Comparison of lifelong and late life exercise on oxidative stress in the cerebellum.

Aging was associated with increased oxidation of DNA, RNA, and lipids in the cerebellum of male rats. DNA and lipid oxidation was reduced by lifelong (94 weeks) voluntary exercise on a running wheel. A reduction in cerebellar lipid oxidation, but not RNA or DNA oxidation, was observed following 3 months of moderate exercise or dietary supplementation of vitamin E, initiated at 18 months of age.

Decoding of calcium oscillations by phosphorylation cycles: analytic results.

Experimental studies have demonstrated that Ca(2+)-regulated proteins are sensitive to the frequency of Ca(2+) oscillations, and several mathematical models for specific proteins have provided insight into the mechanisms involved. Because of the large number of Ca(2+)-regulated proteins in signal transduction, metabolism and gene expression, it is desirable to establish in general terms which molecular properties shape the response to oscillatory Ca(2+) signals. Here we address this question by analyzing in detail a model of a prototypical Ca(2+)-decoding module, consisting of a target protein whose activity is controlled by a Ca(2+)-activated kinase and the counteracting phosphatase.

Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression.

The expression of interleukin-2 (IL-2) is a key event in T helper (Th) lymphocyte activation, controlling both, the expansion and differentiation of effector Th cells as well as the activation of regulatory T cells. We demonstrate that the strength of TCR stimulation is translated into the frequency of memory Th cells expressing IL-2 but not into the amount of IL-2 per cell. This molecular switch decision for IL-2 expression per cell is located downstream of the cytosolic Ca2+ level.

Quality by any other name?: a comparison of three profiling systems for assessing health care quality.

Objective: Many performance measurement systems are designed to identify differences in the quality provided by health plans or facilities. However, we know little about whether different methods of performance measurement provide similar answers about the quality of care of health care organizations. To examine this question, we used three different measurement approaches to assess quality of care delivered in veteran affairs (VA) facilities.

Inter-rater reliability of case-note audit: a systematic review.

Objective: The quality of clinical care is often assessed by retrospective examination of case-notes (charts, medical records). Our objective was to determine the inter-rater reliability of case-note audit.

Methods: We conducted a systematic review of the inter-rater reliability of case-note audit.

The link between maternal interaction style and infant action understanding.

The present study investigates whether the maternal interaction style is related to 6-month-old infants' action interpretation. We tested 6-month-olds ability to interpret an unfamiliar human action as goal-directed using a modified version of the paradigm used by Woodward, A. L.

Area socioeconomic status and mortality after coronary artery bypass graft surgery: the role of hospital volume.

Background: Individuals of low socioeconomic status (SES) have reduced access to coronary artery bypass graft surgery (CABG). It is unknown if low-SES CABG patients have reduced access to hospitals with better outcomes.

Methods: We conducted a retrospective cohort analysis of the California CABG Mortality Reporting Program, consisting of individuals with zip code information who underwent CABG at participating hospitals in 1999-2000 (n = 18,961).

Overestimating outcome rates: statistical estimation when reliability is suboptimal.

Objective: To demonstrate how failure to account for measurement error in an outcome (dependent) variable can lead to significant estimation errors and to illustrate ways to recognize and avoid these errors.

Data Sources: Medical literature and simulation models.

Study Design/data Collection: Systematic review of the published and unpublished epidemiological literature on the rate of preventable hospital deaths and statistical simulation of potential estimation errors based on data from these studies.

Use of central venous catheter-related bloodstream infection prevention practices by US hospitals.

Objective: To examine the extent to which US acute care hospitals have adopted recommended practices to prevent central venous catheter-related bloodstream infections (CR-BSIs).

Participants And Methods: Between March 16, 2005, and August 1, 2005, a survey of infection control coordinators was conducted at a national random sample of nonfederal hospitals with an intensive care unit and more than 50 hospital beds (n=600) and at all Department of Veterans Affairs (VA) medical centers (n=119). Primary outcomes were regular use of 5 specific practices and a composite approach for preventing CR-BSIs.

Control of signal transduction cycles: general results and application to the Jak-Stat pathway.

Signal transduction involves the transitions of proteins between inactive and active states that can be achieved by reversible phosphorylation, nucleo-cytoplasmic transport, and other processes. We consider a network of such state transitions governed by first-order kinetics and analyse how the reactions control the occupancy of the network states. First, a theorem is derived that relates concentration control coefficients and occupancy of the network states.

Physician-level P4P--DOA? Can quality-based payment be resuscitated?

Unlike many areas of the economy where value is relatively easy to measure and reward, healthcare is "messy." Patients bring both clinical heterogeneity and illness-severity complexities to the interchange with their physician. The measurable outcomes or process measures are as likely to be due to patient characteristics as they are to be due to the actions (or inactions) of the patient's provider.

Quantum mechanical charge field molecular dynamics simulation of the TiO2+ ion in aqueous solution.

Structural and dynamical properties of the TiO(2+) ion in aqueous solution have been investigated by using the new ab initio quantum mechanical charge field (QMCF) molecular dynamics (MD) formalism, which does not require any other potential functions except those for solvent-solvent interactions. Both first and second hydration shell have been treated at Hartree-Fock (HF) quantum mechanical level. A Ti-O bond distance of 1.

Competition effects shape the response sensitivity and kinetics of phosphorylation cycles in cell signaling.

Phosphorylation cycles are a core component of cell signaling networks. The response sensitivity and kinetics of these cycles are controlled by thermodynamic, kinetic, and structural factors, including binding affinities, catalytic activities, and the phosphorylation order of multiple sites. Based on mathematical models, we interpret the role of these factors in terms of competition effects.

Quantum mechanical/molecular mechanical simulations of the Tl(III) ion in water.

Classical molecular dynamics (MD) and combined quantum mechanical/molecular mechanical (QM/MM) MD simulations have been performed to investigate the structural and dynamical properties of the Tl(III) ion in water. A six-coordinate hydration structure with a maximum probability of the Tl-O distance at 2.21 A was observed, which is in good agreement with X-ray data.

Tl(I)-the strongest structure-breaking metal ion in water? A quantum mechanical/molecular mechanical simulation study.

Structural and dynamical properties of the Tl(I) ion in dilute aqueous solution have been investigated by ab initio quantum mechanics in combination with molecular mechanics. The first shell plus a part of the second shell were treated by quantum mechanics at Hartree-Fock level, the rest of the system was described by an ab initio constructed potential. The radial distribution functions indicate two different bond lengths (2.

Versatile regulation of multisite protein phosphorylation by the order of phosphate processing and protein-protein interactions.

Multisite protein phosphorylation is a common regulatory mechanism in cell signaling, and dramatically increases the possibilities for protein-protein interactions, conformational regulation, and phosphorylation pathways. However, there is at present no comprehensive picture of how these factors shape the response of a protein's phosphorylation state to changes in kinase and phosphatase activities. Here we provide a mathematical theory for the regulation of multisite protein phosphorylation based on the mechanistic description of elementary binding and catalytic steps.

Patterns and correlates of patient referral to surgeons for treatment of breast cancer.

Purpose: Characteristics of surgeons and their hospitals have been associated with cancer treatments and outcomes. However, little is known about factors that are associated with referral pathways.

Methods: We analyzed tumor registry and survey data from women with breast cancer diagnosed in 2002 and reported to the Detroit and Los Angeles Surveillance, Epidemiology, and End Results registries (n = 1,844; response rate, 77.

Adult fat intake associated with the presence of children in households: findings from NHANES III.

Background: Increasing prevalence of obesity and lifestyle related chronic disease is fundamentally tied to Americans' poor eating habits. Family environment, including the presence of children, may affect adults' diet behavior.

Objective: To compare dietary fat intake between adults with and without minor children in the home.

Stability of different zinc(II)-diamine complexes in aqueous solution with respect to structure and dynamics: a QM/MM MD study.

In the context of our detailed study of the chemical behavior of aquo- and ammine-Zn(II) complexes, ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations were performed at the Hartree-Fock (HF) level for the zinc(II)-diamine complexes in aqueous solution. The initial structures of cis and trans isomers of the tetraaquodiamminezinc(II) complex were found to transform into the triaquodiamminezinc(II) complex by releasing one water ligand after approximately 6 and approximately 22 ps of simulation time, respectively. The structural and dynamical properties of these three zinc complexes, i.

Chimeric rabbit/human Fab and IgG specific for members of the Nogo-66 receptor family selected for species cross-reactivity with an improved phage display vector.

NgR1, NgR2, and NgR3 which constitute the Nogo-66 receptor family are primarily expressed by neurons in the central nervous system (CNS) and believed to limit axonal growth and sprouting following CNS injury. In an attempt to define the expression and decipher the function of individual members of the Nogo-66 receptor family, we previously reported the generation of selective rabbit polyclonal antibodies. Here we exploit the same immune repertoires by phage display technology to generate rabbit monoclonal antibodies (mAbs) with nanomolar affinity to epitopes that are specific for NgR1 and NgR2, respectively, but at the same time conserved between mouse, rat, and human orthologs.

Evaluation of sex differences on mitochondrial bioenergetics and apoptosis in mice.

It has been postulated that the differences in longevity observed between organisms of different sexes within a species can be attributed to differences in oxidative stress. It is generally accepted that differences are due to the higher female estrogen levels. However, in some species males live the same or longer despite their lower estrogen values.

Sr(II) in water: A labile hydrate with a highly mobile structure.

Despite the large number of experimental as well as theoretical investigations available in the literature, some properties of the hydration structure of Sr(II), for example, the coordination number, are still ambiguous. The presented molecular dynamics study based on a most suitable ab initio QM/MM protocol allowed a detailed investigation of structural and dynamical properties of this hydrate, which shows a considerable degree of internal flexebility as well as ligand mobility within the first shell. Despite the high computational effort an exceptionally long QM/MM simulation had to be carried out to obtain sufficient information to investigate first shell ligand exchange reactions.

Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem.

Recent national recommendations have proposed that physicians should titrate lipid therapy to achieve low-density lipoprotein (LDL) cholesterol levels less than 1.81 mmol/L (<70 mg/dL) for patients at very high cardiovascular risk and less than 2.59 mmol/L (<100 mg/dL) for patients at high cardiovascular risk.

Translating infection prevention evidence into practice using quantitative and qualitative research.

Infection control professionals and hospital epidemiologists, using the valid methods of applied epidemiology-surveillance, benchmarking, intervention, evaluation--have largely been responsible for dramatically reducing the incidence of health care-associated infections over the past several decades. However, we believe that the field of infection control can--and should--also be a leader in understanding how research findings can be efficiently and effectively translated into clinical practice. Unfortunately, there is no current reliable information about which preventive practices are being used in US hospitals to prevent common device-related infections.