Occlusion training: pilot study for postoperative lower extremity rehabilitation following primary total knee arthroplasty.

With continued emphasis on the value of healthcare, factors such as quality of life and patient reported outcomes are critical in evaluating high-demand procedures such as knee replacement surgery. Equally important to the surgery itself is maximizing the effectiveness and efficiency of the treatment, both preoperatively and postoperatively, which can have a significant effect the final outcome. Technical outcomes of total knee replacement are generally considered excellent; however, many patients continue to have postoperative pain, functional limitations, and low treatment satisfaction. The recovery process can be difficult and is often prolonged in older patient populations. Blood flow restriction (BFR) training is a resistance exercise performed with a venous tourniquet that stimulates local changes in muscle at low resistance. Herein we report on 3 patients who participated in BFR exercises as an adjunct to their normal physical therapy following total knee arthroplasty.

Notch-1 regulates transcription of the epidermal growth factor receptor through p53.

The Notch pathway plays a key role in the development and is increasingly recognized for its importance in cancer. We demonstrated previously the overexpression of Notch-1 and its ligands in gliomas and showed that their knockdown inhibits glioma cell proliferation and survival. To elucidate the mechanisms downstream of Notch-1 in glioma cells, we performed microarray profiling of glioma cells transfected with Notch-1 small interfering RNA. Notable among downregulated transcripts was the epidermal growth factor receptor (EGFR), known to be overexpressed or amplified in gliomas and prominent in other cancers as well. Further studies confirmed that Notch-1 inhibition decreased EGFR messenger RNA (mRNA) and EGFR protein in glioma and other cell lines. Transfection with Notch-1 increased EGFR expression. Additionally, we found a significant correlation in levels of EGFR and Notch-1 mRNA in primary high-grade human gliomas. Subsequent experiments showed that p53, an activator of the EGFR promoter, is regulated by Notch-1. Experiments with p53-positive and -null cell lines confirmed that p53 partially mediates the effects of Notch-1 on EGFR expression. These results show for the first time that Notch-1 upregulates EGFR expression and also demonstrate Notch-1 regulation of p53 in gliomas. These observations have significant implications for understanding the mechanisms of Notch in cancer and development.