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Full-Text Articles in Medicine and Health Sciences

Neutralizing Antibodies Against West Nile Virus Identified Directly From Human B Cells By Single-Cell Analysis And Next Generation Sequencing, K. Tsioris, N. T. Gupta, A. O. Ogunniyi, R. M. Zimnisky, F. Qian, Y. Yao, X. Wang, J. N. Stern, R. Chari, J. C. Love, +8 Additional Authors Jan 2015

Neutralizing Antibodies Against West Nile Virus Identified Directly From Human B Cells By Single-Cell Analysis And Next Generation Sequencing, K. Tsioris, N. T. Gupta, A. O. Ogunniyi, R. M. Zimnisky, F. Qian, Y. Yao, X. Wang, J. N. Stern, R. Chari, J. C. Love, +8 Additional Authors

Journal Articles

West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited …

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Laminar Profile And Physiology Of The Alpha Rhythm In Primary Visual, Auditory, And Somatosensory Regions Of Neocortex, S. Haegens, A. Barczak, G. Musacchia, M. L. Lipton, A. D. Mehta, P. Lakatos, C. E. Schroeder Jan 2015

Laminar Profile And Physiology Of The Alpha Rhythm In Primary Visual, Auditory, And Somatosensory Regions Of Neocortex, S. Haegens, A. Barczak, G. Musacchia, M. L. Lipton, A. D. Mehta, P. Lakatos, C. E. Schroeder

Journal Articles

The functional significance of the alpha rhythm is widely debated. It has been proposed that alpha reflects sensory inhibition and/or a temporal sampling or "parsing" mechanism. There is also continuing disagreement over the more fundamental questions of which cortical layers generate alpha rhythms and whether the generation of alpha is equivalent across sensory systems. To address these latter questions, we analyzed laminar profiles of local field potentials (LFPs) and concomitant multiunit activity (MUA) from macaque V1, S1, and A1 during both spontaneous activity and sensory stimulation. Current source density (CSD) analysis of laminar LFP profiles revealed alpha current generators in …

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Coping With Congenital Hand Differences, L. E. Franzblau, K. C. Chung, N. Carlozzi, A. Y. T. Chin, K. W. Nellans, J. F. Waljee Jan 2015

Coping With Congenital Hand Differences, L. E. Franzblau, K. C. Chung, N. Carlozzi, A. Y. T. Chin, K. W. Nellans, J. F. Waljee

Journal Articles

Background: Although functional outcomes following reconstruction for congenital hand differences are frequently described, much less is known regarding children's ability to cope with the psychosocial effects of these conditions. The authors qualitatively explored stress and coping mechanisms among children following reconstructive surgery for congenital hand differences. Methods: Forty patients and their parents participated in semistructured interviews examining children's stress related to hand functioning and appearance, emotional responses to stress, and coping strategies. Interviews were audiotaped, transcribed, and analyzed thematically. A consensus taxonomy for classifying content evolved from comparisons of coding by two reviewers. Themes expressed by participants were studied for …

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A New Method For Calculating Femoral Anterior Cortex Point Location And Its Effect On Component Sizing And Placement, M. R. Mahfouz, E. E. A. Fatah, L. Bowers, G. Scuderi Jan 2015

A New Method For Calculating Femoral Anterior Cortex Point Location And Its Effect On Component Sizing And Placement, M. R. Mahfouz, E. E. A. Fatah, L. Bowers, G. Scuderi

Journal Articles

Variation in anterior femoral cortex morphology can cause improper component placement and alignment. When surgical inaccuracies occur, the mechanical properties of the distal femur may be altered, which could result in lower surgical success rates and an increased chance of postoperative complications. The purpose of the study is to come up with a reproducible computational algorithm to simulate what the surgeon does in the operating room. This method could help in surgical preplanning, patient-specific instruments, and implant design. From there, we evaluated (1) the angular difference between reference alignment axes; and (2) whether the location of the anterior cortex point …

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Minimally Invasive Knee Arthroplasty: An Overview, A. J. Tria, G. R. Scuderi Jan 2015

Minimally Invasive Knee Arthroplasty: An Overview, A. J. Tria, G. R. Scuderi

Journal Articles

Minimally invasive surgery (MIS) for arthroplasty of the knee began with surgery for unicondylar knee arthroplasty (UKA). Partial knee replacements were designed in the 1970s and were amenable to a more limited exposure. In the 1990s Repicci popularized the MIS for UKA. Surgeons began to apply his concepts to total knee arthroplasty. Four MIS surgical techniques were developed: quadriceps sparing, mini-mid vastus, mini-subvastus, and mini-medial parapatellar. The quadriceps sparing technique is the most limited one and is also the most difficult. However, it is the least invasive and allows rapid recovery. The mini-midvastus is the most common technique because it …

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Neural Circuitry And Immunity, V. Pavlov, K. J. Tracey Jan 2015

Neural Circuitry And Immunity, V. Pavlov, K. J. Tracey

Journal Articles

No abstract provided.

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Accuracy Of The Abc/2 Score For Intracerebral Hemorrhage: Systematic Review And Analysis Of Mistie, Clear-Ivh, And Clear Iii, A. J. Webb, N. L. Ullman, T. C. Morgan, J. Muschelli, J. Kornbluth, I. A. Awad, S. Mayo, M. Rosenblum, R. Narayan, D. F. Hanley, +14 Additional Authors Jan 2015

Accuracy Of The Abc/2 Score For Intracerebral Hemorrhage: Systematic Review And Analysis Of Mistie, Clear-Ivh, And Clear Iii, A. J. Webb, N. L. Ullman, T. C. Morgan, J. Muschelli, J. Kornbluth, I. A. Awad, S. Mayo, M. Rosenblum, R. Narayan, D. F. Hanley, +14 Additional Authors

Journal Articles

BACKGROUND AND PURPOSE: The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography-based planimetry (CTP). METHODS: In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 …

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Hbsc Disease And Spontaneous Epidural Hematoma With Kernohan's Notch Phenomena, M. Yogarajah, C. C. Agu, B. Sivasambu, M. A. Mittler Jan 2015

Hbsc Disease And Spontaneous Epidural Hematoma With Kernohan's Notch Phenomena, M. Yogarajah, C. C. Agu, B. Sivasambu, M. A. Mittler

Journal Articles

Spontaneous (nontraumatic) acute epidural hematoma is a rare and poorly understood complication of sickle cell disease. A 19-year-old African American male with hemoglobin SC disease (HbSC) presented with generalized body aches and was managed for acute painful crisis. During his hospital stay he developed rapid deterioration of his mental status and computed topography revealed a spontaneous massive epidural hematoma with mass effect and midline shift with Kernohan's notch phenomena for which urgent craniotomy and evacuation was done. We report the first case of HbSC disease associated with catastrophic epidural hematoma progressing to transtentorial herniation and Kernohan's notch phenomena within few …

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Cholinergic Anti-Inflammatory Pathway Activity In Dialysis Patients: A Role For Neuroimmunomodulation?, M. Hilderman, A. R. Qureshi, Y. Al-Abed, F. Abtahi, K. Lindecrantz, B. Anderstam, A. Bruchfeld Jan 2015

Cholinergic Anti-Inflammatory Pathway Activity In Dialysis Patients: A Role For Neuroimmunomodulation?, M. Hilderman, A. R. Qureshi, Y. Al-Abed, F. Abtahi, K. Lindecrantz, B. Anderstam, A. Bruchfeld

Journal Articles

BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through the vagus nerve and the alpha-7-nicotinic acetylcholine receptor (alpha7nAChR) on macrophages and immune cells. Sympathetic/parasympathetic imbalance and chronic inflammation are both linked to poor outcome in dialysis patients. The aim of this study was to investigate CAP activity in these patients. METHODS: Twenty dialysis patients, 12 hemodialysis (HD) and 8 peritoneal dialysis (PD) patients (12 male, 8 female; age range 47-83 years) and 8 controls (5 male, 3 female; age range 31-52 years) were analyzed for C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin-1b (IL-1b), IL-6 and IL-10 at baseline. …

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Genome-Wide Association Study Of Late-Onset Myasthenia Gravis: Confirmation Of Tnfrsf11a, And Identification Of Zbtb10 And Three Distinct Hla Associations, M. F. Seldin, O. K. Alkhairy, A. T. Lee, J. A. Lamb, J. Sussman, R. Pirskanen-Matell, F. Piehl, J. J. Verschuuren, P. K. Gregersen, L. Hammarstrom, +9 Additional Authors Jan 2015

Genome-Wide Association Study Of Late-Onset Myasthenia Gravis: Confirmation Of Tnfrsf11a, And Identification Of Zbtb10 And Three Distinct Hla Associations, M. F. Seldin, O. K. Alkhairy, A. T. Lee, J. A. Lamb, J. Sussman, R. Pirskanen-Matell, F. Piehl, J. J. Verschuuren, P. K. Gregersen, L. Hammarstrom, +9 Additional Authors

Journal Articles

To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of >6 million SNPs in 532 LOMG cases (anti-acetylcholine receptor (AChR) antibody positive, onset age >/=50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations [rs4574025, P = 3.9x10-07, odds ratio (OR) = 1.42] and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9x10-10, OR = 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5x10-06, OR =1.62) encoding the PTPN22 R620W variant noted in early-onset MG (EOMG) and other autoimmune …

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Genome-Wide Meta-Analysis In Alopecia Areata Resolves Hla Associations And Reveals Two New Susceptibility Loci, R. C. Betz, L. Petukhova, S. Ripke, H. Huang, A. Menelaou, S. Redler, A. Lee, P. K. Gregersen, A. M. Christiano, +23 Additional Authors Jan 2015

Genome-Wide Meta-Analysis In Alopecia Areata Resolves Hla Associations And Reveals Two New Susceptibility Loci, R. C. Betz, L. Petukhova, S. Ripke, H. Huang, A. Menelaou, S. Redler, A. Lee, P. K. Gregersen, A. M. Christiano, +23 Additional Authors

Journal Articles

Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a …

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International Genome-Wide Meta-Analysis Identifies New Primary Biliary Cirrhosis Risk Loci And Targetable Pathogenic Pathways, H. J. Cordell, Y. Han, G. F. Mells, Y. Li, G. M. Hirschfield, C. S. Greene, G. Xie, B. D. Juran, K. A. Siminovitch, P. Gregersen, +14 Additional Authors Jan 2015

International Genome-Wide Meta-Analysis Identifies New Primary Biliary Cirrhosis Risk Loci And Targetable Pathogenic Pathways, H. J. Cordell, Y. Han, G. F. Mells, Y. Li, G. M. Hirschfield, C. S. Greene, G. Xie, B. D. Juran, K. A. Siminovitch, P. Gregersen, +14 Additional Authors

Journal Articles

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

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Breast Cancer Risk In Metabolically Healthy But Overweight Postmenopausal Women, M. J. Gunter, X. Xie, X. Xue, G. C. Kabat, T. E. Rohan, S. Wassertheil-Smoller, G. Y. Ho, J. Wylie-Rosett, J. Beasley, H. D. Strickler, +2 Additional Authors Jan 2015

Breast Cancer Risk In Metabolically Healthy But Overweight Postmenopausal Women, M. J. Gunter, X. Xie, X. Xue, G. C. Kabat, T. E. Rohan, S. Wassertheil-Smoller, G. Y. Ho, J. Wylie-Rosett, J. Beasley, H. D. Strickler, +2 Additional Authors

Journal Articles

Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin's mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N = 497) and a subcohort (N = 2,830) …

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Differential Expression Of Circulating Micrornas According To Severity Of Colorectal Neoplasia, G. Y. Ho, H. J. Jung, R. E. Schoen, T. Wang, J. Lin, Z. Williams, J. L. Weissfeld, J. Y. Park, O. Loudig, Y. Suh Jan 2015

Differential Expression Of Circulating Micrornas According To Severity Of Colorectal Neoplasia, G. Y. Ho, H. J. Jung, R. E. Schoen, T. Wang, J. Lin, Z. Williams, J. L. Weissfeld, J. Y. Park, O. Loudig, Y. Suh

Journal Articles

There is a need to develop a colorectal cancer (CRC) screening test that is noninvasive, cost effective, and sensitive enough to detect preneoplastic lesions. This case-control study examined the feasibility of using circulating extracellular microRNAs (miRNAs) to differentiate a spectrum of colorectal neoplasia of various severity and hence for early detection of colorectal neoplasia. Archived serum samples of 10 normal controls and 31 cases, including 10 with nonadvanced adenoma, 10 with advanced adenoma, and 11 with CRC, were profiled for circulating miRNAs using next-generation sequencing. Multiple linear regression, adjusting for age, gender, and smoking status, compared controls and the 3 …

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Oral Bisphosphonate Use And Risk Of Postmenopausal Endometrial Cancer, P. A. Newcomb, M. N. Passarelli, A. I. Phipps, G. L. Anderson, J. Wactawski-Wende, G. Y. Ho, M. J. O'Sullivan, R. T. Chlebowski Jan 2015

Oral Bisphosphonate Use And Risk Of Postmenopausal Endometrial Cancer, P. A. Newcomb, M. N. Passarelli, A. I. Phipps, G. L. Anderson, J. Wactawski-Wende, G. Y. Ho, M. J. O'Sullivan, R. T. Chlebowski

Journal Articles

PURPOSE: Bisphosphonates are common medications used for the treatment of osteoporosis and are also used to reduce metastases to bone in patients with cancer. Several studies, including the Women's Health Initiative (WHI), have found that use of bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies. This study was aimed at examining the effects of bisphosphonates on the risk of endometrial cancer. METHODS: We evaluated the relationship between use of oral bisphosphonates and endometrial cancer risk in a cohort of 89,918 postmenopausal women participating in the WHI. A detailed …

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Acute Zonal Occult Outer Retinopathy; Revisited, A. Tavallali, L. A. Yannuzzi Jan 2015

Acute Zonal Occult Outer Retinopathy; Revisited, A. Tavallali, L. A. Yannuzzi

Journal Articles

No abstract provided.

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Calreticulin Mutated Essential Thrombocythemia Presenting As Acute Coronary Syndrome, B. Nazha, G. Garcia, R. Kandov, M. Odaimi Jan 2015

Calreticulin Mutated Essential Thrombocythemia Presenting As Acute Coronary Syndrome, B. Nazha, G. Garcia, R. Kandov, M. Odaimi

Journal Articles

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by a clonal expansion of megakaryocytes. ET can result in both arterial and venous thrombosis. Involvement of the coronary arteries has been reported. Patients who harbor a CALR mutation are half as likely to suffer a thrombotic event as compared to patients with a JAK2 mutation. We report a case of CALR-mutated ET whose initial disease manifestation was a non-ST segment elevation myocardial infarction.

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Antiplatelet Therapy Duration Following Bare Metal Or Drug-Eluting Coronary Stents: The Dual Antiplatelet Therapy Randomized Clinical Trial, D. J. Kereiakes, R. W. Yeh, J. M. Massaro, P. Driscoll-Shempp, I. T. Meredith, J. Ormiston, J. F. Tanguay, S. Windecker, K. N. Garratt, L. Mauri, +9 Additional Authors Jan 2015

Antiplatelet Therapy Duration Following Bare Metal Or Drug-Eluting Coronary Stents: The Dual Antiplatelet Therapy Randomized Clinical Trial, D. J. Kereiakes, R. W. Yeh, J. M. Massaro, P. Driscoll-Shempp, I. T. Meredith, J. Ormiston, J. F. Tanguay, S. Windecker, K. N. Garratt, L. Mauri, +9 Additional Authors

Journal Articles

IMPORTANCE: Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown. OBJECTIVE: To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) …

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Sleep Deficiency And Deprivation Leading To Cardiovascular Disease, M. Kohansieh, A. N. Makaryus Jan 2015

Sleep Deficiency And Deprivation Leading To Cardiovascular Disease, M. Kohansieh, A. N. Makaryus

Journal Articles

Sleep plays a vital role in an individual's mental, emotional, and physiological well-being. Not only does sleep deficiency lead to neurological and psychological disorders, but also the literature has explored the adverse effects of sleep deficiency on the cardiovascular system. Decreased quantity and quality of sleep have been linked to cardiovascular disease (CVD) risk factors, such as hypertension, obesity, diabetes, and dyslipidemia. We explore the literature correlating primary sleep deficiency and deprivation as a cause for cardiovascular disease and cite endothelial dysfunction as a common underlying mechanism.

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Sleep Disorders, Obesity, Hypertension, And Cardiovascular Risk, S. I. Mcfarlane, O. Ogedegbe, A. N. Makaryus, C. Agyemang, G. Jean-Louis Jan 2015

Sleep Disorders, Obesity, Hypertension, And Cardiovascular Risk, S. I. Mcfarlane, O. Ogedegbe, A. N. Makaryus, C. Agyemang, G. Jean-Louis

Journal Articles

No abstract provided.

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A Proteinuria Cut-Off Level Of 0.7 G/Day After 12 Months Of Treatment Best Predicts Long-Term Renal Outcome In Lupus Nephritis: Data From The Maintain Nephritis Trial, F. Tamirou, B. R. Lauwerys, M. Dall'era, M. Mackay, B. Rovin, R. Cervera, F. A. Houssiau, D. Abramowicz, L. De Bruxelles, R. Westhovens, +35 Additional Authors Jan 2015

A Proteinuria Cut-Off Level Of 0.7 G/Day After 12 Months Of Treatment Best Predicts Long-Term Renal Outcome In Lupus Nephritis: Data From The Maintain Nephritis Trial, F. Tamirou, B. R. Lauwerys, M. Dall'era, M. Mackay, B. Rovin, R. Cervera, F. A. Houssiau, D. Abramowicz, L. De Bruxelles, R. Westhovens, +35 Additional Authors

Journal Articles

BACKGROUND: Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). METHODS: Long-term (at least 7 years) renal function data were available for 90 patients randomised …

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Sustaining The Rheumatology Research Enterprise, A. Davidson, D. Polsky Jan 2015

Sustaining The Rheumatology Research Enterprise, A. Davidson, D. Polsky

Journal Articles

No abstract provided.

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Tyk2 Protein-Coding Variants Protect Against Rheumatoid Arthritis And Autoimmunity, With No Evidence Of Major Pleiotropic Effects On Non-Autoimmune Complex Traits, D. Diogo, L. Bastarache, K. P. Liao, R. R. Graham, R. S. Fulton, J. D. Greenberg, S. Eyre, A. Lee, P. K. Gregersen, R. M. Plenge, +44 Additional Authors Jan 2015

Tyk2 Protein-Coding Variants Protect Against Rheumatoid Arthritis And Autoimmunity, With No Evidence Of Major Pleiotropic Effects On Non-Autoimmune Complex Traits, D. Diogo, L. Bastarache, K. P. Liao, R. R. Graham, R. S. Fulton, J. D. Greenberg, S. Eyre, A. Lee, P. K. Gregersen, R. M. Plenge, +44 Additional Authors

Journal Articles

Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to …

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Widespread Non-Additive And Interaction Effects Within Hla Loci Modulate The Risk Of Autoimmune Diseases, T. Lencz, A. J. Deutsch, B. Han, X. Hu, Y. Okada, S. Eyre, M. Knapp, A. Zhernakova, P. K. Gregersen, S. Raychaudhuri, +27 Additional Authors Jan 2015

Widespread Non-Additive And Interaction Effects Within Hla Loci Modulate The Risk Of Autoimmune Diseases, T. Lencz, A. J. Deutsch, B. Han, X. Hu, Y. Okada, S. Eyre, M. Knapp, A. Zhernakova, P. K. Gregersen, S. Raychaudhuri, +27 Additional Authors

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Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (ncases = 5,337), type 1 diabetes (T1D; ncases = 5,567), psoriasis vulgaris (ncases = 3,089), idiopathic achalasia (ncases = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, …

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Pioglitazone In Early Parkinson's Disease: A Phase 2, Multicentre, Double-Blind, Randomised Trial, T. Simuni, K. Kieburtz, B. Tilley, J. J. Elm, B. Ravina, D. Babcock, M. Emborg, Andrew Feigin, R. Zweig, Parkinson Ninds Exploratory Trials, +38 Additinal Authoris Jan 2015

Pioglitazone In Early Parkinson's Disease: A Phase 2, Multicentre, Double-Blind, Randomised Trial, T. Simuni, K. Kieburtz, B. Tilley, J. J. Elm, B. Ravina, D. Babcock, M. Emborg, Andrew Feigin, R. Zweig, Parkinson Ninds Exploratory Trials, +38 Additinal Authoris

Journal Articles

Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with …

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Inflammatory Bowel Disease As A Risk Factor For Premature Coronary Artery Disease, P. Ruisi, J. N. Makaryus, M. Ruisi, A. N. Makaryus Jan 2015

Inflammatory Bowel Disease As A Risk Factor For Premature Coronary Artery Disease, P. Ruisi, J. N. Makaryus, M. Ruisi, A. N. Makaryus

Journal Articles

BACKGROUND: Crohn's disease and ulcerative colitis are both systemic chronic diseases that alter bowel physiology. The central process in inflammatory bowel disease (IBD) and the associated manifestations are the result of B-cell production of IgG autoantibodies directed against self-antigens in various organ systems including coronary endothelium. Previous studies have demonstrated significant micro-vascular endothelial dysfunction in patients with IBD compared to patients not affected by the disease. We sought to analyze the relation, if any, between IBD and the development of premature coronary artery disease (CAD). METHODS: We queried our hospital database to find IBD patients admitted to the hospital from …

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Prescription For Antidepressant In Reducing Future Alcohol-Related Readmission In Patients Suffering From Depression And Alcohol Use Disorder: A Retrospective Medical Record Review, P. Chan, K. Yomen, J. Turcios, M. Richman Jan 2015

Prescription For Antidepressant In Reducing Future Alcohol-Related Readmission In Patients Suffering From Depression And Alcohol Use Disorder: A Retrospective Medical Record Review, P. Chan, K. Yomen, J. Turcios, M. Richman

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BACKGROUND: Patients suffering from major depressive disorder are more likely to suffer from alcohol use disorder. The data is inconclusive for the effectiveness of antidepressant treatment of patients suffering from both illnesses in regards to improving sobriety and reducing alcohol-related healthcare expenses such as hospitalizations. The objective of this study is to determine if a new prescription of an antidepressant upon inpatient discharge is associated with a reduction in the number of future acute alcohol-related hospital readmissions to the same institution in patients suffering from major depressive disorder and alcohol-use disorder. METHODS: A retrospective, medical record review study was conducted …

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Mu-Opioid Receptor Gene A118 G Variants And Persistent Pain Symptoms Among Men And Women Experiencing Motor Vehicle Collision, S. D. Linnstaedt, J. M. Hu, A. V. Bortsov, A. C. Soward, R. Swor, J. Jones, D. Lee, R. Domeier, P. Hendry, S. A. Mclean, +2 Additional Authors Jan 2015

Mu-Opioid Receptor Gene A118 G Variants And Persistent Pain Symptoms Among Men And Women Experiencing Motor Vehicle Collision, S. D. Linnstaedt, J. M. Hu, A. V. Bortsov, A. C. Soward, R. Swor, J. Jones, D. Lee, R. Domeier, P. Hendry, S. A. Mclean, +2 Additional Authors

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The mu-opioid receptor 1 (OPRM1) binds endogenous opioids. Increasing evidence suggests that endogenous OPRM1 agonists released at the time of trauma may contribute to the development of posttraumatic musculoskeletal pain (MSP). In this prospective observational study, we evaluated the hypothesis that individuals with an AG or GG genotype at the OPRM1 A118 G allele, which results in a reduced response to opioids, would have less severe MSP 6 weeks after motor vehicle collision (MVC). Based on previous evidence, we hypothesized that this effect would be sex-dependent and most pronounced among women with substantial peritraumatic distress. European American men and women …

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Genetic Polymorphisms In The Dopamine Receptor 2 Predict Acute Pain Severity After Motor Vehicle Collision, Y. J. Qadri, A. V. Bortsov, D. C. Orrey, R. A. Swor, D. A. Peak, J. S. Jones, N. K. Rathlev, D. C. Lee, P. L. Hendry, S. A. Mclean, +1 Additional Author Jan 2015

Genetic Polymorphisms In The Dopamine Receptor 2 Predict Acute Pain Severity After Motor Vehicle Collision, Y. J. Qadri, A. V. Bortsov, D. C. Orrey, R. A. Swor, D. A. Peak, J. S. Jones, N. K. Rathlev, D. C. Lee, P. L. Hendry, S. A. Mclean, +1 Additional Author

Journal Articles

Objectives:Dopaminergic signaling is implicated in nociceptive pathways. These effects are mediated largely through dopamine receptors and modulated in part by dopamine transporters. This study tested the hypothesis that genetic variants in the genes encoding dopamine receptor 2 (DRD2) and the dopamine active transporter (SLC6A3) influence acute pain severity after motor vehicle collision.Materials and Methods:European Americans presenting to the emergency department after motor vehicle collision were recruited. Overall pain intensity in emergency department was assessed using a 0 to 10 numeric rating scale. DNA was extracted from blood samples and genotyping of single-nucleotide polymorphisms (SNPs) in the DRD2 and SLC6A3 gene …

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Humoral Immune Response Against Nontargeted Tumor Antigens After Treatment With Sipuleucel-T And Its Association With Improved Clinical Outcome, D. Guhathakurta, N. A. Sheikh, L. Q. Fan, H. Kandadi, T. C. Meagher, S. J. Hall, J. B. Whitmore, M. W. Frohlich, J. B. Trager, C. G. Drake, +7 Additional Authors Jan 2015

Humoral Immune Response Against Nontargeted Tumor Antigens After Treatment With Sipuleucel-T And Its Association With Improved Clinical Outcome, D. Guhathakurta, N. A. Sheikh, L. Q. Fan, H. Kandadi, T. C. Meagher, S. J. Hall, J. B. Whitmore, M. W. Frohlich, J. B. Trager, C. G. Drake, +7 Additional Authors

Journal Articles

PURPOSE: Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). EXPERIMENTAL DESIGN: Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses …

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