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David Sinclair

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https://www.readbyqxmd.com/read/29577959/sirtuin-activators-and-inhibitors-promises-achievements-and-challenges
#1
REVIEW
Han Dai, David A Sinclair, James L Ellis, Clemens Steegborn
The NAD+ -dependent protein lysine deacylases of the Sirtuin family regulate various physiological functions, from energy metabolism to stress responses. The human Sirtuin isoforms, SIRT1-7, are considered attractive therapeutic targets for aging-related diseases, such as type 2 diabetes, inflammatory diseases and neurodegenerative disorders. We review the status of Sirtuin-targeted drug discovery and development. Potent and selective pharmacological Sirt1 activators and inhibitors are available, and initial clinical trials have been carried out...
March 22, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29570999/impairment-of-an-endothelial-nad-h-2-s-signaling-network-is-a-reversible-cause-of-vascular-aging
#2
Abhirup Das, George X Huang, Michael S Bonkowski, Alban Longchamp, Catherine Li, Michael B Schultz, Lynn-Jee Kim, Brenna Osborne, Sanket Joshi, Yuancheng Lu, Jose Humberto Treviño-Villarreal, Myung-Jin Kang, Tzong-Tyng Hung, Brendan Lee, Eric O Williams, Masaki Igarashi, James R Mitchell, Lindsay E Wu, Nigel Turner, Zolt Arany, Leonard Guarente, David A Sinclair
A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1-SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2 S), a DR mimetic and regulator of endothelial NAD+ levels...
March 22, 2018: Cell
https://www.readbyqxmd.com/read/29570992/amino-acid-restriction-triggers-angiogenesis-via-gcn2-atf4-regulation-of-vegf-and-h-2-s-production
#3
Alban Longchamp, Teodelinda Mirabella, Alessandro Arduini, Michael R MacArthur, Abhirup Das, J Humberto Treviño-Villarreal, Christopher Hine, Issam Ben-Sahra, Nelson H Knudsen, Lear E Brace, Justin Reynolds, Pedro Mejia, Ming Tao, Gaurav Sharma, Rui Wang, Jean-Marc Corpataux, Jacques-Antoine Haefliger, Kyo Han Ahn, Chih-Hao Lee, Brendan D Manning, David A Sinclair, Christopher S Chen, C Keith Ozaki, James R Mitchell
Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α...
March 22, 2018: Cell
https://www.readbyqxmd.com/read/29519856/substantial-numerical-decline-in-south-australian-rabbit-populations-following-the-detection-of-rabbit-haemorrhagic-disease-virus-2
#4
Greg Mutze, Nicki De Preu, Trish Mooney, Dylan Koerner, Darren McKenzie, Ron Sinclair, John Kovaliskli, David Peacock
Lagovirus europaeus GI.2, also commonly known as rabbit haemorrhagic disease virus 2, was first detected at two long-term monitoring sites for European rabbits, Oryctolagus cuniculus , in South Australia, in mid-2016. Numbers of rabbits in the following 12-18 months were reduced to approximately 20 per cent of average numbers in the preceding 10 years. The impact recorded at the two South Australian sites, if widespread in Australia and persistent for several years, is likely to be of enormous economic and environmental benefit...
March 8, 2018: Veterinary Record
https://www.readbyqxmd.com/read/29514072/nicotinamide-improves-aspects-of-healthspan-but-not-lifespan-in-mice
#5
Sarah J Mitchell, Michel Bernier, Miguel A Aon, Sonia Cortassa, Eun Young Kim, Evandro F Fang, Hector H Palacios, Ahmed Ali, Ignacio Navas-Enamorado, Andrea Di Francesco, Tamzin A Kaiser, Tyler B Waltz, Ning Zhang, James L Ellis, Peter J Elliott, David W Frederick, Vilhelm A Bohr, Mark S Schmidt, Charles Brenner, David A Sinclair, Anthony A Sauve, Joseph A Baur, Rafael de Cabo
The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD+ , is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways...
March 6, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29514064/therapeutic-potential-of-nad-boosting-molecules-the-in-vivo-evidence
#6
REVIEW
Luis Rajman, Karolina Chwalek, David A Sinclair
Nicotinamide adenine dinucleotide (NAD), the cell's hydrogen carrier for redox enzymes, is well known for its role in redox reactions. More recently, it has emerged as a signaling molecule. By modulating NAD+ -sensing enzymes, NAD+ controls hundreds of key processes from energy metabolism to cell survival, rising and falling depending on food intake, exercise, and the time of day. NAD+ levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility. Restoration of NAD+ levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules that hold the promise of increasing the body's resilience, not just to one disease, but to many, thereby extending healthy human lifespan...
March 6, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29502097/disability-discrimination-and-misdirected-criticism-of-the-quality-adjusted-life-year-framework
#7
David Gt Whitehurst, Lidia Engel
Whose values should count - those of patients or the general public - when adopting the quality-adjusted life year (QALY) framework for healthcare decision making is a long-standing debate. Specific disciplines, such as economics, are not wedded to a particular side of the debate, and arguments for and against the use of patient values have been discussed at length in the literature. In 2012, Sinclair proposed an approach, grounded within patient preference theory, which sought to avoid a perceived unfair discrimination against people with disabilities when using values from the general public...
March 3, 2018: Journal of Medical Ethics
https://www.readbyqxmd.com/read/29473122/medicinal-cannabis-and-the-tyranny-of-distance-policy-reform-required-for-optimizing-patient-and-health-system-net-benefit-in-australia
#8
David Caldicott, Justin Sinclair, Lynnaire Sheridan, Simon Eckermann
No abstract text is available yet for this article.
February 23, 2018: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/29465336/current-emergency-preparedness-resources-and-capabilities-among-academic-health-systems-in-the-united-states
#9
Paul D Biddinger, David Reisman, Robert F Seger, Ann L Prestipino, Julia Sinclair, Barry Wante, Eric Goralnick, Katherine Kemen
OBJECTIVE: Although hospital emergency preparedness efforts have been recognized as important, there has been growing pressure on cost containment, as well as consolidation within the US health care system. There is little data looking at what health care emergency preparedness functions have been, could be, or should be centrally coordinated at a system level. METHODS: We developed a questionnaire for academic health systems and asked about program funding, resources provided, governance, and activities...
February 21, 2018: Disaster Medicine and Public Health Preparedness
https://www.readbyqxmd.com/read/29461666/surgical-management-of-the-recurrent-laryngeal-nerve-in-thyroidectomy-american-head-and-neck-society-consensus-statement
#10
Christopher E Fundakowski, Nathan W Hales, Nishant Agarwal, Marcin Barczyński, Pauline M Camacho, Dana M Hartl, Emad Kandil, Whitney E Liddy, Travis J McKenzie, John C Morris, John A Ridge, Rick Schneider, Jonathan Serpell, Catherine F Sinclair, Samuel K Snyder, David J Terris, R Michael Tuttle, Che-Wei Wu, Richard J Wong, Mark Zafereo, Gregory W Randolph
"I have noticed in operations of this kind, which I have seen performed by others upon the living, and in a number of excisions, which I have myself performed on the dead body, that most of the difficulty in the separation of the tumor has occurred in the region of these ligaments…. This difficulty, I believe, to be a very frequent source of that accident, which so commonly occurs in removal of goiter, I mean division of the recurrent laryngeal nerve." Sir James Berry (1887).
February 20, 2018: Head & Neck
https://www.readbyqxmd.com/read/29413364/arachidonic-acid-supplementation-modulates-blood-and-skeletal-muscle-lipid-profile-with-no-effect-on-basal-inflammation-in-resistance-exercise-trained-men
#11
James F Markworth, Cameron J Mitchell, Randall F D'Souza, Kirsten M M Aasen, Brenan R Durainayagam, Sarah M Mitchell, Alex H C Chan, Andrew J Sinclair, Manohar Garg, David Cameron-Smith
Arachidonic acid (ARA), an omega-6 polyunsaturated fatty acid (PUFA), is the metabolic precursor to the eicosanoid family of lipid mediators. Eicosanoids have potent pro-inflammatory actions, but also act as important autocrine/paracrine signaling molecules in skeletal muscle growth and development. Whether dietary ARA is incorporated into skeletal muscle phospholipids and the resulting impact on intramuscular inflammatory and adaptive processes in-vivo is not known. In the current study, resistance trained men (≥1 year) received dietary supplementation with 1...
January 2018: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/29389245/the-effect-of-dietary-arachidonic-acid-supplementation-on-acute-muscle-adaptive-responses-to-resistance-exercise-in-trained-men-a-randomized-controlled-trial
#12
Cameron J Mitchell, Randall F D'Souza, Vandre Casagrande Figueiredo, Alex Chan, Kirsten M Aasen, Brenan Durainayagam, Sarah M Mitchell, Andrew J Sinclair, Ingrid Marie Egner, Truls Raastad, David Cameron-Smith, James F Markworth
Arachidonic acid (ARA), a polyunsaturated ω-6 fatty acid, acts as precursor to a number of prostaglandins with potential roles in muscle anabolism. It was hypothesized that ARA supplementation might enhance the early anabolic response to resistance exercise (RE) by increasing muscle protein synthesis (MPS) via mammalian target of rapamycin (mTOR) pathway activation, and/or the late anabolic response by modulating ribosome biogenesis and satellite cell expansion. Nineteen men with {greater than or equal to}1 year of resistance training experience were randomized to consume either 1...
February 1, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29322480/intra-operative-video-characterization-of-carotid-artery-pulsation-patterns-in-case-series-with-post-endarterectomy-hypertension-and-hyperperfusion-syndrome
#13
Yiming Xiao, Hassan Rivaz, Hidetoshi Kasuya, Suguru Yokosako, Cristina Mindru, Jeanne Teitelbaum, Denis Sirhan, David Sinclair, Mark Angle, Benjamin W Y Lo
Cerebral hyperperfusion syndrome (CHS) is a complication that can occur after carotid endarterectomy (CEA), the treatment of choice to decrease the subsequent risk of fatal or disabling stroke for patients with symptomatic severe stenosis of the carotid artery. Because of its rarity and complexity, the mechanism of the condition is still unclear, making its prevention via prediction and monitoring challenging. This is especially true during surgery, when multiple factors can induce physiological changes, including blood pressure and baroreceptor functions, which are crucial factors for post-CEA hypertension and CHS...
January 10, 2018: Translational Stroke Research
https://www.readbyqxmd.com/read/29248786/biophysical-risks-to-carbon-sequestration-and-storage-in-australian-drylands
#14
REVIEW
Rachael H Nolan, Jennifer Sinclair, David J Eldridge, Daniel Ramp
Carbon abatement schemes that reduce land clearing and promote revegetation are now an important component of climate change policy globally. There is considerable potential for these schemes to operate in drylands which are spatially extensive. However, projects in these environments risk failure through unplanned release of stored carbon to the atmosphere. In this review, we identify factors that may adversely affect the success of vegetation-based carbon abatement projects in dryland ecosystems, evaluate their likelihood of occurrence, and estimate the potential consequences for carbon storage and sequestration...
February 15, 2018: Journal of Environmental Management
https://www.readbyqxmd.com/read/29189534/pediatric-orthopaedic-surgeons-dissatisfied-in-on-call-practices-despite-improving-call-conditions-the-2015-posna-membership-survey-regarding-trauma-care
#15
Allison Lind, Kevin Latz, Mark R Sinclair, David D Williams
BACKGROUND: To examine the current trends in trauma call coverage of pediatric orthopaedic surgeons in North America and to identify predictors of surgeon on-call satisfaction. METHODS: In 2015, ∼1200 active members of the Pediatric Orthopaedic Society of North America (POSNA) were surveyed regarding emergency room on-call practices. In total, 410 members completed the survey with a response rate of 35%. Information collected included call frequency, practice setting and satisfaction with call...
February 2018: Journal of Pediatric Orthopedics
https://www.readbyqxmd.com/read/29182800/interventions-to-increase-tuberculosis-case-detection-at-primary-healthcare-or-community-level-services
#16
REVIEW
Francis A Mhimbira, Luis E Cuevas, Russell Dacombe, Abdallah Mkopi, David Sinclair
BACKGROUND: Pulmonary tuberculosis is usually diagnosed when symptomatic individuals seek care at healthcare facilities, and healthcare workers have a minimal role in promoting the health-seeking behaviour. However, some policy specialists believe the healthcare system could be more active in tuberculosis diagnosis to increase tuberculosis case detection. OBJECTIVES: To evaluate the effectiveness of different strategies to increase tuberculosis case detection through improving access (geographical, financial, educational) to tuberculosis diagnosis at primary healthcare or community-level services...
November 28, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29146412/skeletal-muscle-overexpression-of-nicotinamide-phosphoribosyl-transferase-in-mice-coupled-with-voluntary-exercise-augments-exercise-endurance
#17
Sheila R Costford, Bram Brouwers, Meghan E Hopf, Lauren M Sparks, Mauro Dispagna, Ana P Gomes, Heather H Cornnell, Chris Petucci, Peter Phelan, Hui Xie, Fanchao Yi, Glenn A Walter, Timothy F Osborne, David A Sinclair, Randall L Mynatt, Julio E Ayala, Stephen J Gardell, Steven R Smith
OBJECTIVE: Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme in the salvage pathway that produces nicotinamide adenine dinucleotide (NAD+ ), an essential co-substrate regulating a myriad of signaling pathways. We produced a mouse that overexpressed NAMPT in skeletal muscle (NamptTg) and hypothesized that NamptTg mice would have increased oxidative capacity, endurance performance, and mitochondrial gene expression, and would be rescued from metabolic abnormalities that developed with high fat diet (HFD) feeding...
January 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29118320/nicotinamide-mononucleotide-nmn-supplementation-ameliorates-the-impact-of-maternal-obesity-in-mice-comparison-with-exercise
#18
Golam Mezbah Uddin, Neil A Youngson, Bronte M Doyle, David A Sinclair, Margaret J Morris
Maternal overnutrition increases the risk of long-term metabolic dysfunction in offspring. Exercise improves metabolism partly by upregulating mitochondrial biogenesis or function, via increased levels of nicotinamide adenine dinucleotide (NAD+ ). We have shown that the NAD+ precursor, nicotinamide mononucleotide (NMN) can reverse some of the negative consequences of high fat diet (HFD) consumption. To investigate whether NMN can impact developmentally-set metabolic deficits, we compared treadmill exercise and NMN injection in offspring of obese mothers...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117315/interdisciplinary-perspectives-on-sun-safety
#19
Alan C Geller, Nina G Jablonski, Sherry L Pagoto, Jennifer L Hay, Joel Hillhouse, David B Buller, W Larry Kenney, June K Robinson, Richard B Weller, Megan A Moreno, Barbara A Gilchrest, Craig Sinclair, Jamie Arndt, Jennifer M Taber, Kasey L Morris, Laura A Dwyer, Frank M Perna, William M P Klein, Jerry Suls
Overexposure to the sun is associated with an increased risk of melanoma and nonmelanoma skin cancer, but indications of improvements in sun protection behavior are poor. Attempts to identify emerging themes in skin cancer control have largely been driven by groups of experts from a single field. In December 2016, 19 experts from various disciplines convened for Interdisciplinary Perspectives on Skin Cancer, a 2-day meeting hosted by the National Academy of Sciences. The group discussed knowledge gaps, perspectives on sun exposure, implications for skin cancer risk and other health outcomes, and new directions...
January 1, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29112879/myocardial-strain-computed-at-multiple-spatial-scales-from-tagged-magnetic-resonance-imaging-estimating-cardiac-biomarkers-for-crt-patients
#20
Matthew Sinclair, Devis Peressutti, Esther Puyol-Antón, Wenjia Bai, Simone Rivolo, Jessica Webb, Simon Claridge, Thomas Jackson, David Nordsletten, Myrianthi Hadjicharalambous, Eric Kerfoot, Christopher A Rinaldi, Daniel Rueckert, Andrew P King
Abnormal cardiac motion can indicate different forms of disease, which can manifest at different spatial scales in the myocardium. Many studies have sought to characterise particular motion abnormalities associated with specific diseases, and to utilise motion information to improve diagnoses. However, the importance of spatial scale in the analysis of cardiac deformation has not been extensively investigated. We build on recent work on the analysis of myocardial strains at different spatial scales using a cardiac motion atlas to find the optimal scales for estimating different cardiac biomarkers...
January 2018: Medical Image Analysis
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