Johnsenwalter1017

Inhibition of adipogenesis is an important strategy for obesity treatment. Rocaglamide-A (Roc-A) is a natural herbal medicine isolated from the genus Aglaia (family Meliaceae), which has a cyclopenta[b]benzofuran core structure. Roc-A exhibits various pharmacological effects against diverse human cancer cells. However, the exact role of Roc-A during adipogenesis in adipocytes has not been studied at all. In this study, we demonstrate that Roc-A is crucial for reducing adipogenesis via downregulating PPARγ transcriptional activity. Consistently, Western-blot and RT-PCR analyses clearly showed that Roc-A inhibits the expression of PPARγ target genes and lipogenic markers in a dose-dependent manner along with suppression of lipid accumulation, in both 3T3-L1 cells and mouse adipose-derived stem cells. Mechanistically, Roc-A significantly decreased STAT3 phosphorylation in a dose-dependent manner in 3T3-L1 adipocytes. In particular, we confirmed that Roc-A effectively suppressed the expression of genes involved in cell-cycle regulation, such as cyclin A, B, D1, and E1, early during mitotic clonal expansion in 3T3-L1 adipocytes, and this effect was abolished by the JAK2/STAT3 activator FGF2. Taken together, our results demonstrated that Roc-A reduces adipogenesis by inhibiting PPARγ transactivation and STAT3 phosphorylation and thus may serve as a therapeutic target in obesity.

Twelve-lead electrocardiogram (ECG) represents the first-line approach for cardiovascular assessment in patients with Covid-19.

We sought to describe and compare admission ECG findings in 3 different hospital settings intensive-care unit (ICU) (invasive ventilatory support), respiratory care unit (RCU) (non-invasive ventilatory support) and Covid-19 dedicated internal-medicine unit (IMU) (oxygen supplement with or without high flow). We also aimed to assess the prognostic impact of admission ECG variables in Covid-19 patients.

We retrospectively analyzed the admission 12-lead ECGs of 1124 consecutive patients hospitalized for respiratory distress and Covid-19 in a single III-level hospital. Age, gender, main clinical data and in-hospital survival were recorded.

548 patients were hospitalized in IMU, 361 in RCU, 215 in ICU. Arrhythmias in general were less frequently found in RCU (16% vs 26%, p<0.001). Deaths occurred more frequently in ICU patients (43% vs 20-21%, p<0.001). After pooling predictors of mortality (age, intensity of care setting, heart rate, ST-elevation, QTc prolongation, Q-waves, right bundle branch block, and atrial fibrillation), the risk of in-hospital death can be estimated by using a derived score. Three zones of mortality risk can be identified <5%, score <5 points; 5-50%, score 5-10, and >50%, score >10 points. The accuracy of the score assessed at ROC curve analysis was 0.791.

ECG differences at admission can be found in Covid-19 patients according to different clinical settings and intensity of care. A simplified score derived from few clinical and ECG variables may be helpful in stratifying the risk of in-hospital mortality.

ECG differences at admission can be found in Covid-19 patients according to different clinical settings and intensity of care. A simplified score derived from few clinical and ECG variables may be helpful in stratifying the risk of in-hospital mortality.The efficiencies of a proton recoil neutron telescope for neutron energies ranging from 4 MeV to 20 MeV were calculated for different geometries given by Bame et al., for the case of an isotropic point neutron source colinear with the radiator and charge particle detector that are parallel & coaxial to each other. An analytical expression for the efficiency was obtained as a function of the radiator size, detector aperture, source-radiator & radiator-detector distances and n-p differential scattering cross section. The relativistic transformation of n-p differential scattering cross section from center-of-mass to laboratory system was used in the calculations, taking into account the angular anisotropy of the n-p scattering. The accuracies of the calculations were checked by comparing with published efficiency values by Thomas & Axton and Bame et al. The difference between calculated and published efficiencies were small and, in most cases, it was below 1%. Finally, efficiency of the telescope was calculated using the latest n-p scattering cross section data from the evaluated nuclear data file (ENDF) VII for neutron energies ranging from 4 MeV to 20 MeV.Interest in targeted cancer therapy with alpha-emitting radionuclides is growing. To evaluate emerging radiotherapeutic agents requires precise activity measurements for consistent dose-response relationships and patient-specific dosimetry. National metrology institutes around the world have reported on the development and comparison of activity standards for medically important alpha emitters. This review describes the relevant methods and models underpinning these standards, the generation of new nuclear decay data, and the impacts on preclinical and clinical activity assays using radionuclide calibrators and γ-ray spectrometry.A clinical pathway (CP) is a tool for effectively managing a care process. There are several research efforts on developing clinical pathways (CPs) in the process mining domain. However, the nature of the data affects data analysis results, and patient clinical variability makes it challenging to develop CPs. Thus, it is crucial to determine candidate care processes that can be standardized as CPs before applying process mining techniques. This paper proposed a method for assessing CP feasibility regarding clinical complexity using clinical order logs from electronic health records. The proposed method consists of data preparation, activity & trace homogeneity evaluations, and process inspection using process mining. Each step consists of metrics to measure the homogeneity of processes and a visualization method to demonstrate the diversity of processes based on the log. The case study was conducted with five surgical groups of patients from a tertiary hospital in South Korea to validate the proposed method. The five groups of patients were successfully assessed. In addition, the visualization methods helped clinical experts grasp the diversity of care processes.The occurrence and development of diseases are related to the dysfunction of biomolecules (genes, metabolites, etc.) and the changes of molecule interactions. Identifying the key molecules related to the physiological and pathological changes of organisms from omics data is of great significance for disease diagnosis, early warning and drug-target prediction, etc. A novel feature selection algorithm based on the feature individual distinguishing ability and feature influence in the biological network (FS-DANI) is proposed for defining important biomolecules (features) to discriminate different disease conditions. The feature individual distinguishing ability is evaluated based on the overlapping area of the feature effective ranges in different classes. FS-DANI measures the feature network influence based on the module importance in the correlation network and the feature centrality in the modules. The feature comprehensive weight is obtained by combining the feature individual distinguishing ability and feature influence in the network. Then crucial feature subset is determined by the sequential forward search (SFS) on the feature list sorted according to the comprehensive weights of features. FS-DANI is compared with the six efficient feature selection methods on ten public omics datasets. The ablation experiment is also conducted. Experimental results show that FS-DANI is better than the compared algorithms in accuracy, sensitivity and specificity on the whole. On analyzing the gastric cancer miRNA expression data, FS-DANI identified two miRNAs (hsa-miR-18a* and hsa-miR-381), whose AUCs for distinguishing gastric cancer samples and normal samples are 0.959 and 0.879 in the discovery set and an independent validation set, respectively. Hence, evaluating biomolecules from the molecular level and network level is helpful for identifying the potential disease biomarkers of high performance.Both matrix stiffening and remodeling of calcium signaling occur in breast cancers, with downstream consequences linked to the progression of the disease. However, the potential intersection between calcium signaling and matrix stiffness has not been fully assessed in models of cancer. Here, we describe the assessment of calcium signaling in breast cancer cells at high and low matrix stiffness using novel gel culture models (gelatin methacryloyl and polydimethylsiloxane) and MDA-MB-231 breast cancer cells expressing the calcium sensor GCaMP6m. Remodeling of ATP-stimulated cytosolic calcium responses in cells on different matrices was assessed using a high throughput fluorescence imaging plate reader. Our data reveal that matrices of higher stiffness attenuate ATP-induced sustained calcium influx in MDA-MB-231 breast cancer cells. This matrix-mediated attenuation of sustained calcium influx was dependent on the store-operated calcium channel component ORAI1. MEDICA16 These studies suggest that calcium signaling in breast cancer cells can be altered as a consequence of matrix stiffness; modulation of such pathways may represent a new mechanism to target calcium signaling to regulate tumor progression in breast cancer.

Reverse total shoulder arthroplasty (RSA) associated with modified L'Episcopo (isolated LD) or L'Episcopo (combined TM and LD) procedures had been confirmed to effectively overcome the expected external rotation deficit in patient with postero-superior massive cuff tear and teres minor deficiency. The objective of this study was to evaluate the radiological bony lesions of the lateral proximal humerus following RSA combined with tendon transfer, and to determine whether these bony lesions affect the clinical outcome.

A retrospective review of 24 RSAs (mean age 68.71 years, range 52-83) associated with modified L'Episcopo procedure (9) and L'Episcopo procedure (15) was performed. X-rays were assessed for lateral cortex lesions and were categorized into either intact, irregular or complete lytic appearances. In addition, signs of stem loosening were assessed. Clinical outcome measures included range of motion, SSV, VAS, and Constant-Murley scores.

With a mean follow-up of 44.71 months (12-97; SD 27.42), e appeared in non-cemented stems. Yet, no case of humeral loosening was detected and these lesions did not seem to affect the clinical outcome. The use of cemented straight standard-length humeral stems should be positively considered in RSA associated with LD\TM tendon transfer.

IV; retrospective study.

IV; retrospective study.

Although the use of short stem and stemless shoulder prosthesis is trending, the surgical outcome may vary due to varying biomechanics. Objectives were to evaluate and compare the short-term clinical results and radiological changes between anatomical total shoulder arthroplasty (TSA) and reverse TSA (rTSA) with a short-stem humeral design.

There is no clinical and radiological difference between TSA and rTSA using a short-stem humeral design.

This retrospective study included 66 patients who underwent TSA and rTSA (33 patients each) with a minimum 2-year follow-up. Radiographic findings, including preoperative Tingart cortical index (TCI), postoperative filling ratios of metaphysis (FRmet) and diaphysis (FRdia), bone adaptations, and osteolysis around the humeral stem at the immediate postoperative period, and the most recent follow-up were measured. Pre and postoperative Constant-Murley score, subjective shoulder value (SSV), and complications were noted.

At a mean follow-up of 27 (range 24-50) months, FRmet was significantly higher in rTSA group than the TSA group (0.