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Introduction: Fanconi anemia (FA) is an inherited disorder characterized by bone marrow failure, congenital malformations, and predisposition to malignancies. Alterations in hematopoietic stem cells (HSC) have been reported, but little is known regarding the bone marrow (BM) stroma. Thus, the characterization of Mesenchymal Stromal Cells (MSC) would help to elucidate their involvement in the BM failure. Methods: We characterized MSCs of 28 FA patients (FA-MSC) before and after treatment (hematopoietic stem cell transplantation, HSCT; or gene therapy, GT). Phenotypic and functional properties were analyzed and compared with MSCs expanded from 26 healthy donors (HD-MSCs). FA-MSCs were genetically characterized through, mitomycin C-test and chimerism analysis. Furthermore, RNA-seq profiling was used to identify dysregulated metabolic pathways. Results: Overall, FA-MSC had the same phenotypic and functional characteristics as HD-MSC. Of note, MSC-GT had a lower clonogenic efficiency. These findings were not confirmed in the whole FA patients' cohort. Transcriptomic profiling identified dysregulation in HSC self-maintenance pathways in FA-MSC (HOX), and was confirmed by real-time quantitative polymerase chain reaction (RT-qPCR). Discussion: Our study provides a comprehensive characterization of FA-MSCs, including for the first time MSC-GT and constitutes the largest series published to date. Interestingly, transcript profiling revealed dysregulation of metabolic pathways related to HSC self-maintenance. Taken together, our results or findings provide new insights into the pathophysiology of the disease, although whether these niche defects are involved in the hematopoietic defects seen of FA deserves further investigation.
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BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.
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The school environment is of great relevance in the prevention of drug use in students because it is where they spend most of their time and, since education is compulsory until upper secondary school in Spain, interventions in this area can reach the majority of children up to that stage. The objective of this systematic review is to determine the level of efficacy of the school preventive programs that have been implemented in Spain. Following the PRISMA recommendations, a systematic literature search was carried out in the Web of Science, PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases. The search yielded 274 studies, of which 29 studies were selected. It was found that 48 drug addiction prevention programs have been implemented in Spanish school context, of which only 18 (37.5%) had an evaluation of their effectiveness following the criteria and standards of effective prevention. Conversely, the programs that were not evaluated are far from these standards in their design. It is concluded that there are two models of school prevention of drug addiction in Spain: a model that meets this description; and another model classified as "pseudo-prevention", since its design does not meet the standards of effective prevention nor has its preventive efficacy been demonstrated.
El ámbito escolar adquiere una gran relevancia en la prevención del consumo de drogas en estudiantes, ya que es donde pasan una mayor parte del tiempo y, puesto que en España la enseñanza es obligatoria hasta los 16 años, las intervenciones en este ámbito pueden alcanzar a la mayoría de niños en esa etapa. El objetivo de esta revisión sistemática fue determinar qué nivel de eficacia presentan los programas preventivos escolares que se han implementado en España. Siguiendo las recomendaciones PRISMA, se llevó a cabo una búsqueda bibliográfica sistemática en las bases de datos Web of Science, PubMed/MEDLINE, Embase, Scopus y Cochrane Library. La búsqueda arrojó 274 estudios, de los cuales fueron seleccionados 29 estudios. Se ha identificado que en España se han implementado 48 programas preventivos en drogodependencias en el contexto escolar, de los cuales tan solo 18 (37,5%) cuentan con evaluación de su eficacia siguiendo los criterios y estándares de una prevención eficaz. Por el contrario, los programas que no han sido evaluados distan en su diseño de estos estándares. Se concluye que en España conviven dos modelos de prevención escolar de las drogodependencias: un modelo que responde a esta denominación; y otro modelo calificado como "pseudo-prevención", dado que su diseño no se ajusta a los estándares de la prevención eficaz ni su eficacia preventiva ha sido demostrada.
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Objective: . Acute myocardial infarction-related cardiogenic shock (AMI-CS) is often accompanied by tachycardia, which, in turn, increases myocardial oxygen consumption and hinders the use of ventricular assist devices, such as intra-aortic balloon pump. Evidence suggests that ivabradine may reduce heart rate (HR) without affecting other hemodynamic parameters. The aim of the present study was to determine the effect of ivabradine on reducing HR and changes in other hemodynamic parameters such as cardiac index (CI), in patients with AMI-CS and tachycardia. Materials and methods: . A single-center, open label, randomized clinical trial included patients diagnosed with AMI-CS and tachycardia with >100 beats per minute (BPM). Heart rate, cardiac index, and other hemodynamic parameters measured by pulmonary flotation catheter were compared at 0, 6, 12, 24, and 48 hours after randomization. Results: . A total of 12 patients were randomized; 6 received standard therapy, and 6 received ivabradine in addition to standard therapy. Baseline clinical characteristics were similar at randomization. A statistically significant lower heart rate was found at 12 hours (p=0.003) and 48 hours (p=0.029) after randomization, with differences of -23.3 (-8.2 to -38.4) BPM and -12.6 (-0.5 to -25.9) BPM, respectively. No differences in cardiac index, or any other evaluated hemodynamic parameters, length of hospital stay, nor mortality rate were noted between both groups. Conclusions: . The use of ivabradine in patients with AMI-CS was associated with a significant reduction in heart rate at 12 and 48 h, without affecting other hemodynamic parameters.
Objetivo: . El choque cardiogénico relacionado con el infarto agudo de miocardio (AMI-CS, por sus siglas en inglés) suele ir acompañado de taquicardia, lo que, a su vez, aumenta el consumo de oxígeno miocárdico y dificulta el uso de dispositivos de asistencia ventricular, como la bomba de balón intraaórtico. La evidencia sugiere que la ivabradina puede reducir la frecuencia cardíaca (FC) sin afectar otros parámetros hemodinámicos. El objetivo del presente estudio fue determinar el efecto de la ivabradina en la reducción de la FC y los cambios en otros parámetros hemodinámicos como el índice cardíaco (CI) en pacientes con AMI-CS y taquicardia. Materiales y métodos: Se incluyeron pacientes diagnosticados con AMI-CS y taquicardia con >100 latidos por minuto (LPM) en un ensayo clínico aleatorizado de un solo centro. La frecuencia cardíaca, el índice cardíaco y otros parámetros hemodinámicos medidos mediante catéter de flotación pulmonar se compararon a las 0, 6, 12, 24 y 48 h después de la aleatorización. Resultados: Se aleatorizaron un total de 12 pacientes; 6 recibieron terapia estándar y 6 recibieron ivabradina además de la terapia estándar. Las características clínicas basales fueron similares en la aleatorización. Se encontró una frecuencia cardíaca significativamente más baja a las 12 h (p=0,003) y a las 48 h (p=0,029) después de la aleatorización, con diferencias de -23,3 (-8,2 a -38,4) LPM y -12,6 (-0,5 a -25,9) LPM, respectivamente. No se observaron diferencias en el índice cardíaco, en ningún otro parámetro hemodinámico evaluado; tampoco en la duración de la estancia hospitalaria, ni en la tasa de mortalidad entre ambos grupos. Conclusiones: El uso de ivabradina en pacientes con AMI-CS se asoció con una reducción significativa en la frecuencia cardíaca a las 12 y 48 h, sin afectar otros parámetros hemodinámicos.
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While cytostatic chemotherapy targeting DNA is known to induce genotoxicity, leading to cell cycle arrest and cytokine secretion, the impact of these drugs on fibroblast-epithelial cancer cell communication and metabolism remains understudied. Our research focused on human breast fibroblast RMF-621 exposed to nonlethal concentrations of cisplatin and doxorubicin, revealing reduced proliferation, diminished basal and maximal mitochondrial respirations, heightened mitochondrial ROS and lactate production, and elevated MCT4 protein levels. Interestingly, RMF-621 cells enhanced glucose uptake, promoting lactate export. Breast cancer cells MCF-7 exposed to conditioned media (CM) from drug-treated stromal RMF-621 cells increased MCT1 protein levels, lactate-driven mitochondrial respiration, and a significantly high mitochondrial spare capacity for lactate. These changes occurred alongside altered mitochondrial respiration, mitochondrial membrane potential, and superoxide levels. Furthermore, CM with doxorubicin and cisplatin increased migratory capacity in MCF-7 cells, which was inhibited by MCT1 (BAY-8002), glutamate dehydrogenase (EGCG), mitochondrial pyruvate carrier (UK5099), and complex I (rotenone) inhibitors. A similar behavior was observed in T47-D and ZR-75-1 breast cancer cells. This suggests that CM induces metabolic rewiring involving elevated lactate uptake to sustain mitochondrial bioenergetics during migration. Treatment with the mitochondrial-targeting antioxidant mitoTEMPO in RMF-621 and the addition of an anti-CCL2 antibody in the CM prevented the promigratory MCF-7 phenotype. Similar effects were observed in THP1 monocyte cells, where CM increased monocyte recruitment. We propose that nonlethal concentrations of DNA-damaging drugs induce changes in the cellular environment favoring a promalignant state dependent on mitochondrial bioenergetics.
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PURPOSE OF REVIEW: Heart failure (HF) represents a pathology in constant growth, but, despite the fact that a significant proportion of its population is comprised of elderly patients, they are not adequately represented in clinical trials or registries. They constitute a heterogeneous population with their particularities and interaction of the multiple comorbidities that characterize this age group, which makes the clinical course, prognosis and outcomes of the disease different. RECENT FINDINGS: Compared to men, women with HF tend to be older, with a greater burden of non-cardiovascular comorbidities, less ischemic heart disease and preserved ventricular function in most cases. This fact translates into worse self-perceived quality of life, with lower hospitalization and mortality rates. Moreover, paradoxically, women are less likely to receive treatment recommended by clinical practice guidelines, including revascularization and device placement. As there are not enough representative studies of this population, the reasons for these results with better prognosis and relatively benign impact in the elderly female population are unknown, which is why it is necessary to continue with research in order to obtain greater evidence of the exposed gaps.
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Background: Despite established vaccination programs, vaccine-preventable diseases persist among about 900,000 Forcibly Displaced Myanmar Nationals (FDMN)/Rohingya refugees in the world's largest refugee settlement in Bangladesh. Health service providers (HSPs) play a key role in the delivery of childhood vaccination programs. This study explored their views on individual and context barriers and drivers to childhood vaccination in this setting. Methods: Informed by the theoretical framework of the Capability-Opportunity-Motivation-Behavior (COM-B) model for behavior change, this qualitative study collected data through eight focus group discussions (FGDs) with community health workers (CHWs) and vaccinators in selected camps with high or low vaccination coverage rates, and through 11 in-depth interviews (IDIs) with key informants working in strategic, management, and administrative roles. Findings: Barriers and drivers were evident across all COM factors for HSPs and caregivers. Among HSPs, knowledge around vaccination acted both as a barrier and driver, while communication skills and confidence in vaccination served as drivers. Caregivers' lack of awareness of vaccination, concerns and mistrust were described as main barriers. Context barriers included information system deficiencies, family dynamics, HSPs' working conditions, and vaccination site accessibility. Context drivers included effective communication, mobilization, and incentives. Differences between high and low coverage camps in Cox's Bazar included variations in HSPs' knowledge, communication strategies, incentive use, and stakeholder collaboration. Discussion: For better vaccination coverage in the camps, context-related changes regarding collaboration, health workforce and the use of incentives seem necessary. Caregivers' mistrust toward vaccination needs to be considered under the social and historical background of the Rohingya community, and further addressed with targeted communication and campaigning.
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Grupos Focales , Investigación Cualitativa , Refugiados , Vacunación , Humanos , Bangladesh , Refugiados/psicología , Refugiados/estadística & datos numéricos , Mianmar , Femenino , Masculino , Adulto , Vacunación/psicología , Vacunación/estadística & datos numéricos , Personal de Salud/psicología , Personal de Salud/estadística & datos numéricos , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , MotivaciónRESUMEN
Perceived physical literacy contributes to the understanding of individuals' physical activity (PA) engagement. It is important a scale is validated in the population of interest. Also, the type of administration may affect reliability and validity. So, the aim of this study was twofold: 1) to examine evidence of validity and reliability of the Spanish version of the Physical Literacy for Children Questionnaire (PL-C Quest) in a cohort of children and adolescents and 2) to assess two versions of administering the scale. The study was conducted in two stages, depending on the administration format of the PL-C Quest (double-dichotomous, and four-point response style) in a cohort of 2004 (n1 = 916; n2 = 1088) students. In both administration forms, evidence of validity (relation with other variables, i.e., concurrent and predictive, and structural validity), invariance (between boys and girls) and reliability (test-retest and internal consistency) were examined. There was evidence of validity for both administration types, with adequate reliability and good to excellent test-retest reliability for both administration forms. Both methods of administration for the PL-C Quest can capture perceived physical literacy in Spanish 8- to 14-year-old children and early adolescents.
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Ejercicio Físico , Humanos , Femenino , Masculino , Adolescente , Niño , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Alfabetización en Salud , Psicometría/métodos , EspañaRESUMEN
Background: Advances in multiple myeloma (MM) treatment have shifted the therapeutic landscape. Understanding patients' perspectives can assist physicians in helping patients make informed decisions. This study aimed to understand the patient decision-making process and gain insights into patient perspectives on B-cell maturation antigen (BCMA)-targeted therapies for MM. Methods: An 18-question survey was completed by patients with MM enrolled in HealthTree® Cure Hub, an online portal helping patients with plasma cell dyscrasias navigate their disease. Results: From October 28, 2022, to January 12, 2023, 325 patients with MM participated in the survey. The mean age (standard deviation) of the respondents was 66 (8) years; 54% were female and 90% were White. Among 218 patients with complete clinical records in the database, the median (min, max) lines of therapy (LOT) was 2 (1,16). Among 61 (28%) patients who had received ≥4 LOTs, 55 (90%) were triple-class exposed. Of the 290 patients who responded to the question about openness to new therapies, 76 (26%) were open to trying a new therapy immediately and 125 (43%) wanted more information on safety and efficacy. Most respondents reported likely or very likely to try a BCMA CAR T-cell therapy (60%) or a bispecific antibody (74%) and some needed more information to decide (16% for CAR T-cell therapy and 13% for bispecific antibody). The most requested information included efficacy, side effects (SEs), eligibility, and administration process for both CAR T-cell and bispecific therapies. When 2 therapies with the same efficacy and duration of response were offered, 69% of respondents would prefer the therapy with a lower risk of severe SEs but requires continuous dosing with no treatment-free interval, and 31% preferred a therapy given once followed by a treatment-free interval but with a potentially higher risk of severe SEs. To receive an effective therapy, the top acceptable trade-offs included frequent monitoring of SEs and initiating a new therapy in a hospital setting, and the least acceptable compromise was caregiver burden. Conclusions: This study found a high level of openness in patients with MM to try BCMA-targeted therapies. Information on efficacy, safety, availability, and eligibility may assist patients on decision-making.
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Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.
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Background: Implant-based breast augmentation is a gold standard procedure for transfeminine patients to create a more feminine-appearing chest. In many cases, ancillary procedures are performed simultaneously to achieve an optimal aesthetic result. Objectives: To determine the clinical outcomes of patients undergoing feminizing gender-affirming breast surgery in a single academic institution. Methods: A retrospective electronic chart review of feminizing gender-affirming breast surgery patients at Mayo Clinic, Rochester, from 2017 to 2022 was conducted. Patients' demographics and surgical outcomes were gathered. A survival analysis was performed to obtain the time-to-event complication rate. Results: Over 5 years, 46 patients (92 breasts) were included. The mean age was 39 years (standard deviation [SD] ±15), and most had an above-normal body mass index (BMI) (58.7%). Thirty (65%) had previous gender-affirming surgeries. The mean implant volume was 289â mL (SD ±95; 140-520). Most implants were placed in a subglandular plane (81%) with an inframammary fold incision (91.3%). All implants used were smooth, round cohesive silicone gel implants. Ancillary procedures were performed in 32 patients (69.57%). Eight patients presented complications (4 major vs 4 minor) in a median postoperative follow-up of 372 vs 392 days; at 1-month follow-up, the probability of a complication having occurred is 2.17% (95% CI: 0%-6.3%) vs 5% (95% CI: 0%-11.5%), and at 1 year, the probability is 10.21% (95% CI: 0%-20.9%) vs 12.5% (95% CI: 0%-23.4%), which remains the same up to 4 years. Conclusions: Breast augmentation with implants is a safe procedure to achieve feminization of the breast with a low rate of complications.
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Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.
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Hibridación Fluorescente in Situ , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Hibridación Fluorescente in Situ/métodos , Mapeo Cromosómico/métodos , Trastornos de Fallo de la Médula Ósea/genética , Aberraciones Cromosómicas , Adolescente , Análisis Citogenético/métodos , Enfermedades de la Médula Ósea/genética , Cariotipificación/métodos , Adulto JovenRESUMEN
Breast cancer is the most common invasive neoplasm and the leading cause of cancer death in women worldwide. The main cause of mortality in cancer patients is invasion and metastasis, where the epithelial-mesenchymal transition (EMT) is a crucial player in these processes. Pharmacological therapy has plants as its primary source, including isoflavonoids. Brazilin is an isoflavonoid isolated from Haematoxilum brasiletto that has shown antiproliferative activity in several cancer cell lines. In this study, we evaluated the effect of Brazilin on canonical markers of EMT such as E-cadherin, vimentin, Twist, and matrix metalloproteases (MMPs). By Western blot, we evaluated E-cadherin, vimentin, and Twist expression and the subcellular localization by immunofluorescence. Using gelatin zymography, we determined the levels of secretion of MMPs. We used Transwell chambers coated with matrigel to determine the in vitro invasion of breast cancer cells treated with Brazilin. Interestingly, our results show that Brazilin increases 50% in E-cadherin expression and decreases 50% in vimentin and Twist expression, MMPs, and cell invasion in triple-negative breast cancer (TNBC) MDA-MB-231 and to a lesser extend in MCF7 ER+ breast cancer cells. Together, these findings position Brazilin as a new molecule with great potential for use as complementary or alternative treatment in breast cancer therapy in the future.
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Benzopiranos , Neoplasias de la Mama , Cadherinas , Transición Epitelial-Mesenquimal , Femenino , Humanos , Benzopiranos/farmacología , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/efectos de los fármacos , Metaloproteinasas de la Matriz/metabolismo , Metaloproteinasas de la Matriz/genética , Células MCF-7 , Invasividad Neoplásica/genética , Proteínas Nucleares , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Proteína 1 Relacionada con Twist/metabolismo , Proteína 1 Relacionada con Twist/genética , Vimentina/metabolismo , Vimentina/genéticaRESUMEN
Air leak syndrome (ALS) is described in human medicine as a constellation of clinical disorders including pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema, pneumothorax, pneumoperitoneum, pneumoretroperitoneum and subcutaneous emphysema. The pathogenesis of ALS depends on the anatomy of the mediastinum and its associations with thoracic, abdominal and cervical connective tissues, as well as a physical phenomenon referred to as the Macklin effect. Various animal species develop diverse combinations of these lesions, although ALS has not been recognized in animals. However, this term aids pathologists in addressing this disease compilation. The aim of this retrospective study is to illustrate examples of ALS in animals by arbitrarily selecting 13 cases in dogs, cats, pinnipeds, sea otters and harbour porpoises. ALS can be classified into three groups based on aetiology: iatrogenic, secondary or spontaneous. Iatrogenic ALS was diagnosed in two cats with tracheal laceration following endotracheal intubation. Secondary ALS was identified in two dogs, one with acute respiratory distress syndrome and the other due to grass awn migration. Secondary ALS in pinnipeds was diagnosed following severe pulmonary parasitism, uraemic pneumonia and oesophageal perforation. The other marine mammals developed ALS following trauma. Spontaneous ALS was also diagnosed in one cat and one dog without any apparent predisposing causes.
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Neumotórax , Animales , Gatos , Neumotórax/veterinaria , Neumotórax/etiología , Perros , Enfisema Mediastínico/veterinaria , Estudios Retrospectivos , Enfermedades de los Gatos/patología , Enfermedades de los Perros/patología , Femenino , Masculino , Enfisema Subcutáneo/veterinaria , Enfisema Subcutáneo/etiología , Neumoperitoneo/veterinariaRESUMEN
Introduction: The clinical success of chimeric antigen receptor-modified T cells (CAR-T cells) for hematological malignancies has not been reproduced for solid tumors, partly due to the lack of cancer-type specific antigens. In this work, we used a novel combinatorial approach consisting of a versatile anti-FITC CAR-T effector cells plus an FITC-conjugated neuroblastoma (NB)-targeting linker, an FITC-conjugated monoclonal antibody (Dinutuximab) that recognizes GD2. Methods: We compared cord blood (CB), and CD45RA-enriched peripheral blood leukapheresis product (45RA) as allogeneic sources of T cells, using peripheral blood (PB) as a control to choose the best condition for anti-FITC CAR-T production. Cells were manufactured under two cytokine conditions (IL-2 versus IL-7+IL-15+IL-21) with or without CD3/CD28 stimulation. Immune phenotype, vector copy number, and genomic integrity of the final products were determined for cell characterization and quality control assessment. Functionality and antitumor capacity of CB/45RA-derived anti-FITC CAR-T cells were analyzed in co-culture with different anti-GD2-FITC labeled NB cell lines. Results: The IL-7+IL-15+IL-21 cocktail, in addition to co-stimulation signals, resulted in a favorable cell proliferation rate and maintained less differentiated immune phenotypes in both CB and 45RA T cells. Therefore, it was used for CAR-T cell manufacturing and further characterization. CB and CD45RA-derived anti-FITC CAR-T cells cultured with IL-7+IL-15+IL-21 retained a predominantly naïve phenotype compared with controls. In the presence of the NB-FITC targeting, CD4+ CB-derived anti-FITC CAR-T cells showed the highest values of co-stimulatory receptors OX40 and 4-1BB, and CD8+ CAR-T cells exhibited high levels of PD-1 and 4-1BB and low levels of TIM3 and OX40, compared with CAR-T cells form the other sources studied. CB-derived anti-FITC CAR-T cells released the highest amounts of cytokines (IFN-γ and TNF-α) into co-culture supernatants. The viability of NB target cells decreased to 30% when co-cultured with CB-derived CAR-T cells during 48h. Conclusion: CB and 45RA-derived T cells may be used as allogeneic sources of T cells to produce CAR-T cells. Moreover, ex vivo culture with IL-7+IL-15+IL-21 could favor CAR-T products with a longer persistence in the host. Our strategy may complement the current use of Dinutuximab in treating NB through its combination with a targeted CAR-T cell approach.
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Neuroblastoma , Receptores Quiméricos de Antígenos , Humanos , Linfocitos T , Interleucina-15/metabolismo , Interleucina-7/metabolismo , Fluoresceína-5-Isotiocianato , Citocinas/metabolismoRESUMEN
Sound zones are used to reproduce individual audio content to multiple people in a room using a set of loudspeakers with controllable input signals. To allow the reproduction of individual audio to dynamically change, e.g., due to moving listeners, changes in the number of listeners, or changing room transfer functions, an adaptive formulation is proposed. This formulation is based on frequency domain block adaptive filters and given room transfer functions. To reduce computational complexity, the system is extended to subband processing without cross-adaptive filters. The computational savings come from recognizing that sound zones consist of part-solutions which are inherently band limited, hence, several subbands can be ignored. To validate the theoretical findings, a 27-channel loudspeaker array was constructed, and measurements were performed in anechoic and reflective environments. The results show that the subband solution performs identically to a full-rate solution but at a reduced computational complexity.
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Introduction: The purpose of this study is to produce a bibliometric review of the 30 most cited articles related to 6 major domains of body contouring-abdominoplasty, thighplasty, brachioplasty, gluteoplasty, body lift, and liposuction-for resident and fellow education. Methods: The authors utilized the Web of Science Citation Index to identify the 30 most cited articles related to surgery for body contouring published from 1975 to 2020. Articles were classified according to their level of evidence, type of study, and country of publication. Results: A total of 336 articles were reviewed to compile our list. The mean number of citations across the articles was 114.7 ± SD 86.1. The highest prevalence of the papers was published between 2000 and 2009 (n = 15, 50%). The country with the highest number of contributions was the United States (n = 22, 73%). Plastic and Reconstructive Surgery served as the main journal of publication for these papers (n = 22, 73.3%). The majority of articles were designated for clinical-type studies (n = 26, 86.7%). No basic science or prevalence study design papers were listed. In terms of level of evidence (LoE), most papers were assigned IV (n = 11, 36.7%) and III (n = 7, 23.3%). Conclusions: Our study reveals that the most cited papers in body contouring are of LoE III and IV. Although the LoE of plastic surgery research, in general, has improved, in the past decade, a call for higher quality papers remains. Overall, this analysis provides an easy, electronic starting point for residents and fellows interested in understanding the field's evolution.
Introduction : La présente étude vise à produire une analyse bibliométrique de 30 articles influents liés à six grands domaines du remodelage corporel (l'abdominoplastie, le redrapage des cuisses, la brachioplastie, la glutéoplastie, le redrapage du corps et la liposuccion) pour la formation des résidents et des étudiants en stage de perfectionnement postdoctoral. Méthodologie : Les auteurs ont utilisé l'index de citation de Web of Science pour extraire les 30 articles les plus cités sur les opérations de remodelage corporel publiés entre 1975 et 2020. Ils ont classé les articles d'après la qualité des preuves, le type d'étude et le pays de publication. Résultats : Au total, les auteurs ont analysé 336 articles pour compiler leur liste. Les articles contenaient un nombre moyen de 114,7± ÉT 86,1 citations. La plus forte prévalence d'articles a été publiée entre 2000 et 2009 (n = 15, 50 %). La majorité des articles provenaient des États-Unis d'Amérique (n = 22, 73 %), et c'est la revue Plastic and Reconstructive Surgery© qui en a publié le plus (n = 22, 73,3 %). La plupart des articles prenaient la forme d'études de type clinique (n = 26, 86,7 %). Aucun article de science fondamentale ni étude de prévalence n'a été répertorié. Pour ce qui est de la qualité des preuves, la plupart des articles ont obtenu un classement de IV (n = 11, 36,7 %) et de III (n = 7, 23,3 %). Conclusions : L'étude révèle que la qualité de preuve de la plupart des articles dans ce domaine était de III et IV. Même si la chirurgie plastique se prête moins bien aux études randomisées et contrôlées que la médecine, elle mérite des articles comportant une meilleure qualité de preuves. Grâce à la présente analyse, les résidents et les étudiants en stage de perfectionnement peuvent accéder rapidement et facilement à des concepts influents pour comprendre l'évolution du domaine par voie électronique. Termes MeSH : abdominoplastie, bibliométrie, chirurgie plastique, études transversales, liposuccion, remodelage corporel.
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Portal vein thrombosis is a rare complication after laparoscopic sleeve gastrectomy, a widely performed bariatric surgery procedure. Occasionally, the development of portal vein thrombosis can progress to more severe conditions, including portal hypertension and cavernomatosis, thereby presenting a complex and challenging clinical scenario. The management of such complications often requires careful consideration; however, surgical intervention in the form of a splenorenal shunt is an exceptional indication. We present the case of a 33-year-old female patient who had previously undergone laparoscopic sleeve gastrectomy in 2014 and subsequently developed portal thrombosis, followed by cavernomatosis and associated complications of portal hypertension. A proximal splenorenal shunt procedure and splenectomy were successfully performed to manage portal hypertension. The presentation of this clinical case aims to contribute to the available evidence and knowledge surrounding this rare and challenging pathology.
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Importance: Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial. Objective: To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI. Data Sources: PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched. Study Selection: Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction. Main Outcome Measures: The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI. Results: A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients. Conclusion and Relevance: Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.
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Anticonvulsivantes , Lesiones Traumáticas del Encéfalo , Convulsiones , Humanos , Lesiones Traumáticas del Encéfalo/complicaciones , Anticonvulsivantes/uso terapéutico , Convulsiones/prevención & control , Convulsiones/etiologíaRESUMEN
Metal-air batteries are an emerging technology with great potential to satisfy the demand for energy in high-consumption applications. However, this technology is still in an early stage, facing significant challenges such as a low cycle life that currently limits its practical use. Poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymer has already demonstrated its efficiency as catalyst for oxygen reduction reaction (ORR) discharge as an alternative to traditional expensive and nonsustainable metal catalysts. Apart from that, in most electrochemical processes, three phenomena are needed: redox activity and electronic and ionic conduction. Material morphology is important to maximize the contact area and optimize the 3 mechanisms to obtain high-performance devices. In this work, porous scaffolds of PEDOT-organic ionic plastic crystal (OIPC) are prepared through vapor phase polymerization to be used as porous self-standing cathodes. The scaffolds, based on abundant elements, showed good thermal stability (200 °C), with potential ORR reversible electrocatalytic activity: 60% of Coulombic efficiency in aqueous medium after 200 cycles.