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BackgroundMedian overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.Patients and methodsExpression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies.ResultsExpression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years.ConclusionThe OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

BackgroundRucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.MethodsIn this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0-1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.FindingsBetween April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4-22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4-6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16-0·34]; p

The influence of infection-control practices on bloodstream infection (BSI) risk was examined in a home health care setting in which three needleless devices were used consecutively. A case-control study and a retrospective cohort study were conducted. Risk factors for BSI included lower education level, younger age, having a central venous catheter (CVC) with multiple ports, or having a tunneled CVC. Among patients with a tunneled CVC, those at greatest risk had been allowed to shower rather than bathe and to get their exit site wet (P<.01). A high proportion (49%) of isolates were hydrophilic gram-negative bacteria, suggesting water sources of infection. In the cohort study, the BSI rate decreased as the frequency of changing the needleless device end cap increased from once weekly up to every 2 days, suggesting that the mechanism for BSI may involve contamination from the end cap. These findings may help to develop infection-control measures specific to home health care. Copyright © 1999 The University of Chicago [ABSTRACT FROM AUTHOR]

Abstract Background Despite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood. Results We show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. Using a xenograft model we demonstrated that cyr61/CCN1 silencing in Panc-1-SP cells reverses the stemness features and tumor initiating potency of these cells. Moreover, our results imply a miRNA-based mechanism for the regulation of aggressive behaviors of pancreatic cancer cells by Cyr61/CCN1. Conclusions In conclusion, the discovery of the involvement of Cyr61/CCN1 in pancreatic carcinogenesis may represent an important marker for PDAC and suggests Cyr61/CCN1 can be a potential cancer therapeutic target.

Abstract Background New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes and their recruitment in the tumor angiogenesis process. Results We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under in vitro conditions and recruited to bind with blood vessels on gel-foam under in vivo conditions. The degree of recruitment of pericytes into in vitro neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1) in mesenchymal stem cells. Conclusion These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.

Abstract HIV-1 Rev protein regulates the expression of HIV-1 transcripts by binding to a highly structured stem loop structure called the Rev Responsive Element (RRE) present in the genomic and partially spliced RNAs. Genetic variation in this structure is likely to affect binding of Rev protein and ultimately overall gene expression and replication. We characterized RRE sequences from 13 HIV-1 infected individuals from North India which also included two mother-child pairs following vertical transmission. We observed high degree of conservation of sequences, including the 9-nt (CACUAUGGG) long sequence in stem-loop B, required for efficient binding of Rev protein. All of our 13 RRE sequences possessed G to A (position 66) mutation located in the critical branched-stem-loop B which is not present in consensus C or B sequence. We derived a consensus RRE structure which showed interesting changes in the stem-loop structures including the stem-loop B. Mother-Child RRE sequences showed conservation of unique polymorphisms as well as some new mutations in child RRE sequences. Despite these changes, the ability to form multiple essential stem-loop structures required for Rev binding was conserved. RRE RNA derived from one of the samples, VT5, retained the ability to bind Rev protein under in vitro conditions although it showed alternate secondary structure. This is the first study from India describing the structural and possible functional implications due to very unique RRE sequence heterogeneity and its possible role in vertical transmission and gene expression.

In Georgia, children in high-risk counties are at increased risk for lead exposure. Those children and others in high-risk groups, such as families receiving Medicaid and Peach Care for Kids (i.e., health coverage for children in low-income families), are screened for blood lead levels (BLLs). Such screening, however, might not include all children at high risk for having BLLs above the reference levels (≥5 μg/dL) in the state. In our study, Bayesian methods were used to estimate the predictive density of the number of children <6 years with BLLs of 5-9 μg/dL in a targeted county from each of five selected regions of Georgia. Furthermore, the estimated mean number of children with BLLs of 5-9 μg/dL in each targeted county, along with its 95% credible interval, were calculated. The model revealed likely underreporting of some children <6 years with BLLs of 5-9 μg/dL in counties of Georgia. Further investigation might help reduce underreporting and better protect children who are at risk for lead poisoning.

This research aims to examine how the prior experiences of the chief executive officer (CEO) and board influence the focal firm's Corporate Social Responsibility (CSR) activities. Further, the present study examines how CEO overconfidence influences the diffusion of CSR activities. The authors theorize that overconfident CEOs are influenced more by the corporate strategies they experienced on other boards and less by the corporate strategies experienced by other directors. Through longitudinal analyses of the CSR profiles a sample of S&P 500 companies for the period 2006-2013, the study shows that CEO and board prior CSR experience are positively related to the firm's current CSR activities. The authors find a significant positive moderating effect of CEO overconfidence on the relationship between CEO prior CSR and the focal firm's CSR. The theory and results highlight how CEO and board prior CSR exposure may influence the focal firm's stances toward CSR and that CEO overconfidence may have differential effects on these relationships., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al-Shammari, Al-Shammari, Banerjee and Doty.)

Background: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs., Methods: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity., Results: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade., Conclusions: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs., Competing Interests: Declaration of Competing Interest SB: Institutional grants from Astrazeneca, Tesaro, GSK. Personal fees for advisory boards/lectures: Amgen, Astrazeneca, Clovis, Genmab, GSK, Immunogen, Mersana, MSD, Merck Sereno, Mersana, Oncxerna, Pfizer, Roche, Takeda, Tesaro, outside the submitted work. KS: Research funding to institution, Bayer and Amgen. Personal fees from Merck, Amgen, Servier, BMS, IPSEN, Competitive Drug Development, outside the submitted work. AC: Grants from Cancer Research UK and Astrazeneca, personal fees from AstraZeneca, GSK, Tesaro, Clovis Oncology, Eisai, outside the submitted work. RL: Personal fees from Tesaro and Roche outside the submitted work. MH: Research funding to institution Merck, BMS, Clovis Oncology. Honoraria for Advisory Boards/ Lectures: Amgen, AZ, Clovis Oncology, GSK, MSD, Roche outside the submitted work. CG: Research funding to institution: AstraZeneca, Novartis, Aprea, Nucana, Tesaro, BerGen Bio. Honorary for advisory boards/lectures: Roche, AstraZeneca, MSD, GSK, Tesaro, Nucana, Clovis, Foundation One, Sierra Oncology, Cor2Ed, Takeda. PS: Grant from University of Sydney. RE: Personal fees from Arquer Diagnostics, GSK, Clovis oncology outside submitted work. MF: personal fees from Astra Zeneca, MSD, GSK, Tesaro, Lilly, Takeda and Novartis; institutional grants from Astra Zeneca, Novartis and Beigene, other from Abbvie and ACT Genomics outside the submitted work. All other authors (MT, ROC, DM, SN, VMM, TB, JCG, PTG, OM, LA, CK, KC, LD, NB) report no disclosures of interest., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features., Experimental Design: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting., Results: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations., Conclusions: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications. See related commentary by McMullen et al., p. 5271 ., (©2020 American Association for Cancer Research.)

Sarcoma 180 (S-180) tumour cell line is a stable murine tumour cell line with 98-99% stumour takes capacity in Swiss albino mouse - Mus musculus. 2 Methoxyestradiol (2ME) - a promising anti-neoplastic and anti-angiogenic agent, showed toxicity to host body in higher concentration. Cyclophosphamide (CP), the anti-neoplastic agent has long been used as a chemotherapeutic drug for treatment of different cancers. Our studies have shown that the combination effect of 2ME and CP on S-180 tumour cell line is anti-proliferative and less toxic. The treatment with lower concentrations of 2ME and CP (6.5 mg 2ME/kg body weight + 75 mg CP/kg body weight) antagonistically increased the life span of tumour bearing mice and synergistically inhibited the viable cell population. 2ME or CP treatment individually induces G2/M arrest. The combination treatment of 2ME + CP (6.5 mg 2ME/kg body weight + 75 mg CP/kg body weight) produced a significant increase of cells in the G 0 which is the indication of cell arrest or apoptosis. Reduction of cell viability by 2ME + CP treatments is due to apoptotic cell death. This combination therapy produced a significant inhibitory effect of cell proliferation and augmentation of cell accumulation in the G 0 phase (i.e. apoptosis). Apoptosis is validated by Fluorescence staining of control and treated S-180 tumour cells with Acridine Orange and EtBr dye. Moreover, a steady increase in the frequency of complex chromosomal aberrations (i.e. tri-, qudri-radial translocations) in tumour cells was noted in that particular concentration of combination therapy treated series along with the increase in dead cell frequency and tumour regression pattern. It is assumed that, these chromosomal abnormalities or damages recorded in higher frequency prevent the affected metaphases to enter into the next cell cycle through apoptosis or necrosis. This study introduces a novel combination, where this particular concentration of 2ME + CP (i.e. 6.5 mg 2ME/kg body weight + 75 mg CP/kg body weight) not only enhanced the life span of tumour bearing mouse and decreased the tumour volume antagonistically but also inhibited the viable cell population synergistically, which could serve as a potential effective regimen for cancer treatment.

The main objective of this research was to ascertain the association between organizational characteristics of local health departments (LHDs) and environmental health (EH) services rendered in the community. Data used for the analysis were collected from LHDs by the National Association of County and City Health Officials for its 2013 national profile study of LHDs. We analyzed the data during 2016. Apart from understanding basic characteristics of LHDs in the nation, we introduced new measures of these characteristics, including "EH full-time equivalents" per 100,000 population and "other revenue" (revenues from fees and fines) per capita. The association of these and other organizational characteristics with EH services were measured using likelihood ratio χ 2 and t -tests. Out of 34 EH services considered, LHDs directly provided an average of 12 different services. As many as 41% of the 34 EH services were not available in more than 10% of the communities served by LHDs. About 70% of communities received some services from organizations other than LHDs. All the available organizational characteristics of LHDs had association with some of the EH services. Although we might assume an increase in per capita expenditure could result in an increase in LHDs' direct involvement in providing EH services, we found it to be true only for five (15%) of the EH services. The variation of EH services provided in communities could be explained by a combination of factors such as fee generation, community needs, type of governance, and population size.

Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010. A total of 200 AOC patients with progressive disease were allocated to ≥1 trial each, with a total of 281 allocations. Of these, 135 (68%) patients commenced ≥1 trial (mean 1.4 [1-8]), totaling 216 allocated trials; 65 (32%) patients did not start due to deterioration resulting from rapidly progressive disease (63 patients) or patient choice (2 patients). Response Evaluation Criteria in Solid Tumours (RECIST) complete/partial responses (CR/PR) were observed in 43 (20%) of those starting trials, including those on poly(ADP-ribose) polymerase (PARP) inhibitors (18/79 [23%]), antiangiogenics (9/65 [14%]) and chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR included: fewer prior treatments, platinum-sensitive disease, CR/PR with prior therapy, (the United States-based) Eastern Cooperative Oncology Group (ECOG) performance status score, fewer metastatic sites, higher albumin and haemoglobin levels, lower white cell counts and baseline CA125 levels, germline BRCA1/2 mutations and better RMH Prognostic Score. Mean survival was 32° months for patients who achieved CR/PR. Treatments were generally well tolerated. Most patients with AOC (134/200 [67%]) received ≥1 subsequent line of therapy after phase I trials. Our data suggest that phase I trial referrals should be considered earlier in the AOC treatment pathway and before the onset of rapid disease progression particularly with the emergence of promising novel agents in the era of precision medicine., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

Biogas is a combination of methane, CO 2 , nitrogen, H 2 S and traces of few other gases. Almost any organic waste can be biologically transformed into biogas and other energy-rich organic compounds through the process of anaerobic digestion (AD) and thus helping in sustainable waste management. Although microbes are involved in each step of AD, knowledge about those microbial consortia is limited due to the lack of phylogenetic and metabolic data of predominantly unculturable microorganisms. However, culture-independent methods like PCR-based ribotyping has been successfully employed to get information about the microbial consortia involved in AD. Microbes identified have been found to belong mainly to the bacterial phyla of Proteobacteria, Chloroflexi, Firmicutes and Bacteroidetes. Among the archaeal population, the majority have been found to be methanogens (mainly unculturable), the remaining being thermophilic microbes. Thus, the AD process as a whole could be controlled by regulating the microbial consortia involved in it. Optimization in the feedstock, pH, temperature and other physical parameters would be beneficial for the microbial growth and viability and thus helpful for biogas production in AD. Besides, the biogas production is also dependent upon the activity of several key genes, ion-specific transporters and enzymes, like genes coding for methyl-CoM reductase, formylmethanofuran transferase, formate dehydrogenase present in the microbes. Fishing for these high-efficiency genes will ultimately increase the biogas production and sustain the production plant.

From 1990 to 2004, the reported rates of diarrheal disease (three or more loose stools or a greater than normal frequency in a 24-hour period) on cruise ships decreased 2.4%, from 29.2 cases per 100,000 travel days to 28.5 cases (1,2). Increased rates of acute gastroenteritis illness (diarrhea or vomiting that is associated with loose stools, bloody stools, abdominal cramps, headache, muscle aches, or fever) occurred in years that novel strains of norovirus, the most common etiologic agent in cruise ship outbreaks, emerged (3). To determine recent rates of acute gastroenteritis on cruise ships, CDC analyzed combined data for the period 2008-2014 that were submitted by cruise ships sailing in U.S. jurisdiction (defined as passenger vessels carrying ≥13 passengers and within 15 days of arriving in the United States) (4). CDC also reviewed laboratory data to ascertain the causes of acute gastroenteritis outbreaks and examined trends over time. During the study period, the rates of acute gastroenteritis per 100,000 travel days decreased among passengers from 27.2 cases in 2008 to 22.3 in 2014. Rates for crew members remained essentially unchanged (21.3 cases in 2008 and 21.6 in 2014). However, the rate of acute gastroenteritis was significantly higher in 2012 than in 2011 or 2013 for both passengers and crew members, likely related to the emergence of a novel strain of norovirus, GII.4 Sydney (5). During 2008-2014, a total of 133 cruise ship acute gastroenteritis outbreaks were reported, 95 (71%) of which had specimens available for testing. Among these, 92 (97%) were caused by norovirus, and among 80 norovirus specimens for which a genotype was identified, 59 (73.8%) were GII.4 strains. Cruise ship travelers experiencing diarrhea or vomiting should report to the ship medical center promptly so that symptoms can be assessed, proper treatment provided, and control measures implemented.

Context: A good proportion of patients with undiagnosed pleural effusion (PE) turn into malignancy over a period of time. Identification of positive biomarker may help in selecting the individuals who require close follow-up., Aims: The aims of this study were to evaluate the role of DR-70 immunoassay in suspected malignant PE., Settings and Design: We conducted a cross-sectional study among 89 patients of suspected malignant PE and 50 normal subjects (NS) were taken as control., Materials and Methods: Patients with exudative PE; who had pleural fluid lymphocyte count greater than 50% and adenosine deaminase less than 30 U/L were taken as cases. We had selected NSs among relatives of patients having normal blood chemistry and radiological investigations. Sensitivity and specificity of the test to differentiate malignant and non-malignant PE and also to identify PE with underlying malignancy was analyzed., Results: Mean value of DR-70 in NS was found to be 0.83 ± 0.273 mg/L without any significant difference between males (0.82 mg/L) and females (0.85 mg/L). Mean value of DR-70 in PE with underlying cancer was 5.03 ± 3.79 mg/L. Sensitivity (80%) and specificity (77.78%) of the test was maximum in PE with underlying cancer using cut-off value of 2 mg/L. Mean value DR-70 in malignant PE was 5.18 ± 3.75 mg/L and in non-malignant PE was 3.73 ± 3.74 mg/L without any statistically significant difference (P = 0.08)., Conclusions: DR-70 assay has high sensitivity in detecting underlying lung cancer, but has no role in differentiating malignant PE from non-malignant PE.

Context: Hyponatraemia is one of the common electrolytic disorders which are associated with lung cancer. Hyponatraemia may influence the ECOG performance status at presentation. Also, to the best of our knowledge, we found only limited Indian studies where the ECOG score was correlated with the serum sodium status in lung cancer patients on presentation., Aim: To assess the incidence of hyponatraemia among the patients of carcinoma of the lung before putting them into the specific treatment category for cancer and to check the effects on their ECOG performance status., Settings and Design: A cross-sectional, observational study was conducted on 116 consecutive patients of lung cancer during the period from November 2011 to October 2012., Material and Methods: The patients with a histologically proven diagnosis of lung cancer were grouped initially according to their ECOG performance statuses. The serum sodium value of each patient was measured and the hyponatraemic patients were given treatment according to the protocol. The correlation of the ECOG performance status with the serum sodium of the lung cancer patients was measured. To check for any laboratory error in serum sodium, we selected (n = 58) age, sex and socioeconomic matched control patients., Results: At presentation 44.8% of the lung cancer patients showed hyponatraemia [52/116]. The ECOG score was significantly poor in the advanced clinical stages (ECOG ≤2 Vs ECOG ≥ 3 in NSCLC cases, χ(2) =11.25, P=.0008). The ECOG performance status score at admission showed a negative correlation with the serum sodium status which was measured on admission among all the patients (Pearson correlation coefficient = - 0.186). The clinical stage of the lung cancer also showed a positive correlation with the ECOG score at admission in our study (Pearson correlation coefficient = 0.295)., Conclusion: Hyponatraemia is not an uncommon condition and it should be suspected and screened in each patient, as it may influence the ECOG performance status score, which serves as an important factor in the prognosis of lung cancer.

Endoscopic sinus surgery has developed a new era in the treatment of chronic dacryocystitis. A prospective study was conducted by taking 67 patients having epiphora. Endo DCR was performed under local anaesthesia. Post operative care was given by means of alkaline nasal douching, lacrimal sac massage and endoscopic examination on 1st, 3rd, 6th week. Success rate was found to be 95.5 % which is comparable to external DCR and with added advantages.

Objectives: We assessed changes in transit-associated walking in the United States from 2001 to 2009 and documented their importance to public health., Methods: We examined transit walk times using the National Household Travel Survey, a telephone survey administered by the US Department of Transportation to examine travel behavior in the United States., Results: People are more likely to transit walk if they are from lower income households, are non-White, and live in large urban areas with access to rail systems. Transit walkers in large urban areas with a rail system were 72% more likely to transit walk 30 minutes or more per day than were those without a rail system. From 2001 to 2009, the estimated number of transit walkers rose from 7.5 million to 9.6 million (a 28% increase); those whose transit-associated walking time was 30 minutes or more increased from approximately 2.6 million to 3.4 million (a 31% increase)., Conclusions: Transit walking contributes to meeting physical activity recommendations. Study results may contribute to transportation-related health impact assessment studies evaluating the impact of proposed transit systems on physical activity, potentially influencing transportation planning decisions.

The utility of Etest for antimicrobial susceptibility testing of Yersinia pestis was evaluated in comparison with broth microdilution and disk diffusion for eight agents. Four laboratories tested 26 diverse strains and found Etest to be reliable for testing antimicrobial agents used to treat Y. pestis, except for chloramphenicol and trimethoprim-sulfamethoxazole. Disk diffusion testing is not recommended.

Objective: To identify risk factors for polymicrobial bloodstream infections (BSIs) in pediatric bone marrow transplant (BMT) outpatients attending a newly constructed clinic affiliated with a children's hospital., Methods: All 30 outpatients treated at a new BMT clinic during September 10-21, 2007, were enrolled in a cohort study. The investigation included interviews, medical records review, observations, and bacterial culture and molecular typing of patient and environmental isolates. Data were analyzed using exact conditional logistic regression., Results: Thirteen patients experienced BSIs caused by 16 different, predominantly gram-negative organisms. Presence of a tunneled catheter (odds ratio [OR], 19.9 [95% confidence interval {CI}, 2.4-infinity), catheter access (OR, 13.7 [95% CI, 1.8-infinity]), and flushing of a catheter with predrawn saline (OR, 12.9 [95% CI, 1.0-766.0]) were independently associated with BSI. The odds of experiencing a BSI increased by a factor of 16.8 with each additional injection of predrawn saline (95% CI, 1.8-827.0). Although no environmental source of pathogens was identified, interviews revealed breaches in recommended infection prevention practice and medication handling. Saline flush solutions were predrawn, and multiple doses were obtained from single-dose preservative-free vials to avoid delays in patient care., Conclusion: We speculate that infection prevention challenges in the new clinic, combined with successive needle punctures of vials, facilitated extrinsic contamination and transmission of healthcare-associated pathogens. We recommend that preservative-free single-use vials not be punctured more than once. Use of single-use prefilled saline syringes might prevent multiuse of single-use saline vials. Storage of saline outside a medication supply system might be advisable. Before opening new clinic facilities, hospitals should consider conducting a mock patient flow exercise to identify infection control challenges.

Surveillance for health care-associated infections (HAIs) using administrative data has received attention from health care epidemiologists searching for efficient means to track infections in their institutions. Several states are also considering electronic surveillance that incorporates administrative data as a means to satisfy an increasing demand for mandatory public reporting of HAIs. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis codes have attributes that make them suitable for detecting HAIs; for example, they may facilitate automated surveillance, freeing up infection control personnel to perform other important tasks, such as staff education and outbreak investigation. However, controversy surrounds the appropriate use of ICD-9-CM data in detecting HAIs, and administrative coding data have been criticized for lacking elements necessary for surveillance. Administrative coding data are inappropriate as the sole means of HAI surveillance but may have value to the health care epidemiologist as a way to augment traditional methods.

Mycobacterium avium complex (MAC) and rapidly growing mycobacteria (RGM) such as M. abscessus, M. mucogenicum, M. chelonae, and M. fortuitum, implicated in health care-associated infections, are often isolated from potable water supplies as part of the microbial flora. To understand factors that influence growth in their environmental source, clinical RGM and slowly growing MAC isolates were grown as biofilm in a laboratory batch system. High and low nutrient levels were compared, as well as stainless steel and polycarbonate surfaces. Biofilm growth was measured after 72 h of incubation by enumeration of bacteria from disrupted biofilms and by direct quantitative image analysis of biofilm microcolony structure. RGM biofilm development was influenced more by nutrient level than by substrate material, though both affected biofilm growth for most of the isolates tested. Microcolony structure revealed that RGM develop several different biofilm structures under high-nutrient growth conditions, including pillars of various shapes (M. abscessus and M. fortuitum) and extensive cording (M. abscessus and M. chelonae). Although it is a slowly growing species in the laboratory, a clinical isolate of M. avium developed more culturable biofilm in potable water in 72 h than any of the 10 RGM examined. This indicates that M. avium is better adapted for growth in potable water systems than in laboratory incubation conditions and suggests some advantage that MAC has over RGM in low-nutrient environments.

This article has been retracted.

Pleurodesis is considered as the best palliative therapy for the treatment of symptomatic malignant pleural effusion. Several chemical agents are used for this purpose with variable efficacy and safety. The present study is to compare the effectiveness and safety of talc and povidone iodine as chemical agents for pleurodesis in patients of malignant pleural effusion. Fifty-two patients with malignant pleural effusion admitted in the department of chest of Calcutta National Medical College, Kolkata were selected for the study. Pleurodesis with povidone iodine and talc in slurry was done in 28 and 24 patients respectively. Efficacy and safety of these agents were assessed during a follow-up period of six months. Among the 52 patients, 42 were males and 10 females. Age ranged from 40 to 64 years with mean age of 56.4 years. In 41 patients effusion was secondary to bronchogemic carcinoma, 8 had effusion secondary to breast carcinoma, 1 had effusion due to non-Hodgkin's lymphoma, while primary malignancy was unknown in 2 patients. Among the 24 patients treated with talc pleurodesis, 20 had bronchogenic carcinoma, 3 had breast carcinoma and 1 had unknown primary malignancy. Out of the 28 patients treated with povidone iodine pleurodesis, bronchogenic carcinoma was present in 21 patients, breast carcinoma in 5 patients, non-Hodgkin's lymphoma and unknown primary malignancy was present in 1 patient each. Pleurodesis with talc showed complete success in 19 patients, partial success in 3 patients and failure in 2 patients. Pleurodesis with povidone iodine showed complete response in 24 patients, partial response in 1 patient and failure in 3 patients. Chest pain occurred in 4 patients of talc pleurodesis and 5 patients of povidone iodine pleurodesis, 3 patients of each group had fever. There was no death in the peripleurodesis period. During the 6 months follow-up, 12 patients of talc pleurodesis and 18 patients of povidone iodine pleurodesis died. Talc is slurry and povidone iodine is equally effective and safe pleurodesing agent for symptomatic malignant pleural effusion. However povidone iodine can be preferred option because of easy availability and low cost.

Objective: To determine the timing of community-onset Clostridium difficile-associated disease (CDAD) relative to the patient's last healthcare facility discharge, the association of postdischarge cases with healthcare facility-onset cases, and the influence of postdischarge cases on overall rates and interhospital comparison of rates of CDAD., Design: Retrospective cohort study for the period January 1, 2005, through December 31, 2005., Setting: Catchment areas of 6 acute care hospitals in North Carolina., Methods: We reviewed medical and laboratory records to determine the date of symptom onset, the dates of hospitalization, and stool C. difficile toxin assay results for patients with CDAD who had diarrhea and positive toxin-assay results. Cases were classified as healthcare facility-onset if they were diagnosed more than 48 hours after admission. Cases were defined as community-onset if they were diagnosed in the community or within 48 hours after admission, and were also classified on the basis of the time since the last discharge: if within 4 weeks, community-onset, healthcare facility-associated (CO-HCFA); if 4-12 weeks, indeterminate exposure; and if more than 12 weeks, community-associated. Pearson's correlation coefficient was used to assess the association between monthly rates of healthcare facility-onset, healthcare facility-associated (HO-HCFA) cases and CO-HCFA cases. We performed interhospital rate comparisons using HO-HCFA cases only and using both HO-HCFA and CO-HCFA cases., Results: Of 1046 CDAD cases, 442 (42%) were HO-HCFA cases and 604 (58%) were community-onset cases. Of the 604 community-onset cases, 94 (15%) were CO-HCFA, 40 (7%) were of indeterminate exposure, and 208 (34%) community-associated. A modest correlation was found between monthly rates of HO-HCFA cases and CO-HCFA cases across the 6 hospitals (r = 0.63, P < .001). Interhospital rankings changed for 6 of 11 months if CO-HCFA cases were included., Conclusions: A substantial proportion of community-onset cases of CDAD occur less than 4 weeks after discharge from a healthcare facility, and inclusion of CO-HCFA cases influences interhospital comparisons. Our findings support the use of a proposed definition of healthcare facility-associated CDAD that includes cases that occur within 4 weeks after discharge.

Objective: To compare the cumulative incidence of infections acquired in the pediatric intensive care unit (PICU) and neonatal intensive care unit (NICU)., Design: Estimation of the cumulative incidence of infections with data obtained from the Pediatric Prevention Network (PPN) point-prevalence survey and observed rates from the National Nosocomial Infections Surveillance (NNIS) system., Setting: Ten hospitals participated in both the PPN survey and NNIS system., Participants: All patients present on the PPN survey dates (August 4, 1999, or February 1, 2000) in the NICUs or PICUs of the PPN hospitals were included in the survey. Point prevalences for PICU-acquired and for NICU-acquired infections at these hospitals were calculated from the survey data. The cumulative incidence rates were estimated from the point prevalence rates using a standard formula and a standard method for calculating the time to recovery (ie, on the basis of the assumption that discontinuance of antimicrobial therapy indicates recovery from infection); alternate methods to judge the time to recovery from infection were also explored., Results: The average cumulative incidence of intensive care unit-acquired infection for NICUs and PICUs combined (all units), as measured by NNIS, was 14.1 cases per 100 patients; in comparison, the prevalence was 14.06 cases for 100 patients (median difference, -0.95 cases per 100 patients; 95% confidence interval, -4.6 to 5.0 cases per 100 patients), and the estimated cumulative incidence using the standard method of calculating the time to recovery was 13.8 cases per 100 patients (median difference, -1.5 cases per 100 patients; 95% confidence interval, -9.1 to 2.9 cases per 100 patients). Estimates of cumulative incidence using alternate methods for calculation of time to recovery did not perform as well (range, 4.9-100.9 cases per 100 patients). The average incidence density for all units, as measured by the NNIS system, was 6.8 cases per 1,000 patient-days, and the estimate of incidence density using the standard method of calculating the time to recovery was 3.6 cases per 1,000 patient-days (median difference, 4.3 cases per 1,000 patient-days; 95% confidence interval, 0.9 to 9.2 cases per 1,000 patient-days). Estimated incidence densities using alternate methods for determining recovery time correlated closely with observed incidence densities., Conclusions: In this patient population, the simple point prevalence provided the best estimate of cumulative incidence, followed by use of a standard formula and a standard method of calculating the time to recovery. Estimation of incidence density using alternate methods performed well. The standard formula and method may provide an even better estimate of cumulative incidence than does simple prevalence in general populations.

Gatifloxacin is a broad spectrum fluoroquinolone that offers enhanced Gram-positive activity and anaerobic coverage to other fluoroquinolones. The pharmacokinetic parameters (Cmax, AUCo-t, tmax) of this drug have been evaluated to compare the single dose (400mg) bioavailability of gatifloxacin with the reference formulation. High performance liquid chromatography (HPLC) coupled with U-V detector set at 290 nm has been used to determine plasma concentration of 12 human volunteers as per DCGI (Drug Controller General of India) guidelines. The method has been validated over a linear range of 0.25 to 8 microg/ml from plasma. The minimum quantifiable concentration has been set at 0.25 microg/ml (% CV < 10%). The pharmacokinetic parameters are: Cmax = 4.366 +/- 0.44 microg/ml at tmax = 1.83 +/- 0.44 hour, AUCO0-t = 25.26 +/- 2.91 microg hour/ml, AUCo-inf = 33.68 +/- 4.31 microg hour/ml, Kel = 0.094 +/- 0.024/hour and t1/2 = 8.0 +/- 1.92 hour.

Four swab materials were evaluated for their efficiency in recovery of Bacillus anthracis spores from steel coupons. Cotton, macrofoam, polyester, and rayon swabs were used to sample coupons inoculated with a spore suspension of known concentration. Three methods of processing for the removal of spores from the swabs (vortexing, sonication, or minimal agitation) and two swab preparations (premoistened and dry) were evaluated. Results indicated that premoistened swabs were more efficient at recovering spores than dry swabs (14.3% vs. 4.4%). Vortexing swabs for 2 min during processing resulted in superior extraction of spores when compared to sonicating them for 12 min or subjecting them to minimal agitation. Premoistened macrofoam and cotton swabs that were vortexed during processing recovered the greatest proportions of spores with a mean recovery of 43.6% (standard deviation [SD] 11.1%) and 41.7% (SD 14.6%), respectively. Premoistened and vortexed polyester and rayon swabs were less efficient, at 9.9% (SD 3.8%) and 11.5% (SD 7.9%), respectively.

We reviewed Clostridium difficile-associated disease (CDAD) data from the intensive care unit (ICU) and hospital-wide surveillance components of the National Nosocomial Infections Surveillance System hospitals during 1987-2001. ICU CDAD rates increased significantly only in hospitals with >500 beds (P<.01) and correlated with the duration of ICU stay (r=0.82; P<.05). Hospital-wide (non-ICU) rates increased only in hospitals with <250 beds (P<.01) and in general medicine patients versus surgery patients (P<.0001). CDAD predominated in general hospitals versus other facility types, and rates were significantly higher during winter versus nonwinter months (P<.01). Thus, prevention efforts should be targeted to high-risk groups in these settings.

The newly developed proton pump inhibitor rabeprazole sodium is expected to have beneficial effects in the treatment of peptic ulcer. The pharmacokinetic parameters (C(max), AUC(o-t), t(max)) of this drug have been evaluated to compare the single dose (20 mg) bioavailability of rabeprazole sodium with the standard reference. High performance liquid chromatography (HPLC) coupled with UV detector set at 280 nm has been used to determine plasma concentration of 12 human volunteers as per Drugs Controller General of India (DCGI) guidelines. The method has been validated over a linear range of 20-480 ng/ml from plasma. The minimum quantifiable concentration was set at 10 ng/ml [co-efficient of variance (CV) < 10%]. By comparing AUC(o-t) the relative bioavailability of test preparation has been found to be 100.88% of that of reference preparation.

2-Methoxyestradiol (2-ME2) was reported to elicit both stimulation and inhibition of tumor angiogenesis and growth depending on the dosage used. However, the mechanism(s) of the biphasic action of 2-ME2 has been elusive. Here we describe a regulatory role of vascular endothelial growth factor-A (VEGF-A) in the biphasic effects on estrogen receptor (ER)+ GH3 rat pituitary tumor cells and MCF-7 human breast tumor cells depending on the dosage of 2-ME2 used. We observed that acute exposure to 2-ME2, irrespective of dosage, did not alter cellular proliferation, but enhanced the VEGF-A mRNA level. As the treatment duration increased, biphasic effect was elicited. A concentration of 1 microM 2-ME2 increased both cell proliferation and VEGF-A levels in these cells, whereas higher doses exhibited reversed impact. A low dose of 2-ME2 also increased the VEGF-A mRNA expression in ER-alpha-transfected human mammary epithelial cells (HMECs). The effect was reversed in ER- cells. The enhanced expression of VEGF-A mRNA could be blocked by the pure estrogen antagonist, ICI 182,780, and reveal that the upregulation of VEGF-A expression by 2-ME2 is mediated through ER-alpha. Furthermore, the biphasic effect of 2-ME2 on cell proliferation can be modulated by administrating VEGF-A antibodies or VEGF-A proteins. Studies also demonstrate that the VEGF-A protein, induced by 2-ME2, is functionally active and upregulates the proliferation of adjacent endothelial cells.

A convenient, sensitive and simple method for the determination of rofecoxib in human plasma is presented. The analytical technique is based on reversed phase high performance liquid chromatography coupled with UV detector (Knauer, Germany) set at 272 nm. The retention time of rofecoxib after recovery from plasma, was 8.9 minutes. The method has been validated over a linear range of 50-450 ng/ml from plasma. After validation the method was used to study the pharmacokinetic profile of rofecoxib in 6 healthy volunteers as per DCGI guidelines after administration of a single oral dose (50 mg). The extraction efficiency from plasma varied from 93.95-99.58%. The minimum quantifiable concentration was set at 50 ng/ml (% CV < 10%). The pharmacokinetic parameters were Cmax = 318.58 +/- 30.65 ng/ml at tmax = 2.66 +/- 0.25 hours, AUC0-t = 4007.88 +/- 438.32 ng hour/ml, AUC0-yen = 5454.66 +/- 822.29 ng hour/ml, Kel = 0.0433 +/- 0.0067/hour, and t1/2 = 16.36 +/- 2.89 hours.

Computer-assisted analysis of pulsed-field gel electrophoresis (PFGE) libraries can facilitate comparisons of fragment patterns present on multiple gels. We evaluated the ability of the Advanced Analysis (version 4.01) and Database (version 1.12) modules of the Phoretix gel analysis software package (Nonlinear USA, Inc., Durham, N.C.) to accurately match DNA fragment patterns. Two gels containing 38 lanes of SmaI-digested Enterococcus faecalis OG1RF DNA were analyzed to assess the impact of (i) varying the lane position of the standards, (ii) using gel plugs made at different times, and (iii) normalizing the fragment patterns by using molecular weight (MW) algorithms versus retardation factor (R(f)) algorithms. Two sets of PFGE libraries (one containing SmaI restriction patterns from 62 Enterococcus faecium isolates and the other containing SmaI restriction patterns of 89 Staphylococcus aureus isolates) were analyzed to assess the impact of varying the matching tolerance algorithm (designated as the vector box setting [VBS]) in the Phoretix software. Varying the lane position of standards on a gel and using gel plugs made on different days resulted in different VBSs, although it was not possible to judge whether those differences were statistically significant. Normalization of E. faecalis OG1RF fragment patterns by R(f) and MW methodology yielded no statistically significant differences in variability between the same fragment on different lanes. Suboptimal VBSs decreased the specificity with which related isolates were grouped together in dendrograms. The optimal VBS for analysis of PFGE fragment patterns from E. faecalis isolates differed from that for S. aureus isolates and sometimes was not that recommended by the manufacturer. Thus, computer-assisted analysis of PFGE patterns seemed to compensate for the intra- and intergel variation evaluated in the present study, and optimizing the software for the species to be tested was a critical preliminary step before further PFGE library analysis.

The survival of two strains of Yersinia pestis (avirulent A1122 and virulent Harbin) on the surfaces of four materials was investigated. Viability was evaluated with epifluorescence microscopy by using the metabolic stain cyanoditolyl tetrazolium chloride and plate counts. Small numbers of cells suspended in phosphate buffer survived 2 to 4 h after visible drying on stainless steel, polyethylene, or glass and beyond 48 h on paper. Cells suspended in brain heart infusion broth (BHI) persisted more than 72 h on stainless steel, polyethylene, and glass. Small numbers of cells suspended in BHI were still viable at 120 h on paper. These data suggest that Y. pestis maintains viability for extended periods (last measured at 5 days) under controlled conditions.

A cross-sectional survey was conducted upon 500 respondents, comprising of 250 adults and 250 children who did consume antibiotics in the previous three months. Data were analysed to determine the patterns of utilisation, compliance and awareness regarding antibiotic medication amongst a selected urban population at Kolkata. Antibiotic consumption without prescription was evident amongst 41.2% of adults in comparison to that of 8.4% in children (P < 0.01). Compliance to daily dosage was observed in 40.8% of adults in comparison to 82.8% in children (P < 0.01). Awareness pattern regarding antibiotics were reported to have been more in the children group (16.4%) while compared to the adults (8%). The knowledge regarding antibiotic resistance remained more or less similar in both the groups. The study concludes that high over the counter (OTC) sale and inadequate compliance to antibitotic medication needs further intervention approach towards information, education and communication (IEC) to all concerned.