Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease.

Tissue-resident lymphocytes play a key role in immune surveillance, but it remains unclear how these inherently stable cell populations respond to chronic inflammation. In the setting of celiac disease (CeD), where exposure to dietary antigen can be controlled, gluten-induced inflammation triggered a profound depletion of naturally occurring Vγ4+/Vδ1+ intraepithelial lymphocytes (IELs) with innate cytolytic properties and specificity for the butyrophilin-like (BTNL) molecules BTNL3/BTNL8. Creation of a new niche with reduced expression of BTNL8 and loss of Vγ4+/Vδ1+ IELs was accompanied by the expansion of gluten-sensitive, interferon-γ-producing Vδ1+ IELs bearing T cell receptors (TCRs) with a shared non-germline-encoded motif that failed to recognize BTNL3/BTNL8. Exclusion of dietary gluten restored BTNL8 expression but was insufficient to reconstitute the physiological Vγ4+/Vδ1+ subset among TCRγδ+ IELs. Collectively, these data show that chronic inflammation permanently reconfigures the tissue-resident TCRγδ+ IEL compartment in CeD. VIDEO ABSTRACT.

IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease.

Coeliac disease is a complex, polygenic inflammatory enteropathy caused by exposure to dietary gluten that occurs in a subset of genetically susceptible individuals who express either the HLA-DQ8 or HLA-DQ2 haplotypes1,2. The need to develop non-dietary treatments is now widely recognized3, but no pathophysiologically relevant gluten- and HLA-dependent preclinical model exists. Furthermore, although studies in humans have led to major advances in our understanding of the pathogenesis of coeliac disease4, the respective roles of disease-predisposing HLA molecules, and of adaptive and innate immunity in the development of tissue damage, have not been directly demonstrated. Here we describe a mouse model that reproduces the overexpression of interleukin-15 (IL-15) in the gut epithelium and lamina propria that is characteristic of active coeliac disease, expresses the predisposing HLA-DQ8 molecule, and develops villous atrophy after ingestion of gluten. Overexpression of IL-15 in both the epithelium and the lamina propria is required for the development of villous atrophy, which demonstrates the location-dependent central role of IL-15 in the pathogenesis of coeliac disease. In addition, CD4+ T cells and HLA-DQ8 have a crucial role in the licensing of cytotoxic T cells to mediate intestinal epithelial cell lysis. We also demonstrate a role for the cytokine interferon-γ (IFNγ) and the enzyme transglutaminase 2 (TG2) in tissue destruction. By reflecting the complex interaction between gluten, genetics and IL-15-driven tissue inflammation, this mouse model provides the opportunity to both increase our understanding of coeliac disease, and develop new therapeutic strategies.

The commitment function of angry facial expressions.

What function do facial expressions have? We tested the hypothesis that some expressions serve as honest signals of subjective commitments-in particular, that angry faces increase the effectiveness of threats. In an ultimatum game, proposers decided how much money to offer a responder while seeing a film clip depicting an angry or a neutral facial expression, together with a written threat that was either inherently credible (a 50-50 split) or less credible (a demand for 70% of the money). Proposers offered greater amounts in response to the less credible threat when it was accompanied by an angry expression than when it was accompanied by a neutral expression, but were unaffected by the expression when dealing with the credible threat. This finding supports the hypothesis that angry expressions are honest signals that enhance the credibility of threats.

Socioeconomic Influence on Speech Rehabilitation After Total Laryngectomy.

OBJECTIVE: Speech rehabilitation following a total laryngectomy significantly impacts the quality of life. Indwelling prosthetic voice restoration provides optimal outcomes; however, the long-term maintenance of these devices carries considerable financial costs, which are not universally covered by insurance. This investigation aimed to analyze associations between socioeconomic factors and outcomes in postlaryngectomy speech rehabilitation. STUDY DESIGN: Retrospective cohort analysis. SETTING: Academic tertiary-care center from May 2014 to September 2021. METHODS: In patients undergoing total laryngectomy, the incidence of tracheoesophageal puncture with indwelling vocal prostheses (TEP-VP) placement within the first postoperative year was compared among household income, demographic factors, and disease characteristics. Functional and maintenance outcomes served as secondary endpoints. RESULTS: Seventy-seven patients were included. Forty-five (58%) underwent indwelling TEP-VP (41 primaries). Eighty-nine percent of patients with annual incomes greater than $50k underwent TEP-VP compared to only 35% with incomes less than $50k/year. TEP-VP was performed in 85% of patients with commercial insurance, 70% with Medicare, 42% with Medicaid, and 0% with no insurance. On multivariate analysis, annual household incomes greater than $50k were predicted for TEP-VP placement (odds ratio: 12.7 [2.45-65.8], p = .002). The utilization of postoperative speech therapy and functional communication outcomes were similar among socioeconomic groups. Twelve patients were unable to afford supplies within the first year, with differences noted among insurance (p = .015) and income status (p = .003). CONCLUSION: Disparities in vocal and speech rehabilitation following laryngectomy may disproportionally affect underserved patients.

Narcissistic and dependent traits and behavior in four archetypal 2-person, 2-choice games.

Introduction: The characteristic behaviors we use to define personality pathology arise from specific interpersonal interactions. In an effort to create a laboratory-based context in which behavior might be expected to be influenced by particular personality traits, we used four 2-person, 2-choice games (the Prisoner's Dilemma, Chicken, Leader, and Hero games) to create a simulated interaction and focused specifically on narcissism and dependency. Method: An online sample of 1137 (35% male, M age = 38.46 years, SD age = 13.20) participants completed brief, self-reported measures of trait narcissism and dependency and played one of the four games. Before deciding how to act or react, participants received either no message, a promise to cooperate, or a threat to defect from a (confederate) partner. Results: When receiving no message, those who cooperated in the Prisoner's Dilemma had lower trait narcissism, while those who defected in the Chicken and Leader games had higher trait narcissism. Also with no message, participants who cooperated in the Hero game had higher trait dependency. Promises only affected the relationship between trait narcissism in the Leader game while threats only affected the relationship between trait dependency in the Chicken game. Discussion: These findings add to the limited behavioral research on personality pathology and largely support established interpersonal conceptualizations and models. Future work might extend these findings using even more ecologically valid approaches to explore the behavioral correlates of personality traits that have important implications for interpersonal interactions.

Increased adherence to ACOG diagnostic guidelines for HDP following a workshop in Bolivia, a LMIC.

OBJECTIVES: Hypertensive disorders of pregnancy (HDP) exert a heavy mortality burden in low- to middle-income countries (LMIC). ACOG revised HDP diagnostic guidelines to improve identifying pregnancies at greatest risk but whether they are used in LMIC is unknown. STUDY DESIGN: We held a workshop to review ACOG guidelines in La Paz, Bolivia (BO) and then reviewed prenatal, labor and delivery records for all HDP diagnoses and twice as many controls at its three largest delivery sites during the year before and the nine months after a workshop (n = 1376 cases, 2851 controls during the two periods). MAIN OUTCOME MEASURES: HDP diagnoses, maternal, and infant characteristics. RESULTS: Bolivian and ACOG criteria identified similar frequencies of gestational hypertension (GH) or eclampsia, but preeclampsia with severe features (sPE) was under- and preeclampsia without severe features (PE) over-reported during both periods. Increases occurred after the workshop in testing for proteinuria and the detection of abnormal laboratory values and severe hypertension in HDP women. Any adverse maternal outcome occurred more frequently after the workshop in women with BO PE or sPE diagnoses who met ACOG sPE criteria. CONCLUSIONS: Utilization of ACOG guidelines increased following the workshop and improved identification of PE or sPE pregnancies with adverse maternal outcomes. Continued use of a CLAP perinatal form recognizing HELLP as the only kind of sPE resulted in under-reporting of sPE. FUNDING: NIH TW010797, HD088590, HL138181.

The course of dysphoric affective and cognitive states in borderline personality disorder: a 10-year follow-up study.

The current study aimed to assess dysphoric states among 290 patients with borderline personality disorder (BPD) and 72 non-borderline axis II comparison subjects other personality disorders, (OPD) over a 10-year course of prospective follow-up. Additionally, we assessed the severity of these states among borderline patients who had and had not recovered both symptomatically and psychosocially. The Dysphoric Affect Scale (DAS) - a 50-item self-report measure of affective and cognitive states thought to be common among borderline patients and specific to the disorder - was administered at five waves of prospective follow-up. Affective and cognitive DAS items were separately analyzed, yielding respective subscores. Borderline patients reported more severe dysphoric states compared to OPD subjects at baseline. However, the severity of affective and cognitive states declined significantly for both groups taken together over 10 years of follow-up. Within the BPD group, recovered subjects reported less severe dysphoric states compared to non-recovered subjects at baseline. Results also showed a significant decline in DAS scores over time, but at a greater rate for recovered subjects. In sum, while the severity of dysphoric states declines significantly over time, inner distress remains an area of vulnerability for borderline subjects. Additionally, the severity and pervasiveness of these states may affect recovery over time.

ACOG and local diagnostic criteria for hypertensive disorders of pregnancy (HDP) in La Paz-El Alto, Bolivia: A retrospective case-control study.

Background: Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal death in low- to middle-income countries (LMIC). The American College of Obstetricians and Gynecologists (ACOG) updated diagnostic guidelines to align signs and symptoms with those associated with maternal death. We performed an observational study to ask whether ACOG guidelines were employed and associated with adverse outcomes in La Paz-El Alto, Bolivia, an LMIC. Methods: Medical records for all HDP discharge diagnoses (n = 734) and twice as many controls (n = 1647) were reviewed for one year at the three largest delivery sites. For the 690 cases and 1548 controls meeting inclusion criteria (singleton, 18-45 maternal age, local residence), health history, blood pressures, symptoms, lab tests, HDP diagnoses (i.e., gestational hypertension [GH]; preeclampsia [PE]; haemolysis, low platelets, high liver enzymes [HELLP] syndrome, eclampsia), and adverse outcomes were recorded. Bolivian diagnoses were compared to ACOG guidelines using accuracy analysis and associated with adverse outcomes by logistic regression. Findings: Both systems agreed with respect to eclampsia, but only 27% of all Bolivian HDP diagnoses met ACOG criteria. HDP increased adverse maternal- or perinatal-outcome risks for both systems, but ACOG guidelines enabled more pre-delivery diagnoses, graded maternal-risk assessment, and targeting of HDP terminating in maternal death. Interpretation: Bolivia diagnoses agreed with ACOG guidelines concerning end-stage disease (eclampsia) but not the other HDP due mainly to ACOG's recognition of a broader range of severe features. ACOG guidelines can aid in identifying pregnancies at greatest risk in LMICs, where most maternal and perinatal deaths occur. Funding: NIH TW010797, HD088590, HL138181, UL1 TR002535.

Narcissistic and dependent behaviors in the Battle of the Sexes game.

We used the 2-person, 2-choice Battle of the Sexes game to model dominant and submissive behaviors in individuals with narcissistic and dependent traits in an online sample. In the Battle of the Sexes, participants share an interest in coordinating an outcome (either A or B). However, one player prefers they coordinate on Outcome A, whereas the other prefers they both coordinate on Outcome B. When provoked by a preemptive commitment (Experiment 1), we found that narcissistic traits were positively associated with dominant behavior, whereas dependent traits were positively associated with submissive behavior. In contrast, we found no association between either narcissistic or dependent traits and behavior in a condition without a preemptive commitment (Experiment 2). These findings are consistent with an interpersonal conceptualization of narcissistic and dependent personality disorders, though only when responding to provocation. These findings support the idea that narcissistic and dependent traits can be successfully modeled using economic games. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Type 2 diabetes in younger adults: the emerging UK epidemic.

There is an emerging epidemic of type 2 diabetes (T2DM) in younger adults. They represent an extreme phenotype: likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black or minority ethnic origin, and come from less affluent socioeconomic groups. An accurate diagnosis of T2DM in younger adults, while essential to guide management, can be challenging even for the experienced diabetologist. Comorbidities such as hypertension, nephropathy and hyperlipidaemia are prevalent in this group, and, despite the lack of longitudinal data, they represent a very high risk group, with a need for aggressive management. This focused review of the epidemiology, aetiology, clinical outcomes, comorbidities and management of younger adults with T2DM will provide the non-specialist with up-to-date insight into the UK's emerging epidemic.

A Novel Test of the Duchenne Marker: Smiles After Botulinum Toxin Treatment for Crow's Feet Wrinkles.

Smiles that vary in muscular configuration also vary in how they are perceived. Previous research suggests that "Duchenne smiles," indicated by the combined actions of the orbicularis oculi (cheek raiser) and the zygomaticus major muscles (lip corner puller), signal enjoyment. This research has compared perceptions of Duchenne smiles with non-Duchenne smiles among individuals voluntarily innervating or inhibiting the orbicularis oculi muscle. Here we used a novel set of highly controlled stimuli: photographs of patients taken before and after receiving botulinum toxin treatment for crow's feet lines that selectively paralyzed the lateral orbicularis oculi muscle and removed visible lateral eye wrinkles, to test perception of smiles. Smiles in which the orbicularis muscle was active (prior to treatment) were rated as more felt, spontaneous, intense, and happier. Post treatment patients looked younger, although not more attractive. We discuss the potential implications of these findings within the context of emotion science and clinical research on botulinum toxin.

In smiles we trust? Smiling in the context of antisocial and borderline personality pathology.

Research suggests that people behave more cooperatively towards those who smile and less cooperatively towards those with personality pathology. Here, we integrated these two lines of research to model the combined effects of smiles and personality pathology on trust. In two experiments, participants read vignettes portraying a person with either borderline personality disorder, antisocial personality disorder, or no personality pathology. These portrayals were paired with a brief video clip that showed a person with either a neutral expression or a smile. Participants then played a Trust game with the "person" presented using each vignette and video clip combination. In Experiment 1, rates of trust were lower in response to the borderline and antisocial personality disorder vignettes compared with the control vignette. Interestingly, the effect of smiles was dependent upon personality. Although participants were more trusting of smiling confederates portrayed as having borderline personality disorder or no pathology, they were less trusting of confederates portrayed as having antisocial personality disorder if they smiled. In Experiment 2, run with a second set of personality vignettes, rates of trust were lower in response to both personality disorder vignettes and higher in response to smiles with no significant interaction. Together, these results suggest that information regarding both the current emotional state as well as the personality traits of a partner are important for creating trust.

Emotional Tears: An Honest Signal of Trustworthiness Increasing Prosocial Behavior?

How do our emotional tears affect the way we are treated? We tested whether tears, paired with either a neutral or a sad facial expression, elicited prosocial behavior among perceivers. Participants viewed a video clip depicting a confederate partner with or without tears displaying either a neutral or sad facial expression before making a behavioral decision in one of two economic games. In a Trust game (Experiment 1), participants who played the role of the investor were more likely to share an endowment after viewing a confederate trustee with tears (paired with either a neutral or a sad facial expression) in comparison to a confederate trustee without tears. However, in a Dictator game (Experiment 2), participants who played the role of allocator were no more likely to share an endowment after viewing a confederate recipient with tears (paired with either a neutral or sad facial expression) in comparison to a confederate recipient without tears. Taken together, these findings suggest that tears increase prosocial behavior by increasing trustworthiness as opposed to generally increasing other-regarding altruistic tendencies.

Face Value and Cheap Talk: How Smiles Can Increase or Decrease the Credibility of Our Words.

How do our facial expressions affect the credibility of our words? We test whether smiles, either uninhibited or inhibited, affect the credibility of a written statement. Participants viewed a confederate partner displaying a neutral expression, non-Duchenne smile, Duchenne smile, or controlled smile, paired with a written statement. Participants then made a behavioral decision based on how credible they perceived the confederate's statement to be. Compared to a neutral expression, Experiment 1 found that participants were more likely to believe the confederate's statement when it was paired with a deliberate Duchenne smile and less likely to believe the confederate's statement when it was paired with a deliberate controlled smile. Experiment 2 replicated these findings with spontaneously emitted expressions. These findings provide evidence that uninhibited facial expressions can increase the credibility accompanying statements, while inhibited ones can decrease credibility.

Impact of depression on response to comedy: a dynamic facial coding analysis.

Individuals suffering from depression show diminished facial responses to positive stimuli. Recent cognitive research suggests that depressed individuals may appraise emotional stimuli differently than do nondepressed persons. Prior studies do not indicate whether depressed individuals respond differently when they encounter positive stimuli that are difficult to avoid. The authors investigated dynamic responses of individuals varying in both history of major depressive disorder (MDD) and current depressive symptomatology (N = 116) to robust positive stimuli. The Facial Action Coding System (Ekman & Friesen, 1978) was used to measure affect-related responses to a comedy clip. Participants reporting current depressive symptomatology were more likely to evince affect-related shifts in expression following the clip than were those without current symptomatology. This effect of current symptomatology emerged even when the contrast focused only on individuals with a history of MDD. Specifically, persons with current depressive symptomatology were more likely than those without current symptomatology to control their initial smiles with negative affect-related expressions. These findings suggest that integration of emotion science and social cognition may yield important advances for understanding depression.

Riparian plant material inputs to the Murray River, Australia: composition, reactivity, and role of nutrients.

By changing riparian plants from Eucalypts to pasture and exotic deciduous trees, modern development has altered the type of carbon assimilated by Australian rivers. To investigate influences of plant litter substrates on biochemical oxygen demand, plant materials entering the Murray River were analyzed for their composition and mineralization potential. Plant materials were distinguished compositionally by two principal components, structural carbon and macronutrients, as: (i) Eucalyptus leaves, (ii) Eucalyptus bark and Casuarina cunninghamiana seed cone, (iii) grasses, (iv) macrophytes, (v) aquatic herbs, (vi) non-eucalypt leaf (Salix, Casuarina, Acacia). Ratios of C/P (1879-14524) and C/N (65-267) were relatively high in Eucalyptus bark, while mean N/P (7-60) ratios were similar among plant materials. Terrestrial weathering increased C/P and C/N ratios, while N/P ratios remained similar, due to greater loss of N and P relative to C. Aerobic decay experiments showed that nutrient supplementation accelerated decay of all organic substrates, except for grasses that decayed efficiently without supplementation. Aquatic herbs also had substantial carbon availability, macrophytes and non-eucalypt leaves had intermediate carbon availability, while eucalypt leaf and bark had intermediate to low carbon availabilities. Because biochemical oxygen demand varies with organic substrates sampled from the Murray River, and also with soluble nutrient availability, it is plausible that that modern changes to riverine plant communities and land use have influenced the biogeochemistry of this river toward faster, and more complete, processing of allochthonous carbon.

Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication.

The Communicative Function of Sad Facial Expressions.

What are the communicative functions of sad facial expressions? Research shows that people feel sadness in response to losses but it's unclear whether sad expressions function to communicate losses to others and if so, what makes these signals credible. Here we use economic games to test the hypothesis that sad expressions lend credibility to claims of loss. Participants play the role of either a proposer or recipient in a game with a fictional backstory and real monetary payoffs. The proposers view a (fictional) video of the recipient's character displaying either a neutral or sad expression paired with a claim of loss. The proposer then decided how much money to give to the recipient. In three experiments, we test alternative theories by using situations in which the recipient's losses were uncertain (Experiment 1), the recipient's losses were certain (Experiment 2), or the recipient claims failed gains rather than losses (Experiment 3). Overall, we find that participants gave more money to recipients who displayed sad expressions compared to neutral expressions, but only under conditions of uncertain loss. This finding supports the hypothesis that sad expressions function to increase the credibility of claims of loss.

The Financial Impact of Advanced Kidney Disease on Canada Pension Plan and Private Disability Insurance Costs.

BACKGROUND: Many working-age individuals with advanced chronic kidney disease (CKD) are unable to work, or are only able to work at a reduced capacity and/or with a reduction in time at work, and receive disability payments, either from the Canadian government or from private insurers, but the magnitude of those payments is unknown. OBJECTIVE: The objective of this study was to estimate Canada Pension Plan Disability Benefit and private disability insurance benefits paid to Canadians with advanced kidney failure, and how feasible improvements in prevention, identification, and early treatment of CKD and increased use of kidney transplantation might mitigate those costs. DESIGN: This study used an analytical model combining Canadian data from various sources. SETTING AND PATIENTS: This study included all patients with advanced CKD in Canada, including those with estimated glomerular filtration rate (eGFR) <30 mL/min/m2 and those on dialysis. MEASUREMENTS: We combined disability estimates from a provincial kidney care program with the prevalence of advanced CKD and estimated disability payments from the Canada Pension Plan and private insurance plans to estimate overall disability benefit payments for Canadians with advanced CKD. RESULTS: We estimate that Canadians with advanced kidney failure are receiving disability benefit payments of at least Can$217 million annually. These estimates are sensitive to the proportion of individuals with advanced kidney disease who are unable to work, and plausible variation in this estimate could mean patients with advanced kidney disease are receiving up to Can$260 million per year. Feasible strategies to reduce the proportion of individuals with advanced kidney disease, either through prevention, delay or reduction in severity, or increasing the rate of transplantation, could result in reductions in the cost of Canada Pension Plan and private disability insurance payments by Can$13.8 million per year within 5 years. LIMITATIONS: This study does not estimate how CKD prevention or increasing the rate of kidney transplantation might influence health care cost savings more broadly, and does not include the cost to provincial governments for programs that provide income for individuals without private insurance and who do not qualify for Canada Pension Plan disability payments. CONCLUSIONS: Private disability insurance providers and federal government programs incur high costs related to individuals with advanced kidney failure, highlighting the significance of kidney disease not only to patients, and their families, but also to these other important stakeholders. Improvements in care of individuals with kidney disease could reduce these costs.

MISE EN CONTEXTE: De nombreux individus en âge de travailler et atteints d'insuffisance rénale chronique (IRC) de stade avancé sont incapables d'occuper un emploi ou se voient dans l'obligation de travailler à temps réduit ou à des postes ne requérant pas de trop grandes capacités physiques. La situation de ces individus les contraint à recevoir des prestations d'invalidité, soit de la part du gouvernement du Canada, soit auprès d'assureurs privés. On ne connaît toutefois pas l'ampleur réelle de ces prestations. OBJECTIF DE L'ÉTUDE: Évaluer le montant des prestations d'invalidité versées par le Régime de pensions du Canada et par des assureurs privés à des Canadiens vivant avec l'IRC de stade avancé. Déterminer à quel point des améliorations possibles au niveau de la prévention, du diagnostic et de l'intervention précoce, et d'une meilleure accessibilité à la transplantation rénale pourraient soit réduire ces coûts, soit retarder ou raccourcir les périodes de paiement. MODÈLE DE L'ÉTUDE: Il s'agit d'un modèle analytique combinant des données canadiennes provenant de diverses sources. PARTICIPANTS: Tous les patients canadiens atteints d'IRC de stade avancé, y compris ceux présentant un débit de filtration glomérulaire (DFGe) <30 mL/min/1,73 m2 et les patients sous hémodialyse. MESURES: Estimés en matière de prestations d'invalidité dans le cadre d'un programme provincial de soins en néphrologie, jumelés à la prévalence de l'IRC de stade avancé, de même que le montant approximatif des prestations d'invalidité versées par le Régime de pensions du Canada et les régimes d'assurance privés. RÉSULTATS: Nous estimons que les Canadiens souffrant d'IRC de stade avancé reçoivent au moins 217 millions de dollars par an en prestations d'invalidité. Cette estimation dépend de la proportion de personnes incapables de travailler et donc, une variation possible de cette estimation pourrait signifier que les patients atteints d'IRC de stade avancé reçoivent en fait jusqu'à 260 millions de dollars par an en prestations d'invalidité. Les stratégies applicables pour réduire la proportion de personnes atteintes d'une maladie rénale de stade avancé, soit par le biais de la prévention, du ralentissement de la progression de la maladie ou de la diminution de sa gravité, ou alors par l'augmentation du nombre de transplantations pourraient réduire le montant des prestations versées par le Régime de pensions du Canada et les régimes d'assurance privée de 13,8 millions de dollars par an en cinq ans. LIMITES DE L'ÉTUDE: Cette étude ne tient pas compte de la manière dont la prévention de l'IRC ou l'augmentation du nombre de transplantations rénales seraient susceptibles de permettre d'économiser sur les coûts en santé de façon plus globale. CONCLUSIONS: Les fournisseurs d'assurance-invalidité privée et les programmes du gouvernement fédéral supportent des coûts très élevés face aux personnes atteintes d'IRC de stade avancé. Ce constat met en lumière la portée de l'insuffisance rénale non seulement pour les patients et leurs familles, ou pour le système de santé, mais également pour ces autres intervenants majeurs. Des améliorations dans les soins prodigués aux personnes souffrant de maladies rénales pourraient contribuer à réduire ces coûts.

Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease.

Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (TH1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pTreg) conversion and promoting TH1 immunity to dietary antigen. Initiation of TH1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pTreg conversion, which was mediated by type-1 interferon. Last, our study in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the development of CeD.