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| 2. |
- Boxall, A. B. A., et al.
(författare)
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Pharmaceuticals and Personal Care Products in the Environment: What Are the Big Questions?
- 2012
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:9, s. 1221-1229
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. OBJECTIVE: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. DATA SOURCES: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. DATA SYNTHESIS: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, a effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. CONCLUSIONS: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.
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| 3. |
- Sangeorzan, Irina, et al.
(författare)
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Toward Shared Decision-Making in Degenerative Cervical Myelopathy : Protocol for a Mixed Methods Study
- 2023
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Ingår i: JMIR Research Protocols. - : JMIR Publications. - 1929-0748. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this.Objective: The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes.Methods: Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders.Results: Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway.Conclusions: This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community.
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| 4. |
- Brunet-Ratnasingham, Elsa, et al.
(författare)
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Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized COVID-19 patients. Integrated analysis using k-means reveal four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors are delineated by high and low antibody responses. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
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| 5. |
- Brunet-Ratnasingham, Elsa, et al.
(författare)
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Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1, s. 4177-
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Tidskriftsartikel (refereegranskat)abstract
- Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
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| 6. |
- Miloudi, Khalil, et al.
(författare)
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NOTCH1 signaling induces pathological vascular permeability in diabetic retinopathy
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 116:10, s. 4538-4547
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic macular edema is a major complication of diabetes resulting in loss of central vision. Although heightened vessel leakiness has been linked to glial and neuronal-derived factors, relatively little is known on the mechanisms by which mature endothelial cells exit from a quiescent state and compromise barrier function. Here we report that endothelial NOTCH1 signaling in mature diabetic retinas contributes to increased vascular permeability. By providing both human and mouse data, we show that NOTCH1 ligands JAGGED1 and DELTA LIKE-4 are up-regulated secondary to hyperglycemia and activate both canonical and rapid noncanonical NOTCH1 pathways that ultimately disrupt endothelial adherens junctions in diabetic retinas by causing dissociation of vascular endothelial-cadherin from beta-catenin. We further demonstrate that neutralization of NOTCH1 ligands prevents diabetes-induced retinal edema. Collectively, these results identify a fundamental process in diabetes-mediated vascular permeability and provide translational rational for targeting the NOTCH pathway (primarily JAGGED1) in conditions characterized by compromised vascular barrier function.
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| 7. |
- Svensson, Anneli, et al.
(författare)
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Natural Course of Electrocardiographic Features in Arrhythmogenic Right Ventricular Cardiomyopathy and Their Relation to Ventricular Arrhythmic Events.
- 2024
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 13:16
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Tidskriftsartikel (refereegranskat)abstract
- Electrocardiographic abnormalities are common in arrhythmogenic right ventricular cardiomyopathy and are included in the 2010 Task Force Criteria. Their time course, however, remains uncertain. In this retrospective observational study, we aimed to assess the long-term evolution of electrocardiographic characteristics and their relation to ventricular arrhythmias.Three hundred fifty-three patients with arrhythmogenic right ventricular cardiomyopathy as per the 2010 Task Force Criteria with 6871 automatically processed 12-lead digital ECGs were included. The relationship between the electrocardiographic parameters and the risk of ventricular arrhythmias was assessed at 10years from the first ECG. Electrocardiographic parameters were compared between the first contact ECG, the ECG at diagnosis, and the most recent ECG. Median time between the first and the latest ECG was 6 [interquartile range, 1-14] years. Reductions of QRS voltage, R- and T-wave amplitudes between the first, diagnostic, and the latest ECGs were observed across precordial and extremity leads. Mean QRS duration increased from 96 to 102ms (P<0.001), terminal activation duration (V1) from 47 to 52ms (P<0.001), and QTc from 419 to 432 ms (P<0.001). T-wave inversions in leads V3 to V6 and aVF at first ECG were associated with ventricular arrhythmias (adjusted hazard ratio [HRadj][V3], 2.03 [95% CI, 1.23-3.34] and HRadj[aVF], 1.87 [95% CI, 1.13-3.08]).Depolarization and repolarization parameters evolved over time in patients with arrhythmogenic right ventricular cardiomyopathy, supporting the progressive nature of arrhythmogenic right ventricular cardiomyopathy. Electrocardiographic abnormalities may be detected before diagnosis and might, although not fulfilling the 2010 Task Force Criteria, be markers of early disease. T-wave inversion in leads V3 or aVF before diagnosis was associated with ventricular arrhythmias during follow-up.
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| 8. |
- Tetreault, Hannah M., et al.
(författare)
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Low Temperature Tolerance in the Perennial Sunflower Helianthus maximiliani
- 2016
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Ingår i: The American midland naturalist. - : University of Notre Dame. - 0003-0031 .- 1938-4238. ; 175:1, s. 91-102
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Tidskriftsartikel (refereegranskat)abstract
- Species distributed across diverse climate and thermal conditions represent opportune systems for studying tolerance of low temperature stress. We examined variation in cold acclimation capacity and freezing tolerance among three natural populations (Texas, Kansas, and Manitoba) of the perennial sunflower species Helianthus maximiliani, originally collected across 2134 km in central North America. Tolerance to low temperatures was evaluated through leaf electrolyte leakage assays that quantify loss of cellular electrolytes into an aqueous medium due to plasma membrane damage. Freezing tolerance was highest for plants from the northernmost latitude (Manitoba population) under both non cold-acclimated and cold-acclimated experimental conditions. Individuals from Kansas and Texas populations exhibited lower freezing tolerance compared to Manitoba but did not differ from one another. Plants from all populations retain the ability to increase freezing tolerance through the process of cold acclimation. Freezing tolerance of Manitoba x Texas F1 hybrids was statistically indistinguishable from plants from the Texas population and possible explanations for these observations are discussed. Analysis of flowering specimens from herbaria records of corresponding regional locations indicates considerable variation in flowering phenology whereby flowering occurs progressively earlier with increasing latitude. This phenological variation may provide an additional mechanism of coping with low temperature stress through temporal avoidance.
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