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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458128/aggregation-prone-regions-in-hypk-help-it-to-form-sequestration-complex-for-toxic-protein-aggregates
#2
Debasish Kumar Ghosh, Ajit Roy, Akash Ranjan
Protein aggregates result from altered structural conformations and they can perturb cellular homeostasis. Prevention mechanisms, which function against protein aggregation by modulatory processes, are diverse and redundant. In this study, we have characterized Huntingtin interacting protein K (HYPK) as a global aggregation-regulatory protein. We report the mechanistic details of how HYPK's aggregation-prone regions allow it to sense and prevent other toxic protein's aggregation by forming unique annular-shaped sequestration complexes...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458113/poorer-positive-affect-in-response-to-self-paced-exercise-among-the-obese
#3
Hassan M Elsangedy, Paulo H D Nascimento, Daniel G S Machado, Kleverton Krinski, Sarah J Hardcastle, Sérgio G DaSilva
We aimed to investigate the association between body mass index (BMI) and affective response, ratings of perceived exertion (RPE), and physiological responses during self-paced exercise. Sixty-six women were divided into three groups accordingly with the BMI: obese (n = 22: 33.5 ± 8.5 yr; 34.9 ± 4.1 kg∙m-2 ), overweight (n = 22: 34.8 ± 8.6 yr; 26.4 ± 1.3 kg∙m-2 ), and normal-weight (n = 22: 30.8 ± 9.3 yr; 22.0 ± 1.6 kg∙m-2 ). They underwent a graded exercise test and a 20-min self-paced walking session on a treadmill...
February 16, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29458088/antibiotics-use-among-palestine-refugees-attending-unrwa-primary-health-care-centers-in-jordan-a-cross-sectional-study
#4
Maysun Al Baz, Michael R Law, Rawan Saadeh
The irrational use of antibiotics is increasing in Jordanian refugee camps and consequently so too is bacterial resistance. About one-third of health expenditures at UNRWA health centers in Jordan are attributed to antibiotics. OBJECTIVE: We studied knowledge, attitude and behaviour of Palestine refugees attending UNRWA health centers in Jordan regarding antibiotic use in order to plan public health interventions accordingly. METHODS: A cross-sectional, interviewer-administered survey among 250 adult Palestine refugees at four different health centres was conducted...
February 16, 2018: Travel Medicine and Infectious Disease
https://www.readbyqxmd.com/read/29457856/dual-input-regulation-and-positional-control-in-hybrid-oligonucleotide-discotic-supramolecular-wires
#5
Miguel Ángel Alemán García, Eva Magdalena Estirado, Lech-Gustav Milroy, Luc Brunsveld
The combination of oligonucleotides and synthetic supramolecular systems allows for novel and long needed modes of regulation of the self-assembly of both molecular elements. Discotic molecules were conjugated with short oligonucleotides and their assembly into responsive supramolecular wires studied. The self-assembly of the discotics provides additional stability for DNA-duplex formation due to a cooperative effect. Reversely, the appended oligonucleotides allow for positional control of the discotic elements within the supramolecular wire...
February 19, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29457141/extrahepatic-toxicity-of-acetaminophen-critical-evaluation-of-the-evidence-and-proposed-mechanisms
#6
Stefanie Kennon-McGill, Mitchell R McGill
Research on acetaminophen (APAP) toxicity over the last several decades has focused on the pathophysiology of liver injury, but increasing attention is being paid to other known and possible adverse effects. It has been known for decades that APAP causes acute kidney injury, but confusion exists regarding prevalence, and the mechanisms have not been well investigated. More recently, a number of experimental, clinical and epidemiological studies have reported evidence for pulmonary, endocrine, neurological and neurodevelopmental toxicity, but the quality of evidence from those studies varies...
January 15, 2018: Journal of Clinical and Translational Research
https://www.readbyqxmd.com/read/29456864/curative-gnrha-treatment-has-an-unexpected-repressive-effect-on-sertoli-cell-specific-genes
#7
Katharina Gegenschatz-Schmid, Gilvydas Verkauskas, Philippe Demougin, Vytautas Bilius, Darius Dasevicius, Michael B Stadler, Faruk Hadziselimovic
Background: Follicle stimulating hormone and testosterone stimulate Sertoli cells to support germ cell function and differentiation. During mini-puberty, when gonadotropin (GnRH) stimulates increases in plasma luteinizing hormone (LH) and testosterone levels, gonocytes are transformed into Ad spermatogonia. In cryptorchidism, impaired gonadotropin secretion during mini-puberty results in insufficient LH and testosterone secretion, impaired gonocyte transition to Ad spermatogonia, and perturbed Sertoli cell proliferation...
2018: Basic and Clinical Andrology
https://www.readbyqxmd.com/read/29456528/mutation-in-esbl-plasmid-from-escherichia-coli-o104-h4-leads-autoagglutination-and-enhanced-plasmid-dissemination
#8
Mickaël Poidevin, Mari Sato, Ipek Altinoglu, Manon Delaplace, Chikara Sato, Yoshiharu Yamaichi
Conjugative plasmids are one of the main driving force of wide-spreading of multidrug resistance (MDR) bacteria. They are self-transmittable via conjugation as carrying the required set of genes and cis -acting DNA locus for direct cell-to-cell transfer. IncI incompatibility plasmids are nowadays often associated with extended-spectrum beta-lactamases producing Enterobacteria in clinic and environment. pESBL-EA11 was isolated from Escherichia coli O104:H4 outbreak strain in Germany in 2011. During the previous study identifying transfer genes of pESBL-EA11, it was shown that transposon insertion at certain DNA region of the plasmid, referred to as Hft, resulted in great enhancement of transfer ability...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29456181/an-ultraconserved-element-containing-lncrna-preserves-transcriptional-dynamics-and-maintains-esc-self-renewal
#9
Alessandro Fiorenzano, Emilia Pascale, Miriam Gagliardi, Sara Terreri, Mariarosaria Papa, Gennaro Andolfi, Marco Galasso, Guidantonio Malagoli Tagliazucchi, Cristian Taccioli, Eduardo Jorge Patriarca, Amelia Cimmino, Maria Rosaria Matarazzo, Gabriella Minchiotti, Annalisa Fico
Ultraconserved elements (UCEs) show the peculiar feature to retain extended perfect sequence identity among human, mouse, and rat genomes. Most of them are transcribed and represent a new family of long non-coding RNAs (lncRNAs), the transcribed UCEs (T-UCEs). Despite their involvement in human cancer, the physiological role of T-UCEs is still unknown. Here, we identify a lncRNA containing the uc.170+, named T-UCstem1, and provide in vitro and in vivo evidence that it plays essential roles in embryonic stem cells (ESCs) by modulating cytoplasmic miRNA levels and preserving transcriptional dynamics...
February 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29456179/the-chromatin-remodeler-bptf-activates-a-stemness-gene-expression-program-essential-for-the-maintenance-of-adult-hematopoietic-stem-cells
#10
Bowen Xu, Ling Cai, Jason M Butler, Dongliang Chen, Xiongdong Lu, David F Allison, Rui Lu, Shahin Rafii, Joel S Parker, Deyou Zheng, Gang Greg Wang
Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia...
February 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29456137/lineage-biased-hematopoietic-stem-cells-are-regulated-by-distinct-niches
#11
Sandra Pinho, Tony Marchand, Eva Yang, Qiaozhi Wei, Claus Nerlov, Paul S Frenette
The spatial localization of hematopoietic stem cells (HSCs) in the bone marrow (BM) remains controversial, with some studies suggesting that they are maintained in homogeneously distributed niches while others have suggested the contributions of distinct niche structures. Subsets of quiescent HSCs have been reported to associate with megakaryocytes (MK) or arterioles in the BM. However, these HSC subsets have not been prospectively defined. Here, we show that platelet and myeloid-biased HSCs, marked by von Willebrand factor (vWF) expression, are highly enriched in MK niches...
February 9, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29455696/targeting-habits-in-anorexia-nervosa-a-proof-of-concept-randomized-trial
#12
Joanna E Steinglass, Deborah R Glasofer, Emily Walsh, Gabby Guzman, Carol B Peterson, B Timothy Walsh, Evelyn Attia, Stephen A Wonderlich
BACKGROUND: Habits are behavioral routines that are automatic and frequent, relatively independent of any desired outcome, and have potent antecedent cues. Among individuals with anorexia nervosa (AN), behaviors that promote the starved state appear habitual, and this is the foundation of a recent neurobiological model of AN. In this proof-of-concept study, we tested the habit model of AN by examining the impact of an intervention focused on antecedent cues for eating disorder routines...
February 19, 2018: Psychological Medicine
https://www.readbyqxmd.com/read/29455516/core-shell-microneedle-gel-for-self-regulated-insulin-delivery
#13
Jinqiang Wang, Yanqi Ye, Jicheng Yu, Anna R Kahkoska, Xudong Zhang, Chao Wang, Wujin Sun, Ria D Corder, Zhaowei Chen, Saad A Khan, John B Buse, Zhen Gu
A bioinspired glucose-responsive insulin delivery system for self-regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core-shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H2 O2 ) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel...
February 19, 2018: ACS Nano
https://www.readbyqxmd.com/read/29455442/in-search-of-executive-impairment-in-pathological-gambling-a-neuropsychological-study-on-non-treatment-seeking-gamblers
#14
Alexandros Kapsomenakis, Panagiotis G Simos, Georgios Konstantakopoulos, Dimitrios S Kasselimis
Pathological gambling is characterized by a persisting maladaptive and recurrent behavior with severe social and psychological consequences. There is evidence of strong comorbidity with psychiatric manifestations as well as cognitive mainly involving executive functions. This study aimed to investigate impairment in executive functions and working memory, and personality traits in a sample of Greek gamblers. Twenty-four men involved in various gambling activities were recruited from ecological settings as probable pathological gamblers...
February 17, 2018: Journal of Gambling Studies
https://www.readbyqxmd.com/read/29455303/extracellular-matrix-regulation-of-fibroblast-function-redefining-our-perspective-on-skin-aging
#15
REVIEW
Megan A Cole, Taihao Quan, John J Voorhees, Gary J Fisher
The dermal extracellular matrix (ECM) comprises the bulk of skin and confers strength and resiliency. In young skin, fibroblasts produce and adhere to the dermal ECM, which is composed primarily of type I collagen fibrils. Adherence allows fibroblasts to spread and exert mechanical force on the surrounding ECM. In this state, fibroblasts display a "youthful" phenotype characterized by maintenance of the composition and structural organization of the dermal ECM. During aging, fibroblast-ECM interactions become disrupted due to fragmentation of collagen fibrils...
February 17, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29454875/does-the-level-of-emotional-intelligence-affect-the-degree-of-success-in-nursing-studies
#16
Dganit Sharon, Keren Grinberg
BACKGROUND: Emotional intelligence (EI) reflects the general capacity to comprehend emotions (in ourselves and in others), to regulate emotions, and to cope effectively with emotional situations. The study program in nursing is varied, and includes theoretical and practical aspects, but teaching EI is not part of the core curriculum. We argue that teaching EI should not only be included in the curriculum, but that EI tests should be included in the admissions process. OBJECTIVE: This study reviews the relationship between EI level and the degree of success in nursing studies, and its importance...
February 7, 2018: Nurse Education Today
https://www.readbyqxmd.com/read/29454841/hypocretin-orexin-deficiency-decreases-cocaine-abuse-liability
#17
Nadia Steiner, Clara Rossetti, Takeshi Sakurai, Masashi Yanagisawa, Luis de Lecea, Pierre J Magistretti, Olivier Halfon, Benjamin Boutrel
Compelling evidence indicates that hypocretin/orexin signaling regulates arousal, stress and reward-seeking behaviors. However, most studies on drug reward-related processes have so far described the effects of pharmacological blockers disrupting hypocretin/orexin transmission. We report here an extensive study on cocaine-related behaviors in hypocretin/orexin-deficient mice (KO) and their heterozygous (HET) and wildtype (WT) littermates. We evaluated behavioral sensitization following repeated administrations and preference for an environment repeatedly paired with cocaine injections (15 mg/kg)...
February 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29454304/first-and-second-eye-cataract-surgery-and-driver-self-regulation-among-older-drivers-with-bilateral-cataract-a-prospective-cohort-study
#18
Seraina Agramunt, Lynn B Meuleners, Michelle L Fraser, Kyle C Chow, Jonathon Q Ng, Vignesh Raja
BACKGROUND: Driving a car is the most common form of transport among the older population. Common medical conditions such as cataract, increase with age and impact on the ability to drive. To compensate for visual decline, some cataract patients may self-regulate their driving while waiting for cataract surgery. However, little is known about the self-regulation practices of older drivers throughout the cataract surgery process. The aim of this study is to assess the impact of first and second eye cataract surgery on driver self-regulation practices, and to determine which objective measures of vision are associated with driver self-regulation...
February 17, 2018: BMC Geriatrics
https://www.readbyqxmd.com/read/29454294/parents-and-early-adolescents-self-efficacy-about-anger-regulation-and-early-adolescents-internalizing-and-externalizing-problems-a-longitudinal-study-in-three-countries
#19
Laura Di Giunta, Anne-Marie R Iselin, Jennifer E Lansford, Nancy Eisenberg, Carolina Lunetti, Eriona Thartori, Emanuele Basili, Concetta Pastorelli, Dario Bacchini, Liliana Maria Uribe Tirado, Maria Gerbino
The present study examines whether early adolescents' self-efficacy beliefs about anger regulation mediate the relation between parents' self-efficacy beliefs about anger regulation and early adolescents' internalizing and externalizing problems. Participants were 534 early adolescents (T1: M age = 10.89, SD = .70; 50% female), their mothers (n = 534), and their fathers (n = 431). Families were drawn from Colombia, Italy, and the USA. Follow-up data were obtained two (T2) and three (T3) years later. At T1 and T3, parents' self-efficacy beliefs were self-reported and internalizing and externalizing problems were assessed via mothers', fathers', and early adolescents' reports...
February 14, 2018: Journal of Adolescence
https://www.readbyqxmd.com/read/29454182/the-positive-effect-of-venlafaxine-on-central-motor-conduction
#20
Chunyong Li, Fuda Liu, Haiyan Peng, Yongjun Huang, Xuezhu Song, Qi Xie, Yingkai Li, Yan Liu
OBJECTIVES: Using the triple stimulation technique (TST) and conventional transcranial magnetic stimulation (TMS), this study was designed to investigate the effect of venlafaxine on central motor conduction in healthy adults. PATIENTS AND METHODS: In this crossover, self-controlled trial, eight healthy adult volunteers were randomly divided into groups A and B. In group A, the volunteers were administered 1 venlafaxine capsule once daily for 7 consecutive days, followed by a 3-day break...
February 12, 2018: Clinical Neurology and Neurosurgery
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