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1.  Review of Institute of Medicine and National Research Council Recommendations for One Health Initiative 
Emerging Infectious Diseases  2013;19(12):1913-1917.
Human health is inextricably linked to the health of animals and the viability of ecosystems; this is a concept commonly known as One Health. Over the last 2 decades, the Institute of Medicine (IOM) and the National Research Council (NRC) have published consensus reports and workshop summaries addressing a variety of threats to animal, human, and ecosystem health. We reviewed a selection of these publications and identified recommendations from NRC and IOM/NRC consensus reports and from opinions expressed in workshop summaries that are relevant to implementation of the One Health paradigm shift. We grouped these recommendations and opinions into thematic categories to determine if sufficient attention has been given to various aspects of One Health. We conclude that although One Health themes have been included throughout numerous IOM and NRC publications, identified gaps remain that may warrant targeted studies related to the One Health approach.
PMCID: PMC3840875  PMID: 24274461
zoonoses; animal diseases; veterinary medicine; public health; environmental medicine; vectors; disease reservoirs; medicine; world health
2.  Multidrug Resistance in Salmonella enterica Serotype Typhimurium from Humans in France (1993 to 2003) 
Journal of Clinical Microbiology  2006;44(3):700-708.
The aim of this study was to determine the distribution of the antimicrobial resistance phenotypes (R types), the phage types and XbaI-pulsed-field gel electrophoresis (PFGE) types, the genes coding for resistance to β-lactams and to quinolones, and the class 1 integrons among a representative sample of Salmonella enterica serotype Typhimurium isolates collected from humans in 2002 through the French National Reference Center for Salmonella (NRC-Salm) network. The trends in the evolution of antimicrobial resistance of serotype Typhimurium were reviewed by using NRC-Salm data from 1993, 1997, 2000, and 2003. In 2002, 3,998 isolates of serotype Typhimurium were registered at the NRC-Salm among 11,775 serotyped S. enterica isolates (34%). The most common multiple antibiotic resistance pattern was resistance to amoxicillin, chloramphenicol, streptomycin and spectinomycin, sulfonamides, and tetracycline (ACSSpSuTe R type), with 156 isolates (48.8%). One isolate resistant to extended-spectrum cephalosporins due to the production of TEM-52 extended-spectrum β-lactamase was detected (0.3%), and one multidrug-resistant isolate was highly resistant to ciprofloxacin (MIC > 32 mg/liter). We found that 57.2% of the isolates tested belonged to the DT104 clone. The main resistance pattern of DT104 isolates was R type ACSSpSuTe (83.2%). However, evolutionary changes have occurred within DT104, involving both loss (variants of Salmonella genomic island 1) and acquisition of genes for drug resistance to trimethoprim or to quinolones. PFGE profile X1 was the most prevalent (74.5%) among DT104 isolates, indicating the need to use a more discriminatory subtyping method for such isolates. Global data from the NRC-Salm suggested that DT104 was the main cause of multidrug resistance in serotype Typhimurium from humans from at least 1997 to 2003, with a roughly stable prevalence during this period.
PMCID: PMC1393144  PMID: 16517842
3.  International External Quality Assurance for Laboratory Diagnosis of Diphtheria ▿  
Journal of Clinical Microbiology  2009;47(12):4037-4042.
The diphtheria surveillance network (DIPNET) encompassing National Diphtheria Reference Centers from 25 European countries is a Dedicated Surveillance Network recognized by the European Commission. A key DIPNET objective is the quality assessment of microbiological procedures for diphtheria across the European Union and beyond. A detailed questionnaire on the level of reference laboratory services and an external quality assessment (EQA) panel comprising six simulated throat specimens were sent to 34 centers. Twenty-three centers are designated National Diphtheria Reference Centers, with the laboratory in the United Kingdom being the only WHO Collaborating Centre. A variety of screening and identification tests were used, including the cysteinase test (20/34 centers), pyrazinamidase test (17/34 centers), and commercial kits (25/34 centers). The classic Elek test for toxigenicity testing is mostly used (28/34 centers), with variations in serum sources and antitoxin concentrations. Many laboratories reported problems obtaining Elek reagents or media. Only six centers produced acceptable results for all six specimens. Overall, 21% of identification and 13% of toxigenicity reports were unacceptable. Many centers could not isolate the target organism, and most found difficulties with the specimens that contained Corynebacterium striatum as a commensal contaminant. Nineteen centers generated either false-positive or negative toxigenic results, which may have caused inappropriate medical management. The discrepancies in this diphtheria diagnostics EQA alarmingly reflect the urgent need to improve laboratory performance in diphtheria diagnostics in Europe, standardize feasible and robust microbiological methods, and build awareness among public health authorities. Therefore, DIPNET recommends that regular workshops and EQA distributions for diphtheria diagnostics should be supported and maintained.
PMCID: PMC2786670  PMID: 19828749
4.  A sentinel network of microbiological laboratories as a tool for surveillance of infectious diseases in Belgium. 
Epidemiology and Infection  1991;106(2):297-303.
In the development of a surveillance programme for infectious diseases in Belgium, a national network of microbiological laboratories has been responsible, since February 1983, for the weekly registration of certain pathogenic agents. Thus, the main epidemiological features of a selected number of infections in Belgium can be characterized.
PMCID: PMC2271998  PMID: 2019299
5.  A Study to Evaluate the Effect of Nutritional Intervention Measures on Admitted Children in Selected Nutrition Rehabilitation Centers of Indore and Ujjain Divisions of the State of Madhya Pradesh (India) 
The state of Madhya Pradesh has 1.3 million severely malnourished children. Nutrition rehabilitation centers (NRCs) were started in the state to control severe malnutrition and decrease the prevalence of severe malnourished children to less than 1% among children aged 1–5 years.
Materials and Methods:
The present study was conducted from November 2008 to October 2009; 100 children admitted to seven different NRCs in Indore and Ujjain divisions of Madhya Pradesh were observed during their stay at NRCs and the follow-up period to analyze the effect of interventional measures on select anthropometric indicators. Mothers of the children were interviewed on health issues and therapeutic feeding practices at the NRCs using a predesigned and pretested interview schedule.
The study group consisted of 48 boys and 52 girls; 60% were between 13 and 36 months of age. 93 children were analyzed for anthropometric indicators following a dropout rate of 7%. A statistically significant difference was obtained between the weight of children at admission and discharge (t=14.552, P<0.001); difference of mid upper arm circumference (MUAC) at admission and discharge was statistically significant (t=9.548, P<0.001). The average weight gain during the stay at the centers was 9.25 ± 5.89 g/kg/day. Though the number of severe malnourished children decreased from 85 to 43 following the stay at NRCs (χ2 = 44.195, P<0.001); 48.78% of the children lost weight within 15 days of discharge from the NRCs. Dropout rates of 9.89%, 23.07%, 42.65%, and 61.76% for the study group were obtained during the follow-up period of 6 months for the four follow-up visits conducted 15 days, 1, 3, and 6 months after discharge. The mothers of the children lacked adequate information on health issues and composition and preparation of therapeutic diets at the centers.
The NRCs were effective in improving the condition of admitted children, but the effects were not sustained following discharge due to high drop-out rate and lack of adequate parental awareness. There is an urgent need to link these centers with community-based models for follow-up and improve health education measures to maintain the gains achieved.
PMCID: PMC3361793  PMID: 22654284
Nutrition rehabilitation centers; severe acute malnutrition; therapeutic feeds
6.  Particulate Matter (PM) Research Centers (1999–2005) and the Role of Interdisciplinary Center-Based Research 
Environmental Health Perspectives  2008;117(2):167-174.
The U.S. Environmental Protection Agency funded five academic centers in 1999 to address the uncertainties in exposure, toxicity, and health effects of airborne particulate matter (PM) identified in the “Research Priorities for Airborne Particulate Matter” of the National Research Council (NRC). The centers were structured to promote interdisciplinary approaches to address research priorities of the NRC. In this report, we present selected accomplishments from the first 6 years of the PM Centers, with a focus on the advantages afforded by the interdisciplinary, center-based research approach. The review highlights advances in the area of ultrafine particles and traffic-related health effects as well as cardiovascular and respiratory effects, mechanisms, susceptibility, and PM exposure and characterization issues.
Data sources and synthesis
The collective publications of the centers served as the data source. To provide a concise synthesis of overall findings, authors representing each of the five centers identified a limited number of topic areas that serve to illustrate the key accomplishments of the PM Centers program, and a consensus statement was developed.
The PM Centers program has effectively applied interdisciplinary research approaches to advance PM science.
PMCID: PMC2649215  PMID: 19270783
acute effects; biological mechanisms; chronic effects; criteria pollutants; dosimetry; exposure assessment; morbidity; mortality; particulate matter
7.  Do recent data from the Seychelles Islands alter the conclusions of the NRC Report on the toxicological effects of methylmercury? 
In 2000, the National Research Council (NRC), an arm of the National Academy of Sciences, released a report entitled, "Toxicological Effects of Methylmercury." The overall conclusion of that report was that, at levels of exposure in some fish- and marine mammal-consuming communities (including those in the Faroe Islands and New Zealand), subtle but significant adverse effects on neuropsychological development were occurring as a result of in utero exposure. Since the release of that report, there has been continuing discussion of the public health relevance of current levels of exposure to Methylmercury. Much of this discussion has been linked to the release of the most recent longitudinal update of the Seychelles Island study. It has recently been posited that these findings supercede those of the NRC committee, and that based on the Seychelles findings, there is little or no risk of adverse neurodevelopmental effects at current levels of exposure. In this commentary, members of the NRC committee address the conclusions from the NRC report in light of the recent Seychelles data. We conclude that no evidence has emerged since the publication of the NRC report that alters the findings of that report.
PMCID: PMC365028  PMID: 14754462
8.  The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans. 
Environmental Health Perspectives  2003;111(8):1074-1092.
In 1998 Congress mandated expanded U.S. Environmental Protection Agency (U.S. EPA) health effects research on ambient air particulate matter (PM) and a National Research Council (NRC) committee to provide research oversight. The U.S. EPA currently supports intramural and extramural PM research, including five academically based PM centers. The PM centers in their first 2.5 years have initiated research directed at critical issues identified by the NRC committee, including collaborative activities, and sponsored scientific workshops in key research areas. Through these activities, there is a better understanding of PM health effects and scientific uncertainties. Future PM centers research will focus on long-term effects associated with chronic PM exposures. This report provides a synopsis of accomplishments to date, short-term goals (during the next 2.5 years) and longer-term goals. It consists of six sections: biological mechanisms, acute effects, chronic effects, dosimetry, exposure assessment, and the specific attributes of a coordinated PM centers program.
PMCID: PMC1241556  PMID: 12826479
9.  A Discussion of Exposure Science in the 21st Century: A Vision and a Strategy 
Environmental Health Perspectives  2013;121(4):405-409.
Background: The National Research Council (NRC) of the National Academy of Sciences recently published the report Exposure Science in the 21st Century: A Vision and a Strategy. The expert committee undertaking this report included expertise from ecology, chemistry, exposure science, toxicology, public health, bioethics, engineering, medicine, and policy.
Objective: Our aim is to inform members of the scientific community in fields aligned with environmental and public health so they are more able to appreciate the full breadth of the vision and understand the framework developed in order to move the vision forward.
Discussion: Although the NRC report was commissioned by the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences, it is solely the consensus product of the independent volunteer committee, whose findings were subject to the rigorous peer-review procedures of the NRC. In addition to reviewing the history and current status of exposure science, the report lays out a vision for the future and makes recommendations that include both short-term and long-term milestones.
Conclusion: To accomplish the vision presented in the NRC report, resources will be needed to complete studies, develop and use analyses of exposure, and build databases associated with individual and population exposures, as well as to train the next generation of exposure scientists. Important excerpts as well as paraphrased statements from the report appear in this commentary; however, the general observations and comments are our own.
PMCID: PMC3620766  PMID: 23380895
eco-exposome; exposome; exposure assessment; exposure science; National Research Council
10.  Community-Driven Standards-Based Electronic Laboratory Data-Sharing Networks 
Public Health Reports  2010;125(Suppl 2):47-56.
Public health laboratories (PHLs) are critical components of the nation's health-care system, serving as stewards of valuable specimens, delivering important diagnostic results to support clinical and public health programs, supporting public health policy, and conducting research. This article discusses the need for and challenges of creating standards-based data-sharing networks across the PHL community, which led to the development of the PHL Interoperability Project (PHLIP). Launched by the Association of Public Health Laboratories and the Centers for Disease Control and Prevention in September 2006, PHLIP has leveraged a unique community-based collaborative process, catalyzing national capabilities to more effectively share electronic laboratory-generated diagnostic information and bolster the nation's health security. PHLIP is emerging as a model of accelerated innovation for the fields of laboratory science, technology, and public health.
PMCID: PMC2846802  PMID: 20521375
11.  A WWW Implementation of National Recommendations for Protecting Electronic Health Information 
In March of 1997, the National Research Council (NRC) of the National Academy of Sciences issued the report, “For the Record: Protecting Electronic Health Information.” Concluding that the current practices at the majority of health care facilities in the United States are insufficient, the Council delineated both technical and organizational approaches to protecting electronic health information. The Beth Israel Deaconess Medical Center recently implemented a proof-of-concept, Web-based, cross-institutional medical record, CareWeb, which incorporates the NRC security and confidentiality recommendations. We report on our WWW implementation of the NRC recommendations and an initial evaluation of the balance between ease of use and confidentiality.
PMCID: PMC61263  PMID: 9391933
12.  Integrated primary health care in Australia 
To fulfil its role of coordinating health care, primary health care needs to be well integrated, internally and with other health and related services. In Australia, primary health care services are divided between public and private sectors, are responsible to different levels of government and work under a variety of funding arrangements, with no overarching policy to provide a common frame of reference for their activities.
Description of policy
Over the past decade, coordination of service provision has been improved by changes to the funding of private medical and allied health services for chronic conditions, by the development in some states of voluntary networks of services and by local initiatives, although these have had little impact on coordination of planning. Integrated primary health care centres are being established nationally and in some states, but these are too recent for their impact to be assessed. Reforms being considered by the federal government include bringing primary health care under one level of government with a national primary health care policy, establishing regional organisations to coordinate health planning, trialling voluntary registration of patients with general practices and reforming funding systems. If adopted, these could greatly improve integration within primary health care.
Careful change management and realistic expectations will be needed. Also other challenges remain, in particular the need for developing a more population and community oriented primary health care.
PMCID: PMC2787230  PMID: 19956377
primary health care; health policy; integration; Australia
13.  Whether western normative laboratory values used for clinical diagnosis are applicable to Indian population? An overview on reference interval 
Reference Intervals denote normative values related to laboratory parameters/analytes used by diagnostic centers for clinical diagnosis. International guidelines recommend that every country must establish reference intervals for healthy individuals belonging to a group of homogeneous population. Considering enormous racial and ethnic diversity of Indian population, it is mandatory to establish reference intervals specific to Indian population. The overview on reference interval describes why the national organizations in India need to initiate nationwide efforts to establish its own laboratory standards for apparently healthy reference individuals belonging to our polygenetic, polyethnic, polyracial, multilinguistic and multicultural predominantly rural and appreciable urban Indian population with varied dietary habits.
PMCID: PMC3453230  PMID: 23105819
Reference Intervals; Normative Value; Indian Population
14.  Risk Factors for Methicillin Resistant Staphylococcus aureus: A Multi-Laboratory Study 
PLoS ONE  2014;9(2):e89579.
The present study aimed to investigate the dose response relationship between the prescriptions of antimicrobial agents and infection/colonization with methicillin resistant Staphylococcus aureus (MRSA) taking additional factors like stay in a health care facility into account.
Multi-centre retrospective study on a cohort of patients that underwent microbiological diagnostics in Belgium during 2005. The bacteriological results retrieved from 17 voluntary participating clinical laboratories were coupled with the individual antimicrobial consumption patterns (July 2004-December 2005) and other variables as provided by pooled data of health insurance funds. Multivariate analysis was used to identify risk factors for MRSA colonization/infection.
A total of 6844 patients of which 17.5% died in the year 2005, were included in a logistic regression model. More than 97% of MRSA was associated with infection (clinical samples), and only a minority with screening/colonization (1.59%). Factors (95% CI) significantly (p≤<0.01) associated with MRSA in the final multivariate model were: admission to a long term care settings (2.79–4.46); prescription of antibiotics via a hospital pharmacy (1.30–2.01); age 55+ years (3.32–5.63); age 15–54 years (1.23–2.16); and consumption of antimicrobial agent per DDD (defined daily dose) (1.25–1.40).
The data demonstrated a direct dose-response relationship between MRSA and consumption of antimicrobial agents at the individual patient level of 25–40% increased risk per every single day. In addition the study indicated an involvement of specific healthcare settings and age in MRSA status.
PMCID: PMC3935888  PMID: 24586887
15.  First Neisseria gonorrhoeae Genotyping Analysis in France: Identification of a Strain Cluster with Reduced Susceptibility to Ceftriaxone ▿  
Journal of Clinical Microbiology  2009;47(11):3540-3545.
Sexually transmitted infections are a major public health problem in France and other European countries. Particularly, surveillance data about Neisseria gonorrhoeae infections have clearly indicated an increase in the incidence of gonorrhoea in France in 2006. The French laboratories participated on voluntary basis in the RENAGO (Réseau National du Gonocoque) network and sent all of their collected strains to the National Reference Center for Neisseria gonorrhoeae. In this first French molecular epidemiological study, 93 isolates collected in 2006 and representative of the French gonorrhoea epidemiology were selected. Antibiotic susceptibility to six antibiotics was determined, and serotyping and N. gonorrhoeae multiantigen sequence typing (NG-MAST) were performed. NG-MAST identified 53 sequence types (STs), of which 13 STs contained 2 to 16 isolates. The major STs identified in France were previously described elsewhere. However, two newly described STs, ST1479 and ST1987, had only been found in France until now. ST1479 was characterized by a multiple-resistance phenotype, whereas ST1987 presented a susceptibility phenotype. Moreover, among the predominant French STs, ST225, which had already been described in many countries, comprised isolates (14/16) resistant to ciprofloxacin and with reduced susceptibility to ceftriaxone. Thus, the surveillance of resistance to antibiotics is a priority in order to adapt treatment and decrease the transmission of resistant strains. Of note, no predominant ST was identified among rectal isolates from men who have sex with men.
PMCID: PMC2772602  PMID: 19794054
16.  International Circumpolar Surveillance, An Arctic Network for the Surveillance of Infectious Diseases 
Emerging Infectious Diseases  2008;14(1):18-24.
Hospitals, public health agencies, and reference laboratories work together to detect and control infectious disease in Arctic regions.
Peoples of the Arctic and sub-Arctic regions live in social and physical environments that differ substantially from those of their more southern-dwelling counterparts. The cold northern climate keeps people indoors, amplifying the effects of household crowding, smoking, and inadequate ventilation on person-to-person spread of infectious disease. The emergence of antimicrobial drug resistance among bacterial pathogens, the reemergence of tuberculosis, the entrance of HIV into Arctic communities, and the specter of pandemic influenza or the sudden emergence and introduction of new viral pathogens such as severe acute respiratory syndrome are of increasing concern to residents, governments, and public health authorities. The International Circumpolar Surveillance system is a network of hospital, public health agencies, and reference laboratories throughout the Arctic linked together to collect, compare, and share uniform laboratory and epidemiologic data on infectious diseases and assist in the formulation of prevention and control strategies.
PMCID: PMC2600151  PMID: 18258072
Arctic; surveillance; infectious diseases; perspective
17.  Establishment of National Laboratory Standards in Public and Private Hospital Laboratories 
Iranian Journal of Public Health  2013;42(1):96-101.
In September 2007 national standard manual was finalized and officially announced as the minimal quality requirements for all medical laboratories in the country. Apart from auditing laboratories, Reference Health Laboratory has performed benchmarking auditing of medical laboratory network (surveys) in provinces. 12th benchmarks performed in Tehran and Alborz provinces, Iran in 2010 in three stages. We tried to compare different processes, their quality and accordance with national standard measures between public and private hospital laboratories. The assessment tool was a standardized checklist consists of 164 questions. Analyzing process show although in most cases implementing the standard requirements are more prominent in private laboratories, there is still a long way to complete fulfillment of requirements, and it takes a lot of effort. Differences between laboratories in public and private sectors especially in laboratory personnel and management process are significant. Probably lack of motivation, plays a key role in obtaining less desirable results in laboratories in public sectors.
PMCID: PMC3595627  PMID: 23514840
Standards; Hospital; Laboratory; Iran
18.  Evaluating Healthcare Information Technology Outside of Academia: Observations from the National Resource Center for Healthcare Information Technology at the Agency for Healthcare Research and Quality 
The National Resource Center for Health Information Technology (NRC) was formed in the fall of 2004 as part of the Agency for Healthcare Research and Quality (AHRQ) health IT portfolio to support its grantees. One of the core functions of the NRC was to assist grantees in their evaluation efforts of Health IT. This manuscript highlights some common challenges experienced by health IT project teams at nonacademic institutions, including inappropriately scoped and resourced evaluation efforts, inappropriate choice of metrics, inadequate planning for data collection and analysis, and lack of consideration of qualitative methodologies. Many of these challenges can be avoided or overcome. The strategies adopted by various AHRQ grantees and the lessons learned from their projects should become part of the toolset for current and future implementers of health IT as the nation moves rapidly towards its widespread adoption.
PMCID: PMC2744713  PMID: 19567800
19.  Intersubject Variability of Risk from Perchlorate in Community Water Supplies 
Environmental Health Perspectives  2006;114(7):975-979.
This article is a brief review and summary of the estimated incremental risks (increases in hazard quotient or decreases in thyroid uptake of iodine) to pregnant women (and hence their fetuses) associated with perchlorate exposure in community water supplies (CWSs). The analysis draws on the recent health effects review published in 2005 by the National Research Council (NRC). We focus on the potential level of risk borne by the NRC-identified most sensitive subpopulation (pregnant women and hence their fetuses). Other members of the population should be at a level of risk below that calculated here, and so protection of the sensitive subpopulation would protect the general public health. The analysis examines the intersubject distribution of risks to this sensitive subpopulation at various potential drinking water concentrations of perchlorate and also draws on estimates of the national occurrence of perchlorate in U.S. CWSs to estimate the variability of risks under defined regulatory scenarios. Results suggest that maximum contaminant levels (MCLs) of up to 24.5 μg/L should pose little or no incremental risk to the large majority of individuals in the most sensitive subpopulations exposed in the United States at current levels of perchlorate in water. The protectiveness of an MCL of 24.5 μg/L depends, however, on whether the study subjects in the health effects data used here may be assumed to have been exposed to background (non-drinking water) contributions of perchlorate.
PMCID: PMC1513330  PMID: 16835046
Monte Carlo analysis; perchlorate; risk; sensitive subpopulations; water
20.  MRI evaluation of neoadjuvant low-dose fractionated radiotherapy with concurrent chemotherapy in patients with locally advanced breast cancer 
The British Journal of Radiology  2012;85(1019):e995-e1103.
We address the diagnostic performance of breast MRI and the efficacy of neoadjuvant radiochemotherapy (NRC) treatment (NRC protocol) vs conventional neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer.
The NRC protocol consists of six anthracycline/taxane cycles and concomitant low-dose radiotherapy on breast tumour volume. Breast MRI was performed at baseline and after the last therapy cycle in 18 and 36 patients undergoing the NRC protocol or conventional NAC (propensity matching).
In both groups, we observed reduced tumour dimensions after the last cycle (p<0.001), and the response evaluation criteria in solid tumours (RECIST) class directly correlated with the tumour regression grade class after the last cycle (p<0.001). Patients in the NRC group displayed a higher frequency of complete/partial response than those in the NAC group (p=0.034). 17 out of 18 patients in the NRC group met the criteria for avoiding mastectomy based on final MRI evaluation. The RECIST classification displayed a superior diagnostic performance in the prediction of the response to treatment [area under the receiver operating characteristic curve (AUC)=0.72] than time-to-intensity curves and apparent diffusion coefficient (AUC 0.63 and 0.61). The association of the three above criteria yielded a better diagnostic performance, both in the general population (AUC=0.79) and in the NRC and the NAC group separately (AUC=0.82 and AUC=0.76).
The pathological response is predicted by MRI performed after the last cycle, if both conventional MRI and diffusion imaging are integrated. The NRC treatment yields oncological results superior to NAC.
Advances in knowledge
MRI could be used to establish the neoadjuvant protocol in breast cancer patients.
PMCID: PMC3500823  PMID: 22763034
21.  Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts 
Breast Cancer Research : BCR  2011;13(5):R102.
Cationic antimicrobial peptides (CAPs) defend against microbial pathogens; however, certain CAPs also exhibit anticancer activity. The purpose of this investigation was to determine the effect of the pleurocidin-family CAPs, NRC-03 and NRC-07, on breast cancer cells.
MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) and acid phosphatase cell-viability assays were used to assess NRC-03- and NRC-07-mediated killing of breast carcinoma cells. Erythrocyte lysis was determined with hemolysis assay. NRC-03 and NRC-07 binding to breast cancer cells and normal fibroblasts was assessed with fluorescence microscopy by using biotinylated-NRC-03 and -NRC-07. Lactate dehydrogenase-release assays and scanning electron microscopy were used to evaluate the effect of NRC-03 and NRC-07 on the cell membrane. Flow-cytometric analysis of 3,3'-dihexyloxacarbocyanine iodide- and dihydroethidium-stained breast cancer cells was used to evaluate the effects of NRC-03 and NRC-07 on mitochondrial membrane integrity and reactive oxygen species (ROS) production, respectively. Tumoricidal activity of NRC-03 and NRC-07 was evaluated in NOD SCID mice bearing breast cancer xenografts.
NRC-03 and NRC-07 killed breast cancer cells, including drug-resistant variants, and human mammary epithelial cells but showed little or no lysis of human dermal fibroblasts, umbilical vein endothelial cells, or erythrocytes. Sublethal doses of NRC-03 and, to a lesser extent, NRC-07 significantly reduced the median effective concentration (EC50) of cisplatin for breast cancer cells. NRC-03 and NRC-07 bound to breast cancer cells but not fibroblasts, suggesting that killing required peptide binding to target cells. NRC-03- and NRC-07-mediated killing of breast cancer cells correlated with expression of several different anionic cell-surface molecules, suggesting that NRC-03 and NRC-07 bind to a variety of negatively-charged cell-surface molecules. NRC-03 and NRC-07 also caused significant and irreversible cell-membrane damage in breast cancer cells but not in fibroblasts. NRC-03- and NRC-07-mediated cell death involved, but did not require, mitochondrial membrane damage and ROS production. Importantly, intratumoral administration of NRC-03 and NRC-07 killed breast cancer cells grown as xenografts in NOD SCID mice.
These findings warrant the development of stable and targeted forms of NRC-03 and/or NRC-07 that might be used alone or in combination with conventional chemotherapeutic drugs for the treatment of breast cancer.
PMCID: PMC3262215  PMID: 22023734
22.  The Vitek analyser for routine bacterial identification and susceptibility testing: protocols, problems, and pitfalls. 
Journal of Clinical Pathology  1998;51(4):316-323.
Automated and semiautomated technology in microbiology has seen great advances in recent years. The choice of automated equipment for the identification and susceptibility testing of bacteria in a routine diagnostic laboratory depends on speed, accuracy, ease of use, and cost factors. The Vitek analyser (bioMerieux, UK) was installed in a busy diagnostic teaching hospital laboratory in London. This report describes one year's experience. Changes to work practice as a result of incorporating the equipment into the laboratory, and the advantages and disadvantages of automation in key areas are described in detail, together with possible solutions to problems. The Vitek analyser was found to be valuable for the speed and accuracy with which results were available for the common bacterial pathogens. Results of susceptibility testing were standardised according to NCCLS guidelines and used breakpoint MICs to ascertain susceptibility and resistance; they were an improvement on disc testing. This equipment is not a reference facility for difficult to identify organisms and many manual techniques, including some disc susceptibility testing, will have to be retained by the laboratory.
PMCID: PMC500679  PMID: 9659247
23.  Communicable Diseases Prioritized for Surveillance and Epidemiological Research: Results of a Standardized Prioritization Procedure in Germany, 2011 
PLoS ONE  2011;6(10):e25691.
To establish strategic priorities for the German national public health institute (RKI) and guide the institute's mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research.
We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups.
127 pathogens were scored. Eighty-six experts participated in the weighting; “Case fatality rate” was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus.
While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings.
PMCID: PMC3186774  PMID: 21991334
24.  Intensified Tuberculosis Case Finding among Malnourished Children in Nutritional Rehabilitation Centres of Karnataka, India: Missed Opportunities 
PLoS ONE  2013;8(12):e84255.
Severe acute malnutrition (SAM) is the most serious form of malnutrition affecting children under-five and is associated with many infectious diseases including Tuberculosis (TB). In India, nutritional rehabilitation centres (NRCs) have been recently established for the management of SAM including TB. The National TB Programme (NTP) in India has introduced a revised algorithm for diagnosing paediatric TB. We aimed to examine whether NRCs adhered to these guidelines in diagnosing TB among SAM children.
A cross-sectional study involving review of records of all SAM children identified by health workers during 2012 in six tehsils (sub-districts) with NRCs (population: 1.8 million) of Karnataka, India.
Of 1927 identified SAM children, 1632 (85%) reached NRCs. Of them, 1173 (72%) were evaluated for TB and 19(2%) were diagnosed as TB. Of 1173, diagnostic algorithm was followed in 460 (37%). Among remaining 763 not evaluated as per algorithm, tuberculin skin test alone was conducted in 307 (41%), chest radiography alone in 99 (13%) and no investigations in 337 (45%). The yield of TB was higher among children evaluated as per algorithm (4%) as compared to those who were not (0.3%) (OR: 15.3 [95%CI: 3.5-66.3]). Several operational challenges including non-availability of a full-time paediatrician, non-functioning X-ray machine due to frequent power cuts, use of tuberculin with suboptimal strength and difficulties in adhering to a complex diagnostic algorithm were observed.
This study showed that TB screening in NRCs was sub-optimal in Karnataka. Some children did not reach the NRC, while many of those who did were either not or sub-optimally evaluated for TB. This study pointed to a number of operational issues that need to be addressed if this collaborative strategy is to identify more TB cases amongst malnourished children in India.
PMCID: PMC3865256  PMID: 24358350
25.  Serogroup C meningococci in Italy in the era of conjugate menC vaccination 
To assess changes in the pattern of Invasive Meningococcal Disease (IMD) in Italy after the introduction of conjugate menC vaccine in the National Vaccine Plan 2005–2007 and to provide information for developing timely and appropriate public health interventions, analyses of microbiological features of isolates and clinical characteristics of patients have been carried out. In Italy, the number of serogroup C meningococci fell progressively following the introduction of the MenC conjugate vaccine, recommended by the Italian Ministry of Health but implemented according to different regional strategies.
IMD cases from January 2005 through July 2008 reported to the National Meningococcal Surveillance System were considered for this study. Serogrouping and sero/subtyping were performed on 179 serogroup C strains received at the National Reference Laboratory of the Istituto Superiore di Sanità. Antibiotic susceptibility testing was possible for 157 isolates. MLST (Multilocus sequence typing), porA VRs (Variable Region) typing, PFGE (Pulsed Field Gel Electrophoresis), VNTR (Variable Number Tandem Repeats) analyses were performed on all C:2a and C:2b meningococci (n = 147), following standard procedures.
In 2005 and 2008, IMD showed an incidence of 0.5 and 0.3 per 100,000 inhabitants, respectively. While the incidence due to serogroup B remained stable, IMD incidence due to serogroup C has decreased since 2006. In particular, the decrease was significant among infants. C:2a and C:2b were the main serotypes, all C:2a strains belonged to ST-11 clonal complex and all C:2b to ST-8/A4. Clinical manifestations and outcome of infections underlined more severe disease caused by C:2a isolates. Two clusters due to C:2a/ST-11 meningococci were reported in the North of Italy in December 2007 and July 2008, respectively, with a high rate of septicaemia and fatal outcome.
Public health surveillance of serogroup C invasive meningococcal disease and microbiological/molecular characterization of the isolates requires particular attention, since the hyper-invasive ST-11 predominantly affected adolescents and young adults for whom meningococcal vaccination was not recommended in the 2005–2007 National Vaccine Plan.
PMCID: PMC2739211  PMID: 19698137

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