Understanding Mycobacterium abscessus pulmonary and disseminated disease

2017 Summer.Includes bibliographical references.Mycobacterium abscessus is an emerging human pathogen which is difficult to treat and results in increased mortality. Moreover, the cause of increasing case rates and also the pathogenesis of M. abscessus are poorly understood. M. abscessus belongs to the family of nontuberculous mycobacteria (NTM) classified as members of the rapidly growing mycobacteria (RGM). These environmental pathogens are ubiquitous and found in shower heads, tap water, natural water sources, and soil. Humans contract pulmonary or disseminated infections with M. abscessus by breathing in the aerosolized bacteria or ingesting contaminated water. Immunocompromised individuals such as HIV or AIDS patients, are more susceptible to infection with M. abscessus as are those with cystic fibrosis, bronchiectasis, and individuals on tumor necrosis factor α (TNFα) inhibitors. Strangely, an increasing population of patients becoming infected with M. abscessus are immunocompetent, tall, slender, Caucasian, non-smoking women. To expand our understanding of M. abscessus pathogenesis we developed mouse models that maintain high levels of bacterial infection to study immune responses induced by clinical strains of M. abscessus. Our results support the hypothesis that this bacteria can only persist in our animal models that possess a deficiency in macrophages and T cell function. Clustered bacterial strains obtained from Cystic Fibrosis patients are more virulent than unclustered bacterial strains obtained from Cystic Fibrosis patients. Additionally, counts of viable mycobacterial colony forming units and histological analysis in (Severe Combined Immunodeficiency) SCID mice on a beige background infected with clustered versus unclustered M. abscessus strains which were isolated from Cystic Fibrosis patients also supported the increased virulence exhibited by the clustered strains. Lastly, we show that major human M. abscessus outbreak strains, when infecting IL-3, GM-CSF deficient mice on an IL-2, Rag2 deficient background (GM/Rag-dblKO mice), result in increased bacterial replication and organ pathology and impaired protective immunity against this pathogen

Comparison of Staphylococcus aureus isolates associated with food intoxication with isolates from human nasal carriers and human infections

Staphylococcus aureus represents an organism of striking versatility. While asymptomatic nasal colonization is widespread, it can also cause serious infections, toxinoses and life-threatening illnesses in humans and animals. Staphylococcal food poisoning (SFP), one of the most prevalent causes of foodborne intoxication worldwide, results from oral intake of staphylococcal enterotoxins leading to violent vomiting, diarrhea and cramps shortly upon ingestion. The aim of the present study was to compare isolates associated with SFP to isolates collected from cases of human nasal colonization and clinical infections in order to investigate the role of S. aureus colonizing and infecting humans as a possible source of SFP. Spa typing and DNA microarray profiling were used to characterize a total of 120 isolates, comprising 50 isolates collected from the anterior nares of healthy donors, 50 isolates obtained from cases of clinical infections in humans and 20 isolates related to outbreaks of staphylococcal food poisoning. Several common spa types were found among isolates of all three sources (t015, t018, t056, t084). DNA microarray results showed highly similar virulence gene profiles for isolates from all tested sources. These results suggest contamination of foodstuff with S. aureus colonizing and infecting food handlers to represent a source of SF

Higher education, mature students and employment goals: policies and practices in the UK

This article considers recent policies of Higher Education in the UK, which are aimed at widening participation and meeting the needs of employers. The focus is on the growing population of part-time students, and the implications of policies for this group. The article takes a critical perspective on government policies, using data from a major study of mature part-time students, conducted in two specialist institutions in the UK, a London University college and a distance learning university. Findings from this study throw doubt on the feasibility of determining a priori what kind of study pathway is most conducive for the individual in terms of employment gains and opportunities for upward social mobility. In conclusion, doubts are raised as to whether policies such as those of the present UK government are likely to achieve its aims. Such policies are not unique to the UK, and lessons from this country are relevant to most of the developed world

Gender, foundation degrees and the knowledge economy

This article questions the concept of ‘education for employment’, which constructs a discourse of individual and societal benefit in a knowledge‐driven economy. Recent policy emphasis in the European Union promotes the expansion of higher education and short‐cycle vocational awards such as the intermediate two‐year Foundation Degree recently introduced into England and Wales. Studies of vocational education and training (VET) and the knowledge economy have focused largely on the governance of education and on the development and drift of policy. Many VET programmes have also been considered for their classed, raced and gendered take‐up and subsequent effect on employment. This article builds on both fields of study to engage with the finer cross‐analyses of gender, social class, poverty, race and citizenship. In its analysis of policy texts the article argues that in spite of a discourse of inclusivity, an expanded higher education system has generated new inequalities, deepening social stratification. Drawing on early analyses of national quantitative data sets, it identifies emerging gendered, classed and raced patterns and considers these in relation to occupationally and hierarchically stratified labour markets, both within and without the knowledge economy

Cell transformation assays for prediction of carcinogenic potential: State of the science and future research needs

Copyright @ 2011 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting

A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant staphylococcus aureus pandemic

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens

"After my husband's circumcision, I know that I am safe from diseases": Women's Attitudes and Risk Perceptions Towards Male Circumcision in Iringa, Tanzania.

While male circumcision reduces the risk of female-to-male HIV transmission and certain sexually transmitted infections (STIs), there is little evidence that circumcision provides women with direct protection against HIV. This study used qualitative methods to assess women's perceptions of male circumcision in Iringa, Tanzania. Women in this study had strong preferences for circumcised men because of the low risk perception of HIV with circumcised men, social norms favoring circumcised men, and perceived increased sexual desirability of circumcised men. The health benefits of male circumcision were generally overstated; many respondents falsely believed that women are also directly protected against HIV and that the risk of all STIs is greatly reduced or eliminated in circumcised men. Efforts to engage women about the risks and limitations of male circumcision, in addition to the benefits, should be expanded so that women can accurately assess their risk of HIV or STIs during sexual intercourse with circumcised men