Medicine and Health Sciences Commons^™

Safety Of Paclitaxel-Coated Balloon Angioplasty For Femoropopliteal Peripheral Artery Disease, Kenneth Ouriel, Mark A. Adelman, Kenneth Rosenfield, Dierk Scheinert, Marianne Brodmann, Constantino Peña, Patrick Geraghty, Arthur Lee, Roseann White, Daniel G. Clair

2010-2019 OA Pubs

OBJECTIVES: The aim of this study was to assess safety outcomes of femoropopliteal drug-coated balloon (DCB) angioplasty using patient-level data from the Lutonix clinical program.

BACKGROUND: A recent systematic review and meta-analysis of heterogenous trials and summary-level data identified increased long-term mortality in patients treated with paclitaxel-coated balloons and stents.

METHODS: We evaluated DCB angioplasty (n = 1,093) and uncoated balloon angioplasty (percutaneous transluminal angioplasty [PTA]) (n = 250) outcomes in LEVANT 1 (The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis), LEVANT 2 (Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries), and …

The Community Structure Of Functional Brain Networks Exhibits Scale-Specific Patterns Of Inter- And Intra-Subject Variability, Richard F Betzel, Maxwell A Bertolero, Evan M Gordon, Caterina Gratton, Nico U F Dosenbach, Danielle S Bassett

2010-2019 OA Pubs

The network organization of the human brain varies across individuals, changes with development and aging, and differs in disease. Discovering the major dimensions along which this variability is displayed remains a central goal of both neuroscience and clinical medicine. Such efforts can be usefully framed within the context of the brain's modular network organization, which can be assessed quantitatively using computational techniques and extended for the purposes of multi-scale analysis, dimensionality reduction, and biomarker generation. Although the concept of modularity and its utility in describing brain network organization is clear, principled methods for comparing multi-scale communities across individuals and time …

Immune Globulin Subcutaneous, Human - Klhw 20% For Primary Humoral Immunodeficiency: An Open-Label, Phase Iii Study, John W Sleasman, William R Lumry, Iftikhar Hussain, H James Wedner, James B Harris, Kecia L Courtney, Elsa Mondou, Jiang Lin, Mark R Stein

2010-2019 OA Pubs

No abstract provided.

Pharmacokinetics Of Once-Daily Extended-Release Tacrolimus Tablets Versus Twice-Daily Capsules In De Novo Liver Transplant, Derek A Dubay, Lewis Teperman, Kimi Ueda, Andrew Silverman, William Chapman, Angel E Alsina, Carmelina Tyler, Daniel R Stevens

2010-2019 OA Pubs

The pharmacokinetics of once-daily extended-release tacrolimus tablets (LCPT) in de novo liver transplantation have not been previously reported. In this phase II, randomized, open-label study, de novo liver transplant recipients were randomized to LCPT 0.07-0.13 mg/kg/day (taken once daily; n = 29) or twice-daily immediate-release tacrolimus capsules (IR-Tac) at 0.10-0.15 mg/kg/day (divided twice daily; n = 29). Subsequent doses of both drugs were adjusted to maintain tacrolimus trough concentrations of 5 to 20 ng/mL through day 90, and 5-15 ng/mL thereafter. Twenty-four-hour pharmacokinetic profiles were obtained on days 1, 7, and 14, with trough concentration and efficacy/safety monitoring through year …

Apples To Apples? Neural Correlates Of Emotion Regulation Differences Between High- And Low-Risk Adolescents, Michael T Perino, João F Guassi Moreira, Ethan M Mccormick, Eva H Telzer

2010-2019 OA Pubs

Adolescence has been noted as a period of increased risk taking. The literature on normative neurodevelopment implicates aberrant activation of affective and regulatory regions as key to inhibitory failures. However, many of these studies have not included adolescents engaging in high rates of risky behavior, making generalizations to the most at-risk populations potentially problematic. We conducted a comparative study of nondelinquent community (n = 24, mean age = 15.8 years, 12 female) and delinquent adolescents (n = 24, mean age = 16.2 years, 12 female) who completed a cognitive control task during functional magnetic resonance imaging, where behavioral inhibition was …

Neoadjuvant Folfirinox In Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review And Patient-Level Meta-Analysis, Quisette P Janssen, Andrea Wang-Gillam, Et Al.

2010-2019 OA Pubs

BACKGROUND: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated.

METHODS: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.

RESULTS: We included 24 studies …

Discovery Of Selective Toxoplasma Gondii Dihydrofolate Reductase Inhibitors For The Treatment Of Toxoplasmosis, Allen T Hopper, Adam Brockman, Andy Wise, Julie Gould, Jennifer Barks, Joshua B Radke, L. David Sibley, Yongmao Zou, Stephen Thomas

2010-2019 OA Pubs

A safer treatment for toxoplasmosis would be achieved by improving the selectivity and potency of dihydrofolate reductase (DHFR) inhibitors, such as pyrimethamine (1), for Toxoplasma gondii DHFR ( TgDHFR) relative to human DHFR ( hDHFR). We previously reported on the identification of meta-biphenyl analog 2, designed by in silico modeling of key differences in the binding pocket between TgDHFR and hDHFR. Compound 2 improves TgDHFR selectivity 6.6-fold and potency 16-fold relative to 1. Here, we report on the optimization and structure-activity relationships of this arylpiperazine series leading to the discovery of 5-(4-(3-(2-methoxypyrimidin-5-yl)phenyl)piperazin-1-yl)pyrimidine-2,4-diamine 3. Compound 3 has a TgDHFR IC

Gen-1 Immunotherapy For The Treatment Of Ovarian Cancer, Premal H Thaker, Nicholas Borys, Jason Fewell, Khursheed Anwer

2010-2019 OA Pubs

GEN-1 is a gene-based immunotherapy, comprising a human IL-12 gene expression plasmid and a synthetic plasmid delivery system, delivered intraperitoneally (ip.) to produce local and persistent levels of a pleiotropic immunocytokine, IL-12, at the tumor site in patients with advanced ovarian cancer. The goal of local and persistent IL-12 delivery is to remodel the highly immunosuppressive tumor microenvironment to favor immune stimulation while avoiding serious systemic toxicities, a major limitation of recombinant IL-12 therapy. Safe and sustained local production of IL-12 and related immunocytokines at the tumor site could produce potentially more favorable immunological changes in the tumor microenvironment and …

White Matter Damage, Neuroinflammation, And Neuronal Integrity In Hand, Aljoharah Alakkas, David B Clifford, Et Al.

2010-2019 OA Pubs

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds …

Association Between Reductions Of Number Of Cigarettes Smoked Per Day And Mortality Among Older Adults In The United States, Maki Inoue-Choi, Patricia Hartge, Yikyung Park, Christian C Abnet, Neal D Freedman

2010-2019 OA Pubs

Many smokers do not quit but instead reduce the number of cigarettes they smoke per day (CPD) over their lifetime. Yet the associations of such changes in CPD with health risks are unclear. We examined the association of changes in CPD with subsequent death in the period 2004-2011 among 253,947 participants of the National Institutes of Health-AARP Diet and Health Study. Using a questionnaire assessing responders' history of smoking cigarettes, we identified cigarette smokers who quit, decreased, maintained, or increased their CPD between ages 25-29 and 50-59 years. Hazard ratios and 95% confidence intervals were obtained from multivariable adjusted Cox …

Reward Improves Response Inhibition By Enhancing Attentional Capture, Yanqing Wang, Todd S Braver, Shouhang Yin, Xueping Hu, Xiangpeng Wang, Antao Chen

2010-2019 OA Pubs

Reward plays a crucial role in enhancing response inhibition. While it is generally assumed that the process of response inhibition involves attentional capture and the stopping of action, it is unclear whether this reflects a direct impact of reward on response inhibition or rather an indirect mediation via attentional capture. Here, we employed a revised stop-signal task (SST) that separated these two cognitive elements, by including a continue signal that required the same motor response as in go trials, but also attention to a cue, as in stop trials. We first confirmed the engagement of the right inferior frontal gyrus …

Understanding The Association Between Negative Symptoms And Performance On Effort-Based Decision-Making Tasks: The Importance Of Defeatist Performance Beliefs, L Felice Reddy, William P Horan, Deanna M Barch, Robert W Buchanan, James M Gold, Stephen R Marder, Jonathan K Wynn, Jared Young, Michael F Green

2010-2019 OA Pubs

Effort-based decision-making paradigms are increasingly utilized to gain insight into the nature of motivation deficits. Research has shown associations between effort-based decision making and experiential negative symptoms; however, the associations are not consistent. The current study had two primary goals. First, we aimed to replicate previous findings of a deficit in effort-based decision making among individuals with schizophrenia on a test of cognitive effort. Second, in a large sample combined from the current and a previous study, we sought to examine the association between negative symptoms and effort by including the related construct of defeatist beliefs. The results replicated previous …

White Matter Diffusion Alterations Precede Symptom Onset In Autosomal Dominant Alzheimer's Disease, Miguel Ángel Araque Caballero, Tammie Benzinger, Anne M Fagan, Randall J Bateman, Celeste Karch, John C Morris, Jason Hassenstab, Et Al.

2010-2019 OA Pubs

White matter alterations are present in the majority of patients with Alzheimer's disease type dementia. However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease. In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease. Here, we assessed mean diffusivity alterations in the white matter …

Infectious Complications After Deployment Trauma: Following Wounded Us Military Personnel Into Veterans Affairs Care, Jay R Mcdonald, Stephen Y Liang, Ping Li, Salwa Maalouf, Clinton K Murray, Amy C Weintrob, Elizabeth R Schnaubelt, Janis Kuhn, Anuradha Ganesan, William Bradley, David R Tribble, Infectious Disease Clinical Research Program Trauma Infectious Disease Outcomes Study Group

2010-2019 OA Pubs

BACKGROUND: Infectious complications related to deployment trauma significantly contribute to the morbidity and mortality of wounded service members. The Trauma Infectious Disease Outcomes Study (TIDOS) collects data on US military personnel injured in Iraq and Afghanistan in an observational cohort study of infectious complications. Patients enrolled in TIDOS may also consent to follow-up through the Department of Veterans Affairs (VA). We present data from the first 337 TIDOS enrollees to receive VA healthcare.

METHODS: Data were collected from the Department of Defense (DoD) Trauma Registry, TIDOS infectious disease module, DoD and VA electronic medical records, and telephone interview. Cox proportional …

Randomized, Double-Blind, Phase Ii Study Of Temozolomide In Combination With Either Veliparib Or Placebo In Patients With Relapsed-Sensitive Or Refractory Small-Cell Lung Cancer, M Catherine Pietanza, Saiama N Waqar, Et Al

2010-2019 OA Pubs

Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m

Transcription Factor Gata4 Associates With Mesenchymal-Like Gene Expression In Human Hepatoblastoma Cells, Tea Soini, Katja Eloranta, Marjut Pihlajoki, Antti Kyrönlahti, Oyediran Akinrinade, Noora Andersson, Jouko Lohi, Mikko P Pakarinen, David B Wilson, Markku Heikinheimo

2010-2019 OA Pubs

GATA4, a transcription factor crucial for early liver development, has been implicated in the pathophysiology of hepatoblastoma, an embryonal tumor of childhood. However, the molecular and phenotypic consequences of GATA4 expression in hepatoblastoma are not fully understood. We surveyed GATA4 expression in 24 hepatoblastomas using RNA in situ hybridization and immunohistochemistry. RNA interference was used to inhibit GATA4 in human HUH6 hepatoblastoma cells, and changes in cell migration were measured with wound healing and transwell assays. RNA microarray hybridization was performed on control and GATA4 knockdown HUH6 cells, and differentially expressed genes were validated by quantitative polymerase chain reaction or …

Left Frontal Hub Connectivity Delays Cognitive Impairment In Autosomal-Dominant And Sporadic Alzheimer's Disease, Nicolai Franzmeier, Anne M Fagan, Katrina Paumier, Tammie Benzinger, John C Morris, Randall J Bateman, Et Al.

2010-2019 OA Pubs

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left …

Insights Into Onchocerca Volvulus Population Biology Through Multilocus Immunophenotyping, Carmelle T Norice-Tra, José Ribeiro, Sasisekhar Bennuru, Michael P Fay, Rahul Tyagi, Makedonka Mitreva, Thomas B Nutman

2010-2019 OA Pubs

We have developed a serologically based immunophenotyping approach to study Onchocerca volvulus (Ov) population diversity. Using genomic sequence data and polymerase chain reaction-based genotyping, we identified nonsynonymous single-nucleotide polymorphisms (SNPs) in the genes of 16 major immunogenic Ov proteins: Ov-CHI-1/Ov-CHI-2, Ov16, Ov-FAR-1, Ov-CPI-1, Ov-B20, Ov-ASP-1, Ov-TMY-1, OvSOD1, OvGST1, Ov-CAL-1, M3/M4, Ov-RAL-1, Ov-RAL-2, Ov-ALT-1, Ov-FBA-1, and Ov-B8. We assessed the immunoreactivity of onchocerciasis patient sera (n = 152) from the Americas, West Africa, Central Africa, and East Africa against peptides derived from 10 of these proteins containing SNPs. Statistically significant variation in immunoreactivity among the regions was seen in SNP-containing peptides …