Prevalence, risk factors, and treatment outcomes of isoniazid- and rifampicin-mono-resistant pulmonary tuberculosis in Lima, Peru

Background : Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes. Methods : A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Lowenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment. Results : Of 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1-4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95% CI: 1.9-47.8). Isoniazid mono-resistant patients had a higherrisk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24,8%, p<0.01). Conclusion : A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes

A comparison of mean winds and gravity wave activity in the northern and southern polar MLT

Mean winds and waves observed in the mesosphere and lower thermosphere with MF radars located at Davis (69°S, 78°E) and Poker Flat (65°N, 147°W) are compared. Measurements covering the period from 1999 to mid 2000 show differences in the strength of the horizontal wind fields. In the southern hemisphere the zonal and meridional winds reach their maximum values near the summer solstice, but are delayed by 2–3 weeks in the northern hemisphere. Gravity wave variances also show significant differences, as do the strength of vertical velocities.Andrew Dowdy and Robert A. Vincent, Kiyoshi Igarashi and Yasuhiro Murayama, Damian J. Murph

Molecular Mechanisms Underlying Migratory and Immune-Evasion Properties of Circulating Tumor Cells

Metastasis is the leading cause of cancer deaths worldwide. However, there exist only limited treatment options and they are often ineffective. An important aspect of metastasis that requires study, but has previously been understudied is circulating tumor cells (CTCs). CTCs are a critical step in the metastatic cascade. They can be analyzed for the identification of key mechanisms in metastasis. To this end, we isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prostate cancer (CRPC). From these mouse models, primary tumor and CTC lines were established. Functional characterization of cells revealed CTCs to be more migratory than primary tumor cells. Additionally, CTCs underwent epithelial-to-mesenchymal transition (EMT) as observed through E-cadherin decrease and SLUG and fibronectin (FN1) increases. Taking advantage of the intact immune system present in the BALB/c syngeneic mouse model we used, we investigated the major histocompatibility complex class I (MHCI) cell surface molecule present on tumor cells and recognizable by cytotoxic T lymphocytes (CTLs). MHCI expression was decreased in CTCs. To investigate additional immune-evading mechanisms, CTC secretory profiles were examined. Endostatin, C-X-C motif chemokine 5 (CXCL5), and proliferin secretions were decreased in CTCs in comparison to primary tumor cells. Moreover, decreased intracellular endostatin expression was found in CTCs. Taken together, our findings suggest that CTCs exhibit distinct characteristics from primary tumor cells. Given that CTCs were more migratory and expressed higher levels of Fibronectin (FN1), SLUG, and Integrin B1 (ITGB1), we investigated FN1, SLUG, and ITGB1 relationship to CTC migration and one another. Knockdown studies of FN1, SLUG, and ITGB1 confirmed each to be important for CTC migration. Furthermore, FN1 was observed to regulate ITGB1 and SLUG. FN1’s regulation of these two molecules, however, involves two separate and independent pathways by which FN1 increases migration. Finally, we tested whether FN1 required ITGB1 and SLUG to exert its effects on CTC migration. We observed that while FN1 was able to induce migration, it required ITGB1 and SLUG to maximally enhance CTC migration. FN1 was previously mostly known for its role in being an extracellular matrix (ECM) protein, frequently overexpressed in cancers. Very little is known about FN1’s intracellular role and ability to regulate other molecules. This is the first time to our knowledge that FN1 is being reported to regulate ITGB1 and SLUG as a molecular mechanism for CTC migration. Further CTC studies will undoubtedly uncover additional important mechanisms of cancer metastasis

\u3cem\u3eMycobacterium marinum\u3c/em\u3e Infection After Exposure to Coal Mine Water

Mycobacterium marinum infection has been historically associated with exposure to aquariums, swimming pools, fish, or other marine fauna. We present a case of M marinum left wrist tenosynovitis and elbow bursitis associated with a puncture injury and exposure to coal mine water in Illinois

Tuberculosis and Cardiovascular Disease: Linking the Epidemics

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, subsets of mycobacteria actively replicate during latent tuberculosis infection (LTBI), and recent studies suggest that LTBI is associated with persistent chronic inflammation that may lead to CVD. Recent epidemiologic work has shown that the risk of CVD in persons who develop tuberculosis is higher than in persons without a history of tuberculosis, even several years after recovery from tuberculosis. Together, these data suggest that tuberculosis may play a role in the pathogenesis of CVD. Further research to investigate a potential link between tuberculosis and CVD is warranted

Detection and characterisation of an Endogenous Betaretrovirus in Australian Wild Deer

Endogenous retroviruses (ERVs) are the remnants of past retroviral infections that once invaded the host’s germline and were vertically transmitted. ERV sequences have been reported in mammals, but their distribution and diversity in cervids are unclear. Using next-generation sequencing, we identified a nearly complete genome of an endogenous betaretrovirus in fallow deer (Dama dama). Further genomic analysis showed that this provirus, tentatively named cervid endogenous betaretrovirus 1 (CERV β1), has typical betaretroviral genome features (gag-pro-pol-env) and the betaretrovirus-specific dUTPase domain. In addition, CERV β1 pol sequences were detected by PCR in the six non-native deer species with wild populations in Australia. Phylogenetic analyses demonstrated that CERV β1 sequences from subfamily Cervinae clustered as sister taxa to ERV-like sequences in species of subfamily Muntiacinae. These findings, therefore, suggest that CERV β1 endogenisation occurred after the split of these two subfamilies (between 3.3 and 5 million years ago). Our results provide important insights into the evolution of betaretroviruses in cervids

Tuberculosis and Risk of Acute Myocardial Infarction: A Propensity Score-Matched Analysis

Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs with Mycobacterium tuberculosis infection is unclear. We assessed if tuberculosis disease increased the risk of acute myocardial infarction (AMI). We identified patients with tuberculosis index claims from a large de-identified database of ~15 million adults enrolled in a U.S. commercial insurance policy between 2008 and 2010. Tuberculosis patients were 1:1 matched to patients without tuberculosis claims using propensity scores. We compared the occurrence of index AMI claims between the tuberculosis and non-tuberculosis cohorts using Kaplan–Meier curves and Cox Proportional Hazard models. Data on 2026 patients with tuberculosis and 2026 propensity-matched patients without tuberculosis were included. AMI was more frequent in the tuberculosis cohort compared with the non-tuberculosis cohort, 67 (3·3%) vs. 32 (1·6%) AMI cases, respectively, P \u3c 0·01. Tuberculosis was associated with an increased risk of AMI (adjusted hazard ratio (HR) 1·98, 95% confidence intervals (CI) 1·3–3·0). The results were similar when the analysis was restricted to pulmonary tuberculosis (adjusted HR 2·43, 95% CI 1·5–4·1). Tuberculosis was associated with an increased risk of AMI. CVD risk assessment should be considered in tuberculosis patients. Mechanistic studies of tuberculosis and CVD are warranted

Geo-statistical methods to analyse changes in pre-Hispanic settlement patterns in the Río Ica catchment, Peru

Within arid regions allochthonous rivers as a main source of fresh water play a significant role in the spatial organisation of human occupation.This study aims at a comprehensive view on changes in the prehistoric occupation patterns within the Río Ica catchment on the southern coast of Peru. Results of different research projects are integrated. The heterogeneous character of the catchment allows us to define three sub-sections which differ greatly in terms of vegetation, relief and water regime.Based on quantitative geo-statistical methods we analyse spatio-temporal changes in human occupation from the Early Horizon (c. 1000–200 BC) through to the Inca Late Horizon (AD 1450–1532) in the context of environmental conditions, as well as socio-economic processes. Examining known archaeological sites we are able to assess the significance of environmental location factors for pre-Hispanic settlements. In addition, areas of high human interaction are identified on the basis of a classification of archaeological sites according to their function (craft/industry, cult, cooperation and trade). We thereby transfer the concept of central place theory to the spatial distribution of archaeological remains, introducing a novel approach to identifying central functions in a spatially explicit way.Our results crystallise the changing character of occupation in the study area over more than two millennia. They contribute to the ongoing debate on the decline of the Nasca culture, endorsing a complex combination of natural and socio-economic reasons. Furthermore, the results support the concept of a more widespread exchange and cooperation during ‘Horizon’ periods in the study area and likewise indicate that the disappearance of a supra-regional administrative polity during ‘Intermediate’ periods might have led to higher human activity in smaller scale societies, as reflected in a more diverse spatial organisation in terms of geomorphometric units and central areas

Ansiedad y transtornos del sueño en estudiantes de medicina URP

Introduccion: Los desordenes del sueño (DS) son reconocidos como un problema de salud publica, con importantes consecuencias sociales y psiquiatricas, especificamente en la vida academica de los estudiantes. El objetivo de este estudio fue evaluar los DS en un grupo de estudiantes universitarios y estimar la relacion entre ansiedad e insomnio. Metodología: Se realizó un estudio transversal, analitico y observacional en la Facultad de Medicina Humana de la Universidad Ricardo Palma, durante el año académico 2017. Dos cuestionarios validados, fueron admnistrados personalmente a 132 estudiantes despues de obtener su consentimiento informado: El Inventario de Ansiedad de Beck (BAI), que es un instrumento autoaplicable de 21 ítems, desarrollado para estimar los niveles de ansiedad y para los DS el cuestionario de sueño de Oviedo ritmo sueño-vigilia del paciente, el cual consta de 15 ítems, que ayuda al diagnóstico de insomnio e hipersomnia según los criterios diagnósticos CIE-10 y DSM IV. Resultados: La edad media hallada fue de 24.07 +- 2.14 ( 20-34 ), Según estado civil el 67.42% eran solteros. La prevalencia de insomnio según CIE10 fue de 31.8 % (95% CI: 27.3-39.2%) mas frecuentes en estudiantes mujeres (61.9%) que en hombres (38.9%); y según DSM IV fue de fue de 3.8 % (95% CI: 2.9- 8.4%) mas frecuentes en estudiantes mujeres (80%) que en hombres (20%) . La prevalencia de ansiedad clinicamente significativa (moderada y severa) fue de 9.1%, mas frecuente en en estudiantes mujeres (66.6%) que en hombres (33.3%). Se encontró una asociacion estadisticamente significativa entre ansiedad e insomnio DSM IV con un OR:7.8 IC95% 1.16-52.26 p: 0.01 ; de los estudiantes con insomnio el 40 % presentaban ansiedad versus el 9% de aquellos sin insomnio tenian ansiedad (p<0.01). Conclusión: La magnitud del insomnio en estudiantes universitarios de la Universidad Ricardo Palma evidencia la importancia de examinar la salud del sueño en esta poblacion. La asociacion entre ansiedad e insomnio es significativa, remarcando la importancia de detectar y tratar oportunamente la ansiedad y no solo el insomnio.Trabado de investigacio

Prevalencia de Eimeria sp y estudio morfométrico de ooquistes hallados en canes domésticos de Perú

La eimeriosis es una enfermedad causada por un protozoario del género Eimeria que afecta a todos los animales silvestres y domésticos. Dado que en Perú no existen reportes previos y en otras regiones de Latinoamérica la prevalencia es nula o baja en perros domésticos, el objetivo del presente trabajo fue determinar la prevalencia de Eimeria sp en canes de la ciudad de Cajamarca mediante un análisis coproparasitológico, utilizando el método de Faust y efectuando el estudio morfométrico de los ooquistes. Se obtuvieron aleatoriamente 206 muestras fecales en la zona Este de Cajamarca, las cuales fueron inmediatamente procesadas en el Laboratorio de Parasitología Veterinaria de la Universidad Nacional de Cajamarca, Perú. La prevalencia de Eimeria sp fue de 10,68% en canes domésticos. En el estudio morfométrico de los ooquistes, se determinaron medidas de largo y ancho, que presentaron promedios de 21,73 pm de largo y 17,77 pm de ancho para la forma ovoide; 16,40 pm de largo y 15,31 pm de ancho para la forma esférica, y finalmente 25,54 y 18,51 pm respectivamente para la forma elipsoidal. Estos resultados prueban la presencia e infección leve por Eimeria sp en perros domésticos en la serranía norte del Perú, sugiriendo además, futuros estudios del protozoario para evitar riesgos o afecciones a la salud pública