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https://www.readbyqxmd.com/read/29453445/alterations-in-interhemispheric-gamma-band-connectivity-are-related-to-the-emergence-of-auditory-verbal-hallucinations-in-healthy-subjects-during-nmda-receptor-blockade
#1
Thiebes Stephanie, Steinmann Saskia, Curic Stjepan, Polomac Nenad, Andreou Christina, Eichler Iris-Carola, Eichler Lars, Zöllner Christian, Gallinat Jürgen, Leicht Gregor, Mulert Christoph
Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29450684/application-and-impact-of-run-in-studies
#2
Michael Fralick, Jerry Avorn, Jessica M Franklin, Abdurrahman Abdurrob, Aaron S Kesselheim
BACKGROUND: A run-in phase is often employed prior to randomization in a clinical trial to exclude non-adherent patients, placebo responders, active drug non-responders, or patients who do not tolerate the active drug. This may impact the generalizability of trial results. OBJECTIVE: To determine if clinical outcomes differed between randomized controlled trials with run-in phases compared with randomized controlled trials of the same medication without run-in phases...
February 15, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29445414/effects-of-a-new-nutraceutical-combination-on-cognitive-function-in-hypertensive-patients
#3
Giuseppe Giugliano, Alessia Salemme, Sara De Longis, Marialuisa Perrotta, Valentina D'Angelosante, Alessandro Landolfi, Raffaele Izzo, Valentina Trimarco
Background: Chronic increased arterial blood pressure has been associated with executive dysfunction, slowing of attention and mental processing speed, and later with memory deficits. Due to the absence of a concrete therapeutic approach to this pathophysiological process, in the last decades there has been an increasing interest in the use of nutraceuticals, especially those with antioxidant properties, which own strong neuroprotective potential, that may help to improve cognitive function and to delay the onset of dementia...
2018: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/29444618/pathophysiology-of-drug-induced-weight-and-metabolic-effects-findings-from-an-rct-in-healthy-volunteers-treated-with-olanzapine-iloperidone-or-placebo
#4
Jacob S Ballon, Utpal B Pajvani, Laurel Es Mayer, Zachary Freyberg, Robin Freyberg, Ignacio Contreras, Michael Rosenbaum, Rudolph L Leibel, Jeffrey A Lieberman
Second generation antipsychotics are prescribed for an increasing number of psychiatric conditions, despite variable associations with weight gain, dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent causal relationships between these medications and metabolic effects have been inadequately defined and are potentially confounded by genetic risk of mental illness, attendant lifestyle, and concomitant medications. Therefore, we conducted a study in which 24 healthy volunteers were randomized to olanzapine (highly weight-gain liability), iloperidone (less weight-gain liability), or placebo treatment for 28 days under double-blind conditions...
February 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29444133/a-long-term-mechanistic-computational-model-of-physiological-factors-driving-the-onset-of-type-2-diabetes-in-an-individual
#5
Joydeep Sarkar, Gaurav Dwivedi, Qian Chen, Iris E Sheu, Mark Paich, Colleen M Chelini, Paul M D'Alessandro, Samuel P Burns
A computational model of the physiological mechanisms driving an individual's health towards onset of type 2 diabetes (T2D) is described, calibrated and validated using data from the Diabetes Prevention Program (DPP). The objective of this model is to quantify the factors that can be used for prevention of T2D. The model is energy and mass balanced and continuously simulates trajectories of variables including body weight components, fasting plasma glucose, insulin, and glycosylated hemoglobin among others on the time-scale of years...
2018: PloS One
https://www.readbyqxmd.com/read/29441949/effect-of-serotonin-transporter-genotype-on-self-reported-efficacy-and-activity-changes-of-brain-prefrontal-area-in-response-to-placebo
#6
M Isawa, R Tashiro, C Naruse, Y Yamaguchi, H Itoh, T Nishimura, M Tomi, H Shimada, H Saito, M Mochizuki, E Nakashima
Patients benefit from drug therapy not only through pharmacological mechanisms, but also through non-pharmacological action (placebo effect), which may be mediated in part by the prefrontal area of the brain. We consider that the difference between responders and non-responders to placebo might be related to polymorphisms in the serotonin transporter-linked polymorphic region (5-HTTLPR). To study this idea, we performed a randomized double-blind clinical trial using caffeine and lactose (placebo). Activity in the prefrontal area of the brain was measured in terms of blood flow by means of near-infrared spectroscopy (NIRS) as an objective indicator...
January 2, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29433687/effects-of-a-fixed-herbal-drug-combination-ze-185-to-an-experimental-acute-stress-setting-in-healthy-men-an-explorative-randomized-placebo-controlled-double-blind-study
#7
Sibylle Meier, Manuel Haschke, Catherine Zahner, Esther Kruttschnitt, Jürgen Drewe, Evangelia Liakoni, Felix Hammann, Jens Gaab
BACKGROUND: Considering the negative effects of stress on health, there is a growing interest in stress-reducing interventions. The present study examines the effects of a fixed combination of valerian, passion flower, lemon balm, and butterbur extracts (Ze 185) on biological and affective responses to a standardized psychosocial stress paradigm. PURPOSE: The aim of the present study was to investigate the efficacy of Ze 185 on cortisol and anxiety stress responses to acute psychosocial stress in healthy subjects...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29432350/an-exploratory-reanalysis-of-the-randomized-trial-on-efficacy-of-corticosteroids-as-rescue-therapy-for-the-late-phase-of-acute-respiratory-distress-syndrome
#8
G Umberto Meduri, Lisa Bridges, Reed A C Siemieniuk, Mehmet Kocak
OBJECTIVES: In the Acute Respiratory Distress Syndrome Network randomized controlled trial, methylprednisolone treatment was associated with increased return to mechanical ventilation with partial loss of early improvements. We hypothesize a causal relationship between protocol-driven rapid discontinuation of methylprednisolone post extubation and return to mechanical ventilation. To explore this possibility, we investigated the timing that events occurred in each treatment arm during active treatment intervention (efficacy) and after stopping therapy...
February 9, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29432219/calcitonin-gene-related-peptide-pathway-mabs-and-migraine-prevention
#9
Koen Paemeleire, Antoinette MaassenVanDenBrink
PURPOSE OF REVIEW: Monoclonal antibodies (mAbs) targeting the calcitonin-gene-related peptide (CGRP) pathway have been developed for episodic and chronic migraine prevention, either through binding the CGRP ligand (eptinezumab, fremanezumab, galcanezumab) or the CGRP receptor (erenumab). We provide an update on published Phase 2 and Phase 3 trials, safety/tolerability data, pharmacokinetics and mechanism of action of these biologicals. RECENT FINDINGS: The efficacy data from Phase 2 trials are corroborated by those from published Phase 3 trials, with a multitude of publications expected in 2018...
February 9, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29427292/intranasal-oxytocin-modulates-neural-functional-connectivity-during-human-social-interaction
#10
James K Rilling, Xiangchuan Chen, Xu Chen, Ebrahim Haroon
Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model...
February 10, 2018: American Journal of Primatology
https://www.readbyqxmd.com/read/29426874/oxytocin-curbs-calorie-intake-via-food-specific-increases-in-the-activity-of-brain-areas-that-process-reward-and-establish-cognitive-control
#11
Maartje S Spetter, Gordon B Feld, Matthias Thienel, Hubert Preissl, Maike A Hege, Manfred Hallschmid
The hypothalamic neurohormone oxytocin decreases food intake via largely unexplored mechanisms. We investigated the central nervous mediation of oxytocin's hypophagic effect in comparison to its impact on the processing of generalized rewards. Fifteen fasted normal-weight, young men received intranasal oxytocin (24 IU) or placebo before functional magnetic resonance imaging (fMRI) measurements of brain activity during exposure to food stimuli and a monetary incentive delay task (MID). Subsequently, ad-libitum breakfast intake was assessed...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29426300/effect-of-calcitriol-on-serum-hepcidin-in-individuals-with-chronic-kidney-disease-a-randomized-controlled-trial
#12
Bhupesh Panwar, Diane McCann, Gordana Olbina, Mark Westerman, Orlando M Gutiérrez
BACKGROUND: Anemia is highly prevalent in chronic kidney disease (CKD). Elevated hepcidin concentrations are an important mediator of disordered iron metabolism, a key mechanism underlying anemia of CKD. Vitamin D was recently shown to reduce serum hepcidin concentrations in healthy individuals. We examined whether treatment with calcitriol reduces serum hepcidin in individuals with CKD. METHODS: A total of 40 participants with stage 3 or 4 CKD (eGFR 15-60 ml/min/1...
February 9, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29426008/colchicine-lack-of-effectiveness-in-symptom-and-inflammation-modification-in-knee-osteoarthritis-colkoa-a-randomized-controlled-trial
#13
Ying-Ying Leung, Benjamin Haaland, Janet L Huebner, Steven Bak-Siew Wong, Madeline Tjai, Chunyan Wang, Balram Chowbay, Julian Thumboo, Bibhas Chakraborty, Mann Hong Tan, Virginia B Kraus
OBJECTIVES: Uric acid may activate an innate immune response in osteoarthritis (OA), contributing to disease pathology and progression. We evaluated the effectiveness of colchicine on pain and function in symptomatic knee OA (KOA) and the underlying mechanism of action. METHODS: COLKOA was a double-blind, placebo-controlled, randomized trial comparing 16 weeks of treatment with 0.5 mg twice-daily oral colchicine to placebo for KOA. The primary endpoint was ≥30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16...
February 6, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29425906/effects-of-vagal-neuromodulation-on-feeding-behavior
#14
Nicole A Pelot, Warren M Grill
Implanted vagus nerve stimulation (VNS) for obesity was recently approved by the FDA. However, its efficacy and mechanisms of action remain unclear. Herein, we synthesize clinical and preclinical effects of VNS on feeding behavior and energy balance and discuss engineering considerations for understanding and improving the therapy. Clinical cervical VNS (≤30 Hz) to treat epilepsy or depression has produced mixed effects on weight loss as a side effect, albeit in uncontrolled, retrospective studies. Conversely, preclinical studies (cervical and subdiaphragmatic VNS) mostly report decreased food intake and either decreased weight gain or weight loss...
February 6, 2018: Brain Research
https://www.readbyqxmd.com/read/29424930/inhaled-mannitol-for-cystic-fibrosis
#15
REVIEW
Sarah J Nevitt, Judith Thornton, Clare S Murray, Tiffany Dwyer
BACKGROUND: Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe...
February 9, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29424007/inspiratory-muscle-training-improves-exercise-capacity-with-thoracic-load-carriage
#16
Ren-Jay Shei, Robert F Chapman, Allison H Gruber, Timothy D Mickleborough
Thoracic load carriage (LC) exercise impairs exercise performance compared to unloaded exercise, partially due to impaired respiratory mechanics. We investigated the effects of LC on exercise and diaphragmatic fatigue in a constant-load exercise task; and whether inspiratory muscle training (IMT) improved exercise capacity and diaphragmatic fatigue with LC. Twelve recreationally active males completed three separate running trials to exhaustion (Tlim ) at a fixed speed eliciting 70% of their V˙O2max . The first two trials were completed either unloaded (UL) or while carrying a 10 kg backpack (LC)...
February 2018: Physiological Reports
https://www.readbyqxmd.com/read/29423947/the-effects-of-a-ccr3-inhibitor-axp1275-on-allergen-induced-airway-responses-in-adults-with-mild-to-moderate-atopic-asthma
#17
G M Gauvreau, J M FitzGerald, L P Boulet, R M Watson, L Hui, H Villineuve, T X Scime, A R Schlatman, C Obminski, J Kum, S Boehme, T W Ly, K B Bacon, P M O'Byrne
BACKGROUND: CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. OBJECTIVE: This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. METHODS: Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind crossover study to compare early and late allergen-induced asthmatic responses, methacholine PC20 , blood and sputum eosinophils, and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo...
February 9, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29421005/systematic-review-and-meta-analysis-of-endovascular-and-surgical-revascularization-for-patients-with-chronic-lower-extremity-venous-insufficiency-and-varicose-veins
#18
Sreekanth Vemulapalli, Kishan Parikh, Remy Coeytaux, Victor Hasselblad, Amanda McBroom, Abigail Johnston, Giselle Raitz, Matthew J Crowley, Kathryn R Lallinger, W Schuyler Jones, Gillian D Sanders
BACKGROUND: Chronic lower extremity venous disease (LECVD) is twice as prevalent as coronary heart disease, and invasive therapies to treat LECVD accounted for an estimated $290 million in Medicare expenditures in 2015. Despite increasing use of these invasive therapies, their comparative effectiveness is unknown. METHODS: We conducted a systematic review and meta-analysis of treatments for patients (symptomatic and asymptomatic) with lower extremity varicosities and/or lower extremity chronic venous insufficiency/incompetence/reflux...
February 2018: American Heart Journal
https://www.readbyqxmd.com/read/29419569/statin-effects-on-myocardial-fibrosis-markers-in-people-living-with-hiv
#19
Christopher deFilippi, Robert Christenson, Jessica Joyce, Elli A Park, Ashley Wu, Kathleen V Fitch, Sara E Looby, Michael T Lu, Udo Hoffmann, Steven K Grinspoon, Janet Lo
BACKGROUND: In observational studies, HIV patients have higher levels of soluble ST2 (sST2), galectin-3, growth differentiation factor-15 (GDF-15) than non-HIV controls. As statins exert pleiotropic immunomodulatory effects that may affect markers of myocardial fibrosis, the objective of the current study is to determine if biomarkers of myocardial fibrosis reflecting subclinical pathology may be modified by statin therapy in patients with HIV. SETTING: and Methods: 40 HIV+ men and women participated in a single center 12-month randomized, double-blind placebo controlled trial of atorvastatin 40mg qd vs...
February 6, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29419533/effect-of-treating-vitamin-d-deficiency-in-uncontrolled-type-2-diabetes-a-randomized-placebo-controlled-study
#20
Margaret C Lo, Layla Abushamat, Lazarus K Mramba
BACKGROUND: Literature increasingly supports the inverse relationship of vitamin D (VitD) level and type 2 diabetes (T2DM). Proposed protective mechanisms of VitD include its anti-inflammatory effects, increased insulin secretion via pancreatic β-cell stimulation, and downregulation of parathyroid hormone levels. Interventional studies show mixed results of VitD therapy in prediabetic patients with VitD deficiency or diabetic patients with normal VitD levels. STUDY QUESTION: Does high-dose VitD replacement improve glycemic control and microalbuminuria (MAU) in uncontrolled T2DM and concurrent VitD deficiency? STUDY DESIGN: This placebo-controlled, double-blinded study randomized 30 subjects aged 30-65 years with an elevated HbA1c level of 7...
February 5, 2018: American Journal of Therapeutics
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