Expression of Viral Antigen by the Liver Leads to Chronic Infection Through the Generation of Regulatory T Cells

Referred to by David E. Kaplan " Does Massive Antigen Burden Allow Hepatic Viruses to Induce Regulatory T Cells and Their Tolerance and Persistence?" CMGH Cellular and Molecular Gastroenterology and Hepatology, Volume 1, Issue 3, May 2015, Pages 259-261International audienceThe constant exposure of the liver to food and bacterial antigens through the mesenteric circulation requires it to maintain tolerance while preserving the ability to mount an effective immune response against pathogens. We investigated the contribution of the liver's tolerogenic nature on the establishment of chronic viral infections. Methods: TTR-NP mice, which express the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) specifically in hepatocytes under control of a modified transthyretin (TTR) promoter, were infected with the Armstrong (Arm) or WE acute strains of LCMV. Results: The infection persisted for at least 147 days in TTR-NP mice. Expression of NP by the liver induced a strong peripheral tolerance against NP that was mediated by interleukin-10-secreting CD4+ regulatory T cells, leading to high PD-1 (programmed death-1) expression and reduced effector function of virus-specific T cells. Despite an active immune response against LCMV, peripheral tolerance against a single viral protein was sufficient to induce T-cell exhaustion and chronic LCMV Armstrong (Arm) or WE infection by limiting the antiviral T-cell response in an otherwise immunocompetent host. Regulatory T-cell depletion of chronically infected TTR-NP mice led to functional restoration of LCMV-specific CD4+ and CD8+ Tcell responses and viral clearance. Conclusions: Expression of a viral antigen by hepatocytes can induce a state of peripheral tolerance mediated by regulatory Tcells that can lead to the establishment of a chronic viral infection. Strategies targeting regulatory T cells in patients chronically infected with hepatotropic viruses could represent a promising approach to restore functional antiviral immunity and clear infection

Retrospective case control study of pet ferrets with cystine urolithiasis in Quebec, Canada : epidemiological and clinical features

Objective: To describe epidemiological and clinical features of cystine urolithiasis in pet ferrets. Methods: Retrospective case control study on medical records from four private clinics and one teaching hospital for pet ferrets diagnosed with cystine urolithiasis confirmed by spectrophotometry presented between July 2014 and July 2019 in Quebec, Canada; these cases were then compared to a reference population of 210 ferrets (controls) presented at the same facilities over the same timeframe. Results: Among the 36 identified cases, most affected ferrets were neutered males (32/36, 89%) and the mean age at presentation was 1.8 (± 1.0 standard deviation) year. Grain-free diets of six different brands were offered for at least three weeks prior to the presentation to 34/36 (94%) of the included cases. The ferrets that developed cystine urolithiasis were 57.9 times (Odds ratio [OR], 95% Confidence interval [95% CI]: 11.0, 304.8) more likely to receive a grain-free diet compared to the reference population. No significant difference in the values for the energy, protein, cysteine, and methionine contents were detected between the grainfree and the cereal-based diets offered to these pet ferrets. Among ferrets with uroliths, those with urethral calculi were 4.7 times (OR, 95% CI: 2.1, 10.4) more likely to develop an acute urinary tract obstruction. Conclusion: Although a definitive causation could not be drawn solely from these clinical cases, this case control study highlights a possible nutritional aetiology in the complex pathogenesis of cystine urolithiasis in ferrets

Alzheimer’s Prevention Initiative Generation Program: Development of an APOE genetic counseling and disclosure process in the context of clinical trials

IntroductionAs the number of Alzheimer’s disease (AD) prevention studies grows, many individuals will need to learn their genetic and/or biomarker risk for the disease to determine trial eligibility. An alternative to traditional models of genetic counseling and disclosure is needed to provide comprehensive standardized counseling and disclosure of apolipoprotein E (APOE) results efficiently, safely, and effectively in the context of AD prevention trials.MethodsA multidisciplinary Genetic Testing, Counseling, and Disclosure Committee was established and charged with operationalizing the Alzheimer’s Prevention Initiative (API) Genetic Counseling and Disclosure Process for use in the API Generation Program trials. The objective was to provide consistent information to research participants before and during the APOE counseling and disclosure session using standardized educational and session materials.ResultsThe Genetic Testing, Counseling, and Disclosure Committee created a process consisting of eight components: requirements of APOE testing and reports, psychological readiness assessment, determination of AD risk estimates, guidance for identifying providers of disclosure, predisclosure education, APOE counseling and disclosure session materials, APOE counseling and disclosure session flow, and assessing APOE disclosure impact.DiscussionThe API Genetic Counseling and Disclosure Process provides a framework for largeâ scale disclosure of APOE genotype results to study participants and serves as a model for disclosure of biomarker results. The process provides education to participants about the meaning and implication(s) of their APOE results while also incorporating a comprehensive assessment of disclosure impact. Data assessing participant safety and psychological wellâ being before and after APOE disclosure are still being collected and will be presented in a future publication.Highlightsâ ¢Participants may need to learn their risk for Alzheimer’s disease to enroll in studies.â ¢Alternatives to traditional models of apolipoprotein E counseling and disclosure are needed.â ¢An alternative process was developed by the Alzheimer’s Prevention Initiative.â ¢This process has been implemented by the Alzheimer’s Prevention Initiative Generation Program.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153071/1/trc2jtrci201909013.pd

Acceptability and Feasibility of the Telehealth Bariatric Behavioral Intervention to Increase Physical Activity: Protocol for a Single-Case Experimental Study

Background: Regular physical activity (PA) is recommended to optimize weight and health outcomes in patients who have undergone metabolic and bariatric surgery (MBS). However, >70% of patients have low PA levels before MBS that persist after MBS. Although behavioral interventions delivered face-to-face have shown promise for increasing PA among patients who have undergone MBS, many may experience barriers, preventing enrollment into and adherence to such interventions. Delivering PA behavior change interventions via telehealth to patients who have undergone MBS may be an effective strategy to increase accessibility and reach, as well as adherence. Objective: This paper reports the protocol for a study that aims to assess the feasibility and acceptability of the protocol or methods and the Telehealth Bariatric Behavioral Intervention (TELE-BariACTIV). The intervention is designed to increase moderate-to-vigorous intensity PA (MVPA) in patients awaiting bariatric surgery and is guided by a multitheory approach and a patient perspective. Another objective is to estimate the effect of the TELE-BariACTIV intervention on presurgical MVPA to determine the appropriate sample size for a multicenter trial. Methods: This study is a multicenter trial using a repeated (ABAB’A) single-case experimental design. The A phases are observational phases without intervention (A1=pre-MBS phase; A2=length personalized according to the MBS date; A3=7 months post-MBS phase). The B phases are interventional phases with PA counseling (B1=6 weekly pre-MBS sessions; B2=3 monthly sessions starting 3 months after MBS). The target sample size is set to 12. Participants are inactive adults awaiting sleeve gastrectomy who have access to a computer with internet and an interface with a camera. The participants are randomly allocated to a 1- or 2-week baseline period (A1). Protocol and intervention feasibility and acceptability (primary outcomes) will be assessed by recording missing data, refusal, recruitment, retention, attendance, and attrition rates, as well as via web-based acceptability questionnaires and semistructured interviews. Data collected via accelerometry (7-14 days) on 8 occasions and via questionnaires on 10 occasions will be analyzed to estimate the effect of the intervention on MVPA. Generalization measures assessing the quality of life, anxiety and depressive symptoms, and theory-based constructs (ie, motivational regulations for PA, self-efficacy to overcome barriers to PA, basic psychological needs satisfaction and frustration, PA enjoyment, and social support for PA; secondary outcomes for a future large-scale trial) will be completed via web-based questionnaires on 6-10 occasions. The institutional review board provided ethics approval for the study in June 2021. Results: Recruitment began in September 2021, and all the participants were enrolled (n=12). Data collection is expected to end in fall 2023, depending on the MBS date of the recruited participants. Conclusions: The TELE-BariACTIV intervention has the potential for implementation across multiple settings owing to its collaborative construction that can be offered remotely

Healthcare professionals' intentions to use wiki-based reminders to promote best practices in trauma care: a survey protocol

<p>Abstract</p> <p>Background</p> <p>Healthcare professionals are increasingly using wikis as collaborative tools to create, synthesize, share, and disseminate knowledge in healthcare. Because wikis depend on collaborators to keep content up-to-date, healthcare professionals who use wikis must adopt behaviors that foster this collaboration. This protocol describes the methods we will use to develop and test the metrological qualities of a questionnaire that will assess healthcare professionals' intentions and the determinants of those intentions to use wiki-based reminders that promote best practices in trauma care.</p> <p>Methods</p> <p>Using the Theory of Planned Behavior, we will conduct semi-structured interviews of healthcare professionals to identify salient beliefs that may affect their future use of wikis. These beliefs will inform our questionnaire on intended behavior. A test-retest of the survey will verify the questionnaire's stability over time. We will interview 50 healthcare professionals (25 physicians and 25 allied health professionals) working in the emergency departments of three trauma centers in Quebec, Canada. We will analyze the content of the interviews and construct and pilot a questionnaire. We will then test the revised questionnaire with 30 healthcare professionals (15 physicians and 15 allied health professionals) and retest it two weeks later. We will assess the internal consistency of the questionnaire constructs using Cronbach's alpha coefficients and determine their stability with the intra-class correlation (ICC).</p> <p>Discussion</p> <p>To our knowledge, this study will be the first to develop and test a theory-based survey that measures healthcare professionals' intentions to use a wiki-based intervention. This study will identify professionals' salient beliefs qualitatively and will quantify the psychometric capacities of the questionnaire based on those beliefs.</p

La pertinence culturelle et linguistique dans les outils linguistiques informatisés couramment utilisés au Québec

Cajolet-Laganière Hélène, Langlois Marie-France, Martel Pierre. La pertinence culturelle et linguistique dans les outils linguistiques informatisés couramment utilisés au Québec. In: Revue belge de philologie et d'histoire, tome 79, fasc. 3, 2001. Langues et littératures modernes - Moderne taal- en letterkunde. pp. 861-881

Guía C: Diseño de programas de eficiencia energética

El presente volumen hace parte de la Serie de Guías de Eficiencia Energética de la División de Energía del Banco Interamericano de Desarrollo, cuya publicación responde a la carencia de información de fácil acceso y en castellano sobre temas relativos a la eficiencia energética en los países de América Latina y el Caribe. Esta guía contiene ejemplos concretos de proyectos realizados en el ámbito regional y mundial. Cada volumen trata de aspectos específicos de la eficiencia energética, como por ejemplo las formas de financiamiento y el diseño de programas, las justificaciones que subyacen a la intervención gubernamental en este campo, los marcos institucionales necesarios, iniciativas de estándares y etiquetado, compañías de servicios energéticos y contratos de servicios energéticos por desempeño. La Guía C: Diseño de programas de eficiencia energética está dirigida a ejecutores de medidas de eficiencia energética en instituciones locales, y en particular a aquellos funcionarios de gobiernos locales que vayan a emprender programas de eficiencia energética, o que deseen mejorar y/o transformar sus prácticas en dichos programas. Adicionalmente, se quiere llegar a aquellos funcionarios de empresas de energía que se propongan a implementar medidas de eficiencia energética --bien sea en el área de gestión de demanda (DSM, por sus siglas en inglés) o en respuesta a la existencia de una nueva norma--, y a quienes se desempeñan en instituciones locales (secretarías de gobierno, departamentos, ministerios y entes reguladores) y quieran familiarizarse plenamente con el diseño (o reforma) del marco institucional, jurídico y regulatorio de la eficiencia energética.

Analysis of the Hubble diagram of type SNe Ia supernovae and of gamma-ray bursts. A comparison between two models

A paper by Harmut Traunm\"uller [1] showed from statistical studies of observational data that the most adequate equation to represent observations on magnitude and redshift from 892 type 1a supernovae is $\mu = 5\,log[(1+z)\,ln(1+z)] + const.$ Comparing the Hubble diagram calculated from the observed redshift data of 280 supernovae with Hubble diagrams inferred on the basis of two cosmological models in the range of z = 0.0104 to 8.1, Laszlo Marosi [2] found in a quite independant study that the best fit function to represent observations is $\mu= 44.109769 \,z^{0.059883}$. Noting that differences between the different cosmological models become more pronouced in a photon time-of-fligth $t_s$ vs. $z$ repr\'esentation, he also noted that the best equation to account for observations may also be written $z = -1+e^{2.024\,\,10^{-18} \,\,ts}$. In the light of these observational data, we compare the theoretical Hubble diagram obtained with the flat $\Lambda CDM$ model to the ones we have obtained few years ago [3, 4, 5] from a model that we call here the "light model" for the sake of clarity. Our conclusions are that values calculated on the basis of the $\Lambda CDM$ model exhibit poor agreement with the presently available data while the light model agrees exactly with observations and conclusions of statistical studies [1] and [2] (independently of the values of $\Omega_k$, $\Omega_M$ or $\Omega_{\Lambda}$). Our model giving no accelerating expansion of the universe, we conclude that this latter is not necessary and that models can exist which lead exactly to observations without having to consider any accelerating expansion of the universe. In an Appendix, we discuss some aspects of the model and we present a brief overview of some of its key results

Guía C: Diseño de programas de eficiencia energética

El propósito de este capítulo, parte de una serie sobre eficiencia energética, es presentar los elementos básicos del diseño y de la implementación de programas de eficiencia energética, los cuales sirven para acelerar la transición de mercado hacia un uso más racional de la energía. Incluye una discusión de las barreras principales a los programas de eficiencia energética, los tipos de programas, el ciclo del programa y estudios de caracterización de mercado.Eficiencia energética, Mercados de energía, Política ambiental, Manual C 2-24-11 M4.indd