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https://www.readbyqxmd.com/read/28544992/pharmacokinetics-pharmacodynamics-and-tolerability-of-usl261-midazolam-nasal-spray-randomized-study-in-healthy-geriatric-and-non-geriatric-adults
#1
Alexander K Berg, Michael J Myrvik, Peter J Van Ess
AIM: Characterize pharmacokinetics, pharmacodynamics, and safety/tolerability of USL261 in geriatric adults to inform its potential for treating bouts of increased seizure activity. METHODS: Phase 1, randomized, double-blind, 2-way crossover study in healthy geriatric (≥65years; n=18) and non-geriatric (18-40years; n=12) adults evaluated single USL261 doses (2.5 and 5.0mg) administered intranasally. Pharmacokinetic parameters were estimated for midazolam and 1-hydroxymidazolam (active metabolite), including area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), time to Cmax (Tmax), and half-life (t1/2)...
May 22, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28544918/senior-driving-under-the-influence-a-five-year-retrospective-study-of-alcoholized-road-users-aged-70-and-over
#2
Benjamin Kirsch, Christoph G Birngruber, Reinhard Dettmeyer
The demographic development in Germany shows a steady increase to senior citizens. The driving suitability of older road-users is of large social and political concern, because awareness and reactivity can be influenced by age-related diseases and potential medication, particularly in combination with the consumption of alcohol. This study provides an overview of senior road-users under the influence of alcohol. Therefore, 404 cases of drunken-driving by road-users aged 70 and over within the purview of the Institute of Legal Medicine at Justus-Liebig-University, Giessen, from the years 2009-2013 were evaluated in retrospect...
May 10, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28544616/biochemical-isolation-of-myonuclei-employed-to-define-changes-to-the-myonuclear-proteome-that-occur-with-aging
#3
Alicia A Cutler, Eric B Dammer, Duc M Doung, Nicholas T Seyfried, Anita H Corbett, Grace K Pavlath
Skeletal muscle aging is accompanied by loss of muscle mass and strength. Examining changes in myonuclear proteins with age would provide insight into molecular processes which regulate these profound changes in muscle physiology. However, muscle tissue is highly adapted for contraction and thus comprised largely of contractile proteins making the nuclear proteins difficult to identify from whole muscle samples. By developing a method to purify myonuclei from whole skeletal muscle, we were able to collect myonuclei for analysis by flow cytometry, biochemistry, and mass spectrometry...
May 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28544226/short-term-rapamycin-treatment-increases-ovarian-lifespan-in%C3%A2-young-and-middle-aged-female-mice
#4
Xiaowei Dou, Yan Sun, Jiazhao Li, Jing Zhang, Dandan Hao, Wenwen Liu, Rui Wu, Feifei Kong, Xiaoxu Peng, Jing Li
Although age-related ovarian failure in female mammals cannot be reversed, recent strategies have focused on improving reproductive capacity with age, and rapamycin is one such intervention that has shown a potential for preserving the ovarian follicle pool and preventing premature ovarian failure. However, the application is limited because of its detrimental effects on follicular development and ovulation during long-term treatment. Herein, we shortened the rapamycin administration to 2 weeks and applied the protocol to both young (8 weeks) and middle-aged (8 months) mouse models...
May 22, 2017: Aging Cell
https://www.readbyqxmd.com/read/28544158/molecular-and-physiological-manifestations-and-measurement-of-aging-in-humans
#5
REVIEW
Sadiya S Khan, Benjamin D Singer, Douglas E Vaughan
Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age...
May 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28544105/ensemble-coding-of-faces-occurs-in-children-and-develops-dissociably-from-coding-of-individual-faces
#6
Gillian Rhodes, Markus Neumann, Louise Ewing, Samantha Bank, Ainsley Read, Laura M Engfors, Rachel Emiechel, Romina Palermo
Ensemble coding allows adults to access useful information about average properties of groups, sometimes even in the absence of detailed representations of individual group members. This form of coding may emerge early in development with initial reports of ensemble coding for simple properties (size, numerosity) in young children and even infants. Here we demonstrate that ensemble coding of faces, which provides information about average properties of social groups, is already present in 6-8-year-old children...
May 21, 2017: Developmental Science
https://www.readbyqxmd.com/read/28543858/survival-improvement-in-human-retinal-pigment-epithelial-cells-via-fas-receptor-targeting-by-mir-374a
#7
Nooshin Tasharrofi, Fatemeh Kouhkan, Masoud Soleimani, Zahra-Sheila Soheili, Mahboubeh Kabiri, Mohaddeseh Mahmoudi Saber, Farid Abedin Dorkoosh
Oxidative conditions of the eye could contribute to retinal cells loss through activating the Fas-L/Fas pathway. This phenomenon is one of the leading causes of some ocular diseases like age-related macular degeneration (AMD). By targeting proteins at their mRNA level, microRNAs (miRNAs) can regulate gene expression and cell function. The aim of the present study is to investigate Fas targeting by miR-374a and find whether it can inhibit Fas-mediated apoptosis in primary human retinal pigment epithelial (RPE) cells under oxidative stress...
May 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542382/uv-b-induced-fibrillization-of-crystallin-protein-mixtures
#8
Sibel Cetinel, Valentyna Semenchenko, Jae-Young Cho, Mehdi Ghaffari Sharaf, Karim F Damji, Larry D Unsworth, Carlo Montemagno
Environmental factors, mainly oxidative stress and exposure to sunlight, induce the oxidation, cross-linking, cleavage, and deamination of crystallin proteins, resulting in their aggregation and, ultimately, cataract formation. Various denaturants have been used to initiate the aggregation of crystallin proteins in vitro. All of these regimens, however, are obviously far from replicating conditions that exist in vivo that lead to cataract formation. In fact, it is our supposition that only UV-B radiation may mimic the observed in vivo cause of crystallin alteration leading to cataract formation...
2017: PloS One
https://www.readbyqxmd.com/read/28542375/human-plasma-metabolomics-in-age-related-macular-degeneration-amd-using-nuclear-magnetic-resonance-spectroscopy
#9
Inês Laíns, Daniela Duarte, António S Barros, Ana Sofia Martins, João Gil, John B Miller, Marco Marques, Tânia Mesquita, Ivana K Kim, Maria da Luz Cachulo, Demetrios Vavvas, Isabel M Carreira, Joaquim N Murta, Rufino Silva, Joan W Miller, Deeba Husain, Ana M Gil
PURPOSE: To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. METHODS: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28542264/child-mortality-hypothalamic-pituitary-adrenal-axis-activity-and-cellular-aging-in-mothers
#10
Cindy K Barha, Katrina G Salvante, Courtney W Hanna, Samantha L Wilson, Wendy P Robinson, Rachel M Altman, Pablo A Nepomnaschy
Psychological challenges, including traumatic events, have been hypothesized to increase the age-related pace of biological aging. Here we test the hypothesis that psychological challenges can affect the pace of telomere attrition, a marker of cellular aging, using data from an ongoing longitudinal-cohort study of Kaqchikel Mayan women living in a population with a high frequency of child mortality, a traumatic life event. Specifically, we evaluate the associations between child mortality, maternal telomere length and the mothers' hypothalamic-pituitary-adrenal axis (HPAA), or stress axis, activity...
2017: PloS One
https://www.readbyqxmd.com/read/28542257/long-term-results-after-limited-macular-translocation-surgery-for-wet-age-related-macular-degeneration
#11
Hisaaki Oshima, Takeshi Iwase, Kohei Ishikawa, Kentaro Yamamoto, Hiroko Terasaki
PURPOSE: To evaluate the long-term results of limited macular translocation (LMT) surgery with radial chorioscleral outfolding in patients with wet age-related macular degeneration (AMD) and subfoveal choroidal neovascularization (CNV). In addition, to identify the factors associated with the final best-corrected visual acuity (BCVA). METHODS: The medical records of 20 eyes of 20 consecutive patients (65.2±9.8 years) who had undergone LMT for the treatment of wet AMD and were followed for at least 5 years, were reviewed...
2017: PloS One
https://www.readbyqxmd.com/read/28542141/an-enhanced-bioluminescence-based-annexin-v-probe-for-apoptosis-detection-in-vitro-and-in-vivo
#12
Trajen Head, Peter Dau, Stephanie Duffort, Pirouz Daftarian, Pratibha M Joshi, Roberto Vazquez-Padron, Sapna K Deo, Sylvia Daunert
The process of controlled cellular death known as apoptosis has an important central role not only in normal homeostatic maintenance of tissues, but also in numerous diseases such as cancer, neurodegenerative, autoimmune, and cardiovascular diseases. As a result, new technologies with the capability to selectively detect apoptotic cells represent a central focus of research for the study of these conditions. We have developed a new biosensor for the detection of apoptotic cells, incorporating the targeted selectivity for apoptotic cells from Annexin V with the sensitivity of bioluminescence signal generation from a serum-stable mutant of Renilla luciferase (RLuc8)...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28540926/entorhinal-cortical-deep-brain-stimulation-rescues-memory-deficits-in-both-young-and-old-mice-genetically-engineered-to-model-alzheimer-s-disease
#13
Frances Xia, Adelaide Yiu, Scellig Sd Stone, Soojin Oh, Andres M Lozano, Sheena A Josselyn, Paul W Frankland
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Deep brain stimulation (DBS) has been used to treat a variety of brain disorders and shows promise in alleviating cognitive symptoms in some AD patients (Laxton et al., 2010). We previously showed that DBS of the entorhinal cortex (EC) enhances spatial memory formation in normal (wild-type) mice (Stone et al., 2011). Here we tested the effects of EC-DBS on the progressive cognitive deficits in a genetically-based mouse model of AD...
May 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28540866/electrophysiological-signatures-of-atypical-intrinsic-brain-connectivity-networks-in-autism
#14
Guofa Shou, Matthew W Mosconi, Jun Wang, Lauren E Ethridge, John A Sweeney, Lei Ding
OBJECTIVE: Abnormal local and long-range brain connectivity have been widely reported in autism spectrum disorder (ASD), yet the nature of these abnormalities and their functional relevance at distinct cortical rhythms remains unknown. Investigations of intrinsic connectivity networks (ICNs) and their coherence across whole brain networks hold promise for determining whether patterns of functional connectivity abnormalities vary across frequencies and networks in ASD. In the present study, we aimed to probe atypical intrinsic brain connectivity networks in ASD from resting-state electroencephalography (EEG) data via characterizing the whole brain network...
May 25, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28540848/myoclonic-jerks-are-commonly-associated-with-absence-seizures-in-early-onset-absence-epilepsy
#15
Hala Nasser, Elisa Lopez-Hernandez, Adina Ilea, Neli Le Morvan, Vanina Bellavoine, Catherine Delanoë, Stéphane Auvin
Typical absence seizures are observed in various epilepsy syndromes, however, few series have focused on early-onset absence epilepsy (EOAE). We aimed to evaluate the occurrence of this seizure type in children under 4 years of age in order to evaluate their electroclinical characteristics and outcome. We retrospectively studied (2006-2014) the electroclinical features of children with normal development and typical absence seizures starting before the age of 4 (with available pre-treatment video-EEG). Nine patients were included...
May 24, 2017: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/28540659/neuroprotective-benefits-of-aerobic-exercise-and-organoselenium-dietary-supplementation-in-hippocampus-of-old-rats
#16
José L Cechella, Marlon R Leite, Simone Pinton, Gilson Zeni, Cristina W Nogueira
The progressive decline of neurological functions, such as learning and memory, is an unavoidable consequence of aging. Our previous work suggested that the combination of physical exercise and a diet supplemented with diphenyl diselenide improves age-related memory decline in rats. The present study investigated the effects of physical exercise and a diet supplemented with diphenyl diselenide on the levels of proteins involved in the hippocampal neuroprotection to figure out the mechanisms related to the beneficial effects of this intervention in aged rats...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28540638/in-silico-dose-prediction-for-long-acting-rilpivirine-and-cabotegravir-administration-to-children-and-adolescents
#17
Rajith K R Rajoli, David J Back, Steve Rannard, Caren Freel Meyers, Charles Flexner, Andrew Owen, Marco Siccardi
BACKGROUND AND OBJECTIVES: Long-acting injectable antiretrovirals represent a pharmacological alternative to oral formulations and an innovative clinical option to address adherence and reduce drug costs. Clinical studies in children and adolescents are characterised by ethical and logistic barriers complicating the identification of dose optimisation. Physiologically-based pharmacokinetic modelling represents a valuable tool to inform dose finding prior to clinical trials. The objective of this study was to simulate potential dosing strategies for existing long-acting injectable depot formulations of cabotegravir and rilpivirine in children and adolescents (aged 3-18 years) using physiologically-based pharmacokinetic modelling...
May 24, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28540603/positioning-novel-biologicals-in-ckd-mineral-and-bone-disorders
#18
REVIEW
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Adrian Covic, Sandro Mazzaferro
Renal osteodystrophy (ROD), the histologic bone lesions of chronic kidney disease (CKD), is now included in a wider syndrome with laboratory abnormalities of mineral metabolism and extra-skeletal calcifications or CKD-mineral and bone disorders (CKD-MBD), to highlight the increased burden of mortality. Aging people, frequently identified as early CKD, could suffer from either the classical age-related osteoporosis (OP) or ROD. Distinguishing between these two bone diseases may not be easy without bone biopsy...
May 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28540446/lipid-per-oxidation-in-mitochondria-an-emerging-target-in-the-ageing-process
#19
REVIEW
O S Ademowo, H K I Dias, D G A Burton, H R Griffiths
Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation...
May 24, 2017: Biogerontology
https://www.readbyqxmd.com/read/28540180/hemoglobin-and-mean-platelet-volume-predicts-diffuse-t1-mri-white-matter-volume-decrease-in-sickle-cell-disease-patients
#20
Soyoung Choi, Adam M Bush, Matthew T Borzage, Anand A Joshi, William J Mack, Thomas D Coates, Richard M Leahy, John C Wood
Sickle cell disease (SCD) is a life-threatening genetic condition. Patients suffer from chronic systemic and cerebral vascular disease that leads to early and cumulative neurological damage. Few studies have quantified the effects of this disease on brain morphometry and even fewer efforts have been devoted to older patients despite the progressive nature of the disease. This study quantifies global and regional brain volumes in adolescent and young adult patients with SCD and racially matched controls with the aim of distinguishing between age related changes associated with normal brain maturation and damage from sickle cell disease...
2017: NeuroImage: Clinical
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