tbuckley/cabot-search huggingface dataset:
Relationship Between Concussion and Neuropsychological Performance in College Football Players
Authors: Michael W. Collins, Scott H. Grindel, Mark R. Lovell, Duane E. Dede, David J. Moser, Benjamin R. Phalin, Sally Nogle, Michael Wasik, David Cordry, Michelle Klotz Daugherty, Samuel F. Sears, Guy Nicolette, Peter Indelicato, Douglas B. McKeag
Journal: JAMA (1999)

ContextDespite the high prevalence and potentially serious outcomes associated with concussion in athletes, there is little systematic research examining risk factors and short- and long-term outcomes.ObjectivesTo assess the relationship between concussion history and learning disability (LD) and the association of these variables with neuropsychological performance and to evaluate postconcussion recovery in a sample of college football players.Design, Setting, and ParticipantsA total of 393 athletes from 4 university football programs across the United States received preseason baseline evaluations between May 1997 and February 1999. Subjects who had subsequent football-related acute concussions (n=16) underwent neuropsychological comparison with matched control athletes from within the sample (n=10).Main Outcome MeasuresClinical interview, 8 neuropsychological measures, and concussion symptom scale ratings at baseline and after concussion.ResultsOf the 393 players, 129 (34%) had experienced 1 previous concussion and 79 (20%) had experienced 2 or more concussions. Multivariate analysis of variance yielded significant main effects for both LD (P&lt;.001) and concussion history (P=.009), resulting in lowered baseline neuropsychological performance. A significant interaction was found between LD and history of multiple concussions and LD on 2 neuropsychological measures (Trail-Making Test, Form B [P=.007] and Symbol Digit Modalities Test [P=.009]), indicating poorer performance for the group with LD and multiple concussions compared with other groups. A discriminant function analysis using neuropsychological testing of athletes 24 hours after acute in-season concussion compared with controls resulted in an overall 89.5% correct classification rate.ConclusionsOur study suggests that neuropsychological assessment is a useful indicator of cognitive functioning in athletes and that both history of multiple concussions and LD are associated with reduced cognitive performance. These variables may be detrimentally synergistic and should receive further study.
Pathology of incipient pancreatic cancer
Authors: R.H. Hruban, R.E. Wilentz, M. Goggins, G.J.A. Offerhaus, C.J. Yeo, S.E. Kern
Journal: Annals of Oncology (1999)

An understanding of incipient pancreatic neoplasia is an essential foundation for the future development of effective screening tests for pancreatic cancer. Only when we understand early pancreatic neoplasms will we be able to detect tumors that are curable with surgical resection.Two approaches have helped define incipient pancreatic neoplasia. First, the histologic examination of pancreata has helped identify the most common histologic lesions in pancreatic tissues adjacent to infiltrating carcinomas. The assumption is that some of these lesions represent the precursors to the infiltrating cancers. Second, advances in molecular genetics now make it possible to define the genetic alterations present in small lesions. The demonstration that a suspected precursor lesion and an infiltrating pancreatic carcinoma share the same genetic alterations would help establish that the lesion is indeed a precursor to infiltrating pancreatic carcinoma.A spectrum of intraductal proliferations in the pancreas has been found associated with infiltrating adenocarcinoma of the pancreas. These lesions, called "duct lesions," have even been identified in pancreata years before patients develop infiltrating carcinoma. Molecular genetic analysis of these lesions has revealed that they frequently harbor many of the same alterations present in infiltrating carcinoma of the pancreas. These alterations include activation of K-ras and inactivation of p16, p53 and, rarely BRCA2.From these morphologic and molecular observations, we can now develop a progression model for the development of infiltrating carcinoma of the pancreas. Infiltrating carcinomas of the pancreas may arise from pancreatic duct lesions, and the progression of duct lesions to infiltrating cancer is associated with the accumulation of generalized and specific genetic alterations.
CPTH6, a Thiazole Derivative, Induces Histone Hypoacetylation and Apoptosis in Human Leukemia Cells
Authors: Daniela Trisciuoglio, Ylenia Ragazzoni, Andrea Pelosi, Marianna Desideri, Simone Carradori, Chiara Gabellini, Giovanna Maresca, Riccardo Nescatelli, Daniela Secci, Adriana Bolasco, Bruna Bizzarri, Chiara Cavaliere, Igea D'Agnano, Patrizia Filetici, Lucia Ricci-Vitiani, Maria Giulia Rizzo, Donatella Del Bufalo
Journal: Clinical Cancer Research (2011)

We previously identified novel thiazole derivatives able to reduce histone acetylation and histone acetyltransferase (HAT) activity in yeast. Among these compounds, 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl]hydrazone (CPTH6) has been selected and used throughout this study.The effect of CPTH6 on histone acetylation, cell viability and differentiation, cell-cycle distribution, and apoptosis in a panel of acute myeloid leukemia and solid tumor cell lines has been evaluated.Here, we showed that CPTH6 leads to an inhibition of Gcn5 and pCAF HAT activity. Moreover, it inhibits H3/H4 histones and α-tubulin acetylation of a panel of leukemia cell lines. Concentration- and time-dependent inhibition of cell viability, paralleled by accumulation of cells in the G(0)/G(1) phase and depletion from the S/G(2)M phases, was observed. The role of mitochondrial pathway on CPTH6-induced apoptosis was shown, being a decrease of mitochondrial membrane potential and the release of cytochrome c, from mitochondria to cytosol, induced by CPTH6. Also the involvement of Bcl-2 and Bcl-xL on CPTH6-induced apoptosis was found after overexpression of the two proteins in leukemia cells. Solid tumor cell lines from several origins were shown to be differently sensitive to CPTH6 treatment in terms of cell viability, and a correlation between the inhibitory efficacy on H3/H4 histones acetylation and cytotoxicity was found. Differentiating effect on leukemia and neuroblastoma cell lines was also induced by CPTH6.These results make CPTH6 a suitable tool for discovery of molecular targets of HAT and, potentially, for the development of new anticancer therapies, which warrants further investigations.
Endoscopic submucosal dissection of an unusual flat rectal neoplasm
Authors: Francesco Azzolini, Paolo Cecinato, Veronica Iori, Loredana De Marco, Ramona Zecchini, Cristina Fodero, Cristiana Tioli, Romano Sassatelli
Journal: Gut (2014)

A 63-year-old woman was admitted to our gastroenterology unit to undergo a screening colonoscopy, scheduled for faecal occult blood test positivity. During the procedure, a flat, rectal granular lesion was found. With the use of magnification and narrow band image (NBI) technology, the lesion was diagnosed as a laterally spreading tumour (LST), granular mixed type, 30 mm in maximum diameter (figure 1). The pit pattern was unclassifiable and vascular pattern was similar to the type IV of the classification proposed by Inoue regarding the microvasculature pattern of the oesophagus for diagnosis and evaluation of the squamous cell carcinoma. The …
Brain abscess in rheumatoid arthritis
Authors: C-S Lee
Journal: Annals of the Rheumatic Diseases (2003)

A 62 year old man had RA for five years that had been diagnosed according to the 1987 American Rheumatic Association criteria. His disease was well controlled with disease modifying antirheumatic agents (DMARDs). However, the DMARDs were discontinued in March 2000, and he entered a leflunomide clinical trial from April 2000 to August 2000. He improved during the trial. After the trial ended and the leflunomide was discontinued, his joint pain and swelling resumed, so DMARDs were started again.

In December 2000, he arrived in our emergency department with the sudden onset of a disturbance of consciousness, fever, chills, throbbing headache, and left limb weakness for a few days. On physical examination, his temperature was 38.3°C, and he had slurred speech, …
Tetrahydrobiopterin depletion and NOS2 uncoupling contribute to heart failure-induced alterations in atrial electrophysiology
Authors: Yoshinori Nishijima, Arun Sridhar, Ingrid Bonilla, Murugesan Velayutham, Mahmood Khan, Radmila Terentyeva, Chun Li, Periannan Kuppusamy, Terry S. Elton, Dmitry Terentyev, Sandor Györke, Jay L. Zweier, Arturo J. Cardounel, Cynthia A. Carnes
Journal: Cardiovascular Research (2011)

Heart failure is a common antecedent to atrial fibrillation; both heart failure and atrial fibrillation are associated with increased myocardial oxidative stress. Chronic canine heart failure reduces atrial action potential duration and atrial refractoriness. We hypothesized that inducible nitric oxide synthase 2 (NOS2) contributes to atrial oxidative stress and electrophysiologic alterations. A 16-week canine tachypacing model of heart failure was used (n= 21). At 10 weeks, dogs were randomized to either placebo (n = 12) or active treatment (n = 9) with NOS cofactor, tetrahydrobiopterin (BH4, 50 mg), and NOS substrate (l-arginine, 3 g) twice daily for 6 weeks. A group of matched controls (n = 7) was used for comparison. Heart failure increased atrial NOS2 and reduced atrial BH4, while l-arginine was unchanged. Treatment reduced inducible atrial fibrillation and normalized the heart failure-induced shortening of the left atrial myocyte action potential duration. Treatment increased atrial [BH4] while [l-arginine] was unchanged. Treatment did not improve left ventricular function or dimensions. Heart failure-induced reductions in atrial [BH4] resulted in NOS uncoupling, as measured by NO and superoxide anion (O2·−) production, while BH4 and l-arginine treatment normalized NO and O2·−. Heart failure resulted in left atrial oxidative stress, which was attenuated by BH4 and l-arginine treatment. Chronic non-ischaemic heart failure results in atrial oxidative stress and electrophysiologic abnormalities by depletion of BH4 and uncoupling of NOS2. Modulation of NOS2 activity by repletion of BH4 may be a safe and effective approach to reduce the frequency of atrial arrhythmias during heart failure.
Developing a Screening Program to Detect Sight-Threatening Diabetic Retinopathy in South India
Authors: Perumalsamy Namperumalsamy, Praveen K. Nirmalan, Kim Ramasamy
Journal: Diabetes Care (2003)

OBJECTIVE—To develop a screening protocol for detection of sight-threatening diabetic retinopathy in south India. RESEARCH DESIGN AND METHODS—We performed ophthalmic examinations, including posterior segment examination, using indirect ophthalmoscopy to detect sight-threatening retinopathy in patients with diabetes in screening camps targeting a high-risk population. RESULTS—We examined 3,949 persons with diabetes in 32 screening camps over a 13-month period beginning July 2001. Most of the patients (93.6%) were aware of their diabetic status, and 84.2% of those aware of their diabetes status were on treatment. One-fifth of those screened had evidence for any retinopathy; only 6.1% of these persons had evidence of past ophthalmic treatment for retinopathy. Only one-quarter of those diagnosed with worse than mild retinopathy came for follow-up to the base hospital within 2 months. CONCLUSIONS—Screening high-risk groups for sight-threatening retinopathy using indirect ophthalmoscopy may be a useful short-term alternative for India until retinal photography becomes affordable. In addition to strategies to improve coverage, strategies for better follow-up of subjects screened also need to be evolved.
Cardiac troponin T and familial hypertrophic cardiomyopathy: an energetic affair
Authors: Ketty Schwartz, Jean-Jacques Mercadier
Journal: Journal of Clinical Investigation (2003)

It has long been noted that while patients with familial hypertrophic cardiomyopathy due to cardiac troponin T (cTnT) mutations often suffer sudden cardiac death, they do not develop significant ventricular hypertrophy, suggesting that a distinct cellular mechanism apart from alterations in myocardial contractility is responsible. A new study has revealed that a single missense mutation in cTnT causes a striking disruption to energy metabolism, leading to cardiomyopathy.
Rescue of cardiomyocyte dysfunction by phospholamban ablation does not prevent ventricular failure in genetic hypertrophy
Authors: Qiujing Song, Albrecht G. Schmidt, Harvey S. Hahn, Andrew N. Carr, Beate Frank, Luke Pater, Mike Gerst, Karen Young, Brian D. Hoit, Bradley K. McConnell, Kobra Haghighi, Christine E. Seidman, Jonathan G. Seidman, Gerald W. Dorn, Evangelia G. Kranias
Journal: Journal of Clinical Investigation (2003)

Cardiac hypertrophy, either compensated or decompensated, is associated with cardiomyocyte contractile dysfunction from depressed sarcoplasmic reticulum (SR) Ca(2+) cycling. Normalization of Ca(2+) cycling by ablation or inhibition of the SR inhibitor phospholamban (PLN) has prevented cardiac failure in experimental dilated cardiomyopathy and is a promising therapeutic approach for human heart failure. However, the potential benefits of restoring SR function on primary cardiac hypertrophy, a common antecedent of human heart failure, are unknown. We therefore tested the efficacy of PLN ablation to correct hypertrophy and contractile dysfunction in two well-characterized and highly relevant genetic mouse models of hypertrophy and cardiac failure, Galphaq overexpression and human familial hypertrophic cardiomyopathy mutant myosin binding protein C (MyBP-C(MUT)) expression. In both models, PLN ablation normalized the characteristically prolonged cardiomyocyte Ca(2+) transients and enhanced unloaded fractional shortening with no change in SR Ca(2+) pump content. However, there was no parallel improvement in in vivo cardiac function or hypertrophy in either model. Likewise, the activation of JNK and calcineurin associated with Galphaq overexpression was not affected. Thus, PLN ablation normalized contractility in isolated myocytes, but failed to rescue the cardiomyopathic phenotype elicited by activation of the Galphaq pathway or MyBP-C mutations.
Role of the JAK/STAT Pathway in Rat Carotid Artery Remodeling After Vascular Injury
Authors: Yukihiko Seki, Hisashi Kai, Rei Shibata, Tsuyoshi Nagata, Hideo Yasukawa, Akihiko Yoshimura, Tsutomu Imaizumi
Journal: Circulation Research (2000)

Abstract —In cultured vascular smooth muscle cells (VSMCs), Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are expressed constitutively and play a role in angiotensin II (Ang II)–induced intracellular signaling and proliferation. However, little is known regarding the relevance of these proteins to the process of vascular remodeling. The role of JAK and STAT proteins in vascular remodeling and their functional coupling with Ang II were examined in balloon-injured rat carotid artery. Immunoreactive Jak2, Tyk2, Stat1, and Stat3 were not detected in the intact artery. Immunohistostaining showed transient expressions of these JAKs and STATs in medial and neointimal VSMCs at days 2 and 5, respectively, with a peak at day 7 in both layers. The expressions declined to insignificant levels by day 14. Ang II type 1 receptors (AT 1 s) were coexpressed in the medial and neointimal VSMCs expressing Jak2 and Stat3. The Jak2 and Stat3 inductions in the injured artery were accompanied by constitutive Jak2 and Stat3 phosphorylations, which were enhanced by ex vivo Ang II stimulation via AT 1 . Additionally, a Jak2 inhibitor, AG490, blocked the Ang II–induced Stat3 phosphorylation. Furthermore, local treatment with AG490 inhibited constitutive Stat3 phosphorylation and neointimal VSMC replication and subsequently reduced neointima formation in the injured artery. In conclusion, JAK and STAT proteins were inducible in medial and neointimal VSMCs after vascular injury and were functionally coupled to AT 1 . The inductions of JAKs and STATs would be involved in the mechanisms of neointima formation after vascular injury. ( Circ Res. 2000;87:12-18.)
Common Genetic Variants on 6q24 Associated With Exceptional Episodic Memory Performance in the Elderly
Authors: Sandra Barral, Stephanie Cosentino, Kaare Christensen, Anne B. Newman, Thomas T. Perls, Michael A. Province, Richard Mayeux
Journal: JAMA Neurology (2014)

IMPORTANCE There are genetic influences on memory ability as we age, but no specific genes have been identified.OBJECTIVE To use a cognitive endophenotype, exceptional episodic memory (EEM) performance, derived from nondemented offspring from the Long Life Family Study (LLFS) to identify genetic variants that may be responsible for the high cognitive performance of LLFS participants and further replicate these variants using an additional 4006 nondemented individuals from 4 independent elderly cohorts.DESIGN, SETTING, AND PARTICIPANTS A total of 467 LLFS participants from 18 families with 2 or more offspring that exhibited exceptional memory performance were used for genome-wide linkage analysis.Adjusted multivariate linear analyses in the 40-megabase region encompassing the linkage peak were conducted using 4 independent replication data sets that included 4006 nondemented elderly individuals.Results of the individual replication cohorts were combined by meta-analysis.MAIN OUTCOME MEASURE Episodic memory scores computed as the mean of the 2 standardized measures of Logical Memory IA and IIA.RESULTS Heritability estimates indicated a significant genetic component for EEM (h 2 = 0.21; SE = 0.09).Genome-wide linkage analysis revealed that EEM was linked to the 6q24 region (maximum logarithm of odds score, 3.64).Association analysis in LLFS families identified single-nucleotide polymorphisms (SNPs) nominally associated with EEM in the 40-megabase window encompassing the linkage peak.Replication in one cohort identified a set of 26 SNPs associated with episodic memory (P Յ .05).Meta-analysis of the 26 SNPs using the 4 independent replication cohorts found SNPs rs9321334 and rs6902875 to be nominally significantly associated with episodic memory (P = .009and P = .013,respectively).With meta-analysis restricted to individuals lacking an APOE ε4 allele, SNP rs6902875 became statistically significant (meta-analysis, P = 6.7 × 10 -5 ).Haplotype analysis incorporating the 2 SNPs flanking rs6902875 (rs9321334 and rs4897574) revealed that the A-A-C haplotype was significantly associated with episodic memory performance (P = 2.4 × 10 -5 ).This genomic region harbors monooxygenase dopamine β-hydroxylase-like 1 gene (MOXD1), implicated in the biosynthesis of norepinephrine, which is prominently involved in cognitive functions. CONCLUSIONS AND RELEVANCEThe results provide strong evidence for potential candidate genes related to EEM on 6q24.Identifying the genes will help in understanding the biological basis of memory performance and allow interventions for enhancement of cognitive function.
The Stroop smartphone application is a short and valid method to screen for minimal hepatic encephalopathy
Authors: Jasmohan S. Bajaj, Leroy R. Thacker, Douglas M. Heuman, Michael Fuchs, Richard K. Sterling, Arun J. Sanyal, Puneet Puri, Mohammad S. Siddiqui, Richard T. Stravitz, Iliana Bouneva, Velimir Luketic, Nicole Noble, Melanie B. White, Pamela Monteith, Ariel Unser, James B. Wade
Journal: Hepatology (2013)

Minimal hepatic encephalopathy (MHE) detection is difficult because of the unavailability of short screening tools. Therefore, MHE patients can remain undiagnosed and untreated. The aim of this study was to use a Stroop smartphone application (app) (EncephalApp_Stroop) to screen for MHE. The app and standard psychometric tests (SPTs; 2 of 4 abnormal is MHE, gold standard), psychometric hepatic encephalopathy score (PHES), and inhibitory control tests (ICTs) were administered to patients with cirrhosis (with or without previous overt hepatic encephalopathy; OHE) and age-matched controls from two centers; a subset underwent retesting. A separate validation cohort was also recruited. Stroop has an "off" state with neutral stimuli and an "on" state with incongruent stimuli. Outcomes included time to complete five correct runs as well as number of trials needed in on (Ontime) and off (Offtime) states. Stroop results were compared between controls and patients with cirrhosis with or without OHE and those with or without MHE (using SPTs, ICTs, and PHES). Receiver operating characteristic analysis was performed to diagnose MHE in patients with cirrhosis with or without previous OHE. One hundred and twenty-five patients with cirrhosis (43 previous OHE) and 134 controls were included in the original cohort. App times were correlated with Model for End-Stage Liver Disease (Offtime: r = 0.57; Ontime: r = 0.61; P < 0.0001) and were worst in previous OHE patients, compared to the rest and controls. Stroop performance was also significantly impaired in those with MHE, compared to those without MHE, according to SPTs, ICTs, and PHES (all P < 0.0001). A cutoff of >274.9 seconds (Ontime plus Offtime) had an area under the curve of 0.89 in all patients and 0.84 in patients without previous OHE for MHE diagnosis using SPT as the gold standard. The validation cohort showed 78% sensitivity and 90% specificity with the >274.9-seconds Ontime plus Offtime cutoff. App result patterns were similar between the centers. Test-retest reliability in controls and those without previous OHE was good; a learning effect on Ontime in patients with cirrhosis without previous OHE was noted.The Stroop smartphone app is a short, valid, and reliable tool for screening of MHE.
Retention of Low-Density Lipoprotein in Atherosclerotic Lesions of the Mouse
Authors: Maria Gustafsson, Malin Levin, Kristina Skålén, Jeanna Perman, Vincent Fridén, Pernilla Jirholt, Sven-Olof Olofsson, Sergio Fazio, MacRae F. Linton, Clay F. Semenkovich, Gunilla Olivecrona, Jan Borén
Journal: Circulation Research (2007)

Direct binding of apolipoprotein (apo)B-containing lipoproteins to proteoglycans is the initiating event in atherosclerosis, but the processes involved at later stages of development are unclear. Here, we investigated the importance of the apoB-proteoglycan interaction in the development of atherosclerosis over time and investigated the role of lipoprotein lipase (LPL) to facilitate low-density lipoprotein (LDL) retention at later stages of development. Atherosclerosis was analyzed in apoB transgenic mice expressing LDL with normal (control LDL) or reduced proteoglycan-binding (RK3359-3369SA LDL) activity after an atherogenic diet for 0 to 40 weeks. The initiation of atherosclerosis was delayed in mice expressing RK3359-3369SA LDL, but they eventually developed the same level of atherosclerosis as mice expressing control LDL. Retention studies in vivo showed that although higher levels of 131I-tyramine cellobiose-labeled control LDL (131I-TC-LDL) were retained in nonatherosclerotic aortae compared with RK3359-3369SA 131I-TC-LDL, the retention was significantly higher and there was no difference between the groups in atherosclerotic aortae. Lower levels of control 125I-TC-LDL and RK3359-3369SA 125I-TC-LDL were retained in atherosclerotic aortae from ldlr-/- mice transplanted with lpl-/- compared with lpl+/+ bone marrow. Uptake of control LDL or RK3359-3369SA LDL into macrophages with specific expression of human catalytically active or inactive LPL was increased compared with control macrophages. Furthermore, transgenic mice expressing catalytically active or inactive LPL developed the same extent of atherosclerosis. Thus, retention of LDL in the artery wall is initiated by direct LDL-proteoglycan binding but shifts to indirect binding with bridging molecules such as LPL.