S. Sayers - Academia.edu (original) (raw)

Papers by S. Sayers

Nucleic Acids Research, 2011

Protective antigens are specifically targeted by the acquired immune response of the host and are... more Protective antigens are specifically targeted by the acquired immune response of the host and are able to induce protection in the host against infectious and non-infectious diseases. Protective antigens play important roles in vaccine development, as biological markers for disease diagnosis, and for analysis of fundamental host immunity against diseases. Protegen is a web-based central database and analysis system that curates, stores and analyzes protective antigens. Basic antigen information and experimental evidence are curated from peer-reviewed articles. More detailed gene/protein information (e.g. DNA and protein sequences, and COG classification) are automatically extracted from existing databases using internally developed scripts. Bioinformatics programs are also applied to compute different antigen features, such as protein weight and pI, and subcellular localizations of bacterial proteins. Presently, 590 protective antigens have been curated against over 100 infectious d...

To determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health-r... more To determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health-related quality of life (HRQL) in heart failure (HF). Methods and results Adults with chronic HF were enrolled into a prospective cohort study. Data were obtained from 280 subjects enrolled from three sites in the northeastern USA; 242 completed the 6-month study. At baseline, cohorts with and without EDS were identified using the Epworth Sleepiness Scale. Each EDS group was further subdivided into those with and without impaired cognition using a battery of five neuropsychological tests. Two disease-specific measures, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Functional Outcomes of Sleep Questionnaire (FOSQ), were used to measure HRQL. General linear modelling of square-transformed variables was used to test the hypothesis that cohort membership was a significant predictor of HRQL. At 6 months the remaining sample was 62.5 [standard deviation (SD) 12] years old, mostly male (63%), white (65%), and functionally compromised [72% New York Heart Association (NYHA) class III/IV]. The cohort with both EDS and impaired cognition had the lowest KCCQ overall summary score (60.5 + 22.5) compared with the cohort without EDS or impaired cognition (74.6 + 17.4, P ≤ 0.001). A similar effect was seen on the FOSQ (16.0 + 2.8 vs. 18.5 + 2.2, P , 0.001). Conclusion Impaired cognition alone did not explain poor HRQL, but the addition of EDS poses a significant risk for poor HRQL. Interventions designed to influence EDS may improve HRQL in this population.

The molecular events linking lipid accumulation in atherosclerotic plaques to complications such ... more The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-Apoe Ϫ/Ϫ mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K (Ctsk) expression. We now show increased cathepsin K immunostaining and increased cysteinyl proteinase activity using near infrared fluorescence imaging over proximal aortas of Apoe Ϫ/Ϫ , Npc1 Ϫ/Ϫ mice. In mechanistic studies, cholesterol loading of macrophage plasma membranes (cyclodextrin-cholesterol) or endosomal system (AcLDLϩU18666A or Npc1 null mutation) activated Toll-like receptor (TLR) signaling, leading to sustained phosphorylation of p38 mitogen-activated protein kinase and induction of p38 targets, including Ctsk, S100a8, Mmp8, and Mmp14. Studies in macrophages from knockout mice showed major roles for TLR4, following plasma membrane cholesterol loading, and for TLR3, after late endosomal loading. TLR signaling via p38 led to phosphorylation and activation of the transcription factor Microphthalmia transcription factor, acting at E-box elements in the Ctsk promoter. These studies suggest that free cholesterol enrichment of either plasma or endosomal membranes in macrophages leads to activation of signaling via various TLRs, prolonged p38 mitogen-activated protein kinase activation, and induction of Mmps, Ctsk, and S100a8, potentially contributing to plaque complications. (Circ Res. 2009;104:455-465.

Background: Excessive daytime sleepiness may be determined by a number of factors including perso... more Background: Excessive daytime sleepiness may be determined by a number of factors including personal characteristics, co-morbidities and socioeconomic conditions. In this study we identified factors associated with excessive daytime sleepiness in 2 First Nation communities in rural Saskatchewan. Methods: Data for this study were from a 2012-13 baseline assessment of the First Nations Lung Health Project, in collaboration between two Cree First Nation reserve communities in Saskatchewan and researchers at the University of Saskatchewan. Community research assistants conducted the assessments in two stages. In the first stage, brochures describing the purpose and nature of the project were distributed on a house by house basis. In the second stage, all individuals age 17 years and older not attending school in the participating communities were invited to the local health care center to participate in interviewer-administered questionnaires and clinical assessments. Excessive daytime sleepiness was defined as Epworth Sleepiness Scale score > 10. Results: Of 874 persons studied, 829 had valid Epworth Sleepiness Scale scores. Of these, 91(11.0%) had excessive daytime sleepiness; 12.4% in women and 9.6% in men. Multivariate logistic regression analysis indicated that respiratory comorbidities, environmental exposures and loud snoring were significantly associated with excessive daytime sleepiness. Conclusions: Excessive daytime sleepiness in First Nations peoples living on reserves in rural Saskatchewan is associated with factors related to respiratory co-morbidities, conditions of poverty, and loud snoring.

Family Practice, 2006

Sayers SL, White T, Zubritsky C, Oslin DW. Family involvement in the care of healthy medical outp... more Sayers SL, White T, Zubritsky C, Oslin DW. Family involvement in the care of healthy medical outpatients. Family Practice 2006; 23: 317-324. Background. Although the involvement of patients' family members in office visits has been examined extensively, less is known about the involvement of family members in supporting patients' medical care outside of office visits.

Nucleic Acids Research, 2011

Protective antigens are specifically targeted by the acquired immune response of the host and are... more Protective antigens are specifically targeted by the acquired immune response of the host and are able to induce protection in the host against infectious and non-infectious diseases. Protective antigens play important roles in vaccine development, as biological markers for disease diagnosis, and for analysis of fundamental host immunity against diseases. Protegen is a web-based central database and analysis system that curates, stores and analyzes protective antigens. Basic antigen information and experimental evidence are curated from peer-reviewed articles. More detailed gene/protein information (e.g. DNA and protein sequences, and COG classification) are automatically extracted from existing databases using internally developed scripts. Bioinformatics programs are also applied to compute different antigen features, such as protein weight and pI, and subcellular localizations of bacterial proteins. Presently, 590 protective antigens have been curated against over 100 infectious d...

To determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health-r... more To determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health-related quality of life (HRQL) in heart failure (HF). Methods and results Adults with chronic HF were enrolled into a prospective cohort study. Data were obtained from 280 subjects enrolled from three sites in the northeastern USA; 242 completed the 6-month study. At baseline, cohorts with and without EDS were identified using the Epworth Sleepiness Scale. Each EDS group was further subdivided into those with and without impaired cognition using a battery of five neuropsychological tests. Two disease-specific measures, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Functional Outcomes of Sleep Questionnaire (FOSQ), were used to measure HRQL. General linear modelling of square-transformed variables was used to test the hypothesis that cohort membership was a significant predictor of HRQL. At 6 months the remaining sample was 62.5 [standard deviation (SD) 12] years old, mostly male (63%), white (65%), and functionally compromised [72% New York Heart Association (NYHA) class III/IV]. The cohort with both EDS and impaired cognition had the lowest KCCQ overall summary score (60.5 + 22.5) compared with the cohort without EDS or impaired cognition (74.6 + 17.4, P ≤ 0.001). A similar effect was seen on the FOSQ (16.0 + 2.8 vs. 18.5 + 2.2, P , 0.001). Conclusion Impaired cognition alone did not explain poor HRQL, but the addition of EDS poses a significant risk for poor HRQL. Interventions designed to influence EDS may improve HRQL in this population.

The molecular events linking lipid accumulation in atherosclerotic plaques to complications such ... more The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-Apoe Ϫ/Ϫ mice bearing a null mutation in the Npc1 gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K (Ctsk) expression. We now show increased cathepsin K immunostaining and increased cysteinyl proteinase activity using near infrared fluorescence imaging over proximal aortas of Apoe Ϫ/Ϫ , Npc1 Ϫ/Ϫ mice. In mechanistic studies, cholesterol loading of macrophage plasma membranes (cyclodextrin-cholesterol) or endosomal system (AcLDLϩU18666A or Npc1 null mutation) activated Toll-like receptor (TLR) signaling, leading to sustained phosphorylation of p38 mitogen-activated protein kinase and induction of p38 targets, including Ctsk, S100a8, Mmp8, and Mmp14. Studies in macrophages from knockout mice showed major roles for TLR4, following plasma membrane cholesterol loading, and for TLR3, after late endosomal loading. TLR signaling via p38 led to phosphorylation and activation of the transcription factor Microphthalmia transcription factor, acting at E-box elements in the Ctsk promoter. These studies suggest that free cholesterol enrichment of either plasma or endosomal membranes in macrophages leads to activation of signaling via various TLRs, prolonged p38 mitogen-activated protein kinase activation, and induction of Mmps, Ctsk, and S100a8, potentially contributing to plaque complications. (Circ Res. 2009;104:455-465.

Background: Excessive daytime sleepiness may be determined by a number of factors including perso... more Background: Excessive daytime sleepiness may be determined by a number of factors including personal characteristics, co-morbidities and socioeconomic conditions. In this study we identified factors associated with excessive daytime sleepiness in 2 First Nation communities in rural Saskatchewan. Methods: Data for this study were from a 2012-13 baseline assessment of the First Nations Lung Health Project, in collaboration between two Cree First Nation reserve communities in Saskatchewan and researchers at the University of Saskatchewan. Community research assistants conducted the assessments in two stages. In the first stage, brochures describing the purpose and nature of the project were distributed on a house by house basis. In the second stage, all individuals age 17 years and older not attending school in the participating communities were invited to the local health care center to participate in interviewer-administered questionnaires and clinical assessments. Excessive daytime sleepiness was defined as Epworth Sleepiness Scale score > 10. Results: Of 874 persons studied, 829 had valid Epworth Sleepiness Scale scores. Of these, 91(11.0%) had excessive daytime sleepiness; 12.4% in women and 9.6% in men. Multivariate logistic regression analysis indicated that respiratory comorbidities, environmental exposures and loud snoring were significantly associated with excessive daytime sleepiness. Conclusions: Excessive daytime sleepiness in First Nations peoples living on reserves in rural Saskatchewan is associated with factors related to respiratory co-morbidities, conditions of poverty, and loud snoring.

Family Practice, 2006

Sayers SL, White T, Zubritsky C, Oslin DW. Family involvement in the care of healthy medical outp... more Sayers SL, White T, Zubritsky C, Oslin DW. Family involvement in the care of healthy medical outpatients. Family Practice 2006; 23: 317-324. Background. Although the involvement of patients' family members in office visits has been examined extensively, less is known about the involvement of family members in supporting patients' medical care outside of office visits.