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Sensitivity impairment

Hartmut T Bocker, Theresa Heinrich, Lutz Liebmann, J Christopher Hennings, Eric Seemann, Melanie Gerth, Igor Jakovcevski, Julia Preobraschenski, Michael M Kessels, Martin Westermann, Dirk Isbrandt, Reinhard Jahn, Britta Qualmann, Christian A Hübner
Brain functions are extremely sensitive to pH changes because of the pH-dependence of proteins involved in neuronal excitability and synaptic transmission. Here, we show that the Na+/H+ exchanger Nhe1, which uses the Na+ gradient to extrude H+, is expressed at both inhibitory and excitatory presynapses. We disrupted Nhe1 specifically in mice either in Emx1-positive glutamatergic neurons or in parvalbumin-positive cells, mainly GABAergic interneurons. While Nhe1 disruption in excitatory neurons had no effect on overall network excitability, mice with disruption of Nhe1 in parvalbumin-positive neurons displayed epileptic activity...
December 12, 2018: Cerebral Cortex
Alexander V Maltsev, Natalia V Bal, Pavel M Balaban
For several decades, the ability of protein synthesis inhibitors (PSI) to suppress the long-term potentiation (LTP) of hippocampal responses is known. It is considered that mechanisms of such impairment are related to a cessation of translation and a delayed depletion of the protein pool required for maintenance of synaptic plasticity. The present study demonstrates that cycloheximide or anisomycin applications reduce amplitudes of the field excitatory postsynaptic potentials as well as the presynaptically mediated form of plasticity, the paired-pulse facilitation after LTP induction in neurons of the CA1 area of hippocampus...
December 9, 2018: Neuropharmacology
Cynthia L Blanco, Amalia Gastaldelli, Diana G Anzueto, Lauryn A Winter, Steven R Seidner, Donald C McCurnin, Hanyu Liang, Martin A Javors, Ralph A DeFronzo, Nicolas Musi
Premature baboons exhibit peripheral insulin resistance and impaired insulin signaling. 5' AMP-activated protein kinase (AMPK) activation improves insulin sensitivity by enhancing glucose uptake (via increased glucose transporter type 4 [GLUT4] translocation and activation of the extracellular signal-regulated kinase [ERK]/ atypical protein kinase C [aPKC] pathway), and increasing fatty acid oxidation (via inhibition of acetyl-CoA carboxylase 1 [ACC]), while downregulating gluconeogenesis (via induction of small heterodimer partner [SHP] and subsequent downregulation of the gluconeogenic enzymes: phosphoenolpyruvate carboxykinase [PEPCK], glucose 6-phosphatase [G6PASE], fructose- 1,6-bisphosphatase 1 [FBP1], and forkhead box protein 1 [FOXO1])...
2018: PloS One
Manisha Nautiyal, Hossam A Shaltout, Mark C Chappell, Debra I Diz
Hypertensive transgenic (mRen2)27 rats exhibit impaired baroreflex sensitivity (BRS) for control of heart rate (HR). Intracerebroventricular (ICV) infusion of Ang-(1-7) improves indices of vagal BRS independent of lowering mean arterial pressure (MAP), while AT1 receptor blockade normalizes MAP and indices of sympathetic tone without correcting the vagal BRS. Scavenging cellular reactive oxygen species (ROS) with tempol in brain fails to correct either hypertension or sympathovagal balance in these animals, despite reports that mitochondrial ROS contributes to Ang II-infusion hypertension...
December 10, 2018: Journal of Cardiovascular Pharmacology
Xiao-Hong Zhu, Wei Chen
Brain relies on glucose and oxygen metabolisms to generate biochemical energy in the form of adenosine triphosphate (ATP) for supporting electrophysiological activities and neural signaling under resting or working state. Aging is associated with declined mitochondrial functionality and decreased cerebral energy metabolism, and thus, is a major risk factor in developing neurodegenerative diseases including Alzheimer's disease (AD). However, there is an unmet need in the development of novel neuroimaging tools and sensitive biomarkers for detecting abnormal energy metabolism and impaired mitochondrial function, especially in an early stage of the neurodegenerative diseases...
2018: Frontiers in Aging Neuroscience
Yousef D Alqurashi, Takashi Nakamura, Valentin Goverdovsky, James Moss, Michael I Polkey, Danilo P Mandic, Mary J Morrell
Objectives: Detecting sleep latency during the Multiple Sleep Latency Test (MSLT) using electroencephalogram (scalp-EEG) is time-consuming. The aim of this study was to evaluate the efficacy of a novel in-ear sensor (in-ear EEG) to detect the sleep latency, compared to scalp-EEG, during MSLT in healthy adults, with and without sleep restriction. Methods: We recruited 25 healthy adults (28.5±5.3 years) who participated in two MSLTs with simultaneous recording of scalp and in-ear EEG...
2018: Nature and Science of Sleep
Chiara V Colombo, Luca Menin, Riccardo Ranieri, Diego Bonetti, Michela Clerici, Maria Pia Longhese
The Mre11-Rad50-Xrs2 (MRX) complex acts together with the Sae2 protein to initiate resection of DNA double-strand breaks (DSBs) and to regulate a checkpoint response that couples cell cycle progression with DSB repair. Sae2 supports resistance to DNA damage and downregulates the signalling activities of MRX, Tel1 and Rad53 checkpoint proteins at the sites of damage. How these functions are connected to each other is not known. Here, we describe the separation-of-function sae2-ms mutant that, similar to SAE2 deletion, upregulates MRX and Tel1 signalling activities at DSBs by reducing Mre11 endonuclease activity...
December 11, 2018: Genetics
Daniele Coutinho, Antonio Carlos Farias, Erico Pereira Gomes Felden, Mara L Cordeiro
OBJECTIVE: Examine the Strengths and Difficulties Questionnaire (SDQ) responses of parents and teachers for children with ADHD comorbid with major depressive disorder (MDD), with an emphasis on determining how well the respondent groups' responses correlate, and how well the results obtained perform as predictors of clinical diagnosis. METHOD: The SDQ was completed by parents and teachers of ( n = 215 participants, 7-12 years old) in ADHD, MDD, ADHD + MDD, and healthy control groups...
December 12, 2018: Journal of Attention Disorders
Ida T Fonkoue, Seth D Norrholm, Paul J Marvar, Yunxiao Li, Melanie L Kankam, Barbara O Rothbaum, Jeanie Park
Posttraumatic stress disorder (PTSD) is characterized by increased sympathetic nervous system (SNS) activity, blunted parasympathetic nervous system (PNS) activity, and impaired baroreflex sensitivity (BRS), which contribute to accelerated cardiovascular disease. Patients with PTSD also have chronic stress-related elevations in resting blood pressure (BP), often in the prehypertensive range; yet, it is unclear if elevated resting blood pressure (ERBP) augments these autonomic derangements in PTSD. We hypothesized that compared with normotensive PTSD (N-PTSD), those with ERBP (E-PTSD) have further increased SNS, decreased PNS activity, and impaired BRS at rest and exaggerated SNS reactivity, PNS withdrawal, and pressor responses during stress...
December 1, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Emilia Hagman, Anna E Ek, Claude Marcus
BACKGROUND: Impaired fasting glycemia (IFG) reflects an intermediate hyperglycemia in the fasting state. Which fasting glucose level that actually is associated with impaired insulin-glucose homeostasis in children and adolescents with obesity is unknown. OBJECTIVE: The aim of this study was to investigate how insulin and glucose homeostasis in children and adolescents with obesity in Sweden varies within different fasting glucose levels in the non-diabetic range...
December 10, 2018: Pediatric Diabetes
Terrence E Murphy, Thomas M Gill, Linda S Leo-Summers, Evelyne A Gahbauer, Margaret A Pisani, Lauren E Ferrante
OBJECTIVES: To address the competing risk of death in longitudinal studies of older persons, we demonstrate sensitivity analyses that evaluate robustness of associations between exposures and three outcome types: dichotomous, count, and time to event. DESIGN: A secondary analysis of data from a prospective cohort study. SETTING: Community-based data from the Precipitating Events Project in New Haven, CT. PARTICIPANTS: Persons 70 years and older who were initially community dwelling and without disability in the four basic activities of daily living (N = 754)...
December 8, 2018: Journal of the American Geriatrics Society
Estela Lorza-Gil, Jane C de Souza, Marta García-Arévalo, Jean F Vettorazzi, Ana Carolina Marques, Alessandro G Salerno, Jose Roberto Trigo, Helena C F Oliveira
New onset of diabetes is associated with the use of statins. We have recently demonstrated that pravastatin-treated hypercholesterolemic LDL receptor knockout (LDLr-/- ) mice exhibit reductions in insulin secretion and increased islet cell death and oxidative stress. Here, we hypothesized that these diabetogenic effects of pravastatin could be counteracted by treatment with the antioxidant coenzyme Q 10 (CoQ 10 ), an intermediate generated in the cholesterol synthesis pathway. LDLr -/- mice were treated with pravastatin and/or CoQ 10 for 2 months...
December 7, 2018: Journal of Cellular Physiology
Marco Lucioni, Marco Lionello, Piernicola Machin, Federica Sovran, Fabio Canal, Andy Bertolin, Giuseppe Rizzotto
BACKGROUND: Given the relevance of any tumor invasion of the arytenoid cartilage or crico-arytenoid unit to the planning open partial horizontal laryngectomy (OPHL) for laryngeal squamous cell carcinoma (LSCC), it is important to have a reliable radiological test to assess impairments of these structures. METHODS: We retrospectively compared the endoscopic, radiological, and pathological findings in patients with glottic LSCC who underwent OPHL. RESULTS: The endoscopic finding of a reduced (impaired or absent) vocal cord motility proved more sensitive, with better positive and negative predictive values, but less specific than the radiological finding of complete arytenoid sclerosis in detecting histologically assessable infiltration of the arytenoid cartilage...
December 7, 2018: Head & Neck
Shan Huang, Yong Xu, Wen-Fang Peng, Jie Cheng, Hui-Hua Li, Li-Sha Shen, Li-Li Xia
Asymmetric dimethylarginine (ADMA) plays a vital role in the regulation of insulin sensitivity and has been shown as a potential marker for various disease, including type 2 diabetes mellitus (DM2). However, the correlation between ADMA and impaired glucose tolerance (IGT) and obesity has not been studied. A total of 195 subjects were involved in our study. The characteristics of the subjects in the study cohort were measured and analyzed. We found that the serum ADMA and C-reactive protein levels were significantly increased in IGT and diabetic patients, whereas the levels of lipoprotein A and adiponectin were decreased, especially in diabetic patients with obesity...
December 7, 2018: Journal of Cellular Physiology
E M Messmer
BACKGROUND: Neurotrophic keratopathy is characterized by corneal surface alterations, persistent corneal epithelial defects and/or corneal ulcerations associated with corneal sensory abnormalities. Due to the variable clinical picture neurotrophic keratopathy is often overlooked or diagnosed too late in the course of the disease. OBJECTIVE: Discussion of the clinical picture of neurotrophic keratopathy and recommendations for correct diagnosis. MATERIAL AND METHODS: Analysis of the existing literature and discussion of basic recent publications...
December 7, 2018: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
Julia Spaniol, Francesco Di Muro, Elisa Ciaramelli
The ventromedial prefrontal cortex (vmPFC) is known to play a key role in reward processing and decision making. However, its relative contribution to affect-rich ("hot") and affect-poor ("cold") decisions is not fully understood. Damage to vmPFC is associated with impaired performance on laboratory tasks of decision making under ambiguity and risk. In the current study, we tested the hypothesis that vmPFC is critical for adaptive risk taking under "hot" conditions specifically...
December 7, 2018: Cognitive, Affective & Behavioral Neuroscience
Britta Wilms, Elena M Leineweber, Matthias Mölle, Rodrigo Chamorro, Claudia Pommerenke, Gabriela Salinas-Riester, Christian Sina, Hendrik Lehnert, Henrik Oster, Sebastian M Schmid
Context: Chronodisruption as caused by e.g. perturbations of 24h-rhythms of physiology and behavior clearly may promote the development of metabolic diseases. Objective: To assess the acute effects of sleep curtailment on circadian regulation, i.e. morning-to-evening-differences, of white adipose tissue (WAT) transcriptome in normal-weight men. Design: Fifteen healthy men aged 18-30years (mean±SEM: 24.0±0.9years) were studied. In randomized, balanced order they underwent three separate nights with regular sleep duration (8h sleep between 2300-0700h), sleep restriction (4h sleep between 0300-0700h), and sleep deprivation (SD; no sleep at all)...
December 6, 2018: Journal of Clinical Endocrinology and Metabolism
Timothy J Reynolds, Joseph Paul Coviello, Michael Costello
Background and Purpose: There have been few published studies regarding the treatment of patients with non-ossifying fibromas (NOFs), either conservatively or operatively. The purpose of this case report is to discuss the clinical presentation and conservative management of a teenage athlete diagnosed with a proximal humerus NOF. Case Description: The subject was a 13-year-old male middle school student with a diagnosis of left shoulder pain over the prior year preventing him from participating in sports activities...
December 2018: International Journal of Sports Physical Therapy
Eri Amano, Shogo Funakoshi, Kumiko Yoshimura, Seiki Hirano, Satoko Ohmi, Hiroshi Takata, Yoshio Terada, Shimpei Fujimoto
Background: Recently, an integrated network analysis has revealed dysregulation in the metabolism of mannose, a glucose epimer, in severely obese individuals without diabetes. In addition, fasting plasma mannose levels (M0 ) are associated with insulin resistance independent of BMI. Since the association between mannose and insulin sensitivity (IS) in those with impaired glucose tolerance remains unknown, we aimed to investigate this association in individuals without severe obesity but with varying degrees of glucose tolerance...
2018: Diabetology & Metabolic Syndrome
Ciro De Luca, Anna Maria Colangelo, Lilia Alberghina, Michele Papa
Coagulation and the immune system interact in several physiological and pathological conditions, including tissue repair, host defense, and homeostatic maintenance. This network plays a key role in diseases of the central nervous system (CNS) by involving several cells (CNS resident cells, platelets, endothelium, and leukocytes) and molecular pathways (protease activity, complement factors, platelet granule content). Endothelial damage prompts platelet activation and the coagulation cascade as the first physiological step to support the rescue of damaged tissues, a flawed rescuing system ultimately producing neuroinflammation...
2018: Frontiers in Cellular Neuroscience
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