The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway.

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2-/-) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2-/- mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2-/- mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing ß cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.

Dendritic cells and regulatory T cells expressing CCR4 provide resistance to coxsackievirus B5-induced pancreatitis.

Type B coxsackieviruses (CVB) are enteroviruses responsible for a common infectious myocarditis and pancreatitis. DCs and regulatory T cells (Tregs) are key players in controlling virus replication and regulating the immune response and tissue damage, respectively. However, the mechanisms underlying cellular migration to target tissues remain unclear. In the present study, we found that CVB5 infection induced CCL17 production and controlled the migration of CCR4+ DCs and CCR4+ Tregs to the pancreatic lymph nodes (pLN). CVB5 infection of CCR4-/- mice reduced the migration of the CD8α+ DC subset and reduced DC activation and production of IFN-ß and IL-12. Consequently, CCR4-/- mice presented decreased IFN-γ-producing CD4+ and CD8+ T cells, an increased viral load and more severe pancreatitis. In addition, CCR4-/- mice had impaired Treg accumulation in pLN as well as increased T lymphocyte activation. Adoptive transfer of CCR4+ Tregs but not CCR4- Tregs was able to regulate T lymphocyte activation upon CVB5 infection. The present data reveal a previously unknown role for CCR4 in coordinating immune cell migration to CVB-infected tissues and in controlling subsequent pancreatitis. These new insights may contribute to the design of future therapies for acute and chronic infection of non-polio enteroviruses.

Contribuições da clínica da parentalidade no atendimento de um caso de obesidade infantil / Contributions of the clinic of parentality in the psychological treatment of a child obesity case / Contribuciones de la clínica de la parentalidad en un caso de obesidad infantil

Estudos a respeito da obesidade indicam que, para além de questões genéticas, seu surgimento pode estar associado às primeiras relações interpessoais. O presente artigo tem como objetivo discutir as contribuições que a clínica da parentalidade pode trazer para o tratamento da obesidade infantil a partir de recortes de um caso clínico. Para tanto, será apresentado o conceito de parentalidade, sua derivação clínica e questões da contemporaneidade que interferem no processo de se tornar pai e mãe. A interpretação do material clínico revelou que o comportamento de comer compulsivo da criança estava relacionado à fragilização parental, em acordo com os dados da literatura. Assim, trabalhar no contexto da clínica da parentalidade pode favorecer a melhora do sintoma na medida em que liberta a criança de um legado inenarrável e fortalece tanto o lugar subjetivo da criança quanto as funções parentais. Além disso, nos casos necessários, pode contribuir para a construção de uma demanda para terapia familiar.

Studies about obesity show that, in addition to possible genetic constitution, its appearance may be associated with early interpersonal relationships. This paper aims to discuss, through clips of a clinical case, contributions that the clinic of parentality may have for the treatment of infantile obesity. For this purpose, the concept of parentality, its clinical derivation and issues related to contemporaneity which interfere in the process of becoming a mother and a father will be introduced. The interpretation of the clinical material revealed that the child behavior of eating compulsively was related to parental fragility, according to the scientific literature. Thus, working in the context of the clinic of parentality may favor relieving of the symptom as it releases the child of an unspeakable legacy and strengthens its subjective position and parental functions. Furthermore, when necessary, it's possible to contribute for bringing up a demand for family therapy.

Estudios con respeto a la obesidad indican que, además de cuestiones genéticas, su surgimiento puede estar asociado a las primeras relaciones interpersonales. El presente artículo tiene por objetivo discutir las contribuciones que la clínica de la parentalidad puede traer para el tratamiento de la obesidad infantil, a partir de recortes de un caso clínico. Para tanto, será presentado el concepto de parentalidad, su derivación clínica y cuestiones de la contemporaneidad que interfieren en el proceso de tornarse padre y madre. La interpretación del material clínico reveló que el comportamiento de comer compulsivo del niño estaba relacionado a la fragilidad parental, de acuerdo con los datos de la literatura. Así, trabajar en el contexto de la clínica de la parentalidad puede favorecer la mejora del síntoma en la medida en que liberta el niño de un legado inenarrable y fortalece tanto el lugar subjetivo del niño como las funciones parentales. Además, en los casos en que es necesario, pueden contribuir para la construcción de una demanda para terapia familiar.

Duration of temporary catheter use for hemodialysis: an observational, prospective evaluation of renal units in Brazil.

BACKGROUND: For chronic hemodialysis, the ideal permanent vascular access is the arteriovenous fistula (AVF). Temporary catheters should be reserved for acute dialysis needs. The AVF is associated with lower infection rates, better clinical results, and a higher quality of life and survival when compared to temporary catheters. In Brazil, the proportion of patients with temporary catheters for more than 3 months from the beginning of therapy is used as an evaluation of the quality of renal units. The aim of this study is to evaluate factors associated with the time between the beginning of hemodialysis with temporary catheters and the placement of the first arteriovenous fistula in Brazil. METHODS: This is an observational, prospective non-concurrent study using national administrative registries of all patients financed by the public health system who began renal replacement therapy (RRT) between 2000 and 2004 in Brazil. Incident patients were eligible who had hemodialysis for the first time. Patients were excluded who: had hemodialysis reportedly started after the date of death (inconsistent database); were younger than 18 years old; had HIV; had no record of the first dialysis unit; and were dialyzed in units with less than twenty patients. To evaluate individual and renal unit factors associated with the event of interest, the frailty model was used (N = 55,589). RESULTS: Among the 23,824 patients (42.9%) who underwent fistula placement in the period of the study, 18.2% maintained the temporary catheter for more than three months until the fistula creation. The analysis identified five statistically significant factors associated with longer time until first fistula: higher age (Hazard-risk - HR 0.99, 95% CI 0.99-1.00); having hypertension and cardiovascular diseases (HR 0.94, 95% CI 0.9-0.98) as the cause of chronic renal disease; residing in capitals cities (HR 0.92, 95% CI 0.9-0.95) and certain regions in Brazil - South (HR 0.83, 95% CI 0.8-0.87), Midwest (HR 0.88, 95% CI 0.83-0.94), Northeast (HR 0.91, 95% CI 0.88-0.94), or North (HR 0.88, 95% CI 0.83-0.94) and the type of renal unit (public or private). CONCLUSION: Monitoring the provision of arteriovenous fistulas in renal units could improve the care given to patients with end stage renal disease.