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Coronavirus infectious diseases 2019 (COVID-19), a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a serious public health threat worldwide. So far, there are no drugs and vaccines whose efficacy has been well-proven. After the outbreak, there has been a massive search for anti-SARS-CoV-2 medications, focusing on approved drugs because repurposing approved drugs will take less time to reach clinical usage than new drugs. This article summarizes the studies using in silico and in vitro approaches to identify therapeutic candidates among approved drugs that target the SARS-CoV-2 life cycle.Microtubule is a key component of cytoskeleton and has been considered as an important target for the treatment of cancer. learn more In particular, the tubulin taxane-site inhibitors such as taxol analogs and epothilones have achieved great success in clinical trials. However, the structural basis of many taxane-site inhibitors is still lacking in exploring their mechanism of action. We here reported crystal complex structures for three taxane-site inhibitors, Ixabepilone, Epothilone B, and Epothilone D, which were determined to 2.4 Å, 2.4 Å, and 2.85 Å, respectively. The crystal structures revealed that these taxane-site inhibitors possess similar binding modes to that of Epothilone A at the taxane site, e.g. making critical hydrogen-bonding interactions with multiple residues on the M-loop, which facilitating the tubulin polymerization. Furthermore, we summarized the binding modes of almost all taxane-site inhibitors and identified novel taxane-site ligands with simpler chemical structures through virtual screening. On this basis, new derivatives with higher binding affinity to tubulin were designed and developed, which can form additional hydrogen bond interactions with tubulin. Overall, this work determined the mechanism of action of epothilones and provided a structural basis to design reasonably novel taxane-site inhibitors with simpler structure and improved pharmacokinetic properties.

Multiple sclerosis (MS) is a demyelinating disease requiring multidisciplinary care coordination. Recent development of diagnosis criteria and disease modifying treatments have encouraged the setup of regional team meetings by MS expert centers, known as CRC Sep, to improve the quality of care provided to patients with complex cases. The CRC Sep in Caen initiated regional telemedicine meetings named Télé-SEP, operating since 2016. The objective of this study was to evaluate the Télé-SEP used by neurologists, on MS patient care management in Normandy.

An internal ex-itinere evaluation was conducted with a retrospective descriptive observational study from July 2016 to June 2018. The Télé-SEP meetings were organized with 41 neurologists using a regional telemedicine platform (Therap-e). Data were collected from online records and a declarative voluntary survey. Twenty indicators were classified in the categories volume of activity, clinical profile, quality and impact.

Fifteen meetings were organized with a median of 13 senior neurologists. One hundred forty MS cases were discussed and there was a 33% increase in the second year of Télé-SEP. Median patient age was 44 years with a 72-month median length of disease. Most patient cases required second-line treatment. Relapsing remitting MS was diagnosed in 51.4% of cases. Télé-SEP satisfaction rate was 4.5/5 and 96% of neurologists applied the medical decisions and recommendations given in the meetings.

Without Télé-SEP, 54.5% of patients would have been referred to a physical expert consultation in the CRC Sep. This study showed the feasibility and relevance of regional telemedicine team meetings for MS cases in the Normandy region.

Without Télé-SEP, 54.5% of patients would have been referred to a physical expert consultation in the CRC Sep. This study showed the feasibility and relevance of regional telemedicine team meetings for MS cases in the Normandy region.

Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive tumor. This study aims to describe the clinical characteristics and outcomes of CCSK patients in one of the largest pediatric medical centers in China.

We included all patients diagnosed with CCSK between January 2008 and March 2019 at the Children's Hospital of Chongqing Medical University, China. The patients' demographics, clinical presentation, and management were reviewed. Follow-up was continued until December 2019.

In total, 41 CCSK patients (66% male) with a median age of 24 months (range 3-108 months) were identified. The stage distributions of stages I, II, III and IV were 42%, 34%, 24% and 0%, respectively. Preoperative chemotherapy was administered to 7/41 patients. All patients underwent radical nephrectomy and postoperative chemotherapy. The median number of lymph nodes sampled was 4 (range 1-12). Radiotherapy was applied in 8/41 patients. The 5-year event-free survival (EFS) and overall survival (OS) were 63.9% and 78.8%, respectively. Of the 41 patients, 11 patients experienced relapse at a median time of 19 months (range 5-72 months). The most common site of recurrence was the tumor bed (9/11). Young age was a significant adverse prognostic factor for EFS.

The overall outcome of CCSK patients in our hospital is poorer than that in developed regions. More research is needed to clarify the underlying causes of poorer outcomes in young patients and improve outcomes.

Retrospective study.

LEVEL IV.

LEVEL IV.

The objective of this study was to examine the effect of a novel mindfulness-based time-out intervention on state of mindfulness among emergency nurses and, accordingly, on patient satisfaction.

A pre-post intervention design among nurses in the emergency department was used with a between-subjects factor of patients who were nested within each nurse. The study was conducted between January 2017 and June 2018 among 48 nurses in the emergency department of a public tertiary academic hospital. For each nurse, a consecutive sample of 20 patients who attended the emergency department was recruited (n= 1920 patients; 960 in each phase). The mindfulness-based time-out intervention was based on theoretical mindfulness principles and carried out every 4 hours with direct communication to the patient at their bedside. Nurses' sociodemographic and professional characteristics and trait mindfulness were collected preintervention. Pre- and postintervention, data was collected on patients' sociodemographic and satisfaction, nurses' state mindfulness, and ED workload.