Comparing the effectiveness of tissue flossing applied to ankle joint versus calf muscle on exercise performance in female adults: An observational, randomized crossover trial.

BACKGROUND: The prevalence of ankle sprains in females has higher than in males. A deficit in ankle dorsiflexion range of motion (DFROM) is a substantial contributor to ankle injuries, resulting in hampering exercise performance. Tissue flossing improves joint ROM and enhances performance. However, evidence of how floss band (FB) intervention influences the ankle joint and calf muscle is still lacking, particularly in women. We investigated comparing the effectiveness of FB applied to ankle joint versus calf muscle on exercise performance. METHODS: This study was a randomized, counterbalanced crossover trial. Eighteen recreationally women received functional movements without wrapping FB (WF), movements with wrapping the FB around the ankle joint (FAG), and movements with wrapping the FB around the calf muscle (FCM). Main outcome measures included ankle dorsiflexion range of motion (DFROM), pressure pain threshold (PPT), agility test before and 5 (POST5), 30 (POST30), and 60 (POST60) minutes after each of the three interventions in random order. Two-way repeated measures analysis of variance and effect size (Cohen's d) were statistically analyzed. RESULTS: FAG significantly increased ankle DFROM at POST5 (p = 0.01, d = 0.5), POST30 (p = 0.03, d = 0.48), and POST60 (p = 0.001, d = 0.75). FCM significantly increased at POST30 (p = 0.01, d = 0.35) and POST60 (p = 0.004, d = 0.37). Furthermore, FAG significantly improved agility at POST5 (p < 0.001, d = 0.39), POST30 (p = 0.004, d = 0.44), and POST60 (p = 0.007, d = 0.45); however, FCM only did at POST5 (p = 0.04, d = 0.29). The pressure pain threshold on the calf muscle did not significantly change. CONCLUSIONS: FAG and WF enhance ankle ROM and agility immediately. Moreover, FAG demonstrates a prolonged effect of agility for 1 h. Practitioners may take this information into account for choosing efficient applications.

Uncovering synthetic lethal interactions for therapeutic targets and predictive markers in lung adenocarcinoma.

Two genes are called synthetic lethal (SL) if their simultaneous mutation leads to cell death, but mutation of either individual does not. Targeting SL partners of mutated cancer genes can selectively kill cancer cells, but leave normal cells intact. We present an integrated approach to uncover SL gene pairs as novel therapeutic targets of lung adenocarcinoma (LADC). Of 24 predicted SL pairs, PARP1-TP53 was validated by RNAi knockdown to have synergistic toxicity in H1975 and invasive CL1-5 LADC cells; additionally FEN1-RAD54B, BRCA1-TP53, BRCA2-TP53 and RB1-TP53 were consistent with the literature. While metastasis remains a bottleneck in cancer treatment and inhibitors of PARP1 have been developed, this result may have therapeutic potential for LADC, in which TP53 is commonly mutated. We also demonstrated that silencing PARP1 enhanced the cell death induced by the platinum-based chemotherapy drug carboplatin in lung cancer cells (CL1-5 and H1975). IHC of RAD54B↑, BRCA1↓-RAD54B↑, FEN1(N)↑-RAD54B↑ and PARP1↑-RAD54B↑ were shown to be prognostic markers for 131 Asian LADC patients, and all markers except BRCA1↓-RAD54B↑ were further confirmed by three independent gene expression data sets (a total of 426 patients) including The Cancer Genome Atlas (TCGA) cohort of LADC. Importantly, we identified POLB-TP53 and POLB as predictive markers for the TCGA cohort (230 subjects), independent of age and stage. Thus, POLB and POLB-TP53 may be used to stratify future non-Asian LADC patients for therapeutic strategies.

Estimated Financing Amount Needed for Essential Medicines in China, 2014.

BACKGROUND: At the present time, the government is considering to establish the independent financing system for essential medicines (EMs). However, it is still in the exploration phase. The objectives of this study were to calculate and estimate financing amount of EMs in China in 2014 and to provide data evidence for establishing financing mechanism of EMs. METHODS: Two approaches were adopted in this study. First, we used a retrospective research to estimate the cost of EMs in China in 2014. We identified all the 520 drugs listed in the latest national EMs list (2012) and calculated the total sales amount of these drugs in 2014. The other approach included the steps that first selecting the 109 most common diseases in China, then identifying the EMs used to treat them, and finally estimating the total cost of these drugs. RESULTS: The results of the two methods, which showed the estimated financing amounts of EMs in China in 2014, were 17,776.44 million USD and 19,094.09 million USD, respectively. CONCLUSIONS: Comparing these two results, we concluded that the annual budget needed to provide for the EMs in China would be about 20 billion USD. Our study also indicated that the irrational drug use continued to plague the health system with intravenous fluids and antibiotics being the typical examples, as observed in other studies.

Template-based de novo design for type II kinase inhibitors and its extented application to acetylcholinesterase inhibitors.

There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo design protocol to discover new inhibitors that preserve and also optimize the binding interactions of the type II kinase template. First, sorafenib (Nexavar) and nilotinib (Tasigna), two type II inhibitors with different ligand-receptor interactions, were selected as the template compounds. The five-step protocol can reassemble each drug from a large fragment library. Our procedure demonstrates that the selected template compounds can be successfully reassembled while the key ligand-receptor interactions are preserved. Furthermore, to demonstrate that the algorithm is able to construct more potent compounds, we considered kinase inhibitors and other protein dataset, acetylcholinesterase (AChE) inhibitors. The de novo optimization was initiated using a template compound possessing a less than optimal activity from a series of aminoisoquinoline and TAK-285 inhibiting type II kinases, and E2020 derivatives inhibiting AChE respectively. Three compounds with greater potency than the template compound were discovered that were also included in the original congeneric series. This template-based lead optimization protocol with the fragment library can help to design compounds with preferred binding interactions of known inhibitors automatically and further optimize the compounds in the binding pockets.