tbuckley/cabot-search huggingface dataset:
Traffic-Related Air Pollution, Blood Pressure, and Adaptive Response of Mitochondrial Abundance
Authors: Jia Zhong, Akin Cayir, Letizia Trevisi, Marco Sanchez-Guerra, Xinyi Lin, Cheng Peng, Marie-Abèle Bind, Diddier Prada, Hannah Laue, Kasey J.M. Brennan, Alexandra Dereix, David Sparrow, Pantel Vokonas, Joel Schwartz, Andrea A. Baccarelli
Journal: Circulation (2015)

Background— Exposure to black carbon (BC), a tracer of vehicular-traffic pollution, is associated with increased blood pressure (BP). Identifying biological factors that attenuate BC effects on BP can inform prevention. We evaluated the role of mitochondrial abundance, an adaptive mechanism compensating for cellular-redox imbalance, in the BC-BP relationship. Methods and Results— At ≥1 visits among 675 older men from the Normative Aging Study (observations=1252), we assessed daily BP and ambient BC levels from a stationary monitor. To determine blood mitochondrial abundance, we used whole blood to analyze mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA) using quantitative polymerase chain reaction. Every standard deviation increase in the 28-day BC moving average was associated with 1.97 mm Hg (95% confidence interval [CI], 1.23–2.72; P &lt;0.0001) and 3.46 mm Hg (95% CI, 2.06–4.87; P &lt;0.0001) higher diastolic and systolic BP, respectively. Positive BC-BP associations existed throughout all time windows. BC moving averages (5-day to 28-day) were associated with increased mtDNA/nDNA; every standard deviation increase in 28-day BC moving average was associated with 0.12 standard deviation (95% CI, 0.03–0.20; P =0.007) higher mtDNA/nDNA. High mtDNA/nDNA significantly attenuated the BC-systolic BP association throughout all time windows. The estimated effect of 28-day BC moving average on systolic BP was 1.95-fold larger for individuals at the lowest mtDNA/nDNA quartile midpoint (4.68 mm Hg; 95% CI, 3.03–6.33; P &lt;0.0001), in comparison with the top quartile midpoint (2.40 mm Hg; 95% CI, 0.81–3.99; P =0.003). Conclusions— In older adults, short-term to moderate-term ambient BC levels were associated with increased BP and blood mitochondrial abundance. Our findings indicate that increased blood mitochondrial abundance is a compensatory response and attenuates the cardiac effects of BC.
P0892 : Impact of HCV infection in a HIV cohort followed over 18 years: past and present
Authors: A. Mena, I. Rodriguez Osorio, H. Meijide, Á. Castro Iglesias, S. López Calvo, P. Vázquez Rodríguez, B. Pernas, M. Grandal, J. Domingo Pedreira, E. Poveda
Journal: Journal of Hepatology (2015)
Spleen enlargement is a risk factor for thrombosis in essential thrombocythemia: Evaluation on 1,297 patients
Authors: Alessandro Andriani, Roberto Latagliata, Barbara Anaclerico, Antonio Spadea, Angela Rago, Ambra Di Veroli, Francesca Spirito, Raffaele Porrini, Marianna De Muro, Sabrina Crescenzi Leonetti, Nicoletta Villivà, Cinzia De Gregoris, Enrico Montefusco, Nicola Polverelli, Cristina Santoro, Massimo Breccia, Giuseppe Cimino, Ignazio Majolino, Maria Gabriella Mazzucconi, Nicola Vianelli, Giuliana Alimena, Marco Montanaro, Francesca Palandri
Journal: American Journal of Hematology (2016)

Spleen enlargement, present in 10–20% of Essential Thrombocythemia (ET) patients at diagnosis, is a feature clinically easy to assess, confirmable by echography with a very low chance of misinterpretation. Nonetheless, the clinical and prognostic role of splenomegaly has been seldom evaluated. From 1979 to 2013, 1297 ET patients retrospectively collected in the database of the Lazio Cooperative Group and Bologna University Hospital were evaluable for spleen enlargement at diagnosis and included in the analysis. On the whole, spleen was enlarged in 172/1297 (13.0%) patients; in most cases (94.8%) splenomegaly was mild (≤5 cm). Patients with splenomegaly were younger, predominantly male, presented higher platelet count and JAK2 V617F allele burden and had a lower incidence of concomitant cardiovascular risk factors. At least one thrombotic event during follow‐up occurred in 97/1,125 (8.6%) patients without spleen enlargement compared to 27/172 (15.7%) patients with spleen enlargement ( P = 0.003). Despite comparable use of cytoreductive/antiplatelet therapies in the two groups, the cumulative risk of thrombosis at 5 years was significantly higher in patients with baseline splenomegaly (9.8% versus 4.4% in patients without splenomegaly, P = 0.012). In multivariate analysis exploring risk factors for thrombosis, splenomegaly retained its negative prognostic role, together with previous thrombosis, leucocyte count and male gender. Baseline splenomegaly seems to be an independent additional risk factor for thrombosis in nonstrictly WHO‐defined ET patients. This data could be useful in the real‐life clinical management of these patients. Am. J. Hematol. 91:318–321, 2016. © 2016 Wiley Periodicals, Inc.
Zoledronic acid inhibits adjuvant letrozole-associated bone loss in postmenopausal Japanese women with early breast cancer.
Authors: S. Takahashi, T. Iwase, N. Kohno, T. Ishikawa, T. Taguchi, M. Takahashi, J. Horiguchi, S. Nakamura, M. Fukunaga, S. Noguchi
Journal: Journal of Clinical Oncology (2011)

9075 Background: The primary analysis at 12 months (12M) of the Z-/ZO-FAST studies demonstrated that the loss of bone mineral density (BMD) could be effectively prevented by zoledronic acid (ZA). But there has been few definitive data about aromatase inhibitor (AI)-associated bone loss in Asian women. This study was designed to evaluate an upfront or delayed strategy of bone protection therapy with ZA administered at 4mg every 6Ms in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole (LET) to compare with results of the Z-/ZO-FAST studies in Western countries. Methods: Postmenopausal women with hormone receptor positive early breast cancer receiving adjuvant LET were randomly assigned to receive either upfront or delayed-start ZA (4mg intravenously every 6Ms). The delayed group received ZA when lumbar spine (L2-L4) BMD decreased to less than young adult mean (YAM) – 2.0 S.D or when a nontraumatic fracture occurred. The primary endpoint of this study was to compare the percent change in L1-L4 BMD at 12M between the groups. Secondary endpoints included percent changes in L2-L4 and total hip (TH) BMD and changes in serum bone turnover markers at 12M. Results: The upfront and delayed groups included 94 and 95 patients, respectively. At 12M, L1-L4, L2-L4, TH BMD significantly decreased by 2.0%, 2.4%, 2.4%, respectively, in the delayed group. L1-L4 BMD was 4.9% higher in the upfront group than in the delayed group (95% CI, 3.9-5.8%; p<0.001). L2-L4 BMD was 5.6% higher (95% CI, 4.5-6.6%; p< 0.001), and TH BMD was 4.4% higher (95% CI, 3.3-5.4%; p<0.001). In the upfront group, mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 23.6% (p< 0.001) and 39.4% (p<0.001), respectively, at 12M, whereas concentrations tended to increase in the delayed group by 9.4% (p=0.26) and 10.2% (p= 0.46), respectively. Conclusions: At 12M, upfront ZA therapy prevented bone loss in postmenopausal Japanese women who were receiving adjuvant LET, confirming the Z-/ZO-FAST study results in Western countries.
Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage
Authors: Robert Szulcek, Chris M. Happé, Nina Rol, Ruud D. Fontijn, Chris Dickhoff, Koen J. Hartemink, Katrien Grünberg, Ly Tu, Wim Timens, George D. Nossent, Marinus A. Paul, Thomas A. Leyen, Anton J. Horrevoets, Frances S. de Man, Christophe Guignabert, Paul B. Yu, Anton Vonk-Noordegraaf, Geerten P. van Nieuw Amerongen, Harm J. Bogaard
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Altered pulmonary hemodynamics and fluid flow-induced high shear stress (HSS) are characteristic hallmarks in the pathogenesis of pulmonary arterial hypertension (PAH). However, the contribution of HSS to cellular and vascular alterations in PAH is unclear.We hypothesize that failing shear adaptation is an essential part of the endothelial dysfunction in all forms of PAH and tested whether microvascular endothelial cells (MVECs) or pulmonary arterial endothelial cells (PAECs) from lungs of patients with PAH adapt to HSS and if the shear defect partakes in vascular remodeling in vivo.PAH MVEC (n = 7) and PAH PAEC (n = 3) morphology, function, protein, and gene expressions were compared with control MVEC (n = 8) under static culture conditions and after 24, 72, and 120 hours of HSS.PAH MVEC showed a significantly delayed morphological shear adaptation (P = 0.03) and evidence of cell injury at sites of nonuniform shear profiles that are critical loci for vascular remodeling in PAH. In clear contrast, PAEC isolated from the same PAH lungs showed no impairments. PAH MVEC gene expression and transcriptional shear activation were not altered but showed significant decreased protein levels (P = 0.02) and disturbed interendothelial localization of the shear sensor platelet endothelial cell adhesion molecule-1 (PECAM-1). The decreased PECAM-1 levels were caused by caspase-mediated cytoplasmic cleavage but not increased cell apoptosis. Caspase blockade stabilized PECAM-1 levels, restored endothelial shear responsiveness in vitro, and attenuated occlusive vascular remodeling in chronically hypoxic Sugen5416-treated rats modeling severe PAH.Delayed shear adaptation, which promotes shear-induced endothelial injury, is a newly identified dysfunction specific to the microvascular endothelium in PAH. The shear response is normalized on stabilization of PECAM-1, which reverses intimal remodeling in vivo.
RETRACTED: Plasma PCSK9 Levels and Clinical Outcomes in the TNT (Treating to New Targets) Trial
Authors: Roeland Huijgen, S. Matthijs Boekholdt, Benoit J. Arsenault, Weihang Bao, Jean-Michel Davaine, Fatiha Tabet, Francine Petrides, Kerry-Anne Rye, David A. DeMicco, Philip J. Barter, John J.P. Kastelein, Gilles Lambert
Journal: Journal of the American College of Cardiology (2012)
Abstract 17534: Afferent Vagal Nerve Stimulation Dose Dependently Inhibits Sympathetic Nerve Activity Through the Resetting of Baroreflex Central Arc
Authors: Yasuhiro Oga, Takuya Kishi, Keita Saku, Takamori Kakino, Akiko Nishizaki, Kana Fujii, Takahiro Arimura, Masataka Ikeda, Tomomi Ide, Kenji Sunagawa
Journal: Circulation (2014)

Background: Arterial baroreflex is a powerful regulator of the sympathetic nerve activity (SNA) and arterial pressure (AP). Although vagal nerve stimulation (VNS) has been developed as a neuro-modulatory therapy for heart failure, the impact of VNS on baroreflex and SNA remains unknown. Since the afferent fibers of vagal nerves and of baroreceptors converge in the nucleus tractus solitarii, we investigated how the selective afferent VNS (AVNS) impacts on baroreflex in regulating SNA and AP. Methods: We used 6 anesthetized Sprague-Dawley rats (530±11g). We vascularly isolated bilateral carotid sinuses and servo-controlled intra-sinus pressure (CSP). We measured AP, CSP and splanchnic SNA simultaneously. We attached an electrode to the vagal nerve. We established the baseline intensity (voltage) of VNS that reduced heart rate by 10-20%. We then sectioned the vagal nerve at the caudal side of the electrode. We conducted AVNS at 3 doses, baseline, 2xbaseline and 4xbaseline. We changed CSP stepwise from 60 to 160mmHg to analyze static baroreflex function with/without AVNS. To estimate dynamic baroreflex function, we perturbed CSP using binary random sequence (mean AP±20mmHg) and compared the transfer functions (TF) with/without AVNS. Results: AVNS dose-dependently shifted the CSP-SNA relation downward (p&lt;0.05, Fig. 1) without changing the maximum gain, while did not affect the SNA-AP relation (Fig. 2). The TF of CSP-SNA relation approximated a high pass filter characteristics. AVNS dose-dependently decreased the dynamic gain (Control: 0.72±0.20, baseline: 0.46±0.14, 2xbaseline: 0.38±0.12, 4xbaseline: 0.20±0.08 %/mmHg, p&lt;0.05), whereas did not affect the TF of SNA-AP relation. Conclusions: AVNS dose-dependently suppresses SNA by resetting the static CSP-SNA relation, i.e., the baroreflex central arc. However, AVNS reduces the dynamic gain of baroreflex central arc. We conclude that AVNS lowers SNA at the expense of compromising dynamic AP stabilization.
Phase II study of thymoglobulin, cyclosporine and G-CSF for initial treatment of aplastic anemia and low risk myelodysplastic syndrome
Authors: R. J. Garg, N. Shah, G. Garcia-Manero, S. Stefan Faderl, J. E. Cortes, C. Koller, M. Beran, G. Borthakur, H. M. Kantarjian, F. Ravandi
Journal: Journal of Clinical Oncology (2008)

7093 Background: Aplastic anemia (AA) is commonly treated with equine anti-thymocyte globulin (ATG) and cyclosporine with response rates up to 65%. Thymoglobulin has been used successfully in relapsed/refractory AA, reducing the risk associated with re- administration of equine preparations. Immunosuppressive therapy is also effective in some patients (pts) with myelodysplastic syndrome (MDS). Methods: In this single-arm, phase II study, we investigated efficacy (primary endpoint) and safety (secondary endpoint) of combined thymoglobulin, cyclosporine and G-CSF as a first-line therapy for pts with AA (goal: 30 pts) or low-risk MDS (goal: 30 pts, low or intermediate-1 International Prognostic Scoring System). Thymoglobulin 3.5 mg/kg (or 2.5mg/kg/d for pts ≥55 years) was given for 4 days in the first 10 pts and for 5 days in the remaining pts. Methylprednisone (1 mg/kg/d) was given for 5 days, followed by a tapering dose of oral prednisone. Cyclosporine (5 mg/kg), and G-CSF (5 μg/kg) were also given daily and continued for 6 months or longer. All pts received prophylactic broad-spectrum antibiotics. Responses were assessed approximately 1 to 3 months after therapy. Results: Thirty pts have been enrolled on study; 3 pts chose alternative therapies and 1 pt died before initiation of treatment. Thus 26 (12 with AA and 14 with MDS) have received treatment. Of these, 1 pt was lost to follow-up and 3 have been on study for ≤ 2 months; therefore 10 with AA and 12 with MDS were evaluable. Median age was 65 years (21 - 82) for AA pts and 63 years (47 - 78) for MDS pts. All 10 (100%) AA pts responded (4 CRs, 5 PRs, 1 HI-N). Three of 12 (21%) MDS pts responded (1 CR, 2 PRs). For AA pts median time to response (TTR) was 92 days (30–346) and median response duration was 282 days (14–827). For MDS pts median TTR was 122 days (77–139) and median response duration was 33 days (19–476). Grade 3/4 toxicities were mainly cytopenias and neutropenic fever, occurring in 19 pts (86%). Other grade 3 toxicities included pneumonia, hyperglycemia, elevated ALT and abdominal pain (in 1 patient each). Conclusions: The combination of thymoglobulin, cyclosporine and G-CSF is safe and effective in first-line treatment of AA and has significant activity in low-risk MDS. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genzyme Genzyme
Pandemic Influenza A (H1N1) 2009 and mortality in the United Kingdom: risk factors for death, April 2009 to March 2010
Authors: R  G Pebody, E McLean, H Zhao, P Cleary, S Bracebridge, K Foster, A Charlett, P Hardelid, P Waight, J Ellis, A Bermingham, M Zambon, B Evans, R Salmon, J McMenamin, B Smyth, M Catchpole, J  M Watson
Journal: Eurosurveillance (2010)

This paper describes the epidemiology of fatal pandemic influenza A(H1N1) cases in the United Kingdom (UK) since April 2009 and in particular risk factors associated with death. A fatal case was defined as a UK resident who died between 27 April 2009 and 12 March 2010, in whom pandemic influenza A(H1N1) infection was confirmed by laboratory or recorded on death certificate. Case fatality ratios (CFR) were calculated using the estimated cumulative number of clinical cases as the denominator. The relative risk of death was estimated by comparing the population mortality rate in each risk group, with those not in a risk group. Across the UK, 440 fatal cases were identified. In England, fatal cases were mainly seen in young adults (median age 43 years, 85% under 65 years), unlike for seasonal influenza. The majority (77%) of cases for whom data were available (n=308) had underlying risk factors for severe disease. The CFR in those aged 65 years or over was nine per 1,000 (range 3 - 26) compared to 0.4 (range 0.2 to 0.9) for those aged six months to 64 years. In the age group between six month and 64 years, the relative risk for fatal illness for those in a risk group was 18. The population attributable fractions in this age group were highest for chronic neurological disease (24%), immunosuppression (16%) and respiratory disease (15%). The results highlight the importance of early targeted effective intervention programmes.
Arthroscopic surgery for degenerative knee: Overused, ineffective, and potentially harmful
Authors: Andy Carr
Journal: British Journal of Sports Medicine (2015)

This article presents a review of the neuroanatomy and neurophysiology of joint receptors. The role of joint receptors in signaling position and movement has been studied since the early part of this century. Morphological descriptions and reflexive and kinesthetic contributions of articular receptors in the regulation of motor behavior have been identified in studies on anesthetized animals and to a lesser extent in studies on human subjects. Areas for future laboratory and clinical research include articular receptor input in motor learning and relearning tasks as well as standardization of methodology and responses for assessing joint position.
Final Results from a Cancer Research Uk First in Man Phase I Trial of Ima950 (A Novel Multi Peptide Vaccine) Plus Gm-Csf in Patients with Newly Diagnosed Glioblastoma
Authors: S. Halford, R. Rampling, A. James, S. Peoples, P. Mulholland, O. Al-Salihi, C. Twelves, C. McBain, S. Jefferies, S. Kutscher, N. Hilf, L. McGuigan, J. Peters, K. Roberts, O. Schoor, J. Ritchie, H. Singh-Jasuja
Journal: Annals of Oncology (2014)
CXCL13 drives spinal astrocyte activation and neuropathic pain via CXCR5
Authors: Bao-Chun Jiang, De-Li Cao, Xin Zhang, Zhi-Jun Zhang, Li-Na He, Chun-Hua Li, Wen-Wen Zhang, Xiao-Bo Wu, Temugin Berta, Ru-Rong Ji, Yong-Jing Gao
Journal: Journal of Clinical Investigation (2016)

Recent studies have implicated chemokines in microglial activation and pathogenesis of neuropathic pain. C-X-C motif chemokine 13 (CXCL13) is a B lymphocyte chemoattractant that activates CXCR5. Using the spinal nerve ligation (SNL) model of neuropathic pain, we found that CXCL13 was persistently upregulated in spinal cord neurons after SNL, resulting in spinal astrocyte activation via CXCR5 in mice. shRNA-mediated inhibition of CXCL13 in the spinal cord persistently attenuated SNL-induced neuropathic pain. Interestingly, CXCL13 expression was suppressed by miR-186-5p, a microRNA that colocalized with CXCL13 and was downregulated after SNL. Spinal overexpression of miR-186-5p decreased CXCL13 expression, alleviating neuropathic pain. Furthermore, SNL induced CXCR5 expression in spinal astrocytes, and neuropathic pain was abrogated in Cxcr5–/– mice. CXCR5 expression induced by SNL was required for the SNL-induced activation of spinal astrocytes and microglia. Intrathecal injection of CXCL13 was sufficient to induce pain hypersensitivity and astrocyte activation via CXCR5 and ERK. Finally, intrathecal injection of CXCL13-activated astrocytes induced mechanical allodynia in naive mice. Collectively, our findings reveal a neuronal/astrocytic interaction in the spinal cord by which neuronally produced CXCL13 activates astrocytes via CXCR5 to facilitate neuropathic pain. Thus, miR-186-5p and CXCL13/CXCR5-mediated astrocyte signaling may be suitable therapeutic targets for neuropathic pain.
Ultra Deep Sequencing (UDS) Allows More Sensitive Detection Of Tyrosine Kinase Inhibitor (TKI)-Resistant BCR-ABL Mutations That Would Influence Therapeutic Decision At The Time Of Switchover To Second- Or Third-Line Therapy
Authors: Simona Soverini, Caterina De Benedittis, Katerina Machova Polakova, Adela Brouckova, Fausto Castagnetti, Gabriele Gugliotta, Francesca Palandri, Cristina Papayannidis, Ilaria Iacobucci, Claudia Venturi, Manuela Mancini, Elisa Leo, Hana Klamova, Stefania Paolini, Domenico Russo, Gianantonio Rosti, Michele Baccarani, Michele Cavo, Giovanni Martinelli
Journal: Blood (2013)
Abstract 15137: Vector Flow Mapping is a Novel Useful Technique in Assessing Inertia Force of Late Systolic Aortic Flow and Left Ventricular Early Diastolic Function
Authors: Kazuaki Wakami, Kenta Hachiya, Syunsuke Murai, Tsuyoshi Ito, Hiroshi Fujita, Toshihiko Goto, Hidekatsu Fukuta, Hidekatsu Fukuta, Tomomitsu Tani, Nobuyuki Ohte
Journal: Circulation (2014)

Background: We previously reported that the inertia force (IF) of blood flowing out of left ventricle (LV) during late-systole produces greater LV elastic recoil force and brings faster LV relaxation. Vector flow mapping (VFM TM , Hitachi-Aloka) enables us to see blood flow velocity vectors that are generated from conventional color Doppler imaging data at any phase of cardiac cycle without angle dependency. Using VFM, kinetic energy (KE) of ejecting blood flow during systole at the LV outflow tract (LVOT) can be obtained. Thus, we investigated whether the KE obtained at the LVOT during late systole (KE-ls) had any relations with the IF and invasively obtained LV function parameters. Method: Study subjects were 33 patients who underwent diagnostic cardiac catheterization and echocardiographic examination on the same day. Color Doppler images were acquired in the apical 3-chamber view. The frame rate ranged was from 40 to 51 frames per minute. Data analyses were performed offline using the commercially available software (DAS-RS1 TM, Hitachi-Aloka). A data sampling area was set at the level just below the aortic valve in the LVOT. The KE-ls was computed as the sum of KE values computed in frame by frame basis during late-systole; late-systole was defined as the latter one-third of ejecting time. LV pressure wave was obtained using a catheter-tipped micromanometer, and then, the first derivative of LV pressure (dP/dt) and a time constant τ of LV pressure decay during isovolumic relaxation were calculated. From LV pressure-dP/dt relationships (phase loop), the IF was determined. Results: A significant positive correlation was observed between the KE-ls and the IF (r=0.79, p&lt;0.0001). The log transformed KE-ls had significant correlations with both peak negative dP/dt (r=0.53, p&lt;0.01) and the time constant τ (r=-0.67, p&lt;0.0001). Conclusion: VFM is a new useful technique to see blood flow in the LV chamber. Noninvasively obtained KE-ls using VFM, which may be a noninvasive surrogate for the IF, has significant correlations with the parameters of LV relaxation.