Gotfredsenernstsen7080

The National Quality Strategy to transform the US health care system is predicated upon Donald Berwick et al.'s "Triple Aim" envisioning the simultaneous pursuit of improved care, better population health, and reduced costs.1 More recently, emphasis has been placed on improving the value of health care as defined by "achieving the best patient health outcomes (quality + experience) at the lowest cost."2 US health care expenditures are projected to grow at an average annual rate of 5.4% during this decade, reaching 19.7% of the gross domestic product or an estimated 6.1 billion dollars by 2028.3 Compared with 36 high-income countries, including Canada, the US spends nearly twice as much on health care yet has the lowest life expectancy and highest suicide rate.4 However, solely targeting reduction in mental health care costs is not a solution, because the mental and general health care systems are inextricably linked5 and for children span multiple care sectors (eg, schools, child welfare, juvenile justice). In this issue of the Journal, Ansari et al.6 validates the complexity of physically ill children with a comorbid psychiatric disorder among more than 50,000 admissions to an acute-care pediatric specialty hospital within Canada's publicly funded health care system. Almost one out of 10 admissions for a physical illness had a documented comorbid psychiatric disorder, which is consistent with US pediatric hospital discharges.7 Children who were older, more clinically complex, and with prior hospitalizations were more likely to be among inpatient admissions with a comorbid psychiatric disorder. With outstanding methodologic rigor, the data suggest that pediatric inpatient admissions with comorbid psychiatric disorders had a nearly 10% longer length of stay and higher costs per admission compared with inpatient admissions without a comorbid psychiatric disorder---a difference in total cumulative costs of more than CAN$11.3 million (equivalent of about US$8.4 million).Wiggins et al.1 recently used data from 3 longitudinal studies spanning preschool and early school children to form an empirically derived framework for early childhood disruptive mood dysregulation disorder (EC-DMDD), ie, a theoretical entity based on all DMDD criteria except the age at onset. The authors showed that the presence of EC-DMDD strongly predicted irritability-related syndromes at early school-ages. The most striking result is that virtually all youths with DMDD had chronic irritability in preschool years (>99%), a finding that challenges the view that DMDD cannot be diagnosed before 6 years of age. In our opinion, the developmental view on DMDD adopted by the authors is particularly welcome to address some of the nosological issues encountered with this disorder.Neurotransmitters, such as γ-aminobutyric acid, glutamate, acetyl choline, glycine and the monoamines, facilitate the crosstalk within the central nervous system. The designated neurotransmitter transporters (NTTs) both release and take up neurotransmitters to and from the synaptic cleft. NTT dysfunction can lead to severe pathophysiological consequences, e.g. epilepsy, intellectual disability, or Parkinson's disease. Genetic point mutations in NTTs have recently been associated with the onset of various neurological disorders. Some of these mutations trigger folding defects in the NTT proteins. Correct folding is a prerequisite for the export of NTTs from the endoplasmic reticulum (ER) and the subsequent trafficking to their pertinent site of action, typically at the plasma membrane. Recent studies have uncovered some of the key features in the molecular machinery responsible for transporter protein folding, e.g., the role of heat shock proteins in fine-tuning the ER quality control mechanisms in cells. The therapeutic significance of understanding these events is apparent from the rising number of reports, which directly link different pathological conditions to NTT misfolding. For instance, folding-deficient variants of the human transporters for dopamine or GABA lead to infantile parkinsonism/dystonia and epilepsy, respectively. From a therapeutic point of view, some folding-deficient NTTs are amenable to functional rescue by small molecules, known as chemical and pharmacological chaperones.Obesity and the metabolic syndrome (MetS), which have reached pandemic proportions significantly increase the risk for type 2 diabetes, cardiovascular disease, and other serious conditions. Recent data with COVID-19 patients indicate that obesity also is a significant risk factor for this novel viral disease and poor outcome of associated critical illness. These findings considerably change the view of obesity as a driver of serious, but slowly-progressing chronic diseases, and emphasize the urgency to explore new therapeutic approaches. Inflammation is a recognized driver of metabolic derangements in obesity and MetS, and a core feature of COVID-19 pathobiology. Recent advances in our understanding of inflammatory regulation have highlighted the role of the nervous system and the vagus nerve-based inflammatory reflex. read more Current bioelectronic and pharmacological therapeutic explorations centered on the inflammatory reflex offer new approaches for conditions characterized by immune and metabolic dysregulation and for ameliorating the escalating burden of obesity, MetS, and COVID-19.

Smoking is associated with numerous inflammatory and autoimmune conditions. The goal of this study was to examine whether increased expression of G-protein-coupled receptor 15 (GPR15) on helper T cells in smokers could predispose to these conditions through its relationship with inflammatory biomarkers.

We used flow cytometric measurement of GPR15

CD3

CD4

helper T cells and serum assays for C-reactive protein (CRP) and 17 cytokines drawn from peripheral blood samples from a cohort of n=62 primarily African American young adults (aged 27-35years). These variables were examined cross-sectionally in conjunction with serum biomarkers of tobacco (cotinine) and cannabis (tetrahydrocannabinol) use and lifestyle factors potentially impacting immune function in correlational analyses and linear regression models.

Tobacco and cannabis smoking were strongly associated with increased GPR15 expression on helper T cells (p<0.001), which was in turn was strongly associated with the ratio of pro-inflammatory to anti-inflammatory cytokines (p<0.