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Gastric outlet obstruction is a complication of advanced tumors. It causes upper gastrointestinal obstruction, with progressive malnutrition and reduced survival. Currently, gastrojejunostomy or stent placement (SP) are feasible alternatives for the treatment of malignant gastric outlet obstruction. The aim of this study is to compare the efficacy and survival of both techniques.Single-center observational and prospective study of 58 patients with gastric outlet obstruction who underwent surgical treatment with stomach-partitioning gastrojejunostomy (SPGJ) or SP with self-expanding intraluminal prostheses between 2007 and 2018.Thirty patients underwent SPGJ and 28 SP. The mean age of the first group was significantly lower (69 vs. 78 years, respectively; P=.001). There were no statistically significant differences in terms of sex, perioperative risk or tumor etiology. Postoperative complications were non-significantly higher in the SPGJ group (P=.156). SP was associated with a shorter hospital stay (P=.02) and faster oral intake (P.0001). However, SP had significantly higher rates of persistent and recurrent obstruction (P=.048 and .01, respectively), poorer energy targets (P=.009) and shorter survival (9.61 vs. 4.47 months; P=.008).SPGJ presents greater luminal permeability, better oral intake and greater survival than SP. SP is preferable for non-surgical patients with a limited short-term prognosis.

Traditional applanation tonometry techniques lack the necessary accuracy and reliability for measuring the intraocular pressure (IOP), and there is still a need for a reliable technique for in vivo diagnosis. A single laser-induced cavitation bubble event was optically monitored in order to precisely measure the first collapse time of the cavitation bubble, which presents a direct dependence on the liquid pressure. This can certainly be done within the IOP range. We now extend the partial transmittance modulation (STM) technique to determine its feasibility for directly measuring the IOP by studying the nanosecond (ns) pulsed laser-induced cavitation bubble dynamics for an externally pressurized fresh ex vivo porcine eye. The results demonstrate that it is possible to monitor the IOP by detecting the light of a continuous-wave (CW) laser beam which is intensity modulated by the bubble itself. This technique currently presents a measurement resolution of about 4 mmHg in the 5 to 50 mmHg pressure range, indicating the feasibility of this approach for measuring IOP. This technique provides a direct measurement within the anterior eye chamber, avoiding common pitfalls in IOP diagnosis, such as errors due to patient movement, varying physical properties of the eye globe, or central cornea thickness (CCT) effects.

Coronary endothelial dysfunction is associated with atherosclerosis and myocardial infarction in subjects with type 2 diabetes mellitus (T2DM). Vascular endothelial cells are referred to as small and polygonal mononuclear cells. However, multi-nucleated and large endothelial cells (named as multinucleated variant endothelial cells [MVECs]) have been reported in the aorta, wherein their abundance correlates with atherosclerosis severity. The role of MVECs in coronary endothelium remains obscure. We hypothesized that simulated diabetic conditions increase the number of MVECs and affect their mitochondrial structure/function in cultured coronary endothelium. The in vitro model of diabetes consisted in the treatment of bovine coronary artery endothelial cells (BCAECs) with high-insulin (100 nmol/L, HI) for three days followed by high-glucose (20 mmol/L, HG) and HI for nine additional days. Simulated diabetic conditions increased the abundance of MVECs compared to normal glucose (NG, 5.5 mM). MVECs had a higher nucleic acid content (7.2-Fold), cell diameter (2.2-Fold), and cell area (11.4-Fold) than mononuclear cells. Immunodetection of von-Willebrand factor (endothelial cell marker) in MVECs was positive. The mitochondrial mass was reduced, and mitochondrial membrane potential increased in mononuclear cells cultured in HG+HI compared to mononuclear cells grown in NG. However, the opposite mitochondrial findings were noted in MVECs compared to mononuclear cells. Mass spectrometry-based quantitative proteomic and gene ontology analysis suggested augmented mitochondrial autophagy, apoptosis, and inflammation suppression in cells cultured under HG+HI compared to NG conditions. These findings show that simulated diabetes increases the abundance of MVECs, and that mitochondrial structure and function are differentially affected between MVECs and mononuclear cells.

The relationship of disabled persons with their environment is fundamental. Attitudes towards them, understood as the social constructs of those around them, play a key role in a person’s development and future, as they are one of the fundamental elements that can facilitate or hinder the inclusion process. Our work examines the need to implement educational and awareness-raising actions and programs that contemplate intervention strategies based on education and direct contact with disabled persons. The main objective of the study was to analyze the effect of a Program for Changing Attitudes towards Persons with Disabilities on a group of secondary school students (11 to 15 years of age), assigning 770 to the experimental group and 105 to the control group. The evaluation instrument used was the “Brief Questionnaire of Attitudes towards Persons with Disabilities for Adolescents, CBAD-12A”. The results have demonstrated the efficacy of the intervention for the experimental group, as it was possible to attribute the changes in attitude to the effect of the Program. Specifically, an improvement in attitudes was found in all three factors of the questionnaire (Acceptance-Rejection, Competence and Opportunity) after the intervention.

Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm.

Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm.

Pharmacological concentrations of biotin have pleiotropic effects. Several reports have documented that biotin supplementation decreases hyperglycemia. We have shown that a biotin-supplemented diet increased insulin secretion and the mRNA abundance of proteins regulating insulin transcription and secretion. We also found enlarged pancreatic islets and modified islet morphology. Other studies have shown that pharmacological concentrations of biotin modify tissue structure. Although biotin administration is considered safe, little attention has been given to its effect on tissue structure. In this study, we investigated the effect of biotin supplementation on hepatic morphology and liver toxicity markers. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 8 weeks. Versus the control mice, biotin-supplemented mice had an altered portal triad with dilated sinusoids, increased vascularity, and bile conducts. Furthermore, we observed an increased proportion of nucleomegaly and binucleated hepatocytes. In spite of the liver morphological changes, no differences were observed in the serum liver damage indicators, oxidative stress markers, or antioxidant enzymes. Our data demonstrate for the first time that biotin supplementation affects liver morphology in normal mice, and that these modifications are not paralleled with damage markers.

Lung cancer is one of the most common types of cancer, accounting for approximately 15% of all cancer cases worldwide. Apoptosis is the dominant defense mechanism against tumor development. The balance between pro- and antiapoptotic members of the Bcl-2 protein family can determine cellular fate. The venom of predatory marine snails Conus is estimated to have 100&ndash, 400 toxins called conotoxins. The family of &alpha, conotoxins is known to consist of selective antagonists of nicotinic acetylcholine receptors (nAChRs). Lung cancer cells overexpress several subunits of nAChRs and are considered as an excellent target for new anticancer drugs. We compared the cytotoxic effect of two synthetic peptides derived from Californiconus californicus, Cal14.1a, and Cal14.1b, which only differ by one amino acid in their sequence, and compared their proapoptotic balance by Bax and Bcl-2 mRNA expression. We determined the caspase-3 and -7 activation to demonstrate apoptosis induction. Results showed that Cal14.1a induces a high Bax/Bcl-2 ratio in H1299 (lung cancer cells). Although Cal14.1b has a cytotoxic effect on H1299 cells, reducing cell viability by 30%, it does not increase the Bax/Bcl-2 ratio, which could be explained by the Glu in the 15th residue, which is crucial for the ability of Cal14.1a to induce apoptosis.

RESUMEN Antecedentes: el síndrome de intestino irritable tipo estreñimiento (SII-E) es una patología prevalente, compleja y multifactorial que representa un desafío tanto desde el punto de vista diagnóstico como terapéutico. Objetivo: evaluar la efectividad, seguridad y satisfacción de linaclotida en pacientes con SII-E. Métodos: estudio prospectivo, unicéntrico y observacional realizado en pacientes con diagnóstico de SII-E. Los pacientes recibieron tratamiento con linaclotida (Constella(r), Allergan Inc., Irvine, CA), 290 microgramos/24 horas, una cápsula 30 minutos antes del desayuno. La variable primaria de efectividad fue el número de deposiciones por semana. Las variables secundarias incluían el grado de satisfacción y el registro de la frecuencia e intensidad de los síntomas (dolor e hinchazón), medidos mediante una escala visual analógica (EVA) de once niveles (0-10), y recogidas mediante un diario que se entregó al paciente. Resultados: treinta pacientes, todas mujeres, fueron incluidas consecutivamente. La mediana del tiempo de seguimiento fue de 18 meses. La media (deviación estándar [DE]) de deposiciones por semana aumentó desde 0,9 (0,6) al inicio del estudio hasta 4,7 (3,7) al final del mismo (p < 0,0001). Resultados similares fueron observados con el dolor (5,7 [2,3] frente a 3,1 [2,8] al inicio y al final del estudio, respectivamente, p < 0,0001) y con la hinchazón (6,8 [1,6] frente a 2,9 [2,5] al inicio y final del estudio, respectivamente, p < 0,0001). El grado medio (DE) de satisfacción al final del estudio fue 6,7 (3,0). Conclusiones: el tratamiento con linaclotida en pacientes con SII-E en el entorno de la práctica clínica se ha mostrado eficaz y seguro a largo plazo. ABSTRACT Background: constipation-predominant irritable bowel syndrome (C-IBS) is a prevalent, complex and multifactorial disorder that represents a challenge in terms of diagnosis and therapeutic management. Objective: to evaluate the effectiveness, safety and treatment satisfaction of linaclotide in C-IBS patients. Methods: prospective, single-center and observational study conducted in patients diagnosed with C-IBS. The patients were treated with linaclotide (Constella(r), Allergan Inc., Irvine, CA), once-daily via an oral capsule of 290-µg, 30 minutes before breakfast. The primary effectiveness endpoint was the number of bowel movements per week. The secondary endpoints included treatment satisfaction and changes from baseline in frequency and severity of symptoms (abdominal pain and bloating). This was assessed via an 11-point visual analog scale (VAS) reported by the patients in a daily register. Results: thirty female patients were consecutively included. The median follow-up time was 18 months. The mean (standard deviation [SD]) number of weekly bowel movements significantly increased from 0.9 (0.6) at baseline to 4.7 (3.9) at the end of follow-up, p < 0.0001. Abdominal pain significantly decreased from 5.7 (2.3) at baseline to 3.1 (2.8) at the end of the follow-up period, p < 0.0001. Similarly, bloating significantly decreased from 6.8 (1.6) to 2.9 (2.5) at the beginning and end of the treatment period, respectively, p < 0.0001. The mean (SD) degree of satisfaction at the end of the study was 6.7 (3.0). Conclusions: long-term linaclotide treatment in patients with C-IBS is effective and safe in the clinical setting.

RESUMEN Introducción: el drenaje biliar endoscópico guiado por ultrasonografía (DBUSE) es una alternativa al drenaje biliar percutáneo transhepático (CTPH) ante fallo de la colangiografía retrógrada endoscópica (CPRE). Métodos: descripción retrospectiva de seis casos de drenaje biliar guiado por ultrasonografía endoscópica, mediante coledocoduodenostomía (USE-CDS), así como de sus características clínicas, procedimiento endoscópico, complicaciones y posterior seguimiento. Resultados: todos nuestros casos presentaban obstrucción biliar distal de etiología maligna. En cuatro de los seis pacientes se concluyó el procedimiento con buen drenaje posterior. Registramos dos complicaciones tardías por migración de prótesis, sin muertes relacionadas con el procedimiento. El tiempo medio de seguimiento fue de seis meses. Conclusión: la USE-CDS se plantea como una opción terapéutica válida, no exenta de complicaciones, en casos seleccionados y en manos de un equipo de endoscopistas expertos ante fallos del drenaje por CPRE, y como alternativa al CTPH. ABSTRACT Introduction: endoscopic ultrasound-guided biliary drainage (EUS-BD) is an alternative to percutaneous trans-hepatic biliary drainage (PTBD) in cases of failed endoscopic retrograde cholangiopancreatography (ERCP). Methods: this is a retrospective description of six cases of endoscopic ultrasound-guided biliary drainage via choledochoduodenostomy (EUCD), as well as the clinical characteristics, endoscopic procedure, complications and monitoring. Results: all cases had malignant distal biliary obstruction. The procedure was concluded with good drainage in four out of six patients. Two late complications were recorded that were caused by stent migration and there were no deaths related with the procedure. The average monitoring period was six months. Conclusions: EUCD can be considered as a valid therapeutic choice in some selected cases and when performed by a team of expert endoscopists in cases of failed ERCP drainage or as an alternative to PTBD. However, the procedure has some associated complications.

We have reported on the capacity of (−)-epicatechin ((−)-EPI) to stimulate mitochondrial biogenesis (MiB) in mouse skeletal muscle (SkM). However, the mechanisms mediating the effects of (−)-EPI are not fully understood. We previously identified a role of the G-protein coupled estrogen receptor (GPER) in modulating the vascular effects of (−)-EPI. We therefore tested the hypothesis that GPER mediates (at least in part) the stimulatory effects of (−)-EPI on MiB in SkM cells. As an in vitro model, we employed mouse SkM-derived C2C12 myoblasts differentiated into myotubes. Using confocal microscopy, we detected GPER at the cell surface and cytoplasm in C2C12 myotubes. Treatment with (−)-EPI (3 and 10 µM) resulted in the stimulation of MiB as per increases in mitochondrial inner (MitoTracker Red FM fluorescence staining) and outer membrane (porin protein levels) markers, transcription factors involved in MiB stimulation (i.e., nuclear respiratory factor-2 [NRF-2] and mitochondrial transcription factor A [TFAM] protein levels) and citrate synthase (CS) activity levels. (−)-EPI-treated myotubes were longer and wider compared to vehicle-treated myotubes. The effects of (−)-EPI on myotube mitochondria and cell size were larger in magnitude to those observed with the GPER agonist G-1. The chemical blockade and down-regulation (siRNA) of GPER evidenced a partial and complete blockade of measured endpoints following (−)-EPI- or G-1-treatment, respectively. Altogether, results indicate that GPER is expressed in muscle cells and appears to mediate to a significant extent, the stimulatory effects of (−)-EPI on MiB. Thus, GPER activation may account for the stimulatory effects of (−)-EPI on SkM structure/function.

Background Delivery of therapeutic agents as erythropoietin (EPO) into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO (NeuroEPO) has shown neuroprotective actions in preclinical models. In the current study, the safety of NeuroEPO was evaluated for the first time in humans. Methods A phase I, randomized, parallel, open-label study was carried out in healthy volunteers. They received, intranasally, 1 mg of NeuroEPO every 8 h during 4 days (Group A) or 0.5 mg of NeuroEPO (Group B) with the same schedule. The working hypothesis was that intranasal NeuroEPO produce

We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.

Lung cancer is one of the most common types of cancer in men and women and a leading cause of death worldwide resulting in more than one million deaths per year. The venom of marine snails Conus contains up to 200 pharmacologically active compounds that target several receptors in the cell membrane. Due to their diversity and specific binding properties, Conus toxins hold great potential as source of new drugs against cancer. We analyzed the cytotoxic effect of a 17-amino acid synthetic peptide (s-cal14.1a) that is based on a native toxin (cal14.1a) isolated from the sea snail Conus californicus. Cytotoxicity studies in four lung cancer cell lines were complemented with measurement of gene expression of apoptosis-related proteins Bcl-2, BAX and the pro-survival proteins NFκB-1 and COX-2, as well as quantification of caspase activity. Our results showed that H1299 and H1437 cell lines treated with s-call4.1a had decreased cell viability, activated caspases, and reduced expression of the pro-survival protein NFκB-1. To our knowledge, this is the first report describing activation of apoptosis in human lung cancer cell lines by s-cal14.1a and we offer insight into the possible mechanism of action.