Post-Reperfusion Myocardial Infarction Long-Term Survival Improvement Using Adenosine Regulation With Acadesine

ObjectivesThe purpose of this study was to assess the safety and efficacy of the adenosine regulating agent (ARA) acadesine for reducing long-term mortality among patients with post-reperfusion myocardial infarction (MI).BackgroundNo prospectively applied therapy exists that improves long-term survival after MI associated with coronary artery bypass graft (CABG) surgery—a robust model of ischemia/reperfusion injury. Pretreatment with the purine nucleoside autocoid adenosine mitigates the extent of post-ischemic reperfusion injury in animal models. Therefore, we questioned whether use of the ARA acadesine—by increasing interstitial adenosine concentrations in ischemic tissue—would improve long-term survival after post-reperfusion MI.MethodsAt 54 institutions, 2,698 patients undergoing CABG surgery were randomized to receive placebo (n = 1,346) or acadesine (n = 1,352) by intravenous infusion (0.1 mg/kg/min; 7 h) and in cardioplegia solution (placebo or acadesine; 5 μg/ml). Myocardial infarction was prospectively defined as: 1) new Q-wave and MB isoform of creatine kinase (CK-MB) elevation (daily electrocardiography; 16 serial CK-MB measurements); or 2) autopsy evidence. Vital status was assessed over 2 years, and outcomes were adjudicated centrally.ResultsPerioperative MI occurred in 100 patients (3.7%), conferring a 4.2-fold increase in 2-year mortality (p < 0.001) compared with those not suffering MI. Acadesine treatment, however, reduced that mortality by 4.3-fold, from 27.8% (15 of 54; placebo) to 6.5% (3 of 46; acadesine) (p = 0.006), with the principal benefit occurring over the first 30 days after MI. The acadesine benefit was similar among diverse subsets, and multivariable analysis confirmed these findings.ConclusionsAcadesine is the first therapy proven to be effective for reducing the severity of acute post-reperfusion MI, substantially reducing the risk of dying over the 2 years after infarction

Asiatic acid attenuates malignancy of human metastatic ovarian cancer cells via inhibition of epithelial-tomesenchymal transition

Purpose: To investigate the anticancer effects of asiatic acid on human metastatic ovarian cancer cells.Methods: Human metastatic ovarian cancer cell line SKOV-3 was treated with various concentrations of asiatic acid for 24 and 48 h. Cell proliferation, migration, invasion and morphology were analyzed by CCK-8, Transwell and immunofluorescence assays, respectively. Epithelial-to-mesenchymal transitionrelated gene and protein expressions were analyzed by quantitative polymerase chain reaction (qPCR) and Western blotting.Results: Asiatic acid (10 μM) significantly suppressed SKOV-3 cell migration and invasion (both p &lt; 0.01). Moreover, epithelial markers (E-cad and KRT-7/14/19) were elevated, while mesenchymal markers (vimetin, N-cad and ZEB1/2) were suppressed after asiatic acid treatment, at both mRNA and protein levels. Inhibition of epithelial-to-mesenchymal transition was further evidenced by immunofluorescence staining of pan-cytokeratin and F-actin.Conclusion: Asiatic acid attenuates the malignancy of human metastatic ovarian cancer cells via epithelial-to-mesenchymal transition inhibition, and thus, is a therapeutic agent for ovarian cancer management.Keywords: Asiatic acid, Ovarian cancer, Metastasis, Epithelial-to-mesenchymal transition, Vometi

Discrimination in Healthcare Settings is Associated with Disability in Older Adults: Health and Retirement Study, 2008–2012

BACKGROUNDAs our society ages, improving medical care for an older population will be crucial. Discrimination in healthcare may contribute to substandard experiences with the healthcare system, increasing the burden of poor health in older adults. Few studies have focused on the presence of healthcare discrimination and its effects on older adults.OBJECTIVEWe aimed to examine the relationship between healthcare discrimination and new or worsened disability.DESIGNThis was a longitudinal analysis of data from the nationally representative Health and Retirement Study administered in 2008 with follow-up through 2012.PARTICIPANTSSix thousand and seventeen adults over the age of 50 years (mean age 67years, 56.3% female, 83.1% white) were included in this study.MAIN MEASURESHealthcare discrimination assessed by a 2008 report of receiving poorer service or treatment than other people by doctors or hospitals (never, less than a year=infrequent; more than once a year=frequent). Outcome was self-report of new or worsened disability by 2012 (difficulty or dependence in any of six activities of daily living). We used a Cox proportional hazards model adjusting for age, race/ethnicity, gender, net worth, education, depression, high blood pressure, diabetes, cancer, lung disease, heart disease, stroke, and healthcare utilization in the past 2years.KEY RESULTSIn all, 12.6 % experienced discrimination infrequently and 5.9% frequently. Almost one-third of participants (29%) reporting frequent healthcare discrimination developed new or worsened disability over 4years, compared to 16.8% of those who infrequently and 14.7% of those who never experienced healthcare discrimination (p < 0.001). In multivariate analyses, compared to no discrimination, frequent healthcare discrimination was associated with new or worsened disability over 4years (aHR = 1.63, 95% CI 1.16–2.27).CONCLUSIONSOne out of five adults over the age of 50 years experiences discrimination in healthcare settings. One in 17 experience frequent healthcare discrimination, and this is associated with new or worsened disability by 4years. Future research should focus on the mechanisms by which healthcare discrimination influences disability in older adults to promote better health outcomes for an aging population.Electronic supplementary materialThe online version of this article (doi:10.1007/s11606-015-3233-6) contains supplementary material, which is available to authorized users

Genome-wide analysis of the U-box E3 ubiquitin ligase family role in drought tolerance in sesame (Sesamum indicum L.)

Plant U-box (PUB) proteins belong to a class of ubiquitin ligases essential in various biological processes. Sesame (Sesamum indicum L.) is an important and worldwide cultivated oilseed crop. However few studies have been conducted to explore the role of PUBs in drought tolerance in sesame. This study identified a total of 56 members of the sesame PUB family (SiPUB) genes distributed unevenly across all 13 chromosomes. Based on phylogenetic analysis, all 56 SiPUB genes were classified into six groups with various structures and motifs. Cis-acting element analysis suggested that the SiPUB genes are involved in response to various stresses including drought. Based on RNA-seq analysis and quantitative real-time PCR, we identified nine SiPUB genes with significantly different expression profiles under drought stress. The expression patterns of six SiPUB genes in root, leaf and stem tissues corroborated the reliability of the RNA-seq datasets. These findings underscore the importance of SiPUB genes in enhancing drought tolerance in sesame plants. Our study provides novel insights into the evolutionary patterns and variations of PUB genes in sesame and lays the foundation for comprehending the functional characteristics of SiPUB genes under drought-induced stress conditions

Comparison of Two Azithromycin Distribution Strategies for Controlling Trachoma in Nepal

OBJECTIVE: The study compares the effectiveness of two strategies for distributing azithromycin in an area with mild-to-moderate active trachoma in Nepal. METHODS: The two strategies investigated were the use of azithromycin for 1) mass treatment of all children, or 2) targeted treatment of only those children who were found to be clinically active, as well as all members of their household. FINDINGS: Mass treatment of children was slightly more effective in terms of decreasing the prevalence of clinically active trachoma (estimated by clinical examination) and of chlamydial infection (estimated by DNA amplification tests), although neither result was statistically significant. CONCLUSION: Both strategies appeared to be effective in reducing the prevalence of clinically active trachoma and infection six months after the treatment. Antibiotic treatment reduced the prevalence of chlamydial infection more than it did the level of clinically active trachoma

Eliminating Trachoma in Areas with Limited Disease

The common wisdom is that a trachoma program cannot eliminate ocular chlamydia from a community, just reduce infection to a level where there would be minimal blindness. We describe the success of multiple mass antibiotic treatments, demonstrating that complete elimination of infection may be an attainable goal in an area with modest disease

Patient-physician mistrust and violence against physicians in Guangdong Province, China: a qualitative study.

OBJECTIVE: To better understand the origins, manifestations and current policy responses to patient-physician mistrust in China. DESIGN: Qualitative study using in-depth interviews focused on personal experiences of patient-physician mistrust and trust. SETTING: Guangdong Province, China. PARTICIPANTS: One hundred and sixty patients, patient family members, physicians, nurses and hospital administrators at seven hospitals varying in type, geography and stages of achieving goals of health reform. These interviews included purposive selection of individuals who had experienced both trustful and mistrustful patient-physician relationships. RESULTS: One of the most prominent forces driving patient-physician mistrust was a patient perception of injustice within the medical sphere, related to profit mongering, knowledge imbalances and physician conflicts of interest. Individual physicians, departments and hospitals were explicitly incentivised to generate revenue without evaluation of caregiving. Physicians did not receive training in negotiating medical disputes or humanistic principles that underpin caregiving. Patient-physician mistrust precipitated medical disputes leading to the following outcomes: non-resolution with patient resentment towards physicians; violent resolution such as physical and verbal attacks against physicians; and non-violent resolution such as hospital-mediated dispute resolution. Policy responses to violence included increased hospital security forces, which inadvertently fuelled mistrust. Instead of encouraging communication that facilitated resolution, medical disputes sometimes ignited a vicious cycle leading to mob violence. However, patient-physician interactions at one hospital that has implemented a primary care model embodying health reform goals showed improved patient-physician trust. CONCLUSIONS: The blind pursuit of financial profits at a systems level has eroded patient-physician trust in China. Restructuring incentives, reforming medical education and promoting caregiving are pathways towards restoring trust. Assessing and valuing the quality of caregiving is essential for transitioning away from entrenched profit-focused models. Moral, in addition to regulatory and legal, responses are urgently needed to restore trust

Aging Characteristics of Lithium Titanate Batteries under Ultrahigh Discharge Rate

The aging characteristics of lithium titanate batteries under ultra-high discharge rate were studied in this paper. The discharge characteristics is highly temperature-dependent under 55C discharge rate. The capacity retention rate is about 73% after 100 cycles of 55C discharge. The in-situ analysis incremental capacity analysis (ICA) was used to analyze the aging mechanism, and it was found that the main reason for the capacity fading was the loss of active material of the positive electrode, which leads to an increase of polarization resistance under 55C discharge rate

Weight Loss Associated with Cholinesterase Inhibitors in Individuals with Dementia in a National Healthcare System.

ObjectivesTo determine whether initiation of cholinesterase inhibitors is associated with significant weight loss in a real-word clinical setting.DesignRetrospective cohort study from 2007 to 2010 comparing weight loss in individuals with dementia newly prescribed cholinesterase inhibitors and those newly prescribed other chronic medications.SettingNational Veterans Affairs data.ParticipantsIndividuals aged 65 and older with a diagnosis of dementia who received a new prescription for a cholinesterase inhibitor or other new chronic medication.MeasurementsThe primary outcome was time to 10-pound weight loss over 12 months. Propensity score matching was used to control for the likelihood of receiving a cholinesterase inhibitor based on baseline characteristics. Data were analyzed in a priori defined subgroups according to age, comorbid burden, and initial weight.ResultsOf 6,504 individuals that met study criteria, 1,188 started on cholinesterase inhibitors were matched to 2,189 started on other medications. The propensity-matched cohorts were well balanced on baseline covariates. Participants initiated on cholinesterase inhibitors had a higher risk of weight loss than matched controls at 12 months (hazard ratio = 1.23, 95% confidence interval (CI) = 1.07-1.41). At 12 months, 29.3% of participants taking cholinesterase inhibitors had experienced weight loss, compared with 22.8% of nonusers, corresponding to a number needed to harm of 21.2 (95% CI = 12.5-71.4) over 1 year. There were no significant differences in the risk of weight loss within subgroups.ConclusionThese results are consistent with the available data from randomized controlled trials. Clinicians should consider the risk of weight loss when prescribing cholinesterase inhibitors

Use of Renally Inappropriate Medications in Older Veterans: A National Study.

ObjectivesTo determine how many ambulatory older adults with chronic kidney disease receive medications that are contraindicated or dosed excessively given their level of renal function.DesignCross-sectional retrospective study.SettingU.S. Department of Veterans Affairs (VA) clinics.ParticipantsIndividuals aged 65 and older with a creatinine clearance (CrCl) of 15 to 49 mL/min (N = 83,850; mean age 80; 96% male).MeasurementsForty medications that require dose adjustment or are contraindicated in people with impaired renal function were examined. Medication use and CrCl (calculated using the Cockroft-Gault equation) were assessed using VA pharmacy, laboratory, and other data sources as of October 2007.ResultsThirteen percent of older veterans with a CrCl of 30 to 49 mL/min and 32% of those with a CrCl of 15 to 29 mL/min received one or more drugs that were contraindicated or prescribed at an excessive dose given the individual's level of renal function. The strongest risk factor for renally inappropriate prescribing was number of medications used; the risk of receiving renally inappropriate medications was 5.5 times as high (95% confidence interval = 5.1-5.9) in older adults taking 10 or more medications as in those taking one to three medications. Ranitidine, allopurinol, and metformin together accounted for 76% of renally misprescribed medications in individuals with a CrCl of 30 to 49 mL/min. Glyburide, ranitidine, gemfibrozil, carvedilol, and allopurinol accounted for 47% of renally misprescribed drugs for individuals with a CrCl of 15 to 29 mL/min.ConclusionInappropriate prescribing of renally cleared medications is common in ambulatory older veterans, with only a few medications accounting for most of these prescribing problems