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https://read.qxmd.com/read/30761901/golden-exosomes-selectively-target-brain-pathologies-in-neurodegenerative-and-neurodevelopmental-disorders
#1
Nisim Perets, Oshra Betzer, Ronit Shapira, Shmuel Brenstein, Ariel Angel, Tamar Sadan, Uri Ashery, Rachela Popovtzer, Daniel Offen
Exosomes, nano-vesicles that are secreted by different cell types, enable intercellular communication at local or distant sites. Though they have been found to cross the blood brain barrier, their migration and homing abilities within the brain remain unstudied. We have recently developed a method for longitudinal and quantitative in vivo neuroimaging of exosomes, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with gold nanoparticles as labeling agents. Here, we used this technique to track the migration and homing patterns of intranasally administrated exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) in different brain pathologies, including stroke, autism, Parkinson's disease and Alzheimer's disease...
February 14, 2019: Nano Letters
https://read.qxmd.com/read/30710467/beyond-medical-actionability-public-perceptions-of-important-actions-in-response-to-hypothetical-genetic-testing-results
#2
David J Seiffert, Patricia McCarthy Veach, Bonnie LeRoy, Weihua Guan, Heather Zierhut
Rationales for returning results from whole genome sequencing (WGS) and genetic testing have historically focused on medical utility. Understanding the wide array of actions individuals might take following genetic testing results could have important implications for clinical care. We aimed to survey the public regarding their perceptions of the importance of a wide variety of different actions one might take upon receiving hypothetical results from a WGS test where the results indicate a high risk of developing a genetic condition...
February 2, 2019: Journal of Genetic Counseling
https://read.qxmd.com/read/30706777/exosome-like-nanoparticles-a-new-type-of-nanocarrier
#3
Mário Fernandes, Ivo Lopes, José Teixeira, Cláudia Botelho, Andreia C Gomes
Nanoparticles are one of the most used systems for imaging or therapeutic drug delivery. Exosomes are nanovesicular carriers that transport cargo for intercellular communication. These nanovesicles are linked to the pathology of some major diseases, in some cases with a central role in their progression. The use of these carriers to transport therapeutic drugs is a recent and promising approach to treat diseases such as cancer and Alzheimer disease. The physiological production of these structures is limited impairing its collection and subsequent purification...
January 29, 2019: Current Medicinal Chemistry
https://read.qxmd.com/read/30706743/-together-make-a-visit-together-make-a-plan-messaging-to-adult-children-with-concerns-about-a-parent-s-memory-loss
#4
Amy Jordan, Amy Bleakley, Kristin Harkins, Tigist Hailu, Kyle Cassidy, Sara Hachey, Jason Karlawish
Using the integrative model (IM), we developed and tested messages to encourage adults to accompany their parent to a memory doctor for a cognitive evaluation. We conducted in-depth interviews (n = 60) with African American and White adults with a parent age 65+ to identify key beliefs. Next, we carried out an IM-based telephone survey with a representative sample of the target population (n = 541). Analyses revealed that attitudes varied depending on the gender of the parent. Resulting messages featuring mothers countered the fear of hearing bad news and the belief that mother does not want to be accompanied to the doctor's office...
February 1, 2019: Health Communication
https://read.qxmd.com/read/30705771/-rest-rs3796529-genotype-and-rate-of-functional-deterioration-in-alzheimer-s-disease
#5
Poyin Huang, Cheng-Sheng Chen, Yuan-Han Yang, Mei-Chuan Chou, Ya-Hsuan Chang, Chiou-Lian Lai, Hsuan-Yu Chen, Ching-Kuan Liu
Recently, REST (RE1-silencing transcription factor) gene has been shown to be lost in Alzheimer's disease (AD), and a missense minor REST allele rs3796529-T has been shown to reduce the rate of hippocampal volume loss. However, whether the REST rs3796529 genotype is associated with the rate of functional deterioration in AD is unknown. A total of 584 blood samples from Taiwanese patients with AD were collected from January 2002 to December 2013. The diagnosis of AD was based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria...
February 2019: Aging and Disease
https://read.qxmd.com/read/30698089/preapproval-information-exchange-perspectives-of-u-s-population-health-decision-makers-on-preferences-for-early-engagement-with-investigational-therapies
#6
Diana Brixner, Tatia C Woodward, Nik Seifter, Joseph Biskupiak, Martin Marciniak, Peter Neumann, Gary Oderda
BACKGROUND: Preapproval information exchange (PIE) is the communication of clinical and health care economic information (HCEI) on therapies in development between U.S. population health decision makers (PHDMs) and drug manufacturers before regulatory approval. Early access to HCEI can help PHDMs plan budgets, inform formulary coverage decisions, and accelerate policy development to improve patient access to innovative health technologies. While recent FDA guidelines and proposed legislation aim to clarify definitions and execution of PIE, the level of U...
February 2019: Journal of Managed Care & Specialty Pharmacy
https://read.qxmd.com/read/30689517/computational-approach-to-suggest-a-new-multi-target-directed-ligand-as-a-potential-medication-for-alzheimer-s-disease
#7
Mahboobeh Eslami, Navid Nezafat, Manica Negahdaripour, Younes Ghasemi
Acetylcholinesterase (AChE) enzyme and myeloid differentiation 2 protein (MD2) are two critical proteins involved in Alzheimer's disease (AD). Since the nature of the active site of AChE and the binding pocket of MD2 are similar, some ligands can inhibit both of them appropriately. Oxidative stress has also been known as an important cause of AD. Designing an effective common inhibitor with antioxidant activity to inhibit AChE and MD2 proteins is the main goal of this work. In this regard, we used tacrine molecule with a high ligand efficiency (LE) and dehydrozingerone (DHZ) with anti-inflammatory, antioxidant and anti-Alzheimer activities...
January 28, 2019: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/30687918/-the-microbiota-gut-brain-axis-and-its-great-projections
#8
REVIEW
M Gomez-Eguilaz, J L Ramon-Trapero, L Perez-Martinez, J R Blanco
INTRODUCTION: The microbiota is the set of millions of microorganisms that coexist in a symbiotic way in our body. It is mainly located in the digestive tract, being distributed in function of the chemical properties and the functions of the different organs. The factors that influence its composition are multiple (diet, individual habits, diseases or drugs). It also participates in several functions of the organism such as metabolism, immunity or even the function of the central nervous system...
February 1, 2019: Revista de Neurologia
https://read.qxmd.com/read/30683583/the-evaluation-of-mental-disorders-research-reported-in-british-and-irish-newspapers-between-2002-and-2013-and-a-comparison-with-the-relative-disease-burdens-and-with-research-outputs-in-the-two-countries
#9
Atia Sultana, Grant Lewison, Elena Pallari
Mental disorders are a major contributor to the disease burden in Europe. We studied how research on them was communicated to British and Irish newspaper readers through an analysis of stories in the Daily Mail (DML) and The Guardian (GDN) in the UK and the Irish Times (IET) in Ireland, in 2002-13, and whether the coverage reflected the relative burdens of mental disorders, or the amount of research, in the two countries. The cited papers were identified through the newspapers' archive or the Factiva database, and their details and those of the research they cited from the Web of Science, with 1,128 stories in total...
January 15, 2019: Health Policy
https://read.qxmd.com/read/30645585/early-alterations-in-hippocampal-perisomatic-gabaergic-synapses-and-network-oscillations-in-a-mouse-model-of-alzheimer-s-disease-amyloidosis
#10
Jan-Oliver Hollnagel, Shehabeldin Elzoheiry, Karin Gorgas, Stefan Kins, Carlo Antonio Beretta, Joachim Kirsch, Jochen Kuhse, Oliver Kann, Eva Kiss
Several lines of evidence imply changes in inhibitory interneuron connectivity and subsequent alterations in oscillatory network activities in the pathogenesis of Alzheimer's Disease (AD). Recently, we provided evidence for an increased immunoreactivity of both the postsynaptic scaffold protein gephyrin and the GABAA receptor γ2-subunit in the hippocampus of young (1 and 3 months of age), APPPS1 mice. These mice represent a well-established model of cerebral amyloidosis, which is a hallmark of human AD. In this study, we demonstrate a robust increase of parvalbumin immunoreactivity and accentuated projections of parvalbumin positive (PV+) interneurons, which target perisomatic regions of pyramidal cells within the hippocampal subregions CA1 and CA3 of 3-month-old APPPS1 mice...
2019: PloS One
https://read.qxmd.com/read/30641141/creb-signals-as-pbmc-based-biomarkers-of-cognitive-dysfunction-a-novel-perspective-of-the-brain-immune-axis
#11
REVIEW
Nancy Bartolotti, Orly Lazarov
To date, there is no reliable biomarker for the assessment or determination of cognitive dysfunction in Alzheimer's disease and related dementia. Such a biomarker would not only aid in diagnostics, but could also serve as a measure of therapeutic efficacy. It is widely acknowledged that the hallmarks of Alzheimer's disease, namely, amyloid deposits and neurofibrillary tangles, as well as their precursors and metabolites, are poorly correlated with cognitive function and disease stage and thus have low diagnostic or prognostic value...
January 11, 2019: Brain, Behavior, and Immunity
https://read.qxmd.com/read/30629763/brain-derived-and-circulating-vesicle-profiles-indicate-neurovascular-unit-dysfunction-in-early-alzheimer-s-disease
#12
Xavier Gallart-Palau, Aida Serra, Yoshiki Hase, Chee Fan Tan, Christopher P Chen, Raj N Kalaria, Siu Kwan Sze
Vascular factors that reduce blood flow to the brain are involved in apparition and progression of dementia. We hypothesized that cerebral hypoperfusion (CH) might alter the molecular compositions of brain intercellular communication mechanisms while affecting the neurovascular unit in preclinical and clinical human dementias. To test that hypothesis, mice were subjected to bilateral common carotid stenosis (BCAS) and the molecular compositions of brain-derived and circulating extracellular vesicles (EVs) were assessed...
January 10, 2019: Brain Pathology
https://read.qxmd.com/read/30628766/obtaining-information-from-family-caregivers-to-inform-hospital-care-for-people-with-dementia-a-pilot-study
#13
Christine Toye, Susan Slatyer, Eleanor Quested, Mary Bronson, Andrew Hill, Janet Fountaine, Hannah V Uren, Lakkhina Troeung, Sean Maher
AIM: We aimed to implement a systematic nurse-caregiver conversation, examining fidelity, dose and reach of implementation; how implementation strategies worked; and feasibility and mechanisms of the practice change. BACKGROUND: Appropriate hospital care for people living with dementia may draw upon: information from the patient and family caregiver about the patient's perspective, preferences and usual support needs; nursing expertise; and opportunities the nurse has to share information with the care team...
January 10, 2019: International Journal of Older People Nursing
https://read.qxmd.com/read/30599271/dfunctional-connectivity-between-hippocampus-and-lateral-septum-is-affected-in-very-young-alzheimer-s-transgenic-mouse-model
#14
Siddhartha Mondragón-Rodríguez, Ning Gu, Caroline Fasano, Fernando Peña-Ortega, Sylvain Williams
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β and tau proteins, which are believed to lead to neural damage that translates into brain dysfunction and cognitive deficits. Brain dysfunction can be evaluated by measuring single neuron activity (spikes), global neural activity (local field potentials, LFPs) and the interaction between them. Considering that the dynamic interactions between the hippocampal pyramidal cells and lateral septum are important for proper structure function, we used the complete septo-hippocampal preparation from 30-day-old controls and J20-AD transgenic mice to record changes in spiking activity from the lateral septum and its relationship with LFP activity from the CA1 area...
December 29, 2018: Neuroscience
https://read.qxmd.com/read/30594990/planning-ahead-with-dementia-what-role-can-advance-care-planning-play-a-review-on-opportunities-and-challenges
#15
Francesca Bosisio, Ralf J Jox, Laura Jones, Eve Rubli Truchard
Advance directives emerged in the 1960s with the goal of empowering people to exert control over their future medical decisions. However, it has become apparent, over recent years, that advance directives do not sufficiently capture the temporal and relational aspects of planning treatment and care. Advance care planning (ACP) has been suggested as a way to emphasise communication between the patient, their surrogate decision maker and healthcare professional(s) in order to anticipate healthcare decisions in the event that the patient loses decision-making capacity, either temporarily or permanently...
December 17, 2018: Swiss Medical Weekly
https://read.qxmd.com/read/30594810/pridopidine-stabilizes-mushroom-spines-in-mouse-models-of-alzheimer-s-disease-by-acting-on-the-sigma-1-receptor
#16
Daniel Ryskamp, Lili Wu, Jun Wu, Dabin Kim, Gerhard Rammes, Michal Geva, Michael Hayden, Ilya Bezprozvanny
There is evidence that cognitive decline in Alzheimer's disease (AD) results from deficiencies in synaptic communication (e.g., loss of mushroom-shaped 'memory spines') and neurodegenerative processes. This might be treated with sigma-1 receptor (S1R) agonists, which are broadly neuroprotective and modulate synaptic plasticity. For example, we previously found that the mixed muscarinic/S1R agonist AF710B prevents mushroom spine loss in hippocampal cultures from APP knock-in (APP-KI) and presenilin-1-M146 V knock-in (PS1-KI) mice...
December 27, 2018: Neurobiology of Disease
https://read.qxmd.com/read/30594788/tongluojiunao-a-traditional-chinese-medication-with-neuroprotective-ability-a-review-of-the-cellular-molecular-and-physiological-mediators-of-tljn-s-effectiveness
#17
REVIEW
Bahram Bibak, Manouchehr Teymouri, Ameneh Mohammadi, Ali Haghbin, Yanshu Pan, Jamal Kasaian, Peiman Alesheikh
The pressing need to discover more effective drugs for various CNS disorders has resurrected the idea of investigating the effectiveness of traditional medicines in modern science. Tongluojiunao (TLJN) is an example of revived modern herbal preparation based on traditional Chinese medicine (TCM) with a long history of administration for various types of cerebrovascular injuries and neurodegenerative diseases. TLJN is prepared from the herbal roots of Panax notoginseng (Sanchi) and dried fruits of Gardenia jasminoides (Cape Jasmine), and so far, it has demonstrated promising results in patients with vascular dementia and cerebral ischemic stroke...
December 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/30587029/-if-only-they-could-understand-me-acute-hospital-care-experiences-of-patients-with-alzheimer-s-disease
#18
Anders Møller Jensen, Birthe D Pedersen, Rolf Bang Olsen, Rhonda L Wilson, Lise Hounsgaard
Patients with dementia as co-morbidity find hospital stays challenging, because the focus is primarily on the somatic cause for the admission, with less emphasis on the needs pertaining to dementia-related support and care. This results in poorer holistic outcomes, compared to patients without dementia, and an increased cost for the healthcare sector and, society as a whole. The quest is to make hospitals a dementia-friendly context, because this is likely to lead to better patient outcomes for people with dementia generally; however, further research is required to understand where gains may be made in this regard...
December 26, 2018: Dementia
https://read.qxmd.com/read/30585210/regenerative-effects-of-heme-oxygenase-metabolites-on-neuroinflammatory-diseases
#19
REVIEW
Huiju Lee, Yoon Kyung Choi
Heme oxygenase (HO) catabolizes heme to produce HO metabolites, such as carbon monoxide (CO) and bilirubin (BR), which have gained recognition as biological signal transduction effectors. The neurovascular unit refers to a highly evolved network among endothelial cells, pericytes, astrocytes, microglia, neurons, and neural stem cells in the central nervous system (CNS). Proper communication and functional circuitry in these diverse cell types is essential for effective CNS homeostasis. Neuroinflammation is associated with the vascular pathogenesis of many CNS disorders...
December 25, 2018: International Journal of Molecular Sciences
https://read.qxmd.com/read/30582723/insights-into-the-inhibitory-mechanism-of-a-resveratrol-and-clioquinol-hybrid-against-a%C3%AE-42-aggregation-and-protofibril-destabilization-a-molecular-dynamics-simulation-study
#20
Rajneet Kaur Saini, Suniba Shuaib, Deepti Goyal, Bhupesh Goyal
Amyloid-β (Aβ) peptide instinctively aggregate and form plaques in the brain of Alzheimer's disease (AD) patients. At present, there is no cure or treatment for AD, and significant effort has, therefore, been made to discover potent drugs against AD. Previous studies reported that a resveratrol and clioquinol hybrid compound [(E)-5-(4-hydroxystyryl)quinolone-8-ol], C1, strongly inhibit Aβ42 aggregation and disassemble preformed fibrils. However, the atomic level details of the inhibitory mechanism of C1 against Aβ42 aggregation and protrofibril disassembly remains elusive...
December 24, 2018: Journal of Biomolecular Structure & Dynamics
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