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ABSTRACT: Herein, we combined different bioinformatics tools and databases (BV-BRC, ResFinder, RAST, and KmerResistance) to perform a prediction of antimicrobial resistance (AMR) in the genomic sequences of 107 Corynebacterium striatum isolates for which trustable antimicrobial susceptibility (AST) phenotypes could be retrieved. Then, the reliabilities of the AMR predictions were evaluated by different metrics: area under the ROC curve (AUC); Major Error Rates (MERs) and Very Major Error Rates (VMERs); Matthews Correlation Coefficient (MCC); F1-Score; and Accuracy. Out of 15 genes that were reliably detected in the C. striatum isolates, only tetW yielded predictive values for tetracycline resistance that were acceptable considering Food and Drug Administration (FDA)’s criteria for quality (MER < 3.0% and VMER with a 95% C.I. ≤1.5–≤7.5); this was accompanied by a MCC score higher than 0.9 for this gene. Noteworthy, our results indicate that other commonly used metrics (AUC, F1-score, and Accuracy) may render overoptimistic evaluations of AMR-prediction reliabilities on imbalanced datasets. Accordingly, out of 10 genes tested by PCR on additional multidrug-resistant Corynebacterium spp. isolates (n = 18), the tetW gene rendered the best agreement values with AST profiles (94.11%). Overall, our results indicate that genome-based AMR prediction can still be challenging for MDR clinical isolates of emerging Corynebacterium spp.

An experimental study is presented, simulating the firing process of artisanal red brick in a laboratory muffle. Under controlled heating conditions, the influence of both temperature and time on both the compressive strength and surface color of model bricks are evaluated. A production run and numerical simulations of laboratory brick heating are used to define the experimental conditions in the laboratory. A statistical model replicates the behavior of the compressive resistance at different temperatures, both in the muffle furnace and in production. Brick color has a more representative tone of a well-burned brick when created at the burning temperatures suggested in the literature.

Background: Alzheimer’s disease is a neurodegenerative disease that has no cure. The drugs used to treat Alzheimer’s disease are based on the inhibition of the enzyme acetylcholinesterase (AChE). In this sense, marine fungal metabolites represent an alternative source for the discovery of drugs based on AChE inhibition (IAChE). The present research carried out a bioprospecting study of marine fungi with acetylcholinesterase inhibition potential. Results: A total of 17 marine fungi were isolated from three stony corals from the Veracruz Reef System. The fungal genera identified were Geotrichum, Curvularia, Penicillium, Aspergillus, and Daldinia. The IAChE was evaluated from the broth and biomass extracts of each fungal strain. As a result, Daldinia eschscholtzii was one of the three fungi with the greatest IAChE effect (32.7%). Subsequently, a bio-directed chromatographic purification of the methanolic extract of the biomass of D. eschscholtzii was carried out. The FRL8.1 fraction was the most active with an IAChE of 41.0%, a value close to Galantamine positive control (44.0%). Furthermore, compound analysis was carried out by GC-MS. Finally, it was determined that the metabolites responsible for the inhibitory effect are probably 4,7-dihydroxycoumarin and 5-nitro-2-naphthalenamine, which was demonstrated by their interactions with the AChE enzyme receptor through molecular docking studies. Conclusions: Coral-associated marine fungi produce secondary metabolites that inhibit acetylcholinesterase. This is the first report of D. eschscholtzii isolated from the stony coral Siderastrea siderea. Finally, we consider that more studies are needed to demonstrate the IAChE potential of marine fungi associated with corals or other marine organisms.How to cite: Olivo-Flores KG, Couttolenc A, Suárez-Medellín J, et al. Acetylcholinesterase inhibition exerted by the extract of Daldinia eschscholtzii, a marine fungus associated with the coral Siderastrea siderea: GC–MS analysis and molecular docking of identified compounds. Electron J Biotechnol 2024;72. https://doi.org/10.1016/j.ejbt.2024.08.001.

Cystoliths are an uncommon manifestation of urolithiasis. They are typically observed in male patients who are over the age of 45. A giant bladder calculus is a stone that is greater than 4 cm in diameter and weighs more than 100 g. We report the case of a 43- year-old female who was admitted to the urology department with dysuria, lower abdominal pain, fever, nausea, and microscopic hematuria. Mild tenderness in the suprapubic region was noted during the patient's physical examination. A hyperdense image measuring 7.2 x 6.4 cm was revealed during an abdominal CT scan, which confirmed the diagnosis. A 280 g stone, measuring 9 x 8 x 4 cm, was extracted through open cystolithotomy. In the female population, bladder calculus formation is uncommon. The standard treatment is open cystolithotomy, and computed tomography is a valuable tool for confirming the diagnosis.

Spinal Arteriovenous Metameric Syndrome is a rare and complex nonhereditary genetic vascular disorder, affecting multiple layers of tissues at the same metamere, including the spinal cord. We present a case of a 20-year-old man who presented to the emergency department with sudden headache and transient loss of consciousness. Cranial computed tomography scan revealed subarachnoid hemorrhage predominantly in the cerebellar cisterns, fourth ventricle, extending to the basal cisterns. Cerebral angiography showed no abnormalities. Cervical angiographic acquisitions demonstrated a spinal metameric arteriovenous malformation (AVM) at the C3 and C4 levels. Cervical magnetic resonance imaging also confirmed the metameric AVM, revealing both intradural intramedullary and extra-dural vascular lesions in the vertebrae and adjacent soft tissues. The patient was referred for endovascular treatment. Although quite rare, the association between cervical spinal arteriovenous shunt diseases and intracranial hemorrhage has been reported. The bleeding in this case may be attributed to venous reflux into intracranial veins.

Introduction: Acute leukemias (ALs) are aggressive diseases that lead to death without medical attention. We evaluated the association between delays in diagnosis and poor outcomes in AL by evaluating the symptom onset to treatment intervals in adults with newly diagnosed AL and their effect on an early death (ED). Methods: We assessed adults diagnosed with AL between 2015 and 2020 and evaluated baseline characteristics, the patient interval (PI), diagnostic interval (DI), treatment interval (TI) and the total time interval (TTI) to determine ED-associated factors. Main results: We assessed 102 patients with acute lymphoblastic leukemia (ALL), 57 with acute myeloblastic leukemia (AML) and 29 with acute promyelocytic leukemia (APL). Median interval days were PI 14, DI 10, TI 4 and TTI 31.5. The TI and TTI intervals were lower in APL than in ALL and AML; TI 1 vs. 4 and 3 (p = 0.001) and TTI 21 vs. 31 and 35 (p = 0.016). The 30-day and 60-day EDs were 13.8% and 20.7%, mainly infections. ECOG > 2 (OR = 15.0) and PI < 7 days (OR = 4.06) were associated with 30-day ED; AML (OR = 2.69), high-risk (OR = 3.34), albumin < 3.5 g/dl (OR = 5) and platelets < 20 × 103/uL (OR = 2.71) with a 60-day ED. Conclusion: None of the interval-delays were associated with an ED. Intervals seemed to be longer in patients without an ED, except for the TI, probably because of “the waiting time paradox.” Aggressive manifestations of disease may lead to shorter diagnostic intervals, but increased mortality.

This study investigated the accuracy of mortality attributions assigned by the US News and World Report (USNWR) to the diabetes and endocrinology specialty. We reviewed medical records of all consecutive Medicare fee-for-service inpatients at Mayo Clinic, Florida (Jacksonville, Florida) with a Medicare Severity Diagnosis Related Group included in the USNWR Diabetes & Endocrinology specialty cohort admitted from November 2018 to April 2022, with documented mortality in our institution’s electronic health record within 30 days of the index admission. A clinician adjudicated the primary cause of death, categorizing it as diabetes or endocrine, cancer, failure to thrive, or other. Among 49 deceased patients, only 7 (14.3%) had diabetes or an endocrine-related cause of death. Cancer (49.0%) and failure to thrive (30.6%) were the leading causes. This substantial discrepancy (86% misattribution) suggests USNWR’s methodology might not precisely reflect the quality of care, potentially misleading patients and impacting hospital rankings.

Joubert Syndrome, manifests in a spectrum of neurological symptoms. This case describes a 7-year-old girl with perinatal complications, and subsequent neurodevelopmental challenges. An MRI confirmed the diagnosis of Joubert syndrome, with the distinctive “molar tooth sign” being a key imaging characteristic. Approximately 25% of cases exhibit nephronophthisis, impacting kidney function, further complicating the clinical picture. Diagnosis relies on imaging and management necessitates a multidisciplinary approach, addressing symptoms and complications, with prognosis linked to the presence of organic disease. The case emphasizes the significance of a multidisciplinary strategy, including genetic counseling, and underscores the diverse manifestations of this syndrome. Prenatal identification through ultrasound and MRI plays a crucial role in diagnosing and treating this rare condition.

Resumen: En los últimos años se ha apreciado un cambio notable en la práctica clínica cardiovascular en cardiología y cirugía. El objetivo del estudio CARDIOXCARDIO es conocer la opinión de los profesionales respecto al modo de trabajo y las relaciones entre especialidades. Se realizó una encuesta remitida simultáneamente a los 4.442 miembros de la Sociedad Española de Cirugía Cardiovascular y Endovascular (SECCE) y de la Sociedad Española de Cardiología (SEC), de la cual se obtuvieron 385 respuestas válidas. El 59% de los encuestados eran varones, mayoritariamente especialistas (el 7,3% residentes), y el 74,8% pertenecía al ámbito de la cardiología, predominantemente en centros públicos (88,3%). Mediante una escala Likert de 1 a 5 (de peor a mejor), los encuestados puntuaron la relación entre cirugía y cardiología con una media de 3,57 ± 0,9 puntos. La opinión de los cardiólogos sobre los cirujanos alcanzó una puntuación media de 3,83 ± 0,8 y viceversa, una media de 3,92 ± 0,72. Además, proporcionaron múltiples sugerencias de mejora que se discuten en detalle, con ciertas diferencias de criterio entre especialidades. La implementación de estrategias basadas en las sugerencias de los profesionales, junto con un enfoque proactivo en la mejora continua, podría tener un impacto sustancial en la calidad de la atención cardiovascular en España. Abstract: In recent years, there has been a notable shift in cardiovascular clinical practice within cardiology and surgery. The CARDIOXCARDIO study aimed to identify professionals’ opinions on working practices and relations between specialties. A survey was simultaneously sent to the 4442 members of the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the Spanish Society of Cardiology (SEC), yielding 385 valid responses. More than half (59%) of respondents were men, mostly specialists (7.3% residents), and 74.8% worked in the field of cardiology, predominantly in public centers (88.3%). Using a Likert scale ranging from 1 to 5 (worst to best), respondents rated relations between surgery and cardiology with an average of 3.57 ± 0.9 points. Cardiologists rated surgeons with a mean score of 3.83 ± 0.8, while surgeons gave cardiologists a mean score of 3,92 ± 0.72. In addition, respondents provided numerous suggestions for improvement, which are discussed in detail, highlighting certain discrepancies in criteria between specialties. Implementing strategies based on the suggestions of professionals, together with a proactive approach to continuous improvement, could substantially enhance the quality of cardiovascular care in Spain.

The relationship between diabetes and the development of kidney complications is well known, but the understanding of prediabetes and insulin resistance with impaired kidney function has been scarcely assessed. Various factors could explain this phenomenon, from the lack of standardization in the definitions of prediabetes, to the erratic and inconsistent evidence in large-scale epidemiological and cohort studies. It seems that the pathophysiological pathway of prediabetes could be related to inflammation and neurohormonal hyperactivation, factors present even before the onset of diabetes, which might be the main drivers of glomerular hyperfiltration, albuminuria, and impaired glomerular filtration rate. It is possible that existing treatments for the management of diabetes, as metformin or SGLT2 inhibitors may also be useful in patients with prediabetes with evidence of functional and structural kidney damage. The purpose of this review is to summarize the evidence regarding the relationship between prediabetes (preDM) and the development of CKD. Resumen: La relación entre diabetes y el desarrollo de complicaciones renales es bien conocida; sin embargo la asociación entre prediabetes y la resistencia a la insulina con el daño en la función renal apenas ha sido evaluada. Varios factores podrían explicar este fenómeno, desde la falta de estandarización en las definiciones de prediabetes, hasta la errática e inconsistente evidencia en estudios epidemiológicos y de cohortes a gran escala. Parece que las vías fisiopatológicas en la prediabetes podrían estar relacionadas con inflamación y la hiperactivación del sistema neuro-hormonal, factores presentes incluso antes de la aparición de la diabetes, que podrían ser los principales impulsores de la hiperfiltración glomerular, albuminuria y alteración de la tasa de filtración glomerular. Es posible que los tratamientos existentes para el control de la diabetes, como metformina o los inhibidores SGLT2 también pueden ser útiles en pacientes con prediabetes con evidencia de daño renal funcional o estructural. El propósito de esta revisión es resumir la evidencia sobre la relación entre la prediabetes (preDM) y el desarrollo de la ERC.

Aorticopulmonary paragangliomas are exceedingly rare tumors in pediatric populations. Complete surgical resection is the only curative treatment. However, resection is challenging due to the vascularity of paragangliomas and their close relationship with the great vessels. We present the resection of an aorticopulmonary paraganglioma that encased the main pulmonary artery bifurcation, compressed the left main coronary artery, and was densely adherent to the ascending aorta and right pulmonary artery via a median sternotomy with bypass. This case underscores the importance of complete resection for pediatric patients, despite the technical challenges.

This paper addresses the way in which the expansion zones of the metropolitan areas of Medellín and Rionegro are currently moving from the communal relations that marked their rural life to anonymous relations in which notions of neighborliness are gradually disappearing. Understanding the urban as a social condition and not only as a physical expression of the territory, but the urban is also no longer the opposite of the rural, nor is it synonymous with the city. The urban constitutes a phenomenon where anonymity and individuality are privileged in a space. This process takes place in a rural space where part of its heritage is the landscape and unneighborly relations. We assume the notion of the peri-urban limit as a space of undefinition that extends from the periphery of the Aburrá Valley to some of the rural hamlets of the Territorial Subsystem: Alto Grande - La Ramada, in the San Nicolas Valley; places where the communal is disappearing to give way to new urban dynamics. The article constitutes a theoretical contribution to the interpretation of the new realities observed in the peri-urban fringes of many contemporary metropolises, not only because of the debate it opens on the ways of understanding current urban-rural problems, but also because it suggests other perspectives for territorial planning based on the readings of the new social realities that are established there.

In light of the potential interest of Interdigital H-mode (IH) cavities for accelerating carbon ion beams beyond 5 MeV/u, we are reviewing the key geometric elements of the regular cells and end cells to optimize performance in terms of power efficiency, achievable voltage, and dipole field correction.

Background: Using cell lines to explore the function of organic compounds is fundamental in biotechnology. Evaluating new additives intended to improve animal production is challenging due to the complexity and uncertainty of in vivo testing. This study investigated the action of a compound with antioxidant properties using cells from terrestrial (LMH cells line) and aquatic vertebrates (CHSE-214). Results: The results of our study provide reassuring evidence of the compound’s safety for use in animal production. The compound demonstrated no adverse effects on cell viability, indicating its potential for safe application. Furthermore, the compound’s antioxidant properties were evident, with a 100% recovery in both cell lines when exposed to hydrogen peroxide 0.1 mM. It also effectively reduced cellular ageing caused by metabolic processes, as measured by the TBARS formation in both cell lines, from 5 MDA µM/mg protein to 2.5 MDA µM/mg protein when used at 0.05 or 0.5 g/L. Notably, this action did not increase cell membrane oxidation, further supporting its safety profile. Conclusions: These findings indicate that the compound has an antioxidant effect and can be used independently or in combination with metabolic stimulants in the diets of production animals. Applying this additive and its possible synergy with other compounds could help reduce oxidative stress and improve growth in animal production. The data generated in this study provide a solid basis for designing diets incorporating this additive to observe improvements in animal production based on activity observed at the cellular level.How to cite: Olivares- Ferretti P, Maguregui E, Chavez V, et al. Novel antioxidant additive ENTAN molecule for animal production: Evaluation at the cellular level. Electron J Biotechnol 2024;71. https://doi.org/10.1016/j.ejbt.2024.07.001.

This study proposes a chemical recycling pathway for valorizing the cellulosic component of municipal waste streams such as textile, cleaning wipes, corrugated cardboard, contaminated cardboard (i.e. a pizza box), paper-plastic laminate (PPL) coffee cups and cigarette butts (CBs). The goal of this study is to establish an experimental procedure that allows to test a broad range of cellulose-containing waste materials, laying the groundwork for commercial deployment of their chemical recycling. The cellulose contained in these materials is transformed into 5-chloromethylfurfural (CMF), a precursor for bio-based plastics, without affecting the plastic counterpart (if present). We employ a biphasic system concept using aqueous HCl solutions for CMF formation and in situ extraction from the reaction medium using immiscible organic solvents, enabling straightforward product separation. This method allows to hydrolyze cellulosic materials from waste without affecting PET or polyolefin plastic also present, facilitating the subsequent recycling of this plastic as well. This study serves as a foundation to assess the feasibility of using cellulose-containing waste streams for chemical recycling and to offer recommendations on selecting optimal reaction procedures.

The objective of this study is to explore the current state of research concerning the cost-effectiveness of wearable health technologies, excluding hearing aids, owing to extensive previous investigation. A systematic review was performed using PubMed, EMBASE/MEDLINE, Google Scholar, and Cumulated Index to Nursing and Allied Health Literature to search studies evaluating the cost-effectiveness of wearable health devices in terms of quality-adjusted life years and incremental cost-effectiveness ratio. The search was conducted on March 28, 2023, and the date of publication did not limit the search. The search yielded 10 studies eligible for inclusion. These studies, published between 2012 and 2023, spanned various locations globally. The studies used data from hypothetical cohorts, existing research, randomized controlled trials, and meta-analyses. They covered a diverse range of wearable technologies applied in different health care settings, including respiratory rate monitors, pedometers, fall-prediction devices, hospital-acquired pressure injury prevention monitors, seizure detection devices, heart rate monitors, insulin therapy sensors, and wearable cardioverter defibrillators. The time horizons in the cost-effectiveness analyses ranged from less than a year to a lifetime. The studies indicate that wearable technologies can increase quality-adjusted life years and be cost-effective and potentially cost-saving. However, the cost-effectiveness depends on various factors, such as the type of device, the health condition being addressed, the specific perspective of the health economic analysis, local cost and payment structure, and willingness-to-pay thresholds. The use of wearables in health care promises improving outcomes and resource allocation. However, more research is needed to fully understand the long-term benefits and to strengthen the evidence base for health care providers, policymakers, and patients.

Resumen: Introducción: el estudio tuvo como objetivo verificar el avance de implementación del modelo pedagógico orientado a competencias en posgrados de una facultad de Medicina, ya que la misma implementó una nueva malla curricular desde el año 2016, lográndose una primera cohorte de egresados, quienes buscarán consolidar su formación en subespecialidades que oferta la unidad académica. Métodos: estudio cualitativo con enfoque hermenéutico, interpretativo, con docentes y residentes de último año de posgrados seleccionados. Los datos fueron obtenidos mediante entrevistas semiestructuradas y grupos focales. Se analizaron los programas formativos. El modelo pedagógico orientado a competencias en posgrado fue la categoría principal que orientó los interrogantes, siendo analizadas las siguientes dimensiones: gestión académica, ejercicio docente, aprendizaje del profesional estudiante y estructura curricular. La recolección de datos concluyó una vez obtenida la saturación teórica. Resultados: analizando 22 entrevistas a docentes y grupos focales a 16 residentes de último año de posgrado, se identificó que el modelo pedagógico actualmente implementado, es mayoritariamente por contenidos, con innovaciones insuficientemente desarrolladas. Docentes con heterogénea formación e involucramiento en educación superior e implementación del nuevo modelo. Residentes de especialidades percibidos como espectadores, no involucrados en el proceso formativo que debió integrarse en posgrado para asegurar las competencias necesarias señaladas. Conclusión: en el ámbito de posgrado prevalece el modelo pedagógico por contenidos, sin que la orientación por competencias haya tenido continuidad, verificándose la necesidad de intervenciones en formación docente, involucramiento discente, mejoramiento de infraestructura y aseguramiento de la calidad educativa, para saturar los objetivos del plan estratégico institucional. Abstract: Introduction: The objective of the study was to verify the progress of implementation of the pedagogical model oriented to postgraduate competencies of a medical school, since it implemented a new curricular framework since 2016, achieving a first cohort of graduates, who will seek to consolidate their training in subspecialties offered by the academic unit. Methods: Qualitative study with a hermeneutic, interpretive approach with teachers and final year residents of selected postgraduate courses. The data were obtained through semi-structured interviews and focus groups. The training programs were analyzed. The pedagogical model oriented to postgraduate competencies was the main category that guided the questions, the following dimensions being analyzed: academic management, teaching practice, professional student learning and curricular structure. Data collection concluded once theoretical saturation was obtained. Results: Analyzing 22 interviews with teachers and focus groups with 16 final-year postgraduate residents, it was identified that the pedagogical model currently implemented is mostly content-based, with insufficiently developed innovations. Teachers with heterogeneous training and involvement in higher education and implementation of the new model. Residents of specialties perceived as spectators, not involved in the training process that should have been integrated into the postgraduate degree to ensure the necessary competencies indicated. Conclusion: In the postgraduate field, the pedagogical model by content prevails, without the orientation by competencies having had continuity, verifying the need for interventions in teacher training, student involvement, improvement of infrastructure and assurance of educational quality, to saturate the objectives of the plan institutional strategic.

Objetivo: Investigar os efeitos de ligação do 5-hidroximetilfurfural (5-HMF) e Voxelotor na Hemoglobina A (HbA), para avaliação da afinidade, cooperatividade heme-heme e efeito Bohr. Material e métodos: Utilizou-se hemolisado isolado de amostras de sangue periférico de 3 voluntários adultos saudáveis que assinaram o TCLE (CAAE: 62849022.5.0000.5404). A Hb foi purificada por cromatografia de exclusão molecular em colunas de Sephadex 25G (Sigma-Aldrich; Missouri, USA) em tampão Hepes 50 mM (Sigma-Aldrich; Missouri, USA) e por cromatografia de troca iônica (Amberlite MB3; Sigma-Aldrich; Missouri, USA). Obteve-se Curvas de Dissociação de Oxigênio (CDO) por espectrofotometria (DU800 Beckman Coulter-Fullerton, EUA) a 25oC, 70uM de Hb e relação estequiométrica Hb:composto de 1:1.5 (Voxelotor ou 5-HMF). Também realizou-se experimentos com Inositol Hexafosfato (IHP, Sigma-Aldrich) 1 mM como mimético do 2,3-BPG. A afinidade de oxigênio foi determinada com a obtenção de P50 (pressão parcial de O2 necessária para saturação de 50% da Hb total). Cooperatividade heme-heme foi calculada pela Constante de Hill (n), em que n = 1 indica interação não cooperativa e n = 2 indica interação heme-heme cooperativa. Os experimentos foram realizados nos pHs 6,5, 7,0 e 7,5 para avaliação de Efeito Bohr. Resultados: Voxelotor aumentou significativamente a afinidade pela Hb nos pHs 6,5 (p = 0.004) e 7,0 (p = 0.0104) em comparação a stripped HbA (controle) e em todos os pHs em comparação com 5-HMF (p = 0.0448, p = 0.0109 e p = 0.0047). Amostras com 5-HMF não tiveram alterações comparado com o controle. Na presença de IHP, houve diferença significativa de P50 nas amostras com Voxelotor em todos os pHs (6,5 p = 0.0038, 7,0 p = 0.043 e 7,5 p = 0.0007), demonstrando mudança significativa no alosterismo proteico e efeito Bohr positivo. Foi observada também diferença significativa entre 5-HMF e Voxelotor em pH 7,0 (p = 0.0275). Em relação à cooperatividade heme-heme, o Voxelotor apresentou valores de n abaixo de 1 para HbA stripped, indicando uma ligação não cooperativa, semelhantemente às mioglobinas. Diferenças significativas nos valores de n foram observadas entre Voxelotor e controle nos pHs 6.5 (p = 0.0114) e 7.0 (p = 0.0331), e entre Voxelotor e 5-HMF em todos os pHs (p = 0.0047, p = 0.026 e p = 0.0248, respectivamente). Com IHP, não foram encontradas diferenças significativas na cooperatividade heme-heme entre os grupos, e os valores de n foram aproximadamente 2, indicando que a ligação de Hb-O2 permaneceu cooperativa e sensível à ligação de fosfatos orgânicos, como o IHP. Discussão: Este trabalho sugere que o Voxelotor, atualmente utilizado no tratamento da anemia falciforme, possa aumentar a afinidade da HbA pelo O2 reduzindo drasticamente a cooperatividade heme-heme, mas permitindo que a mesma ainda se mostre sensível a variações de pH ou mesmo à presença de fosfatos orgânicos. Conclusão: Voxelotor aumentou significativamente a afinidade Hb-O2 em diferentes pHs, tanto em ambientes ácidos quanto alcalinos, modulando o alosterismo da Hb na presença de H+ e fosfatos. Estes achados mostram propriedades ainda não descritas do Voxelotor quanto a dinâmicas de ligação entre Hb e O2 e podem ser investigadas posteriormente como uma alternativa terapêutica em situações de baixa captação pulmonar de oxigênio e acidose.

Introdução: Estima-se que sejam transfundidos 85 milhões de Concentrados de Hemácias (CH) anualmente. Atualmente o principal dispositivo de armazenamento de hemocomponentes é composto por poli(cloreto de vinila) (PVC), de matriz fóssil, com conhecidos riscos de toxicidade apesar de suas propriedades conservantes. Objetivo: Triar bioplásticos como alternativa ao PVC, com menor toxicidade e maior potencial sustentável. Materiais e métodos: Foram selecionadas 12 composições (blendas): biofilmes de amido de mandioca (concentrações de 0,250, 0,125 e 0,093 g/mL); glucomanana konjac (KGM), KGM combinada a sericina (do casulo do bicho da seda); fibroína da seda; acetato de celulose; poli(ácido lático) (PLA, extraído da cana de açúcar) em combinação a poli(butileno adipato co-tereftalato) (PBAT, sintético; proporções 45:55, 55:45 e 14:86) e biofilmes de PLA:PBAT 14:86+poli-limoneno (PLM, 5 e 10%), extraído da casca de laranja. Os materiais foram caracterizados por espectroscopia Raman (B&W Tek; New Jersey, EUA) e FTIR-ATR (Agilent; California, EUA), antes e após esterilização UV (40 minutos). CHs foram isolados de sangue periférico de 3 voluntários saudáveis (anticoagulante CPDA 1:9) que assinaram TCLE após aprovação do CEP/Unicamp (CAAE: 71037223.9.0000.5404). Os biofilmes foram expostos aos CHs por 24h, 4ºC para avaliação de hemólise (método de Harboe) e à análise microbiológica. Os dados foram comparados ao plástico PVC como controle. Resultados e discussão: Todos os materiais mantiveram suas características originais após a esterilização UV, exceto PLA:PBAT 55:45, que revelou transmitâncias diferentes nas regiões 722, 937, 1267, 1716 e 2958 cm−1 em FT-IR, indicando possíveis alterações estruturais decorrentes da exposição ao UV. Quanto à hemólise, não foram observadas diferenças significativas entre o controle e demais biofilmes, exceto os derivados de amido 0,125 g/mL e de KGM, com resultados significativamente maiores (4,01% de hemólise; p = 0,02, e 0,28%; p = 0,01). Salienta-se a redução do volume plasmático em amostras incubadas com as blendas de amido, o que potencialmente favoreceria a hemólise. Em biofilmes de fibroína da seda ou sericina houve a formação de coágulos. Os materiais com maior hemocompatibilidade foram as blendas de PLA:PBAT, mais hidrofóbicas (proporções 55:45; 14:86+5% PLM e 14:86+10% PLM), com hemólises médias de 0,08% 0,07% e 0,09%, respectivamente, bem como a blenda de acetato de celulose (0,19%). A esterilização foi eficaz em todos os filmes, exceto amido 0,125 g/mL, KGM+sericina e fibroína. As blendas PLA:PBAT e KGM mostraram-se estéreis anteriormente à esterilização. Discussão: Materiais naturais geralmente apresentam alta biocompatibilidade, baixa toxicidade e imunogenicidade reduzida. Os polímeros incluídos neste estudo têm sido estudados como scaffolds , implantes e sistemas de transporte de ativos, mas não como dispositivos para bolsas de sangue. Este é o primeiro estudo que busca bioplásticos para este fim. Nossos dados apontam que materiais mais hidrofóbicos são mais inertes e estáveis, capazes de prevenir a coagulação e a adsorção à superfície polimérica. Conclusão: Os biofilmes de PLA:PBAT+PLM apresentaram resultados mais promissores: menor hemólise, ausência de coágulos e potencialmente estéreis. Serão estudados na próxima fase, com maior tempo de incubação e avaliação de parâmetros bioquímicos.

Objetivo: Avaliar a eficácia funcional da hemoglobina (Hb) em concentrado de hemácias (CH) em bolsas de sangue suplementadas com 2,3-Bifosfoglicerato (2,3-BPG), inositol hexafosfato (IHP) e hidroximetilfurfural (5-HMF). Material e métodos: Dois Concentrados de Hemácias (CH), concedidos por voluntários saudáveis que assinaram o termo de Consentimento Livre e Esclarecido (CAAE: 72004423.7.0000.5404), foram fracionados em 4 bolsas pediátricas, cada qual suplementada com seu respectivo composto: 2,3-BPG, 5-HMF, IHP e solução NaCl 0,9% (controle). A concentração adicionada de cada composto foi determinada em estudos de dose prévios, considerando a viabilidade celular e funcionalidade da Hb, através dos quais determinou-se as concentrações de 0,05mM de IHP e 0,5mM de 2,3-BPG e 5-HMF. A Hb foi isolada dos CHs nos tempos de 2, 17 e 35 dias de armazenamento (D2, D17 e D35) e purificadas por duas cromatografia de exclusão molecular (colunas Sephadex 25G - Sigma-Aldrich; Missouri, USA) e troca iônica (Amberlite MB3; Sigma-Aldrich; Missouri, USA). A interação Hb-O2 foi avaliada pela obtenção de curva de dissociação Hb-O2 (CDO), por espectrofotometria (DU 800, Beckman Coulter-Fullerton, EUA), a temperatura controlada de 25C, e concentração de Hb a 70uM. Foram determinadas P50, para avaliação de afinidade e Constante de Hill (n) para cooperatividade heme-heme em pH 7,4mM (tampão Hepes 50mM,Sigma Aldrich). Os experimentos também foram reproduzidos com adição de IHP 1mM, efetor alostérico mimético ao 2,3-BPG. A formação de meta-Hb também foi monitorada por espectrofotometria. Resultados: O composto 2,3-BPG promoveu queda da P50 ao longo do tempo de armazenamento, com desvio à esquerda da curva CDO da Hb stripped (D2-doador 1; D17-doador 2; D35-doadores 1 e 2). O polissacarídio 5-HMF resultou na redução da P50 no D35 das amostras stripped e no D2 e D17 no estado stripped + IHP. Em relação à formação de meta-Hb, observou-se pico de formação no D17 para todas as bolsas, incluindo controle. Apesar disso, foi observada redução de formação de meta-Hb em bolsas suplementadas em relação ao controle, particularmente naquelas com adição de 5-HMF e IHP (D35). Discussão: 2,3-BPG é metabólito eritrocitário que reduz a afinidade da Hb pelo O2, conforme observado em nossos estudos de dose. Interessantemente, após o armazenamento, este composto, assim como os demais efetores alostéricos, resultaram no aumento da afinidade da Hb pelo O2 e redução de formação de meta-Hb (particularmente no D35). O 5-HMF é um polissacarídeo capaz de aumentar a afinidade Hb-O2 in vitro, efeito também observado no estudo de dose do estudo. Já nos CHs armazenados, seu efeito foi parcialmente observado, em alguns tempos de armazenamento, possivelmente pela baixa dose de incubação. Já o IHP (mimético do 2,3-BPG para a Hb) apresentou resultados funcionais semelhantes ao controle, com o diferencial de redução de formação de meta-Hb. Conclusão: Este é um estudo preliminar e deverá ser completado com o estudo de mais um CH para efetiva comparação estatística. No entanto, os resultados são bastante promissores. A suplementação de bolsas de sangue com compostos que alterem seu metabolismo celular e que também desempenhem papel no alosterismo proteico pode ser interessante para a melhoria da eficácia funcional da Hb armazenada em CHs.

Objetivos: investigar a qualidade dos concentrados de hemácias suplementados com 2,3-bifosfoglicerato (2,3-BPG), hexafosfato de inositol (IHP) e hidroximetilfurfural (5-HMF), avaliando o potencial desses compostos em reduzir danos de armazenamento e manter a integridade celular das hemácias para transfusões. Material e métodos: Concentrados de Hemácias (CH), concedidos por dois voluntários saudáveis que assinaram o termo de Consentimento Livre e Esclarecido (CAAE: 72004423.7.0000.5404), foram fracionados em 4 bolsas pediátricas suplementadas, respectivamente com os compostos: 2,3-BPG (0,05mM, Sigma-Aldrich, EUA), 5-HMF (0,05mM, Sigma-Aldrich, EUA) e IHP (0,5mM, Sigma-Aldrich, EUA), além do controle (adicionada solução NaCl 0,9% em mesmo volume dos compostos). Foram realizadas as seguintes análises nos dias 2, 17 e 35 de armazenamento (D2, D17 e D35): quantificação de 2,3-BPG (2,3-DPG ELISA Kit, CUSABIO, EUA); ATP (ATP Assay Kit, Sigma-Aldrich, EUA); glicose (Bioclin, Brasil); e lactato (Bioclin, Brasil), determinação de pH (Quimis, Brasil), hemólise (método de Harboe) e avaliação da morfologia eritrocitária por microscopia óptica (Nikon, Japão). Resultados: A concentração de 2,3-BPG variou durante o armazenamento, aumentando em média 1,95 μmol/mL até o 17ºdia e diminuindo cerca de 2,3 μmol/mL aos 35 dias. O ATP manteve-se estável nos grupos controle, IHP e 2,3-BPG, mas apresentou variações e tendência de aumento nas bolsas suplementadas com 5-HMF. A hemólise aumentou gradualmente na bolsa controle (0,11 a 0,14%), assim como nas bolsas com IHP e 2,3-BPG. O 5-HMF manteve níveis mais baixos de hemólise (0,08% a 0,1%). A concentração de glicose reduziu ao longo do tempo em todas as condições, com o 5-HMF retardando esse consumo no 17ºdia. O lactato aumentou em todas as condições, refletindo o consumo de glicose, com maiores concentrações nas bolsas controle (25,84 mmol/L) e com 5-HMF (26,16 mmol/L) aos 35 dias. Análises de microscopia mostraram esferoequinócitos após 17 e 35 dias de armazenamento em todas as condições, associadas à diminuição do pH e das concentrações de ATP. Discussão: O aumento inicial de 2,3-BPG pode ser atribuído à atividade glicolítica elevada nos primeiros dias, que aumenta a produção de ATP, essencial para a síntese de 2,3-BPG. A subsequente queda de 2,3-BPG após 17 dias sugere uma perda da capacidade das hemácias de manter funções metabólicas. O aumento no lactato é consistente com o consumo de glicose e a produção de ácido lático pela glicólise. A estabilidade do ATP na maioria dos grupos, exceto com 5-HMF, indica que este composto pode modular o metabolismo energético eritrocitário. A bolsa com 5-HMF apresentou os níveis mais baixos de hemólise, possivelmente devido a propriedades antioxidantes. A redução da glicose ao longo do tempo é esperada, mas o 5-HMF retardou esse consumo, indicando um possível efeito protetor. Conclusão: A variação de 2,3-BPG e a estabilidade do ATP, exceto com 5-HMF, fornecem insights sobre o metabolismo das hemácias armazenadas. A menor hemólise com 5-HMF sugere seu potencial como aditivo para melhorar a preservação das hemácias, com benefícios adicionais na estabilidade do pH e no consumo retardado de glicose. O estudo é preliminar e deverá ser complementado com a análise de mais um CH para devida comparação estatística.

Summary: Background: Surgical care holds significant importance in healthcare, especially in low and middle-income countries, as at least 50% of the 4.2 million deaths within the initial 30 days following surgery take place in these countries. The Lancet Commission on Global Surgery proposed six indicators to enhance surgical care. In Colombia, studies have been made using secondary data. However, strategies to reduce perioperative mortality have not been implemented. This study aims to describe the fourth indicator, perioperative mortality rate (POMR), with primary data in Colombia. Methods: A multicentre prospective cohort study was conducted across 54 centres (hospitals) in Colombia. Each centre selected a 7-day recruitment period between 05/2022 and 01/2023. Inclusion criteria involved patients over 18 years of age undergoing surgical procedures in operating rooms. Data quality was ensured through a verification guideline and statistical analysis using mixed-effects multilevel modelling with a case mix analysis of mortality by procedure-related, patient-related, and hospital-related conditions. Findings: 3807 patients were included with a median age of 48 (IQR 32–64), 80.3% were classified as ASA I or II, and 27% of the procedures had a low-surgical complexity. Leading procedures were Orthopedics (19.2%) and Gynaecology/Obstetrics (17.7%). According to the Clavien–Dindo scale, postoperative complications were distributed in major complications (11.7%, 10.68–12.76) and any complication (31.6%, 30.09–33.07). POMR stood at 1.9% (1.48–2.37), with elective and emergency surgery mortalities at 0.7% (0.40–1.23) and 3% (2.3–3.89) respectively. Interpretation: The POMR was higher than the ratio reported in previous national studies, even when patients had a low–risk profile and low-complexity procedures. The present research represents significant public health progress with valuable insights for national decision-makers to improve the quality of surgical care. Funding: This work was supported by Universidad del Rosario and Fundación Cardioinfantil-Instituto de Cardiología grant number CTO-057-2021, project-ID IV-FGV017.

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Anthropogenic pressures on marine ecosystems are increasing worldwide, causing loss of biodiversity and ecosystem functioning, and driving species towards risk of extinction. To protect vulnerable species and habitats, Marine Protected Areas (MPAs) are increasingly established worldwide as conservation measures. Seahorses act as flagship species for coastal ecosystem conservation due to their charismatic appearance and high vulnerability to habitat degradation. Here, the habitat suitability of the two European seahorse species, Hippocampus hippocampus and Hippocampus guttulatus, was assessed along the western Iberian Peninsula, using an ensemble species distribution modelling approach. Furthermore, the coverage of their core habitat (relative habitat suitability (HS) ≥ 0.5) with MPAs was estimated. The results show that the main drivers for habitat suitability were distance to the coast, aspect of the seafloor, tidal amplitude, and temperature. However, the importance differed between the two species. The suitable habitat of H. hippocampus extended to higher distances to the coast, while H. guttulatus were mostly restricted to areas in the vicinity of the coast and facing away from the open sea (i.e., the westerly aspect of the seafloor). Furthermore, temperature contributes more to the variation in habitat suitability in H. hippocampus than in H. guttulatus. The areas with the highest habitat suitability are estuarine or inlet waters and sheltered coasts in northwestern Spain, central and south of Portugal. Both species’ core habitats are covered by about 19–20 % with implemented protected areas in Portugal. In comparison, there is less coverage for both species in Spain, with 12 % for H. guttulatus and 6 % for H. hippocampus. Besides, zones of full protection cover less than 0.5 % of the core habitat while the rest of the protected areas provide only moderate to low restrictions and do not specifically address the protection of seahorses in their management plans. The results provide useful information on the distribution and the different habitat preferences of the two species, indications for further monitoring of populations, and recommendations for efficient spatial conservation areas that can protect the species and other associated vulnerable species and habitats.

Allosteric regulation plays a crucial role in modulating protein functions and represents a promising strategy in drug development, offering enhanced specificity and reduced toxicity compared to traditional active site inhibition. Existing computational methods for predicting allosteric sites on proteins often rely on static protein surface pocket features, normal mode analysis or extensive molecular dynamics simulations encompassing both the protein function modulator and the protein itself. In this study, we introduce an innovative methodology that employs a per amino acid residue classifier to distinguish allosteric site-forming residues (AFRs) from non-allosteric, or free residues (FRs). Our model, STINGAllo, exhibits robust performance, achieving Distance Center Center (DCC) success rate when all AFRs were predicted within pockets identified by FPocket, overall DCC, F1 score and a Matthews correlation coefficient (MCC) of 78 %, 60 %, 64 % and 64 % respectively. Furthermore, we identified key descriptors that characterize the internal protein nanoenvironment of AFRs, setting them apart from FRs. These descriptors include the sponge effect, distance to the protein centre of geometry (cg), hydrophobic interactions, electrostatic potentials, eccentricity, and graph bottleneck features.

We assessed the impact of probiotics on outcomes related to caries in children and/or adolescents without underlying systemic diseases. We performed a comprehensive meta-analysis of randomised controlled trials (RCTs). Searches were performed in Embase, PubMed, Scopus and Web of Science until March 2023 for RCTs assessing probiotics with a minimum intake duration of 0.2 months vs. control (no treatment or placebo) and reporting at least one primary or secondary outcome. Primary outcomes were number of carious, Streptococcus mutans count, and Lactobacillus count; secondary outcomes were bacterial plaque index, gingival index, salivary pH, and bleeding index. We performed meta-analyses with random effects models and the inverse variance method. Effects were described as mean difference (MD) with their 95% confidence intervals (95%CI). The risk of bias was assessed with the RoB 2.0 tool. The GRADE methodology was used to assess the quality of evidence (QoE). Nineteen RCTs were included (n = 2622), with a follow-up range of 0.2 to 108 months. Probiotics had no effect on reduction of dental caries (MD -0.24 carious pieces, 95%CI -0.72 to 0.23; I2 = 52%, low QoE) or Lactobacillus count (MD -0.78 CFU/mL, 95%CI -1.65 to 0.09; I2= 52%, very low QoE) vs. control. However, probiotics probably reduced S. mutans count vs. control (MD -0.40 CFU/mL, 95%CI -0.57 to -0.24; I2 = 11%, moderate QoE). Probiotics had no effect on bacterial plaque index (MD 0.21 units of bacterial plaque, 95%CI -0. 55-0.96; I2 = 80%, very low QoE), gingival index (MD 0.04 units of gingival index, 95%CI -0.18 to 0.27; I2= 0%, low QoE), and salivary pH (MD -0.12 pH units, 95%CI -0.72 to 0.48; I2 = 92%, very low QoE) vs. control. Probiotics were found to likely reduce S. mutans counts. However, no significant effect of probiotics was observed in reducing other outcomes compared to the control group.

Chronic wounds and burns are a worldwide healthcare problem that erodes patients’ well-being and healthcare systems. This silent and costly epidemic requires new, cost-efficient solutions to improve patients’ physical and economic welfare. Eschar-degrading vegetal and bacterial proteases have been utilized as a solution. However, these proteins are evolutionarily far from those present in human wound healing. Serine protease (SP) and annexin (ANX) proteins interact within the skin healing process. A homology-based identification pipeline can help in discovering selective human SP and ANX analogs in the epithelial tissue of the fast-healing species, Pangasius hypophthalmus. In the present work, we found 14 candidates for RT-PCR in P. hypophthalmus using homology inference. The genetically detected candidates were then structurally and sequentially analyzed to understand their possible relation to SPs and ANXs involved in human wound healing. A total of six TBLASTN/BLASTX candidates (four SPs and two ANXs) were detected in P. hypophthalmus skin. Structural analysis revealed that all SP candidates resembled human KLK4, KLK5, KLK6, and KLK8, whereas all ANX only resembled human ANXA4. Structure and sequence analysis revealed high conservation of ANX Ca2+ binding sites (GDXD) and SP catalytic triad (HDS) motifs. In addition, structural analysis revealed that SP substrate selectivity position 186 was the main difference between human KLK5 and P. hypophthalmus SPs. These findings may allow the proposal and testing of more selective formulations, broadening treatments beyond debridement.

Background: Despite recent improvements in melanoma survival rates, persistent inequalities pose barriers to care for some patients. Objective: To assess the influence of social determinants of health (SDoH) on melanoma treatment outcomes. Methods: A systematic review (Prospective Register of Systematic Reviews CRD42022346854) of manuscripts that examined the association between SDoH and melanoma treatment-related outcomes in the United States was conducted using 5 databases. Results: The analysis encompassed data from 12 retrospective manuscripts. The SDoH domains most frequently investigated were health care access and quality (n = 6 manuscripts, 50%) and economic stability (n = 7, 58.3%). Other domains included social and community context (n = 5, 41.7%) and education access (n = 3, 25%). These findings revealed significant correlations between poor melanoma survival and low levels of economic stability, limited education, government health insurance, and being uninsured and unmarried. Limitations: Many SDoH were not analyzed at the patient level. SDoH are vast categories, but manuscripts usually analyze one aspect of a particular category. Conclusions: These results highlight the need for physicians to recognize the substantial impact of SDoH on melanoma outcomes and to adopt more comprehensive strategies focused on patient-centered care. Integrating social support mechanisms into clinical practice emerges as a key mechanism to promote equitable and effective interventions.

Many bioinformatics tools are available for the quantitative analysis of proteomics experiments. Most of these tools use a dedicated statistical model to derive absolute quantitative protein values from mass spectrometry (MS) data. Here, we present iSanXoT, a standalone application that processes relative abundances between MS signals and then integrates them sequentially to upper levels using the previously published Generic Integration Algorithm (GIA). iSanXoT offers unique capabilities that complement conventional quantitative software applications, including statistical weighting and independent modeling of error distributions in each integration, aggregation of technical or biological replicates, quantification of posttranslational modifications, and analysis of coordinated protein behavior. iSanXoT is a standalone, user-friendly application that accepts output from popular proteomics pipelines and enables unrestricted creation of quantification workflows and fully customizable reports that can be reused across projects or shared among users. Numerous publications attest the successful application of diverse integrative workflows constructed using the GIA for the analysis of high-throughput quantitative proteomics experiments. iSanXoT has been tested with the main operating systems. Download links for the corresponding distributions are available at https://github.com/CNIC-Proteomics/iSanXoT/releases.

Objective: To examine the association of left atrial (LA) function with incident chronic kidney disease (CKD) and assess the clinical utility of adding LA function to a CKD risk prediction equation. Patients and Methods: We included 4002 Atherosclerosis Risk in Communities study participants without prevalent CKD (mean ± SD age, 75±5 years; 58% female, 18% Black). Left atrial function (reservoir, conduit, and contractile strain) was evaluated by 2D-echocardiograms on 2011 to 2013. Chronic kidney disease was defined as greater than 25% decline in estimated glomerular filtration rate of less than 60 mL/min/1.73 m2, end-stage kidney disease, or hospital records. Cox proportional hazards models were used. Risk prediction and decision curve analyses evaluated 5-year CKD risk by diabetes status. Results: Median follow-up was 7.2 years, and 598 participants developed incident CKD. Incidence rate for CKD was 2.29 per 100 person-years. After multivariable adjustments, the lowest quintile of LA reservoir, conduit, and contractile strain (vs highest quintile) had a higher risk of CKD (hazard ratios [95% CIs]: 1.94 [1.42-2.64], 1.62 [1.19-2.20], and 1.49 [1.12-1.99]). Adding LA reservoir strain to the CKD risk prediction equation variables increased the C-index by 0.026 (95% CI: 0.005-0.051) and 0.031 (95% CI: 0.006-0.058) in participants without and with diabetes, respectively. Decision curve analysis found the model with LA reservoir strain had a higher net benefit than the model with CKD risk prediction equation variables alone. Conclusion: Lower LA function is independently associated with incident CKD. Adding LA function to the CKD risk prediction enhances prediction and yields a higher clinical net benefit. These findings suggest that impaired LA function may be a novel risk factor for CKD.

Words and terms evoke responses in us, independently of their original meaning. Precise language matters because terminology can affect conservation. For example, current deforestation rates put the Amazon in the spotlight of global conservation, particularly after the “savannization of the Amazon” was proposed. This term associates cleared or degraded forests with savannas, reinforcing prejudices against natural savannas. The Cerrado is the world’s largest and richest savanna, but receives less conservation attention and resources. Firstly, we showed a multisector Cerrado neglect: number of protected areas, non-governmental organizations, academic human resources, and companies were larger in the Amazon, but deforested area was proportionally smaller. Secondly, we analyzed the academic use of “savannization of the Amazon.” In all 481 studies using this term, human action was implied, and most meant that degraded Amazon does not become old-growth savanna. We propose abandoning the use of “savannization of the Amazon”, promoting the support and attention the Cerrado needs.

Introduction and objectives: Concerns regarding the consequences of ionizing radiation (IR) have been increasing in the field of interventional cardiology (IC). There is little information on reported national and local radiation diagnostic reference levels (DRLs) in catheterization laboratories in Portugal. This study was designed to assess the IR dose exposure during complex percutaneous coronary intervention (PCI), and to set the respective DRLs and future achievable doses (ADs). Methods: This was a retrospective cohort study which took place between 2019 and 2020, including patients who underwent complex PCI. Complex PCI was defined as all procedures that encompass treatment of chronic total occlusions (CTO) or left main coronary artery. DRLs were defined as the 75th percentile of the distribution of the median values of air kerma area product (PKA) and cumulative air kerma (Ka,r). ADs were set at the 50th percentile of the study dose distribution. Multivariate analysis was performed using linear regression to identify predictors significantly associated with radiation dose (Ka,r). Results: A total of 242 patients were included in the analysis. Most patients underwent a CTO procedure (146, 60.3%). Patients were aged 67.9±11.2 years and mostly male (81.4%). DRLs were set in Ka,r (3012 mGy) and PKA (162 Gy cm2) for complex PCI. ADs were also set in Ka,r (1917 mGy) and PKA (101 Gy cm2). Independent predictors of Ka,r with a positive correlation were PKA (0.893, p

In this study, we employ the Laplace Variational Iterational Method (LVIM) as a sophisticated mathematical tool to investigate into the complex dynamics of cancer cells under the influence of chemotherapy. The LVIM, a method combining Laplace transformations and variational iteration techniques, is specifically adapted to address a system of time fractional differential equations (FDEs) that characterizes the temporal behavior of cancer cells. To enhance the efficacy of our approach, we introduce a semi-analytic version of LVIM, which proves to be a powerful and versatile tool for solving mathematical problems involving fractional derivatives. The focus of our analysis centers on elucidating the impact of chemotherapy, with a particular emphasis on drug diffusion within cancer cells and the fractality of DNA walks. Through numerical exploration encompassing varying fractional order derivatives, our study exposes nonlinear behaviors that remain secret in systems featuring only integer order derivatives. Notably, the methodology we propose is not only applicable to the specific cases examined in this research but also exhibits broad versatility, making it suitable for exploring the effects of different drugs and types of cancers. This research contributes valuable insights into the dynamics of cancer cells, aiding in the understanding of the implications for therapeutic strategies in the context of cancer treatment.

Introduction and objectives: Catheter ablation (CA) is effective in the treatment of ventricular tachycardia (VT). Although some observational data suggest patients with non-ischemic cardiomyopathy (NICM) have less favorable outcomes when compared to those with an ischemic etiology (ICM), direct comparisons are rarely reported. We aimed to compare the outcomes of VT ablation in a propensity-score matched population of ICM or NICM patients. Methods: Single-center retrospective study of consecutive patients undergoing VT ablation from 2012 to 2023. A propensity score (PS) was used to match ICM and NICM patients in a 1:1 fashion according to age, sex, left ventricular ejection fraction (LVEF), NYHA class, electrical storm (ES) at presentation, and previous endocardial ablation. The outcomes of interest were VT-free survival and all-cause mortality. Results: The PS yielded two groups of 71 patients each (mean age 63±10 years, 92% male, mean LVEF 35±10%, 36% with ES at presentation, and 23% with previous ablation), well matched for baseline characteristics. During a median follow-up of 2.3 (interquartile range IQR 1.3–3.8) years, patients with NICM had a significantly lower VT-free survival (53.5% vs. 69.0%, log-rank p=0.037), although there were no differences regarding all-cause mortality (22.5% vs. 16.9%, log-rank p=0.245). Multivariate analysis identified NICM (HR 2.34 [95% CI 1.32–4.14], p=0.004), NYHA class III/IV (HR 2.11 [95% CI 1.11–4.04], p=0.024), and chronic kidney disease (HR 2.23 [95% CI 1.25–3.96], p=0.006), as independent predictors of VT recurrence. Conclusion: Non-ischemic cardiomyopathy patients were at increased risk of VT recurrence after ablation, although long-term mortality did not differ. Resumo: Introdução e objetivos: A ablação por cateter (CA) é eficaz no tratamento da taquicardia ventricular (TV). Embora dados observacionais sugiram que doentes com miocardiopatia não isquémica (NICM) apresentem piores resultados do que aqueles com etiologia isquémica (ICM), comparações diretas são escassamente reportadas. O objetivo foi comparar os resultados da ablação de TV numa população propensity-matched de doentes com NICM ou ICM. Métodos: Estudo retrospetivo unicêntrico de doentes submetidos ablação de TV, de 2012 a 2023. Usado propensity-score (PS) para emparelhar doentes com NICM e ICM numa proporção 1:1 de acordo com idade, sexo, fração de ejeção ventricular esquerda (FEVE), classe de NYHA, tempestade arrítmica à admissão e ablação endocárdica prévia. Os outcomes de interesse foram sobrevida livre de TV e morte por todas as causas. Resultados: O PS resultou em dois grupos de 71 doentes (idade 63 ± 10 anos, 93% do sexo masculino, FEVE 35 ± 10%, 36% com apresentação em tempestade arrítmica e 23% com ablação prévia). Durante um follow-up de 2,3 (1,3–3,8) anos, os doentes com NICM apresentaram menor sobrevida livre de TV (53,5% versus 69,0%, P log-rank = 0,037), apesar de não haver diferenças significativas em relação à mortalidade (22,5% versus 16,9%, P log-rank = 0,245). A análise multivariada identificou NICM (HR 2,34 [IC 95% 1,32–4,14], P = 0,004), NYHA III ou IV (HR 2,11 [IC 95% 1,11–4,04], P = 0,024) e doença renal crónica (HR 2,23 [IC 95% 1,25–3,96], P = 0,006) como preditores independentes de recidiva de TV. Conclusão: Doentes com NICM apresentam maior risco de recidiva de TV, apesar de não haver diferenças significativas na mortalidade a longo prazo.

The evolution of urban morphology and urban mobility reveals a complex and multidimensional relation that has been historically linked to the evolution of technology and its influence on people's behaviour, desires, and needs. The increasing level of digitalization of human interactions in both social and work environments has created a new paradigm for urban mobility. Alongside, sustainability concerns are also accelerating the design of new policies for improving citizens’ quality of life in urban areas. To address this new paradigm, municipalities need to consider new methodologies encompassing the different dimensions of the urban environment. This can be achieved if key stakeholders participate in co-creating and co-designing new solutions for urban mobility. In this paper we propose a multidisciplinary approach to these problems, supported by service-dominant logic concepts. The approach was used to design the CoDUMIS framework that brings together four dimensions of urban areas (social, urban, technological, and organizational). The application of the framework to four distinct cases, in Portuguese municipalities, resulted in a set of guidelines that help municipalities to improve their services and policies in a participatory environment, involving all the stakeholders.

Introduction: Therapeutic failure in patients with malaria can occur due to various factors and polymorphisms in enzymes of the Cytochrome P450 (CYP450) family, responsible for around 90% of the metabolization of chloroquine and primaquine, can generate individuals who are low, intermediate or fast metabolizers of antimalarial drugs. Objective: We evaluated the relationship between these polymorphisms and the biometalization of antimalarial drugs worldwide through a systematic review using the PRISMA statement. Methodology: The research question was structured in the PICO format (Population = people infected with Plasmodium vivax; Intervention = people without vivax malaria; Comparison = polymorphisms in the CPY450 gene; Outcome = biometabolization of antimalarial drugs is influenced by polymorphisms in the CYP450 gene). The investigation in the databases (Medline through Pubmed, Google scholar, Science direct and Scopus) was carried out by grouping descriptors (DECs/Mesh) with Boolean operators (AND/OR). Duplicate articles were excluded, as well as those with in vitro research, which did not meet the objective of the study and which, when applying the Joanna Briggs Institute questionnaire, had ≤ 50% ''yes'' answers. Results: Of the 187,935 articles retrieved, only 12 were selected for this review, adding up to 2050 individuals. The majority (75%) of the articles reported an interaction between polymorphisms in the CYP2A6, CYP2D6, CYP2B6, CYP3A4 and CYP3A5 genes in individuals infected with Plasmodium falciparum and interference in drug metabolization. As for Plasmodium vivax (25%), the SNP in the CYP2D6 gene was the most frequently reported cause of therapeutic failure. As for the phenotype regarding biometabolization, 65% were normal, 25% low, 5% fast and 5% null metabolizers. Conclusions: It is important to develop measures aimed at profiling genetic biomarkers and their respective phenotypes in populations from endemic areas, in order to prevent relapses from P. vivax and treatment failure for both plasmodia; important for establishing malaria prevention and control measures. Keywords: Molecular Epidemiology, Pharmacogenetics, Plasmodium, Public Health. Conflicts of interest: There was no conflicts of interest. Ethics and financing: Declarations of interest: None.

Introdução/objetivos: Dados brasileiros sobre a carga do vírus sincicial respiratório (VSR) em adultos são limitados. As vacinas contra o VSR recentemente aprovadas visam reduzir a carga do VSR em adultos mais velhos. Este estudo tem como objetivo usar uma abordagem de modelagem para estimar a carga do VSR e projetar o potencial impacto na saúde pública da introdução da Vacina VSR Adjuvantada (RSVPreF3) para imunização de adultos com 60 anos ou mais no Brasil. Materiais e métodos: Um modelo de Markov estático de ciclo mensal foi desenvolvido para avaliar o número de casos sintomáticos de VSR com e sem vacinação. O modelo captura casos de VSR em pacientes com doença respiratória aguda (DRA-VSR), doença do trato respiratório inferior (DTRI-VSR), doença do trato respiratório superior (DTRS-VSR), complicações de pneumonia devido à DTRI-VSR, hospitalizações (assumidas conservadoramente apenas às DTRI-VSR) e mortes em um período de três anos. A cobertura vacinal para uma dose única considerada no modelo foi de 30% a 70%. Os dados demográficos são valores específicos do Brasil (2024) provenientes das Nações Unidas. Os dados epidemiológicos foram recuperados de banco de dados público (FluNet) e complementados por revisão sistemática da literatura. A eficácia da vacina foi obtida do estudo clínico de fase 3 AReSVi-006 (NCT04886596). Resultados: No Brasil, a coorte incluiu 33.859.754 adultos ≥ 60 anos. Na ausência de vacinação, o modelo projetou 6.641.784 casos de DRA-VSR (3.480.113 de DTRS-VSR e 3.161.671 de DTRI- VSR), 243.205 casos de pneumonia, 264.214 hospitalizações e 25.083 mortes por VSR em três anos. Com a cobertura aumentando de 30% para 70%, o modelo projetou que a vacinação pode prevenir de 780.189 a 1.820.442 casos de DRA-VSR (264.146 a 616.341 de DTRS-VSR e 516.043 a 1.204.101 de DTRI-VSR), 39.696 a 92.623 casos de pneumonia, 43.125 a 100.624 hospitalizações e 4.094 a 9.553 mortes por VSR. O número necessário para vacinar para prevenir um caso de DRA-VSR e um caso de DTRI-VSR foi estimado em 13 e 20, respectivamente. Conclusões: Os resultados revelam que aproximadamente 20% da população brasileira com idade ≥ 60 anos está em risco de infecção por VSR nos próximos três anos, e a carga ao sistema de saúde é substancial. A prevenção por meio da vacinação com RSVPreF3 tem o potencial de produzir consideráveis benefícios, reduzindo a morbidade, a utilização de serviços de saúde e a mortalidade associadas às infecções por VSR. Palavras-chave: Vírus Sincicial Respiratório, Vacina VSR Adjuvantada, ≥ 60 anos. Conflitos de interesse: RH, AG, BdV, LM, OC, DVO and JG are GSK employees. AG and JG hold shares in GSK. These authors declare no other financial and non-financial relationships and activities. Ética e financiamentos: Estudo financiado por: GlaxoSmithKline Biologicals SA (GSK study identifier: VEO-000975).

Introdução: A mobilização e participação da comunidade é fundamental em programas de prevenção/controlo de doenças transmitidas por vetores. Em Portugal, mosquitos do género Aedes aegypti estão estabelecidos na Ilha da Madeira, tendo ocorrido em 2012 o primeiro surto de febre de dengue (DENV-1) nesta região, com 1084 casos confirmados laboratorialmente. Objetivos do estudo: Caracterizar opiniões e atitudes da população madeirense face à utilização de mosquitos geneticamente modificados (MGM) como estratégia de controlo vetorial. Materiais e métodos: Foi aplicado um questionário a adultos residentes nas freguesias com cota abaixo dos 200 metros do município do Funchal, Região Autónoma da Madeira (S.Martinho, Stª Maria Maior, Sé, S.Pedro, Stª Luzia, Imaculado Coração de Maria) em março-abril 2019. Selecionaram-se aleatoriamente as residências para aplicação do questionário; em cada residência foi selecionado aleatoriamente um indivíduo; utilizou-se uma amostragem estratificada por sexo. Os participantes indicaram o seu grau de concordância com afirmações existentes no questionário. Resultados: Participaram no estudo 1270 indivíduos, idade média 53,5 anos, 44,6% do género masculino, 52,4% com ≥ 12 anos de escolaridade. Concordância com as afirmações: “Se libertassem MGM na minha rua, sentiria receio” concordam (C) 58,8%, discordam (D) 16,8, indiferente (I) 8%; “O medo dos efeitos da utilização dos MGM faz com que prefira técnicas tradicionais” C 46,8%, D 20,5%, I 13,4%; “os MGM devem ser rejeitados por não serem naturais” C 33,7%, D 29,6%, I 11,9%; “Como a maioria dos casos de dengue não são graves devemos continuar a utilizar estratégias tradicionais” C 47,9%, D 30,5%, I 8,3%. As mulheres (p = 0,017) e os menos letrados (p < 0,001) mostram mais receio da utilização de MGM. A análise conjunta das 4 questões indica que 37% têm atitude anti-MGM, 17% são moderadamente contra MGM, 7% mostra atitude moderadamente favorável, 16% são totalmente a favor, 23% têm atitude indiferente/indefinida. 53/151 respondentes (35,1%) consideravam que após libertação de MGM a população pode sentir-se mais incomodada/picada. Conclusões: Mais de metade dos participantes no estudo encontra-se no espetro anti-MGM e 1/4 tem uma atitude indefinida quanto à utilização de MGM para controlo de vetores. Se no futuro se optar por esta estratégia de controlo de vetores na Madeira há que compreender os motivos geradores desta atitude de oposição e desenvolver ações educativas abrangentes. Palavras-chave: Dengue, Ilha da Madeira, Controlo Vetorial, Atitudes. Conflitos de interesse: Sem qualquer conflito de interesses para nenhum dos autores. Ética e financiamentos: Sem qualquer conflito de interesses para nenhum dos autores.

Introdução: Em 2005 foram detetados, pela primeira vez, mosquitos da espécie Aedes aegypti em Portugal, na Região Autónoma da Madeira. Em 2012 a região sofreu um surto de dengue, sendo registados 1084 casos. É consensual a necessidade do envolvimento das comunidades nas intervenções de controlo vetorial. Objetivos do estudo: Caracterizar conhecimentos da população da Madeira sobre a utilização de mosquitos geneticamente modificados (MGM) como estratégia de controlo vetorial. Materiais e métodos: Foi aplicado um questionário a adultos residentes nas freguesias do município do Funchal com cota abaixo dos 200 metros (São Martinho, Santa Maria Maior, Sé, São Pedro, Santa Luzia, Imaculado Coração de Maria) em março-abril 2019. Selecionaram-se aleatoriamente as residências para aplicação do questionário; em cada residência foi selecionado aleatoriamente um indivíduo; utilizou-se uma amostragem estratificada por sexo. Resultados: Participaram no estudo 1270 indivíduos, idade média 53,5 anos, 44,6% do género masculino, 29% com 12° ano de escolaridade, 23,4% com licenciatura/mestrado. No subgrupo (11,9%, IC a 95% [10,2; 13,8] 151/1270) que ouviu falar/leu sobre MGM, 42% conhecem as técnicas de supressão e 36% as de substituição; Fontes de informação: TV 57,6%, internet 51%, jornais 40,4%. Respostas: “Os MGM não são compatíveis com uso de estratégias tradicionais” Desconheço (D) 15,2%, verdade (V) 16,5%, falso (F) 56,3%, possível (P) 6,6%; “Libertar MGM pode não ser suficiente para controlar o número de mosquitos e de doentes” D 5,3%, V 61,5%, F 3,3%, P 25,2%; “Utilizar MGM diminui o número de mosquitos e doentes apenas em situações/lugares específicos” D 13,9%, V 43%, F 11,3%, P 25,8%; “Com o tempo os MGM perdem eficácia” D 35,7%, V 15,2%, F 23,2%, P 17,2%; “Os custos de libertação de MGM são superiores aos das estratégias tradicionais” D 32%, V 43%, F 16%. Quem tem maior nível de escolaridade ouviu falar/leu sobre MGM (p < 0,001) e responde mais vezes adequadamente às questões colocadas (p < 0,005). Conclusões: A grande maioria da população da Madeira nunca ouviu falar/leu sobre MGM. Verifica-se elevado nível de desconhecimento do possível controlo de vetores com utilização de MGM e compatibilidade com as estratégias tradicionais. Torna-se essencial aumentar a informação da população para garantir os pressupostos de transparência, entendimento mútuo e envolvimento ativo da comunidade se no futuro se desejar utilizar esta abordagem de controlo de vetores no território. Palavras-chave: Dengue, Ilha da Madeira, Controlo Vetorial, Conhecimentos. Conflito de interesse: Sem qualquer conflito de interesses para nenhum dos autores. Ética e financiamentos: Sem qualquer conflito de interesses para nenhum dos autores.

Polybrominated diphenyl ethers (PBDEs) are substances used as flame retardants that can be released into the environment through volatilization, leaching, and abrasion throughout the useful life of the articles that contain them, especially at the end of their life cycle because PBDEs do not chemically bind to the initial materials (electrical and electronic equipment, textiles, materials used in transport vehicles, toys, among others). Research has shown that the toxic effects and risks of PBDEs to ecosystems and human health are greater than their benefits owing to their neurotoxicity, toxicity to the endocrine and reproductive systems, and possible carcinogenicity. This review shows the current situation of management of waste containing PBDEs (plastics, sludge, soil, and ash) and the characterization, valorization, treatment, and final disposal of these wastes, to minimize their impacts on ecosystems and human health are analyzed. Wastes with concentrations greater than 1000 mg/kg of PBDE should be considered as hazardous waste. This research identifies the methods available to reduce the risk in their management; at the same time, it provides innovative ideas for the integrated management of PBDE-containing wastes, prioritizing their valorization and disposal.

We are far from understanding the spatial patterns of dryland soil carbon and nitrogen stocks and how they vary among different land cover types. We used data from 12,000 sites from 129 countries in global drylands to estimate soil organic carbon (SOC) and total nitrogen (STN) stocks in different land cover types, explore the factors driving their spatial distribution, and predict the trends under different climate scenarios in global drylands. SOC and STN stocks in the upper 100 cm reached 419.5 and 38.2 Pg, respectively, with the upper 0–30 cm accounting for half of them. The largest SOC stocks were found in forests, shrublands and grasslands, while STN stocks peaked in forests, bare areas and croplands. The factors driving the spatial patterns of SOC and STN varied among soil depths, with mean annual temperature, pH and aridity being the main factors driving the spatial patterns in SOC and STN density for 0–30 cm, and soil texture the strongest factor for 60–100 cm. Under the Representative Concentration Pathways (RCP) 4.5 scenario, SOC and STN stocks were predicted to decrease by 3.6 % and 4.0 %, respectively, from 2020 to 2100, whereas under the RCP 8.5 scenario, the projected decreases were 5.9 % and 6.4 % respectively. Our results indicate that if we want to accurately predict C and N accumulation, and design effective mitigation measures in terrestrial ecosystems under future climatic scenarios, we need to better explore the drivers that operate at the deeper soil depths, which also accumulate a significant amount of SOC and STN.

Resumen: La atención a las mujeres víctimas de violencia presenta a los profesionales de la salud situaciones que exigen una profunda reflexión al plantear conflictos entre los principios fundamentales de la bioética. La deliberación para la resolución de estos conflictos nos debe llevar a la adopción de cursos de acción intermedios en los que ninguno de los principios afectados quede totalmente comprometido, pero siempre atendiendo al debido cumplimiento de la normativa legal y deontológica.Dentro de estos conflictos debe tenerse en consideración la posible afectación de la autonomía de la víctima, condicionada por la relación de dominio respecto a su agresor, característica fundamental de la violencia de género. No obstante, el hecho de que exista una obligación legal de emitir un parte de lesiones o la comunicación de la sospecha fundada de maltrato no es suficiente para obviar el hecho de que la persona, en este caso víctima, debe ser partícipe del proceso, de manera que el/la médico/a tiene la obligación de informar a su paciente sobre este mandato legal, dedicando para ello todo el tiempo y la atención que sean necesarios para lograr que la víctima comprenda la finalidad y los beneficios de dar cumplimiento a la norma.En cualquier caso, y más allá de la necesaria adecuación de la conducta del profesional a los preceptos vigentes, debe atenderse al principio ético de beneficencia, por el cual la mejor actuación del profesional reside precisamente en proporcionar a la víctima medios que permitan evitar la reiteración de nuevas agresiones, implementando medidas de prevención que tienen su origen en el certero diagnóstico de la situación de violencia y en la comunicación de esta a las autoridades. Abstract: Caring for female victims of violence presents health professionals with situations that require careful consideration due to the conflicts raised between the fundamental principles of bioethics. During this process, intermediate courses of action should be adopted in which none of the affected principles is totally compromised, yet always take into account due compliance with legal and deontological regulations.Within these conflicts, the possible impact on the autonomy of the victim must be taken into consideration, conditioned by the relationship of dominance with respect to their aggressor, a fundamental characteristic of gender violence. However, the fact that there is a legal obligation to issue an injury report or to communicate a well-founded suspicion of abuse is not enough to ignore the fact that the person, in this case the victim, must be a participant in the process. As such, the doctor has the obligation to inform his or her patient about this legal requirement, dedicating all the time and attention necessary to ensure that the victim understands the purpose and benefits of complying with this.In any case, and beyond the appropriate adaptation of the professional's conduct to current precepts, the ethical principle of care must be adhered to, by which the best thing the professional can do is to provide the victim with the means to avoid the repetition of new attacks, implementing prevention measures that have their origin in the accurate diagnosis of the situation of violence and in the communication of this to the authorities.

The uncertainty associated with the future of viruses such as SARS-CoV-2 poses a challenge to public health officials because of its implications for welfare, economics and population health. In this document, we develop an age-stratified epidemiological-mathematical model to predict various health outcomes, considering the effectiveness of COVID-19 vaccines. The analytical model proposed and developed for this research is based on the approach constructed by the COVID-19 International Modelling Consortium. Following this approach, this paper innovates at the frontier of knowledge by including the various variants of SARS-CoV-2 in the Consortium model. Furthermore, for the first time in international literature, a complete compilation of the formal mathematical development of this entire quantitative model is presented. Our model accurately fits the observed historical data of new infections, cumulative mortality, symptomatic infections, hospitalisations, and Intensive Care Units admissions, capturing the waves of contagion that have occurred in Bogotá, Colombia. In turn, the prognosis obtained indicates a considerable decrease in the incidence and lethality caused by SARS-CoV-2 under current conditions, thus evidencing the effectiveness of vaccines against infection, hospitalisation, and death. This model enables the evaluation of different scenarios in response to changes in the dynamics of this infectious disease, providing information to policymakers for real-world evidence-based decision-making.