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Respiratory syncytial virus (RSV) infections pose a significant challenge to healthcare systems due to their impact on older adults, particularly those who are frail. Implementing an appropriate vaccination policy for these patients could help reduce healthcare resource utilization and costs while enhancing the quality of life for elderly individuals and their families. This narrative review aims to present the latest evidence on RSV and the available vaccines. Of the five vaccines evaluated, three have demonstrated significant efficacy in individuals over 60 years of age. Based on the current evidence, it is recommended that individuals over 75 be offered RSV vaccination, with priority given to those with chronic heart or lung conditions, frailty, or who reside in long-term care facilities., (Copyright © 2025 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

In long bones, glucocorticoids are known to cause a decrease in bone formation and an increase in bone resorption, leading to a condition of osteoporosis also during growth. However, there are few studies on the effect of glucocorticoids on alveolar bone. The aim of the present study was to evaluate the impact of chronic administration of glucocorticoids on osteocytes and the lacuno-canalicular system of maxillary and mandibular alveolar bone in growing rats. Male Wistar rats were administered intramuscular dexamethasone (7 mg/kg b.w.) or saline solution once a week for 5 weeks. After euthanasia, mandibles and upper maxillae were resected and processed for micro-computed tomography, histological, and immunohistochemical evaluation. Glucocorticoids induced morphological changes in the lacuno-canalicular system and apoptosis of alveolar bone osteocytes and had no effect on SOST/sclerostin osteocyte expression. Our findings suggest that the deleterious effect of glucocorticoids on alveolar bone is associated with osteocyte apoptosis and lacuno-canalicular system changes, whereas Wnt/β catenin pathway regulation in osteocytes appears to play no significant role in the pathogenesis of glucocorticoid-induced bone loss., (© 2025 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

High-dose post-transplantation cyclophosphamide (HD-PTCy), given at 50 mg/kg/day on days +3/+4, is a standard-of-care graft-versus-host disease (GVHD) prophylaxis for allogeneic hematopoietic cell transplantation (HCT). Our murine MHC-haploidentical HCT studies suggested intermediate-dose PTCy produces superior GVHD control compared with HD-PTCy and PTCy is maximally effective on day +4. We conducted a single-institutional prospective phase I/II trial (NCT03983850) to reduce PTCy dosing to 25 mg/kg/day on days +3/+4 or on day +4 only for myeloablative HLA-haploidentical bone marrow HCT using PTCy, sirolimus, and mycophenolate mofetil. Among 35 patients, 89% were ethnic/racial minorities, 46% had high/very-high-risk disease, and median comorbidity-score was 3. The phase I dose-limiting-toxicity, grade III-IV acute GVHD, was not observed after either reduced-PTCy dose-level. PTCy 25 mg/kg/day on days +3/+4 (intermediate-dose (ID)-PTCy; n=23), the phase II dose, resulted in no grade II-IV acute GVHD; 2-year cumulative incidences of chronic GVHD requiring systemic immunosuppression, non-relapse mortality, and relapse were 13%, 17%, and 22%, and 2-year overall survival, disease-free survival, and GVHD-free/relapse-free survival were 61%, 61%, and 52%. In exploratory analysis compared with HD-PTCy (n=5), ID-PTCy resulted in significantly faster engraftment and T-cell reconstitution, fewer transfusions, less mucositis, and reduced severity of BK-virus-associated cystitis; area-under-the-curve exposure of 4-hydroxycyclophosphamide (4HCY), a key cyclophosphamide metabolite, correlated with these outcomes but not with chronic GVHD occurrence. Ideal-body-weight-based PTCy dosing best approximated 4HCY exposure. Intermediate-dose PTCy is effective and has apparent clinical benefits compared with HD-PTCy. Before broader implementation, further studies are needed to confirm these findings and define optimal PTCy dosing across various donor/graft types. NCT03983850., (Copyright © 2025 American Society of Hematology.)

Summary: We present NetworkCommons, a platform for integrating prior knowledge, omics data, and network inference methods, facilitating their usage and evaluation. NetworkCommons aims to be an infrastructure for the network biology community that supports the development of better methods and benchmarks, by enhancing interoperability and integration., Availability and Implementation: NetworkCommons is implemented in Python and offers programmatic access to multiple omics datasets, network inference methods, and benchmarking setups. It is a free software, available at https://github.com/saezlab/networkcommons, and deposited in Zenodo at https://doi.org/10.5281/zenodo.14719118  ., Supplementary Data: Contribution guidelines, additional figures, and descriptions for data, knowledge, methods, evaluation strategies and their implementation are available in the Supplementary Data and in the NetworkCommons documentation at https://networkcommons.readthedocs.io/., (© The Author(s) 2025. Published by Oxford University Press.)

Synthetic riboswitches, genetic regulatory elements composed entirely of RNA, have been engineered to control a variety of mechanisms at the level of both transcription and translation in all domains of life. The efficiency of riboswitch regulation can be increased by inserting two of them into an mRNA sequence in close proximity, resulting in a tandem riboswitch. The tandem state results in improved regulation beyond that of a single riboswitch by allowing both binding pockets to contribute to a higher dynamic range. The focus of this study was to create a novel tandem riboswitch design by integrating the binding pockets of two different riboswitches into one continuous structure, thereby creating a dual-input hybrid riboswitch. These hybrids remain compact in size with a shorter sequence length compared to a tandem riboswitch, while taking advantage of the binding pockets and scaffold sequences provided by both parental riboswitches. Through rational design, hybrid constructs derived from the combination of tetracycline-, tobramycin-, neomycin-, and paromomycin-binding riboswitches were engineered that significantly increase the dynamic range (e.g., from 14- to 36-fold for tobramycin) while increasing their expression levels in the absence of ligand (e.g., 28% to 68% expression for tetracycline). This study expands the toolbox of synthetic riboswitches and establishes general design guidelines applicable to similar riboswitches. Additionally, the dual-input state makes hybrid riboswitches an interesting target for the design of genetic regulators following Boolean logic.

Background: Type 2 diabetes is the fastest-growing global health concern, and its global prevalence is projected to affect 643 million individuals by 2030. Social media platforms, like Facebook, have become crucial channels for healthcare organisations to engage with the public to promote prevention and disease management, especially in low-resource settings like Honduras. This study aims to perform a retrospective analysis of Honduran healthcare organisations' Facebook posts to understand how effectively they engage diabetes-related content with their followers., Methods: The top 10 followed healthcare organisations' Facebook pages were taken as a sample. Data were retrieved from October 2023 to March 2024. Diabetic-related posts were identified using keywords and categorised based on their contents and features., Results: Findings reveal significant disparities in the frequencies of posts and public engagement among different types of organisations. The majority of posts were classified under the miscellaneous category and text+image feature. Recipes and food-related posts were liked and shared the most among the followers., Conclusion: The results of the study found that patients' engagement with diabetes-related content was low in social media. The gap between patients' participation and engagement highlights the need for reassessment and refinement of social media communication strategies for healthcare organisations to empower patients with diabetes through social media and increase public engagement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts' confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers., Competing Interests: Declaration of interests JD is a cofounder and scientific adviser of GMT Science and MaaT Pharma. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) is treatment-resistant and generally considered incurable. The development of prostate-specific membrane antigen positron emission-computed tomography (PSMA PET/CT) has generated immense expectations due to its diagnostic accuracy in prostate cancer (PCa). PSMA expression of the primary tumor, quantified by SUVmax, is a predictor of oncological outcomes. The role of PSMA-PET/CT SUVmax in metachronous mHSPC treated with ADT plus second-generation antiandrogens (ARSI) is unknown. The main aim of this study was to evaluate 68 Ga-PSMA-11expression (SUVmax) as a potential prognostic biomarker in patients with metachronous mHSPC treated with ADT and first or second-generation antiandrogens. A second aim was to determine the association between PSMA SUVmax and PSA response to hormone therapy., Material and Methods: Patients diagnosed with metachronous mHSPC between July 2017 and February 2023 who developed biochemical recurrence following radical surgery (with or without salvage radiotherapy and/or ADT) or external radiation therapy (with or without ADT) were included. All patients underwent 68  Ga-PSMA-11 PET/CT imaging and the SUVmax value was determined for all measurable locations. The SUVmax value was used for the semiquantitative analysis. The Wilcoxon method was used to compare responders (PSA reduction ≥ 50%) to non-responders (PSA reduction < 50%). The SUVmax value and hormone therapy were evaluated as independent variables relative to the PSA response rate or PSA reduction using the linear regression method. A mixed-effects model (ANOVA) was used for the comparisons., Results: A total of 82 patients were included. Median follow-up was 11.7 months. On the linear regression analysis, patients with a high SUVmax treated with ADT + ARSI showed a greater PSA response (p = 0.034) than those treated with ADT + first-generation antiandrogens. In the mixed-effects model, SUVmax was significant (p = 0.041). On the univariate analysis, PSA at recurrence (HR, 3.2; 95% CI: 1.07-13.6; p = 0.078) and the number of metastases (HR, 4.77; 95% CI 1.1-26.1: p = 0.002) were associated with the type of hormone therapy administered., Conclusions: PSMA-PET/CT SUVmax is a prognostic biomarker that can be used to predict a PSA response to ADT + ARSI in patients with metachronous mHSPC. However, these findings need to be confirmed in larger prospective studies., Competing Interests: Declarations. Conflict of interest: The Author(s) declare(s) that there is no conflict of interest. Ethical approval: Authors declared that this study has been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent: All participants provided signed informed consent., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Chronic granulomatous disease (CGD) is a disorder of immunity characterized by phagocyte dysfunction. Mold infections in patients with CGD are often severe and disseminated. We present patient characteristics, microbiological data, and outcomes for 26 patients with CGD who received hematopoietic cell transplantation (HCT) or gene therapy-modified cells (GT) between 2008 and 2019, with proven fungal infection either before or during their transplant. All patients engrafted, and all but one GT recipient had neutrophil recovery and evidence of functional correction. Eighteen patients (69%) are currently alive and 19 patients (73% of total, 90% of patients with repeat imaging performed) had evidence of radiographic improvement. With 3 exceptions, deaths were not principally related to the fungal infection and duration of antecedent infection did not correlate with death. Aspergillus species accounted for the majority of disease (50%), followed by Phellinus species (18%). Osteomyelitis and disseminated disease were common, as only 11 patients (42%) had disease restricted to pneumonia. Triazole therapy was used in all 26 patients, with combination therapy used in 25 (96%). HCT or gene therapy, with appropriate antifungal therapy, are viable therapies for refractory fungal infections in patients with CGD., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All participants signed written informed consent forms including consent to publish images. The patents were participants separate clinical trials, all of which were separately approved by the NIH Institutional Review Board (Approval numbers 16-I-0032, 000186-I, 19-I-0080). All procedures were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Climate-related disasters pose significant risks to mental health and well-being globally. Individuals from disaster-prone regions, such as Puerto Rico, are at even greater risk. The devastating effects of recurrent hurricanes, compounded with pre-existing structural disparities (e.g., poverty and corruption), can further exacerbate psychosocial vulnerabilities and drive mass migration to the United States mainland. Most research on mental health among climate migrants focuses on risks, whereas promotive factors such as thriving are often overlooked. In the present study, we estimated a longitudinal structural equation model to examine the predictive effect of psychological thriving (i.e., optimism, life satisfaction) on sociocultural thriving (i.e., income, happiness, comfort, job satisfaction), mental distress (i.e., internalizing symptoms, post-traumatic stress) and cultural stressors using three waves of data from 319 adult Hurricane Maria survivor migrants (HMSMs) who relocated to the U.S. mainland between 2017 and 2020. We also examined the mediating effect of prosocial behavior and collective efficacy in this association. Our findings indicate various direct, simple mediation, and serial mediation paths between baseline psychological thriving and outcomes. Life satisfaction and collective efficacy mediated most of the predicted indirect pathways. These results suggest that, despite facing complex challenges, HMSMs are not only adapting to their mainland communities but are also thriving., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Hemorrhagic shock secondary to trauma is a leading cause of pediatric mortality in the United States. Timely intervention is crucial to prevent many of these deaths. Children and adults exhibit distinct responses to trauma due to varying blood volume ratios and injury patterns. Pediatric patients with hypotension face a heightened risk of shock, demanding a more assertive resuscitation., Methods: This study is a review of the literature on LTOWB transfusion in pediatric trauma. We conducted electronic database searches until December 2022, using keywords related to LTOWB and pediatric trauma resuscitation. Randomized/non-randomized, retrospective/prospective studies were considered, assessing serological safety, adverse reactions, clinical outcomes, and cost-effectiveness., Results: Six articles were ultimately reviewed. No adverse reactions related to hemolysis biomarkers were observed. Clinical outcomes exhibited no significant differences in mortality, hospital, or ventilator days between LTOWB and component therapy (CT). However, LTOWB transfusion resulted in faster resolution of base deficit, lower INR, and reduced requirement for additive plasma and platelet transfusions. In military and massive transfusion cases, LTOWB was associated with decreased mortality and lower transfusion volumes. One article suggested potential economic advantages., Conclusions: LTOWB transfusion appears to be a promising option for pediatric trauma resuscitation, offering benefits in rapid administration and component balance. While some studies indicate potential advantages in clinical outcomes and cost-effectiveness, the current evidence is limited and requires further investigation. Future research should focus on large-scale studies to validate these findings, especially concerning economic benefits, and develop standardized protocols for LTOWB use in pediatric settings., Levels of Evidence: Treatment Study, LEVEL III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This study aimed to analyze the European Hernia Society Quality of Life (EHS-QoL) in abdominal wall reconstruction by comparing preoperative scores with those at 1 and 2 postoperative years., Methods: Data from 105 patients with complex incisional hernias were collected preoperatively and at 1 and 2 years postoperatively. Statistical analyses included three ART ANOVA models to compare scores among the three time points and within each time point's items., Results: The EHS score significantly decreased from preoperative (Mdn ​= ​57) to 1 year (Mdn ​= ​10.5) and 2 years postoperative (Mdn ​= ​8). The most significant changes occurred between preoperative and 1-year measurements, particularly in pain levels during activities and limitations in heavy labor and activities outside the home., Conclusion: Patients' quality of life notably improved at 1 year post-surgery, with some reaching near-maximum levels, and this improvement was generally sustained or increased at 2 years post-surgery., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest on the present manuscrip. Dr Garcia-Urena received honorarium from lectures and workshops supported by Gore, Telabio, Dipromed and Dynamesh. Dr Lopez-Monclus receive honorarium from lectures and workshops supported by Gore, Medtronic, Dipromed and B Braun. The rest of the authors does not communicate any indirect or direct conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Only a few studies have investigated the role of diet on the risk of chronic kidney disease (CKD) in European populations and have mainly focused on the Mediterranean diet. This is the first study to evaluate the association between various diet quality indices and CKD incidence in British adults., Objective: To study the relationship between a set of 6 different diet quality indices and CKD incidence among British adults., Methods: A prospective cohort with 106,870 participants from the UK Biobank, followed from 2009 to 2012 through 2021. Food consumption was obtained from ≥2 24-h dietary assessments. Dietary patterns were assessed using previously established indices: Alternate Mediterranean Index (aMED), Alternative Healthy Eating Index 2010, dietary approaches to stop hypertension (DASH), healthful plant-based diet index (hPDI), unhealthful plant-based diet index (uPDI), and dietary inflammatory index (DII). Incident CKD was obtained from clinical records, death registries, and self-reports. Analyses were performed with Cox regression models and adjusted for the main confounders., Results: After a median follow-up of 9.27 y, 2934 cases of CKD were ascertained. Hazard ratios (95% confidence interval) of CKD for the highest compared with lowest tertile of adherence to each diet score were 0.84 (0.76, 0.93) for aMED, 0.94 (0.85, 1.03) for alternative healthy eating index 2010, 0.77 (0.70, 0.85) for DASH, 0.79 (0.72, 0.87) for hPDI, 1.27 (1.16, 1.40) for uPDI, and 1.20 (1.18, 1.33) for DII. The results were robust in sensitivity analyses., Conclusions: In British adults, higher adherence to the aMED, DASH, and hPDI patterns was associated with lower risk of CKD, whereas greater adherence to the uPDI and DII patterns was associated with greater risk., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The growing tendency towards 'urbanization' is promoting an increase in resource consumption and waste generation, which requires proper waste separation management with active participation of the population. To this end, it is essential to know the personal modifiable factors that predict recycling. The primary aim of the present study is to develop and evaluate the psychometric properties of a Spanish language questionnaire designed to measure determinants of household waste separation for recycling purposes (ReDom Questionnaire). A cross-cultural adaptation, translation and psychometric evaluation was undertaken of an extant questionnaire originally developed in Swedish, and the resultant Spanish questionnaire was then subjected to reliability and validity testing. The questionnaire was developed using survey data from 759 respondents and 33 participants performed the retest to assess reliability. The resultant 'ReDom Questionnaire' is composed of three factors that draw on relevant elements of the COM-B framework: motivation (seven items), physical opportunity (three items) and social opportunity (three items). The accuracy of the scores is adequate both in terms of internal consistency (factorial weights >0.60; comparative fit index = 0.994; root mean square error of approximation = 0.049; root mean square residual (RMSR) = 0.053) and reliability (Pearson correlation >0.65; Cronbach's alpha >0.75). In conclusion, the Spanish ReDom Questionnaire showed adequate psychometric properties and appears useful for assessing the determinants of household waste separation., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In the presence of neurological insult, how language and memory networks jointly reorganise provides insights into mechanisms of neuroplasticity and can inform presurgical planning. As (re)organisation is often studied within a single cognitive modality, how language and memory interact during (re)organisation in response to epilepsy and the implications for memory outcomes is less clear. We investigated (1) the rates and patterns of joint (re)organisation and (2) their associations with pre- and postsurgical memory function., Methods: Individuals with epilepsy (n=162) from three neurosurgical centres underwent the Wada procedure. We examined colateralisation patterns (ie, concordance/discordance) between language and both global and verbal memory (n=34), and associations with clinical characteristics and preoperative and postoperative memory outcomes., Results: Overall concordance between language and memory colateralisation was minimal-to-weak across both global memory and verbal memory (kappa=0.28-0.44). Discordance was primarily observed in individuals with left-lateralised language, of whom 52% and 32% showed discordance in global and verbal memory, respectively. Discordance was most pronounced in left hemisphere epilepsy and mesial temporal sclerosis. Conversely, right-lateralised language consistently predicted right-lateralised memory (95%-100%), regardless of seizure laterality or memory type. While discordance was not associated with presurgical memory function, discordance predicted superior postsurgical memory outcomes following surgery in the language-dominant hemisphere (p<0.05; η p 2 =0.30)., Conclusions: When language dominance is atypical, memory tends to colateralise. However, when language remains typical, concordance with memory is weak, particularly for left hemisphere seizure onset. An interhemispheric shift in language may trigger a shift in memory, possibly to maintain efficient communication between medial temporal and neocortical language networks. In contrast, memory appears able to reorganise in isolation, with discordance predicting better postsurgical memory outcomes without detriment to presurgical function. Our findings support the continued need for separate presurgical mapping of language and memory lateralisation, particularly in the case of typical language dominance and left hemisphere seizures., Competing Interests: Competing interests: CRM is a consultant for Neurona Therapeutics. SB receives stocks from Apple. The remaining do not have any conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The purpose of this paper is to summarize a panel discussion at the 2024 World Stuttering and Cluttering Organization Congress that aimed to explore and reflect on the shifting landscape of stuttering therapy across the lifespan. The panel comprised of speech-language pathologists who have experience in stuttering therapy as clients, professionals, and researchers. The panel members reflect on the research, their professional experiences, and their own personal journey toward a more acceptance-based therapy and its outcomes. The paper concludes with the panel's reflections on the future of stuttering therapy across the lifespan., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Farzan Irani reports a relationship with Texas State University that includes: employment. Geoffrey A. Coalson reports a relationship with Arthur M. Blank Center For Stuttering Education and Research - University of Texas at Austin that includes: employment. Jack Rodriguez reports a relationship with Arthur M. Blank Center for Stuttering Education and Research - University of Texas at Austin. that includes: employment. Michael Boyle reports a relationship with Montclair State University that includes: employment. Eric Swartz reports a relationship with Texas A&M University at Kingsville that includes: employment. Michael Azios reports a relationship with University of Louisiana at Lafayette that includes: employment. Scott Palasik reports a relationship with University of Akron that includes: employment. Jack Rodriguez received travel and participation in the World Congress on Stuttering and Cluttering reported in this manuscript was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award number 1R13DC021874–01. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background and Objectives: The study seeks to elucidate the pathways by which the Caregiver TLC psycho-educational program impacts the psychological health of caregivers by examining the degree to which changes in self-efficacy, personal gains, and emotional support mediate the changes on perceived depression, anxiety and burden., Research Design and Methods: Using pre-post data from the Caregiver TLC randomized controlled trial (n = 81) for each outcome and mediator pair, a series of multiple regression models were executed to test the degree to which the program's total effects on changes in depression, burden and anxiety from baseline to post-intervention are due to changes in each mediator variable from pre- and post-intervention assessments. Caregivers were primarily female (85%), White (62 %), Black (38%), with a median age of 62 and household income of $75,000+. Caregivers reported caring for a person with dementia (69%) or chronic health conditions (31%)., Results: Mediation path modeling indicated that changes in self-efficacy affected by participation in the Caregiver TLC program, mediating between 32% and 63% of the total treatment effect on the outcome variables. Change in personal gains and change in emotional support also demonstrated meaningful mediation effects, albeit smaller in magnitude., Discussion and Implications: Results confirm that the observed positive impact of the Caregiver TLC program is due to changes in self-efficacy (in particular) and to a lesser degree to changes in personal gains and emotional support. These results confirm that strengthening caregivers perceived self-efficacy to manage stress plays a significant role in improving psychosocial functioning., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background : A transperineal approach to prostate biopsy is now recommended to reduce the risk of infectious complications associated with the transrectal route. Our aim is to compare the efficacy of transrectal- and transperineal-guided biopsies involving the magnetic resonance imaging (MRI) of index lesions in detecting significant prostate cancer (sPCas), and to evaluate the role of systematic biopsies. Methods : In a prospective and multicenter trial conducted in an opportunistic early detection program for sPCa in Catalonia (Spain), between 2021 and 2023, 4029 men suspected of having PCa underwent multiparametric MRI followed by guided and systematic biopsies. From this cohort, we retrospectively selected 1376 men with reports of the size and localization of their index lesions. A matched group of 325 pairs of men subjected to transrectal and transperineal biopsy were chosen to account for confounding variables. We compared sPCa detection rates determined via index lesions and systematic biopsies, as well as by lesion localization. Results : Transperineal and transrectal biopsies detected sPCa in 49.5% vs. 40.6% overall ( p = 0.027), 44.6% vs. 30.8% from index lesions ( p = 0.001), and 24.3% vs. 35.1% from systematic biopsies ( p = 0.003). SPCa detection rates were higher in transperineal biopsies across all index lesion localizations, with significant increases in the anterior zone (47.8% vs. 20.8% at the mid-base, p = 0.039, and 52.9% vs. 24.2% at the apex, p = 0.024) and central zone (33.3% vs. 5.9%, p = 0.003). With regards to SPCa detected only in systematic biopsies, 10.5% of cases were detected in transrectal biopsies and 4.9% of cases were detected in transperineal biopsies ( p = 0.012). Conclusions : Targeted biopsies conducted via the transperineal route showed higher sPCa detection rates than transrectal biopsies, particularly for anterior and apical lesions, with systematic biopsies showing reduced utility.

Background: Catheter ablation is an effective treatment of atrial fibrillation. Pulsed field ablation (PFA) has emerged as a novel energy modality that relies on high-voltage electric fields to achieve cardiac tissue ablation. Data on its efficacy in the elderly are scarce., Objective: This study aimed to evaluate the procedural details and clinical outcomes of PFA in patients >75 years old., Methods: Consecutive patients with atrial fibrillation >75 years old undergoing PFA with the Farapulse system were enrolled at 6 high-volume centers. Procedural details and clinical outcomes were compared with those of patients undergoing second-generation cryoballoon ablation (CBA) and radiofrequency ablation (RFA)., Results: Of 983 patients, 221 underwent PFA, 216 CBA, and 546 RFA. Procedure times were shorter with PFA (72 ± 30 minutes) compared with CBA (77 ± 27 minutes) and RFA (99 ± 23 minutes; P < .001). Extra-pulmonary vein ablation was performed in 74.2% PFA, 9.7% CBA, and 42.1% RFA (P < .001). The major complication rate was 1.01% (n = 10) and was not significantly different between groups (1 PFA, 2 CBA, and 7 RFA; P = .578). Minor complications were observed in 1.4% PFA, 5.1% CBA, and 3.5% RFA (P = .093). The 1-year atrial tachyarrhythmia freedom in the propensity score-matched population was 77.2% with PFA, 80.8% with CBA, and 74.9% with RFA; P = .52)., Conclusion: PFA is a safe and effective option for elderly patients, offering the advantage of enabling extra-pulmonary vein ablation without the concern of thermal injury risk., Competing Interests: Disclosures Dr de Asmundis received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, LivaNova, Boston Scientific, AtriCure, Acutus Medical, and Daiichi Sankyo. Dr Chierchia received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. The other authors report no relationships relevant to the contents of this study., (Copyright © 2025 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

This study examined relationships among caregiver burden, depressive symptoms, and key processes related to psychological flexibility (experiential avoidance, cognitive fusion, values-driven actions, and mindfulness) in 157 family caregivers of individuals with dementia in the United States. Path analyses were used. Participants' mean age was 59.5 years, ranging between 24 and 87 years. The model fit indices indicated excellent fit to the data. Caregiver burden had a direct effect on depressive symptoms (51.6 % of the total effect), while indirect effects accounted for 48.4%. The largest indirect effect was through values-driven action (14.6% of the total effect), followed by the paths through cognitive fusion → experiential avoidance (13.5%) and through mindfulness → cognitive fusion → experiential avoidance (8.7%). Targeting these key processes related to psychological flexibility with interventions such as acceptance and commitment therapy may help reduce the negative impact of caregiver burden on depressive symptoms in these caregivers., Competing Interests: Declaration of Conflicting InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has been hampered by a lack of technologies. Here, we adapted retrograde tracing using rabies viruses to investigate and manipulate neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across the brain, engaging in widespread functional communication, with cholinergic neurons driving glioblastoma invasion. We uncovered patient-specific and tumor-cell-state-dependent differences in synaptogenic gene expression associated with neuron-tumor connectivity and subsequent invasiveness. Importantly, radiotherapy enhanced neuron-tumor connectivity by increased neuronal activity. In turn, simultaneous neuronal activity inhibition and radiotherapy showed increased therapeutic effects, indicative of a role for neuron-to-glioma synapses in contributing to therapeutic resistance. Lastly, rabies-mediated genetic ablation of tumor-connected neurons halted glioblastoma progression, offering a viral strategy to tackle glioblastoma. Together, this study provides a framework to comprehensively characterize neuron-tumor networks and target glioblastoma., Competing Interests: Declaration of interests J.S.-R. reports funding from GSK, Pfizer, and Sanofi and fees/honoraria from Travere Therapeutics, Stadapharm, Astex, Owkin, Pfizer, and Grunenthal., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Photodynamic therapy (PDT) involves the topical application of a photosensitizer and its activation by visible light, leading to the generation of protoporphyrin IX (PpIX) and reactive oxygen species. Daylight photodynamic therapy (dPDT), a variant utilizing natural sunlight as the energy source, enhances procedural flexibility by eliminating the need for specialized equipment. dPDT has been effectively used in dermatology to treat various cutaneous disorders, including neoplastic and infectious diseases. Traditionally, skin preparation and photosensitizer application are performed by trained practitioners, limiting the accessibility of dPDT for broader populations. However, recent studies suggest that these preparatory steps can be managed by patients or caregivers, enabling fully self-applied, home-based dPDT protocols. This review systematically examines the current evidence on self-applied dPDT (SA-dPDT), emphasizing molecular mechanisms and its efficacy in managing premalignant and other cutaneous conditions.

Background/Objectives: Patients on chronic anticoagulation undergoing metabolic surgery represent an increased risk of complications, including both bleeding and thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE). The optimal perioperative management of patients who are receiving chronic anticoagulation therapy (CAT) is complex. In the colorectal surgery literature, patients on CAT have a 10% rate of peri-procedural bleeding and a 3% rate of thromboembolism. The aim of this study was to evaluate and compare the safety and postoperative outcomes between patients with and without CAT undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at a tertiary referral center in the United Arab Emirates (UAE). Methods: All patients who underwent primary bariatric surgery between September 2015 and July 2019 were retrospectively reviewed. The first group included patients with CAT, and the second group included patients without CAT. Demographics, perioperative outcomes, and postoperative results were examined. Results: Our study included 542 patients, 22 (4%) with CAT and 520 (96%) without CAT. Mean age was 46.3 ± 10.5 years in the CAT group and 36.0 ± 11.7 years in the non-CAT group ( p < 0.001); median BMI was 41.8 (range 33.1-61.3) and 42.7 (range 30.1-78.4) kg/m 2 , respectively ( p = 0.52). The CAT group had significantly higher rates of hypertension (77.2% vs. 32.5%, p < 0.001), obstructive sleep apnea (81.8% vs. 31.5%, p < 0.001), and coronary artery disease (31.8% vs. 2.8%, p < 0.001). In the CAT group, 8/22 (36.4%) patients underwent Roux-en-Y gastric bypass and 14/22 (63.6%) sleeve gastrectomy, compared to 228/520 (43.8%) and 292/520 (56.2%), respectively, in the non-CAT group ( p = 0.51). There were no statistically significant differences in postoperative emergency department (ED) visits (18.1% vs. 24.2%, p = 0.51), early major complications (4.5% vs. 3.4%, p = 0.54), readmission rates within 30 days (4.5% vs. 3.6%, p = 0.56), or late complications (4.5% vs. 4.2%, p = 0.60). Mean length of stay was significantly longer in the CAT group (4.6 vs. 2.6 days, p < 0.001). The mean follow-up was 10 ± 7.3 months for the CAT cohort and 11 ± 9.7 months for the non-CAT cohort ( p = 0.22). Weight loss outcomes at 12 months were comparable, with a percent total body weight loss (TBWL) of 27.0 ± 7.3% in the CAT group and 28.9 ± 8.3% in the non-CAT group ( p = 0.29). There were no deaths in either group. Conclusions: In this series, at a tertiary referral center in the UAE, metabolic surgery is safe for CAT patients. Multidisciplinary preoperative preparation might be warranted to avert potential complications.

Objective: ASTHMAXcel Perception is an expansion of prior ASTHMAXcel mobile health applications for children with asthma. ASTHMAXcel Perception was evaluated for its ability to improve asthma control and perception of airflow limitation., Methods: Patients with asthma ages 15-21 were randomized to receive ASTHMAXcel Perception with peak expiratory flow (PEF) feedback or usual care (UC). A baseline visit was followed by 3 intervention sessions across 6 weeks in the intervention group. Assessments in both groups were designed to occur at baseline, 6-week (primary time point), and 3-month follow-up. Self-reported asthma control (primary outcome), asthma quality of life, asthma knowledge, medication adherence, healthcare utilization, app usage, and perception of airflow limitation (measured by comparing self-reported PEF guess to actual PEF) were assessed., Results: 45 patients were enrolled (PEF n = 22, UC n = 23). At 6 weeks, the PEF group reported better asthma control than the UC group (18.7 vs 16.7, p < .05). In the PEF group, accurate perception increased from baseline to 6-weeks (48% vs 77%, p = 0.01) and from baseline to 3-months (48% vs 74%, p = 0.009). Over-perception decreased from baseline to 6-weeks (26% vs 5%, p = 0.041). The number of logins was associated with greater accuracy in perception of airflow limitation from baseline to 2-weeks (r = 0.91, p = 0.002) and 2-weeks to 4-weeks (r = 0.77, p < .05). No significant differences were found in asthma quality of life, asthma knowledge, medication adherence, or healthcare utilization between the two groups., Conclusion: ASTHMAXcel Perception improved asthma control and was associated with greater accuracy in perception of airflow limitation.

Social stress during adolescence results in long lasting weight gain, obesity, and enhanced food hoarding behavior in hamsters. We wanted to determine whether stress also enhanced conditioned place preference-like behavior (CPP-like) for food reward, as would be expected from studies with substances like cocaine. Our experimental animals were exposed daily to aggressive adults for two weeks in early puberty, while also trained to explore a V-shaped maze containing a food reward at one end. They were tested for CPP-like behavior on the last day of social stress. Our results showed that while stress enhanced weight gain, food intake, food efficiency, and body fat, it caused a reduction of Place Preference as compared to controls. In fact, the correlated relationship between Place Preference and body fat was inverted by stress exposure: while it was positively correlated in controls, it was mildly negatively correlated in stressed hamsters. These unexpected data illustrate the extent of adaptive behavior in foraging animals once a resource has become untrustworthy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Acute respiratory infections are a significant challenge in primary care and hospital settings. Viruses are the most common etiology and the overlapping symptomatology among major respiratory viruses, such as influenza, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus, requires the use of diagnostic tests that deliver early and accurate results. With the increasing availability of rapid antigen tests (RATS), it is tempting to prefer them over polymerase chain reaction (PCR) tests. However, compelling arguments support the existing recommendations in some European countries to maintain PCR testing for patient management throughout the year. RATs show sensitivities below 30% with lower viral loads, which are common and can have significant clinical implications. RATs perform well at lower cycle threshold (Ct) values, with sensitivity reaching 97.9% for Ct values below 20, which drops significantly for values above 25. Factors affecting viral load include disease stage, vaccination status, and viral variants, all of which can compromise the accuracy of antigen tests. Multi-target PCR tests effectively overcome these issues, ensuring reliable diagnosis. Additionally, the early detection of paucisymptomatic cases is essential in primary care and hospital settings to facilitate isolation and prevent secondary infections. Economic analyses support the use of comprehensive PCR tests, such as triplex-type tests, detecting SARS-CoV-2, influenza viruses, and RSV, as a first-line approach, as they can reduce case numbers and healthcare resource utilization. Maintaining PCR testing year-round is therefore crucial for the effective management of respiratory infections.

Background: Individuals with psychosis symptoms are at high risk for suicidal ideation and attempts. The prevalence and correlates of suicidal ideation and attempts in clinical high risk for psychosis (CHR-P) have yet to be clarified. This study reports on the prevalence and clinical correlates of suicidal ideation and attempts in a clinical CHR-P sample., Method: Participants (n = 135) included CHR-P clients at a CHR-P community specialty clinic, who participated in a clinical assessment between 2017 and 2022. Assessments measured attenuated psychosis symptoms, suicidal ideation and attempts, clinical covariates, and functioning. Frequency analyses assessed the prevalence of lifetime suicidal ideation and attempts and t-test and Chi-square identified clinical correlates. Logistic regression assessed the relationship between significant clinical correlates and lifetime suicide attempts., Results: Sixty-five percent of participants at CHR-P endorsed lifetime suicidal ideation, while 22.2% reported at least one lifetime attempt. Correlates for lifetime suicidal ideation included self-reported gender expansive identity, hopelessness, depression, trauma, obsessive compulsive symptoms, insight: reflectiveness, trauma diagnoses, mood disorder diagnoses, and perceptual abnormalities/hallucinations. Significant correlates for lifetime suicide attempts included self-reported hopelessness, depression, trauma diagnosis and mood disorder diagnosis., Conclusion: CHR-P clients are at a higher risk for suicidal ideation and attempts compared to the general population. Correlates of suicidal ideation and attempts may be diagnostically heterogeneous and therefore interventions should be tailored to specific clinical needs. Clients with trauma-disorder diagnoses may be at highest risk for suicidal ideation and attempts. Continued intervention and longitudinal research is needed to clarify causal risk factors and establish evidence-based treatments for suicidal ideation and attempts in CHR-P., (© 2024 John Wiley & Sons Australia, Ltd.)

Poultry can act as a reservoir of Salmonella enterica serotype Infantis (S. Infantis) of clinical and epidemiological importance because it triggers foodborne disease outbreaks and presents antibiotic multiresistance. The present study aimed to determine antimicrobial resistance in S. Infantis isolates from poultry livers, litter and chicken carcasses from Lima, Peru, during 2022-2023. S. Infantis was isolated from 10.1 % (27/267), 4.7 % (4/86), and 8 % (2/25) of the bird, litter and carcass samples, respectively. All isolates showed resistance to nalidixic acid (NA). In addition, 94 %, 76 %, 70 %, 48 %, and 45 % of the isolates showed resistance to tetracycline (TET), amoxicillin (AMX), chloramphenicol (C), gentamicin (GEN) and trimethoprim/sulfamethoxazole (TS), respectively. All isolates showed susceptibility to imipinem and amoxicillin/clavulanic acid. Of the isolates, 93.9 % displayed multidrug resistance. The most frequent resistance pattern was C-AMX-NA-GEN-TET (24.2 %, n=8), determined even from carcass isolates, followed by C-AMX-NA-TET (18.2 %, n=6), and C-AMX-NA-GEN-TS-TET (12.1 %, n=4). The presence of these multidrug-resistant S. Infantis isolates is a threat to food safety and public health., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with the publication “Multiple antibiotic resistance of Salmonella Infantis in the Peruvian poultry production chain: detection in birds, the farming environment and chicken carcasses.” and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We also confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: DOCK8 deficiency is a primary immunodeficiency in which allogeneic hematopoietic cell transplantation (HCT) represents the only known cure. We tested the ability of a busulfan-based regimen to achieve reliable engraftment and high levels of donor chimerism with acceptable toxicity in a prospective clinical trial in DOCK8 deficiency., Objectives: To both evaluate the ability of HCT to reverse the clinical phenotype and to correct the immunologic abnormalities by 1 year post HCT., Methods: We conducted a prospective HCT trial for recipients with DOCK8 deficiency. Subjects were recruited from October 5, 2010, to December 30, 2022. Donor sources included fully matched related and unrelated donors and haploidentical donors. The reduced toxicity, myeloablative conditioning regimen contained no serotherapy. Graft-versus-host disease (GVHD) prophylaxis included either a calcineurin inhibitor with methotrexate or post-HCT cyclophosphamide (PT/Cy) followed by tacrolimus and mycophenolate mofetil. The trial was later amended to study PT/Cy in all patients. (Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 [NCT01176006].) RESULTS: Thirty-six subjects, both children and adults (median age 16.4 years), underwent HCT for DOCK8 deficiency. Most patients, 33 of 36 (92%), achieved full (≥98%) donor chimerism in whole blood as early as day +30. With a median potential follow-up of 7.4 years, 29 (80.6%) were alive with no evidence of new DOCK8 deficiency-related complications. PT/Cy was effective in reducing the risk of acute GVHD in patients who had received matched unrelated donor and haploidentical transplants, but it was associated with transient delays in immune-reconstitution and hemorrhagic cystitis., Conclusions: A busulfan-based HCT regimen using PT/Cy for GVHD prophylaxis and a broad range of donor types and hematopoietic cell sources were well tolerated, leading to the reversal of the clinical immunophenotype., Competing Interests: Disclosure statement This work was supported in part by the Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research; the Warren Grant Magnuson Clinical Center (ZIA BC 011823 to N. Shah, ZID BC 012026 to S.-Y. Pai); National Institute of Allergy and Infectious Diseases (1ZIAAI001193 to H. Su); National Institute of Diabetes, Digestive, and Kidney Diseases; and National Institute of Arthritis and Musculoskeletal and Skin Diseases. The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Published by Elsevier Inc.)

We report a case of Acanthamoeba infection in an HCT recipient with steroid-refractory GVHD. We highlight the multiple challenges that free-living ameba infections present to the clinician, the clinical laboratory, transplant infectious disease for review, hospital epidemiology if nosocomial transmission is considered, and public health officials, as exposure source identification can be a significant challenge. Transplant physicians should include Acanthamoeba infections in their differential diagnosis of a patient with skin, sinus, lung, and/or brain involvement., (© 2024 The Author(s). Transplant Infectious Disease published by Wiley Periodicals LLC.)

Background: One-Anastomosis Gastric Bypass (OAGB) is becoming popular, but some patients may need to convert to Roux-en-Y Gastric Bypass (RYGB) due weight-related difficulties or postoperative complications. The data on conversions is currently limited to 30-day or short-term follow-up studies. As such, the objective of this study was to evaluate the indications and mid-term outcomes for OAGB conversions to RYGB at a tertiary referral center in the United Arab Emirates., Methods: A retrospective analysis was conducted on patients who underwent conversion from OAGB to RYGB between February 2016 and May 2023. Demographic information, indications for conversion, intraoperative details, and mid-term outcomes were collected and analyzed., Results: Sixty-four patients underwent conversion from previous OAGB to RYGB. The cohort was 73.4% female (n = 47) with a mean age of 40.8 years. Indications for conversion included acid reflux (n = 28, 43.7%), intractable nausea/vomiting (n = 20, 31.2%), protein-calorie malnutrition (n = 7, 10.9%), anastomotic ulcer (n = 6, 9.3%) and weight recidivism (n = 3, 4.7%). The mean operative time was 238 ± 78.3 min. During the procedure, three intraoperative complications occurred: two cases of bleeding and one case of bowel perforation; all successfully addressed during surgery. The median hospital stay was 3 ± 15.8 days. Three patients (4.6%) experienced major postoperative complications comprising 2 anastomotic leaks and 1 small bowel obstruction. The mean follow-up time was 26.2 ± 19.7 months, with 96.2% of patients reporting resolution of symptoms. There were no mortalities., Conclusions: Acid reflux is representing 43.7% of the indications for conversion from OAGB to RYGB. The symptom resolution rate holds significance, standing at a remarkable 96.8%. Despite surgical technique advancements, the complication rate after conversions remains significant at 4.6%, with no mortality reported. OAGB patients should be informed about these risks prior to undergoing conversions from OAGB to RYGB., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The 313-variant polygenic risk score (PRS 313 ) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS 313 across different European populations which could influence risk estimation has not been performed., Methods: We explored the distribution of PRS 313 across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank. The mean PRS was calculated by country in the BCAC dataset and by country of birth in the UK Biobank. We explored different approaches to reduce the observed heterogeneity in the mean PRS across the countries, and investigated the implications of the distribution variability in risk prediction., Results: The mean PRS 313 differed markedly across European countries, being highest in individuals from Greece and Italy and lowest in individuals from Ireland. Using the overall European PRS 313 distribution to define risk categories, leads to overestimation and underestimation of risk in some individuals from these countries. Adjustment for principal components explained most of the observed heterogeneity in the mean PRS. The mean estimates derived when using an empirical Bayes approach were similar to the predicted means after principal component adjustment., Conclusions: Our results demonstrate that PRS distribution differs even within European ancestry populations leading to underestimation or overestimation of risk in specific European countries, which could potentially influence clinical management of some individuals if is not appropriately accounted for. Population-specific PRS distributions may be used in breast cancer risk estimation to ensure predicted risks are correctly calibrated across risk categories., Competing Interests: Declarations. Ethics approval and consent to participate: All study participants gave written informed consent, and all the Breast Cancer Association Consortium studies were approved by the relevant ethics committees. The Breast Cancer Association Consortium data have been used under the application with access number 712. The use of the UK Biobank has been approved under application ID102655. Consent for publication: Not applicable. Competing interests: The following authors declare conflicts not directly relevant to this work as stated below: U.M. has a patent (no: EP10178345.4) for Breast Cancer Diagnostics and held personal shares in Abcodia Ltd between 2011 and 2021. She has research collaborations with Mercy Bioanalytics, iLOF, RNA Guardian and Micronoma in the field of early detection of cancer. P.A.F. conducts research funded by Amgen, Novartis and Pfizer. He received Honoraria from Roche, Novartis and Pfizer. R.A.M. is a Consultant for Pharmavite., (© 2024. The Author(s).)

Gate dielectrics are essential components in nanoscale field-effect transistors (FETs), but they often face significant instabilities when exposed to harsh environments, such as radioactive conditions, leading to unreliable device performance. In this paper, we evaluate the performance of ultrascaled transition metal dichalcogenide (TMD) FETs equipped with vacuum gate dielectric (VGD) as a means to circumvent oxide-related instabilities. The nanodevice is computationally assessed using a quantum simulation approach based on the self-consistent solutions of the Poisson equation and the quantum transport equation under the ballistic transport regime. The performance evaluation includes analysis of the transfer characteristics, subthreshold swing, on-state and off-state currents, current ratio, and scaling limits. Simulation results demonstrate that the investigated VGD TMD FET, featuring a gate-all-around (GAA) configuration, a TMD-based channel, and a thin vacuum gate dielectric, collectively compensates for the low dielectric constant of the VGD, enabling exceptional electrostatic control. This combination ensures superior switching performance in the ultrascaled regime, achieving a high current ratio and steep subthreshold characteristics. These findings position the GAA-VGD TMD FET as a promising candidate for advanced radiation-hardened nanoelectronics.

Background: Risk stratification for sudden cardiac death (SCD) in patients with nonischemic cardiomyopathy (NICM) remains challenging., Objectives: This study aimed to investigate the impact of epicardial adipose tissue (EAT) on SCD in NICM patients., Methods: Our study cohort included 173 consecutive patients (age 53 ± 14 years, 73% men) scheduled for primary prevention implantable cardioverter-defibrillators (ICDs) implantation who underwent preimplant cardiovascular magnetic resonance. EAT volume surrounding both ventricles was manually quantified from cine left ventricular short-axis images by summation of the EAT volume of each slice using the modified Simpson rule. The primary endpoint was appropriate ICD therapy., Results: During the mean follow-up of 3.6 years, 24 patients (14%) experienced an endpoint. An inverse and proportional relationship was evident between EAT and subsequent ICD therapies ( P  = 0.004). Even after adjusting for left ventricular mass and ejection fraction, EAT was significantly lower in patients with ICD therapy than those without. Low EAT was independently associated with an increased risk of ICD therapy in NICM patients (HR ad per 10 mL/m 2 decrease, 1.65; 95% CI: 1.17-2.42; P  = 0.007). EAT ≤50 mL/m 2 demonstrated a 3-fold increase in SCD event risk, with an estimated likelihood of 57% at 5 years. When considered with other potential risk factors, EAT provided incremental prognostic value in predicting ICD therapy., Conclusions: Low ventricular EAT was associated with increased SCD risk in NICM patients receiving primary prevention ICD implantation, even in the presence of other risk markers. These data suggest a potential clinical role of EAT in selecting NICM patients who would benefit most from ICD implantation., Competing Interests: Dr Nezafat has received a research agreement with Siemens Healthineers, the manufacturer of MRI systems. Dr Nezafat has received grant funding by the 10.13039/100000002NIH 1R01HL129185, 1R01HL129157, 1R01HL127015, R01HL158098, and R01HL154744 (Bethesda, Maryland, USA). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Cross-national comparisons of dementia prevalence are essential for identifying unique determinants and cultural-specific risk factors, but methodological differences in dementia classification across countries hinder global comparisons. This study maps the 10/66 algorithm for dementia classification, widely used and validated in low- and middle-income countries (LMICs), to the U.S. Aging, Demographics, and Memory Study (ADAMS), the dementia sub-study of the Health and Retirement Study, and assesses its performance in ADAMS. We identified the subset of 10/66 algorithm items comparably measured in ADAMS, then used these items to re-train the 10/66 algorithm against the ADAMS clinical dementia diagnosis, employing k-fold cross-validation to assess performance. We compared the modified 10/66 algorithm to four other dementia classification algorithms previously validated in ADAMS, both for overall dementia estimation as well as for estimating education gradients. The modified 10/66 algorithm had higher sensitivity (87%) and specificity (93%) than the comparison algorithms. All of the algorithms over-estimated the education gradient in dementia, although the modest ADAMS sample size precludes precise comparisons of education gradient accuracy. Overall, we found that the modified 10/66 algorithm performs well in classifying dementia status in the U.S. Our results support the validity of risk factor comparisons between U.S. and 10/66 LMIC dementia datasets., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Infant growth predicts long-term obesity and cardiovascular disease. Previous interventions designed to prevent obesity in the first 2 years of life have been largely unsuccessful. Obesity prevalence is high among traditional racial and ethnic minority groups., Objective: To compare the effectiveness of adding a digital childhood obesity prevention intervention to health behavior counseling delivered by pediatric primary care clinicians., Design, Setting, and Participants: Individually randomized, parallel-group trial conducted at 6 US medical centers and enrolling patients shortly after birth. To be eligible, parents spoke English or Spanish, and children were born after 34 weeks' gestational age. Study enrollment occurred between October 2019 and January 2022, with follow-up through January 2024., Interventions: In the clinic-based health behavior counseling (clinic-only) group, pediatric clinicians used health literacy-informed booklets at well-child visits to promote healthy behaviors (n = 451). In the clinic + digital intervention group, families also received health literacy-informed, individually tailored, responsive text messages to support health behavior goals and a web-based dashboard (n = 449)., Main Outcomes and Measures: The primary outcome was child weight-for-length trajectory over 24 months. Secondary outcomes included weight-for-length z score, body mass index (BMI) z score, and the percentage of children with overweight or obesity., Results: Of 900 randomized children, 86.3% had primary outcome data at the 24-month follow-up time point; 143 (15.9%) were Black, non-Hispanic; 405 (45.0%) were Hispanic; 185 (20.6%) were White, non-Hispanic; and 165 (18.3%) identified as other or multiple races and ethnicities. Children in the clinic + digital intervention group had a lower mean weight-for-length trajectory, with an estimated reduction of 0.33 kg/m (95% CI, 0.09 to 0.57) at 24 months. There was also an adjusted mean difference of -0.19 (95% CI, -0.37 to -0.02) for weight-for-length z score and -0.19 (95% CI, -0.36 to -0.01) for BMI z score. At age 24 months, 23.2% of the clinic + digital intervention group compared with 24.5% of the clinic-only group had overweight or obesity (adjusted risk ratio, 0.91 [95% CI, 0.70 to 1.17]) based on the Centers for Disease Control and Prevention criteria of BMI 85th percentile or greater. At that age, 7.4% of the clinic + digital intervention group compared with 12.7% of the clinic-only group had obesity (adjusted risk ratio, 0.56 [95% CI, 0.36 to 0.88])., Conclusions and Relevance: A health literacy-informed digital intervention improved child weight-for-length trajectory across the first 24 months of life and reduced childhood obesity at 24 months. The intervention was effective in a racially and ethnically diverse population that included groups at elevated risk for childhood obesity., Trial Registration: ClinicalTrials.gov Identifier: NCT04042467.

Importance: Paraesophageal hernias can cause severe limitations in quality of life and life-threatening complications. Even though minimally invasive paraesophageal hernia repair (MIS-PEHR) is safe and effective, anatomic recurrence rates remain notoriously high. Retrospective data suggest that suturing the stomach to the anterior abdominal wall after repair-an anterior gastropexy-may reduce recurrence, but this adjunct is currently not the standard of care., Objective: To determine whether anterior gastropexy reduces 1-year recurrence after MIS-PEHR., Design, Setting, and Participants: This registry-based randomized clinical trial was conducted by 10 surgeons at 3 academic hospitals within the Cleveland Clinic Enterprise. Between June 26, 2019, and July 24, 2023, 348 patients were assessed for eligibility, and 240 patients were enrolled and randomized. Statistical analysis was performed from January to March 2024., Intervention: Enrolled patients were randomized to and received either an anterior gastropexy (n = 119) or no anterior gastropexy (n = 121)., Main Outcome: The primary outcome was recurrence as determined by reherniation of the stomach greater than 2 cm above the diaphragm on routine imaging at 1 year or reoperation. Secondary outcomes included quality of life as measured by the Gastroesophageal Reflux Health-Related Quality of Life survey, additional foregut symptom questionnaire, and patient satisfaction at 30 days and 1 year., Results: A total of 240 patients were randomized to either anterior gastropexy (n = 119; 104 [97%] women; median [IQR] age, 70 [64-75] years) or no anterior gastropexy (n = 121; 97 [80%] women; median [IQR] age, 68 [62-73] years) at the end of their MIS-PEHR. At 1 year, 188 patients (78%) had completed follow-up. By intention-to-treat analysis, 1-year recurrence was significantly lower in patients who received an anterior gastropexy (15% vs 36%; risk difference, 0.21 [95% CI, 0.09-0.33]), which remained significant after risk-adjusted regression analysis (hazard ratio, 0.38 [95% CI, 0.23-0.60]). Of 13 reoperations (5.4%) for recurrence in the first year, 3 (2.5%) were in the anterior gastropexy group and 10 (8.2%) were in the no-gastropexy group (P = .052). Two patients (1.7%) had their anterior gastropexy sutures removed for pain. There were no significant differences in quality-of-life outcomes at 30 days and 1 year between treatment groups., Conclusions and Relevance: This randomized clinical trial found that the addition of an anterior gastropexy to MIS-PEHR is superior to no gastropexy in regard to reducing 1-year paraesophageal hernia recurrence. These results suggest that an anterior gastropexy should be routinely used in the context of minimally invasive paraesophageal hernia repair., Trial Registration: ClinicalTrials.gov Identifier: NCT04007952.

Background: Cerebrospinal fluid (CSF) biomarkers of synaptic dysfunction, neuroinflammation, and glial response, complementing Alzheimer's disease (AD) core biomarkers, have improved the pathophysiological characterization of the disease. Here, we tested the hypothesis that the co-expression of multiple CSF biomarkers will help the identification of AD-like phenotypes when biomarker positivity thresholds are not met yet., Methods: Two hundred and seventy cognitively unimpaired adults with family history (FH) of sporadic AD (mean age = 60.6 ± 4.85 years, 64.8% women) underwent lumbar puncture, magnetic resonance imaging (n = 266) and positron emission tomography imaging (n = 239) protocols, and clinical evaluations. CSF Aβ 42 , Aβ 40 , p-tau 181 , p-tau 217, p-tau 231, NfL, neurogranin, sTREM2, YKL40, GFAP, S100, α-Synuclein, SYT1, and SNAP25 were measured. Participants were clustered based on CSF biomarker co-expression with an agglomerative algorithm. The predictive value of the classification against brain and cognitive outcomes was evaluated., Results: Three clusters (C) were identified. Higher Aβ burden and CSF p-tau was the hallmark of C1. The other two clusters showed lower Aβ burden but higher expression of glial (C2) or synaptic markers (C3). Participants in C1 showed an AD-like clinical phenotype, comprising participants with the overall highest percentage of two parent FH and APOE-ε4 carriers, in addition to comprising more females compared to C2. C3 displayed better vascular health compared to C1. C2 were older and comprised a lower percentage of females compared to C3. C1 showed an AD-like gray matter reduction in medial temporal (notably hippocampus) and frontal regions that were not observed in Aβ 42/40  + compared with Aβ 42/40  - . Furthermore, Aβ 42/40  - participants in C1 showed GM reduction in inferior temporal areas compared with Aβ 42/40  + participants overall. C1 membership also predicted cognitive decline in executive function, but not memory, beyond Aβ + status, overall suggesting a better prognosis in Aβ 42/40  + participants without C1 membership. Additionally, C1 displayed a higher rate of conversion to Aβ + (25%) over time., Conclusions: Our results suggest that examining multiple CSF biomarkers reflecting diverse pathological pathways may complement and/or outperform AD core biomarkers and thresholding approaches to identify individuals showing a clinical and cognitive AD-like phenotype, including higher conversion to Aβ + , GM reductions and cognitive decline. The clinical utility of this approach warrants further investigation and replication in other cohorts., Competing Interests: Declarations. Ethics approval and consent to participate: The ALFA + study (ALFA-FPM-0311) was approved by the Independent Ethics Committee “Parc de Salut Mar,” Barcelona, and registered at Clinicaltrials.gov (identifier: NCT02485730) on June 10, 2015. All participants signed the informed consent form that had also been approved by the Independent Ethics Committee “Parc de Salut Mar,” Barcelona. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments and comparable ethical standards. Consent for publication: NA. Competing interests: H.Z. has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). G.K. is a full‑time employee of Roche Diagnostics GmbH. C.Q.-R. is a full‑time employee of Roche Diagnostics International Ltd. O.G-R. has given lectures in symposia sponsored by Roche Diagnostics, and receives support for research (to the institution) from F- Hoffmann La Roche. M.S.-C. has given lectures in symposia sponsored by Roche Diagnostics, S.L.U, Roche Farma, S.A and Amirall. He has served as a consultant and at advisory boards for Roche Diagnostics International Ltd and Grifols S.L. He was granted with a project funded by Roche Diagnostics International Ltd; payments were made to the institution (BBRC). He received in-kind support for research (to the institution) from Roche Diagnostics International Ltd, Avid Radiopharmaceuticals, Inc., Eli Lilly and Janssen Research & Development., (© 2024. The Author(s).)

In this paper, a new label-free DNA nanosensor based on a top-gated (TG) metal-ferroelectric-metal (MFM) graphene nanoribbon field-effect transistor (TG-MFM GNRFET) is proposed through a simulation approach. The DNA sensing principle is founded on the dielectric modulation concept. The computational method employed to evaluate the proposed nanobiosensor relies on the coupled solutions of a rigorous quantum simulation with the Landau-Khalatnikov equation, considering ballistic transport conditions. The investigation analyzes the effects of DNA molecules on nanodevice behavior, encompassing potential distribution, ferroelectric-induced gate voltage amplification, transfer characteristics, subthreshold swing, and current ratio. It has been observed that the feature of ferroelectric-induced gate voltage amplification using the integrated MFM structure can significantly enhance the biosensor's sensitivity to DNA molecules, whether in terms of threshold voltage shift or drain current variation. Additionally, we propose the current ratio as a sensing metric due to its ability to consider all DNA-induced modulations of electrical parameters, specifically the increase in on-state current and the decrease in off-state current and subthreshold swing. The obtained results indicate that the proposed negative-capacitance GNRFET-based DNA nanosensor could be considered an intriguing option for advanced point-of-care testing.

Heat pumps are an energy-efficient and increasingly cost-effective solution for reducing greenhouse gas emissions in the building sector. However, other clean energy technologies, such as rooftop solar, are less likely to be adopted in underserved communities, and thus policies incentivizing their adoption may funnel support to well-resourced communities. Unlike previously studied technologies, the effects of heat pumps on household energy bills may be positive or negative depending on local climate, energy costs, building features, and other factors. Here, we propose a framework for assessing heat pump inequities across the US. We find that households in communities of color and with higher percentages of renters are less likely to use heat pumps across the board. Moreover, communities of color are least likely to use heat pumps in regions where they are most likely to reduce energy bills. Public policies must address these inequities to advance beneficial electrification and energy justice., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Marfan syndrome is an inherited connective tissue disorder that affects the cardiovascular, musculoskeletal, and ocular systems. It is caused by pathogenic variants in the fibrillin-1 gene ( FBN1 ). Fibrillin is a primary component of microfibrils, which are found throughout the extracellular matrix (ECM) and provide elasticity and resilience to connective tissue. Microfibrils also play a role in signaling by sequestering growth factors and interacting with cell surface receptors. In many tissues, microfibrils are interwoven with elastin, collagens, and other elements of the ECM. However, uniquely in the ciliary zonule of the eye, microfibrils exist in cell-free bundles largely devoid of other components. This structure offers a rare opportunity to study a pure population of fibrillin microfibrils in a relatively native state. Here, we briefly review the organization of the zonule and describe recent experiments in which we measure zonular biomechanics, providing insights into microfibril dynamics that would be challenging to obtain in other contexts.

Background: In recent years, human microbiome research has flourished and has drawn attention from both healthcare professionals and general consumers as the human microbiome is now recognized as having a significant influence on human health. This has led to the emergence of companies offering microbiome testing services. Some of these services are sold directly to the consumer via companies' websites or via medical laboratory websites., Methodology: In order to provide an overview of the consumer experience proposed by these microbiome testing services, one single faecal sample was sent to six different companies (five based in Europe and one based in the USA). Two out of the six testing kits were commercialized by medical laboratories, but without any requirement for a medical prescription. The analyses and reports received were discussed with a panel of experts (21 experts from 8 countries) during an online workshop., Results: This workshop led to the identification of several limitations and challenges related to these kits, including over-promising messages from the companies, a lack of transparency in the methodology used for the analysis and a lack of reliability of the results. The experts considered the interpretations and recommendations provided in the different reports to be premature due to the lack of robust scientific evidence and the analyses associated with the reports to be of limited clinical utility. The experts also discussed the grey areas surrounding the regulatory status of these test kits, including their positioning in the European market. The experts recommended a distinction between regulatory requirements based on the intended use or purpose of the kit: on the one hand, test kits developed to satisfy consumer curiosity, with a clear mention of this objective, and no mention of any disease or risk of disease, and on the other hand, in vitro diagnostic (IVD) CE-marked test kits, which could go deeper into the analysis and interpretation of samples, as such a report would be intended for trained healthcare professionals., Conclusions: Recommendations or actions, specific to the context of use of microbiome testing kits, are listed to improve the quality and the robustness of these test kits to meet expectations of end users (consumers, patients and healthcare professionals). The need for standardization, robust scientific evidence, qualification of microbiome-based biomarkers and a clear regulatory status in Europe are the main issues that will require attention in the near future to align laboratory development with societal needs and thus foster translation into daily health practice., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Donor has consent for publication. Competing interests: JS is co-founder and CSO of MyMicroZoo. RdL is co-founder and CTO of GMT Science. The other authors declare that they have no competing interests., (© 2024. The Author(s).)

Objective: To examine the impact of coping styles in older adults with asthma on the prospective relationship between depressive symptoms and asthma outcomes, and how their perceptions of social support influenced their coping styles., Methods: Adults 60 and over with asthma were recruited and interviewed about their experiences of asthma, depression, and other psychosocial factors over three time points (Baseline, 6-month, and 12-month visits). Structural equation models examined the mediating roles of coping styles in the relationship between depressive symptoms (assessed by BDI-II) and asthma outcomes (i.e., asthma control, asthma quality of life, asthma-related distress, asthma-related hospitalizations, and oral corticosteroid use) and the mediating role of perceived social support in the relationship between depressive symptoms and coping style., Results: 455 participants were included in this study. Overall, 33.9% of the study population self-identified as Black and 32.8% as Hispanic. Depressive symptoms at baseline predicted less spiritual coping at 6 months (β =  - 0.15, p = 0.03), more negative coping at 6 months (β = 0.44, p < .0001), and worse asthma outcomes at 12 months (β = 0.31, p < .0001). None of the coping styles significantly mediated the relationship between depressive symptoms and asthma outcomes. Perceived social support mediated the relationship between depressive symptoms and positive coping, such that more depressive symptoms predicted less perceived social support, which in turn resulted in less positive coping engagement (β =  - 0.06, p = 0.03)., Conclusions: This study demonstrates that in older adults with asthma depressive symptoms impact perceived social support, coping strategy selection (including spiritual coping), and subsequent asthma outcomes., Competing Interests: Declarations. Conflict of interest: No conflict of interests among the authors. Ethics approval: The study was approved by the Icahn School of Medicine at Mount Sinai Institutional Review Board. Consent to participate: Informed consent was obtained from all individual participants included in the study. Human and animal rights and Informed Consent: All procedures followed were in accordance with ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The ADA testing strategy for protein therapeutics was established almost two decades ago when assay methodologies were rudimentary, and serious immunogenicity-related safety issues had recently been observed with some biotherapeutics. The current testing paradigm employs multiple tiers and stringent cut points to minimize false negatives, reflecting a conservative stance towards ADA analysis. The development of highly sensitive ADA assay platforms and technologies such as humanized or fully human monoclonal antibody (mAb) drugs has put the traditional, resource-intensive 3-tiered testing approach under scrutiny. ADA data from clinical studies for three different mAb programs were re-assessed to explore the feasibility of a simplified 1-tiered ADA testing strategy with a 1% false positive cut point versus the traditional 3-tiered approach. The analysis demonstrated moderate to strong correlations between screening results (signal-to-noise, S/N) and those of confirmation and titer results, with the vast majority of samples (~ 97%) across all studies having the same ADA positive/negative classification with either testing approach. Furthermore, at the subject level, over 92% had the same ADA category (pre-existing, treatment-emergent, treatment-boosted) under both testing approaches. The re-categorized subjects had low titer ADA responses with no observed clinical implications on pharmacokinetics, efficacy, or safety. Finally, the treatment-emergent ADA incidences were comparable between the 1-tiered and 3-tiered approaches. The results demonstrate that the 1-tiered testing strategy is suitable for ADA assessment in these programs and is likely more widely applicable. Additionally, the 1-tiered approach could expedite data delivery and reduce resource needs in clinical development without compromising data quality or clinical interpretation., Competing Interests: Declarations. Conflict of Interest: All authors are employees of Regeneron Pharmaceuticals, Inc., and may hold stock and/or stock options in the company. Disclosure: The views expressed in this article are those of the authors and do not reflect the official policy of Regeneron Pharmaceuticals., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background/Objectives : Exsanguination is a leading cause of preventable death in military and civilian settings due to extensive blood loss and hemorrhagic shock, which trigger systemic effects such as impaired tissue perfusion, hypoxia, inflammation, and multi-organ dysfunction. Standard resuscitation restores blood volume but fails to address critical aspects of hemorrhagic shock, including inflammation, coagulopathy, and reperfusion injury. To address these limitations, novel phospholipid nanoparticle (PNP)-based resuscitative fluids, VBI-S and VBI-1, were developed to modulate nitric oxide (NO) levels, improving hemodynamic stability, tissue oxygenation, and reducing inflammatory injury. This study assessed the potential of novel phospholipid nanoparticle fluids, VBI-S and VBI-1, as resuscitative agents for severe hemorrhagic shock by evaluating their ability to regulate nitric oxide, restore blood pressure, and mitigate ischemia-reperfusion injury. Methods: This study involved two phases with Sprague Dawley rats (n = 6 per group). Phase one, lasting 4 h, included four groups: blood, Ringer's lactate, VBI-S, and VBI-1. Phase two, lasting 12 h, comprised sham, blood, and VBI-1 groups. Under anesthesia, one femoral artery was catheterized for blood pressure monitoring, and blood withdrawal from the other induced apnea. Reanimation was performed using an intra-arterial infusion of shed blood, Ringer's lactate, VBI-S, or VBI-1. Tissue samples were analyzed histologically and for oxidative DNA damage via immunofluorescence. Chemiluminescence and rheology assessed nitric oxide interactions and viscosity. Data were analyzed using ANOVA. Results : VBI-1 and shed blood increased mean arterial pressure (MAP) from <10 mmHg to survivable levels sustained for 12 h, with VBI-1 showing significantly higher MAP at 3-4 h. Rats treated with Ringer's lactate died within 30 min. Histology revealed reduced organ damage in VBI-1-treated rats compared to shed blood. Immunohistochemistry indicated significantly less oxidative DNA damage ( p < 0.001) in VBI-1-treated rats. VBI-1 exhibited superior viscosity and nitric oxide binding. Conclusions: VBI-1 demonstrates strong potential as a resuscitative fluid, offering blood pressure restoration, reduced oxidative damage, and enhanced tissue perfusion, with significant implications for use in resource-limited and pre-hospital settings.