Improvement in Renal Function and Reduction in Serum Uric Acid with Intensive Statin Therapy in Older Patients: A Post Hoc Analysis of the SAGE Trial.

BackgroundImprovement in renal function and decreases in serum uric acid (SUA) have been reported following prolonged high-intensity statin (HMG-CoA reductase inhibitor) therapy. This post hoc analysis of the SAGE trial examined the effect of intensive versus less intensive statin therapy on renal function, safety, and laboratory parameters, including SUA, in elderly coronary artery disease (CAD) patients (65-85 years) with or without chronic kidney disease (CKD).MethodsPatients were randomized to atorvastatin 80 mg/day or pravastatin 40 mg/day and treated for 12 months. Patients were stratified using Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rates (eGFRs) in CKD (eGFR <60 mL/min/1.73 m(2)) and non-CKD populations.ResultsOf the 893 patients randomized, 858 had complete renal data and 418 of 858 (49%) had CKD (99% Stage 3). Over 12 months, eGFR increased with atorvastatin and remained stable with pravastatin (+2.38 vs. +0.18 mL/min/1.73 m(2), respectively; p < 0.0001). MDRD eGFR improved significantly in both CKD treatment arms; however, the increased eGFR in patients without CKD was significantly greater with atorvastatin (+2.08 mL/min/1.73 m(2)) than with pravastatin (-1.04 mL/min/1.73 m(2)). Modest reductions in SUA were observed in both treatment arms, but a greater fall occurred with atorvastatin than with pravastatin (-0.52 vs. -0.09 mg/dL, p < 0.0001). Change in SUA correlated negatively with changes in eGFR and positively with changes in low-density lipoprotein cholesterol. Reports of myalgia were rare (3.6% CKD; 5.7% non-CKD), and there were no episodes of rhabdomyolysis. Elevated serum alanine and aspartate transaminase to >3 times the upper limit of normal occurred in 4.4% of atorvastatin- and 0.2% of pravastatin-treated patients.ConclusionIntensive management of dyslipidemia in older patients with stable coronary heart disease may have beneficial effects on renal function and SUA

A study o f single and two-phase flows in devices with narrow flow passages

In many industries, the depressurisation of gas-saturated solutionseis controlled to regulate bubble formation. Carbonated drink dispensers need to depressurise solutions with minimum bubble formation, whereas dissolved air flotation nozzles need to produce the maximum number of micro-bubbles. Four commercial carbonated drink dispensers were tested. The dispenser predicted to retain the most dissolved carbon dioxide at the outlet had a narrow annular gap of 0.1mm at the narrowest point. The pressure drop across this device varied linearly with water flow rate. When tested with two-phase air and water flow, the pressure drop decreased with increasing air flow at given water flowrates. This unusual behaviour was thought to be due to the narrow flow path. Carbon dioxide-saturated water tests supported these results as the pressure drop was found to be lower than the single-phase water tests. Thus under similar conditions, devices that create less turbulence would retain more dissolved gas. Flow in coils was investigated, as they have flow characteristics that were potentially suitable for carbonated drink dispensing. Compared to straight pipes, flow in coils remained laminar until higher Reynolds numbers. The friction factors were also higher in coils than straight pipes. Coils made from 0.0025m internal diameter polyurethane tubing were tested, with coil diameters of 0.029m, 0.079m and 0.139m and lengths of 2, 3, 3.7, 5 and 7m. A method of estimating the friction factors in coils by treating them as a series of 90° bends was proposed. The calculated results agreed with the present small tube experiments and with data from published literature for a range of tube diameters. At a given pressure drop, the shortest coil with the smallest coil diameter had the greatest dissolved gas concentration at the outlet and the highest flowrate. Furthermore, the concentration of dissolved gas at the coil outlet was greater than at the nozzle outlet.Ph

Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope

AbstractBackground: Selective protein import into the cell nucleus occurs in two steps: binding to the nuclear envelope, followed by energy-dependent transit through the nuclear pore complex. A 60 kD protein, importin, is essential for the first nuclear import step, and the small G protein Ran/TC4 is essential for the second. We have previously purified the 60 kD importin protein (importin 60) as a single polypeptide.Results We have identified importin 90, a 90 kD second subunit that dissociates from importin 60 during affinity chromatography on nickel (II)–nitrolotriacetic acid–Sepharose, a technique that was originally used to purify importin 60. Partial amino-acid sequencing of Xenopus importin 90 allowed us to clone and sequence its human homologue; the amino-acid sequence of importin 90 is strikingly conserved between the two species. We have also identified a homologous budding yeast sequence from a database entry. Importin 90 potentiates the effects of importin 60 on nuclear protein import, indicating that the importin complex is the physiological unit responsible for import. To assess whether nuclear localization sequences are recognized by cytosolic receptor proteins, a biotin-tagged conjugate of nuclear localization signals linked to bovine serum albumin was allowed to form complexes with cytosolic proteins in Xenopus egg extracts; the complexes were then retrieved with streptavidin–agarose. The pattern of bound proteins was surprisingly simple and showed only two predominant bands: those of the importin complex. We also expressed the human homologue of importin 60, Rch1p, and found that it was able to replace its Xenopus counterpart in a functional assay. We discuss the relationship of importin 60 and importin 90 to other nuclear import factors.Conclusion Importin consists of a 60 and a 90 kD subunit. Together, they constitute a cytosolic receptor for nuclear localization signals that enables import substrates to bind to the nuclear envelope

Valuing Persistent ISR Resources

AFCEA-GMU C4I Center Symposium, Challenges in C4I, George Mason University, Fairfax, VA., May 25This paper describes how to optimize PISR resources to maximize VIRT

Decreased MCM2-6 in Drosophila S2 cells does not generate significant DNA damage or cause a marked increase in sensitivity to replication interference.

A reduction in the level of some MCM proteins in human cancer cells (MCM5 in U20S cells or MCM3 in Hela cells) causes a rapid increase in the level of DNA damage under normal conditions of cell proliferation and a loss of viability when the cells are subjected to replication interference. Here we show that Drosophila S2 cells do not appear to show the same degree of sensitivity to MCM2-6 reduction. Under normal cell growth conditions a reduction of >95% in the levels of MCM3, 5, and 6 causes no significant short term alteration in the parameters of DNA replication or increase in DNA damage. MCM depleted cells challenged with HU do show a decrease in the density of replication forks compared to cells with normal levels of MCM proteins, but this produces no consistent change in the levels of DNA damage observed. In contrast a comparable reduction of MCM7 levels has marked effects on viability, replication parameters and DNA damage in the absence of HU treatment

Tracking Assaultâ injured, Drugâ using Youth in Longitudinal Research: Followâ up Methods

ObjectivesViolence is one of the leading causes of death among youth ages 14 to 24. Hospitalâ and emergency department (ED)â based violence prevention programs are increasingly becoming a critical part of public health efforts; however, evaluation of prevention efforts is needed to create evidenceâ based best practices. Retention of study participants is key to evaluations, although little literature exists regarding optimizing followâ up methods for violently injured youth. This study aims to describe the methods for retention in youth violence studies and the characteristics of hardâ toâ reach participants.MethodsThe Flint Youth Injury (FYI) Study is a prospective study following a cohort of assaultâ injured, drugâ using youth recruited in an urban ED, and a comparison population of drugâ using youth seeking medical or nonâ violenceâ related injury care. Validated survey instruments were administered at baseline and four followâ up time points (6, 12, 18, and 24 months). Followâ up contacts used a variety of strategies and all attempts were coded by type and level of success. Regression analysis was used to predict contact difficulty and followâ up interview completion at 24 months.ResultsA total of 599 patients (ages 14â 24) were recruited from the ED (mean ± SD age = 20.1 ± 2.4 years, 41.2% female, 58.2% African American), with followâ up rates at 6, 12, 18, and 24 months of 85.3%, 83.7% 84.2%, and 85.3%, respectively. Participant contact efforts ranged from two to 53 times per followâ up time frame to complete a followâ up appointment, and more than 20% of appointments were completed off site at community locations (e.g., participantsâ homes, jail/prison). Participants who were younger (p < 0.05) and female (p < 0.01) were more likely to complete their 24â month followâ up interview. Participants who sought care in the ED for assault injury (p < 0.05) and had a substance use disorder (p < 0.01) at baseline required fewer contact attempts to complete their 24â month followâ up, while participants reporting a fight within the immediate 3 months before their 24â month followâ up (p < 0.01) required more intensive contact efforts.ConclusionsThe FYI study demonstrated that achieving high followâ up rates for a difficultâ toâ track, violentlyâ injured ED population is feasible through the use of established contact strategies and a variety of interview locations. Results have implications for followâ up strategies planned as part of other violence prevention studies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146571/1/acem13495_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146571/2/acem13495.pd