Combinatory cytotoxic effects produced by E1B-55kDa-deleted adenoviruses and chemotherapeutic agents are dependent on the agents in esophageal carcinoma

We examined possible combinatory antitumor effects of replication-competent type 5 adenoviruses (Ad) lacking E1B-55kDa molecules (Ad-delE1B55) and chemotherapeutic agents in nine human esophageal carcinoma cells. Ad-delE1B55 produced cytotoxic effects on all the carcinoma cells and the cytotoxicity is not directly linked with the p53 status of the tumors or with the infectivity to respective tumors. A combinatory treatment with Ad-delE1B55 and an anticancer agent, 5-fluorouracil (5-FU), mitomycin C or etoposide, produced greater cytotoxic effects than that with either the Ad or the agent. Administration of 5-FU could minimally inhibit the viral replication and a simultaneous treatment with the Ad and 5-FU achieved better cytotoxicity than sequential treatments. We also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU in vivo. Cisplatin, however, did not achieve the combinatory effects in most of the cells tested. These data indicate that the Ad-delE1B55 produce combinatory antitumor effects with a chemotherapeutic agent irrespective of the administration schedule, but the effects depend on an agent in esophageal carcinoma

EULAR definition of difficult-to-treat rheumatoid arthritis

Background: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have ‘difficult-to-treat RA’. However, uniform terminology and an appropriate definition are lacking. Objective: The Task Force in charge of the „Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis” aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to treat RA, as the first step. Methods: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting). Results: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: 1) Treatment according to EULAR rec-ommendation and failure of ≥2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy (unless contraindicated); 2) presence of at least one of the follow-ing: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; 3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient. Conclusions: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research

Phase curve and geometric albedo of WASP-43b measured with CHEOPS, TESS, and HST WFC3/UVIS

Context. Observations of the phase curves and secondary eclipses of extrasolar planets provide a window onto the composition and thermal structure of the planetary atmospheres. For example, the photometric observations of secondary eclipses lead to the measurement of the planetary geometric albedo, Ag, which is an indicator of the presence of clouds in the atmosphere. Aims: In this work, we aim to measure the Ag in the optical domain of WASP-43b, a moderately irradiated giant planet with an equilibrium temperature of ~1400 K. Methods: For this purpose, we analyzed the secondary eclipse light curves collected by CHEOPS together with TESS along with observations of the system and the publicly available photometry obtained with HST WFC3/UVIS. We also analyzed the archival infrared observations of the eclipses and retrieve the thermal emission spectrum of the planet. By extrapolating the thermal spectrum to the optical bands, we corrected for the optical eclipses for thermal emission and derived the optical Ag. Results: The fit of the optical data leads to a marginal detection of the phase-curve signal, characterized by an amplitude of 160 ± 60 ppm and 80−50+60 ppm in the CHEOPS and TESS passbands, respectively, with an eastward phase shift of ~50° (1.5σ detection). The analysis of the infrared data suggests a non-inverted thermal profile and solar-like metallicity. The combination of the optical and infrared analyses allows us to derive an upper limit for the optical albedo of Ag< 0.087, with a confidence of 99.9%. Conclusions: Our analysis of the atmosphere of WASP-43b places this planet in the sample of irradiated hot Jupiters, with monotonic temperature-pressure profile and no indication of condensation of reflective clouds on the planetary dayside

The phase curve and the geometric albedo of WASP-43b measured with CHEOPS, TESS and HST WFC3/UVIS

peer reviewe

Temporal profiling of the coding and noncoding murine cytomegalovirus transcriptomes

The global transcriptional program of murine cytomegalovirus (MCMV), involving coding, noncoding, and antisense transcription, remains unknown. Here we report an oligonucleotide custom microarray platform capable of measuring both coding and noncoding transcription on a genome-wide scale. By profiling MCMV wild-type and immediate-early mutant strains in fibroblasts, we found rapid activation of the transcriptome by 6.5 h postinfection, with absolute dependency on ie3, but not ie1 or ie2, for genomic programming of viral gene expression. Evidence is also presented to show, for the first time, genome-wide noncoding and bidirectional transcription at late stages of MCMV infection

Update on hypertrophic cardiomyopathy and a guide to the guidelines

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, affecting 1 in 500 individuals worldwide. Existing epidemiological studies might have underestimated the prevalence of HCM, however, owing to limited inclusion of individuals with early, incomplete phenotypic expression. Clinical manifestations of HCM include diastolic dysfunction, left ventricular outflow tract obstruction, ischaemia, atrial fibrillation, abnormal vascular responses and, in 5% of patients, progression to a 'burnt-out' phase characterized by systolic impairment. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. The majority of individuals with HCM, however, have normal or near-normal life expectancy, owing in part to contemporary management strategies including family screening, risk stratification, thromboembolic prophylaxis, and implantation of cardioverter-defibrillators. The clinical guidelines for HCM issued by the ACC Foundation/AHA and the ESC facilitate evaluation and management of the disease. In this Review, we aim to assist clinicians in navigating the guidelines by highlighting important updates, current gaps in knowledge, differences in the recommendations, and challenges in implementing them, including aids and pitfalls in clinical and pathological evaluation. We also discuss the advances in genetics, imaging, and molecular research that will underpin future developments in diagnosis and therapy for HCM

Recommendations for the assessment and optimization of adherence to disease modifying drugs in chronic inflammatory rheumatic diseases: a process based on literature review and consensus

International audienc

Recommandations pour l'évaluation et l'optimisation de l'adhésion aux traitements de fond dans les rhumatismes inflammatoires chroniques : les Rencontres d'Experts en Rhumatologie 2017, un processus base sur des revues de la literature et un consensus

International audienc