Window screening, ceilings and closed eaves as sustainable ways to control malaria in Dar es Salaam, Tanzania.

BACKGROUND\ud \ud Malaria transmission in Africa occurs predominantly inside houses where the primary vectors prefer to feed. Human preference and investment in blocking of specific entry points for mosquitoes into houses was evaluated and compared with known entry point preferences of the mosquitoes themselves.\ud \ud METHODS\ud \ud Cross-sectional household surveys were conducted in urban Dar es Salaam, Tanzania to estimate usage levels of available options for house proofing against mosquito entry, namely window screens, ceilings and blocking of eaves. These surveys also enabled evaluation of household expenditure on screens and ceilings and the motivation behind their installation.\ud \ud RESULTS\ud \ud Over three quarters (82.8%) of the 579 houses surveyed in Dar es Salaam had window screens, while almost half (48.9%) had ceilings. Prevention of mosquito entry was cited as a reason for installation of window screens and ceilings by 91.4% (394/431) and 55.7% (127/228) of respondents, respectively, but prevention of malaria was rarely cited (4.3%, 22/508). The median cost of window screens was between US $21-30 while that of ceilings was between US$301-400. The market value of insecticide-treated nets, window screening and ceilings currently in use in the city was estimated as 2, 5 and 42 million US$. More than three quarters of the respondents that lacked them said it was too expensive to install ceilings (82.2%) or window screens (75.5%).\ud \ud CONCLUSION\ud \ud High coverage and spending on screens and ceilings implies that these techniques are highly acceptable and excellent uptake can be achieved in urban settings like Dar es Salaam. Effective models for promotion and subsidization should be developed and evaluated, particularly for installation of ceilings that prevent entry via the eaves, which are the most important entry point for mosquitoes that cause malaria, a variety of neglected tropical diseases and the nuisance which motivates uptake

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan

INTRODUCTION: Although breast carcinoma (BC) is the most common malignancy affecting Jordanian females and the affected population in Jordan is younger than that in the West, no information is available on its biological characteristics. Our aims in this study are to evaluate the expression of estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu overexpression in BC in Jordan, and to compare the expression of these with other prognostic parameters for BC such as histological type, histological grade, tumor size, patients' age, and number of lymph node metastases. METHOD: This is a retrospective study conducted in the Department of Pathology at Jordan University of Science and Technology. A confirmed 91 cases of BC diagnosed in the period 1995 to 1998 were reviewed and graded. We used immunohistochemistry to evaluate the expression of ER, PR, and Her-2. Immunohistochemical findings were correlated with age, tumor size, grade and axillary lymph node status. RESULTS: Her-2 was overexpressed in 24% of the cases. The mean age of Her-2 positive cases was 42 years as opposed to 53 years among Her-2 negative cases (p = 0.0001). Her-2 expression was inversely related to ER and PR expression. Her-2 positive tumors tended to be larger than Her-2 negative tumors with 35% overexpression among T3 tumors as opposed to 22% among T2 tumors (p = 0.13). Her-2 positive cases tended to have higher rates of axillary metastases, but this did not reach statistical significance. ER and PR positive cases were seen in older patients with smaller tumor sizes. CONCLUSION: Her-2 overexpression was seen in 24% of BC affecting Jordanian females. Her-2 overexpression was associated with young age at presentation, larger tumor size, and was inversely related to ER and PR expression. One-fifth of the carcinomas were Her-2 positive and ER negative. This group appears to represent an aggressive form of BC presenting at a young age with large primary tumors and a high rate of four or more axillary lymph node metastases

Big conductance calcium-activated potassium channel openers control spasticity without sedation.

BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans. KEY RESULTS: VSN16R had nanomolar activity in tissue-based, functional assays and dose-dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000-fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1 /CB2 /GPPR55 cannabinoid-related receptors in receptor-based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium-activated potassium (BKCa ) channel. Drug-induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural-excitability and controlling spasticity. CONCLUSIONS AND IMPLICATIONS: We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper-excitability in spasticity

Atherosclerosis in young Brazilians suffering violent deaths: a pathological study

<p>Abstract</p> <p>Background</p> <p>Atherosclerosis is the leading cause of coronary heart disease and ischemic stroke, which can cause sudden death in adulthood. In general, the clinical manifestations of cardiovascular diseases are caused by atherosclerosis, which is a process that starts during middle age. More recent studies indicate that the atherosclerotic process begins during childhood.</p> <p>Methods</p> <p>To evaluate the extent of atherosclerotic disease in young Brazilians, we conducted a study of the pathological alterations in the major arteries of victims of violent death. Samples of the right carotid artery, left coronary artery, and thoracic aorta of young victims of violent death were analyzed and graded in accordance with the histological atherosclerotic lesion types proposed by the American Heart Association. Samples were collected from 100 individuals who had died from external causes, aged from 12 to 33 years.</p> <p>Results</p> <p>The majority of cases (83%) were male, and 66% of deaths were homicides caused by firearms. The median age was 20.0 years and mean body mass index was 20.9 kg/m². Of the right carotid artery specimens, 3% were normal, 55% had type I, 40% had type II, 1% had type III, and 1% had type IV atherosclerotic lesions. Of the left coronary artery specimens, 5% were normal, 48% had type I, 41% had type II, 3% had type III, and 3% had type IV lesions. Of the thoracic aorta specimens, none were normal, 13% had type I, 64% had type II, 22% had type III, and 1% had type IV lesions. Overall, 97.34% of arteries examined had some degree of atherosclerosis. The most common histological type was type II (foam cells). No thoracic aorta specimens were normal, and the coronary artery specimens had the most atherosclerosis.</p> <p>Conclusions</p> <p>Our results show a high prevalence of atherosclerotic lesions among young people in Brazil. Intervention should be undertaken to decrease the rate of sudden cardiac death in the adult population.</p

Emergent Properties of Patch Shapes Affect Edge Permeability to Animals

Animal travel between habitat patches affects populations, communities and ecosystems. There are three levels of organization of edge properties, and each of these can affect animals. At the lowest level are the different habitats on each side of an edge, then there is the edge itself, and finally, at the highest level of organization, is the geometry or structure of the edge. This study used computer simulations to (1) find out whether effects of edge shapes on animal behavior can arise as emergent properties solely due to reactions to edges in general, without the animals reacting to the shapes of the edges, and to (2) generate predictions to allow field and experimental studies to test mechanisms of edge shape response. Individual animals were modeled traveling inside a habitat patch that had different kinds of edge shapes (convex, concave and straight). When animals responded edges of patches, this created an emergent property of responding to the shape of the edge. The response was mostly to absolute width of the shapes, and not the narrowness of them. When animals were attracted to edges, then they tended to collect in convexities and disperse from concavities, and the opposite happened when animals avoided edges. Most of the responses occurred within a distance of 40% of the perceptual range from the tip of the shapes. Predictions were produced for directionality at various locations and combinations of treatments, to be used for testing edge behavior mechanisms. These results suggest that edge shapes tend to either concentrate or disperse animals, simply because the animals are either attracted to or avoid edges, with an effect as great as 3 times the normal density. Thus edge shape could affect processes like pollination, seed predation and dispersal and predator abundance

Evaluation of biological pathways involved in chemotherapy response in breast cancer

INTRODUCTION: Our goal was to examine the association between biological pathways and response to chemotherapy in estrogen receptor-positive (ER+) and ER-negative (ER-) breast tumors separately. METHODS: Gene set enrichment analysis including 852 predefined gene sets was applied to gene expression data from 51 ER- and 82 ER+ breast tumors that were all treated with a preoperative paclitaxel, 5-fluoruracil, doxorubicin, and cyclophosphamide chemotherapy. RESULTS: Twenty-seven (53%) ER- and 7 (9%) ER+ patients had pathologic complete response (pCR) to therapy. Among the ER- tumors, a proliferation gene signature (false discovery rate [FDR] q = 0.1), the genomic grade index (FDR q = 0.044), and the E2F3 pathway signature (FDR q = 0.22, P = 0.07) were enriched in the pCR group. Among the ER+ tumors, the proliferation signature (FDR q = 0.001) and the genomic grade index (FDR q = 0.015) were also significantly enriched in cases with pCR. Ki67 expression, as single gene marker of proliferation, did not provide the same information as the entire proliferation signature. An ER-associated gene set (FDR q = 0.03) and a mutant p53 gene signature (FDR q = 0.0019) were enriched in ER+ tumors with residual cancer. CONCLUSION: Proliferation- and genomic grade-related gene signatures are associated with chemotherapy sensitivity in both ER- and ER+ breast tumors. Genes involved in the E2F3 pathway are associated with chemotherapy sensitivity among ER- tumors. The mutant p53 signature and expression of ER-related genes were associated with lower sensitivity to chemotherapy in ER+ breast tumors only.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Oil and Gas Projects in the Western Amazon: Threats to Wilderness, Biodiversity, and Indigenous Peoples

This 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.The western Amazon is the most biologically rich part of the Amazon basin and is home to a great diversity of indigenous ethnic groups, including some of the world’s last uncontacted peoples living in voluntary isolation. Unlike the eastern Brazilian Amazon, it is still a largely intact ecosystem. Underlying this landscape are large reserves of oil and gas, many yet untapped. The growing global demand is leading to unprecedented exploration and development in the region. Without improved policies, the increasing scope and magnitude of planned extraction means that environmental and social impacts are likely to intensify. We review the most pressing oil- and gas-related conservation policy issues confronting the region. These include the need for regional Strategic Environmental Impact Assessments and the adoption of roadless extraction techniques. We also consider the conflicts where the blocks overlap indigenous peoples’ territories

Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients

BACKGROUND: Molecular markers and the rich biological information they contain have great potential for cancer diagnosis, prognostication and therapy prediction. So far, however, they have not superseded routine histopathology and staging criteria, partly because the few studies performed on molecular subtyping have had little validation and limited clinical characterization. METHODS: We obtained gene expression and clinical data for 412 breast cancers obtained from population-based cohorts of patients from Stockholm and Uppsala, Sweden. Using the intrinsic set of approximately 500 genes derived in the Norway/Stanford breast cancer data, we validated the existence of five molecular subtypes – basal-like, ERBB2, luminal A/B and normal-like – and characterized these subtypes extensively with the use of conventional clinical variables. RESULTS: We found an overall 77.5% concordance between the centroid prediction of the Swedish cohort by using the Norway/Stanford signature and the k-means clustering performed internally within the Swedish cohort. The highest rate of discordant assignments occurred between the luminal A and luminal B subtypes and between the luminal B and ERBB2 subtypes. The subtypes varied significantly in terms of grade (p < 0.001), p53 mutation (p < 0.001) and genomic instability (p = 0.01), but surprisingly there was little difference in lymph-node metastasis (p = 0.31). Furthermore, current users of hormone-replacement therapy were strikingly over-represented in the normal-like subgroup (p < 0.001). Separate analyses of the patients who received endocrine therapy and those who did not receive any adjuvant therapy supported the previous hypothesis that the basal-like subtype responded to adjuvant treatment, whereas the ERBB2 and luminal B subtypes were poor responders. CONCLUSION: We found that the intrinsic molecular subtypes of breast cancer are broadly present in a diverse collection of patients from a population-based cohort in Sweden. The intrinsic gene set, originally selected to reveal stable tumor characteristics, was shown to have a strong correlation with progression-related properties such as grade, p53 mutation and genomic instability