tbuckley/cabot-search huggingface dataset:
Association of Lowering Default Pill Counts in Electronic Medical Record Systems With Postoperative Opioid Prescribing
Authors: Alexander S. Chiu, Raymond A. Jean, Jessica R. Hoag, Mollie Freedman-Weiss, James M. Healy, Kevin Y. Pei
Journal: JAMA Surgery (2018)

Reliance on prescription opioids for postprocedural analgesia has contributed to the opioid epidemic. With the implementation of electronic medical record (EMR) systems, there has been increasing use of computerized order entry systems for medication prescriptions, which is now more common than handwritten prescriptions. The EMR can autopopulate a default number of pills prescribed, and 1 potential method to alter prescriber behavior is to change the default number presented via the EMR system.To investigate the association of lowering the default number of pills presented when prescribing opioids in an EMR system with the amount of opioid prescribed after procedures.A prepost intervention study was conducted to compare postprocedural prescribing patterns during the 3 months before the default change (February 18 to May 17, 2017) with the 3 months after the default change (May 18 to August 18, 2017). The setting was a multihospital health care system that uses Epic EMR (Hyperspace 2015 IU2; Epic Systems Corporation). Participants were all patients in the study period undergoing 1 of the 10 most common operations and discharged by postoperative day 1.The default number of opioid pills autopopulated in the EMR when prescribing discharge analgesia was lowered from 30 to 12.Linear regression estimating the change in the median number of opioid pills and the total dose of opioid prescribed was performed. Opioid doses were converted into morphine milligram equivalents (MME) for comparison. The frequency of patients requiring analgesic prescription refills was also evaluated.There were 1447 procedures (mean [SD] age, 54.4 [17.3] years; 66.9% female) before the default change and 1463 procedures (mean [SD] age, 54.5 [16.4] years; 67.0% female) after the default change. After the default change, the median number of opioid pills prescribed decreased from 30 (interquartile range, 15-30) to 20 (interquartile range, 12-30) per prescription (P < .001). The percentage of prescriptions written for 30 pills decreased from 39.7% (554 of 1397) before the default change to 12.9% (183 of 1420) after the default change (P < .001), and the percentage of prescriptions written for 12 pills increased from 2.1% (29 of 1397) before the default change to 24.6% (349 of 1420) after the default change (P < .001). Regression analysis demonstrated a decrease of 5.22 (95% CI, -6.12 to -4.32) opioid pills per prescription after the default change, for a total decrease of 34.41 (95% CI, -41.36 to -27.47) MME per prescription. There was no statistical difference in opioid refill rates (3.0% [4 of 135] before the default change vs 1.5% [2 of 135] after the default change, P = .41).Lowering the default number of opioid pills prescribed in an EMR system is a simple, effective, cheap, and potentially scalable intervention to change prescriber behavior and decrease the amount of opioid medication prescribed after procedures.
α-Toxin Induces Platelet Aggregation and Liver Injury during Staphylococcus aureus Sepsis
Authors: Bas G.J. Surewaard, Ajitha Thanabalasuriar, Zhutian Zeng, Christine Tkaczyk, Taylor S. Cohen, Bart W. Bardoel, Selina K. Jorch, Carsten Deppermann, Juliane Bubeck Wardenburg, Rachelle P. Davis, Craig N. Jenne, Kendall C. Stover, Bret R. Sellman, Paul Kubes
Journal: Cell Host & Microbe (2018)
Lung epithelial cell-derived IL-25 negatively regulates LPS-induced exosome release from macrophages
Authors: Zhi-Gang Li, Melanie J. Scott, Tomasz Brzóska, Prithu Sundd, Yue-Hua Li, Timothy R. Billiar, Mark A. Wilson, Ping Wang, Jie Fan
Journal: Military Medical Research (2018)

Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome (MODS) following pulmonary and systemic infection. Alveolar macrophages (AMϕ) are at the center of ALI pathogenesis. Emerging evidence has shown that cell-cell interactions in the lungs play an important regulatory role in the development of acute lung inflammation. However, the underneath mechanisms remain poorly addressed. In this study, we explore a novel function of lung epithelial cells (LEPCs) in regulating the release of exosomes from AMϕ following LPS stimulation. For the in vivo experiments, C57BL/6 wildtype (WT) mice were treated with lipopolysaccharide (LPS) (2 mg/kg B.W.) in 0.2 ml of saline via intratracheal aerosol administration. Bronchoalveolar lavage fluid was collected at 0–24 h after LPS treatment, and exosomes derived from AMϕ were measured. For the in vitro studies, LEPCs and bone marrow-derived Mϕ (BMDM) were isolated from WT or TLR4−/− mice and were then cocultured in the Transwell™ system. After coculture for 0–24 h, the BMDM and supernatant were harvested for the measurement of exosomes and cytokines. We demonstrate that LPS induces macrophages (Mϕ) to release exosomes, which are then internalized by neighboring Mϕ to promote TNF-α expression. The secreted interleukin (IL)-25 from LEPCs downregulates Rab27a and Rab27b expression in Mϕ, resulting in suppressed exosome release and thereby attenuating exosome-induced TNF-α expression and secretion. These findings reveal a previously unidentified crosstalk pathway between LEPCs and Mϕ that negatively regulates the inflammatory responses of Mϕ to LPS. Modulating IL-25 signaling and targeting exosome release may present a new therapeutic strategy for the treatment of ALI.
Nature Exposure Gets a Boost From a Cluster Randomized Trial on the Mental Health Benefits of Greening Vacant Lots
Authors: Michael Jerrett, Matilda van den Bosch
Journal: JAMA Network Open (2018)

Eugenia C. South, MD, MS; Bernadette C. Hohl, PhD; Michelle C. Kondo, PhD; John M. MacDonald, PhD; Charles C. Branas, PhD
Effects of In Vivo Nitroglycerin Treatment on Activity and Expression of the Guanylyl Cyclase and cGMP-Dependent Protein Kinase and Their Downstream Target Vasodilator-Stimulated Phosphoprotein in Aorta
Authors: AlexanderMülsch, MatthiasOelze, StefanKlöss, HankeMollnau, AndreaTöpfer, AlbertSmolenski, UlrichWalter, Johannes-PeterStasch, AscanWarnholtz, UlrichHink, ThomasMeinertz, ThomasMünzel
Journal: Circulation (2001)

Background—Chronic in vivo treatment with nitroglycerin (NTG) induces tolerance to nitrates and cross-tolerance to nitrovasodilators and endothelium-derived nitric oxide (NO). We previously identified increased vascular superoxide formation and reduced NO bioavailability as one causal mechanism. It is still controversial whether intracellular downstream signaling to nitrovasodilator-derived NO is affected as well. Methods and Results—We therefore studied the effects of 3-day NTG treatment of rats and rabbits on activity and expression of the immediate NO target soluble guanylyl cyclase (sGC) and on the cGMP-activated protein kinase I (cGK-I). Tolerance was induced either by chronic NTG infusion via osmotic minipumps (rats) or by NTG patches (rabbits). Western blot analysis, semiquantitative reverse transcription–polymerase chain reaction, and Northern blot analysis revealed significant and comparable increases in the expression of sGC α1 and β1 subunit protein and mRNA. Studies with the oxidative fluoresc...
Mitochondrial fidelity and metabolic agility control immune cell fate and function
Authors: Michael N. Sack
Journal: Journal of Clinical Investigation (2018)

Remodeling of mitochondrial metabolism plays an important role in regulating immune cell fate, proliferation, and activity. Furthermore, given their bacterial ancestry, disruption in mitochondrial fidelity leading to extravasation of their content initiates and amplifies innate immune surveillance with a myriad of physiologic and pathologic consequences. Investigations into the role of mitochondria in the immune system have come to the fore, and appreciation of mitochondrial function and quality control in immune regulation has enhanced our understanding of disease pathogenesis and identified new targets for immune modulation. This mitochondria-centered Review focuses on the role of mitochondrial metabolism and fidelity, as well as the role of the mitochondria as a structural platform, for the control of immune cell polarity, activation, and signaling. Mitochondria-linked disease and mitochondrially targeted therapeutic strategies to manage these conditions are also discussed.
Data replication matters to an underpowered study, but replicated hypothesis corroboration counts
Authors: Erich H. Witte, Frank Zenker
Journal: Behavioral and Brain Sciences (2018)

Abstract Before replication becomes mainstream, the potential for generating theoretical knowledge better be clear. Replicating statistically significant nonrandom data shows that an original study made a discovery; replicating a specified theoretical effect shows that an original study corroborated a theory. Yet only in the latter case is replication a necessary, sound, and worthwhile strategy.
Properties of oscillatory neuronal activity in the basal ganglia and thalamus in patients with Parkinson’s disease
Authors: G. Du, P. Zhuang, M. Hallett, Y.-Q. Zhang, J.-Y. Li, Y.-J. Li
Journal: Translational Neurodegeneration (2018)

The cardinal features of Parkinson's disease (PD) are bradykinesia, rigidity and rest tremor. Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms. This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus (STN) DBS (n = 11), unilateral pallidotomy (n = 9) and unilateral thalamotomy (n = 9) were studied. Microelectrode recordings in the STN, globus pallidus internus (GPi) and ventral oral posterior/ventral intermediate of thalamus (Vop/Vim) were performed. Electromyography of the contralateral limbs was recorded. Single unit characteristics including interspike intervals were analyzed. Spectral and coherence analyses were assessed. Mean spontaneous firing rate (MSFR) of neurons was calculated. Analysis of variance and X2 test were performed.Of 76 STN neurons, 39.5% were 4-6 Hz band oscillatory neurons and 28.9% were β frequency band (βFB) oscillatory neurons. The MSFR was 44.2 ± 7.6 Hz. Of 62 GPi neurons, 37.1% were 4-6 Hz band oscillatory neurons and 27.4% were βFB neurons. The MSFR was 80.9 ± 9.6 Hz. Of 44 Vop neurons, 65.9% were 4-6 Hz band oscillatory neurons and 9% were βFB neurons. The MSFR was 24.4 ± 4.2 Hz. Of 30 Vim oscillatory neurons, 70% were 4-6 Hz band oscillatory neurons and 13.3% were βFB neurons. The MSFR was 30.3 ± 3.6 Hz. Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim (P < 0.05). Conversely, the proportion of 4-6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi (P < 0.05). The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons (P < 0.005).The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism. β oscillatory activity is more prominent in basal ganglia than in thalamus suggesting that the activity likely results from dopaminergic depletion. While both basal ganglia and thalamus have tremor activity, the thalamus appears to play a more important role in tremor production, and basal ganglia β oscillatory activity might be the trigger.
Top research priorities for stroke genetics
Authors: Daniel Woo, Christopher D Anderson, Jane Maguire, Myriam Fornage, Jin-Moo Lee, Sudha Seshadri, Hugh S Markus, Jennifer J Majersik, Jordi Jimenez-Conde, Katherine Crawford, Arne G Lindgren, Stephanie Debette
Journal: The Lancet Neurology (2018)
Elevated Cytosolic Na+ Increases Mitochondrial Formation of Reactive Oxygen Species in Failing Cardiac Myocytes
Authors: MichaelKohlhaas, TingLiu, AndreasKnopp, TanjaZeller, Mei FangOng, MichaelBöhm, BrianO'Rourke, ChristophMaack
Journal: Circulation (2010)

Background— Oxidative stress is causally linked to the progression of heart failure, and mitochondria are critical sources of reactive oxygen species in failing myocardium. We previously observed that in heart failure, elevated cytosolic Na+ ([Na+]i) reduces mitochondrial Ca2+ ([Ca2+]m) by accelerating Ca2+ efflux via the mitochondrial Na+/Ca2+ exchanger. Because the regeneration of antioxidative enzymes requires NADPH, which is indirectly regenerated by the Krebs cycle, and Krebs cycle dehydrogenases are activated by [Ca2+]m, we speculated that in failing myocytes, elevated [Na+]i promotes oxidative stress. Methods and Results— We used a patch-clamp–based approach to simultaneously monitor cytosolic and mitochondrial Ca2+ and, alternatively, mitochondrial H2O2 together with NAD(P)H in guinea pig cardiac myocytes. Cells were depolarized in a voltage-clamp mode (3 Hz), and a transition of workload was induced by β-adrenergic stimulation. During this transition, NAD(P)H initially oxidized but recovered when...
DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis
Authors: Cavin K. Ward-Caviness, Jennifer E. Huffman, Karl Everett, Marine Germain, Jenny van Dongen, W. David Hill, Min A. Jhun, Jennifer A. Brody, Mohsen Ghanbari, Lei Du, Nicholas S. Roetker, Paul S. de Vries, Melanie Waldenberger, Christian Gieger, Petra Wolf, Holger Prokisch, Wolfgang Koenig, Christopher J. O’Donnell, Daniel Levy, Chunyu Liu, Vinh Truong, Philip S. Wells, David-Alexandre Trégouët, Weihong Tang, Alanna C. Morrison, Eric Boerwinkle, Kerri L. Wiggins, Barbara McKnight, Xiuqing Guo, Bruce M. Psaty, Nona Sotoodehnia, Dorret I. Boomsma, Gonneke Willemsen, Lannie Ligthart, Ian J. Deary, Wei Zhao, Erin B. Ware, Sharon L. R. Kardia, Joyce B. J. Van Meurs, Andre G. Uitterlinden, Oscar H. Franco, Per Eriksson, Anders Franco-Cereceda, James S. Pankow, Andrew D. Johnson, France Gagnon, Pierre-Emmanuel Morange, Eco J. C. de Geus, John M. Starr, Jennifer A. Smith, Abbas Dehghan, Hanna M. Björck, Nicholas L. Smith, Annette Peters
Journal: Blood (2018)
Enzymatically Modified Nonoxidized Low-Density Lipoprotein Induces Interleukin-8 in Human Endothelial Cells
Authors: PrapatSuriyaphol, DominicFenske, UlrichZähringer, Shan-RuiHan, SucharitBhakdi, MatthiasHusmann
Journal: Circulation (2002)

Background— Treatment of low-density lipoprotein (LDL) with a protease and cholesterolesterase transforms the lipoprotein to an entity that resembles lipoprotein particles in atherosclerotic lesions, which have a high content of free cholesterol, reflecting extensive de-esterification in the intima. Because de-esterification would occur beneath the endothelium, we examined the effects of enzymatically modified LDL (E-LDL) on cultured endothelial cells. Methods and Results— Incubation of endothelial cells with E-LDL provoked selective accumulation of interleukin (IL)-8 mRNA and production of the cytokine. Chemical analyses and depletion experiments indicated that the effect was caused by the presence of free fatty acids in the altered lipoprotein. Reconstitution studies demonstrated that the oleic and linoleic acids associated with E-LDL are particularly effective IL-8 inducers. The effects of E-LDL on endothelial cells could be abrogated with albumin. Conclusion— IL-8 is required for rolling monocytes to ...
Metastatic soft tissue sarcoma, an analysis of systemic therapy and impact on survival.
Authors: Samuel John Harris, Marco Maruzzo, Khin Thway, Omar Al-Muderis, Robin Lewis Jones, Aisha Miah, Charlotte Benson, Ian Robert Judson
Journal: Journal of Clinical Oncology (2015)

10545 Background: Patients (pts) with metastatic Soft Tissue Sarcoma (STS) are known to have poor outcomes with median overall survival (OS) reported to be circa 12 months. Recent publications have reported median OS circa18 months. We performed a retrospective analysis of all pts with metastatic STS treated at the Royal Marsden between 1991-2010 to examine OS trends. Methods: Adult pts with metastatic STS from 1991-2010 were studied, excluding pts with GIST, those referred for a second opinion or lost to follow-up within 2 months. Pts were grouped into time periods of 5 years: T1-T4. Pts were censored at 4 years from diagnosis. OS rates were calculated using Kaplan-Meier and log-rank tests. An univariate analysis of age, sex, systemic therapy, tumour grade, time to metastatic disease and histology was performed. Results: 2747 pts were identified: 54% female, 75% < 65yrs, median age 53 yrs. Leiomyosarcoma was the commonest diagnosis: 28%; pleomorphic sarcoma: 9%; liposarcoma: 8%. Median OS was 17.5 months. The median OS of T1-T4 was 14.8, 17.9, 18.4 and 17.3 mths. The only significant difference was T1 to T3 (p = 0.026). Nearly 60% of pts in T1-T3 had ≥ 1 line systemic therapy, which fell to 50% in T4. The percentage of elderly pts increased from 18 to 31% in T4. Systemic therapy was associated with a highly statistically significant increase in median OS from 12.5 to 19.3 mths (HR 0.63 p = 0.0003). Higher grade, shorter time to metastatic disease (except if synchronous) and age > 65 were associated with significantly poorer outcomes. Endometrial stromal sarcoma and low grade fibromyxoid sarcomas had the best outcomes, median OS > 10 yrs. Pleomorphic sarcoma, angiosarcoma & sarcoma NOS had the worst outcomes, OS < 12 mths. Conclusions: The median OS of 17.5 months was longer than previous estimates of circa 12 months, consistent with recent reports, and demonstrates improvement compared to the 1980's and early 1990's. However, no further improvements in OS were seen over the past 15 years, in part due to increasing numbers of elderly patients. Although subject to multiple biases, especially fitness for treatment, the substantial improvement in OS in patients receiving treatment is encouraging and may be evidence for a benefit from systemic therapy in patients with metastatic STS.
Abstract 18166: Increasing Endothelialization of BMS and DES With Intra-arterial AdVEGF-A Gene Therapy in Porcine Coronary Arteries
Authors: Jarkko P Hytonen, Paavo Halonen, Santeri Tarvainen, Jouni Taavitsainen, Antti Kuivanen, Arto Koistinen, Johanna Laakkonen, Juha Hartikainen, Seppo Yla-Herttuala
Journal: Circulation (2015)

We aimed to increase stent endothelialization with gene therapy known to promote endothelial proliferation. In addition, we evaluated OCT and angioscopy imaging as tools for detecting endothelium with comparison to robust ex-vivo analyses including scanning electron microscopy (SEM), multiphoton microscopy and immunohistology. 24 stents, BMS and DES, were implanted into naïve porcine coronary arteries and received either AdVEGF-A or control AdLacZ gene therapy with a porous drug delivery catheter. Stents were imaged in-vivo with angiography, OCT and angioscopy immediately after stenting and one week and two weeks after stenting and gene therapy. At d14 the stents were collected for histology, multi-photon microscopy and scanning electron microscopy for assessment of endothelialization. Strut coverage was analyzed from SEM images and graded 0 (no coverage) to 3 (fully covered). Angioscopy pullbacks were analyzed for thrombus in the stented artery and graded similarly 0 (no thrombus) to 3 (occlusive thrumbus). Initial SEM analyses from stented arteries two weeks after intervention showed increased strut coverage with BMS after VEGF-A gene therapy compared to control LacZ (2.8±0.4 vs. 1.8±0.4, p=0.0031, respectively, a) and b) in figure). Gene therapy did not change strut coverage in DES with stent coverage of 1.6±0.5 and 1.8±0.4, p=NS, AdLacZ and AdVEGF-A respectively. Angioscopic thrombus formation was low in all groups with a trend towards less thrombi on BMS groups (0.2±0.4 and 0.3±0.5 in AdLacZ and AdVEGF-A) compared to DES (0.8±0.8 and 0.8±0.7 in AdLacZ and AdVEGF, c) in figure with red thrombus at 4 o'clock). AdVEGF-A treatment at the time of stenting increased coverage of BMS but did not improve healing of DES two weeks after stenting. Likely the strong cytotoxic drugs in DES hamper stent healing even with local supraphysiological growth factor concentrations. Angioscopy may be useful in assessment of arterial healing after treatment with a coronary stent.
De novo sensitization to <i>Aspergillus fumigatus</i> in adult asthma over a 10‐year observation period
Authors: K. Watai, Y. Fukutomi, H. Hayashi, Y. Nakamura, Y. Hamada, Y. Tomita, C. Mitsui, Y. Kamide, K. Sekiya, K. Asano, M. Taniguchi
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Anisotropic Conduction Properties in Canine Atria Analyzed by High-Resolution Optical Mapping
Authors: TakahiroKoura, MotokiHara, SusumuTakeuchi, KenichiOta, YasumasaOkada, ShunichiroMiyoshi, AtsushiWatanabe, KazumiShiraiwa, HideoMitamura, ItsuoKodama, SatoshiOgawa
Journal: Circulation (2002)

Background— Anisotropic conduction properties may provide a substrate for reentrant arrhythmias. We investigated the age-dependent changes of structural and functional anisotropy in isolated right atria from infant (1 to 2 months), young (6 to 12 months), and old (6 to 10 years) dogs. Methods and Results— The histology of the mapped atrial tissues (a small subepicardial area, 2.8×4.2 mm) was characterized by an age-dependent increase of myofiber width and fat cell infiltration between myofibers. Cx43 was distributed homogeneously over the entire cell surface in infant dogs, whereas it progressively polarized to the cell termini with increasing age. The activation sequences were analyzed by high-resolution optical mapping using a voltage-sensitive dye. Activation fronts from the pacing site proceeded more rapidly along fiber orientation (longitudinal) than across it (transverse). Infant dogs showed “elliptical” isochrones with a smooth transition between longitudinal and transverse propagation, whereas old...