Publications

For placental mammals, the transition from the in utero maternal environment to postnatal life requires the activation of thermogenesis to maintain their core temperature. This is primarily accomplished by induction of uncoupling protein 1 (UCP1) in brown and beige adipocytes, the principal sites for uncoupled respiration. Despite its importance, how placental mammals license their thermogenic adipocytes to participate in postnatal uncoupled respiration is not known. Here, we provide evidence that the "alarmin" IL-33, a nuclear cytokine that activates type 2 immune responses, licenses brown and beige adipocytes for uncoupled respiration. We find that, in absence of IL-33 or ST2, beige and brown adipocytes develop normally but fail to express an appropriately spliced form of Ucp1 mRNA, resulting in absence of UCP1 protein and impairment in uncoupled respiration and thermoregulation. Together, these data suggest that IL-33 and ST2 function as a developmental switch to license thermogenesis during the perinatal period. PAPERCLIP.

BACKGROUND

Current legal efforts to document human rights violations typically include interviews in which survivors are asked to provide detailed descriptions of their traumatic experiences during a single meeting. Research on similar interview techniques used as part of a mental health treatment (eg, debriefing) has raised concerns that they might worsen mental health-more than doubling the risk of post-traumatic stress disorder in some studies. While controversy over the mental health impact of debriefing continues, debriefing treatments have been discontinued in most clinics nearly 2 decades ago. The purpose of this article is to promote the development and integration of preventative measures to limit potential mental health damage associated with legal endeavours to address human rights violations and international crimes.

METHODS AND FINDINGS

Given the recent growth of the field of global mental health and its current capacity to provide feasible, acceptable, effective care in low-resource settings, we propose a research agenda to identify the mental health impact of current human rights legal practices and test a model of scalable medicolegal care that minimises risk by integrating mental health monitoring and applying up-to-date models of trauma treatment, including multiple meeting sessions, as indicated.

CONCLUSIONS

As the fields of global health, human rights law, international criminal law and transitional justice increasingly overlap in their efforts to assist communities affected by grave violence, we propose that synchronising efforts may offer important opportunities to improve mental health for survivors.

OBJECTIVES

This study sought to perform a systematic review and meta-analysis to understand the prognostic value of myocardial scarring as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging in patients with known or suspected cardiac sarcoidosis.

BACKGROUND

Although CMR is increasingly used for the diagnosis of cardiac sarcoidosis, the prognostic value of CMR has been less well described in this population.

METHODS

PubMed, Cochrane CENTRAL, and metaRegister of Controlled Trials were searched for CMR studies with ≥1 year of prognostic data. Primary endpoints were all-cause mortality and a composite outcome of arrhythmogenic events (ventricular arrhythmia, implantable cardioverter-defibrillator shock, sudden cardiac death) plus all-cause mortality during follow-up. Summary effect estimates were generated with random-effects modeling.

RESULTS

Ten studies were included, involving a total of 760 patients with a mean follow-up of 3.0 ± 1.1 years. Patients had a mean age of 53 years, 41% were male, 95.3% had known extracardiac sarcoidosis, and 21.6% had known cardiac sarcoidosis. The average ejection fraction was 57.8 ± 9.1%. Patients with LGE had higher odds for all-cause mortality (odds ratio [OR]: 3.06; p < 0.03) and higher odds of the composite outcome (OR: 10.74; p < 0.00001) than those without LGE. Patients with LGE had an increased annualized event rate of the composite outcome (11.9% vs. 1.1%; p < 0.0001).

CONCLUSIONS

In patients with known or suspected cardiac sarcoidosis, the presence of LGE on CMR imaging is associated with increased odds of both all-cause mortality and arrhythmogenic events.