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30, P = 0.003), and PHS with pachydrusen (φ 0.20, P = 0.040). Over a mean follow-up of 74.8months, new drusen co-localizing to PHS were noted in 22 (21.0%) eyes (φ 0.54, P < 0.001).

We observed a trend of pachydrusen appearing in conjunction with PHS in PCV or PNV. Frequent localization of new drusen to these choroidal lesions was observed over long-term follow-up. PHS may be a form of late-staining "forme fruste" drusen, possibly associated with micro-ischemic changes to the choriocapillaris.

We observed a trend of pachydrusen appearing in conjunction with PHS in PCV or PNV. Frequent localization of new drusen to these choroidal lesions was observed over long-term follow-up. PHS may be a form of late-staining "forme fruste" drusen, possibly associated with micro-ischemic changes to the choriocapillaris.

As critical parameter after extravasation of cytotoxic vesicants, anthracyclines were determined in removed tissue from patients requiring surgical intervention due to tissue necrosis. We monitored their distribution within the affected lesion to establish a possible dose-toxicity relation.

From six patients scheduled for surgery, removed tissue flaps were systematically analysed by HPLC (epirubicin 5 subjects; doxorubicin 1 subject).

After extravasation, tissue concentrations were highly variable with an individual anthracycline distribution pattern ranging from a few nanograms up to 17µg per 100mg tissue, which indicated a substantial difference in tissue sensitivity among patients. The resection borders coincided with the extension of the erythema and guided the surgical intervention after demarcation of the lesion, which occurred usually 2 or 3weeks after extravasation. At that time, drug was hardly detected at the resection borders. Wound drains were negative for the extravasated drugs while showing a time profile of vascular growth factors and inflammatory cytokines, which was highly similar to routine surgery. In all six patients, surgical debridement with immediate wound closure led to healing within approximately 2weeks, when therapy was resumed in all patients with reasonable time delay.

Surgical intervention after demarcation of the extravasation lesion allows for almost uninterrupted continuation of treatment independent of the amount of extravasated anthracycline. Gefitinib As even minor amounts of the vesicants may trigger tissue necrosis, preventive measures merit the highest priority.

Surgical intervention after demarcation of the extravasation lesion allows for almost uninterrupted continuation of treatment independent of the amount of extravasated anthracycline. As even minor amounts of the vesicants may trigger tissue necrosis, preventive measures merit the highest priority.

Limited value is achieved in systemic chemotherapy for oral squamous cell carcinoma (OSCC), due to cancer cell resistance against cytotoxic agents. Tumor suppressor activities of selenium-binding protein 1 (SELENBP1) have been shown in multiple human cancers except for OSCC. The aim of this study is to clarify the biological functions and potential mechanism of SELENBP1 in OSCC.

SELENBP1 expression and its clinical significance in OSCC were analyzed from The Cancer Genome Atlas (TCGA) database. Quantitative polymerase chain reaction (qPCR) or western blot was applied to determine SELENBP1, NRF2 and KEAP1 mRNA or protein levels. Sulforhodamine B assay (SRB) was performed to examine the cytotoxic effects of 5-fluorouracil (5-FU) and cisplatin on OSCC cells. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to investigate the role of SELENBP1 in KEAP1 transcription.

SELENBP1 downregulation is positively correlated with a poor prognosis for OSCC patients. SELENBP1 knockdown enhances resistance of OSCC cells to 5-FU and cisplatin, while SENENBP1 overexpression displays the opposite effects. Mechanistically, SELENBP1 reduces NRF2 protein levels by promoting its polyubiquitination and degradation. SELENBP1 induces KEAP1 transcription by binding to KEAP1 promoter. Downregulation of SELENBP1 is induced by miR-4786-3p binding to the 3' untranslated region (UTR) of SELENBP1.

SENENBP1 is identified as a novel protective biomarker for OSCC patients. Targeting at the miR-4786-3p-SELENBP1-KEAP1-NRF2 signaling axis may enhance the efficacy of chemotherapy for OSCC.

SENENBP1 is identified as a novel protective biomarker for OSCC patients. Targeting at the miR-4786-3p-SELENBP1-KEAP1-NRF2 signaling axis may enhance the efficacy of chemotherapy for OSCC.Evidence from the Global Burden of Disease studies suggests that osteoarthritis (OA) is a significant cause of disability globally; however, it is less clear how much of this burden exists in low-income and lower middle-income countries. This study aims to determine the prevalence of OA in people living in low-income and lower middle-income countries. Four electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science) were systematically searched from inception to October 2018 for population-based studies. We included studies reporting the prevalence of OA among people aged 15 years and over in low-income and lower middle-income countries. The prevalence estimates were pooled across studies using random effects meta-analysis. Our study was registered with PROSPERO, number CRD42018112870.The search identified 7414 articles, of which 356 articles were selected for full text assessment. 34 studies were eligible and included in the systematic review and meta-analysis. The pooled prevalence of OA was 16·05% (95% confidence interval (CI) 12·55-19·89), with studies demonstrating a substantial degree of heterogeneity (I2 = 99·50%). The pooled prevalence of OA was 16.4% (CI 11·60-21.78%) in South Asia, 15.7% (CI 5·31-30·25%) in East Asia and Pacific, and 14.2% (CI 7·95-21·89%) in Sub Saharan Africa. The meta-regression analysis showed that publication year, study sample size, risk of bias score and country-income categories were significantly associated with the variations in the prevalence estimates. The prevalence of OA is high in low-income and lower middle-income countries, with almost one in six of the study participants reported to have OA. With the changing population demographics and the shift to the emergence of non-communicable diseases, targeted public health strategies are urgently needed to address this growing epidemic in the aging population.