Modular approach to triazole-linked 1,6-α-D-oligomannosides to the discovery of inhibitors of Mycobacterium tuberculosis cell wall synthetase.

Aiming at developing inhibitors of mannosyltransferases, the enzymes that participate in the biosynthesis of the cell envelope of Mycobacterium tuberculosis, the synthesis of a range of designed triazole-linked 1,6-oligomannosides up to a hexadecamer has been accomplished by a modular approach centered on the Cu(I)-catalyzed azide-alkyne cycloaddition as key process. The efficiency and fidelity of the cycloaddition are substantiated by high yields (76-96%) and exclusive formation of the expected 1,4-disubstituted triazole ring in all oligomer assembling reactions. Key features of oligomers thus prepared are the anomeric carbon-carbon bond of all mannoside residues and the 6-deoxymannoside capping residue.

[Change of protocol in the verbal autopsy method and measure of malaria mortality in rural areas in Senegal].

In rural Senegal, three populations have been followed up since several decades and the malaria mortality trend has been observed since the mid-1980s. However, limits are associated with the verbal autopsy method used to determine causes of death, especially deaths due to malaria. A change in protocol occurred in recent years in two of these three sites with the involvement of two physicians (instead of only one) in the diagnosis.

Secular trends of candidemia in a tertiary care hospital.

Background: Candidemias account for 8% to 15% of hospital-acquired bloodstream infections. They have been associated with previous exposure to antimicrobials and are considered high-morbidity infections with high treatment costs. This study characterizes candidemias in a tertiary care hospital and assesses their incidence rates, clinical and microbiological features, and use of antifungals.

Bloodstream infection after kidney transplantation: epidemiology, microbiology, associated risk factors, and outcome.

Background: Bloodstream infection (BSI) is associated with both relevant morbidity and mortality rates after kidney transplantation.

Methods: From January 1, 2000 to January 31, 2006, all episodes of BSI were retrospectively assessed through the review of medical records in two tertiary teaching Hospitals in Sao Paulo, Brazil, where 3308 transplant procedures were performed during this period. Contaminants and polymicrobial infections were excluded.

Measuring rates of hand hygiene adherence in the intensive care setting: a comparative study of direct observation, product usage, and electronic counting devices.

Objective: To compare 3 measures of hand hygiene adherence-direct observation, product usage, and electronic counting devices-in an intensive care unit.

Design: A 12-week observational study.

Setting: A 40-bed medical-surgical intensive care unit at a private tertiary care hospital.

Photoinduced addition of glycosyl thiols to alkynyl peptides: use of free-radical thiol-yne coupling for post-translational double-glycosylation of peptides.

Double glycosylation of cysteine-containing peptides has been carried out by a one-pot two-step sequence comprising selective S-propargylation followed by photoinduced (lambda (max) 365 nm) free-radical hydrothiolation with glycosyl thiols. Conditions were established for the sequential introduction of two different thiol residues such as a glycosyl and a biotinyl derivative.

Central neuropathic pain: an unusual case of painful ejaculation responding to topiramate.

Introduction: Painful ejaculation (PE) is an uncommon condition and it is usually associated with prostatitis, chronic pelvic pain syndrome, benign prostatic hyperplasia, ejaculatory duct obstruction, radical prostatectomy, and prostate radiation. Topiramate (TPM) is a new antiepileptic drug with recognized efficacy in neuropathic pain.

Aim: The study is aimed to evaluate TPM efficacy in ejaculation pain.

Tight glucose control versus intermediate glucose control: a quasi-experimental study.

Intensive insulin treatment is associated with an increased risk of hypoglycaemia. The purpose of this study was to evaluate two different strategies: tight glucose control (TGC) versus intermediate glucose control (IGC). In this quasi-experimental study, 130 critically ill patients were assigned to receive either the TGC protocol (n=65), according to which blood glucose levels were maintained between 4.

Recombinant peptides as new immunogens for the control of the bovine tick, Rhipicephalus (Boophilus) microplus.

A candidate vaccine that effectively controls Rhipicephalus microplus ticks in livestock is an attractive strategy in bovine management because of the expensive and labor-intensive treatment of animals with acaricides. However, the complex nature of ectoparasites has imposed restrictions on the development of such a vaccine, and its future efficacy is still under debate. Using Phage Display technology, we developed specific immunogens that mimic R.

Low compliance with alcohol gel compared with chlorhexidine for hand hygiene in ICU patients: results of an alcohol gel implementation program.

Although the introduction of alcohol based products have increased compliance with hand hygiene in intensive care units (ICU), no comparative studies with other products in the same unit and in the same period have been conducted. We performed a two-month-observational prospective study comparing three units in an adult ICU, according to hand hygiene practices (chlorhexidine alone-unit A, both chlorhexidine and alcohol gel-unit B, and alcohol gel alone-unit C, respectively). Opportunities for hand hygiene were considered according to an institutional guideline.

Synthesis of sugar-based silica gels by copper-catalysed azide-alkyne cycloaddition via a single-step azido-activated silica intermediate and the use of the gels in hydrophilic interaction chromatography.

Novel sugar-based silica gels were prepared by exploiting the copper-catalysed azide-alkyne cycloaddition (CuAAC) of two different sugar alkynes, namely, ethynyl C-galactoside 1 and propargyl O-lactoside 2, with new single-step azido-activated silica gels. The fully characterised stationary phases were generally used for hydrophilic interaction chromatography (HILIC), with particular application in the stereoselective separation of monosaccharides. Dynamic HILIC (DHILIC) experiments were performed to evaluate the influence of mutarotation on the chromatographic peak shapes of two interconverting sugar anomers.

The EPHB6 receptor tyrosine kinase is a metastasis suppressor that is frequently silenced by promoter DNA hypermethylation in non-small cell lung cancer.

Purpose: Loss of EPHB6 receptor tyrosine kinase expression in early-stage non-small cell lung carcinoma (NSCLC) is associated with the subsequent development of distant metastasis. Here, we analyzed the regulation and function of EPHB6 in lung cancer metastasis.

Experimental Design: The expression levels of EPHB6 were compared among normal lung tissue (n = 9), NSCLC without metastasis (n = 39), and NSCLC with metastasis (n = 39) according to the history of the patients.

Impact of a program to prevent central line-associated bloodstream infection in the zero tolerance era.

Background: Central line-associated bloodstream infection (CLABSI) is one of the most important health care-associated infections in the critical care setting.

Methods: A quasiexperimental study involving multiple interventions to reduce the incidence of CLABSI was conducted in a medical-surgical intensive care unit (ICU) and in 2 step-down units (SDUs). From March 2005 to March 2007 (phase 1 [P1]), some Centers for Disease Control and Prevention evidence-based practices were implemented.

A theoretical study of the copper(I)-catalyzed 1,3-dipolar cycloaddition reaction in dabco-based ionic liquids: the anion effect on regioselectivity.

The regioselectivity of copper(I)-catalyzed synthesis of 1,2,3-triazoles in dabco-based ionic liquids has been investigated at the DFT level using a supermolecular approach. The analysis of the theoretical results shows that the coordination ability of the ionic liquid (IL) anion to copper(I) catalyst and to all the other species containing the copper (intermediates and transition states) can significantly affect product distribution. Possible catalyst sequestering effects and the ability to stabilize selectively new intermediate species have been envisaged, as probable mechanisms throughout IL anions can affect copper catalyzed reactions inside performed.

Reduction in risk-taking behaviors among MSM in Senegal between 2004 and 2007 and prevalence of HIV and other STIs. ELIHoS Project, ANRS 12139.

An epidemiological survey conducted in Senegal in 2004 among men having sex with men (MSM) revealed high HIV prevalence and a high rate of risky behaviors within this population. Consequently, several prevention campaigns targeting MSM were implemented. A second survey was carried out in 2007 to assess the impact of these measures.

Immobilization of calix[4]arene-based glycoclusters on TiO2 nanoparticles via click Cu(I)-catalyzed azide-alkyne coupling.

We present the first type of tetraazide-functionalized calix[4]arene TiO(2) nanoparticles and their coupling to propargyl glycosides under Cu(I)-catalysis (click reaction), resulting in the immobilization of calix[4]arene-based glycoclusters on the TiO(2) surface.

Synthesis and applications of ionic liquids derived from natural sugars.

Aiming to develop environmentally compatible chemical syntheses, the replacement of traditional organic solvents with ionic liquids (ILs) has attracted considerable attention. ILs are special molten salts with melting points below 100 degrees C that are typically constituted of organic cations (imidazolium, pyridinium, sulfonium, phosphonium, etc.) and inorganic anions.

Evolution of malaria mortality and morbidity after the emergence of chloroquine resistance in Niakhar, Senegal.

Background: Recently, it has been assumed that resistance of Plasmodium to chloroquine increased malaria mortality. The study aimed to assess the impact of chemoresistance on mortality attributable to malaria in a rural area of Senegal, since the emergence of resistance in 1992, whilst chloroquine was used as first-line treatment of malaria, until the change in national anti-malarial policy in 2003.

Methods: The retrospective study took place in the demographic surveillance site (DSS) of Niakhar.

Positive deviance: a new strategy for improving hand hygiene compliance.

Objective: To evaluate the effectiveness of a positive deviance strategy for the improvement of hand hygiene compliance in 2 adult step-down units.

Design: A 9-month, controlled trial comparing the effect of positive deviance on compliance with hand hygiene.

Setting: Two 20-bed step-down units at a tertiary care private hospital.

Pancytopenia associated with levetiracetam treatment.

Levetiracetam is a pyrrolidine derivate that is approved for the treatment of seizures. It has a favourable pharmacokinetic profile, no clearly established pharmacological interactions, good tolerability and offers the possibility of rapid treatment. We describe a case of pancytopenia and multiple infections observed in the context of levetiracetam treatment.

Discovery of azetidinyl ketolides for the treatment of susceptible and multidrug resistant community-acquired respiratory tract infections.

Respiratory tract bacterial strains are becoming increasingly resistant to currently marketed macrolide antibiotics. The current alternative telithromycin (1) from the newer ketolide class of macrolides addresses resistance but is hampered by serious safety concerns, hepatotoxicity in particular. We have discovered a novel series of azetidinyl ketolides that focus on mitigation of hepatotoxicity by minimizing hepatic turnover and time-dependent inactivation of CYP3A isoforms in the liver without compromising the potency and efficacy of 1.

Single and dual glycoside clustering around calix[4]arene scaffolds via click thiol-ene coupling and azide-alkyne cycloaddition.

We present the first synthesis of calix[4]arene-based S-glycoclusters via photoinduced multiple thiol-ene coupling of tetra- and octa-allyl calix[4]arenes with peracetylated glucosyl thiol (67-88% yields). Moreover we describe the dual clustering at the upper and lower rim of a calix[4]arene with two different sugars (galactose and glucose) via sequential copper(i)-catalyzed azide-alkyne cycloaddition and photoinduced thiol-ene coupling.