Chronic back pain (CBP) is a major global health problem, while its treatment is hampered by a lack of efficacy and restricted safety profile of common frontline therapies. The present trial aims to determine whether a 3-week open-label placebo treatment reduces pain intensity and subjective and objective functional disability in patients with CBP. This randomized controlled trial, following a pretest–posttest design, enrolled 127 patients with CBP (pain duration >12 weeks) from the Back Pain Center, Neurology, University Hospital Essen, Germany. Patients randomized to the open-label placebo group received a 3-week open-label placebo treatment. Patients in the treatment as usual (TAU) group received no intervention. Both groups continued TAU. Primary outcome was the change in pain intensity. Secondary outcomes included patient-reported functional disability and objective measures of spine mobility and depression, anxiety, and stress. One hundred twenty two patients with CBP were randomized to the open-label placebo group (N = 63) or TAU group (N = 59). Open-label placebo application led to a larger reduction of pain intensity (−0.62 ± 0.23 vs 0.11 ± 0.17, all M ± SE, P = 0.001, d = −0.44) as well as patient-reported functional disability (3.21 ± 1.59 vs 0.65 ± 1.15, P = 0.020, d = −0.45) and depression scores (−1.07 ± 0.55 vs 0.37 ± 0.39, P = 0.010, d = −0.50) compared with TAU only. Open-label placebo treatment did not affect objective mobility parameters, anxiety and stress. Our study demonstrates that a 3-week open-label placebo treatment is safe, well tolerated and reduces pain, disability, and depressive symptoms in CBP. Trial registration: German Clinical Trials Register, DRKS00012712.
Fbw7, the substrate recognition subunit of SCF(Fbw7) ubiquitin ligase, mediates the turnover of multiple proto-oncoproteins and promotes its own degradation. Fbw7-dependent substrate ubiquitination is antagonized by the Usp28 deubiquitinase. Here, we show that Usp28 preferentially antagonizes autocatalytic ubiquitination and stabilizes Fbw7, resulting in dose-dependent effects in Usp28 knockout mice. Monoallelic deletion of Usp28 maintains stable Fbw7 but drives Fbw7 substrate degradation. In contrast, complete knockout triggers Fbw7 degradation and leads to the accumulation of Fbw7 substrates in several tissues and embryonic fibroblasts. On the other hand, overexpression of Usp28 stabilizes both Fbw7 and its substrates. Consequently, both complete loss and ectopic expression of Usp28 promote Ras-driven oncogenic transformation. We propose that dual regulation of Fbw7 activity by Usp28 is a safeguard mechanism for maintaining physiological levels of proto-oncogenic Fbw7 substrates, which is equivalently disrupted by loss or overexpression of Usp28.
A new approach to short tandem repeat (STR) typing of DNA extracted from telogen shed hairs is presented. Newly designed primer pairs with annealing positions close to the repeat units of the STR loci HUMFES, HUMTH01 and HUMTPOX were used for amplification. The typing results were compared to those obtained by the commonly used primer pairs by means of success rates. The primer pairs capable of producing very short amplicons (< 106 bp with HUMFES, < 86 bp with HUMTH01 and < 87 bp with HUMTPOX) described in this study significantly increased the success rates when typing telogen hairs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.