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Three new pyrrolobenzoxazine sesquiterpenoids, talatrachyoxazines A - C (1  - 3 ), together with fourteen known compounds (4  - 17 ), were isolated from the fungus Talaromyces trachyspermus EU23. Their structures were identified by spectroscopic evidence and mass spectrometry. The absolute configurations of 1  - 3 were determined by NOESY data and comparison of their calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 showed cytotoxic activity against HelaS3, KB, HT-29, MCF-7, and HepG2 cell lines with IC50 values of 7, 11, 10, 12, and 10 µM, respectively. Compounds 1 and 14 showed weak antibacterial activity against the gram-positive bacteria Bacillus cereus and Bacillus subtilis, while 1  - 3 and 14 showed weak antibacterial activity against the gram-negative bacterium Pseudomonas aeruginosa. In addition, compound 1 showed weak antibacterial activity against Escherichia coli.

The aim of this study was to assess risk factors for prescription of potentially inappropriate medication (PIM) to nursing home residents using the PRISCUS list in 2017.

Using claims data (AOK) we analysed insured nursing home residents aged 65 or older in 2017. The PRISCUS list was used to identify PIMs. A multivariate logistic regression analysis was performed to analyse risk factors.

The study population in 2017 included 259 328 nursing home residents, out of them 25.5% received at least one potentially inappropriate medication (women 25.6%/men 24.9%). Female and younger aged nursing home residents had a higher risk for at least one PRISCUS prescription. Polypharmacy, an increasing number of attending physicians, and hospital stays were additional risk factors for a PRISCUS prescription. Furthermore, regional (Bundesland) variations contributed to differences in PRISCUS prescriptions.

The frequent PIM prescriptions in nursing home residents are a relevant topic regarding drug therapy safety. Regional differences, which cannot be explained by nursing home resident characteristics, show options for modifications and the need for further research.

The frequent PIM prescriptions in nursing home residents are a relevant topic regarding drug therapy safety. Regional differences, which cannot be explained by nursing home resident characteristics, show options for modifications and the need for further research.

 Colorectal cancer (CRC) diagnosed following a cancer-negative colonoscopy is termed post-colonoscopy CRC (PCCRC). In addition to calculating PCCRC rates, the World Endoscopy Organization (WEO) recommends review of individual PCCRC cases, including categorization into interval/non-interval PCCRCs, and root cause analysis to determine the most plausible explanation. We aimed to test the usability, reproducibility, and outcomes of the WEO algorithms.

 All CRC cases diagnosed from January 2015 to December 2016 in a single organization were cross referenced with local endoscopy and pathology databases to identify cases of PCCRC. We assessed 1) WEO most plausible explanation for PCCRC; and 2) WEO PCCRC interval/non-interval subtype categorization. Interobserver agreement was measured using Cohen's kappa (κ). Cases with interobserver variation underwent panel discussion to reach consensus.

 Among 527 patients with CRC, 48 PCCRCs were identified. A consistent most plausible explanation was found in 97 % of cas intervals.

Diabetic cardiomyopathy (DCM) is one of the complications experienced by patients with diabetes. In recent years, long noncoding RNAs (lncRNAs) havebeen investigated because of their role in the progression of various diseases, including DCM. The purpose of this study was to explore the role of lncRNA GAS5 in high-glucose (HG)-induced cardiomyocyte injury and apoptosis.

We constructed HG-induced AC16 cardiomyocytes and a streptozotocin-induced rat diabetes model. GAS5 was overexpressed and knocked out at the cellular level, and GAS5 was knocked down by lentiviruses at the animal level to observe its effect on myocardial injury. Real-time quantitative polymerase chain reaction was used to detect the expression of GAS5. Cell proliferation and apoptosis after GAS5 knockout were detected byCCK-8, TUNEL, and flow cytometry assays. ELISA was used to detectthe changes in myocardial enzyme content in cells and animal myocardial tissues during the action of GAS5 on myocardial injury.

GAS5 expression was up-regulated in HG-treated AC16 cardiomyocytes and the rat diabetic myocardial injury model. The down-regulation of GAS5 inhibited HG-induced myocardial damage. This work proved that GAS5 konckdown reversed cardiomyocyte injury and apoptosis by targeting miR-138 to down-regulate CYP11B2.

We confirmed for the first time that the down-regulation of GAS5 could reverse CYP11B2 via the miR-138 axis to reverse HG-induced cardiomyocyte injury. This research might provide anew direction for explaining the developmental mechanism of DCM and potential targets for the treatment of myocardial injury.

We confirmed for the first time that the down-regulation of GAS5 could reverse CYP11B2 via the miR-138 axis to reverse HG-induced cardiomyocyte injury. This research might provide a new direction for explaining the developmental mechanism of DCM and potential targets for the treatment of myocardial injury.

To investigate the clinical characteristics of patients with difficult-to-treat rheumatoid arthritis (D2T RA) and the usefulness of switching drugs with different mode of action in the real world.

We reviewed all consecutive patients with RA treated at Keio University Hospital between 2016 and 2017with a definition of D2T RA. We analysed clinical characteristics and evaluated the usefulness of changing drugs according to mode of action.

Among 1709 patients with RA, 173 (10.1%) were D2T RA. The reason for the D2T RA was multi-drug resistance in 59 patients (34.1%), comorbidity in 17 (9.8%), and socioeconomic reasons in 97 (56.1%). The multi-drug resistance group had significantly higher tender joint count and evaluator global assessment than the other groups despite receiving the most intensive treatment. selleck chemicals The comorbidity group showed a significantly older age and higher rheumatic disease comorbidity index. Although changing the drug to another with a different mode of action was useful, the proportion of patients who achieved remission or low disease activity decreased as the number of switches increased.