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https://www.readbyqxmd.com/read/29332582/dual-bace-1-gsk-3%C3%AE-inhibitors-to-combat-alzheimer-s-disease-a-focus-review
#1
Angela Rampa, Silvia Gobbi, Rita Maria Concetta Di Martino, Federica Belluti, Alessandra Bisi
In industrialized countries, Alzheimer's disease represents the most devastating neurodegenerative disorder in elderly people and the search for a disease modifying agent is still justified by this unmet need. Several possible targets have been explored to find an appropriate drug therapy, and in this review dual inhibitors of beta secretase and glycogen synthase kinase 3, recently reported in literature, will be appraised. Applying a ligand-based approach, the triazinone core emerged as a suitable scaffold to simultaneously bind the aspartic dyad of BACE-1 and the ATP site of GSK-3β, leading to a series of small molecules endowed with a balanced micromolar affinity and a promising pharmacokinetic profile...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332562/the-delicate-balance-between-the-good-and-the-bad-il-1-proinflammatory-effects-in-endometriosis
#2
Justyna Sikora, Simone Ferrero, Aleksandra Mielczarek-Palacz, Zdzislawa Kondera-Anasz
BACKGROUND: Endometriosis is an inflammatory gynaecological disease with an associated chronic inflammation. Interleukin(IL)-1 is one of the most important immune and proinflammatory factors, produced mainly by monocytes and macrophages. Studies indicate the role of the cytokine from IL-1 family in endometrium-related disorders, particularly in endometriosis. METHODS: The information about the impact of cytokine from IL-1 cytokine family on the pathogenesis and development of endometriosis was obtained with an electronic literature search based on the PubMed and Medline databases, spanning the period of January 1950 to July 2017 and includes associated references in the published studies...
January 10, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29332239/which-parameters-are-relevant-in-sagittal-balance-analysis-of-the-cervical-spine-a-literature-review
#3
REVIEW
Fong Poh Ling, T Chevillotte, A Leglise, W Thompson, C Bouthors, Jean-Charles Le Huec
INTRODUCTION: Cervical spine is part of the spine with the most mobility in the sagittal plane. It is important for surgeons to have reliable, simple and reproducible parameters to analyse the cervical. MATERIAL AND METHOD: This study is a systematic review and a critique of current parameters to help improve the study of cervical spinal balance. We conducted a systematic search of PUBMED/MEDLINE for literature published since January 2014. Only studies written in English and containing abstracts were considered for inclusion...
January 13, 2018: European Spine Journal
https://www.readbyqxmd.com/read/29331064/controlling-the-temporal-structure-of-brain-oscillations-by-focused-attention-meditation
#4
Mona Irrmischer, Simon J Houtman, Huibert D Mansvelder, Michael Tremmel, Ulrich Ott, Klaus Linkenkaer-Hansen
Our focus of attention naturally fluctuates between different sources of information even when we desire to focus on a single object. Focused attention (FA) meditation is associated with greater control over this process, yet the neuronal mechanisms underlying this ability are not entirely understood. Here, we hypothesize that the capacity of attention to transiently focus and swiftly change relates to the critical dynamics emerging when neuronal systems balance at a point of instability between order and disorder...
January 13, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29330326/loss-of-balance-between-striatal-feedforward-inhibition-and-corticostriatal-excitation-leads-to-tremor
#5
Yael Oran, Izhar Bar-Gad
Fast spiking interneurons (FSIs) exert powerful inhibitory control over the striatum and are hypothesized to balance the massive excitatory cortical and thalamic input to this structure. We recorded neuronal activity in the dorsolateral striatum and globus pallidus (GP) concurrently with the detailed movement kinematics of freely behaving female rats prior to and following selective inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to the appearance of episodic rest tremor in the body part that depended on the somatotopic location of the injection within the striatum...
January 12, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29330044/effects-of-acupuncture-on-the-heart-rate-variability-cortisol-levels-and-behavioural-response-induced-by-thunder-sound-in-beagles
#6
Carolina Elisabetta Martins Maccariello, Carla Caroline Franzini de Souza, Laura Morena, Daniel Penteado Martins Dias, Magda Alves de Medeiros
Sound stimuli such as fireworks, firearms, and claps of thunder have been used as a stress reactivity model for dogs. Acupuncture has been widely used to treat and prevent physiological and behavioural disorders induced by stress. Our study aims to evaluate the effects of acupuncture on cardiac autonomic modulation (heart rate variability - HRV), behavioural (reactivity) and endocrine (cortisol levels) responses in dogs exposed to sounds of thunder. Twenty-four laboratory beagles (12 males and 12 females, 1-6years old) with no history of phobia to thunder were subjected to a sound stimulus that consisted of a standardized recording of thunder over a 150s period with a maximum intensity of 103-104dB...
January 9, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29329999/understanding-melanocortin-4-receptor-control-of-neuronal-circuits-toward-novel-therapeutics-for-obesity-syndrome
#7
REVIEW
Sang Hyeon Ju, Gyu-Bon Cho, Jong-Woo Sohn
It is well known that melanocortin-4 receptors (MC4Rs) and central melanocortin pathways regulate food intake, energy expenditure, and glucose homeostasis. Importantly, MC4R deficiency is the most common monogenic cause of human obesity. Interestingly, MC4Rs expressed by distinct central nuclei are responsible for the different physiological function of MC4R stimulation. In addition, MC4Rs activate multiple intracellular and/or synaptic signaling molecules for the regulation of neuronal circuits. Therefore, MC4Rs and the downstream signal molecules are plausible targets for development of novel therapeutics against obesity and obesity-related metabolic disorders...
January 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29329237/mtor-pathways-in-cancer-and-autophagy
#8
REVIEW
Mathieu Paquette, Leeanna El-Houjeiri, Arnim Pause
TOR (target of rapamycin), an evolutionarily-conserved serine/threonine kinase, acts as a central regulator of cell growth, proliferation and survival in response to nutritional status, growth factor, and stress signals. It plays a crucial role in coordinating the balance between cell growth and cell death, depending on cellular conditions and needs. As such, TOR has been identified as a key modulator of autophagy for more than a decade, and several deregulations of this pathway have been implicated in a variety of pathological disorders, including cancer...
January 12, 2018: Cancers
https://www.readbyqxmd.com/read/29329064/user-acceptability-of-the-diagnosis-of-prolonged-grief-disorder-how-do-professionals-think-about-inclusion-in-icd-11
#9
Leonie Dietl, Birgit Wagner, Thomas Fydrich
BACKGROUND: For the next edition of the International Statistical Classification of Diseases (ICD-11) it is proposed to include prolonged grief disorder as a new diagnosis. The diagnosis describes persistent intensive and disabling grief reactions to bereavement (WHO, 2016b). The aim of the present survey was to determine the extent to which the diagnosis is accepted by practitioners in the healthcare and psychosocial field. METHODS: A total of 2088 German-speaking professionals in the fields of psychotherapy, psychology, counselling, medicine and palliative care completed the online survey...
January 3, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29327340/shank3-deficient-thalamocortical-neurons-show-hcn-channelopathy-and-alterations-in-intrinsic-electrical-properties
#10
Mengye Zhu, VinayKumar Idikuda, Jianbing Wang, Fusheng Wei, Virang Kumar, Nikhil Shah, Christopher B Waite, Qinglian Liu, Lei Zhou
Shank3 is a scaffolding protein that is highly enriched in excitatory synapses. Mutations in Shank3 gene have been linked to neuropsychiatric disorders especially the Autism Spectrum Disorders (ASD). Shank3 deficiency is known to cause impairments in synaptic transmission, but its effects on basic neuronal electrical properties that are more localized to the soma and proximal dendrites remain unclear. Here we confirmed that in heterologous expression systems two different Shank3 isoforms, Shank3A and Shank3C, significant increase the surface expression of the hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel...
January 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29321672/phenotypic-interpretation-of-complex-chromosomal-rearrangements-informed-by-nucleotide-level-resolution-and-structural-organization-of-chromatin
#11
Cinthya J Zepeda-Mendoza, Alexandra Bardon, Tammy Kammin, David J Harris, Helen Cox, Claire Redin, Zehra Ordulu, Michael E Talkowski, Cynthia C Morton
Molecular characterization of balanced chromosomal abnormalities constitutes a powerful tool in understanding the pathogenic mechanisms of complex genetic disorders. Here we report a male with severe global developmental delay in the presence of a complex karyotype and normal microarray and exome studies. The subject, referred to as DGAP294, has two de novo apparently balanced translocations involving chromosomes 1 and 14, and chromosomes 4 and 10, disrupting several different transcripts of adhesion G protein-coupled receptor L2 (ADGRL2) and protocadherin 15 (PCDH15)...
January 10, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29319170/sirt6-deacetylase-transcriptionally-regulates-glucose-metabolism-in-heart
#12
Danish Khan, Mohsen Sarikhani, Subhajit Dasgupta, Babukrishna Maniyadath, Anwit Shriniwas Pandit, Sneha Mishra, Faiz Ahamed, Abhinav Dubey, Nowrin Fathma, Hanudatta S Atreya, Ullas Kolthur-Seetharam, Nagalingam R Sundaresan
Sirtuins are a family of enzymes, which govern a number of cellular processes essential for maintaining physiological balance. SIRT6, a nuclear localized sirtuin, is implicated in the development of metabolic disorders. The role of SIRT6 in regulation of cardiac metabolism is unexplored. Although glucose is not the primary energy source of heart, defects in glucose oxidation have been linked to heart failure. SIRT6+/- mice hearts exhibit increased inhibitory phosphorylation of PDH subunit E1α. SIRT6 deficiency enhances FoxO1 nuclear localization that results in increased expression of PDK4...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29318783/tak-063-a-novel-pde10a-inhibitor-with-balanced-activation-of-direct-and-indirect-pathways-provides-a-unique-opportunity-for-the-treatment-of-schizophrenia
#13
REVIEW
Kazunori Suzuki, Haruhide Kimura
The basal ganglia regulates motor, cognitive, and emotional behaviors. Dysfunction of dopamine system in this area is implicated in the pathophysiology of schizophrenia characterized by positive symptoms, negative symptoms, and cognitive deficits. Medium spiny neurons (MSNs) are principal output neurons of striatum in the basal ganglia. Similar to current antipsychotics with dopamine D2 receptor antagonism or partial agonism, phosphodiesterase 10A (PDE10A) inhibitors activate indirect pathway MSNs, leading to the expectation of therapeutic potential for the treatment of psychosis...
January 9, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29318455/4-6-dimethoxyisoflavone-7-o-%C3%AE-d-glucopyranoside-wistin-is-a-peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-agonist-in-mouse-hepatocytes
#14
Misato Suzuki, Fumiya Nakamura, Emi Taguchi, Maho Nakata, Fumi Wada, Momoka Takihi, Tomoyo Inoue, Shinji Ohta, Hiroyuki Kawachi
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that regulate lipid and glucose metabolism. PPARα mainly affects fatty acid metabolism, and its activation lowers lipid levels. PPARγ is involved in the regulation of adipogenesis, insulin sensitivity, energy balance, and lipid biosynthesis. We have previously reported that 4',6-dimethoxyisoflavone-7-O-β-D-glucopyranoside (wistin) can activate PPARγ. The purpose of the present study is to investigate the PPARα agonist activity of wistin...
January 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29318284/screening-for-adolescent-idiopathic-scoliosis-us-preventive-services-task-force-recommendation-statement
#15
David C Grossman, Susan J Curry, Douglas K Owens, Michael J Barry, Karina W Davidson, Chyke A Doubeni, John W Epling, Alex R Kemper, Alex H Krist, Ann E Kurth, C Seth Landefeld, Carol M Mangione, Maureen G Phipps, Michael Silverstein, Melissa A Simon, Chien-Wen Tseng
Importance: Adolescent idiopathic scoliosis, a lateral curvature of the spine of unknown cause with a Cobb angle of at least 10°, occurs in children and adolescents aged 10 to 18 years. Idiopathic scoliosis is the most common form and usually worsens during adolescence before skeletal maturity. Severe spinal curvature may be associated with adverse long-term health outcomes (eg, pulmonary disorders, disability, back pain, psychological effects, cosmetic issues, and reduced quality of life)...
January 9, 2018: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29317536/golgi-stress-response-reprograms-cysteine-metabolism-to-confer-cytoprotection-in-huntington-s-disease
#16
Juan I Sbodio, Solomon H Snyder, Bindu D Paul
Golgi stress response is emerging as a physiologic process of comparable importance to endoplasmic reticulum (ER) and mitochondrial stress responses. However, unlike ER stress, the identity of the signal transduction pathway involved in the Golgi stress response has been elusive. We show that the Golgi stressor monensin acts via the PKR-like ER kinase/Activating Transcription Factor 4 pathway. ATF4 is the master regulator of amino acid metabolism, which is induced during amino acid depletion and other forms of stress...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29317453/targeting-anticoagulant-protein-s-to-improve-hemostasis-in-hemophilia
#17
Raja Prince, Luca Bologna, Mirko Manetti, Daniela Melchiorre, Irene Rosa, Natacha Dewarrat, Silvia Suardi, Poorya Amini, José A Fernández, Laurent Burnier, Claudia Quarroz, Maria Desiré Reina Caro, Yasuhiro Matsumura, Johanna A Kremer Hovinga, John H Griffin, Hans-Uwe Simon, Lidia Ibba-Manneschi, François Saller, Sara Calzavarini, Anne Angelillo-Scherrer
Improved treatments are needed for hemophilia A and B, bleeding disorders affecting 400,000 people worldwide. We investigated whether targeting protein S could promote hemostasis in hemophilia by re-balancing coagulation. Protein S is an anticoagulant acting as cofactor for activated protein C and tissue factor pathway inhibitor (TFPI). This dual role makes PS a key regulator of thrombin generation. Here, we report that targeting protein S rebalances coagulation in hemophilia. Protein S gene targeting in hemophilic mice protected them against bleeding, especially when intra-articular...
January 9, 2018: Blood
https://www.readbyqxmd.com/read/29317210/quality-indicators-in-the-treatment-of-patients-with-depression-bipolar-disorder-or-schizophrenia-consensus-study
#18
Miquel Bernardo, Consuelo de Dios, Víctor Pérez, Emilio Ignacio, Manuel Serrano, Eduard Vieta, José Joaquín Mira, Mercedes Guilabert, Miquel Roca
OBJECTIVE: To define a set of indicators for mental health care, monitoring quality assurance in schizophrenia, depression and bipolar disorders in Spain. MATERIAL AND METHOD: Qualitative research. Consensus-based study involving 6 psychiatrists on the steering committee and a panel of 43 psychiatrists working in several health services in Spain. An initial proposal of 44 indicators for depression, 42 for schizophrenia and 58 for bipolar disorder was elaborated after reviewing the literature...
January 6, 2018: Revista de Psiquiatrí́a y Salud Mental
https://www.readbyqxmd.com/read/29316800/pro-dopamine-regulator-kb220z-attenuates-hoarding-and-shopping-behavior-in-a-female-diagnosed-with-sud-and-adhd
#19
Thomas McLaughlin, Kenneth Blum, Bruce Steinberg, Edward J Modestino, Lyle Fried, David Baron, David Siwicki, Eric R Braverman, Rajendra D Badgaiyan
Background Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution. Case presentation C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type...
January 10, 2018: Journal of Behavioral Addictions
https://www.readbyqxmd.com/read/29316320/human-microbiota-blood-group-antigens-and-disease
#20
REVIEW
D Rose Ewald, Susan C J Sumner
Far from being just "bugs in our guts," the microbiota interacts with the body in previously unimagined ways. Research into the genome and the microbiome has revealed that the human body and the microbiota have a long-established but only recently recognized symbiotic relationship; homeostatic balance between them regulates body function. That balance is fragile, easily disturbed, and plays a fundamental role in human health-our very survival depends on the healthy functioning of these microorganisms. Increasing rates of cardiovascular, autoimmune, and inflammatory diseases, as well as epidemics in obesity and diabetes in recent decades are believed to be explained, in part, by unintended effects on the microbiota from vaccinations, poor diets, environmental chemicals, indiscriminate antibiotic use, and "germophobia...
January 9, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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