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PubMed2026

Self-healing materials for food packaging: Design principles, activation mechanisms and implications for food safety.

Self-healing materials (SHMs), originally developed to restore mechanical integrity, have recently attracted growing interest in food packaging. By autonomously repairing physical damage, SHMs help preserve packaging integrity, barrier performance, food safety, and shelf-life during storage and transportation. This review summarizes recent advances in the design principles, activation mechanisms, material systems and food packaging applications of SHMs. Key healing strategies, including microencapsulation, dynamic covalent bond exchange, reversible non-covalent interactions and responsiveness to external stimuli such as temperature, pH, and humidity, are discussed. Representative material systems, including biopolymer-based films, hydrogels, nanocomposites, and stimuli-responsive polymers are evaluated with respect to their relevance to packaging animal-derived foods, fruits, and vegetables. Performance evaluation methods, sustainability implications, and food-contact safety concerns are addressed. Despite promising healing efficiency and mechanical resilience, challenges remain regarding production cost, food-grade safety, migration risks, trigger compatibility and stability under fluctuating environmental conditions. Future research should focus on scalable manufacturing, standardized evaluation protocols, repeated damage-healing safety assessment, regulatory compliance, and integration with intelligent packaging technologies.

Food Packaging↗

PubMed2026

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n = 60) and a control group (n = 60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P < 0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P < 0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans↗

PubMed2026

Enhancing Self Care Among Oral Cancer Survivors Using a Digital Approach: The Empowered Survivor Trial.

BACKGROUND: Oral and oropharyngeal cancer survivors experience debilitating physical and psychosocial challenges. Little knowledge exists on the efficacy of interventions to enhance self-efficacy in managing these challenges, increase survivorship preparedness, and improve health-related quality of life (HRQoL). METHODS: Individuals (n = 643) diagnosed with oral or oropharyngeal cancer diagnosed within past 3 years were randomized to a digital intervention, Empowered Survivor (ES) or a Generic Online Intervention (GO). Primary (self-efficacy, preparedness, HRQoL) and secondary outcomes (self-care activities) were measured at Baseline, 2-months, and 6-months. RESULTS: Participants assigned to ES reported greater self-efficacy and increased self-care activities of oral self-exams, swallowing, and mobility exercises than those assigned to GO (self-efficacy: 2 months, p = 0.003, 6-months, p < 0.001; self-care activities). CONCLUSIONS: The ES enhanced self-efficacy and increased self-care activities. Further examinations of survivorship preparedness and HRQoL in oral and oropharyngeal cancer are warranted. TRIAL REGISTRATION: Registered on clinicaltrials. gov as NCT04713449.

Humans↗

PubMed2026

Symptoms and treatment response to florensocatib and inhaled tobramycin in bronchiectasis: Post hoc analysis of two randomized trials.

Inhaled antibiotics and DPP-1 inhibitors improve clinical outcomes in bronchiectasis, but whether baseline symptom burden predicts differential treatment responses remains unclear. In this post hoc analysis of two multicenter randomized trials (SAVE-BE, n = 224; TORNASOL, n = 357), we evaluate the association between baseline Quality of Life-Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and treatment effects of florensocatib and inhaled tobramycin. In SAVE-BE, florensocatib reduces exacerbation rates versus placebo (relative risk [RR], 0.47; 95% confidence interval [CI], 0.33-0.67; p < 0.0001), with RRs of 0.53 and 0.40 observed in patients with high and low symptom burdens, respectively, but no significant symptomatic improvement. In TORNASOL, tobramycin produces clinically meaningful QoL-B-RSS improvements (exceeding the 8-point cutoff in high-symptom patients) and ameliorates bronchitic symptoms, with greater benefits in those with higher baseline symptom burden. These hypothesis-generating findings suggest that baseline symptom burden may identify differential responses to anti-inflammatory versus anti-infective therapies in bronchiectasis and support its potential as a simple, practical stratification tool to guide personalized treatment.

Humans↗

PubMed2026

Eating Experiences During Cancer Treatment in Adolescents and Young Adults: A Systematic Literature Review and Meta-Synthesis.

Adolescents and young adults (AYAs) aged 15-39 with cancer face distinct challenges during treatment, with eating consistently emerging as one of the most distressing and underrecognized concerns. At a critical life stage, AYAs must navigate illness-related consequences that profoundly affect well-being. Eating reflects these broader challenges and is identified as a key issue requiring health care attention. To address this, we synthesized evidence on AYAs' eating experiences and well-being during mealtime-related activities to inform health care practice. Qualitative and mixed-method studies were identified through searches across CINAHL, Embase, PubMed, Scopus, and Web of Science for studies published up to May 2025, supplemented by snowball searches. Of 3214 records, 74 full-text articles were reviewed, and 18 met the inclusion criteria. These represented 302 AYAs, 73 relatives, and 88 health care professionals. Studies were analyzed using Joanna Briggs Institute review methods and GRADE-CERQual to support clinical interpretability. The meta-synthesis identified one core theme: "Eating as an embodied struggle and act of agency," with three subthemes: (a) living through physical and sensory disruption, (b) carrying the weight of new emotions and shifting relations, and (c) finding ways through gaps in support. Eating emerged as a disrupted, emotionally charged, yet agentic act requiring sensitive, individualized approaches. Thirteen evidence-informed recommendations were developed to guide clinical application. These emphasize early nutritional screening, dietetic support, flexible meal options, respectful family involvement, and psychosocially attuned care. Future research should codevelop and evaluate tailored interventions that address AYAs' embodied, emotional, and social needs to improve eating-related quality of life during cancer treatment.

Humans↗

PubMed2026

Vaginal Hysterectomy Versus Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery Hysterectomy; Results of a Randomised Controlled Trial.

OBJECTIVE: To compare Vaginal Hysterectomy (VH) with Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) hysterectomy (VANH) as a day-care procedure. DESIGN: Single-blind, multicentre randomised controlled trial. SETTING: Two Dutch non-academic teaching hospitals. POPULATION: Women aged ≥ 18 years undergoing hysterectomy for benign indications. METHODS: Women were randomised 1:2 (VH or VANH). Primary outcome was SDD. Secondary outcomes included operative time, rate of elective salpingectomies, intraoperative blood loss, complications (Clavien-Dindo), pain scores (NRS) and analgesic use, post-operative recovery (RI-10), and quality of life (EQ-5D-5L). Analyses were performed on an intention-to-treat basis. RESULTS: A total of 113 patients were included in the analyses (n = 42 VH, and n = 71 VANH). SDD occurred significantly more frequently in the VANH group (87.3%) than VH group (71.4%; OR 2.76, 95% CI 1.04-7.25; p = 0.04). VANH was associated with a significantly shorter operative time (median 55 min versus 65 min; p = 0.005), less blood loss (median 50 mL vs. 150 mL; p < 0.001) and more often elective opportunistic salpingectomy compared to VH (100% vs. 77.4%; p = 0.008). NRS were significantly lower in the VANH group the first hour post-operative (3 vs. 1, p < 0.001). Post-operative complications (VH 9.5% vs. VANH 15.5%; p = 0.34), readmission (VH 4.8% vs. VANH 8.5%; p = 0.47), analgesic use, recovery, and quality of life were not statistically significant. CONCLUSIONS: VANH is a safe and effective alternative to VH, offering a higher likelihood of SDD, shorter operative time, reduced blood loss, and more often an elective salpingectomy, without increased complications or differences in pain, recovery, or quality of life.

Humans↗

PubMed2026

Longitudinal Neurocognitive Changes for Patients With Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Systematic Review With Structured Narrative Synthesis.

OBJECTIVES: Neurocognitive changes in hematological malignancies (HM) and as a sequela of hematopoietic stem cell transplantation (HSCT) remain under-recognized. These changes may substantially affect patients' quality of life. Therefore, this review systematically evaluated longitudinal neurocognitive changes in patients with HM undergoing HSCT. METHODS: Following PRISMA guidelines, PubMed, Scopus, and CINAHL were searched on October 30, 2025. Longitudinal studies assessing neurocognitive changes in patients with HM undergoing HSCT, with or without healthy controls, were included. Risk of bias was assessed using an adapted National Institutes of Health quality assessment tool for before-after studies. Effect sizes with 95% confidence intervals were calculated to quantify changes in neurocognitive performance. RESULTS: Nine of 2012 studies met the inclusion criteria, with overall moderate study quality. Improvements may occur post-HSCT; however, allogeneic HSCT and myeloablative conditioning were main risk factors identified for persistent cognitive decline. In line with white matter damage, executive function and attention/processing speed impairments likely represent core deficits, which may affect other cognitive impairments. Post-HSCT changes depend on task characteristics, cognitive load, and conditioning intensity. CONCLUSIONS: Future research should emphasize regular neurocognitive assessment to guide cognitive rehabilitation, implement pre-transplant cognitive rehabilitation strategies to mitigate post-HSCT cognitive decline, and enhance treatment outcomes.

Humans↗

PubMed2026

Artificial intelligence enabled social robotic interventions (PARO) in Australian dementia care: A systematic review and meta-analysis.

BACKGROUND: Although there is a growing body of research indicating that Personal Robot/Social Robot could be used in various aspects of care for individuals with dementia, little is known about how well these types of interventions work in an actual hospital setting in Australia. AIMS & OBJECTIVES: The objective of the present systematic review and meta-analysis is to assess the effectiveness of PARO-based socially assistive robotic intervention in terms of its effectiveness outcomes towards the reduction of dementia-related behavioural and psychological symptoms in Australian based healthcare settings. METHODS: A systematic search was conducted across five electronic databases, including MEDLINE (PubMed), EMBASE, CINAHL, PsycINFO, and the Cochrane Library, to identify randomised controlled trials (RCTs) investigating PARO-based socially assistive robotic interventions for dementia in Australian healthcare settings. This review was registered with PROSPERO (CRD420251251916) and followed the PRISMA 2020 guidelines. In addition, the Cochrane Risk of Bias tool (RoB 2) was used to evaluate the risk of bias across all studies. Pooled standardised mean differences (SMD) with 95 % confidence intervals (CI) were calculated for agitation, anxiety, and depression. Heterogeneity across studies was evaluated using the I2 statistic. RESULTS: Six RCTs involving 1444 participants were identified for inclusion in this review. AI-enabled socially assistive robotic interventions, specifically the PARO therapeutic robot, significantly reduced agitation and anxiety when compared to standard treatment or control conditions. The pooled analysis showed that agitation [SMD = -0.44 (95 % CI: -0.70, -0.18) p = 0.0008] and anxiety [SMD = -0.59 (95 % CI: -0.91, -0.27) p = 0.0003] were reduced significantly, while the decrease in depression [SMD = -0.44 (95 % CI: -0.95, -0.07) p = 0.09] scores was non-significant among dementia patients receiving PARO-based socially assistive robotic interventions as compared to the control. The overall risk of bias across all six studies was considered low to moderate. CONCLUSION: PARO-based socially assistive robotic interventions may provide preliminary evidence of effectiveness in reducing agitation and anxiety in individuals with dementia in Australian healthcare, but the evidence regarding the reduction of depression remains unclear. Therefore, additional high-quality trials with consistent methodology and extended follow-up will be necessary to determine both the short-term and long-term clinical efficacy and practicality of implementing these interventions into practice.

Humans↗

PubMed2026

Bacterially produced dsRNA targeting SePGRP-LB reduces population fitness of Spodoptera exigua (Lepidoptera: Noctuidae) and increases its susceptibility to SeMNPV.

The beet armyworm, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), is an important agricultural pest, and S. exigua multiple nucleopolyhedrovirus (SeMNPV) is a host-specific biological control agent. However, baculovirus efficacy can be limited by host antiviral responses. S. exigua peptidoglycan recognition protein LB (SePGRP-LB) has been identified as an antiviral immune factor, suggesting that its suppression may increase larval susceptibility to SeMNPV. In this study, bacterially produced double-stranded RNA targeting SePGRP-LB (bac-dsPGRP-LB) was orally delivered to larvae to induce RNA interference. Feeding bac-dsPGRP-LB reduced SePGRP-LB transcript levels by 24.0% to 65.7% over 7 d. SePGRP-LB knockdown prolonged fifth-instar larval development, reduced female pupal weight, shortened male adult longevity and the oviposition period, and decreased fecundity by approximately 51%. Life table analysis further showed significant reductions in the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0) following bac-dsPGRP-LB treatment. During SeMNPV infection, co-feeding with bac-dsPGRP-LB significantly suppressed SePGRP-LB expression, increased the SeMNPV genomic load, and reduced larval survival compared with the SeMNPV + bac-dsGFP treatment. These findings identify SePGRP-LB as a promising RNAi target for simultaneously reducing S. exigua fitness and enhancing its susceptibility to SeMNPV under laboratory conditions.

SePGRP-LB↗

PubMed2026

Relationship between participant-reported outcomes, residual beta cell function and metabolic parameters in youth with newly diagnosed type 1 diabetes.

AIMS/HYPOTHESIS: Clinical trials of interventions to preserve beta cell function in new-onset type 1 diabetes frequently employ participant-reported outcome measures (PROMs). However, the expected changes in PROMs scores immediately following diagnosis and their association with residual beta cell function, metabolic markers and continuous glucose monitoring (CGM) are unclear. METHODS: Repeated PROMs including Paediatric Quality of Life Inventory diabetes module (PedsQL) and hypoglycaemia fear survey (HFS) were recorded from participants aged 10-18 years with newly diagnosed type 1 diabetes and their parents in two clinical trials: CLOuD (N=97, hybrid closed loop [HCL] vs multiple daily injections [MDI]) and USTEKID (N=72, ustekinumab immunotherapy vs placebo). Scores were compared with serial mixed meal-stimulated C-peptide levels (AUC C-peptide), HbA1c and CGM data. RESULTS: PedsQL and HFS scores for children/adolescents and their parents showed wide variation between individuals but did not change substantially within individuals over the first 48 months from diagnosis. Baseline scores were highly predictive of scores at 12-48 months (p<0.001). PedsQL scores were higher (better) in those reported by children/adolescents than by their parents (p<0.01). In contrast, HFS scores were higher in parents than children (p<0.001), indicating more fear. Strong correlations were observed between child and parent scores (p<0.001). No significant improvement in these scores was detected following intervention (ustekinumab or HCL). Meta-analysis revealed modest but statistically significant associations between HbA1c and PedsQL (β(std)=-0.11; 95% CI -0.20, -0.03) and HFS (β(std)=0.11; 95% CI 0.00, 0.21), and between CGM time in range and PedsQL (β(std)=0.14; 95% CI 0.03, 0.26) but not HFS (β(std)=-0.05; 95% CI -0.16, 0.06). Beta cell function (AUC C-peptide) was strongly associated with HbA1c (β(std)=-0.29; 95% CI -0.39, -0.20) and CGM time in range (β(std)=0.41; 95% CI 0.30, 0.52). Higher beta cell function showed a trend towards better PedsQL (β(std)=0.11; 95% CI -0.03, 0.25) and lower HFS (β(std)=-0.05; 95% CI -0.17, 0.07) but this did not reach statistical significance. CONCLUSIONS/INTERPRETATION: PedsQL and HFS scores changed little during the first 48 months after diagnosis of type 1 diabetes. These scores showed modest but statistically significant associations with measures of glucose management (HbA1c and CGM time in range), whereas the relationships with residual beta cell function (C-peptide) were weaker and did not reach significance. The modest size of these effects suggests current PROMs capture only limited aspects of the clinical benefit associated with beta cell preservation. Future research should incorporate psychometric instruments that are specifically adapted for young people using modern diabetes technologies and undergoing disease-modifying therapy, to ensure outcomes are meaningfully represented in early-stage type 1 diabetes trials.

Adolescent↗

PubMed2026

Efficacy and safety of rib-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation at two different targets for primary palmar hyperhidrosis: a randomized controlled trial.

OBJECTIVES: To compare the efficacy and safety of computed tomography-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation (RFT) targeting the upper versus lateral margin of the fourth rib head for severe primary palmar hyperhidrosis (PPH). METHODS: Patients with severe PPH were randomly divided into Group U (upper margin target) and Group L (lateral margin target). Outcome measures included 1-year recurrence rate, Hyperhidrosis Disease Severity Scale (HDSS), Dermatology Life Quality Index (DLQI), palm skin temperature, finger perfusion index (PI), compensatory hyperhidrosis and patient satisfaction. RESULTS: Both groups (n = 55 each, 110 sides) successfully underwent RFT. No preprocedural PI differences were found (p > 0.05). Immediately post-RFT, PI in Group L was significantly higher than in Group U (left p = 0.025, right p = 0.013). No significant differences in HDSS grades were observed between groups before and at 1 day, 2 weeks, 1 month and 3 months post-procedure. However, at 6 and 12 months, Group L showed significantly lower HDSS grades (left p = 0.033 and 0.016; right p = 0.039 and 0.025) and lower DLQI scores (p = 0.037 and 0.024) than Group U. Patient satisfaction did not differ within 6 months, but Group L had significantly higher satisfaction at 12 months (p = 0.036). CONCLUSIONS: Targeting the lateral margin of the fourth rib head for RFT achieved greater efficacy, better quality of life and higher patient satisfaction compared to the upper margin target.

Humans↗

PubMed2026

Cost-effectiveness analysis of a virtually administered pain coping skills training intervention in women with breast cancer in underserved areas.

OBJECTIVES: Women with cancer who live in medically underserved areas could benefit from behavioral pain interventions, but access is limited. A randomized trial reported that a 4-session virtual program incorporating pain coping skills training (mPCST) was effective in improving pain outcomes compared to an attention-control condition. We performed a cost-effectiveness analysis of mPCST vs. control. METHODS: Data on medical resource use, therapist time, and participants' attendance at intervention sessions and time associated with travel and using a mobile app were collected. The 5-level EuroQol 5-Dimension (EQ-5D-5L), a preference-weighted measure of health-related quality of life (HRQOL), was administered at baseline, after the intervention period, and 3 and 6 months later. Medicare payments were used to value medical resource use and therapist time to deliver mPCST. Patient time was valued using the average US wage. RESULTS: Medical resource utilization was similar for both groups, but hospitalizations trended higher in the mPCST group. EQ-5D-5L preference weights were higher by an average of 0.066 (p = 0.04) with mPCST across the follow-up period, representing an incremental gain of 0.04 quality-adjusted life years (QALYs) (95% CI: 0.00-0.08). When including the base-case cost of mPCST of \$500 vs. \$0 for the control group, the incremental cost-effectiveness ratio (ICER) was \$12,725 per QALY (95% CI: 5,566-69,343). Including the value of patient time added \$303 to mPCST costs resulting in an ICER of \$20,438 per QALY (95% CI: 9,051-111,403). SIGNIFICANCE OF RESULTS: mPCST is a cost-effective program that improves HRQOL for women with cancer living in medically underserved areas.

Humans↗

PubMed2026

A status update on the unkept promise of high-frequency spinal cord stimulation for treatment-refractory chronic migraine.

INTRODUCTION: Chronic migraine (CM) refractory to conventional pharmacotherapy (r-CM) remains a debilitating neurological condition with limited therapeutic options. High-frequency spinal cord stimulation at 10 kilohertz (HF-SCS) has recently emerged as a distinct neuromodulatory paradigm for this patient population. Unlike traditional spinal cord stimulation, HF-SCS operates above the frequency range that generates paresthesia, thereby eliminating stimulation-induced sensation while potentially engaging unique analgesic mechanisms. AREAS COVERED: This focused narrative review synthesizes the available clinical evidence, technical considerations, and mechanistic hypotheses specifically pertaining to cervical HF-SCS for refractory chronic migraine (r-CM). The authors further provide their expert perspectives on the future of this technology as a treatment option for refractory chronic migraine. EXPERT OPINION: Current data from prospective open-label studies and retrospective case series suggest that cervical HF-SCS may reduce monthly migraine days, facilitate conversion from chronic to episodic migraine patterns in some implanted patients, and may improve headache-related disability and quality of life over at least 52 weeks of follow-up. The paresthesia-free nature of HF-SCS confers a distinct advantage for both patient tolerability and future trial design, as it permits sham-controlled methodologies that have historically been impossible with conventional neurostimulation. However, these findings remain preliminary and should be considered hypothesis-generating pending confirmation in adequately powered randomized sham-controlled trials.

Humans↗

PubMed2026

The burden of male breast cancer (MBC) in the GBD Central, Eastern, and Western Europe Regions from 1990 to 2023: Results from the Global Burden of Disease Study 2023.

PURPOSE: Male breast cancer (MBC) is underrepresented in cancer statistics: this study aimed to assess the burden of MBC in Central, Eastern, and Western Europe from 1990 to 2023, using data from the Global Burden of Disease (GBD) Study 2023. METHODS: Estimates from GBD 2023 were analyzed to determine the MBC incidence, mortality, and disability-adjusted life years, their all-ages and age-standardized rates, and the 1990 through 2023 annual percent change. These estimates were compared to those for the GBD Super Regions and the Socio-Demographic Index quintile countries. RESULTS: In Central Europe, age-standardized incidence rates (ASIR) increased from 0.54 (0.40-0.76) to 1.05 (0.70-1.52), age-standardized mortality rates (ASMR) from 0.29 (0.25-0.34) to 0.40 (0.36-0.45), and age-standardized disability life-year rates (ASDR) from 7.19 (6.15-8.41) to 9.63 (8.52-11.07). In Eastern Europe, ASIR remained relatively stable, changing from 0.81 (0.56-1.19) to 0.60 (0.38-0.92), whereas ASMR decreased from 0.40 (0.33-0.49) to 0.21 (0.16-0.25) and ASDR from 10.54 (8.69-12.89) to 5.55 (4.52-6.85). In Western Europe, ASIR increased from 0.47 (0.33-0.67) to 0.88 (0.59-1.24), whereas ASMR (0.22 [0.19-0.25] vs. 0.24 [0.21-0.27]) and ASDR (5.20 [4.49-5.97] vs. 5.75 [4.96-6.66]) remained stable. CONCLUSIONS: The burden of MBC is increasing across Europe, particularly in the Central region, with huge regional differences. Population growth and variations over time impacted on the metrics. Even with a composite European scenario, the mortality-to-incidence ratio markedly declined in the three areas.

Humans↗

PubMed2026

Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.

In periods of sustained hyper-nutrition, pancreatic β-cells undergo functional compensation through transcriptional upregulation of gene programs driving insulin secretion. This adaptation is essential for maintaining systemic glucose homeostasis and metabolic health. Using single nuclei multiomics, we have mapped the early transcriptional adaptive mechanisms in murine islets of Langerhans exposed to high-fat diet (HFD) for 1 and 3 wk. We show that β-cells exhibit the largest transcriptional response to HFD, characterized by early activation of pro-inflammatory eRegulons and down-regulation of β-cell identity genes, particularly in a distinct subset of β-cells. These observations extend to humans, where the prevalence of an β-cells with a high inflammatory signature is increased in diabetes. Collectively, these observations point to cellular crosstalk through pro-inflammatory signaling as a central and early driver of β-cell dysfunction that limits the compensatory capacity of β-cells, which is closely linked to the development of diabetes.

Animals↗

PubMed2026

Effect of a PROtein-enriched MEDiterranean diet and EXercise (PROMED-EX) on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline: the PROMED-EX randomized controlled trial.

BACKGROUND: Undernutrition in older adults is associated with adverse health outcomes including cognitive decline, yet evidence for effective preventive strategies is limited. OBJECTIVES: The objective of this study was to investigate effects of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in "at risk" community-dwelling older adults. METHODS: A total of 105 participants (69% female; aged 67.7 ± 6.1 y) at risk of undernutrition and cognitive decline were randomized to 1 of 3 groups: 1) PROMED-EX (personalized dietary counseling plus home-based exercise); 2) PROMED (personalized dietary counseling only); or 3) CON (healthy eating leaflet). The primary outcome was change in nutritional status at 6 mo, measured by the Mini Nutritional Assessment (MNA; 0-30 points). Secondary outcomes included neurocognitive test battery (NTB) z-score, PROMED diet quality score (0-14), physical performance, and health-related quality of life. Analyses followed an intention-to-treat approach using linear regression to assess between-group differences in 6-mo outcomes. RESULTS: At baseline, the mean MNA score was 22.5 ± 2.3. After 6 mo, nutritional status improved significantly in both intervention groups compared with CON: mean differences in MNA were 2.7 [95% confidence interval (CI): 1.3, 4.2] for PROMED and 2.9 (95% CI: 1.5, 4.3) for PROMED-EX (both P < 0.001). Cognitive function also improved, with NTB z-score differences of 0.3 (95% CI: 0.1, 0.5; P = 0.01) in PROMED and 0.2 (95% CI: 0.0, 0.4; P = 0.02) in PROMED-EX compared with CON. Diet quality scores significantly increased with mean differences of 4.0 (95% CI: 2.9, 5.0) for PROMED and 3.9 (95% CI: 2.8, 4.9) for PROMED-EX compared with CON (both P < 0.001). Despite low adherence to exercise, additional benefits were observed for physical performance and quality of life. CONCLUSIONS: Dietary intervention improved nutritional status in community-dwelling older adults at risk of undernutrition. Correcting undernutrition could help to slow cognitive decline and promote physical health and quality of life during aging. This study was registered at clinicaltrials.gov as NCT05166564.

Humans↗

PubMed2026

Aquablation/AquaBeam Waterjet Therapy for Benign Prostatic Hyperplasia: Three-Year Functional and Ejaculatory Outcomes in a Multicenter Real-World Italian Cohort.

OBJECTIVE: To evaluate the 3-year functional outcomes of Aquablation/AquaBeam waterjet therapy for bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), with particular attention to urinary symptoms, quality of life, continence, ejaculatory function, and complications. METHODS: We performed a retrospective analysis of a prospectively maintained multicenter database including 218 consecutive men who underwent Aquablation/AquaBeam for symptomatic BPH between January 2019 and January 2022 at three referral centers. Functional outcomes assessed preoperatively and during follow-up included International Prostate Symptom Score (IPSS), IPSS quality-of-life item (IPSS-QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR), continence, and ejaculatory function. Median follow-up was 36 months. Ejaculatory preservation was evaluated only in patients with preserved antegrade ejaculation at baseline. RESULTS: Median age was 61 years (IQR 57-66), median prostate-specific antigen (PSA) was 2.52 ng/mL (IQR 0.40-21.60), and median prostate volume was 55 mL (IQR 40-73). Median operative time was 56 min, while median catheterization time and length of hospital stay were both 48 h. Functional improvements were evident from the 3-month follow-up and remained stable through 36 months. At 36 months, median IPSS improved to 5 and median Qmax to 18 mL/s. Median PSA changed modestly from 2.52 ng/mL at baseline to 2.75 ng/mL at 36 months. No cases of de novo urinary incontinence were observed throughout follow-up. Among patients with preserved antegrade ejaculation at baseline, 87% maintained antegrade ejaculation at 36 months. Most postoperative complications were minor (Clavien-Dindo grade I-II, 20.2%). One grade III rectal injury occurred (0.5%). Median hemoglobin decreased from 15.2 g/dL preoperatively to 14.0 g/dL before hospital discharge, and two patients required blood transfusion. During the 36-month follow-up, no surgical retreatment was required, whereas 11 patients (5.0%) received temporary medical retreatment. CONCLUSION: In this multicenter real-world cohort, Aquablation/AquaBeam was safe and effective over 3 years, providing durable improvement in lower urinary tract symptoms and quality of life while preserving continence and antegrade ejaculation in most patients. These findings support Aquablation/AquaBeam as a valuable minimally invasive surgical option for selected men with BPH, particularly those who prioritize preservation of ejaculatory function. Longer-term and comparative studies are warranted. TRIAL REGISTRATION: 48281.

Humans↗

PubMed2026

Induced degradation of Ufd1 reveals regulation of cohesin by the VCP/p97Ufd1-Npl4 complex.

The AAA ATPase VCP/p97 has emerged as a critical regulator of ubiquitin and chromatin-associated processes but progress in understanding has been hampered by the complexity of p97 functions and the various p97 cofactors involved. Here, we combined ubiquitin profiling with acutely induced degradation of the Ufd1 subunit of the p97 ubiquitin adapter, Ufd1-Npl4, in human cells. We identified a set of chromatin regulators, HUS1, XRCC1, MORF4L1, and the cohesin subunit RAD21 as targets of p97Ufd1-Npl4 We find that RAD21 is ubiquitylated and targeted by p97Ufd1-Npl4 specifically in S phase to remove a subpopulation of cohesin from chromatin. Acute degradation of Ufd1 in S phase, after replication licensing is completed, impedes replication and leads to replication-associated DNA damage. Our findings suggest that a fraction of cohesin rings need to be removed by p97Ufd1-Npl4 from DNA to allow unhindered replication and reveal a critical function of p97 that ensures genome stability.

Cell Cycle Proteins↗