Digital Commons Network^™

Altered Lysosomal Proteins In Neural-Derived Plasma Exosomes In Preclinical Alzheimer Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin L. Abner, Ronald C. Petersen, Bruce L. Miller, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy.

METHODS: Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker.

RESULTS: Mean exosomal levels of cathepsin D, lysosome-associated membrane …

Recessive Mutations In Polr1c Cause A Leukodystrophy By Impairing Biogenesis Of Rna Polymerase Iii., Isabelle Thiffault, Nicole I Wolf, Diane Forget, Kether Guerrero, Luan T. Tran, Karine Choquet, Mathieu Lavallée-Adam, Christian Poitras, Bernard Brais, Grace Yoon, Laszlo Sztriha, Richard I. Webster, Dagmar Timmann, Bart P. Van De Warrenburg, Jürgen Seeger, Alíz Zimmermann, Adrienn Máté, Cyril Goizet, Eva Fung, Marjo S. Van Der Knaap, Sébastien Fribourg, Adeline Vanderver, Cas Simons, Ryan J. Taft, John R. Yates, Benoit Coulombe, Geneviève Bernard

Manuscripts, Articles, Book Chapters and Other Papers

A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first …

A Randomized Controlled Trial Of Exercise In Spinal And Bulbar Muscular Atrophy., Joseph A Shrader, Ilona Kats, Angela Kokkinis, Cris Zampieri, Ellen Levy, Galen O Joe, Joshua G. Woolstenhulme, Bart E Drinkard, Michaele R Smith, Willie Ching, Laboni Ghosh, Derrick Fox, Sungyoung Auh, Alice B Schindler, Kenneth H Fischbeck, Christopher Grunseich

Physical Therapy and Health Care Sciences Faculty Publications

OBJECTIVE: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA).

METHODS: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up …

Fetal, Neonatal, Infant, And Child International Growth Standards: An Unprecedented Opportunity For An Integrated Approach To Assess Growth And Development., Cutberto Garza

Global Health Faculty Publications

The recent publication of fetal growth and gestational age-specific growth standards by the International Fetal and Newborn Growth Consortium for the 21st Century Project and the previous publication by the WHO of infant and young child growth standards based on the WHO Multicentre Growth Reference Study enable evaluations of growth from ∼9 wk gestation to 5 y. The most important features of these projects are the prescriptive approach used for subject selection and the rigorous testing of the assertion that growth is very similar among geographically and ethnically diverse nonisolated populations when health, nutrition, and other care needs are met …

Hand Use Predicts The Structure Of Representations In Sensorimotor Cortex., Naveed Ejaz, Masashi Hamada, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Fine finger movements are controlled by the population activity of neurons in the hand area of primary motor cortex. Experiments using microstimulation and single-neuron electrophysiology suggest that this area represents coordinated multi-joint, rather than single-finger movements. However, the principle by which these representations are organized remains unclear. We analyzed activity patterns during individuated finger movements using functional magnetic resonance imaging (fMRI). Although the spatial layout of finger-specific activity patterns was variable across participants, the relative similarity between any pair of activity patterns was well preserved. This invariant organization was better explained by the correlation structure of everyday hand movements than …

Changes In Visual And Sensory-Motor Resting-State Functional Connectivity Support Motor Learning By Observing., Heather R Mcgregor, Paul L Gribble

Brain and Mind Institute Researchers' Publications

Motor learning occurs not only through direct first-hand experience but also through observation (Mattar AA, Gribble PL. Neuron 46: 153-160, 2005). When observing the actions of others, we activate many of the same brain regions involved in performing those actions ourselves (Malfait N, Valyear KF, Culham JC, Anton JL, Brown LE, Gribble PL. J Cogn Neurosci 22: 1493-1503, 2010). Links between neural systems for vision and action have been reported in neurophysiological (Strafella AP, Paus T. Neuroreport 11: 2289-2292, 2000; Watkins KE, Strafella AP, Paus T. Neuropsychologia 41: 989-994, 2003), brain imaging (Buccino G, Binkofski F, Fink GR, Fadiga L, …

Set Theory: Nephrology ∩ Urology, Jerry Yee

Nephrology Articles

No abstract provided.

Clinical Utility Of Lactate Dehydrogenase In Determining The Severity Of Hemolysis In Sickle Cell Anemia., Samir K. Ballas

Cardeza Foundation for Hematologic Research

No abstract provided.

Paracrine Effect Of Nrg1 And Hgf Drives Resistance To Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Mizue Terai, Ken Kageyama, Shinji Ozaki, Peter Mccue, Takami Sato, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Uveal melanoma patients with metastatic disease usually die within one year, emphasizing an urgent need to develop new treatment strategies for this cancer. MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic uveal melanoma patients. In this study, we screened for growth factors that elicited resistance in newly characterized metastatic uveal melanoma cell lines to clinical-grade MEK inhibitors, trametinib and selumetinib. We show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1 and sustained HGF-mediated activation of AKT. Individually targeting ERBB3 and …

Beta-Blocker Use And 30-Day All-Cause Readmission In Medicare Beneficiaries With Systolic Heart Failure, Vikas Bhatia, Kumar Sanam, Taimoor Hashim, Prakash Deedwania, Wilbert S. Aronow, Ross Fletcher, Ali Ahmed

NYMC Faculty Publications

BACKGROUND: Beta-blockers improve outcomes in patients with systolic heart failure. However, it is unknown whether their initial negative inotropic effect may increase 30-day all-cause readmission, a target outcome for Medicare cost reduction and financial penalty for hospitals under the Affordable Care Act.

METHODS: Of the 3067 Medicare beneficiaries discharged alive from 106 Alabama hospitals (1998-2001) with a primary discharge diagnosis of heart failure and ejection fraction

RESULTS: Beta-blocker use was not associated with 30-day all-cause readmission (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.64-1.18) or heart failure readmission (HR 0.95; 95% CI, 0.57-1.58), but was significantly associated with lower …

Can Dentistry Have Two Contracts With The Public?, David A. Nash

Oral Health Science Faculty Publications

The social contract is an implicit agreement between parts of society and society as a whole. Since the Middle Ages, the learned professions, recently including dentistry, have had a covenantal relationship with the public based on trust, exchanging monopoly privileges for benefiting the public good. Unlike commercial trade in commodities, professional relationships are grounded in ensuring an adequate level of oral health to all. A second contract is emerging where dentists relate to society as business operators, exchanging commodity services for a price. Recent actions by the Federal Trade Commission and the U.S. Supreme Court make it unlikely that dentistry …

Placental Dna Methylation Related To Both Infant Toenail Mercury And Adverse Neurobehavioral Outcomes, Jennifer Zeynab Joukhadar Maccani, Devin C. Koestler, Barry Lester, E Andres Houseman, David A. Armstrong, Karl T. Kelsey, Carmen J. Marsit

Dartmouth Scholarship

Background:

Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly.

Objectives:

We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes.

Methods:

The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina’s Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU …

Influence Of Linker Length And Composition On Enzymatic Activity And Ribosomal Binding Of Neomycin Dimers, Derrick Watkins, Sunil Kumar, Keith D. Green, Dev P. Arya, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by …

Novel Use Of Glidescope Indirect Laryngoscopy For Insertion Of A Minnesota Tube For Variceal Bleeding, Adam B. Schlichting, Jayna Gardner-Gray, Gina Hurst

Emergency Medicine Articles

BACKGROUND: With improvements in endoscopic and interventional radiologic therapies, insertion of gastroesophageal balloon tamponade catheters, commonly known as Sengstaken-Blakemore or Minnesota tubes, is a rarely performed procedure for esophageal or gastric variceal bleeding. In small hospitals or freestanding emergency departments, endoscopic or interventional radiology (IR) therapies might not be available, so patients with exsanguinating variceal bleeding must be stabilized or temporized for transport to larger hospitals. Occasionally, tamponade devices are necessary as a rescue therapy for failed endoscopic or IR therapies or can be used as definitive therapy in select cases. In addition to being rarely performed, there are multiple …

Vascular Regulation Via Kir Channels And Na+ /K+-Atpase, Anne R. Crecelius, Frank A. Dinenno

Health and Sport Science Faculty Publications

Despite the longstanding knowledge that blood flow increases in proportion to metabolic activity of skeletal muscle, the underlying mechanisms that govern this response have only recently been identified.¹ Given the role of endothelial cells in mediating exercise hyperemia,² interest has been focused on endothelium-derived vasodilation occurring via the synthesis of nitric oxide (NO) and vasodilating prostaglandins (PGs; i.e. prostacyclin) or endothelium- derived hyperpolarization. A number of studies performed in humans have established a minimal-to-modest role for NO and PGs during mild- and moderate- intensity exercise. In animal preparations, prevention of hyperpolarization attenuates contraction-induced hyperemia; however, performing similar studies …

Treatment Of Severe Metabolic Alkalosis With Continuous Renal Replacement Therapy: Bicarbonate Kinetic Equations Of Clinical Value, Lenar Yessayan, Jerry Yee, Stan Frinak, David Kwon, Balazs Szamosfalvi

Nephrology Articles

Concomitant severe metabolic alkalosis, hypernatremia, and kidney failure pose a therapeutic challenge. Hemodialysis to correct azotemia and abnormal electrolytes results in rapid correction of serum sodium, bicarbonate, and urea but presents a risk for dialysis disequilibrium and brain edema. We describe a patient with Zollinger-Ellison syndrome with persistent encephalopathy, severe metabolic alkalosis (highest bicarbonate 81 mEq/L), hypernatremia (sodium 157 mEq/L), and kidney failure despite 30 hours of intravenous crystalloids and proton pump inhibitor. We used continuous renal replacement therapy (RRT) with delivered hourly urea clearance of ~3 L/hour (24 hour sustained low efficiency dialysis with regional citrate anticoagulation protocol at …

Long-Term Oncological Outcomes Of A Phase Ii Trial Of Neoadjuvant Chemohormonal Therapy Followed By Radical Prostatectomy For Patients With Clinically Localised, High-Risk Prostate Cancer., Jonathan L. Silberstein, Stephen A. Poon, Daniel D. Sjoberg, Alexandra C. Maschino, Andrew J. Vickers, Aaron Bernie, Badrinath R. Konety, William Kevin Kelly, James A. Eastham

Department of Urology Faculty Papers

OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer.

PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only.

RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. …

Risk Analysis Of Prostate Cancer In Practical, A Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci., Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel Fitzgerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton

Department of Medical Oncology Faculty Papers

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.

RESULTS: The prostate cancer risk for men in the top 1% of the …

Hla-Dqa1 And Plcg2 Are Candidate Risk Loci For Childhood-Onset Steroid-Sensitive Nephrotic Syndrome., Rasheed A. Gbadegesin, Adebowale Adeyemo, Nicholas J A Webb, Larry A A. Greenbaum, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arundhati Kale, Debbie Gipson, Tarak Srivastava, Jen-Jar Lin, Deepa Chand, Tracy E. Hunley, Patrick D. Brophy, Arvind Bagga, Aditi Sinha, Michelle N. Rheault, Joanna Ghali, Kathy Nicholls, Elizabeth Abraham, Halima S. Janjua, Abiodun Omoloja, Gina-Marie Barletta, Yi Cai, David D. Milford, Catherine O'Brien, Atif Awan, Vladimir Belostotsky, William E. Smoyer, Alison Homstad, Gentzon Hall, Guanghong Wu, Shashi Nagaraj, Delbert Wigfall, John Foreman, Michelle P. Winn, Mid-West Pediatric Nephrology Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were …

Obesity Early In Adulthood Increases Risk But Does Not Affect Outcomes Of Hepatocellular Carcinoma, Manal M. Hassan, Reham Abdel-Wahab, Ahmed Kaseb, Ahmed Shalaby, Alexandria Phan, Hashem El-Serag, Ernest Hawk, Jeff Morris, Kanwal Pratap Singh Raghav, Ju-Seog Lee, Jean-Nicolas Vauthey, Gehan Bortus, Harrys Torres, Christopher Amos, Robert Wolff, Donghui Li

Dartmouth Scholarship

Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to accurately determine body mass index (BMI), and many factors contribute to the development of HCC. We performed a case–control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC.

A Comparative Effectiveness Meta-Analysis Of Drugs For The Prophylaxis Of Migraine Headache, Jeffrey L. Jackson, Elizabeth Cogbill, Rafael Santana-Davila, Christina Eldredge, William Collier, Andrew Gradall, Neha Sehgal, Jessica Kuester

School of Information Faculty Publications

OBJECTIVE: To compare the effectiveness and side effects of migraine prophylactic medications.

DESIGN: We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models.

DATA SOURCES: PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration.

RESULTS: Placebo controlled trials included alpha blockers (n = 9), angiotensin converting enzyme inhibitors …

Development And Implementation Of A Clinical Pathway Approach To Simulation-Based Training For Foregut Surgery., Kiyoyuki W. Miyasaka, Joseph Buchholz, Denise Lamarra, Giorgos C. Karakousis, Rajesh Aggarwal

Student Papers, Posters & Projects

INTRODUCTION: Contemporary demands on resident education call for integration of simulation. We designed and implemented a simulation-based curriculum for Post Graduate Year 1 surgery residents to teach technical and nontechnical skills within a clinical pathway approach for a foregut surgery patient, from outpatient visit through surgery and postoperative follow-up.

METHODS: The 3-day curriculum for groups of 6 residents comprises a combination of standardized patient encounters, didactic sessions, and hands-on training. The curriculum is underpinned by a summative simulation "pathway" repeated on days 1 and 3. The "pathway" is a series of simulated preoperative, intraoperative, and postoperative encounters in following up …

Tooth Retrospective Dosimetry Using Electron Paramagnetic Resonance: Influence Of Irradiated Dental Composites, Céline M. Desmet, Andrej Djurkin, Ana Maria Dos Santos-Goncalvez, Ruhong Dong, Maciej M. Kmiec, Kyo Kobayashi, Kevin Rychert, Sébastien Beun, Julian G. Leprince, Gaëtane Leloup, Philippe Levêque, Bernard Gallez

Dartmouth Scholarship

In the aftermath of a major radiological accident, the medical management of overexposed individuals will rely on the determination of the dose of ionizing radiations absorbed by the victims. Because people in the general population do not possess conventional dosimeters, after the fact dose reconstruction methods are needed. Free radicals are induced by radiations in the tooth enamel of victims, in direct proportion to dose, and can be quantified using Electron Paramagnetic Resonance (EPR) spectrometry, a technique that was demonstrated to be very appropriate for mass triage. The presence of dimethacrylate based restorations on teeth can interfere with the dosimetric …

Procollagen C-Endopeptidase Enhancer Protein 2 (Pcpe2) Reduces Atherosclerosis In Mice By Enhancing Scavenger Receptor Class B1 (Sr-Bi)-Mediated High-Density Lipoprotein (Hdl)-Cholesteryl Ester Uptake, Ricquita D. Pollard, Christopher N. Blesso, Manal Zabalawi, Brian Fulp, Mark Gerelus, Xuewei Zhu, Erica W. Lyons, Nebil Nuradin, Omar L. Francone, Xiang-An Li, Daisy Sahoo, Michael J. Thomas, Mary G. Sorci-Thomas

Pediatrics Faculty Publications

Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr^-/-, PCPE2^-/- mice, which had elevated HDL levels compared with LDLr^-/- mice with similar …

Chromatin To Clinic: The Molecular Rationale For Parp1 Inhibitor Function., Felix Y. Feng, Johann S. De Bono, Mark A. Rubin, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have potential clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed.

Links Between Anr And Quorum Sensing In Pseudomonas Aeruginosa Biofilms, John H. Hammond, Emily F. Dolben, T. Jarrod Smith, Sabin Bhuju, Deborah Hogan

Dartmouth Scholarship

In Pseudomonas aeruginosa, the transcription factor Anr controls the cellular response to low oxygen or anoxia. Anr activity is high in oxygen-limited environments, including biofilms and populations associated with chronic infections, and Anr is necessary for persistence in a model of pulmonary infection. In this study, we characterized the Anr regulon in biofilm-grown cells at 1% oxygen in the laboratory strain PAO1 and in a quorum sensing (QS)-deficient clinical isolate, J215. As expected, transcripts related to denitrification, arginine fermentation, high-affinity cytochrome oxidases, and CupA fimbriae were lower in the Δanr derivatives. In addition, we observed that transcripts associated with quorum …

Network-Based Stratification Analysis Of 13 Major Cancer Types Using Mutations In Panels Of Cancer Genes., Xue Zhong, Hushan Yang, Shuyang Zhao, Yu Shyr, Bingshan Li

Department of Medical Oncology Faculty Papers

BACKGROUND: Cancers are complex diseases with heterogeneous genetic causes and clinical outcomes. It is critical to classify patients into subtypes and associate the subtypes with clinical outcomes for better prognosis and treatment. Large-scale studies have comprehensively identified somatic mutations across multiple tumor types, providing rich datasets for classifying patients based on genomic mutations. One challenge associated with this task is that mutations are rarely shared across patients. Network-based stratification (NBS) approaches have been proposed to overcome this challenge and used to classify tumors based on exome-level mutations. In routine research and clinical applications, however, usually only a small panel of …

Whole Genome Capture Of Vector-Borne Pathogens From Mixed Dna Samples: A Case Study Of Borrelia Burgdorferi, Giovanna Carpi, Katharine S. Walter, Stephen J. Bent, Anne Gatewood Hoen, Maria Diuk-Wasser, Adalgisa Caccone

Dartmouth Scholarship

Background:

Rapid and accurate retrieval of whole genome sequences of human pathogens from disease vectors or animal reservoirs will enable fine-resolution studies of pathogen epidemiological and evolutionary dynamics. However, next generation sequencing technologies have not yet been fully harnessed for the study of vector-borne and zoonotic pathogens, due to the difficulty of obtaining high-quality pathogen sequence data directly from field specimens with a high ratio of host to pathogen DNA.

Results:

We addressed this challenge by using custom probes for multiplexed hybrid capture to enrich for and sequence 30 Borrelia burgdorferi genomes from field samples of its arthropod vector. Hybrid …

Parametric Mapping Of Contrasted Ovarian Transvaginal Sonography., Katrina Korhonen, Ryan Moore, Andrej Lyshchik, Arthur C. Fleischer

Department of Radiology Faculty Papers

The purpose of this study was to assess the accuracy of parametric analysis of transvaginal contrast-enhanced ultrasound (TV-CEUS) for distinguishing benign versus malignant ovarian masses. A total of 48 ovarian masses (37 benign and 11 borderline/malignant) were examined with TV-CEUS (Definity; Lantheus, North Billerica, MA; Philips iU22; Philips Medical Systems, Bothell, WA). Parametric images were created offline with a quantification software (Bracco Suisse SA, Geneva, Switzerland) with map color scales adjusted such that abnormal hemodynamics were represented by the color red and the presence of any red color could be used to differentiate benign and malignant tumors. Using these map …

Bilateral Papillitis And Unilateral Focal Chorioretinitis As The Presenting Features Of Syphilis., Christy E. Benson, Mohamed K. Soliman, Alexander Knezevic, Daisy D. Xu, Quan D. Nguyen, Diana V V. Do

Journal Articles: Ophthalmology

BACKGROUND: Syphilis is a multisystem bacterial infection caused by Treponema pallidum. The incidence of infection in the United States has risen by more than 75% since the year 2000, when it was at a low of 2.1 per 100,000 people. Ocular involvement may occur in any stage of infection and may present in a variety of ways, with posterior uveitis being the most common manifestation. We report a case of ocular syphilis infection with an unusual presentation of bilateral non-granulomatous panuveitis with papillitis and unilateral focal chorioretinitis.

FINDINGS: This is a retrospective case report with literature review. A 39-year-old Caucasian …