Consenso mexicano sobre probióticos en gastroenterología

Introducción: El uso de los probióticos es común en la práctica clínica. Existe un número signi-ficativo de estudios que apoyan la eficacia de los probióticos en algunos trastornos digestivos.Sin embargo, el desconocimiento de la evidencia científica y las diferentes presentaciones ycomposiciones microbianas de los probióticos disponibles dificultan su prescripción.Objetivo: Proveer al clínico de una revisión consensuada sobre los probióticos y recomendacio-nes de su uso en gastroenterología.Material y métodos: Se seleccionaron los ensayos clínicos controlados, metaanálisis y revisio-nes sistemáticas publicados hasta 2015, usando los términos MESH: probiotics, gastrointestinaldiseases, humans, adults and children. Se utilizó la metodología Delphi. Diecisiete gastroente-rólogos de adultos y 12 de ni˜nos elaboraron enunciados los cuales fueron votados hasta obteneracuerdo > 70%. Para cada enunciado se evaluó el nivel de evidencia basado en el sistema GRADE.Resultados y conclusiones: Se generaron 11 enunciados sobre conceptos generales de probió-ticos y 27 enunciados sobre uso de probióticos en enfermedades gastrointestinales tanto enni˜nos como en adultos. El grupo de consenso recomienda el uso de probióticos en las siguientescondiciones clínicas: prevención de la diarrea asociada a antibióticos, tratamiento de la diarreaaguda infecciosa, prevención de infección por Clostridium difficile y enterocolitis necrosante,para disminuir los eventos adversos de la terapia de erradicación del Helicobacter pylori, elalivio de los síntomas del síndrome de intestino irritable, en el estre˜nimiento funcional deladulto, para inducir y mantener la remisión en pacientes con colitis ulcerosa crónica idiopáticay pouchitis, y en la encefalopatía hepática oculta y manifiesta.© 2016 Asociaci´on Mexicana de Gastroenterolog´ıa. Publicado por Masson Doyma M´exico S.A.Este es un art´ıculo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). ASTRACT Introduction: Probiotics are frequently prescribed in clinical practice. Their efficacy in treatinggastrointestinal disorders is supported by a significant number of clinical trials. However, thecorrect prescription of these agents is hampered due to a lack of knowledge of the scientificevidence and to the different presentations and microbial compositions of the probiotics thatare currently available.Aim: To provide the clinician with a consensus review of probiotics and recommendations fortheir use in gastroenterology.Materials and methods: Controlled clinical trials, meta-analyses, and systematic reviewspublished up to 2015 were selected, using the MESH terms: probiotics, gastrointestinal diseases,humans, adults, AND children. The Delphi method was employed. Eighteen gastroenterologiststreating adult patients and 14 pediatric gastroenterologists formulated statements that werevoted on until agreement > 70% was reached. The level of evidence based on the GRADE systemwas evaluated for each statement.Results and conclusions: Eleven statements on the general concepts of probiotics and 27 sta-tements on the use of probiotics in gastrointestinal diseases in both adults and children wereformulated. The consensus group recommends the use of probiotics under the following clini-cal conditions: the prevention of diarrhea associated with antibiotics, the treatment of acuteinfectious diarrhea, the prevention of Clostridium difficile infection and necrotizing enteroco-litis, the reduction of adverse events from Helicobacter pylori eradication therapy, relief fromirritable bowel syndrome symptoms, the treatment of functional constipation in the adult, and the induction and maintenance of remission in patients with ulcerative colitis and pouchitis,and the treatment of covert and overt hepatic encephalopathy.© 2016 Asociaci´on Mexicana de Gastroenterolog´ıa. Published by Masson Doyma M´exico S.A. Thisis an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Population structure and paternal admixture landscape on present-day Mexican-mestizos revealed by Y-STR haplotypes

The purpose of this study was to identify genotype variants in the beta-casein (CSN2) and kappa-case (CSN3) genes using the PCR-RFLP method in a population of 202 Holstein cattle from two highly technified farms in the state of Jalisco, Mexico. We further assessed the association of these variants with milk production during a second lactation period. In the first population (n = 102), the genotypic frequencies for CSN2 were A1 = 0.387 and A2 = 0.613, while for CSN3, they were A = 0.829 and B = 0.172. In the second population (n = 100), the genotypic frequencies for CSN2 were A1 = 0.430 and A2 = 0.570, while for CSN3, they were A = 0.795 and B = 0.205. No differences in frequency distribution were noted in either population, and both genes were in Hardy-Weinberg equilibrium. There was greater genetic diversity for the CSN2 gene (0.477 and 0.493) than for the CSN3 gene (0.286 and 0.328) in both populations, with no significant differences between them. The fixation index was low for both genes, suggesting that there was no significant decrease in heterozygosity. The same genetic changes occur in both genes, and give their high similarity index (0.99 and 0.99). The statistical association analysis between genotypes of both genes and milk production revealed there were no significant differences between populations. Furthermore, no significant additive or dominant effects of both casein genes on milk production were identified within our population samples. " 2014, Pakistan Agricultural Scientists Forum. All rights reserved.",,,,,,,,,"http://hdl.handle.net/20.500.12104/43724","http://www.scopus.com/inward/record.url?eid=2-s2.0-84908335020&partnerID=40&md5=d902406f03d7d2354c7683ac6de6a803",,,,,,"5",,"Journal of Animal and Plant Sciences",,"131

Polymorphisms in beta and kappa-casein are not associated with milk production in two highly technified populations of holstein cattle in Mexico

The purpose of this study was to identify genotype variants in the beta-casein (CSN2) and kappa-case (CSN3) genes using the PCR-RFLP method in a population of 202 Holstein cattle from two highly technified farms in the state of Jalisco, Mexico. We further assessed the association of these variants with milk production during a second lactation period. In the first population (n = 102), the genotypic frequencies for CSN2 were A1 = 0.387 and A2 = 0.613, while for CSN3, they were A = 0.829 and B = 0.172. In the second population (n = 100), the genotypic frequencies for CSN2 were A1 = 0.430 and A2 = 0.570, while for CSN3, they were A = 0.795 and B = 0.205. No differences in frequency distribution were noted in either population, and both genes were in Hardy-Weinberg equilibrium. There was greater genetic diversity for the CSN2 gene (0.477 and 0.493) than for the CSN3 gene (0.286 and 0.328) in both populations, with no significant differences between them. The fixation index was low for both genes, suggesting that there was no significant decrease in heterozygosity. The same genetic changes occur in both genes, and give their high similarity index (0.99 and 0.99). The statistical association analysis between genotypes of both genes and milk production revealed there were no significant differences between populations. Furthermore, no significant additive or dominant effects of both casein genes on milk production were identified within our population samples. © 2014, Pakistan Agricultural Scientists Forum. All rights reserved

Nested PCR detection of Theileria equi infection and frequency in horses imported into Mexico

The purpose of this study was to assess the frequency of Theileria equi in horses imported into Mexico. During different stages of quarantine, 348 blood samples were taken from clinically healthy horses imported into Mexico from 2011 to 2013. Nested PCR (nPCR) of the Merozoite Antigen-1 (EMA-1) gene was performed for pathogen detection. In total, 93 horses tested positive for T. equi resulting in a 26.72% frequency with a 95% Confidence Interval (CI) of 22.07-31.37%. This is the first molecular diagnostics study to identify T. equi-positive horses imported into Mexico these results highlight the importance of nPCR analysis for T. equi in clinically healthy imported horses. © Medwell Journals, 2014

Cellular senescence promotes skin carcinogenesis through p38MAPK and p44/p42MAPK signaling

Cellular senescence entails an irreversible growth arrest that evolved in part to prevent cancer. Paradoxically, senescent cells secrete pro-inflammatory and growth-stimulatory molecules, termed the senescence-associated secretory phenotype (SASP), which is correlated with cancer cell proliferation in culture and xenograft models. However, at what tumor stage and how senescence and SASP act on endogenous tumor growth in vivo is unknown. To understand the role of senescence in cancer etiology, we subjected p16-3MR transgenic mice, which permit the identification and selective elimination of senescent cells in vivo, to the well-established two-step protocol of squamous cell skin carcinoma (SCC), in which tumorigenesis is initiated by a carcinogen 7,12-dimethylbenz[α]anthracene (DMBA) and then promoted by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We show that TPA promotes skin carcinogenesis by inducing senescence and SASP. Systemic induction of senescence in non-tumor bearing p16-3MR mice using a chemotherapy followed by the two-step carcinogenesis protocol potentiated the conversion of benign papillomas to carcinomas by elevating p38 MAPK and MAPK/ERK signaling. Ablation of senescent cells reduced p38 MAPK and MAPK/ERK signaling, thereby preventing the progression of benign papillomas to carcinomas. Thus, we show for the first time that senescent cells are tumor promoters, not tumor initiators, and that they stimulate skin carcinogenesis by elevating p38 MAPK and MAPK/ERK signaling. These findings pave the way for developing novel therapeutics against senescence-fueled cancers