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Background and Aims: Diabetes mellitus is one of the more prevalent chronic diseases globally, and healthcare expenditures for diabetes care are on the rise. Intensive diabetes treatment has been associated with reducing the risk of chronic complications. However, hypoglycemia, the most common adverse effect, poses a significant risk to individuals' lives and is linked to high costs for healthcare systems., Methods: We conducted a retrospective cross-sectional study to determine direct costs by identifying emergency room visits due to hypoglycemia events using diagnostic codes during January 2017 to June 2019. Direct costs were calculated using billed data from the payer and information on outpatient treatment regimens. Differences in median costs were estimated based on length of stay and type of outpatient treatment., Results: Data from 101 patients and the same number of events were included. Women represented (62.4%) of the patients, the median age was 70 (IQR 59.5-80). Blood glucose levels at admission ranged from 12 mg/dL to 67 mg/dL. Most patients were on insulin for outpatient treatment. The median cost of care per hypoglycemia episode was US $345.35 (IQR US $202-727.8), and the cost per episode was higher in patients treated with regimens that included sulfonylureas., Conclusions: The management of patients admitted to the emergency department with a diagnosis of hypoglycemia places a significant burden on the Colombian healthcare system, primarily due to the associated hospitalization costs. Patients treated with regimens that included sulfonylureas incurred higher costs per episode. Prevention, patient education, and individualized treatment approaches could help alleviate the burden of hypoglycemia on both patients and the healthcare system.

Introduction: Asthma severe imposes important economic burden on health systems, especially with the incorporation of new drugs. Recently, tezepelumab has been approved to prevent exacerbations in patients. This study explores the economically justifiable price of tezepelumab for preventing exacerbations in patients with severe asthma., Materials and Methods: A static model was developed using the decision tree microsimulation to estimate the quality-adjusted life years of two interventions: a single intramuscular dose of tezepelumab versus not applying tezepelumab. This analysis was made during a time horizon of 50 year and from a third-payer perspective., Results: Based on thresholds of U$4828, U$ 5128, and U$19 992 per QALY evaluated in this study, we established economically justifiable drug acquisition prices of U$ 795, U$ 835, and U$ 3384 per dose of Tezepelumab. Tezepelumab not was cost-effective using a WTP of U$4828 and U$ 5128. It only was cost effective at WTP of U$19 992 per QALY., Conclusion: The economically justifiable cost for tezepelumab in Colombia is between U$795 to U$3384 per dose, depending on the WTP used to decide its implementation. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

Male frogs emit stereotypical advertisement calls to attract mates and deter conspecific rivals. The evolution of these calls is thought to be linked to anatomical constraints and the acoustic characteristics of their surroundings. The acoustic adaptation hypothesis (AAH) posits that species evolve calls that maximize propagation distance and reduce signal degradation in the environment where they are emitted. We applied phylogenetic comparative analyses to study the association of body size, vegetation density, type of aquatic ecosystem, and calling site on the evolution of acoustic traits in Cophomantini, a large radiation of Neotropical treefrogs (Hylidae). We obtained and analyzed body size, acoustic, and habitat data from a total of 112 species (58% of Cophomantini), using the most inclusive available phylogeny. We found a significant negative correlation between peak frequency, body size, and calling site, but contrary to the predictions of the AAH, we did not find support for associations among call traits and environmental characteristics. Although spectral allometry is explained by an anatomical constraint, it could also be maintained by female choice. We recommend that future studies strive to incorporate factors such as female mate preferences, eavesdropping by predators or parasites, and genetic drift., (© 2024 The Author(s). Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Cryptococcosis predominantly affects immunocompromised individuals, particularly those with advanced HIV disease, with meningitis being the most severe form and linked to high mortality. Diagnosis typically relies on rapid Cryptococcus antigen (CrAg) testing, and antigen titer quantification helps in early detection and assessing disease severity. However, conventional titer methods are often more expensive than qualitative antigen detection. This study assessed the diagnostic performance of a semi-quantitative Lateral Flow Assay (CrAgSQ LFA, IMMY™) for CrAg detection in serum and cerebrospinal fluid (CSF) collected between 2014-2022. The CrAgSQ LFA was compared to the standard CrAg LFA (IMMY™) and Clarus Cryptococcal Ag enzyme immunoassay (EIA-CrAg, IMMY™). The CrAgSQ LFA demonstrated 100% sensitivity and specificity in both serum and CSF, with perfect agreement (kappa 1.00) with the CrAg LFA. Comparing the CrAgSQ LFA with the titer measurement results obtained using CrAg LFA, in category 1+, titers ranged from 1:2-1:20; in 2+, from 1:5-1:40; in 3+, from 1:20-1:2560; and in category 4+, from 1:320-1:2560.Titer results for the CrAgSQ LFA aligned well with CrAg LFA, and operator agreement was strong, with weighted kappa values of 0.926 and 0.966. The CrAg-EIA showed a sensitivity of 84% and specificity of 100% using the manufacture cut-off (> 0.265), which improved to 96% sensitivity with an optimized cut-off value (>0.145). Overall, the CrAgSQ LFA demonstrated high accuracy and reliability, suggesting it could be a valuable tool for diagnosing cryptococcosis in the Americas., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Introduction: Limited information is available on the association between depressive symptoms and waist circumference (WC) in individuals with normal weight. This study aimed to analyze the association between depressive symptoms and WC among individuals aged 18 years or older with normal weight in the Peruvian population between 2019 and 2021., Methods: Analytical cross-sectional study. Data from the Peruvian Demographic and Health Survey (2019-2021) were analyzed. The sample consisted of 26 933 participants. The outcome variable was WC. The exposure variables included the overall Patient Health Questionnaire-9 (PHQ-9) score and severity of depressive symptoms. Generalized linear models of the Gaussian family estimated the effects with β coefficients for the associations between WC and depressive symptoms stratified by age and sex., Results: A significant inverse association was observed between depressive symptoms and WC in young (< 35 years) individuals of both sexes. In young males, a dose-response relationship emerged, with greater severity of depressive symptoms associated with progressively lower WC. Specifically, inverse associations were found for moderate (β = -1.74, 95% CI: -3.25 to -0.23), moderately severe (β = -2.81, 95% CI: -4.71 to -0.91), and severe (β = -2.75, 95% CI: -5.11 to -0.40) depressive symptoms., Conclusions: Among young individuals of both sexes with a normal weight, depressive symptoms were inversely associated with WC. These findings underscore the need for nuanced considerations of age and sex when exploring the interplay of depression and abdominal adiposity in individuals with normal weight., (© 2024 Wiley Periodicals LLC.)

Background: Interleukin-6 (IL-6) inhibitors recently emerged as a promising therapy for neuromyelitis optica spectrum disorder (NMOSD)., Objective: We performed a systematic review and meta-analysis comparing IL-6 inhibitors to placebo or traditional immunosuppressants in NMOSD., Methods: We searched PubMed, Embase, and Cochrane Central for eligible studies. Efficacy endpoints included hazard ratio (HR) for relapse, annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) change over time. Safety outcomes comprised any adverse event, serious adverse events and infections. Statistical analysis was performed using RevMan Web and R studio package meta. Heterogeneity was assessed with I² statistics., Results: Four studies involving 361 patients (228 treated with IL-6 inhibitors) were included. IL-6 inhibitors significantly reduced HR for relapse (HR 0.35; 95 % CI 0.23, 0.55); p < 0.00001; I² = 0 %) and ARR (mean difference -0.79 relapses/year; 95 % CI -1.54, -0.03; p = 0.04; I² = 96 %) compared to placebo or traditional immunosuppressants. No significant differences were observed in EDSS change over 24 weeks of follow-up (mean difference -0.18; 95 % CI -0.41, 0.05; p = 0.93; I² = 0 %), adverse events (odds ratio (OR) 1.59; 95 % CI 0.45, 5.63; p = 0.48; I² = 48 %), serious adverse events (OR 0.76; 95 % CI 0.40, 1.44; p = 0.50; I² = 0 %) and infection rates (OR 1.10; 95 % CI 0.67, 1.79; p = 0.71; I² = 0 %)., Conclusion: IL-6 inhibitors demonstrate superior efficacy in preventing relapses in NMOSD compared to placebo or traditional immunosuppressants, without a notable increase in safety risks., Competing Interests: Declaration of competing interest GN, ML, GM, FP, YS, PM, LM and VK: None. AF: Clinical researcher involved in ongoing trials funded by ROCHE, MERCK, NOVARTIS, NOVONORDISK, HYPERA, ACADIA., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Importance: Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer's Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations., Objective: To consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states., Evidence Review: PubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms "biomarker" OR "amyloid" OR "tau" OR "neurodegeneration" OR "preclinical" OR "CSF" OR "PET" OR "plasma" AND "Alzheimer's disease." The references of relevant articles were also searched., Findings: In the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease., Conclusions and Relevance: The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.

Objectives: Sarcoidosis is a disease whose prevalence varies considerably worldwide. In Colombia, the Ministry of Health has strengthened the Comprehensive System of Social Protection Information (SISPRO) to collect data on the provision of health services at the national level, thus providing a source of information available for research. This study aims to estimate the prevalence of sarcoidosis using consultation records collected between January 2018 and December 31, 2022., Study Design: Cross-sectional study., Methods: A descriptive cross-sectional study was conducted using the SISPRO database and the relevant International Classification of Diseases (ICD-10) codes for sarcoidosis (D860, D861, D862, D863, D868, D869, G532, M633)., Results: During the mentioned period, a total of 6828 patients were identified, of which 66.9 % were women (4571 patients). The prevalence of sarcoidosis was estimated at 12.8 cases per 100,000 inhabitants, being higher in the age group of 60-69 years., Conclusions: The information obtained from this study highlights the importance of continuing to monitor and evaluate the burden of sarcoidosis in the country, which can contribute to a better understanding of the disease's epidemiology and, in turn, to the planning of early diagnosis and timely treatment strategies., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dengue virus, transmitted mainly by Aedes aegypti mosquitoes, is a significant public health challenge in tropical and subtropical countries, with an incidence that is growing at an alarming rate. The release of Wolbachia-carrying mosquitoes has been suggested as a strategy to reduce the incidence of multiple arboviruses. In Medellín, Colombia, large-scale releases of Wolbachia-infected Ae. aegypti mosquitoes were performed between 2017 and 2022 by the World Mosquito Program to facilitate population replacement. In this study, we evaluated the prevalence and distribution of Wolbachia-infected Ae. aegypti two years after completion of these releases. We conducted the sampling across 19 communes in Medellín, using 416 ovitraps to collect Ae. aegypti eggs from epidemiological weeks 26 to 41 in 2023. Upon hatching the collected eggs, we identified and pooled adult female Ae. aegypti for DNA extraction. Subsequently, we conducted PCR assays for the detection of Wolbachia infection in these mosquitoes. We used maximum likelihood estimation (MLE) and Bayesian methods to estimate the prevalence of Wolbachia infection, while using QGIS to analyze spatial distribution of infection in the region. A total of 774 female Ae. aegypti mosquitoes from 182 pools were evaluated. We detected Wolbachia in 33.5 % of pools, with an estimated individual minimum infection rate of 9.5 % and a maximum of 33.2 %. The prevalence varied significantly across communes, with the highest rates observed in the northeastern and southwestern areas. Spatial analysis revealed a highly heterogeneous island-like distribution of Wolbachia across Medellín with a few hotspots. The observed Wolbachia prevalence in this work was lower than previously reported. We suspect a decline in the prevalence of Wolbachia-infected Ae. aegypti mosquitoes in Medellín following the completion of their release., Competing Interests: Declaration of competing interest The authors 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

A major challenge in defining the vector status of phlebotomine sand flies is selecting the appropriate criteria. Vectors can be graded by importance, with successful transmission as the highest grade. Potential vectors are often identified based on high frequency in transmission foci, anthropophily, and more recently by identification of DNA in field samples. However, a species' ability to transmit a pathogen depends not only on its intrinsic biology of sand fly-Leishmania interactions but also on ecological parameters, which are rarely evaluated. This study aimed to analyze the literature data describing characteristics of Colombian sand flies related to their role as vectors of Leishmaniinae parasites. Based on information contained in scientific publications using combinations of five criteria, sand fly species were graded into five levels, and 26 species were considered as potential or proven leishmaniasis vectors in Colombia. Levels one to four refer to potential or suspected status, while level five denotes proven vectors. Studying vectors in a regional context is crucial because species' behaviors vary with environmental and ecological conditions, meaning a species may be a key vector in one area but not in another. A better understanding of vector-parasite interactions will aid in developing innovative control strategies and formulating significant epidemiological perspectives., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Asthma imposes a crucial economic burden on health systems, especially with the incorporation of new drugs. Recently, mepolizumab has been approved to prevent exacerbations in patients with eosinophilic asthma. This study explores the economically justifiable price of mepolizumab for preventing exacerbations in children with severe asthma., Materials and Methods: A model was developed using the microsimulation to estimate the quality-adjusted costs and life years of two interventions: mepolizumab versus not applying standard treatment without mepolizumab. This analysis was made during a time horizon of 50 years and from a third-payer perspective., Results: Mepolizumab was cost-effective using a WTP of U$ 19,992 per QALY, but not at a WTP of U$ 4828, U$ 5128 per QALY. The economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of U$ 4828, and U$ 5128 respectively. At the current price of Mepolizumab, U$ 780 per dose, only using a WTP higher than U$ 10,300 per QALY mepolizumab will be the best alternative to no mepolizumab., Conclusion: Our study shows that the economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of 4828 and 5180 respectively. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country., (© 2024 Wiley Periodicals LLC.)

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the elbow and upper extremity, including the tendons (lateral epicondylitis, medial epicondylitis, biceps tendonitis, triceps tendonitis), articular cartilage (osteoarthritis, osteochondral lesions), and bone (fractures, nonunions, avascular necrosis, osteonecrosis). Promising and established treatment modalities include hyaluronic acid; botulinum toxin; corticosteroids; leukocyte-rich and leukocyte-poor platelet-rich plasma; autologous blood; bone marrow aspirate comprising mesenchymal stromal cells (alternatively termed medicinal signaling cells and frequently mesenchymal stem cells [MSCs]) and bone marrow aspirate concentrate; MSCs harvested from adipose and skin (dermis) sources; vascularized bone grafts; bone morphogenic protein scaffold made from osteoinductive and conductive β-tricalcium phosphate and poly-ε-caprolactone with hydrogels, human MSCs, and matrix metalloproteinases; and collagen sponge. Autologous blood preparations such as autologous blood injections and platelet-rich plasma show positive outcomes for nonresponsive tendinopathy. In addition, cellular therapies such as tissue-derived tenocyte-like cells and MSCs show a promising ability to regulate degenerative processes by modulating tissue response to inflammation and preventing continuous degradation and support tissue restoration. LEVEL OF EVIDENCE: Level V, expert opinion., Competing Interests: Disclosures All authors (T.L., F.T., Z.S., P.P.R., and S.C-R.) 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 © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Gastroparesis is a delay in gastric emptying without mechanical obstruction, lacking a clear pathophysiological mechanism, but with multiple histological abnormalities including loss of interstitial cells of Cajal, which may alter slow waves. We can assess slow waves with electrogastrography., Objectives: To determine the prevalence and range of abnormalities in gastric slow waves in adults with gastroparesis using electrogastrography., Methods: We systematically searched Medline, Embase, LILACS, Web of Science, and Cochrane Register of Controlled Trials. We included studies with patients older than 18 years with gastroparesis, assessed using electrogastrography. We evaluated the percentage of duration of the recording in which the dominant power was in normogastria, tachygastria, and bradygastria; dominant frequency; power ratio; change in post-stimulus dominant power; and dominant frequency instability coefficient. Methodological quality was assessed using the Joanna Briggs Institute tool. Data were synthesized using narrative summary and meta-analysis., Results: A total of 3730 articles were reviewed, including 31 articles with 1545 patients and 340 controls. Compared to controls, gastroparetics patients had less normogastria (fasting: 50.3% versus 65.8%) (post-stimulus: 54.3% versus 66.5%), more bradygastria (fasting: 37.7% versus 13%) (post-stimulus: 31.9% versus 16.3%), and more tachygastria (fasting: 16.1% versus 4.6%) (post-stimulus: 18.3% versus 5.2%). Gastroparetics had less change in post-stimulus dominant power (1.45 dB versus 5.03 dB) and less power ratio (1.4 versus 5.26)., Conclusions: Gastroparetic patients present abnormalities in the frequency and changes in the post-stimulus power of slow waves, possibly secondary to a reduced number of interstitial cells of Cajal, as described in these patients., Competing Interests: Declarations. Conflict of interest: The authors have not disclosed any competing interests., (© 2024. The Author(s).)

Acute undifferentiated febrile illness (AUFI) is the main cause of medical attention in the tropics worldwide. Malaria, arboviral diseases, and leptospirosis are the most important etiologies. These are highly endemic in the Urabá antioqueño, Colombia, being the main causes of fever in several municipalities in this region. However, up-to-date data regarding the infecting species and serotypes are lacking. Thus, we characterized the etiology of AUFI, focusing on malaria, arboviruses, and leptospirosis in this region and the circulating infecting species. An active surveillance was conducted between January and April 2022, and July and October 2023 in two local hospitals in the Urabá antioqueño. Febrile patients were enrolled voluntarily. Malaria, arboviral diseases, and leptospirosis were screened through direct, serological, molecular, and rapid diagnostic methods. Amplicons obtained for dengue virus (DENV) and Leptospira spp. were analyzed through phylogenetic analysis. A total of 184 febrile patients were enrolled. A confirmed etiology was detected in 43.4% of patients from Apartadó and 61.2% from Turbo. Malaria was the most frequent cause in both municipalities, which was caused mainly by Plasmodium falciparum in Apartadó and Plasmodium vivax in Turbo. Dengue virus serotype 1 genotype V, DENV genotype Asian-American, and DENV genotype Cosmopolitan were identified, as well as pathogenic Leptospira species closely related to Leptospira santarosai and Leptospira noguchii. The present study confirms the importance of malaria, dengue fever, and leptospirosis in the Urabá antioqueño. Plasmodium falciparum and P. vivax were identified, as well as two DENV serotypes and three DENV genotypes and two different Leptospira species.

Competing Interests: 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.

Disease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating mutation carriers from non-carrier controls 10-20 years before the estimated onset of clinical symptoms, depending on the statistical model used. However, after symptom onset the rate of change in CSF NfL continued to increase steadily, whereas the rate of change in plasma NfL leveled off. Both plasma and CSF NfL changes were associated with grey-matter atrophy, but not with Aβ-PET changes, supporting a temporal decoupling of Aβ deposition and neurodegeneration. These observations support NfL in both CSF and blood as an early marker of neurodegeneration but suggest that NfL measured in the CSF may be better suited for monitoring clinical trial outcomes in symptomatic AD patients., Competing Interests: Competing interests R.J.B. receives research funding from the US NIH, Biogen, AbbVie, Bristol Myers Squibb, Novartis, the US National Intelligence Authority, US National Institute of Neurological Disorders and Stroke, Centene, the Rainwater Foundation, the BrightFocus Foundation, the Association for Frontotemporal Degeneration Biomarkers Initiative, Coins for Alzheimer’s Research Trust Fund, the Good Ventures Foundation, Hoffman–La Roche, CogState, Signant, the Cure Alzheimer’s Research Trust Fund, Eisai, and C2N Diagnostics; receives royalties or licenses from C2N Diagnostics payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Korean Dementia Association, the American Neurological Association, Fondazione Prada, Weill Cornell Medical College, Harvard University, Beeson, and Adler Symposium. G.S.D. receives research funding from the US NIH, the Alzheimer’s Association, and the Chan–Zuckerberg Initiative; consulting fees from Parabon Nanolabs and Arialysis Therapeutics; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from PeerView Media, Continuing Education, Eli Lilly, DynaMed, and SixSense Concierge. E.M. receives research funding from the US National Intelligence Authority, Eisai, Eli Lilly, Roche, and the Gerald and Henrietta Rauenhorst Foundation; consulting fees from AstraZeneca, Sanofi, and Merck; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Alzheimer Association, Projects in Knowledge, and Neurology Live. H.Z. has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, 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, Novo Nordisk, 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). J.L. is a consultant for and receives grants, contracts, and royalties from Eisai, Eli Lilly, the German Center of Neurodegenerative Diseases, the German Ministry for Research and Education, the Anton and Petra Ehrmann Foundation, the Luneburg Foundation, Innovationsfonds, the Michael J Fox Foundation, CurePSP, the Jerome LeJeune Foundation, the Alzheimer Forschungs Initiative, Deutsche Stiftung Down Syndrom, Else Kroner Fresenius Stiftung, and MODAG. JLlG receives research funding from the NIH-NIA, the Alzheimer’s Association, the Michael J. Fox Foundation, the Foundation for Barnes-Jewish Hospital and the McDonnell Academy. M.J. receives payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Eisai. All other authors declare no competing interests., (© 2024. The Author(s).)

Large-scale afforestation programmes are generally presented as effective ways of increasing the terrestrial carbon sink while preserving water availability and biodiversity. Yet, a meta-analysis of both numerical and observational studies suggests that further research is needed to support this view. The use of inappropriate concepts (e.g., the biotic pump theory), the poor simulation of key processes (e.g., tree mortality, water use efficiency), and the limited model ability to capture recent observed trends (e.g., increasing water vapour deficit, terrestrial carbon uptake) should all draw our attention to the limitations of available theories and Earth System Models. Observations, either based on remote sensing or on early afforestation initiatives, also suggest potential trade-offs between terrestrial carbon uptake and water availability. There is thus a need to better monitor and physically understand the observed fluctuations of the terrestrial water and carbon cycles to promote suitable nature-based mitigation pathways depending on pre-existing vegetation, scale, as well as baseline and future climates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Herpes simplex virus (HSV) types 1 and 2 produce the most common sexually transmitted infection in women, with a higher incidence reported in developing countries. When the first infection occurs during the perinatal period, it can spread, resulting in high morbidity and mortality of the mother and child, in addition to mainly neurological sequelae in the newborn. Despite having reliable laboratory tests, the diagnosis of herpes simplex virus infection in this population is complex since the clinical presentation ranges from asymptomatic or with non-specific symptoms without lesions on the skin or mucous membranes. For this reason, a high clinical suspicion is necessary. Here, we present the case of a mother with disseminated herpes simplex virus type 2 infection with viral hepatitis and fetal death, highlighting the importance of suspecting the diagnosis in febrile women with systemic compromise during the perinatal period, even in the absence of rash.

Introduction. Aedes aegypti is an important vector of arboviral diseases like dengue among others. Traditional control strategies, such as the use of insecticides, have lost effectiveness due to the emergence of resistance in mosquito populations. Biological control and fungi applied for biocontrol are presented as viable and ecological alternatives. Objective. To evaluate in vitro pathogenicity of Trichoderma sp. isolates obtained from Urabá (Antioquia) on larvae of Ae. aegypti, and to determine the mean lethal concentration and mean lethal time of the most pathogenic isolate. Materials and methods. Using the sentinel larvae method of Ae. aegypti, fungi were isolated from water bodies in the Urabá region (Antioquia). The isolates were characterized morphologically and molecularly to determine their taxonomic identity. Pathogenicity tests were performed in vitro on Ae. aegypti larvae in the L2/L3 stages. Subsequently, a strain was selected to establish its mean lethal concentration and mean lethal time. Results. Trichoderma sp. strain AP-91 caused high mortality in larval populations of Ae. aegypti. We estimated a mean lethal concentration of 1.8 × 107 conidia/ml and a mean lethal time of 20.67 hours. Conclusion. The strain AP-91 showed potential for its use as biological control of Ae. aegypti, making it a suitable candidate for scale-up cultures applied to integrated vector management. This research suggests exploring compounds and enzymes produced by the AP-91 strain to understand better its pathogenicity.

Introduction: Rabies virus infection can cause fatal brain disease in mammals. Any species is susceptible to infection. Any effort aimed at recognizing infected animals and performing first actions in the event of transmission is mandatory., Objective: To determine knowledge, attitudes, and practice profiles regarding rabies, or hydrophobia, in a municipality of Colombia, using a multiple correspondence analysis., Materials and Methods: A descriptive observational study involving 71 pet owners was carried out in the municipality of Ibagué (Tolima). A questionnaire-based survey collected data on rabies knowledge, attitudes, practices, and demographic information. The survey was conducted between October and November 2021, and the data analysis involved descriptive statistics and multiple correspondence analysis., Results: The study revealed a commendable level of rabies awareness among the urban residents in the study municipality. However, there are causes of concern as they allow stray animals to enter their homes and are not aware of the importance of notifying dead animals. The respondents demonstrated a humane approach to bite management and emphasized the importance of wound cleaning. Additionally, they expressed a strong desire for more information to enhance their knowledge and awareness of the disease., Conclusion: The findings of this study provide valuable insights for improving rabies prevention efforts and promoting public health. Health education, evidence-based strategies, and community participation are essential for successful disease control and educational gaps addressing related to sociocultural factors.

Background: One of the greatest challenges to conducting multicenter research studies in low and middle-income countries (LMICs) is the heterogeneity in regulatory processes across sites. Previous studies have reported variations in requirements with a lack of standardization in the Institutional Review Board (IRB) processes between centers, imposing barriers for approval, participation, and development of multicenter research., Objectives: To describe the regulatory process, variability and challenges faced by pediatric researchers in LMICs during the IRB process of an international multicenter observational point prevalence study (Global PARITY)., Design: A 16-question multiple-choice online survey was sent to site principal investigators (PIs) at PARITY study participating centers to explore characteristics of the IRB process, costs, and barriers to research approval. A shorter survey was employed for sites that expressed interest in participating in Global PARITY and started the approval process, but ultimately did not participate in data collection (non-participating sites) to assess IRB characteristics., Results: Of the 91 sites that sought IRB approval, 46 were successful in obtaining approval and finishing the data collection process. The survey was completed by 46 (100%) participating centers and 21 (47%) non-participating centers. There was a significant difference between participating and non-participating sites in IRB approval of a waiver consent and in the requirement for a legal review of the protocol. The greatest challenge to research identified by non-participating sites was a lack of research time and the lack of institutional support., Conclusions: Global collaborative research is crucial to increase our understanding of pediatric critical care conditions in hospitals of all resource-levels and IRBs are required to ensure that this research complies with ethical standards. Critical barriers restrict research activities in some resource limiting countries. Increasing the efficiency and accessibility of local IRB review could greatly impact participation of resource limited sites and enrollment of vulnerable populations., Competing Interests: 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., (© 2024 Lopez-Baron, Abbas, Caporal, Agulnik, Attebery, Holloway, Kissoon, Mulgado-Aguas, Amegan-Aho, Majdalani, Ocampo, Pascal, Miller, Kanyamuhunga, Tekleab, Bacha, González-Dambrauskas, Bhutta, Kortz, Murthy, Remy and the Global Health Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network.)

Background: Latin America's diverse genetic makeup, shaped by centuries of admixture, presents a unique opportunity to study Alzheimer's disease dementia (AD) and frontotemporal dementia (FTD). Our aim is to identify genetic variations associated with AD and FTD within this population., Methods: The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat) recruited 2,162 participants with AD, FTD, and healthy controls from six Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico, and Peru). All participants underwent array, exome, and/or whole-genome sequencing. Population structure was analyzed using Principal Component Analysis and ADMIXTURE, projecting the ReDLat population onto the 1000 Genomes Project database. To identify genes associated with autosomal dominant, autosomal recessive, or X-linked forms of adult-onset dementia, we searched the Online Mendelian Inheritance in Man database and analyzed pedigree information. Variant interpretation followed guidelines from the American College of Medical Genetics and Genomics, and the Guerreiro algorithm was applied for the PSEN1 and PSEN2 genes., Results: Global ancestry analysis of the ReDLat cohort revealed a predominant mix of American, African, and European ancestries. Uniquely, Brazil displayed an additional East Asian component accurately reflecting the historical admixture patterns from this region. We identified 17 pathogenic variants, a pathogenic C9orf72 expansion, and 44 variants of uncertain significance. Among our cohort, 70 families exhibited autosomal dominant inheritance of neurodegenerative diseases, with 48 families affected by AD and 22 by FTD. In families with AD, We discovered a novel variant in the PSEN1 gene, c.519G>T (p.Leu173Phe), along with other previously described variants seen in the region, such as c.356C>T (p.Thr119Ile). In families with FTD, the most commonly associated gene was GRN , followed by MAPT . Notably, we identified a patient meeting criteria for FTD who carried a pathogenic variant in SOD1 , c.388G>A (p.Phe21Leu), which had previously been reported in another FTD patient from the same geographical region., Conclusions: This study provides the first snapshot of genetic contributors to AD and FTD in a multisite cohort across Latin America. It will be critical to evaluate the generalizability of genetic risk factors for AD and FTD across diverse ancestral backgrounds, considering distinct social determinants of health and accounting for modifiable risk factors that may influence disease risk and resilience across different cultures., Competing Interests: Competing interests J.S.Y and K.S.K collaborate with the scientific advisory board of the Epstein Family Alzheimer’s Research Collaboration. C.J., M.A.N., H.L., D.V. and M.J.K.’s participation in this project was part of a competitive contract awarded to DataTecnica LLC by the National Institutes of Health to support open science research. M.A.N. also owns stock from Character Bio Inc and Neuron23 Inc.

Objective: Pooling multisite resting-state electroencephalography (rsEEG) datasets may introduce bias due to batch effects (i.e., cross-site differences in the rsEEG related to scanner/sample characteristics). The Combining Batches (ComBat) models, introduced for microarray expression and adapted for neuroimaging, can control for batch effects while preserving the variability of biological covariates. We aim to evaluate four ComBat harmonization methods in a pooled sample from five independent rsEEG datasets of young and old adults., Methods: RsEEG signals (n = 374) were automatically preprocessed. Oscillatory and aperiodic rsEEG features were extracted in sensor space. Features were harmonized using neuroCombat (standard ComBat used in neuroimaging), neuroHarmonize (variant with nonlinear adjustment of covariates), OPNested-GMM (variant based on Gaussian Mixture Models to fit bimodal feature distributions), and HarmonizR (variant based on resampling to handle missing feature values). Relationships between rsEEG features and age were explored before and after harmonizing batch effects., Results: Batch effects were identified in rsEEG features. All ComBat methods reduced batch effects and features' dispersion; HarmonizR and OPNested-GMM ComBat achieved the greatest performance. Harmonized Beta power, individual Alpha peak frequency, Aperiodic exponent, and offset in posterior electrodes showed significant relations with age. All ComBat models maintained the direction of observed relationships while increasing the effect size., Conclusions: ComBat models, particularly HarmonizeR and OPNested-GMM ComBat, effectively control for batch effects in rsEEG spectral features., Significance: This workflow can be used in multisite studies to harmonize batch effects in sensor-space rsEEG spectral features while preserving biological associations., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Primaquine, the only widely available treatment to prevent relapsing Plasmodium vivax malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years., Methods: We undertook a systematic review (Jan 1, 2000-July 26, 2024) for P vivax efficacy studies with at least one treatment group that was administered primaquine over multiple days, that enrolled children younger than 15 years, that followed up patients for at least 28 days, and that had data available for inclusion by June 30, 2022. Patients were excluded if they were aged 15 years or older, presented with severe malaria, received adjunctive antimalarials within 14 days of diagnosis, commenced primaquine more than 7 days after starting schizontocidal treatment, had a protocol violation in the original study, or were missing data on age, sex, or primaquine dose. Available individual patient data were collated and standardised. To evaluate efficacy, the risk of recurrent P vivax parasitaemia between days 7 and 180 was assessed by time-to-event analysis for different total mg/kg primaquine doses (low total dose of ∼3·5 mg/kg and high total dose of ∼7 mg/kg). To evaluate tolerability and safety, the following were assessed by daily mg/kg primaquine dose (low daily dose of ∼0·25 mg/kg, intermediate daily dose of ∼0·5 mg/kg, and high daily dose of ∼1 mg/kg): gastrointestinal symptoms (vomiting, anorexia, or diarrhoea) on days 5-7, haemoglobin decrease of at least 25% to less than 7g/dL (severe haemolysis), absolute change in haemoglobin from day 0 to days 2-3 or days 5-7, and any serious adverse events within 28 days. This study is registered with PROSPERO, CRD42021278085., Findings: In total, 3514 children from 27 studies and 15 countries were included. The cumulative incidence of recurrence by day 180 was 51·4% (95% CI 47·0-55·9) following treatment without primaquine, 16·0% (12·4-20·3) following a low total dose of primaquine, and 10·2% (8·4-12·3) following a high total dose of primaquine. The hazard of recurrent P vivax parasitaemia in children younger than 15 years was reduced following primaquine at low total doses (adjusted hazard ratio [HR] 0·17, 95% CI 0·11-0·25) and high total doses (0·09, 0·07-0·12), compared with no primaquine. In 525 children younger than 5 years, the relative rates of recurrence were also reduced, with an adjusted HR of 0·33 (95% CI 0·18-0·59) for a low total dose and 0·13 (0·08-0·21) for a high total dose of primaquine compared with no primaquine. The rate of recurrence following a high total dose was reduced compared with a low dose in children younger than 15 years (adjusted HR 0·54, 95% CI 0·35-0·85) and children younger than 5 years (0·41, 0·21-0·78). Compared with no primaquine, children treated with any dose of primaquine had a greater risk of gastrointestinal symptoms on days 5-7 after adjustment for confounders, with adjusted risks of 3·9% (95% CI 0-8·6) in children not treated with primaquine, 9·2% (0-18·7) with a low daily dose of primaquine, 6·8% (1·7-12·0) with an intermediate daily dose of primaquine, and 9·6% (4·8-14·3) with a high daily dose of primaquine. In children with 30% or higher glucose-6-phosphate dehydrogenase (G6PD) activity, there were few episodes of severe haemolysis following no primaquine (0·4%, 95% CI 0·1-1·5), a low daily dose (0·0%, 0·0-1·6), an intermediate daily dose (0·5%, 0·1-1·4), or a high daily dose (0·7%, 0·2-1·9). Of 15 possibly drug-related serious adverse events in children, two occurred following a low, four following an intermediate, and nine following a high daily dose of primaquine., Interpretation: A high total dose of primaquine was highly efficacious in reducing recurrent P vivax parasitaemia in children compared with a low dose, particularly in children younger than 5 years. In children treated with high and intermediate daily primaquine doses compared with low daily doses, there was no increase in gastrointestinal symptoms or haemolysis (in children with 30% or higher G6PD activity), but there were more serious adverse events., Funding: Medicines for Malaria Venture, Bill & Melinda Gates Foundation, and Australian National Health and Medical Research Council., Competing Interests: Declaration of interests JKB reports institutional research funding from MMV, GSK, Wellcome Trust, and Sanaria; participation on the US National Institutes of Health data safety monitoring board; and membership of the editorial board of Travel Medicine and Infectious Disease and the guidelines development group for malaria control and elimination, Global Malaria Programme, WHO. RJC, JKB, and RNP report contributions to Up-to-Date. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations., Methods: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.8 years from the Dominantly Inherited Alzheimer's Network. Weekly exercise volume was measured via questionnaire and associations with brain volume (magnetic resonance imaging), cerebrospinal fluid biomarkers, and brain amyloid beta (Aβ) measured by positron emission tomography were investigated., Results: Greater volume of weekly exercise at baseline was associated with slower accumulation of brain Aβ at preclinical disease stages β = -0.16 [-0.23 to -0.08], and a slower decline in multiple brain regions including hippocampal volume β = 0.06 [0.03 to 0.08]., Discussion: Exercise is associated with more favorable profiles of AD-related biomarkers in individuals with ADAD mutations. Exercise may have therapeutic potential for delaying the onset of AD; however, randomized controlled trials are vital to determine a causal relationship before a clinical recommendation of exercise is implemented., Highlights: Greater self-reported weekly exercise predicts slower declines in brain volume in autosomal dominant Alzheimer's disease (ADAD). Greater self-reported weekly exercise predicts slower accumulation of brain amyloid beta in ADAD. Associations varied depending on closeness to estimated symptom onset., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Limited information is available on gastric diseases in neonatal foals as compared with extensive studies in young, adult, and geriatric horses. Reports on fetuses are scarce., Objectives: Assess at necropsy stomachs of horse, donkey and mule fetuses in the third trimester of gestation to characterize lesions present during intrauterine life., Animals: Forty-six fetal stomachs from both sexes (21 horses, 21 donkeys, and 4 mules) in the third trimester of gestation were collected from a processing plant immediately after slaughter., Methods: Measurements of longitudinal and transverse axes, weight and volume and gastric fluid pH were taken, and glandular and squamous mucosae were inspected. All findings of the gastric mucosa and measurements of the stomachs were presented descriptively. Groups were compared statistically, with significance level set at P < .05 for all evaluations., Results: All gastric contents had pH >5.8, and mules had larger stomachs and higher weights compared with horses (P < .05). Macroscopic lesions were classified as hyperemic, punctate, and erosive. Histopathologically, lesions were consistent with a chronic inflammatory process., Conclusions and Clinical Importance: Our study provides evidence of macroscopic and histopathological lesions in the gastric mucosae of equid fetuses in the last trimester of gestation. Relevant information for perinatology and neonatology is provided regarding the prevalence and classification of preulcerous lesions in equids before birth., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Crib-biting is a stereotyped oral behavior with poorly understood etiology and pathophysiology. The relationship between the gut microbiome and brain function has been described in behavioral disorders such as schizophrenia, depression and anxiety in humans. In horses, studies of behavioral problems and the microbiome are very limited. This study aimed to characterize the fecal microbiome and the predicted functional profile of horses with and without aerophagia. Fecal samples were collected from 12 Colombian Creole Horses of both sexes, divided into two groups: group 1, composed of six horses with crib-biting (3 females and 3 males), average body weight of 330 ± 10 kg, age of 7.0 ± 1.2 years and body condition score (BCS) of 5/9 ± 1 and group 2, consisting of six horses without crib-biting (3 females and 3 males), average body weight of 335 ± 5 kg, age 6.5 ± 1 years and BCS of 6/9 ± 1. From each horse in both groups fecal total DNA was obtained and 16S ribosomal RNA gene amplicons were sequenced to characterize the bacterial community structure. Community structure and differential abundance analyses revealed significant differences between the two conditions (p < 0.05). Specifically, the fecal microbiota at the family level in crib-biting horses, showing a decrease in Bacteroidales and an increase in Bacillota and Clostridia, differed from that of healthy horses without crib-biting, consistent with findings from previous studies. Furthermore, metagenome prediction suggests metabolic profile changes in bacterial communities between both conditions in horses. Further studies are required to validate the role of the microbiota-gut-brain axis in the etiology of crib-biting and other abnormal and stereotyped behaviors., Competing Interests: Declaration of competing interest The authors 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 © 2024. Published by Elsevier Inc.)

Objective: To assess the correlation of dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV) and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation., Design: Observational study of a historical cohort., Setting: University hospital in Medellin, Colombia., Participants: Patients aged 15 and above with a confirmed COVID-19 diagnosis admitted to the ICU and requiring mechanical ventilation., Interventions: Measurement of VD/VT, CMV, and VR in COVID-19 patients., Main Variables of Interest: VD/VT, CMV, VR, demographic data, oxygenation indices and ventilatory parameters., Results: During the study period, 1047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. The multivariate analysis revealed independent associations to in-hospital mortality, higher VD/VT (HR 1.24; 95%CI 1.003-1.525; p = 0.046), age (HR 1.024; 95%CI 1.014-1.034; p < 0.001), and SOFA score at onset (HR: 1.036; 95%CI: 1.001-1.07; p = 0.017)., Conclusions: VD/VT demonstrated an association with mortality in COVID-19 patients with ARDS on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Measures of manganese (Mn) status in cattle vary among studies, and no single criterion accurately predicts or diagnoses Mn deficiency and pathologic outcomes. Mn deficiency causes congenital joint laxity and dwarfism (CJLD) when total dietary intake is <20 ppm Mn dry matter (DM) for most of the pregnancy. However, the recommended dietary intake of 40 ppm DM can also result in clinical Mn deficiency. Some studies have found that CJLD occurs in calves from cows fed red clover or silage but not in calves from cows fed hay. The concentration of Mn in the liver is the best indicator of Mn status in neonates and adults but cannot be interpreted in fetuses. Serum, plasma, and whole blood concentrations of Mn are unreliable indicators of bovine Mn status. The primary objective of our report is to present evidence linking CJLD to a primary or secondary Mn deficiency. To predict and diagnose Mn deficiency in cattle, we propose using a combination of clinical signs, dietary Mn, liver Mn at birth and beyond, positive response to Mn supplementation or the replacement of silage with other forages, and ruling out other causes of malformations. By following these recommendations, we expect that CJLD and gestational death will decrease as hepatic Mn concentrations increase at birth. Many publications we reviewed are not statistically sound, and future research should include a statistician from the initial discussions of the study through the final publication., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest concerning this article’s research, authorship, and publication.

This pilot study evaluated the impact of pistachio consumption on cognitive performance and mood in overweight young adults. Pistachios were characterized (chemical and nutraceutical), and a baseline-final, uncontrolled nutritional intervention was performed (28 g of pistachio/28 days). Psychometric tests were applied to estimate cognitive performance and mood; anthropometric evaluation, biochemical analysis, and plasma antioxidant activity were included. The main component of nuts was lipids (48.1%). Pistachios consumption significantly (p ≤ 0.05) reduced waist circumference (-1.47 cm), total cholesterol (-10.21 mg/dL), LDL (-6.57 mg/dL), and triglycerides (-21.07 mg/dL), and increased plasma antioxidant activity. Pistachio supplementation improved risk tolerance (p ≤ 0.006) and decision-making strategy (p ≤ 0.002; BART-task), executive functions (BCST-task; p ≤ 0.006), and selective and sustained attention (Go/No-Go-test; p ≤ 0.016). The mood state was positively modulated (p ≤ 0.05) for anxiety, anger-hostility, and sadness-depression. These results show for the first time the benefits of pistachio consumption on cognitive performance and mood in overweight young adults., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that can apparently influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aims: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model., Approach and Results: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts., Conclusions: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ ., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Colorectal cancer (CRC) is a multifactorial disease driven by genetic and epigenetic alterations that modulate specific metabolic pathways. Despite the availability of effective treatments like 5-fluorouracil (5-FU), pharmacological therapy for CRC still faces significant challenges, including drug resistance, toxicity, and limited specificity. Therefore, discovering new compounds remains critical to overcoming these barriers and expanding treatment options. This study evaluated the cytotoxicity of fluorinated quaternary ammonium salts (FQAS) library in CRC-derived cell lines with premetastatic and metastatic phenotypes. The genetic and epigenetic background of the CRC cell lines and the selectivity of cytotoxicity compared to nontumor cells and between different CRC stages were also assessed. Additionally, the in silico pharmacological properties of these FQASs were analyzed. Results showed that FQASs 9-14 exhibited significant cytotoxic activity against both premetastatic and metastatic CRC cell lines, with FQASs 9 , 13 , and 14 displaying selective toxicity toward CRC cells over normal murine colorectal cells. However, in silico studies indicated poor oral bioavailability for these compounds, suggesting that an injection-based delivery route may be more effective for targeting CRC cells. In conclusion, CF 3 -containing FQASs are promising therapeutic candidates for CRC treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Adriana Milena Olarte Aponte et al.)

Objective: To identify women's technological capabilities and describe their appropriation and use of technology in a community in a vulnerable area of Colombia., Method: Observational cross-sectional study conducted in the subregion of Urabá, Colombia. A survey was conducted in primary health care centers, in which 1478 women between 18 and 49 years of age responded to questions about their technological capabilities, their experience with the use of web-based information, and their appropriation of technology., Results: Access to and use of information and communication technologies (ICTs) varied according to age, educational level, and socioeconomic stratum, with observed differences in preferences and critical consumption of information., Conclusion: The women in this study faced multiple access barriers to appropriate use of ICTs for health promotion. The appropriation of these tools in Colombia, specifically in the Urabá subregion, is a complex challenge that requires a comprehensive and multidimensional approach., Competing Interests: Conflicto de intereses Ninguno declarado por los autores.

Background: Surgical-related incidents are a common cause of in-hospital adverse events. Surgical patient safety would benefit from evidence-based practices, but a comprehensive collection of patient safety recommendations is still lacking. This study aimed to compile and assess the perioperative patient safety recommendations for adults., Method: A systematic review of clinical practice guidelines was conducted using Medline, Embase, Cochrane, Virtual Health Library Regional Portal, and Trip Database from 2012 to 2022. Eligibility criteria followed a PICAR strategy for patient safety recommendations in the perioperative care continuum. Guidelines were appraised for quality, particularly focusing on the 'rigour of development' domain of the AGREE-II tool for those containing strong recommendations. Descriptive analyses were conducted, emphasizing guideline quality, recommendation strength, and the supporting level of evidence., Results: From the 267 guidelines, 4666 perioperative patient safety recommendations were extracted, of which 44.9% (2095) were strongly recommended. Of these, 322 had the highest level of evidence, but only 18 guidelines met high standards in the AGREE-II 'rigour of development' domain. A subset of 78 recommendations ranked the highest in the strength of recommendation, level of evidence, and rigour of development of their guidelines. A gap was found within pre-admission and post-discharge care recommendations., Discussion: This review highlights the noteworthy variability in the methodological quality of the guidelines, and a discordance between strength of recommendation and evidence level of the available perioperative patient safety recommendations. These findings provide valuable information for advising policy decisions and promoting best practices to enhance global surgical safety., Registration: PROSPERO (CRD42022347449)., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: Cardiovascular diseases are characterized by chronic inflammation, leading to increased inflammatory markers that can cause cell damage and death. Phase angle has emerged as a marker of cellular health. It is considered a prognostic factor in various acute and chronic conditions. However, few studies have examined its association with cardiovascular disease risk measures. This study aims to investigate the relationship between phase angle, the general Framingham risk score, and the HEARTS cardiovascular risk score., Methods: This cross-sectional study included a convenience sample of adult patients of 2 primary health care services. Phase angle was measured using multifrequency bioimpedance analysis at 50 kHz. The risk of cardiovascular events was calculated using the Framingham and HEARTS risk scores. Statistical analysis included generalized linear regression models, unadjusted and adjusted according to sex and age, to determine the association between scores, risk factors, and phase angle., Results: The study included 164 individuals with a mean age 52.2 (SD 17.9). According to the HEARTS score, low-risk patients had higher phase angle values than those with high or very high risk [ß = -0.57 (95% CI -0.95; -0.19), P = 0.003]. Framingham scores showed a trend toward significance for higher mean phase angle values in low-risk than high-risk patients [ß = -0.43 (95% CI -0.88 to 0.02), P = 0.06]., Conclusion: Phase angle values were lower in high and very high-risk patients than in low-risk patients, which shows that phase angle is a promising risk predictor for patients with cardiovascular diseases., (© 2024. The Author(s).)