Validation of the ALS Assay in Adult Patients with Culture Confirmed Pulmonary Tuberculosis

BACKGROUND: We have earlier shown that Bacille Calmette-Guérin (BCG) vaccine-specific IgG Antibodies in Lymphocyte Supernatant (ALS) can be used for diagnosis of active tuberculosis (TB) in adults and children. METHODOLOGY/PRINCIPAL FINDINGS: The ALS method was validated in a larger cohort (n = 212) of patients with suspicion of pulmonary TB using multiple antigens (BCG, LAM, TB15.3, TB51A, CFP10-ESAT6-A, CFP, CW) from Mycobacterium tuberculosis. The sensitivity and specificity of the ALS assay was calculated using non-TB patients as controls. The sensitivity and the specificity were highest with BCG vaccine (90% and 88% respectively) followed by LAM (89% and 87% respectively). Simultaneous assessment of multiple antigen-specific antibodies increased sensitivity (91%) and specificity (88%). Using higher lymphocyte count in smaller volume of culture media increased detection and reduced the assay duration to ∼30 hrs. Twenty one patients with clinical findings strongly suggestive of TB finally diagnosed as non-TB patients were positive by the ALS assay, of which 9 (43%) were positive for 7 antigens and 19 (90%) for at least 3 antigens. CONCLUSIONS/SIGNIFICANCE: Our findings show that simultaneous detection of antigens improves the diagnostic potential of the ALS assay; the modified method increases sensitivity and can provide results in <48 hours, and enable detection of some cases of pulmonary TB that are not detectable by standard methods

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Rituximab suppresses disease activity after natalizumab withdrawal: an exploratory study

Background Natalizumab is highly effective in reducing multiple sclerosis disease activity; however it carries a risk of progressive multifocal leukoencephalopathy, that represents the main reason of drug discontinuation. After natalizumab withdrawal, reactivation of disease is soon observed and, until now, it is not known which treatment strategy should be followed after natalizumab discontinuation. Aim of this study is to evaluate rituximab efficacy in controlling disease activity after natalizumab withdrawal

Movies and TV Influence Tobacco Use in India: Findings from a National Survey

Background: Exposure to mass media may impact the use of tobacco, a major source of illness and death in India. The objective is to test the association of self-reported tobacco smoking and chewing with frequency of use of four types of mass media: newspapers, radio, television, and movies. Methodology/Principal Findings: We analyzed data from a sex-stratified nationally-representative cross-sectional survey of 123,768 women and 74,068 men in India. All models controlled for wealth, education, caste, occupation, urbanicity, religion, marital status, and age. In fully-adjusted models, monthly cinema attendance is associated with increased smoking among women (relative risk [RR]: 1·55; 95% confidence interval [CI]: 1·04–2·31) and men (RR: 1·17; 95% CI: 1·12–1·23) and increased tobacco chewing among men (RR: 1·15; 95% CI: 1·11–1·20). Daily television and radio use is associated with higher likelihood of tobacco chewing among men and women, while daily newspaper use is related to lower likelihood of tobacco chewing among women. Conclusion/Significance: In India, exposure to visual mass media may contribute to increased tobacco consumption in men and women, while newspaper use may suppress the use of tobacco chewing in women. Future studies should investigate the role that different types of media content and media play in influencing other health behaviors

Scaling up community-based obesity prevention in Australia: Background and evaluation design of the Health Promoting Communities: Being Active Eating Well initiative

Background : There is only limited evidence available on how best to prevent childhood obesity and community-based interventions hold promise, as several successful interventions have now been published. The Victorian Government has recently funded six disadvantaged communities across Victoria, Australia for three years to promote healthy eating and physical activity for children, families, and adults in a community-based participatory manner. Five of these intervention communities are situated in Primary Care Partnerships and are the subject of this paper. The interventions will comprise a mixture of capacity-building, environmental, and whole-of-community approaches with targeted and population-level interventions. The specific intervention activities will be determined locally within each community through stakeholder and community consultation. Implementation of the interventions will occur through funded positions in primary care and local government. This paper describes the design of the evaluation of the five primary care partnership-based initiatives in the \u27Go for your life\u27 Health Promoting Communities: Being Active Eating Well (HPC:BAEW) initiative.Methods/Design : A mixed method and multi-level evaluation of the HPC:BAEW initiative will capture process, impact and outcome data and involve both local and state-wide evaluators. There will be a combined analysis across the five community intervention projects with outcomes compared to a comparison group using a cross-sectional, quasi-experimental design. The evaluation will capture process, weight status, socio-demographic, obesity-related behavioral and environmental data in intervention and comparison areas. This will be achieved using document analysis, paper-based questionnaires, interviews and direct measures of weight, height and waist circumference from participants (children, adolescents and adults).Discussion : This study will add significant evidence on how to prevent obesity at a population level in disadvantaged and ethnically diverse communities. The outcomes will have direct influence on policy and practice and guide the development and implementation of future obesity prevention efforts in Australia and internationally.<br /

Cystatin C: A Candidate Biomarker for Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurologic disease characterized by progressive motor neuron degeneration. Clinical disease management is hindered by both a lengthy diagnostic process and the absence of effective treatments. Reliable panels of diagnostic, surrogate, and prognostic biomarkers are needed to accelerate disease diagnosis and expedite drug development. The cysteine protease inhibitor cystatin C has recently gained interest as a candidate diagnostic biomarker for ALS, but further studies are required to fully characterize its biomarker utility. We used quantitative enzyme-linked immunosorbent assay (ELISA) to assess initial and longitudinal cerebrospinal fluid (CSF) and plasma cystatin C levels in 104 ALS patients and controls. Cystatin C levels in ALS patients were significantly elevated in plasma and reduced in CSF compared to healthy controls, but did not differ significantly from neurologic disease controls. In addition, the direction of longitudinal change in CSF cystatin C levels correlated to the rate of ALS disease progression, and initial CSF cystatin C levels were predictive of patient survival, suggesting that cystatin C may function as a surrogate marker of disease progression and survival. These data verify prior results for reduced cystatin C levels in the CSF of ALS patients, identify increased cystatin C levels in the plasma of ALS patients, and reveal correlations between CSF cystatin C levels to both ALS disease progression and patient survival

Community health and medical provision: impact on neonates (the CHAMPION trial)

BACKGROUND: The trial aims to evaluate whether neonatal mortality can be reduced through systemic changes to the provision and promotion of healthcare. Neonatal mortality rates in India are high compared to other low income countries, and there is a wide variation of rates across regions. There is evidence that relatively inexpensive interventions may be able to prevent up to 75% of these deaths. One area with a particularly high rate is Mahabubnagar District in Andhra Pradesh, where neonatal mortality is estimated to be in the region of 4-9%. The area suffers from a vicious cycle of both poor supply of and small demand for health care services. The trial will assess whether a package of interventions to facilitate systemic changes to the provision and promotion of healthcare may be able to substantially reduce neonatal mortality in this area and be cost-effective. If successful, the trial is designed so that it should be possible to substantially scale up the project in regions with similarly high neonatal mortality throughout Andhra Pradesh and elsewhere. METHODS/DESIGN: This trial will be a cluster-randomised controlled trial involving 464 villages in Mahabubnagar District. The package of interventions will first be introduced in half of the villages with the others serving as controls. The trial will run for a period of three years. The intervention in the trial has two key elements: a community health promotion campaign and a system to contract out healthcare to non-public institutions. The health promotion campaign will include a health education campaign, participatory discussion groups, training of village health workers and midwives, and improved coordination of antenatal services. The intervention group will also have subsidized access to pregnancy-related healthcare services at non-public lth centres (NPHCs). The primary outcome of the trial will be neonatal mortality. Secondary outcomes will include age at and cause of neonatal death, neonatal morbidity, maternal mortality and morbidity, health service usage, costs and several process and knowledge outcomes. DISCUSSION: The trial will be run by independent research and service delivery arms and supervised by a trial steering committee. A data monitoring committee will be put in place to monitor the trial and recommend stopping/continuation according to a Peto-Haybittle rule. The primary publication for the trial will follow CONSORT guidelines for cluster randomised controlled trials. Criteria for authorship of all papers, presentations and reports resulting from the study will conform to ICMJE standards

Influence of Perineurial Cells and Toll-Like Receptors 2 and 9 on Herpes simplex Type 1 Entry to the Central Nervous System in Rat Encephalitis

Herpes simplex encephalitis (HSE) is a rare disease with high mortality and significant morbidity among survivors. We have previously shown that susceptibility to HSE was host-strain dependent, as severe, lethal HSE developed after injection of human Herpes simplex type 1 virus (HSV-1) into the whiskers area of DA rats, whereas PVG rats remained completely asymptomatic. In the present study we investigated the early immunokinetics in these strains to address the underlying molecular mechanisms for the observed difference. The virus distribution and the immunological responses were compared in the whiskers area, trigeminal ganglia and brain stem after 12 hours and the first four days following infection using immunohistochemistry and qRT-PCR. A conspicuous immunopathological finding was a strain-dependent difference in the spread of the HSV-1 virus to the trigeminal ganglia, only seen in DA rats already from 12 hpi. In the whiskers area infected perineurial cells were abundant in the susceptible DA strain after 2 dpi, whereas in the resistant PVG rats HSV-1 spread was confined only to the epineurium. In both strains activation of Iba1+/ED1+ phagocytic cells followed the distribution pattern of HSV-1 staining, which was visible already at 12 hours after infection. Notably, in PVG rats higher mRNA expression of Toll-like receptors (Tlr) -2 and -9, together with increased staining for Iba1/ED1 was detected in the whiskers area. In contrast, all other Tlr-pathway markers were expressed at higher levels in the susceptible DA rats. Our data demonstrate the novel observation that genetically encoded properties of the host nerve and perineurial cells, recruitment of phagocyting cells together with the low expression of Tlr2 and -9 in the periphery define the susceptibility to HSV-1 entry into the nervous system

The taper of cast post preparation measured using innovative image processing technique

<p>Abstract</p> <p>Background</p> <p>No documentation in the literature about taper of cast posts. This study was conducted to measure the degree of cast posts taper, and to evaluate its suitability based on the anatomy aspects of the common candidate teeth for post reconstruction.</p> <p>Methods</p> <p>Working casts for cast posts, prepared using Gates Glidden drills, were collected. Impressions of post spaces were made using polyvinyl siloxan putty/wash technique. Digital camera with a 10' high quality lens was used for capturing two digital images for each impression; one in the Facio-Lingual (FL) and the other in the Mesio-Distal (MD) directions. Automated image processing program was developed to measure the degree of canal taper. Data were analyzed using Statistical Package for Social Sciences software and One way Analysis of Variance.</p> <p>Results</p> <p>Eighty four dies for cast posts were collected: 16 for each maxillary anterior teeth subgroup, and 18 for each maxillary and mandibular premolar subgroup. Mean of total taper for all preparations was 10.7 degree. There were no statistical differences among the total taper of all groups (P = .256) or between the MD and FL taper for each subgroup. Mean FL taper for the maxillary first premolars was lower significantly (P = .003) than the maxillary FL taper of the second premolars. FL taper was higher than the MD taper in all teeth except the maxillary first premolars.</p> <p>Conclusions</p> <p>Taper produced did not reflect the differences among the anatomy of teeth. While this technique deemed satisfactory in the maxillary anterior teeth, the same could not be said for the maxillary first premolars. Careful attention to the root anatomy is mandatory.</p