Draft Genome Sequence of Frankia Strain G2, a Nitrogen-Fixing Actinobacterium Isolated from Casuarina equisetifolia and Able To Nodulate Actinorhizal Plants of the Order Rhamnales

Frankia sp. strain G2 was originally isolated from Casuarina equisetifolia and is characterized by its ability to nodulate actinorhizal plants of the Rhamnales order, but not its original host. It represents one of the largest Frankia genomes so far sequenced (9.5 Mbp)

Pilot randomized crossover study comparing the efficacy of transnasal disposable endosheath with standard endoscopy to detect Barrett's esophagus.

BACKGROUND AND STUDY AIMS: The transnasal endosheath endoscope is a new disposable technology with potential applicability to the primary care setting. The aim of this study was to evaluate the efficacy of transnasal endosheath endoscopy (TEE) for the detection of Barrett's esophagus, by comparing the diagnostic accuracy of TEE with that of standard endoscopy. PATIENTS AND METHODS: This was a prospective, randomized, crossover study performed in a single tertiary referral center. Consecutive patients undergoing surveillance for Barrett's esophagus or referred for diagnostic assessment were recruited. All patients were randomized to undergo TEE followed by standard endoscopy or the reverse. Endoscopy experiences and patient preferences were evaluated using a questionnaire. Endoscopic and histologic diagnosis of Barrett's esophagus, and optical image quality of both endoscopic procedures, were compared. RESULTS: A total of 21 of 25 patients completed the study. TEE had sensitivity and specificity of 100 % for an endoscopic diagnosis of Barrett's esophagus, and of 66.7 % and 100 %, respectively, for the histologic diagnosis of Barrett's esophagus. The mean optical quality of standard endoscopy was significantly better than that of TEE (7.11 ± 0.42 vs. 4.06 ± 0.27; P < 0.0001). However, following endoscopy, patients reported a significantly better experience with TEE compared with standard endoscopy (7.05 ± 0.49 vs. 4.35 ± 0.53; P = 0.0006), with 60 % preferring TEE and 25 % preferring sedated standard endoscopy. CONCLUSIONS: In this study, TEE had equal accuracy for an endoscopic diagnosis of Barrett's esophagus compared with standard endoscopy, at the expense of reduced image quality and a lower yield of intestinal metaplasia on biopsy. TEE was better tolerated and preferred by patients. Hence, TEE needs further evaluation in primary care as an initial diagnostic tool.This study was supported by funding from Cambridge Experimental Cancer Medicine Centre, NIHR Cambridge Biomedical Research Centre, and a core grant for RCF from the Medical Research Council. M.K.S. was supported by the BUPA Foundation.This is the author accepted manuscript. The final version is available from Thieme Publishing Group via http://dx.doi.org/10.1055/s-0034-139331

Empathic mediators for distance learning courses

Conferência Internacional realizada em Lisboa de 15-16 de novembro de 2018.Online distance learning introduces several challenges, such as the dependence of online tools, the asynchronous communication between teachers and students, and the lack of synchronous social engagement level that inclassroom teaching can leverage. The existence of an online tutor 24 hours/day would be an interesting asset to potentially work as an additional learning support tool. The Virtual Tutoring project aims at the development of solutions involving anthropomorphic 3D avatars that work as both virtual online tutors in the Moodle e-learning platform as well as coaches in a mobile application that interact empathically with the students by predicting their emotional state and selecting appropriate emotion regulation strategies. This paper presents the current status of the project, preliminary evaluations with students, and future developments.This work was developed in the context of the FCT project PTDC/IVC-PEC/3963/2014 with the support of the R&D units of his authors.info:eu-repo/semantics/publishedVersio

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Rate control is the key-Tachycardia induced Cardiomyopathy

Introduction: Tachycardia-induced cardiomyopathy is the systolic dysfunction that results from tachyarrhythmias. It presents symptoms of heart failure and can be reversed with rate control or normalization to sinus rhythm. The aim of presenting this case report is to the awareness of tachycardia-induced cardiomyopathy, which if recognized early can be reversed by the treatment. Case Presentation: A 62-year-old male with a history of tobacco use presented with orthopnea, palpitations, and exertional dyspnea. A month ago, he was seen by his primary care physician for palpitations and was diagnosed with new-onset atrial fibrillation. There was a gradual progression of his exertional symptoms to NYHA class IV that prompted him to come to the emergency room. Upon admission, he was noted to have atrial fibrillation with the rapid ventricular response at 140 bpm. An echocardiogram revealed an LV ejection fraction of 20 % with dilated LV and RV chambers. His heart rate was controlled with metoprolol and digoxin. He was started on a heart failure regimen. Ischemic cardiac workup was unremarkable. He was subsequently followed up in the clinic. The repeat cardiac echocardiogram was noted for marked improvement of LV systolic function and of the patient\u27s symptoms. He was continued on rate control and heart failure medications. Conclusion: Tachycardia-induced cardiomyopathy can result from various tachyarrhythmias including atrial fibrillation with a rapid ventricular response. In such cases, cardiomyopathy may develop over a few weeks to over a few years. Once tachycardia-induced cardiomyopathy is suspected, treatment should focus on rate control in addition to the management of heart failure. Our case demonstrates how increased awareness of tachycardia-induced cardiomyopathy helps in timely diagnosis and can be reversible

Ornamental Chasmophytes of Urumbikkara Hills, Western Ghats Region of Idukki District, Kerala, India

The present study on the ornamental chasmophytes in the rocky habitats of Urumbikkara hills of Idukki district, Kerala reveals that, there are about 52 species of ornamental chasmophytic plants belonging to 46 genera and 29 families were collected because of their aesthetic value in both domestic and rock garden practices. These chasmophytes also possess certain biological peculiarities with different interesting adaptations and flower colour which can attract many people for making domestic or rock garden for ornamental purposes and psychological beneficial

Stability of Expansion Attained with Sel-ligating Bracket System

Background: The Self-ligating system with in-built mechanism to secure the arch wire advocates comfort for the patient and clinician, reduces the chair side time and produces an expansion of the arch. Damon philosophy emphasises on light forces just enough to move teeth. The intra arch expansion is achieved by boarder arch wires, increasing the inter-canine, inter-premolar and inter-molar distance. The stability of the expansion achieved over the retention period determines the success of the treatment. For the clinician, it’s a challenge to assert the merits for the self-ligating brackets as there are limited studies evaluating the stability of the transverse expansion achieved in both adults and adolescents. This literature review focuses on the transverse expansion achieved by self-ligating systems in the long term and to evaluate if there are any variations in the results achieved in adolescents and adults

Investigation of LKB1 Ser⁴³¹ phosphorylation and Cys⁴³³ farnesylation using mouse knockin analysis reveals an unexpected role of prenylation in regulating AMPK activity

The LKB1 tumour suppressor protein kinase functions to activate two isoforms of AMPK (AMP-activated protein kinase) and 12 members of the AMPK-related family of protein kinases. The highly conserved C-terminal residues of LKB1 are phosphorylated (Ser(431)) by PKA (cAMP-dependent protein kinase) and RSK (ribosomal S6 kinase) and farnesylated (Cys(433)) within a CAAX motif. To better define the role that these post-translational modifications play, we created homozygous LKB1(S431A/S431A) and LKB1(C433S/C433S) knockin mice. These animals were viable, fertile and displayed no overt phenotypes. Employing a farnesylation-specific monoclonal antibody that we generated, we established by immunoprecipitation that the vast majority, if not all, of the endogenous LKB1 is prenylated. Levels of LKB1 localized at the membrane of the liver of LKB1(C433S/C433S) mice and their fibroblasts were reduced substantially compared with the wild-type mice, confirming that farnesylation plays a role in mediating membrane association. Although AMPK was activated normally in the LKB1(S431A/S431A) animals, we unexpectedly observed in all of the examined tissues and cells taken from LKB1(C433S/C433S) mice that the basal, as well as that induced by the AMP-mimetic AICAR (5-amino-4-imidazolecarboxamide riboside), AMPK activation, phenformin and muscle contraction were significantly blunted. This resulted in a reduced ability of AICAR to inhibit lipid synthesis in primary hepatocytes isolated from LKB1(C433S/C433S) mice. The activity of several of the AMPK-related kinases analysed [BRSK1 (BR serine/threonine kinase 1), BRSK2, NUAK1 (NUAK family, SNF1-like kinase 1), SIK3 (salt-inducible kinase 3) and MARK4 (MAP/microtubule affinity-regulating kinase 4)] was not affected in tissues derived from LKB1(S431A/S431A) or LKB1(C433S/C433S) mice. Our observations reveal for the first time that farnesylation of LKB1 is required for the activation of AMPK. Previous reports have indicated that a pool of AMPK is localized at the plasma membrane as a result of myristoylation of its regulatory AMPKβ subunit. This raises the possibility that LKB1 farnesylation and myristoylation of AMPKβ might promote the interaction and co-localization of these enzymes on a two-dimensional membrane surface and thereby promote efficient activation of AMPK

International Consortium on Mammographic Density:methodology and population diversity captured across 22 countries

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses