Centella asiatica (CICA)

Platinum nanoparticles (PtNP) have received considerable attention in the nanomedicine field due to their magnetic, catalytic, and optical properties. However, the potential toxicity of PtNP has not been properly evaluated yet, and current information on the possible risks related to their use is still limited. On this basis, the main objective of this systematic review was to gather available data on PtNP biological behaviour and potential harmful effects, as well as to highlight the gaps of knowledge that need to be filled in to progress in their use in clinical practice. A total of 441 studies were obtained and reviewed from the initial search; 108 fulfilled the selection criteria and were included in the revision. Mainly in vitro but also in vivo studies were reported using a variety of biological systems and animal models, with no data from human epidemiological studies published so far. All these studies were extensively evaluated to provide useful information on the PtNP biocompatibility and their potential to be employed for medical purposes. In particular, information on the physicochemical features of the PtNP influencing their biological behaviour, methods employed for toxicity evaluation, biological systems used, and outcomes addressed were analysed and discussed. In general, the results obtained showed a good biocompatibility of these NP, although some of them detected significant toxicity highly dependent of size, concentration/dose, coating, or exposed biological system. Furthermore, anticancer or protective effects were also described for PtNP in several revised studies. These findings encourage to continue exploring the benefits of PtNP for clinical practice.

BACKGROUND AND OBJECTIVES: Delayed rupture following flow diverter (FD) placement in intradural internal carotid artery aneurysms (ICA-Ans) is a well-documented life-threatening complication. Delayed rupture of extradural ICA aneurysms (EICA-Ans) after FD placement is rare, and no comprehensive analysis has been conducted. This study systematically reviewed cases of delayed rupture of EICA-Ans after FD placement and investigated the anatomical features associated with this complication. METHODS: We performed a systematic review of the literature and identified 18 cases of delayed rupture after FD placement of EICA-Ans. These were analyzed alongside 2 cases from our institution. As a comparison group, we reviewed 24 patients treated with FD for unruptured EICA-Ans without delayed rupture at our institution. Anatomical features, including the cavernous internal carotid artery (C-ICA) angulation and aneurysm neck location relative to the horizontal segment of the C-ICA, were evaluated. RESULTS: Among patients with delayed rupture, 15 of 17 aneurysms exhibited severe C-ICA angulation (<90°), and 16 of 17 aneurysms had proximally located necks in the horizontal segment. These features were significantly more frequent in the delayed rupture group than in the nondelayed rupture group (15/17 vs. 5/24; P < 0.001). CONCLUSIONS: Severe C-ICA angulation and proximal aneurysm neck location may increase mechanical stress after FD placement, potentially contributing to a delayed rupture. The identification of high-risk anatomical features can optimize patient selection and procedural strategies.

Osteoarthritis (OA) is a degenerative joint disease marked by inflammation, cartilage degradation, and pain, leading to a significant decline in quality of life. Recent advancements in extracellular vesicle (EV) research have introduced new therapeutic possibilities, with small extracellular vesicles (sEV) emerging as a promising strategy for OA treatment. sEV, particularly those derived from mesenchymal stem cells (MSCs), synoviocytes, chondrocytes, and induced pluripotent stem cells (iPSCs), demonstrate substantial anti-inflammatory and regenerative properties. These nanosized vesicles facilitate intercellular communication, delivering bioactive molecules that can modulate the joint microenvironment, promote chondrogenesis, and alleviate pain. Preclinical and early clinical studies indicate that sEV-based therapies may slow disease progression and enhance cartilage repair in OA patients. Despite the promising potential, challenges remain, including standardizing isolation techniques, understanding underlying mechanisms, and navigating regulatory pathways. This systematic review analyzes relevant publications published between 2019 and 2025, highlighting the therapeutic and biomarker potential of sEV in OA. Although there is substantial ongoing research into sEV and biomarkers, the fundamental understanding of OA pathogenesis remains largely unchanged, with most studies continuing to focus on established mechanisms of cartilage degradation, inflammation, and subchondral bone changes. The findings suggest that while therapeutic research into sEV is progressing, advancements in unraveling new pathophysiological mechanisms of OA are more limited. Further research is essential to optimize therapeutic protocols and establish clinical efficacy, marking sEV-based therapies as a promising but evolving approach for OA treatment.

BACKGROUND: Articular cartilage injuries can lead to pain, stiffness, and reduced mobility, and may eventually progress to osteoarthritis (OA). Despite substantial research efforts, effective therapies capable of regenerating cartilage are still lacking. Mesenchymal stromal cells (MSCs) are known for their differentiation and immunomodulatory capabilities, yet challenges such as limited survival post-injection and inconsistent therapeutic outcomes hinder their clinical application. Recent evidence suggests that the beneficial effects of MSCs are largely mediated by their secreted small extracellular vesicles (sEVs), which have been shown to promote tissue repair and reduce inflammation. MSC-derived sEVs have shown promise in mitigating cartilage degradation and chondrocyte apoptosis, positioning them as a promising alternative to MSC-based therapies for OA treatment. This review explores the potential and limitations of MSC-derived sEVs in cartilage regeneration. MAIN TEXT: This systematic review was conducted following PRISMA guidelines, with a comprehensive search of the Web of Science and Scopus databases for studies published between 2019 and 2024. A total of 223 records were identified, of which 132 articles were assessed for eligibility based on general selection criteria. After full-text screening, 60 articles were initially selected, comprising 58 in vitro studies and 40 in vivo studies. Following further exclusion based on specific criteria, 33 in vitro and 28 in vivo studies from a total of 47 scientific papers were included in the final qualitative synthesis. Most studies indicate that MSC-derived sEVs enhance chondrocyte proliferation, improve cartilage extracellular matrix composition, and reduce matrix-degrading enzymes and inflammation, thereby delaying OA progression. CONCLUSION: A growing body of evidence supports the use of MSC-derived sEVs as a therapeutic tool for preventing OA progression, with most studies reporting beneficial effects on cartilage structure and function. However, challenges remain in optimizing and standardizing sEVs isolation, dosage, and delivery methods for clinical application. Further research is necessary to elucidate

Stingless bees (tribe Meliponini), comprising over 600 known species within the largest group of eusocial bees, play a critical role in ecosystem functioning through their pollination services. They contribute to the reproduction of numerous plant species, including many economically important crops such as cacao, coffee, and various fruits. Beyond their ecological significance, stingless bees hold cultural and economic importance for many native and rural communities, where they are managed for their honey, pollen, and propolis for nutritional and health purposes. The overwhelming majority of studies on pesticide toxicity and risk assessment on bees are conducted on the model species Apis mellifera in the United States and Europe, where stingless bees are absent. In May 2023, the European Food Safety Authority (EFSA) published its revised guidance document on the risk assessment of plant protection products (PPPs) for bees, including, beyond honey bees, other bee species from Bombus and Osmia genera. Despite the Meliponini widespread distribution in tropical and subtropical regions, the impact of pesticides on stingless bees remains largely unexplored. Here, we present a systematic review of stingless bee toxicological studies which highlights a substantial knowledge gap. Up to October of 2024, only 144 research articles on the effects of pesticides on Meliponini had been identified, 80 % of those were conducted in a single country (Brazil). The number of bee species and PPPs tested is extremely low, with just five species accounting for almost 50 % of the collected data and only 79 PPPs tested, among which biopesticides were the most common. Concerning the experimental methodologies, there is a significant lack of studies focusing on chronic exposure and field assays, as well as a scarcity of studies focusing on sublethal effects. Furthermore, we pinpoint to areas where research is needed for the development of risk assessment guidelines to protect these vital pollinators.

OBJECTIVE: To report evidence on microbiota and its relationship with inflammaging, the innate immune system and osteoarthritis (OA) in human patients. DESIGN: A systematic review was performed in accordance with PRISMA and following the PICO model. Web of Science, Scopus, Cochrane Library for clinical trials and PubMed were searched. The analysis was focused on human OA patients, and the outcome was mainly microbiota identification, improvement or deterioration of OA pain, stiffness or inflammation. RESULTS: After screening, 24 studies fulfilled the inclusion criteria. There is not a standardised procedure yet, as microbiota analysis in OA is relatively new. The 16S rRNA gene is the most used in bacterial phylogeny and taxonomy studies as it is highly conserved. Selected articles hypothesise about the correlation between the altered composition of the gut microbiota and OA severity, which seems to affect the immune composition by disrupting gut permeability and releasing pro-inflammatory factors. Five preliminary clinical trials used pro-prebiotics to treat OA patients, and although their results are not conclusive and the methodology needs to be improved, it might indicate a favourable approach for further studies in the prevention of OA. CONCLUSIONS: Several hypotheses have been made on the associations between microbiota changes and inflammation. They mainly advocate that those changes in the gastrointestinal tract affect gut permeability, which alters the immune system, leading to OA progression. Research advances, along with the continual growth and improvement of technology, mark this 'microbiota-inflammaging-OA' axis as a promising line of investigation.

BACKGROUND: The effective treatment for patients with acute ischemic stroke (AIS) with cervical internal carotid pseudo-occlusion (cICA-PO) requires comprehensive research on the safety and outcomes of endovascular thrombectomy (EVT). However, there are limited data available, highlighting the need for further research to ensure better treatment strategies and improve the quality of care for these patients. PURPOSE: This study aims to assess the management and outcomes in this population group compared with patients with true carotid occlusion. DATA SOURCES: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive systematic review was conducted by using PubMed, Embase, Web of Science, and Scopus from database inception to November 2023. STUDY SELECTION: The size of the included studies ranged from 16 patients to 146 patients. Through the 4 full-text articles, a total of 259 patients were collected. We compared outcomes between patients with cICA-PO compared with patients with true carotid occlusions undergoing EVT due to AIS. We excluded studies with patients with carotid pseudo-occlusion without stroke, review articles, duplicate studies, overlapped data that included the same patients presented in another included study, case reports, case series with fewer than 5 patients, and meeting abstracts that did not contain the outcomes of interest. We did not pose any limitations regarding sample size or patient characteristics. DATA ANALYSIS: We utilized the R statistical software (V.4.3.1; R package meta) to conduct the analysis of all the data obtained. We calculated the OR for binary variables, and the corresponding 95% CI. To synthesize the data, random-effect models, as well as forest plots were generated to visually represent the synthesis of the data. Additionally, we assessed heterogeneity by using Cochran Q and I 2 tests. A P value < .05 for the Q statistic or I 2 more than 50% suggests notable heterogeneity. Based on a small number of studies (<10), the assessment of publication bias could not be reliably performed. DATA SYNTHESIS: This meta-analysis encompassed data from 4 studies. Patients with cICA-PO

OBJECTIVE: The cortical iliac crest autograft (CICA)/structural allograft (SA) has still been recognized as the gold standard for the ACDF technique for its high degree of histocompatibility and osteoinduction ability though the flourishing and evolving cage development. However, there was no further indication for using CICA/SA in ACDF based on basic information of inpatients. Our operative experience implied that applying CICA/SA has an advantage on faster fusion but not the long-term fusion rate. Therefore, our study aimed to compare the fusion rates between CICA and cage, between SA and cage, and between CICA/CA and cage. METHODS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a comprehensive literature search of electronic databases including PubMed, Embase, Cochrane Library and Web of Science was conducted to identify these clinical trials that investigated the postoperative 3, 6, 12 and 24 months fusion rates of CICA/structural SA versus cage. Assessment of risk of bias, data extraction and statistical analysis were then carried out by two independent authors with the resolve-by-consensus method. The primary outcome was fusion rate at 3, 6, 12 and 24 months postoperatively. The secondary outcomes were also meta-analyzed such as hardware complications, operative duration and hospitalization time. Our meta-analysis was registered with PROSPERO (Identifier: CRD42022345247). RESULT: A total of 3451 segments (2398 patients) derived from 34 studies were included after the screening of 3366 articles. The segmental fusion rates of CICA were higher than cages at 3 (P = 0.184, I2 = 40.9%) and 6 (P = 0.147, I2 = 38.8%) months postoperatively, but not 12 (P = 0.988, I2 = 0.0%) and 24 (P = 0.055, I2 = 65.6%) months postoperatively. And there was no significant difference in segmental fusion rates between SA and cage at none of 3 (P = 0.047, I2 = 62.2%), 6 (P = 0.179, I2 = 41.9%) and 12 (P = 0.049, I2 = 58.0%) months after operations. As for secondary outcomes, the CICA was inferior to cages in terms of hardware complications, operative time, blood loss, hospitalization time, interbody height, disk height and Odom rating. The

BACKGROUND: Parents influence their children's lifestyles through modeling and support, which modifies how children approach physical activity. As such, this systematic review aims to know the influence of parental involvement in children's active lifestyles and the influence of parenting styles on children's practice and motivation towards physical activity. METHODOLOGY: PubMed, Google Scholar, Scopus, ResearchGate, and Web of Science databases were searched from 15 July 2022 to 30 August 2022. The publication date of the included manuscripts was between November 2012 and January 2021. The methodological quality of the studies was analyzed using the Scale for Evaluating Scientific Articles in Social and Human Science. Furthermore, it was utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. RESULTS: The sample of the 10 included studies (in which different self-report measures were administered) was 1,957 children and their parents. In one study, parental involvement across limits decreased sedentary behaviours. In another, parent-child co-participation in physical activity improved participation in it. In one study, democratic parents predicted moderate-vigorous physical activity. In another, authoritarian styles were associated with sports practice. In another, permissive styles were associated with the worst physical activity practice. In one study, permissive parents were not significantly related to physical activity. In another, negligent parents were negatively associated with sports practice. In two studies, parenting styles were not associated with physical activity. In a study, the autonomy support of permissive parents and the structure of democratic parents is related to autonomous motivations. The coercive control of authoritarian parents and the lack of structure of negligent parents are related to non-self-determined motivations or amotivation. CONCLUSIONS: Parental involvement contributes to children's participation in physical activity. There is no unanimity in the results obtained in parenting styles and the practice of physical activity. Democratic and permissive styles are associated with self-determined motiv

Marine mammals, due to their long life span, key position in the food web, and large lipid deposits, often face significant health risks from accumulating contaminants. This systematic review examines published literature on pollutant-induced adverse health effects in the International Union for Conservation of Nature (IUCN) red-listed marine mammal species. Thereby, identifying gaps in literature across different extinction risk categories, spatial distribution and climatic zones of studied habitats, commonly used methodologies, researched pollutants, and mechanisms from cellular to population levels. Our findings reveal a lower availability of exposure-effect data for higher extinction risk species (critically endangered 16%, endangered 15%, vulnerable 66%), highlighting the need for more research. For many threatened species in the Southern Hemisphere pollutant-effect relationships are not established. Non-destructively sampled tissues, like blood or skin, are commonly measured for exposure assessment. The most studied pollutants are POPs (31%), metals (30%), and pesticides (17%). Research on mixture toxicity is scarce while pollution-effect studies primarily focus on molecular and cellular levels. Bridging the gap between molecular data and higher-level effects is crucial, with computational approaches offering a high potential through in vitro to in vivo extrapolation using (toxico-)kinetic modelling. This could aid in population-level risk assessment for threatened marine mammals.

Low- and middle-income countries face substantial challenges in immunizing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including high costs, limited access, and insufficient local manufacturing. To address these issues, we developed and locally manufactured the AVX/COVID-12 vaccine using a cost-effective Newcastle disease virus LaSota platform to express a stabilized SARS-CoV-2 spike protein (HexaPro-S). We evaluated the AVX/COVID-12 vaccine in a phase 2/3 parallel-group, double-blind, active-controlled, noninferiority trial with 4056 volunteers, demonstrating its safety, good tolerability, and ability to induce neutralizing antibodies against ancestral SARS-CoV-2 and the Omicron BA.2 and BA.5 variants. It also stimulated interferon-γ-producing CD8+ T cells and met the World Health Organization's noninferiority criteria compared to AZ/ChAdOx-1-S. No vaccinated participants experienced severe disease, hospitalization, or death. These findings support the use of AVX/COVID-12 as a booster to help achieve and maintain population immunity while addressing global inequities in vaccine distribution, and it has been approved for adult booster use in Mexico.

OBJECTIVES: To evaluate the effect of coconut oil on the oral bacteriome and inflammatory response in patients with periodontitis by integrating next-generation sequencing analyses of pathogenic bacterial shifts and quantification of inflammatory markers, thereby assessing its potential as a natural adjunct to standard nonsurgical periodontal therapy. MATERIALS AND METHODS: A triple-blind clinical trial was conducted with 30 participants diagnosed with periodontitis, randomized into 3 groups: (1) coconut oil, (2) chlorhexidine and (3) placebo. Saliva and gingival crevicular fluid (GCF) samples were collected before treatment, one month after treatment, and one month post-non-surgical periodontal therapy. Bacterial DNA was extracted, and the V3-V4 region of the 16 S rRNA gene was PCR-amplified and sequenced using Illumina MiSeq technologies. Inflammatory biomarkers, including Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were quantified from GCF samples. RESULTS: Coconut oil treatment significantly reduced pathogenic bacterial families such as Spirochaetaceae and Tannerellaceae while promoting beneficial bacteria such as Streptococcaceae. At the genus and species levels, coconut oil reduced pathogens such as Tannerella forsythia and Treponema denticola along with increase in beneficial bacteria such as Streptococcus. The subgingival microbial dysbiosis index improved significantly in both coconut oil and chlorhexidine groups. Furthermore, the coconut oil demonstrated a reduction in IL-6 and TNF-α levels, indicating decreased local inflammation. CONCLUSIONS: Coconut oil treatment significantly modulated the oral microbiome and reduced inflammatory markers in patients with periodontitis, suggesting its potential as a natural and effective adjunct in periodontal therapy. CLINICAL RELEVANCE: This study highlights coconut oil's potential as a natural adjunct in periodontal therapy, effectively reducing pathogenic bacteria and inflammatory markers (IL-6, TNF-α). It offers a safe alternative to chlorhexidine, promoting microbiome balance and improved periodontal health. [Image: see text] © 2025. The Author(s).

PURPOSE: This study aimed to construct and validate a nomogram that incorporated clinical data and preoperative blood markers to differentiate BPGTs from MPGTs more efficiently and at low cost. METHODS: We retrospectively analyzed patients who underwent parotidectomy and histopathological diagnosis at the First Affiliated Hospital of Guangxi Medical University from January 2013 to June 2022. Subjects were randomly divided into training and validation sets with a 7:3 ratio. In the training set, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to select the most relevant features from 19 variables and built a nomogram using logistic regression. We evaluated the model's performance using receiver-operating characteristic (ROC) curves, calibration curves, clinical decision curve analysis (DCA), and clinical impact curve analysis (CICA). RESULTS: The final sample consisted of 644 patients, of whom 108 (16.77%) had MPGTs. The nomogram included four features: current smoking status, pain/tenderness, peripheral facial paralysis, and lymphocyte-to-monocyte ratio (LMR). The optimal cut-off value for the nomogram was 0.17. The areas under the ROC curves (AUCs) of the nomogram were 0.748 (95% confidence interval [CI] = 0.689-0.807) and 0.754 (95% CI = 0.636-0.872) in the training and validation sets, respectively. The nomogram also showed good calibration, high accuracy, moderate sensitivity, and acceptable specificity in both sets. The DCA and CICA demonstrated that the nomogram had significant net benefits for a wide range of threshold probabilities (0.06-0.88 for the training set; 0.06-0.57 and 0.73-0.95 for the validation set). CONCLUSION: The nomogram based on clinical characteristics and preoperative blood markers was a reliable tool for discriminating BPGTs from MPGTs preoperatively. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: Clinically-evaluated nutraceuticals are candidates for Alzheimer's disease (AD) prevention and treatment. Phase I studies showed biological safety of the nutraceutical BrainUp-10®, while a pilot trial demonstrated efficacy for treatment. Cell studies demonstrated neuroprotection. BrainUp-10® blocks tau self-assembly. Apathy is the most common of behavioral alterations. OBJECTIVE: The aim was to explore efficacy of BrainUp-10® in mitigating cognitive and behavioral symptoms and in providing life quality, in a cohort of Chilean patients with mild to moderate AD. METHODS: The was a multicenter, randomized, double blind, placebo-controlled phase II clinical study in mild to moderate AD patients treated with BrainUp-10® daily, while controls received a placebo. Primary endpoint was Apathy (AES scale), while secondary endpoints included Mini-Mental State Examination (MMSE), Trail Making Test (TMT A and TMT B), and Neuropsychiatry Index (NPI). AD blood biomarkers were analyzed. Laboratory tests were applied to all subjects. RESULTS: 82 patients were enrolled. The MMSE score improved significantly at week 24 compared to baseline with tendency to increase, which met the pre-defined superiority criteria. NPI scores improved, the same for caregiver distress at 12th week (p = 0.0557), and the alimentary response (p = 0.0333). Apathy tests showed a statistically significant decrease in group treated with BrainUp-10®, with p = 0.0321 at week 4 and p = 0.0480 at week 12 treatment. A marked decrease in homocysteine was shown with BrainUp-10® (p = 0.0222). CONCLUSION: Data show that BrainUp-10® produces a statistically significant improvement in apathy, ameliorating neuropsychiatric distress of patients. There were no compound-related adverse events. BrainUp-10® technology may enable patients to receive the benefits for their cognitive and behavioral problems.

BACKGROUND: To evaluate if early improvements in pain and function with subcutaneous tanezumab are meaningful and sustained over 24 weeks. METHODS: Patients with moderate-to-severe osteoarthritis (hip or knee) in Europe and Japan were randomized to placebo, tanezumab 2.5 mg or tanezumab 5 mg (baseline, Week 8 and Week 16). Outcomes included: average daily index joint pain score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales, rescue medication use, WOMAC responders (within-patient ≥30% reduction in WOMAC Pain or Physical Function), Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders (within-patient) and Patient-reported Treatment Impact Assessment-Modified questionnaire. RESULTS: Patients received placebo (n = 282), tanezumab 2.5 mg (n = 283) or tanezumab 5 mg (n = 284). Changes from baseline in average daily index joint pain (within the first week) and WOMAC subscales (Week 2 through Week 24) were greater for each tanezumab group versus placebo (least squares [LS] mean, unadjusted p ≤ .05). Rescue medication use (days/week) was lower for each tanezumab group versus placebo from Week 2 through Week 12 (LS mean, unadjusted p ≤ .05) but not at Week 16 or 24. A higher proportion of each tanezumab group than placebo achieved ≥30% reduction from baseline in WOMAC Pain or Physical Function, or OMERACT-OARSI response (Week 2 through Week 24, unadjusted p ≤ .05), or were satisfied with treatment at Week 24 (unadjusted p ≤ .05). CONCLUSIONS: Subcutaneous tanezumab, compared with placebo, reduced pain within the first week, and pain and function were improved throughout 24 weeks. The proportions of responders and patients satisfied were higher with tanezumab than placebo. ClinicalTrials.gov:NCT02709486. SIGNIFICANCE: This exploratory analysis of data from a placebo-controlled, Phase 3 study of patients with moderate-to-severe osteoarthritis of the hip or knee for whom standard analgesics were not effective or could not be taken, found that onset of efficacy of subcutaneous tanezumab was within the first week, and efficacy was maintained through the 24-week treatment period. Tanezumab w

BACKGROUND: The glycocalyx layer is a key structure in the endothelium. Tourniquet-induced ischemic periods are used during orthopedic surgery, and the reactive oxygen species generated after ischemia-reperfusion may mediate the shedding of the glycocalyx. Here, we describe the effects of tourniquet-induced ischemia-reperfusion and compare the effects of sevoflurane and propofol on the release of endothelial biomarkers after ischemia-reperfusion in knee-ligament surgery. METHODS: This pilot, single-center, blinded, randomized, controlled trial included 16 healthy patients. After spinal anesthesia, hypnosis was achieved with sevoflurane or propofol according to randomization. During the perioperative period, five venous blood samples were collected for quantification of syndecan-1, heparan sulfate, and thrombomodulin from blood serum by using ELISA assays kits. Sample size calculation was performed to detect a 25% change in the mean concentration of syndecan-1 with an alpha of 0.05 and power of 80%. RESULTS: For our primary outcome, a two-way ANOVA with post-hoc Bonferroni correction analysis showed no differences in syndecan-1 concentrations between the sevoflurane and propofol groups at any time point. In the sevoflurane group, we noted an increase in syndecan-1 concentrations 90 min after tourniquet release in the sevoflurane group from 34.6 ± 24.4 ng/mL to 47.9 ± 29.8 ng/mL (Wilcoxon test, p < 0.01) that was not observed in patients randomized to the propofol group. The two-way ANOVA showed no intergroup differences in heparan sulfate and thrombomodulin levels. CONCLUSIONS: Superficial endothelial damage without alterations in the cell layer integrity was observed after tourniquet knee-ligament surgery. There was no elevation in serum endothelial biomarkers in the propofol group patients. Sevoflurane did not show the protective effect observed in in vitro and in vivo studies. TRIAL REGISTRATION: The trial was registered in www.clinicaltrials.gov (ref: NCT03772054, Registered 11 December 2018).

BACKGROUND AND PURPOSE: The optimal management of patients with tandem lesions (TL), or cervical internal carotid artery (c-ICA) steno-occlusive pathology and ipsilateral intracranial occlusion, who are undergoing endovascular thrombectomy (EVT) remains unknown. We sought to establish the feasibility of a trial designed to address this question. MATERIALS AND METHODS: The Endovascular Acute Stroke Intervention (EASI) study was a single-centre randomized trial comparing EVT to medical therapy for large-vessel occlusion stroke. Patients with TL receiving EVT were randomly allocated to acute c-ICA stenting or no stenting. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0-2 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) at 24hours and mortality at 90 days. RESULTS: Of 301 patients included in EASI between 2013 and 2018, 24 (8.0%) with TL were randomly allocated to acute stenting (n=13) or no stenting (n=11). Baseline characteristics were balanced. Eight (61.5%; 95% CI 35.5%-82.3%) and 7 (63.6%; 95% CI 35.4%-84.9%) patients, respectively, had a favorable outcome (mRS 0-2; P=1.0). One non-stented patient had a symptomatic intracerebral hemorrhage. CONCLUSIONS: This pilot trial of patients with TL undergoing EVT suggests that a sufficiently powered larger TL trial comparing acute c-ICA stenting to no stenting is feasible. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02157532.

BACKGROUND: Communities In Charge of Alcohol (CICA) takes an Asset Based Community Development (ABCD) approach to reducing alcohol harm. Through a cascade training model, supported by a designated local co-ordinator, local volunteers are trained to become accredited 'Alcohol Health Champions' to provide brief opportunistic advice at an individual level and mobilise action on alcohol availability at a community level. The CICA programme is the first time that a devolved UK region has attempted to coordinate an approach to building health champion capacity, presenting an opportunity to investigate its implementation and impact at scale. This paper describes the protocol for a stepped wedge randomised controlled trial of an Alcohol Health Champions programme in Greater Manchester which aims to strengthen the evidence base of ABCD approaches for health improvement and reducing alcohol-related harm. METHODS: A natural experiment that will examine the effect of CICA on area level alcohol-related hospital admissions, Accident and Emergency attendances, ambulance call outs, street-level crime and anti-social behaviour data. Using a stepped wedged randomised design (whereby the intervention is rolled out sequentially in a randomly assigned order), potential changes in health and criminal justice primary outcomes are analysed using mixed-effects log-rate models, differences-in-differences models and Bayesian structured time series models. An economic evaluation identifies the set-up and running costs of CICA using HM Treasury approved standardised methods and resolves cost-consequences by sector. A process evaluation explores the context, implementation and response to the intervention. Qualitative analyses utilise the Framework method to identify underlying themes. DISCUSSION: We will investigate: whether training lay people to offer brief advice and take action on licensing decisions has an impact on alcohol-related harm in local areas; the cost-consequences for health and criminal justice sectors, and; mechanisms that influence intervention outcomes. As well as providing evidence for the effectiveness of this intervention to reduce the harm from alcohol, this evaluatio

BACKGROUND: Understanding the breeding patterns of Aedes aegypti in households and the factors associated with infestation are important for implementing vector control. The baseline survey of a cluster randomised controlled trial of community mobilisation for dengue prevention in Mexico and Nicaragua collected information about the containers that are the main breeding sites, identified possible actions to reduce breeding, and examined factors associated with household infestation. This paper describes findings from the Mexican arm of the baseline survey. METHODS: In 2010 field teams conducted household surveys and entomological inspections in 11,995 households from 90 representative communities in the three coastal regions of Guerrero State, Mexico. We characterized Ae. aegypti breeding sites and examined the effect of two preventive measures: temephos application in water containers, and keeping the containers covered. We examined associations with household infestation, using bivariate and multivariate analysis adjusted for clustering effects. RESULTS: We conducted entomological inspections in 11,995 households. Among 45,353 water containers examined, 6.5% (2958/45,353) were positive for larvae and/or pupae. Concrete tanks (pilas) and barrels (tambos) together accounted for 74% of pupal productivity. Both covering water containers and inserting temephos were independently associated with a lower risk of presence of larvae or pupae, with the effect of covering (OR 0.22; 95% CIca 0.15-0.27) stronger than that of temephos (OR 0.66; 95% CIca 0.53-0.84). Having more than four water containers was associated with household infestation in both rural areas (OR 1.42; 95% CIca 1.17-1.72) and urban areas (1.81; 1.47-2.25), as was low education of the household head (rural: 1.27; 1.11-1.46, and urban: 1.39; 1.17-1.66). Additional factors in rural areas were: household head without paid work (1.31; 1.08-1.59); being in the Acapulco region (1.91; 1.06-3.44); and using anti-mosquito products (1.27; 1.09-1.47). In urban areas only, presence of temephos was associated with a lower risk of household infestation (0.44; 0.32-0.60). CONCLUSION: Concrete tanks and barrels account

BACKGROUND: Dengue is a serious public health issue that affects households in endemic areas in terms of health and also economically, imposing costs for prevention and treatment of cases. The Camino Verde cluster-randomised controlled trial in Mexico and Nicaragua assessed the impact of evidence-based community engagement in dengue prevention. The Mexican arm of the trial was conducted in 90 randomly selected communities in three coastal regions of Guerrero State. This study reports an analysis of a secondary outcome of the trial: household use of and expenditure on anti-mosquito products. We examined whether the education and mobilisation activities of the trial motivated people to spend less on anti-mosquito products. METHODS: We carried out a household questionnaire survey in the trial communities in 2010 (12,312 households) and 2012 (5349 households in intervention clusters, 5142 households in control clusters), including questions about socio-economic status, self-reported dengue illness, and purchase of and expenditure on insecticide anti-mosquito products in the previous month. We examined expenditures on anti-mosquito products at baseline in relation to social vulnerability and we compared use of and expenditures on these products between intervention and control clusters in 2012. RESULTS: In 2010, 44.2% of 12,312 households reported using anti-mosquito products, with a mean expenditure of USD4.61 per month among those who used them. Socially vulnerable households spent less on the products. In 2012, after the intervention, the proportion of households who purchased anti-mosquito products in the last month was significantly lower in intervention clusters (47.8%; 2503/5293) than in control clusters (53.3%; 2707/5079) (difference - 0.05, 95% CIca -0.100 to -0.010). The mean expenditure on the products, among those households who bought them, was USD6.43; 30.4% in the intervention clusters and 36.7% in the control clusters spent more than this (difference - 0.06, 95% CIca -0.12 to -0.01). These expenditures on anti-mosquito products represent 3.3% and 3.8% respectively of monthly household income for the poorest 10% of the population in 2012. CONCLUSIONS:

BACKGROUND: Periodontitis is a prevalent chronic disease commonly managed with nonsurgical therapy and adjunctive antimicrobial rinses, though their side effects can hinder long-term use. Coconut oil has emerged as a potential natural alternative due to its antimicrobial and anti-inflammatory effects. This study aimed to evaluate the clinical and patient-reported outcomes of periodontal patients treated with nonsurgical therapy with or without coconut oil as an adjunctive method. METHODS: Thirty participants with stage II-III periodontitis were randomly assigned to three groups: coconut oil, 0.12% chlorhexidine, and placebo (coconut-flavored water) mouth rinse for one month, followed by nonsurgical periodontal therapy. A blinded examiner assessed the plaque index, bleeding on probing, probing pocket depth, clinical attachment level, saliva pH, tooth color, sulfur compounds in breath, and patient-reported outcomes, including the Oral Health Impact Profile-14 before starting the use of mouth rinse (T1), one month after starting the mouth rinse (T2) and one month after nonsurgical periodontal therapy (T3). RESULTS: Compared with the placebo, both coconut oil and chlorhexidine significantly reduced the plaque index at T2 (p = 0.001; p = 0.006), bleeding on probing at T2 (p = 0.001; p = 0.001) and T3 (p = 0.006; p = 0.009), probing depth at T2 (p = 0.001; p = 0.001), clinical attachment level at T2 (p = 0.001; p = 0.015) and sulfur compounds at T2(p = 0.045; p = 0.003). Compared with chlorhexidine, coconut oil was more effective at decreasing clinical attachment loss at T2 (p = 0.006). At T2, chlorhexidine was associated with increased burning sensation (p = 0.03) and color changes (p < 0.001), whereas coconut oil reduced the degree of mouth dryness perception (p < 0.001). Coconut oil and chlorhexidine improved breath perception (p = 0.003; p = 0.030). Patients preferred the placebo over coconut oil or chlorhexidine (p = 0.006; p = 0.015). The quality of life significantly improved in the coconut oil group at T2 (p = 0.024). CONCLUSIONS: Compared with placebo, coconut oil and chlorhexidine improved periodontal parameters. However, coconut oil reduces mouth dryness an

INTRODUCTION: Frailty influences dementia risk and severity. However, its role in differentiating dementia subtypes and associations with brain structural and functional alterations remain understudied, especially in Latin America. METHODS: Multi-Partner Consortium to Expand Dementia Research in Latin America data included 3461 participants (cognitively unimpaired [CU], Alzheimer's disease [AD], and frontotemporal lobar degeneration [FTLD]) from Latin America using a frailty index constructed from 32 health-related variables. XGBoost-logistic regression models tested group discrimination, and voxel-based morphometry plus functional connectivity analyses explored neural correlates. RESULTS: Frailty distinguished CU from AD (area under the curve [AUC] = 0.85) and CU from FTLD (AUC = 0.88) but not AD from FTLD (AUC = 0.59). Higher frailty was linked to widespread gray matter loss, with temporal involvement in CU and stronger frontotemporal effects in dementia, particularly FTLD. Connectivity analyses showed fronto-temporo-posterior reductions and increased connectivity across the frailty network. DISCUSSION: Findings position frailty as a promising marker for identifying AD and FTLD relative to CU individuals, linked with brain health alterations in Latin American populations. © 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Olive mill wastewater (OMWW) is a major environmental stressor in Mediterranean regions, producing phytotoxic effluents that may threaten aquatic ecosystems. However, the ecological effects of OMWW discharges are rarely assessed, especially in filter feeders organisms such as freshwater bivalves. Given this gap, the present study evaluated the long-term effects of OMWW exposure (14 days) on four native (Unio delphinus, Unio tumidiformis, Anodonta anatina, and Potomida littoralis) and one non-native (Corbicula fluminea) freshwater bivalve species. Under controlled laboratory conditions specimens from the five species were exposed to three treatments: two OMWW concentrations (C1: 8.77 mg/L and C2: 21.31 mg/L of organic matter) and a control (CTL: 0 mg/L). At the end of the experiment, neurotoxicity (acetylcholinesterase- AChE) and oxidative stress (superoxide dismutase - SOD, Thiobarbituric acid reactive substances - TBARs) biomarkers were assessed in the gills and in the digestive gland. Results demonstrated higher sensitivity of native species-especially U. tumidiformis- showing an overall ineffectiveness of antioxidant mechanisms (SOD) to neutralize reactive oxygen species (ROS), leading to TBARs accumulation and neural inhibition (AChE). In contrast, the non-native species C. fluminea respond to the lower OMWW concentration used reducing basal activities such as SOD and AChE, which may be interpreted as a reduction in their metabolic rate, leading to minimal energy expenditure. Moreover, C. fluminea exhibited a biphasic response characterized by enzymatic downregulation at lower concentrations and enzymatic upregulation at higher levels, suggesting a higher physiological plasticity compared to native species. Overall, this study underscore the ecological importance of bivalves as sentinel species to assess OMWW pollution, supporting the objectives of the EU Water Framework Directive.

Ensuring microbial safety in drinking water remains a challenge, particularly for ageing infrastructure and complex treatment processes. Because water treatment works sit at the interface between source-water ecosystem integrity and public-health protection, failures in particle control also have broader environmental-safety implications. Here, we investigated the repeated detection of Serratia fonticola (a coliform) across multiple stages of a water treatment works (WTW). Sixty-seven isolates, obtained from raw, interstage, and final waters, were analysed via whole-genome sequencing. Phylogenomic and average nucleotide identity analyses (>99.94%) confirmed a single, near-clonal strain that is adapted to the WTW and is genetically distinct from raw-water isolates. Variant calling revealed minimal differences, suggesting the organism's repeated detection was not caused by multiple sources but rather a single persistence variant. The variant carried antimicrobial resistance genes, including a FONA-family β-lactamase and blaSFDC, together with plasmid-encoded toxin-antitoxin systems; however, none of the isolates possessed known high-level chlorine-resistance genes. Flow cytometry-based disinfection assays demonstrated that free-floating S. fonticola was rapidly inactivated by modest chlorine doses, achieving a > 3-log reduction with a Ct of around 10 mg·min L⁻¹ . However, floc-associated cells showed markedly higher resilience, requiring a Ct of approximately 100 mg·min L⁻¹ to achieve a ∼2.5-log reduction, indicating strong physicochemical protection of the organism within flocs. These findings suggest that physical shielding, rather than intrinsic chlorine tolerance, facilitates S. fonticola survival through the treatment process. The invariable presence of a specific plasmid in nearly all of the WTW isolates suggests that it may confer traits enhancing resilience to chlorine and promote survival within biofilms. Optimising filtration and minimising floc carry-over, alongside strategies to remove biofilm, may therefore be key to preventing final-water detections of this opportunistic organism.

An in-depth understanding of ecosystem services is essential for informing policy decisions and supporting the sustainable management of local resources. Subtidal marine forests, dominated by large brown seaweeds, are biodiversity-rich habitats that deliver key ecosystem services to society, including the provision of fishery resources. In this context, the present study identifies and economically values the fishery resources associated with these habitats, using Northern Portugal as the study region. To achieve this, we conducted in situ video (2 min 34 s ± 0 min 58 s) surveys along the regional coast to identify fishery resources associated with subtidal macroalgal forests and assess Marine Protected Area (MPA) effects. In parallel, analyses of official landing data (2021-2024) allowed us to estimate the economic value of marine forest-dependent resources exploited by small-scale fisheries (SSF). A total of 298 fish belonging to six families were recorded, with pouting (Trisopterus luscus) and sea bass (Dicentrarchus labrax) showing the highest abundances. The commercially valuable purple sea urchin (Paracentrotus lividus) was also identified, with significantly higher abundance inside the MPA. Landing data revealed that regional SSF captured 111-122 different fishery resources annually, generating 7.61±0.6 × 106€ yr-1. Among these, 44 species were identified as dependent on macroalgal forests. The economic value of this subset was estimated at 1.83±0.2 × 106€ per year, with the common octopus (Octopus vulgaris) alone contributing 1.00±0.2 × 106€ per year. Our results confirm that subtidal macroalgal forests in Northern Portugal not only support a characteristic assemblage of non-benthic ichthyofauna but also deliver key ecosystem services by sustaining fishery resources exploited by SSF. These findings highlight the socio-economic relevance of these foundational habitats and the need for effective conservation and management to ensure their long-term sustainability. © The Author(s) 2026. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact [email protected] for reprints and

Photobacteriosis is a major threat to marine aquaculture, and the siderophore transporter FrpA represents a promising target for effective subunit vaccine development. In this study, we evaluated Montanide GEL 02 PR and phosphatidylcholine-based liposomes as aqueous and safer alternatives to Freund's adjuvant for an FrpA-based subunit vaccine in Solea senegalensis. Fish were immunized with recombinant FrpA formulated with either adjuvant, and induction of FrpA-specific IgM antibody levels was measured. Vaccine efficacy was subsequently assessed by analysis of innate immune gene expression following early pathogen exposure and by survival analysis after infection challenge. Vaccination with rFrpA-Montanide GEL 02 PR induced the highest levels of specific IgM antibodies and conferred strong protection against photobacteriosis, achieving survival rates comparable to those reported for bacterin-based vaccines. This formulation also promoted a rapid and coordinated up-regulation of immune-related genes, including transferrin (tf), lysozyme C1 (lysC1), and complement components C1q and C7. In contrast, rFrpA encapsulated in liposomes elicited weaker immune responses and limited protection. Overall, our results demonstrate that an FrpA-based subunit vaccine formulated with Montanide GEL 02 PR represents a promising strategy for controlling photobacteriosis in aquaculture. © 2026 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.

Cancer immunotherapy has transformed the clinical management of several malignancies; however, its efficacy remains limited in tumors with low mutational burden and restricted availability of classical mutation-derived neoantigens. In this context, increasing evidence indicates that the tumor immunopeptidome extends far beyond canonical protein-coding regions, incorporating peptides derived from non-coding transcripts through non-canonical translation mechanisms. Long non-coding RNAs (lncRNAs), traditionally regarded as transcriptional or post-transcriptional regulators, have recently emerged as an unexpected source of small open reading frame-encoded peptides (lncPEPs). A subset of these peptides is processed and presented by major histocompatibility complex class I molecules, generating tumor-specific neoantigens capable of eliciting CD8+ T cell responses. Owing to the high tissue and context specificity of lncRNA expression, lncRNA-derived neoantigens offer unique advantages over mutation-based targets, including increased tumor selectivity and potential recurrence across patient subsets. In this review, we synthesize current knowledge on the biogenesis, detection, and immunogenic potential of lncRNA-derived peptides, highlighting experimental and computational strategies for their identification within the cancer immunopeptidome. We discuss the challenges associated with their validation and clinical translation, as well as their relevance for the development of vaccines and adoptive T cell-based therapies. Finally, we illustrate these concepts using epithelial ovarian cancer as a representative model of low-mutational-burden tumors, where lncRNA-derived neoantigens may help overcome current limitations of immunotherapy and enable patient stratification for personalized treatment approaches.

Invasive fungal infections, especially those caused by Candida spp., have been classified as a serious global threat. The emergence of species intrinsically resistant to current drugs, along with the increase in acquired resistance, places significant pressure on the need to develop novel and more effective antifungal agents. A limited number of studies have shown the potential of palladium organometallic complexes as promising antifungal alternatives. Although the mechanism of antifungal activity of these complexes remains unaddressed, the findings support the idea that designing palladium (II) complexes could represent the next generation of antifungals. In this work, we synthesized four cyclopalladated complexes, 1a, 1b, 2a, and 2b, from Schiff base-amine phosphanes and evaluated their antifungal potential. Specifically, we assessed their spectrum of activity against several medically relevant Candida spp., their capacity to overcome resistance to current antifungal drugs, antibiofilm properties, uptake by fungal cells, in vivo toxicity, and intracellular effects. The most promising complexes, 1b and 2b, induce strong oxidative stress and lipid peroxidation, inhibit lipolysis, and disrupt vacuole integrity. Moreover, the rational design of the complexes allowed us to infer important structure-activity relationships. Our findings highlight the potential of palladium complexes as promising scaffolds for future antifungal therapeutic strategies and open new horizons for further development.

Cyanobacteria of the Microcystis genus often form blooms in freshwater and estuarine environments, producing microcystin, a toxin harmful to animals and humans. The analysis of water samples for the detection of toxic Microcystis is usually time-consuming and not effective when the organisms are in pre-bloom concentrations, resulting in exposure of animals and humans to toxins. Thus, early detection of the presence of microcystin-producing Microcystis is crucial. In this work, we present a method based on loop-mediated isothermal amplification (LAMP) to detect the presence of Microcystis cells capable of producing microcystins. Specific primers were designed for the mcyJ gene (biosynthetic gene cluster mcy) and detection of LAMP products was visualized using different approaches, including a fluorescent dye in the reaction mix (pre-stained LAMP), the addition of a posteriori staining using SybrGreen (post-stained LAMP), colorimetric, and lateral flow reaction stripes. The limit of detection (LoD) of the LAMP assay was estimated based on DNA quantification by quantitative real-time PCR (qPCR). The pre-stained, post-stained and colorimetric assays applied to Microcystis NIES cultures achieved the same detection limit of 28 pg/μL of DNA corresponding to 1490 ± 620 toxic Microcystis cells mL-1, within 12.2 min, with 100% sensitivity. The lateral flow reached the lowest LoD, giving a positive signal at a DNA concentration of 2.8 pg/μL (equivalent to ca. 150 toxic Microcystis cells mL-1). The method was applied successfully to various natural water samples. The LAMPs can be optimized for local in-situ use, enabling rapid adaptive monitoring and management of aquatic ecosystems.

The physical and social exposome affects human aging, and brain clocks may track its effects. However, most studies neglect multidomain exposures (physical, social and political) across diverse settings globally and their associations with brain aging. In this study, we characterized the associations between 73 country-level physical and social exposomal factors and multimodal brain age in 18,701 participants from 34 countries (healthy individuals and those with Alzheimer's disease, frontotemporal lobar degeneration or mild cognitive impairment). Exposome effects were assessed using generalized additive models and meta-analytic frameworks. Aggregated exposome models explained up to 15.5-fold more variance than individual exposures (delta Akaike information criterion (ΔAIC): 2,034-3,127). Physical exposome was primarily associated with accelerated structural brain aging (limbic, subcortical and cerebellar regions), whereas social exposome was more strongly associated with functional brain aging (frontotemporal and limbic networks). Exposome burden accounted for 3.3-9.1-fold higher risk of accelerated aging, exceeding effects of clinical diagnoses. Findings were out-of-sample validated in cross-sectional and longitudinal designs, remained consistent across clinical subgroups and persisted after adjustment for demographics, age correction bias, cognition, scanner type and data quality. The exposome accelerates brain aging in health and disease, underscoring the need to address physical, social and political inequities. © 2026. The Author(s), under exclusive licence to Springer Nature America, Inc.