Last data update: Jun 24, 2024. (Total: 47078 publications since 2009)
Records 1-30 (of 33 Records) |
Query Trace: Parkinson A [original query] |
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Prolonged Mpox disease in people with advanced HIV: characterization of Mpox skin lesions
O'Shea J , Zucker J , Stampfer S , Cash-Goldwasser S , Minhaj FS , Dretler A , Cheeley J , Chaudhuri S , Gallitano SM , Gunaratne S , Parkinson M , Epling B , Morcock DR , Sereti I , Deleage C . J Infect Dis 2023 We report three complicated and prolonged cases of mpox in people with advanced HIV not on antiretroviral therapy (ART) at mpox diagnosis. Multiple medical countermeasures were used, including prolonged tecovirimat treatment and immune optimization with ART initiation. Immunofluorescence of skin biopsies demonstrated a dense immune infiltrate of predominantly myeloid and CD8+ T-cells, with a strong type-I interferon local response. RNAscope detected abundant replication of monkeypox virus (MPXV) in epithelial cells and dendritic cells. These data suggest that prolonged mpox in people with advanced HIV may be due to ongoing MPXV replication, warranting aggressive medical countermeasures and immune optimization. |
Improving reporting standards for polygenic scores in risk prediction studies (preprint)
Wand H , Lambert SA , Tamburro C , Iacocca MA , O'Sullivan JW , Sillari C , Kullo IJ , Rowley R , Dron JS , Brockman D , Venner E , McCarthy MI , Antoniou AC , Easton DF , Hegele RA , Khera AV , Chatterjee N , Kooperberg C , Edwards K , Vlessis K , Kinnear K , Danesh JN , Parkinson H , Ramos EM , Roberts MC , Ormond KE , Khoury MJ , Janssens Acjw , Goddard KAB , Kraft P , MacArthur JAL , Inouye M , Wojcik GL . medRxiv 2020 2020.04.23.20077099 Polygenic risk scores (PRS), often aggregating the results from genome-wide association studies, can bridge the gap between the initial discovery efforts and clinical applications for disease risk estimation. However, there is remarkable heterogeneity in the reporting of these risk scores. This lack of adherence to reporting standards hinders the translation of PRS into clinical care. The ClinGen Complex Disease Working Group, in a collaboration with the Polygenic Score (PGS) Catalog, have updated the Genetic Risk Prediction (GRIPS) Reporting Statement to the current state of the field and to enable downstream utility. Drawing upon experts in epidemiology, statistics, disease-specific applications, implementation, and policy, this 22-item reporting framework defines the minimal information needed to interpret and evaluate a PRS, especially with respect to any downstream clinical applications. Items span detailed descriptions of the study population (recruitment method, key demographic and clinical characteristics, inclusion/exclusion criteria, and outcome definition), statistical methods for both PRS development and validation, and considerations for potential limitations of the published risk score and downstream clinical utility. Additionally, emphasis has been placed on data availability and transparency to facilitate reproducibility and benchmarking against other PRS, such as deposition in the publicly available PGS Catalog. By providing these criteria in a structured format that builds upon existing standards and ontologies, the use of this framework in publishing PRS will facilitate translation of PRS into clinical care and progress towards defining best practices.Summary In recent years, polygenic risk scores (PRS) have increasingly been used to capture the genome-wide liability underlying many human traits and diseases, hoping to better inform an individual’s genetic risk. However, a lack of adherence to existing reporting standards has hindered the translation of this important tool into clinical and public health practice; in particular, details necessary for benchmarking and reproducibility are underreported. To address this gap, the ClinGen Complex Disease Working Group and Polygenic Score (PGS) Catalog have updated the Genetic Risk Prediction (GRIPS) Reporting Statement into the 22-item Polygenic Risk Score Reporting Statement (PRS-RS). This framework provides the minimal information expected of authors to promote the validity, transparency, and reproducibility of PRS by encouraging authors to detail the study population, statistical methods, and potential clinical utility of a published score. The widespread adoption of this framework will encourage rigorous methodological consideration and facilitate benchmarking to ensure high quality scores are translated into the clinic.Competing Interest StatementMIM is on the advisory panels Pfizer, Novo Nordisk, and Zoe Global; Honoraria: Merck, Pfizer, Novo Nordisk, and Eli Lilly; Research funding: Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Pfizer, Roche, Sanofi Aventis, Servier & Takeda. As of June 2019, he is an employee of Genentech with stock and stock options in Roche. No other authors have competing interests to declare.Funding StatementClinGen is primarily funded by the National Human Genome Research Institute (NHGRI), through the following three grants: U41HG006834, U41HG009649, U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the following three grants: U24HD093483, U24HD093486, U24HD093487. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additionally, the views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Research reported in this publication was supported by the National Human Genome Research Institute of the National Institutes of Health under Award Number U41HG007823 (EBI-NHGRI GWAS Catalog, PGS Catalog). In addition, we acknowledge funding from the European Molecular Biology Laboratory. Individuals were funded from the following sources: MIM was a Wellcome Investigator and an NIHR Senior Investigator with funding from NIDDK (U01-DK105535); Wellcome (090532, 098381, 106130, 203141, 212259). MI, SAL, and JD were supported by core funding from: the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). SAL is supported by a Canadian Institutes of Health Research postdoctoral fellowship (MFE-171279). JD holds a British Heart Foundation Personal Chair and a National Institute for Health Research Senior Investigator Award. This work was also supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesN/A |
Comparative genomics of the major parasitic worms (preprint)
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . bioRxiv 2017 236539 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause. |
Comparative genomics of the major parasitic worms
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . Nat Genet 2019 51 (1) 163-174 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms. |
Improving reporting standards for polygenic scores in risk prediction studies.
Wand H , Lambert SA , Tamburro C , Iacocca MA , O'Sullivan JW , Sillari C , Kullo IJ , Rowley R , Dron JS , Brockman D , Venner E , McCarthy MI , Antoniou AC , Easton DF , Hegele RA , Khera AV , Chatterjee N , Kooperberg C , Edwards K , Vlessis K , Kinnear K , Danesh JN , Parkinson H , Ramos EM , Roberts MC , Ormond KE , Khoury MJ , Janssens Acjw , Goddard KAB , Kraft P , MacArthur JAL , Inouye M , Wojcik GL . Nature 2021 591 (7849) 211-219 Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice. |
Prevalence of serum antibodies to Coxiella burnetii in Alaska Native persons from the Pribilof Islands
Kersh GJ , Fitzpatrick K , Pletnikoff K , Brubaker M , Bruce M , Parkinson A . Zoonoses Public Health 2019 67 (1) 89-92 BACKGROUND: Q fever is a febrile illness caused by infection with the bacterium Coxiella burnetii. It is most often transmitted by inhalation of the bacteria after it is shed by infected livestock. Recent studies have found very high C. burnetii infection rates among marine mammals, but it is not known if shedding by marine mammals creates a risk of Q fever among humans. To better understand infection of humans with exposure to marine mammals, the prevalence of antibodies against C. burnetii in serum samples taken from Alaskan Native persons residing on the Pribilof Islands was evaluated. The Pribilof Islands support large populations of northern fur seals infected with C. burnetii that may increase the risk of exposure for island residents. METHODS: Serum testing for IgG antibodies against C. burnetii (phase I and phase II) was performed, and demographic data were analysed utilizing banked serum specimens drawn from island residents from 1980 to 2000. RESULTS: The overall seroprevalence rate was 11.6% (95% CI = 9.3%-14.4%; 72/621). This is higher than the previously reported 3.1% (95% CI = 2.1%-4.3%) seroprevalence for the U.S. POPULATION: CONCLUSIONS: These results suggest that Alaskan Native persons may be at higher risk for exposure to C. burnetii than the general US. population, possibly due to proximity to large populations of infected marine mammals. |
Human seroprevalence to 11 zoonotic pathogens in the U.S. Arctic, Alaska
Miernyk KM , Bruden D , Parkinson AJ , Hurlburt D , Klejka J , Berner J , Stoddard RA , Handali S , Wilkins PP , Kersh GJ , Fitzpatrick K , Drebot MA , Priest JW , Pappert R , Petersen JM , Teshale E , Hennessy TW , Bruce MG . Vector Borne Zoonotic Dis 2019 19 (8) 563-575 BACKGROUND: Due to their close relationship with the environment, Alaskans are at risk for zoonotic pathogen infection. One way to assess a population's disease burden is to determine the seroprevalence of pathogens of interest. The objective of this study was to determine the seroprevalence of 11 zoonotic pathogens in people living in Alaska. METHODS: In a 2007 avian influenza exposure study, we recruited persons with varying wild bird exposures. Using sera from this study, we tested for antibodies to Cryptosporidium spp., Echinococcus spp., Giardia intestinalis, Toxoplasma gondii, Trichinella spp., Brucella spp., Coxiella burnetii, Francisella tularensis, California serogroup bunyaviruses, and hepatitis E virus (HEV). RESULTS: Eight hundred eighty-seven persons had sera tested, including 454 subsistence bird hunters and family members, 160 sport bird hunters, 77 avian wildlife biologists, and 196 persons with no wild bird exposure. A subset (n = 481) of sera was tested for California serogroup bunyaviruses. We detected antibodies to 10/11 pathogens. Seropositivity to Cryptosporidium spp. (29%), California serotype bunyaviruses (27%), and G. intestinalis (19%) was the most common; 63% (301/481) of sera had antibodies to at least one pathogen. Using a multivariable logistic regression model, Cryptosporidium spp. seropositivity was higher in females (35.7% vs. 25.0%; p = 0.01) and G. intestinalis seropositivity was higher in males (21.8% vs. 15.5%; p = 0.02). Alaska Native persons were more likely than non-Native persons to be seropositive to C. burnetii (11.7% vs. 3.8%; p = 0.005) and less likely to be seropositive to HEV (0.4% vs. 4.1%; p = 0.01). Seropositivity to Cryptosporidium spp., C. burnetii, HEV, and Echinococcus granulosus was associated with increasing age (p </= 0.01 for all) as was seropositivity to >/=1 pathogen (p < 0.0001). CONCLUSION: Seropositivity to zoonotic pathogens is common among Alaskans with the highest to Cryptosporidium spp., California serogroup bunyaviruses, and G. intestinalis. This study provides a baseline for use in assessing seroprevalence changes over time. |
Tuberculosis in the circumpolar region, 2006-2012
Bourgeois AC , Zulz T , Bruce MG , Stenz F , Koch A , Parkinson A , Hennessy T , Cooper M , Newberry C , Randell E , Proulx JF , Hanley BE , Soini H , Arnesen TM , Mariandyshev A , Jonsson J , Soborg B , Wolfe J , Balancev G , De Neergaard RB , Archibald CP . Int J Tuberc Lung Dis 2018 22 (6) 641-648 Setting: The northern circumpolar jurisdictions Canada (Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Russian Federation (Arkhangelsk), Sweden and the United States (Alaska). Objective : To describe and compare demographic, clinical and laboratory characteristics, including drug resistance and treatment completion, of tuberculosis (TB) cases in the northern circumpolar populations. Design: Descriptive analysis of all active TB cases reported from 2006 to 2012 for incidence rate (IR), age and sex distribution, sputum smear and diagnostic site characteristics, drug resistance and treatment completion rates. Results : The annual IR of TB disease ranged from a low of 4.3 per 100 000 population in Northern Sweden to a high of 199.5/100 000 in Nunavik, QC, Canada. For all jurisdictions, IR was higher for males than for females. Yukon had the highest proportion of new cases compared with retreatment cases (96.6%). Alaska reported the highest percentage of laboratory-confirmed cases (87.4%). Smear-positive pulmonary cases ranged from 25.8% to 65.2%. Multidrug-resistant cases ranged from 0% (Northern Canada) to 46.3% (Arkhangelsk). Treatment outcome data, available up to 2011, demonstrated >80% treatment completion for four of the 10 jurisdictions. Conclusion: TB remains a serious public health issue in the circumpolar regions. Surveillance data contribute toward a better understanding and improved control of TB in the north. |
Giardia and Cryptosporidium antibody prevalence and correlates of exposure among Alaska residents, 2007-2008
Mosites E , Miernyk K , Priest JW , Bruden D , Hurlburt D , Parkinson A , Klejka J , Hennessy T , Bruce MG . Epidemiol Infect 2018 146 (7) 1-7 Giardia duodenalis and Cryptosporidium spp. are common intestinal protozoa that can cause diarrhoeal disease. Although cases of infection with Giardia and Cryptosporidium have been reported in Alaska, the seroprevalence and correlates of exposure to these parasites have not been characterised. We conducted a seroprevalence survey among 887 residents of Alaska, including sport hunters, wildlife biologists, subsistence bird hunters and their families and non-exposed persons. We tested serum using a multiplex bead assay to evaluate antibodies to the Giardia duodenalis variant-specific surface protein conserved structural regions and to the Cryptosporidium parvum 17- and 27-kDa antigens. Approximately one third of participants in each group had evidence of exposure to Cryptosporidium. Prevalence of Giardia antibody was highest among subsistence hunters and their families (30%), among whom positivity was associated with lack of community access to in-home running water (adjusted prevalence ratio [aPR] 1.15, 95% confidence interval (CI) 1.02-1.28) or collecting rain, ice, or snow to use as drinking water (aPR 1.09, 95% CI 1.01-1.18). Improving in-home water access for entire communities could decrease the risk of exposure to Giardia. |
Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti-Helicobacter pylori IgG antibodies
Miernyk KM , Bulkow LR , Gold BD , Bruce MG , Hurlburt DH , Griffin PM , Swerdlow DL , Cook K , Hennessy TW , Parkinson AJ . Helicobacter 2018 23 (3) e12482 BACKGROUND: Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection. METHODS: A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old. RESULTS: We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age >/= 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered. CONCLUSIONS: Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity. |
No geographic correlation between Lyme disease and death due to 4 neurodegenerative disorders, United States, 2001-2010
Forrester JD , Kugeler KJ , Perea AE , Pastula DM , Mead PS . Emerg Infect Dis 2015 21 (11) 2036-9 Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were identified. Lyme disease incidence per US state was not correlated with rates of death due to ALS, MS, or Parkinson disease; however, an inverse correlation was detected between Lyme disease and Alzheimer disease. The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions. |
Climate change in the North American Arctic: a One Health perspective
Dudley JP , Hoberg EP , Jenkins EJ , Parkinson AJ . Ecohealth 2015 12 (4) 713-25 Climate change is expected to increase the prevalence of acute and chronic diseases among human and animal populations within the Arctic and subarctic latitudes of North America. Warmer temperatures are expected to increase disease risks from food-borne pathogens, water-borne diseases, and vector-borne zoonoses in human and animal populations of Arctic landscapes. Existing high levels of mercury and persistent organic pollutant chemicals circulating within terrestrial and aquatic ecosystems in Arctic latitudes are a major concern for the reproductive health of humans and other mammals, and climate warming will accelerate the mobilization and biological amplification of toxic environmental contaminants. The adverse health impacts of Arctic warming will be especially important for wildlife populations and indigenous peoples dependent upon subsistence food resources from wild plants and animals. Additional research is needed to identify and monitor changes in the prevalence of zoonotic pathogens in humans, domestic dogs, and wildlife species of critical subsistence, cultural, and economic importance to Arctic peoples. The long-term effects of climate warming in the Arctic cannot be adequately predicted or mitigated without a comprehensive understanding of the interactive and synergistic effects between environmental contaminants and pathogens in the health of wildlife and human communities in Arctic ecosystems. The complexity and magnitude of the documented impacts of climate change on Arctic ecosystems, and the intimacy of connections between their human and wildlife communities, makes this region an appropriate area for development of One Health approaches to identify and mitigate the effects of climate warming at the community, ecosystem, and landscape scales. |
The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: expert commentary
McMahon BJ , Bruce MG , Koch A , Goodman KJ , Tsukanov V , Mulvad G , Borresen ML , Sacco F , Barrett D , Westby S , Parkinson AJ . Epidemiol Infect 2015 144 (2) 1-9 Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to 'test and treat' those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment of H. pylori in high-prevalence countries. They concluded that in Arctic countries where H. pylori prevalence exceeds 60%, treatment of persons with H. pylori infection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia. |
Incidence and prevalence of Parkinson's disease among Navajo people living in the Navajo nation
Gordon PH , Mehal JM , Holman RC , Bartholomew ML , Cheek JE , Rowland AS . Mov Disord 2015 30 (5) 714-20 Parkinson's disease (PD) is largely unstudied among American Indians. Unique populations might harbor clues to elusive causes. We describe the incidence and prevalence of PD among Navajo people residing in the Navajo Nation, home to the largest American Indian tribe in the United States. We analyzed 2001-2011 inpatient and outpatient visit data for Navajo people obtained from the Indian Health Service, which provides health care to American Indian people living on the Navajo Reservation. Cases were defined by at least two inpatient or outpatient visits with the diagnosis of PD. Crude and age-adjusted incidence and prevalence rates were calculated overall as well as by age, sex, region of residence, and time period. Five hundred twenty-four Navajo people with median age-at-onset of 74.0 years were diagnosed with PD during the study period, yielding an average annual crude incidence rate of 22.5/100,000. Age-specific incidence was 232.0 for patients 65 years of age or older and 302.0 for 80 years of age or older. Age-adjusted incidence was 35.9 overall (238.1 for ≥65 years), was higher in men than in women (47.5 vs. 27.7; P < 0.001), varied by region (P = 0.03), and was similar between time periods (2002-2004 vs. 2009-2011). The age-adjusted point prevalence rate was 261.0. The rate of PD among Navajo People appears to be as high as or higher than rates reported in many other populations. Rates increased to the highest age group, consistent with population-based studies. Further investigation is warranted to examine risk factors for PD in this remote population. (c) 2015 International Parkinson and Movement Disorder Society. |
Climate change and infectious diseases in the Arctic: establishment of a circumpolar working group
Parkinson AJ , Evengard B , Semenza JC , Ogden N , Borresen ML , Berner J , Brubaker M , Sjostedt A , Evander M , Hondula DM , Menne B , Pshenichnaya N , Gounder P , Larose T , Revich B , Hueffer K , Albihn A . Int J Circumpolar Health 2014 73 25163 The Arctic, even more so than other parts of the world, has warmed substantially over the past few decades. Temperature and humidity influence the rate of development, survival and reproduction of pathogens and thus the incidence and prevalence of many infectious diseases. Higher temperatures may also allow infected host species to survive winters in larger numbers, increase the population size and expand their habitat range. The impact of these changes on human disease in the Arctic has not been fully evaluated. There is concern that climate change may shift the geographic and temporal distribution of a range of infectious diseases. Many infectious diseases are climate sensitive, where their emergence in a region is dependent on climate-related ecological changes. Most are zoonotic diseases, and can be spread between humans and animals by arthropod vectors, water, soil, wild or domestic animals. Potentially climate-sensitive zoonotic pathogens of circumpolar concern include Brucella spp., Toxoplasma gondii, Trichinella spp., Clostridium botulinum, Francisella tularensis, Borrelia burgdorferi, Bacillus anthracis, Echinococcus spp., Leptospira spp., Giardia spp., Cryptosporida spp., Coxiella burnetti, rabies virus, West Nile virus, Hantaviruses, and tick-borne encephalitis viruses. |
Reinfection after successful eradication of Helicobacter pylori in three different populations in Alaska
Bruce MG , Bruden DL , Morris JM , Reasonover AL , Sacco F , Hurlburt D , Hennessy TW , Gove J , Parkinson A , Sahagun G , Davis P , Klejka J , McMahon BJ . Epidemiol Infect 2014 143 (6) 1-11 We performed a study to determine rates of reinfection in three groups followed for 2 years after successful treatment: American Indian/Alaska Native (AI/AN) persons living in urban (group 1) and rural (group 2) communities, and urban Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori infection based on a positive urea breath test (13C-UBT). After successful treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6, 12 and 24 months. At each visit, participants were asked about medication use, illnesses and risk factors for reinfection. We followed 229 persons for 2 years or until they became reinfected. H. pylori reinfection occurred in 36 persons; cumulative reinfection rates were 14.5%, 22.1%, and 12.0% for groups 1, 2, and 3, respectively. Study participants who became reinfected were more likely to have peptic ulcer disease (P = 0.02), low education level (P = 0.04), or have a higher proportion of household members infected with H. pylori compared to participants who did not become reinfected (P = 0.03). Among all three groups, reinfection occurred at rates higher than those reported for other US populations (<5% at 2 years); rural AI/AN individuals appear to be at highest risk for reinfection. |
Genomic analysis of the causative agents of coccidiosis in domestic chickens.
Reid AJ , Blake DP , Ansari HR , Billington K , Browne HP , Bryant JM , Dunn M , Hung SS , Kawahara F , Miranda-Saavedra D , Malas T , Mourier T , Naghra H , Nair M , Otto TD , Rawlings ND , Rivailler P , Sanchez-Flores A , Sanders M , Subramaniam C , Tay YL , Woo Y , Wu X , Barrell B , Dear PH , Doerig C , Gruber A , Ivens AC , Parkinson J , Rajandream MA , Shirley MW , Wan KL , Berriman M , Tomley FM , Pain A . Genome Res 2014 24 (10) 1676-85 Global production of chickens has trebled in the past two decades and they are now the most important source of dietary animal protein worldwide. Chickens are subject to many infectious diseases that reduce their performance and productivity. Coccidiosis, caused by apicomplexan protozoa of the genus Eimeria, is one of the most important poultry diseases. Understanding the biology of Eimeria parasites underpins development of new drugs and vaccines needed to improve global food security. We have produced annotated genome sequences of all seven species of Eimeria that infect domestic chickens, which reveal the full extent of previously described repeat-rich and repeat-poor regions and show that these parasites possess the most repeat-rich proteomes ever described. Furthermore, while no other apicomplexan has been found to possess retrotransposons, Eimeria is home to a family of chromoviruses. Analysis of Eimeria genes involved in basic biology and host-parasite interaction highlights adaptations to a relatively simple developmental life cycle and a complex array of co-expressed surface proteins involved in host cell binding. |
Mortality among 24,865 workers exposed to polychlorinated biphenyls (PCBs) in three electrical capacitor manufacturing plants: a ten-year update
Ruder AM , Hein MJ , Hopf NB , Waters MA . Int J Hyg Environ Health 2013 217 176-87 The objective of this analysis was to evaluate mortality among a cohort of 24,865 capacitor-manufacturing workers exposed to polychlorinated biphenyls (PCBs) at plants in Indiana, Massachusetts, and New York and followed for mortality through 2008. Cumulative PCB exposure was estimated using plant-specific job-exposure matrices. External comparisons to US and state-specific populations used standardized mortality ratios, adjusted for gender, race, age and calendar year. Among long-term workers employed 3 months or longer, within-cohort comparisons used standardized rate ratios and multivariable Poisson regression modeling. Through 2008, more than one million person-years at risk and 8749 deaths were accrued. Among long-term employees, all-cause and all-cancer mortality were not elevated; of the a priori outcomes assessed only melanoma mortality was elevated. Mortality was elevated for some outcomes of a priori interest among subgroups of long-term workers: all cancer, intestinal cancer and amyotrophic lateral sclerosis (women); melanoma (men); melanoma and brain and nervous system cancer (Indiana plant); and melanoma and multiple myeloma (New York plant). Standardized rates of stomach and uterine cancer and multiple myeloma mortality increased with estimated cumulative PCB exposure. Poisson regression modeling showed significant associations with estimated cumulative PCB exposure for prostate and stomach cancer mortality. For other outcomes of a priori interest - rectal, liver, ovarian, breast, and thyroid cancer, non-Hodgkin lymphoma, Alzheimer disease, and Parkinson disease - neither elevated mortality nor positive associations with PCB exposure were observed. Associations between estimated cumulative PCB exposure and stomach, uterine, and prostate cancer and myeloma mortality confirmed our previous positive findings. |
Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone
Irwin DJ , Abrams JY , Schonberger LB , Leschek EW , Mills JL , Lee VM , Trojanowski JQ . JAMA Neurol 2013 70 (4) 462-8 IMPORTANCE: Growing evidence of cell-to-cell transmission of neurodegenerative disease (ND)-associated proteins (NDAPs) (ie, tau, Abeta, and alpha-synuclein) suggests possible similarities to the infectious prion protein (PrPsc) in spongiform encephalopathies. There are limited data on the potential human-to-human transmission of NDAPs associated with Alzheimer disease (AD) and other non-PrPsc ND. OBJECTIVE: To examine evidence for human-to-human transmission of AD, Parkinson disease (PD), and related NDAPs in cadaveric human growth hormone (c-hGH) recipients. DESIGN: We conducted a detailed immunohistochemical analysis of pathological NDAPs other than PrPsc in human pituitary glands. We also searched for ND in recipients of pituitary-derived c-hGH by reviewing the National Hormone and Pituitary Program (NHPP) cohort database and medical literature. SETTING: University-based academic center and agencies of the US Department of Health and Human Services. PARTICIPANTS: Thirty-four routine autopsy subjects (10 non-ND controls and 24 patients with ND) and a US cohort of c-hGH recipients in the NHPP. MAIN OUTCOME MEASURES: Detectable NDAPs in human pituitary sections and death certificate reports of non-PrPsc ND in the NHPP database. RESULTS: We found mild amounts of pathological tau, Abeta, and alpha-synuclein deposits in the adeno/neurohypophysis of patients with ND and control patients. No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic lateral sclerosis (ALS) were found among US NHPP c-hGH recipients, including 2 of the 796 decedents in the originally confirmed NHPP c-hGH cohort database. CONCLUSIONS AND RELEVANCE: Despite the likely frequent exposure of c-hGH recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease, this population of NHPP c-hGH recipients does not appear to be at increased risk of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH recipients despite the absence of pathological deposits of ALS-associated proteins (TDP-43, FUS, and ubiquilin) in human pituitary glands. In this unique in vivo model of human-to-human transmission, we found no evidence to support concerns that NDAPs underlying AD and PD transmit disease in humans despite evidence of their cell-to-cell transmission in model systems of these disorders. Further monitoring is required to confirm these conclusions. |
The effect of Helicobacter pylori infection on iron stores and iron deficiency in urban Alaska Native adults
Miernyk K , Bruden D , Zanis C , McMahon B , Sacco F , Hennessy T , Parkinson A , Bruce M . Helicobacter 2013 18 (3) 222-8 BACKGROUND: Helicobacter pylori (H. pylori) infection has been correlated with low serum ferritin and iron deficiency. As a secondary analysis of a study of H. pylori reinfection, we investigated the association of H. pylori infection and the effect of its eradication on serum ferritin and iron deficiency. METHODS: Alaska Native adults undergoing esophagogastroduodenoscopy had sera collected and a (13) C urea breath test (UBT) was performed. Those H. pylori positive were treated with an antibiotic regimen; those who tested negative 2 months after treatment were evaluated at 4, 6, 12, and 24 months by UBT and serum ferritin with an immunoradiometric assay. We excluded persons from further analysis if they were prescribed iron by their provider. RESULTS: We measured serum ferritin for 241 persons; 121/241 were H. pylori positive. The geometric mean ferritin (GMF) for persons with and without H. pylori infection was 37 mcg/L and 50 mcg/L, respectively (p = .04). At enrollment, 19/121 H. pylori-positive persons had iron deficiency compared with 8/120 H. pylori negative (p = .02). Among 66 persons tested at 24 months, the GMF was higher at 24 months (49.6 mcg/L) versus enrollment (36.5 mcg/L; p = .02). Six of 11 persons with iron deficiency at enrollment no longer had iron deficiency and had a higher GMF (p = .02) 24 months after treatment. CONCLUSIONS: H. pylori infection was correlated with lower serum ferritin and iron deficiency. After H. pylori eradication, serum ferritin increased and approximately half of persons resolved their iron deficiency. Testing for H. pylori infection and subsequent treatment of those positive could be considered in persons with unexplained iron deficiency. |
Neurodegenerative causes of death among retired National Football League players
Lehman EJ , Hein MJ , Baron SL , Gersic CN . Neurology 2012 79 (19) 1970-4 OBJECTIVE: To analyze neurodegenerative causes of death, specifically Alzheimer disease (AD), Parkinson disease, and amyotrophic lateral sclerosis (ALS), among a cohort of professional football players. METHODS: This was a cohort mortality study of 3,439 National Football League players with at least 5 pension-credited playing seasons from 1959 to 1988. Vital status was ascertained through 2007. For analysis purposes, players were placed into 2 strata based on characteristics of position played: nonspeed players (linemen) and speed players (all other positions except punter/kicker). External comparisons with the US population used standardized mortality ratios (SMRs); internal comparisons between speed and nonspeed player positions used standardized rate ratios (SRRs). RESULTS: Overall player mortality compared with that of the US population was reduced (SMR 0.53, 95% confidence interval [CI] 0.48-0.59). Neurodegenerative mortality was increased using both underlying cause of death rate files (SMR 2.83, 95% CI 1.36-5.21) and multiple cause of death (MCOD) rate files (SMR 3.26, 95% CI 1.90-5.22). Of the neurodegenerative causes, results were elevated (using MCOD rates) for both ALS (SMR 4.31, 95% CI 1.73-8.87) and AD (SMR 3.86, 95% CI 1.55-7.95). In internal analysis (using MCOD rates), higher neurodegenerative mortality was observed among players in speed positions compared with players in nonspeed positions (SRR 3.29, 95% CI 0.92-11.7). CONCLUSIONS: The neurodegenerative mortality of this cohort is 3 times higher than that of the general US population; that for 2 of the major neurodegenerative subcategories, AD and ALS, is 4 times higher. These results are consistent with recent studies that suggest an increased risk of neurodegenerative disease among football players. (Neurology 2012;79:1-1) |
The International Polar Year: continuing the Arctic human health legacy
Parkinson AJ . Int J Circumpolar Health 2011 70 (5) 447-9 The International Polar Year (IPY) presenteda unique opportunity to further advance thecircumpolar human health agendas of theInternational Union for Circumpolar Healthand the Arctic Council. The Arctic HumanHealth Initiative (AHHI) was an IPY coordinatingproject that aimed to serve as a focalpoint for human health research, education, outreach, and communication activities duringIPY (2007–2009). |
Diagnostic accuracy of tests for Helicobacter pylori in an Alaska Native population
Bruden DL , Bruce MG , Miernyk KM , Morris J , Hurlburt D , Hennessy TW , Peters H , Sacco F , Parkinson AJ , McMahon BJ . World J Gastroenterol 2011 17 (42) 4682-8 AIM: To evaluate the accuracy of two non-invasive tests in a population of Alaska Native persons. High rates of Helicobacter pylori (H. pylori) infection, H. pylori treatment failure, and gastric cancer in this population necessitate documentation of infection status at multiple time points over a patient's life. METHODS: In 280 patients undergoing endoscopy, H. pylori was diagnosed by culture, histology, rapid urease test, (13)C urea breath test (UBT), and immunoglobulin G antibodies to H. pylori in serum. The performances of (13)C-UBT and antibody test were compared to a gold standard defined by a positive H. pylori test by culture or, in case of a negative culture result, by positive histology and a positive rapid urease test. RESULTS: The sensitivity and specificity of the (13)C-UBT were 93% and 88%, respectively, relative to the gold standard. The antibody test had an equivalent sensitivity of 93% with a reduced specificity of 68%. The false positive results for the antibody test were associated with previous treatment for an H. pylori infection [relative risk (RR) = 2.8]. High levels of antibodies to H. pylori were associated with chronic gastritis and male gender, while high scores in the (13)C-UBT test were associated with older age and with the H. pylori bacteria load on histological examination (RR = 4.4). CONCLUSION: The (13)C-UBT outperformed the antibody test for H. pylori and could be used when a non-invasive test is clinically necessary to document treatment outcome or when monitoring for reinfection. |
Manganese accumulation in nail clippings as a biomarker of welding fume exposure and neurotoxicity
Sriram K , Lin GX , Jefferson AM , Roberts JR , Andrews RN , Kashon ML , Antonini JM . Toxicology 2011 291 73-82 Occupational exposure to welding fumes (WF) is thought to cause Parkinson's disease (PD)-like neurological dysfunction. An apprehension that WF may accelerate the onset of PD also exists. Identifying reliable biomarkers of exposure and neurotoxicity are therefore critical for biomonitoring and neurological risk characterization of WF exposure. Manganese (Mn) in welding consumables is considered the causative factor for the neurological deficits seen in welders. Hence, we sought to determine if Mn accumulation in blood or nail clippings can be a marker for adverse exposure and neurotoxicity. To model this, rats were exposed by intratracheal instillation to dissolved or suspended fume components collected from gas metal arc-mild steel (GMA-MS) or manual metal arc-hard surfacing (MMA-HS) welding. Trace element analysis revealed selective Mn accumulation in dopaminergic brain areas, striatum (STR) and midbrain (MB), following exposure to the two fumes. This caused dopaminergic abnormality as evidenced by loss of striatal tyrosine hydroxylase (Th; 25-32% decrease) and Parkinson disease (autosomal recessive, early onset) 7 (Park7; 25-46% decrease) proteins. While blood Mn was not detectable, Mn levels in nails strongly correlated with the pattern of Mn accumulation in the striatum (R(2)=0.9386) and midbrain (R(2)=0.9332). Exposure to manganese chloride (MnCl(2)) caused similar Mn accumulation in STR, MB and nail. Our findings suggest that nail Mn has the potential to be a sensitive and reliable biomarker for long-term Mn exposure and associated neurotoxicity. The non-invasive means by which nail clippings can be collected, stored, and transported with relative ease, make it an attractive surrogate for biomonitoring WF exposures in occupational settings. |
Characterization of Helicobacter pylori cagA and vacA genotypes among Alaskans and their correlation with clinical disease.
Miernyk K , Morris J , Bruden D , McMahon B , Hurlburt D , Sacco F , Parkinson A , Hennessy T , Bruce M . J Clin Microbiol 2011 49 (9) 3114-21 Helicobacter pylori infection is common in Alaska. The development of severe H. pylori disease is partially determined by the virulence of the infecting strain. Here we present vacA and cagA genotype data for H. pylori strains isolated from Alaskans and their correlation with clinical disease. We enrolled patients scheduled for esophagogastroduodenoscopy and positive for H. pylori infection. Gastric biopsy specimens from the stomach antrum and fundus were cultured. We performed PCR analysis of the H. pylori vacA gene and for the presence of the cagA gene and cagA empty site. We genotyped 515 H. pylori samples from 220 Native and 66 non-Native Alaskans. We detected the cagA gene in 242/286 (85%) persons; of 222 strains that could be subtyped, 95% (212) were non-Asian cagA and 3% (6) were East Asian cagA. After removing mixed infections (n = 17), 83% of H. pylori strains had either the vacA s1m1 (120/269) or s2m2 (103/269) genotype. Sixty-six percent (68/103) of H. pylori strains with the vacA s2m2 genotype also contained the cagA gene. Infection with an H. pylori strain having the cagA gene or vacA s1m1 genotype (compared with s1m2 and s2m2) was associated with a decreased risk of esophagitis (P = 0.003 and 0.0003, respectively). Infection with an H. pylori strain having the vacA s1m1 genotype (compared with s1m2 and s2m2) was associated with an increased risk of peptic ulcer disease (PUD) (P = 0.003). The majority of H. pylori strains in this study carried the non-Asian cagA gene and either the vacA s1m1 or s2m2 genotype. A majority of H. pylori strains with the vacA s2m2 genotype also contained the cagA gene. There was an association of H. pylori genotype with esophagitis and PUD. |
Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program
McMahon BJ , Bulkow LR , Singleton RJ , Williams J , Snowball M , Homan C , Parkinson AJ . Hepatology 2011 54 (3) 801-7 Alaska Native people experienced the highest rates of acute and chronic hepatitis B virus (HBV) infection, and hepatocellular carcinoma (HCC) in the United States. We examine the effect of a universal newborn immunization with hepatitis B vaccine and mass population screening immunization program initiated in 1984 on rates of HBV and HCC in children 25 years later. During this time period, the population of Alaska Native people grew from an estimated 75,000 to 130,000 persons. A surveillance system to detect acute HBV infection in Alaska Native facilities was established in 1981. Cases of HCC in children under 20 years of age were identified using a National Cancer Institute (NCI) funded Cancer Registry established in 1969 coupled with an active surveillance program of screening persons with chronic HBV semiannually for alpha-fetoprotein since 1982. The incidence of acute symptomatic HBV infection in persons < 20 years of age fell from cases 19/100,000 in 1981-1982 to 0/100,000 in 1993-94, respectively. No cases of acute HBV have occurred in children since 1992. The incidence of HCC in persons < 20 years decreased from 3/100,000 in 1984-1988 to zero in 1995-1999 and no cases have occurred since 1999. The number of identified HBsAg-positive children < 20 years in the Alaska Native Population declined from 657 in 1987 to two in 2008. Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Native has eliminated HCC and acute symptomatic HBV infection among Alaska Native children and this approach is the best way to prevent HBV related disease in children. (HEPATOLOGY 2011.). |
The international circumpolar surveillance interlaboratory quality control program for Streptococcus pneumoniae, 1999 - 2008
Reasonover A , Zulz T , Bruce MG , Bruden D , Jette L , Kaltoft M , Lambertsen L , Parkinson A , Rudolph K , Lovgren M . J Clin Microbiol 2010 49 (1) 138-43 The International Circumpolar Surveillance (ICS) Project was initiated in 1999 to conduct population-based surveillance for invasive pneumococcal disease in select regions of the Arctic. An inter-laboratory quality control (QC) program for pneumococcal serotyping and antibiotic susceptibility testing was incorporated into ICS by reference laboratories in Northern Canada (Laboratoire de Sante Publique du Quebec (LSPQ) in Sainte-Anne de Bellevue, Quebec, National Centre for Streptococcus (NCS) in Edmonton, Alberta) and Alaska (Arctic Investigations Program, (AIP). The World Health Organization's Collaborating Centre for Reference and Research on Pneumococci at Statens Serum Institute (SSI) in Copenhagen, Denmark, joined the QC Program in 2004. The Iceland Reference Laboratory (IRL) in Reykjavik joined the QC Program in 2006, but due to low sample sizes data from IRL are not included in this report. From 1999 through 2008, 190 isolates were distributed among four laboratories (AIP, NCS, LSPQ, and SSI). The overall serotype concordance was 95.8%, and overall serogroup concordance was 97.4%. The overall modal MIC concordance for testing by broth microdilution (BMD) and agar dilution was >96% for all the antibiotics except for erythromycin (92.1%) and clindamycin (89.5%). MIC comparisons between the Etest(R) and broth microdilution (BMD) resulted in lower concordance for erythromycin (73.9%), clindamycin (65.5%), and trimethoprim-sulfamethoxazole (80%); however categorical concordance (susceptible, resistant) remained high at 98.6%, 89.1%, and 90.9%, respectively. Our data demonstrate a high correlation of serotyping and antimicrobial susceptibility testing results between four participating laboratories. |
SNPs in CAST are associated with Parkinson disease: a confirmation study
Allen AS , Satten GA . Am J Med Genet B Neuropsychiatr Genet 2010 153B (4) 973-9 Using data from the National Institutes of Neurological disease and Stroke's (NINDS) study of Parkinson disease (PD), we recently reported that single nucleotide polymorphisms (SNPs) in a region containing the Calpastatin (CAST) gene were associated with PD. Here we follow up this finding with an analysis of the Center for Inherited Disease Research's (CIDR) genome-wide association study in familial PD. After adjusting for population stratification and multiple testing, we find a significant association (P = 0.0167) between PD and SNP rs1559085 in CAST. These findings confirm CAST/PD associations in a second, independent, dataset and suggest that CAST be prioritized for further investigation. |
Improving human health in the Arctic: the expanding role of the Arctic Council's Sustainable Development Working Group
Parkinson AJ . Int J Circumpolar Health 2010 69 (3) 304-13 Human health is now a critical component of the Arctic Council's sustainable development program. The newly formed Arctic Human Health Expert Group (AHHEG), a subsidiary body of experts within the Sustainable Development Working Group (SDWG), will focus on identifying human health priorities that will improve the health of Arctic residents; engage experts in the field to evaluate possible actions; strengthen co-operation and collaboration between Arctic Council working groups and other Arctic co-operatives; and promote the translation of research into actions that will improve the health of Arctic peoples. |
A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone
Jang SW , Liu X , Yepes M , Shepherd KR , Miller GW , Liu Y , Wilson WD , Xiao G , Blanchi B , Sun YE , Ye K . Proc Natl Acad Sci U S A 2010 107 (6) 2687-92 Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation, synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic profile that limits its therapeutic potential. Here we report the identification of 7,8-dihydroxyflavone as a bioactive high-affinity TrkB agonist that provokes receptor dimerization and autophosphorylation and activation of downstream signaling. 7,8-Dihydroxyflavone protected wild-type, but not TrkB-deficient, neurons from apoptosis. Administration of 7,8-dihydroxyflavone to mice activated TrkB in the brain, inhibited kainic acid-induced toxicity, decreased infarct volumes in stroke in a TrkB-dependent manner, and was neuroprotective in an animal model of Parkinson disease. Thus, 7,8-dihydroxyflavone imitates BDNF and acts as a robust TrkB agonist, providing a powerful therapeutic tool for the treatment of various neurological diseases. |
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