Association of disease severity and genetic variation during primary Respiratory Syncytial Virus infections.

BACKGROUND: Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored. METHODS: Nasal swabs from children (< 8 months-old) infected with RSV in Rochester, NY between 1977-1998 clinically presenting with either mild or severe disease during their first cold-season were used. Whole-genome RSV sequences were obtained using overlapping PCR and next-generation sequencing. Both whole-genome phylogenetic and non-phylogenetic statistical approaches were performed to associate RSV genotype with disease severity. RESULTS: The RSVB subtype was statistically associated with disease severity. A significant association between phylogenetic clustering of mild/severe traits and disease severity was also found. GA1 clade sequences were associated with severe disease while GB1 was significantly associated with mild disease. Both G and M2-2 gene variation was significantly associated with disease severity. We identified 16 residues in the G gene and 3 in the M2-2 RSV gene associated with disease severity. CONCLUSION: These results suggest that phylogenetic lineage and the genetic variability in G or M2-2 genes of RSV may contribute to disease severity in young children undergoing their first infection.

Estimation of protein function using template-based alignment of enzyme active sites.

BACKGROUND: The accumulation of protein structural data occurs more rapidly than it can be characterized by traditional laboratory means. This has motivated widespread efforts to predict enzyme function computationally. The most useful/accurate strategies employed to date are based on the detection of motifs in novel structures that correspond to a specific function. Functional residues are critical components of predictively useful motifs. We have implemented a novel method, to complement current approaches, which detects motifs solely on the basis of distance restraints between catalytic residues. RESULTS: ProMOL is a plugin for the PyMOL molecular graphics environment that can be used to create active site motifs for enzymes. A library of 181 active site motifs has been created with ProMOL, based on definitions published in the Catalytic Site Atlas (CSA). Searches with ProMOL produce better than 50% useful Enzyme Commission (EC) class suggestions for level 1 searches in EC classes 1, 4 and 5, and produce some useful results for other classes. 261 additional motifs automatically translated from Jonathan Barker's JESS motif set [Bioinformatics 19:1644-1649, 2003] and a set of NMR motifs is under development. Alignments are evaluated by visual superposition, Levenshtein distance and root-mean-square deviation (RMSD) and are reasonably consistent with related search methods. CONCLUSION: The ProMOL plugin for PyMOL provides ready access to template-based local alignments. Recent improvements to ProMOL, including the expanded motif library, RMSD calculations and output selection formatting, have greatly increased the program's usability and speed, and have improved the way that the results are presented.

Examining vertebrobasilar artery stroke in two Canadian provinces.

STUDY DESIGN: Ecological study. OBJECTIVES: To determine the annual incidence of hospitalized vertebrobasilar artery (VBA) stroke and chiropractic utilization in Saskatchewan and Ontario between 1993 and 2004. To determine whether at an ecological level, the incidence of VBA stroke parallels the incidence of chiropractic utilization. SUMMARY OF BACKGROUND DATA: Little is known about the incidence and time trends of VBA stroke diagnoses in the population. Chiropractic manipulation to the neck is believed to be a risk factor for VBA stroke. No study has yet found an association between chiropractic utilization and VBA diagnoses at the population level. METHODS: All hospitalizations with discharge diagnoses of VBA stroke were extracted from administrative databases for Saskatchewan and Ontario. We included incident cases that were diagnosed between January 1993 and December 2004 for Saskatchewan and from April 1993 to March 2002 for Ontario. VBA cases that had previously been hospitalized for any stroke or transient ischemic attack (TIA) were excluded. Chiropractic utilization was measured using billing data from Saskatchewan Health and Ontario Health Insurance Plan. Denominators were derived from Statistics Canada's annual population estimates. RESULTS: The incidence rate of VBA stroke was 0.855 per 100,000 person-years for Saskatchewan and 0.750 per 100,000 person-years for Ontario. The annual incidence rate spiked dramatically with a 360% increase for Saskatchewan in 2000. There was a 38% increase for the 2000 incidence rate in Ontario. The rate of chiropractic utilization did not increase significantly during the study period. CONCLUSION: In Saskatchewan, we observed a dramatic increase in the incidence rate in 2000 and there was a corresponding relatively small increase in chiropractic utilization. In Ontario, there was a small increase in the incidence rate; however, chiropractic utilization decreased. At the ecological level, the increase in VBA stroke does not seem to be associated with an increase in the rate of chiropractic utilization.

Examining vertebrobasilar artery stroke in two Canadian provinces.

STUDY DESIGN: Ecological study. OBJECTIVES: To determine the annual incidence of hospitalized vertebrobasilar artery (VBA) stroke and chiropractic utilization in Saskatchewan and Ontario between 1993 and 2004. To determine whether at an ecological level, the incidence of VBA stroke parallels the incidence of chiropractic utilization. SUMMARY OF BACKGROUND DATA: Little is known about the incidence and time trends of VBA stroke diagnoses in the population. Chiropractic manipulation to the neck is believed to be a risk factor for VBA stroke. No study has yet found an association between chiropractic utilization and VBA diagnoses at the population level. METHODS: All hospitalizations with discharge diagnoses of VBA stroke were extracted from administrative databases for Saskatchewan and Ontario. We included incident cases that were diagnosed between January 1993 and December 2004 for Saskatchewan and from April 1993 to March 2002 for Ontario. VBA cases that had previously been hospitalized for any stroke or transient ischemic attack (TIA) were excluded. Chiropractic utilization was measured using billing data from Saskatchewan Health and Ontario Health Insurance Plan. Denominators were derived from Statistics Canada's annual population estimates. RESULTS: The incidence rate of VBA stroke was 0.855 per 100,000 person-years for Saskatchewan and 0.750 per 100,000 person-years for Ontario. The annual incidence rate spiked dramatically with a 360% increase for Saskatchewan in 2000. There was a 38% increase for the 2000 incidence rate in Ontario. The rate of chiropractic utilization did not increase significantly during the study period. CONCLUSION: In Saskatchewan, we observed a dramatic increase in the incidence rate in 2000 and there was a corresponding relatively small increase in chiropractic utilization. In Ontario, there was a small increase in the incidence rate; however, chiropractic utilization decreased. At the ecological level, the increase in VBA stroke does not seem to be associated with an increase in the rate of chiropractic utilization.