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

CRECIMIENTO Y PROPAGACIÓN DE LIMNOBIUM LAEVIGATUM (HYDROCHARITACEAE) BAJO DIFERENTES CONCENTRACIONES DE NUTRIENTES

Limnobium laevigatum es una macrófita flotante ampliamente distribuida en los países del neotrópico. Debido a su potencial como biorremediador es importante conocer las mejores condiciones que permitan su propagación. Uno de los factores más importantes es la concentración de nutrientes en el medio. Por ello, el presente trabajo tiene como objetivo conocer la concentración de nutrientes a la cual se logra una propagación óptima de L. laevigatum bajo condiciones de laboratorio cuantificando parámetros de crecimiento como la biomasa, área ocupada, tamaño de las raíces y producción de hojas. Para ello se monitorearon en laboratorio durante 21 días estos parámetros morfológicos en plantas sometidas a cinco concentraciones de nutrientes (0x, 12,5X, 25X, 50X y 100X proporcional a la concentración de nutrientes). La mayor producción de hojas, peso fresco, número de rametos y área foliar se alcanzó con los tratamientos de concentraciones intermedias en nutrientes (12,5X y 25X). Los tratamientos 0X y 12,5X tuvieron un mayor crecimiento radicular que el resto de tratamientos. La clorosis fue mayor en el tratamiento 0X y fue disminuyendo progresivamente conforme aumentó la concentración de nutrientes en los tratamientos. Los tratamientos 50X y 100X presentaron una mayor cantidad de hojas muertas que los tratamientos 0X, 12,5X y 25X. La tasa de crecimiento relativo fue mayor en el tratamiento 12,5X donde se obtuvo un valor de 0,1239. Se discute el rol de los nutrientes en las diferentes respuestas fisiológicas de la especie en estudio; y se compara las tasas de crecimiento de esta especie con otras especies de plantas acuáticas flotantes

Delayed Emergence from General Anesthesia

The incidence of perioperative morbidity associated with varying degrees of untreated thyroid disease is unknown, however major complications have been reported including severe hypotension or cardiac arrest, extreme sensitivity to opioids and anesthetics with prolonged unconsciousness, and myxedema coma. Myxedema coma is a rare and life-threatening illness the outcome of which has not been robustly studied in large numbers, partly due to its low incidence. This case illustrates the differential diagnosis of delayed emergence from general anesthesia and the value of a complete history and physical exam. Although delayed emergence from general anesthesia is not uncommon, recognizing the cause and instituting timely treatment is imperative in conditions where delayed therapy can increase morbidity and mortality

El registro del género Eremotherium (Xenarthra, Megatheriidae) en el Pleistoceno tardío de Venezuela

Los Megatheriidae del Pleistoceno tardío están representados por dos géneros: Megatherium, cuyo registro incluye las zonas templadas, desde el sur de la Patagonia Argentina hasta el oeste del Ecuador, y Eremotherium, de distribución intertropical, abarcando desde Carolina del Sur (EEUU) hasta Rio Grande do Sul (Brasil). El objetivo del presente trabajo es dar a conocer el material de Eremotherium registrado en Venezuela, identificado a partir de los restos dentarios y esqueletarios provenientes de las localidades de los estados Cojedes (Zanja de Lira), Distrito Capital (Tazón), Falcón (Muaco, Taima Taima, Guaibacoa) y Lara (San Miguel). El material de Eremotherium incluye un cráneo procedente del Sitio de Muaco (MGUCV-VF-1178), el cual presenta un rostro maxilonasal relativamente elongado y deprimido, con un arco cigomático que se origina por delante del primer molariforme (M1), y un margen postpalatino amplio y arqueado que se extiende a nivel del quinto diente (M5). Como en Eremotherium, en vista oclusal, las series dentarias superiores presentan el borde interno arqueado, los molariformes son menos hipsodontes que en Megatherium y las crestas y valles de los dientes son más agudos y ligeramente oblicuos. En las mandíbulas de San Miguel (MCNC-X-295) y Zanja de Lira (FLSCN-P-912), la protuberancia ventral es menos pronunciada que en Megatherium, congruente con el índice de hipsodoncia moderado de 0,74 en Eremotherium, y el margen central de la sínfisis se extiende a nivel del primer diente (m1), mientras que en Megatherium este borde se proyecta hasta el segundo (m2). Para analizar la morfometría de los elementos apendiculares, una prueba de Kruskal Wallis demostró que las dimensiones estimadas en los astrágalos (altura proximodistal y largo anteroposterior) y en los húmeros (anchura distal y longitud total) recuperados en Falcón y Cojedes son indistinguibles de Eremotherium. En cambio, sí difieren significativamente de Megatherium (α=0,00) cuyas proporciones suelen ser más robustasSesiones libresFacultad de Ciencias Naturales y Muse

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

Contribución preliminar a la caracterización paleoecológica de megamamíferos del Pleistoceno tardío de Venezuela

La fauna extinta del Pleistoceno tardío de Venezuela comprende mamíferos herbívoros gigantes, pertenecientes a los órdenes Pilosa (Megatheriidae, Mylodontidae), Proboscidea (Gomphotheriidae) y Litopterna (Macrauchenidae). Este trabajo es una aproximación al estudio de la paleodieta de los megaherbívoros del Cuaternario venezolano, aportando los primeros datos paleoecológicos obtenidos a partir de las estimaciones de masa corporal y la aplicación de diferentes indicadores de dieta en los grupos mencionados. Para los perezosos terrestres, se utilizó el índice de hipsodoncia (HI) que es el cociente de la altura del cuerpo mandibular y la longitud de la fila de molariformes. En Eremotherium (Megatheriidae) un HI = 0,74 sugiere un consumo limitado de plantas abrasivas y una tendencia a alimentarse de la vegetación blanda del ecotono bosque-sabana. En Glossotherium cf. G. tropicorum Hoffstetter (Mylodontidae), la hipsodoncia es todavía menor (0,60), aunque su hocico ancho le permitiría ingerir grandes bocados de gramíneas y hojas de vegetación arbórea en un ambiente mixto. La masa corporal fue calculada utilizando ecuaciones alométricas. Los promedios obtenidos son 5.680kg en Eremotherium, 1.002,6kg en Glossotherium, 1.042,8kg en Macrauchenia y 6.688kg en Stegomastodon (Gomphotheriidae), similares a las reportadas en estudios anteriores. El crecimiento moderado de los molares de Macrauchenia, junto a un cuello y miembros locomotores alargados, sugieren adaptaciones para ramonear y pacer en un ambiente mixto de sabana arbolada. En Stegomastodon y Cuvieronius (Gomphotheriidae), el índice de microdesgaste (MI) se calculó dividiendo los números de ralladuras y hoyuelos microscópicos, cuantificados en el esmalte de los molares. Un MI inferior a 1,5 indica una dieta arbustiva y superior a 1,5 una a base de gramíneas. En ambos géneros se obtuvo un MI promedio de 1,70, con valores individuales que oscilan entre 1,08 (ramoneador) y 2,60 (pastoreador), sugiriendo un ambiente mixto, posiblemente una sabana con parches de vegetación arbórea para finales del Pleistoceno.Sesiones libresFacultad de Ciencias Naturales y Muse

Impact of the Mass Drug Administration for malaria in response to the Ebola outbreak in Sierra Leone

Background: As emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate–amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014–January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres. Methods: The coverage of the two rounds of MDA with ASAQ was estimated by relating the number anti-malarial medicines distributed to the estimated resident population. Segmented time-series analysis was applied to weekly data collected from 49 primary health units (PHUs) and 11 hospitals performing malaria parasitological testing during the study period, to evaluate trends of malaria cases and Ebola alerts during the post-MDA weeks compared to the pre-MDA weeks in MDA- and non-MDA-cheifdoms. Results: After two rounds of the MDA, the number of suspected cases tested with rapid diagnostic test (RDT) decreased significantly by 43 % (95 % CI 38–48 %) at week 1 and remained low at week 2 and 3 post-first MDA and at week 1 and 3 post-second MDA; RDT positive cases decreased significantly by 47 % (41–52 %) at week 1 post-first and remained lower throughout all post-MDA weeks; and the RDT test positivity rate (TPR) declined by 35 % (32–38 %) at week 2 and stayed low throughout all post-MDA weeks. The total malaria (clinical + confirmed) cases decreased significantly by 45 % (39–52 %) at week 1 and were lower at week 2 and 3 post-first MDA; and week 1 post-second MDA. The proportion of confirmed malaria cases (out of all-outpatients) fell by 33 % (29–38 %) at week 1 post-first MDA and were lower during all post-MDA weeks. On the contrary, the non-malaria outpatient cases (cases due to other health conditions) either remained unchanged or fluctuated insignificantly. The Ebola alerts decreased by 30 % (13–46 %) at week 1 post-first MDA and much lower during all the weeks post–second MDA. Conclusions: The MDA achieved its goals of reducing malaria morbidity and febrile cases that would have been potentially diagnosed as suspected Ebola cases with increased risk of nosocomial infections. The intervention also helped reduce patient case-load to the severely strained health services at the peak of the Ebola outbreak and malaria transmission. As expected, the effect of the MDA waned in a matter of few weeks and malaria intensity returned to the pre-MDA levels. Nevertheless, the approach was an appropriate public health intervention in the context of the Ebola epidemic even in high malaria transmission areas of Sierra Leone

Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ^1H molecular diffusion NMR and ^(19)F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ^1H molecular diffusion nuclear magnetic resonance (NMR) and ^(19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ^(19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

Padrão Tipo A de comportamento, estresse ocupacional e sintomas musculoesqueléticos em trabalhadores de colarinho branco

Musculoskeletal disorders have a multifactorial etiology, where not only physical factors, but also psychosocial ones in the workplace interact with the individual characteristics and psychological demands of employees, predisposing them to the development of such conditions. Because not all people will respond in the same way to the stressors that affect them, the relationship between the Type A behavior pattern, occupational stress and musculoskeletal symptoms was investigated. The study design was cross-correlational and the statistical analysis was carried out using Pearson's correlation (p < .05), Student's t test and multiple linear regression. 100 white-collar employees from the public sector from southern Puerto Rico participated, selected by availability. PCTA predominated, the anatomical regions with the highest symptomatic frequency were: neck, shoulders, upper and lower back; and the level of occupational stress reported was low average. A statistically significant relationship was found between PCTA, occupational stress and musculoskeletal symptoms; not so between occupational stress and symptoms. Differences were reported between employees with PCTA and PCTB and the results of the regression model indicate that the independent variables explain about 7% of the variability of symptoms. It is concluded that the sample of white-collar employees who exhibit PCTA have a higher incidence of suffering from pain, discomfort or numbness in the region of the neck and upper back and are more prone and susceptible to stress.Los desórdenes musculoesqueletales poseen una etiología multifactorial, donde no solo los factores físicos, sino también los psicosociales del área de trabajo interactúan con las características individuales y las demandas psicológicas de los empleados, predisponiéndolos al desarrollo de tales condiciones. Debido a que no todas las personas responderán de igual forma ante los estresores que le afectan, se investigó la relación entre el patrón de conducta Tipo A, el estrés ocupacional y los síntomas musculoesqueletales. El diseño del estudio fue transversal-correlacional y el análisis estadístico se llevó a cabo mediante correlación de Pearson (p < .05), prueba t de student y regresión lineal múltiple. Participaron 100 empleados de cuello blanco del sector público del sur de Puerto Rico, seleccionados por disponibilidad. Predominó el PCTA, las regiones anatómicas con mayor frecuencia sintomática fueron: cuello, hombros, espalda alta y baja; y el nivel de estrés ocupacional reportado fue promedio bajo. Se halló relación estadísticamente significativa entre el PCTA, el estrés ocupacional y los síntomas musculoesqueletales; no así entre el estrés ocupacional y los síntomas. Se reportaron diferencias entre los empleados con PCTA y PCTB y los resultados del modelo de regresión indican que las variables independientes explican cerca del 7 % de la variabilidad de los síntomas. Se concluye que la muestra de empleados de cuello blanco que exhiben PCTA, tienen mayor incidencia a padecer de dolor, molestia o entumecimiento en la región del cuello y espalda alta y son más propensos y susceptibles al estrés.Os distúrbios musculoesqueléticos têm etiologia multifatorial, onde não só os fatores físicos, mas também os psicossociais do ambiente de trabalho interagem com as características individuais e demandas psicológicas dos funcionários, predispondo-os ao desenvolvimento dessas condições. Como nem todas as pessoas responderão da mesma forma aos estressores que as afetam, a relação entre o padrão de comportamento do Tipo A, o estresse ocupacional e os sintomas musculoesqueléticos foi investigada. O desenho do estudo foi correlacional cruzado e a análise estatística foi realizada por meio de correlação de Pearson (p < .05), teste t de Student e regressão linear múltipla. Participaram 100 funcionários administrativos do setor público do sul de Porto Rico, selecionados de acordo com a disponibilidade. Predominou a PCTA, as regiões anatômicas com maior frequência sintomática foram: pescoço, ombros, parte superior e inferior das costas; e o nível de estresse ocupacional relatado foi de média baixa. Foi encontrada relação estatisticamente significativa entre PCTA, estresse ocupacional e sintomas musculoesqueléticos; não é assim entre estresse ocupacional e sintomas. Diferenças foram relatadas entre funcionários com PCTA e PCTB e os resultados do modelo de regressão indicam que as variáveis ​​independentes explicam cerca de 7% da variabilidade dos sintomas. Conclui-se que a amostra de funcionários de colarinho branco que apresentam PCTA tem maior incidência de dor, desconforto ou dormência na região do pescoço e parte superior das costas e são mais propensos e suscetíveis ao estresse

DNA binds to a specific site of the adhesive blood-protein von Willebrand factor guided by electrostatic interactions.

Neutrophils release their intracellular content, DNA included, into the bloodstream to form neutrophil extracellular traps (NETs) that confine and kill circulating pathogens. The mechanosensitive adhesive blood protein, von Willebrand Factor (vWF), interacts with the extracellular DNA of NETs to potentially immobilize them during inflammatory and coagulatory conditions. Here, we elucidate the previously unknown molecular mechanism governing the DNA-vWF interaction by integrating atomistic, coarse-grained, and Brownian dynamics simulations, with thermophoresis, gel electrophoresis, fluorescence correlation spectroscopy (FCS), and microfluidic experiments. We demonstrate that, independently of its nucleotide sequence, double-stranded DNA binds to a specific helix of the vWF A1 domain, via three arginines. This interaction is attenuated by increasing the ionic strength. Our FCS and microfluidic measurements also highlight the key role shear-stress has in enabling this interaction. Our simulations attribute the previously-observed platelet-recruitment reduction and heparin-size modulation, upon establishment of DNA-vWF interactions, to indirect steric hindrance and partial overlap of the binding sites, respectively. Overall, we suggest electrostatics-guiding DNA to a specific protein binding site-as the main driving force defining DNA-vWF recognition. The molecular picture of a key shear-mediated DNA-protein interaction is provided here and it constitutes the basis for understanding NETs-mediated immune and hemostatic responses