tbuckley/cabot-search huggingface dataset:
An updated comparison of high- and low-viscosity cement vertebroplasty in the treatment of osteoporotic thoracolumbar vertebral compression fractures: A retrospective cohort study
Authors: Zhao-fei Zhang, Jun-long Yang, Huan-chang Jiang, Zhen Lai, Feng Wu, Yong-quan Pan, Zhi-xiang Liu
Journal: International Journal of Surgery (2017)
Abstract P100: Gene Targeting of <i>Npr1</i> Reveals Its Repressive Role in Cardiac Hypertrophy and Proinflammatory Cytokine Gene Expression
Authors: Kailash N Pandey, Elangovan Vellaichamy
Journal: Circulation Research (2011)

The objective of the present study was to examine whether genetically determined differences in the Npr1 gene (coding for guanylyl cyclase/natriuretic peptide receptor-A; GC-A/NPRA) affect the expression of cardiac pro-inflammatory cytokines and nuclear factor kappa-B (NF-kB) levels in Npr1 gene-targeted mice. The Npr1 gene-disrupted null mutant ( Npr1 −/− ; 0-copy) mice had 32-38 mmHg higher systolic blood pressure (SBP) and 60% greater heart weight to body weight (HW:BW) ratio, however, Npr1 gene-duplicated mice ( Npr1 ++/++ ; 4-copy) exhibited 10-15 mmHg lower SBP with no change in the HW:BW ratio compared with wild-type ( Npr1 +/+ ; 2-copy) mice. Significant up-regulation of interleukin-6 (IL-6; 2-fold tumor necrosis factor-alpha), TNF-α; 4-fold), and transforming growth factor-beta (TGF-β1; 4-fold), along with increases in NF-κB and activating protein-1 (AP-1) binding activities (170% and 130%, p &lt; 0.01, respectively), were increased in the Npr1 −/− mice hearts. Conversely, a significant decrease in cytokine gene expression and NF-κB and AP-1 binding activities were found in gene-duplicated mice hearts compared with wild-type mice. The ventricular guanylyl cyclase (GC) activity and cGMP levels were reduced by almost 10-fold and 5-fold, respectively, in Npr1 -/- mice. However, GC activity and cGMP levels were increased, respectively, by almost 9-fold and 6-fold, respectively, in gene-duplicated mice. The present results provide direct evidence that duplication of Npr1 gene in mice represses the inflammatory cytokine gene expression via inhibition NF-κB- and AP-1-mediated signaling mechanisms, and is associated with cardiac protection.
GITR ligand fusion protein agonist enhances the tumor antigen–specific CD8 T-cell response and leads to long-lasting memory
Authors: Nick M. Durham, Nick Holoweckyj, Randall S. MacGill, Kelly McGlinchey, Ching Ching Leow, Scott H. Robbins
Journal: Journal for ImmunoTherapy of Cancer (2017)

The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations.We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy. In TC-1, GITRL-FP was also combined with concurrent administration of an E7-SLP vaccine. We evaluated tumor growth inhibition by tumor volume measurements as well as changes in CD8 T cell populations and function including cytokine production using flow cytometry. Additionally, we interrogated how these therapies resulted in tumor antigen-specific responses using MHC-I dextramer staining and antigen-specific restimulations.In this study, we demonstrate that a GITR ligand fusion protein (GITRL-FP) is an effective modulator of antigen-specific CD8 T cells. In a CT26 mouse tumor model, GITRL-FP promoted expansion of antigen-specific T cells, depletion of regulatory T cells (Tregs), and generation of long-lasting CD8 T cell memory. This memory expansion was dependent on the dose of GITRL-FP and resulted in complete tumor clearance and protection from tumor rechallenge. In contrast, in TC-1 tumor-bearing mice, GITRL-FP monotherapy could not prime an antigen-specific CD8 T cell response and was unable to deplete Tregs. However, when combined with a vaccine targeting E7, treatment with GITRL-FP resulted in an augmentation of the vaccine-induced antigen-specific CD8 T cells, the depletion of Tregs, and a potent antitumor immune response. In both model systems, GITR levels on antigen-specific CD8 T cells were higher than on all other CD8 T cells, and GITRL-FP interacted directly with primed antigen-specific CD8 T cells.When taken together, our results demonstrate that the delivery of GITRL-FP as a therapeutic can promote anti-tumor responses in the presence of tumor-specific CD8 T cells. These findings support further study into combination partners for GITRL-FP that may augment CD8 T-cell priming as well as provide hypotheses that can be tested in human clinical trials exploring GITR agonists including GITRL-FP.
Association of Streptococcal Throat Infection With Mental Disorders
Authors: Sonja Orlovska, Claus Høstrup Vestergaard, Bodil Hammer Bech, Merete Nordentoft, Mogens Vestergaard, Michael Eriksen Benros
Journal: JAMA Psychiatry (2017)

<h3>Importance</h3> Streptococcal infection has been linked with the development of obsessive-compulsive disorder (OCD) and tic disorders, a concept termed<i>pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection</i>(PANDAS). However, previous studies of this association have been small, and the results have been conflicting. <h3>Objective</h3> To investigate the risk of mental disorders, specifically OCD and tic disorders, after a streptococcal throat infection. <h3>Design, Setting, and Participants</h3> A population-based cohort study was conducted using data from the nationwide Danish registers from January 1, 1996, to December 31, 2013, with up to 17 years of follow-up. The Danish National Health Service Register provided information on individuals with the registration of a streptococcal test. Data analysis was conducted from January 1, 2016, to February 28, 2017. <h3>Main Outcomes and Measures</h3> Individuals were followed up in the nationwide Psychiatric Central Register for a diagnosis of any mental disorder, OCD, or tic disorders. Incidence rate ratios (IRRs) were calculated by Poisson regression analysis. <h3>Results</h3> Of the 1 067 743 children (&lt;18 years of age) included in the study (519 821 girls and 547 922 boys), 638 265 received a streptococcal test, 349 982 of whom had positive test results at least once. Individuals with a positive streptococcal test result had an increased risk of any mental disorder (n = 15 408; IRR, 1.18; 95% CI, 1.15-1.21;<i>P</i> &lt; .001), particularly of OCD (n = 556; IRR, 1.51; 95% CI, 1.28-1.77;<i>P</i> &lt; .001) and tic disorders (n = 993; IRR, 1.35; 95% CI, 1.21-1.50;<i>P</i> &lt; .001), compared with individuals without a streptococcal test. Furthermore, the risk of any mental disorder and OCD was more elevated after a streptococcal throat infection than after a nonstreptococcal infection. Nonetheless, individuals with a nonstreptococcal throat infection also had an increased risk of any mental disorder (n = 11 315; IRR, 1.08; 95% CI, 1.06-1.11;<i>P</i> &lt; .001), OCD (n = 316; IRR, 1.28; 95% CI, 1.07-1.53;<i>P</i> = .006), and tic disorders (n = 662; IRR, 1.25; 95% CI, 1.12-1.41;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This large-scale study investigating key aspects of the PANDAS hypothesis found that individuals with a streptococcal throat infection had elevated risks of mental disorders, particularly OCD and tic disorders. However, nonstreptococcal throat infection was also associated with increased risks, although less than streptococcal infections for OCD and any mental disorder, which could also support important elements of the diagnostic concept of pediatric acute-onset neuropsychiatric syndrome.
Weight Reduction: Diet and Dishes
Journal: JAMA (1942)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Predicting dihydropyrimidine deshydrogenase (DPD) deficiency in cancer patients: Enzymatic activity in lymphocytes vs uracil/dihydrouracil (U/UH2) ratio determination in plasma
Authors: Joseph Ciccolini, Marie-Christine Etienne-Grimaldi, Nicole Renée, Jean-Louis Formento, Pierre Cuq, Maurice Schneider, Bruno Lacarelle, Gérard Milano
Journal: Cancer Research (2005)

3998   DPD gene polymorphism may lead to dramatic systemic overexposure to 5-FU with subsequent sharp increase in related-toxicities, and possible fatal outcome in patients treated with standard dosage of drug. Actual implication rate of DPD deficiency in iatrogeny of fluoropyrimidines remains to be determined, since usually, little investigation on DPD status is routinely carried out in patients presenting with such severe toxicities. Beside this, impact of DPD gene polymorphism in widely prescribed capecitabine (Xeloda®) toxic profile remains unclear. The aim of the present work was to validate clinically an alternative, simplified method for indexing patients regarding their DPD status, as an attempt to detect next those at risk with fluoropyrimidine drugs. In this study, we performed a retrospective investigation in 35 patients presenting with unanticipated, severe toxicities, including 2 lethal ones, after 5-FU continuous infusion (n=33) and capecitabine intake (n=2). DPD status was evaluated following a basic U/UH2 plasma ratio method (Ciccolini  et al. , J Clin Pham Ther, 2004, 29(4) 307-15). When possible, evaluation of 5-FU plasma concentration was performed. Impaired DPD function was observed in 24 out of 35 patients (68%) displaying severe or lethal toxicities with 5-FU or capecitabine, an implication rate significantly higher than the ones usually reported in the literature. In concordance with DPD impairment, drug exposures up to 15-times higher than the standard ones normally expected in our institute were observed too. Our results show therefore that implication of DPD deficiency in 5-FU-induced toxicities is actually far more frequent than the rate usually suggested in previous studies. Importantly, it was shown for the first time that one grade-III toxicity, and one toxic-death after capecitabine intake could be linked as well with DPD impairment. Systematic detection of patients at risk prior to fluoropyrimidine administration with subsequent dose tailoring should be therefore considered, including when oral capecitabine is scheduled. Besides, the methodology presented here proved to be a simple, rapid and reliable way to predict 5-FU and capecitabine severe toxicities at low cost.
Angiotensin Receptor Blockers Reduce Cardiovascular Events, Including the Risk of Myocardial Infarction
Authors: Franz H. Messerli, Sripal Bangalore
Journal: Circulation (2017)

More than a decade ago, the 15 245-patient VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation), 1 designed to show "that for the same level of blood-pressure (BP) control, valsartan-based treatment would be superior to amlodipine-based treatment in reduction of cardiac morbidity and mortality," unexpectedly fell short in that myocardial infarction (MI) was 19% more common in the valsartan arm than in the amlodipine arm.Because renin-angiotensin system inhibitors, specifically ACEIs, previously were documented to have cardioprotective properties, failure in doing so in VALUE was blamed on valsartan and the ARBs as a class.An accompanying editorial stating that ARBs "may increase MI-and patients may need to be told" 2 caused a tempest in the teapot and led to extensive scrutiny of outcome data with this drug class.Subsequently, a number of investigators have proposed the concept of an "MI paradox" associated with ARBs.There was little question that at the time, in 2004, the editorialists had a point.However, many more solid randomized trials have been completed with results published since then that gradually but relentlessly challenged the above point of view. 3In the following, we analyze in aggregate the evidence of the comparative efficacy and safety of ACEIs and ARBs.When we look at experimental data and cardiac surrogate end points such as regression of left ventricular hypertrophy, no clear differences between ACEIs and ARBs have been demonstrated despite the fact that ARBs activate the potentially deleterious angiotensin II receptor type 2.
Abstract P249: Cardiac Troponin I Pro82Ser Variant Impairs Myofilament Cooperativity, Induces Diastolic Dysfunction, and Blunts β-Adrenergic Response
Authors: Aisha Frazier, Genaro A Ramirez-Correa, Djahida Bedja, Xiaoxu Shen, Wei Dong Gao, Guangshuo Zhu, Oscar H Cingolani, Eiki Takimoto, Anne M Murphy
Journal: Circulation Research (2011)

Cardiac troponin I is a key regulatory protein for muscle contraction and necessary for an adequate β-adrenergic response. The Proline 82 Serine (P82S) sequence variant of troponin I gene ( TNNI3 ) is associated with late onset hypertrophic cardiomyopathy (HCM). Our preliminary data has shown that cTnIP82S is heterozygous in 3% of African Americans and is associated with increased LV mass in hypertensive black men. We hypothesize that cTnIP82S variant could influence the hypertrophic response to hypertension and/or the malignancy of the phenotypic expression when combined with known HCM disease causing myofilament mutations. We created a transgenic cTnIP82S mouse model. Echocardiography at baseline in older Tg and NTg mice (64-65 wks) showed impaired ejection time and relaxation, Tg display longer isovolumetric relaxation time (IVRT) (Tg 29.7±0.26 vs NTg 23± 0.23 msec, n=8 vs n=7 p&lt;0.05) and a significantly higher TEI index. In the young NTg and Tg (17 wks) there were no echocardiographic differences. However, preliminary data suggest that 1 wk after transverse aortic coarctation (TAC), diastolic dysfunction was evident in Tg, and 10 weeks after TAC LV mass was also increased compared to NTg. Skinned fibers studies showed in the Tg mice borderline lower maximal Force (F max ) and myofilament calcium sensitivity, whereas n Hill showed a marked depression (Tg 1.72±0.17 vs NTg 3.09±0.44, n=7 vs n=5, p&lt;0.05), this effect was not due to the global myofilament phosphorylation pattern. In addition, intact twitching cardiac muscle studies in Tg mice revealed an impaired dose-dependent β-adrenergic acceleration of relaxation, evidenced by a failure to increase relaxation ([-dF/dt min]/[+dF/dt max]) and accelerate calcium transients decay after isoproterenol. Pressure-volume (PV) loop studies confirm that Tg mice fail to increase: Δ change in dP/dt max (NTg 4,928.3±7.7 vs Tg 843.3±10.7, n=4 vs n=4 p&lt;0.05) in response to isoproterenol. TnIP82S variant is near a region of TnI-TnT interaction; this could explain its dramatic effects on myofilament cooperativity. Overall these studies suggest that the expression of cTnIP82S variant in the mice heart induces diastolic dysfunction, impairs relaxation at baseline and after β-adrenergic stimulation.
Comparison of spiral versus block curriculum styles in preparing medical students to diagnose and manage concussions
Authors: Alexander D Wright, Sarah K Fraser, Jonathan D Smirl, Paul van Donkelaar
Journal: British Journal of Sports Medicine (2017)

Objective Examine differences between the recently implemented integrated spiral (year 1) and conventional block (years 2-4) MD curriculum at University of British Columbia (UBC) with respect to knowledge of concussion diagnosis and management. Design Cross-sectional survey Setting UBC undergraduate MD program Participants An online survey was distributed to all 1152 students currently enrolled in UBC medical school. To date, 123 surveys have been returned (10.7% response rate) with 58 first year students (integrated spiral curriculum) and 65 students in years 2-4 (conventional block curriculum). Females made up 60% of responses. Interventions Online survey, hosted by FluidSurveys (Fluidware, Ottawa, ON), distributed through email. Outcome measures Questions focused on demographic data, knowledge of concussion definitions, and management considerations. Main results Majority of responses revealed both curriculums have promoted a strong understanding of concussion definition and related symptoms (84% correct response rate). Only 8.1% of participants believed that functional imaging (MRI or CT) is a mandatory assessment tool for concussions. Differences between the conventional and integrated curriculums included: understanding concussions can occur without direct impact to the head (91.4% integrated vs. 69.2% conventional: χ2(1)=43.325, p&lt;0.001) and identifying long-term consequences of repetitive concussive injuries (dementia: 91.4% integrated vs. 66.2% conventional; death or severe disability with second impact syndrome: 77.6% integrated vs. 55.4% conventional). Conclusions The findings from this study reveal a number of positive signs regarding the evolution of medical education in terms of concussion diagnosis and management. The integrated curriculum is taking further steps in advancing concussion knowledge in medical education. Competing interests None.
Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial
Authors: Eve Hornsby, Paul E. Pfeffer, Nancy Laranjo, William Cruikshank, Marina Tuzova, Augusto A. Litonjua, Scott T. Weiss, Vincent J. Carey, George O'Connor, Catherine Hawrylowicz
Journal: Journal of Allergy and Clinical Immunology (2017)

BackgroundProgramming of the immune system during fetal development can influence asthma-related risk factors and outcomes in later life. Vitamin D is a well-recognized immune modulator, and deficiency of this nutrient during pregnancy is hypothesized to influence disease development in offspring.ObjectiveWe sought to investigate the effect on neonatal immunity of maternal supplementation with 4400 IU/d vitamin D3 during the second and third trimesters of pregnancy by using a subset of cord blood samples from a randomized, double-blind, placebo-controlled clinical trial (the Vitamin D Antenatal Asthma Reduction Trial).MethodsCord blood samples from neonates born to mothers supplemented with 4400 IU/d (n = 26) or 400 IU/d (n = 25) of vitamin D3 were analyzed for immune cell composition by flow cytometry, Toll-like receptor (TLR) expression by quantitative PCR, and cytokine secretion after stimulation with mitogenic, TLR, and T-cell stimuli by cytometric bead array. Responsiveness to the glucocorticoid dexamethasone was determined.ResultsSupplementation of mothers with 4400 IU of vitamin D3 resulted in an enhanced broad-spectrum proinflammatory cytokine response of cord blood mononuclear cells to innate and mitogenic stimuli (P = .0009), with an average 1.7- to 2.1-fold increase in levels of several proinflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-6, and IL-8) across stimuli, a higher gene expression level of TLR2 (P = .02) and TLR9 (P = .02), a greater than 4-fold increase in IL-17A (P = .03) production after polyclonal T-cell stimulation, and an enhanced IL-10 response of cord blood mononuclear cells to dexamethasone treatment in culture (P = .018).ConclusionVitamin D exposure during fetal development influences the immune system of the neonate, which can contribute to protection from asthma-related, including infectious, outcomes in early life.Graphical abstract
Racial disparities in concussion knowledge and awareness in american adolescent athletes
Authors: Jessica Wallace, Tracey Covassin, Sally Nogle, Daniel Gould, Jeffrey Kovan
Journal: British Journal of Sports Medicine (2017)

Objective To examine if concussion knowledge and awareness disparities exists between underserved African American (AA) adolescent athletes and Caucasian athletes; and, if disparities exist between AAs with and without access to a full-time athletic trainer (AT). Design Cross-sectional. Setting Participants from 14 US high schools (9 within underserved, AA communities and 5 within predominantly Caucasian communities) completed a one-time paper and pencil knowledge of concussion questionnaire. Participants 577 athletes (372 AA, 205 Caucasian). All participants completed concussion education mandated by the government; participants without documentation of completion were excluded. Intervention Race and AT access were the independent variables. Outcome measures Knowledge of concussion was examined using a validated instrument that included 35 questions. Participants were instructed to identify signs and symptoms of concussion, complications of multiple concussions, and answer questions pertaining to general concussion awareness among distractors. Total knowledge was calculated by summing the number of correct answers out of 35. Scores could range from 0 to 35. Scores closer to 35 represented greater knowledge. Data were analysed with frequency statistics and independent t-tests. Knowledge score was the dependent variable; p=0.05. Main results Caucasian adolescents have greater concussion knowledge than AA adolescents (t (2, 575)=5.47, p&lt;0.001). AA adolescents with access to an AT have more knowledge than AAs lacking access to an AT (t (2, 370)=2.58, p=0.01). Conclusions Participation of AA adolescents in concussion-risk sports, such as football, is very high; therefore, education efforts in underserved communities must address the knowledge gap and disparity of care. Competing interests None.
La technique capillaire améliore la qualité des prélèvements biopsiques échoendoscopiques des tumeurs solides pancréatiques
Authors: M Barret, R El Haddad, F Beuvon, S Grabar, S Leblanc, B Terris, R Coriat, S Chaussade, F Prat
Journal: Endoscopy (2016)

La ponction échoendoscopique est la technique de référence pour diagnostiquer les lésions solides pancréatiques. Nous avons cherché à comparer la technique de prélèvement standard avec aspiration a la technique capillaire, plus récemment décrite, dans laquelle aucune aspiration n'est utilisée, le stylet étant retiré progressivement de l'aiguille à ponction.