Digital Commons Network^™

Abl Kinase Regulation By Braf/Erk And Cooperation With Akt In Melanoma, Aditi Jain, Rakshamani Tripathi, Courtney P. Turpin, Chi Wang, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

The melanoma incidence continues to increase, and the disease remains incurable for many due to its metastatic nature and high rate of therapeutic resistance. In particular, melanomas harboring BRAF^V600E and PTEN mutations often are resistant to current therapies, including BRAF inhibitors (BRAFi) and immune checkpoint inhibitors. Abl kinases (Abl/Arg) are activated in melanomas and drive progression; however, their mechanism of activation has not been established. Here we elucidate a novel link between BRAF^V600E/ERK signaling and Abl kinases. We demonstrate that BRAF^V600E/ERK play a critical role in binding, phosphorylating and regulating Abl localization and Abl/Arg activation …

Determining The Optimal Target Blood Pressure After Thrombectomy: High Or Low?, Katja E. Wartenberg, Stephan A. Mayer

Neurology Articles

No abstract provided.

Polymer Nanoassemblies With Hydrophobic Pendant Groups In The Core Induce False Positive Sirna Transfection In Luciferase Reporter Assays, Steven Rheiner, Derek Alexander Reichel, Piotr G. Rychahou, Tadahide Izumi, Hsin-Sheng Yang, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Poly(ethylene glycol)-conjugated polyethylenimine (PEG-PEI) is a widely studied cationic polymer used to develop non-viral vectors for siRNA therapy of genetic disorders including cancer. Cell lines stably expressing luciferase reporter protein typically evaluate the transfection efficacy of siRNA/PEG-PEI complexes, however recent findings revealed that PEG-PEI can reduce luciferase expression independent of siRNA. This study elucidates a cause of the false positive effect in luciferase assays by using polymer nanoassemblies (PNAs) made from PEG, PEI, poly-(L-lysine) (PLL), palmitate (PAL), and deoxycholate (DOC): PEG-PEI (2P), PEG-PEI-PAL (3P), PEG-PLL (2P′), PEG-PLL-PAL (3P′), and PEG-PEI-DOC (2PD). In vitro transfection and western blot assays of luciferase …

Recognizing The Continuous Nature Of Expression Heterogeneity And Clinical Outcomes In Clear Cell Renal Cell Carcinoma, Xiaona Wei, Yukti Choudhury, Weng-Khong Lim, John Anema, Richard J. Kahnoski, Brian Lane, John Ludlow, Masayuki Takahashi, Hiro-Omi Kanayama, Arie Belldegrun, Hyung L. Kim, Craig G. Rogers, David Nicol, Bin T. Teh, Min-Han Tan

Urology Articles

Clear cell renal cell carcinoma (ccRCC) has been previously classified into putative discrete prognostic subtypes by gene expression profiling. To investigate the robustness of these proposed subtype classifications, we evaluated 12 public datasets, together with a new dataset of 265 ccRCC gene expression profiles. Consensus clustering showed unstable subtype and principal component analysis (PCA) showed a continuous spectrum both within and between datasets. Considering the lack of discrete delineation and continuous spectrum observed, we developed a continuous quantitative prognosis score (Continuous Linear Enhanced Assessment of RCC, or CLEAR score). Prognostic performance was evaluated in independent cohorts from The Cancer Genome …

In Vivo Study Of Plasmodium Falciparum Chloroquine Susceptibility In Three Departments Of Haiti, Christian P. Raccurt, Philippe Brasseur, Micheline Cicéron, Dana M. Parke, Marcus J. Zervos, Jacques Boncy

Global Health Initiative Articles

BACKGROUND: Malaria is considered a public health priority in Haiti, with a goal to eliminate by year 2020. Chloroquine is the first-line treatment recommended by the Ministry of Public Health and Population. In order to verify the suitability of chloroquine for uncomplicated malaria treatment, an in vivo study of susceptibility of Plasmodium falciparum to chloroquine was conducted from January 2013 to March 2015 in six localities in the south of Haiti.

RESULTS: Sixty-one patients who presented with confirmed P. falciparum malaria were included in the study and followed until day 28 after having taken 25 mg/kg of chloroquine orally over …

Heterozygous De Novo Ubtf Gain-Of-Function Variant Is Associated With Neurodegeneration In Childhood., Simon Edvardson, Claudia M Nicolae, Pankaj B Agrawal, Cyril Mignot, Katelyn Payne, Asuri Narayan Prasad, Chitra Prasad, Laurie Sadler, Caroline Nava, Thomas E Mullen, Amber Begtrup, Berivan Baskin, Zöe Powis, Avraham Shaag, Boris Keren, George-Lucian Moldovan, Orly Elpeleg

Paediatrics Publications

Ribosomal RNA (rRNA) is transcribed from rDNA by RNA polymerase I (Pol I) to produce the 45S precursor of the 28S, 5.8S, and 18S rRNA components of the ribosome. Two transcription factors have been defined for Pol I in mammals, the selectivity factor SL1, and the upstream binding transcription factor (UBF), which interacts with the upstream control element to facilitate the assembly of the transcription initiation complex including SL1 and Pol I. In seven unrelated affected individuals, all suffering from developmental regression starting at 2.5-7 years, we identified a heterozygous variant, c.628G>A in UBTF, encoding p.Glu210Lys in UBF, which …

Idarucizumab For Dabigatran Reversal - Full Cohort Analysis., Charles V. Pollack, Paul A. Reilly, Joanne Van Ryn, John W. Eikelboom, Stephan Glund, Richard A. Bernstein, Robert Dubiel, Menno V. Huisman, Elaine M. Hylek, Chak-Wah Kam, Pieter W. Kamphuisen, Jörg Kreuzer, Jerrold H. Levy, Gordon Royle, Frank W. Sellke, Joachim Stangier, Thorsten Steiner, Peter Verhamme, Bushi Wang, Laura Young, Jeffrey I. Weitz

Department of Emergency Medicine Faculty Papers

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran.

METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration …

Free Flap Reconstruction Monitoring Techniques And Frequency In The Era Of Restricted Resident Work Hours, Urjeet A. Patel, David Hernandez, Yelizaveta Shnayder, Mark K. Wax, Matthew M. Hanasono, Joshua D. Hornig, Tamer Ghanem, Matthew Old, Ryan S. Jackson, Levi G. Ledgerwood, Patrik Pipkorn, Lawrence Lin, Adrian Ong, Joshua B. Greene, James Bekeny, Yin Yiu, Salem I. Noureldine, David X. Li, Joel Fontanarosa, Evan Greenbaum, Jeremy D. Richmon

Otolaryngology Articles

Importance: Free flap reconstruction of the head and neck is routinely performed with success rates around 94% to 99% at most institutions. Despite experience and meticulous technique, there is a small but recognized risk of partial or total flap loss in the postoperative setting. Historically, most microvascular surgeons involve resident house staff in flap monitoring protocols, and programs relied heavily on in-house resident physicians to assure timely intervention for compromised flaps. In 2003, the Accreditation Council for Graduate Medical Education mandated the reduction in the hours a resident could work within a given week. At many institutions this new era …

Two Novel Susceptibility Loci For Prostate Cancer In Men Of African Ancestry, David V Conti, Bettina F Drake, Adam S Kibel, Et Al.

2010-2019 OA Pubs

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] …

Parents' Experiences And Perceptions When Classifying Their Children With Cerebral Palsy: Recommendations For Service Providers., Natalie V Scime, Doreen J Bartlett, Laura K Brunton, Robert J Palisano

Physical Therapy Publications

AIMS: This study investigated the experiences and perceptions of parents of children with cerebral palsy (CP) when classifying their children using the Gross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), and the Communication Function Classification System (CFCS). The second aim was to collate parents' recommendations for service providers on how to interact and communicate with families.

METHODS: A purposive sample of seven parents participating in the On Track study was recruited. Semi-structured interviews were conducted orally and were audiotaped, transcribed, and coded openly. A descriptive interpretive approach within a pragmatic perspective was used during analysis.

RESULTS: …

Therapeutic Considerations For Antihyperglycemic Agents In Diabetic Kidney Disease., Joshua J Neumiller, Radica Alicic, Katherine Tuttle

Articles, Abstracts, and Reports

Diabetic kidney disease is among the most frequent complications of diabetes, with approximately 50% of patients with ESRD attributed to diabetes in developed countries. Although intensive glycemic management has been shown to delay the onset and progression of increased urinary albumin excretion and reduced GFR in patients with diabetes, conservative dose selection and adjustment of antihyperglycemic medications are necessary to balance glycemic control with safety. A growing body of literature is providing valuable insight into the cardiovascular and renal safety and efficacy of newer antihyperglycemic medications in the dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, and sodium-glucose cotransporter 2 inhibitor …

Mindfulness-Based Stress Reduction In Women With Overweight Or Obesity: A Randomized Clinical Trial., Nazia Raja-Khan, Katrina Agito, Julie Shah, Christy M Stetter, Theresa S Gustafson, Holly Socolow, Allen R Kunselman, Diane K. Reibel, Richard S Legro

Marcus Institute of Integrative Health Faculty Papers

OBJECTIVE: To evaluate the feasibility and cardiometabolic effects of mindfulness-based stress reduction (MBSR) in women with overweight or obesity.

METHODS: Eighty-six women with BMI ≥ 25 kg/m

RESULTS: Compared to health education, the MBSR group demonstrated significantly improved mindfulness at 8 weeks (mean change from baseline, 4.5 vs. -1.0; P = 0.03) and significantly decreased perceived stress at 16 weeks (-3.6 vs. -1.3, P = 0.01). In the MBSR group, there were significant reductions in fasting glucose at 8 weeks (-8.9 mg/dL, P = 0.02) and at 16 weeks (-9.3 mg/dL, P = 0.02) compared to baseline. Fasting glucose did …

Substance Use Disorders, Violence, Mental Health, And Hiv: Differentiating A Syndemic Factor By Gender And Sexuality, Kiyomi Tsuyuki, Eileen V. Pitpitan, Maria A. Levi-Minzi, Lianne A. Urada, Steven P. Kurtz, Jamila K. Stockman, Hilary L. Surratt

Center for Health Services Research Faculty Publications

This paper measures syndemic substance use disorder, violence, and mental health and compares the syndemic among HIV-infected heterosexual men, heterosexual women, and men who have sex with men (MSM). Data were from a sample of high needs substance-using, HIV-infected people in South Florida between 2010 and 2012 (n = 481). We used confirmatory factor analysis to measure a syndemic latent variable and applied measurement invariance models to identify group differences in the data structure of syndemic co-morbidities among heterosexual men, heterosexual women, and MSM. We found that variables used to measure the syndemic fit each sub-group, supporting that substance use …

Brain Microvascular Injury And White Matter Disease Provoked By Diabetes-Associated Hyperamylinemia, Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E. Saatman, Peter T. Nelson, John T. Slevin, Larry B. Goldstein, Geert Jan Biessels, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.

METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses …

High Agreement Between Benchtop And Point-Of-Care Dipcard Tests For Ethyl Glucuronide., Emily Leickly, Jordan Skalisky, Sterling Mcpherson, Michael F Orr, Michael G Mcdonell

Articles, Abstracts, and Reports

No abstract provided.

Identification Of Changes In Neuronal Function As A Consequence Of Aging And Tauopathic Neurodegeneration Using A Novel And Sensitive Magnetic Resonance Imaging Approach, Sarah N. Fontaine, Alexandria Ingram, Ryan A. Cloyd, Shelby E. Meier, Emily Miller, Danielle N. Lyons, Grant K. Nation, Elizabeth Mechas, Blaine Weiss, Chiara Lanzillotta, Fabio Di Domenico, Frederick A. Schmitt, David K. Powell, Moriel H. Vandsburger, Jose Francisco Abisambra

Sanders-Brown Center on Aging Faculty Publications

Tauopathies, the most common of which is Alzheimer’s disease (AD), constitute the most crippling neurodegenerative threat to our aging population. Tauopathic patients have significant cognitive decline accompanied by irreversible and severe brain atrophy, and it is thought that neuronal dysfunction begins years before diagnosis. Our current understanding of tauopathies has yielded promising therapeutic interventions but have all failed in clinical trials. This is partly due to the inability to identify and intervene in an effective therapeutic window early in the disease process. A major challenge that contributes to the definition of an early therapeutic window is limited technologies. To address …

A Naturally Generated Decoy Of The Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance In Tumors, Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S. J. Elenitoba-Johnson, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 proapoptotic function. Conversely, PAF, which contains this VASA …

Surgical Implications And Variability In The Use Of The Flat Epithelial Atypia Diagnosis On Breast Biopsy Specimens., Laura S Samples, Mara H Rendi, Paul D Frederick, Kimberly H Allison, Heidi D Nelson, Thomas R Morgan, Donald L Weaver, Joann G Elmore

Articles, Abstracts, and Reports

OBJECTIVES: Flat epithelial atypia (FEA) is a relatively new diagnostic term with uncertain clinical significance for surgical management. Any implied risk of invasive breast cancer associated with FEA is contingent upon diagnostic reproducibility, yet little is known regarding its use.

MATERIALS AND METHODS: Pathologists in the Breast Pathology Study interpreted one of four 60-case test sets, one slide per case, constructed from 240 breast biopsy specimens. An electronic data form with standardized diagnostic categories was used; participants were instructed to indicate all diagnoses present. We assessed participants' use of FEA as a diagnostic term within: 1) each test set; 2) …

A Tnf-Jnk-Axl-Erk Signaling Axis Mediates Primary Resistance To Egfr Inhibition In Glioblastoma., Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib

Articles, Abstracts, and Reports

Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in …

Hypomethylation Of Cntfrα Is Associated With Proliferation And Poor Prognosis In Lower Grade Gliomas., Kun Fan, Xiaowen Wang, Jingwen Zhang, Romela Irene Ramos, Haibo Zhang, Chunjie Li, Dan Ye, Jiansheng Kang, Diego M Marzese, Dave S B Hoon, Wei Hua

Articles, Abstracts, and Reports

Ciliary neurotrophic factor receptor α subunit (CNTFRα) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFRα regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFRα was overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and normal brain specimens in TCGA datasets and in an independent cohort. Bioinformatics analysis revealed a CpG shore of the CNTFRα gene regulated its mRNA expression in TCGA datasets. This observation was further validated with clinical specimens and functionally verified using demethylating agents. Additionally, we observed that independent …

Risk Factors For 30-Day Mortality In Patients With Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections, Pedro Ayau, Ana C. Bardossy, Guillermo Sanchez, Ricardo Ortiz, Daniela Moreno, Pamela Hartman, Khulood Rizvi, Tyler Prentiss, Mary B. Perri, Meredith Mahan, Vanthida Huang, Katherine Reyes, Marcus J. Zervos

Global Health Initiative Articles

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections (BSI) are a major health care problem accounting for a large percentage of nosocomial infections. The aim of this study was to identify risk factors associated with 30-day mortality in patients with MRSA BSI.

METHODS: This was a retrospective study performed in Southeast Michigan. Over a 9- year period, a total of 1,168 patients were identified with MRSA BSI. Patient demographics and clinical data were retrieved and evaluated using electronic medical health records.

RESULTS: 30-day mortality during the 9-year study period was 16%. Significant risk factors for 30-day mortality were age, cancer, …

Effectiveness Of Switching Smoking-Cessation Medications Following Relapse, Bryan W. Heckman, K. Michael Cummings, Karin A. Kasza, Ron Borland, Jessica L. Burris, Geoffrey T. Fong, Ann Mcneill, Matthew J. Carpenter

Psychology Faculty Publications

Introduction—Nicotine dependence is a chronic disorder often characterized by multiple failed quit attempts (QAs). Yet, little is known about the sequence of methods used across multiple QAs or how this may impact future ability to abstain from smoking. This prospective cohort study examines the effectiveness of switching smoking-cessation medications (SCMs) across multiple QAs.

Methods—Adult smokers (aged ≥ 18 years) participating in International Tobacco Control surveys in the United Kingdom, U.S., Canada, and Australia (N=795) who: (1) completed two consecutive surveys between 2006 and 2011; (2) initiated a QA at least 1 month before each survey; and (3) provided …

A Wellness Study Of 108 Individuals Using Personal, Dense, Dynamic Data Clouds., Nathan D Price, Andrew T Magis, John C Earls, Gustavo Glusman, Roie Levy, Christopher Lausted, Daniel T Mcdonald, Ulrike Kusebauch, Christopher L Moss, Yong Zhou, Shizhen Qin, Robert L Moritz, Kristin Brogaard, Gilbert S Omenn, Jennifer C Lovejoy, L Hood

Articles, Abstracts, and Reports

Personal data for 108 individuals were collected during a 9-month period, including whole genome sequences; clinical tests, metabolomes, proteomes, and microbiomes at three time points; and daily activity tracking. Using all of these data, we generated a correlation network that revealed communities of related analytes associated with physiology and disease. Connectivity within analyte communities enabled the identification of known and candidate biomarkers (e.g., gamma-glutamyltyrosine was densely interconnected with clinical analytes for cardiometabolic disease). We calculated polygenic scores from genome-wide association studies (GWAS) for 127 traits and diseases, and used these to discover molecular correlates of polygenic risk (e.g., genetic risk …

Risk Factors For 30-Day Mortality In Patients With Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections, Pedro Ayau, Ana C. Bardossy, Guillermo Sanchez, Ricardo Ortiz, Daniela Moreno, Pamela Hartman, Khulood Rizvi, Tyler Prentiss, Mary Perri, Meredith Mahan, Vanthida Huang, Kate Reyes, Marcus J. Zervos

Infectious Diseases Articles

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections (BSI) are a major health care problem accounting for a large percentage of nosocomial infections. The aim of this study was to identify risk factors associated with 30-day mortality in patients with MRSA BSI.

METHODS: This was a retrospective study performed in Southeast Michigan. Over a 9- year period, a total of 1,168 patients were identified with MRSA BSI. Patient demographics and clinical data were retrieved and evaluated using electronic medical health records.

RESULTS: 30-day mortality during the 9-year study period was 16%. Significant risk factors for 30-day mortality were age, cancer, …

Blocking An N-Terminal Acetylation-Dependent Protein Interaction Inhibits An E3 Ligase, Daniel C. Scott, Jared T. Hammill, Jaeki Min, David Y. Rhee, Michele Connelly, Vladislav O. Sviderskiy, Deepak Bhasin, Yizhe Chen, Su-Sien Ong, Sergio C. Chai, Asli N. Goktug, Guochang Huang, Julie K. Monda, Jonathan Low, Ho Shin Kim, Joao A. Paulo, Joe R. Cannon, Anang A. Shelat, Taosheng Chen, Ian R. Kelsall, Arno F. Alpi, Vishwajeeth Pagala, Xusheng Wang, Junmin Peng, Bhuvanesh Singh, J. Wade Harper, Brenda A. Schulman, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

N-terminal acetylation is an abundant modification influencing protein functions. Because ∼80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation–dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. The inhibitors are …

Hematologic Toxicity Of Concurrent Administration Of Radium-223 And Next-Generation Antiandrogen Therapies., Tu Dan, Harriet B. Eldredge-Hindy, Jean Hoffman-Censits, Jianqing Lin, William K. Kelly, Leonard G. Gomella, Costas D. Lallas, Edouard J. Trabulsi, Mark D. Hurwitz, Adam P. Dicker, Robert B. Den

Department of Radiation Oncology Faculty Papers

PURPOSE/OBJECTIVES: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease., David W Fardo, Laura E Gibbons, Shubhabrata Mukherjee, M Maria Glymour, Wayne Mccormick, Susan M Mccurry, James D Bowen, Eric B Larson, Paul K Crane

Articles, Abstracts, and Reports

INTRODUCTION: Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS: We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS: …

The Impact Of Smoking On Sentinel Node Metastasis Of Primary Cutaneous Melanoma., Maris S Jones, Peter C Jones, Stacey L Stern, David Elashoff, Dave S B Hoon, John Thompson, Nicola Mozzillo, Omgo E Nieweg, Dirk Noyes, Harald J Hoekstra, Jonathan S Zager, Daniel F Roses, Alessandro Testori, Brendon J Coventry, Mark B Smithers, Robert Andtbacka, Doreen Agnese, Erwin Schultz, Eddy C Hsueh, Mark Kelley, Schlomo Schneebaum, Lisa Jacobs, Tawnya Bowles, Mohammed Kashani-Sabet, Douglas Johnson, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy.

METHODS: Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis.

RESULTS: Current smoking was strongly associated with SLN metastasis (p = 0.004), even after adjusting for other predictors of metastasis. Among …

A Randomized Placebo-Controlled Trial Of N-Acetylcysteine For Cannabis Use Disorder In Adults, Kevin M. Gray, Susan C. Sonne, Erin A. Mcclure, Udi E. Ghitza, Abigail G. Matthews, Aimee L. Mcrae-Clark, Kathleen M. Carroll, Jennifer S. Potter, Katharina Wiest, Larissa J. Mooney, Albert Hasson, Sharon L. Walsh, Michelle R. Lofwall, Shanna Babalonis, Robert W. Lindblad, Steven Sparenborg, Aimee Wahle, Jacqueline S. King, Nathaniel L. Baker, Rachel L. Tomko, Louise F. Haynes, Ryan G. Vandrey, Frances R. Levin

Behavioral Science Faculty Publications

Background—Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults.

Methods—In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All …

Using Neonatal Skin To Study The Developmental Programming Of Aging, Leryn J. Reynolds, Brett J. Dickens, Benjamin B. Green, Carmen J. Marsit, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Numerous studies have examined how both negative and positive maternal exposures (environmental contaminants, nutrition, exercise, etc.) impact offspring risk for age-associated diseases such as obesity, type 2 diabetes, hypertension, and others. The purpose of this study was to introduce the foreskin as a novel model to examine developmental programming in human neonates, particularly in regard to adipogenesis and insulin receptor signaling, major contributors to age-associated diseases such as obesity and diabetes. Neonatal foreskin was collected following circumcision and primary dermal fibroblasts were isolated to perform adipocyte differentiation and insulin stimulation experiments. Human neonatal foreskin primary fibroblasts take up lipid when …