Molecular diagnosis of cystic fibrosis by RNA obtained from nasal epithelial cells.

BACKGROUND: The diagnosis of cystic fibrosis (CF) is established when characteristic clinical signs are coupled with biallelic CFTR pathogenic variants. No previously reported non-canonical splice site variants have to be considered as variants of uncertain significance unless their effect on splicing has been validated. METHODS: Two variants identified by next-generation sequencing were evaluated. We assayed their effects on splicing employing RNA analysis and real-time expression quantification from RNA obtained from the nasal epithelial cells of a patient with clinically suspected CF and of two patients with milder phenotypes (CFTR-related disorders). RESULTS: The variant c.164+2dup causes skipping of exon 2 (p.(Ser18_Glu54del)) and exon 2 plus 3 (p.(Ser18Argfs*16)) in CFTR mRNA. Exon 2 expression in the patient heterozygous for c.164+2dup was decreased to 7 % of the exon 2 expression in the controls. The synonymous variant c.1584G>A causes a partial skipping of exon 11. The exon 11 expression in the two patients heterozygous for this variant was 22 % and 42 % of that of the controls, respectively. CONCLUSION: We conclude that variant c.164+2dup affects mRNA processing and can be considered a CF-causing variant. The results of the functional assay also showed that the p.(Glu528=) variant, usually categorized as a neutral variant based on epidemiological data, partially affects mRNA processing in our patients. This finding would allow us to reclassify the variant as a CFTR-related variant with incomplete penetrance. RNA obtained from nasal epithelial cells is an easy and accurate tool for CFTR functional studies in patients with unclassified splice variants.

Dependency-related skin lesions in the prone critical patient. Incidence study.

OBJECTIVE: To determine the incidence of dependence-related skin lesions (DRSL) in patients in prone position (PP) and to identify the predisposing factors. METHOD: Follow-up study in two polyvalent intensive care units. Patients undergoing invasive mechanical ventilation and PP with no skin lesions on admission were included. We recorded the 3 types of DRSL: (pressure ulcers [PU], moisture-associated skin damage [MASD] and friction injuries [FI]), demographic variables, diagnosis, length of stay, PP episodes, postural changes, APACHE II (Acute Physiology and Chronic Health Disease Classification System), prealbumin level on admission, body mass index (BMI), diabetes, hypertension, smoking, peripheral vascular disease (PVD), vasoactive drugs, Braden scale and mortality. Bivariate analysis: chi-square test, t-test or Mann-Whitney U test. Multivariate analysis: logistic regression. RESULTS: Forty nine patients were included and 170PP were performed.Forty-one DRSL appeared in 22 patients with a cumulative incidence of 44.9% (95%CI: 31.6-58.7). PU accounted for 63.4% (73.1% facial; 76.9% stage II), 12.2% were MASD (60% inguinal; 60% stage II) and 24.4% were FI (50% thoracic; 70% stage III). The median age of the lesion group (LG) was 66.5 [61.8-71.3] vs. 64 [43-71] years old in the non-lesion group (NLG), p=0.04. Eighty percent of the LG had PVD vs. 20% of the NLG, p=0.03. The median total hours on PP of the LG was 96.9 [56.1-149.4] vs. 38.2 [18.8-57] of the NIG, p<0.001. Multivariate analysis selected total PP hours (OR=1.03; 95%CI:1.01-1.05) and PVD (OR=8.9; 95%CI:1.3-58.9) as predisposing factors for developing DRSL. CONCLUSIONS: There is a high incidence of skin lesions related to prone decubitus dependence, mostly pressure lesions, although of low severity.The accumulated hours in probe position and peripheral vascular disease favor their development.

Oral Focal Mucinosis of the Tongue: A Rare Localization for a Rare Entity.

ABSTRACT: Oral focal mucinosis (OFM) is a rare connective tissue disorder that is characterized by the excessive production of hyaluronic acid due to myxoid degeneration of submucosal connective tissue. The disorder typically presents as an asymptomatic nodule or mass in the gingiva or hard palate, and OFM of the tongue is even more unusual. In this report, we present a case of OFM on the tongue in a 72-year-old female patient who presented with a symptomatic lump that had been growing for 6 months on the dorsum of her tongue. The patient reported discomfort and pain while speaking and swallowing, and the lump was visually apparent on examination. OFM is a benign condition that does not have any specific clinical or radiographical features that distinguish it from other more common oral lesions, such as lipoma or fibroma. Therefore, histopathological examination is essential for a definitive diagnosis. The management of OFM typically involves surgical excision of the lesion. In this case, complete surgical removal of the lesion under general anesthesia was performed, and the patient was followed up for 10 months postoperatively. During the follow-up period, there was no evidence of recurrence, and the patient reported significant improvement in her symptoms. In conclusion, OFM is a rare connective tissue disorder that can occur in the oral cavity. Although OFM of the tongue is even rarer, it should be considered in the differential diagnosis of oral lesions. Histopathological examination is essential for definitive diagnosis, and surgical excision is typically the preferred treatment modality.

Outcomes of Valvular Endocarditis in Patients With and Without Pericardial Effusion: A National Inpatient Sample Study.

Over the last decade, hospitalizations for infective endocarditis (IE) have been steadily increasing, leading to a significant healthcare burden. Pericardial effusion (PCE) has been identified as a serious complication of IE, yet no significant association with mortality has been established. Our study aims to further analyze and understand the significance of PCE in patients with IE. We performed a retrospective analysis using the national inpatient sample database to identify all the hospital admissions with IE using ICD 10 codes and stratified them into 2 groups based on the presence of PCE. The outcomes of interest were inhospital mortality, inhospital complications, need for cardiac surgery, and length of stay. From 2015 Q4-2019, a total of 76,260 hospitalizations were included (weighted: 381,300), of which 2.7% included a PCE diagnosis. Hospitalizations with a PCE diagnosis included patients that were younger (51 vs 61, P < 0.001), as well as slightly more males (58.0% vs 55.2%, P = 0.011), and black patients (16.9% vs 12.9%, P < 0.001). PCE was associated with higher in-hospital death (12.7% vs 9.0%, P < 0.001), longer lengths of stay (12 days vs 7 days, P < 0.001), higher rates of cardiac surgery (22.4% vs 7.3%, P < 0.001). The rates of heart failure, heart block, renal failure, cardiogenic shock, and embolic stroke were higher on PCE group. We found that presence of PCE is associated with higher inhospital mortality, longer length of stay, and greater utilization of cardiac surgery, as well as presence of heart failure, heart block, cardiogenic shock, and embolic stroke.

Cation leak through the ATP1A3 pump causes spasticity and intellectual disability.

ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic ATP1A3 variants produce several distinct neurological syndromes, yet the molecular basis for phenotypic variability is unclear. We report a novel recurrent variant, ATP1A3(NM_152296.5):c.2324C>T; p.(Pro775Leu), in nine individuals associated with the primary clinical features of progressive or non-progressive spasticity and developmental delay/intellectual disability. No patients fulfil diagnostic criteria for ATP1A3-associated syndromes, including alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism or cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss (CAPOS), and none were suspected of having an ATP1A3-related disorder. Uniquely among known ATP1A3 variants, P775L causes leakage of sodium ions and protons into the cell, associated with impaired sodium binding/occlusion kinetics favouring states with fewer bound ions. These phenotypic and electrophysiologic studies demonstrate that ATP1A3:c.2324C>T; p.(Pro775Leu) results in mild ATP1A3-related phenotypes resembling complex hereditary spastic paraplegia or idiopathic spastic cerebral palsy. Cation leak provides a molecular explanation for this genotype-phenotype correlation, adding another mechanism to further explain phenotypic variability and highlighting the importance of biophysical properties beyond ion transport rate in ion transport diseases.

[Physical activity programs that include self-efficacy in school children with obesity: a systematic review]. / Programas de actividad física que incluyen la autoeficacia en escolares con obesidad: revisión sistemática.

Introduction: Introduction: this research aims to carry out a systematic review of physical activity programs that improve self-efficacy in children and adolescents with obesity, to realize their characteristics and thus design a more comprehensive and effective program for this population. Objective: to analyze the characteristics of physical activity programs that improve self-efficacy in children and adolescents with obesity, through a systematic review. Methodology: systematic review of observational-descriptive design; the search was realized in databases of the health area: PubMed, ERIC, Cochrane, Redalyc, and Google academic. Free access articles in English and Spanish from the last 10 years were selected. The temporality was from March 2012 to May 2022. The descriptors used were; "physical activity program", "training program", "self-efficacy", "children", "adolescents", and "obesity". Results: six studies were included (n = 10). Different types of interventions that improved self-efficacy in the participant were identified, such as recreational activities, traditional games, sports, and structured activities for health care. The methodology implemented and the timing and duration were key variables to show positive changes in childhood overweight and obesity (6 a 19 years). Conclusions: it is crucial to identify the principal health care characteristics included in programs focused on increasing self-efficacy in childhood. These features lay the foundation for designing comprehensive programs.

Introducción: Introducción: se pretende realizar una revisión sistemática de los programas de actividad física que incluyan y mejoren la autoeficacia en niños y adolescentes con obesidad con la finalidad de analizar sus características y diseñar un programa integral y efectivo en esta población. Objetivo: analizar las características de los programas de actividad física que mejoran la autoeficacia en niños y adolescentes con obesidad a través de una revisión sistemática. Metodología: revisión sistemática de diseño observacional-descriptiva; se realizó la búsqueda en bases de datos del área de la Salud: PubMed, ERIC, Cochrane, Redalyc y Google académico. Se seleccionaron artículos originales de libre acceso en inglés y español de los últimos 10 años. La temporalidad fue de marzo 2012 a mayo de 2022. Los descriptores utilizados fueron: "physical activity program", "training program", "auto efficacy", "children", "teenagers" y "obesity". Resultados: seis estudios fueron incluidos (n = 10). Se identificaron diferentes tipos de intervenciones tales como actividades recreativas, de juegos tradicionales, deportivos y actividades estructuradas para el cuidado de la salud, mismas que mejoraron la autoeficacia en el participante. La metodología implementada y la temporalidad y duración fueron variables clave para evidenciar cambios positivos en el sobrepeso y obesidad infantil (6 a 19 años). Conclusiones: es importante identificar las características de los programas orientados a la mejora de la autoeficacia en la etapa de la infancia y adolescencia. Sus características principales pueden utilizarse para diseñar programas integrales.

Dispositivos de Avance Mandibular para el Manejo del Ronquido y la Apnea del Sueño. Actitudes de los Odontólogos Generales y los Especialistas Médicos para Proporcionarlos

RESUMEN: El objetivo de este estudio fue determinar las actitudes y la conciencia de los odontólogos y especialistas médicos sobre la provisión de dispositivos de avance mandibular (DAM) para el tratamiento de los ronquidos y la apnea del sueño. Se llevó a cabo un estudio observacional descriptivo de corte transversal, donde se seleccionaron por conveniencia 53 odontólogos (generales y especialistas) y 5 médicos especialistas en medicina del sueño en la ciudad de Guadalajara, México. Quienes respondieron un cuestionario específico desarrollado por Jauhar et al. (2008) dirigido a conocer la actitud de los odontólogos y médicos especialistas para la provisión de los DAM y otros aspectos relacionados con el ronquido y la apnea obstructiva del sueño (AOS). El 94 % de los odontólogos respondió estar interesado en capacitarse en ronquido y AOS. Y en el grupo de los médicos especialistas se encontró que el 80 % cree que los odontólogos sí tienen un papel para ayudar a los pacientes con ronquido y AOS, el 60 % cree que los odontólogos pueden contribuir con la realización de DAM y el 40 % considera que los odontólogos deben remitir a un especialista del sueño. Existe una actitud muy positiva de los odontólogos para ser parte del grupo interdisciplinario para el tratamiento del ronquido y de la apnea obstructiva del sueño, pero este estudio nos muestra además que a pesar de la disposición para utilizar los DAM, la formación y capacitación no es suficiente. Por otra parte, hay una actitud positiva de los médicos especialistas que consideran que los odontólogos juegan un papel importante en ayudar a los pacientes con ronquidos o con apnea del sueño, pero se evidencia que en su gran mayoría no usan los DAM como parte de un posible tratamiento.

ABSTRACT: The objective of this study was to determine the attitudes and awareness of dentists and medical specialists on the provision of mandibular advancement devices (MAD) for the treatment of snoring and sleep apnea. This is a cross-sectional descriptive observational study, where 53 dentists (general and specialists) and 5 sleep medicine specialists in the city of Guadalajara, Mexico were selected for convenience. The selected group answered a specific questionnaire developed by Jauhar et al., to know the attitude of dentists and medical specialists for the provision of MAD and other aspects related to snoring and obstructive sleep apnea (OSA). 94 % of dentists responded to be interested in training in snoring and OSA. And of the group of medical specialists, 80 % consider that dentists have a role in helping patients with snoring and OSA, 60 % believe that dentists can contribute to MAD and 40 % believe that dentists should refer a sleep specialist. There is a very positive attitude by the dentists to be part of the interdisciplinary group for the treatment of snoring and obstructive sleep apnea, but this study also shows that despite the willingness to use MAD, education and training is not enough. There is a positive attitude of specialist doctors who consider that dentists play an important role in helping patients with snoring or with sleep apnea, but it is evident that the majority do not use MAD as part of a possible treatment.

Patrones de susceptibilidad de gramnegativos en un hospital pediátrico de tercer nivel: 2013 vs. 2018 / Gram-negative susceptibility patterns in a tertiary pediatric hospital: 2013 vs. 2018

Resumen Introducción: Los gramnegativos continúan siendo los causantes de infecciones asociadas a la atención a la salud (IAAS). Material y métodos:: Analizamos la resistencia antimicrobiana de patógenos durante el 2013 vs. 2018 y lo comparamos con lo publicado en 2006 vs. 2012. Resultados: Identificamos nueve patógenos gramnegativos, de un total de 404 aislamientos, con una prevalencia en 2013 (N = 227 [0.22]) vs. 2018 (N = 177 [0.17]) y una incidencia por egresos (6,607 en el 2013 y 7,778 en el 2018) del 3.4 y 2.2% respectivamente. Destacaron tres patógenos: Klebsiella pneumoniae (129 [31.93%]), Pseudomonas aeruginosa (85 [21.03%]) y Escherichia coli (80 [19.80%]). Estos, llamados patógenos ESKAPE-E, prevalecieron como causantes de IAAS. Identificamos un aumento en los patrones de resistencia para muchos patógenos en 2018. Conclusión: La multirresistencia a patógenos ESKAPE-E es un serio problema de salud pública, por carecer de alternativas terapéuticas para enfrentar este reto. Los mapas de resistencia bacteriana ayudan en la prescripción antibiótica.

Abstract Background: Gram-negatives continue to be the cause of infections associated with health care (HCAI). Material and methods: We analyzed the antimicrobial resistance of pathogens during 2013 vs. 2018 and we compare it with what was published in 2006 vs. 2012. Results: We identified 9 gram-negative pathogens, out of a total of 404 isolates, with a prevalence in 2013 (N = 227 [0.22]) vs. 2018 (N = 177 [0.17]) and an incidence due to discharges (6,607 in 2013 and 7,778 in 2018) of 3.4 and 2.2%, respectively.Three pathogens stood out Klebsiella pneumoniae (129 [31.93%]), Pseudomonas aeruginosa (85 [21.03%]) and Escherichia coli (80 [19.80%]). These, called ESKAPE-E pathogens, prevailed as the cause of HCAI. We identified an increase in resistance patterns for many pathogens in 2018. Conclusion: Multi-resistance to ESKAPE-E pathogens is a serious public health problem, due to the lack of therapeutic alternatives to face this challenge. Bacterial resistance maps help in antibiotic prescription.

Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved.

Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and ß-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology.

Síndrome de Cotard en trastorno depresivo recurrente: reporte de caso / Cotard Syndrome in recurrent depressive disorder: case report

El Síndrome de Cotard también conocido como delirio de negación o nihilista, fue descrito por el neurólogo francés Julius Cotard en junio de 1880. Desde esa época hasta fines del siglo XX se ha reportado en la literatura científica aproximadamente 100 casos. Que presentaban sintomatología depresiva, ansiosa, delusiones nihilistas concernientes al cuerpo y a la existencia, delusiones hipocondriacas y de inmortalidad, así como alucinaciones auditivas y visuales. Se presenta el caso de una mujer de 73 años, natural de Ayacucho, con antecedentes de agresión sexual a los 12 años, y episodios de intento de suicidio en dos oportunidades, siendo diagnosticada de depresión a los 40 años, recibió tratamiento con quetiapina, trazadona y clonazepam. Se mantuvo con evolución fluctuante, empeoraron sus síntomas con factores estresantes como el fallecimiento de su mamá, esposo y cirugías a las que fue sometida. Actualmente presenta ánimo triste y ansioso, llanto diario, ideas de culpa, minusvalía y tanáticas, insomnio de conciliación, delusiones nihilistas concernientes al cuerpo, refiriendo que su estómago y vejiga no funciona, por tal motivo no desea comer ni ingerir agua. Debido al rechazo total a ingesta de alimentos e ideación suicida persistente fue hospitalizada para recibir tratamiento psiquiátrico y soporte nutricional.

The Cotard Syndrome, also known as delirium of negation or nihilistic delirium, was described by the French neurologist, Julius Cotard, on June 1880. From that time until the end of the 20th century, in scientific literature, approximately 100 cases were reported that presented symptoms of depression, anxiety, nihilist delusions concerning the body and existence, hypochondriacal and immortality delusions, as well as auditory and visual hallucinations. We present the case of a female patient, 73-years old, from Ayacucho, with a history of sexual assault at the age of 12 and suicidal attempts on 2 occasions, diagnosed with depression at 40 years of age, received treatment with quetiapine, trazadone and clonazepam. She remained with fluctuating medical progress, with symptoms worsening with stressors such as the death of her mother and husband and when she underwent surgeries. Currently, she presents sad and anxious mood, daily crying, ideas of guilt, disability and death, insomnia of conciliation, nihilistic delusive ideas concerning the body, referring that her stomach and bladder do not work, reason why she doesn't want to eat or drink water. Due to the total refusal of food intake and persistent suicidal ideation, she was hospitalized to receive psychiatric treatment and nutritional support. It is concluded that there are few cases reported on the use of psychotherapy in Cotard's syndrome. Therefore, this case in which psychotherapy was indicated to reduce anxious-affective symptoms, to avoid isolation of the person and to redirect his personal and social life, is important.

Articulation of the Sustainable Development Goals with de circular economy paradigm / Articulación de los objetivos de desarrollo sostenible con el paradigma de la economía circulara

RESUMEN Con base en diversas investigaciones de las autoras en el ramo medioambiental de la Industria Minero-Metalúrgica de México, se plantea un estudio que tiene como objetivo describir, desde la perspectiva teórica de la Economía Circular, indicadores en función de los Objetivos de Desarrollo Sostenible: Industria, Innovación e Infraestructura, y Producción y Consumo Responsable en relación con las fases del Modelo de Economía Circular (MEC), para formular propuestas de medición de productividad en búsqueda del equilibrio económico, social y ambiental que promueve la Sustentabilidad. A partir de una metodología de corte cualitativo basada en un Estudio de Caso realizado en una unidad minera se obtienen resultados que permiten establecer indicadores en relación con cada fase del MEC, generando conclusiones que dirigen a mediciones particulares que en conjunto permitirán la obtención de valores de productividad ligados a la circularidad gestando acciones sustentables.

ABSTRACT Based on diverse investigations of the authors in the environmental branch of the Mining-Metallurgic Industry of Mexico, a study is proposed that has as objective to describe from the theoretical perspective of the Circular Economy, indicators in function of the Objectives of Sustainable Development: Industry, Innovation and Infrastructure and Production and Responsible Consumption in relation to the phases of the Model of Circular Economy (MCE), to formulate proposals of measurement of productivity in search of the economic, social and environmental balance, that Sustainability promotes. From a qualitative methodology based on a Case Study carried out in a mining unit, results are obtained that allow the establishment of indicators in relation to each phase of the MCE, generating conclusions that lead to particular measurements that together will allow the obtaining of productivity values linked to circularity by managing sustainable actions.

Symptomatic heterozygous X-Linked myotubular myopathy female patient with a large deletion at Xq28 and decrease expression of normal allele.

X-linked myotubular myopathy (XLMTM; OMIM 310400) is a centronuclear congenital muscular disorder of X-linked recessive inheritance. Although female carriers are typically asymptomatic, affected heterozygous females have been described. Here, we describe the case of a sporadic female patient with suspicion of centronuclear myopathy and a heterozygous large deletion at Xq28 encompassing the MAMLD1, MTM1, MTMR1, CD99L2, and HMGB3 genes. The deletion was first detected using a custom next generation sequencing (NGS)-based multigene panel and finally characterized by comparative genomic hybridization array and multiplex ligation probe assay techniques. In this patient we have confirmed, by MTM1 mRNA quantification, a MTM1 gene expression less than the expected 50 percent in patient muscle. The significant 20% reduction in MTM1 mRNA expression in muscle, precludes low level of the normal myotubularin protein as the cause of the phenotype in this heterozygous female. We have also found that BIN1 expression in patient muscle biopsy was significantly increased, and postulate that BIN1 expression will be increased in XLMTM patient muscle as an attempt to maintain muscle function.

Uso del mindfulness sobre indicadores de estrés en deportistas durante la etapa competitiva: revisión sistemática / Use of mindfulness on indicators of stress in athletes during the competitive stage: systematic review

El mindfulness es una práctica meditativa que ha probado disminuir el estrés psicofisiológico. Propósito: analizar, si el mindfulness es efectivo para disminuir el estrés psicofisiológico, en deportistas de alto rendimiento en temporada competitiva. Se realizó una búsqueda de estudios clínicos que incluyeran diferentes técnicas meditativas para la reducción del estrés en deportistas durante la fase competitiva. En PubMed, Scopus y Web of Science (1985 al 10 de agosto del 2019), se buscaron las combinaciones de palabras mindfulness, meditation, yoga, sport, athlete, intervention, stress, cortisol. Se localizaron sólo siete trabajos, tres de ellos con información cuantitativa, un cuantitativo y tres de metodología mixta. En los siete estudios encontrados (153 sujetos; 134 hombres y 19 mujeres) sus autores mencionan que el mindfulness fue efectivo para la reducción del estrés en los atletas durante la etapa competitiva.

Mindfulness is a meditative practice that has proven to reduce psycho-physiological stress. Purpose: Analyze if mindfulness is effective to reduce psycho-physiological stress in athletes during their competitive season. Clinical studies that included different meditative techniques for stress reduction in athletes during the competitive phase was searched for in databases such as PubMed, Scopus and Web of Science (1985 to August 10, 2019), using the combinations of the words mindfulness, meditation, yoga, sport, athlete, intervention, stress, and cortisol. Only seven papers were located, three of them with a quantitative design, one as quantitative and three with mixed methodology. In the seven studies found (153 subjects; 134 men and 19 women) their authors mention that mindfulness was effective for reducing stress in athletes during the competitive season.

Physiological levels of folic acid reveal purine alterations in Lesch-Nyhan disease.

Lesch-Nyhan disease (LND), caused by a deficient salvage purine pathway, is characterized by severe neurological manifestations and uric acid overproduction. However, uric acid is not responsible for brain dysfunction, and it has been suggested that purine nucleotide depletion, or accumulation of other toxic purine intermediates, could be more relevant. Here we show that purine alterations in LND fibroblasts depend on the level of folic acid in the culture media. Thus, physiological levels of folic acid induce accumulation of 5-aminoimidazole-4-carboxamide riboside 5'-monophosphate (ZMP), an intermediary of de novo purine biosynthetic pathway, and depletion of ATP. Additionally, Z-nucleotide derivatives (AICAr, AICA) are detected at high levels in the urine of patients with LND and its variants (hypoxanthine-guanine phosphoribosyltransferase [HGprt]-related neurological dysfunction and HGprt-related hyperuricemia), and the ratio of AICAr/AICA is significantly increased in patients with neurological problems (LND and HGprt-related neurological dysfunction). Moreover, AICAr is present in the cerebrospinal fluid of patients with LND, but not in control individuals. We hypothesize that purine alterations detected in LND fibroblasts may also occur in the brain of patients with LND.

Systematic genetic analysis of early-onset gout: ABCG2 is the only associated locus.

OBJECTIVE: The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout. METHODS: Participants with gout in the Genetics of Gout in Aotearoa study with available genotyping were included (n = 1648). Early-onset gout was defined as the first presentation of gout <40 years of age. Single nucleotide polymorphisms (SNPs) for the 10 loci most strongly associated with serum urate were genotyped. Allelic association of the SNPs with early-onset gout was tested using logistic regression in an unadjusted model and in a model adjusted for sex, body mass index, tophus presence, flare frequency, serum creatinine and highest serum urate. The analysis was also done in two replication cohorts: Eurogout (n = 704) and Ardea (n = 755), and data were meta-analysed. RESULTS: In the Genetics of Gout in Aotearoa study, there were 638 (42.4%) participants with early-onset gout. The ABCG2 rs2231142 gout risk T-allele was present more frequently in participants with early-onset gout compared with the later-onset group. For the other SNPs tested, no differences in risk allele number were observed. In the allelic association analysis, the ABCG2 rs2231142 T-allele was associated with early-onset gout in unadjusted and adjusted models. Analysis of the replication cohorts confirmed the association of early-onset gout with the ABCG2 rs2231142 T-allele, but not with other serum urate-associated SNPs. In the meta-analysis, the odds ratio (95% CI) for early-onset gout for the ABCG2 rs2231142 T-allele was 1.60 (1.41, 1.83). CONCLUSION: In contrast to other serum urate-raising variants, the ABCG2 rs2231142 T-allele is strongly associated with early-onset gout.

[Study of conizations of the cervix after five years of cervical cancer screening with co-testing]. / Estudio de piezas de conización tras cinco años de cribado de cáncer de cérvix con co-test.

OBJECTIVE: Uterine Cervical Cancer (UCC) screening has changed with the introduction of the High Risk Human Papilloma Virus test (HRHPV) and its evaluation is necessary. The objective of this study is to analyze the effectiveness of UCC screening with activities aimed at early detection and treatment to modify the natural history of the process and improve its prognosis. METHODS: Cytology and HR-HPV (co-testing) were performed according to the SEGO protocol of 2010 between 2011 and 2015 with follow-up until 2017. The HR-HPV DNA test was HC2 Hybrid Capture (Digene®) at the beginning (16.1% of the cases) and Cobas 4800 (Roche®) afterwards. Target population: Barbastro´s health area. The initial treatment was conization with loop (LLETZ). Sensitivity and Positive Predictive Value of tests were studied, as well as the association between demographic and pathological variables. RESULTS: 238 high-grade dysplasias (HSIL) or more (CIN2+) were detected with a mean age of 37.9±10.3 years and 60.0% were genotype 16 and/or 18 positive. 220 patients (92.4%) underwent conization completed thereafter with reconization or hysterectomy in 25 cases (11.4%). HSIL was diagnosed in 220 cases (92.4%) and invasive carcinoma in 18 (7.6%), 7 microinvasive (2.9%). 14.4% of cones had no HSIL (negative cone) and 83.2% got free margins. 52.0% had involvement in a single quadrant and the mean horizontal extension was 3.5±3.1mm. Only in 14 (6.7%) patients the disease (HR-HPV positive) persisted after treatment. A statistically significant association was found in our cases between affected borders and age over 45 years (p=0.005). CONCLUSIONS: The co-test has detected small preinvasive lesions, localized in a single quadrant and microinvasive cancers . Loop conization was effective, achieving the cure of 93.3% of the patients.

OBJETIVO: El cribado del cáncer de cérvix uterino (CCU) ha cambiado con la introducción del test del virus del Papiloma Humano de alto riesgo (VPH-AR) y es necesaria su evaluación. El objetivo de este estudio fue analizar la eficacia del cribado del CCU con las actividades orientadas a la detección y tratamiento precoz para modificar la historia natural del proceso y mejorar su pronóstico. METODOS: Se realizó un cribado con citología y VPH-AR (co-test) según el protocolo SEGO de 2010 entre los años 2011 y 2015 con seguimiento hasta 2017. El test de ADN VPH-AR fue Captura de Híbridos HC2 (Digene ®) al inicio (16,1% de los casos) y Cobas 4800 (Roche®) después. La población diana fue el Área de salud de Barbastro. El tratamiento inicial fue la conización con asa (LLETZ). Se estudió la sensibilidad y el valor predictivo positivo de los test, así como la asociación entre variables demográficas y patológicas. RESULTADOS: Se detectaron 238 displasias de alto grado (HSIL) o mayor con una media de edad de 37,9±10,3 años y el 60,0% fueron positivas a los genotipos 16 y/o 18. Se conizaron 220 pacientes (92,4%) y en 25 (11,4%) se precisó reconización o histerectomía. Se diagnosticó HSIL en 220 pacientes (92,4%) y carcinoma invasor en 18 (7,6%), 7 microinvasores (2,9%). En el 14,4% de los conos no se halló HSIL (conos blancos) y el 83,2% tuvo bordes libres. El 52,0% tenía afectación en un solo cuadrante y el tamaño tuvo de media 3,5±3,1mm. Sólo 14 pacientes (6,7%) continuaban enfermas (VPH-AR positivo) tras tratamiento. Se halló, en nuestros casos, asociación estadísticamente significativa entre bordes afectados y edad mayor de 45 años (p=0,005). CONCLUSIONES: El co-test ha detectado lesiones preinvasoras, pequeñas, localizadas en un solo cuadrante y carcinomas microinvasores. La conización con asa fue eficaz logrando la curación del 93,3% de las pacientes.

Experimental ischemia/reperfusion model impairs endocannabinoid signaling and Na+/K+ ATPase expression and activity in kidney proximal tubule cells.

LLC-PK1 cells, an immortalized epithelial cell line derived from pig renal proximal tubules, express all the major players of the endocannabinoid system (ECS) such as CB1, CB2 and TRPV1 receptors, as well as the main enzymes involved in the biosynthesis and degradation of the major endocannabinoids named 2-arachidonoylglycerol, 2-AG and anandamide, AEA. Here we investigated whether the damages caused by ischemic insults either in vitro using LLC-PK1 cells exposed to antimycin A (an inductor of ATP-depletion) or in vivo using Wistar rats in a classic renal ischemia and reperfusion (IR) protocol, lead to changes in AEA and 2-AG levels, as well as altered expression of genes from the main enzymes involved in the regulation of the ECS. Our data show that the mRNA levels of the CB1 receptor gene were downregulated, while the transcript levels of monoacylglycerol lipase (MAGL), the main 2-AG degradative enzyme, were upregulated in LLC-PK1 cells after IR model. Accordingly, IR was accompanied by a significant reduction in the levels of 2-AG and AEA, as well as of the two endocannabinoid related molecules, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in LLC-PK1 cells. In kidney cortex homogenates, only AEA levels were significantly decreased. In addition, we found that in both the in vitro and in vivo model IR caused a reduction in the expression and activity of the Na+/K+ ATPase. These changes were reversed by the CB1/CB2 agonist WIN55,212, in a CB1-receptor dependent manner in the LLC-PK1 IR model. In conclusion, the ECS and Na+/K+ ATPase are down-regulated following IR in LLC-PK1 cells and rat kidney. We suggest that CB1 agonists might represent a potential strategy to reverse the consequences of IR injury in kidney tissues.

GLUT9 influences uric acid concentration in patients with Lesch-Nyhan disease.

BACKGROUND: Patients with deficient hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity present hyperuricemia and/or hyperuricosuria, with a variable degree of neurological manifestations. Hyperuricemia in HPRT deficiency is due to uric acid overproduction and is frequently treated with allopurinol. Renal uric acid excretion is sharply increased in these patients. In recent years, several renal tubular urate transporter single nucleotide polymorphisms (SNPs), including those of the GLUT9, ABCG2 and URAT1 genes, have been described that influence the renal handling of uric acid and modulate serum urate levels. In the present study, we analyzed whether GLUT9, ABCG2 and URAT1 gene SNPs are able to influence uric acid levels and allopurinol response in patients with HPRT deficiency. METHODS: Three SNPs, URAT1 rs11231825, GLUT9 rs16890979 and ABCG2 rs2231142, previously associated in our population with hyperuricemia and gout, were analyzed in 27 patients with HPRT deficiency treated with allopurinol for at least 5 years. RESULTS: Patients with HPRT deficiency having allele A of rs16890979 in the GLUT9 gene present with a lower serum urate concentration at diagnosis, before allopurinol treatment is instituted, and need lower allopurinol doses to maintain serum urate levels between 268 and 446 µmol/L (4.5 and 7.5 mg/dL). No relationship between rs2231142 in the ABCG2 gene or rs11231825 in the URAT1 gene and serum urate levels or allopurinol response was found in our patients with HPRT deficiency. CONCLUSIONS: GLUT9 SNPs influence the renal handling of uric acid and modulate serum urate levels and the response to treatment in patients with uric acid overproduction due to HPRT deficiency.

Ecuaciones antropométricas para el cálculo de grasa corporal en adultos jóvenes / Anthropometric equations for calculating body fat in young adults

Dado que para la población Latinoamericana se cuenta con escasas ecuaciones antropométricas validadas para determinar porcentaje de masa grasa (% MG), se diseñaron ecuaciones antropométricas prácticas para calcular el % MG en adultos jóvenes. Se realizaron mediciones antropométricas por técnicas validadas, y se calculó el % MG por densitometría (BodPod) y biompedancia. Se reclutaron 284 voluntarios (18-35 años), de uno y otro sexo. Las ecuaciones se diseñaron por regresión lineal múltiple por el método de todas las regresiones posibles y se validaron por su grado de bondad de ajuste (R2), error estándar de estimación (EEE) y por validación cruzada. En hombres: % MG por densitométría R2 = 0.78, EEE = 3.64 %, p < 0.001; % MG por bioimpedancia R2 = 0.76, EEE = 2.48 %, p < 0.001. En mujeres: % MG por densitométría R2 = 0.98, EEE = 4.02%, p < 0.001; % MG por bioimpedancia R2= 0.99, EEE = 2.37 %, p < 0.001. Las ecuaciones aquí diseñadas presentan sencillez, alta validez y confiabilidad, siendo útiles en la clínica y campo deportivo(AU)

Given that in Latin America we have few validated anthropometric equations to determine percentage of fat mass (% MG), practical anthropometric equations were designed to calculate the % MG in young adults. Anthropometric measurements were made by validated techniques, and % MG was calculated by densitometry (BodPod) and bioimpedance. We recruited 284 volunteers (18-35 years), men and women. The equations were designed by multiple linear regression by the method of all possible regressions, and validated by their degree of goodness of fit (R2), standard error of estimation (SES), and cross-validation. In men: % MG by densitometry R2 = 0.78, SES = 3.64%, p <0.001; % MG by bioimpedance R2 = 0.76, SES = 2.48%, p <0.001. In women: % MG by densitometry R2 = 0.98, SES = 4.02 %, p <0.001; % MG by bioimpedance R2 = 0.99, SES = 2.37 %, p <0.001. The equations here designed have simplicity, high validity, and reliability, being useful in the clinic and sports field(AU)

Aicar effect in early neuronal development.

The neurological manifestations of Lesch-Nyhan disease (LND) have been attributed to the effect of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency on nervous system development. An increase has been reported in the levels of 5-aminoimidazole-4-carboxamide-1-ß-D-ribotide (AICAR) and its triphosphate form ZTP in the red blood cells of patients with LND. AICAR accumulation in the brain has been hypothesized as the cause of some of the neurological symptoms of patients with LND. In this study, we examined the effect of AICAR on the differentiation of neurons in the well-established human NTERA-2 cl.D1 (NT2/D1) embryonic carcinoma neurogenesis model. NT2/D1 cells were differentiated along neuroectodermal lineages after exposure to 10-µM retinoic acid (RA), with or without the addition of 25-µM AICAR to the culture medium. The effect of AICAR on RA differentiation were examined through changes in the expression of genes essential to neuronal differentiation, as well as genes from the Wnt/ß-catenin, transforming growth factor beta (TGFß) and sonic hedgehog (SHH) pathways. Results: RA-induced differentiation in the NT2/D1 cells significantly increased the expression of MAP2, NRG1, NRP1, NRP2, NEUROG1 and EN1 genes (genes linked to neural differentiation) compared with undifferentiated NT2/D1 cells. We found that AICAR increased the expression of the SHH gene and the WNT2 and WNT7B genes but did not influence the expression of genes whose overexpression characterize early neurodevelopmental processes. Conclusion: The relevance of the AICAR related changes in the SHH and Wnt/ß-catenin pathway genes expression in the physiopathology of LND warrants further exploration.