Glucocorticoid-regulated localization of cell surface glycoproteins in rat hepatoma cells is mediated within the Golgi complex.

Glucocorticoid hormones regulate the post-translational maturation and sorting of cell surface and extracellular mouse mammary tumor virus (MMTV) glycoproteins in M1.54 cells, a stably infected rat hepatoma cell line. Exposure to monensin significantly reduced the proteolytic maturation and externalization of viral glycoproteins resulting in a stable cellular accumulation of a single 70,000-Mr glycosylated polyprotein (designated gp70). Cell surface- and intracellular-specific immunoprecipitations of monensin-treated cells revealed that gp70 can be localized to the cell surface only in the presence of 1 microM dexamethasone, while in uninduced cells gp70 is irreversibly sequestered in an intracellular compartment. Analysis of oligosaccharide processing kinetics demonstrated that gp70 acquired resistance to endoglycosidase H with a half-time of 65 min in the presence or absence of hormone. In contrast, gp70 was inefficiently galactosylated after a 60-min lag in uninduced cells while rapidly acquiring this carbohydrate modification in the presence of dexamethasone. Furthermore, in the absence or presence of monensin, MMTV glycoproteins failed to be galactosylated in hormone-induced CR4 cells, a complement-selected sorting variant defective in the glucocorticoid-regulated compartmentalization of viral glycoproteins to the cell surface. Since dexamethasone had no apparent global effects on organelle morphology or production of total cell surface-galactosylated species, we conclude that glucocorticoids induce the localization of cell surface MMTV glycoproteins by regulating a highly selective step within the Golgi apparatus after the acquisition of endoglycosidase H-resistant oligosaccharide side chains but before or at the site of galactose attachment

Endurance training slows breast tumor growth in mice by suppressing Treg cells recruitment to tumors

BACKGROUND: Aerobic exercise has been shown to slow tumor progression in rodents and humans, but the mechanisms behind this effect are still unclear. Here we show that aerobic exercise in the form of chronic endurance training suppresses tumor recruitment of FoxP3+ Treg cells thus enhancing antitumor immune efficiency. METHODS: Adult wild-type and athymic BALB/c female mice were endurance-trained for 8 weeks. Circulating leukocytes as well as muscle and liver mtDNA copy number were compared to aged-matched concurrent sedentary controls to establish systemic effects. 4 T1 murine mammary tumor cells were injected subcutaneously to the 4th mammary pad at the end of the training period. Tumor growth and survival rates were compared, together with antitumor immune response. RESULTS: Exercised wild-type had 17% slower growth rate, 24% longer survival, and 2-fold tumor-CD+ 8/FoxP3+ ratio than sedentary controls. Exercised athymic BALB/c females showed no difference in tumor growth or survival rates when compared to sedentary controls. CONCLUSIONS: Cytotoxic T cells are a significant factor in endurance exercise-induced suppression of tumor growth. Endurance exercise enhances antitumor immune efficacy by increasing intratumoral CD8+/FoxP3+ ratio

Relación entre la ruptura del contrato psicológico y satisfacción laboral con el desempeño laboral en docentes de una institución de educación superior en Bogotá D.C.

Trabajo de InvestigaciónEste estudio tuvo como objetivo verificar la correlación entre la ruptura del contrato psicológico y la satisfacción laboral con el desempeño en el trabajo de los docentes de una institución de educación superior en la ciudad de Bogotá, en el documento se presentan la metodología utilizada y el análisis estadístico de los resultados de la aplicación de tres instrumentos, ratificando lo expuesto en otras investigaciones en donde se establecen relaciones significativas entre las variables de Ruptura del Contrato Psicológico, Satisfacción y Desempeño laboral.RESUMEN 1. MARCO TEÓRICO 2. MÉTODO 3. RESULTADOS 4. DISCUSIÓN REFERENCIAS APÉNDICESMaestríaMagister en Psicologí

Health systems and global progress towards malaria elimination, 2000-2016

As more countries progress towards malaria elimination, a better understanding of the most critical health system features for enabling and supporting malaria control and elimination is needed.; All available health systems data relevant for malaria control were collated from 23 online data repositories. Principal component analysis was used to create domain specific health system performance measures. Multiple regression model selection approaches were used to identify key health systems predictors of progress in malaria control in the 2000-2016 period among 105 countries. Additional analysis was performed within malaria burden groups.; There was large heterogeneity in progress in malaria control in the 2000-2016 period. In univariate analysis, several health systems factors displayed a strong positive correlation with reductions in malaria burden between 2000 and 2016. In multivariable models, delivery of routine services and hospital capacity were strongly predictive of reductions in malaria cases, especially in high burden countries. In low-burden countries approaching elimination, primary health center density appeared negatively associated with progress while hospital capacity was positively correlated with eliminating malaria.; The findings presented in this manuscript suggest that strengthening health systems can be an effective strategy for reducing malaria cases, especially in countries with high malaria burden. Potential returns appear particularly high in the area of service delivery

Spatio-seasonal modeling of the incidence rate of malaria in Mozambique

<p>Abstract</p> <p>Background</p> <p>The objective was to study the seasonal effect on the spatial distribution of the incidence of malaria in children under 10 years old living in the Manhiça district, Mozambique.</p> <p>Methods</p> <p>The data of the clinical malaria incidence were obtained from a study of two cohorts of children followed from December 1996 to July 1999. The cases were obtained by the active detection method. Hierarchical Bayesian models were used to model the incidence of malaria, including spatial correlation nested to climatic season. The models were compared with the deviance information criterion. The age and gender of the children were also taken into account.</p> <p>Results</p> <p>The incidence of malaria is associated with age, period and climate season. The incidence presents a clear spatial pattern, with a higher incidence in the neighbourhoods situated in the north and northeast of the Manhiça area. The transmission of malaria is highest during the wet season but the spatial pattern of malaria does not differ from that during the dry season.</p> <p>Conclusion</p> <p>The incidence of malaria in Manhiça presents a spatial pattern which is independent of the seasonal climatic conditions. The climate modifies the incidence of malaria in the entire region but does not change the spatial pattern of the incidence of this disease. These findings may be useful for the planning of malaria control activities. These activities can be performed taking account that the neighbourhoods with more incidence of malaria do not change over the annual climate seasons.</p

A randomized comparison of two anemia treatment regimens in Tanzanian children.

We used a prospective, open-label randomized trial to evaluate two treatment regimens in Tanzanian children two months to four years of age presenting to a hospital with a packed cell volume (PCV) < 25%. Treatment was either standard (14 days of ferrous sulfate and an antimalarial) or extended (three months of ferrous sulfate and three antimalarial treatments). The prevalence of anemia was measured two weeks after completion of treatment and six months after recruitment. Two weeks after completing treatment, the prevalence of PCV < 33% was 58% in the standard treatment arm and 44% in the extended treatment group (P = 0.04), and the mean PCV was significantly higher in the extended treatment arm (32.1%, SD = 4.5% versus 30.8%, SD = 4.9%; P = 0.031). However, there was no difference in the prevalence of PCV < 25% in the first survey, and the benefits of extended therapy were only apparent six months after recruitment in children compliant with the extended treatment (odds ratio of PCV < 25% = 0.16, P = 0.06). Compliance was satisfactory in only 39% (82 of 209) of the children in the first week of treatment. Extending the duration of therapy and improving compliance may have health benefits for anemic children in malaria-endemic settings

Levels and trends of demographic indices in southern rural Mozambique: evidence from demographic surveillance in Manhica district

Background: In Mozambique most of demographic data are obtained using census or sample survey including indirect estimations. A method of collecting longitudinal demographic data was introduced in southern Mozambique since 1996 (DSS -Demographic Surveillance System in Manhiça district, Maputo province), but the extent to which it yields demographic measures that are typical of southern rural Mozambique has not been evaluated yet. Methods: Data from the DSS were used to estimate the levels and trends of fertility, mortality and migration in Manhiça, between 1998 and 2005. The estimates from Manhiça were compared with estimates from Maputo province using the 1997 National census and 1997 Demographic and Health Survey (DHS). The DHS data were used to estimate levels and trends of adult mortality using the siblings' histories and the orphanhood methods. Results: The populations in Manhiça and in Maputo province are young (44% <15 years in Manhiça and 42% in Maputo); with reduced adult males when compared to females (all ages sex ratio of 78.7 in Manhiça and 89 in Maputo). Fertility in Manhiça is at a similar level as in Maputo province and has remained around 5 children per woman, during the eight years of surveillance in Manhiça. Although the infant mortality rate (IMR) in Mozambique has decreased during the last two decades (from 148 deaths per 1000 live births in 1980 to 101 in 2003), it has remained stable around 80 in Manhiça during the surveillance period. Adult mortality has increased both in Manhiça (probability of dying from ages 15 to 60 increased from 0.4 in 1998 to 0.6 in 2005 in Manhiça, from 0.3 in 1992 to 0.4 in 1997 in Maputo province and from 0.1 in 1980 to 0.6 in 2000 in Mozambique). Consequently, the life expectancy decreased from 53 to 46 in Manhiça and from 42 years in 1997 to 38 in 2004 in Mozambique. Migration is high in Manhiça but tends to stabilise after the movements of resettlement that followed the end of the civil war in 1992. Conclusion: The population under demographic surveillance in Manhiça district presents characteristics that are typical of southern rural Mozambique, with predominance of young people and reduction of adult males. Labour migration and excess adult male mortality are the major factors for the reduction of adult males. Mortality is high and only infant mortality has started to stabilise while adult mortality has increased, and as consequence, life expectancy has decreased. The Manhiça DSS is an adequate tool to report demographic measures for southern rural Mozambique

Mefloquine for preventing malaria in pregnant women

Background: The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine. Objectives: To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate: • the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and • the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine.Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials. Selection criteria: Randomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen. Data collection and analysis: Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting. Main results: Six trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria. Two trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo. Study participants included women of all gravidities and of all ages (four trials) or > 18 years (two trials). Gestational age at recruitment was > 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes. When compared with sulfadoxine-pyrimethamine, IPTp-mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high-certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low-certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high-certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate-certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high-certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I2 statistic = 0%; high-certainty evidence). IPTp-mefloquine increased drug-related vomiting (RR 4.76, 95% CI 4.13 to 5.49; 6272 participants, 2 studies; high-certainty evidence) and dizziness (RR 4.21, 95% CI 3.36 to 5.27; participants = 6272, 2 studies; high-certainty evidence). When compared with cotrimoxazole, IPTp-mefloquine plus cotrimoxazole probably results in a 48% reduction in maternal peripheral parasitaemia at delivery (RR 0.52, 95% CI 0.30 to 0.93; 989 participants, 2 studies; moderate-certainty evidence) and a 72% reduction in placental malaria (RR 0.28, 95% CI 0.14 to 0.57; 977 participants, 2 studies; high-certainty evidence) but has little or no effect on the incidence of clinical malaria episodes during pregnancy (IRR 0.76, 95% CI 0.33 to 1.76, 1 study; high-certainty evidence) and probably no effect on maternal anaemia at delivery (RR 0.94, 95% CI 0.73 to 1.20; 1197 participants, 2 studies; moderate-certainty evidence), low birth weight rates (RR 1.20, 95% CI 0.89 to 1.60; 1220 participants, 2 studies; moderate-certainty evidence), and rates of spontaneous abortion and stillbirth (RR 1.12, 95% CI 0.42 to 2.98; 1347 participants, 2 studies; very low-certainty evidence). Mefloquine was associated with higher risks of drug-related vomiting (RR 7.95, 95% CI 4.79 to 13.18; 1055 participants, one study; high-certainty evidence) and dizziness (RR 3.94, 95% CI 2.85 to 5.46; 1055 participants, 1 study; high-certainty evidence). Authors' conclusions: Mefloquine was more efficacious than sulfadoxine-pyrimethamine in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women

Spatio-temporal analysis of mortality among children under the age of five in Manhiça (Mozambique) during the period 1997-2005

<p>Abstract</p> <p>Background</p> <p>Reducing childhood mortality is the fourth goal of the Millennium Development Goals agreed at the United Nations Millennium Summit in September 2000. However, childhood mortality in developing countries remains high. Providing an accurate picture of space and time-trend variations in child mortality in a region might generate further ideas for health planning actions to achieve such a reduction. The purpose of this study was to examine the spatio-temporal variation for child mortality rates in Manhiça, a district within the Maputo province of southern rural Mozambique during the period 1997-2005 using a proper generalized linear mixed model.</p> <p>Results</p> <p>The results showed that childhood mortality in all the area was modified from year to year describing a convex time-trend but the spatial pattern described by the neighbourhood-specific underlying mortality rates did not change during the entire period from 1997 to 2005, where neighbourhoods with highest risks are situated in the peripheral side of the district. The spatial distribution, though more blurred here, was similar to the spatial distribution of child malaria incidence in the same area. The peak in mortality rates observed in 2001 could have been caused by the precipitation system that started in early February 2000, following which heavy rains flooded parts of Mozambique's southern provinces. However, the mortality rates at the end of the period returned to initial values.</p> <p>Conclusions</p> <p>The results of this study suggest that the health intervention programmes established in Manhiça to alleviate the effects of flooding on child mortality should cover a period of around five years and that special attention might be focused on eradicating malaria transmission. These outcomes also suggest the utility of suitably modelling space-time trend variations in a region when a point effect of an environmental factor affects all the study area.</p