Estimating the effectiveness of simian immunodeficiency virus-specific CD8+ T cells from the dynamics of viral immune escape.

Antiviral CD8(+) T cells are thought to play a significant role in limiting the viremia of human and simian immunodeficiency virus (HIV and SIV, respectively) infections. However, it has not been possible to measure the in vivo effectiveness of cytotoxic T cells (CTLs), and hence their contribution to the death rate of CD4(+) T cells is unknown. Here, we estimated the ability of a prototypic antigen-specific CTL response against a well-characterized epitope to recognize and kill infected target cells by monitoring the immunodominant Mamu-A*01-restricted Tat SL8 epitope for escape from Tat-specific CTLs in SIVmac239-infected macaques.

The Longitudinal Influence of Coparenting Conflict on Parental Negativity and Adolescent Maladjustment.

This study addresses two limitations of coparenting research: first, little research on coparenting has been conducted with families of adolescents, and second, there is little understanding regarding the child and family contexts in which coparenting is most salient. The longitudinal relation of coparenting conflict to parenting and adolescent maladjustment across 3 years was investigated among 516 2-parent, 2-adolescent families. Coparenting conflict predicted as much or more unique variance in parenting and adolescent adjustment as did marital quality and disagreement together.

Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal--part II.

As reported in a previous paper, the main objective of the new commission of the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP) was the harmonisation of approaches for the validation of quantitative analytical procedures. In a series of meetings, members of this Commission have first tried to review the objectives of analytical methods and the objectives of validation methods and to recommend the use of two-sided beta-expectation tolerance intervals for total error of validation samples (accuracy profile) in the acceptance/rejection of analytical method in validation phase. In the context of the harmonization, the other objectives were: (i) to propose a consensus on the norms usually recognized, while widely incorporating the ISO terminology; (ii) to recommend to validate the analytical procedure accordingly to the way it will be used in routine; (iii) to elaborate a rational, practical and statistically reliable strategy to assure the quality of the analytical results generated.

Community and team member factors that influence the operations phase of local prevention teams: the PROSPER Project.

This study examined the longitudinal predictors of quality of functioning of community prevention teams during the "operations" phase of team development. The 14 community teams were involved in a randomized-trial of a university-community partnership project, PROSPER (Spoth et al., Prevention Science, 5(1): 31-39, 2004b), that implements evidence-based interventions intended to support positive youth development and reduce early substance use, as well as other problem behaviors.

Multiple immunizations with adenovirus and MVA vectors improve CD8+ T cell functionality and mucosal homing.

Recombinant adenovirus vectors and MVA vectors were used in prime boost vaccine regimens to address the impact of repeated immunizations on transgene product-specific CD8(+) T cell frequencies, phenotypes, function, and localization. We show that a regimen with three immunizations incorporating MVA, human adenovirus serotype 5 and chimpanzee-derived adenoviruses serotype 68 or 7 yields high transgene product-specific CD8(+) T cell frequencies in spleen, blood, lymph nodes, and peritoneal lavage. Furthermore, upon triple immunization increased frequencies of transgene-specific T cells were measured at mucosal sites such as mesenteric lymph nodes, intestinal epithelium, and Peyer's patches.

Human embryonic stem cell transplantation to repair the infarcted myocardium.

Objective: To test the hypothesis that human embryonic stem cells (hESCs) can be guided to form new myocardium by transplantation into the normal or infarcted heart, and to assess the influence of hESC-derived cardiomyocytes (hESCMs) on cardiac function in a rat model of myocardial infarction (MI).

Methods: Undifferentiated hESCs (0.5-1x10(6)), human embryoid bodies (hEBs) (4-8 days; 0.

Depletion of CD8+ cells in sooty mangabey monkeys naturally infected with simian immunodeficiency virus reveals limited role for immune control of virus replication in a natural host species.

SIV infection of sooty mangabeys (SMs), a natural host species, does not cause AIDS despite high-level virus replication. In contrast, SIV infection of nonnatural hosts such as rhesus macaques (RMs) induces an AIDS-like disease. The depletion of CD8+ T cells during SIV infection of RMs results in marked increases in plasma viremia, suggesting a key role for CD8+ T cells in controlling levels of SIV replication.

Aggregating indices of risk and protection for adolescent behavior problems: the Communities That Care Youth Survey.

Purpose: To facilitate research on adolescent risk and protection regarding behavior problems, and to facilitate community decision-making regarding resource allocation for intervention programs, by creating a reduced set of coherent aggregate indices of adolescent risk and protection.

Methods: We examined the 31 risk and protective factor scales in the Communities That Care Youth Survey (CTC-YS). Data came from two waves of the CTC-YS administered to sixth through 12th graders in Pennsylvania (2001 n = 43,842; 2003 n =101,988).

The association of endothelial dysfunction and cardiovascular events in healthy subjects and patients with cardiovascular disease.

Background: Endothelial dysfunction is recognized as a major factor in the development of atherosclerosis and it has a prognostic value.

Objectives: To detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects and patients with cardiovascular disease.

Methods: We prospectively assessed brachial artery flow-mediated dilatation in 110 consecutive subjects (46 CVD patients and 64 healthy controls), mean age 57 +/- 11 years; 68 were men.

Substance-use outcomes at 18 months past baseline: the PROSPER Community-University Partnership Trial.

Background: The study's objective was to examine the effects of "real-world," community-based implementation of universal preventive interventions selected from a menu, including effects specific to higher- and lower-risk subsamples.

Design: School districts were selected based on size and location, and then randomly assigned to a control condition or to an experimental condition in a cohort sequential design.

Setting/participants: The study included 28 public school districts in Iowa and Pennsylvania that were located in rural towns and small cities, ranging in size from 6975 to 44,510.

Using correlational analyses to improve prevention strategies based on survey data from youth.

Community coalition prevention models often select interventions based on the types of risk factors (outcome predictors) that are elevated. Variances and correlations between predictors and targeted behaviors also may vary between communities and provide information to improve the selection of interventions. Community differences in risk factor levels and correlations between predictors and problem behaviors were examined using a child self-report computer assessment (ALEXSA); prevention.

Parenting and adolescent antisocial behavior and depression: evidence of genotype x parenting environment interaction.

Background: Little is known about the interplay of genotypes and malleable risk factors in influencing adolescent psychiatric symptoms and disorders. Information on these processes is crucial in designing programs for the prevention of psychiatric disorders.

Objective: To assess whether latent genetic factors and measured parent-child relationships interact (G x E) in predicting adolescent antisocial behavior and depression.

Insulin resistance is associated with increased risk of major cardiovascular events in patients with preexisting coronary artery disease.

Background: Over the past years it has been recognized that insulin resistance (IR) is an independent risk factor for the development of diabetes, whereas its association with cardiovascular events remains controversial. The aim of our study was to explore the association between IR per se and cardiovascular events among patients with preexisting coronary artery disease.

Methods: The mean follow-up period of this prospective study was 6.

Validation of analytical methods based on accuracy profiles.

Validation is a very living field in analytical chemistry as illustrated by the numerous publications addressing this topic. But, there is some ambiguity in this concept and the abundant vocabulary often does not help the analytical chemist. This paper presents a new method based on the fitness-for-purpose approach of the validation.

Kruppel-like factor 4 regulates endothelial inflammation.

The vascular endothelium plays a critical role in vascular homeostasis. Inflammatory cytokines and non-laminar blood flow induce endothelial dysfunction and confer a pro-adhesive and pro-thrombotic phenotype. Therefore, identification of factors that mediate the effects of these stimuli on endothelial function is of considerable interest.

Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.

Objective: Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress.

Design: Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls.

Impact of the metabolic syndrome on the clinical outcomes of non-clinically diagnosed diabetic patients with acute coronary syndrome.

The aim of this study is to explore the impact of metabolic syndrome (MS) on the outcome of patients with non-clinically diagnosed diabetes with acute coronary syndrome (ACS) based on a comprehensive nationwide registry during a 1-year follow-up. In the ACS Israeli Survey, 1,060 consecutive patients with non-clinically diagnosed diabetes were admitted due to ACS; 359 patients with MS features on admission were compared with 701 subjects without MS. A modified National Cholesterol Education Program Adult Treatment Panel III definition of MS was used in patients who presented with > or =3 of the 5 components: (1) hyperglycemia, defined as occasional blood glucose on admission >140 mg/dl; (2) preexisting hypertension; (3) body mass index >28 kg/m(2); (4) high-density lipoprotein cholesterol < or =40 mg/dl (men) or < or =50 mg/dl (women); and (5) triglycerides > or =150 mg/dl.

Detection of acute HIV infections in an urban HIV counseling and testing population in the United States.

The southeastern United States has an increasing burden of HIV, particularly among blacks, women, and men who have sex with men. To evaluate HIV nucleic acid amplification testing (NAAT) and antibody-based algorithms in determination of HIV incidence, detection of acute HIV infections, and surveillance of drug-resistant virus transmission in the urban southeastern United States, we conducted a cross-sectional analysis of prospectively collected data from 2202 adults receiving HIV testing and counseling at 3 sites in Atlanta, GA from October 2002 through January 2004. After standard testing with an HIV enzyme immunoassay (EIA) and Western blot confirmation, HIV-positive specimens were tested with 2 standardized assays to detect recent infection.

Adaptation of a diverse simian immunodeficiency virus population to a new host is revealed through a systematic approach to identify amino acid sites under selection.

Simian immunodeficiency viruses (SIV) have had considerable success at crossing species barriers; both human immunodeficiency virus (HIV)-1 and HIV-2 have been transmitted on multiple occasions from SIV-infected natural host species. However, the precise evolutionary and ecological mechanisms characterizing a successful cross-species transmission event remain to be elucidated. Here, in addition to expanding and clarifying our previous description of the adaptation of a diverse, naturally occurring SIVsm inoculum to a new rhesus macaque host, we present an analytical framework for understanding the selective forces driving viral adaptation to a new host.

Prior heart failure among patients with acute coronary syndromes is associated with a higher incidence of in-hospital heart failure.

Background: There are few data regarding the impact of prior heart failure (P-HF) on the presentation, course and outcomes of acute coronary syndromes (ACS).

Methods And Results: We prospectively analyzed all ACS patients admitted in all cardiology wards in Israel during February and March, 2004. Of the 2098 patients, 156(7.

Multiple equilibria in complex chemical reaction networks: extensions to entrapped species models.

In two earlier papers, means were provided to decide the capacity of complex chemical reaction networks, taken with mass-action kinetics, to admit multiple equilibria in the context of the isothermal homogeneous continuous flow stirred tank reactor (CFSTR). In such a reactor, all species are deemed to be in the outflow, a fact which has an important bearing on the nature of the governing equations. In contrast, one can imagine CFSTR-like models of the cell in which certain large molecules (e.

Long-term effect of bezafibrate on pancreatic beta-cell function and insulin resistance in patients with diabetes.

Objective: Development of insulin resistance (IR) and the progressive failure of the pancreatic beta-cell function (BCF) may be important in the pathogenesis of type 2 diabetes. Influence of peroxisome proliferator-activated receptors ligand bezafibrate on BCF and IR in patients with diabetes is unknown. The present study was aimed to investigate the long-term effect of bezafibrate on these parameters in diabetic patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study.

Cough assist strategy for pulmonary toileting in ventilator-dependent spinal cord injured patients.

The limited innervation of muscles supporting pulmonary functioning in spinal cord injured (SCI) patients indicates that these individuals are at a particularly high risk for atelectasis and other sequelae of ventilator dependency. As an alternative strategy to endotracheal suctioning for secretion management, our acute rehabilitation facility utilizes an assistive cough device. This device has not been commonly utilized in the SCI population, and studies concerning this device have primarily focused on individuals with neuromuscular diseases.