[Relationship between frailty and functional status in lung transplant candidates]. / Relación entre la fragilidad y la capacidad funcional en los pacientes candidatos a trasplante de pulmón.

INTRODUCTION: Lung transplant (LT) is one of the therapeutic options for patients with terminal respiratory diseases. It is highly important to incorporate the functional status and frailty assessment into the selection process of candidates for LT. OBJECTIVES: Identify the prevalence of frailty in the LT waiting list. Study the relationship between frailty, functional status, Lung Allocation Score (LAS) and muscular dysfunction. METHODOLOGY: Descriptive transversal study of patients on the waiting list for LT. POPULATION: 74 patients with chronic respiratory diseases assessed by the lung transplant committee and accepted to be transplanted in a university hospital in Barcelona. The outcome variables were frailty status was evaluate for SPPB test, functional capacity was evaluate for the six-minute walking test (6MWT) and muscular dysfunction. The results were analyzed with the statistical package STATA 12. RESULTS: Sample of 48 men and 26 women, with a median age of 56.55 years (SD 10.87. The prevalence of frailty assessed with the SPPB was 33.8% (8.1% are in frailty and 25.7% are in a state of pre-frailty). There is a relationship between the SPPB, 6MWT and maximal inspiratory pressure, but not with others force values. There is a relationship between the risk of frailty (scores below 9 in SPPB) and the meters walked in 6 but not with the LAS. CONCLUSIONS: The risk of frailty in patients with terminal chronic respiratory diseases is high. Frailty is related with functional capacity, but not with LAS.

Ophthalmic wild olive (ACEBUCHE) oil nanoemulsions exert oculoprotective effects against oxidative stress induced by arterial hypertension.

Oxidative stress plays a key role in several systemic and ocular diseases, including hypertensive eye diseases. In this context, we previously showed that oral administration of wild olive (acebuche, ACE) oil from Olea europaea var. sylvestris can counteract ocular damage secondary to arterial hypertension by modulating excess reactive oxygen species (ROS) produced by the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Therefore, this work describes the development of an ACE oil-based formulation for ocular administration as a local therapy to counteract hypertension-related oxidative damage. Specifically, ACE oil nanoemulsions (NEs) were successfully produced and characterized, exhibiting appropriate features for ophthalmic administration, including a nanometer size (<200 nm), moderate negative ZP, adequate osmolality and pH, and colloidal stability in biorelevant fluids. Likewise, the NEs presented a shear thinning behavior, especially convenient for ocular instillation. In vivo evaluation was performed through either intravitreal injection or topical ophthalmic administration in mice with hypertension induced via administration of Nω-nitro-L-arginine-methyl-ester (L-NAME). Both routes of administration reduced hypertensive morphological alterations and demonstrated a noticeable antioxidant effect thanks to the reduction of the activity/expression of NADPH oxidase in cornea and retina. Thus, an ACE oil ophthalmic formulation represent a promising therapy for ocular pathologies associated with arterial hypertension.

Ythdf2 regulates cardiac remodeling through its mRNA target transcripts.

m6A mRNA methylation controls cardiomyocyte function and increased overall m6A levels are a stereotyping finding in heart failure independent of the underlying etiology. However, it is largely unknown how the information is read by m6A reader proteins in heart failure. Here we show that the m6A reader protein Ythdf2 controls cardiac function and identified a novel mechanism how reader proteins control gene expression and cardiac function. Deletion of Ythdf2 in cardiomyocytes in vivo leads to mild cardiac hypertrophy, reduced heart function, and increased fibrosis during pressure overload as well as during aging. Similarly, in vitro the knockdown of Ythdf2 results in cardiomyocyte growth and remodeling. Mechanistically, we identified the eucaryotic elongation factor 2 as post-transcriptionally regulated by Ythdf2 using cell type specific Ribo-seq data. Our study expands our understanding on the regulatory functions of m6A methylation in cardiomyocytes and how cardiac function is controlled by the m6A reader protein Ythdf2.

Efectividad de la diatermia por radiofrecuencia en el tratamiento de las patologías de rodilla. Una revisión sistemática / Effectiveness of radiofrequency diathermy in the treatment of knee pathologies. A systematic review

Objetivo La diatermia es una terapia que permite aumentar la temperatura y el metabolismo de los tejidos biológicos mediante la emisión de radiaciones electromagnéticas. A pesar de que esta forma de terapia está ampliamente extendida, no existen revisiones acerca de su utilidad en el tratamiento de patologías de rodilla. Por eso, en la presente revisión bibliográfica se valoró la efectividad de la diatermia por radiofrecuencia como tratamiento conservador en el abordaje de diferentes patologías de rodilla. Material y métodos Se realizó una búsqueda de ensayos clínicos controlados y aleatorizados en las bases de datos PubMed, Web of Science (WOS) y Scopus con las palabras clave «Radiofrequency», «Capacitive», «Resistive», «Dielectric», «Knee» y «Diathermy». Se seleccionaron ensayos clínicos aleatorizados publicados desde 2011 hasta la fecha actual, en inglés y en español. Para valorar la calidad de estos, se usó la escala PEDro. Resultados Cuatro ensayos clínicos aleatorizados fueron seleccionados atendiendo a los criterios de inclusión y exclusión. Todos ellos mostraron resultados positivos a favor del grupo experimental en las variables de dolor percibido y funcionalidad. Conclusión La diatermia por radiofrecuencia es una terapia no invasiva eficaz para mejorar la funcionalidad y reducir el dolor a corto plazo en pacientes con diferentes patologías de rodilla (AU)

Objective Radiofrequency diathermy is a treatment technique that increase temperature and metabolism of the biologic tissues by the emission of electromagnetic radiation. Even though this therapy is widely used, there are no reviews about its effectiveness in the treatment of knee pathologies. For this reason, the aim of this systematic review is to assess the efficacy of radiofrequency diathermy as conservative treatment for different knee pathologies. Methods A bibliographic search of randomized clinical trials was carried out in Pubmed, Scopus and WOS, using «Radiofrequency», «Capacitive», «Resistive», «Dielectric», «Knee» and «Diathermy» as descriptors. Only randomized clinical trials in English and Spanish from 2011 to date were chosen. PEDro scale was used to assess the quality of the studies. Results Four randomized clinical trials were selected according to the inclusion and exclusion criteria. All studies showed positive results in favor to the experimental group regarding pain reduction and knee function. Conclusions Radiofrequency diathermy is an effective non-invasive therapy to improve the quality of life, the functionality and the pain in short-term in patients with different knee conditions (AU)

Ecotoxicological risk assessment in soils contaminated by Pb and As 20 years after a mining spill.

This study evaluates the potential toxicity of the soils of the Guadiamar Green Corridor (GGC) affected by the Aznalcóllar mine spill (Andalusia, Spain), one of the most important mining accidents in Europe in recent decades. Twenty years after the accident, although the area is considered to be recovered, residual contamination in soils persists, and the bioavailability of some contaminants, such as As, is showing trends of increasing. Therefore, the potential residual toxicity in 84 soil samples was evaluated by bioassays with lettuce (Latuca sativa L.), earthworms (Eisenia andrei) and determining the microbial activity by basal respiration and metabolic quotient. The selected soils sampled along the GGC were divided into 4 types according to their physicochemical properties. In the closest part of the mine two soil types appear (SS1 and SS2), originally decarbonated and loamy, with a reduction in lettuce root elongation of 57% and 34% compared to the control, as well as a the highest metabolic quotient (23.9 and 18.1 ng CcO2 µg Cmicrob-1 h-1, respectively) with the highest risk of Pb and As toxicity. While, located in the middle and final part of the affected area of the spill (SS3 and SS4), soils presented alkaline pH, finer textures and the lowest metabolic quotient (<9.5 ng CcO2 µg Cmicrob-1 h-1). In addition, due to Pb and As exceeded the Guideline values established in the studied area, the human toxicity risk was determined according to US-EPA methodology. Although the total contents were higher than the Guidelines established, the obtained hazard quotients for both contaminants were less than one, so the risk for human health was discarded. However, monitoring over time of the toxicity risks of the GGC soils would be advisable, especially due to the existence of areas where residual contamination persist, and soil hazard quotient obtained for As in children was higher and close to unity.

Validez de contenido de un ECOE en el pregrado de fisioterapia para el razonamiento clínico / Validity of content of a ECOE in the physiotherapy undergraduate for clinical reasoning

Introducción: El Examen Clínico Objetivo Estructurado (ECOE) es una metodología de evaluación que permite medir de manera válida las competencias clínicas en estudiantes de fisioterapia a través de estaciones previamente estandarizadas. Objetivo: Determinar la validez de contenido del instrumento ECOE-LM 2017 para la medición de competencias clínicas en el examen, evaluación, diagnóstico, pronóstico e intervención de una persona con lumbalgia mecánica en fisioterapia. Métodos: Se diseñó un instrumento de seis estaciones evaluado con la técnica de juicio de expertos, para posteriormente calcular la confiabilidad interobservador a través de Fleiss’ Kappa, por medio del ReCal; adicionalmente se identificó el índice de aceptabilidad. Resultados: Se obtiene un índice kappa de 0,82 (casi perfecto) que da cuenta de una buena confiabilidad para el instrumento. Conclusiones: Se cuenta con un instrumento con una buena concordancia para su empleo en los procesos educativos. (AU)

Introduction: The Objective Structured Clinical Examination (ECOE) is an evaluation methodology that allows to validly measure clinical competencies in Physiotherapy students through previously standardized stations. Objective: To determine the content validity of the ECOE-LM 2017 instrument for the measurement of clinical competencies in the examination, evaluation, diagnosis, prognosis and intervention of a person with mechanical low back pain in Physiotherapy. Methods: An instrument of six stations evaluated with the expert judgment technique was designed to subsequently calculate the inter-observer reliability, through Fleiss’ Kappa, by means of the ReCal, additionally the acceptability index was identified. Results: A Kappa index of 0.82 (almost perfect) is obtained, which shows good reliability for the instrument. Conclusions: There is an instrument with good agreement for its use in educational processes. (AU)

Social environment as a modulator of immunosenescence.

Immune system aging, a process known as immunosenescence, involves a striking rearrangement affecting all immune cells, resulting in an increased rate of infections and a major incidence of autoimmune diseases and cancer. Nonetheless, differences in how individuals of the same chronological age carry out this immunosenescence establishment and thus the aging rate have been reported. In the context of neuroimmunoendocrine communication and its role in the response to stress situations, growing evidence suggests that social environments profoundly influence all physiological responses, especially those linked to immunity. Accordingly, negative contexts (loneliness in humans/social isolation in rodents) were associated with immune impairments and decreased lifespan. However, positive social environments have been correlated with adequate immunity and increased lifespan. Therefore, the social context in which an individual lives is proposed as a decisive modulator of the immunosenescence process and, consequently, of the rate of aging. In this review, the most important findings regarding how different social environments (negative and positive) modulate immunosenescence and therefore the aging rate, as well as the role of stress responses, hormesis, and resilience in these environments will be explained. Finally, several possible molecular mechanisms underlying the effects of negative and positive environments on immunosenescence will be suggested.

Protocol for assessing mortality reduction with the early use of noninvasive ventilation in prehospital emergency services: A multicentre, observational cohort study in Madrid, Spain.

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.

Fiabilidad interobservador de tres métodos de fotogrametría para medir la lordosis lumbar / Interobserver reliability in three scales used in photogrammetry to measure lumbar lordosis

Antecedentes y objetivo Actualmente, se considera la radiografía como la prueba estándar para medir la lordosis lumbar; sin embargo, requiere de una preparación especial y, además, existe el riesgo de exposición a radiación ionizante la cual es nociva para la salud. El costo en los equipos utilizados y la exposición a la radiación son factores que limitan la aplicación de este tipo de pruebas diagnósticas. La fotogrametría es capaz de identificar las particularidades de la postura corporal que permiten reconocer ángulos como el de la lordosis lumbar. Se hace necesario ampliar el conocimiento acerca de la fiabilidad a partir de estándares que proporcionen al profesional en fisioterapia protocolos con medidas reproducibles que le faciliten la toma de decisiones relacionadas con esta condición. Por lo tanto, el objetivo de este estudio es determinar la fiabilidad inter-evaluador de tres formas de fotogrametría para medir la lordosis lumbar en personas con dolor lumbar no específico. Metodología Se realizó un análisis de lordosis lumbar mediante dos programas (Kinovea y ADiBAS Posture) a una muestra de 26 personas con dolor lumbar. Se empleó Kinovea para la evaluación en 2D por medio del test de flechas y el ángulo lordótico. ADiBAS Posture se utilizó para calcular la lordosis en 3D. Tres evaluadores hicieron medidas a partir de las fotografías, usando tres protocolos de medición definidos para el estudio. Resultados El análisis llevado a cabo a través de ADiBAS Posture presenta un coeficiente de correlación intraclase (CCI) muy bueno, mientras que el test de flechas y ángulo lordótico resultaron tener CCI buenos. Por otra parte, la prueba de ángulo lordótico presentó diferencias significativas mientras que el de flechas y el análisis efectuado en 3D no presentaron diferencias significativas (p > 0,05). Conclusiones El análisis en 3D y el test de flechas para determinar la lordosis lumbar son pruebas con un nivel de fiabilidad muy bueno (AU)

Background and objective Radiography is currently considered the gold standard test for measuring lumbar lordosis. However, it requires special preparation and there is also a risk of exposure to ionizing radiation, which is harmful to health. The cost of the equipment used and exposure to radiation are factors that limit the application of this type of diagnostic test. Photogrammetry can identify distinctive features allowing recognition of angles such as those of lumbar lordosis. Knowledge needs to be increased on reliability based on standards that provide the physiotherapist protocols with reproducible measures that facilitate decision-making related to this condition. Therefore, the objective of this study is to determine the inter-rater reliability of three forms of photogrammetry to measure lumbar lordosis in people with non-specific low back pain. Methodology An analysis of lumbar lordosis was carried out with two software programmes (Kinovea and ADiBAS Posture) in a sample of 26 people. Kinovea was used for 2D evaluation by means of the arrow test and the lordotic angle. ADiBAS Posture was used to measure lordosis in 3D. Three assessors made measurements from the photographs using the three measurement protocols defined for the study. Results ADiBAS Posture analysis showed extremely good CCI, while the arrow and lordotic angle test proved to have good CCIs. On the other hand, the lordotic angle test showed significant differences while the arrow test and the 3D analysis showed no significant differences (p > 0.05). Conclusions The 3D analysis and arrow test to determine lumbar lordosis are tests with a particularly good level of reliability (AU)

¿Ayuda la rehabilitación cardíaca a posponer el trasplante cardíaco en la miocardiopatía dilatada? Caso clínico / Does cardiac rehabilitation help postpone heart transplantation in dilated cardiomyopathy? Clinical case

Antecedentes y objetivo La miocardiopatía dilatada es una causa frecuente de trasplante cardíaco y los programas de rehabilitación cardíaca han demostrado ser útiles como parte del tratamiento. El objetivo principal de este trabajo es exponer un caso clínico donde se muestra el impacto del tratamiento de rehabilitación en un paciente con esta enfermedad. Descripción del caso Se presenta el caso de un paciente de 25 años con diagnóstico de miocardiopatía dilatada con New York Heart Association (NYHA) III y fracción de eyección del ventrículo izquierdo (FEVI) del 10%. Presentaba intolerancia al ejercicio, disnea a pequeños-moderados esfuerzos y en espera de trasplante cardíaco. Intervención Ante estos hallazgos, es derivado a programa de rehabilitación cardíaca hospitalaria de alto riesgo para optimizarlo antes del trasplante, donde realizó un programa de ejercicio físico (resistencia aeróbica, fuerza muscular periférica y respiratoria), educación sanitaria y soporte psicológico. Resultados Tras 4 meses de tratamiento el paciente presenta una mejoría clínica y funcional notoria, logrando posponer el trasplante cardíaco. Discusión Los programas de rehabilitación cardíaca pueden suponer un avance terapéutico en la miocardiopatía dilatada. Estos pueden mejorar tanto la tolerancia al ejercicio como parámetros de funcionalidad y en algunos pacientes la fracción de eyección (AU)

Background and objective Dilated cardiomyopathy is a frequent cause of heart transplantation. Cardiac rehabilitation programmes have proven helpful as part of treatment. The main aim of this paper is to present a clinical case showing the impact of rehabilitation treatment on a patient with this pathology. Case description We present the case of a 25-year-old patient diagnosed with dilated cardiomyopathy with New York Heart Association (NYHA) III and 10% left ventricular ejection fraction (LVEF). He had exercise intolerance, dyspnoea on mild-moderate exertion and is awaiting heart transplantation. Intervention Given these findings, the patient was referred to a high-risk hospital cardiac rehabilitation programme for optimization prior to transplantation, where he carried out a programme of physical exercise (aerobic resistance, peripheral muscle, and respiratory strength), health education and psychological support. Results After 4 months of treatment, the patient shows marked clinical and functional improvement, and therefore heart transplantation can be postponed. Discussion Cardiac rehabilitation programmes can be a therapeutic advance in dilated cardiomyopathy. They can improve both exercise tolerance and functionality parameters and, in some patients, the ejection fraction. In this article, an exhaustive review of the rehabilitation treatment of dilated cardiomyopathy is performed (AU)

Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival.

BACKGROUND: Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. RESULTS: Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. CONCLUSIONS: Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival.

Prevalence of clinical manifestations and orthopedic alterations in patients with lipedema: A prospective cohort study.

Lipedema is a chronic disease seen frequently in women that causes abnormal fat deposition in the lower limbs and associated bruising and pain. Despite increasing knowledge concerning lipedema, there are still aspects of diagnosis that need further investigation. We performed a prospective, observational cohort study to describe prevalence of clinical characteristics present in patients with lipedema in an attempt to establish diagnostic criteria. Participants were consecutive patients with lipedema presenting at a public hospital in Spain from September 2012 to December 2019. Patients were examined for the following signs and symptoms of lipedema: symmetrical involvement; disproportion between the upper and lower part of the body; sparing of the feet; pain; bruising; Stemmer' sign; pitting test; fibrosis; venous insufficiency; upper limbs involvement; vascular spiders; skin coldness; and lymphangitis attacks. In addition, orthopedic alterations were examined in all patients. We recruited 138 patients (median age=47.6 years; mean BMI=29.9 Kg/m2). Using waist-to-height-ratio, 41.3% of the patients were slim or healthy. The most frequent type of lipedema was Type III (71%), and most were in stage 1 and 2. The features of lipedema with a prevalence >80% were symmetrical involvement, unaffected feet, pain, bruising, vascular spiders, and disproportion. Pain was nociceptive in 60.2% and neuropathic in 33.1%, and there was a reduced social or working activities in 37.9%. Orthopedic alterations including cavusfeet or valgus-knees were observed in 1/3 of the patients. X-ray of the knees was performed in 63 patients and knee osteoarthritis diagnosed in 37. We found that the most frequent manifestations of lipedema were bilateral involvement, unaffected feet, pain, easy bruising, vascular spiders, and disproportion between the upper and lower parts of the body. These should be considered as major criteria for diagnosis. In addition, our findings on the prevalence of orthopedic alterations in patients with lipedema highlights the need for a multidisciplinary and integrated approach.

SARS-CoV-2 immunochromatographic IgM/IgG rapid test in pregnancy: A false friend?

BACKGROUND: An increasing body of evidence has revealed that SARS-CoV-2 infection in pregnant women could increase the risk of adverse maternal and fetal outcomes. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted. Therefore, rapid antibody tests have been suggested as an efficient screening tool during pregnancy. CASES: We analysed the clinical performance during pregnancy of a rapid, lateral-flow immunochromatographic assay for qualitative detection of SARS-CoV-2 IgG/IgM antibodies. We performed a universal screening including 169 patients during their last trimester of pregnancy. We present a series of 14 patients with positive SARS-CoV-2 immunochromatographic assay rapid test result. Immunochromatographic assay results were always confirmed by chemiluminescent microparticle immunoassays for quantitative detection of SARS-CoV-2 IgG and IgM+IgA antibodies as the gold standard. We observed a positive predictive value of 50% and a false positive rate of 50% in pregnant women, involving a significantly lower diagnostic performance than reported in non-pregnant patients. DISCUSSION: Our data suggest that although immunochromatographic assay rapid tests may be a fast and profitable screening tool for SARS-CoV-2 infection, they may have a high false positive rate and low positive predictive value in pregnant women. Therefore, immunochromatographic assay for qualitative detection of SARS-CoV-2 IgG/IgM antibodies must be verified by other test in pregnant patients.

Social Environment Ameliorates Behavioral and Immune Impairments in Tyrosine Hydroxylase Haploinsufficient Female Mice.

The social environment can influence the functional capacity of nervous and immune systems, and consequently the state of health, especially in aged individuals. Adult female tyrosine hydroxylase haploinsufficient (TH-HZ) mice exhibit behavioral impairments, premature immunosenescence and oxidative- inflammatory stress. All these deteriorations are associated with a lower lifespan than wild type (WT) counterparts. The aim was to analyze whether the cohabitation with WT animals could revert or at least ameliorate the deterioration in the nervous and immune systems that female TH-HZ mice show at adult age. Female TH-HZ and WT mice at age of 3-4 weeks were divided into following groups: control TH-HZ (5 TH-HZ mice in the cage; TH-HZ100%), control WT (5 WT mice in the cage; WT100%), TH-HZ > 50% and WT < 50% (5 TH-HZ with 2 WT mice in each cage) as well as TH-HZ < 50% and WT > 50% (2 TH-HZ and 5 WT mice in each cage). At the age of 37-38 weeks, all mice were submitted to a battery of behavioral tests, evaluating sensorimotor abilities, exploratory capacities and anxiety-like behaviors. Subsequently, peritoneal leukocytes were extracted and several immune functions as well as oxidative and inflammatory stress parameters were analyzed. The results showed that the TH-HZ < 50% group had improved behavioral responses, especially anxiety-like behaviors, and the immunosenescence and oxidative stress of their peritoneal leukocytes were ameliorated. However, WT mice that cohabited with TH-HZ mice presented higher anxiety-like behaviors and deterioration in immune functions and in their inflammatory stress parameters. Thus, this social environment is capable of ameliorating the impairments associated with a haploinsufficiency of the th gene. Graphical Abstract.

Caracterización clínica y sociodemográfica de los pacientes con tinnitus en un centro especializado de Medellín / Clinical and sociodemographic characteristics of patients with tinnitus at specialized unit in Medellín

Resumen Introducción: teniendo en cuenta la repercusión del tinnitus en la calidad de vida de los pacientes, el objetivo de este estudio es conocer las características específicas clínicas y sociodemográficas de los pacientes que asistieron ambulatoriamente a la unidad especializada de tinnitus de la Clínica Orlant, ubicada en la ciudad de Medellín, Colombia. Comprender las peculiaridades de los pacientes con acúfenos constituye un enfoque para proponer medidas de prevención y tratamiento dirigido, siendo este el primer estudio con estas características que se realiza en Colombia. Materiales y métodos: estudio retrospectivo de pacientes referidos por primera vez a la consulta especializada de tinnitus en el centro de especialistas en Otorrinolaringología y Otología, Clínica Orlant, en un año. Se obtuvo información demográfica y se recopilaron datos de las historias clínicas. Resultados: se incluyeron 61 pacientes, cuya edad media fue de 52,5 años. El 54,1 % presentó tinnitus bilateral, el 78,7 % refirió tono agudo y el 59 % intensidad moderada. Entre los síntomas asociados, el 67,2 % refirió sensación de giro y el 80,3 % desequilibrio o inestabilidad. El 23 % tenía hipertensión arterial, 5 pacientes recibieron ototóxicos, el 34,4 % tuvo exposición crónica al ruido y el 8,2 % hipoacusia súbita. El 21,3 % tenía diagnóstico de trastorno psiquiátrico. El 65,5 % diagnóstico de hipoacusia, el 52,5 % bilateral y el 54,1 % de tipo neurosensorial Conclusión: las características del tinnitus más comunes fueron la presentación bilateral, duración mayor de tres meses, tonalidad aguda y de intensidad moderada. Se encontró una representación similar de algunas características en la población de otras áreas geográficas.

Equines as reservoirs of human fascioliasis: transmission capacity, epidemiology and pathogenicity in Fasciola hepatica-infected mules.

Fascioliasis is a zoonotic disease caused by liver flukes transmitted by freshwater lymnaeid snails. Donkey and horse reservoir roles have been highlighted in human endemic areas. Liver fluke infection in mules has received very limited research. Their role in disease transmission, epidemiological importance and Fasciola hepatica pathogenicity are studied for the first time. Prevalence was 39.5% in 81 mules from Aconcagua, and 24.4% in 127 from Uspallata, in high-altitude areas of Mendoza province, Argentina. A mean amount of 101,242 eggs/mule/day is estimated. Lymnaeids from Uspallata proved to belong to ribosomal DNA internal transcribed spacer (ITS) markers ITS-1 and ITS-2 combined haplotype 3C of Galba truncatula. These lymnaeids were experimentally susceptible to infection by egg miracidia from mules. Infectivity, number of cercariae/snail and shedding period fit the enhanced F. hepatica/G. truncatula transmission pattern at very high altitude. This indicates that the mule is able to maintain the F. hepatica cycle independently. Individual burdens of 20 and 97 flukes were found. Mule infection susceptibility is intermediate between donkey and horse, although closer to the latter. Anatomo-pathology and histopathology indicate that massive infection may cause mule death. Haematological value decreases of red blood cells, haemoglobin, leucocytes and lymphocytes indicate anaemia and strong immunosuppression. Strongly increased biochemical marker values indicate liver function alterations. The mule probably played a role in the past exchanges with Chile and Bolivia through Mendoza province. Evidence suggests that mules could contribute to the spread of both F. hepatica and G. truncatula to human fascioliasis-endemic areas in these countries.

Colaboración con el Hospital Puerta de Hierro en el ensayo clínico «CON PLAS-19» para el tratamiento de pacientes potencialmente graves con plasma hiperinmune de donantes convalecientes de COVID-19. Obtención en el Centro de Transfusión de las FAS (CTFAS) / Collaboration with Hospital Puerta de Hierro in the clinical trial «CON PLAS-19» for the treatment of potentially serious patients with hyperinmune plasma of COVID-19 convalescent donors. obtaining at the Centro de Transfusión de las Fuerzas Armadas (CTFAS)

Desde hace tiempo se utilizan tratamientos para algunas enfermedades infecciosas con plasma hiperinmune de donantes convalecientes de esa enfermedad con resultados prometedores. Ante la pandemia de COVID-19 se plantea su eficacia dado que no existen tratamientos óptimos para abordar la enfermedad. El Comité Científico de Seguridad Transfusional del Ministerio de Sanidad permite la realización de ensayos clínicos y estudios observacionales para avanzar en este terreno mientras se obtiene un tratamiento eficaz

Treatments for some infectious diseases with hyperimmune plasma from convalescent donors of this disease have been used for some time with promising results. In the face of the COVID-19 pandemic, its efficacy arises since there are no optimal treatments to tackle the disease. The Scientific Committee on Transfusion Safety of the Ministry of Health allows clinical trials and observational studies to be carried out to advance in this field while obtaining effective treatment

The ratio of prematurely aging to non-prematurely aging mice cohabiting, conditions their behavior, immunity and lifespan.

Adult prematurely aging mice (PAM) show behavioral deterioration, premature immunosenescence and increased oxidative stress, impairments that are associated with their shorter lifespan, compared to the corresponding exceptional non-prematurely aging mice (ENPAM). When PAM live in a predominantly ENPAM environment (2/5, respectively) they exhibit an improvement of immunity and redox state in their spleen and thymus leukocytes, and an increased lifespan. Nevertheless, it is unknown if other PAM/ENPAM ratios could affect behavioral and peritoneal leukocyte functions of PAM and change their lifespan. ENPAM and PAM were divided into the following groups: C-ENPAM (8 ENPAM in the cage); C-PAM (8 PAM in the cage); ENPAM>50% and PAM<50% (5 ENPAM/2 PAM in each cage); ENPAM = 50% and PAM = 50% (4 ENPAM/4 PAM in each cage), and PAM>50% and ENPAM<50% (5 PAM/2 ENPAM in each cage). After two months, mice were submitted to a battery of behavioral tests. Several functions and oxidative stress parameters were then assessed in their peritoneal leukocytes. Animals were maintained in these conditions to analyze their lifespan. The results showed that PAM>50%, PAM = 50% and PAM<50% exhibited better behavioral responses, immunity and redox states in their peritoneal leukocytes than C-PAM. This improvement was higher when the number of ENPAM in the cage was increased, with most of the parameters in PAM<50% reaching similar values to those in C-ENPAM, and an increased lifespan. However, ENPAM that cohabited with PAM showed, in general, an impairment of parameters studied. In conclusion, the PAM/ENPAM cohabitation ratio is relevant to behavior and immunity.

Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature.

Posttransplant high-dose cyclophosphamide (PTCy) effectively prevents GvHD after haploidentical SCT. However, its use in HLA-matched SCT has been less explored. Fifty-six consecutive patients who underwent allo-SCT for hematological malignancies have been included in this prospective single-center protocol. Donors have been HLA-identical siblings, fully-matched unrelated or 1-allele-mismatched unrelated donors in 30%, 32%, and 37% of cases, respectively. Nine patients have received a TBI-containing MAC regimen, while the remaining (84%) received RIC platforms based on Fludarabine plus Busulfan/Melphalan. Due to the high graft failure (GF) rate (21%) in a preliminary analysis in the allo-RIC cohort (n = 29), protocol amendments have been implemented, with no further cases of GF after the introduction of mini-thiotepa (0/18). The overall incidence of grade II-IV acute GvHD is 24% (95% CI: 17-31%) with four steroid-refractory cases. Severe chronic GvHD has occurred in only 1 of 43 evaluable cases. The 1-year NRM and relapse are 18% (95% CI: 12-26%) and 30% (18-42%) and the OS and DFS are 78% and 64%, respectively. These outcomes support the feasibility of using PTCy as a SOC outside the haplo-setting, albeit mini-thiotepa (3 mg/kg) was incorporated in the standard allo-RIC platforms to prevent GF. Despite the limitations of a single-center experience and the short follow-up, these protocols show promising results with particular benefit in reducing the occurrence of moderate-to-severe GvHD.

Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder.

BACKGROUND AND PURPOSE: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. METHODS: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. RESULTS: The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. CONCLUSION: Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.