Comprehensive characterization of γ-aminobutyric acid (GABA) production by Levilactobacillus brevis CRL 2013: insights from physiology, genomics, and proteomics.

Introduction: Levilactobacillus brevis CRL 2013, a plant-derived lactic acid bacterium (LAB) with immunomodulatory properties, has emerged as an efficient producer of γ-aminobutyric acid (GABA). Notably, not all LAB possess the ability to produce GABA, highlighting the importance of specific genetic and environmental conditions for GABA synthesis. This study aimed to elucidate the intriguing GABA-producing machinery of L. brevis CRL 2013 and support its potential for safe application through comprehensive genome analysis. Methods: A comprehensive genome analysis of L. brevis CRL 2013 was performed to identify the presence of antibiotic resistance genes, virulence markers, and genes associated with the glutamate decarboxylase system, which is essential for GABA biosynthesis. Then, an optimized chemically defined culture medium (CDM) was supplemented with monosodium glutamate (MSG) and yeast extract (YE) to analyze their influence on GABA production. Proteomic and transcriptional analyses were conducted to assess changes in protein and gene expression related to GABA production. Results: The absence of antibiotic resistance genes and virulence markers in the genome of L. brevis CRL 2013 supports its safety for potential probiotic applications. Genes encoding the glutamate decarboxylase system, including two gad genes (gadA and gadB) and the glutamate antiporter gene (gadC), were identified. The gadB gene is located adjacent to gadC, while gadA resides separately on the chromosome. The transcriptional regulator gadR was found upstream of gadC, with transcriptional analyses demonstrating cotranscription of gadR with gadC. Although MSG supplementation alone did not activate GABA synthesis, the addition of YE significantly enhanced GABA production in the optimized CDM containing glutamate. Proteomic analysis revealed minimal differences between MSG-supplemented and non-supplemented CDM cultures, whereas YE supplementation resulted in significant proteomic changes, including upregulation of GadB. Transcriptional analysis confirmed increased expression of gadB and gadR upon YE supplementation, supporting its role in activating GABA production. Conclusion: These findings provide valuable insights into the influence of nutrient composition on GABA production. Furthermore, they unveil the potential of L. brevis CRL 2013 as a safe, nonpathogenic strain with valuable biotechnological traits which can be further leveraged for its probiotic potential in the food industry.

Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis.

Introduction: Non-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival. Results: We identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55-58) versus 72 months (95% CI 71-73) (hazard ratio (HR) 1.14, 95% CI 1.12-1.15, p = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62-69) versus NHW 69 months (95% CI 97-71) (HR 1.02, 95% CI 0.98-1.07, p = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility (p < 0.001); NHB race had more effect in patients <65 years old (HR 1.44, 95% CI 1.39-1.49, p < 0.001) than in those ≥65 (HR 1.13, 95% CI 1.11-1.15, p < 0.001). In the VA, age stratification was not significant (p = 0.21). Discussion: Racial disparities in CRC survival in the general US population are significantly attenuated in Medicare-aged patients. This pattern is not present in the VA, suggesting that access to care may be an important component of racial disparities in this disease.

Recent progress in adverse events of carboxylic acid non-steroidal anti-inflammatory drugs (CBA-NSAIDs) and their association with the metabolism: the consequences on mitochondrial dysfunction and oxidative stress, and prevention with natural plant extracts.

INTRODUCTION: Carboxylic acid non-steroidal anti-inflammatory drugs (CBA-NSAIDs) are extensively used worldwide due to their antipyretic, analgesic, and anti-inflammatory effects. CBA-NSAIDs have reasonable margin of safety at therapeutic doses, and in the current climate, do not possess addiction potential like opioid drugs. Studies have revealed that various adverse events of CBA-NSAIDs are related mitochondrial dysfunction and oxidative stress. AREAS COVERED: This review article summarizes adverse events induced by CBA-NSAIDs, mechanisms of mitochondrial damage, oxidative stress, and metabolic interactions. Meanwhile, this review discusses the treatment and prevention of CBA-NSAIDs damage by natural plant extracts based on antioxidant effects. EXPERT OPINION: CBA-NSAIDs can induce reactive oxygen species (ROS) production, mediate DNA, protein and lipid damage, lead to imbalance of cell antioxidant status, change of mitochondrial membrane potential, activate oxidative stress signal pathway, thus leading to oxidative stress and cell damage. Adverse events caused by CBA-NSAIDs often exhibit dose and time dependence. In order to avoid adverse events caused by CBA-NSAIDs, it is necessary to provide detailed patient consultation and eliminate influencing factors. Moreover, constructive research studies on the organ-specific toxicity and mechanism of natural plant extracts in preventing and treating metabolic abnormalities of CBA-NSAIDs, will provide important value for warning and guidance for use of CBA-NSAIDs.

Development and Implementation of a Safety Incident Report System for Health Care Discipline Students During Clinical Internships: Observational Study.

BACKGROUND: Patient safety is a fundamental aspect of health care practice across global health systems. Safe practices, which include incident reporting systems, have proven valuable in preventing the recurrence of safety incidents. However, the accessibility of this tool for health care discipline students is not consistent, limiting their acquisition of competencies. In addition, there is no tools to familiarize students with analyzing safety incidents. Gamification has emerged as an effective strategy in health care education. OBJECTIVE: This study aims to develop an incident reporting system tailored to the specific needs of health care discipline students, named Safety Incident Report System for Students. Secondary objectives included studying the performance of different groups of students in the use of the platform and training them on the correct procedures for reporting. METHODS: This was an observational study carried out in 3 phases. Phase 1 consisted of the development of the web-based platform and the incident registration form. For this purpose, systems already developed and in use in Spain were taken as a basis. During phase 2, a total of 223 students in medicine and nursing with clinical internships from universities in Argentina, Brazil, Colombia, Ecuador, and Spain received an introductory seminar and were given access to the platform. Phase 3 ran in parallel and involved evaluation and feedback of the reports received as well as the opportunity to submit the students' opinion on the process. Descriptive statistics were obtained to gain information about the incidents, and mean comparisons by groups were performed to analyze the scores obtained. RESULTS: The final form was divided into 9 sections and consisted of 48 questions that allowed for introducing data about the incident, its causes, and proposals for an improvement plan. The platform included a personal dashboard displaying submitted reports, average scores, progression, and score rankings. A total of 105 students participated, submitting 147 reports. Incidents were mainly reported in the hospital setting, with complications of care (87/346, 25.1%) and effects of medication or medical products (82/346, 23.7%) being predominant. The most repeated causes were related confusion, oversight, or distractions (49/147, 33.3%) and absence of process verification (44/147, 29.9%). Statistically significant differences were observed between the mean final scores received by country (P<.001) and sex (P=.006) but not by studies (P=.47). Overall, participants rated the experience of using the Safety Incident Report System for Students positively. CONCLUSIONS: This study presents an initial adaptation of reporting systems to suit the needs of students, introducing a guided and inspiring framework that has garnered positive acceptance among students. Through this endeavor, a pathway toward a safety culture within the faculty is established. A long-term follow-up would be desirable to check the real benefits of using the tool during education. TRIAL REGISTRATION: Trial Registration: ClinicalTrials.gov NCT05350345; https://clinicaltrials.gov/study/NCT05350345.

Disparities for Hispanic Adults with metabolic dysfunction-associated steatotic liver disease in the US: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) is reported to be higher in Hispanic adults in the United States (US), though rates vary substantially across studies and have increased given the evolving obesity epidemic. This systematic review and meta-analysis quantifies MASLD disease burden and severity in contemporary cohorts to characterize health disparities experienced by adult Hispanic individuals in the US. METHODS: We searched MEDLINE, Embase and Cochrane databases per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies from 2010 to December 2023 were included to capture data representative of current populations given the obesity epidemic. Studies from overlapping cohorts were excluded. Meta-analyses were conducted using random-effects models to estimate pooled prevalence and relative risk (RR) with 95% confidence intervals (CIs). RESULTS: We identified 22 studies, comprising 756,088 subjects, of which 62,072 were Hispanic. The pooled prevalence (95% CI) in US Hispanic adults was 41% (95% CI: 30-52%) for MASLD, 61% (95% CI: 39-82%) for metabolic dysfunction-associated steatohepatitis (MASH), 27% (95% CI: 15-39%) for MASH-associated advanced fibrosis (AF), and 5% (95% CI: 1-8%) for MASH cirrhosis. Compared to non-Hispanic adults, Hispanic adults had a RR of 1.50 (95% CI: 1.32-1.69) for MASLD, 1.42 (95% CI: 1.04-1.93) for MASH, 1.37 (95% CI: 0.96-1.96) for MASH-associated AF and 0.93 (95% CI: 0.49-1.77) for MASH cirrhosis. CONCLUSION: Health disparities for US Hispanic adults continue to worsen with significantly higher relative risk of MASLD and MASH compared to non-Hispanic adults. Public health efforts to optimize screening and care delivery for adult Hispanic population are urgently needed.

Identifying pesticides of high concern for ecosystem, plant, animal, and human health: A comprehensive field study across Europe and Argentina.

The widespread and excessive use of pesticides in modern agricultural practices has caused pesticide contamination of the environment, animals, and humans, with confirmed serious health consequences. This study aimed to identify the 20 most critical substances based on an analysis of detection frequency (DF) and median concentrations (MC) across environmental and biological matrices. A sampling campaign was conducted across 10 case study sites in Europe and 1 in Argentina, each encompassing conventional and organic farming systems. We analysed 209 active substances in a total of 4609 samples. All substances ranked among the 20 most critical were detected in silicon wristbands worn by humans and animals and indoor dust from both farming systems. Five of them were detected in all environmental matrices. Overall, higher values of DF and MC, including in the blood plasma of animals and humans, were recorded in samples of conventional compared to organic farms. The differences between farming systems were greater in the environmental samples and less in animal and human samples. Ten substances were detected in animal blood plasma from conventional farms and eight in animal blood plasma from organic farms. Two of those, detected in both farming systems, are classified as hazardous for mammals (acute). Five substances detected in animal blood plasma from organic farms and seven detected in animal blood plasma from conventional farms are classified as hazardous for mammals (dietary). Three substances detected in human blood plasma are classified as carcinogens. Seven of the substances detected in human blood plasma are classified as endocrine disruptors. Six substances, of which five were detected in human blood plasma, are hazardous for reproduction/development. Efforts are needed to elucidate the unknown effects of mixtures, and it is crucial that such research also considers biocides and banned substances, which constitute a baseline of contamination that adds to the effect of substances used in agriculture.

Psychological distress, health-promoting lifestyle and sociodemographic factors in Honduran university students: a structural equation model.

This study sought to analyze an explanatory model on the relationship among sociodemographic factors, health-promoting lifestyle behaviors and psychological distress (depression, anxiety and stress) in college students. This is an observational, analytical and cross-sectional study conducted on a national sample of 4203 students who entered a macro university in Honduras in 2021, 2022 and 2023. We used a sociodemographic survey, the Health-Promoting Lifestyle Profile (HPLP-II) and the Depression, Anxiety and Stress Scales (DASS-21). Univariate analysis and a multivariate structural equation model were conducted. The average HPLP-II score was 117.45 (±â€…23.41), and the average DASS-21 score was 20.06 (±â€…14.16). The multivariate model showed a good data fit (comparative fit index = 0.951; Tucker-Lewis index = 0.957; root mean square error of approximation = 0.067 [90% CI = 0.067-0.068]). Results indicate that being a woman (ß = 0.11; p < 0.001) and being enrolled in biological and health sciences (ß = 0.09; p < 0.001) significantly predict HPLP-II scores. Furthermore, being a woman (ß = 0.17; p < 0.001), age (ß = 0.10; p < 0.001) and having pre-existing medical conditions (ß = 0.16; p < 0.001) significantly explain part of the variance of DASS-21. A significant reverse relationship between health-promoting behavior and psychological distress was shown (r = -0.36; p < 0.001). This study identifies protective and risky sociodemographic factors linked to health-promoting lifestyle behaviors and psychological distress. Our findings have implications for developing comprehensive intervention policies and strategies to promote health in higher education settings.

A Comprehensive Approach to Parkinson's Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects.

Parkinson's disease (PD) is a gradually worsening neurodegenerative disorder affecting the nervous system, marked by a slow progression and varied symptoms. It is the second most common neurodegenerative disease, affecting over six million people in the world. Its multifactorial etiology includes environmental, genomic, and epigenetic factors. Clinical symptoms consist of non-motor and motor symptoms, with motor symptoms being the classic presentation. Therapeutic approaches encompass pharmacological, non-pharmacological, and surgical interventions. Traditional pharmacological treatment consists of administering drugs (MAOIs, DA, and levodopa), while emerging evidence explores the potential of antidiabetic agents for neuroprotection and gene therapy for attenuating parkinsonian symptoms. Non-pharmacological treatments, such as exercise, a calcium-rich diet, and adequate vitamin D supplementation, aim to slow disease progression and prevent complications. For those patients who have medically induced side effects and/or refractory symptoms, surgery is a therapeutic option. Deep brain stimulation is the primary surgical option, associated with motor symptom improvement. Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy and a portable infusion pump succeeded in reducing "off" time, where non-motor and motor symptoms occur, and increasing "on" time. This article aims to address the general aspects of PD and to provide a comparative comprehensive review of the conventional and the latest therapeutic advancements and emerging treatments for PD. Nevertheless, further studies are required to optimize treatment and provide suitable alternatives.

Comorbidities and use of health services in people with diabetes mellitus according to risk levels by adjusted morbidity groups.

BACKGROUND: People with diabetes mellitus frequently have other comorbidities and involve greater use of primary and hospital care services. The aim of this study was to describe the comorbidities and use of primary and hospital care services of people with diabetes according to their risk level by adjusted morbidity groups (AMG) and to analyse the factors associated with the utilisation of these services. METHODS: Cross-sectional study. People with diabetes were identified within the population of patients with chronic conditions of an urban health care centre by the AMG stratification tool integrated into the primary health care electronic clinical record of the Community of Madrid. Sociodemographic, functional, clinical characteristics and annual health care services utilisation variables were collected. Univariate, bivariate and Poisson regression analyses were performed. RESULTS: A total of 1,063 people with diabetes were identified, representing 10.8% of patients with chronic conditions within the health centre. A total of 51.4% were female, the mean age was 70 years, 94.4% had multimorbidity. According to their risk level, 17.8% were high-risk, 40.6% were medium-risk and 41.6% were low-risk. The most prevalent comorbidities were hypertension (70%), dyslipidaemia (67%) and obesity (32.4%). Almost 50% were polymedicated. Regarding health services utilisation, 94% were users of primary care, and 59.3% were users of hospital care. Among the main factors associated with the utilisation of both primary and hospital care services were AMG risk level and complexity index. In primary care, utilisation was also associated with the need for primary caregivers, palliative care and comorbidities such as chronic heart failure and polymedication, while in hospital care, utilisation was also associated with comorbidities such as cancer, chronic obstructive pulmonary disease or depression. CONCLUSIONS: People with diabetes were older, with important needs for care, many associated comorbidities and polypharmacy that increased in parallel with the patient's risk level and complexity. The utilisation of primary and hospital care services was very high, being more frequent in primary care. Health services utilization were principally associated with functional factors related to the need of care and with clinical factors such as AMG medium and high-risk level, more complexity index, some serious comorbidities and polymedication.

Significant tricuspid regurgitation is associated with adverse outcomes in patients with transthyretin amyloid cardiomyopathy.

Objectives: Patients diagnosed with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience poor outcomes due to the development of heart failure (HF). Tricuspid regurgitation (TR) has been found to be correlated with adverse outcomes in patients with HF. This study aims to assess whether the presence of significant TR is associated to adverse cardiac outcomes in patients diagnosed with ATTR-CM. Materials and methods: Retrospective study of ATTR-CM patients enrolled in the Institutional Registry of Amyloidosis (NCT01347047). Patients were categorized based on the presence of significant TR (moderate or severe according to current guidelines criteria) or absence of significant TR. All patients were followed up for 2 years to assess the incidence of the composite outcome of death or HF hospitalization. Results: A total of 93 ATTR-CM patients were included. The mean age at diagnosis was 82.5 [IQR 75 - 86] years, 86% were male, and the mean left ventricular ejection fraction was 52% [IQR 43 - 60]. Among them, 32.3% (n = 30) patients had significant TR. Patients with significant TR had higher NTpro-BNP values (5308 vs 2454, pg/mL, p = 0.004), and a lower left ventricular ejection fraction (44 vs. 56%, p = 0.0002) compared to patients without significant TR. The incidence of the primary outcome was higher in patients with significant TR (77% vs. 30%, p<0.001). In a multivariate Cox regression analysis, only NTpro-BNP, as a numerical variable (HR 1.00, 95% CI 1.00005-1.0002, p = 0.001), and significant TR (HR 2.23, 95% CI 1.12-4.42, p=0.021) were independently associated with the composite outcome of death or HF hospitalization. Conclusions: In patients diagnosed with ATTR-CM, the presence of significant TR was associated with worse outcomes.

Objetivos: Los pacientes con diagnóstico de miocardiopatía amiloidótica por transtiretina (ATTR) suelen presentar mal pronóstico, principalmente por el desarrollo de insuficiencia cardiaca (IC). Se ha descrito que la insuficiencia tricúspidea (IT) está relacionada con peor pronóstico en pacientes con IC. Este estudio tiene como objetivo evaluar el impacto pronóstico de la IT significativa en pacientes con diagnóstico de amiloidosis ATTR. Materiales y métodos: Estudio de cohorte retrospectiva. Se incluyeron pacientes con diagnóstico de amiloidosis ATTR pertenecientes al registro institucional de amiloidosis de nuestra institución (NCT01347047). Los pacientes fueron divididos según la presencia o no de IT significativa (moderada o severa, de acuerdo a las guías de práctica clínica actuales). Se realizó un seguimiento con censura a los 2 años para evaluar la incidencia del punto final primario combinado de muerte u hospitalizaciones por IC. Resultados: Se incluyeron 93 pacientes con diagnóstico de amiloidosis ATTR. La mediana de edad fue de 82,5 años [RIC 75-85], 86% fueron hombres. La mediana de fracción de eyección ventricular izquierda fue de 52% [RIC 43-60]. El 32,3% (n=30) de pacientes presentaron IT significativa al momento del diagnóstico de la amiloidosis ATTR. Aquellos con IT significativa tuvieron valores superiore de NT-proBNP (5308 vs. 2454, pg/mL, p=0.004) y menor mediana de fracción de eyección ventricular izquierda (44% vs. 56%, p=0,0002) comparado con los pacientes sin IT significativa. En el seguimiento a 2 años, la incidencia del punto final primario combinado fue mayor en pacientes con IT significativa (77% vs. 30%, p<0,001). En un modelo de regresión de Cox multivariada, solo el NT-proBNP (HR 1,00, 95% CI 1,00005-1,0002, p=0,001) y la IT significativa (HR 2.23, 95% CI 1.12-4.42, p=0.021) estuvieron asociadas de forma independiente con la ocurrencia del punto final primario combinado. Conclusiones: En pacientes con diagnóstico de miocardiopatía amiloidótica por ATTR, la presencia de IT significativa se asoció a peor pronóstico en el seguimiento.

Highly (regio)selective hydroformylation of olefins using self-assembling phosphines.

New phosphines with self-assembling 6-pyridinone moities were prepared, characterized, and examined in the hydroformylation of diverse olefins. Testing various known and novel ligands in the presence of [Rh(acac)(CO)2] under industrially relevant conditions, the hydroformylation of 1-octene proceeds best with 6,6'-(phenylphosphanediyl)bis(pyridin-2(1H)-one) (DPONP). Control experiments and modelling studies indicate dimerization of this ligand at higher temperatures (>100 °C). The optimal catalyst system is able to conserve high product linearity (>90%) for a broad range of olefins at industrially-employed temperatures at low ligand loading.

The innovative double or triple dental abutment-implant: Case study with a 3-to-12-year follow-up.

BACKGROUND: The aim of this case study is to present the rationality and scientific evidence of a new design for a double (DA) and triple (TA) dental abutment-implant with their specific new concept of biodynamic optimized peri-implant tissue (BOPiT). METHODS: The innovative design of these abutments with a paraboloid geometry was based on BOPiT, simultaneously involving the principles of mechanobiology, biotensegrity, and mechanotransduction. Thus, 37 consecutive individuals/43 cases rehabilitated with single dental implant using the innovative DA (n = 28) and TA (n = 15) on 43 implants were included in this case study. The DA and TA support 2 or 3 dental crowns on a single implant, respectively. Clinic and radiographic examinations were presented at T1 (loading after 4 months) and T2 [final examination with an average follow-up time of 7.2 years (>3 to 12 years)]. RESULTS: At T2, mean scores for plaque index, peri-implant bleeding on probing, and peri-implant probing depth were low, depicting healthy peri-implant conditions. All radiographic images showed insignificant annual marginal bone loss (0.022 ± 0.05 mm) when compared to T1, reflecting great bone stability. CONCLUSION: DA and TA, based on the BOPiT concept, represent an advantageous, simple and non-invasive mechanism for the longevity and healthy regulation of the peri-implant tissues.

Cierre de conducto arterioso persistente con dispositivo OcclutechTM, experiencia en un país andino / Closure of patent ductus arteriosus with OcclutechTM device, experience in an andean country

Resumen Objetivo: Presentar la experiencia en un país andino con el dispositivo OcclutechTM Duct Occluder para el cierre del conducto arterioso persistente. Método: Estudio observacional, retrospectivo, de corte transversal con análisis estadístico básico. Periodo: diciembre/2014 a diciembre/2022. Datos: historia clínica, informes de laboratorio de cateterismo. Resultados: Cuarenta y seis pacientes; de sexo femenino 71.3%, de sexo masculino 28.7%; edad: 0.6-38 años (mediana [Me]: 5.2); peso: 6.3-60 kg (Me: 16.5). Procedencia: andina 91.3%, costa 8.7%. Tipos de conducto arterioso persistente: E 54.4%, A 32.6%, D 13%. Diámetro ductal mínimo: 1.8-11.8 mm (Me: 3.5). Presión media de la arteria pulmonar previo a la oclusión: 14-67 mmHg (Me: 27). Índice de resistencias vasculares pulmonares previo a la oclusión: 0.28-4.9 UW/m2 (Me: 1.3). Fueron catalogados como conductos arteriosos persistentes hipertensivos seis de ellos. Tasa de oclusión: inmediata el 47.8%, a las 24 horas el 81%, a los seis meses el 100%. Tiempo de fluoroscopia: 2-13.8 minutos (Me: 4). Complicaciones: un dispositivo migrado. Seguimiento: 1-6.5 años. Conclusiones: El dispositivo OcclutechTM Duct Occluder fue efectivo y seguro para el cierre de conducto arterioso persistente tipo E, A y D en habitantes de baja y alta altitud, ya sea que estos hubieran sido niños o adultos, incluso cuando estos conductos arteriosos fueron hipertensivos.

Abstract Objective: To communicate the experience in an Andean country with the OcclutechTM Duct Occluder device for the closure of patent ductus arteriosus. Method: Observational, retrospective, cross-sectional study with basic statistical analysis. Period: December/2014 to December/2022. Data: medical chart, reports of catheterization. Results: Forty-six patients, female 71.3%, male 28.7%; age: 0.6-38 years-old (median [Me]: 5.2); weight: 6.3-60 kg (Me: 16.5). Origin: andean 91.3%, coast 8.7%. Types of patent ductus arteriosus: E 54.4%, A 32.6%, D 13%. Minimum ductal diameter: 1.8-11.8 mm (Me: 3.5). Mean pulmonary artery pressure prior to occlusion: 14-67 mmHg (Me: 27). Pulmonary vascular resistance index prior to occlusion: 0.28-4.9 WU/m2 (Me: 1.3). Six of them were classified as hypertensive patent ductus arteriosus. Occlusion rate: 47.8% immediate, 81% at 24 hours, 100% after six months. Fluoroscopy time: 2-13.8 minutes (Me: 4). Complications: a migrated device. Follow-up: 1-6.5 years. Conclusions: OcclutechTM Duct Occluder device was effective and safe for the closure of patent ductus arteriosus type E, A and D in low-altitude and high-altitude dwellers, whether they were children or adults, even when these ductus arteriosus were hypertensive.

A two-years real-word study with fingolimod: early predictors of efficacy and an association between EBNA-1 IgG titers and multiple sclerosis progression.

Background: Although fingolimod, a sphingosine 1-phosphate receptor agonist, has shown to be an effective treatment reducing relapse rate and also slowing down the disability progression in relapsing-remitting multiple sclerosis (RRMS) patients, it is important to quickly identify those suboptimal responders. Objective: The main objective was to assess different clinical, radiological, genetic and environmental factors as possible early predictors of response in MS patients treated with fingolimod for 24 months. The secondary objective was to analyze the possible contribution of the environmental factors analyzed to the progression and activity of the disease along the 2-years of follow-up. Methods: A retrospective study with 151 patients diagnosed with MS, under fingolimod treatment for 24 months, with serum samples at initiation and six months later, and with clinical and radiological data at initiation and 24 months later, were included in the study. Clinical and radiological variables were collected to establish NEDA-3 (no evidence of disease activity: patients without relapses, disability progression and new T2 lesions or Gd+ lesions) and EDA (evidence of disease activity: patients with relapses and/or progression and/or new T2 lesions or gadolinium-positive [Gd+] lesions) conditions. Human leukocyte antigen II (HLA-II), EBNA-1 IgG and VCA IgG from Epstein-Barr virus (EBV) and antibody titers against Human herpesvirus 6A/B (HHV-6A/B) were also analyzed. Results: A total of 151 MS patients fulfilled the inclusion criteria: 27.8% was NEDA-3 (37.5% among those previously treated with high efficacy therapies >24 months). The following early predictors were statistically significantly associated with NEDA-3 condition: sex (male; p=0.002), age at baseline (older; p=0.009), relapses 2-years before fingolimod initiation ≤1 (p=0.010), and absence of Gd+ lesions at baseline (p=0.006). Regarding the possible contribution of the environmental factors included in the study to the activity or the progression of the disease, we only found that EBNA-1 IgG titers decreased in 20.0% of PIRA (progression independent from relapse activity) patients vs. 73.3% of RAW (relapse-associated worsening) patients (p=0.006; O.R. = 11.0). Conclusion: MS patients that are male, older, and with a low clinical and radiological activity at fingolimod initiation have a greater probability to reach NEDA-3 condition after two years with this therapy. An intriguing association of EBV with the progression of the disease has also been described, but it should be further study in a larger cohort to confirm these results.

A Randomized Control Trial of Dexketoprofen/Vitamin B (Thiamine, Pyridoxine and Cyanocobalamin) Fixed-Dose Combination in Post-Traumatic Grade I-II Cervical Sprains.

BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).

Internal and external validation of indocyanine green plasma disappearance rate to discard liver grafts before procurement.

Backgrounds/Aims: Thirty percent of liver grafts in donors after brain death (DBD) in Spain are rejected by procurement surgeons owing to marginal graft quality. Poor donor indocyanine green (ICG) clearance has been associated with graft discard and malfunction. This study aimed to internally and externally validate the predictive value of ICG-plasma disappearance rate (ICG-PDR) to reject grafts before donation and set a cut-off to avoid missing any potential effective donors. Methods: Between March 2017 and August 2023, ICG clearance test was performed immediately before procurement in 71 DBD. The surgeon was blinded to test results. Univariate and multivariate analyses were performed to detect independent predictors of graft discard. Discrimination and calibration of predictors were assessed and a cut-off with 100% specificity was set. External validation was performed on 17 donors evaluated by three other transplantation teams. Results: In the training cohort, 30 of 71 grafts were discarded for transplantation. ICG-PDR was the only donor variable independently associated with graft discard. The area under receiver operating characteristic curve for ICG-PDR was 0.875 (95% confidence interval: 0.768-0.947) and good calibration was observed. Below a PDR of 13.5%/min, no graft was accepted for transplantation. These results were successfully validated using the external cohort of donors. Conclusions: ICG clearance test performed in DBD was internally and externally validated to predict liver graft discard. It could be used as a screening tool before donation to avoid unnecessary costs of travel and human resources.

Development and evaluation of two educational sessions on take-home lead exposure prevention for construction workers and their families.

Take-home exposures occur when workers accidentally bring workplace contaminants home. Regular job responsibilities may expose construction workers to lead, which extends to their households via the take-home pathway. The present study aimed to develop and evaluate 2 educational sessions addressing take-home lead exposure tailored to construction workers and their families. Educational materials on take-home lead exposure and prevention strategies were designed following guidance from US government institutions and experts on construction work, lead exposure, and educational interventions. The educational materials were pilot-tested with construction workers and their family members during in-person or online sessions in English or Spanish. Changes in knowledge of take-home lead exposure were assessed through pre- and post-testing and open-ended feedback was collected from both participants and session facilitators. The study sample comprised 44 participants, including 33 workers and 11 family members. Among all participants, 81% were male, 46% were Hispanic or Latino, and the average age was 29 years. Post-test scores (µ = 93%, SD = 10%) were higher than pre-test scores (µ = 82%, SD = 19%), and younger participants (<30 years) were more likely to have a lower pre-test score compared to older participants (≥30 years). Overall, feedback from participants and facilitators was positive, indicating appropriate duration, appealing visuals, and ease of engagement through the training activities. Effective public health education for lead-exposed construction workers and their families is needed to reduce lead exposure disparities, especially among children of workers. Interventions must recognize that take-home exposures are not isolated to occupational or home environments.

Colchicine in acute heart failure: Rationale and design of a randomized double-blind placebo-controlled trial (COLICA).

AIMS: Heart failure (HF) elicits a pro-inflammatory state, which is associated with impaired clinical outcomes, but no anti-inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin-1 axis are overactivated during episodes of acute HF. Colchicine, an anti-inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients. METHODS: COLICA is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new-onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m2). The primary efficacy endpoint is the time-averaged proportional change in NT-proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events. CONCLUSION: COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF.

Cancer Screening in Low- and Middle-Income Countries.

The worldwide cancer burden is growing, and populations residing in low- and middle-income countries (LMICs) are experiencing a disproportionate extent of this growth. Breast, colorectal, and cervical cancers are among the top 10 most frequently diagnosed malignancies, and they also account for a substantial degree of cancer mortality internationally. Effective screening strategies are available for all three of these cancers. Individuals from LMICs face substantial cost and access barriers to early detection programs, and late stage at diagnosis continues to be a major cause for cancer mortality in these communities. This chapter will review the epidemiology of breast, colorectal, and cervical cancers, and will explore prospects for improving global control through novel approaches to screening in cost-constrained environments.