Medicine and Health Sciences Commons^™

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Natural History Of Gutter-Related Type Ia Endoleaks After Snorkel/Chimney Endovascular Aneurysm Repair., Brant W Ullery, Kenneth Tran, Nathan K Itoga, Ronald L Dalman, Jason T Lee

Articles, Abstracts, and Reports

OBJECTIVE: Alternative endovascular strategies using parallel or snorkel/chimney (chimney endovascular aneurysm repair [ch-EVAR]) techniques have been developed to address the lack of widespread availability and manufacturing limitations with branched/fenestrated aortic devices for the treatment of complex abdominal aortic aneurysms. Despite high technical success and midterm patency of snorkel stent configurations, concerns remain regarding the perceived increased incidence of early gutter-related type Ia endoleaks. We aimed to evaluate the incidence and natural history of gutter-related type Ia endoleaks following ch-EVAR.

METHODS: Review of medical records and available imaging studies, including completion angiography and serial computed tomographic angiography, was performed for all …

A Randomized Controlled Trial Of Ethyl Glucuronide-Based Contingency Management For Outpatients With Co-Occurring Alcohol Use Disorders And Serious Mental Illness., Michael G Mcdonell, Emily Leickly, Sterling Mcpherson, Jordan Skalisky, Debra Srebnik, Frank Angelo, Roger Vilardaga, Jenny R Nepom, John M Roll, Richard K Ries

Articles, Abstracts, and Reports

OBJECTIVE: The authors examined whether a contingency management intervention using the ethyl glucuronide (EtG) alcohol biomarker resulted in increased alcohol abstinence in outpatients with co-occurring serious mental illnesses. Secondary objectives were to determine whether contingency management was associated with changes in heavy drinking, treatment attendance, drug use, cigarette smoking, psychiatric symptoms, and HIV-risk behavior.

METHOD: Seventy-nine (37% female, 44% nonwhite) outpatients with serious mental illness and alcohol dependence receiving treatment as usual completed a 4-week observation period and were randomly assigned to 12 weeks of contingency management for EtG-negative urine samples and addiction treatment attendance, or reinforcement only for study …

Thin Melanoma With Nodal Involvement: Analysis Of Demographic, Pathologic, And Treatment Factors With Regard To Prognosis., Giorgos Karakousis, Phyllis A Gimotty, Edmund K Bartlett, Myung-Shin Sim, Madalyn G Neuwirth, Douglas Fraker, Brian J Czerniecki, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although only a small proportion of thin melanomas result in lymph node metastasis, the abundance of these lesions results in a relatively large absolute number of patients with a diagnosis of nodal metastases, determined by either sentinel lymph node (SLN) biopsy or clinical nodal recurrence (CNR).

METHODS: Independent cohorts with thin melanoma and either SLN metastasis or CNR were identified at two melanoma referral centers. At both centers, SLN metastasis patients were included. At center 1, the CNR cohort included patients with initial negative clinical nodal evaluation followed by CNR. At center 2, the CNR cohort was restricted to …

Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca²⁺]_i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca²⁺]_i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca²⁺ channels.

Results

In CA3 pyramidal neurons, kainic …

A Prospective Study Of Maternal, Fetal And Neonatal Outcomes In The Setting Of Cesarean Section In Low- And Middle-Income Countries., Margo S. Harrison, Omrana Pasha, Sarah Saleem, Sumera Ali, Elwyn Chomba, Waldemar A. Carlo, Ana L. Garces, Nancy F. Krebs, K. Michael Hambidge, Shivaprasad S. Goudar, Bhala Kodkany, Sangappa Dhaded, Richard J. Derman, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Janet L. Moore, Dennis Wallace, Elizabeth M. Mcclure, Menachem Miodovnik, Marion Koso-Thomas, Jose Belizan, Antoinette K. Tshefu, Melissa Bauserman, Robert L. Goldenberg

Global Health Articles

INTRODUCTION: Cesarean section (CS) rates are increasing globally with an unclear effect on pregnancy outcomes. The study objective was to quantify maternal and perinatal morbidity and mortality associated with CS compared with vaginal delivery (VD) both within and across sites in low- and middle-income countries.

MATERIAL AND METHODS: A prospective population-based study including home and facility births in 337 153 women with a VD and 47 308 women with a CS from 2010 to 2015 was performed in Guatemala, India, Kenya, Pakistan, Zambia and Democratic Republic of Congo. Women were enrolled during pregnancy; delivery and 6-week follow-up data were collected. …

Buprenorphine Physician Supply: Relationship With State-Level Prescription Opioid Mortality, Hannah K. Knudsen, Jennifer R. Havens, Michelle R. Lofwall, Jamie L. Studts, Sharon L. Walsh

Behavioral Science Faculty Publications

Background: Buprenorphine is an effective treatment for opioid use disorder but the supply of buprenorphine physicians is currently inadequate to address the nation’s prescription opioid crisis. Perception of need due to rising opioid overdose rates is one possible reason for physicians to adopt buprenorphine. This study examined associations between rates of growth in buprenorphine physicians and prescription opioid overdose mortality rates in US states.

Methods: The total buprenorphine physician supply and number of physicians approved to treat 100 patients (per 100,000 population) were measured from June 2013 to January 2016. States were divided into two groups: those with rates of …

White Matter Hyperintensity Associations With Cerebral Blood Flow In Elderly Subjects Stratified By Cerebrovascular Risk, Ahmed A. Bahrani, David K. Powell, Guoqiang Yu, Eleanor S. Johnson, Gregory A. Jicha, Charles D. Smith

Biomedical Engineering Faculty Publications

Objective: This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. Methods: Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluidattenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slicebased techniques. Results: dWMHs but not …

A Rare Case Of Vascular Ring And Coarctation Of The Aorta In Association With Charge Syndrome., Jonathan B. Wagner, Joshua Q. Knowlton, Peter Pastuszko, Sanket Shah

Manuscripts, Articles, Book Chapters and Other Papers

A male neonate presented with CHARGE syndrome, a multiorgan genetic disorder involving the Coloboma of the eyes, congenital Heart defects, nasal choanal Atresia, growth and development Retardation, Genitourinary disorders, and Ear anomalies and deafness. Moreover, he had a rare case of vascular ring-consisting of a right aortic arch with retroesophageal brachiocephalic artery-combined with coarctation of the mid-aortic arch. He underwent both vascular ring and aortic arch repair at our institution. To our knowledge, this is the 4th documented case of this exceedingly rare type of aortic arch anomaly combined with aortic arch obstruction. Moreover, it is the first confirmed case …

Long-Term Excess Risk Of Stroke In People With Type 2 Diabetes In Sweden According To Blood Pressure Level: A Population-Based Case-Control Study., C Hedén Ståhl, M Lind, A-M Svensson, M Kosiborod, S Gudbjörnsdottir, A Pivodic, Mark A. Clements, A Rosengren

Manuscripts, Articles, Book Chapters and Other Papers

AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden.

METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged ≥ 18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n = 1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals …

Peer Victimization In Adolescents With Severe Obesity: The Roles Of Self-Worth And Social Support In Associations With Psychosocial Adjustment., Jennifer Reiter-Purtill, Marissa A. Gowey, Heather Austin, Kevin Smith, Dana L. Rofey, Todd M. Jenkins, Beth H. Garland, Meg H. Zeller, Teenview Study Group And In Cooperation With Teen-Labs Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Objective: To examine the associations of peer victimization with internalizing symptoms, externalizing symptoms, social competence, and academic performance in a clinical sample of adolescents with severe obesity, and whether self-worth and social support affect these associations.

Methods: Multisite cross-sectional data from 139 adolescents before weight loss surgery ( M age = 16.9; 79.9% female, 66.2% White; M Body Mass Index [BMI] = 51.5 kg/m 2 ) and 83 nonsurgical comparisons ( M age = 16.1; 81.9% female, 54.2% White; M BMI = 46.9 kg/m 2 ) were collected using self-reports with standardized measures.

Results: As a group, participants did not …

Glucocorticoid Receptor Polymorphisms And Outcomes In Pediatric Septic Shock., Natalie Z. Cvijanovich, Nick Anas, Geoffrey L. Allen, Neal J. Thomas, Michael T. Bigham, Scott L. Weiss, Julie Fitzgerald, Paul A. Checchia, Keith Meyer, Michael Quasney, Rainer Gedeit, Robert J. Freishtat, Jeffrey Nowak, Shekhar S. Raj, Shira Gertz, Jocelyn R. Grunwell, Amy Opoka, Hector R. Wong

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock.

DESIGN: We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids. The primary outcome variable was complicated course, defined as 28-day mortality or the persistence of two or more organ failures …

Multiple Organ Dysfunction In Children Mechanically Ventilated For Acute Respiratory Failure., Scott L. Weiss, Lisa A. Asaro, Heidi R. Flori, Geoffrey L. Allen, David Wypij, Martha A Q Curley, Randomized Evaluation Of Sedation Titration For Respiratory Failure (Restore) Study Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: The impact of extrapulmonary organ dysfunction, independent from sepsis and lung injury severity, on outcomes in pediatric acute respiratory failure is unclear. We sought to determine the frequency, timing, and risk factors for extrapulmonary organ dysfunction and the independent association of multiple organ dysfunction syndrome with outcomes in pediatric acute respiratory failure.

DESIGN: Secondary observational analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure cluster-randomized prospective clinical trial conducted between 2009 and 2013.

SETTING: Thirty-one academic PICUs in the United States.

PATIENTS: Two thousand four hundred forty-nine children mechanically ventilated for acute respiratory failure enrolled in Randomized …

In Vivo Characterization Of Cyp2d6*12, *29 And *84 Using Dextromethorphan As A Probe Drug: A Case Report., Andrea Gaedigk, Greyson P. Twist, Emily G. Farrow, Jennifer Lowry, Sarah E. Soden, Neil A. Miller

Manuscripts, Articles, Book Chapters and Other Papers

CYP2D6*84 was first described in a Black South African subject, however, its function remains unknown. Astrolabe, a probabilistic scoring tool developed in our laboratory to call genotypes from whole genome sequence, identified CYP2D6*84 in a trio. The father presented with intermediate metabolism when challenged with the CYP2D6 probe drug dextromethorphan (DM/dextrorphan [DX] = 0.0839). Since his second allele, CYP2D6*12, is nonfunctional, the observed activity is derived by CYP2D6*84. This finding suggests that the allele's hallmark P267H causes decreased activity toward DM and that this allele should receive a value of 0.5 for Activity Score calculations. The mother's DM/DX of 0.0543 …

Tobacco Product Use Among Lesbian, Gay, And Bisexual Adolescents., Hongying Dai

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Sexual minority youth face health disparities and a high risk of substance abuse. This study sought to fully characterize the disparity of tobacco use and risk factors in this high-risk subpopulation.

METHODS: Using data from the 2015 Youth Risk Behavior Survey, the current use of various tobacco products (cigarettes, smokeless tobacco, cigars, and e-cigarettes) was compared according to sex and distinct sexual identities (lesbian, gay, bisexual, and unsure). Heterosexual/straight adolescents served as the control group.

RESULTS: Of 14 703 respondents, 88.8% were heterosexual/straight, 2.0% were lesbian or gay, 6.0% were bisexual, and 3.2% were unsure about their sexual identity. …

Renin-Angiotensin Ii-Aldosterone System Blockers And Time To Renal Replacement Therapy In Children With Ckd., Alison G. Abraham, Aisha Betoko, Jeffrey J. Fadrowski, Christopher Pierce, Susan L. Furth, Bradley A. Warady, Alvaro Muñoz

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin-angiotensin II-aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD.

METHODS: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m

RESULTS: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more …

A Rare Case Of Vascular Ring And Coarctation Of The Aorta In Association With Charge Syndrome, Jonathan B Wagner, Joshua Q Knowlton, Peter Pastuszko, Sanket S Shah

The Texas Heart Institute Journal

A male neonate presented with CHARGE syndrome, a multiorgan genetic disorder involving the Coloboma of the eyes, congenital Heart defects, nasal choanal Atresia, growth and development Retardation, Genitourinary disorders, and Ear anomalies and deafness. Moreover, he had a rare case of vascular ring—consisting of a right aortic arch with retroesophageal brachiocephalic artery—combined with coarctation of the mid-aortic arch. He underwent both vascular ring and aortic arch repair at our institution.

To our knowledge, this is the 4th documented case of this exceedingly rare type of aortic arch anomaly combined with aortic arch obstruction. Moreover, it is the first confirmed case …

Diet And Polycystic Kidney Disease: A Pilot Intervention Study., Jacob M. Taylor, Jill M. Hamilton-Reeves, Debra K. Sullivan, Cheryl A. Gibson, Catherine Creed, Susan E. Carlson, Donald E. Wesson, Jared J. Grantham

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND & AIMS: Dietary sodium, protein, acid precursors, and water have been linked to cyst growth in polycystic kidney disease; yet, no studies in patients have examined the feasibility of using a dietary intervention that controls all of these factors. The aim of this study was to determine if a diet, appropriate for persons of most ages, reduces the excretion of sodium, urea, acid, and decreases mean urine osmolality while gaining acceptance by patients with autosomal dominant polycystic kidney disease (ADPKD).

METHODS: Twelve adults with ADPKD enrolled in a pre-post pilot feasibility study and served as their own controls. Individuals …

Clinician-Performed Bedside Ultrasound In Improving Diagnostic Accuracy In Patients Presenting To The Ed With Acute Dyspnea., Dimitrios Papanagnou, Michael Secko, John Gullett, Michael Stone, Shahriar Zehtabchi

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Diagnosing acute dyspnea is a critical action performed by emergency physicians (EP). It has been shown that ultrasound (US) can be incorporated into the work-up of the dyspneic patient; but there is little data demonstrating its effect on decision-making. We sought to examine the impact of a bedside, clinician-performed cardiopulmonary US protocol on the clinical impression of EPs evaluating dyspneic patients, and to measure the change in physician confidence with the leading diagnosis before and after US.

METHODS: We conducted a prospective observational study of EPs treating adult patients with undifferentiated dyspnea in an urban academic center, excluding those …

Prolonged Sinus Pauses Upon Termination Of Paroxysmal Atrial Fibrillation: Abnormal Right Atrial Electrophysiologic And Electroanatomic Findings, Zhengyu Bao, Hongwu Chen, Bing Yang, Michael Shehata, Weizhu Ju, Fengxiang Zhang, Gang Yang, Kai Gu, Mingfang Li, Kejiang Cao, Xunzhang Wang, Minglong Chen

The Texas Heart Institute Journal

The efficacy of pulmonary vein antral isolation for patients with prolonged sinus pauses (PSP) on termination of atrial fibrillation has been reported. We studied the right atrial (RA) electrophysiologic and electroanatomic characteristics in such patients.

Forty patients underwent electroanatomic mapping of the RA: 13 had PSP (group A), 13 had no PSP (group B), and 14 had paroxysmal supraventricular tachycardia (control group C). Group A had longer P-wave durations in lead II than did groups B and C (115.5 ± 15.4 vs 99.5 ± 10.9 vs 96.5 ± 10.4 ms; P=0.001), and RA activation times (106.8 ± 13.8 vs …

Expectations For Treatment In Pediatric Weight Management And Relationship To Attrition., Erinn T. Rhodes, Richard E. Boles, Kimberly Chin, Amy Christison, Elizabeth Getzoff Testa, Kimberly Guion, Mary Jane Hawkins, Carter R. Petty, Bethany Sallinen Gaffka, Melissa Santos, Laura Shaffer, Jared Tucker, Sarah Hampl

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Attrition in pediatric weight management negatively impacts treatment outcomes. A potentially modifiable contributor to attrition is unmet family expectations. This study aimed to evaluate the association between adolescent and parent/guardian treatment expectations and attrition.

PATIENTS AND METHODS: A prospective, nonrandomized, uncontrolled, single-arm pilot trial was conducted among 12 pediatric weight management programs in the Children's Hospital Association's FOCUS on a Fitter Future collaborative. Parents/guardians and adolescents completed an expectations/goals survey at their initial visit, with categories including healthier food/drinks, physical activity/exercise, family support/behavior, and weight management goals. Attrition was assessed at 3 months.

RESULTS: From January to August 2013, …

Evaluating Parents' Self-Efficacy For Diabetes Management In Pediatric Type 1 Diabetes., Amy E. Noser, Susana R. Patton, Jason Van Allen, Michael B. Nelson, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

Objective: To examine the factor structure and construct validity of the Maternal Self-Efficacy for Diabetes Management Scale (MSED) in 135 youth ( Mage  = 13.50  ±  1.83 years), with type 1 diabetes mellitus.

Method: The study used exploratory factor analysis (EFA) to examine the factor structure and correlations to examine relationships among MSED factors and select parent and child diabetes-related health behaviors and outcomes.

Results: EFA identified an 11-item three-factor solution (χ 2 (25, n  = 133)  = 40.22, p  < .03, RMSEA = 0.07, CFI = 0.98, TLI = 0.97), with factors corresponding to parents' perceived ability to manage their child's diabetes (MSED-M), problem-solve issues surrounding glycemic control (MSED-P), and teach their child about diabetes care (MSED-T). Correlational analyses revealed significant associations between the MSED-M and MSED-T and parent-reported optimism and youth's diabetes-specific self-efficacy. The MSED-T was also associated with glycated hemoglobin and self-monitoring blood glucose.

Conclusions: Results provide preliminary evidence for the reliability and validity of a three-factor solution of the MSED.

The Randomized, Controlled Trial Of Late Surfactant: Effects On Respiratory Outcomes At 1-Year Corrected Age., Roberta L. Keller, Eric C. Eichenwald, Anna Maria Hibbs, Elizabeth E. Rogers, Katherine C. Wai, Dennis M. Black, Philip L. Ballard, Jeanette M. Asselin, William E Truog, Jeffrey D. Merrill, Mark C. Mammel, Robin H. Steinhorn, Rita M. Ryan, David J. Durand, Catherine M. Bendel, Ellen M. Bendel-Stenzel, Sherry E. Courtney, Ramasubbareddy Dhanireddy, Mark L. Hudak, Frances R. Koch, Dennis E. Mayock, Victor J. Mckay, Jennifer Helderman, Nicolas F. Porta, Rajan Wadhawan, Lisa Palermo, Roberta A. Ballard, Tolsurf Study Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control).

STUDY DESIGN: Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported …

Genomic Contraindications For Heart Transplantation., Danton S. Char, Gabriel Lázaro-Muñoz, Aliessa Barnes, David Magnus, Michael J. Deem, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Genome sequencing raises new ethical challenges. Decoding the genome produces new forms of diagnostic and prognostic information; however, the information is often difficult to interpret. The connection between most genetic variants and their phenotypic manifestations is not understood. This scenario is particularly true for disorders that are not associated with an autosomal genetic variant. The analytic uncertainty is compounded by moral uncertainty about how, exactly, the results of genomic testing should influence clinical decisions. In this Ethics Rounds, we present a case in which genomic findings seemed to play a role in deciding whether a patient was to be listed …

Increasing Ed Use Of Jet Injection Of Lidocaine For Iv-Related Pain Management., Shobhit Jain, Mary A. Hegenbarth, Sharon Humiston, Erin Gunter, Lynn Anson, Joan Giovanni

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVE: Venipuncture is a leading cause of procedural pain for children. Jet injection of lidocaine (JIL; J-Tip) has been demonstrated to be effective in controlling intravenous (IV) placement-related pain and, due to its rapid onset, is particularly suited to emergency department (ED) use. Our objective was to increase JIL use with IV placements in our ED from 11% at baseline to 50% within 12 months.

METHODS: We initiated the project at our urban, tertiary pediatric ED in July 2014. We surveyed medical and nursing teams to identify barriers to JIL use. We initiated changes at monthly intervals: (1) …

GabaB Receptor Attenuation Of GabaA Currents In Neurons Of The Mammalian Central Nervous System, Wen Shen, Changlong Nan, Peter T. Nelson, Harris Ripps, Malcolm M. Slaughter

Pathology and Laboratory Medicine Faculty Publications

Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABA_B receptor can suppress the ionotropic GABA_A receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains in Xenopus oocytes by microtransplantation …

Metabolic And Molecular Insights Into An Essential Role Of Nicotinamide Phosphoribosyltransferase., Li Q. Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P. Heruth, Chengpeng Bi, R Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N. Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt-/-) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25.24±2.22% body weight loss, after the tamoxifen induction of NamptF/F × Cre mice. These results substantiate that Nampt …

A Statistical Method For The Conservative Adjustment Of False Discovery Rate (Q-Value)., Yinglei Lai

Epidemiology Faculty Publications

BACKGROUND: q-value is a widely used statistical method for estimating false discovery rate (FDR), which is a conventional significance measure in the analysis of genome-wide expression data. q-value is a random variable and it may underestimate FDR in practice. An underestimated FDR can lead to unexpected false discoveries in the follow-up validation experiments. This issue has not been well addressed in literature, especially in the situation when the permutation procedure is necessary for p-value calculation.

RESULTS: We proposed a statistical method for the conservative adjustment of q-value. In practice, it is usually necessary to calculate p-value by a permutation procedure. …

Phase I First-In-Human Study Of Venetoclax In Patients With Relapsed Or Refractory Non-Hodgkin Lymphoma., Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A Humerickhouse, Gary B Gordon, John F Gerecitano

Articles, Abstracts, and Reports

Purpose B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor. Patients and Methods A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts. Treatment commenced with a 3-week dose ramp-up period for most patients in dose-escalation cohorts and for all patients in safety expansion. Results NHL subtypes included …

Polymer Micelle Formulation For The Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy And Pharmacokinetic Studies In Mice, Ji Eun Park, Se-Eun Chun, Derek Alexander Reichel, Jee Sun Min, Su-Chan Lee, Songhee Han, Gongmi Ryoo, Yunseok Oh, Shin-Hyung Park, Heon-Min Ryu, Kyung Bo Kim, Ho-Young Lee, Soo Kyung Bae, Younsoo Bae, Wooin Lee

Pharmaceutical Sciences Faculty Publications

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic …