Antioxidant therapies and oxidative stress in Friedreich's ataxia: the right path or just a diversion?

Friedreich's ataxia is the commonest autosomal recessive ataxia among population of European descent. Despite the huge advances performed in the last decades, a cure still remains elusive. One of the most studied hallmarks of the disease is the increased production of oxidative stress markers in patients and models. This feature has been the motivation to develop treatments that aim to counteract such boost of free radicals and to enhance the production of antioxidant defenses. In this work, we present and critically review those 'antioxidant' drugs that went beyond the disease's models and were approved for its application in clinical trials. The evaluation of these trials highlights some crucial aspects of the FRDA research. On the one hand, the analysis contributes to elucidate whether oxidative stress plays a central role or whether it is only an epiphenomenon. On the other hand, it comments on some limitations in the current trials that complicate the analysis and interpretation of their outcome. We also include some suggestions that will be interesting to implement in future studies and clinical trials

Still´s disease in adults. Case presentation

Still´s disease in adults is an entity with a possible autoimmune origin, of unknown etiology and infrequent presentation. It is characterized by high fever, netrophylic leukocytosis, and transient exanthema. The values of seric ferritin over 3 000 ng/mL are of great value to determine the diagnosis. It is described the case of a 28 year old male patient with chronic febrile syndrome, cutaneous rash, odynophagia and arthritis. Laboratory tests were performed which showed leukocytosis, high level of hepatic enzymes and seric ferritin. The low incidence of this disease, its complicated form of presentation, so as the non- existence of any confirming test for its diagnosis, motivated the authors to describe a patient with Still´s disease of the adult

Implementation and Knowledge of the Clinical Practice Guide for Palliative Care in the Ecuadorian Primary Care Level

Ecuador assumed the commitment of including Palliative Care (PC) in its health policies. In 2014, the Ministry of Public Health (Ministerio de Salud Pública, MSP) approved the Clinical Practice Guide for Palliative Care (Guía de Práctica Clínica sobre Cuidados Paliativos, GPCCP), with application at the national level, as a mandatory internal regulation in all institutions belonging to the National Health System. In 2021, there is no evidence about the degree of implementation. The objective was to evaluate the implementation (I) of the GPCCP guide and the knowledge (C) of the health personnel working in the Zone 7 Health Centers (HCs). This is a cross-sectional, descriptive, and prospective study. A total of 292 professionals were interviewed: managers (38), physicians (150), and nurses (104). Three surveys based on the GPCCP guide were elaborated: one for the implementation, which was applied to the individuals in charge, and the others to assess the health professionals’ knowledge. The SPSS program was used, version 25. In the three groups, more than half of the participants had no training in PC, 91.2% of the HCs have the GPCCP guide, there is PC medical history (MH) in 38.2%, and morphine is used in 14.7%. The implementation of the GPCCP guide was inadequate in 52.9% of the cases. Only 25% treat the agony symptoms and 30%, delirium; 4.4% acknowledge the use of morphine in dyspnea, and 13.3% identify the subcutaneous route as the first choice for hydration at the end-of-life phase. Strategies to implement the GPCCP guide and to improve the health personnel’s knowledge must be implemented in Zone 7 centers

Intention to consume alcohol among adolescents in technical vocational education

Introduction: Excessive consumption of alcoholic beverages by adolescents, constitutes an emerging health problem, whose solution has become a global priority. The immediate determinant for the execution of a behavior is the intention of the individual, so it is a precise moment to apply preventive actions. Objectives: To explore the intention to consume alcohol and its relationship with sociodemographic and consumption variables. Methods: A descriptive cross-sectional study was carried out with 143 adolescents between 15 and 18 years of age, selected by simple random sampling. They were administered the alcohol use intention questionnaire. Results: 84.6% of the adolescents had consumed alcohol; 45.5% were 18 years old and 57.9% were male. The age of onset of consumption was 15 years for 41.3 %. The mean score on the attitude scale was significantly higher in consumers (p= 0.000). Attitude is the dimension that contributed most to the initiation of alcohol consumption (Wald= 14.56; p= 0.000). Conclusions: Adolescents are characterized by being mostly consumers of alcoholic beverages, with a predominance of male sex and an average age of onset of consumption of 15 years. The fundamental variable favoring the intention to consume alcohol is the positive attitude towards consumption, frequently reinforced in the social and family environment

Desarrollo y validación de un método analítico para la deterninación de disolventes residuales por Espacio de Cabeza Estático-Cromatografía Gaseosa Capilar en policosanol

En el proceso de obtención de policosanol son utilizados los disolventes n-hexano y acetona que son eliminados posteriormente en las etapas de secado correspondientes. El objetivo de este trabajo fue desarrollar y validar un método analítico que permitiera la determinación de posibles residuos de disolventes en lotes de policosanol, utilizando la técnica de Espacio de Cabeza Estático - Cromatografía Gaseosa Capilar (ECE-CGC). Se optimizaron los parámetros de operación del cromatógrafo de gases, así como los del análisis por Espacio de Cabeza: temperatura de equilibrio entre las fases: 30 ºC, temperatura de la línea de transferencia: 150 ºC, temperatura de la válvula de conmutación: 120 ºC, tiempo de equilibrio entre las fases: 10 min, tiempo de inyección: 2 s y flujo de gas de arrastre (argón): 5 mL/min. Los criterios fundamentales de validación estudiados fueron: linealidad, proporcionalidad, precisión en condiciones de repetibilidad y reproducibilidad, exactitud, sensibilidad y limite de detección. Los criterios de aceptación en todos los casos fueron tomados de la Sección Catalana de Normas de Buena Fabricación y Control de Calidad (Validación de Métodos Analíticos). En el estudio de linealidad, para el hexano de 39,5 a 118,5 ppm y para la acetona de 47,52 a 42,56 ppm, se encontraron coeficientes de variación de los factores de respuesta inferiores al 5 % y valores aceptables para la varianza del error experimental total y la desviación estándar de la pendiente, lo que denota una buena linealidad

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Etapa familiar que se inicia con el nacimiento del primer hijo

Las etapas evolutivas de la familia como grupo, son un tema poco abordado en la literatura médica, de ahí que nos entusiasmara la idea de profundizar en aquella que se inicia con el nacimiento del primer hijo, por considerarla un período en la vida familiar y personal de muchas expectativas y tareas nuevas a afrontar. Con carácter descriptivo, longitudinal y retrospectivo evaluamos cuál es el conflicto fundamental que perciben los padres en esta etapa, sentimientos que genera el afrontar ese evento que la define y los intentos de solución, a los problemas de este período. Trabajamos con 2 grupos: 1 que tuviera a su descendiente matriculado en el Círculo Infantil, y otro con niños que se desarrollan únicamente en el ambiente familiar. Entre los resultados encontramos que además de ser hijos deseados, los padres refieren participación en la atención de éstos reconociéndose a la madre como figura fundamental en la toma de decisiones. La afectación económica es el conflicto principal percibido por ambos padres en los 2 grupos estudiados, no encontrándose diferencias importantes entre los 2 grupos de familias que participaron en el estudio, al menos en la mayoría de las variables exploradasAs the evolutive stages of the family as a group are little appoached by medical literature, we decided to deepen in that one that starts with the birth of the first child for considering it as a period of many expectations and new tasks to undertake in the family and personal life. A descriptive, longitudinal and retrospective evaluation of the fundamental conflict perceived by the parents in this stage, of the feelings resulting from facing that event that defines it and of the attempts to solve the problems arising during that period was made. We worked with 2 groups: one with the child enrolled in the day care center and the other with children that developed in the family environment only. Among the results, we found that besides being desired children, fathers recognized their participation in their attention and considered that mothers played a fundamental role in the decision-making. The economic affectation was the main conflict observed in both parents from the 2 studied groups. No significant differences were found at least in most of the variables explored in the 2 groups of families that participated in the stud

Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model

Friedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in the FXN gene, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling. In the present study, we have analyzed in both, unicellular and multicellular models of FRDA, calcium management and integrity of MAMs. We observed that function of MAMs is compromised in our cellular model of FRDA, which was improved upon treatment with antioxidants. In agreement, promoting mitochondrial calcium uptake was sufficient to restore several defects caused by frataxin deficiency in Drosophila Melanogaster. Remarkably, our findings describe for the first time frataxin as a member of the protein network of MAMs, where interacts with two of the main proteins implicated in endoplasmic reticulum-mitochondria communication. These results suggest a new role of frataxin, indicate that FRDA goes beyond mitochondrial defects and highlight MAMs as novel therapeutic candidates to improve patient's conditions