Induction of antiviral interferon-stimulated genes by neuronal STING promotes the resolution of pain in mice.

Inflammation and pain are intertwined responses to injury, infection, or chronic diseases. While acute inflammation is essential in determining pain resolution and opioid analgesia, maladaptive processes occurring during resolution can lead to the transition to chronic pain. Here we found that inflammation activates the cytosolic DNA-sensing protein stimulator of IFN genes (STING) in dorsal root ganglion nociceptors.

Information and vaccine hesitancy: Evidence from the early stage of the vaccine roll-out in 28 European countries.

The success of mass vaccination programs against SARS-CoV-2 hinges on the public's acceptance of the vaccines. During a vaccine roll-out, individuals have limited information about the potential side-effects and benefits. Given the public health concern of the COVID pandemic, providing appropriate information fast matters for the success of the campaign.

The neuronal tyrosine kinase receptor ligand ALKAL2 mediates persistent pain.

The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase known for its oncogenic potential that is involved in the development of the peripheral and central nervous system. ALK receptor ligands ALKAL1 and ALKAL2 were recently found to promote neuronal differentiation and survival. Here, we show that inflammation or injury enhanced ALKAL2 expression in a subset of TRPV1+ sensory neurons.

Gut-innervating TRPV1+ Neurons Drive Chronic Visceral Pain via Microglial P2Y12 Receptor.

Background & Aims: Chronic abdominal pain is a common symptom of inflammatory bowel diseases (IBDs). Peripheral and central mechanisms contribute to the transition from acute to chronic pain during active disease and clinical remission. Lower mechanical threshold and hyperexcitability of visceral afferents induce gliosis in central pain circuits, leading to persistent visceral hypersensitivity (VHS).

TRPV1 Activation Promotes β-arrestin2 Interaction with the Ribosomal Biogenesis Machinery in the Nucleolus:Implications for p53 Regulation and Neurite Outgrowth.

Transient receptor potential vanilloids TRPV1) are non-selective cation channels that sense and transduce inflammatory pain signals. We previously reported that activation of TRPV1 induced the translocation of β-arrestin2 (ARRB2) from the cytoplasm to the nucleus, raising questions about the functional role of ARRB2 in the nucleus. Here, we determined the ARRB2 nuclear signalosome by conducting a quantitative proteomic analysis of the nucleus-sequestered L395Q ARRB2 mutant, compared to the cytosolic wild-type ARRB2 (WT ARRB2), in a heterologous expression system.

TACAN Is an Ion Channel Involved in Sensing Mechanical Pain.

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain.

TRPV1 promotes opioid analgesia during inflammation.

Pain and inflammation are inherently linked responses to injury, infection, or chronic diseases. Given that acute inflammation in humans or mice enhances the analgesic properties of opioids, there is much interest in determining the inflammatory transducers that prime opioid receptor signaling in primary afferent nociceptors. Here, we found that activation of the transient receptor potential vanilloid type 1 (TRPV1) channel stimulated a mitogen-activated protein kinase (MAPK) signaling pathway that was accompanied by the shuttling of the scaffold protein β-arrestin2 to the nucleus.

Inhibition of Ca 3.2 calcium channels: A new target for colonic hypersensitivity associated with low-grade inflammation.

Background And Purpose: Abdominal pain associated with low-grade inflammation is frequently encountered in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) during remission. Current treatments are not very effective and new therapeutic approaches are needed. The role of Ca 3.

Impact of rocker sole footwear on plantar pressure distribution during standing and walking in adult obese women.

Obesity increases the stresses applied to the foot. Ergonomic rocker sole shoes increase energy expenditure of standing and walking in obese individuals but could potentially alter plantar pressure distribution. The aim of this study was to compare plantar pressure distribution during standing and walking between rocker sole and flat-bottomed shoes in obese subjects.

Cardiometabolic risk factors differ among adolescents with obesity in three European countries - a cross-sectional study.

Aim: We aimed to compare modifiable cardiometabolic risk factors among treatment-seeking adolescents with obesity in Italy, Germany and Norway.

Methods: This retrospective, registry-based, cross-sectional cohort study included 2,327 (59% girls) 12-18 year-old adolescents with obesity from three tertiary care outpatient clinics in Europe, between 1999 and 2015. The prevalence of cardiometabolic risk factors was compared between clinics, and multivariate logistic regression models including gender, age, waist circumference and body mass index were used to assess the associations between population and cardiometabolic risk.

Ergogenic effects of beetroot juice supplementation during severe-intensity exercise in obese adolescents.

Previous studies showed a higher O cost of exercise, and therefore, a reduced exercise tolerance in patients with obesity during constant work rate (CWR) exercise compared with healthy subjects. Among the ergogenic effects of dietary nitrate ([Formula: see text]) supplementation in sedentary healthy subjects, a reduced O cost and enhanced exercise tolerance have often been demonstrated. The aim of this study was to evaluate the effects of beetroot juice (BR) supplementation, rich in [Formula: see text], on physiological variables associated with exercise tolerance in adolescents with obesity.

Feasibility, Validity, and Reliability of the Italian Pediatric Quality of Life Inventory Multidimensional Fatigue Scale for Adults in Inpatients with Severe Obesity.

Objective: This study was aimed to examine the feasibility, validity, and reliability of the Italian Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL™ MFS) for adult inpatients with severe obesity.

Methods: 200 inpatients (81% females) with severe obesity (BMI ≥ 35 kg/m2) completed the PedsQL MFS (General Fatigue, Sleep/Rest Fatigue and Cognitive Fatigue domains), the Fatigue Severity Scale, and the Center for Epidemiologic Studies Depression Scale immediately after admission to a 3-week residential body weight reduction program. A randomized subsample of 48 patients re-completed the PedsQL MFS after 3 days.

External validation of equations to estimate resting energy expenditure in 14952 adults with overweight and obesity and 1948 adults with normal weight from Italy.

Background & Aims: We cross-validated 28 equations to estimate resting energy expenditure (REE) in a very large sample of adults with overweight or obesity.

Methods: 14952 Caucasian men and women with overweight or obesity and 1498 with normal weight were studied. REE was measured using indirect calorimetry and estimated using two meta-regression equations and 26 other equations.

Reproducibility of clinician-friendly physical performance measures in individuals with obesity.

Objective: To evaluate the reproducibility (reliability and agreement) of different physical performance measures in individuals with obesity.

Methods: Forty subjects (20 men, 20 women), mean age 29 years, mean body mass index (BMI) 42 kg/m2 completed several clinician-friendly performance-based tests (walking, stair-climbing, sit-to-stand, static balance, flexibility and strength) on 2 different occasions (test-retest design). Intraclass correlation coefficients (reliability) and smallest detectable changes (agreement) were calculated for each outcome measure.

Respiratory muscle endurance training reduces the O cost of cycling and perceived exertion in obese adolescents.

In obesity, the increased O cost of breathing negatively affects the O cost of exercise and exercise tolerance. The purpose of the study was to determine whether, in obese adolescents, the addition of respiratory muscle endurance training (RMET) (isocapnic hyperpnea) to a standard body mass reduction program decreases the O cost of exercise and perceived exertion. Nine male obese adolescents [16.

GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in Obese Patients with Fibromyalgia Syndrome.

Reportedly, fibromyalgia (FM) is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or <-2 SDS), underwent the combined GHRH plus arginine test. Four out of 16 obese women with FM (25%) had low IGF-1 SDS values, 2 cases of this subgroup (12.

Hedonic eating in Prader-Willi syndrome is associated with blunted PYY secretion.

Hedonic and homeostatic hunger represent two different forms of eating: just for pleasure or following energy deprivation, respectively. Consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and some specific endocannabinoids in normal-weight subjects and patients with morbid obesity. To date, the effects of palatable food on these mediators in Prader-Willi syndrome (PWS) are still unknown.

A simple strategy for culturing morphologically-conserved rat hypothalamic tanycytes.

Hypothalamic tanycytes are specialized bipolar ependymal cells that line the floor of the third ventricle. Given their strategic location, tanycytes are believed to play several key functions including being a selective barrier and controlling the amount of hypothalamic-derived factors reaching the anterior pituitary. The in vitro culture of these cells has proved to be difficult.

Melanocortin 4 receptor constitutive activity inhibits L-type voltage-gated calcium channels in neurons.

The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied.

Effects of a multidisciplinary body weight reduction program on static and dynamic thoraco-abdominal volumes in obese adolescents.

The objective of this study was to characterize static and dynamic thoraco-abdominal volumes in obese adolescents and to test the effects of a 3-week multidisciplinary body weight reduction program (MBWRP), entailing an energy-restricted diet, psychological and nutritional counseling, aerobic physical activity, and respiratory muscle endurance training (RMET), on these parameters. Total chest wall (VCW), pulmonary rib cage (VRC,p), abdominal rib cage (VRC,a), and abdominal (VAB) volumes were measured on 11 male adolescents (Tanner stage: 3-5; BMI standard deviation score: >2; age: 15.9 ± 1.

Anticipatory and consummatory effects of (hedonic) chocolate intake are associated with increased circulating levels of the orexigenic peptide ghrelin and endocannabinoids in obese adults.

Background: Hedonic hunger refers to consumption of food just for pleasure and not to maintain energy homeostasis. Recently, consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in normal-weight subjects. To date, the effects of hedonic hunger, and in particular of chocolate craving, on these mediators in obese subjects are still unknown.

Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons.

The growth hormone secretagogue receptor type 1a (GHSR1a) has the highest known constitutive activity of any G protein-coupled receptor (GPCR). GHSR1a mediates the action of the hormone ghrelin, and its activation increases transcriptional and electrical activity in hypothalamic neurons. Although GHSR1a is present at GABAergic presynaptic terminals, its effect on neurotransmitter release remains unclear.

Assessment of fat-free mass from bioelectrical impedance analysis in obese women with Prader-Willi syndrome.

Background: Fat-free mass (FFM) is lower in obese subjects with Prader-Willi syndrome (PWS) than in obese subjects without PWS. FFM prediction equations developed in non-PWS subjects may, thus, not work in PWS subjects.

Aim: To test whether the estimation of FFM from bioelectrical impedance analysis (BIA) in PWS subjects requires population-specific equations.

Acute respiratory muscle unloading by normoxic helium-O₂ breathing reduces the O₂ cost of cycling and perceived exertion in obese adolescents.

Purpose: In obesity, an increased work of breathing contributes to a higher O2 cost of exercise and negatively affects exercise tolerance. The purpose of the study was to determine whether, in obese adolescents, acute respiratory muscle unloading via normoxic helium-O2 breathing reduces the O2 cost of cycling and perceived exertion.

Methods: Nine males [age 16.