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Renal Athersosclerotic reVascularization Evaluation (RAVE Study): Study protocol of a randomized trial [NCT00127738]

BACKGROUND: It is uncertain whether patients with renal vascular disease will have renal or mortality benefit from re-establishing renal blood flow with renal revascularization procedures. The RAVE study will compare renal revascularization to medical management for people with atherosclerotic renal vascular disease (ARVD) and the indication for revascularization. Patients will be assessed for the standard nephrology research outcomes of progression to doubling of creatinine, need for dialysis, and death, as well as other cardiovascular outcomes. We will also establish whether the use of a new inexpensive, simple and available ultrasound test, the renal resistance index (RRI), can identify patients with renal vascular disease who will not benefit from renal revascularization procedures[1]. METHODS/DESIGN: This single center randomized, parallel group, pilot study comparing renal revascularization with medical therapy alone will help establish an infrastructure and test the feasibility of answering this important question in clinical nephrology. The main outcome will be a composite of death, dialysis and doubling of creatinine. Knowledge from this study will be used to better understand the natural history of patients diagnosed with renal vascular disease in anticipation of a Canadian multicenter trial. Data collected from this study will also inform the Canadian Hypertension Education Program (CHEP) Clinical Practice Guidelines for the management of Renal and Renal Vascular Disease. The expectation is that this program for ARVD, will enable community based programs to implement a comprehensive guidelines based diagnostic and treatment program, help create an evidence based approach for the management of patients with this condition, and possibly reduce or halt the progression of kidney disease in these patients. DISCUSSION: Results from this study will determine the feasibility of a multicentered study for the management of renovascular disease

Blood pressure and cholesterol level checks as dynamic interrelated screening examinations

This study analysed the determinants of screening uptake for blood pressure and cholesterol level checks. Furthermore, it investigated the presence of possible spillover effects from one type of cardiovascular screening to another type of cardiovascular screening. A dynamic random effects bivariate panel probit model with initial conditions (Wooldridge-type estimator) was adopted for the estimation. The outcome variables were the participation in blood pressure and cholesterol level checks by individuals in a given year. The balanced panel sample of 21,138 observations was constructed from 1,626 individuals from the British Household Panel Survey (BHPS) between 1996 and 2008. The analysis showed the significance of past screening behaviour for both cardiovascular screening examinations. For both cardiovascular screening examinations state dependence exist. The study also shows a significant spillover effect of the cholesterol level check on the blood pressure check and vice versa. Also a poorer health status led to a higher uptake for both types of screening examinations. Changes in recommendations have to consider the fact that taking part in one type of cardiovascular screening examination can influence the decision to take part in the other type of cardiovascular screening examination

Molecular detection of rifampin and isoniazid resistance to guide chronic TB patient management in Burkina Faso

<p>Abstract</p> <p>Background</p> <p>Drug-resistant tuberculosis (DR-TB) is considered a real threat to the achievement of TB control. Testing of mycobacterial culture and testing of drug susceptibility (DST) capacity are limited in resource-poor countries, therefore inadequate treatment may occur, favouring resistance development. We evaluated the molecular assay GenoType^®MTBDR<it>plus </it>(Hain Lifescience, Germany) in order to detect DR-TB directly in clinical specimens as a means of providing a more accurate management of chronic TB patients in Burkina Faso, a country with a high TB-HIV co-infection prevalence.</p> <p>Methods</p> <p>Samples were collected in Burkina Faso where culture and DST are not currently available, and where chronic cases are therefore classified and treated based on clinical evaluation and sputum-smear microscopy results. One hundred and eight chronic TB patients (sputum smear-positive, after completing a re-treatment regimen for pulmonary TB under directly observed therapy) were enrolled in the study from December 2006 to October 2008. Two early morning sputum samples were collected from each patient, immediately frozen, and shipped to Italy in dry ice. Samples were decontaminated, processed for smear microscopy and DNA extraction. Culture was attempted on MGIT960 (Becton Dickinson, Cockeysville, USA) and decontaminated specimens were analyzed for the presence of mutations conferring resistance to rifampin and isoniazid by the molecular assay GenoType^®MTBDR<it>plus</it>.</p> <p>Results</p> <p>We obtained a valid molecular test result in 60/61 smear-positive and 47/47 smear-negative patients.</p> <p>Among 108 chronic TB cases we identified patients who (i) harboured rifampin- and isoniazid-susceptible strains (n 24), (ii) were negative for MTB complex DNA (n 24), and (iii) had non-tuberculous mycobacteria infections (n 13). The most represented mutation conferring rifampin-resistance was the D516V substitution in the hotspot region of the <it>rpoB </it>gene (43.8% of cases). Other mutations recognized were the H526D (15.6%), the H526Y (15.6%), and the S531L (9.4%).</p> <p>All isoniazid-resistant cases (n 36) identified by the molecular assay were carrying a S315T substitution in the <it>katG </it>gene. In 41.7% of cases, a mutation affecting the promoter region of the <it>inhA </it>gene was also detected.</p> <p>Conclusion</p> <p>The GenoType^®MTBDR<it>plus </it>assay performed directly on sputum specimens improves the management of chronic TB cases allowing more appropriate anti-TB regimens.</p

Computational Analysis and Experimental Validation of Gene Predictions in Toxoplasma gondii

Toxoplasma gondii is an obligate intracellular protozoan that infects 20 to 90% of the population. It can cause both acute and chronic infections, many of which are asymptomatic, and, in immunocompromised hosts, can cause fatal infection due to reactivation from an asymptomatic chronic infection. An essential step towards understanding molecular mechanisms controlling transitions between the various life stages and identifying candidate drug targets is to accurately characterize the T. gondii proteome.We have explored the proteome of T. gondii tachyzoites with high throughput proteomics experiments and by comparison to publicly available cDNA sequence data. Mass spectrometry analysis validated 2,477 gene coding regions with 6,438 possible alternative gene predictions; approximately one third of the T. gondii proteome. The proteomics survey identified 609 proteins that are unique to Toxoplasma as compared to any known species including other Apicomplexan. Computational analysis identified 787 cases of possible gene duplication events and located at least 6,089 gene coding regions. Commonly used gene prediction algorithms produce very disparate sets of protein sequences, with pairwise overlaps ranging from 1.4% to 12%. Through this experimental and computational exercise we benchmarked gene prediction methods and observed false negative rates of 31 to 43%.This study not only provides the largest proteomics exploration of the T. gondii proteome, but illustrates how high throughput proteomics experiments can elucidate correct gene structures in genomes

Modeling Planarian Regeneration: A Primer for Reverse-Engineering the Worm

A mechanistic understanding of robust self-assembly and repair capabilities of complex systems would have enormous implications for basic evolutionary developmental biology as well as for transformative applications in regenerative biomedicine and the engineering of highly fault-tolerant cybernetic systems. Molecular biologists are working to identify the pathways underlying the remarkable regenerative abilities of model species that perfectly regenerate limbs, brains, and other complex body parts. However, a profound disconnect remains between the deluge of high-resolution genetic and protein data on pathways required for regeneration, and the desired spatial, algorithmic models that show how self-monitoring and growth control arise from the synthesis of cellular activities. This barrier to progress in the understanding of morphogenetic controls may be breached by powerful techniques from the computational sciences—using non-traditional modeling approaches to reverse-engineer systems such as planaria: flatworms with a complex bodyplan and nervous system that are able to regenerate any body part after traumatic injury. Currently, the involvement of experts from outside of molecular genetics is hampered by the specialist literature of molecular developmental biology: impactful collaborations across such different fields require that review literature be available that presents the key functional capabilities of important biological model systems while abstracting away from the often irrelevant and confusing details of specific genes and proteins. To facilitate modeling efforts by computer scientists, physicists, engineers, and mathematicians, we present a different kind of review of planarian regeneration. Focusing on the main patterning properties of this system, we review what is known about the signal exchanges that occur during regenerative repair in planaria and the cellular mechanisms that are thought to underlie them. By establishing an engineering-like style for reviews of the molecular developmental biology of biomedically important model systems, significant fresh insights and quantitative computational models will be developed by new collaborations between biology and the information sciences