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Article ; Online: Toxoplasma gondii infection and its implications within the central nervous system.

Matta, Sumit K / Rinkenberger, Nicholas / Dunay, Ildiko R / Sibley, L David

2021 Volume 19, Issue 7, Page(s) 467–480

Abstract: Toxoplasma gondii is a parasite that infects a wide range of animals and causes zoonotic infections in humans. Although it normally only results in mild illness in healthy individuals, toxoplasmosis is a common opportunistic infection with high mortality ...

Abstract	Toxoplasma gondii is a parasite that infects a wide range of animals and causes zoonotic infections in humans. Although it normally only results in mild illness in healthy individuals, toxoplasmosis is a common opportunistic infection with high mortality in individuals who are immunocompromised, most commonly due to reactivation of infection in the central nervous system. In the acute phase of infection, interferon-dependent immune responses control rapid parasite expansion and mitigate acute disease symptoms. However, after dissemination the parasite differentiates into semi-dormant cysts that form within muscle cells and neurons, where they persist for life in the infected host. Control of infection in the central nervous system, a compartment of immune privilege, relies on modified immune responses that aim to balance infection control while limiting potential damage due to inflammation. In response to the activation of interferon-mediated pathways, the parasite deploys an array of effector proteins to escape immune clearance and ensure latent survival. Although these pathways are best studied in the laboratory mouse, emerging evidence points to unique mechanisms of control in human toxoplasmosis. In this Review, we explore some of these recent findings that extend our understanding for proliferation, establishment and control of toxoplasmosis in humans.
MeSH term(s)	Animals ; Central Nervous System Infections/immunology ; Central Nervous System Infections/parasitology ; Central Nervous System Infections/pathology ; Chronic Disease ; Humans ; Interferons/immunology ; Toxoplasma/growth & development ; Toxoplasma/pathogenicity ; Toxoplasma/physiology ; Toxoplasmosis/drug therapy ; Toxoplasmosis/immunology ; Toxoplasmosis/parasitology ; Virulence
Chemical Substances	Interferons (9008-11-1)
Language	English
Publishing date	2021-02-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/s41579-021-00518-7
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Article: Factors associated with postpartum contraception in Togo, West Africa.

Baker, Helen / McGee, Blake / Rochat, Roger / Hepburn, Kenneth / Hennink, Monique / Sibley, Lynn

African journal of reproductive health

2023 Volume 26, Issue 2, Page(s) 26–37

Abstract: The health benefits of postpartum contraception are well established. Using 2013/14 Togo Demographic and Health Survey (DHS) data, we examine the association between contraceptive use among women who gave birth within 24 months of the DHS and four health ...

Abstract	The health benefits of postpartum contraception are well established. Using 2013/14 Togo Demographic and Health Survey (DHS) data, we examine the association between contraceptive use among women who gave birth within 24 months of the DHS and four health service use indicators - antenatal care, institutional delivery, postpartum care, and immunization of the last child - in addition to socio-demographic factors. Factors associated with postpartum contraceptive use in Togo included having their last birth in a health facility, having a postnatal check within two months of birth, youngest child receiving the first diphtheria-pertussis-tetanus vaccine, wanting to space children more than two years from last birth or not have more children, living outside the Savanes region, husband's desire for number of children agreeing with the woman's, and increasing breastfeeding duration. These findings highlight the need for programming which strengthens the integration of contraception into reproductive and immunization services in Togo.
Language	English
Publishing date	2023-08-16
Publishing country	Nigeria
Document type	Journal Article
ZDB-ID	2111906-5
ISSN	1118-4841
ISSN	1118-4841
DOI	10.29063/ajrh2022/v26i2.3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A scoping review to identify and describe the characteristics of theories, models and frameworks of health research partnerships.

Tittlemier, B J / Cooper, J / Steliga, D / Woodgate, R L / Sibley, K M

Health research policy and systems

2022 Volume 20, Issue 1, Page(s) 69

Abstract: Background: Engaging users of health research, namely knowledge users, as partners in the research process may to lead to evidence that is more relevant to the users. This may optimize the uptake of evidence in healthcare practice, resulting in improved ...

Abstract	Background: Engaging users of health research, namely knowledge users, as partners in the research process may to lead to evidence that is more relevant to the users. This may optimize the uptake of evidence in healthcare practice, resulting in improved health outcomes or more efficient healthcare systems. However, barriers to involving knowledge users in the research process exist. Theories, models and frameworks may help guide the process of involving knowledge users and address barriers to engaging with knowledge users in research; however, there is little evidence identifying or describing the theories, models and frameworks of health research partnerships. Objectives: Identify and describe theories, models and frameworks of health research partnerships. Report on concepts of knowledge user engagement represented in identified theories, models and frameworks. Methods: We conducted a scoping review. Database (MEDLINE, Embase, CINAHL, PCORI) and ancestry and snowball searches were utilized. Included articles were written in English, published between January 2005 and June 2021, specific to health, a research partnership, and referred to a theory, model or framework. No critical appraisal was conducted. We developed a coding framework to extract details related to the publication (e.g. country, year) and theory, model or framework (e.g. intended users, theoretical underpinning, methodology, methods of development, purpose, concepts of knowledge user engagement). One reviewer conducted data extraction. Descriptive statistics and narrative synthesis were utilized to report the results. Results: We identified 21 874 articles in screening. Thirty-nine models or frameworks were included in data analysis, but no theory. Two models or frameworks (5%) were underpinned by theory. Literature review was the method (n = 11, 28%) most frequently used to develop a model or framework. Guiding or managing a partnership was the most frequently reported purpose of the model/framework (n = 14, 36%). The most represented concept of knowledge user engagement was principles/values (n = 36, 92%). Conclusions: The models and frameworks identified could be utilized by researchers and knowledge users to inform aspects of a health research partnership, such as guidance or implementation of a partnership. Future research evaluating the quality and applicability of the models and frameworks is necessary to help partners decide which model or framework to implement.
MeSH term(s)	Delivery of Health Care ; Humans ; Knowledge ; Narration ; Research Design ; Research Personnel
Language	English
Publishing date	2022-06-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2101196-5
ISSN	1478-4505 ; 1478-4505
ISSN (online)	1478-4505
ISSN	1478-4505
DOI	10.1186/s12961-022-00877-4
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Article ; Online: The intrinsically disordered protein TgIST from Toxoplasma gondii inhibits STAT1 signaling by blocking cofactor recruitment.

Huang, Zhou / Liu, Hejun / Nix, Jay / Xu, Rui / Knoverek, Catherine R / Bowman, Gregory R / Amarasinghe, Gaya K / Sibley, L David

Nature communications

2022 Volume 13, Issue 1, Page(s) 4047

Abstract: Signal transducer and activator of transcription (STAT) proteins communicate from cell-surface receptors to drive transcription of immune response genes. The parasite Toxoplasma gondii blocks STAT1-mediated gene expression by secreting the intrinsically ... ...

Abstract	Signal transducer and activator of transcription (STAT) proteins communicate from cell-surface receptors to drive transcription of immune response genes. The parasite Toxoplasma gondii blocks STAT1-mediated gene expression by secreting the intrinsically disordered protein TgIST that traffics to the host nucleus, binds phosphorylated STAT1 dimers, and occupies nascent transcription sites that unexpectedly remain silenced. Here we define a core region within internal repeats of TgIST that is necessary and sufficient to block STAT1-mediated gene expression. Cellular, biochemical, mutational, and structural data demonstrate that the repeat region of TgIST adopts a helical conformation upon binding to STAT1 dimers. The binding interface is defined by a groove formed from two loops in the STAT1 SH2 domains that reorient during dimerization. TgIST binding to this newly exposed site at the STAT1 dimer interface alters its conformation and prevents the recruitment of co-transcriptional activators, thus defining the mechanism of blocked transcription.
MeSH term(s)	Interferon-gamma/metabolism ; Intrinsically Disordered Proteins/genetics ; Intrinsically Disordered Proteins/metabolism ; Phosphorylation ; STAT1 Transcription Factor/metabolism ; Signal Transduction ; Toxoplasma ; src Homology Domains
Chemical Substances	Intrinsically Disordered Proteins ; STAT1 Transcription Factor ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2022-07-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-31720-7
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Article ; Online: G Protein-Coupled Receptor Kinase 2 Selectively Enhances β-Arrestin Recruitment to the D

Sánchez-Soto, Marta / Boldizsar, Noelia M / Schardien, Kayla A / Madaras, Nora S / Willette, Blair K A / Inbody, Laura R / Dasaro, Christopher / Moritz, Amy E / Drube, Julia / Haider, Raphael S / Free, R Benjamin / Hoffman, Carsten / Sibley, David R

Biomolecules

2023 Volume 13, Issue 10

Abstract: The D2 dopamine receptor (D2R) signals through both G proteins and β-arrestins to regulate important physiological processes, such as movement, reward circuitry, emotion, and cognition. β-arrestins are believed to interact with G protein-coupled ... ...

Abstract	The D2 dopamine receptor (D2R) signals through both G proteins and β-arrestins to regulate important physiological processes, such as movement, reward circuitry, emotion, and cognition. β-arrestins are believed to interact with G protein-coupled receptors (GPCRs) at the phosphorylated C-terminal tail or intracellular loops. GPCR kinases (GRKs) are the primary drivers of GPCR phosphorylation, and for many receptors, receptor phosphorylation is indispensable for β-arrestin recruitment. However, GRK-mediated receptor phosphorylation is not required for β-arrestin recruitment to the D2R, and the role of GRKs in D2R-β-arrestin interactions remains largely unexplored. In this study, we used GRK knockout cells engineered using CRISPR-Cas9 technology to determine the extent to which β-arrestin recruitment to the D2R is GRK-dependent. Genetic elimination of all GRK expression decreased, but did not eliminate, agonist-stimulated β-arrestin recruitment to the D2R or its subsequent internalization. However, these processes were rescued upon the re-introduction of various GRK isoforms in the cells with GRK2/3 also enhancing dopamine potency. Further, treatment with compound 101, a pharmacological inhibitor of GRK2/3 isoforms, decreased β-arrestin recruitment and receptor internalization, highlighting the importance of this GRK subfamily for D2R-β-arrestin interactions. These results were recapitulated using a phosphorylation-deficient D2R mutant, emphasizing that GRKs can enhance β-arrestin recruitment and activation independently of receptor phosphorylation.
MeSH term(s)	Arrestins/metabolism ; beta-Arrestins/metabolism ; G-Protein-Coupled Receptor Kinases/metabolism ; Phosphorylation ; Protein Isoforms/metabolism ; Receptors, Dopamine/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Humans ; HEK293 Cells
Chemical Substances	Arrestins ; beta-Arrestins ; G-Protein-Coupled Receptor Kinases (EC 2.7.11.16) ; Protein Isoforms ; Receptors, Dopamine ; Receptors, G-Protein-Coupled ; GRK2 protein, human (EC 2.7.11.15)
Language	English
Publishing date	2023-10-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom13101552
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Article ; Online: A scoping review to identify and describe the characteristics of theories, models and frameworks of health research partnerships

B. J. Tittlemier / J. Cooper / D. Steliga / R. L. Woodgate / K. M. Sibley

Health Research Policy and Systems, Vol 20, Iss 1, Pp 1-

2022 Volume 19

Abstract: Abstract Background Engaging users of health research, namely knowledge users, as partners in the research process may to lead to evidence that is more relevant to the users. This may optimize the uptake of evidence in healthcare practice, resulting in ... ...

Abstract	Abstract Background Engaging users of health research, namely knowledge users, as partners in the research process may to lead to evidence that is more relevant to the users. This may optimize the uptake of evidence in healthcare practice, resulting in improved health outcomes or more efficient healthcare systems. However, barriers to involving knowledge users in the research process exist. Theories, models and frameworks may help guide the process of involving knowledge users and address barriers to engaging with knowledge users in research; however, there is little evidence identifying or describing the theories, models and frameworks of health research partnerships. Objectives Identify and describe theories, models and frameworks of health research partnerships. Report on concepts of knowledge user engagement represented in identified theories, models and frameworks. Methods We conducted a scoping review. Database (MEDLINE, Embase, CINAHL, PCORI) and ancestry and snowball searches were utilized. Included articles were written in English, published between January 2005 and June 2021, specific to health, a research partnership, and referred to a theory, model or framework. No critical appraisal was conducted. We developed a coding framework to extract details related to the publication (e.g. country, year) and theory, model or framework (e.g. intended users, theoretical underpinning, methodology, methods of development, purpose, concepts of knowledge user engagement). One reviewer conducted data extraction. Descriptive statistics and narrative synthesis were utilized to report the results. Results We identified 21 874 articles in screening. Thirty-nine models or frameworks were included in data analysis, but no theory. Two models or frameworks (5%) were underpinned by theory. Literature review was the method (n = 11, 28%) most frequently used to develop a model or framework. Guiding or managing a partnership was the most frequently reported purpose of the model/framework (n = 14, 36%). The most represented ...
Keywords	Frameworks ; Knowledge translation ; Models ; Research partnerships ; Theories ; Public aspects of medicine ; RA1-1270
Subject code	306
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Response to the comments on "Human health risk assessment of pharmaceuticals and personal care products in plant tissue due to biosolids and manure amendments, and wastewater irrigation".

Prosser, R S / Sibley, P K

Environment international

2015 Volume 84, Page(s) 209–212

MeSH term(s)	Cosmetics/analysis ; Humans ; Manure ; Pharmaceutical Preparations/analysis ; Plants/chemistry ; Soil Pollutants/analysis ; Waste Water
Chemical Substances	Cosmetics ; Manure ; Pharmaceutical Preparations ; Soil Pollutants ; Waste Water
Language	English
Publishing date	2015-11
Publishing country	Netherlands
Document type	Comment ; Letter
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2015.07.007
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Article ; Online: Human health risk assessment of pharmaceuticals and personal care products in plant tissue due to biosolids and manure amendments, and wastewater irrigation.

Prosser, R S / Sibley, P K

Environment international

2015 Volume 75, Page(s) 223–233

Abstract: Amending soil with biosolids or livestock manure provides essential nutrients in agriculture. Irrigation with wastewater allows for agriculture in regions where water resources are limited. However, biosolids, manure and wastewater have all been shown to ...

Abstract	Amending soil with biosolids or livestock manure provides essential nutrients in agriculture. Irrigation with wastewater allows for agriculture in regions where water resources are limited. However, biosolids, manure and wastewater have all been shown to contain pharmaceuticals and personal care products (PPCPs). Studies have shown that PPCPs can accumulate in the tissues of plants but the risk that accumulated residues may pose to humans via consumption of edible portions is not well documented. This study reviewed the literature for studies that reported residues of PPCPs in the edible tissue of plants grown in biosolids- or manure-amended soils or irrigated with wastewater. These residues were used to determine the estimated daily intake of PPCPs for an adult and toddler. Estimated daily intake values were compared to acceptable daily intakes to determine whether PPCPs in plant tissue pose a hazard to human health. For all three amendment practices, the majority of reported residues resulted in hazard quotients <0.1. Amendment with biosolids or manure resulted in hazard quotients ≥0.1 for carbamazepine, diphenhydramine, salbutamol, triclosan, and sulfamethazine. Irrigation with wastewater resulted in hazard quotients of ≥0.1 for ambrettolid, carbamazepine, diclofenac, flunixin, lamotrigine, metoprolol, naproxen, sildenafil and tonalide. [corrected]. Many of the residues that resulted in hazard quotients ≥0.1 were due to exposing plants to concentrations of PPCPs that would not be considered relevant based on concentrations reported in biosolids and manure or unrealistic methods of exposure, which lead to artificially elevated plant residues. Our assessment indicates that the majority of individual PPCPs in the edible tissue of plants due to biosolids or manure amendment or wastewater irrigation represent a de minimis risk to human health. Assuming additivity, the mixture of PPCPs could potentially present a hazard. Further work needs to be done to assess the risk of the mixture of PPCPs that may be present in edible tissue of plants grown under these three amendment practices.
MeSH term(s)	Adult ; Agriculture/methods ; Child, Preschool ; Cosmetics/analysis ; Humans ; Infant ; Manure ; Middle Aged ; Pharmaceutical Preparations/analysis ; Plants/chemistry ; Risk Assessment ; Soil Pollutants/analysis ; Waste Water ; Young Adult
Chemical Substances	Cosmetics ; Manure ; Pharmaceutical Preparations ; Soil Pollutants ; Waste Water
Language	English
Publishing date	2015-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2014.11.020
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Article ; Online: Study protocol of a randomized trial of STRIPES: a schoolyear, peer-delivered high school intervention for students with ADHD.

Macphee, Fiona L / Brewer, Stephanie K / Sibley, Margaret H / Graziano, Paulo / Raiker, Joseph S / Coxe, Stefany J / Martin, Pablo / Van Dreel, Shauntal J / Rodriguez, Mercedes Ortiz / Lyon, Aaron R / Page, Timothy F

BMC psychology

2023 Volume 11, Issue 1, Page(s) 268

Abstract: Background: Youth with ADHD are at risk of academic impairments, dropping out of high school, and dysfunction in young adulthood. Interventions delivered early in high school could prevent these harmful outcomes, yet few high school students with ADHD ... ...

Abstract	Background: Youth with ADHD are at risk of academic impairments, dropping out of high school, and dysfunction in young adulthood. Interventions delivered early in high school could prevent these harmful outcomes, yet few high school students with ADHD receive treatment due to limited access to intervention providers. This study will test a peer-delivered intervention (STRIPES) for general education 9th grade students with impairing ADHD symptoms. Methods: A type 1 hybrid effectiveness-implementation design will be used to evaluate the effectiveness of STRIPES and explore the intervention's implementability. Analyses will test the impact of STRIPES vs. enhanced school services control on target mechanisms and determine whether differences in basic cognitive profiles moderate intervention response. The acceptability and feasibility of STRIPES and treatment moderators will also be examined. Discussion: This study will generate knowledge about the effectiveness and implementability of STRIPES, which will inform dissemination efforts in the future. A peer-delivered high school intervention for organization, time management, and planning skills can provide accessible and feasible treatment targeting declines in academic motivation, grades, and attendance during the ninth-grade year. Trial registration: This study is registered on OSF Registries (10.17605/OSF.IO/Q8V6S).
MeSH term(s)	Adolescent ; Humans ; Young Adult ; Adult ; Attention Deficit Disorder with Hyperactivity ; Schools ; Students ; Motivation ; Registries ; Randomized Controlled Trials as Topic
Language	English
Publishing date	2023-09-05
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	2705921-2
ISSN	2050-7283 ; 2050-7283
ISSN (online)	2050-7283
ISSN	2050-7283
DOI	10.1186/s40359-023-01291-3
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Article ; Online: An Assessment of the Toxicity of Pesticide Mixtures in Periphyton from Agricultural Streams to the Mayfly Neocloeon triangulifer.

Ijzerman, Moira M / Raby, Melanie / Izma, Gab B / Kudla, Yaryna M / Letwin, Nicholas V / Gallant, Melanie J / Schiffer, Stephanie R / Atkinson, Brian J / Rooney, Rebecca C / Sibley, Paul K / Prosser, Ryan S

Environmental toxicology and chemistry

2023 Volume 42, Issue 10, Page(s) 2143–2157

Abstract: Residual concentrations of pesticides are commonly found outside the intended area of application in Ontario's surface waters. Periphyton are a vital dietary component for grazing organisms in aquatic ecosystems but can also accumulate substantial levels ...

Abstract	Residual concentrations of pesticides are commonly found outside the intended area of application in Ontario's surface waters. Periphyton are a vital dietary component for grazing organisms in aquatic ecosystems but can also accumulate substantial levels of pesticides from the surrounding water. Consequently, grazing aquatic organisms are likely subjected to pesticide exposure through the consumption of pesticide-contaminated periphyton. The objectives of the present study were to determine if pesticides partition into periphyton in riverine environments across southern Ontario and, if so, to determine the toxicity of pesticides in periphyton when fed to the grazing mayfly Neocloeon triangulifer. Sites with low, medium, and high pesticide exposure based on historic water quality monitoring data were selected to incorporate a pesticide exposure gradient into the study design. Artificial substrate samplers were utilized to colonize periphyton in situ, which were then analyzed for the presence of approximately 500 pesticides. The results demonstrate that periphyton are capable of accumulating pesticides in agricultural streams. A novel 7-day toxicity test method was created to investigate the effects of pesticides partitioned into periphyton when fed to N. triangulifer. Periphyton collected from the field sites were fed to N. triangulifer and survival and biomass production recorded. Survival and biomass production significantly decreased when fed periphyton colonized in streams with catchments dominated by agricultural land use (p < 0.05). However, the relationship between pesticide concentration and survival or biomass production was not consistent. Using field-colonized periphyton allowed us to assess the dietary toxicity of environmentally relevant concentrations of pesticide mixtures; however, nutrition and taxonomic composition of the periphyton may vary between sites. Environ Toxicol Chem 2023;42:2143-2157. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
MeSH term(s)	Animals ; Pesticides/toxicity ; Rivers/chemistry ; Ephemeroptera ; Periphyton ; Ecosystem ; Water Pollutants, Chemical/toxicity ; Environmental Monitoring
Chemical Substances	Pesticides ; Water Pollutants, Chemical
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	46234-2
ISSN	1552-8618 ; 0730-7268
ISSN (online)	1552-8618
ISSN	0730-7268
DOI	10.1002/etc.5698
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