Therapeutic Effect of Alpha Lipoic Acid in a Rat Preclinical Model of Preeclampsia: Focus on Maternal Signs, Fetal Growth and Placental Function.

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19-16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE.

The lived experience of mothers living with fibromyalgia syndrome: A phenomenological inquiry.

INTRODUCTION: Fibromyalgia syndrome (FMS) is a complex chronic pain condition that negatively impacts women's daily lives, particularly their roles as mothers and wives. A phenomenological qualitative study was conducted to explore the lived experiences of motherhood and daily life among women diagnosed with fibromyalgia. METHODS: A sample of 10 women affected by FMS was recruited between January and February 2020. Participants were interviewed in a face-to-face, in-depth interview using a semi-structured interview guide. Data were collected until saturation, and Colaizzi's method was used to analyse data. RESULTS: This qualitative analysis identified five themes: A trauma preceding diagnosis, Pervasive feelings of misunderstanding, A struggle to maintain strength among limitations, Challenges in fulfilling maternal roles, and Persistent sexual discomfort. The latter two themes emerged as the most prominent. CONCLUSION: These findings highlight the significant impact of fibromyalgia on women's family lives and suggest the need for a more comprehensive care programme.

Novel Leptin-Cardiac TRH pathway responsible for the cardiac alterations in the Hyperleptinemic obesity.

The association between hypertension and obesity-induced cardiac damage is usually accepted. However, no studies have been focused on cardiac alterations in obesity, independently of blood pressure increase. It is well known that Cardiac TRH induces Left Ventricular Hypertrophy (LVH) and fibrosis, and its inhibition prevents the development of hypertrophy. Also, it has been described that the adiponectin leptin induces TRH expression. Thus, we hypothesized that in obesity, the increase in TRH induced by hyperleptinemia is responsible for LVH, until now mostly attributed to pressure load. We studied obese Agouti mice suffering from hypertension with hyperleptinemia and found a significant LVH development with increased TRH gene expression. Consequently, we found higher fibrotic (collagens and TGF-ß) and hypertrophic markers (BNP and ß-MHC) expression vs lean black controls. As pressure could explain these results, we treated obese mice with diuretic (hydrochlorothiazide 20 mg/kg/day) since weaning. Diuretic treatment was successful as the diuretic group was normotensive in contrast to control obese mice. Nevertheless, both groups showed LVH development, higher cardiac precursor TRH gene and peptide expressions and elevated fibrotic and hypertrophic markers expression, pointing out that obesity-induced LVH is not due to hypertension. In addition, we performed Cardiac TRH inhibition by specific siRNA injection compared to control siRNA treatment and evaluated cardiac damage. As expected, expressions and protein increase in hypertrophic and fibrotic markers observed in the AG mouse with the native cTRH system were not seen in the AG mouse with the cTRH silencing. Indeed, the AG + TRH-siRNA group showed hypertrophic markers expression and fibrosis measurements similar to the lean BL mice. On the whole, these results point out that the novel Leptin-Cardiac TRH pathway is responsible for the cardiac alterations present in hyperleptinemic obesity, independent of blood pressure, and cTRH long-term silencing since early stages totally prevent LVH development and cardiac fibrosis.

Valproate decreases transgenerationally blood pressure by affecting thyrotropin-releasing hormone promoter DNA methylation and gene expression in spontaneously hypertensive rat.

Central TRH, a neuropeptide, is involved in cardiovascular regulation. We demonstrated that the overexpression of diencephalic TRH (dTRH) in SHR rats can be prevented by antisense treatment, normalizing blood pressure (BP). Valproate (VPA) is an inhibitor of histone deacetylases (HDAC) which modulates gene expression through epigenetic modifications such as DNA methylation. AIMS: Study the role of HDAC inhibition in the regulation of dTRH gene expression and its effect on the pathogenesis of hypertension. MAIN METHODS: We treated 7-weeks-old male and female SHR and WKY rats with VPA for 10 weeks and evaluated BP, dTRH mRNA and methylation gene status. KEY FINDINGS: VPA attenuated the elevated BP and dTRH mRNA expression characteristic of SHR. Indeed, we found a significant 62% reduction in dTRH mRNA expression in the SHR + VPA group compared to control SHR. The decrease TRH mRNA expression induced by VPA was confirmed "in vitro" in a primary neuron culture using trichostatin A. With methylation specific PCR we demonstrated a significant increase in TRH promoter DNA methylation level in SHR + VPA group compared to control SHR. After 2 weeks of treatment interruption, rats were mated. Although they did not receive any treatment, the offspring born from VPA-treated SHR parents showed similar changes in BP, dTRH expression and methylation status, implying a transgenerational inheritance. Our findings suggest that dTRH modulation by epigenetics mechanism affects BP and could be inherited by the next generation in SHR rats.

Hyperoxia: Effective Mechanism of Hyperbaric Treatment at Mild-Pressure.

HBOT increases the proportion of dissolved oxygen in the blood, generating hyperoxia. This increased oxygen diffuses into the mitochondria, which consume the majority of inhaled oxygen and constitute the epicenter of HBOT effects. In this way, the oxygen entering the mitochondria can reverse tissue hypoxia, activating the electron transport chain to generate energy. Furthermore, intermittent HBOT is sensed by the cell as relative hypoxia, inducing cellular responses such as the activation of the HIF-1α pathway, which in turn, activates numerous cellular processes, including angiogenesis and inflammation, among others. These effects are harnessed for the treatment of various pathologies. This review summarizes the evidence indicating that the use of medium-pressure HBOT generates hyperoxia and activates cellular pathways capable of producing the mentioned effects. The possibility of using medium-pressure HBOT as a direct or adjunctive treatment in different pathologies may yield benefits, potentially leading to transformative therapeutic advancements in the future.

Efficient Oligomerization of Aromatic Amino Acids Induced by Gaps in Four-Helix Bundles of DNA or RNA.

The formation of peptides from amino acids is one of the processes associated with life. Because of the dominant role of translation in extant biology, peptide-forming processes that are RNA induced are of particular interest. We have previously reported the formation of phosphoramidate-linked peptido RNAs as the products of spontaneous condensation reactions between ribonucleotides and free amino acids in aqueous solution. We now asked whether four-helix bundle (4HB) DNA or RNA folding motifs with a single- or double-nucleotide gap next to a 5'-phosphate can act as reaction sites for phosphoramidate formation. For glycine, this was found to be the case, whereas phenylalanine and tryptophan showed accelerated formation of peptides without a covalent link to the nucleic acid. Free peptides with up to 11 tryptophan or phenylalanine residues were found in precipitates forming in the presence of gap-containing DNA or RNA 4HBs. Control experiments using motifs with just a nick or primer alone did not have the same effect. Because folded structures with a gap in a double helix are likely products of hybridization of strands formed in statistically controlled oligomerization reactions, our results are interesting in the context of prebiotic scenarios. Independent of a putative role in evolution, our findings suggest that for some aromatic amino acids an RNA-induced pathway for oligomerization exists that does not have a discernable link to translation.

Analysis of Post-Colonoscopy Colorectal Cancer and Its Subtypes in a Screening Programme.

Using the algorithm of the World Endoscopy Organisation (WEO), we have studied retrospectively all colorectal cancers, both detected and non-detected by the Basque Country screening programme from 2009 to 2017. In the screening programme 61,335 colonoscopies were performed following a positive Faecal Immunochemical test (FIT) (≥20 µg Hb/g faeces) and the 128 cases of post-colonoscopy colorectal cancer (PCCRC) detected were analysed. Among them, 50 interval type PCCRCs were diagnosed (before the recommended surveillance), 0.8 cases per 1000 colonoscopies performed, and 78 non-interval type PCCRCs (in the surveillance carried out at the recommended time or delayed), 1.3 per 1000 colonoscopies. Among the non-interval type PCCRCs, 61 cases were detected in the surveillance carried out at the recommended time (type A) and 17 when the surveillance was delayed (type B), 1 case per 1000 colonoscopies performed and 0.28 cases per 1000 colonoscopies performed, respectively. Interval type PCCRC is less frequent than non-interval type PCCRC. In interval type PCCRCs, CRCs detected in advanced stages (stages III-IV) were significantly more frequent than those detected in early stages, compared to those of non-interval type PCCRCs (OR = 3.057; 95% CI, 1.410-6.625; p < 0.005). Non-interval type B PCCRCs are less frequent than non-interval type A PCCRCs, but the frequency of advanced stages is higher in interval type B PCCRCs.

Impacto en la actividad asistencial y la salud de los profesionales de Atención Primaria durante el confinamiento / Impact on healthcare activities and the health of Primary Care professionals during lockdown

Objetivo: conocer el impacto del confinamiento en los hábitos de vida, la salud física y emocional de los trabajadores de Atención Primaria.Método: estudio transversal. Encuesta online a trabajadores que desempeñaron su actividad en dos centros de salud de Vizcaya, uno con atención presencial a pacientes con patología compatible con COVID-19 y otro que desarrolló actividad telefónica con pacientes con otras patologías. Se realizó un análisis descriptivo. Se compararon las variables categóricas mediante Chi cuadrado o test exacto de Fisher.Resultados: participaron 70 (54,29%) profesionales de 138, mayoritariamente enfermeras y médicos (71% en centro de salud con atención presencial y 72% en centro de salud con atención telefónica). No se encontraron diferencias en cuanto a la práctica de ejercicio físico ni alimentación, excepto en el consumo de comida precocinada casi todos los días (83,67% en centro con atención telefónica frente al 9,52% en centro con atención presencial, p< 0,001). Los sujetos de estudio han percibido un empeoramiento durante el confinamiento en relación al tiempo de actividad física (p= 0,027), alimentación (p< 0,001), tiempo delante de las pantallas (p= 0,010), salud física (p= 0,007) y bienestar emocional. Sin embargo, se ha percibido una mejoría en ambos grupos en relación a la tolerancia a la frustración (p< 0,001). El grupo con actividad presencial ha tenido un mayor impacto negativo en sus hábitos durante el confinamiento.Conclusiones: el confinamiento tuvo un cierto impacto en los hábitos de vida, la salud física y emocional de los trabajadores de Atención Primaria, y fue más acusado en el centro en el que desempeñaron su actividad laboral de forma presencial.(AU)

Objective: to understand the impact of lockdown on the lifestyle and physical and emotional health of Primary Care workers.Method: a cross-sectional study: an online survey for workers who performed their activity in two health centres in Bilbao, one with face-to-face assistance for patients with conditions compatible with COVID-19, and the other one conducting activity by telephone with patients presenting other conditions. A descriptive analysis was conducted; categorical variables were compared through Chi Square or Fisher’s Exact Test.Results: seventy (70 – 54.29%) professionals participated, out of 138; the majority were nurses and doctors (71% in the health centre with face-to-face care and 72% in the health centre with telephone care). No differences were found regarding physical exercise or diet, except in the fact of eating ready-made food almost every day (83.67% in the centre with care by telephone vs. 9.52% in the centre with face-to-face care, p< 0,001). The subjects of the study have perceived worsening during lockdown regarding their time of physical activity (p= 0.027), diet (p< 0.001), time spent in front of screens (p= 0.010), physical health (p= 0.007) and emotional wellbeing. However, an improvement was perceived in both arms regarding tolerance to frustration (p< 0.001). The arm with face-to-face activity has experienced a greater negative impact on their lifestyle during lockdown.Conclusions: lockdown has had some impact on the lifestyle and physical and emotional health of Primary Care workers, and this has been more pronounced in the centre where they performed their work activity face-to-face.(AU)

Cardiac Thyrotropin-releasing Hormone Inhibition Improves Ventricular Function and Reduces Hypertrophy and Fibrosis After Myocardial Infarction in Rats.

BACKGROUND: Cardiac thyrotropin-releasing hormone (TRH) is a tripeptide with still unknown functions. We demonstrated that the left ventricle (LV) TRH system is hyperactivated in spontaneously hypertensive rats and its inhibition prevented cardiac hypertrophy and fibrosis. Therefore, we evaluated whether in vivo cardiac TRH inhibition could improve myocardial function and attenuate ventricular remodeling in a rat model of myocardial infarction (MI). METHODS AND RESULTS: In Wistar rats, MI was induced by a permanent left anterior descending coronary artery ligation. A coronary injection of a specific small interfering RNA against TRH was applied simultaneously. The control group received a scrambled small interfering RNA. Cardiac remodeling variables were evaluated one week later. In MI rats, TRH inhibition decreased LV end-diastolic (1.049 ± 0.102 mL vs 1.339 ± 0.102 mL, P < .05), and end-systolic volumes (0.282 ± 0.043 mL vs 0.515 ± 0.037 mL, P < .001), and increased LV ejection fraction (71.89 ± 2.80% vs 65.69 ± 2.85%, P < .05). Although both MI groups presented similar infarct size, small interfering RNA against TRH treatment attenuated the cardiac hypertrophy index and myocardial interstitial collagen deposition in the peri-infarct myocardium. These effects were accompanied by attenuation in the rise of transforming growth factor-ß, collagen I, and collagen III, as well as the fetal genes (atrial natriuretic peptide, B-type natriuretic peptide, and beta myosin heavy chain) expression in the peri-infarct region. In addition, the expression of Hif1α and vascular endothelial growth factor significantly increased compared with all groups. CONCLUSIONS: Cardiac TRH inhibition improves LV systolic function and attenuates ventricular remodeling after MI. These novel findings support the idea that TRH inhibition may serve as a new therapeutic strategy against the progression of heart failure.

Cardiovascular and body weight regulation changes in transgenic mice overexpressing thyrotropin-releasing hormone (TRH).

Thyrotropin-releasing hormone (TRH) plays several roles as a hormone/neuropeptide. Diencephalic TRH (dTRH) participates in the regulation of blood pressure in diverse animal models, independently of the thyroid status. The present study aimed to evaluate whether chronic overexpression of TRH in mice affects cardiovascular and metabolic variables. We developed a transgenic (TG) mouse model that overexpresses dTrh. Despite having higher food consumption and water intake, TG mice showed significantly lower body weight respect to controls. Also, TG mice presented higher blood pressure, heart rate, and locomotor activity independently of thyroid hormone levels. These results and the higher urine noradrenaline excretion observed in TG mice suggest a higher metabolic rate mediated by sympathetic overflow. Cardiovascular changes were impeded by siRNA inhibition of the diencephalic Trh overexpression. Also, the silencing of dTRH in the TG mice normalized urine noradrenaline excretion, supporting the view that the cardiovascular effects of TRH involve the sympathetic system. Overall, we show that congenital dTrh overexpression leads to an increase in blood pressure accompanied by changes in body weight and food consumption mediated by a higher sympathetic overflow. These results provide new evidence confirming the participation of TRH in cardiovascular and body weight regulation.

Short-term doxorubicin cardiotoxic effects: involvement of cardiac Thyrotropin Releasing Hormone system.

Doxorubicin is an antineoplastic in the anthracycline class widely used for the treatment of several solid tumors and blood cancers. Cardiotoxicity is the major dose-limiting adverse effect of the drug. Chronic and accumulated doxorubicin administration cause myocyte damage and myocardial fibrosis. Doxorubicin-associated cardiotoxicity can be also observed after a short-course drug treatment even without clinical evidence of cardiac disease. Nevertheless, acute underlying mechanisms involved in the initiation of drug-induced cardiotoxicity remain poorly explored despite their similarities with pathophysiological conditions where cardiac TRH (cTRH) plays a central role. We showed that cTRH mediates myocardial injury induced by hypertension, and angiotensin II. Further, cTRH overexpression induces cardiac apoptosis, hypertrophy and fibrosis. AIM: To demonstrate that cTRH could mediate acute doxorubicin cardiotoxicity. MAIN METHOD: A single injection of doxorubicin (10 mg kg/day i.p.) was used to evaluate acute cardiac damage in a short-term experimental model of doxorubicin-induced cardiotoxicity. While inhibiting cTRH by small interfering RNA (siRNA), we evaluated the progression of cardiotoxicity. KEY FINDINGS: We found a doxorubicin-induced TRH overexpression in the LV, which was associated with apoptosis, hypertrophy and fibrosis. siRNA-mediated cTRH suppression prevented the doxorubicin-associated cardiac histological lesions. SIGNIFICANCES: doxorubicin requires an active cardiac TRH system to promote heart injury.

Intrahepatic bacterial metataxonomic signature in non-alcoholic fatty liver disease.

OBJECTIVE: We aimed to characterise the liver tissue bacterial metataxonomic signature in two independent cohorts of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosis, as differences in the host phenotypic features-from moderate to severe obesity-may be associated with significant changes in the microbial DNA profile. DESIGN AND METHODS: Liver tissue samples from 116 individuals, comprising of 47 NAFLD overweight or moderately obese patients, 50 NAFLD morbidly obese patients elected for bariatric surgery and 19 controls, were analysed using high-throughput 16S rRNA gene sequencing. RESULTS: Liver bacterial DNA profile significantly differs between morbidly obese and non-morbidly obese patients with NAFLD. Bacteroidetes (p=1.8e-18) and Firmicutes (p=0.0044) were over-represented in morbidly obese patients and Proteobacteria (p=5.2e-10)-specifically Gammaproteobacteria and Alphaproteobacteria, and Deinococcus-Thermus (p=0.00012)-were over-represented in the non-morbidly obese cohort. Cohort-specific analysis of liver microbial DNA signatures shows patterns linked to obesity. The imbalance in Proteobacteria (Alpha or Gamma) among non-morbidly obese patients, and Peptostreptococcaceae, Verrucomicrobia, Actinobacteria and Gamma Proteobacteria DNA among morbidly obese patients was associated with histological severity. Decreased amounts of bacterial DNA from the Lachnospiraceae family were associated with more severe histological features. Proteobacteria DNA was consistently associated with lobular and portal inflammation scores. Microbial DNA composition corresponded to predicted functional differences. CONCLUSION: This is the first comprehensive study showing that the liver tissue of NAFLD patients contains a diverse repertoire of bacterial DNA (up to 2.5×104 read counts). The liver metataxonomic signature may explain differences in the NAFLD pathogenic mechanisms as well as physiological functions of the host.

Restricting Glycolysis Preserves T Cell Effector Functions and Augments Checkpoint Therapy.

Tumor-derived lactic acid inhibits T and natural killer (NK) cell function and, thereby, tumor immunosurveillance. Here, we report that melanoma patients with high expression of glycolysis-related genes show a worse progression free survival upon anti-PD1 treatment. The non-steroidal anti-inflammatory drug (NSAID) diclofenac lowers lactate secretion of tumor cells and improves anti-PD1-induced T cell killing in vitro. Surprisingly, diclofenac, but not other NSAIDs, turns out to be a potent inhibitor of the lactate transporters monocarboxylate transporter 1 and 4 and diminishes lactate efflux. Notably, T cell activation, viability, and effector functions are preserved under diclofenac treatment and in a low glucose environment in vitro. Diclofenac, but not aspirin, delays tumor growth and improves the efficacy of checkpoint therapy in vivo. Moreover, genetic suppression of glycolysis in tumor cells strongly improves checkpoint therapy. These findings support the rationale for targeting glycolysis in patients with high glycolytic tumors together with checkpoint inhibitors in clinical trials.

Indicadores de calidad y satisfacción de los pacientes en la colonoscopia / Quality indicators and patient satisfaction in colonoscopy

Introducción: La colonoscopia es la prueba de confirmación diagnóstica/terapéutica del cáncer colorrectal. La monitorización de la experiencia de las personas que se han realizado la prueba resulta de interés en la mejora de su calidad. El objetivo fue estudiar los factores relacionados con la experiencia y su relación con los indicadores de calidad de las guías de práctica clínica. Pacientes y métodos: Se realizó un estudio transversal observacional, incluyendo indicadores de calidad y experiencia (cuestionario mGHAA9 adaptado e historia clínica) con una muestra de 432 participantes de entre 40-75 años que se realizaron una colonoscopia en 2015. Análisis univariante y multivariante con regresión logística múltiple. Resultados: La satisfacción se asoció en el análisis multivariante con una valoración del tiempo de espera para la colonoscopia como corto (OR=3,80) (1,76-10,90; IC 95%), tener más de 55 años de edad (OR=2,60) (1,19-5,68; IC 95%), una valoración positiva de la experiencia de la preparación (OR=7,34) (3,15-17,09; IC 95%), no referir dolor o molestias durante el procedimiento (OR=3,71) (1,03-13,40; IC 95%) (p=0,006) y la realización de la exploración en un hospital terciario (OR=2,81) (1,17-6,72; IC 95%) (p=0,020). Discusión: El cuestionario mGHAA9 adaptado al castellano es útil para estudiar los factores relativos a la experiencia. Hay aspectos de mejora en los tiempos de espera, limpieza colónica, satisfacción con la preparación y los problemas poscolonoscopia. Se deben implementar intervenciones que permitan mejorar la experiencia de las personas y la calidad de la colonoscopia

Introduction: Colonoscopy is the diagnostic/therapeutic confirmation test for colorectal cancer. The monitoring of the experience of people who have undergone the test is interesting to improve the quality of the colonoscopy. The aim of the project was to study factors affecting patients' experience and their relationship with the quality indicators of the Clinical Practice Guidelines. Patients and methods: An observational cross-sectional study was conducted, including quality and experience indicators (adapted mGHAA-9 questionnaire and clinical history) in a sample of 432 participants aged between 40- and 75-years-old who had undergone a colonoscopy in 2015. Univariate and multivariate analysis with multiple logistic regression. Results: Satisfaction was associated in the multivariate analysis with evaluating the waiting time for the colonoscopy as short (OR=3.80) (1.76-10.90, 95% CI),>55-years-old (OR=2.60) (1.19-5.68, 95% CI), rating the experience with the preparation positively (OR=7.34) (3.15-17.09, 95% CI), not reporting pain or discomfort during the procedure (OR=3.71) (1.03-13.40, 95% CI) (P=.006) and being examined in a tertiary hospital (OR=2.81) (1.17-6.72; 95% CI) (P=.020). Discussion: The mGHAA-9 questionnaire adapted to Spanish is useful to evaluate patient experience factors. There are aspects to improve in terms of waiting time, colon cleansing, satisfaction with preparation and post-colonoscopy problems. Interventions should be implemented to enhance patient experience and colonoscopy quality

Quality indicators and patient satisfaction in colonoscopy. / Indicadores de calidad y satisfacción de los pacientes en la colonoscopia.

INTRODUCTION: Colonoscopy is the diagnostic/therapeutic confirmation test for colorectal cancer. The monitoring of the experience of people who have undergone the test is interesting to improve the quality of the colonoscopy. The aim of the project was to study factors affecting patients' experience and their relationship with the quality indicators of the Clinical Practice Guidelines. PATIENTS AND METHODS: An observational cross-sectional study was conducted, including quality and experience indicators (adapted mGHAA-9 questionnaire and clinical history) in a sample of 432 participants aged between 40- and 75-years-old who had undergone a colonoscopy in 2015. Univariate and multivariate analysis with multiple logistic regression. RESULTS: Satisfaction was associated in the multivariate analysis with evaluating the waiting time for the colonoscopy as short (OR=3.80) (1.76-10.90, 95% CI),>55-years-old (OR=2.60) (1.19-5.68, 95% CI), rating the experience with the preparation positively (OR=7.34) (3.15-17.09, 95% CI), not reporting pain or discomfort during the procedure (OR=3.71) (1.03-13.40, 95% CI) (P=.006) and being examined in a tertiary hospital (OR=2.81) (1.17-6.72; 95% CI) (P=.020). DISCUSSION: The mGHAA-9 questionnaire adapted to Spanish is useful to evaluate patient experience factors. There are aspects to improve in terms of waiting time, colon cleansing, satisfaction with preparation and post-colonoscopy problems. Interventions should be implemented to enhance patient experience and colonoscopy quality.

Colorectal cancer screening program using FIT: quality of colonoscopy varies according to hospital type.

Background and study aims To compare the quality of colonoscopy in a population-based coordinated program of colorectal cancer screening according to type of hospital (academic or non-academic). Patients and methods Consecutive patients undergoing colonoscopy after positive FIT (≥ 20 ug Hb/g feces) between January 2009 and September 2016 were prospectively included at five academic and seven non-academic public hospitals. Screening colonoscopy quality indicators considered were adenoma detection rate, cecal intubation rate, complications and bowel preparation quality. Results A total of 48,759 patients underwent colonoscopy, 34,616 (80 %) in academic hospitals and 14,143 in non-academic hospitals. Among these cases, 19,942 (37.1 %) advanced adenomas and 2,607 (5.3 %) colorectal cancers (CRCs) were detected, representing a total of 22,549 (46.2 %) cases of advanced neoplasia. The adenoma detection rate was 64 %, 63.1 % in academic hospitals and 66.4 % in non-academic hospitals ( P  < 0.001). Rates of advanced adenoma detection, cecal intubation and adequate colonic preparation were 45.8 %, 96.2 % and 88.3 %, respectively, and in all cases were lower (implying worse quality care) in academic hospitals (45.3 % vs 48.7 %; odds ratio [OR] 0.87, 95 % confidence interval [CI] 0.84 - 0.91; 95.9 % vs 97 %; OR 0.48, 95 % CI 0.38 - 0.69; and 86.4 % vs 93 %; OR 0.48, 95 % CI 0.45 - 0.5; respectively; P  < 0.001 in all cases). In 13 patients, all in the academic hospital group, CRC was diagnosed after colonoscopy (0.26 cases × 1000 colonoscopies). Rates of CRC treated by endoscopy were similar in both types of hospital (30 %). The rate of severe complication was 1.2 % (602 patients), with no significant differences by hospital type: bleeding occurred in 1/147 colonoscopies and perforation in 1/329. One patient died within 30 days after screening colonoscopy. Conclusions The quality of colonoscopy was better in non-academic hospitals. The rate of detection of advanced neoplasia was higher in non-academic hospitals and correlated with the rate of post-colonoscopy CRC.

Angiotensin II requires an intact cardiac thyrotropin-releasing hormone (TRH) system to induce cardiac hypertrophy in mouse.

Cardiac tyhrotropin-releasing hormone (TRH) is overexpressed in the hypertrophied left ventricle (LV) of spontaneously hypertensive rats (SHR) and its inhibition prevents both hypertrophy and fibrosis. In a normal heart, the TRH increase induces fibrosis and hypertrophy opening the question of whether TRH could be a common mediator of left ventricular hypertrophy (LVH). We used angiotensin II (AngII) as an inductor of LVH to evaluate if the blockade of LV-TRH prevents hypertrophy and fibrosis in mice. We challenged C57BL/6 adult male mice with an infusion of AngII (osmotic pumps; 2 mg/kg.day) to induce LVH. Groups of mice were injected with an intracardiac siRNA-TRH or scrambled siRNA (siRNA-Con). Body weight, water intake and systolic arterial blood pressure (SABP) were measured daily. AngII significantly increased water intake and SABP (p < .05). Cardiac hypertrophy (heart weight/body weight) was evident in the group with the normal cardiac TRH system. In fact, it was found an AngII-induced increase of TRH precursor mRNA (p < .05) in conjunction with elevated TRH levels measured by immunohistochemistry and western blot. These changes were not observed in the AngII + siRNA-TRH group. Furthermore, AngII increased significantly (p < .05) BNP (hypertrophic marker), collagens I and III and TGF-ß (fibrosis markers) expression in the group with the native cardiac TRH system. These increases were attenuated in the groups with the TRH system blocked despite the high blood pressure. Similar and stronger results were observed "in vitro" with NIH3T3 and H9C2 cell culture models, where, when the TRH system is blocked, AngII stimulus was not able to induce the markers of its fibrotic and hypertrophic effects, so we believe that these effects are independent of any other physiological modifications. Our results point out that cardiac TRH is required for AngII-induced hypertrophic and fibrotic effects.

Grape pomace extract induced beige cells in white adipose tissue from rats and in 3T3-L1 adipocytes.

This study investigated the effects of a grape pomace extract (GPE) rich in phenolic compounds on brown-like adipocyte induction and adiposity in spontaneously hypertensive (SHR) and control normotensive Wistar-Kyoto (WKY) rats fed a high-fat diet (HFD). HFD consumption for 10 weeks significantly increased epididymal white adipose tissue (eWAT) in WKY but not in SHR rats. Supplementation with GPE (300 mg/kg body weight/day) reduced adipocyte diameter and increased levels of proteins that participate in adipogenesis and angiogenesis, i.e., peroxisome-proliferator activated receptor gamma (PPARγ), vascular endothelial grow factor-A (VEGF-A) and its receptor 2 (VEGF-R2), and partially increased the uncoupling protein 1 (UCP-1) in WKY. In both strains, GPE attenuated adipose inflammation. In eWAT from SHR, GPE increased the expression of proteins involved in adipose tissue "browning," i.e., PPARγ-coactivator-1α (PGC-1α), PPARγ, PR domain containing 16 (PRDM16) and UCP-1. In primary cultures of SHR adipocytes, GPE-induced UCP-1 up-regulation was dependent on p38 and ERK activation. Accordingly, in 3T3-L1 adipocytes treated with palmitate, the addition of GPE (30 µM) activated the ß-adrenergic signaling cascade (PKA, AMPK, p38, ERK). This led to the associated up-regulation of proteins involved in mitochondrial biogenesis (PGC-1α, PPARγ, PRDM16 and UCP-1) and fatty acid oxidation (ATGL). These effects were similar to those exerted by (-)-epicatechin and quercetin, major phenolic compounds in GPE. Overall, in HFD-fed rats, supplementation with GPE promoted brown-like cell formation in eWAT and diminished adipose dysfunction. Thus, winemaking residues, rich in bioactive compounds, could be useful to mitigate the adverse effects of HFD-induced adipose dysfunction.

Prospective evaluation of clinical lung ultrasonography in the diagnosis of community-acquired pneumonia in a pediatric emergency department.

OBJECTIVES: To evaluate the applicability and utility of point-of-care lung ultrasonography (POCLUS) for the diagnosis of community-acquired pneumonia (CAP) in a pediatric emergency department. METHODS: A prospective observational study on children with suspected CAP was carried out in a pediatric emergency department from August to December 2014. The evaluation of the chest radiography (CR) by two independent radiologists was considered as a reference standard. POCLUS was performed by pediatricians who were blinded to CR results. Following the WHO criteria, typical CAP was defined as an alveolar consolidation or infiltrate in CR and a visualization of lung consolidation with sonographic air bronchograms in POCLUS. The diagnostic accuracy of POCLUS (sensitivity, specificity, positive, and negative predictive values) was established using CR as a gold standard. RESULTS: We enrolled 200 children with a median age of 29.5 months (interquartile range, 18.5-52.5); 58.1% were males and 42.0% had focal decreased breath sounds and/or crackles. The prevalence of typical CAP according to the radiologist's evaluation was 42.5% (end-point consolidation and/or pleural effusion 56.5%, alveolar infiltrate 43.5%). The sensitivity and specificity of POCLUS were 87.1% [95% confidence interval (CI) 78.0-93.4] and 94.8% (95% CI 89.0-98.1), respectively. The positive and negative predictive values were 92.5% (95% CI 84.4-97.2) and 90.8% (95% CI 84.2-95.3), respectively. CONCLUSION: POCLUS performed by an emergency pediatrician with a limited experience in ultrasonography enables the diagnosis of pneumonia with high accuracy. POCLUS could become a feasible and promising alternative to CR in the diagnosis of suspected CAP, leading to a relevant decrease in children's exposure to ionizing radiations. Further studies specifically carried out in the pediatric outpatient setting are needed.

Fitness-management: el conflictivo devenir de una cultura empresarial / Fitness-Managment: the conflictive becoming of an enterprising culture / Fitness-Management: o conflitivo devenir de uma cultura empresarial

Resumen El artículo analiza el conflictivo devenir de la cultura del fitness en Argentina a partir de las categorías foucaulteanas de dispositivo, prácticas, gubernamentalidad y empresario de sí. En primer lugar, aborda la emergencia del fitness en la escena local y hace hincapié en las objeciones que la comunidad de profesores de educación física realiza a las producciones de este dispositivo cultural. A continuación, analiza las tácticas de conversión cultural que implementa el dispositivo del fitness en su vertiente managerial. Se concluye que el ethos empresarial que caracteriza las formas contemporáneas del fitness trasciende el universo estricto de estas prácticas ya que éste constituye un cimiento fundamental del capitalismo del presente.

Abstract This article analyzes the conflictive becoming of the fitness culture in Argentina, using the foucaultean categories of dispositive, practices, governmentality and self-entrepreneur. In the first place, it boards the emergence of fitness in the local scene, emphasizing in the objections that the community of physical education teachers realizes to the productions of this cultural dispositive. Then, it analyzes the tactics of cultural conversion that the fitness dispositive implements in its managerial side. The conclusion is that the entrepreneur ethos that describes the contemporary forms of fitness transcends the sole universe of these practices, since it establishes a fundamental base of present capitalism.

Resumo O artigo analisa o conflitivo devenir da cultura do fitness na Argentina a partir das categorias foucoultianas do dispositivo, práticas, governamentalidade e empresário de si. Em um primeiro momento, aborda a emergência do fitness na cena local, enfatiza as objeções que a comunidade dos professores de educação física faz às produções desse dispositivo cultural. Depois, analisam-se as táticas de conversão cultural que implantam o dispositivo do fitness na sua vertente gerencial. Conclui-se que o ethos empresarial que carateriza as formas contemporaneas do fitness transcende o universo estrito dessas práticas, já que elas mesmas constituem uma base fundamental do capitalismo do presente.