Surveillance of multidrug resistant bacteria pathogens from female infertility cases

Antibiotic resistance is a public health problem of increasing magnitude. Female reproductive system is vulnerable to a number of diseases. Diseased condition results in infertility, menstrual irregularity, pregnancy loss, and in association with pregnancy, morbidity to both the mother and child increases. In the present work, the bacteria pathogens were isolated from the endometrial sample of 50 female infertility cases among which 42 cases were positive for the pathogens. This study reveals that Escherichia coli was the most dominant, followed by Enterococcus faecalis, Pseudomonas aeruginosa, Streptococcus sp., and Enterobacter. The isolates were characterized and its susceptibility against important antibiotics were performed. Highest sensitivity was observed with gatifloxacin, imipenam and piperacillin and tazobactum. Thus, according to this study, these antibiotics can be recommended against multi drug resistant bacteria pathogens.Keywords: Multidrug resistance, female infertility, bacteria pathogensAfrican Journal of Biotechnology Vol. 12(26), pp. 4129-413

IHTC14-22833 CFD Model Validation and Prediction of Mist/Steam Cooling in a 180-Degree Bend Tubes

ABSTRACT To achieve higher efficiency target of the advanced turbine systems, the closed-loop steam cooling scheme is employed to cool the airfoil. It is proven from the experimental results at laboratory working conditions that injecting mist into steam can significantly augment the heat transfer in the turbine blades with several fundamental studies. The mist cooling technique has to be tested at gas turbine working conditions before implementation. Realizing the fact that conducting experiment at gas turbine working condition would be expensive and time consuming, the computational simulation is performed to get a preliminary evaluation on the potential success of mist cooling at gas turbine working conditions. The present investigation aims at validating a CFD model against experimental results in a 180-degree tube bend and applying the model to predict the mist/steam cooling performance at gas turbine working conditions. The results show that the CFD model can predict the wall temperature within 8% of experimental steam-only flow and 16% of mist/steam flow condition. Five turbulence models have been employed and their results are compared. Inclusion of radiation into CFD model causes noticeable increase in accuracy of prediction. The reflect Discrete Phase Model (DPM) wall boundary condition predicts better than the wall-film boundary condition. The CFD simulation identifies that mist impingement over outer wall is the cause for maximum mist cooling enhancement at 45 0 of bend portion. The computed results also reveals the phenomenon of mist secondary flow interaction at bend portion, adding the mist cooling enhancement at the inner wall. The validated CFD simulation predicts that average of 100% mist cooling enhancement can be achieved by injecting 5% mist at elevated GT working condition

CFD Model Validation and Prediction of Mist/Steam Cooling in a 180-Degree Bend Tubes

To achieve higher efficiency target of the advanced turbine systems, the closed-loop steam cooling scheme is employed to cool the airfoil. It is proven from the experimental results at laboratory working conditions that injecting mist into steam can significantly augment the heat transfer in the turbine blades with several fundamental studies. The mist cooling technique has to be tested at gas turbine working conditions before implementation. Realizing the fact that conducting experiment at gas turbine working condition would be expensive and time consuming, the computational simulation is performed to get a preliminary evaluation on the potential success of mist cooling at gas turbine working conditions. The present investigation aims at validating a CFD model against experimental results in a 180-degree tube bend and applying the model to predict the mist/steam cooling performance at gas turbine working conditions. The results show that the CFD model can predict the wall temperature within 8 % of experimental steam-only flow and 16 % of mist/steam flow condition. Five turbulence models have been employed and their results are compared. Inclusion of radiation into CFD model causes noticeable increase in accuracy of prediction. The reflect Discrete Phase Model (DPM) wall boundary condition predicts better than the wall-film boundary condition. The CFD simulation identifies that mist impingement over outer wall is the cause for maximum mist cooling enhancement at 450 of bend portion. The computed results also reveals the phenomenon of mist secondary flow interaction at bend portion, adding the mist cooling enhancement at the inner wall. The validated CFD simulation predicts that average of 100 % mist cooling enhancement can be achieved by injecting 5 % mist at elevated GT working condition

Added value of IP-10 as a read-out of <em>Mycobacterium tuberculosis</em>:Specific immunity in young children

We have explored the added value of interferon-γ (IFNγ)–inducible protein 10 as a read-out of Mycobacterium tuberculosis–specific immunity in young Indian children, where the sensitivity of the IFNγ release assays for tuberculosis is poor. Reduced frequency of indeterminate results and an increased sensitivity for tuberculosis suggest a potential for fewer missed cases with a combined IFNγ/inducible protein 10 read-out in a 4th generation IFNγ release assays

BLR1 and FCGR1A transcripts in peripheral blood associate with the extent of intrathoracic tuberculosis in children and predict treatment outcome

Biomarkers reflecting the extent of Mycobacterium tuberculosis-induced pathology and normalization during anti-tuberculosis treatment (ATT) would considerably facilitate trials of new treatment regimens and the identification of patients with treatment failure. Therefore, in a cohort of 99 Indian children with intrathoracic tuberculosis (TB), we performed blood transcriptome kinetic analysis during ATT to explore 1) the association between transcriptional biomarkers in whole blood (WB) and the extent of TB disease at diagnosis and treatment outcomes at 2 and 6 months, and 2) the potential of the biomarkers to predict treatment response at 2 and 6 months. We present the first data on the association between transcriptional biomarkers and the extent of TB disease as well as outcome of ATT in children: Expression of three genes down-regulated on ATT (FCGR1A, FPR1 and MMP9) exhibited a positive correlation with the extent of TB disease, whereas expression of eight up-regulated genes (BCL, BLR1, CASP8, CD3E, CD4, CD19, IL7R and TGFBR2) exhibited a negative correlation with the extent of disease. Baseline levels of these transcripts displayed an individual capacity >70% to predict the six-month treatment outcome. In particular, BLR1 and FCGR1A seem to have a potential in monitoring and perhaps tailoring future antituberculosis therapy

The polycomb group protein EZH2 is involved in progression of prostate cancer

Prostate cancer is a leading cause of cancer-related death in males and is second only to lung cancer. Although effective surgical and radiation treatments exist for clinically localized prostate cancer, metastatic prostate cancer remains essentially incurable. Here we show, through gene expression profiling(1), that the polycomb group protein enhancer of zeste homolog 2 (EZH2)(2,3) is overexpressed in hormone-refractory, metastatic prostate cancer. Small interfering RNA (siRNA) duplexes(4) targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induces transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis. Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62896/1/nature01075.pd

Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2

© 2017 The Authors. Published by Nature Publishing Group. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/cddis.2017.176Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs. Here, we report the in vitro and in vivo activity of DS in combination with copper (Cu) against CD34(+)/CD38(+) leukemia stem-like cells sorted from KG1α and Kasumi-1 AML cell lines, as well as primary CD34(+) AML samples. DS plus Cu (DS/Cu) displayed marked inhibition of proliferation, induction of apoptosis, and suppression of colony formation in cultured AML cells while sparing the normal counterparts. DS/Cu also significantly inhibited the growth of human CD34(+)/CD38(+) leukemic cell-derived xenografts in NOD/SCID mice. Mechanistically, DS/Cu-induced cytotoxicity was closely associated with activation of the stress-related ROS-JNK pathway as well as simultaneous inactivation of the pro-survival Nrf2 and nuclear factor-κB pathways. In summary, our findings indicate that DS/Cu selectively targets leukemia stem-like cells both in vitro and in vivo, thus suggesting a promising LSC-targeted activity of this repurposed agent for treatment of relapsed and refractory AML

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

INTRODUCTION: Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling. METHODS: We have measured the expression changes induced by overexpression of the BCAR1 or BCAR3 gene in ZR-75-1 cells and have made direct comparisons with the expression changes after cell stimulation with oestrogen or epidermal growth factor (EGF). A comparison with published gene expression data of cell models and breast tumours is made. RESULTS: Relatively few changes in gene expression were detected in the BCAR-transfected cells, in comparison with the extensive and distinct differences in gene expression induced by oestrogen or EGF. Both BCAR1 and BCAR3 regulate discrete sets of genes in these ZR-75-1-derived cells, indicating that the proliferation signalling proceeds along distinct pathways. Oestrogen-regulated genes in our cell model showed general concordance with reported data of cell models and gene expression association with oestrogen receptor status of breast tumours. CONCLUSIONS: The direct comparison of the expression profiles of BCAR transfectants and oestrogen or EGF-stimulated cells strongly suggests that anti-oestrogen-resistant cell proliferation is not caused by alternative activation of the oestrogen receptor or by the epidermal growth factor receptor signalling pathway

Combining host-derived biomarkers with patient characteristics improves signature performance in predicting tuberculosis treatment outcomes

CITATION: Sivakumaran, Dhanasekaran et al. 2020. Combining host-derived biomarkers with patient characteristics improves signature performance in predicting tuberculosis treatment outcomes. Communications Biology, 3(1):359, doi:10.1038/s42003-020-1087-x.The original publication is available at: https://pubmed.ncbi.nlm.nih.gov/Tuberculosis (TB) is a global health concern. Treatment is prolonged, and patients on anti-TB therapy (ATT) often experience treatment failure for various reasons. There is an urgent need to identify signatures for early detection of failure and initiation of a treatment switch.We investigated how gene biomarkers and/or basic patient characteristics could be used to define signatures for treatment outcomes in Indian adult pulmonary-TB patients treated with standard ATT. Using blood samples at baseline, a 12-gene signature combined with information on gender, previously-diagnosed TB, severe thinness, smoking and alcohol consumption was highly predictive of treatment failure at 6 months. Likewise a 4-protein biomarker signature combined with the same patient characteristics was almost as highly predictive of treatment failure. Combining biomarkers and basic patient characteristics may be useful for predicting and hence identification of treatment failure at an early stage of TB therapy.Publlisher's versio