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Gounder P.P.,Centers for Disease Control and Prevention | Zulz T.,Centers for Disease Control and Prevention | Desai S.,Public Health Agency of Canada | Stenz F.,The National Board of Health | And 4 more authors.
Journal of Infection | Year: 2015

Objective: To determine the incidence of meningitis caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in the North American Arctic during 2000-2010. Methods: Surveillance data were obtained from the International Circumpolar Surveillance network. We defined a case of bacterial meningitis caused by H. influenzae, N. meningitidis, or S. pneumoniae as a culture-positive isolate obtained from a normally sterile site in a resident with a meningitis diagnosis. Results: The annual incidence/100,000 persons for meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae among all North American Arctic residents was: 0.6, 0.5, and 1.5, respectively; the meningitis incidence among indigenous persons in Alaska and Canada (indigenous status not recorded in Greenland) for those three bacteria was: 2.1, 0.8, and 2.4, respectively. The percentage of pneumococcal isolates belonging to a 7-valent pneumococcal conjugate vaccine serotype declined from 2000-2004 to 2005-2010 (31%-2%, p-value <0.01). During 2005-2010, serotype a caused 55% of H. influenzae meningitis and serogroup B caused 86% of meningococcal meningitis. Conclusions: Compared with all North American Arctic residents, indigenous people suffer disproportionately from bacterial meningitis. Arctic residents could benefit from the development of an H. influenzae serotype a vaccine and implementation of a meningococcal serogroup B vaccine. © 2015.


Brea-Calvo G.,Pablo De Olavide University | Haack T.B.,Helmholtz Center for Environmental Research | Haack T.B.,TU Munich | Karall D.,Innsbruck Medical University | And 34 more authors.
American Journal of Human Genetics | Year: 2015

Primary coenzyme Q10 (CoQ10) deficiencies are rare, clinically heterogeneous disorders caused by mutations in several genes encoding proteins involved in CoQ10 biosynthesis. CoQ10 is an essential component of the electron transport chain (ETC), where it shuttles electrons from complex I or II to complex III. By whole-exome sequencing, we identified five individuals carrying biallelic mutations in COQ4. The precise function of human COQ4 is not known, but it seems to play a structural role in stabilizing a multiheteromeric complex that contains most of the CoQ10 biosynthetic enzymes. The clinical phenotypes of the five subjects varied widely, but four had a prenatal or perinatal onset with early fatal outcome. Two unrelated individuals presented with severe hypotonia, bradycardia, respiratory insufficiency, and heart failure; two sisters showed antenatal cerebellar hypoplasia, neonatal respiratory-distress syndrome, and epileptic encephalopathy. The fifth subject had an early-onset but slowly progressive clinical course dominated by neurological deterioration with hardly any involvement of other organs. All available specimens from affected subjects showed reduced amounts of CoQ10 and often displayed a decrease in CoQ10-dependent ETC complex activities. The pathogenic role of all identified mutations was experimentally validated in a recombinant yeast model; oxidative growth, strongly impaired in strains lacking COQ4, was corrected by expression of human wild-type COQ4 cDNA but failed to be corrected by expression of COQ4 cDNAs with any of the mutations identified in affected subjects. COQ4 mutations are responsible for early-onset mitochondrial diseases with heterogeneous clinical presentations and associated with CoQ10 deficiency. © 2015 The Authors. This is an open access article under the CC BY-NC-ND license.


PubMed | Centers for Disease Control and Prevention, Walter Mackenzie Health science Center, Public Health Agency of Canada and The National Board of Health
Type: Journal Article | Journal: The Journal of infection | Year: 2015

To determine the incidence of meningitis caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in the North American Arctic during 2000-2010.Surveillance data were obtained from the International Circumpolar Surveillance network. We defined a case of bacterial meningitis caused by H. influenzae, N. meningitidis, or S. pneumoniae as a culture-positive isolate obtained from a normally sterile site in a resident with a meningitis diagnosis.The annual incidence/100,000 persons for meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae among all North American Arctic residents was: 0.6, 0.5, and 1.5, respectively; the meningitis incidence among indigenous persons in Alaska and Canada (indigenous status not recorded in Greenland) for those three bacteria was: 2.1, 0.8, and 2.4, respectively. The percentage of pneumococcal isolates belonging to a 7-valent pneumococcal conjugate vaccine serotype declined from 2000-2004 to 2005-2010 (31%-2%, p-value <0.01). During 2005-2010, serotype a caused 55% of H. influenzae meningitis and serogroup B caused 86% of meningococcal meningitis.Compared with all North American Arctic residents, indigenous people suffer disproportionately from bacterial meningitis. Arctic residents could benefit from the development of an H. influenzae serotype a vaccine and implementation of a meningococcal serogroup B vaccine.


PubMed | Innsbruck Medical University, University of Bari, Klinikum Reutlingen, Saitama University and 8 more.
Type: Case Reports | Journal: American journal of human genetics | Year: 2015

Primary coenzyme Q10 (CoQ10) deficiencies are rare, clinically heterogeneous disorders caused by mutations in several genes encoding proteins involved in CoQ10 biosynthesis. CoQ10 is an essential component of the electron transport chain (ETC), where it shuttles electrons from complex I or II to complex III. By whole-exome sequencing, we identified five individuals carrying biallelic mutations inCOQ4. The precise function of human COQ4 is not known, but it seems to play a structural role in stabilizing a multiheteromeric complex that contains most of the CoQ10 biosynthetic enzymes. The clinical phenotypes of the five subjects varied widely, but four had a prenatal or perinatal onset with early fatal outcome. Two unrelated individuals presented with severe hypotonia, bradycardia, respiratory insufficiency, and heart failure; two sisters showed antenatal cerebellar hypoplasia, neonatal respiratory-distress syndrome, and epileptic encephalopathy. The fifth subject had an early-onset but slowly progressive clinical course dominated by neurological deterioration with hardly any involvement of other organs. All available specimens from affected subjects showed reduced amounts of CoQ10 and often displayed a decrease in CoQ10-dependent ETC complex activities. The pathogenic role of all identified mutations was experimentally validated in a recombinant yeast model; oxidative growth, strongly impaired in strains lacking COQ4, was corrected by expression of human wild-type COQ4 cDNA but failed to be corrected by expression of COQ4 cDNAs with any of the mutations identified in affected subjects. COQ4 mutations are responsible for early-onset mitochondrial diseases with heterogeneous clinical presentations and associated with CoQ10 deficiency.


Demczuk W.H.B.,Public Health Agency of Canada | Martin I.,Public Health Agency of Canada | Griffith A.,Public Health Agency of Canada | Lefebvre B.,Laboratoire Of Sante Publique Du Quebec | And 10 more authors.
Canadian Journal of Microbiology | Year: 2013

The introduction of the 7-valent pneumococcal vaccine (PCV7) in Canada was very effective in reducing invasive pneumo-coccal disease (IPD) in children; however, increases of non-PCV7 serotypes have subsequently offset some of these reductions. A 13-valent pneumococcal vaccine (PCV13) targeting additional serotypes was implemented between 2010 and 2011, and in 2012 changes in the incidence of disease and the distribution of IPD serotypes began to emerge. The incidence of IPD in children <5 years of age declined from 18.0 to 14.2 cases per 100 000 population between 2010 and 2012; however, the incidence in ages ≥5 years remained relatively unchanged over the 3-year period, at about 9.7 cases per 100 000 population. From 2010 to 2012, PCV13 serotypes declined significantly from 66% (224/339) to 41% (101/244, p < 0.001) in children <5 years of age, and from 54% (1262/2360) to 43% (1006/2353, p < 0.001) in children ≥5 years of age. Serotypes 19A, 7F, 3, and 22F were the most common serotypes in 2012, with 19A decreasing from 19% (521/2727) to 14% (364/2620, p < 0.001), 7F decreasing from 14% (389/2727) to 12% (323/2620, p = 0.04), and 22F increasing from 7% (185/2727) to 11% (279/2620, p < 0.001) since 2010. Serotype 3 increased from 7% (23/339) to 10% (24/244) in <5-year-olds (p = 0.22) over the 3-year period. The highest rates of antimicrobial resistance were observed with clarithromycin (23%), penicillin using meningitis breakpoints (12%), clindamycin (8%), and trimethoprim-sulfamethoxazole (6%). Shifts in the distribution of IPD serotypes and reductions in the incidence of disease suggest that current immunization programs in Canada are effective in reducing the burden of IPD in children. While we acknowledge the limited data on the effectiveness of the PCV13 vaccine, to our knowledge, this study represents one of the first descriptions of the potential impact of the PCV13 vaccine in the Canadian population. Continued surveillance will be important to recognize replacement serotypes, to determine the extent of herd immunity effects in nonpaediatric populations, and to assess the overall effectiveness of PCV13 in reducing IPD in Canada.


Demczuk W.H.B.,Public Health Agency of Canada | Martin I.,Public Health Agency of Canada | Griffith A.,Public Health Agency of Canada | Lefebvre B.,Laboratoire Of Sante Publique Du Quebec | And 4 more authors.
Canadian Journal of Microbiology | Year: 2012

A baseline serotype distribution was established by age and region for 2058 invasive Streptococcus pneumoniae isolates collected during the implementation period of the 13-valent pneumococcal conjugate vaccine (PCV13) program in many parts of Canada in 2010. Serotypes 19A, 7F, and 3 were the most prevalent in all age groups, accounting for 57% in <2 year olds, 62% in 2-4 year olds, 45% in 5-14 year olds, 44% in 15-49 year olds, 41% in 50-64 year olds, and 36% in ≥65 year olds. Serotype 19A was most predominant in Western and Central Canada representing 15% and 22%, respectively, of the isolates from those regions, whereas 7F was most common in Eastern Canada with 20% of the isolates. Other prevalent serotypes include 15A, 23B, 12F, 22F, and 6C. PCV13 serotypes represented 65% of the pneumococci isolated from <2 year olds, 71% of 2-4 year olds, 61% of 5-14 year olds, 60% of 15-49 year olds, 53% of 50-64 year olds, and 49% of the ≥65 year olds. Continued monitoring of invasive pneumococcal serotypes in Canada is important to identify epidemiological trends and assess the impact of the newly introduced PCV13 vaccine on public health.


Hamula C.L.A.,University of Alberta | Hamula C.L.A.,Mount Sinai School of Medicine | Peng H.,University of Alberta | Wang Z.,University of Alberta | And 5 more authors.
Journal of Molecular Evolution | Year: 2015

Aptamers of high affinity and specificity have a wide range of analytic and clinical applications. Selection of DNA or RNA aptamer molecules usually involves systematic evolution of ligands via exponential enrichment (SELEX), in which a random DNA or RNA library is incubated with a target molecule, and the oligonucleotides that bind the target are then separated from the nonbinders, PCR amplified, and used as refined libraries in the next round of selection. Conventional SELEX methodologies require the use of purified target molecules and their immobilization onto a solid support. However, purified targets from cells are not always available, and fixing the target to a support may alter its conformation. To overcome these problems, we have developed a SELEX technique using live bacterial cells in suspension as targets, for selecting DNA aptamers specific to cell-surface molecules. Through the selection of aptamers binding to Lactobacillus acidophilus and Streptococcus pyogenes, we report here optimization of this technique and show how varying selection conditions impact the characteristics of resultant aptamer pools, including the binding affinity, selectivity, and the secondary structures. We found that the use of larger starting library sequence diversity, gel purification of the subsequent pools, and the introduction of counter-selection resulted in a more efficient SELEX process and more selective aptamers. A SELEX protocol with lower starting sequence diversity, the use of heat denaturation, and the absence of counter-selection still resulted in high-affinity aptamer sequences specific to the target cell types; however, the SELEX process was inefficient, requiring 20 rounds, and the aptamers were not specific to the strain of the bacterial cells. Strikingly, two different SELEX methodologies yielded the same sequence that bound strongly to the target S. pyogenes cells, suggesting the robustness of the bacterial cell-SELEX technique. © 2015, Springer Science+Business Media New York.


Lu C.,University of Alberta | Mahmood M.,Walter Mackenzie Health science Center | Jha N.,University of Alberta | Mandal M.,University of Alberta
Pattern Recognition | Year: 2013

In the diagnosis of skin melanoma by analyzing histopathological images, the detection of the melanocytes in the epidermis area is an important step. However, the detection of the melanocytes from the epidermis area is difficult because other keratinocytes that are very similar to the melanocytes are also present. This paper proposes a novel computer-aided technique for detection of the melanocytes in the epidermis area of skin histopathological images. An adaptive threshold technique is first applied to segment all the keratinocytes in the image. In order to distinguish the melanocytes from other keratinocytes, a novel technique based on radial line scanning is proposed to estimate the halo region of the melanocytes. Based on the estimated halo region of all the nuclei, an area ratio of estimated halo region and the nuclei is used to detect the melanocytes from all the keratinocytes. Experimental results on 40 different histopathological images of skin tissue containing 341 melanocytes show that the proposed technique provides a superior performance. © 2012 Elsevier Ltd.


Lu C.,University of Alberta | Mahmood M.,Walter Mackenzie Health science Center | Jha N.,University of Alberta | Mandal M.,University of Alberta
Analytical and Quantitative Cytology and Histology | Year: 2012

Objective: To develop a computer-aided robust nuclei segmentation technique for quantitative histopathological image analysis. Study Design: A robust nuclei segmentation technique for histopathological image analysis is proposed. The proposed technique uses a hybrid morphological reconstruction module to reduce the intensity variation within the nuclei regions and suppress the noise in the image. A local region adaptive threshold selection module based on local optimal threshold is used to segment the nuclei. The technique incorporates domain-specific knowledge of skin histopathological images for more accurate segmentation results. Results: The technique is compared to the manually labeled nuclei locations and nuclei boundaries for the performance evaluations. On different histopathological images of skin epidermis with complex background, containing more than 3000 nuclei, the technique provides a good nuclei detection performance: 88.11% sensitivity rate, 80.02% positive prediction rate and only 5.34% under-segmentation rate compared to the manually labeled nuclei locations. Compared to the 110 manually segmented nuclei regions, the proposed technique provides a good segmentation performance (in terms of the nucleus area, perimeter, and form factor). Conclusion: The proposed technique is able to provide more accurate segmentation performance compared to the existing techniques and can be employed for quantitative analysis of the histopathological images. © Science Printers and Publishers, Inc.


PubMed | University of Alberta and Walter Mackenzie Health science Center
Type: Journal Article | Journal: Journal of molecular evolution | Year: 2015

Aptamers of high affinity and specificity have a wide range of analytic and clinical applications. Selection of DNA or RNA aptamer molecules usually involves systematic evolution of ligands via exponential enrichment (SELEX), in which a random DNA or RNA library is incubated with a target molecule, and the oligonucleotides that bind the target are then separated from the nonbinders, PCR amplified, and used as refined libraries in the next round of selection. Conventional SELEX methodologies require the use of purified target molecules and their immobilization onto a solid support. However, purified targets from cells are not always available, and fixing the target to a support may alter its conformation. To overcome these problems, we have developed a SELEX technique using live bacterial cells in suspension as targets, for selecting DNA aptamers specific to cell-surface molecules. Through the selection of aptamers binding to Lactobacillus acidophilus and Streptococcus pyogenes, we report here optimization of this technique and show how varying selection conditions impact the characteristics of resultant aptamer pools, including the binding affinity, selectivity, and the secondary structures. We found that the use of larger starting library sequence diversity, gel purification of the subsequent pools, and the introduction of counter-selection resulted in a more efficient SELEX process and more selective aptamers. A SELEX protocol with lower starting sequence diversity, the use of heat denaturation, and the absence of counter-selection still resulted in high-affinity aptamer sequences specific to the target cell types; however, the SELEX process was inefficient, requiring 20 rounds, and the aptamers were not specific to the strain of the bacterial cells. Strikingly, two different SELEX methodologies yielded the same sequence that bound strongly to the target S. pyogenes cells, suggesting the robustness of the bacterial cell-SELEX technique.

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