Nicolaisendickey1358

OBJECTIVE The role of the nucleus accumbens (NAc) in chronic neuropathic pain has been suggested, but the role of the NAc in dorsal root ganglion (DRG) neuropathic pain remains unclear. The objective of this study was to determine whether optogenetic stimulation of the NAc influences DRG compression-induced neuropathic pain. MATERIALS AND METHODS We established sham or DRG lesions in female Sprague-Dawley rats by L4-5 DRG root compression, and the animals received unilateral injections of optogenetic virus in the NAc core. We employed reflexive pain tests to assess the alterations between the groups at the light on/off states. To determine thalamic firing, we performed single-unit in vivo extracellular recording. For statistical analysis, we used one- or two-way repeated-measures analysis of variance. RESULTS Compared to sham-operated rats, chronic compressed DRG rats showed elevated behavioral sensitivity and sustained neuronal hyperexcitability in the thalamus. NAc optic stimulation improved pain behaviors and lowered thalamic discharge from ventral posterolateral thalamic nuclei. CONCLUSIONS The NAc core impacts the reward and motivational aspects of chronic neuropathic pain influenced by limbic behaviors to thalamic discharge. Increased thalamic firing activity may result in chronic compressed DRG-induced neuropathic pain, and optogenetic neuromodulation of the NAc can ease chronic pain and thalamic discharge. © 2019 International Neuromodulation Society.INTRODUCTION Nociceptive signals from lumbar intervertebral discs ascend in the sympathetic chain via the L2 dorsal root ganglion (L2 DRG), a potential target for discogenic low back pain in neuromodulation. Positron Emission Tomography/Computed Tomography (PET-CT) measures functional changes in the brain metabolic activity, identified by the changes in the regional cerebral blood flow (rCBF) as determined by the changes of F-18 Fluoro-deoxyglucose (18 F FDG) tracer within brain tissues. METHODS AND MATERIALS Nine patients were recruited to explore the changes in PET-CT imaging at baseline and four-weeks post implantation of bilateral L2 DRG neurostimulation leads and implantable pulse generator (IPG). PET-CT scans were performed 30 min following an IV injection of 250±10% MBq of 18 F FDG tracer. Fifteen frames were acquired in 15 min. PET list-mode raw data were reconstructed and normalized appropriately to a brain anatomical atlas. RESULTS Nine patients were recruited to the study, where PET-CT imaging datalation Society.The genetic aetiology and the molecular mechanisms that characterize high-risk neuroblastoma are still little understood. The majority of high-risk neuroblastoma patients do not take advantage of current induction therapy. So far, one of the main reasons liable for cancer therapeutic failure is the acquisition of resistance to cytotoxic anticancer drugs, because of the DNA repair system of tumour cells. PARP1 is one of the main DNA damage sensors involved in the DNA repair system and genomic stability. We observed that high PARP1 mRNA level is associated with unfavourable prognosis in 3 public gene expression NB patients' datasets and in 20 neuroblastomas analysed by qRT-PCR. Among 4983 SNPs in PARP1, we selected two potential functional SNPs. We investigated the association of rs907187, in PARP1 promoter, and rs2048426 in non-coding region with response chemotherapy in 121 Italian patients with high-risk NB. Results showed that minor G allele of rs907187 associated with induction response of patients (P = .02) and with decrease PARP1 mRNA levels in NB cell line (P = .003). Furthermore, rs907187 was predicted to alter the binding site of E2F1 transcription factor. Specifically, allele G had low binding affinity with E2F1 whose expression positively correlates with PARP1 expression and associated with poor prognosis of patients with NB. By contrast, we did not find genetic association for the SNP rs2048426. These data reveal rs907187 as a novel potential risk variant associated with the failure of induction therapy for high-risk NB. © 2020 Università degli Studi di Napoli Federico II. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.SCOPE Evidence gathered in the last decades suggests that lipotoxicity and inflammation are the main factors connecting adipose tissue dysfunction to the development of metabolic diseases such as insulin resistance, nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, and certain types of cancer, among others. The mechanistic target of rapamycin (mTOR) is a serine threonine kinase that functions as the catalytic entity of two multiprotein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). These complexes are important components of signaling pathways activated by nutrients, growth factors, and inflammatory mediators and are therefore directly involved in the regulation of adipocyte and macrophage metabolism and function. METHODS AND RESULTS In this article, studies that evaluate the involvement of mTORC1 and 2 in the regulation of macrophage and adipocyte function and their implication in the development of metabolic-disease-associated adipose tissue dysfunction are reviewed. CONCLUSION In adipocytes, optimal levels of mTORC1 activity are required for its pro-lipogenic actions, while in macrophages, mTORC1 regulates features of both M1 and M2 polarization. mTORC2, on the other hand, promotes glucose uptake and de novo lipogenesis in adipocytes and counteracts macrophage inflammatory response. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Low-grade canine cutaneous mast cell tumour (cMCT) with metastasis at the time of treatment is uncommonly reported, with few studies focusing on this specific clinical entity. The specific objective of this study was to systematically review the veterinary literature and perform a meta-analysis summarizing the clinical presentation, treatments reported and clinical outcomes from dogs with histologically low-grade cMCT and metastasis present at initial treatment. A total of 980 studies were screened with eight publications providing data on 121 dogs ultimately included. The most common treatments were surgery with adjuvant chemotherapy in 83/121 (69%) dogs; combined surgery, radiation and chemotherapy in 17/121 (14%) dogs; chemotherapy alone in 12/121 (10%) dogs and surgery alone in 7/121 (6%) dogs. Dogs with distant metastasis (n = 22) experienced significantly shorter survival compared with those with regional lymph node (RLN) metastasis (n = 99; median 194 vs 637 days; P  less then  .01). Two variables were significantly associated with increased risk of death presence of distant (vs RLN) metastasis (hazard ratio = 2.60; P  less then  .01) and not receiving surgery as a component of treatment (hazard ratio = 3.79; P  less then  .01). Risk of bias was judged to be low in terms of selection and performance bias but high in terms of detection and exclusion bias. In conclusion, dogs with cMCT and RLN metastasis can be expected to live significantly longer than those with distant metastasis, and surgery appears to have a role in extending survival of metastatic low-grade cMCT. © 2020 John Wiley & Sons Ltd.AIM To determine whether teachers' reports of student academic performance can suffice for research purposes by comparing it with a curriculum-based standardised test. METHODS In this longitudinal cohort study of children born at risk of neonatal hypoglycaemia, teachers' global assessment of student performance was compared with assessment tools for teaching and learning (asTTle) at 9-10 years. Performance on asTTLe was rated as being below, at or above that expected on the national curriculum for year and term of schooling. Teachers similarly rated the child's performance against the national curriculum. RESULTS Of 125 children assessed, 104 had paired data for analysis. On asTTLe, 28% were rated below, 55% at and 17% above the expected curriculum level in reading and 24, 54 and 22%, respectively, in mathematics. Equivalent teacher ratings were 23, 58 and 19% in reading and 36, 55 and 9% in mathematics, respectively. However, there was limited agreement between asTTle and teacher rating of achievement in reading (κ = 0.23 (95% confidence interval 0.07-0.40)) and no significant agreement in mathematics (κ = 0.07 (95% confidence interval -0.09-0.22)). Only 45% of children performing below the curriculum level in reading and 52% in mathematics were correctly identified by teachers. CONCLUSION In cohort studies, teacher ratings cannot substitute standardised educational testing. © 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).BACKGROUND Perturbation in cell adhesion and growth factor signalling in satellite cells results in decreased muscle regenerative capacity. Cdon (also called Cdo) is a component of cell adhesion complexes implicated in myogenic differentiation, but its role in muscle regeneration remains to be determined. METHODS We generated inducible satellite cell-specific Cdon ablation in mice by utilizing a conditional Cdon allele and Pax7 CreERT2 . To induce Cdon ablation, mice were intraperitoneally injected with tamoxifen (tmx). Using cardiotoxin-induced muscle injury, the effect of Cdon depletion on satellite cell function was examined by histochemistry, immunostaining, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Isolated myofibers or myoblasts were utilized to determine stem cell function and senescence. To determine pathways related to Cdon deletion, injured muscles were subjected to RNA sequencing analysis. RESULTS Satellite cell-specific Cdon ablation causes impaired muscle regeneration with fibrosisrcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.BACKGROUND Heart rate acceleration and deceleration capacities are novel parameters that can quantify sympathetic and vagal modulation. However, how acceleration and deceleration capacities associated with circadian blood pressure (BP) variation remains unknown. METHODS A total of 141 patients with essential hypertension were included in our study. Based on the nocturnal decline rate of systolic BP (SBP), patients were divided into two groups, as dippers and nondippers. Baseline demographic characteristics, ambulatory blood pressure monitoring (ABPM) parameters, Holter recordings, and echocardiographic parameters were collected. RESULTS The absolute values of acceleration capacity (AC) (-7.75 [-8.45 ~ -6.3] ms vs. -6.6 [-8.25 ~ -5.2] ms, p = .047) and deceleration capacity (DC) (7.35 [6.1 ~ 8.1] ms vs. 6.3 [5.1 ~ 7.6] ms, p = .042) were significantly higher in dippers than in nondippers. By multivariate logistic regression analysis, left atrial diameter (LAd) was found to be an independent risk factor for nondipper status in acceleration capacity model (odds ratio 1.174, 95% confidence interval 1.019-1.354, p = .027) and deceleration model (odds ratio 1.146, 95% confidence interval 1.003-1.309, p = .045). Sleep SBP was positively correlated to acceleration capacity (r = .256, p = .002) and negatively correlated to deceleration capacity (r = -.194, p = .021). CONCLUSIONS The absolute values of acceleration capacity and deceleration capacity were higher in patients with dipper hypertension than in patients with nondipper hypertension. However, acceleration and deceleration capacities were not independent risk factors for blunted BP variation. Sleep SBP seemed to be better correlated to the impairment of autonomic nervous system (ANS) function than other ABPM parameters. © 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals, Inc.