Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania

Objective: To evaluate the diagnostic performance of two rapid detection tests (RDTs) for HIV 1/2 in plasma and in whole blood samples. Methods: More than 15,000 study subjects above the age of two years participated in two rounds of a cohort study to determine the prevalence of HIV. HIV testing was performed using the Determine HIV 1/2 test (Abbott) in the first (2006/2007) and the HIV 1/2 STAT-PAK Dipstick Assay (Chembio) in the second round (2007/2008) of the survey. Positive results were classified into faint and strong bands depending on the visual appearance of the test strip and confirmed by ELISA and Western blot. Results: The sensitivity and specificity of the Determine RDT were 100% (95% confidence interval = 86.8 to 100%) and 96.8% (95.9 to 97.6%) in whole blood and 100% (99.7 to 100%) and 97.9% (97.6 to 98.1%) in plasma respectively. Specificity was highly dependent on the tested sample type: when using whole blood, 67.1% of positive results were false positive, as opposed to 17.4% in plasma. Test strips with only faint positive bands were more often false positive than strips showing strong bands and were more common in whole blood than in plasma. Evaluation of the STAT-PAK RDT in plasma during the second year resulted in a sensitivity of 99.7% (99.1 to 99.9%) and a specificity of 99.3% (99.1 to 99.4%) with 6.9% of the positive results being false. Conclusions: Our study shows that the Determine HIV 1/2 strip test with its high sensitivity is an excellent tool to screen for HIV infection, but that – at least in our setting – it can not be recommended as a confirmatory test in VCT campaigns where whole blood is used

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Biophysical suitability, economic pressure and land-cover change: a global probabilistic approach and insights for REDD+

There has been a concerted effort by the international scientific community to understand the multiple causes and patterns of land-cover change to support sustainable land management. Here, we examined biophysical suitability, and a novel integrated index of “Economic Pressure on Land” (EPL) to explain land cover in the year 2000, and estimated the likelihood of future land-cover change through 2050, including protected area effectiveness. Biophysical suitability and EPL explained almost half of the global pattern of land cover (R 2 = 0.45), increasing to almost two-thirds in areas where a long-term equilibrium is likely to have been reached (e.g. R 2 = 0.64 in Europe). We identify a high likelihood of future land-cover change in vast areas with relatively lower current and past deforestation (e.g. the Congo Basin). Further, we simulated emissions arising from a “business as usual” and two reducing emissions from deforestation and forest degradation (REDD) scenarios by incorporating data on biomass carbon. As our model incorporates all biome types, it highlights a crucial aspect of the ongoing REDD + debate: if restricted to forests, “cross-biome leakage” would severely reduce REDD + effectiveness for climate change mitigation. If forests were protected from deforestation yet without measures to tackle the drivers of land-cover change, REDD + would only reduce 30 % of total emissions from land-cover change. Fifty-five percent of emissions reductions from forests would be compensated by increased emissions in other biomes. These results suggest that, although REDD + remains a very promising mitigation tool, implementation of complementary measures to reduce land demand is necessary to prevent this leakage

Prediction of Obesity in Children at 5 years: A Cohort Study

Objective To examine determinants of moderate and severe obesity in children at 5 years of age. Methodology A prospective cohort of mothers were enrolled at first antenatal visit, and interviewed shortly after delivery, at 6 months and 5 years. Detailed health, psychological and social questionnaires were completed at each phase by mothers, and child health questionnaires at 6 months and 5 years. At 5 years 4062 children were assessed physically, the Peabody Picture Vocabulary Test administered and mothers completed a modified Child Behaviour Checklist. Moderate obesity was defined as BMI between 85th and 94th percentiles inclusively, and severe obesity as a BMI greater than the 94th percentile. Results Independent predictors of severe obesity at 5 years were birthweight, female gender, maternal BMI and paternal BMI. Moderate obesity at 5 years was predicted by birthweight, paternal BMI and sleeplessness at 6 months, while small for gestational age (SGA) status and feeding problems at 6 months were protective factors for moderate obesity. Obesity was not associated with problems of language comprehension or behaviour. Conclusions Findings of this study suggest that biological rather than psychosocial factors are the major determinants of obesity at 5 years

Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to promote resolution of inflammation

Terminally differentiated neutrophils are short-lived but the key effector cells of the innate immune response, and have a prominent role in the pathogenesis and propagation of many inflammatory diseases. Delayed apoptosis, which is responsible for their extended longevity, is critically dependent on a balance of intracellular survival versus pro-apoptotic proteins. Here, we elucidate the mechanism by which the cyclin-dependent kinase (CDK) inhibitor drugs such as R-roscovitine and DRB (5,6-dichloro-1-beta--ribofuranosylbenzimidazole) mediate neutrophil apoptosis. We demonstrate (by a combination of microarray, confocal microscopy, apoptosis assays and western blotting) that the phosphorylation of RNA polymerase II by CDKs 7 and 9 is inhibited by R-roscovitine and that specific effects on neutrophil transcriptional capacity are responsible for neutrophil apoptosis. Finally, we show that specific CDK7 and 9 inhibition with DRB drives resolution of neutrophil-dominant inflammation. Thus, we highlight a novel mechanism that controls both primary human neutrophil transcription and apoptosis that could be targeted by selective CDK inhibitor drugs to resolve established inflammation

Complement system activation contributes to the ependymal damage induced by microbial neuraminidase

Background In the rat brain, a single intracerebroventricular injection of neuraminidase from Clostridium perfringens induces ependymal detachment and death. This injury occurs before the infiltration of inflammatory blood cells; some reports implicate the complement system as a cause of these injuries. Here, we set out to test the role of complement. Methods The assembly of the complement membrane attack complex on the ependymal epithelium of rats injected with neuraminidase was analyzed by immunohistochemistry. Complement activation, triggered by neuraminidase, and the participation of different activation pathways were analyzed by Western blot. In vitro studies used primary cultures of ependymal cells and explants of the septal ventricular wall. In these models, ependymal cells were exposed to neuraminidase in the presence or absence of complement, and their viability was assessed by observing beating of cilia or by trypan blue staining. The role of complement in ependymal damage induced by neuraminidase was analyzed in vivo in two rat models of complement blockade: systemic inhibition of C5 by using a function blocking antibody and testing in C6-deficient rats. Results The complement membrane attack complex immunolocalized on the ependymal surface in rats injected intracerebroventricularly with neuraminidase. C3 activation fragments were found in serum and cerebrospinal fluid of rats treated with neuraminidase, suggesting that neuraminidase itself activates complement. In ventricular wall explants and isolated ependymal cells, treatment with neuraminidase alone induced ependymal cell death; however, the addition of complement caused increased cell death and disorganization of the ependymal epithelium. In rats treated with anti-C5 and in C6-deficient rats, intracerebroventricular injection of neuraminidase provoked reduced ependymal alterations compared to non-treated or control rats. Immunohistochemistry confirmed the absence of membrane attack complex on the ependymal surfaces of neuraminidase-exposed rats treated with anti-C5 or deficient in C6. Conclusions These results demonstrate that the complement system contributes to ependymal damage and death caused by neuraminidase. However, neuraminidase alone can induce moderate ependymal damage without the aid of complement

Growth and energy and protein intake of preterm newborns in the first year of gestation-corrected age

CONTEXT: There are few longitudinal studies that analyze the growth and nutritional status parameters of children born prematurely. OBJECTIVE: To evaluate the growth and dietary intake of preterm newborns in the first year of gestation-corrected age. DESIGN: Prospective clinical study. SETTING: Tertiary care hospital. PATIENTS: 19 children (7 male) who were born prematurely, with birth weight between 1000g and 2000g, which was adequate for the gestational age. PROCEDURES: At 3, 6, 9 and 12 months of gestation-corrected age, children were evaluated in relation to weight, height and cephalic perimeter, using the National Center for Health Statistics as the standard reference, and the Rozalez-Lopez and Frisancho standards for brachial perimeter and triceps and subscapular skinfolds. The calculated dietary intake was compared to the Recommended Dietary Allowances. MAIN MEASUREMENTS: The Z score was calculated for the weight/age, height/age and weight/height relationships, and the percentiles of the perimeters and skinfolds were considered. Dietary intake records were made using the 24-hour Dietary Recall and the Food Frequency Intake Questionnaire methods. The Virtual Nutri software was used to calculate energy and protein intake. RESULTS: The weight/age, height/age and weight/height relationships and the brachial perimeter and triceps skinfold were statistically greater in the first semester in relation to the second. The cephalic perimeter remained above the 50th percentile for the ages studied and there was no difference in the subscapular skinfold between the first and second semesters, remaining below the 50th percentile. The calorie and protein intake, although statistically lower in the first than in the second semester, always remained above the recommended. CONCLUSIONS: The pace of growth is greater in the first semester than in the second, not reaching the standard expected for full-term newborns, with the exception of the cephalic perimeter, which remains adequate. Calorie/protein intake shows an inverse relationship with growth speed, remaining above the recommended for full-term newborns, although with difficulty in depositing subcutaneous fat, in spite of the high caloric intake.CONTEXTO: Atualmente há estudos longitudinais limitados que definem parâmetros de crescimento e estado nutricional de crianças nascidas prematuras. OBJETIVO: Avaliar o crescimento e a ingestão dietética em recém-nascidos pré-termo no primeiro ano de idade corrigida. TIPO DE ESTUDO: Estudo clínico prospectivo. LOCAL: Hospital de cuidados terciários. PACIENTES: 19 crianças (sete do sexo masculino) nascidas prematuras, adequadas para a idade gestacional, com peso de nascimento entre 1.000 g e 2.000 g, acompanhadas aos 3, 6, 9 e 12 meses de idade corrigida. PROCEDIMENTOS: Aos 3, 6, 9 e 12 meses de idade corrigida, as crianças foram avaliadas quanto ao peso, estatura e perímetros utilizando-se, como padrão de referência, o National Center of Health Statistics e quanto à circunferência braquial e às dobras cutâneas triciptal e subescapular, utilizando-se o padrão de Ronalez-Lopez e de Frisancho. A ingestão dietética calculada foi comparada às Recommended Dietary Allowances. RESULTADOS: As relações peso/idade, estatura/idade, peso/estatura, circunferência braquial e dobra cutânea do tríceps foram estatisticamente maiores no primeiro semestre em relação ao segundo. O perímetro cefálico manteve-se acima do percentil 50 nas idades estudadas e a dobra cutânea subescapular não mostrou diferença entre o primeiro e o segundo semestres, mantendo-se abaixo do percentil 50. A ingestão de calorias e proteínas, apesar de estatisticamente menor no primeiro do que no segundo semestre, permaneceu sempre maior do que o recomendado. CONCLUSÕES: O ritmo de crescimento mostra maior velocidade no primeiro semestre do que no segundo, não atingindo o padrão esperado para os recém-nascidos a termo, com exceção do perímetro cefálico, que se mantém adequado. A ingestão de calorias/proteínas mostra relação inversa com o ritmo de crescimento, permanecendo acima do recomendado para nascidos a termo, havendo, porém, dificuldade de deposição de gordura subcutânea, apesar da alta ingestão calórica.Universidade PaulistaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Logic programming and artificial neural networks in breast cancer detection

About 90% of breast cancers do not cause or are capable of producing death if detected at an early stage and treated properly. Indeed, it is still not known a specific cause for the illness. It may be not only a beginning, but also a set of associations that will determine the onset of the disease. Undeniably, there are some factors that seem to be associated with the boosted risk of the malady. Pondering the present study, different breast cancer risk assessment models where considered. It is our intention to develop a hybrid decision support system under a formal framework based on Logic Programming for knowledge representation and reasoning, complemented with an approach to computing centered on Artificial Neural Networks, to evaluate the risk of developing breast cancer and the respective Degree-of-Confidence that one has on such a happening.This work has been supported by FCT – Fundação para a Ciência e Tecnologia within the Project Scope UID/CEC/00319/2013

Genetic variation in Wnt/β-catenin and ER signalling pathways in female and male elite dancers and its associations with low bone mineral density: a cross-section and longitudinal study.

The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are related to genetic variants at the Wnt/β-catenin and ER pathways. Some athletes (e.g. gymnasts, dancers, swimmers) are at increased risk for low bone mineral density (BMD) which, if untreated, can lead to osteoporosis. To investigate the association of genetic polymorphisms in the oestrogen receptor (ER) and the Wnt/β-catenin signalling pathways with low BMD in elite and pre-elite dancers (impact sport athletes). The study included three phases: (1) 151 elite and pre-elite dancers were screened for the presence of low BMD and traditional osteoporosis risk factors (low body weight, menstrual disturbances, low energy availability); (2) a genetic association study was conducted in 151 elite and pre-elite dancers and age- and sex- controls; (3) serum sclerostin was measured in 101 pre-elite dancers and age- and sex-matched controls within a 3-year period. Eighty dancers revealed low BMD: 56.3% had at least one traditional osteoporosis risk factor, whereas 28.6% did not display any risk factor (37.2% revealed traditional osteoporosis risk factors, but had normal BMD). Body weight, menstrual disturbances and energy availability did not fully predict bone mass acquisition. Instead, genetic polymorphisms in the ER and Wnt/β-catenin pathways were found to be risk factors for low BMD in elite dancers. Sclerostin was significantly increased in dancers compared to controls during the 3-year follow-up (p < 0.05)

Dual requirement of cytokine and activation receptor triggering for cytotoxic control of murine cytomegalovirus by NK cells

Natural killer (NK) cells play a critical role in controlling murine cytomegalovirus (MCMV) and can mediate both cytokine production and direct cytotoxicity. The NK cell activation receptor, Ly49H, is responsible for genetic resistance to MCMV in C57BL/6 mice. Recognition of the viral m157 protein by Ly49H is sufficient for effective control of MCMV infection. Additionally, during the host response to infection, distinct immune and non-immune cells elaborate a variety of pleiotropic cytokines which have the potential to impact viral pathogenesis, NK cells, and other immune functions, both directly and indirectly. While the effects of various immune deficiencies have been examined for general antiviral phenotypes, their direct effects on Ly49H-dependent MCMV control are poorly understood. To specifically interrogate Ly49H-dependent functions, herein we employed an in vivo viral competition approach to show Ly49H-dependent MCMV control is specifically mediated through cytotoxicity but not IFNγ production. Whereas m157 induced Ly49H-dependent degranulation, efficient cytotoxicity also required either IL-12 or type I interferon (IFN-I) which acted directly on NK cells to produce granzyme B. These studies demonstrate that both of these distinct NK cell-intrinsic mechanisms are integrated for optimal viral control by NK cells