Endoplasmic Reticulum Calcium Regulates the Retrotranslocation of Trypanosoma Cruzi Calreticulin to the Cytosol

For most secretory pathway proteins, crossing the endoplasmic reticulum (ER) membrane is an irreversible process. However, in some cases this flow can be reversed. For instance, misfolded proteins retained in the ER are retrotranslocated to the cytosol to be degraded by the proteasome. This mechanism, known as ER associated degradation (ERAD), is exploited by several bacterial toxins to gain access to the cytosol. Interestingly, some ER resident proteins can also be detected in the cytosol or nucleus, calreticulin (CRT) being the most studied. Here we show that in Trypanosoma cruzi a minor fraction of CRT localized to the cytosol. ER calcium depletion, but not increasing cytosolic calcium, triggered the retrotranslocation of CRT in a relatively short period of time. Cytosolic CRT was subsequently degraded by the proteasome. Interestingly, the single disulfide bridge of CRT is reduced when the protein is located in the cytosol. The effect exerted by ER calcium was strictly dependent on the C-terminal domain (CRT-C), since a CRT lacking it was totally retained in the ER, whereas the localization of an unrelated protein fused to CRT-C mirrored that of endogenous CRT. This finding expands the regulatory mechanisms of protein sorting and may represent a new crossroad between diverse physiological processes

Characterization of patients with acquired encephalic injury submitted to surgery for the correction of deformities in lower limbs inferior members

Objetivo: Identificar as características demográficas e clínicas dos pacientes com Lesão Encefálica Adquirida (LEA) submetidos a cirurgias ortopédicas para correção de deformidades em membros inferiores (MMII), e analisar quais procedimentos cirúrgicos foram mais realizados nesses pacientes. Métodos: estudo transversal com revisão de 103 prontuários de pacientes submetidos a cirurgia ortopédica para correção de deformidade em membros inferiores no período de 2012 a 2014.  Resultados: Os pacientes com diagnóstico de Traumatismo Cranioencefálico (TCE) e sequela de dupla hemiparesia foram os frequentemente submetidos à cirurgia de correção de partes moles, sendo que o alongamento de tríceps sural a técnica mais realizada. Conclusão: Os pacientes vítimas de TCE foram submetidos a correções cirúrgicas de MMII, seguidos pelos pacientes vítimas de Acidente Vascular Cerebral (AVC), com faixa etária entre 39 e 51 anos, respectivamente, e predominância do sexo masculino, em todos os grupos. As técnicas mais realizadas envolveram a correção de deformidades no pé e tornozelo. Observamos que o tempo transcorrido entre a lesão e o procedimento cirúrgico fora igual ou superior a quatro anos, sendo comum que pacientes chegassem aos centros de reabilitação com deformidades, já instaladas, devido à espera para ingressar em algum serviço.Objective: to identify the demographic and clinical characteristics of patients with acquired brain injury (ABI) submitted to orthopedic surgeries to correct lower limb deformities (LLDF), and to analyze which surgical procedures were more commonly performed in these patients. Methods: Cross-sectional study with a review of 103 medical records of patients undergoing orthopedic surgery for correction of lower limb deformity in the period from 2012 to 2014.  Results: Patients diagnosed with cranioencephalic trauma (CET) and sequelae of double hemiparesis were the ones frequently submitted to soft tissue correction surgery, and the triceps stretching sural was the most accomplished technique. Conclusion: Patients who were victims of CET underwent surgical correction of lower limbs, followed by patients with stroke, with age range between 39 and 51 years, respectively, and male predominance, in all groups. The most accomplished techniques involved the correction of foot and ankle deformities. We observed that the time elapsed between the lesion and the surgical procedure was equal to or greater than four years, and it was common for patients to arrive at rehabilitation centers with deformities, already installed, due to waiting to be admitted in some health service

Routine HIV Screening in France: Clinical Impact and Cost-Effectiveness

BACKGROUND. In France, roughly 40,000 HIV-infected persons are unaware of their HIV infection. Although previous studies have evaluated the cost-effectiveness of routine HIV screening in the United States, differences in both the epidemiology of infection and HIV testing behaviors warrant a setting-specific analysis for France. METHODS/PRINCIPAL FINDINGS. We estimated the life expectancy (LE), cost and cost-effectiveness of alternative HIV screening strategies in the French general population and high-risk sub-populations using a computer model of HIV detection and treatment, coupled with French national clinical and economic data. We compared risk-factor-based HIV testing ("current practice") to universal routine, voluntary HIV screening in adults aged 18-69. Screening frequencies ranged from once to annually. Input data included mean age (42 years), undiagnosed HIV prevalence (0.10%), annual HIV incidence (0.01%), test acceptance (79%), linkage to care (75%) and cost/test (€43). We performed sensitivity analyses on HIV prevalence and incidence, cost estimates, and the transmission benefits of ART. "Current practice" produced LEs of 242.82 quality-adjusted life months (QALM) among HIV-infected persons and 268.77 QALM in the general population. Adding a one-time HIV screen increased LE by 0.01 QALM in the general population and increased costs by €50/person, for a cost-effectiveness ratio (CER) of €57,400 per quality-adjusted life year (QALY). More frequent screening in the general population increased survival, costs and CERs. Among injection drug users (prevalence 6.17%; incidence 0.17%/year) and in French Guyana (prevalence 0.41%; incidence 0.35%/year), annual screening compared to every five years produced CERs of €51,200 and €46,500/QALY. CONCLUSIONS/SIGNIFICANCE. One-time routine HIV screening in France improves survival compared to "current practice" and compares favorably to other screening interventions recommended in Western Europe. In higher-risk groups, more frequent screening is economically justifiable.Haute Autorite de Sante; the Institut de Veille Sanitaire; Sidaction; the Agence Nationale de Recherches sur le SIDA et les hepatites virales; the National Institute of Allergy and Infectious Diseases (R01 AI042006, K24 AI062476, P30 AI42851); the National Institute of Mental Health (R01 MH65869); the National Institute on Drug Abuse (R01 DA015612

Avian haemosporidians in the cattle egret (Bubulcus ibis) from central-western and southern Africa: high diversity and prevalence

We described the geographic distribution of 82 haemosporidian lineages (Plasmodium, Haemoproteus, and Leucocytozoon) in the cattle egret sampled in five countries in central-western and southern Africa. Seventy-three lineages have not previously been reported. We determined the prevalence of three haemosporidians in the samples. We investigated the influence of the internal environment of the host and environmental variables on the Plasmodium diversity and whether environmental variables may explain spatial variations in the prevalence of Plasmodium. We screened DNA from 509 blood samples from nestlings in 15 African colonies for infection by sequencing the cytochrome b gene of parasites. The molecular phylogenetic analysis was performed using Bayesian methods and including sequences from the MalAvi and GeneBank databases. We found 62 new Plasmodium lineages in a clade with MYCAME02, which is a lineage described in waterbirds and recently identified in birds of prey as Plasmodium paranucleophilum. Two Haemoproteus lineages identified in cattle egret formed a distinct group with Haemoproteus catharti and MYCAMH1 (Haemoproteus spp.). Seven Leucocytozoon lineages found in the cattle egret clustered with Leucocytozoon californicus. We found different Plasmodium diversities among the colonies sampled, demonstrating that the internal environment of the host is not the primary determinant of diversity. A linear mixed-effects multivariate model showed that precipitation was positively associated with Plasmodium diversity when controlling for the effects of temperature, colony composition (mixed and non-mixed species) and country. Moreover, a generalized mixed model showed that temperature was positively associated with the prevalence of Plasmodium when controlling for precipitation, elevation and country. We conclude that the cattle egret is a good model for future haemosporidian studies, as we found a significant number of new lineages in this host, which occupies regions with different climate characteristics where environmental variables exert an influence on the diversity and prevalence of Plasmodium

Host life-history traits predict haemosporidian parasite prevalence in tanagers (Aves: Thraupidae)

Vector-borne parasites are important ecological drivers influencing life-history evolution in birds by increasing host mortality or susceptibility to new diseases. Therefore, understanding why vulnerability to infection varies within a host clade is a crucial task for conservation biology and for understanding macroecological life-history patterns. Here, we studied the relationship of avian life-history traits and climate on the prevalence of Plasmodium and Parahaemoproteus parasites. We sampled 3569 individual birds belonging to 53 species of the family Thraupidae. Individuals were captured from 2007 to 2018 at 92 locations. We created 2 phylogenetic generalized least-squares models with Plasmodium and Parahaemoproteus prevalence as our response variables, and with the following predictor variables: climate PC1, climate PC2, body size, mixed-species flock participation, incubation period, migration, nest height, foraging height, forest cover, and diet. We found that Parahaemoproteus and Plasmodium prevalence was higher in species inhabiting open habitats. Tanager species with longer incubation periods had higher Parahaemoproteus prevalence as well, and we hypothesize that these longer incubation periods overlap with maximum vector abundances, resulting in a higher probability of infection among adult hosts during their incubation period and among chicks. Lastly, we found that Plasmodium prevalence was higher in species without migratory behaviour, with mixed-species flock participation, and with an omnivorous or animal-derived diet. We discuss the consequences of higher infection prevalence in relation to life-history traits in tanagers.Fil: Aguiar de Souza Penha, Victor. Universidade Federal do Paraná; BrasilFil: Maia Chaves Bicalho Domingos, Fabricius. Universidade Federal do Paraná; BrasilFil: Fecchio, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Bell, Jeffrey A.. University of South Dakota; Estados UnidosFil: Weckstein, Jason D.. No especifíca;Fil: Ricklefs, Robert E.. University of Missouri; Estados UnidosFil: Martins Braga, Erika. Universidade Federal de Minas Gerais; BrasilFil: de Abreu Moreira, Patrícia. Universidade Federal de Ouro Preto; BrasilFil: Soares, Leticia. University of Western Australia; AustraliaFil: Latta, Steven. No especifíca;Fil: Tolesano Pascoli, Graziela. Universidade do Brasília; BrasilFil: Alquezar, Renata Duarte. Universidade do Brasília; BrasilFil: Del Claro, Kleber. Universidade Federal de Uberlandia; BrasilFil: Tonelli Manica, Lilian. Universidade Federal do Paraná; Brasi

Antibodies That Induce Phagocytosis of Malaria Infected Erythrocytes: Effect of HIV Infection and Correlation with Clinical Outcomes

HIV infection increases the burden of disease of malaria in pregnancy, in part by impairing the development of immunity. We measured total IgG and phagocytic antibodies against variant surface antigens of placental-type CS2 parasites in 187 secundigravidae (65% HIV infected). In women with placental malaria infection, phagocytic antibodies to CS2VSA were decreased in the presence of HIV (p = 0.011) and correlated positively with infant birth weight (coef = 3.57, p = 0.025), whereas total IgG to CS2VSA did not. Phagocytic antibodies to CS2VSA are valuable tools to study acquired immunity to malaria in the context of HIV co-infection. Secundigravidae may be an informative group for identification of correlates of immunity

Coverage, Adherence and Costs of Intermittent Preventive Treatment of Malaria in Children Employing Different Delivery Strategies in Jasikan, Ghana

BACKGROUND: Intermittent preventive treatment of malaria in children (IPTc) involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected. IPTc provides a high level of protection against uncomplicated and severe malaria, with monthly sulphadoxine-pyrimethamine plus amodiaquine (SP&AQ) and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens. A key challenge is the identification of a cost-effective delivery strategy. METHODS: A community randomized trial was undertaken in Jasikan district, Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways. Twelve villages were randomly selected to receive IPTc from village health workers (VHWs) or facility-based nurses working at health centres' outpatient departments (OPD) or EPI outreach clinics. Children aged 3 to 59 months-old received one IPT course (three doses) in May, June, September and October. Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective. RESULTS: The economic cost per child receiving at least the first dose of all 4 courses was US$4.58 when IPTc was delivered by VHWs, US$4.93 by OPD nurses and US$5.65 by EPI nurses. The unit economic cost of receiving all 3 doses of all 4 courses was US$7.56 and US$8.51 when IPTc was delivered by VHWs or facility-based nurses respectively. The main cost driver for the VHW delivery was supervision, reflecting resources used for travelling to more remote communities rather than more intense supervision, and for OPD and EPI delivery, it was the opportunity cost of the time spent by nurses in dispensing IPTc. CONCLUSIONS: VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district, Ghana. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119132

Predicting the Lay Preventive Strategies in Response to Avian Influenza from Perceptions of the Threat

Background: The identification of patterns of behaviors that lay people would engage in to protect themselves from the risk of infection in the case of avian influenza outbreak, as well as the lay perceptions of the threat that underlie these risk reduction strategies. Methodology/Principal Findings: A population-based survey (N = 1003) was conducted in 2008 to understand and describe how the French public might respond to a possible outbreak. Factor analyses highlighted three main categories of risk reduction strategies consisting of food quality assurance, food avoidance, and animal avoidance. In combination with the fear of contracting avian influenza, mental representations associated with the manifestation and/or transmission of the disease were found to significantly and systematically shape the behavioral responses to the perceived threat. Conclusions/Significance: This survey provides insight into the nature and predictors of the protective patterns that might be expected from the general public during a novel domestic outbreak of avian influenza

Long-Term Weekly Iron-Folic Acid and De-Worming Is Associated with Stabilised Haemoglobin and Increasing Iron Stores in Non-Pregnant Women in Vietnam

BACKGROUND: The prevalence of anaemia and iron deficiency in women remains high worldwide. WHO recommends weekly iron-folic acid supplementation where anaemia rates in non-pregnant women of reproductive age are higher than 20%. In 2006, a demonstration project consisting of weekly iron-folic acid supplementation and regular de-worming was set up in two districts in a northern province in Vietnam where anaemia and hookworm rates were 38% and 76% respectively. In 2008 the project was expanded to all districts in the province, targeting some 250,000 women. The objectives of this study were to: 1) examine changes in haemoglobin, iron stores and soil transmitted helminth infection prevalence over three years and 2) assess women's access to and compliance with the intervention. METHODS AND FINDINGS: The study was a semi-cross-sectional, semi-longitudinal panel design with a baseline survey, three impact surveys at three-, twelve- and thirty months after commencement of the intervention, and three compliance surveys after ten weeks, eighteen and thirty six months. RESULTS: After thirty months, mean haemoglobin stabilised at 130.3 g/L, an increase of 8.2 g/L from baseline, and mean serum ferritin rose from 23.9 µg/L to 52 µg/L. Hookworm prevalence fell from 76% to 22% over the same period. After thirty six months, 81% of the target population were receiving supplements and 87% were taking 75% or more of the supplements they received. CONCLUSIONS: Weekly iron-folic acid supplementation and regular de-worming was effective in significantly and sustainably reducing the prevalence of anaemia and soil transmitted helminth infections and high compliance rates were maintained over three years