HIV-Specific Cellular Immune Response Is Inversely Correlated with Disease Progression as Defined by Decline of CD4+ T Cells in Relation to HIV RNA Load

The average time between infection with human immunodeficiency virus (HIV) and development of acquired immune deficiency syndrome is ∼8 years. However, progression rates vary widely, depending on several determinants, including HIV-specific immunity, host genetic factors, and virulence of the infecting strain. In untreated HIV-infected patients with different progression rates, we examined HIV-specific T cell responses in combination with host genetic markers, such as chemokine/chemokine-receptor (CCR) polymorphisms and human leukocyte antigen (HLA) genotypes. HIV-specific CD4+ T cell responses and, to a lesser extent, HIVspecific CD8+ T cell responses were inversely correlated with progression rate. Slower progression was not related to polymorphisms in CCR genes, HLA genotype, or GB virus C coinfection. These data suggest that HIV-specific T cell responses are involved in protecting the host from disease progressio

Impaired Negative Selection of T Cells in Hodgkin's Disease Antigen CD30–Deficient Mice

AbstractCD30 is found on Reed–Sternberg cells of Hodgkin's disease and on a variety of non-Hodgkin's lymphoma cells and is up-regulated on cells after Epstein–Barr virus, human T cell leukemia virus, and HIV infections. We report here that the thymus in CD30-deficient mice contains elevated numbers of thymocytes. Activation-induced death of thymocytes after CD3 cross-linking is impaired both in vitro and in vivo. Breeding the CD30 mutation separately into αβTCR- or γδTCR-transgenic mice revealed a gross defect in negative but not positive selection. Thus, like TNF-receptors and Fas/Apo-1, the CD30 receptor is involved in cell death signaling. It is also an important coreceptor that participates in thymic deletion

A Vaccine against Nicotine for Smoking Cessation: A Randomized Controlled Trial

BACKGROUND: Tobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period. METHODOLOGY/PRINCIPAL FINDINGS: 229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qbeta (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012). CONCLUSIONS: Whereas Nicotine-Qbeta did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction. TRIAL REGISTRATION: Swiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616

Internal consistency, factor structure and construct validity of the French version of the Hospital Survey on Patient Safety Culture

To assess the psychometric properties of the French-language version of the Hospital Survey on Patient Safety Culture (HSOPSC)

Epitranscriptomics of cancer

The functional impact of modifications of cellular RNAs, including mRNAs, miRNAs and lncRNAs, is a field of intense study. The role of such modifications in cancer has started to be elucidated. Diverse and sometimes opposite effects of RNA modifications have been reported. Some RNA modifications promote, while others decrease the growth and invasiveness of cancer. The present manuscript reviews the current knowledge on the potential impacts of N6-Methyladenosine, Pseudouridine, Inosine, 2'O-methylation or methylcytidine in cancer's RNA. It also highlights the remaining questions and provides hints on research avenues and potential therapeutic applications, whereby modulating dynamic RNA modifications may be a new method to treat cancer

Numbering questionnaires had no impact on the response rate and only a slight influence on the response content of a patient safety culture survey: a randomized trial

In self-completed surveys, anonymous questionnaires are sometimes numbered so as to avoid sending reminders to initial nonrespondents. This number may be perceived as a threat to confidentiality by some respondents, which may reduce the response rate, or cause social desirability bias. In this study, we evaluated whether using nonnumbered vs. numbered questionnaires influenced the response rate and the response content

Asymmetric C(sp3)-H/C(Ar) coupling reactions. Highly enantio-enriched indolines via regiodivergent reaction of a racemic mixture

N-Aryl, N-branched alkyl carbamates react with in situ generated chiral Pd-NHC catalysts by coupling a Pd-Ar moiety with an aliphatic C–H bond at high temperature to give enantioenriched 2-substituted and 2,3-disubstituted indolines. Prochiral precursors give single products with very high asymmetric induction. Chiral racemic precursors react in a regiodivergent reaction of a racemic mixture to yield enantioenriched indolines resulting from either methyl C–H activation or asymmetric methylene C–H activation. In favorable cases this can result in a complete separation of an enatiomeric mixture into two different highly enantioenriched indolines