. Only prospective controlled trials assessing PBMT effects on postoperative pain, swelling, ROM, or functional performance following TKA or THA were included. Case reports, uncontrolled studies, and trials focusing on unrelated outcomes were excluded. Article selection involved title, abstract, and full-text screening, with additional studies identified through reference lists. The review is registered in PROSPERO (CRD420251123169). RESULTS: Four randomized controlled trials (RCTs; n = 133 participants) met the inclusion criteria, three studies focused on TKA, and one study examined THA. PBMT significantly improved postoperative pain and edema reduction in three trials, while two studies demonstrated enhanced ROM and functional outcomes compared with control or placebo interventions. PEDro scores ranged from 8 to 10, indicating moderate-to-high methodological quality. CONCLUSIONS: PBMT shows promising short-term benefits in reducing postoperative pain and swelling and improving functional performance after knee or hip arthroplasty. However, due to heterogeneity in treatment parameters and limited high-quality trials, conclusive evidence remains insufficient. Future large-scale RCTs with standardized PBMT parameters and extended follow-up are warranted to confirm its clinical efficacy.

Humans↗
PubMed2026

Solutions for engaging priority populations in HIV cure research: a hybrid Delphi consensus-building process.

BACKGROUND: To achieve consensus on barriers and strategies to improve the engagement of three priority populations - Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research. METHODS: We assembled a panel of 54 experts assigned to six groups in a hybrid Delphi process: (1) HIV community members, (2) biomedical researchers, (3) medical providers, (4) funders and private industry members, (5) bioethicists and regulators, and (6) social scientists. Over 18 months, we conducted four iterative survey rounds and three group discussions to identify barriers and strategies to arrive at a consensus on how to engage these priority populations in HIV cure research. RESULTS: For Black and Latino/a/x populations, the panellists identified inadequate outreach and a lack of accessible educational information as primary barriers and emphasised community-driven engagement and partnerships with trusted leaders as key strategies. For cisgender women, logistical hurdles, caregiving responsibilities and time constraints were identified as major barriers, with flexible trial designs and equitable compensation proposed as solutions. For transgender women, the lack of transgender-focused research design, including misrepresentation and exclusion, was identified as a key barrier, while centring transgender-specific needs in study design achieved consensus as the most effective strategy. CONCLUSION: Among all four priority populations, investment in outreach, engagement along the research process, better integration of health needs with research, and enhanced incentives are not novel ideas, but remain obviously ignored in a way that has led to underrepresentation of people in HIV cure research, who carry the greatest burden of HIV in the U.S. SUMMARY: This paper uses a hybrid Delphi process to identify and reach consensus on key barriers and strategies to engage underrepresented groups: Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research across the United States.

Humans↗
PubMed2026

Altered reproductive hormone profiles in systemic lupus erythematosus - A systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) shows a marked female predominance during reproductive years, possibly suggesting hormonal factors in its pathogenesis. However, evidence regarding reproductive hormone alterations in SLE remains inconsistent. OBJECTIVES: To systematically review studies assessing reproductive hormone levels in adult SLE patients compared with healthy controls and across disease activity states. METHODS: Following PRISMA guidelines and a pre-registered protocol (PROSPERO CRD42024544730), PubMed and Scopus were searched (May 2024). Eligible observational studies reported estradiol, testosterone, progesterone, prolactin, FSH, LH, DHEA-S, DHEA or androstenedione in SLE patients versus controls or by disease activity. Random-effects meta-analyses were conducted. RESULTS: Eighty-three studies were included (5389 individuals for SLE vs. controls; 2067 for active vs. inactive SLE). Prolactin was consistently higher in SLE (MD 8.07&#xa0;ng/mL; 95% CI 4.69-11.45; p&#xa0;<&#xa0;0.001) and even more during flare (MD 5.83&#xa0;ng/mL; 95% CI 3.88-7.78; p&#xa0;<&#xa0;0.001). Estradiol showed non-significant overall elevations but was significantly higher in women with active disease (MD 8.55&#xa0;pg/mL; 95% CI 1.37-15.73; p&#xa0;=&#xa0;0.03). DHEA-S was found to be significantly lower in SLE (MD -1.00&#xa0;&#x3bc;g/mL; 95% CI -1.5 to -0.50; p&#xa0;=&#xa0;0.002) but too few studies evaluated its dynamics during flares. FSH and LH were significantly higher in men with SLE. Other hormones were inconsistent. Only three small heterogeneous studies evaluated hormonal changes during flares. CONCLUSIONS: Prolactin excess and androgen deficiency are consistent features of SLE, particularly in women, while elevated gonadotropins are mainly seen in men. Estradiol is higher during active disease but other data are inconsistent. Longitudinal studies are limited, with prolactin the only hormone consistently linked to disease activity and full hormonal profiles during flares are largely unstudied.

Humans↗
PubMed2026

Impact of education protocols and physiotherapeutic management in improving pain, symptoms, activities of daily living, and quality of life in patients with knee osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis is a debilitating condition of the knee joint and the major cause of disability globally, with an increased economic burden on healthcare. Patient education (PE) has emerged as a primary care treatment approach in chronic conditions. This review aims to evaluate the effectiveness of PE along with exercise in reducing pain, alleviating symptoms, improving activities of daily living, and promoting quality of life among individuals with knee osteoarthritis. METHOD: A systematic search was conducted across three electronic databases, PubMed, Cochrane Library, and PEDro. The search was limited to between 2020 and 2025, and included only randomized controlled trials. The Cochrane Risk of Bias Tool and the PEDro Scale were used to evaluate the methodological evidence. Statistical synthesis was analysed using mean differences (MDs) with 95% confidence intervals (CIs) under a random-effects model. RESULTS: Eight trials were included, of which four studies evaluated the four Knee Injury and Osteoarthritis Outcome Score (KOOS) domains, and three studies evaluated the Visual Analogue Scale (VAS) and KOOS activities of daily living domain in patients with knee osteoarthritis. For the meta-analysis, we assessed all five domains of the KOOS scale and VAS. Statistical analysis of the studies showed a significant reduction in pain (VAS) for the PE along with exercise group (MD&#xa0;=&#xa0;-3.28, 95% CI (-4.85; -1.70), and I2&#xa0;=&#xa0;69.6%), but there was no significant improvement in the domains of the KOOS scale. CONCLUSION: The study highlights the importance of PE along with exercise in reducing pain. It might not be more effective when compared with exercise therapy as a standalone intervention in improving ADLs, QoL, and symptoms, but it has demonstrated some degree of effectiveness. It additionally promotes self-management and self-efficacy as a physiotherapeutic rehabilitation treatment intervention.

Humans↗
PubMed2026

Characterizing Submental Neuromuscular Activity of Swallowing Rehabilitation: An Electromyographic Evaluation of Rehabilitative Maneuvers in Healthy Adults.

PURPOSE: The effortful swallow (ES), the Mendelsohn maneuver (MM), and isometric tongue presses (TPs) are widely used swallowing maneuvers/exercises to improve elements of swallowing, such as muscle strength and biomechanics. However, the underlying neuromuscular mechanisms of these exercises remain unclear, potentially limiting our ability to specify treatment targets and improve treatment efficacy. This study aimed to compare submental neuromuscular activation patterns during the ES, MM, TPs, and typical swallows in healthy young and older adults. METHOD: As part of a larger randomized crossover validation study, 60 healthy adults (30 young and 30 older) completed typical swallows and three maneuvers using a wearable submental surface electromyographic (sEMG) system (i-Phagia). Outcome variables included (a) normalized mean sEMG amplitude and (b) time to peak sEMG amplitude. Linear mixed models were used to examine effects of task, age, and sex on both outcomes. RESULTS: Normalized mean amplitude was significantly different across tasks. Post hoc pairwise comparisons confirmed that all three maneuvers produced higher normalized mean sEMG amplitude than typical swallows, with the ES eliciting the highest amplitude across age groups. Time to peak amplitude differed significantly across tasks, with typical swallows requiring the shortest time to reach peak amplitude, followed by the ES, MM, and TP. CONCLUSIONS: The ES required the highest neuromuscular effort with the shortest time to reach peak amplitude, suggesting its potential for targeting submental muscle power. Typical swallows required the least neuromuscular effort with the shortest time to reach peak amplitude, suggesting their potential for training submental muscle speed. The MM and TP may also improve submental muscle strength; however, given their temporal requirements (longer durations), they may be more beneficial for targeting coordination and endurance, though more research in this area is warranted. These findings underscore the importance of task-specific neuromuscular profiling to inform mechanism-based swallowing rehabilitation. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.32948549.

Humans↗
PubMed2026

Implementation factors shaping British Columbia's drug decriminalization pilot: A systematic review with narrative synthesis.

BACKGROUND: In January 2023, British Columbia (BC) became the first Canadian province to implement a legally sanctioned drug decriminalization policy, removing criminal penalties for adults possessing 2.5 g or less of opioids, cocaine, methamphetamine, and MDMA. Introduced as a three-year pilot, it aimed to reframe substance use as a public health issue, reduce stigma, and improve health and social service engagement. Criminal penalties were reintroduced for drug possession in most public spaces in May 2024, and the pilot ended in January 2026. Its termination has been interpreted as policy failure; this review aimed to examine how the pilot was implemented in practice and to identify factors that shaped its operationalization and early implementation-relevant outcomes. METHODS: We conducted a systematic review with narrative synthesis of peer-reviewed literature examining implementation-relevant aspects of BC's decriminalization pilot. Six databases were searched (January-February 2026) for studies published May 31, 2022-February 1, 2026. The protocol was registered in PROSPERO (CRD420251271694). RESULTS: Twenty-seven studies were included. Four cross-cutting implementation barriers were identified: pilot design features, public and cross-sector communication gaps, limited frontline training, and insufficient funding and infrastructure. Design features included the 2.5 g possession threshold, misalignment with real-world drug use patterns; the three-year timeframe, which constrained system-level effects; and the May 2024 amendment, which introduced additional instability. The pilot was implemented without commensurate investment in harm reduction, treatment, or housing infrastructure, within already constrained systems. CONCLUSION: BC's decriminalization pilot suggests the effects of legal reform are shaped by implementation context. Early outcomes may reflect design features, institutional readiness, and system capacity rather than legal change alone; longer-term impacts remain uncertain. Future reforms should align legal change with coordinated implementation, operational guidance, public communication, and adequate service infrastructure.

British Columbia↗
PubMed2026

The musculoskeletal pain literacy questionnaire (MSK-PLq) - Part 1: Development of a preliminary version through a systematic review and Delphi consensus.

OBJECTIVE: Chronic musculoskeletal (MSK) pain is a leading cause of disability worldwide, and self-management is a first-line approach recommended by international clinical guidelines. Access to evidence-based information that enhances health literacy may support patients' engagement in their self-management and treatment decision-making, potentially reducing disease burden and pain. However, no tool currently exists to assess health literacy specifically in MSK pain. This study aimed to develop and describe the preliminary version of a knowledge-based questionnaire to evaluate MSK pain literacy, the Musculoskeletal Pain-Literacy questionnaire (MSK-PLq). METHODS: A systematic literature review identified existing health literacy instruments and generated a preliminary list of domains. A two-round Delphi study with 22 panellists (19 experts and three people living with chronic MSK pain), followed by consensus meetings, was used to refine domains and items (&#x2265;70% agreement). Readability was assessed using the Flesch Reading Ease (FRE) score and three stakeholders were consulted to review the questionnaire for comprehensibility, clarity, and face validity. RESULTS: Six domains were retained (Understand, Access, Appraise, Apply, Digital, Beliefs), comprising 20 items in the preliminary version of MSK-PLq. Readability was acceptable (mean FRE 74, indicating fairly easy reading), and subject feedback supported the questionnaire's clarity and face validity. CONCLUSIONS: The preliminary version of the MSK-PLq is proposed as the first knowledge-based tool to assess functional, interactive, and critical aspects of MSK pain literacy. It may have applications in clinical practice, research, education, and digital health, by informing tailored patient education and supporting self-management strategies, although further psychometric validation is required.

Humans↗
PubMed2026

Virtual reality physical education and adolescents' exercise interest and physical fitness: An explanatory sequential mixed-methods randomized trial with exploratory pathway analysis.

Traditional physical education (PE) faces declining student interest and limited fitness gains. Virtual reality (VR) offers immersive, gamified experiences, but evidence regarding its effectiveness and explanatory pathways remains limited. This explanatory sequential mixed-methods randomized trial assigned 360 adolescents (aged 13-16) from three middle schools to either VR-supported PE (n&#xa0;=&#xa0;180) or conventional PE (n&#xa0;=&#xa0;180) for 12&#xa0;weeks, with a 4-week follow-up. Outcomes included exercise interest (validated scale), physical fitness (coordination via MABC-2, cardiorespiratory endurance via the 20-m shuttle run, explosive power via the standing long jump, and speed via the 10-m sprint), and accelerometer-measured physical activity. The qualitative component involved 38 unique students: 32 completed individual semi-structured interviews, and six additional students participated only in focus groups. Three-level linear mixed-effects models and exploratory structural equation modeling were used. The VR group showed significantly greater improvements in exercise interest (d&#xa0;=&#xa0;0.78), coordination (d&#xa0;=&#xa0;0.62), cardiorespiratory endurance (d&#xa0;=&#xa0;0.55), and speed (d&#xa0;=&#xa0;0.48) than the control group (all p&#xa0;<&#xa0;0.001), but not in explosive power (d&#xa0;=&#xa0;0.12, p&#xa0;=&#xa0;0.148). Effects were partially retained at follow-up (interest d&#xa0;=&#xa0;0.65, coordination d&#xa0;=&#xa0;0.48, endurance d&#xa0;=&#xa0;0.42, and speed d&#xa0;=&#xa0;0.30), a pattern not fully consistent with a purely novelty-driven explanation. Exploratory mediation identified exercise interest as a statistically compatible explanatory pathway (indirect effect&#xa0;=&#xa0;0.34, 95% CI [0.22, 0.46]), although the timing of measurement precludes causal interpretation. Qualitative findings contextualized these results by highlighting immersion, feedback, self-efficacy, and perceived transfer. VR-supported PE may enhance adolescents' exercise interest and selected fitness dimensions, but its limited effect on explosive power and possible novelty contribution indicate that it should complement, rather than replace, conventional PE. Longer-term studies are needed.

Humans↗
PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans↗
PubMed2026

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.

Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg &#xd7; 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.

Adult↗