The Biased G-Protein-Coupled Receptor Agonism Bridges the Gap between the Insulin Receptor and the Metabolic Syndrome.

Insulin signaling, as mediated through the insulin receptor (IR), plays a critical role in metabolism. Aberrations in this signaling cascade lead to several pathologies, the majority of which are classified under the umbrella term "metabolic syndrome". Although many of these pathologies are associated with insulin resistance, the exact mechanisms are not well understood. One area of current interest is the possibility of G-protein-coupled receptors (GPCRs) influencing or regulating IR signaling. This concept is particularly significant, because GPCRs have been shown to participate in cross-talk with the IR. More importantly, GPCR signaling has also been shown to preferentially regulate specific downstream signaling targets through GPCR agonist bias. A novel study recently demonstrated that this GPCR-biased agonism influences the activity of the IR without the presence of insulin. Although GPCR-IR cross-talk has previously been established, the notion that GPCRs can regulate the activation of the IR is particularly significant in relation to metabolic syndrome and other pathologies that develop as a result of alterations in IR signaling. As such, we aim to provide an overview of the physiological and pathophysiological roles of the IR within metabolic syndrome and its related pathologies, including cardiovascular health, gut microflora composition, gastrointestinal tract functioning, polycystic ovarian syndrome, pancreatic cancer, and neurodegenerative disorders. Furthermore, we propose that the GPCR-biased agonism may perhaps mediate some of the downstream signaling effects that further exacerbate these diseases for which the mechanisms are currently not well understood.

Epilepsia partialis continua in relapsing-remitting multiple sclerosis: A possible distinct relapse phenotype.

Epilepsia partialis continua (EPC) is a rare phenomenon in multiple sclerosis (MS). We describe a patient with relapsing-remitting MS and three episodes of EPC, with refractoriness to anti-seizure drugs but corticosteroid-responsiveness. No lesions likely attributable to her episodes of EPC were seen on 1.5 Tesla MRI, which we hypothesize was due to the small volume of presumed cortical/juxtacortical lesions involving the primary motor cortex. The association with relapsing-remitting disease, corticosteroid responsiveness, and dissemination of episodes of EPC in both space and time in our patient suggest that EPC may represent a distinct relapse phenotype in MS.

The crucial role of primary care providers in the long-term follow-up of adult survivors of childhood cancer.

Purpose: The potential physical or psychosocial factors that play a role in the progression of childhood cancer survivors into adulthood are essential in the identification of an effective patient-centred approach to therapy. Despite the presence of guidelines published by the Children's Oncology Group, knowledge of the long-term health sequelae for the care of survivors is sub-optimal. Here, the pertinent clinical issues that may affect survivors of childhood cancer are outlined for primary care providers (PCPs). Methods: This literature search identified articles using PubMed, EMBASE Ovid, and the Cochrane Library to determine high-quality, multicenter randomized controlled trials, systematic reviews, meta-analyses, and practice guidelines from December 1998 to December 2018. The keywords of the search were primary care providers; childhood cancer survivors; long-term care and mental health. Guidelines and research using retrospective studies are used to compile evidence to address PCP's involvement and to describe the factors involved in the adult onset of psychological disorders in survivors of childhood cancer. A focus of this article is to use the literature that evaluated pediatric cancer survivors for at least five years post diagnosis and had received cancer treatment including chemotherapy, radiation, bone marrow transplant, or surgery. Additional research focused on primary care physicians addressing the care of childhood cancer survivors. Here, we aim to provide PCPs and physicians with a critical yet concise update on the recent advancements for this important healthcare topic. This paper presents an overview of previously published reviews and, as such, requires no ethics approval. Results: Childhood cancer survivors can develop symptoms of depression and suffer from low self-esteem from their diagnosis and treatment regimens. These symptoms can result in functional impairment. Child diagnosis also affects parental health, resulting in the experience of psychological, emotional and traumatic stress. The feeling of helplessness and guilt on parents leads to the potentiation of depression on the child survivor. Conclusions: Primary care providers, in collaboration with clinician specialists, must be vigilant in providing consistent long-term care. This approach will ensure clear constant communication to help address the challenges faced by the families and survivors as they progress through adulthood. Implications for cancer survivors: Encouraging primary care providers to become knowledgeable and comfortable in utilizing appropriate resources is achieved through consultation with oncology or psychiatric specialists or with online resources for safer management of childhood cancer survivors. The implications for this patient population would ultimately allow for a more patient-centred approach to therapy.