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https://www.readbyqxmd.com/read/29906735/patterns-of-disease-control-and-survival-in-patients-with-melanoma-brain-metastases-undergoing-immune-checkpoint-blockade
#1
Laura Milsch, Anja Gesierich, Sophia Kreft, Elisabeth Livingstone, Lisa Zimmer, Matthias Goebeler, Dirk Schadendorf, Bastian Schilling
OBJECTIVES: Immune-checkpoint blockers (ICBs) significantly prolong overall survival (OS) in patients with advanced melanoma. Limited data are available on the efficacy and clinical benefit in patients with melanoma brain metastases (MBMs). The aim of this study was to determine whether ICB is active in an unselected cohort treated of patients with known brain metastases and if disease control correlates with the survival. METHODS: A total of 385 patients with metastatic malignant melanoma treated with ICB as monotherapy between 2005 and 2017 in two tertiary referral centres were included...
June 12, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29905825/targeting-the-incretin-glucagon-system-with-triagonists-to-treat-diabetes
#2
Megan E Capozzi, Richard D DiMarchi, Matthias H Tschöp, Brian Finan, Jonathan E Campbell
Glucagon-like peptide-1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of GLP-1R-directed strategies is sub-maximal, and the only potent, sustainable treatment for metabolic dysfunction is bariatric surgery, necessitating the development of novel therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular peptides with activity at each of their respective receptors...
June 13, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29904585/recent-advances-in-deep-brain-stimulation-in-psychiatric-disorders
#3
REVIEW
Anne-Hélène Clair, William Haynes, Luc Mallet
Deep brain stimulation (DBS) has been offered to patients suffering of severe and resistant neuropsychiatric disorders like Obsessive Compulsive Disorder (OCD), Gilles de la Tourette Syndrome (TS) and Major Depression (MDD). Modulation of several targets within the cortico-striato-thalamo-cortical circuits can lead to a decrease of symptom severity in those patients. This review focuses on the recent clinical outcomes in DBS in psychiatric disorders. Studies on OCD and TS are now focusing on the long-term effects of DBS, with encouraging results regarding not only the decrease of symptoms, but also quality of life...
2018: F1000Research
https://www.readbyqxmd.com/read/29904450/efficacy-of-the-reactive-oxygen-metabolite-test-as-a-predictor-of-initial-heart-failure-hospitalization-in-elderly-patients-with-chronic-heart-failure
#4
Takashi Hitsumoto
Background: The reactive oxygen metabolites (d-ROMs) test has recently been explored as a novel marker of oxidative stress in vivo and used in clinical settings. Conversely, data regarding the utility of the d-ROMs test as a predictor of patients with chronic heart failure (CHF) are limited. This prospective study aims to elucidate the efficacy of the d-ROMs test as a predictor of initial heart failure (HF) hospitalization in elderly patients with CHF. Methods: A total of 428 elderly outpatients with CHF with no history of HF hospitalization (108 males, 320 females; mean age, 75 ± 7 years) were enrolled...
June 2018: Cardiology Research
https://www.readbyqxmd.com/read/29904344/altered-brain-regional-homogeneity-following-electro-acupuncture-stimulation-at-sanyinjiao-sp6-in-women-with-premenstrual-syndrome
#5
Yong Pang, Huimei Liu, Gaoxiong Duan, Hai Liao, Yanfei Liu, Zhuo Feng, Jien Tao, Zhuocheng Zou, Guoxiang Du, Rongchao Wan, Peng Liu, Demao Deng
Background : Premenstrual syndrome (PMS) is a menstrual cycle-related disorder which causes physical and mood changes prior to menstruation and is associated with the functional dysregulation of the brain. Acupuncture is an effective alternative therapy for treating PMS, and sanyinjiao (SP6) is one of the most common acupoints used for improving the symptoms of PMS. However, the mechanism behind acupuncture's efficacy for relieving PMS symptoms remains unclear. The aim of this study was to identify the brain response patterns induced by acupuncture at acupoint SP6 in patients with PMS...
2018: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/29903896/dual-mapk-inhibition-is-an-effective-therapeutic-strategy-for-a-subset-of-class-ii-braf-mutant-melanoma
#6
Matthew Dankner, Mathieu Lajoie, Dan Moldoveanu, Tan-Trieu Nguyen, Paul Savage, Shivshankari Rajkumar, Xiu Huang, Maria Lvova, Alexei Protopopov, Dana Vuzman, David Hogg, Morag Park, Marie-Christine Guiot, Kevin Petrecca, Catalin Mihalcioiu, Ian R Watson, Peter M Siegel, April A N Rose
PURPOSE: Dual MAPK pathway inhibition (dMAPKi) with BRAF and MEK inhibitors improves survival in BRAF V600E/K mutant melanoma, but the efficacy of dMAPKi in non-V600 BRAF mutant tumors is poorly understood. We sought to characterize the responsiveness of class II (enhanced kinase activity, dimerization dependent) BRAF mutant melanoma to dMAPKi. EXPERIMENTAL DESIGN: Tumors from patients with BRAF WT, V600E (class I) and L597S (class II) metastatic melanoma were used to generate patient-derived-xenografts (PDX)...
June 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29903620/computational-motility-models-of-neurogastroenterology-and-neuromodulation
#7
Bradley B Barth, Xiling Shen
The success of neuromodulation therapies, particularly in the brain, spinal cord, and peripheral nerves, has been greatly aided by computational, biophysical models. However, treating gastrointestinal disorders with electrical stimulation has been much less explored, partly because the mode of action of such treatments is unclear, and selection of stimulation parameters is often empirical. Progress in gut neuromodulation is limited by the comparative lack of biophysical models capable of simulating neuromodulation of gastrointestinal function...
August 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29901235/long-term-negative-impact-of-an-inappropriate-first-antiepileptic-medication-on-the-efficacy-of-a-second-antiepileptic-medication-in-mice
#8
Jodi L Pawluski, Mathieu Kuchenbuch, Sarah Hadjadj, Gabriel Dieuset, Nathalie Costet, Laurent Vercueil, Arnaud Biraben, Benoît Martin
Childhood absence epilepsy (CAE) is one of the most frequent epilepsies in infancy. The first-line recommended therapy for CAE is based on the prescription of the narrow-spectrum ethosuximide and the broad-spectrum valproic acid, which have similar efficacy in the first 12 months. Nevertheless, some antiepileptic drugs (AEDs) may worsen seizure duration and type in this syndrome. In line with this, we have encountered a case of identical twins with CAE and early exposure to different antiseizure drugs leading to divergent outcomes...
June 14, 2018: Epilepsia
https://www.readbyqxmd.com/read/29901032/emotion-recognition-and-its-relation-to-prefrontal-function-and-network-in-heroin-plus-nicotine-dependence-a-pilot-study
#9
Hada Fong-Ha Ieong, Zhen Yuan
Many patients with substance use disorders (SUDs) live in a stressful environment, and comorbidity is not uncommon. Understanding the neural mechanisms underlying heroin and nicotine dependences and their relationships to social cognition could facilitate behavioral therapy efficacy. We aimed to provide a translational approach that leads to identifying potential biomarkers for opioid use disorder (OUD) susceptibility during recovery. We examined the clinical characters and the relationships between theory of mind (ToM) and executive functions in three groups: heroin plus nicotine-dependent (HND) patients who had remained heroin abstinent ( <mml:math xmlns:mml="http://www...
April 2018: Neurophotonics
https://www.readbyqxmd.com/read/29899691/brain-functional-connectivity-changes-after-transcranial-direct-current-stimulation-in-epileptic-patients
#10
Franca Tecchio, Carlo Cottone, Camillo Porcaro, Andrea Cancelli, Vincenzo Di Lazzaro, Giovanni Assenza
Focal epilepsy is a network pathology, where the brain connectivity of the epileptic focus (EF) influences seizure frequency and cortical dysfunction. Growing evidence supports a clinical efficacy of cathodal transcranial direct current stimulation (ctDCS) in drug-resistant epilepsy (DRE). ctDCS effects can be merely attributed to the inhibition of cortical excitability, which is abnormally increased in epilepsy, but its effect on brain network of DRE patients has never been reported. We aimed at exploring the hypothesis that functional connectivity (FC) changes may explain part of ctDCS clinical effects in DRE patients...
2018: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/29899027/single-trial-phase-entrainment-of-theta-oscillations-in-sensory-regions-predicts-human-associative-memory-performance
#11
Danying Wang, Andrew Clouter, Qiaoyu Chen, Kimron L Shapiro, Simon Hanslmayr
Episodic memories are rich in sensory information and often contain integrated information from different sensory modalities. For instance, we can store memories of a recent concert with visual and auditory impressions being integrated in one episode. Theta oscillations have recently been implicated in playing a causal role synchronizing and effectively binding the different modalities together in memory. However, an open question is whether momentary fluctuations in theta synchronization predict the likelihood of associative memory formation for multisensory events...
June 13, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29898393/activity-induced-regulation-of-synaptic-strength-through-the-chromatin-reader-l3mbtl1
#12
Wenjie Mao, Anna C Salzberg, Motokazu Uchigashima, Yuto Hasegawa, Hanno Hock, Masahiko Watanabe, Schahram Akbarian, Yuka Imamura Kawasawa, Kensuke Futai
Homeostatic synaptic downscaling reduces neuronal excitability by modulating the number of postsynaptic receptors. Histone modifications and the subsequent chromatin remodeling play critical roles in activity-dependent gene expression. Histone modification codes are recognized by chromatin readers that affect gene expression by altering chromatin structure. We show that L3mbtl1 (lethal 3 malignant brain tumor-like 1), a polycomb chromatin reader, is downregulated by neuronal activity and is essential for synaptic response and downscaling...
June 12, 2018: Cell Reports
https://www.readbyqxmd.com/read/29897645/iron-deposition-quantification-applications-in-the-brain-and-liver
#13
Fuhua Yan, Naying He, Huimin Lin, Ruokun Li
Iron has long been implicated in many neurological and other organ diseases. It is known that over and above the normal increases in iron with age, in certain diseases there is an excessive iron accumulation in the brain and liver. MRI is a noninvasive means by which to image the various structures in the brain in three dimensions and quantify iron over the volume of the object of interest. The quantification of iron can provide information about the severity of iron-related diseases as well as quantify changes in iron for patient follow-up and treatment monitoring...
June 13, 2018: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/29897434/the-c-abl-inhibitor-radotinib-hcl-is-neuroprotective-in-a-preclinical-parkinson-s-disease-mouse-model
#14
Saebom Lee, Sangjune Kim, Yong Joo Park, Seung Pil Yun, Seung-Hwan Kwon, Donghoon Kim, Dong Yeon Kim, Jae Soo Shin, Dae Jin Cho, Gong Yeal Lee, Hyun Soo Ju, Hyo Jung Yun, Jae Hong Park, Wonjoong Richard Kim, Eun Ah Jung, Seulki Lee, Han Seok Ko
Accumulating evidence suggests that the nonreceptor tyrosine kinase c-Abl plays an important role in the progression of Parkinson's disease (PD) and c-Abl inhibition could be neuroprotective in PD and related α-synucleinopathies. Nilotinib, a c-Abl inhibitor, has shown improved motor and cognitive symptoms in PD patients. However, issues concerning blood-brain barrier (BBB) penetration, lack of selectivity, and safety still remain. Radotinib HCl is a selective Bcr-Abl kinase inhibitor that not only effectively access the brain, but also exhibits greater pharmacokinetic properties and safety profiles compared to Nilotinib and other c-Abl inhibitors...
April 20, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29896314/mental-stress-as-consequence-and-cause-of-vision-loss-the-dawn-of-psychosomatic-ophthalmology-for-preventive-and-personalized-medicine
#15
REVIEW
Bernhard A Sabel, Jiaqi Wang, Lizbeth Cárdenas-Morales, Muneeb Faiq, Christine Heim
The loss of vision after damage to the retina, optic nerve, or brain has often grave consequences in everyday life such as problems with recognizing faces, reading, or mobility. Because vision loss is considered to be irreversible and often progressive, patients experience continuous mental stress due to worries, anxiety, or fear with secondary consequences such as depression and social isolation. While prolonged mental stress is clearly a consequence of vision loss, it may also aggravate the situation. In fact, continuous stress and elevated cortisol levels negatively impact the eye and brain due to autonomous nervous system (sympathetic) imbalance and vascular dysregulation; hence stress may also be one of the major causes of visual system diseases such as glaucoma and optic neuropathy...
June 2018: EPMA Journal
https://www.readbyqxmd.com/read/29896307/image-guided-chemotherapy-with-specifically-tuned-blood-brain-barrier-permeability-in-glioma-margins
#16
Xihui Gao, Qi Yue, Yikang Liu, Dandan Fan, Kun Fan, Sihan Li, Jun Qian, Limei Han, Fang Fang, Fulin Xu, Daoying Geng, Liang Chen, Xin Zhou, Ying Mao, Cong Li
Blood-brain barrier (BBB) disruption is frequently observed in the glioma region. However, the tumor uptake of drugs is still too low to meet the threshold of therapeutic purpose. Method: A tumor vasculature-targeted nanoagonist was developed. Glioma targeting specificity of the nanoagonist was evaluated by in vivo optical imaging. BBB permeability at the glioma margin was quantitatively measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Single-photon emission computed tomography imaging/computed tomography (SPECT/CT) quantitatively determined the glioma uptake of the radiolabeled model drug...
2018: Theranostics
https://www.readbyqxmd.com/read/29896293/three-dimensional-transcranial-microbubble-imaging-for-guiding-volumetric-ultrasound-mediated-blood-brain-barrier-opening
#17
Ryan M Jones, Lulu Deng, Kogee Leung, Dallan McMahon, Meaghan A O'Reilly, Kullervo Hynynen
Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening recently entered clinical testing for targeted drug delivery to the brain. Sources of variability exist in the current procedures, motivating the development of real-time monitoring and control techniques to improve treatment safety and efficacy. Here we used three-dimensional (3D) transcranial microbubble imaging to calibrate FUS exposure levels for volumetric BBB opening. Methods: Using a sparse hemispherical transmit/receive ultrasound phased array, pulsed ultrasound was focused transcranially into the thalamus of rabbits during microbubble infusion and multi-channel 3D beamforming was performed online with receiver signals captured at the subharmonic frequency...
2018: Theranostics
https://www.readbyqxmd.com/read/29896158/prebiotics-supplementation-impact-on-the-reinforcing-and-motivational-aspect-of-feeding
#18
Anne-Sophie Delbès, Julien Castel, Raphaël G P Denis, Chloé Morel, Mar Quiñones, Amandine Everard, Patrice D Cani, Florence Massiera, Serge H Luquet
Energy homeostasis is tightly regulated by the central nervous system which responds to nervous and circulating inputs to adapt food intake and energy expenditure. However, the rewarding and motivational aspect of food is tightly dependent of dopamine (DA) release in mesocorticolimbic (MCL) system and could be operant in uncontrolled caloric intake and obesity. Accumulating evidence indicate that manipulating the microbiota-gut-brain axis through prebiotic supplementation can have beneficial impact of the host appetite and body weight...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29895964/tau-targeting-therapies-for-alzheimer-disease
#19
REVIEW
Erin E Congdon, Einar M Sigurdsson
Alzheimer disease (AD) is the most common form of dementia. Pathologically, AD is characterized by amyloid plaques and neurofibrillary tangles in the brain, with associated loss of synapses and neurons, resulting in cognitive deficits and eventually dementia. Amyloid-β (Aβ) peptide and tau protein are the primary components of the plaques and tangles, respectively. In the decades since Aβ and tau were identified, development of therapies for AD has primarily focused on Aβ, but tau has received more attention in recent years, in part because of the failure of various Aβ-targeting treatments in clinical trials...
June 12, 2018: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29894705/plasma-biomarkers-in-a-placebo-controlled-trial-comparing-tdcs-and-escitalopram-efficacy-in-major-depression
#20
André R Brunoni, Frank Padberg, Erica Leandro Marciano Vieira, Antônio Lucio Teixeira, André F Carvalho, Paulo Andrade Lotufo, Wagner F Gattaz, Isabela Martins Benseñor
BACKGROUND: Transcranial direct current stimulation (tDCS) holds promise as a therapeutic intervention for major depressive disorder (MDD). A more precise understanding of its underlying mechanisms may aid in the identification of subsets of patients responsive to tDCS within the context of precision psychiatry. OBJECTIVE: In this ancillary investigation of the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS), we investigated whether plasma levels of several cytokines and neurotrophic factors associated with major depression or antidepressant response predicted tDCS effects...
June 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
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