108 research outputs found
Mesonic Excitations of QGP: Study with an Effective Model
We study the correlations between quark-antiquark pairs in different quantum
number channels in a deconfined plasma by using an effective model of QCD.
Using the three flavour PNJL model, the finite temperature spectral functions
for different mesonic states are studied at zero and nonzero quark chemical
potentials. It is found that in the channel resonance structures survive
above the chiral transition temperature \tc, while the kaonic states seem to
get washed off just above \tc. The sensitivity of the structures to the
anomaly term are carefully investigated.Comment: 15page
Drug utilization pattern in out-patients with respiratory tract infections in a rural teaching hospital: a prospective observational study
Background: Respiratory tract infections are common clinical problems in the general population. Antimicrobials are the mainstay in the management and irrational use of them may increase resistance to bacteria and the total cost of treatment. Objectives: To evaluate the pattern of drug prescriptions for respiratory tract infections in Medicine and Pediatric outpatient departments of a rural teaching hospital.Methods: Over a period of 18 months, 391 prescriptions of outpatients with respiratory tract infection were collected. The drugs prescribed, their dose and duration of treatment were recorded. DU 90% was calculated.Results: The mean (±SEM) age of the patients was38.55±0.9 years and there were 204 (52.1%) men and 187 (42.1%) women. The most common disorder among the patients was acute rhinitis (61.1%) while the least common was acute bronchitis (1.3%). Microbial culture and sensitivity was done in 23 patients and Klebsiella pneumonia (8.2%) and enterococcus (0.07%) was the most common and least common organism respectively. Penicillins (50.9%), cephalosporins (26.7%), antitubercular drugs (8.5%), macrolides (4.8) constituted DU 90%. Monotherapy was advocated in 91.7% and multidrug therapy in 8.3% of patients. The average number of antimicrobials prescribed per prescription was 0.52. Two thirds (67.6%) of the prescribed drugs were from the national list of essential medicines 2011 (NLEM).Conclusions: Penicillins and cephalosporins were the commonly used antibiotics for respiratory tract infection in outpatients of a rural teaching hospital and two thirds of the prescribed drugs were essential medicines
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Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice.
Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. Tumor relapse following chemotherapy treatment has long been a significant challenge towards completely curing cancer. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to relapse following drug treatment in advanced bladder cancer. Transcriptomic profiling of bladder cancer xenograft tumors by RNA-sequencing analysis, before and after relapse, following a 21-day cisplatin/gemcitabine drug treatment regimen identified methionine adenosyltransferase 1a (MAT1A) as one of the significantly upregulated genes following drug treatment. Survey of patient tumor sections confirmed elevated levels of MAT1A in individuals who received chemotherapy. Overexpression of MAT1A in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting MAT1A upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy
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XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies.
Treatment options for high grade urothelial cancers are limited and have remained largely unchanged for several decades. Selinexor (KPT-330), a first in class small molecule that inhibits the nuclear export protein XPO1, has shown efficacy as a single agent treatment for numerous different malignancies, but its efficacy in limiting bladder malignancies has not been tested. In this study we assessed selinexor-dependent cytotoxicity in several bladder tumor cells and report that selinexor effectively reduced XPO1 expression and limited cell viability in a dose dependent manner. The decrease in cell viability was due to an induction of apoptosis and cell cycle arrest. These results were recapitulated in in vivo studies where selinexor decreased tumor growth. Tumors treated with selinexor expressed lower levels of XPO1, cyclin A, cyclin B, and CDK2 and increased levels of RB and CDK inhibitor p27, a result that is consistent with growth arrest. Cells expressing wildtype RB, a potent tumor suppressor that promotes growth arrest and apoptosis, were most susceptible to selinexor. Cell fractionation and immunofluorescence studies showed that selinexor treatment increased nuclear RB levels and mechanistic studies revealed that RB ablation curtailed the response to the drug. Conversely, limiting CDK4/6 dependent RB phosphorylation by palbociclib was additive with selinexor in reducing bladder tumor cell viability, confirming that RB activity has a role in the response to XPO1 inhibition. These results provide a rationale for XPO1 inhibition as a novel strategy for the treatment of bladder malignancies
Radiative contribution to neutrino masses and mixing in SSM
In an extension of the minimal supersymmetric standard model (popularly known
as the SSM), three right handed neutrino superfields are introduced to
solve the -problem and to accommodate the non-vanishing neutrino masses
and mixing. Neutrino masses at the tree level are generated through parity
violation and seesaw mechanism. We have analyzed the full effect of one-loop
contributions to the neutrino mass matrix. We show that the current three
flavour global neutrino data can be accommodated in the SSM, for both
the tree level and one-loop corrected analyses. We find that it is relatively
easier to accommodate the normal hierarchical mass pattern compared to the
inverted hierarchical or quasi-degenerate case, when one-loop corrections are
included.Comment: 51 pages, 14 figures (58 .eps files), expanded introduction, other
minor changes, references adde
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology
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Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology
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