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https://www.readbyqxmd.com/read/28317237/disruption-of-the-cx43-mir21-pathway-leads-to-osteocyte-apoptosis-and-increased-osteoclastogenesis-with-aging
#1
Hannah M Davis, Rafael Pacheco-Costa, Emily G Atkinson, Lucas R Brun, Arancha R Gortazar, Julia Harris, Masahiro Hiasa, Surajudeen A Bolarinwa, Toshiyuki Yoneda, Mircea Ivan, Angela Bruzzaniti, Teresita Bellido, Lilian I Plotkin
Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency...
March 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28299518/addressing-the-first-90-a-highly-effective-partner-notification-approach-reaches-previously-undiagnosed-sexual-partners-in-tanzania
#2
Catherine Kahabuka, Marya Plotkin, Alice Christensen, Charlene Brown, Mustafa Njozi, Renatus Kisendi, Werner Maokola, Erick Mlanga, Ruth Lemwayi, Kelly Curran, Vincent Wong
To meet UNAIDS' 90-90-90 treatment goals, effective approaches to HIV testing services (HTSs) are urgently needed. In 2015, a cross-sectional study was conducted to evaluate effectiveness and feasibility of partner notification for HTS in Tanzania. Men and women newly diagnosed with HIV were enrolled as index clients, listed sexual partners, and given options to notify and link their partners to HTS. Of 653 newly diagnosed individuals, 390 index clients were enrolled, listed 438 sexual partners, of whom 249 (56...
March 15, 2017: AIDS and Behavior
https://www.readbyqxmd.com/read/28289064/what-is-wrong-with-pertussis-vaccine-immunity-the-problem-of-waning-effectiveness-of-pertussis-vaccines
#3
Nicolas Burdin, L K Handy, S A Plotkin
Pertussis is resurgent in some countries, particularly those in which children receive acellular pertussis (aP) vaccines in early infancy and boosters later in life. Immunologic studies show that, whereas whole-cell pertussis (wP) vaccines orient the immune system toward Th1/Th17 responses, acellular pertussis vaccines orient toward Th1/Th2 responses. Although aP vaccines do provide protection during the first years of life, the change in T-cell priming results in waning effectiveness of aP as early as 2-3 years post-boosters...
March 13, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28229472/human-capital-gaps-in-vaccine-development-an-issue-for-global-vaccine-development-and-global-health
#4
Andrea Cawein, Emilio Emini, Michael Watson, Joanna Dailey, John Donnelly, Dina Tresnan, Tom Evans, Stanley Plotkin, William Gruber
Despite the success of vaccines in reducing the morbidity and mortality associated with infectious diseases, many infectious diseases, both newly emerging and well known, lack vaccines. The global capability for beginning-to-end vaccine development has become limited, primarily owing to a scarcity of human capital necessary to guide the development of novel vaccines from the laboratory to the marketplace. Here, we identify and discuss the gaps in human capital necessary for robust vaccine development and make recommendations to begin to address these deficiencies...
February 23, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28211981/first-report-of-factors-associated-with-satisfaction-in-patients-with-neurofibromatosis
#5
Eric Riklin, Mojtaba Talaei-Kheoi, Vanessa L Merker, Monica R Sheridan, Justin T Jordan, Scott R Plotkin, Ana-Maria Vranceanu
Patient satisfaction is an integral part of quality health care. We assessed whether health literacy and psychosocial factors are associated with patient satisfaction among adults with neurofibromatosis. Eighty adults (mean age = 44 years; 55% female, 87% white) with NF (50% NF1, 41% NF2, and 9% schwannomatosis) completed an adapted Functional, Communicative, and Critical Health Literacy Questionnaire (FCCHL), the Health Literacy Assessment, a series of Patient Reported Outcome Measures Information System (PROMIS) psychosocial tests, and demographics before the medical visit...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28194556/pancreatoblastoma-an-atypical-presentation-and-a-literature-review
#6
Marisa Terino, Eileen Plotkin, Raffi Karagozian
No abstract text is available yet for this article.
February 14, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28169160/corrigendum-to-discovery-of-benzofuran-propanoic-acid-gpr120-agonists-from-uhts-hit-to-mechanism-based-pharmacodynamic-effects-bioorg-med-chem-lett-26-2016-5724-5728
#7
Matthew Lombardo, Kate Bender, Clare London, Michael A Plotkin, Melissa Kirkland, Joel Mane, Michele Pachanski, Wayne Geissler, John Cummings, Bahanu Habulihaz, Taro E Akiyama, Jerry Di Salvo, Maria Madeira, Joanna Pols, Mary Ann Powles, Michael F Finley, Eric Johnson, Thomas Roussel, Victor N Uebele, Alejandro Crespo, Dennis Leung, Candice Alleyne, Dorina Trusca, Ying Lei, Andrew D Howard, Feroze Ujjainwalla, James R Tata, Christopher J Sinz
No abstract text is available yet for this article.
February 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28166501/using-a-sniff-controller-to-self-trigger-abdominal-functional-electrical-stimulation-for-assisted-coughing-following-cervical-spinal-cord-lesions
#8
Lior Haviv, Hagit Friedman, Uri Bierman, Itzhak Glass, Anton Plotkin, Aharon Weissbrod, Sagit Shushan, Vadim Bluvshtein, Elena Aidinoff, Noam Sobel, Amiram Catz
Individuals with cervical spinal cord lesions (SCL) typically depend on caregivers to manually assist in coughing by pressing against their abdominal wall. Coughing can also be assisted by functional electric stimulation (FES) applied to abdominal muscles via surface electrodes. Efficacy of FES, however, depends on precise temporal synchronization. The sniff-controller is a trigger that enables paralyzed individuals to precisely control external devices through alterations in nasal airflow. We hypothesized that FES self-triggering by sniffcontroller may allow for effective cough timing...
January 31, 2017: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/28161217/reduced-morbidity-with-minimally-invasive-distal-pancreatectomy-for-pancreatic-adenocarcinoma
#9
Anastasia Plotkin, Eugene P Ceppa, Ben L Zarzaur, Elizabeth M Kilbane, Taylor S Riall, Henry A Pitt
BACKGROUND: Minimally invasive distal pancreatectomy (MISDP) has been shown to be safe relative to open distal pancreatectomy (ODP). However, MISDP has been slow to adopt for pancreatic adenocarcinoma (PDAC). This study sought to compare outcomes following MISDP vs. ODP for PDAC. METHODS: Data were prospectively collected from 2011 to 2014 for DP by the American College of Surgeons-National Surgical Quality Improvement Program. Patients without PDAC on surgical pathology were excluded...
February 1, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28138960/high-glucose-alters-the-secretome-of-mechanically-stimulated-osteocyte-like-cells-affecting-osteoclast-precursor-recruitment-and-differentiation
#10
Marta Maycas, María Teresa Portolés, María Concepción Matesanz, Irene Buendía, Javier Linares, María José Feito, Daniel Arcos, María Vallet-Regí, Lilian Plotkin, Pedro Esbrit, Arancha R Gortázar
Diabetes mellitus (DM) induces bone deterioration, while mechanical stimulation promotes osteocyte-driven bone formation. We aimed to evaluate the interaction of acute exposure (24h) to high glucose (HG) with both the pro-survival effect conferred to osteocytic MLO-Y4 cells and osteoblastic MC3T3-E1 cells by mechanical stimulation and the interaction of these cells with osteoclast precursor RAW264.7 cells. We found that 24h of HG (25 mM) pre-exposure prevented both cell survival and ERK and β-catenin nuclear translocation upon mechanical stimulation by fluid flow (FF) (10 min) in both MLO-Y4 and MC3T3-E1 cells...
January 31, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28133811/complex-immune-correlates-of-protection-in-hiv-1-vaccine-efficacy-trials
#11
REVIEW
Georgia D Tomaras, Stanley A Plotkin
Development of an efficacious HIV-1 vaccine is a major priority for improving human health worldwide. Vaccine-mediated protection against human pathogens can be achieved through elicitation of protective innate, humoral, and cellular responses. Identification of specific immune responses responsible for pathogen protection enables vaccine development and provides insights into host defenses against pathogens and the immunological mechanisms that most effectively fight infection. Defining immunological correlates of transmission risk in preclinical and clinical HIV-1 vaccine trials has moved the HIV-1 vaccine development field forward and directed new candidate vaccine development...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28105274/design-synthesis-and-evaluation-of-novel-and-selective-g-protein-coupled-receptor-120-gpr120-spirocyclic-agonists
#12
Jason M Cox, Hong D Chu, Mariappan V Chelliah, John S Debenham, Keith Eagen, Ping Lan, Matthew Lombardo, Clare London, Michael A Plotkin, Unmesh Shah, Zhongxiang Sun, Henry M Vaccaro, Srikanth Venkatraman, Takao Suzuki, Nengxue Wang, Eric R Ashley, Alejandro Crespo, Maria Madeira, Dennis H Leung, Candice Alleyne, Aimie M Ogawa, Sarah Souza, Brande Thomas-Fowlkes, Jerry Di Salvo, Adam Weinglass, Melissa Kirkland, Michele Pachanski, Mary Ann Powles, Effie Tozzo, Taro E Akiyama, Feroze Ujjainwalla, James R Tata, Christopher J Sinz
Type 2 diabetes mellitus (T2DM) is an ever increasing worldwide epidemic, and the identification of safe and effective insulin sensitizers, absent of weight gain, has been a long-standing goal of diabetes research. G-protein coupled receptor 120 (GPR120) has recently emerged as a potential therapeutic target for treating T2DM. Natural occurring, and more recently, synthetic agonists have been associated with insulin sensitizing, anti-inflammatory, and fat metabolism effects. Herein we describe the design, synthesis, and evaluation of a novel spirocyclic GPR120 agonist series, which culminated in the discovery of potent and selective agonist 14...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28099066/new-vaccines-against-epidemic-infectious-diseases
#13
John-Arne Røttingen, Dimitrios Gouglas, Mark Feinberg, Stanley Plotkin, Krishnaswamy V Raghavan, Andrew Witty, Ruxandra Draghia-Akli, Paul Stoffels, Peter Piot
The vaccine-development response to the 2014 Ebola epidemic in West Africa, though a valiant effort, was too little, too late. Three vaccine candidates were tested successfully under challenging conditions. Governments and foundations mobilized funds quickly. Companies and research-and-development..
February 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28096061/connexin37-deficiency-alters-organic-bone-matrix-cortical-bone-geometry-and-increases-wnt-%C3%AE-catenin-signaling
#14
Rafael Pacheco-Costa, Jay R Kadakia, Emily G Atkinson, Joseph M Wallace, Lilian I Plotkin, Rejane D Reginato
Deletion of connexin (Cx) 37 in mice leads to increased cancellous bone mass due to defective osteoclast differentiation. Paradoxically; however, Cx37-deficient mice exhibit reduced cortical thickness accompanied by higher bone strength, suggesting a contribution of Cx37 to bone matrix composition. Thus, we investigated whether global deletion of Cx37 alters the composition of organic bone extracellular matrix. Five-month-old Cx37(-/-) mice exhibited increased marrow cavity area, and periosteal and endocortical bone surface resulting in higher total area in tibia compared to Cx37(+/+) control mice...
January 16, 2017: Bone
https://www.readbyqxmd.com/read/28078311/common-variant-rs356182-near-snca-defines-a-parkinson-s-disease-endophenotype
#15
Christine A Cooper, Nimansha Jain, Michael D Gallagher, Daniel Weintraub, Sharon X Xie, Yosef Berlyand, Alberto J Espay, Joseph Quinn, Karen L Edwards, Thomas Montine, Vivianna M Van Deerlin, John Trojanowski, Cyrus P Zabetian, Alice S Chen-Plotkin
OBJECTIVE: Parkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression. METHODS: We screened 10 SNPs, previously associated with PD risk, for association with tremor-dominant (TD) versus postural-instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi-site replication cohort of 559 PD patients...
January 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27984662/long-term-structural-and-biomass-dynamics-of-virgin-tsuga-canadensis-pinus-strobus-forests-after-hurricane-disturbance
#16
Anthony W D'Amato, David A Orwig, David R Foster, Audrey Barker Plotkin, Peter K Schoonmaker, Maggie R Wagner
The development of old-growth forests in northeastern North America has largely been within the context of gap-scale disturbances given the rarity of stand-replacing disturbances. Using the 10-ha old-growth Harvard Tract and its associated 90-year history of measurements, including detailed surveys in 1989 and 2009, we document the long-term structural and biomass development of an old-growth Tsuga canadensis-Pinus strobus forest in southern New Hampshire, USA following a stand-replacing hurricane in 1938. Measurements of aboveground biomass pools were integrated with data from second- and old-growth T...
December 16, 2016: Ecology
https://www.readbyqxmd.com/read/27909656/outcomes-of-demineralized-bone-matrix-enriched-with-concentrated-bone-marrow-aspirate-in-lumbar-fusion
#17
Remi M Ajiboye, Mark A Eckardt, Jason T Hamamoto, Benjamin Plotkin, Michael D Daubs, Jeffrey C Wang
BACKGROUND: Multiple studies have demonstrated that a significant amount of variability exists in various demineralized bone matrix (DBM) formulations, which casts doubts on its reliability in consistently promoting fusion. Bone marrow aspirate (BMA) is a cellular based graft that contains mesenchymal stem cells (MSCs) and growth factors can confer osteogenic and osteoinductive potential to DBM. The goal of this study was to describe the outcome of DBM enriched with concentrated BMA in patients undergoing combined lumbar interbody and posterolateral fusion...
2016: International Journal of Spine Surgery
https://www.readbyqxmd.com/read/27902447/a-unique-type-of-gsk-3-inhibitor-brings-new-opportunities-to-the-clinic
#18
Avital Licht-Murava, Rom Paz, Lilach Vaks, Limor Avrahami, Batya Plotkin, Miriam Eisenstein, Hagit Eldar-Finkelman
Development of protein kinase inhibitors is a focus of many drug discovery programs. A major problem, however, is the limited specificity of the commonly used adenosine triphosphate-competitive inhibitors and the weak inhibition of the more selective substrate-competitive inhibitors. Glycogen synthase kinase-3 (GSK-3) is a promising drug target for treating neurodegenerative disorders, including Alzheimer's disease (AD), but most GSK-3 inhibitors have not reached the clinic. We describe a new type of GSK-3 inhibitor, L807mts, that acts through a substrate-to-inhibitor conversion mechanism that occurs within the catalytic site of the enzyme...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27900643/first-use-of-patient-reported-outcomes-measurement-information-system-promis-measures-in-adults-with-neurofibromatosis
#19
Mojtaba Talaei-Khoei, Eric Riklin, Vanessa L Merker, Monica R Sheridan, Justin T Jordan, Scott R Plotkin, Ana-Maria Vranceanu
The patient reported outcomes measurement information system (PROMIS) provides clinicians and researchers access to reliable, validated measures of physical, mental, and social well-being. The use of PROMIS can facilitate comparisons among clinical subpopulations and with the U.S. general population. We report on the first study using PROMIS measures in patients with neurofibromatosis (NF). Eighty-six adult patients (mean age = 44; 55% female; 87% white; 50% NF1, 41% NF2 and 9% schwannomatosis) completed a battery of PROMIS computerized adaptive tests (CATs)...
November 29, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27898663/as-simple-as-possible-but-not-simpler-exploring-the-fidelity-of-coarse-grained-protein-models-for-simulated-force-spectroscopy
#20
Mona Habibi, Jörg Rottler, Steven S Plotkin
Mechanical unfolding of a single domain of loop-truncated superoxide dismutase protein has been simulated via force spectroscopy techniques with both all-atom (AA) models and several coarse-grained models having different levels of resolution: A Gō model containing all heavy atoms in the protein (HA-Gō), the associative memory, water mediated, structure and energy model (AWSEM) which has 3 interaction sites per amino acid, and a Gō model containing only one interaction site per amino acid at the Cα position (Cα-Gō)...
November 2016: PLoS Computational Biology
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