Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role

An abnormal acyl-CoA synthetase/stearoyl-CoA desaturase (ACSL/SCD) lipid network fuels colon cancer progression, endowing cells with invasive and migratory properties. Therapies against this metabolic network may be useful to improve clinical outcomes. Because micro-RNAs (miRNAs/miRs) are important epigenetic regulators, we investigated novel miRNAs targeting this pro-tumorigenic axis; hence to be used as therapeutic or prognostic miRNAs. Thirty-one putative common miRNAs were predicted to simultaneously target the three enzymes comprising the ACSL/SCD network. Target validation by quantitative RT-PCR, Western blotting, and luciferase assays showed miR-544a, miR-142, and miR-19b-1 as major regulators of the metabolic axis, ACSL/SCD. Importantly, lower miR-19b-1 expression was associated with a decreased survival rate in colorectal cancer (CRC) patients, accordingly with ACSL/SCD involvement in patient relapse. Finally, miR-19b-1 regulated the pro-tumorigenic axis, ACSL/SCD, being able to inhibit invasion in colon cancer cells. Because its expression correlated with an increased survival rate in CRC patients, we propose miR-19b-1 as a potential noninvasive biomarker of disease-free survival and a promising therapeutic miRNA in CRC.     

病人安全文化与医疗服务结局的关联性分析

目的 探讨病人安全文化与医疗服务结局的关联性。方法 采用自行设计的病案评阅表对我国东、中、西3省（直辖市）18所公立医院的社区获得性肺炎、急性心肌梗塞、急性左心功能衰竭、计划性剖宫产和胆囊结石合并急性胆囊炎5个病种进行调查；通过机构问卷调查，收集医院层面的医疗服务状况数据；采用中国版医疗机构病人安全文化调查量表进行病人安全文化调查。结果 在医院层面上，未发现病人安全文化与医疗服务状况各指标的关联性；在病种层面上，多因素分析也未显示病人安全文化与治愈好转状况、住院天数和住院总费用的关联性。结论 病人安全文化对医疗服务结局的影响不显著，可能是通过间接途径作用于医疗服务结局。     

Survey on Ethical Conduct Thresholds in Cardiologal Medical Practice in Argentina

The purpose of this study was to analyze the attitude of a group of cardiologists on the ethical conducts they would accept or adopt when encountered with different hypothetical situations of medical practice. Between August and September of 2011, 700 Argentine cardiologists were surveyed in situations which posed ethical dilemmas in the patient‐physician relationship, among colleagues or involving financial agreements with employers or the pharmaceutical industry. Ethical conflicts were evidenced in a series of inappropriate conducts such as differential fees, trips and meals sponsored by laboratories, splitting fees, overbilling, self‐referral, charging for patient referral, financial compensation for ordering medical procedures, and various situations derived from the relationship with employers. In general, financial compensation from the pharmaceutical industry was more accepted than the conflictive situations which directly involved patients, colleagues or employers. The rejection of these conducts, the physicians' deontological education and the improvement of financial and organizational conditions in medical practice will help to encourage better medical professionalism and avoid unseemly behaviors.     

Effect of acetaminophen on prostaglandin E2 and prostaglandin F2α synthesis in the renal inner medulla of rat

Effects of acetaminophen on the renal inner medullary production of prostaglandin E₂ and F_2α were compared with the well-known effects of aspirin on this process. Acetaminophen was found to elicit a dose-dependent inhibition of both prostaglandin E₂ and F_2α accumulation in media with a K_i of 100–200 μM. This inhibition could not be accounted for by increased accumulation of prostaglandins within slices. Acetaminophen inhibition was reversed by removal of acetaminophen during the incubation or by addition of arachidonic acid. Similar manipulations did not reverse aspirin or indomethacin-mediated inhibition of prostaglandin synthesis. Thin-layer and gas chromatographic analysis of acetaminophen following incubation with slices demonstrated that this material was identical to authentic acetaminophen. This, in addition to the lack of an effect of glutathione on inhibition, suggests that acetaminophen does not have to be metabolized to exert this inhibition. Arachidonic acid did not alter the metabolism or increase the efflux of acetaminophen. Lower levels of prostaglandin E₂ observed with 5 mM acetaminophen and 1 mM aspirin caused a corresponding decrease in cyclic AMP content. Removal of acetaminophen from the second incubation or addition of arachidonic acid caused increases in both prostaglandin E₂ and cyclic AMP. Aspirin inhibition of cyclic AMP content was not reversed by similar manipulations. In vivo inhibition of inner medullary prostaglandin E₂ and prostaglandin F_2α synthesis was observed 2 h after a 375 mg/kg, intraperitoneal injection of acetaminophen. These data suggest that acetaminophen, like aspirin, is capable of reducing tissue prostaglandin synthesis. However, the mechanisms by which these two analgesic and antipyretic agents elicit their inhibition of prostaglandin synthesis are quite different.     

A latent state space model for estimating brain dynamics from electroencephalogram (EEG) data

Modern neuroimaging technologies have substantially advanced the measurement of brain activity. Electroencephalogram (EEG) as a noninvasive neuroimaging technique measures changes in electrical voltage on the scalp induced by brain cortical activity. With its high temporal resolution, EEG has emerged as an increasingly useful tool to study brain connectivity. Challenges with modeling EEG signals of complex brain activity include interactions among unknown sources, low signal-to-noise ratio, and substantial between-subject heterogeneity. In this work, we propose a state space model that jointly analyzes multichannel EEG signals and learns dynamics of different sources corresponding to brain cortical activity. Our model borrows strength from spatially correlated measurements and uses low-dimensional latent states to explain all observed channels. The model can account for patient heterogeneity and quantify the effect of a subject's covariates on the latent space. The EM algorithm, Kalman filtering, and bootstrap resampling are used to fit the state space model and provide comparisons between patient diagnostic groups. We apply the developed approach to a case-control study of alcoholism and reveal significant attenuation of brain activity in response to visual stimuli in alcoholic subjects compared to healthy controls.     

Numerical evaluation of the efficacy of small-caliber colonoscopes in reducing patient pain during a colonoscopy

Patient pain caused by a colonoscope is one of the main complications in completing a colonoscopy. Currently, randomized controlled trial (RCT) is one of the most used methods to evaluate the efficacy of small-caliber (SC) colonoscopes in reducing patient pain during a colonoscopy, compared with a standard colonoscope (SDC). However, many disturbing factors, including endoscopists’ skills, characteristics of patients and new technical features of the colonoscope (passive bending and high force transmission shaft), limit the reliability and generalizability of each finding in current RCTs. This paper focuses on modeling the insertion of colonoscopes within colon models using an explicit finite element method (FEM). Such a numerical model could overcome the limitations in RCTs. At the same time, it is expected to evaluate the efficacy of the small-caliber colonoscopes in reducing patient pain during a colonoscopy, while considering the effects of patient characteristics, including age, region and gender. The simulation results in this work showed that: compared with the SDC, a SC colonoscope may be more helpful in reducing discomfort for older patients, patients with smaller colon diameters and females.     

Patient Understanding of Discharge Instructions for Home Diabetes Self-Management and Risk for Hospital Readmission and Emergency Department Visits

ObjectiveThe primary objective of this study was to examine the patient comprehension of diabetes self-management instructions provided at hospital discharge as an associated risk of readmission.MethodsNoncritically ill patients with diabetes completed patient comprehension questionnaires (PCQ) within 48 hours of discharge. PCQ scores were compared among patients with and without readmission or emergency department (ED) visits at 30 and 90 days. Glycemic measures 48 hours preceding discharge were investigated. Diabetes Early Readmission Risk Indicators (DERRIs) were calculated for each patient.ResultsOf 128 patients who completed the PCQ, scores were similar among those with 30-day (n = 31) and 90-day (n = 54) readmission compared with no readmission (n = 72) (79.9 ± 14.4 vs 80.4 ± 15.6 vs 82.3 ± 16.4, respectively) or ED visits. Clarification of discharge information was provided for 47 patients. PCQ scores of 100% were achieved in 14% of those with and 86% without readmission at 30 days (P = .108). Of predischarge glycemic measures, glycemic variability was negatively associated with PCQ scores (P = .035). DERRIs were significantly higher among patients readmitted at 90 days but not 30 days.ConclusionThese results demonstrate similar PCQ scores between patients with and those without readmission or ED visits despite the need for corrective information in many patients. Measures of glycemic variability were associated with PCQ scores but not readmission risk. This study validates DERRI as a predictor for readmission at 90 days.