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https://www.readbyqxmd.com/read/28913897/studying-the-progression-of-amyloid-pathology-and-its-therapy-using-translational-longitudinal-model-of-accumulation-and-distribution-of-amyloid-beta
#1
Tatiana Karelina, O Demin, Oleg Demin, Sridhar Duvvuri, Timothy Nicholas
Long term effects of amyloid targeted therapy can be studied using a mechanistic translational model of Aβ distribution and aggregation calibrated on published data in mouse and human species. AD pathology is modelled utilizing age-dependent pathological evolution for rate constants and several variants of explicit functions for Aβ toxicity influencing cognitive outcomes (Adas-cog). Preventive Aβ targeted therapies were simulated to minimize the Aβ difference from healthy physiological levels. Therapeutic targeted simulations provided similar predictions for mouse and human...
September 15, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28899969/tmem16a-ano1-inhibits-apoptosis-via-down-regulation-of-bim-expression
#2
Neal R Godse, Nayel I Khan, Zachary A Yochum, Roberto Gomez-Casal, Carolyn Kemp, Daniel J Shiwarski, Raja Seethala, Scott Kulich, Mukund Seshadri, Timothy F Burns, Umamaheswar Duvvuri
PURPOSE: TMEM16A is a calcium-activated chloride channel that is amplified in a variety of cancers, including 30% of head and neck squamous cell carcinomas (HNSCC), raising the possibility of an anti-apoptotic role in malignant cells. The present study investigated this using a multi-modal, translational investigation. EXPERIMENTAL DESIGN: Combination of 1) in vitro HNSCC cell culture experiments assessing cell viability, apoptotic activation, and protein expression 2) in vivo studies assessing similar outcomes, and 3) molecular and staining analysis of human HNSCC samples...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28715559/interferon-%C3%AE-treatment-of-human-laryngotracheal-stenosis-derived-fibroblasts
#3
Kevin Motz, Idris Samad, Linda X Yin, Michael K Murphy, Madhavi Duvvuri, Dacheng Ding, Alexander T Hillel
Importance: Laryngotracheal stenosis (LTS) is a fibroproliferative disorder of the glottis, subglottis, and trachea. In models of fibrosis from other organ systems, the CD4+ T-cell response has been shown to regulate extracellular matrix deposition. Specifically, helper T cell 2 (TH2) promotes fibrosis, whereas TH1 and associated cytokines have been shown to be antifibrotic. However, this antifibrotic effect of the TH1 response has not been demonstrated in LTS. Objective: To determine whether the TH1 cytokine interferon-γ inhibits the function of LTS-derived fibroblasts in vitro...
July 13, 2017: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28715148/lineage-specific-epitope-profiles-for-hpai-h5-pre-pandemic-vaccine-selection-and-evaluation
#4
Xueting Qiu, Venkata R Duvvuri, Jonathan B Gubbay, Richard J Webby, Ghazi Kayali, Justin Bahl
BACKGROUND: Multiple highly pathogenic avian influenza (HPAI) H5 viruses continue to co-circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation. OBJECTIVES: In this study, we aimed to predict and map the diversity of CD8+ T-cell epitopes among H5 hemagglutinin (HA) gene lineages to estimate CD8+ T-cell immunity in humans induced by vaccine candidates. METHODS: A dataset consisting of 1125 H5 HA sequences collected between 1996 and 2017 from avian and humans was assembled for phylogenetic and lineage-specific epitope analyses...
July 17, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28571112/a-translational-systems-pharmacology-model-for-a%C3%AE-kinetics-in-mouse-monkey-and-human
#5
Tatiana Karelina, Oleg Demin, Timothy Nicholas, Yasong Lu, Sridhar Duvvuri, Hugh A Barton
A mechanistic model of amyloid beta production, degradation and distribution has been constructed for mouse, monkey and human, calibrated and externally verified across multiple data sets. Simulations of single dose avagacestat treatment demonstrate that the Aβ42 brain inhibition may exceed that in CSF. The dose which achieves 50% CSF Aβ40 inhibition for humans (both healthy and with Alzheimer's disease (AD)) is about 1 mpk, one order of magnitude lower than for mouse (10 mpk), mainly because of differences in pharmacokinetics...
June 1, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28570011/effect-of-transcervical-arterial-ligation-on-the-severity-of-postoperative-hemorrhage-after-transoral-robotic-surgery
#6
Mark Kubik, Rajarsi Mandal, William Albergotti, Umamaheswar Duvvuri, Robert L Ferris, Seungwon Kim
BACKGROUND: The value of transcervical arterial ligation during transoral robotic surgery (TORS) as a measure to decrease postoperative bleeding incidence or severity is unclear. METHODS: A retrospective single institution study was performed to identify risk factors for hemorrhage after TORS for oropharyngeal squamous cell carcinoma (SCC). RESULTS: Overall, 13.2% of patients (35/265) experience postoperative hemorrhage. T classification, perioperative use of anticoagulants, surgeon experience >50 cases, and tumor subsite were not predictors of postoperative hemorrhage...
August 2017: Head & Neck
https://www.readbyqxmd.com/read/28524800/swelling-mechanism-of-urea-cross-linked-starch-lignin-films-in-water
#7
Ariyanti Sarwono, Zakaria Man, M Azmi Bustam, Duvvuri Subbarao, Alamin Idris, Nawshad Muhammad, Amir Sada Khan, Zahoor Ullah
Coating fertilizer particles with thin films is a possibility to control fertilizer release rates. It is observed that novel urea cross-linked starch-lignin composite thin films, prepared by solution casting, swell on coming into contact with water due to the increase in volume by water uptake by diffusion. The effect of lignin content, varied from 0% to 20% in steps of 5% at three different temperatures (25°C, 35°C and 45°C), on swelling of the film was investigated. By gravimetric analysis, the equilibrium water uptake and diffusion coefficient decrease with lignin content, indicating that the addition of lignin increases the hydrophobicity of the films...
June 7, 2017: Environmental Technology
https://www.readbyqxmd.com/read/28485188/quantification-of-inflammatory-markers-in-laryngotracheal-stenosis
#8
Kevin M Motz, Linda X Yin, Idris Samad, Dacheng Ding, Michael K Murphy, Madhavi Duvvuri, Alexander T Hillel
Objectives (1) Develop a novel method for serial assessment of gene and protein expression in laryngotracheal stenosis (LTS). (2) Assess cytokine expression and determine an immunophenotype in LTS. Study Design A matched comparison of endolaryngeal brush biopsy samples from laryngotracheal scar and normal airway. Setting Tertiary care hospital, 2015-2016. Methods Brush biopsy specimens of laryngotracheal scar and normal trachea were obtained from 17 patients with LTS at the time of operating room dilation and were used for protein and RNA extraction...
September 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28467606/a-prospective-evaluation-of-short-term-dysphagia-after-transoral-robotic-surgery-for-squamous-cell-carcinoma-of-the-oropharynx
#9
William G Albergotti, Jessica Jordan, Keely Anthony, Shira Abberbock, Tamara Wasserman-Wincko, Seungwon Kim, Robert L Ferris, Umamaheswar Duvvuri
BACKGROUND: Transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) has been associated with improved long-term dysphagia symptomatology compared with chemoradiation. Dysphagia in the perioperative period has been inadequately characterized. The objective of this study was to characterize short-term swallowing outcomes after TORS for OPSCC. METHODS: Patients undergoing TORS for OPSCC were enrolled prospectively. The Eating Assessment Tool 10 (EAT-10) was used as a measure of swallowing dysfunction (score >2) and was administered on postoperative day (POD) 1, 7, and 30...
August 15, 2017: Cancer
https://www.readbyqxmd.com/read/28394767/concurrent-chemoradiotherapy-in-the-adjuvant-treatment-of-high-risk-primary-salivary-gland-malignancies
#10
Brian J Gebhardt, James P Ohr, Robert L Ferris, Umamaheswar Duvvuri, Seungwon Kim, Jonas T Johnson, Dwight E Heron, David A Clump
OBJECTIVES: Adjuvant radiation therapy (RT) is indicated for patients with salivary gland malignancies with risk factors for recurrence following resection. We analyzed patients treated with adjuvant RT with or without concurrent chemotherapy to determine the impact of prognostic and treatment factors. MATERIALS AND METHODS: Retrospective analysis was performed of 128 patients treated with surgical resection followed by intensity-modulated radiotherapy. In total, 31 (24...
April 7, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28383396/role-of-endoscopic-esophageal-dilation-in-managing-eosinophilic-esophagitis-a-systematic-review-and-meta-analysis
#11
REVIEW
Harsha Moole, Kavitha Jacob, Abhiram Duvvuri, Vishnu Moole, Sowmya Dharmapuri, Raghuveer Boddireddy, Achuta Uppu, Srinivas R Puli
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder of the esophagus characterized by mucosal eosinophilic infiltration. Topical glucocorticoids are considered standard line of treatment, whereas endoscopic dilations are performed for patients presenting with treatment-resistant disease or manifestations of dysphagia and/or food impactions. Efficacy and safety of esophageal dilation in these patients are currently unclear. AIMS: Primary outcomes were to evaluate the efficacy, adverse events, and mortality rates of endoscopic esophageal dilation in patients with EoE...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28352657/randomized-placebo-controlled-window-trial-of-egfr-src-or-combined-blockade-in-head-and-neck-cancer
#12
Julie E Bauman, Umamaheswar Duvvuri, William E Gooding, Tanya J Rath, Neil D Gross, John Song, Antonio Jimeno, Wendell G Yarbrough, Faye M Johnson, Lin Wang, Simion Chiosea, Malabika Sen, Jason Kass, Jonas T Johnson, Robert L Ferris, Seungwon Kim, Fred R Hirsch, Kimberly Ellison, John T Flaherty, Gordon B Mills, Jennifer R Grandis
BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II-IVa HNSCC were randomized to 7-21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28349784/fibroblasts-in-hypoxic-conditions-mimic-laryngotracheal-stenosis
#13
COMPARATIVE STUDY
Linda X Yin, Kevin M Motz, Idris Samad, Madhavi Duvvuri, Michael Murphy, Dacheng Ding, Alexander T Hillel
Objective To elucidate the role of hypoxia and inflammatory pathways in the pathogenesis of iatrogenic laryngotracheal stenosis (iLTS). Study Design (1) Examination of mucosal surface gene expression in human iLTS. (2) In vitro comparison of normal and scar laryngotracheal fibroblasts under normoxic and hypoxic conditions. Setting Tertiary care hospital in a research university (2012-2016). Subjects and Methods Brush biopsies were obtained from normal laryngotracheal tissue and scar in iLTS patients; gene expression was compared...
May 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28298902/global-distribution-and-evolutionary-history-of-enterovirus-d68-with-emphasis-on-the-2014-outbreak-in-ontario-canada
#14
Alireza Eshaghi, Venkata R Duvvuri, Sandra Isabel, Philip Banh, Aimin Li, Adriana Peci, Samir N Patel, Jonathan B Gubbay
Despite its first appearance in 1962, human enterovirus D68 (EV-D68) has been recognized as an emerging respiratory pathogen in the last decade when it caused outbreaks and clusters in several countries including Japan, the Philippines, and the Netherlands. The most recent and largest outbreak of EV-D68 associated with severe respiratory illness took place in North America between August 2014 and January 2015. Between September 1 and October 31 2014, EV-D68 infection was laboratory confirmed among 153/907 (16...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28291261/modeling-anorexia-nervosa-transcriptional-insights-from-human-ipsc-derived-neurons
#15
P D Negraes, F R Cugola, R H Herai, C A Trujillo, A S Cristino, T Chailangkarn, A R Muotri, V Duvvuri
Anorexia nervosa (AN) is a complex and multifactorial disorder occurring predominantly in women. Despite having the highest mortality among psychiatric conditions, it still lacks robust and effective treatment. Disorders such as AN are most likely syndromes with multiple genetic contributions, however, genome-wide studies have been underpowered to reveal associations with this uncommon illness. Here, we generated induced pluripotent stem cells (iPSCs) from adolescent females with AN and unaffected controls...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28275308/success-of-photodynamic-therapy-in-palliating-patients-with-nonresectable-cholangiocarcinoma-a-systematic-review-and-meta-analysis
#16
REVIEW
Harsha Moole, Harsha Tathireddy, Sirish Dharmapuri, Vishnu Moole, Raghuveer Boddireddy, Pratyusha Yedama, Sowmya Dharmapuri, Achuta Uppu, Naveen Bondalapati, Abhiram Duvvuri
AIM: To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma. METHODS: Included studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I(2) statistic...
February 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28249654/transoral-robotic-surgery-for-management-of-cervical-unknown-primary-squamous-cell-carcinoma-updates-on-efficacy-surgical-technique-and-margin-status
#17
Mathew Geltzeiler, Sean Doerfler, Meghan Turner, William Greer Albergotti, Mark Kubik, Seungwon Kim, Robert Ferris, Umamaheswar Duvvuri
IMPORTANCE: Management of cervical unknown primary squamous cell carcinoma (CUP) has evolved with the introduction of transoral robotic surgery (TORS). OBJECTIVES: 1. To describe the efficacy of TORS lingual and palatine tonsillectomy in identifying the primary site of malignancy. 2. To explore how the extent of surgery affects diagnostic yield. 3. To report margin status of TORS resections. DESIGN, SETTING AND PARTICIPANTS: A retrospective, single-center cohort study utilizing a prospectively collected database of CUP patients in a high-volume tertiary referral center...
March 2017: Oral Oncology
https://www.readbyqxmd.com/read/28196200/assessment-of-surgical-learning-curves-in-transoral-robotic-surgery-for-squamous-cell-carcinoma-of-the-oropharynx
#18
William G Albergotti, William E Gooding, Mark W Kubik, Mathew Geltzeiler, Seungwon Kim, Umamaheswar Duvvuri, Robert L Ferris
Importance: Transoral robotic surgery (TORS) is increasingly employed as a treatment option for squamous cell carcinoma of the oropharynx (OPSCC). Measures of surgical learning curves are needed particularly as clinical trials using this technology continue to evolve. Objective: To assess learning curves for the oncologic TORS surgeon and to identify the number of cases needed to identify the learning phase. Design, Setting, and Participants: A retrospective review of all patients who underwent TORS for OPSCC at the University of Pittsburgh Medical Center between March 2010 and March 2016...
June 1, 2017: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28177558/tmem16a-ano1-suppression-improves-response-to-antibody-mediated-targeted-therapy-of-egfr-and-her2-erbb2
#19
Sucheta Kulkarni, Anke Bill, Neal R Godse, Nayel I Khan, Jason I Kass, Kevin Steehler, Carolyn Kemp, Kara Davis, Carol A Bertrand, Avani R Vyas, Douglas E Holt, Jennifer R Grandis, L Alex Gaither, Umamaheswar Duvvuri
TMEM16A, a Ca(2+) -activated Cl(-) channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl(-) channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl(-) channel inhibition...
June 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28167576/phase-relations-in-a-forced-turbulent-boundary-layer-implications-for-modelling-of-high-reynolds-number-wall-turbulence
#20
Subrahmanyam Duvvuri, Beverley McKeon
Phase relations between specific scales in a turbulent boundary layer are studied here by highlighting the associated nonlinear scale interactions in the flow. This is achieved through an experimental technique that allows for targeted forcing of the flow through the use of a dynamic wall perturbation. Two distinct large-scale modes with well-defined spatial and temporal wavenumbers were simultaneously forced in the boundary layer, and the resulting nonlinear response from their direct interactions was isolated from the turbulence signal for the study...
March 13, 2017: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
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