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https://www.readbyqxmd.com/read/29727686/the-post-gwas-era-from-association-to-function
#1
REVIEW
Michael D Gallagher, Alice S Chen-Plotkin
During the past 12 years, genome-wide association studies (GWASs) have uncovered thousands of genetic variants that influence risk for complex human traits and diseases. Yet functional studies aimed at delineating the causal genetic variants and biological mechanisms underlying the observed statistical associations with disease risk have lagged. In this review, we highlight key advances in the field of functional genomics that may facilitate the derivation of biological meaning post-GWAS. We highlight the evidence suggesting that causal variants underlying disease risk often function through regulatory effects on the expression of target genes and that these expression effects might be modest and cell-type specific...
May 3, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29725664/successful-use-of-continuous-vasodilator-infusion-to-treat-critical-vasospasm-threatening-a-distal-bypass
#2
Gregory A Magee, Anastasia Plotkin, Jeniann A Yi, Kathryn E Bowser, David P Kuwayama
Vasospasm immediately after lower extremity arterial bypass may represent an uncommon cause of early graft failure. We report a successful case of catheter-directed, intra-arterial continuous vasodilator infusion to salvage a bypass graft threatened by severe, refractory vasospasm after incomplete response to nicardipine, verapamil, and nitroglycerin boluses. A continuous nitroglycerin infusion was administered for 24 hours, by which time the vasospasm resolved. At 12 months postoperatively, the graft remained patent with normal results of vascular laboratory studies...
March 2018: Journal of Vascular Surgery Cases and Innovative Techniques
https://www.readbyqxmd.com/read/29718326/mumps-a-pain-in-the-neck
#3
Stanley A Plotkin
No abstract text is available yet for this article.
April 30, 2018: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/29717698/life-in-vaccine-science-a-conversation-with-stanley-plotkin-at-the-4th-conference-on-vaccines-in-dubrovnik-croatia-september-2017
#4
Sanjin Musa
No abstract text is available yet for this article.
April 2018: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29700597/cerebrospinal-fluid-neurogranin-concentration-in-neurodegeneration-relation-to-clinical-phenotypes-and-neuropathology
#5
Erik Portelius, Bob Olsson, Kina Höglund, Nicholas C Cullen, Hlin Kvartsberg, Ulf Andreasson, Henrik Zetterberg, Åsa Sandelius, Leslie M Shaw, Virginia M Y Lee, David J Irwin, Murray Grossman, Daniel Weintraub, Alice Chen-Plotkin, David A Wolk, Leo McCluskey, Lauren Elman, Jennifer McBride, Jon B Toledo, John Q Trojanowski, Kaj Blennow
Neurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF). The CSF concentration of Ng is increased in Alzheimer's disease dementia (ADD), and even in the pre-dementia stage. In this prospective study, we used an enzyme-linked immunosorbent assay that quantifies Ng in CSF to test the performance of Ng as a marker of synaptic function. In 915 patients, CSF Ng was evaluated across several different neurodegenerative diseases...
April 26, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29658199/the-added-value-of-the-lateral-chest-radiograph-for-diagnosing-community-acquired-pneumonia-in-the-pediatric-emergency-department
#6
Michalle Soudack, Semion Plotkin, Aviva Ben-Shlush, Lisa Raviv-Zilka, Jeffrey M Jacobson, Michael Benacon, Arie Augarten
BACKGROUND: Opinions differ as to the need of a lateral radiograph for diagnosing community acquired pneumonia in children referred to the emergency department. A lateral radiograph increases the ionizing radiation burden but at the same time may improve specificity and sensitivity in this population. OBJECTIVES: To determine the value of the frontal and lateral chest radiographs compared to frontal view stand-alone images for the management of children with suspected community acquired pneumonia seen in a pediatric emergency department...
January 2018: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/29649040/improvement-in-patient-reported-hearing-after-treatment-with-bevacizumab-in-people-with-neurofibromatosis-type-2
#7
Victoria Huang, Amanda L Bergner, Chris Halpin, Vanessa L Merker, Monica R Sheridan, Brigitte C Widemann, Jaishri O Blakeley, Scott R Plotkin
OBJECTIVE: Assess patient-reported outcomes (PRO) for hearing and tinnitus relative to clinical hearing assessment in people with neurofibromatosis 2 (NF2) associated hearing loss. STUDY DESIGN: Prospective, open label, phase-II clinical trial with PRO administered pre-, post-, and after treatment. SETTING: Three tertiary referral centers. PATIENTS: Fourteen patients with NF2, median age of 30 years (range, 14-79 yr) and progressive hearing loss (median baseline word recognition score, 60%; range, 13-82%)...
April 11, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29622379/vaccination-against-the-human-cytomegalovirus
#8
Stanley A Plotkin, Suresh B Boppana
The human cytomegalovirus (HCMV) is the most important infectious cause of congenital abnormalities and also of infectious complications of transplantation. The biology of the infection is complex and acquired immunity does not always prevent reinfection. Nevertheless, vaccine development is far advanced, with numerous candidate vaccines being tested, both live and inactivated. This article summarizes the status of the candidate vaccines.
April 2, 2018: Vaccine
https://www.readbyqxmd.com/read/29614860/a-rational-structured-epitope-defines-a-distinct-subclass-of-toxic-amyloid-beta-oligomers
#9
Judith Silverman, Ebrima Gibbs, Xubiao Peng, Kris Martens, Claudia Balducci, Jing Wang, Masoud Yousefi, Catherine M Cowan, Guillaume Lamour, Sarah Louadi, Yuxin Ban, Jerome Robert, Sophie Stukas, Gianluigi Forloni, Ging-Yuek R Hsiung, Steven S Plotkin, Cheryl L Wellington, Neil R Cashman
Oligomers of Amyloid-β (AβO) are deemed key in synaptotoxicity and amyloid seeding of Alzheimer's disease (AD). However, the heterogeneous and dynamic nature of AβO, and inadequate markers for AβO subtypes, have stymied effective AβO identification and therapeutic targeting in vivo. We identified an AβO-subclass epitope defined by differential solvent orientation of the lysine 28 sidechain in a constrained loop of serine-asparagine-lysine (cSNK), rarely displayed in molecular dynamics simulations of monomer and fibril ensembles...
April 4, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29604263/cerebrospinal-fluid-%C3%AE-synuclein-contributes-to-the-differential-diagnosis-of-alzheimer-s-disease
#10
Min Shi, Lu Tang, Jon B Toledo, Carmen Ginghina, Hua Wang, Patrick Aro, Poul H Jensen, Daniel Weintraub, Alice S Chen-Plotkin, David J Irwin, Murray Grossman, Leo McCluskey, Lauren B Elman, David A Wolk, Edward B Lee, Leslie M Shaw, John Q Trojanowski, Jing Zhang
INTRODUCTION: The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1-42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis. METHODS: CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases...
March 28, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29600244/extending-beyond-policy-reaching-unaids-three-90-s-in-malawi
#11
Zengani Chirwa, Florence Kayambo, Lolade Oseni, Marya Plotkin, Cyndi Hiner, Chimwemwe Chitsulo, Kelly Curran, Thokozani Kalua, Stacie C Stender
Malawi, like other countries with a generalized HIV epidemic, is striving to reach the ambitious targets set by UNAIDS known as the three 90's for testing, provision of antiretroviral therapy and viral suppression. Assisted by Malawi's progressive policies on HIV/AIDS, it appears possible that Malawi will attain these targets, but only by employing innovative program approaches to service delivery which help fill policy gaps. This article describes how a dedicated cadre of layperson testers and HIV-positive peers appears to have helped attain increases in HIV and viral load testing and retention in care in four districts in Malawi, and situates these innovations in a policy framework analysis...
2018: Frontiers in Public Health
https://www.readbyqxmd.com/read/29557854/cost-and-cost-effectiveness-of-a-demand-creation-intervention-to-increase-uptake-of-voluntary-medical-male-circumcision-in-tanzania-spending-more-to-spend-less
#12
Sergio Torres-Rueda, Mwita Wambura, Helen A Weiss, Marya Plotkin, Katharine Kripke, Joseph Chilongani, Hally Mahler, Evodius Kuringe, Maende Makokha, Augustino Hellar, Carl Schutte, Kokuhumbya J Kazaura, Daimon Simbeye, Gerry Mshana, Natasha Larke, Gissenge Lija, John Changalucha, Anna Vassall, Richard Hayes, Jonathan M Grund, Fern Terris-Prestholt
BACKGROUND: Although voluntary medical male circumcision (VMMC) reduces the risk of HIV acquisition, demand for services is lower among men in most at-risk age groups (ages 20-34 years). A randomised controlled trial was conducted to assess the effectiveness of locally-tailored demand creation activities (including mass media, community mobilisation and targeted service delivery) in increasing uptake of campaign-delivered VMMC among men aged 20-34 years. We conducted an economic evaluation to understand the intervention's cost and cost-effectiveness...
March 19, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29548054/neurofibromatosis-and-schwannomatosis
#13
Scott R Plotkin, Antje Wick
Neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis are a group of related classically inherited but often times sporadic tumor suppressor syndromes. Neuro-oncologists should recognize these syndromes, initiate necessary tests in patients with a clinical suspicion, and support genetic counseling of patients and families. In this review, clinical presentation, diagnostic criteria, day-to-day management including supportive care as well as updates on genetics, and experimental treatment strategies are discussed...
February 2018: Seminars in Neurology
https://www.readbyqxmd.com/read/29467305/csf-tau-and-%C3%AE-amyloid-predict-cerebral-synucleinopathy-in-autopsied-lewy-body-disorders
#14
David J Irwin, Sharon X Xie, David Coughlin, Naomi Nevler, Rizwan S Akhtar, Corey T McMillan, Edward B Lee, David A Wolk, Daniel Weintraub, Alice Chen-Plotkin, John E Duda, Meredith Spindler, Andrew Siderowf, Howard I Hurtig, Leslie M Shaw, Murray Grossman, John Q Trojanowski
OBJECTIVE: To test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD). METHODS: Patients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied. In LBD, neuropathologic criteria defined Lewy body α-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN - AD = 14). Ordinal pathology scores for tau, β-amyloid (Aβ), and SYN pathology were averaged across 7 cortical regions to obtain a global cerebral score for each pathology...
March 20, 2018: Neurology
https://www.readbyqxmd.com/read/29440379/targeting-the-cmet-pathway-augments-radiation-response-without-adverse-effect-on-hearing-in-nf2-schwannoma-models
#15
Yingchao Zhao, Pinan Liu, Na Zhang, Jie Chen, Lukas D Landegger, Limeng Wu, Fu Zhao, Yanxia Zhao, Yanling Zhang, Jing Zhang, Takeshi Fujita, Anat Stemmer-Rachamimov, Gino B Ferraro, Hao Liu, Alona Muzikansky, Scott R Plotkin, Konstantina M Stankovic, Rakesh K Jain, Lei Xu
Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth causes progressive hearing loss, and the standard treatment, including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allow hearing testing...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29429519/a-method-for-the-long-term-cultivation-of-mammalian-cells-in-the-absence-of-oxygen-characterization-of-cell-replication-hypoxia-inducible-factor-expression-and-reactive-oxygen-species-production
#16
Balbina J Plotkin, James W Davis, Luigi Strizzi, Peter Lee, Jayme Christoffersen-Cebi, Joan Kacmar, Orlando J Rivero, Norhan Elsayed, Nicholas Zanghi, Brent Ito, Ira M Sigar
The center of tumors, stem cell niches and mucosal surfaces all represent areas of the body that are reported to be anoxic. However, long-term study of anoxic cell physiology is hindered by the lack of a sustainable method permitting cell cultivation in the complete absence of oxygen. A novel methodology was developed that enabled anoxic cell cultivation (17d maximum time tested) and cell passage. In the absence of oxygen, cell morphology is significantly altered. All cells tested exhibited morphologic changes, i...
February 2018: Tissue & Cell
https://www.readbyqxmd.com/read/29414701/soft-vibrational-modes-predict-breaking-events-during-force-induced-protein-unfolding
#17
Mona Habibi, Steven S Plotkin, Jörg Rottler
We investigate the correlation between soft vibrational modes and unfolding events in simulated force spectroscopy of proteins. Unfolding trajectories are obtained from molecular dynamics simulations of a Gō model of a monomer of a mutant of superoxide dismutase 1 protein containing all heavy atoms in the protein, and a normal mode analysis is performed based on the anisotropic network model. We show that a softness map constructed from the superposition of the amplitudes of localized soft modes correlates with unfolding events at different stages of the unfolding process...
February 6, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29414560/the-relationship-between-structural-mri-fdg-pet-and-memory-in-temporal-lobe-epilepsy-preliminary-results
#18
Justus Berger, Michail Plotkin, Katharina Demin, Martin Holtkamp, Thomas Bengner
Structural and metabolic abnormalities of the temporal lobe are frequently found in temporal lobe epilepsy (TLE). In the present retrospective study, we investigated whether structural abnormalities evident in magnetic resonance imaging (MRI) and hypometabolism evident in [18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) independently influence verbal and nonverbal learning and delayed memory in patients with TLE. Sixty-eight patients with refractory unilateral TLE (35 left TLE, 33 right TLE) were divided into three groups: (1) no evidence of pathology in either MRI or FDG-PET studies (MRI-/PET-, n=15), (2) temporal FDG-PET determined hypometabolism with normal MRI findings (MRI-/PET+, n=21), and (3) evidence of temporal abnormalities in both MRI and FDG-PET studies (MRI+/PET+, n=32)...
March 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29414276/case-4-2018-a-newborn-with-thrombocytopenia-cataracts-and-hepatosplenomegaly
#19
Robert S Baltimore, Katherine Nimkin, Katherine A Sparger, Virginia M Pierce, Stanley A Plotkin
Presentation of Case. Dr. Madeleine I. Matthiesen (Medicine and Pediatrics): A newborn boy was transferred to the neonatal intensive care unit (ICU) of this hospital because of thrombocytopenia and abnormal results on an eye examination for red reflex and on a hearing screening. The patient was..
February 8, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29384852/pain-correlates-with-germline-mutation-in-schwannomatosis
#20
Justin T Jordan, Miriam J Smith, James A Walker, Serkan Erdin, Michael E Talkowski, Vanessa L Merker, Vijaya Ramesh, Wenli Cai, Gordon J Harris, Miriam A Bredella, Marlon Seijo, Alessandra Suuberg, James F Gusella, Scott R Plotkin
Schwannomatosis has been linked to germline mutations in the SMARCB1 and LZTR1 genes, and is frequently associated with pain.In a cohort study, we assessed the mutation status of 37 patients with clinically diagnosed schwannomatosis and compared to clinical data, whole body MRI (WBMRI), visual analog pain scale, and Short Form 36 (SF-36) bodily pain subscale.We identified a germline mutation in LZTR1 in 5 patients (13.5%) and SMARCB1 in 15 patients (40.5%), but found no germline mutation in 17 patients (45...
February 2018: Medicine (Baltimore)
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