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https://www.readbyqxmd.com/read/29777683/probing-the-binding-site-of-novel-selective-positive-allosteric-modulators-at-the-m-1-machr
#1
Elham Khajehali, Celine Valant, Manuela Jörg, Andrew B Tobin, P Jeffrey Conn, Craig W Lindsley, Patrick M Sexton, Peter J Scammells, Arthur Christopoulos
Subtype-selective allosteric modulation of the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) is an attractive approach for the treatment of numerous disorders, including cognitive deficits. The discovery of benzyl quinolone carboxylic acid, BQCA, a selective M1 mAChR positive allosteric modulator (PAM), spurred the subsequent development of newer generation M1 PAMs representing diverse chemical scaffolds, different pharmacodynamic properties and, in some instances, improved pharmacokinetics. Key exemplar molecules from such efforts include PF-06767832 (N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-5-methyl-4-(4-(thiazol-4-yl)benzyl)pyridine-2-carboxamide), VU6004256 (4,6-difluoro-N-(1S,2S)-2-hydroxycyclohexyl-1-((6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl)methyl)-1H-indole-3-carboxamide) and MIPS1780 (3-(2-hydroxycyclohexyl)-6-(2-((4-(1-methyl-1H-pyrazol-4-yl)-benzyl)oxy)phenyl)pyrimidin-4(3H)-one)...
May 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29776901/a-moderated-e-forum-for-adults-with-cardiovascular-disease-usability-study
#2
Rika Tanaka, Anita Banerjee, Jelena Surikova, Jacqueline Tracey, Ada Payne, Heather Ross, Robert Nolan
BACKGROUND: Self-care behaviors are commonly prescribed to manage both cardiovascular disease and hypertension to reduce modifiable risk factors and improve quality of life. Nevertheless, long-term adherence to self-care recommendations for cardiac patients has been problematic. In cardiac patients, moderated online forums have been found to be particularly useful in supporting maintenance of heart-healthy diet and fewer hospital visits. As such, we developed the e-Forum, a Web-based moderated forum designed to promote continued user engagement and long-term self-care adherence...
May 18, 2018: JMIR Human Factors
https://www.readbyqxmd.com/read/29776533/safe-driving-practices-and-factors-associated-with-motor-vehicle-collisions-among-people-with-insulin-treated-diabetes-mellitus-results-from-the-diabetes-and-driving-dad-study
#3
Turky H Almigbal, Abdullah A Alfaifi, Muath A Aleid, Baki Billah, Mohammed J Alramadan, Eman Sheshah, Turki A AlMogbel, Ghassan A Aldekhayel, Mohammed Ali Batais
INTRODUCTION: The aim of this study was to assess the prevalence of people with insulin-treated diabetes mellitus (ITDM) who have discussed issues related to diabetes and driving with their health care providers (HCPs). We also sought to determine the safe driving practices that are currently employed by this group. Finally, we investigated the factors that might increase the risk of motor-vehicle collisions (MVCs) among this group in Saudi Arabia. METHOD: This cross-sectional study surveyed a representative sample of 429 current male drivers with ITDM using a structured questionnaire in Saudi Arabia...
June 2018: Journal of Safety Research
https://www.readbyqxmd.com/read/29776518/factors-associated-with-life-jacket-use-among-cabin-sailboat-and-day-sailor-boaters-in-the-united-states
#4
Natalie Spitzer, Maile T Phillips, Wendy Chow, Thomas W Mangione
INTRODUCTION: In 2015, drowning accounted for 68% of the 626 recreational boating related deaths in the United States. Although life jackets are estimated to prevent between 50% to 80% of boating deaths, approximately 83% of sailboat-related drowning victims were reported to not be wearing life jackets. Life jacket use among adult boaters has remained consistently low across most boat types and may vary by boater, boating, and environmental conditions. Although many risky environmental and boating factors may be associated with a higher risk of boating death, drowning occurs in all situations and it is useful to understand adult life jacket wearing behaviors in differing boating situations...
June 2018: Journal of Safety Research
https://www.readbyqxmd.com/read/29776182/optimal-stabilization-of-boolean-networks-through-collective-influence
#5
Jiannan Wang, Sen Pei, Wei Wei, Xiangnan Feng, Zhiming Zheng
Boolean networks have attracted much attention due to their wide applications in describing dynamics of biological systems. During past decades, much effort has been invested in unveiling how network structure and update rules affect the stability of Boolean networks. In this paper, we aim to identify and control a minimal set of influential nodes that is capable of stabilizing an unstable Boolean network. For locally treelike Boolean networks with biased truth tables, we propose a greedy algorithm to identify influential nodes in Boolean networks by minimizing the largest eigenvalue of a modified nonbacktracking matrix...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775475/perceptions-of-community-safety-and-social-activity-participation-among-youth-in-south-africa
#6
Nicole De Wet, Oluwaseyi Somefun, Ndivhuwo Rambau
BACKGROUND: Crime and violence causes massive disruptions to the health, survival and development of populations. In South Africa, incredibly high rates of crime and violence are noted. The country also has a very large youth population whose health, survival and development are key to economic growth. Among other efforts to encourage healthy youth development and the promotion of social activities such as sports, youth groups, choirs and so forth. This study examines the relationship between perceived community safety and the uptake of social activities among youth in South Africa...
2018: PloS One
https://www.readbyqxmd.com/read/29775472/spatial-pattern-and-determinants-of-anaemia-in-ethiopia
#7
Bedilu Alamirie Ejigu, Eshetu Wencheko, Kiros Berhane
Anaemia is a condition in which the haemoglobin concentration falls below an established cut-off value due to a decrease in the number and size of red blood cells. The current study aimed (i) to assess the spatial pattern and (ii) to identify determinants related to anaemia using the third Ethiopian demographic health survey. To achieve these objectives, this study took into account the sampling weight and the clustered nature of the data. As a result, multilevel modeling has been used in the statistical analysis...
2018: PloS One
https://www.readbyqxmd.com/read/29775405/the-mouse-heart-attack-research-tool-mhart-1-0-database
#8
Kristine Y DeLeon-Pennell, Rugmani Padmanabhan Iyer, Yonggang Ma, Andriy Yabluchanskiy, Rogelio Zamilpa, Ying Ann Chiao, Presley Cannon, Courtney Cates, Elizabeth R Flynn, Ganesh V Halade, Lisandra E de Castro Bras, Merry L Lindsey
The generation of Big Data has enabled systems-level dissections into the mechanisms of cardiovascular pathology. Integration of genetic, proteomic, and pathophysiological variables across platforms and laboratories fosters discoveries through multidisciplinary investigations and minimizes unnecessary redundancy in research efforts. The Mouse Heart Attack Research Tool (mHART) consolidates a large dataset of over 10 years of experiments from a single laboratory for cardiovascular investigators to generate novel hypotheses and identify new predictive markers of progressive left ventricular remodeling following myocardial infarction (MI) in mice...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29775345/novel-soft-pion-theorem-for-long-range-nuclear-parity-violation
#9
Xu Feng, Feng-Kun Guo, Chien-Yeah Seng
The parity-odd effect in the standard model weak neutral current reveals itself in the long-range parity-violating nuclear potential generated by the pion exchanges in the ΔI=1 channel with the parity-odd pion-nucleon coupling constant h_{π}^{1}. Despite decades of experimental and theoretical efforts, the size of this coupling constant is still not well understood. In this Letter, we derive a soft-pion theorem relating h_{π}^{1} and the neutron-proton mass splitting induced by an artificial parity-even counterpart of the ΔI=1 weak Lagrangian and demonstrate that the theorem still holds exact at the next-to-leading order in the chiral perturbation theory...
May 4, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29774589/healthcare-cost-and-utilization-in-nonalcoholic-fatty-liver-disease-real-world-data-from-a-large-us-claims-database
#10
Alina M Allen, Holly K Van Houten, Lindsey R Sangaralingham, Jayant A Talwalkar, Rozalina G McCoy
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The health care burden resulting from the multidisciplinary management of this complex disease is unknown. We assessed the total health care cost and resource utilization associated with a new NAFLD diagnosis, compared to controls with similar comorbidities. We used OptumLabs Data Warehouse, a large national administrative claims database with longitudinal health data of over 100 million individuals enrolled in private and Medicare Advantage health plans...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29773942/relationship-between-diabetes-knowledge-glycemic-control-and-associated-health-conditions
#11
Emily Phillips, Rabia Rahman, Mildred Mattfeldt-Beman
Objective: The purpose of this study was to identify any existing relationship between diabetes knowledge and glycemic control, as well as possible associations with patient health, among patients with type 2 diabetes. Design and Methods: This qualitative study used a validated multiple-choice test (the Michigan Diabetes Knowledge Test) to assess diabetes knowledge among 17 hospital patients between the ages of 18 and 75 years with type 2 diabetes and a recent (within 3 months) A1C laboratory value...
May 2018: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29773925/predictors-of-nest-growth-diminishing-returns-for-subordinates-in-the-paper-wasp-polistes-dominula
#12
Lena Grinsted, Jeremy Field
Abstract: In cooperative breeders, subordinates that have alternative reproductive options are expected to stay and help dominant breeders only as long as they contribute to group productivity, if their fitness is linked with colony success. Female Polistes dominula paper wasps live as cooperative breeders in small groups of typically fewer than 10 females. Subordinates tend to have high-quality outside options, and so could choose alternative breeding tactics if their work efforts increased productivity negligibly...
2018: Behavioral Ecology and Sociobiology
https://www.readbyqxmd.com/read/29773775/case-study-in-international-cooperation-cuba-s-molecular-immunology-center-and-roswell-park-cancer-institute
#13
Rachel Evans, Mary Reid, Brahm Segal, Scott I Abrams, Kelvin Lee
In 1961, the USA severed diplomatic relations with Cuba, and in 1962 an embargo was imposed on trade and financial relations with that country. It was not until five decades later that the USA and Cuba would reestablish relations. This opened the way for the New York State Trade Mission to Cuba in April 2015, during which Cuba's Molecular Immunology Center and Buffalo, New York's Roswell Park Cancer Institute signed a formal agreement that would set in motion biotechnology research collaboration to address one of the most important causes of death in both countries...
April 2018: MEDICC Review
https://www.readbyqxmd.com/read/29773293/usefulness-of-the-forced-oscillation-technique-in-assessing-the-therapeutic-result-of-tracheobronchial-central-airway-obstruction
#14
Masanori Yasuo, Yoshiaki Kitaguchi, Fumiya Kinota, Makoto Kosaka, Kazuhisa Urushihata, Atsuhito Ushiki, Hiroshi Yamamoto, Satoshi Kawakami, Masayuki Hanaoka
BACKGROUND: Pulmonary function tests (PFTs) comprise the traditional method for detecting central airway obstruction (CAO) and evaluating therapeutic effects, but are effort-dependent. By contrast, the forced oscillation technique (FOT) is performed during tidal breathing in an effort-independent mode and is universally used to assess respiratory function in patients with chronic obstructive pulmonary disease (COPD) and asthma. We used the FOT to measure airway resistance and reactance in patients with CAO before and after interventional bronchoscopy and compared the results to data obtained using PFTs...
May 2018: Respiratory Investigation
https://www.readbyqxmd.com/read/29773152/is-expressive-suppression-harmful-for-chinese-american-breast-cancer-survivors
#15
Qian Lu, William Tsai, Qiao Chu, Jing Xie
Emotion regulation strategies are important for cancer survivors' adjustment. Expressive suppression, defined as the active effort of inhibiting the expressive component of an emotional response, has been found to be a maladaptive emotion regulation strategy. These studies, however, have been limited to cross-sectional designs and primarily European American samples. Chinese culture encourages emotion suppression to preserve interpersonal harmony and therefore it may be important to test these emotion regulation processes with this population...
June 2018: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/29772220/cue-awareness-in-avoiding-effortful-control
#16
Timothy L Dunn, Connor Gaspar, Evan F Risko
Based on a recent metacognitive account, cognitive effort is the result of an inferential evaluation made over explicitly available cues. Following from this account, we present here a pre-registered experiment that tested the specific hypothesis that explicit awareness of cues that are aligned with cognitive demand is a prerequisite in avoiding effortful lines of action. We attempted to modulate levels of effort avoidance behavior by introducing an incentive (between-subjects) to monitor two lines of action that, unbeknownst to individuals, varied in the probability of a task switch...
May 14, 2018: Neuropsychologia
https://www.readbyqxmd.com/read/29771865/repeat-hiv-testing-by-transmission-risk-group-and-rurality-of-residence-in-north-carolina
#17
Rachael M Billock, Erika Samoff, Anna B Cope, Lynne A Sampson, Christopher B Hurt, Kimberly A Powers
BACKGROUND: Understanding of repeat HIV testing (RHT) is limited and the impact of rural residence as a potential barrier to RHT is unknown. Rural populations are of particular interest in the Southeastern United States because of their disproportionate HIV burden. METHODS: We used HIV surveillance data from publicly funded HIV testing sites in North Carolina (NC) to assess repeat testing by transmission risk group and residential rurality in a retrospective cohort study...
May 1, 2018: Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/29771601/response-to-third-rubella-vaccine-dose
#18
Lotta Siira, Hanne Nøkleby, Regine Barlinn, Øystein R Riise, Ingeborg S Aaberge, Susanne G Dudman
Limited data exist on the immunogenicity of a third dose of the measles, mumps, and rubella vaccine (MMR). In this study, our aim was to evaluate the long-term rubella immunogenicity afforded by two childhood MMR doses of the Norwegian vaccination program in a cohort of conscripts and to determine the effect of an additional dose of MMR vaccine, in order to inform vaccination policy. Blood samples from Norwegian conscripts (n = 495) taken both before and eight months after administration of a dose of MMR vaccine were tested using an enzyme immunoassay to measure anti-rubella IgG...
May 17, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29770910/creation-and-implementation-of-an-environmental-scan-to-assess-cancer-genetics-services-at-three-oncology-care-settings
#19
Erica M Bednar, Michael T Walsh, Ellen Baker, Kimberly I Muse, Holly D Oakley, Rebekah C Krukenberg, Cara S Dresbold, Sandra B Jenkinson, Amanda L Eppolito, Kelly B Teed, Molly H Klein, Nichole A Morman, Elizabeth C Bowdish, Pauline Russ, Emaline E Wise, Julia N Cooper, Michael W Method, John W Henson, Andrew V Grainger, Banu K Arun, Karen H Lu
An environmental scan (ES) is an efficient mixed-methods approach to collect and interpret relevant data for strategic planning and project design. To date, the ES has not been used nor evaluated in the clinical cancer genetics setting. We created and implemented an ES to inform the design of a quality improvement (QI) project to increase the rates of adherence to national guidelines for cancer genetic counseling and genetic testing at three unique oncology care settings (OCS). The ES collected qualitative and quantitative data from reviews of internal processes, past QI efforts, the literature, and each OCS...
May 16, 2018: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/29770279/testing-methods-to-mitigate-caribbean-yellow-band-disease-on-orbicella-faveolata
#20
Carly J Randall, Elizabeth M Whitcher, Tessa Code, Clayton Pollock, Ian Lundgren, Zandy Hillis-Starr, Erinn M Muller
Outbreaks of coral diseases continue to reduce global coral populations. In the Caribbean, yellow band is a severe and wide-spread disease that commonly affects corals of the Orbicella spp. complex, significantly impeding coral reproduction, and hindering the natural recovery of Orbicella spp. POPULATIONS: Caribbean yellow-band disease (CYBD) lesions may be severe, and often result in the complete loss of coral tissue. The slow spread of CYBD, however, provides an opportunity to test methods to mitigate the disease...
2018: PeerJ
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