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PubMed2026

Safety and efficacy of recombinant botulinum toxin type A (Eveotox®) in patients with post-stroke upper limb spasticity: Results from a Phase Ib/II clinical trial.

Upper limb spasticity is a common and disabling complication of stroke. Botulinum toxin type A (BoNT-A) is widely used for focal spasticity treatment, but naturally derived products may present limitations related to immunogenicity and manufacturing variability. Recombinant botulinum toxin type A, produced by genetic engineering without complexing proteins, may provide improved product consistency. This Ib/II study evaluated the safety, tolerability, and preliminary efficacy of recombinant botulinum toxin type A in adults with post-stroke upper limb spasticity. This multicenter, seamless Ib/II clinical study included an open-label dose-escalation Ib phase and a randomized, double-blind, placebo-controlled II phase. Adult patients with post-stroke upper limb spasticity received a single intramuscular injection of recombinant botulinum toxin type A or placebo. The primary endpoint in Phase II was the change from baseline in the Modified Ashworth Scale (MAS) score of the primary target muscle group at Week 4. Secondary endpoints included MAS and Tardieu scale changes in individual muscle groups, Disability Assessment Scale (DAS), Physician's Global Assessment (PGA), and immunogenicity. The Ib phase showed improvements in MAS, DAS, and PGA, indicating an early efficacy signal. In Phase II, recombinant botulinum toxin type A produced a significant reduction in MAS score of the primary target muscle group at Week 4 compared with placebo, with effects sustained through Week 12. At Week 4, the PGA score in the Eveotox® group showed a statistically significant improvement compared with the placebo group. While MAS and PGA scores showed significant improvement, DAS functional scores did not differ statistically from the placebo group at week 4. The treatment was generally well tolerated, and low incidence of antibodies were observed. Recombinant botulinum toxin type A was safe and effective in reducing post-stroke upper limb spasticity after a single administration. These results support further Phase III clinical evaluation.

Humans↗

PubMed2026

[Analysis of a Chinese pedigree affected with Townes-Brocks syndrome due to a novel variant of SALL1 gene and a literature review].

OBJECTIVE: To analyze a novel exonic variant of the SALL1 gene and its impact on the binding site of SALL protein. METHODS: Clinical data of three children diagnosed with Townes-Brocks syndrome and their family members who had presented at the First Affiliated Hospital of Shandong First Medical University in April 2022 were retrospectively collected. The pathogenic variant was identified through whole-genome sequencing (WGS) and validated by Sanger sequencing. Protein structural prediction was performed using AlphaFold and PyMOL software to construct three-dimensional models of the wild-type and mutant proteins. Additionally, previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-386). RESULTS: The proband was one of triplet sisters born at 34+4 gestational weeks. All three cases had presented with anal atresia and rectovaginal fistula, and case 3 also had toe malformation of left foot. WGS revealed a novel heterozygous c.757C>T (p.Gln253*) variant in the SALL1 gene, which was predicted to be pathogenic. Sanger sequencing confirmed co-segregation of the variant with the disease within the family. Protein structural modeling demonstrated that the variant has introduced a premature stop codon at position 253, resulting in a truncated protein. CONCLUSION: Above finding has enriched the mutation spectrum of the SALL1 gene in association with Townes-Brocks syndrome, which also represented a rare case of anal atresia in triplets, and provided a basis for molecular diagnosis, genetic counseling, and further research.

Humans↗

PubMed2026

Post-exercise rehydration: a randomized cross-over trial comparing a 100% fruit juice, a glucose-based sports drink, and water.

BACKGROUND: Previous studies indicate that sports drinks may improve rehydration, compared to water, an effect likely achieved by manufacturing sports drinks to contain carbohydrates and sodium. However, there is a growing preference for natural products and a "food first" approach to sports nutrition. Fruit juices naturally contain similar concentrations of carbohydrates to sports drinks, but fruit juices may produce a more stable blood glucose profile. Fruit juices also naturally contain electrolytes, particularly potassium, but their potential as effective rehydration alternatives to sports drinks, which have higher sodium concentrations, is not well understood. This study compared the rehydration efficacy and glucose responses following consumption of a 100% fruit juice (Raw Hydrate®; FRU), a glucose-based sports drink (SPO), and water (WAT) after exercise-induced hypohydration. Importantly, rehydration beverages were matched for water volume, rather than total volume, to ensure that any potential differences in water balance were not due to unequal water volumes between trials, a limitation affecting previous rehydration research. METHODS: After familiarization, 17 adults (age: 28 ± 8  years; BMI: 23.8 ± 2.9 kg/m2) completed three trials in a randomized cross-over design. The participants cycled in the heat (~35°C) to induce ~2% body mass loss (BML), then rehydrated over a 1 h period in a laboratory (~21°C) with a water volume equivalent to 150% of BML from either FRU, SPO, or WAT. This was followed by an additional 4 h of seated rest (5 h rehydration period), when blood glucose was measured (0, 0.25, 0.5, 0.75, 1, 1.5, and 2 h after beverage consumption), and all urine produced was collected. RESULTS: During the 5 h rehydration period, there was no effect of trial on total urine volume (FRU: 1266 ± 403 mL, SPO: 1338 ± 361 mL, WAT: 1394 ± 360 mL; P = 0.156) or water retention (FRU: 42 ± 12%, SPO: 37 ± 10%, WAT: 35 ± 11%; P = 0.059). The blood glucose area under the curve differed by trial (P < 0.001), with all beverages significantly different from each other (FRU: 10.12 ± 0.72 mmol/L/2h, SPO: 12.48 ± 1.34 mmol/L/2h, WAT: 7.90 ± 0.47 mmol/L/2h; P < 0.003). CONCLUSION: Rehydration efficacy was similar between all beverages, but each elicited a distinct glycemic response. For sports drink consumers seeking a natural alternative or implementing a "food first" nutritional strategy, switching to a 100% fruit juice will not compromise rehydration effectiveness, but may elicit a lower blood glucose response. Although, it should be noted that an additional three participants were withdrawn from the study because of gastrointestinal issues after consuming the 100% fruit juice. This was likely a product of the present study's design, where a large volume of 100% fruit juice (average ~2,300 mL) was consumed in a short period of time (1 h). Whilst this is a commonly used study design to robustly assess the rehydration efficacy of different beverages, future studies should distribute fluid intake over a longer duration, in order to improve ecological validity and reduce the risk of gastrointestinal issues.

Humans↗

PubMed2026

Immunogenicity and safety of inactivated TZ84- vs. HM175-based hepatitis A vaccines in pediatric populations: A systematic review and meta-analysis.

Individual studies indicate stronger and persistent long-term immunogenicity with TZ84-based than HM175-based hepatitis A vaccines. This systematic review and meta-analysis compared immunogenicity and safety of inactivated TZ84- and HM175-based hepatitis A vaccines in children and adolescents. Studies involving adults, immunocompromised populations, non-comparative designs, non-English publications, and studies with non-extractable outcomes were excluded. MEDLINE/PubMed, Google Scholar, other electronic databases, and grey literature were searched (September-October 2025). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and meta-analyses were performed where appropriate. Seven publications arising from four randomized cohorts (total participants: 3,282) reporting seroconversion rates (SCRs), geometric mean concentrations (GMCs), long-term seroprotection, and adverse events (AEs) were identified. Pooled analyses demonstrated higher SCRs and GMCs with TZ84 than HM175-based vaccines following both one and two doses. SCRs at 1 month [odds ratio (OR): 3.05; 95% confidence interval (CI): 1.88-4.96] and GMCs at 7 months [standardized mean difference (SMD): 0.88; 95% CI: 0.18-1.58; p = .01] both favored TZ84-based vaccines. Long-term follow-up (up to 186 months/15.5 y) showed higher reported anti-HAV antibody concentrations for TZ84-based vaccines. The AEs were comparable between vaccine types (RR: 0.95; 95% CI: 0.76-1.20; p = .69). Evidence was limited by the small number of unique randomized cohorts, geographic concentration in China, heterogeneity across studies, and reliance on surrogate immunogenicity outcomes. Overall, available evidence suggests that TZ84-based hepatitis A vaccines (HAPIBEV™/HEALIVE®) are associated with higher reported antibody responses and greater reported antibody persistence than the HM175-based vaccine (HAVRIX®) in children and adolescents, with comparable safety profiles.Registration: PROSPERO CRD420251154480.

Humans↗

PubMed2026

Pre-clinical immunogenicity and safety evaluation of H2 strain Hepatitis A Inactivated Vaccine in rhesus macaques.

BACKGROUND: Hepatitis A is a viral infection of the liver that can cause mild to severe illness. Currently, two types of HAV vaccines are used worldwide, inactivated hepatitis A vaccines, which are used in most countries, and live attenuated vaccines (H2 and L-A-1 strain), which are mainly used in China. The major disadvantage of live attenuated virus to cause secondary infections among contacts and mutation shifts of the live vaccine strain. The H2 strain was selected for the development of an inactivated hepatitis A vaccine to further reduce biosafety risks. Rhesus macaques high genomic homology with humans and the incubation period after hepatitis A vaccination and human natural infections are similar. We use rhesus macaques to assess immunogenicity and safety of the H2 strain Hepatitis A Inactivated Vaccine. METHODS: The vaccine was assessed in rhesus macaques, divided into four groups (n = 10 per group): the control group (adjuvant buffer; aluminum content 0.35 mg/mL; 2 mL per dose), the low-dose group (320EU, 0.5 mL of 640EU/mL with aluminum content 0.35 mg/mL), the medium-dose group (640EU, 1 mL of 640EU/mL with aluminum content 0.35 mg/mL), and the high-dose group (1280EU, 2 mL of 640EU/mL with aluminum content 0.35 mg/mL). Animals were injected intramuscularly at multiple sites in the hind limbs and received four inoculations at 4-week intervals. Test items including Clinical indicators, immunogenicity indicators and Histopathological examination. RESULTS: No abnormalities were observed in any group in terms of general clinical condition throughout the study period except for slight decreases in body temperature after immunization. Hematological parameters, serum biochemistry indices, and histopathological findings showed fluctuated to different degrees of fluctuation after immunization across all groups. Immunogenicity assessments showed that the inactivated hepatitis A vaccine (H2) induced both humoral and cellular immune responses effectively, and the levels of antibodies increased with certain dose- and time-response trends. CONCLUSION: The inactivated hepatitis A vaccine (H2 strain, human diploid cell) was safe and immunogenic in non-human primates. The results provide strong preclinical support for the further clinical development of this vaccine candidate.

Animals↗

PubMed2026

A Duty to Act.

Explore the source record for details and available documents.

healthcare↗

PubMed2026

De Novo 2.2 Mb 19q13.42-q13.43 Microdeletion Encompassing U2AF2: Support for a Haploinsufficiency Model.

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor involved in the early stages of pre-mRNA splicing. To date, multiple individuals have been reported with predominantly heterozygous missense variants presenting intellectual disability, speech and motor delays, seizures, hypotonia, and thin or hypoplastic corpus callosum. Here, we describe a patient with a de novo 2.2 Mb interstitial deletion involving chromosome 19q13.42-q13.43, encompassing U2AF2, presenting with intellectual disability, epilepsy, corpus callosum hypoplasia, dysmorphic features, and congenital heart disease. The patient's clinical features overlap substantially with those reported in individuals harboring heterozygous U2AF2 variants, supporting haploinsufficiency as a plausible disease mechanism. To our knowledge, this represents the first postnatal report of complete U2AF2 gene deletion. In addition, this is the first detailed phenotypic characterization of a distal 19q chromosomal interstitial deletion, further delineating the clinical spectrum associated with this genomic region.

Humans↗

PubMed2026

A transcription factor-focused CRISPR screen identifies SKI as a BCL11A-independent repressor of ζ-globin.

The regulation of α-like globin genes, particularly the embryonic ζ-globin gene (HBZ), remains incompletely understood. To identify transcriptional regulators of HBZ, we establish a GFP reporter system based on the HBZ-P2A-GFP allele in erythroid cell lines and conduct a CRISPR/Cas9 screen targeting 1639 transcription factors. This screen identifies SKI as a potent HBZ repressor. Functional validation shows that SKI loss increases HBZ expression without impairing erythropoiesis, whereas SKI overexpression suppresses HBZ. Tet-on-inducible SKI overexpression and auxin-inducible SKI degradation indicate that SKI rapidly represses HBZ transcription. Transcriptome profiling further reveals that SKI deletion activates HBZ while minimally affecting other erythroid genes. Mechanistically, genome-wide occupancy analyses show that SKI binds the distal enhancers HS-10 and HS-40, with partial co-occupancy by BCL11A. Despite this overlap, dual knockout of SKI and BCL11A synergistically increases HBZ expression, as does base editing of the SKI-binding site within HS-10. We also identify a naturally occurring variant (chr16:193207G>A) within this enhancer in α-thalassemia patients with elevated ζ-globin levels. Together, these findings establish SKI as a direct, BCL11A-independent transcriptional repressor of ζ-globin. This work advances our understanding of globin gene regulation and suggests targeted ζ-globin reactivation as a potential therapeutic strategy for α-thalassemia.

Enhancer↗

PubMed2026

Sociodemographic and clinical characteristics associated with nocturnal enuresis among children in a tertiary care center in Cairo, Egypt: A cross-sectional study.

BACKGROUND: Nocturnal enuresis (NE) is a significant pediatric health concern that warrants increased attention from healthcare providers, educators, and society. This study aimed to determine the frequency of NE among children attending a tertiary care center in Cairo, Egypt, and to explore their sociodemographic characteristics and associated factors. METHODS: A cross-sectional study was conducted among 1587 children aged 6-16 years attending a tertiary care center in Cairo from December 2022 to February 2024. Data were obtained from parents via a structured questionnaire covering sociodemographic characteristics. Sleep problems were assessed via the Children's Sleep Habits Questionnaire. The multivariate logistic regression analysis was conducted to estimate the odds ratio and identify factors associated with NE. RESULTS: The total prevalence of NE among children attending a tertiary care center was 333 (21%). Our results indicated that being female and being older were associated with a lower likelihood of NE. Low socioeconomic status (OR = 5.559; 95% CI = 1.24-24.88), stressful events (OR = 3.697; 95% CI = 1.73-7.88), a family history of NE (OR = 26.231; 95% CI = 8.617-79.85), and sleep problems (OR = 13.233; 95% CI = 6.082-28.793) were associated with increased odds of NE. Furthermore, consuming caffeinated drinks before sleep, the presence of urinary tract infections, and intestinal infestations were also associated with NE. CONCLUSION: The findings of the present study confirm the multifactorial etiology of NE and identify several associated factors. Integrating these factors into screening and management programs may improve early identification and lead to more effective, tertiary care-specific preventive and therapeutic interventions.

Humans↗

PubMed2026

A Duty to Act.

Explore the source record for details and available documents.

healthcare↗

PubMed2026

The feasibility and efficacy of weighted blankets as a sleep intervention for people with behavioural and psychological symptoms of dementia: a pilot randomised crossover trial.

Sleep disturbances contribute to disease progression in dementia and result in reduced quality of life. Non-pharmacological interventions are recommended for the management of sleep and other behavioural and psychological symptoms of dementia (BPSD), although these interventions can be challenging to implement. This pilot study assessed the feasibility and efficacy of weighted blankets as a sleep intervention for people with BPSD in a neurobehavioural unit. Fourteen residents, serving as their own control, slept two weeks with a weighted blanket and two weeks with usual bedding in a crossover trial. The primary outcomes were sleep duration and efficiency, measured via a Withing's sleep analyser and sleep disordered behaviours, measured by the sleep disorder inventory (SDI). Secondary outcomes included responsive behaviours, measured by the Neuropsychiatric index (NPI), falls incidents, restrictive practice incidents and use of pro re nata psychotropic medications. Generalised Estimation Equation (GEE) method was used for analysis. There was no statistical evidence that weighted blankets improved sleep or behavioural outcomes for people with BPSD, however fewer fall incidents, wakings and restrictive practices were reported during weighted blanket use. Weighted blankets were considered feasible and acceptable with high recruitment rates, nil participant withdrawals and no adverse outcomes, however there was variable compliance to the intervention protocol and the Withings did not adequately measure sleep. Whilst there is insufficient effectiveness evidence for further trials, weighted blankets can be offered to people living with dementia as a low risk sleep intervention option, with the caveat that there is currently no effectiveness evidence.

Behavioural Symptoms↗

PubMed2026

How do women with a history of childhood sexual abuse experience the preconception and perinatal period? A qualitative systematic review.

CONTEXT: Child sexual abuse (CSA) is a public health issue that predominantly affects women and has both short- and long-term consequences. The perinatal period can represent a challenge, but also an opportunity to identify a history of CSA and to provide sensitive care that may help prevent the intergenerational transmission of trauma. AIM: To describe and understand the experiences and coping strategies of women who are survivors of child sexual abuse and are transitioning to motherhood. METHOD: We conducted a systematic review of qualitative studies according to a protocol registered in PROSPERO, following methodological standards and reporting the results according to the ENTREQ guideline. A search was conducted on five databases up to July 2025. Two authors independently selected the articles and assessed their methodological quality. Data were analysed using thematic synthesis and the confidence in the findings was evaluated according to GRADE-CERQual. RESULTS: We included 21 qualitative studies that resulted in six themes. The findings reveal how women who experienced child sexual abuse and are transitioning to motherhood may experience this stage with ambivalence-ranging from revictimisation to identity reconstruction-where perinatal care emerges as a potential healing vehicle throughout this process. CONCLUSIONS: The perinatal period becomes a window of opportunity to heal deep wounds, with perinatal care playing a key role. The findings support trauma-informed perinatal care, underpinned by reflective practice and a holistic approach. Further work is needed to improve the identification of child sexual abuse, enhance professional training and review current practices to ensure sensitive care.

Humans↗

PubMed2026

Donor Human Milk Utilization in a Level 1 Newborn Unit of a High-Volume Delivery Hospital: A Cautionary Tale.

INTRODUCTION: Donor human milk (DHM) is an alternative to formula for supplementation of breastfed newborns and has been associated with higher in-hospital exclusive breast milk feeding rates. Its use has increased substantially, most recently among term newborns, yet there is scarce data to describe patient characteristics and volumes administered. We aimed to characterize DHM utilization in our level 1 nursery. METHODS: We conducted a retrospective cross-sectional study of newborns discharged in 2022 from the level 1 nursery. Variables included sex, gestational age, birth weight, delivery type, hypoglycemia diagnosis, DHM volume, and length of stay. DHM use was compared across preferred language, race, ethnicity, and payer type using chi-square testing. RESULTS: A total of 10,432 discharges were reviewed-those transferred to Neonatal Intensive Care Unit (NICU) or another unit were excluded. Of 9,074 newborns receiving level 1 care, 1,094 (12.1%) received DHM. Newborns born between 35 and 37 weeks gestation, delivered by cesarean section, or diagnosed with hypoglycemia or small for gestational age were more likely to receive DHM (p < 0.05). DHM was also more common among newborns whose birth parent preferred the English language, identified as White or non-Hispanic, or had non-Medicaid insurance (p < 0.05). 6,552.6 ounces were consumed, with a total median of 3.9 ounces per newborn (dose range 2-50 mL). CONCLUSIONS: DHM use in the level 1 nursery varied by clinical and sociodemographic factors, revealing inequities. In addition, some doses exceeded recommended supplemental volumes. Future efforts should focus on ensuring equitable access to DHM, standardized dosing and discontinuation guidelines, and evaluation of impacts on exclusive breastfeeding rates.

Humans↗

PubMed2025

Mixed Methods Findings from a Stepped Wedge Hybrid Implementation Trial of ATTAIN NAV: A Mental Health Family Navigation Intervention for Autistic Youth.

ATTAIN NAV (Access to Tailored Autism Integrated Care through Family Navigation) was delivered by family navigators to promote access to and engagement with mental health services for school-age autistic youth. This study used a mixed method, stepped wedge design to test the effects of family navigation on service and clinical outcomes while gathering information on implementation. Primary care providers from six clinics in California and 56 caregiver-child dyads enrolled in and completed the study. Clinics were randomized to either a technology-enhanced or standard family navigation condition. Caregivers completed assessments at baseline and post about child, family and services outcomes, and a subset participated in a post qualitative interview. Quantitative findings demonstrated improvements in child challenging behavior and parent activation across conditions although these improvements were more pronounced for families in the standard FN condition. At post-intervention, families in the standard FN condition reported higher levels of navigation satisfaction, a shorter time to attend their first mental health appointment, and higher engagement with their navigator. Qualitative findings complemented and expanded the quantitative survey findings. The ATTAIN NAV model of family navigation for autistic children with co-occurring mental health needs demonstrates promising implementation, service, and clinical benefits. Clinical Trials Registration. NCT05344378.

Humans↗

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

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 μg immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 μg/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] μg) compared to the bolus group (300 [200-400] μg; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans↗

PubMed2026

A Letter Matters: ADRB2 rs1042713 c.46A Modulates Anti-osteogenic Effect of Epinephrine in Human Mesenchymal Stem Cells.

Osteoporosis (OP) is a systemic bone disease affecting millions worldwide, characterized by long-term asymptomatic development that manifests in low-energy fractures. Due to their high stability, genetic markers represent a promising strategy for early diagnostics. The ADRB2 rs1042713 polymorphism is one such marker, considered as a potential predictor for OP. Although the anti-osteogenic role of the β2-adrenergic receptor is well-established, debate continues on which allele (G or A) of this polymorphism drives bone deterioration. In this study, we examined the influence of the ADRB2 rs1042713 G/G and A/A variants on osteogenic differentiation in patient-derived mesenchymal stem cells (MSCs) under treatment with the endogenous agonist epinephrine. We show that epinephrine (whose levels are often elevated in comorbid conditions) drastically impairs osteogenic differentiation, specifically at the matrix mineralization stage in MSCs A/A. Epinephrine fails to activate the canonical β2-adrenergic receptor pathway and promotes receptor perinuclear and nuclear localization in MSCs A/A. Crucially, metformin, a common anti-diabetic drug, rescues this anti-osteogenic effect. These results open new perspectives for early diagnostics by identifying epinephrine sensitivity as a critical factor, while also suggesting a potential therapeutic strategy to counteract epinephrine detrimental effect in individuals carrying the ADRB2 rs1042713 A-allele.

Humans↗

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 (≥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↗