The Role of Community Health Workers Within the Continuum of Services for HIV,Viral Hepatitis,and Other STIs Amongst Men Who Have Sex with Men in Europe

Journal of Community Health - Little is known about Community Health Workers (CHWs) who work in non-clinical settings to provide sexual health support around HIV, viral hepatitis, and other...     

A typology of female sex work in the Metropolitan Region of Santiago,Chile

In Chile, sex work takes place covertly in a variety of venues and locations. Formative research using time-location sampling methods is important in order to understand the nature of this diversity. This study used qualitative methods to develop a typology of female sex work in the Metropolitan Region of Santiago, Chile, using semi-structured interviews, focus groups and ethnographic fieldwork during visits to sex work venues. The study identified seven types of venue, which reflect the context and regulatory framework of the country and the structural vulnerabilities that affect female sex workers in Chile. These venues and locations include: cafés con piernas (coffee with legs); nightclubs, topless bars and cabarets; brothels; hotels; street and highway soliciting; massage parlours; and private residences. Formative research methods were helpful in identifying and characterising the venues and locations in which sex work occurred. Barriers to accessing and mapping specific locations were also identified. Recommendations for addressing these barriers include working with non-governmental organisations to map venues and initiate contact with the populations of interest. A comprehensive typology of sex work in the Metropolitan Region of Santiago, Chile, is an essential element for future time-location sampling and bio-behavioural research in the context of second-generation surveillance for HIV and sexually transmitted infections in Chile.     

Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001

STUDY OBJECTIVES: COPD is one of the leading causes of mortality and morbidity in the United States, yet little is known about the prevalence of comorbid conditions and mortality in hospitalized patients with COPD. DESIGN: From the National Hospital Discharge Survey, 1979 to 2001, we evaluated whether or not COPD in adults > or = 25 years old is associated with increased prevalence and in-hospital mortality of several comorbidities. RESULTS: During 1979 to 2001, there were an estimated total of 47,404,700 hospital discharges (8.5% of all hospitalizations in adults > 25 years old) of patients with COPD; 37,540,374 discharges (79.2%) were made with COPD as a secondary diagnosis, and 9,864,278 discharges (20.8%) were made with COPD as the primary diagnosis. The prevalence and in-hospital mortality for pneumonia, congestive heart failure, ischemic heart disease, thoracic malignancies, and respiratory failure were larger in hospital discharges with any mention of COPD. CONCLUSIONS: In a nationally representative sample of hospitalizations, any mention of COPD in the discharge diagnosis is associated with higher hospitalization prevalence and in-hospital mortality from other comorbidities. These results highlight the fact that the burden of disease associated with COPD is likely underestimated.     

La influencia del tipo de abordaje torácico sobre el desarrollo de complicaciones respiratorias tras la esofagectomía

Introduction

A systematic review of the literature was performed with the aim to determine differences in the rate of respiratory complications after esophagectomy for esophageal cancer using minimally invasive access vs traditional thoracic access.

Methods

A literature search was performed using Medline and Cochrane Library, identifying studies that compared the 2 types of thoracic access, regardless of the type of abdominal access (laparotomy/laparoscopy). The studies selected described respiratory complications in absolute numbers and different categories. Studies that considered minithoracotomy as a minimally invasive technique were excluded. Inclusion criteria were: studies decribing the different types of respiratory complications (9 in total), and analysing the most common complications: respiratory infection, respiratory failure and pleural effusion.

Results

Nine studies were selected (one prospective randomized trial and 8 case control studies) including 1,190 patients, 1,167 of which were operated on for esophageal cancer: 482 patients by thoracotomy and 708 by thoracoscopy. Three studies included definitions of respiratory complications, and one stratified them. The more frequent complications that allowed a meta-analysis were: respiratory infections, pleural effusion, and respiratory failure. No significant differences were found between the 2 types of access in the global analysis.

Discussion

The type of thoracic access (thoracotomy or thoracoscopy) does not seem to influence the development of respiratory complications after esophagectomy for cancer. However, the design of the studies analysed, the absence of clear definitions and stratification of the complications makes this conclusion questionable. A consensus on the definition of complications and further prospective randomized clinical trials are necessary.     

Utilization of extracellular information before ligand-receptor binding reaches equilibrium expands and shifts the input dynamic range

Cell signaling systems sense and respond to ligands that bind cell surface receptors. These systems often respond to changes in the concentration of extracellular ligand more rapidly than the ligand equilibrates with its receptor. We demonstrate, by modeling and experiment, a general “systems level” mechanism cells use to take advantage of the information present in the early signal, before receptor binding reaches a new steady state. This mechanism, pre-equilibrium sensing and signaling (PRESS), operates in signaling systems in which the kinetics of ligand-receptor binding are slower than the downstream signaling steps, and it typically involves transient activation of a downstream step. In the systems where it operates, PRESS expands and shifts the input dynamic range, allowing cells to make different responses to ligand concentrations so high as to be otherwise indistinguishable. Specifically, we show that PRESS applies to the yeast directional polarization in response to pheromone gradients. Consideration of preexisting kinetic data for ligand-receptor interactions suggests that PRESS operates in many cell signaling systems throughout biology. The same mechanism may also operate at other levels in signaling systems in which a slow activation step couples to a faster downstream step.Detecting and responding to a chemical gradient is a central feature of a multitude of biological processes (1). For this behavior, organisms use signaling systems that sense information about the extracellular world, transmit this information into the cell, and orchestrate a response. Measurements of the direction and proximity of the extracellular stimuli usually rely on the binding of diffusing chemical particles (ligands) to specific cell surface receptors. Different organisms have evolved different strategies to make use of this information. Small motile organisms, including certain bacteria, use a temporal sensing strategy, measuring and comparing concentration signals over time along their swimming tracks (2). In contrast, some eukaryotic cells, including Saccharomyces cerevisiae, are sufficiently large to implement a spatial sensing mechanism, measuring concentration differences across their cell bodies (3).The observation that some eukaryotes that use spatial sensing exhibit remarkable precision in response to shallow gradients (1–2% differences in ligand concentration between front and rear) (4, 5) has led to several proposed models in which large amplification is achieved by positive feedback loops in the signaling pathways triggered by the ligand-receptor binding (6, 7). Here, we describe a different mechanism, dependent on ligand-receptor binding dynamics, which improves gradient sensing when the concentration of external ligand is close to saturation. We use the budding yeast S. cerevisiae to study the efficiency of this mechanism.Haploid yeast cells exist in two mating types, MATa and MATα (also referred to as a and α cells). Mating occurs when a and α cells sense each other’s secreted mating pheromones: a-factor and α-factor (αF) (8). The pheromone secreted by the nearby mating partner diffuses, forming a gradient surrounding the sensing cell. Pheromone binds a membrane receptor, Ste2, in MATa yeast (9) that activates a pheromone response system (PRS), which cells use to decide whether to fuse with a mating partner or not. At high enough αF concentrations, cells develop a polarized chemotropic growth toward the pheromone source (4). To do that, the nonmotile yeast determines the direction of the potential mating partner measuring on which side there are more bound pheromone receptors, which are initially distributed homogeneously on the cell surface (10). However, this sensing modality can only work when external pheromone is nonsaturating: If all receptors are bound, cells should not be able to determine the direction of the gradient. Surprisingly, even at high pheromone concentrations, yeast tend to polarize in the correct direction (4, 11). Different amplification mechanisms have been proposed to account for the conversion of small differences in ligand concentration across the yeast cell, as is the case for dense mating mixtures, into chemotropic growth (6).We previously studied induction of reporter gene output by the PRS after step increases in the concentration of αF. We found large cell-to-cell variability, the bulk of which was due to large differences in the ability of individual cells to send signal through the system and in their general capacity to express proteins (12). The level of induced gene expression matches well the equilibrium binding curve of αF to receptor (13, 14), a phenomenon known as dose–response alignment (DoRA), common to many other signaling systems (14). In the PRS, DoRA persists for several hours of stimulation.During these studies, we realized that the binding dynamics of αF to its receptor is remarkably slow: At concentrations near the dissociation constant (K_d), binding takes about 20 min to reach 90% of the equilibrium level (15, 16). This dynamics is slow relative not only to the 90-min cell division cycle but also to the pheromone-dependent activation of the mitogen-activated protein kinase (MAPK) Fus3, which takes 2 to 5 min to reach steady-state levels (14). An unavoidable conclusion is that the machinery downstream of the αF receptor must be using pre-equilibrium binding information for its operation.This observation led us to study the consequences of fast and slow ligand-receptor dynamics on the ability of cells to sense extracellular cues. In biology, the rates of ligand binding and unbinding to membrane receptors span a large range, including many cases with dynamics similar to, or even slower than, that of mating pheromone (e.g., rates for EGF, insulin, glucagon, IFN-α1a, and IL-2 in

Bacillus thuringiensis subsp. israelensis Cyt1Aa synergizes Cry11Aa toxin by functioning as a membrane-bound receptor

Bacillus thuringiensis subsp. israelensis produces crystal proteins, Cry (4Aa, 4Ba, 10Aa, and 11Aa) and Cyt (1Aa and 2Ba) proteins, toxic to mosquito vectors of human diseases. Cyt1Aa overcomes insect resistance to Cry11Aa and Cry4 toxins and synergizes the toxicity of these toxins. However, the molecular mechanism of synergism remains unsolved. Here, we provide evidence that Cyt1Aa functions as a receptor of Cry11Aa. Sequential-binding analysis of Cyt1Aa and Cry11Aa revealed that Cyt1Aa binding to Aedes aegypti brush border membrane vesicles enhanced the binding of biotinylated-Cry11Aa. The Cyt1Aa- and Cry11Aa-binding epitopes were mapped by means of the yeast two-hybrid system, peptide arrays, and heterologous competition assays with synthetic peptides. Two exposed regions in Cyt1Aa, loop beta6-alphaE and part of beta7, bind Cry11Aa. On the other side, Cry11Aa binds Cyt1Aa proteins by means of domain II-loop alpha8 and beta-4, which are also involved in midgut receptor interaction. Characterization of single-point mutations in Cry11Aa and Cyt1Aa revealed key Cry11Aa (S259 and E266) and Cyt1Aa (K198, E204 and K225) residues involved in the interaction of both proteins and in synergism. Additionally, a Cyt1Aa loop beta6-alphaE mutant (K198A) with enhanced synergism to Cry11Aa was isolated. Data provided here strongly indicates that Cyt1Aa synergizes or suppresses resistance to Cry11Aa toxin by functioning as a membrane-bound receptor. Bacillus thuringiensis subsp. israelensis is a highly effective pathogenic bacterium because it produces a toxin and also its functional receptor, promoting toxin binding to the target membrane and causing toxicity.     

p21(WAF1/Cip1) is not involved in kainic acid-induced apoptosis in murine cerebellar granule cells

Kainic acid (KA) treatment induced neuronal death and apoptosis in murine cerebellar granule cells (CGNs) cultures from both wild-type and knockout p21(-/-) mice. There was not statistically significant difference in the percentage of neuronal apoptosis among strains. KA-induced neurotoxicity was prevented in the presence of NBQX (20 microM) and GYKI 52446 (20 microM), but not by z-VAD-fmk, suggesting that caspases are not involved in the apoptotic process. Data suggest that p21(WAF/Cip) was unable to modulate KA-induced apoptosis in murine CGNs.     

Vaccination with Live Escherichia coli Expressing Brucella abortus Cu/Zn Superoxide Dismutase Protects Mice against Virulent B. abortus

Vaccination of mice with Escherichia coli expressing Brucella Cu/Zn superoxide dismutase (SOD) [E. coli(pBSSOD)] induced a significant level of protection against virulent Brucella abortus challenge, although this level was not as high as the one reached with B. abortus vaccine strain RB51. In addition, vaccination with E. coli(pBSSOD) induced antibodies to Cu/Zn SOD and a strong proliferative response of splenocytes when stimulated in vitro with a thioredoxin-Cu/Zn SOD fusion protein.