The role of peripheral physiology in the experience of emotion has been debated since the 19th century following the seminal proposal by William James that somatic responses to stimuli determine subjective emotion. Subsequent views have integrated the forebrain's ability to initiate, represent and simulate such physiological events. Modern affective neuroscience envisions an interacting network of "bottom-up" and "top-down" signaling in which the peripheral (PNS) and central nervous systems both receive and generate the experience of emotion. "Feelings" serves as a term for the perception of these physical changes whether emanating from actual somatic events or from the brain's representation of such. "Interoception" has come to represent the brain's receipt and representation of these actual and "virtual" somatic changes that may or may not enter conscious awareness but, nonetheless, influence feelings. Such information can originate from diverse sources including endocrine, immune and gastrointestinal systems as well as the PNS. We here examine physiological feelings from diverse perspectives including current and historical theories, evolution, neuroanatomy and physiology, development, regulatory processes, pathology and linguistics.

Although theoretical models highlight the role of coping motivations in promoting co-development of depression and alcohol use, few longitudinal studies have examined such processes across early adulthood. The current study examined the role of coping in the association between depression and alcohol use across late adolescence and early adulthood. A control sample of adolescents (N = 498) from a longitudinal prevention trial completed the Brief Symptom Inventory, Life Events Coping Inventory, and a self-report survey on alcohol use at ages 17, 22, and 23, as well as the Composite International Diagnostic Interview at age 28-30. Path analyses integrated self-report and diagnostic measures. Although gender differences were observed in mean levels of depression, alcohol use, and the use of substances to cope, we did not find gender differences in structural relations across these domains over time. Substance use coping served as an intervening pathway in the association between alcohol use and depression both at the symptom level from age 17 to 23, and in predicting longer term diagnostic outcomes at ages 28-30. Depressive symptoms in early adulthood were indirectly related to major depressive disorder (MDD) through two independent paths, including the stability of depressive symptoms over time, and through the influence of depression on increasing the tendency to use substances to cope with stress. Our results underscore that coping effects provide unique predictive power across developmental transitions, over and above the stability of depressive symptoms and alcohol use, underscoring coping motives as a promising intervention target that may prevent co-occurring depression and substance use. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Patients with chronic pancreatitis (CP) frequently have genetic risk factors for disease. Many of the identified genes have been connected to trypsinogen activation or trypsin inactivation. The description of CP in patients with mutations in the variable number of tandem repeat (VNTR) domain of carboxyl ester lipase (CEL) presents an opportunity to study the pathogenesis of CP independently of trypsin pathways. We tested the hypothesis that a deletion and frameshift mutation (C563fsX673) in the CEL VNTR causes CP through proteotoxic gain-of-function activation of maladaptive cell signaling pathways including cell death pathways. HEK293 or AR42J cells were transfected with constructs expressing CEL with 14 repeats in the VNTR (CEL14R) or C563fsX673 CEL (CEL maturity onset diabetes of youth with a deletion mutation in the VNTR (MODY)). In both cell types, CEL MODY formed intracellular aggregates. Secretion of CEL MODY was decreased compared with that of CEL14R. Expression of CEL MODY increased endoplasmic reticulum stress, activated the unfolded protein response, and caused cell death by apoptosis. Our results demonstrate that disorders of protein homeostasis can lead to CP and suggest that novel therapies to decrease the intracellular accumulation of misfolded protein may be successful in some patients with CP.

Introduction: The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. Methods: The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). Results: IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Conclusions: Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS.