tbuckley/cabot-search huggingface dataset:
Impact of the mitochondria-targeted antioxidant MitoQ on hypoxia-induced pulmonary hypertension
Authors: Oleg Pak, Susan Scheibe, Azadeh Esfandiary, Mareike Gierhardt, Akylbek Sydykov, Angela Logan, Athanasios Fysikopoulos, Florian Veit, Matthias Hecker, Florian Kroschel, Karin Quanz, Alexandra Erb, Katharina Schäfer, Mirja Fassbinder, Nasim Alebrahimdehkordi, Hossein A. Ghofrani, Ralph T. Schermuly, Ralf P. Brandes, Werner Seeger, Michael P. Murphy, Norbert Weissmann, Natascha Sommer
Journal: European Respiratory Journal (2018)

Increased mitochondrial reactive oxygen species (ROS), particularly superoxide, have been suggested to mediate hypoxic pulmonary vasoconstriction (HPV), chronic hypoxia-induced pulmonary hypertension and right ventricular remodelling. We determined ROS in acute and chronic hypoxia, and investigated the effect of the mitochondria-targeted antioxidant MitoQ under these conditions. The effect of MitoQ or its inactive carrier substance, decyltriphenylphosphonium, on acute HPV (1% O 2 for 10 min) was investigated in isolated blood-free perfused mouse lungs. Mice exposed to chronic hypoxia (10% O 2 for 4 weeks) or after banding of the main pulmonary artery were treated with MitoQ or decyltriphenylphosphonium (50 mg·kg −1 ·day −1 ). Total cellular superoxide and mitochondrial ROS levels were increased in pulmonary artery smooth muscle cells but decreased in pulmonary fibroblasts in acute hypoxia. MitoQ significantly inhibited HPV and acute hypoxia-induced rise in superoxide concentration. ROS was decreased in pulmonary artery smooth muscle cells, while it increased in the right ventricle after chronic hypoxia. Correspondingly, MitoQ did not affect the development of chronic hypoxia-induced pulmonary hypertension but attenuated right ventricular remodelling after chronic hypoxia as well as after pulmonary arterial banding. Increased mitochondrial ROS of pulmonary artery smooth muscle cells mediate acute HPV, but not chronic hypoxia-induced pulmonary hypertension. MitoQ may be beneficial under conditions of exaggerated acute HPV.
TRANSCATHETER VERSUS SURGICAL VALVE REPLACEMENT IN NON-ELDERLY (AGE LESS THAN 65): IN-HOSPITAL OUTCOMES FROM THE NATIONAL INPATIENT SAMPLE
Authors: Tomo Ando, Emmanuel Akintoye, Mohit Pahuja, Alexandros Briasoulis, Arshad Ali Javed, Hisato Takagi, Theodore Schreiber, Cindy Grines, Luis Afonso
Journal: Journal of the American College of Cardiology (2018)
Medical marriages—good or bad?
Authors: Martina Esisi
Journal: BMJ (2007)

<b>Objective:</b> To evaluate EEG findings during therapeutic hypothermia (TH) and to compare EEG patterns with patient outcome. <b>Background</b> In cardiac arrest patients, TH improves survival and neurologic outcome. Continuous EEG monitoring (cEEG) is frequently used during TH. The significance of EEG patterns, including seizures, at various stages of hypothermia and patient outcome are not firmly established. <b>Design/Methods:</b> cEEG comprises part of our standard TH protocol, with cooling to 33 degrees Celsius for 24 hours and re-warming over 24 hours. Clinical data, EEG findings, and outcomes were recorded. Unpaired t-test was calculated. <b>Results:</b> Twenty consecutive patients were reviewed. Eleven were male, average age 61.2(SD 15) years. Arrest occurred out-of-hospital in 16. Initial cardiac rhythms were ventricular fibrillation(5), asystole(5), pulseless electrical activity(8), and ventricular tachycardia(2). cEEG during hypothermia showed global attenuation (GA) in 5, burst suppression (BS) in 4, slowing in 10, PLEDs in 1, and no seizures. EEG findings after hypothermia were GA in 2, BS in 1, slowing in 12, PLEDs in 3, and seizures in 2. Mean modified Rankin scores (MRS) by cEEG pattern for hypothermia (GA 3.6; BS 5.75; slowing 2.7; PLEDs 5) and after rewarming (GA 4.5; BS 5; slowing 2.75; PLEDs 5; seizures 5.5). Mean MRS during hypothermia were 2.7(SD=2.01) for slowing and 4.6(SD=2) for the other patterns combined. Mean MRS after re-warming were 2.75(SD=2.22) for slowing and 5(SD=1.3) for the other patterns combined. Differences in MRS between slowing and other patterns were significant (hypothermia p=0.048; re-warmed p=0.013). <b>Conclusions:</b> The rewarming period from hypothermia may be more predisposed to seizures. Findings of GA, BS, PLEDs, or seizures on cEEG (either during hypothermia or after rewarming) suggested a poorer outcome compared to diffuse slowing. A larger study is needed to validate these findings. <b>Disclosure:</b> Dr. Lombardi has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Tsimerinov has nothing to disclose. Dr. Chung has nothing to disclose. Dr. Eliashiv has received personal compensation for activities with Pfizer Inc, UCB Pharma, Lundbeck Research USA, GlaxoSmithKline, Inc.
Fluoropyrimidine (F) alone versus F plus platinum (P) as first-line chemotherapy in patients (pts) with advanced gastric cancer (AGC) and severe peritoneal metastasis (SPM): A multicenter observational study.
Authors: Hiroyuki Arai, Satoru Iwasa, Narikazu Boku, Masahiro Kawahira, Hirofumi Yasui, Toshiki Masuishi, Kei Muro, Shuichi Hironaka, Naoki Fukuda, Daisuke Takahari, Takako Eguchi Nakajima
Journal: Journal of Clinical Oncology (2018)

121 Background: The standard 1st-line chemotherapy for AGC pts with SPM has not been established. F alone is generally used for their treatment because of difficulty of hydration for dosing of cisplatin (CDDP) in pts with massive ascites, and has shown limited efficacy. It is unclear whether a combination of F and P (CDDP or oxaliplatin): FP improves their clinical outcome. We therefore investigated the efficacy and safety of FP in comparison with F alone. Methods: This retrospective study comprised of AGC pts with SPM and HER2 negative or unknown tumors who received FP or F as 1st-line chemotherapy between Jul 2010 and Sep 2016 at 6 institutions in Japan. SPM was defined as having massive ascites and/or inadequate oral intake requiring intravenous nutrition support. Overall survival (OS), progression-free survival (PFS), response rate of ascites, improvement rate of oral intake, and safety were compared between two treatment groups. Results: A total of 129 pts (64 in FP group, 65 in F group) were included. Patient characteristics (FP vs F) were as follows: median age, 62 vs 67; PS 0/1/2/3/4 (%), 6/64/25/3/2 vs 8/42/42/8/0; massive ascites/inadequate oral intake/both (%), 61/25/14 vs 35/29/35; number of metastatic sites 1-2/3-5 (%), 77/23 vs 78/22; median serum albumin level (g/ml), 3.1 vs 3.1. OS was significantly longer in FP group than F group (median, 9.0 vs 5.0 months; HR 0.56, 95%CI 0.39-0.82; log-rank p &lt; 0.01); it remained significant upon multivariate analysis adjusting for prognostic variables (HR 0.48, 95% CI 0.32-0.73, p &lt; 0.01). Pts in FP group had significantly better PFS in both uni- and multivariate analyses (median, 4.3 vs 2.3 months; HR 0.44, p &lt; 0.01 and HR 0.40, p &lt; 0.01, respectively). Response rate of ascites (51% vs 17%) and improvement rate of oral intake (64% vs 43%) also were better in FP group (p &lt; 0.01 and p = 0.09, respectively). Toxicities were tolerable in both groups, but grade ≥3 neutropenia was more frequent in FP group (36% vs 11%). Conclusions: FP showed significantly better efficacy than F alone, and it could be a promising option as 1st-line treatment for AGC pts with SPM.
Clinical outcomes of patients with histologic variants of urothelial carcinoma treated with tetra-modality bladder-sparing protocol incorporating consolidative partial cystectomy.
Authors: Toshiki Kijima, Soichiro Yoshida, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Kazutaka Saito, Kazunori Kihara, Yasuhisa Fujii
Journal: Journal of Clinical Oncology (2018)

490 Background: Trimodality bladder-sparing therapy has become an accepted treatment for selected patients with muscle-invasive bladder cancer (MIBC). As some of the histologic variants of urothelial carcinoma (VUC) are more resistant to chemotherapy and radiotherapy compared with pure urothelial carcinoma (PUC), it is still controversial whether bladder-sparing therapy provides comparable disease control in VUC. We have developed a tetra-modality bladder-sparing therapy consisting of maximal transurethral resection (TUR), chemoradiotherapy (CRT), and consolidative partial cystectomy, which has theoretical advantage in locoregional control by surgically eliminating chemo- and radio-resistant cells (Koga et al, Urol Oncol 2013, BJU Int 2012). Methods: After maximal TUR and CRT (40Gy + cisplatin), treatment response was evaluated by cytology, imaging and tumor-site rebiopsy. Complete responders were candidate for consolidative partial cystectomy, while radical cystectomy was recommended for others. VUC identified in maximal TUR samples were categorized according to the 2004 World Health Organization Classification. Response rate to CRT, MIBC recurrence-free survival and cancer-specific survival (CSS) were compared between patients with PUC and VUC. Results: Between 1997 and 2016, 153 consecutive patients with cT2-3N0M0 bladder cancer (median age 69, female/male = 33/120, cT2/3 = 99/54) entered tetra-modality bladder-sparing protocol. VUC was identified in 37 (24%) of the patients, including glandular in 12 (8%), squamous in 11 (7%), micropapillary in 8 (5%), sarcomatoid in 2 (1%), microcystic in 2 (1%), and lymphoepithelioma-like in 1 (0.7%). There was no difference in the response rate to CRT between PUC and VUC (71% vs 84%, p = 0.13). Among the patients with PUC (n = 75) and VUC (n = 31) who underwent partial cystectomy, 5-yr MIBC recurrence-free rates were 92% and 100% (p = 0.21), and 5-yr CSS rates were 93% and 94% (p = 0.64), respectively. Conclusions: Tetra-modality bladder-sparing therapy incorporating partial cystectomy could provide favorable locoregional control and survival for patients with VUC.
Leadership excellence for middle grade doctors
Authors: Lucy Evans
Journal: BMJ (2012)

This one day course on leadership excellence aims to deal with the practical and theoretical aspects of leadership to enable NHS doctors (of all levels) to lead more effectively.

This course is aimed at trainees in any specialty, ideally those who are at specialist registrar level (specialty trainee year 3 and upwards). However, trainees at a more junior level are also encouraged.

I was a specialty trainee year 6 in anaesthesia when I did the course; the other participants were at the level of specialist registrar/specialty trainee year 3 or above and from various other specialties.

Non-clinical skills are just as important as clinical skills at …
Effects of Preceding Ethanol Intake on Glucose Response to Low-Dose Glucagon in Individuals With Type 1 Diabetes: A Randomized, Placebo-Controlled, Crossover Study
Authors: Ajenthen Ranjan, Kirsten Nørgaard, Rikke Tetzschner, Isabelle Isa Kristin Steineck, Trine Ryberg Clausen, Jens Juul Holst, Sten Madsbad, Signe Schmidt
Journal: Diabetes Care (2018)

OBJECTIVE This study investigated whether preceding ethanol intake impairs glucose response to low-dose glucagon in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS This was a randomized, crossover, placebo-controlled study in 12 insulin pump–treated individuals (median [interquartile range] age, 37 [31–51] years; HbA1c, 57 [51–59] mmol/mol or 7.3% [6.8–7.5]; and BMI, 23.9 [22–25] kg/m2). During two overnight study visits, a 6 p.m. dinner (1 g carbohydrates/kg) was served with diet drink (placebo) or diet drink and ethanol (0.8 g/kg). After 8–9 h, ethanol was estimated to be metabolized, and a subcutaneous (s.c.) insulin bolus was given to induce mild hypoglycemia. When plasma glucose (PG) was ≤3.9 mmol/L, 100 µg glucagon was given s.c., followed by another s.c. 100 µg glucagon 2 h later. Primary end point was incremental peak PG induced by the first glucagon bolus. RESULTS Ethanol was undetectable before insulin administration at both visits. The insulin doses (mean ± SEM: 2.5 ± 0.4 vs. 2.7 ± 0.4 IU) to induce hypoglycemia (3.7 ± 0.1 vs. 3.9 ± 0.1 mmol/L) did not differ and caused similar insulin levels (28.3 ± 4.6 vs. 26.1 ± 4.0 mU/L) before glucagon administration on ethanol and placebo visits (all, P &amp;gt; 0.05). The first glucagon bolus tended to cause lower incremental peak PG (2.0 ± 0.5 vs. 2.9 ± 0.3 mmol/L, P = 0.06), lower incremental area under the curve (87 ± 40 vs. 191 ± 37 mmol/L × min, P = 0.08), and lower 2-h PG level (3.6 ± 1.0 vs. 4.8 ± 0.4 mmol/L, P = 0.05) after ethanol compared with placebo. The second glucagon bolus had similar responses between visits, but PG remained 1.8 ± 0.7 mmol/L lower after ethanol compared with placebo. CONCLUSIONS The ability of low-dose glucagon to treat mild hypoglycemia persisted with preceding ethanol intake, although it tended to be attenuated.
Authentic compound-free strategy for simultaneous determination of primary coumarins in Peucedani Radix using offline high performance liquid chromatography–nuclear magnetic resonance spectroscopy–tandem mass spectrometry
Authors: Yao Liu, Qingqing Song, Wenjing Liu, Peng Li, Jun Li, Yunfang Zhao, Liang Zhang, Pengfei Tu, Yitao Wang, Yuelin Song
Journal: Acta Pharmaceutica Sinica B (2018)

Herein, a strategy is proposed for the simultaneous determination of primary coumarins in Peucedani Radix (Chinese name: Qianhu). The methodology consists of three consecutive steps: 1) Semi-preparative LC in combination with a home-made automated fraction collection module to fragment the universal metabolome standard into ten fractions (Frs. I–X); 2) LC–accurate MS/MS and quantitative 1H NMR spectroscopy conducted in parallel to acquire the qualitative and quantitative data of each fraction; 3) Robust identification and quantification of components by use of LC coupled to multiple reaction monitoring. In this final step, the most significant fractions (Frs. III–X) were pooled to serve as the pseudo-mixed standard solution. Meticulous online parameter optimization was performed to obtain the optimal parameters, including ion transitions and collision energies. Concerns were particularly paid onto pursuing the parameters being capable of monitoring regio-specific isomers, notably praeruptorin E vs. 3′-isovaleryl-4′-angeloylkhellactone. The quantitative performance of the method was validated according to diverse assays. Eleven primary coumarins (1–11) were unambiguously identified and absolutely quantified, even though no external reference compound was used. Above all, the integrated strategy not only provides a feasible pipeline for the quality assessment of Peucedani Radix, but more importantly, shows the potential for authentic compound-free quantitative evaluation of traditional Chinese medicines.
SURGICAL LEFT ATRIAL APPENDAGE OCCLUSION USING THE ATRICLIP® INCREASES EARLY POSTOPERATIVE ATRIAL FIBRILLATION
Authors: Ricarda M. White, Anne Kroman, Janice Steinhoff, Gail Davenport, Foster Curtis Bryan, Michael DeFrain, Robert C. Sheppard
Journal: Journal of the American College of Cardiology (2018)
CORONARY PLAQUE BURDEN ON CORONARY COMPUTED TOMOGRAPHIC ANGIOGRAPHY IN DIABETICS VERSUS NON-DIABETICS
Authors: Anthony Delicce, Basem Alawneh, Kyla D’Angelo, David Bass, Ofek Hai, Daniel Chikvashvili, Roman Zeltser, Amgad Makaryus
Journal: Journal of the American College of Cardiology (2018)
Mutagenicity and Lung Toxicity of Smoldering vs. Flaming Emissions from Various Biomass Fuels: Implications for Health Effects from Wildland Fires
Authors: Yong Ho Kim, Sarah H. Warren, Q. Todd Krantz, Charly King, Richard Jaskot, William T. Preston, Barbara J. George, Michael D. Hays, Matthew S. Landis, Mark Higuchi, David M. DeMarini, M. Ian Gilmour
Journal: Environmental Health Perspectives (2018)

The increasing size and frequency of wildland fires are leading to greater potential for cardiopulmonary disease and cancer in exposed populations; however, little is known about how the types of fuel and combustion phases affect these adverse outcomes.We evaluated the mutagenicity and lung toxicity of particulate matter (PM) from flaming vs. smoldering phases of five biomass fuels, and compared results by equal mass or emission factors (EFs) derived from amount of fuel consumed.A quartz-tube furnace coupled to a multistage cryotrap was employed to collect smoke condensate from flaming and smoldering combustion of red oak, peat, pine needles, pine, and eucalyptus. Samples were analyzed chemically and assessed for acute lung toxicity in mice and mutagenicity in Salmonella.The average combustion efficiency was 73 and 98% for the smoldering and flaming phases, respectively. On an equal mass basis, PM from eucalyptus and peat burned under flaming conditions induced significant lung toxicity potencies (neutrophil/mass of PM) compared to smoldering PM, whereas high levels of mutagenicity potencies were observed for flaming pine and peat PM compared to smoldering PM. When effects were adjusted for EF, the smoldering eucalyptus PM had the highest lung toxicity EF (neutrophil/mass of fuel burned), whereas smoldering pine and pine needles had the highest mutagenicity EF. These latter values were approximately 5, 10, and 30 times greater than those reported for open burning of agricultural plastic, woodburning cookstoves, and some municipal waste combustors, respectively.PM from different fuels and combustion phases have appreciable differences in lung toxic and mutagenic potency, and on a mass basis, flaming samples are more active, whereas smoldering samples have greater effect when EFs are taken into account. Knowledge of the differential toxicity of biomass emissions will contribute to more accurate hazard assessment of biomass smoke exposures. https://doi.org/10.1289/EHP2200.
Sexual violence against children and adolescents in South Africa: making the invisible visible
Authors: Karen M Devries, Franziska Meinck
Journal: The Lancet Global Health (2018)

Enshrined in the United Nations (UN) Convention on the Rights of the Child (CRC) is every child's right to protection from violence and harm. Although 196 of the 197 UN member states are signatories to the CRC (the USA is the exception), more than 1 billion children experience violence each year.1 However, there is good news—the elimination of violence in childhood now features prominently in the UN Sustainable Development Goals. The newly formed Global Partnership to End Violence Against Children brings together a diverse range of stakeholders committed to eradicating violence against children, and is focusing resources to facilitate change.
Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice
Authors: Nobuyuki Nishizawa, Yoshiya Ito, Koji Eshima, Hirotoki Ohkubo, Ken Kojo, Tomoyoshi Inoue, Joan Raouf, Per-Johan Jakobsson, Satoshi Uematsu, Shizuo Akira, Shuh Narumiya, Masahiko Watanabe, Masataka Majima
Journal: Journal of Hepatology (2018)
Coaching for doctors: a road to salvation
Authors: Neeta Manek
Journal: BMJ (2004)

I n a recent Career Focus article, the deputy chief medical officer Aidan Halligan emphasised the importance of coaching for doctors throughout their careers.1 In fact, coaching is one of the key “seven pillars” of Modernising Medical Careers . But as an education supervisor with more than a decade's experience of working in the NHS, I was not convinced that coaching doctors in the workplace would help them to realise their hopes and aspirations. My view, like that of many others, was that coaching doctors is not the same as coaching athletes. More importantly, as an education supervisor for foundation doctors, I was expected to have the skills to coach the training doctors and help them make good career decisions. But how could I coach juniors if I didn't believe in it, and did I even have the right skills?

It was during this period of jumbled thoughts that two colleagues (a doctor and a director …
Prognostic factors for survival in apatinib-treated gastric cancer: Results from a post-marketing phase IV study (Ahead-G201).
Authors: Shukui Qin, Wenying Deng, Lu Wen, Junsheng Wang, Guifang Zhang, Haijun Zhong, Tongfu Jia, Jianwei Yang, Yi Ba, Yuxian Bai, Xiaoyan Lin, Mei Wang, Lin Wang, Likun Liu, Yifu He, Min Tao, Congying Xie, Feng Ye, Xiang-yuan Wu, Jin Li
Journal: Journal of Clinical Oncology (2018)

19 Background: Easily detectable and reliable prognostic factors for apatinib response in gastric cancer are of great interest. In this study, 42 characteristics were test for their prognostic value. Methods: Data were collected from the ongoing single-arm phase IV trial in patents (pts) with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction after failure of ≥2 lines of chemotherapy. Kaplan–Meier and multivariable Cox analysis were conducted. Results: As of 2017/7/10, 1037 pts were enrolled. 820 were evaluable for survival. The median progression free survival (PFS) and overall survival (OS) was 4.60 and 6.57 m. Age, metastatic lesions, region, treatment interruption, leucocyte decrease and adverse events (AEs) occurrence were independent prognostic factors for PFS, while ECOG PS, disease duration, metastatic lesions, region, developed city, initial dose, treatment interruption, BMI, AST abnormal, hand-foot-skin reaction (HFSR), leucocyte decrease and AE occurrence for OS (Table). Conclusions: Multiple demographics, baseline clinical and laboratory indexes, treatment related indicators and occurrence of AEs can predict the efficacy of apatinib in gastric cancer. Updated results will be reported to guide the clinical application of apatinib. Clinical trial information: NCT02426034. [Table: see text]
Meat Cooking Methods and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies
Authors: Gang Liu, Geng Zong, Kana Wu, Yang Hu, Yanping Li, Walter C. Willett, David M. Eisenberg, Frank B. Hu, Qi Sun
Journal: Diabetes Care (2018)

OBJECTIVE To examine open-flame and/or high-temperature cooking (grilling/barbecuing, broiling, or roasting) and doneness preferences (rare, medium, or well done) for red meat, chicken, and fish in relation to type 2 diabetes (T2D) risk among U.S. adults who consumed animal flesh regularly (≥2 servings/week). RESEARCH DESIGN AND METHODS The prospective studies included 52,752 women from the Nurses’ Health Study (NHS) (followed during 1996–2012), 60,809 women from NHS II (followed during 2001–2013), and 24,679 men from the Health Professionals Follow-Up Study (HPFS) (followed during 1996–2012) who were free of diabetes, cardiovascular disease, and cancer at baseline. Incident cases of T2D were confirmed by validated supplementary questionnaires. RESULTS We documented 7,895 incident cases of T2D during 1.74 million person-years of follow-up. After multivariate adjustments including baseline BMI and total consumption of red meat, chicken, and fish, higher frequency of open-flame and/or high-temperature cooking was independently associated with an elevated T2D risk. When comparing open-flame and/or high-temperature cooking &amp;gt;15 times/month with &amp;lt;4 times/month, the pooled hazard ratio (HR) (95% CI) of T2D was 1.28 (1.18, 1.39; Ptrend &amp;lt;0.001). When comparing the extreme quartiles of doneness-weighted frequency of high-temperature cooking, the pooled HR (95% CI) of T2D was 1.20 (1.12, 1.28; Ptrend &amp;lt;0.001). These associations remained significant when red meat and chicken were examined separately. In addition, estimated intake of heterocyclic aromatic amines was also associated with an increased T2D risk. CONCLUSIONS Independent of consumption amount, open-flame and/or high-temperature cooking for both red meat and chicken is associated with an increased T2D risk among adults who consume animal flesh regularly.