tbuckley/cabot-search huggingface dataset:
Detection of fluoroquinolones resistance mutations in mycobacterium tuberculosis by hydrolysis probes and RFLP
Authors: Veronika Slizen, Aksana Zalutskaya, Larissa Surkova
Journal: European Respiratory Journal (2013)

A single nucleotide polymorphism in codons 88, 90, 91, 94 of  gyrA  gene, associated with the resistance to FQ in MTB, can be detected by variety of methods.  The aim  of the study is to evaluate the method of qPCR with dehydrated reaction mixtures and RFLP for rapid detection of FQ resistant MTB.   Results.  SNPs in 26 FQ resistant MTB have been detected by GenoType MTBDRsl and by dehydrated qPCR mixtures with primers (GyrF 200-218 +GyrR 358-339  and GyrF 78-97 +GyrR 397-379 ) and hydrolysis probes for SNPs: Ala90Val, Ser91Pro, Asp94Gly/His/Asn/Tyr/Ala. Both methods make it possible to detect the following: one, seven and three isolates of MTB carry mutations in codons 88, 90, 91, respectively; and five, two, one and two isolates of MTB have mutations Asp94Gly, Asp94Ala, Asp94His, Asp94Asn/Tyr, respectively. One MTB carries a double mutation Ser90Pro+Asp94Gly and one MTB has an unidentified SNP in codon 94. Dehydrated qPCR reaction mixtures and PCR plates are a convenient tool for detecting a number of different SNPs in one strain. Rehydration of dried PCR mixtures has restored their activity, resulting in the formation of typical fluorescence curves. Mutations have been confirmed by RLFP analysis with  BstUI, TaqI, MluI . Alterations in both codon 90 and 91 can be detected by  MluI , resulting in a two-band pattern (320, 160 bp) in mutated MTB versus a three-band pattern (200, 120, and 80 bp) in wild MTB. Restriction with  TaqI  allowed us to detect mutations in codon 91: mutated and wild MTB have band pattern 220, 100 bp and 120, 100, 80 bp, respectively.  BstUI  restriction makes it possible to detect MBT with or without SNP in codon 90 (band pattern 320, 160 bp versus 180, 140, 80 bp).
Measurements of nasal airflow and patency: a critical review with emphasis on the use of peak nasal inspiratory flow in daily practice
Authors: G. Ottaviano, W. J. Fokkens
Journal: Allergy (2015)

Abstract Objective measures can be used to assist the clinician to diagnose and treat nasal obstruction and also to quantify nasal obstruction in research. Objective measurements of nasal obstruction are as important as objective measurements of lung function. peak nasal inspiratory flow ( PNIF ), acoustic rhinometry ( AR ) and rhinomanometry ( RM ), with their specific peculiarity, assess different aspects of nasal obstruction. From the studies available in the literature, it seems that these methods roughly correlate with each other and that all of them can be alternatively utilized very well in research as well as in clinical practice. This review describes the various methods that can be used to measure nasal patency, airflow and resistance, mainly peak nasal inspiratory flow, rhinomanometry and acoustic rhinometry. PNIF has been demonstrated to be reproducible and as good an indication of objective nasal patency as formal rhinomanometry and has the advantage to be cheap, simple and suitable for serial measurements and for home use even in the paediatric population. PNIF normative data are available for children, adults and elderly subjects, and the availability of unilateral PNIF normal values allows evaluation of nasal sides separately. Just as in the lower airways, objective and subjective evaluation gives different information that together optimizes the diagnosis and the treatment of our patients. We argue that PNIF should be used regularly in every outpatient clinic that treats patients with nasal obstruction.
Abstract 1872: Transmural Dispersion of Repolarization in Human Ventricular Wall
Authors: Alexey V Glukhov, Vadim V Fedorov, Kelley V Foyil, Nader Moazami, Igor R Efimov
Journal: Circulation (2008)

Transmural dispersion of repolartization (DR) has been studied in numerous animal models. Some studies presented evidence of midmyocardial population of M-cells that possess distinctly long action potential duration (APD). We aimed to investigate APD and DR in explanted failing human left ventricles (LV). We optically mapped APD in coronary-perfused human LV wedge preparations (n=4) using CMOS camera in presence of blebbistatin (BB, 10 μ M). Microelectrode recordings were used to validate BB in human LV. RESULTS: During slow pacing (S1S1=2,000ms), APD at the endo-, mid-, and epicardium was 586±27ms, 578±19ms, and 496±14ms, respectively. Maximum APD gradient was 24±5 ms/mm, DR was 35±6 ms. Progressive decrease in S1S1 up to functional refractory period (460±26 ms) induced an inhomogeneous shortening of APD (up to 350±26 ms, 352±36 ms and 346±30 ms, respectively), decrease in APD gradient and DR (4±3 ms/mm and 20±4 ms, respectively, p&lt;0.01) We present for the first time evidence of transmural APD gradient in failing human LV. However, we could not confirm presence of distinct population of M-cells that were found in several animal models.
What's your weakness?
Authors: K. Abbasi
Journal: BMJ (2015)

We all have weaknesses.Tickets to the Chelsea flower show, a test match at the Oval, La Traviata at Glyndebourne, or a Paul McCartney concert at the O 2 arena.What tempts you most?One of these five star events, with hospitality thrown in, surely will?We all have weaknesses, and companies know it.The world of corporate hospitality depends on it.Shouldn't we expect politicians, of all people, to understand that there are no free lunches?The payer wants something from you.It might be something trivial, like your heart, but it might also be your integrity.What if those free tickets were offered by a tobacco company?What's in danger, your heart or your integrity?
Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial
Authors: Clemens Becker, Stephen R Lord, Stephanie A Studenski, Stuart J Warden, Roger A Fielding, Christopher P Recknor, Marc C Hochberg, Serge L Ferrari, Hubert Blain, Ellen F Binder, Yves Rolland, Serge Poiraudeau, Charles T Benson, Stephen L Myers, Leijun Hu, Qasim I Ahmad, Kelli R Pacuch, Elisa V Gomez, Olivier Benichou
Journal: The Lancet Diabetes & Endocrinology (2015)
Dose-Escalation Study of Docetaxel in Combination With Mitoxantrone as First-Line Treatment in Patients With Metastatic Breast Cancer
Authors: Charalambos Kouroussis, Nikos Androulakis, Stelios Kakolyris, John Souglakos, Thanos Kotsakis, Dimitris Mavroudis, Kostas Katsogridakis, Nikos Vardakis, Dora Hatzidaki, George Samonis, John Vlachonikolis, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (1999)

To define the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with mitoxantrone in patients with metastatic breast cancer (MBC).Forty-one chemotherapy-naive patients with MBC (median age, 61 years) were enrolled. Thirty-eight (93%) had performance status (World Health Organization [WHO]) 0, 29 (71%) were postmenopausal, and 21 (51%) had estrogen receptor-negative tumors. Patients received escalated doses of docetaxel (75 to 100 mg/m2) on day 1 and mitoxantrone (8 to 22 mg/m2) on day 8. Treatment was repeated every 3 weeks.A total of 217 chemotherapy cycles were administered. Without recombinant human granulocyte colony-stimulating factor (rhG-CSF) support, the MTD1 occurred at the first dose level (docetaxel 75 mg/m2 and mitoxantrone 8 mg/m2); DLTs were febrile neutropenia, grade 4 neutropenia lasting more than 5 days, and grade 3 diarrhea. With prophylactic rhG-CSF, the MTD2 was docetaxel 100 mg/m2 and mitoxantrone 20 mg/m2; DLTs were febrile neutropenia and grade 4 neutropenia. Nine (22%) patients developed neutropenia after the first cycle of treatment. A total of 19 episodes of febrile neutropenia (9% of the cycles) occurred during the whole period of the study; there were no toxic deaths. At high docetaxel (100 mg/m2) and mitoxantrone (> 12 mg/m2) dose levels, a significant decrease of the absolute lymphocyte number was observed; immunophenotyping revealed that all lymphocyte subpopulations were reduced. Grades 2 and 3 neurosensory toxicity occurred in six patients (15%) and one patient (2%), respectively. No cardiac toxicity was observed. Nine complete responses (22%) and 23 partial responses (56%) were achieved (overall response rate, 78%; 95% confidence interval, 62.5% to 88.8%). The median duration of response was 12.5 months, and the median time to tumor progression was 14.5 months.The reported combination of docetaxel and mitoxantrone with G-CSF support is a safe, intensified, well-tolerated, and effective regimen as first-line treatment in patients with MBC.
Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane.
Authors: Kimberly L. Blackwell, David Miles, Luca Gianni, Ian E Krop, Manfred Welslau, José Baselga, Mark D. Pegram, Do-Youn Oh, Veronique Dieras, Steven R. Olsen, Liang Fang, Michael W Lu, Ellie Guardino, Sunil Verma
Journal: Journal of Clinical Oncology (2012)

LBA1 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
LBA-07 Updated Results of the MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in patients (pts) with BRAF V600E mutated (BRAFm) metastatic colorectal cancer (mCRC)
Authors: E. Van Cutsem, C. Atreya, T. André, J. Bendell, J. Schellens, M. Gordon, A. McRee, T. Yoshino, K. Muro, P. ODwyer, J. Tabernero, G. Middleton, M. Ducreux, R. van Geel, R. Sidhu, J. Greger, F. Rangwala, Y. Liu, Y. Wu, B. Mookerjee, R. Corcoran
Journal: Annals of Oncology (2015)
Chronic rhinosinusitis and airway inflammation in new onset asthma in adults
Authors: S.B. Nijs, C. Georgalas, E.J.M. Weersink, J.E. van den Bergh, B. van den Berg, F.H. Krouwels, P.J. Sterk, W.J. Fokkens, E.H. Bel
Journal: European Respiratory Journal (2011)

Rationale: In severe asthma, chronic rhinosinusitis (CRS) is associated with increased sputum eosinophils [ Brinke, JACI 2002 ]. Many adults with severe asthma have the onset of their disease in adulthood. We hypothesized that the relationship between the severity of CRS and inflammation in the lower airways already exists in the early stages of adult-onset asthma.

Aim: To investigate the relationship between CRS and airway inflammation in adults with new onset asthma.

Methods: Ninety-eight adults (>18yr) with a physician diagnosis of recent (<1yr) onset asthma (age 48 (±16.1)yr, pb FEV1 99 (±18.8)%pred, 61% female, 43% atopic, 20% steroid naive) were recruited. Diagnosis was based on reversibility in FEV1 ≥12%pred and/or PC20 methacholine < 8 mg/ml. Patients with COPD were excluded.

CT-scanning was performed and blindly scored for sinonasal mucosal thickness using LMK score [ Lund Rhinology 1993 ]. Sputum was induced and processed, exhaled nitric oxide (FeNO), pb FEV1 and methacholine challenge were performed and venous blood was taken. LMK scores were related to sputum cell counts, FeNO, lung function and blood using Spearman correlation coefficient.

Results: There was a significantly positive correlation between CT scores and eosinophils in induced sputum (Rs= 0.73, p=<0.001) and peripheral blood (Rs= 0.56, p=<0.001) and level of FeNO (Rs= 0.35, p=0.001). No correlation was found between CT-scan scores and pb FEV1% pred (p= 0.75) or PC20 methacholine (p=0.15).

Conclusion: In adults with recent onset asthma, the degree of CRS and lower airways inflammation are closely related. This implies that patients with recent onset asthma should be checked and treated for upper airways disease, if necessary.
Spatiotemporal proliferation of human stromal cells adjusts to nutrient availability and leads to stanniocalcin-1 expression in vitro and in vivo
Authors: Gustavo A. Higuera, Hugo Fernandes, Tim W.G.M. Spitters, Jeroen van de Peppel, Nils Aufferman, Roman Truckenmueller, Maryana Escalante, Reinout Stoop, Johannes P. van Leeuwen, Jan de Boer, Vinod Subramaniam, Marcel Karperien, Clemens van Blitterswijk, Anton van Boxtel, Lorenzo Moroni
Journal: Biomaterials (2015)
Biology of the eyelash hair follicle: an enigma in plain sight
Authors: R. Paus, I. Burgoa, C.I. Platt, T. Griffiths, E. Poblet, A. Izeta
Journal: British Journal of Dermatology (2015)

Because of their crucial impact on our perception of beauty, eyelashes constitute a prime target for the cosmetic industry. However, when compared with other hair shafts and the mini‐organs that produce them [eyelash hair follicles (ELHFs)], knowledge on the biology underlying growth and pigmentation of eyelashes is still rudimentary. This is due in part to the extremely restricted availability of human ELHFs for experimental study, underappreciation of their important sensory and protective functions and insufficient interest in understanding why they are distinct from scalp hair follicles (HFs) (e.g. ELHFs produce shorter hair shafts, do not possess an arrector pili muscle, have a shorter hair cycle and undergo greying significantly later than scalp HFs). Here we synthesize the limited current knowledge on the biology of ELHFs, in humans and other species, their role in health and disease, the known similarities with and differences from other HF populations, and their intrinsic interethnic variations. We define major open questions in the biology of these intriguing mini‐organs and conclude by proposing future research directions. These include dissecting the molecular and cellular mechanisms that underlie trichomegaly and the development of in vitro models in order to interrogate the distinct molecular controls of ELHF growth, cycling and pigmentation and to probe novel strategies for the therapeutic and cosmetic manipulation of ELHFs beyond prostaglandin receptor stimulation.
Cytotoxic and Oncogenic Activities of 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane and Metabolites to Mouse Embryo Cells in Culture2
Authors: R. Langenbach, R. Gingell
Journal: JNCI Journal of the National Cancer Institute (1975)

The cytotoxic and oncogenic activities of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (001), and its metabolites 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), and bis(p-chlorophenyl)acetic acid, were studied at various equimolar concentrations in an in vitro mouse embryo cell culture system that was malignantly transformable. DODwas the most active compound in producing transformation, whereas DDT and DOE showed slight activity. However, none of the transformed foci had the typical malignantly transformed morphology produced by 7,12-dimethylbenz[a]anthracene and did not produce tumors when inoculated into syngeneic mice.
Limb Salvage in Patients With Diabetes Is Not a Temporary Solution but a Life-Changing Procedure
Authors: Laura Giurato, Erika Vainieri, Marco Meloni, Valentina Izzo, Valeria Ruotolo, Sebastiano Fabiano, Enrico Pampana, Benjamin Lipsky, Roberto Gandini, Luigi Uccioli
Journal: Diabetes Care (2015)

Our limb salvage protocol for patients with diabetes at risk for amputation due to critical limb ischemia, foot ulcer, or gangrene includes early and aggressive surgical debridement, immediate broad-spectrum antibiotic therapy, and peripheral transluminal angioplasty as the first-choice revascularization procedure (1). In 2010 (2), we described the long-term outcomes (mean follow-up 20 ± 13 months) of 456 patients treated with this protocol: ulcers were healed in 62.3% (group A), major amputations performed in 14.7% (group B), death occurred in 14.9% (group C), and ulcers remained unhealed for >12 months in 8.1% (group D). As the long-term efficacy of this approach is still controversial (3), we have now evaluated the limb- or life-related outcomes in the same cohort of patients after a further …
Prevalence of symptoms of chronic bronchitis in Murmansk, Russia
Authors: Pentti Nieminen, Tuula Toljamo, Mark Borisenko, Yuri Payusov, Sergei Lyalyushkin, Arvid Nyberg, Vuokko Kinnula, Dmitry Panychev
Journal: European Respiratory Journal (2011)

Background: Incidence, morbidity and mortality of COPD in the Murmansk region of northwest Russia are high, but statistical figures do not probably reflect the whole problem. As much as 60% of the male population in Russia is smokers. We describe findings of a project which addresses prevention of COPD in Murmansk.

Aims and objectives: 1. What is the proportion of prolonged respiratory symptoms among adult subjects who visit a GP for primary care?

2. What is the distribution of nicotine-dependence among smokers?

3. How motivated they are to quit smoking?

Methods: A survey of 200 Murmansk region adult citizens was performed. Inclusion criteria: adult patient visiting a primary care GP for any medical reason. Venues were one policlinic located in Murmansk city and one hospital policlinic located in a mining area 200 km outside Murmansk.

Results: 200 outpatients were enrolled. Altogether 60.5% had symptoms of chronic bronchitis and 55 (33.0%) had prolonged dyspnoea and wheezing as well. Respiratory symptoms were more common in those subjects, who lived in the mining area. More than half (51.5%) of the subjects had been smokers at some stage of their adult life. A total of 63 (31.5%) were current smokers. The proportion of heavily dependent smokers (FTND 6-7) was 23.8%. Adults living in the mining area were more heavily nicotine dependent. 42.9% of the current smokers had a high motivation to quit smoking.

Conclusions: Significant numbers of primary care patients in Murmansk, Russia experience prolonged respiratory symptoms. Smoking is common in this northern city and there is an urgent need to identify efficient ways for smoking cessation. This study reveals that several smokers have high motivation to quit smoking.
Nutrition of Mouse Ascites Tumor Cells in Primary Culture. I. Large Molecular Substances and Conditioned Media
Authors: J. F. Morgan
Journal: JNCI Journal of the National Cancer Institute (1970)

Primary monolayer cultures were prepared from mouse ascites tumor cells of the Ehrlich-Lettré line and cultivated in chemically defined media. Survival but not propagation of the cells was obtained. The effect of large molecular substances and conditioned media as supplements to the chemically defined media was investigated. Calf serum greatly extended culture survival, as did dialyzed calf serum, but serum ultrafiltrate was relatively ineffective. Fetal calf serum was nearly twice as effective as calf serum in lengthening culture survival. When heated at 56°C for 30 minutes the beneficial effect of calf serum was nearly abolished, but that of fetal calf serum was reduced by only one third. Mouse peritoneal exudate was highly effective in prolonging culture survival, but its effect was largely abolished by heat treatment. Mouse ascites tumor fluid was completely ineffective. Minor effects were noted with some protein hydrolysates and certain tissue extracts but not with large molecular polysaccharides. Conditioned media derived from actively growing Ehrlich-Lettré cultures did not prolong the survival of primary cultures of Ehrlich-Lettré cells, but a marked prolongation was obtained with conditioned media derived from 6C3HED cell cultures. Media derived from secondary mouse embryo cultures also stimulated the Ehrlich-Lettré cells. Differences in effect were observed between serum-free conditioned media and those containing calf serum.
Hyperglycemia as a independent predictor of mortality in acute pulmonary embolism
Authors: Iulia-Cristina Roca, Viviana Aursulesei, Mihai Roca, Mihai-Dan Datcu
Journal: European Respiratory Journal (2011)

Introduction:  Acute pulmonary embolism (APE) is a life threatening disease and one of the main causes of in-hospital mortality. Hyperglycemia secondary to diabetes mellitus, impaired glucose tolerance or stress-induced, occurs frequently in critically ill patients and is associated with adverse outcome. The relationship between hyperglycemia and outcome in APE patients has not been clearly defined.   Aim:  The purpose of the study was to determine the association between hyperglycemia and risk - adjusted mortality in APE patients.   Methods:  We conducted a prospective, cohort study, between 1 January 2004 and 31 December 2009. The patients with APE, admitted in the Ist Medical Cardiology Clinic, in “St Spiridon” University Hospital, Iasi were included. Hyperglycemia was defined as an admission or in-hospital fasting glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations.   Results:  During the study period, we enrolled 326 patients with APE. Mean age of the patients was 62.3 years (range 16 - 95 years), 197 (60%) were females, 30 (9%) were in shock at admission and 36 (11.04%) had diabetes mellitus diagnosis before admission. Fifty seven patients died during hospital stay (17%). Multivariable analysis showed that hyperglycemia was an independent predictor for in-hospital mortality in APE patients (p   Conclusion:  Hyperglycemia is an independent predictor for in-hospital mortality in APE.
Regional Subanalysis of the Phase III Mpact Trial: Nab-Paclitaxel (Nab-P) Plus Gemcitabine (Gem) Vs Gem Alone for Patients (Pts) with Metastatic Pancreatic Cancer (Pc)
Authors: S. Siena, L. Lipton, R. Letourneau, S.A. Tjulandin, C. Guillen Ponce, M. Schwarz, R.K. Ramanathan, T. Macarulla, D. Goldstein, A. Romano, S. Ferrara, D. Penenberg, D.D. Von Hoff
Journal: Annals of Oncology (2014)
Helen S Kennedy
Authors: N. Kennedy
Journal: BMJ (2015)

<h3>Background</h3> Choroidal vascular regulation is mediated by the autonomic nervous system in order to gain proper blood flow control. While the mechanisms behind this control are unknown, neuroregulatory peptides are involved in this process. To better understand choroidal function, we investigate the presence of urocortin-1 (UCN), a neuroregulatory peptide with vascular effects, in the human choroid and its possible intrinsic and extrinsic origin. <h3>Methods</h3> Human choroid and eye-related cranial ganglia (superior cervical ganglion- SCG, ciliary ganglion-CIL, pterygopalatine ganglion-PPG, trigeminal ganglion-TRI) were prepared for immunohistochemistry against UCN, protein–gene product 9.5 (PGP9.5), substance P (SP), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (VAChT). For documentation, confocal laser scanning microscopy was used. <h3>Results</h3> In choroidal stroma, UCN-immunoreactivity was present in nerve fibres, small cells and intrinsic choroidal neurons (ICN). Some UCN+ nerve fibres colocalised for VAChT, while others were VAChT. A similar situation was found with SP: some UCN+ nerve fibres showed colocalisation for SP, while others lacked SP. Colocalisation for UCN and TH was not observed. In eye-related cranial ganglia, only few cells in the SCG, PPG and TRI were UCN+, while many cells of the CIL displayed weak UCN immunoreactivity. <h3>Conclusion</h3> UCN is part of the choroidal innervation. UCN+/VAChT+ fibres could derive from the few cells of the PPG or cells of the CIL, if these indeed supply the choroid. UCN+/SP+ fibres might originate from ICN, or the few UCN+ cells detected in the TRI. Further studies are necessary to establish UCN function in the choroid and its implication for choroidal autonomic control.