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https://www.readbyqxmd.com/read/28346535/caudwell-xtreme-everest-a-prospective-study-of-the-effects-of-environmental-hypoxia-on-cognitive-functioning
#1
Konstadina Griva, Jan Stygall, Mark H Wilson, Daniel Martin, Denny Levett, Kay Mitchell, Monty Mythen, Hugh E Montgomery, Mike P Grocott, Golnar Aref-Adib, Mark Edsell, Tracie Plant, Chris Imray, Debbie Cooke, Jane Harrington, Maryam Khosravi, Stanton P Newman
BACKGROUND: The neuropsychological consequences of exposure to environmental hypobaric hypoxia (EHH) remain unclear. We thus investigated them in a large group of healthy volunteers who trekked to Mount Everest base camp (5,300 m). METHODS: A neuropsychological (NP) test battery assessing memory, language, attention, and executive function was administered to 198 participants (age 44.5±13.7 years; 60% male). These were studied at baseline (sea level), 3,500 m (Namche Bazaar), 5,300 m (Everest Base Camp) and on return to 1,300 m (Kathmandu) (attrition rate 23...
2017: PloS One
https://www.readbyqxmd.com/read/28345579/inhibition-of-delta-secretase-improves-cognitive-functions-in-mouse-models-of-alzheimer-s-disease
#2
Zhentao Zhang, Obiamaka Obianyo, Elfriede Dall, Yuhong Du, Haian Fu, Xia Liu, Seong Su Kang, Mingke Song, Shan-Ping Yu, Chiara Cabrele, Mario Schubert, Xiaoguang Li, Jian-Zhi Wang, Hans Brandstetter, Keqiang Ye
δ-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-β and tau pathology in Alzheimer's disease (AD). Here we report the therapeutic effect of an orally bioactive and brain permeable δ-secretase inhibitor in mouse models of AD. We performed a high-throughput screen and identified a non-toxic and selective δ-secretase inhibitor, termed compound 11, that specifically blocks δ-secretase but not other related cysteine proteases...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345177/pharmacogenomics-of-off-target-adrs
#3
REVIEW
Sarah L Garon, Rebecca K Pavlos, Katie D White, Nancy J Brown, Cosby A Stone, Elizabeth J Phillips
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory although they can manifest with a variety of shared clinical features including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus, and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programs for their prevention...
March 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28345026/oncolytic-adenoviruses-armed-with-tumor-necrosis-factor-alpha-and-interleukin-2-enable-successful-adoptive-cell-therapy
#4
Riikka Havunen, Mikko Siurala, Suvi Sorsa, Susanna Grönberg-Vähä-Koskela, Michael Behr, Siri Tähtinen, João Manuel Santos, Pauliina Karell, Juuso Rusanen, Dirk M Nettelbeck, Anja Ehrhardt, Anna Kanerva, Akseli Hemminki
Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344556/the-immunomodulatory-effects-of-plant-extracts-and-plant-secondary-metabolites-on-chronic-neuroinflammation-and-cognitive-aging-a-mechanistic-and-empirical-review
#5
REVIEW
Christina Kure, Jorinde Timmer, Con Stough
Advances in healthcare have considerably improved the life expectancy of the human population over the last century and this has brought about new challenges. As we live longer the capacity for cognitive aging increases. Consequently, it has been noted that decline in cognitive performance in the elderly in domains of reasoning, problem solving skills, attention, processing speed, working memory and episodic memory is a significant societal problem. Despite the enormity of this issue there are relatively few interventions for cognitive aging...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28344552/adding-recognition-discriminability-index-to-the-delayed-recall-is-useful-to-predict-conversion-from-mild-cognitive-impairment-to-alzheimer-s-disease-in-the-alzheimer-s-disease-neuroimaging-initiative
#6
María J Russo, Jorge Campos, Silvia Vázquez, Gustavo Sevlever, Ricardo F Allegri
Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28342999/hippocampal-ca3-dentate-gyrus-volume-uniquely-linked-to-improvement-in-associative-memory-from-childhood-to-adulthood
#7
Ana M Daugherty, Robert Flinn, Noa Ofen
Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution proton density-weighted images in a sample of healthy participants (age 8-25 years)...
March 22, 2017: NeuroImage
https://www.readbyqxmd.com/read/28342823/evidence-that-increased-kcnj6-gene-dose-is-necessary-for-deficits-in-behavior-and-dentate-gyrus-synaptic-plasticity-in-the-ts65dn-mouse-model-of-down-syndrome
#8
Alexander M Kleschevnikov, Jessica Yu, Jeesun Kim, Larisa V Lysenko, Zheng Zhen, Y Eugene Yu, William C Mobley
Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21). The gene-dose hypothesis argues that a change in the dose of individual genes or regulatory sequences on HSA21 is necessary for creating DS-related phenotypes, including cognitive impairment. We focused on a possible role for Kcnj6, the gene encoding Kir3.2 (Girk2) subunits of a G-protein-coupled inwardly-rectifying potassium channel. This gene resides on a segment of mouse Chromosome 16 that is present in one extra copy in the genome of the Ts65Dn mouse, a well-studied genetic model of DS...
March 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28342697/recent-publications-from-the-alzheimer-s-disease-neuroimaging-initiative-reviewing-progress-toward-improved-ad-clinical-trials
#9
REVIEW
Michael W Weiner, Dallas P Veitch, Paul S Aisen, Laurel A Beckett, Nigel J Cairns, Robert C Green, Danielle Harvey, Clifford R Jack, William Jagust, John C Morris, Ronald C Petersen, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the 450+ publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses...
March 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28342639/sendai-virus-mucosal-vaccination-establishes-lung-resident-memory-cd8%C3%A2-t-cell-immunity-and-boosts-bcg-primed-protection-against-tb-in-mice
#10
Zhidong Hu, Ka-Wing Wong, Hui-Min Zhao, Han-Li Wen, Ping Ji, Hui Ma, Kang Wu, Shui-Hua Lu, Feng Li, Zhong-Ming Li, Tsugumine Shu, Jian-Qing Xu, Douglas B Lowrie, Xiao-Yong Fan
Accumulating evidence has shown the protective role of CD8(+) T cells in vaccine-induced immunity against Mycobacterium tuberculosis (Mtb) despite controversy over their role in natural immunity. However, the current vaccine BCG is unable to induce sufficient CD8(+) T cell responses, especially in the lung. Sendai virus, a respiratory RNA virus, is here engineered firstly as a novel recombinant anti-TB vaccine (SeV85AB) that encodes Mtb immuno-dominant antigens, Ag85A and Ag85B. A single mucosal vaccination elicited potent antigen-specific T cell responses and a degree of protection against Mtb challenge similar to the effect of BCG in mice...
March 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28342422/synergistic-desalination-of-potash-brine-impacted-groundwater-using-a-dual-adsorbent
#11
Nick P Gibb, James J Dynes, Wonjae Chang
The impact of saline mining effluent has been a significant environmental concern. Natural and modified clay-mineral adsorbents have been receiving increasing attention for salinity reduction of brine-impacted water, especially for natural resource extraction sites and surrounding environments. In this study, a dual-adsorbent treatment based on the sequential application of calcined layered double hydroxide (CLDH) and acid-treated zeolite was developed, evaluated and characterized for the desalination of potash brine-impacted groundwater...
March 22, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28341998/ire1-signaling-exacerbates-alzheimer-s-disease-pathogenesis
#12
Claudia Duran-Aniotz, Victor Hugo Cornejo, Sandra Espinoza, Álvaro O Ardiles, Danilo B Medinas, Claudia Salazar, Andrew Foley, Ivana Gajardo, Peter Thielen, Takao Iwawaki, Wiep Scheper, Claudio Soto, Adrian G Palacios, Jeroen J M Hoozemans, Claudio Hetz
Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress...
March 24, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28341234/radioprotective-effect-of-ursolic-acid-in-radiation-induced-impairment-of-neurogenesis-learning-and-memory-in-adolescent-balb-c-mouse
#13
Feng Ru Tang, Weng Keong Loke, Wong Pei Yan, Boo Cheong Khoo
The effect of acute irradiation with 5Gy or fractionated exposure with 0.5Gy continuously for 10days (a total dose of 5Gy) was evaluated in an immature BALB/c mouse model. Radioprotective effect of ursolic acid (at 25mg/kg/daily administered 1h after acute or each of fractionated irradiations, and continuously for 30days) was also investigated. We found that both acute and fractionated irradiation at a total dose of 5Gy did not induce any mortality within 30days after exposure to postnatal day 26 (P26) BALB/c mice, but reduced animal weigh gain in the first few weeks...
March 21, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28341151/mice-heterozygous-for-an-inactivated-allele-of-the-schizophrenia-associated-brd1-gene-display-selective-cognitive-deficits-with-translational-relevance-to-schizophrenia
#14
Per Qvist, Anto P Rajkumar, John P Redrobe, Mette Nyegaard, Jane H Christensen, Ole Mors, Gregers Wegener, Michael Didriksen, Anders D Børglum
Schizophrenia is a debilitating brain disorder characterized by disturbances of emotion, perception and cognition. Cognitive impairments predict functional outcome in schizophrenia and are detectable even in the prodromal stage of the disorder. However, our understanding of the underlying neurobiology is limited and procognitive treatments remain elusive. We recently demonstrated that mice heterozygous for an inactivated allele of the schizophrenia-associated Brd1 gene (Brd1(+/-) mice) display behaviors reminiscent of schizophrenia, including impaired social cognition and long-term memory...
March 21, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28340257/cd8-positive-t-cell-leukoencephalitis-with-astrocytopathy-clinically-presenting-as-neuromyelitis-optica
#15
Diana L Thomas, Jody Manners, Daniel Marker, Joseph Mettenburg, Geoffrey Murdoch, Bryan Stevens, Guoji Wang, Clayton Wiley
We describe a novel disease entity with the clinical and radiologic presentation of neuromyelitis optica (NMO) and widespread CD8-positive T-cell leukoencephalitis and astrocytopathy. The 59-year-old female patient had a complex 2-year neurological history that included early changes in cognition and memory, progressive lower extremity motor dysfunction, and multimodal sensory involvement. MRI of the spinal cord showed increased T2 signal in the central cord extending from C2 through T4. MRI of the brain showed symmetric radial enhancement in periventricular deep white matter without evidence of demyelinating lesions...
March 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28339691/z-guggulsterone-produces-antidepressant-like-effects-in-mice-through-activation-of-the-bdnf-signaling-pathway
#16
Chao Huang, Wen-Feng Hu, Ji-Li Wang, Peng Wang, Yu Gong, Li-Juan Tong, Bo Jiang, Wei Zhang, Yi-Bin Qin, Zhuo Chen, Rong-Rong Yang
Background: Z-guggulsterone, an active compound extracted from the gum resin of the tree commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor (BDNF) signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress (CUS) mouse model of depression. Methods: The effects of Z-guggulsterone were assessed in mice tail suspension test (TST), forced swimming test (FST)...
February 21, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28338440/a-study-of-cognitive-function-in-treatment-refractory-obsessive-compulsive-disorder-treated-with-capsulotomy
#17
Feilong Gong, Peng Li, Bin Li, Shizhen Zhang, Xinjie Zhang, Sen Yang, Hongbin Liu, Wei Wang
OBJECTIVE Anterior capsulotomy (AC) is sometimes used as a last resort for treatment-refractory obsessive-compulsive disorder (OCD). Previous studies assessing neuropsychological outcomes in patients with OCD have identified several forms of cognitive dysfunction that are associated with the disease, but few have focused on changes in cognitive function in OCD patients who have undergone surgery. In the present study, the authors investigated the effects of AC on the cognitive function of patients with treatment-refractory OCD...
March 24, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28337360/perioperative-epirubicin-oxaliplatin-and-capecitabine-chemotherapy-in-locally-advanced-gastric-cancer-safety-and-feasibility-in-an-interim-survival-analysis
#18
Vikas Ostwal, Arvind Sahu, Anant Ramaswamy, Bhawna Sirohi, Subhadeep Bose, Vikas Talreja, Mahesh Goel, Shraddha Patkar, Ashwin Desouza, Shailesh V Shrikhande
PURPOSE: Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. MATERIALS AND METHODS: We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. RESULTS: Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74...
March 2017: Journal of Gastric Cancer
https://www.readbyqxmd.com/read/28337134/acoustic-enhancement-of-sleep-slow-oscillations-and-concomitant-memory-improvement-in-older-adults
#19
Nelly A Papalambros, Giovanni Santostasi, Roneil G Malkani, Rosemary Braun, Sandra Weintraub, Ken A Paller, Phyllis C Zee
Acoustic stimulation methods applied during sleep in young adults can increase slow wave activity (SWA) and improve sleep-dependent memory retention. It is unknown whether this approach enhances SWA and memory in older adults, who generally have reduced SWA compared to younger adults. Additionally, older adults are at risk for age-related cognitive impairment and therefore may benefit from non-invasive interventions. The aim of this study was to determine if acoustic stimulation can increase SWA and improve declarative memory in healthy older adults...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28337114/precondition-of-right-frontal-region-with-anodal-tdcs-can-restore-the-fear-memory-impairment-induced-by-acpa-in-male-mice
#20
Fariborz Manteghi, Mohammad Nasehi, Mohammad-Reza Zarrindast
Fear memory and learning cause behavioural patterns such as fight or flight responses, which increase survival probability, but unfit processing of fear memory and learning can lead to maladaptive behaviours and maladies such as phobias, Post-Traumatic Stress Disorder (PTSD) and anxiety disorders. The growing prevalence of these maladies shows the need to quest novel methods for their treatment. We used anodal transcranial direct current stimulation (tDCS) on the right frontal region as a precondition neuromodulator and arachidonylcyclopropylamide (ACPA), a selective CB1 cannabinoid receptor agonist, as a fear memory impairing agent to assess their effects on contextual and auditory fear conditioning (reliable model for fear studies)...
2017: EXCLI journal
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