Digital Commons Network^™

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From The Children's Oncology Group., Robert B. Gerbing, Todd A. Alonzo, Lillian Sung, Alan S. Gamis, Soheil Meshinchi, Sharon E. Plon, Alison A. Bertuch, Maria M. Gramatges

Manuscripts, Articles, Book Chapters and Other Papers

Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment-related mortality. Telomeres, the repetitive DNA-protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children's Oncology Group study AAML0531, and included those with (n = 53) and without (n …

A Pressure Ulcer And Fall Rate Quality Composite Index For Acute Care Units: A Measure Development Study., Diane K. Boyle, Ananda Jayawardhana, Mary E. Burman, Nancy E. Dunton, Vincent S. Staggs, Sandra Bergquist-Beringer, Byron J. Gajewski

Manuscripts, Articles, Book Chapters and Other Papers

Background: Composite indices are single measures that combine the strengths of two or more individual measures and provide broader, easy-to-use measures for evaluation of provider performance and comparisons across units and hospitals to support quality improvement.

Objective: The study objective was to develop a unit-level inpatient composite nursing care quality performance index-the Pressure Ulcer and Fall Rate Quality Composite Index.

Design: Two-phase measure development study.

Settings: 5144 patient care units in 857 United States hospitals participating in the National Database of Nursing Quality Indictors® during the year 2013.

Methods: The Pressure Ulcer and Fall Rate Quality Composite Index was developed …

Medical Center Staff Attitudes About Spanking., Elizabeth T. Gershoff, Sarah A. Font, Catherine A. Taylor, Rebecca H. Foster, Ann Budzak Garza, Denyse Olson-Dorff, Amy Terreros, Monica Nielsen-Parker, Lisa Spector

Manuscripts, Articles, Book Chapters and Other Papers

Several medical professional organizations, including the American Academy of Pediatrics, recommend that parents avoid hitting children for disciplinary purposes (e.g., spanking) and that medical professionals advise parents to use alternative methods. The extent to which medical professionals continue to endorse spanking is unknown. This study is the first to examine attitudes about spanking among staff throughout medical settings, including non-direct care staff. A total of 2580 staff at a large general medical center and 733 staff at a children's hospital completed an online survey; respondents were roughly divided between staff who provide direct care to patients (e.g., physicians, nurses) and …

Racial Differences In Renal Replacement Therapy Initiation Among Children With A Nonglomerular Cause Of Chronic Kidney Disease., Derek K. Ng, Marva Moxey-Mims, Bradley A. Warady, Susan L. Furth, Alvaro Muñoz

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: African American (AA) adults with chronic kidney disease (CKD) have a faster progression to end-stage renal disease and are less likely to receive a kidney transplant. It is unclear whether AA children experience renal replacement therapy (RRT) for end-stage renal disease sooner than non-AA children after accounting for socioeconomic status (SES).

METHODS: Among children with nonglomerular CKD in the Chronic Kidney Disease in Children study, we investigated time to RRT (i.e., first dialysis or transplant) after CKD onset using parametric survival models and accounted for SES differences by inverse probability weights.

RESULTS: Of 110 AA and 493 non-AA children …

Differential Item Functioning In The Patient Reported Outcomes Measurement Information System Pediatric Short Forms In A Sample Of Children And Adolescents With Cerebral Palsy., Wendy J. Coster, Pengsheng Ni, Mary D. Slavin, Pamela A. Kisala, Ratna Nandakumar, Mary Jane Mulcahey, David S. Tulsky, Alan M. Jette

Department of Occupational Therapy Faculty Papers

AIM: The present study examined the Patient Reported Outcomes Measurement Information System (PROMIS) Mobility, Fatigue, and Pain Interference Short Forms (SFs) in children and adolescents with cerebral palsy (CP) for the presence of differential item functioning (DIF) relative to the original calibration sample.

METHOD: Using the Graded Response Model we compared item parameter estimates generated from a sample of 303 children and adolescents with CP (175 males, 128 females; mean age 15y 5mo) to parameter estimates from the PROMIS calibration sample, which served as the reference group. DIF was assessed in a two-step process using the item response theory-likelihood ratio-differential …

Should Family Presence Be Allowed During Cardiopulmonary Resuscitation?, Karen J. Brasel, John W. Entwistle Iii, Md, Phd, Robert M. Sade

Department of Surgery Faculty Papers

No abstract provided.

Bleeding With Direct Oral Anticoagulants Vs Warfarin: Clinical Experience., John Eikelboom, Geno J. Merli

Department of Surgery Faculty Papers

The risk of bleeding in the setting of anticoagulant therapy continues to be re-evaluated following the introduction of a new generation of direct oral anticoagulants (DOACs). Interruption of DOAC therapy and supportive care may be sufficient for the management of patients who present with mild or moderate bleeding, but in those with life-threatening bleeding, a specific reversal agent is desirable. We review the phase 3 clinical studies of dabigatran, rivaroxaban, apixaban, and edoxaban in patients with nonvalvular atrial fibrillation, in the context of bleeding risk and management.

Ambivalence: Prerequisite For Success In Motivational Interviewing With Adolescents?, Sarah W. Feldstein Ewing, Timothy R. Apodaca, Jacques Gaume

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND AIMS: The exploration and resolution of ambivalence play an essential role in motivational interviewing (MI) theory. However, most adolescent MI studies have not examined ambivalence as a contributor to behaviour change. This paper reviewed research findings on the role of ambivalence in the adolescent change process.

METHODS AND RESULTS: We undertook a narrative review of the published empirical and theoretical literature on ambivalence and mechanisms of change in MI for adolescents and found that current MI evaluations appear not to have access to reliable and valid measures of ambivalence in adolescence or neuroimaging methods to evaluate the mechanisms …

Contribution Of Tactile Dysfunction To Manual Motor Dysfunction In Type Ii Diabetes, Nereyda Ochoa, Gloria R Gogola, Stacey L Gorniak

Faculty, Staff and Student Publications

Introduction:

Changes in sensory and motor functions of the hand in Type II Diabetes (T2D) patients have been reported; there is speculation that these changes are driven by tactile dysfunction. The purpose of this study was to evaluate the effects of tactile feedback on manual function in T2D patients.

Methods:

T2D patients and healthy controls underwent median nerve blocks at the wrist and elbow. All participants underwent traditional timed motor evaluations, force dynamometry, laboratory-based kinetic evaluations, and sensory evaluation.

Results:

Tactile sensation in the T2D group at baseline was found to be equivalent to tactile function of the control group …

Introduction To Direct Oral Anticoagulants And Rationale For Specific Reversal Agents., Charles V. Pollack

Department of Emergency Medicine Faculty Papers

No abstract provided.

Evidence Supporting Idarucizumab For The Reversal Of Dabigatran., Charles V. Pollack

Department of Emergency Medicine Faculty Papers

Idarucizumab is a monoclonal antibody fragment specifically targeted to dabigatran. It has demonstrated prompt and durable reversal of the anticoagulant effects of dabigatran in animal studies and phase 1 studies of young, elderly, and renally impaired volunteers. Although elective invasive procedures and most bleeding complications in dabigatran-treated patients can be managed by temporarily stopping dabigatran therapy and using supportive measures, there are rare clinical situations that require urgent reversal of the anticoagulant effect of dabigatran. The effectiveness and safety of 5 g of intravenous idarucizumab is being investigated in a prospective, open-label, single-cohort study in patients with serious bleeding or …

Duration Of Posttraumatic Amnesia Predicts Neuropsychological And Global Outcome In Complicated Mild Traumatic Brain Injury., Tessa Hart, Thomas A. Novack, Nancy Temkin, Jason Barber, Sureyya S. Dikmen, Ramon Diaz-Arrastia, Joseph Ricker, Dale C. Hesdorffer, Jack Jallo, Nancy H. Hsu, Ross Zafonte

Department of Neurosurgery Faculty Papers

OBJECTIVES: Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI).

PARTICIPANTS: A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 15 in emergency department, with well-defined abnormalities on neuroimaging.

METHODS: Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months.

MEASURES: Glasgow Outcome Scale-Extended, California Verbal Learning Test II, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury.

RESULTS: Despite all having a …

New Findings, Classification And Long-Term Follow-Up Study Based On Mri Characterization Of Brainstem Encephalitis Induced By Enterovirus 71, Hongwu Zeng, Feiqiu Wen, Wenxian Huang, Yungen Gan, Weibin Zeng, Ranran Chen, Yanxia He, Yonker Wang, Zaiyi Liu, Changhong Liang, Kelvin K. L. Wong

Radiology Faculty Publications

Background To report the diversity of MRI features of brainstem encephalitis (BE) induced by Enterovirus 71. This is supported by implementation and testing of our new classification scheme in order to improve the diagnostic level on this specific disease.

Methods Neuroimaging of 91 pediatric patients who got EV71 related BE were hospitalized between March, 2010 to October, 2012, were analyzed retrospectively. All patients underwent pre- and post-contrast MRI scan. Thereafter, 31 patients were randomly called back for follow-up MRI study during December 2013 to August 2014. The MRI signal patterns of BE primary lesion were analyzed and classified according to …

Signaling Through Lrg1, Rho1 And Pkc1 Governs Candida Albicans Morphogenesis In Response To Diverse Cues, Jinglin L. Xie, Nora Grahl, Trevor Sless, Michelle Leach, Sang Hu Kim, Deborah Hogan

Dartmouth Scholarship

The capacity to transition between distinct morphological forms is a key virulence trait for diverse fungal pathogens. A poignant example of a leading opportunistic fungal pathogen of humans for which an environmentally responsive developmental program underpins virulence is Candida albicans. C. albicans mutants that are defective in the transition between yeast and filamentous forms typically have reduced virulence. Although many positive regulators of C. albicans filamentation have been defined, there are fewer negative regulators that have been implicated in repression of filamentation in the absence of inducing cues. To discover novel negative regulators of filamentation, we screened …

P70s6k1 (S6k1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I Γ Degradation And Cell Invasion, Naser Jafari, Qiaodan Zheng, Liqing Li, Wei Li, Lei Qi, Jianyong Xiao, Tianyan Gao, Cai Huang

Markey Cancer Center Faculty Publications

Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 …

The Skp1 Homologs Skr-1/2 Are Required For The Caenorhabditis Elegans Skn-1 Antioxidant/Detoxification Response Independently Of P38 Mapk., Cheng-Wei Wu, Andrew Deonarine, Aaron Przybysz, Kevin Strange, Keith P. Chloe

Molecular Biosciences Faculty Publications

SKN-1/Nrf are the primary antioxidant/detoxification response transcription factors in animals and they promote health and longevity in many contexts. SKN-1/Nrf are activated by a remarkably broad-range of natural and synthetic compounds and physiological conditions. Defining the signaling mechanisms that regulate SKN-1/Nrf activation provides insights into how cells coordinate responses to stress. Nrf2 in mammals is regulated in part by the redox sensor repressor protein named Keap1. In C. elegans, the p38 MAPK cascade in the intestine activates SKN-1 during oxidative stress by promoting its nuclear accumulation. Interestingly, we find variation in the kinetics of p38 MAPK activation and tissues with …

Plant Expression Of Cocaine Hydrolase-Fc Fusion Protein For Treatment Of Cocaine Abuse, Guojun Wang, Ting Zhang, Haifeng Huang, Shurong Hou, Xiabin Chen, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

BACKGROUND: A recently reported cocaine hydrolase (CocH3) fused with fragment crystallizable (Fc) region of human immunoglobulin G1, denoted as CocH3-Fc, is known as a promising therapeutic candidate for the treatment of cocaine overdose and addiction. A challenge for practical therapeutic use of this enzyme exists in the large-scale protein production and, therefore, it is interesting to identify a low-cost and feasible, sustainable source of CocH3-Fc production.

RESULTS: CocH3-Fc was transiently expressed in plant Nicotiana benthamiana leaves. The plant-expressed protein, denoted as pCocH3-Fc, was as active as that expressed in mammalian cells both in vitro and in vivo. However, compared to …

Pleckstrin Homology (Ph) Domain Leucine-Rich Repeat Protein Phosphatase Controls Cell Polarity By Negatively Regulating The Activity Of Atypical Protein Kinase C, Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao

Markey Cancer Center Faculty Publications

The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms. Altered expression of PHLPP1 or PHLPP2 disrupted polarization of Caco2 cells grown in 3D cell cultures …

Can Academic Medicine Lead The Way In The Refugee Crisis?, Amir A Afkhami

Psychiatry and Behavioral Sciences Faculty Publications

The world is currently in the midst of the largest refugee crisis since World War II, with the highest interval of mass displacement in recorded history according to the United Nations. The United States has pledged to maintain its position as one of the world's top resettlement countries in response to this crisis. These new immigrants will arrive with exceptional chronic and acute medical needs, including higher rates of behavioral health disorders. The author describes the health care challenges experienced by refugees seeking asylum in the United States and outlines the ways in which our health care system is currently …

Usage Of Swi (Susceptibility Weighted Imaging) Acquired At 7t For Qualitative Evaluation Of Temporal Lobe Epilepsy Patients With Histopathological And Clinical Correlation: An Initial Pilot Study., Benjamin Y M Kwan, Fateme Salehi, Pavlo Ohorodnyk, Donald H Lee, Jorge G Burneo, Seyed M Mirsattari, David Steven, Robert Hammond, Terry M Peters, Ali R Khan

Brain and Mind Institute Researchers' Publications

OBJECTIVES: Ultra high field MRI at 7T is able to provide much improved spatial and contrast resolution which may aid in the diagnosis of hippocampal abnormalities. This paper presents a preliminary experience on qualitative evaluation of 7T MRI in temporal lobe epilepsy patients with a focus on comparison to histopathology.

METHODS: 7T ultra high field MRI data, using T1-weighted, T2*-weighted and susceptibility-weighted images (SWI), were acquired for 13 patients with drug resistant temporal lobe epilepsy (TLE) during evaluation for potential epilepsy surgery. Qualitative evaluation of the imaging data for scan quality and presence of hippocampal and temporal lobe abnormalities were …

A Continuum Of Admixture In The Western Hemisphere Revealed By The African Diaspora Genome, Rasika A. Mathias, Margaret A. Taub, Christopher R. Gignoux, Wenqing Fu, Shaila Musharoff, Timothy D. O'Connor, Candelaria Vergara, Dara G. Torgerson, Maria Pino-Yanes, Suyash S. Shringarpure, Lili Huang, Nicholas Rafaels, Meher P. Boorgula, Henry R. Johnston, Victor E. Ortega, Albert M. Levin, Wei Song, Raul Torres, Badri Padhukasahasram, Celeste Eng, Delmy-Aracely Mejia-Mejia, Trevor Ferguson, Zhaohui S. Qin, Alan F. Scott, Maria Yazdanbakhsh, James G. Wilson, Javier Marrugo, Leslie A. Lange, Rajesh Kumar, Pedro C Avila, Keoki L. Williams, Harold Watson, Lorraine B. Ware, Christopher Olopade, Olufunmilayo Olopade, Ricardo Oliveira, Carole Ober, Dan L. Nicolae, Deborah Meyers, Alvaro Mayorga, Jennifer Knight-Madden, Tina Hartert, Nadia N. Hansel, Marilyn G. Foreman, Jean G. Ford, Mezbah U. Faruque, Georgia M. Dunston, Luis Caraballo, Esteban G. Burchard, Eugene Bleecker, Maria Ilma Araujo, Edwin Francisco Herrera-Paz, Kimberly Gietzen, Wendy E. Grus, Michael Bamshad, Carlos D. Bustamante, Eimear E. Kenny, Ryan D. Hernandez, Terri H. Beaty, Ingo Ruczinski, Joshua Akey, Kathleen C. Barnes

Center for Health Policy and Health Services Research Articles

The African Diaspora in the Western Hemisphere represents one of the largest forced migrations in history and had a profound impact on genetic diversity in modern populations. To date, the fine-scale population structure of descendants of the African Diaspora remains largely uncharacterized. Here we present genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas. We summarize genetic variation in these populations, quantifying the postcolonial sex-biased European gene flow …

Data From A Pre-Publication Independent Replication Initiative Examining Ten Moral Judgement Effects., Warren Tierney, Martin Schweinsberg, Jennifer Jordan, Deanna M Kennedy, Israr Qureshi, S Amy Sommer, Nico Thornley, Wendy L Bedwell, Sarah E Frick, P Scott Ramsay

Psychology Faculty Publications

We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that …

Global, Regional, And National Life Expectancy, All-Cause Mortality, And Cause-Specific Mortality For 249 Causes Of Death, 1980-2015: A Systematic Analysis For The Global Burden Of Disease Study 2015, H Wang, M Naghavi, M Coggeshall, L Dandona, D Dicker, Sahil Khera, M Tavakkoli, Gbd 2015 Mortality And Causes Of Death Collaborators

NYMC Faculty Publications

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child …

Global, Regional, And National Incidence, Prevalence, And Years Lived With Disability For 310 Diseases And Injuries, 1990-2015: A Systematic Analysis For The Global Burden Of Disease Study 2015, T Vos, C Allen, M Arora, R Barber, Z Bhutta, A Brown, A Carter, D Casey, Sahil Khera, M Tavakkoli, Gbd 2015 Disease And Injury Incidence And Prevalence Collaborators

NYMC Faculty Publications

Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with …

Circnet: A Database Of Circular Rnas Derived From Transcriptome Sequencing Data, Yu-Chen Liu, Jian-Rong Li, Chuan-Hu Sun, Erik Andrews, Rou-Fang Chao, Feng-Mao Lin, Shun-Long Weng, Sheng-Da Hsu, Chieh-Chen Huang, Chao Cheng, Chun-Chi Liu, Hsien-Da Huang

Dartmouth Scholarship

Circular RNAs (circRNAs) represent a new type of regulatory noncoding RNA that only recently has been identified and cataloged. Emerging evidence indicates that circRNAs exert a new layer of post-transcriptional regulation of gene expression. In this study, we utilized transcriptome sequencing datasets to systematically identify the expression of circRNAs (including known and newly identified ones by our pipeline) in 464 RNA-seq samples, and then constructed the CircNet database (http://circnet.mbc.nctu.edu.tw/) that provides the following resources: (i) novel circRNAs, (ii) integrated miRNA-target networks, (iii) expression profiles of circRNA isoforms, (iv) genomic annotations of circRNA isoforms (e.g. 282 948 exon positions), …

Sphingosine 1-Phosphate Activation Of Egfr As A Novel Target For Meningitic Escherichia Coli Penetration Of The Blood-Brain Barrier, Xiangru Wang, Ravi Maruvada, Andrew J. Morris, Jun O. Liu, Michael J. Wolfgang, Dong Jae Baek, Robert Bittman, Kwang Sik Kim

Internal Medicine Faculty Publications

Central nervous system (CNS) infection continues to be an important cause of mortality and morbidity, necessitating new approaches for investigating its pathogenesis, prevention and therapy. Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, which develops following penetration of the blood–brain barrier (BBB). By chemical library screening, we identified epidermal growth factor receptor (EGFR) as a contributor to E. coli invasion of the BBB in vitro. Here, we obtained the direct evidence that CNS-infecting E. coli exploited sphingosine 1-phosphate (S1P) for EGFR activation in penetration of the BBB in vitro and in vivo. We …

Biallelic Mutations In Tbcd, Encoding The Tubulin Folding Cofactor D, Perturb Microtubule Dynamics And Cause Early-Onset Encephalopathy., Elisabetta Flex, Marcello Niceta, Serena Cecchetti, Isabelle Thiffault, Margaret G. Au, Alessandro Capuano, Emanuela Piermarini, Anna A. Ivanova, Joshua W. Francis, Giovanni Chillemi, Balasubramanian Chandramouli, Giovanna Carpentieri, Charlotte A. Haaxma, Andrea Ciolfi, Simone Pizzi, Ganka V. Douglas, Kara Levine, Antonella Sferra, Maria Lisa Dentici, Rolph R. Pfundt, Jean-Baptist Lepichon, Emily G. Farrow, Frank Baas, Fiorella Piemonte, Bruno Dallapiccola, John M. Graham, Carol J. Saunders, Enrico Bertini, Richard A. Kahn, David A. Koolen, Marco Tartaglia

Manuscripts, Articles, Book Chapters and Other Papers

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin …

Throat Swabs And Sputum Culture As Predictors Of P. Aeruginosa Or S. Aureus Lung Colonization In Adult Cystic Fibrosis Patients, Darius Seidler, Mary Griffin, Amanda Nymon, Katja Koeppen, Alix Ashare

Dartmouth Scholarship

Background:

Due to frequent infections in cystic fibrosis (CF) patients, repeated respiratory cultures are obtained to inform treatment. When patients are unable to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower respiratory cultures. There is no clear data in adult subjects demonstrating the adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed to determine the utility of throat swabs in identifying lung colonization with common organisms in adults with CF.

Methods:

Adult CF subjects (n = 20) underwent bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A sputum …

Tumor Vessel Normalization After Aerobic Exercise Enhances Chemotherapeutic Efficacy., Keri L Schadler, Nicholas J Thomas, Peter Galie, Dong Ha Bhang, Kerry C Roby, Prince Addai, Jacob E Till, Kathleen Sturgeon, Alexander Zaslavsky, Christopher S Chen, Sandra Ryeom

Henry M. Rowan College of Engineering Departmental Research

Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical …

Defining And Targeting Health Disparities In Chronic Obstructive Pulmonary Disease, Roy A. Pleasants, Isaretta L. Riley, David M. Mannino

Preventive Medicine and Environmental Health Faculty Publications

The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins. However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures. Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations. Not only does SES affect the risk of developing COPD and …