Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.

OBJECTIVE: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). DESIGN: Double-blind pilot randomised controlled trial. SETTING: Eight neonatal units in South Asia. PATIENTS: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. INTERVENTIONS: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. MAIN OUTCOMES AND MEASURES: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. RESULTS: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. CONCLUSIONS: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. TRIAL REGISTRATION NUMBER: NCT05395195.

Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy: A Multicenter Pilot Randomized Clinical Trial.

Importance: Although whole-body hypothermia is widely used after mild neonatal hypoxic-ischemic encephalopathy (HIE), safety and efficacy have not been evaluated in randomized clinical trials (RCTs), to our knowledge. Objective: To examine the effect of 48 and 72 hours of whole-body hypothermia after mild HIE on cerebral magnetic resonance (MR) biomarkers. Design, Setting, and Participants: This open-label, 3-arm RCT was conducted between October 31, 2019, and April 28, 2023, with masked outcome analysis. Participants were neonates at 6 tertiary neonatal intensive care units in the UK and Italy born at or after 36 weeks' gestation with severe birth acidosis, requiring continued resuscitation, or with an Apgar score less than 6 at 10 minutes after birth and with evidence of mild HIE on modified Sarnat staging. Statistical analysis was per intention to treat. Interventions: Random allocation to 1 of 3 groups (1:1:1) based on age: neonates younger than 6 hours were randomized to normothermia or 72-hour hypothermia (33.5 °C), and those 6 hours or older and already receiving whole-body hypothermia were randomized to rewarming after 48 or 72 hours of hypothermia. Main Outcomes and Measures: Thalamic N-acetyl aspartate (NAA) concentration (mmol/kg wet weight), assessed by cerebral MR imaging and thalamic spectroscopy between 4 and 7 days after birth using harmonized sequences. Results: Of 225 eligible neonates, 101 were recruited (54 males [53.5%]); 48 (47.5%) were younger than 6 hours and 53 (52.5%) were 6 hours or older at randomization. Mean (SD) gestational age and birth weight were 39.5 (1.1) weeks and 3378 (380) grams in the normothermia group (n = 34), 38.7 (0.5) weeks and 3017 (338) grams in the 48-hour hypothermia group (n = 31), and 39.0 (1.1) weeks and 3293 (252) grams in the 72-hour hypothermia group (n = 36). More neonates in the 48-hour (14 of 31 [45.2%]) and 72-hour (13 of 36 [36.1%]) groups required intubation at birth than in the normothermic group (3 of 34 [8.8%]). Ninety-nine neonates (98.0%) had MR imaging data and 87 (86.1%), NAA data. Injury scores on conventional MR biomarkers were similar across groups. The mean (SD) NAA level in the normothermia group was 10.98 (0.92) mmol/kg wet weight vs 8.36 (1.23) mmol/kg wet weight (mean difference [MD], -2.62 [95% CI, -3.34 to -1.89] mmol/kg wet weight) in the 48-hour and 9.02 (1.79) mmol/kg wet weight (MD, -1.96 [95% CI, -2.66 to -1.26] mmol/kg wet weight) in the 72-hour hypothermia group. Seizures occurred beyond 6 hours after birth in 4 neonates: 1 (2.9%) in the normothermia group, 1 (3.2%) in the 48-hour hypothermia group, and 2 (5.6%) in the 72-hour hypothermia group. Conclusions and Relevance: In this pilot RCT, whole-body hypothermia did not improve cerebral MR biomarkers after mild HIE, although neonates in the hypothermia groups were sicker at baseline. Safety and efficacy of whole-body hypothermia should be evaluated in RCTs. Trial Registration: ClinicalTrials.gov Identifier: NCT03409770.

Identification of microorganisms in wet coffee fermentation Coffea arabica Var Catimor and Castillo in Jardín, Antioquia-Colombia, using culture-dependent methods / Identificación de microorganismos en fermentación húmeda de café Coffea arabica Var Catimor y Castillo en Jardín, Antioquia-Colombia, usando métodos cultivo-dependientes

Background: Mild Colombian coffees are recognized worldwide for their high-quality coffee cup. However, there have been some failures in post-harvest practices, such as coffee grain fermentation. These failures could occasionally lead to defects and inconsistencies in quality products and economic losses for coffee farmers. In Colombia, one of the fermentation methods most used by coffee growers is wet fermentation, conducted by submerging the de-pulped coffee beans for enough time in water tanks to remove the mucilage. Objectives: We evaluated the effect of the water (g)/de-pulped coffee (g) ratio (I: 0/25, II: 10/25, III: 20/25) and final fermentation time (24, 48, and 72 hours) on the total number of microbial groups. We also identified microorganisms of interest as starter cultures. Methods: We used a completely randomized experimental design with two factors; the effect of the water (g)/de-pulped coffee (g) ratio (I: 0/25, II: 10/25, III: 20/25) and final fermentation time (24, 48, and 72 hours), for 9 treatments with two replicates. During the coffee fermentation (1,950 g), the pH and °Brix were monitored. Total counts of different microbial groups (mesophiles, coliforms, lactic-acid bacteria, acetic-acid bacteria, and yeasts) were performed. Various isolates of microorganisms of interest as starter cultures (lactic-acid bacteria and yeasts) were identified using molecular sequencing techniques. Results: 21 lactic-acid bacteria (LAB) isolates and 22 yeasts were obtained from the different mini-batch fermentation systems. The most abundant lactic-acid bacteria species found were Lactiplantibacillus plantarum (46%) and Levilactobacillus brevis (31%). Pichia kluivery (39%) and Torulaspora delbrueckii (22%) were the most abundant yeast species. Conclusion The studied factors did not have effect over the microorganism's development. The identified bacterial and yeasts species have potential as starter cultures for better-quality coffees and in fermentation-related applications.

Antecedentes: Los cafés suaves lavados colombianos son reconocidos a nivel mundial por su buena puntuación sensorial; sin embargo, se han detectado fallas en las prácticas de postcosecha, como lo es la fermentación de los granos de café. Dichas fallas pueden causar defectos y carecer de consistencia en la calidad del producto, ocasionando pérdidas económicas para los caficultores. En Colombia, uno de los métodos más usados por los caficultores es la fermentación húmeda, la cual consiste en sumergir los granos de café despulpado en tanques con agua por un período de tiempo que permita la remoción del mucílago. Objetivos: La presente investigación evaluó la incidencia que tienen la proporción agua/granos despulpados de café (I: 0/25, II: 10/25, III: 20/25) y el tiempo final de fermentación (24, 48 y 72 horas) en el recuento final de grupos microbianos. Por otra parte, se identificaron taxonómicamente microorganismos de interés para su uso como cultivos iniciadores. Métodos: Mini-lotes consistieron en café despulpado (1950 g) puesto en recipientes de plástico abiertos y sumergidos en agua. Se aplicó un diseño experimental completamente aleatorizado de dos factores (proporción agua/ granos de café despulpado y tiempo) a tres niveles, para un total de nueve tratamientos con dos replicas. Durante las fermentaciones de café (1,950 g), el pH y los grados ºBrix, fueron monitoreados. Se realizaron los recuentos totales de los diferentes grupos microbianos: mesófilos, coliformes, bacterias ácido-lácticas, bacterias ácido-acéticas y levaduras. Se identificaron molecularmente diferentes aislados con potencial para ser usados como cultivos iniciadores (bacterias ácido-lácticas y levaduras). Resultados: Los resultados obtenidos mostraron que no hubo diferencia estádisticamente significativa entre los tratamientos aplicados y el recuento final de microorganismos. Un total de 21 aislados de bacterias ácido-lácticas (BAL) y 22 levaduras lograron obtenerse a partir de los diferentes sistemas de fermentación en mini-lote. Las especies de bacterias ácido-lácticas con mayor porcentaje acorde a su identificación taxonómica, corresponden a Lactiplantibacillus plantarum (46%), Levilactobacillus brevis (31%). Las especies de levaduras con mayor porcentaje acorde a su identificación taxonómica corresponden a Pichia kluivery (39%) y Torulaspora delbrueckii (22%). Conclusión Los factores estudiados no afectaron el crecimiento de ninguno de los grupos microbianos presentes en la fermentacion del café. Las especies de microorganismos identificados tienen potencial para se usados como cultivos starter o en aplicaciones dentro de las ciencias de fermentación.

[Risk factors associated to adverse drug events in hospitalized patients]. / Factores de riesgo asociados con eventos adversos a medicamentos en pacientes hospitalizados.

OBJECTIVE: To determine prevalence, causes and risk factors of ADE in hospitalized patients. METHODS: Analytical, observational, case-control study of patients with ADE. For statistical analysis, the following were calculated: percentages, frequencies, averages; odds ratio, χ2 test and multiple binary logistic regression. Data analysis was carried out with the Statistical Package, for the Social Sciences 23 program. RESULTS: A 132 patients were registered: 66 cases (26 EM and 40 RAM) and 66 controls; with average age of 35 years (SD 17.41). The prevalence of adverse drug events was 3.6%. The most frequently reported medications: antibiotics and anti-inflammatories. The frequency of adverse events by gender was: 39.3% men and 60.7% women. The services with the greatest patient care: emergencies, surgery; the most frequent route of administration: intravenous (32.3%). The main symptoms: skin. (32.3%) frequent symptoms: cutaneous. Associated symptoms RAM: type A pruritus (OR: 8.5; p = 0.001; IC95%: 0.035-0.393), type B pruritus (OR: 11; p = 0.001; CI95%: 0.021-0.368) urticaria (OR: 19; p = 0.005; IC95%: 0.007-0.412). Risk factors Associated EAM: female (OR: 2.6; p = 0.05; CI95%: 1.33-5.43), history of allergy (OR: 3.4; p = 0.033; CI95%: 1.04-8.40), prolonged hospital stays (OR: 5.4; p = 0.023; IC95%: 3.82-6.74). CONCLUSIONS: Patient safety is a priority when prescribing any drug, which represents a key point in prevention.

OBJETIVO: Determinar la prevalencia, causas y factores de riesgo asociados con eventos adversos a medicamentos en pacientes hospitalizados. MÉTODOS: Estudio de casos y controles, observacional, analítico, llevado a cabo en pacientes con eventos adversos a medicamentos. Para el análisis estadístico se calcularon: porcentajes, frecuencias, promedios; razón de momios, prueba de χ2 y regresión logística binaria múltiple. El análisis de los datos se efectuó con el programa Statistical Package, for the Social Sciencies 23. RESULTADOS: Se registraron 132 pacientes: 66 casos (26 EM y 40 RAM) y 66 controles, con edad promedio de 35 años (DS 17.41). La prevalencia de eventos adversos a medicamentos fue del 3.6%. Los medicamentos reportados con mayor frecuencia: antibióticos y antiinflamatorios. La frecuencia de eventos adversos por género fue: 39.3% hombres y 60.7% mujeres. Los servicios con mayor atención de pacientes: urgencias y cirugía; vía de administración más frecuente: intravenosa (32.3%). Los principales síntomas fueron los cutáneos. Los síntomas asociados con reacción adversa a medicamentos: prurito tipo A (RM: 8.5; p = 0.001; IC95%: 0.035-0.393), prurito tipo B (RM: 11; p = 0.001; IC95%: 0.021-0.368) urticaria (RM: 19; p = 0.005; IC95%: 0.007-0.412). Los factores de riesgo asociados con eventos adversos a medicamentos: mujer (RM: 2.6; p = 0.05; IC95%: 1.33-5.43), antecedente de alergia (RM: 3.4 p = 0.033; (IC95%: 1.04-8.40) y estancia hospitalaria prolongada (RM: 5.4; p = 0.023; IC95%: 3.82-6.74). CONCLUSIONES: La seguridad de los pacientes es una prioridad al momento de prescribir cualquier fármaco, lo que representa un punto clave en la prevención.

Incidence of the Brownian Relaxation Process on the Magnetic Properties of Ferrofluids.

Ferrofluids containing magnetic nanoparticles represent a special class of magnetic materials due to the added freedom of particle tumbling in the fluids. We studied this process, known as Brownian relaxation, and its effect on the magnetic properties of ferrofluids with controlled magnetite nanoparticle sizes. For small nanoparticles (below 10 nm diameter), the Néel process is expected to dominate the magnetic response, whereas for larger particles, Brownian relaxation becomes important. Temperature- and magnetic-field-dependent magnetization studies, differential scanning calorimetry, and AC susceptibility measurements were carried out for 6 and 13.5 nm diameter magnetite nanoparticles suspended in water. We identify clear fingerprints of Brownian relaxation for the sample of large-diameter nanoparticles as both magnetic and thermal hysteresis develop at the water freezing temperature, whereas the samples of small-diameter nanoparticles remain hysteresis-free down to the magnetic blocking temperature. This is supported by the temperature-dependent AC susceptibility measurements: above 273 K, the data show a low-frequency Debye peak, which is characteristic of Brownian relaxation. This peak vanishes below 273 K.

Venous Thromboembolism Characteristics and Outcomes Among RIETE Patients Tested & Untested for Inherited Thrombophilia.

Inherited thrombophilia (IT) workup is commonly pursued in venous thromboembolism (VTE) patients. Recent American Society of Hematology (ASH) guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large prospective RIETE registry was analyzed to compare VTE risk factors, management and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and following its discontinuation. Among 103,818 patients enrolled in RIETE, 21,089 (20.3%) were tested for IT, 8,422 (8.1%) tested positive, and 82,729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors, and less common in those with major risk factors like surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However IT-negative patients with pregnancy or postpartum-related VTE, had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates post-treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities.

miR-146a-/- mice model reveals that NF-κB inhibition reverts inflammation-driven myelofibrosis-like phenotype.

Emerging evidence shows the crucial role of inflammation (particularly NF-κB pathway) in the development and progression of myelofibrosis (MF), becoming a promising therapeutic target. Furthermore, tailoring treatment with currently available JAK inhibitors (such as ruxolitinib or fedratinib) does not modify the natural history of the disease and has important limitations, including cytopenias. Since recent studies have highlighted the role of miR-146a, a negative regulator of the NF-κB pathway, in the pathogenesis of MF; here we used miR-146a-/- (KO) mice, a MF-like model lacking driver mutations, to investigate whether pharmacological inhibition of JAK/STAT and/or NF-κB pathways may reverse the myelofibrotic phenotype of these mice. Specifically, we tested the JAK1/2 inhibitor, ruxolitinib; the NF-κB inhibitor via IKKα/ß, BMS-345541; both inhibitors in combination; or a dual inhibitor of both pathways (JAK2/IRAK1), pacritinib. Although all treatments decreased spleen size and partially recovered its architecture, only NF-κB inhibition, either using BMS-345541 (alone or in combination) or pacritinib, resulted in a reduction of extramedullary hematopoiesis, bone marrow (BM) fibrosis and osteosclerosis, along with an attenuation of the exacerbated inflammatory state (via IL-1ß and TNFα). However, although dual inhibitor improved anemia and reversed thrombocytopenia, the combined therapy worsened anemia by inducing BM hypoplasia. Both therapeutic options reduced NF-κB and JAK/STAT signaling in a context of JAK2V617F-driven clonal hematopoiesis. Additionally, combined treatment reduced both COL1A1 and IL-6 production in an in vitro model mimicking JAK2-driven fibrosis. In conclusion, NF-κB inhibition reduces, in vitro and in vivo, disease burden and BM fibrosis, which could provide benefits in myelofibrosis patients.

The socioeconomic burden of adult attention-deficit/hyperactivity disorder in Spain.

Introduction: The symptoms of attention-deficit/hyperactivity disorder (ADHD) in adults highly interfere with function in multiple dimensions, increasing the economic burden associated with ADHD. The aim of this study was to explore the impact of ADHD in Spanish adults and estimate the associated economic burden within the healthcare, social, economic, and legal domains. Methods: An economic model was developed from a social perspective using a bottom-up approach, based on the scientific literature and a multidisciplinary expert group. Results: The cost incurred per diagnosed adult patient with ADHD included an annual cost of €15,652 and a one-time cost of €7,893 (3,035 M€ and 1,531 M€ for Spain, respectively). Regarding the annual cost, 50% was attributed to costs within the economic domain, of which 53% were work-absenteeism-related. Moreover, 28% was attributed to costs within the social domain, of which 74% were substance-abuse-related. Regarding the one-time cost, 52% was attributed to costs within the healthcare domain, of which approximately 50% were hospitalization-related costs. Moreover, 42% was attributed to costs within the legal domain, of which 62% were imprisonment-related costs. Conclusions: This is the first report on the socioeconomic burden of ADHD in Spanish adults, shedding light on the large burden that adult ADHD poses on the healthcare system and society at large, as symptoms have been shown to impact almost every aspect of life. This is particularly important for undiagnosed/untreated patients with ADHD in Spain, as appropriate treatments have shown positive results in these areas and may reduce its associated socioeconomic burden.

A study on phytogenotoxicity induced by biogenic amines: cadaverine and putrescine.

Among the compounds present in necro-leachate, a liquid released during the process of decomposition of the human body, are the biogenic amines cadaverine and putrescine. Although some studies on necro-leachate have indicated a potential ecotoxicological and public health risk associated with it, the research on this type of contamination is still rather limited. This study presents information about the phytotoxic and cytogenotoxic potential of cadaverine and putrescine, evaluated separately and within a mixture. Phytotoxicity was evaluated through a germination test, the initial growth of seedlings with Lactuca sativa, and cytogenotoxicity through chromosomal aberration and micronucleus tests with Allium cepa. The L. sativa results showed a phytotoxic effect for the evaluated amines, by reducing root (> 90%) and hypocotyl (> 80%) elongation. The co-exposure of cadaverine and putrescine potentiated cytogenotoxic activity by aneugenic action in the meristematic cells of A. cepa. From this result, it is possible to infer the eco-toxicogenic potential of cadaverine and putrescine. This study not only highlights the importance of the phytotoxic and cytogenotoxic effects of these amines but also emphasizes the urgent need for further investigation into contamination originating from cemetery environments. By evaluating the risks associated with necro-leachate, this research is aimed at informing global efforts to protect ecological and public health.

[Post-COVID-19 condition in children and adolescents from a cohort: prevalence and risk factors]. / Enfermedad post-COVID-19 en una cohorte de niños y adolescentes: prevalencia y factores de riesgo.

OBJECTIVE: To determine the prevalence and risk factors of the post-COVID-19 condition of children and adolescents from a cohort. METHODS: Observational and analytical cohort study. Statistical analysis: percentages, frequencies; averages; Odds ratio, χ2 test, and multiple binary logistic regression. Statistical Package, for the Social Sciences 23. RESULTS: Prevalence of the post-COVID-19 condition was: 14.8% of 175 patients who fulfilled the inclusion criteria, 26 developed post-COVID-19 condition, mean age 5.9 years (SD: 5.05), sex: 27% men, 73% women, frequent symptoms: fatigue, runny nose, muscle pain, dyspnea. Symptoms associated with post-COVID-19 condition: muscle pain (OR: 27; p = 0.000; IC95%5.2-139), dysgeusia (OR: 19; p = 0.012; IC95%: 1.9-19), and fatigue (OR: 5; p = 0.001; IC95%: 1.9-13.5). Associated risk factors: female (OR: 3.58; p = 0.023; CI95%: 1.19-10.71), comorbidities (OR: 24.5; p = 0.000; CI95%: 7.52-79), allergic rhinitis (OR: 8.7; p = 0.000; CI95%: 2.66-28.87), atopic dermatitis (OR: 9. 58; p = 0.016 CI95%: 1.51-60.5). CONCLUSIONS: Although the majority of children infected with SARS-CoV-2 recover completely, some of them will develop a post-COVID-19 condition, knowing the most frequent symptoms and associated factors, will allow a better evaluation, for its opportune detection and effective treatment.

OBJETIVO: Determinar la prevalencia y factores de riesgo de la enfermedad post-COVID-19 en una cohorte de niños y adolescentes de Puebla, México. MÉTODOS: Estudio de cohorte, observacional y analítico. Para el análisis estadístico se estimaron: porcentajes, frecuencias, promedios; razón de momios, prueba de χ2 y regresión logística binaria múltiple. Se utilizó el programa Statistical Package, for the Social Sciencies 23. RESULTADOS: La prevalencia de enfermedad post-COVID-19 fue de 14.8% de 175 pacientes que cumplieron con los criterios de inclusión, 26 padecieron la enfermedad post-COVID-19; la edad promedio fue de 5.9 años (DE: 5.05). La distribución por género fue: 27% hombres y 73% mujeres. Los síntomas más frecuentes fueron: fatiga, rinorrea, dolor muscular y disnea. Los síntomas asociados con enfermedad post-COVID-19 incluyeron: dolor muscular (OR: 27; p = 0.000; IC95%: 5.2-139), disgeusia (OR: 19; p = 0.012; IC95%: 1.9-19), fatiga (OR: 5; p = 0.001; IC95%: 1.9-13.5). Los factores riesgo asociados: mujer (OR: 3.58; p = 0.023; IC95%: 1.19-10.71), comorbilidades (OR: 24.5; p = 0.000; IC95%: 7.52-79), rinitis alérgica (OR: 8.7; p = 0.000; IC95%: 2.66-28.87) y dermatitis atópica (OR: 9.58; p = 0.016; IC95%: 1.51-60.5). CONCLUSIONES: Aunque la mayoría de los niños infectados por SARS-CoV-2 se recuperan por completo, algunos evolucionan a enfermedad post-COVID-19. El conocimiento de los síntomas y factores de riesgo asociados con esta enfermedad permitirán una mejor evaluación, detección oportuna y tratamiento eficaz.

Trans narratives on school experiences-This is how we feel.

Introduction: The school environment remains unsafe for many trans people, where they are victims of discrimination, aggression, and bullying, resulting in socioemotional and physical harm to trans individuals. Intersectionality and minority stress are contributing factors in this already challenging education environment. In many cases, the voices of trans people are not heard or listened to at school; therefore, this study aims to listen to their school experiences in order to identify key areas for improvement. Method: This study implemented a narrative research approach where six in-depth interviews were completed with trans participants from the Basque Country, Europe, and the United States of America that focused on five dimensions: being a trans, the role of school, lack of teacher education and training, segregation by gender, and socioemotional wellbeing. The transcriptions of these interviews were coded using Nvivo software in categorical systems in a deductive and inductive way. Results: The results clearly showed that the binary society has a negative impact on trans people. In addition, the educational environment is still hostile for most of them, in which the lack of teacher training and gender identity content in the curriculum has a negative impact on trans people and their experiences at school. Discussion: The findings support the idea that socially ingrained binarism is detrimental to all those who step outside the norm. It can also be said that the earlier the transition is made, the better the effect (clinical as well as socioemotional) on their personal lives. For this early transition to occur, it is necessary to have access to information from an early age.

Antifibrotic treatment adherence, efficacy and outcomes for patients with idiopathic pulmonary fibrosis in Spain: a real-world evidence study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare disorder associated with increased mortality and morbidity. There are currently two drugs approved for IPF but their safety and efficacy profile in real-world settings in Spain is not well understood. METHODS: An observational, multicentre, prospective study was carried out among patients with IPF who started treatment with pirfenidone or nintedanib from 2015 to 2021. Data regarding clinical characteristics, drug adherence, safety profiles and clinical outcomes between these two drugs were collected. RESULTS: 232 patients were included in the analysis. There were no meaningful differences between both groups at baseline. Patients who started pirfenidone showed a decreased risk for treatment withdrawal compared with those starting nintedanib (HR 0.65 (95% CI 0.46 to 0.94; p=0.002)). Time to first adverse event and all-cause mortality was similar between study groups. Risk factors for withdrawal were female sex, diarrhoea and photosensitivity. CONCLUSIONS: in this real-world study, both pirfenidone and nintedanib showed similar efficacy profiles. Pirfenidone was associated with less treatment discontinuations due to side effects.

Reemergencia de la encefalitis equina del oeste (WEEV) en la Argentina: una revisión de aspectos epidemiológicos, virológicos y clínicos de relevancia / Reemergence of western equine encephalitis in Argentina

La encefalitis equina del oeste (WEEV, por su sigla en inglés, Western Equine Encephalitis) es una enfermedad reemergente en Argentina a partir del año 2023. La co-municación inicial fue en 1933, las últimas epizootias ocurrieron en 1983 y el último caso humano se registró en 1996. Se revisan las características del agente causal, la ecología con especial referencia a los vectores iden-tificados en el país, su competencia en la transmisión y el ciclo así como los factores de riesgo para adquirir la enfermedad. La situación epidemiológica en equinos y humanos desde noviembre 2023 hasta marzo 2024 es analizada. Se describen las formas clínicas de presen-tación de la enfermedad humana, las posibilidades evo-lutivas, los datos disponibles en los casos confirmados y el tratamiento. La metodología y algoritmo empleados para el diagnóstico etiológico en el Centro Nacional de Referencia son detallados. Las estrategias para la pre-vención y el control se basan en la vacunación de los equinos, el saneamiento ambiental y el control del foco ante la presentación de la enfermedad animal (vigilancia epidemiológica activa)

Western equine encephalitis (WEE) is a re-emerging dis-ease in Argentina starting in 2023. Since the initial notifi-cation in 1933, the last epizootics occurred in 1983, and the last human case was recorded in 1996.The charac-teristics of the causative agent, the ecology with special reference to vectors identified in the country, their compe-tence in transmission, and the cycle as well as the risks factors for acquiring the disease, are reviewed.The epidemiological situation in horses and humans from November 2023 to March 2024 is analyzed. The clinical presentation of the human disease, its evolutionary po-tential, available data in confirmed cases, and the treat-ment are described.The methodology and algorithm used for the etiological diagnosis at the National Reference Center are detailed. Strategies for prevention and control are based on vaccination of horses, environmental sani-tation and outbreak control in the presence of the animal disease (active epidemiological surveillance)

Viral reprogramming of host transcription initiation.

Viruses are master remodelers of the host cell environment in support of infection and virus production. For example, viruses typically regulate cell gene expression through modulating canonical cell promoter activity. Here, we show that Epstein Barr virus (EBV) replication causes 'de novo' transcription initiation at 29674 new transcription start sites throughout the cell genome. De novo transcription initiation is facilitated in part by the unique properties of the viral pre-initiation complex (vPIC) that binds a TATT[T/A]AA, TATA box-like sequence and activates transcription with minimal support by additional transcription factors. Other de novo promoters are driven by the viral transcription factors, Zta and Rta and are influenced by directional proximity to existing canonical cell promoters, a configuration that fosters transcription through existing promoters and transcriptional interference. These studies reveal a new way that viruses interact with the host transcriptome to inhibit host gene expression and they shed light on primal features driving eukaryotic promoter function.

From sound check to encore: A journey through high-resolution mass spectrometry-based food analyses and metabolomics.

This manuscript presents a comprehensive review of high-resolution mass spectrometry in the field of food analysis and metabolomics. We have followed the historical evolution of metabolomics, its associated techniques and technologies, and its increasing role in food science and research. The review provides a critical comparison and synthesis of tentative identification guidelines proposed for over 15 years, offering a condensed resource for researchers in the field. We have also examined a wide range of recent metabolomics studies, showcasing various methodologies and highlighting key findings as a testimony of the versatility of the field and the possibilities it offers. In doing so, we have also carefully provided a compilation of the software tools that may be employed in this type of studies. The manuscript also explores the prospects of high-resolution mass spectrometry and metabolomics in food science. By covering the history, guidelines, applications, and tools of metabolomics, this review attempts to become a comprehensive guide for researchers in a rapidly evolving field.

Correlation of Blood Hemoglobin Values with Non-Invasive Co-Oximetry Measurement of SpHb in Dogs Undergoing Elective Ovariohysterectomy.

Cardiovascular function monitoring has been suggested as a key parameter to determine patient stability during the anesthetic process. However, the use of pulse co-oximetry has been suggested as a technology to complement the monitoring of this system as a direct way to assess hemoglobin (Hb) blood concentration. Therefore, this study aimed to correlate and determine the measurement bias between Hb blood levels with continuously determined blood hemoglobin concentration (SpHb) and arterial oxygen content values (SpOC), both obtained by noninvasive co-oximetry in dogs undergoing elective ovariohysterectomy (OVH). A total of 85 clinically healthy bitches of different breeds that were admitted for elective OVH surgery were evaluated. These animals underwent SpHb and SpOC capture after the in vivo setting for the duration of the surgical procedure. Likewise, five minutes before the end of the surgical procedure, a blood sample was obtained directly from the jugular vein to determine the blood concentration of Hb (HbLAB). The Bland-Altman analysis showed 95% limits of agreement from -4.22 to 4.99 g/dL with a BIAS (mean difference) of 0.384 ± 2.35 g/dL (r = 0.401). SpHb recordings were correlated with oxygen saturation (SpO2) (r = 0.995), SpOC (r = 0.992) and with perfusion index (PI) (r = 0.418). Therefore, SpHb presents a moderate positive correlation with direct blood concentration of Hb. This possibly shows that continuous measurement of SpHb by noninvasive co-oximetry is a reliable and advanced alternative for monitoring Hb concentration in dogs under anesthesia.

Novel Oliveros-like Clade C Mammarenaviruses from Rodents in Argentina, 1990-2020.

Following an Argentine Hemorrhagic Fever (AHF) outbreak in the early 1990s, a rodent survey for Junín virus, a New World Clade B arenavirus, in endemic areas of Argentina was conducted. Since 1990, INEVH has been developing eco-epidemiological surveillance of rodents, inside and outside the Argentine Hemorrhagic Fever endemic area. Samples from rodents captured between 1993 and 2019 that were positive for Arenavirus infection underwent Sanger and unbiased, Illumina-based high-throughput sequencing, which yielded 5 complete and 88 partial Mammarenaviruses genomes. Previously, 11 genomes representing four species of New World arenavirus Clade C existed in public records. This work has generated 13 novel genomes, expanding the New World arenavirus Clade C to 24 total genomes. Additionally, two genomes exhibit sufficient genetic diversity to be considered a new species, as per ICTV guidelines (proposed name Mammarenavirus vellosense). The 13 novel genomes exhibited reassortment between the small and large segments in New World Mammarenaviruses. This work demonstrates that Clade C Mammarenavirus infections circulate broadly among Necromys species in the Argentine Hemorrhagic Fever endemic area; however, the risk for Clade C Mammarenavirus human infection is currently unknown.

Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year. Objective: To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up. Design, Setting, and Participants: The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle. Interventions: Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy. Main outcomes and measures: The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions. Results: Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, -188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (-28 [95% CI, -63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points. Conclusions and Relevance: In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior. Trial registration: ClinicalTrials.gov Identifier: NCT03208153.