Detection and molecular characterization of vancomycin resistant Staphylococcus aureus from clinical isolates

Until now, few strains of vancomycin resistant Staphylococcus aureus (VRSA) have been reported worldwide. The disk diffusion method for determination of vancomycin sensitivity frequently misclassifies intermediately susceptible isolates to fully susceptible. However, non-automated minimum inhibitory concentration (MIC) detection methods are the gold standards. In the present study, 439 Gram positive clinical isolates were collected. Among them, 220 Staphylococcus aureus were identified. Multiplex polymerase chain reaction (PCR) detection method for vancomycin resistant S. aureus (VRSA) was developed for detection of both vanA gene (for vancomycin resistance) and nuc gene (specific for S. aureus) in a single step PCR compared to conventional non-automated disc diffusion and MIC detection methods. Molecular typing of VRSA isolates was performed using randomly amplified polymorphic (RAPD) DNA assay technique. The results show 10 VRSA isolates detected by disc diffusion method and MIC determination. Five out of them harbored vanA gene that were detected by multiplex PCR and most of them showed low clonal diversity.Key words: Molecular characterization, multiplex polymerase chain reaction (PCR), vancomycin resistant Staphylococcus aureus (VRSA), vanA gene, nuc gene, randomly amplified polymorphic DNA (RAPD) assay technique

In Utero p,p′-DDE Exposure and Infant Neurodevelopment: A Perinatal Cohort in Mexico

BACKGROUND: Evidence suggests that p,p′-dichlorodiphenyldichloroethene (DDE) affects neurodevelopment in infants, although a critical exposure window has not yet been identified. OBJECTIVES: Our goal was to assess the prenatal DDE exposure window and its effect on the psychomotor development index (PDI) and mental development index (MDI) during the first year of life. METHODS: We recruited 244 children whose pregnancies and deliveries were uncomplicated, and whose mothers were monitored throughout the pregnancy. Participating mothers were not occupationally exposed to DDT (dichlorodiphenyltrichloroethane) but were residents of a zone in Mexico with endemic malaria. We measured serum levels of DDE before pregnancy and during each trimester of the pregnancy. We evaluated PDI and MDI of the Bayley Scales for Infant Development (BSID-II), at 1, 3, 6, and 12 months of age. We adjusted for quality of the home environment and maternal intellectual coefficient (IQ). We used generalized mixed-effects models for statistical analysis. RESULTS: Third-trimester DDE level (7.8 ± 2.8 ppb) was significantly higher than the level at baseline, first, and second trimesters, but the differences never exceeded 20%. Only DDE levels during the first trimester of pregnancy were associated with a significant reduction in PDI (every doubled increase of DDE level reduced the PDI 0.5 points). DDE was not associated with MDI. CONCLUSIONS: A critical window of exposure to DDE in utero may be the first trimester of the pregnancy, and psychomotor development is a target of this compound. Residues of DDT metabolites may present a risk of developmental delay for years after termination of DDT use

Requirement Text Detection from Contract Packages to Support Project Definition Determination

Project requirements are wishes and expectations of the client toward the design, construction, and other project management processes. The project definition is typically specified in a contract package including a contract document and many other related documents such as drawings, specifications, and government codes. Project definition determination is critical to the success of a project. Due to the lack of efficient tools for requirement processing, the current practices regarding project scoping still heavily rely on a manual basis which is tedious, time-consuming, and error-prone. This study aims to fill that gap by developing an automated method for identifying requirement texts from contractual documents. The study employed Naïve Bayes to train a classification model that can be used to separate requirement statements from non-requirement statements. An experiment was conducted on a manually labeled dataset of 1191 statements. The results revealed that the developed requirement detection model achieves a promising accuracy of over 90%

Improving obstetric care in low-resource settings: implementation of facility-based maternal death reviews in five pilot hospitals in Senegal

<p>Abstract</p> <p>Background</p> <p>In sub-Saharan Africa, maternal and perinatal mortality and morbidity are major problems. Service availability and quality of care in health facilities are heterogeneous and most often inadequate. In resource-poor settings, the facility-based maternal death review or audit is one of the most promising strategies to improve health service performance. We aim to explore and describe health workers' perceptions of facility-based maternal death reviews and to identify barriers to and facilitators of the implementation of this approach in pilot health facilities of Senegal.</p> <p>Methods</p> <p>This study was conducted in five reference hospitals in Senegal with different characteristics. Data were collected from focus group discussions, participant observations of audit meetings, audit documents and interviews with the staff of the maternity unit. Data were analysed by means of both quantitative and qualitative approaches.</p> <p>Results</p> <p>Health professionals and service administrators were receptive and adhered relatively well to the process and the results of the audits, although some considered the situation destabilizing or even threatening. The main barriers to the implementation of maternal deaths reviews were: (1) bad quality of information in medical files; (2) non-participation of the head of department in the audit meetings; (3) lack of feedback to the staff who did not attend the audit meetings. The main facilitators were: (1) high level of professional qualifications or experience of the data collector; (2) involvement of the head of the maternity unit, acting as a moderator during the audit meetings; (3) participation of managers in the audit session to plan appropriate and realistic actions to prevent other maternal deaths.</p> <p>Conclusion</p> <p>The identification of the barriers to and the facilitators of the implementation of maternal death reviews is an essential step for the future adaptation of this method in countries with few resources. We recommend for future implementation of this method a prior enhancement of the perinatal information system and initial training of the members of the audit committee – particularly the data collector and the head of the maternity unit. Local leadership is essential to promote, initiate and monitor the audit process in the health facilities.</p

QUARITE (quality of care, risk management and technology in obstetrics): a cluster-randomized trial of a multifaceted intervention to improve emergency obstetric care in Senegal and Mali

<p>Abstract</p> <p>Background</p> <p>Maternal and perinatal mortality are major problems for which progress in sub-Saharan Africa has been inadequate, even though childbirth services are available, even in the poorest countries. Reducing them is the aim of two of the main Millennium Development Goals. Many initiatives have been undertaken to remedy this situation, such as the Advances in Labour and Risk Management (ALARM) International Program, whose purpose is to improve the quality of obstetric services in low-income countries. However, few interventions have been evaluated, in this context, using rigorous methods for analyzing effectiveness in terms of health outcomes. The objective of this trial is to evaluate the effectiveness of the ALARM International Program (AIP) in reducing maternal mortality in referral hospitals in Senegal and Mali. Secondary goals include evaluation of the relationships between effectiveness and resource availability, service organization, medical practices, and satisfaction among health personnel.</p> <p>Methods/Design</p> <p>This is an international, multi-centre, controlled cluster-randomized trial of a complex intervention. The intervention is based on the concept of evidence-based practice and on a combination of two approaches aimed at improving the performance of health personnel: 1) Educational outreach visits; and 2) the implementation of facility-based maternal death reviews.</p> <p>The unit of intervention is the public health facility equipped with a functional operating room. On the basis of consent provided by hospital authorities, 46 centres out of 49 eligible were selected in Mali and Senegal. Using randomization stratified by country and by level of care, 23 centres will be allocated to the intervention group and 23 to the control group. The intervention will last two years. It will be preceded by a pre-intervention one-year period for baseline data collection. A continuous clinical data collection system has been set up in all participating centres. This, along with the inventory of resources and the satisfaction surveys administered to the health personnel, will allow us to measure results before, during, and after the intervention. The overall rate of maternal mortality measured in hospitals during the post-intervention period (Year 4) is the primary outcome. The evaluation will also include cost-effectiveness.</p> <p>Trial Registration</p> <p>The QUARITE trial is registered on the Current Controlled Trials website under the number ISRCTN46950658 <url>http://www.controlled-trials.com/</url>.</p

The prognostic impact of anti-cancer immune response: a novel classification of cancer patients

Until now, the anatomic extent of tumor (TNM classification) has been, by far, the most important factor to predict the prognosis of colorectal cancer patients. However, in recent years, data collected from large cohorts of human cancers demonstrated that the immune contexture of the primary tumors is an essential prognostic factor for patients' disease-free and overall survival. Global analysis of tumor microenvironment showed that the nature, the functional orientation, the density, and the location of adaptive immune cells within distinct tumor regions influence the risk of relapse events. An immune classification of the patients was proposed based on the density and the immune cell location within the tumor. The immune classification has a prognostic value that is superior to the TNM classification, and tumor invasion is statistically dependent on the host immune reaction. Tumor and immunological markers predicted by systems biology methods are involved in the shaping of an efficient immune reaction and can serve as targets for novel therapeutic approaches. Thus, the strength of the immune reaction could advance our understanding of cancer evolution and have important consequences in clinical practice

Justified Concern or Exaggerated Fear: The Risk of Anaphylaxis in Percutaneous Treatment of Cystic Echinococcosis—A Systematic Literature Review

Percutaneous treatment (PT) emerged in the mid-1980s as an alternative to surgery for selected cases of abdominal cystic echinococcosis (CE). Despite its efficacy and widespread use, the puncture of echinococcal cysts is still far from being universally accepted. One of the main reasons for this reluctance is the perceived risk of anaphylaxis linked to PTs. To quantify the risk of anaphylactic reactions and lethal anaphylaxis with PT, we systematically searched MEDLINE for publications on PT of CE and reviewed the PT-related complications. After including 124 publications published between 1980 and 2010, we collected a total number of 5943 PT procedures on 5517 hepatic and non-hepatic echinococcal cysts. Overall, two cases of lethal anaphylaxis and 99 reversible anaphylactic reactions were reported. Lethal anaphylaxis occurred in 0.03% of PT procedures, corresponding to 0.04% of treated cysts, while reversible allergic reactions complicated 1.7% of PTs, corresponding to 1.8% of treated echinococcal cysts. Analysis of the literature shows that lethal anaphylaxis related to percutaneous treatment of CE is an extremely rare event and is observed no more frequently than drug-related anaphylactic side effects

CK2 Phosphorylates Sec31 and Regulates ER-To-Golgi Trafficking

Protein export from the endoplasmic reticulum (ER) is an initial and rate-limiting step of molecular trafficking and secretion. This is mediated by coat protein II (COPII)-coated vesicles, whose formation requires small GTPase Sar1 and 6 Sec proteins including Sec23 and Sec31. Sec31 is a component of the outer layer of COPII coat and has been identified as a phosphoprotein. The initiation and promotion of COPII vesicle formation is regulated by Sar1; however, the mechanism regulating the completion of COPII vesicle formation followed by vesicle release is largely unknown. Hypothesizing that the Sec31 phosphorylation may be such a mechanism, we identified phosphorylation sites in the middle linker region of Sec31. Sec31 phosphorylation appeared to decrease its association with ER membranes and Sec23. Non-phosphorylatable mutant of Sec31 stayed longer at ER exit sites and bound more strongly to Sec23. We also found that CK2 is one of the kinases responsible for Sec31 phosphorylation because CK2 knockdown decreased Sec31 phosphorylation, whereas CK2 overexpression increased Sec31 phosphorylation. Furthermore, CK2 knockdown increased affinity of Sec31 for Sec23 and inhibited ER-to-Golgi trafficking. These results suggest that Sec31 phosphorylation by CK2 controls the duration of COPII vesicle formation, which regulates ER-to-Golgi trafficking

Public health, conflict and human rights: toward a collaborative research agenda

Although epidemiology is increasingly contributing to policy debates on issues of conflict and human rights, its potential is still underutilized. As a result, this article calls for greater collaboration between public health researchers, conflict analysts and human rights monitors, with special emphasis on retrospective, population-based surveys. The article surveys relevant recent public health research, explains why collaboration is useful, and outlines possible future research scenarios, including those pertaining to the indirect and long-term consequences of conflict; human rights and security in conflict prone areas; and the link between human rights, conflict, and International Humanitarian Law

Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients

PURPOSE: Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA. EXPERIMENTAL DESIGN: Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. RESULTS: The change in regulatory T cell (CD3(+)CD4(+)CD25(+)CD127(low)) frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623) after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+)CD4(+) T cells (p = 0.0191; hazard ratio = 2.840) and CD3(+)CD8(+) T cells (p = 0.0273; hazard ratio = 2.690), while that of activation markers (CD25, CD69) was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. CONCLUSIONS: Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future prospective immunotherapy trials to further evaluate its predictive validity