339 research outputs found

    Observing GLUT4 Translocation in Live L6 Cells Using Quantum Dots

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    The glucose transporter 4 (GLUT4) plays a key role in maintaining whole body glucose homeostasis. Tracking GLUT4 in space and time can provide new insights for understanding the mechanisms of insulin-regulated GLUT4 translocation. Organic dyes and fluorescent proteins were used in previous studies for investigating the traffic of GLUT4 in skeletal muscle cells and adipocytes. Because of their relative weak fluorescent signal against strong cellular autofluorescence background and their fast photobleaching rate, most studies only focused on particular segments of GLUT4 traffic. In this study, we have developed a new method for observing the translocation of GLUT4 targeted with photostable and bright quantum dots (QDs) in live L6 cells. QDs were targeted to GLUT4myc specifically and internalized with GLUT4myc through receptor-mediated endocytosis. Compared with traditional fluorescence dyes and fluorescent proteins, QDs with high brightness and extremely photostability are suitable for long-term single particle tracking, so individual GLUT4-QD complex can be easily detected and tracked for long periods of time. This newly described method will be a powerful tool for observing the translocation of GLUT4 in live L6 cells

    Cause of Death in Patients With Acute Heart Failure: Insights From RELAX-AHF-2

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    OBJECTIVES: This study sought to better understand the discrepant results of 2 trials of serelaxin on acute heart failure (AHF) and short-term mortality after AHF by analyzing causes of death of patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF-2) trial. BACKGROUND: Patients with AHF continue to suffer significant short-term mortality, but limited systematic analyses of causes of death in this patient population are available. METHODS: Adjudicated cause of death of patients in RELAX-AHF-2, a randomized, double-blind, placebo-controlled trial of serelaxin in patients with AHF across the spectrum of ejection fraction (EF), was analyzed. RESULTS: By 180 days of follow-up, 11.5% of patients in RELAX-AHF-2 died, primarily due to heart failure (HF) (38% of all deaths). Unlike RELAX-AHF, there was no apparent effect of treatment with serelaxin on any category of cause of death. Older patients (≥75 years) had higher rates of mortality (14.2% vs. 8.8%) and noncardiovascular (CV) death (27% vs. 19%) compared to younger patients. Patients with preserved EF (≥50%) had lower rates of HF-related mortality (30% vs. 40%) but higher non-CV mortality (36% vs. 20%) compared to patients with reduced EF. CONCLUSIONS: Despite previous data suggesting benefit of serelaxin in AHF, treatment with serelaxin was not found to improve overall mortality or have an effect on any category of cause of death in RELAX-AHF-2. Careful adjudication of events in the serelaxin trials showed that older patients and those with preserved EF had fewer deaths from HF or sudden death and more deaths from other CV causes and from noncardiac causes. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778)

    Cause of Death in Patients With Acute Heart Failure Insights From RELAX-AHF-2

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    OBJECTIVES: This study sought to better understand the discrepant results of 2 trials of serelaxin on acute heart failure (AHF) and short-term mortality after AHF by analyzing causes of death of patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF-2) trial. BACKGROUND: Patients with AHF continue to suffer significant short-term mortality, but limited systematic analyses of causes of death in this patient population are available. METHODS: Adjudicated cause of death of patients in RELAX-AHF-2, a randomized, double-blind, placebo-controlled trial of serelaxin in patients with AHF across the spectrum of ejection fraction (EF), was analyzed. RESULTS: By 180 days of follow-up, 11.5% of patients in RELAX-AHF-2 died, primarily due to heart failure (HF) (38% of all deaths). Unlike RELAX-AHF, there was no apparent effect of treatment with serelaxin on any category of cause of death. Older patients (≥75 years) had higher rates of mortality (14.2% vs. 8.8%) and noncardiovascular (CV) death (27% vs. 19%) compared to younger patients. Patients with preserved EF (≥50%) had lower rates of HF-related mortality (30% vs. 40%) but higher non-CV mortality (36% vs. 20%) compared to patients with reduced EF. CONCLUSIONS: Despite previous data suggesting benefit of serelaxin in AHF, treatment with serelaxin was not found to improve overall mortality or have an effect on any category of cause of death in RELAX-AHF-2. Careful adjudication of events in the serelaxin trials showed that older patients and those with preserved EF had fewer deaths from HF or sudden death and more deaths from other CV causes and from noncardiac causes. (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF [RELAX-AHF-2]; NCT01870778)

    Exploring reasons for state-level variation in incidence of dialysis-requiring acute kidney injury (AKI-D) in the United States

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    Background: There is considerable state-level variation in the incidence of dialysis-requiring acute kidney injury (AKI-D). However, little is known about reasons for this geographic variation. Methods: National cross-sectional state-level ecological study based on State Inpatient Databases (SID) and the Behavioral Risk Factor Surveillance System (BRFSS) in 2011. We analyzed 18 states and six chronic health conditions (diabetes mellitus [diabetes], hypertension, chronic kidney disease [CKD], arteriosclerotic heart disease [ASHD], cancer (excluding skin cancer), and chronic obstructive pulmonary disease [COPD]). Associations between each of the chronic health conditions and AKI-D incidence was assessed using Pearson correlation and multiple regression adjusting for mean age, the proportion of males, and the proportion of non-Hispanic whites in each state. Results: The state-level AKI-D incidence ranged from 190 to 1139 per million population. State-level differences in rates of hospitalization with chronic health conditions (mostly \u3c 3-fold difference in range) were larger than the state-level differences in prevalence for each chronic health condition (mostly \u3c 2.5-fold difference in range). A significant correlation was shown between AKI-D incidence and prevalence of diabetes, ASHD, and COPD, as well as between AKI-D incidence and rate of hospitalization with hypertension. In regression models, after adjusting for age, sex, and race, AKI-D incidence was associated with prevalence of and rates of hospitalization with five chronic health conditions - diabetes, hypertension, CKD, ASHD and COPD - and rates of hospitalization with cancer. Conclusions: Results from this ecological analysis suggest that state-level variation in AKI-D incidence may be influenced by state-level variations in prevalence of and rates of hospitalization with several chronic health conditions. For most of the explored chronic conditions, AKI-D correlated stronger with rates of hospitalizations with the health conditions rather than with their prevalences, suggesting that better disease management strategies that prevent hospitalizations may translate into lower incidence of AKI-D

    Impaired working speed and executive functions as frontal lobe dysfunctions in young first-degree relatives of schizophrenic patients

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    The aim of the investigation was to detect neuropsychological markers, such as sustained and selective attention and executive functions, which contribute to the vulnerability to schizophrenia especially in young persons. Performance was assessed in 32 siblings and children of schizophrenic patients and 32 matched controls using Wisconsin Card Sorting Test, Colour-Word-Interference-Test, Trail Making Test, and d2-Concentration-Test. The first-degree relatives showed certain impairments on all four tests, in particular, slower times on all time-limited tests. These results suggest the need for more time when completing neuropsychological tasks involving selected and focused attention, as well as cognitive flexibility, as a possible indicator of genetic vulnerability to schizophrenia

    Mechanisms of Cisplatin Nephrotoxicity

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    Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. One of the limiting side effects of cisplatin use is nephrotoxicity. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatin-induced renal cell death. It has also become apparent that inflammation provoked by injury to renal epithelial cells serves to amplify kidney injury and dysfunction in vivo. This review summarizes recent advances in our understanding of cisplatin nephrotoxicity and discusses how these advances might lead to more effective prevention

    Search for stop and higgsino production using diphoton Higgs boson decays

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    Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

    Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

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    This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good
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