Expression of Estrogen Alpha and Beta Receptors in Prostate Cancer and Hyperplasia: Immunohistochemical Analysis

Objectives: Estrogen receptors are believed to play a significant role in the pathogenesis of prostate carcinoma (PCa). The aim of this study is to evaluate the expression of ER-α and ER-β in human benign and malignant prostatic tissue.Patients and Methods: The archival materials of 100 prostatic specimens (65 PCa, 35 BPH) were collected from the Department of Pathology, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia. Seven PCa cases contained foci of high-grade prostate intraepithelial neoplasia (HGPIN). Immunohistochemistry was used to test the protein expression of ER-α and ER-β utilizing monoclonal mouse antihuman antibodies.Results: Among the 65 cases of PCa, ER-α was expressed in 3 cases (4.6%) in epithelial cells and 4 cases (6.1%) in stromal cells. ER-α was not expressed in any of the HGPIN foci. Additionally, ER-α was not expressed in either luminal or basal cells in any of the 35 BPH cases. However it was expressed in 4 cases (11.4%) in stromal cells of BPH. In PCa, ER-β was expressed in 61 cases (93.8%) and 35 cases (53.8%) in the epithelial and stromal cells respectively. ER-β was expressed only in 2 cases (28.5%) out of 7 HGPIN foci. It was expressed in 33 cases (94.3%) of epithelialand stromal cells of BPH. Conclusion: The majority of PCa and BPH exhibited nuclear immunoreactivity for ER-β in both tumor and stromal cells and they are usually negative for ER-α. There is probably partial loss of ER-β in HGPIN. ER-β may have a role in the process of prostatic hyperplasia and malignancy.Key Words: ER-α, ER-β, prostate, hyperplasia, premalignant, cancer,  immunohistochemistr

Management of Renewable Energy for a Shared Facility Controller in Smart Grid

© 2016 IEEE. This paper proposes an energy management scheme to maximize the use of solar energy in the smart grid. In this context, a shared facility controller (SFC) with a number of solar photovoltaic panels in a smart community is considered that has the capability to schedule the generated energy for consumption and trade to other entities. In particular, a mechanism is designed for the SFC to decide on the energy surplus, if there is any, that it can use to charge its battery and sell to the households and the grid based on the offered prices. In this regard, a hierarchical energy management scheme is proposed with a view to reduce the total operational cost to the SFC. The concept of a virtual cost is introduced that aids the SFC to estimate its future operational cost based on some available current information. The energy management is conducted for three different cases, and the optimal cost to the SFC is determined for each case by the theory of maxima and minima. A real-time algorithm is proposed to reach the optimal cost for all cases, and some numerical examples are provided to demonstrate the beneficial properties of the proposed scheme

Phenotyping clonal populations of glioma stem cell reveals a high degree of plasticity in response to changes of microenvironment

The phenotype of glioma-initiating cells (GIC) is modulated by cell-intrinsic and cell-extrinsic factors. Phenotypic heterogeneity and plasticity of GIC is an important limitation to therapeutic approaches targeting cancer stem cells. Plasticity also presents a challenge to the identification, isolation, and propagation of purified cancer stem cells. Here we use a barcode labelling approach of GIC to generate clonal populations over a number of passages, in combination with phenotyping using the established stem cell markers CD133, CD15, CD44, and A2B5. Using two cell lines derived from isocitrate dehydrogenase (IDH)-wildtype glioblastoma, we identify a remarkable heterogeneity of the phenotypes between the cell lines. During passaging, clonal expansion manifests as the emergence of a limited number of barcoded clones and a decrease in the overall number of clones. Dual-labelled GIC are capable of forming traceable clonal populations which emerge after as few as two passages from mixed cultures and through analyses of similarity of relative proportions of 16 surface markers we were able to pinpoint the fate of such populations. By generating tumour organoids we observed a remarkable persistence of dominant clones but also a significant plasticity of stemness marker expression. Our study presents an experimental approach to simultaneously barcode and phenotype glioma-initiating cells to assess their functional properties, for example to screen newly established GIC for tumour-specific therapeutic vulnerabilities

Use of a Semi-field System to Evaluate the Efficacy of Topical Repellents under user Conditions Provides a Disease Exposure free Technique Comparable with Field Data.

Before topical repellents can be employed as interventions against arthropod bites, their efficacy must be established. Currently, laboratory or field tests, using human volunteers, are the main methods used for assessing the efficacy of topical repellents. However, laboratory tests are not representative of real life conditions under which repellents are used and field-testing potentially exposes human volunteers to disease. There is, therefore, a need to develop methods to test efficacy of repellents under real life conditions while minimizing volunteer exposure to disease. A lotion-based, 15% N, N-Diethyl-3-methylbenzamide (DEET) repellent and 15% DEET in ethanol were compared to a placebo lotion in a 200 sq m (10 m x 20 m) semi-field system (SFS) against laboratory-reared Anopheles arabiensis mosquitoes and in full field settings against wild malaria vectors and nuisance-biting mosquitoes. The average percentage protection against biting mosquitoes over four hours in the SFS and field setting was determined. A Poisson regression model was then used to determine relative risk of being bitten when wearing either of these repellents compared to the placebo. Average percentage protection of the lotion-based 15% DEET repellent after four hours of mosquito collection was 82.13% (95% CI 75.94-88.82) in the semi-field experiments and 85.10% (95% CI 78.97-91.70) in the field experiments. Average percentage protection of 15% DEET in ethanol after four hours was 71.29% (CI 61.77-82.28) in the semi-field system and 88.24% (84.45-92.20) in the field. Semi-field evaluation results were comparable to full-field evaluations, indicating that such systems could be satisfactorily used in measuring efficacy of topically applied mosquito repellents, thereby avoiding risks of exposure to mosquito-borne pathogens, associated with field testing

Destabilising microtubule polymerization regulates chondrocyte dedifferentiation and inflammation via nuclear factor kappa b and β-catenin pathway

The role of cell morphological changes in colchicine-inhibited tubulin polymerization of rabbit articular chondrocytes and their involvement in dedifferentiation were investigated. Colchicine treatment resulted in the dedifferentiation of chondrocytes, which was supported by the loss of type II collagen expression and proteoglycan production. Inhibition of tubulin de-polymerization with paclitaxel rescued colchicine-caused dedifferentiation and tubulin polymerization. Additionally, colchicine stimulated β-catenin overexpression, which is characterized by the accumulation of β-catenin into the cytosol determined by immunofluorescence staining. Inhibition of the β-catenin-mediated pathway by siR β-catenin recovered colchicine-caused the suppression of type II collagen expression in the chondrocytes. Treatment with colchicine also induced inflammation, as determined by the increased expression level of cyclooxygenase-2 and decreased IκB-α expression level by western blot analysis. Modulating the expression levels of pIκBα and IκBα via BMS 345541, was able to modulate colchicine-induced inflammatory effect

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study.

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control

A possible role for Phlebotomus (Anaphlebotomus) rodhaini (Parrot, 1930) in transmission of Leishmania donovani

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis (VL, kala azar), caused by <it>Leishmania donovani </it>is a major health problem in Sudan and other East African countries. In this region the only proven vectors of <it>L. donovani </it>are <it>Phlebotomus orientalis </it>in eastern Sudan, Ethiopia and Upper Nile areas of Southern Sudan and <it>Phlebotomus martini </it>in Ethiopia, Kenya and Southern Sudan. In this report, we present the first evidence that <it>Phlebotomus rodhaini </it>may also play a role in maintaining transmission of <it>L. donovani </it>between animal reservoir hosts in eastern Sudan. The study was conducted in a zoonotic focus of visceral leishmaniasis in Dinder National Park, eastern Sudan, where previous work showed high infection rates of <it>L. donovani </it>in <it>P. orientalis</it>. Sand flies, captured by CDC traps were dissected and examined for infection with <it>Leishmania </it>parasites. Parasite isolates were subjected to <it>L. donovani </it>specific PCR. Field experiments were also carried out to compare efficiency of rodent baited and un-baited CDC traps in collection of <it>P. rodhaini </it>and determine its man-biting rate.</p> <p>Results</p> <p>Three female <it>P. rodhain</it>i were found infected with <it>Leishmania </it>parasites in an astonishingly small number of flies captured in three separate field trips. Two of these isolates were typed by molecular methods as <it>L. donovani</it>, while the third isolate was inoculated into a hamster that was subsequently lost. Although <it>P. rodhaini is </it>generally considered a rare species, results obtained in this study indicate that it can readily be captured by rodent-baited traps. Results of human landing collection showed that it rarely bites humans in the area.</p> <p>Conclusion</p> <p>It is concluded that <it>P. rodhaini </it>is a possible vector of <it>L. donovani </it>between animal reservoir hosts but is not responsible for infecting humans. It is suggested that the role of <it>P</it>. <it>rodhaini </it>in transmission of <it>L. donovani </it>in other zoonotic foci of visceral leishmaniasis in Africa should be re-examined.</p

Transplantation for renal failure secondary to enteric hyperoxaluria: a case report

Enteric hyperoxaluria can lead to renal failure. There have only been a few reports of renal transplantation as treatment of endstage renal disease secondary to enteric hyperoxaluria and results have been mixed. This report describes a patient with Crohn's disease who developed chronic renal failure from enteric hyperoxaluria. He subsequently had a successful renal transplant without any post-operative oxalate related complications and has satisfactory renal function almost three years later. Aggressive pre-transplant hemodialysis was not done. The literature associated with renal transplantation for enteric hyperoxaluria is reviewed

Evaluation of Xpert® MTB/RIF and ustar easyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania : a prospective descriptive study

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania.; Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis.; Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %.; Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children