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https://www.readbyqxmd.com/read/28323992/quantification-of-thyroid-cancer-and-multinodular-goiter-risk-in-the-dicer1-syndrome-a-family-based-cohort-study
#1
Nicholas E Khan, Andrew J Bauer, Kris Ann P Schultz, Leslie Doros, Rosamma M Decastro, Alexander Ling, Maya B Lodish, Laura A Harney, Ron G Kase, Ann G Carr, Christopher T Rossi, Amanda Field, Anne K Harris, Gretchen M Williams, Louis P Dehner, Yoav H Messinger, D Ashley Hill, Douglas R Stewart
Context: The risk of thyroid cancer and multinodular goiter (MNG) in the DICER1 syndrome, a rare tumor-predisposition disorder, is unknown. Objective: To quantify the risk of thyroid cancer and MNG in individuals with the DICER1 syndrome. Design: Family-based cohort study. Setting: National Institutes of Health (NIH) Clinical Center (CC). Participants: The National Cancer Institute DICER1 syndrome cohort consisted of 145 individuals with a DICER1 germline mutation and 135 family controls from 48 families...
February 2, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28315665/physician-scientists-in-obstetrics-and-gynecology-predictors-of-success-in-obtaining-independent-research-funding
#2
Ijeoma Okeigwe, Cynthia Wang, Joseph A Politch, Linda J Heffner, Wendy Kuohung
BACKGROUND: Obstetrics and gynecology departments receive the smallest amount of National Institutes of Health (NIH) research funding and have significantly lower application success rates compared to pediatric, internal medicine, and surgery departments. The development of mentored early career development training grants (K awards) has been one strategy implemented by the NIH to help aspiring physician-scientists establish independent research careers. OBJECTIVE: The purpose of this study is to describe the cohort of ob/gyn physician-scientists who were K08, K12, and K23 recipients from 1988-2015 and to identify predictors of success in obtaining independent federal funding, as defined by acquisition of an R01, R21, R34, U01, U54, P01, or P50...
March 15, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28314762/cerebral-microhemorrhages-mechanisms-consequences-and-prevention
#3
Zoltan I Ungvari, Stefano Tarantini, Angelia C Kirkpatrick, Anna Csiszar, Calin I Prodan
The increasing prevalence of multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds") is a significant, newly recognized problem in the aging population of the Western world. CMHs are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function, potentially contributing to cognitive decline, geriatric psychiatric syndromes and gait disorders. Clinical studies show that aging and hypertension significantly increase prevalence of CMHs...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314512/modulation-of-opioid-receptor-affinity-and-efficacy-via-n-substitution-of-9%C3%AE-hydroxy-5-3-hydroxyphenyl-morphan-synthesis-and-computer-simulation-study
#4
Phong M Truong, Sergio A Hassan, Yong-Sok Lee, Theresa A Kopajtic, Jonathan L Katz, Aaron M Chadderdon, John R Traynor, Jeffrey R Deschamps, Arthur E Jacobson, Kenner C Rice
The enantiomers of a variety of N-alkyl-, N-aralkyl-, and N-cyclopropylalkyl-9β-hydroxy-5-(3-hydroxyphenyl)morphans were synthesized employing cyanogen bromide and K2CO3 to improve the original N-demethylation procedure. Their binding affinity to the μ-, δ-, and κ-opioid receptors (ORs) was determined and functional (GTPγ(35)S) assays were carried out on those with reasonable affinity. The 1R,5R,9S-enantiomers (1R,5R,9S)-(-)-5-(3-hydroxyphenyl)-2-(4-nitrophenethyl)-2-azabicyclo[3.3.1]nonan-9-ol (1R,5R,9S-16), (1R,5R,9S)-(-) 2-cinnamyl-5-(3-hydroxyphenyl)-2-azabicyclo[3...
March 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28314118/in-vitro-assay-development-and-hts-of-small-molecule-human-abad-17%C3%AE-hsd10-inhibitors-as-therapeutics-in-alzheimer-s-disease
#5
Laura Aitken, Gemma Baillie, Andrew Pannifer, Angus Morrison, Philip S Jones, Terry K Smith, Stuart P McElroy, Frank J Gunn-Moore
A major hallmark of Alzheimer's disease (AD) is the formation of neurotoxic aggregates composed of the amyloid-β peptide (Aβ). Aβ has been recognized to interact with numerous proteins, resulting in pathological changes to the metabolism of patients with AD. One such mitochondrial metabolic enzyme is amyloid-binding alcohol dehydrogenase (ABAD), where altered enzyme function caused by the Aβ-ABAD interaction is known to cause mitochondrial distress and cytotoxic effects, providing a feasible therapeutic target for AD drug development...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28303917/reduced-regional-grey-matter-volumes-in-pediatric-obstructive-sleep-apnea
#6
Mona F Philby, Paul M Macey, Richard A Ma, Rajesh Kumar, David Gozal, Leila Kheirandish-Gozal
Pediatric OSA is associated with cognitive risk. Since adult OSA manifests MRI evidence of brain injury, and animal models lead to regional neuronal losses, pediatric OSA patients may also be affected. We assessed the presence of neuronal injury, measured as regional grey matter volume, in 16 OSA children (8 male, 8.1 ± 2.2 years, AHI:11.1 ± 5.9 events/hr), and 200 control subjects (84 male, 8.2 ± 2.0 years), 191 of whom were from the NIH-Pediatric MRI database. High resolution T1-weighted whole-brain images were assessed between groups with voxel-based morphometry, using ANCOVA (covariates, age and gender; family-wise error correction, P < 0...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303425/common-data-elements-for-clinical-research-in-mitochondrial-disease-a-national-institute-for-neurological-disorders-and-stroke-project
#7
Amel Karaa, Shamima Rahman, Anne Lombès, Patrick Yu-Wai-Man, Muniza K Sheikh, Sherita Alai-Hansen, Bruce H Cohen, David Dimmock, Lisa Emrick, Marni J Falk, Shana McCormack, David Mirsky, Tony Moore, Sumit Parikh, John Shoffner, Tanja Taivassalo, Mark Tarnopolsky, Ingrid Tein, Joanne C Odenkirchen, Amy Goldstein
OBJECTIVES: The common data elements (CDE) project was developed by the National Institute of Neurological Disorders and Stroke (NINDS) to provide clinical researchers with tools to improve data quality and allow for harmonization of data collected in different research studies. CDEs have been created for several neurological diseases; the aim of this project was to develop CDEs specifically curated for mitochondrial disease (Mito) to enhance clinical research. METHODS: Nine working groups (WGs), composed of international mitochondrial disease experts, provided recommendations for Mito clinical research...
March 16, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28302154/the-israeli-national-genetic-database-a-10-year-experience
#8
Joël Zlotogora, George P Patrinos
BACKGROUND: The Israeli National and Ethnic Mutation database ( http://server.goldenhelix.org/israeli ) was launched in September 2006 on the ETHNOS software to include clinically relevant genomic variants reported among Jewish and Arab Israeli patients. In 2016, the database was reviewed and corrected according to ClinVar ( https://www.ncbi.nlm.nih.gov/clinvar ) and ExAC ( http://exac.broadinstitute.org ) database entries. The present article summarizes some key aspects from the development and continuous update of the database over a 10-year period, which could serve as a paradigm of successful database curation for other similar resources...
March 16, 2017: Human Genomics
https://www.readbyqxmd.com/read/28301572/far-infrared-suppresses-skin-photoaging-in-ultraviolet-b-exposed-fibroblasts-and-hairless-mice
#9
Hui-Wen Chiu, Cheng-Hsien Chen, Yi-Jie Chen, Yung-Ho Hsu
Ultraviolet (UV) induces skin photoaging, which is characterized by thickening, wrinkling, pigmentation, and dryness. Collagen, which is one of the main building blocks of human skin, is regulated by collagen synthesis and collagen breakdown. Autophagy was found to block the epidermal hyperproliferative response to UVB and may play a crucial role in preventing skin photoaging. In the present study, we investigated whether far-infrared (FIR) therapy can inhibit skin photoaging via UVB irradiation in NIH 3T3 mouse embryonic fibroblasts and SKH-1 hairless mice...
2017: PloS One
https://www.readbyqxmd.com/read/28301427/national-institutes-of-health-research-plan-on-rehabilitation
#10
(no author information available yet)
One in five Americans experiences disability that affects their daily function because of impairments in mobility, cognitive function, sensory impairment, or communication impairment. The need for rehabilitation strategies to optimize function and reduce disability is a clear priority for research to address this public health challenge. The National Institutes of Health (NIH) recently published a Research Plan on Rehabilitation that provides a set of priorities to guide the field over the next 5 years. The plan was developed with input from multiple Institutes and Centers within the NIH, the National Advisory Board for Medical Rehabilitation Research, and the public...
April 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28300411/h2s-releasing-polymer-micelles-for-studying-selective-cell-toxicity
#11
Jeffrey C Foster, Scott C Radzinski, Xianlin Zou, Carla V Finkielstein, John B Matson
We report the preparation of S-aroylthiooxime (SATO) functionalized amphiphilic block copolymer micelles that release hydrogen sulfide (H2S), a gaseous signaling molecule of relevance to various physiological and pathological conditions. The micelles release H2S in response to cysteine with a half-life of 3.3 h, which is substantially slower than a related small molecule SATO. Exogenous administration of H2S impacts growth and proliferation of cancer cells; however, the limited control over H2S generation from inorganic sulfide sources results in conflicting reports...
March 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28299635/geroscience-and-the-trans-nih-geroscience-interest-group-gsig
#12
EDITORIAL
Felipe Sierra, Ron Kohanski
Age is by far the major risk factor for most chronic diseases. This has been common knowledge since time immemorial. Aging encompasses the biological changes most often seen as declines of function and increasing burden of disease. The close linkage of these two has led people to believe that aging, like age, is immutable. It is only recently that research into the basic molecular and cellular mechanisms of aging has led to potential interventions that increase lifespan and appear to increase healthspan, as well...
February 2017: Geroscience
https://www.readbyqxmd.com/read/28297759/-expression-and-significance-of-integrin-%C3%AE-5%C3%AE-1-and-fibronectin-in-atherosclerotic-plaques-from-autopsy-specimens
#13
X Yu, Q Q Zhang, B Wang, L Sun
Objective: To investigate the expression of integrin α5β1 and fibronectin in the human aorta and coronary artery, and their effects in the development of atherosclerosis. Methods: One hundred and twenty autopsy aorta and coronary artery specimens were collected, and the expression of CD68, actin, integrin α5β1 and fibronectin was detected by immunohistochemical staining. Atherosclerotic plaques were located by CD68 and actin staining, and the degree of coronary artery stenosis was determined by elastic fiber staining and NIH Scion Image(60...
March 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28296511/targeted-delivery-of-doxorubicin-into-tumor-cells-by-nanostructured-lipid-carriers-conjugated-to-anti-egfrviii-monoclonal-antibody
#14
Saeideh Abdolahpour, Tayebeh Toliyat, Kobra Omidfar, Helmout Modjtahedi, Albert J Wong, Mohammad Javad Rasaee, Susan Kashanian, Maliheh Paknejad
Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the EGF receptor in many human tumors. This variant is tumor specific and highly immunogenic, thus, it can be used as a target for targeted drug delivery toward tumor cells. The major aim of this study was to develop an EGFRvIII-mediated drug delivery system by anti-EGFRvIII monoclonal antibody (MAb) conjugated to doxorubicin (Dox)-loaded nanostructured lipid carriers (NLC) to enhance the targeting specificity and cytotoxic effect of Dox on EGFRvIII-overexpressing cell line...
March 15, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28294316/knockout-of-atg5-leads-to-malignant-cell-transformation-and-resistance-to-src-family-kinase-inhibitor-pp2
#15
Sung-Hee Hwang, Byeal-I Han, Michael Lee
Autophagy can either promote or inhibit cell death in different cellular contexts. In this study, we investigated the role of autophagy in ATG5 knockout (KO) cell line established using CRISPR/Cas9 system. In ATG5 KO cells, RT-PCR and immunoblot of LC3 confirmed the functional gene knockout. We found that knockout of ATG5 significantly increased proliferation of NIH 3T3 cells. In particular, autophagy deficiency enhanced susceptibility to cellular transformation as determined by an in vitro clonogenic survival assay and a soft agar colony formation assay...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28294051/further-evaluation-of-mechanisms-associated-with-the-antidepressant-like-signature-of-scopolamine-in-mice
#16
Anna E Martin, Douglas A Schober, Alexander Nikolayev, Vladimir V Tolstikov, Wesley H Anderson, Richard E Higgs, Ming-Shang Kuo, Anastasia Laksmanan, John T Catlow, Xia Li, Christian C Felder, Jeffrey M Witkin
Conventional antidepressants lack efficacy for many patients (treatment-resistant depression or TRD) and generally take weeks to produce full therapeutic response in others. Emerging data has identified certain drugs such as ketamine as rapidly-acting antidepressants for major depressive disorder and TRD. Scopolamine, a drug used to treat motion sickness and nausea, has also been demonstrated to function as a rapidly-acting antidepressant. The mechanisms associated with efficacy in TRD patients and rapid onset of action have been suggested to involve a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling...
March 9, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28293079/pediatric-gastrointestinal-bleeding-perspectives-from-the-italian-society-of-pediatric-gastroenterology
#17
REVIEW
Claudio Romano, Salvatore Oliva, Stefano Martellossi, Erasmo Miele, Serena Arrigo, Maria Giovanna Graziani, Sabrina Cardile, Federica Gaiani, Gian Luigi de'Angelis, Filippo Torroni
There are many causes of gastrointestinal bleeding (GIB) in children, and this condition is not rare, having a reported incidence of 6.4%. Causes vary with age, but show considerable overlap; moreover, while many of the causes in the pediatric population are similar to those in adults, some lesions are unique to children. The diagnostic approach for pediatric GIB includes definition of the etiology, localization of the bleeding site and determination of the severity of bleeding; timely and accurate diagnosis is necessary to reduce morbidity and mortality...
February 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28292880/plasma-serpinb1-is-related-to-insulin-sensitivity-but-not-pancreatic-%C3%AE-cell-function-in-non-diabetic-adults
#18
Michael Glicksman, Asha Asthana, Brent S Abel, Mary F Walter, Monica C Skarulis, Ranganath Muniyappa
Pancreatic β-cell dysfunction because of reduced β-cell mass and function is a primary determinant in the progression of diabetes. Increase in β-cell mass and compensatory hyperinsulinaemia is frequently associated with insulin-resistant states. Although the humoral factors mediating this compensatory response are unknown, serpinB1, a protease inhibitor, has recently been proposed to be one such factor. In this study, we examine the relationships between plasma serpinB1, insulin sensitivity, and pancreatic β-cell function in non-diabetic individuals...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28287138/biofunctionalized-3-d-carbon-nano-network-platform-for-enhanced-fibroblast-cell-adhesion
#19
A K M Rezaul Haque Chowdhury, Amirhossein Tavangar, Bo Tan, Krishnan Venkatakrishnan
Carbon nanomaterials have been investigated for various biomedical applications. In most cases, however, these nanomaterials must be functionalized biologically or chemically due to their biological inertness or possible cytotoxicity. Here, we report the development of a new carbon nanomaterial with a bioactive phase that significantly promotes cell adhesion. We synthesize the bioactive phase by introducing self-assembled nanotopography and altered nano-chemistry to graphite substrates using ultrafast laser...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286067/future-directions-of-research-and-care-for-urinary-incontinence-in-women-findings-from-the-national-institute-of-diabetes-and-digestive-and-kidney-diseases-niddk-summit-on-urinary-incontinence-clinical-research-in-women
#20
REVIEW
Toby C Chai, Tirsit S Asfaw, Jan E Baker, Becky Clarkson, Pamela Coleman, Susan Hoffstetter, Kimberly Konkel, Missy Lavender, Shailaja Nair, Jenna Norton, Leslee Subak, Anthony Visco, Robert A Star, Tamara Bavendam
PURPOSE: Female urinary incontinence (UI) is prevalent, costly, and morbid. Participants in an NIDDK-sponsored summit reviewed findings from NIH-funded clinical research in UI and discussed the future of UI research. MATERIALS AND METHODS: On March 14 2014, the NIDDK convened a "Summit on Urinary Incontinence Clinical Research in Women." Participants representing a broad range of clinical expertise reviewed completed, NIH-sponsored UI-related studies, including results from community-based, epidemiologic studies such as the Boston Area Community Health (BACH) Survey and from randomized clinical trials such as the Program to Reduce Incontinence by Diet and Exercise (PRIDE) and studies conducted by the Pelvic Floor Disorders Network (PFDN) and the Urinary Incontinence Treatment Network (UITN)...
March 9, 2017: Journal of Urology
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