Analysis of iatrogenic risk related to anticholinergic effects using two scales in acute geriatric inpatient unit

Anticholinergic medications are responsible for most frequent adverse drug effects. Two scales have been elaborated as tools for prescribers: the Anticholinergic Drug Scale (ADS) of Carnahan et al., and the Anticholinergic Risk Scale (ARS) of Rudolph et al. The objective of this study was to analyze the diagnostic performance of both scales for predicting signs related to an anticholinergic effect. Method: Medical records of 1379 patients aged 75 years or older hospitalized in a geriatric acute care unit between 2002 and 2005 were studied. The analyze was made retrospectively, but data were collected prospectively. Results: Risk of appearance of total anticholinergic signs (ADS : OR 1,45, CI 95% [1,03-2,03], p=0,037 and ARS : OR 1,98, CI 95% [1,19-3,28] p<0,01) and peripheral signs (ADS: OR 1,66, CI 95% [1,22-2,26], p<0,01 and ARS : OR 1,81, CI 95% [1,19-2,75], p<0,01) increased when score was >= 3 with both scales, which wasn\u27t the case for central signs. Conclusion: Both scales permitted to detect an increased risk of appearance of total and peripheral anticholinergic signs, but not the centrals as delirium. Interest of total anticholinergic burden remains to be demonstrated, especially for delirium risk assessment

Isolation of Trichophyton concentricum from chronic cutaneous lesions in patients from the Solomon Islands

Tinea imbricata, also known as ‘Tokelau’, is an uncommon superficial mycosis caused by the anthropophilic dermatophyte Trichophyton concentricum. Cutaneous lesions appear characteristically as scaly and concentric rings that may cover all parts of the body. Often acquired in childhood, tinea imbricata is a chronic disease and lichenification is extremely common due to pruritus. The dermatophytosis mainly occurs in the South Pacific, but also in some regions of Southeast Asia and Central or South America. Tinea imbricata usually affects people living in primitive and isolated conditions. Mycological analysis is required for the diagnosis. The epidemiological and mycological study reported here took place in the Solomon Islands from June–September 2006. Skin scrapings were collected from 29 Melanesian patients (aged 8 months to 58 years) with chronic cutaneous lesions and were analysed mycologically in the Laboratory of Parasitology and Mycology of Angers University Hospital (France). Ten patients showed very evocative lesions with a positive direct examination, but T. concentricum was only isolated from three patients. Identification of the strains was confirmed by sequencing of the internal transcribed spacer (ITS) regions. With the increase in international travel, one cannot disregard that this very rare species may be isolated by mycologists in temperate areas from patients coming from endemic foci

Two-to-one resonant multi-modal dynamics of horizontal/inclined cables. Part I : theoretical formulation and model validation

This paper is first of the two papers dealingwith analytical investigation of resonant multimodal dynamics due to 2:1 internal resonances in the finite-amplitude free vibrations of horizontal/inclined cables. Part I deals with theoretical formulation and validation of the general cable model. Approximate nonlinear partial differential equations of 3-D coupled motion of small sagged cables - which account for both spatio-temporal variation of nonlinear dynamic tension and system asymmetry due to inclined sagged configurations - are presented. A multidimensional Galerkin expansion of the solution ofnonplanar/planar motion is performed, yielding a complete set of system quadratic/cubic coefficients. With the aim of parametrically studying the behavior of horizontal/inclined cables in Part II [25], a second-order asymptotic analysis under planar 2:1 resonance is accomplished by the method of multiple scales. On accounting for higher-order effectsof quadratic/cubic nonlinearities, approximate closed form solutions of nonlinear amplitudes, frequencies and dynamic configurations of resonant nonlinear normal modes reveal the dependence of cable response on resonant/nonresonant modal contributions. Depending on simplifying kinematic modeling and assigned system parameters, approximate horizontal/inclined cable models are thoroughly validated by numerically evaluating statics and non-planar/planar linear/non-linear dynamics against those of the exact model. Moreover, the modal coupling role and contribution of system longitudinal dynamics are discussed for horizontal cables, showing some meaningful effects due to kinematic condensation

Rab7A Is Required for Efficient Production of Infectious HIV-1

Retroviruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Rab proteins regulate specific steps in intracellular membrane trafficking by recruiting tethering, docking and fusion factors, as well as the actin- and microtubule-based motor proteins that facilitate vesicle traffic. Using virological tests and RNA interference targeting Rab proteins, we demonstrate that the late endosome-associated Rab7A is required for HIV-1 propagation. Analysis of the late steps of the HIV infection cycle shows that Rab7A regulates Env processing, the incorporation of mature Env glycoproteins into viral particles and HIV-1 infectivity. We also show that siRNA-mediated Rab7A depletion induces a BST2/Tetherin phenotype on HIV-1 release. BST2/Tetherin is a restriction factor that impedes HIV-1 release by tethering mature virus particles to the plasma membrane. Our results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release. Altogether, our results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle

The conserved dileucine- and tyrosine-based motifs in MLV and MPMV envelope glycoproteins are both important to regulate a common Env intracellular trafficking

BACKGROUND: Retrovirus particles emerge from the assembly of two structural protein components, Gag that is translated as a soluble protein in the cytoplasm of the host cells, and Env, a type I transmembrane protein. Because both components are translated in different intracellular compartments, elucidating the mechanisms of retrovirus assembly thus requires the study of their intracellular trafficking. RESULTS: We used a CD25 (Tac) chimera-based approach to study the trafficking of Moloney murine leukemia virus and Mason-Pfizer monkey virus Env proteins. We found that the cytoplasmic tails (CTs) of both Env conserved two major signals that control a complex intracellular trafficking. A dileucine-based motif controls the sorting of the chimeras from the trans-Golgi network (TGN) toward endosomal compartments. Env proteins then follow a retrograde transport to the TGN due to the action of a tyrosine-based motif. Mutation of either motif induces the mis-localization of the chimeric proteins and both motifs are found to mediate interactions of the viral CTs with clathrin adaptors. CONCLUSION: This data reveals the unexpected complexity of the intracellular trafficking of retrovirus Env proteins that cycle between the TGN and endosomes. Given that Gag proteins hijack endosomal host proteins, our work suggests that the endosomal pathway may be used by retroviruses to ensure proper encountering of viral structural Gag and Env proteins in cells, an essential step of virus assembly

Leptospirosis in American Samoa – Estimating and Mapping Risk Using Environmental Data

Leptospirosis is the most common bacterial infection transmitted from animals to humans. Infected animals excrete the bacteria in their urine, and humans can become infected through contact with animals or a contaminated environment such as water and soil. Environmental factors are important in determining the risk of human infection, and differ between ecological settings. The wide range of risk factors include high rainfall and flooding; poor sanitation and hygiene; urbanisation and overcrowding; contact with animals (including rodents, livestock, pets, and wildlife); outdoor recreation and ecotourism; and environmental degradation. Predictive risk maps have been produced for many infectious diseases to identify high-risk areas for transmission and guide allocation of public health resources. Maps are particularly useful where disease surveillance and epidemiological data are poor. The objectives of this study were to estimate leptospirosis seroprevalence at geographic locations based on environmental factors, produce a predictive disease risk map for American Samoa, and assess the accuracy of the maps in predicting infection risk. This study demonstrated the value of geographic information systems and disease mapping for identifying environmental risk factors for leptospirosis, and enhancing our understanding of disease transmission. Similar principles could be used to investigate the epidemiology of leptospirosis in other areas

Leptospirosis in the Asia Pacific region

<p>Abstract</p> <p>Background</p> <p>Leptospirosis is a worldwide zoonotic infection that has been recognized for decades, but the problem of the disease has not been fully addressed, particularly in resource-poor, developing countries, where the major burden of the disease occurs. This paper presents an overview of the current situation of leptospirosis in the region. It describes the current trends in the epidemiology of leptospirosis, the existing surveillance systems, and presents the existing prevention and control programs in the Asia Pacific region.</p> <p>Methods</p> <p>Data on leptospirosis in each member country were sought from official national organizations, international public health organizations, online articles and the scientific literature. Papers were reviewed and relevant data were extracted.</p> <p>Results</p> <p>Leptospirosis is highly prevalent in the Asia Pacific region. Infections in developed countries arise mainly from occupational exposure, travel to endemic areas, recreational activities, or importation of domestic and wild animals, whereas outbreaks in developing countries are most frequently related to normal daily activities, over-crowding, poor sanitation and climatic conditions.</p> <p>Conclusion</p> <p>In the Asia Pacific region, predominantly in developing countries, leptospirosis is largely a water-borne disease. Unless interventions to minimize exposure are aggressively implemented, the current global climate change will further aggravate the extent of the disease problem. Although trends indicate successful control of leptospirosis in some areas, there is no clear evidence that the disease has decreased in the last decade. The efficiency of surveillance systems and data collection varies significantly among the countries and areas within the region, leading to incomplete information in some instances. Thus, an accurate reflection of the true burden of the disease remains unknown.</p

Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity

Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the “intrinsic reactivity” of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant (“Tier 2-like”) viruses, globally sensitive (“Tier 1”) viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of inhibitor/antibody binding to the envelope glycoprotein trimer and by envelope glycoprotein reactivity to the inhibitor/antibody binding event. Quantitative differences in intrinsic reactivity contribute to HIV-1 strain variability in global susceptibility to neutralization and explain the long-observed relationship between increased inhibitor sensitivity and decreased entry requirements for target cell CD4