amplification-free nucleic acid detection. However, these approaches are not truly comparable to RT-qPCR, due to either low sensitivity without pre-amplification 42 or the limitations arising from highly specialized devices and instruments needed. Lastly, it is worth noting that most, if not all, of the existing CRISPR-based methods leverage on the trans-cleavage activity of Cas proteins, while the exploration of the specific cis-cleavage activity-the main mechanism of CRISPR-Cas systems for gene editing-for biosensing remains largely untapped.In this Article, we report a one-step, one-pot isothermal CRISPR-Cas12a assay, which we named 'Endonucleolytically Exponentiated Rolling Circle Amplification with CRISPR-Cas12a' (EXTRA-CRISPR) for the rapid and specific detection of miRNAs with sensitivity comparable to RT-PCR (Fig. 1). The EXTRA-CRISPR assay offers three major distinctions from the existing CRISPR-based biosensing methods. First, it represents a strategy to simultaneously harness both cis-cleavage and trans-cleavage activities of the CRISPR-Cas12a system. It exploits the specific cis-cleavage activity to transform conventional linear RCA to enable exponential amplification of target sequences, in addition to the trans-cleavage reaction for amplicon detection and signal amplification. Second, by engineering a modular padlock probe design and the reaction kinetics, we incorporate multiple reactions for target-mediated ligation, RCA, Cas12a binding and nucleolytic cleavage into one collaboratively coupled reaction network, creating a robust one-step, single-tube isothermal assay for miRNA analysis. Third, this one-pot isothermal miRNA assay affords comparable analytical performance with standard RT-qPCR, including high sensitivity with a single-digit femtomolar detection limit, single-nucleotide specificity and rapid and flexible turnaround (from 20 min to 3 h for the entire analysis depending on targets and samples). Lastly, one-pot EXTRA-CRISPR technology vastly simplifies the assay workflow and negates the need for specialized instruments, which provides an adaptable modality for POC diagnostics.As proof of concept of potential applications, we adapted the EXTRA-CRISPR assay to quantifying miRNA biomarkers in extracellular vesicles (EVs) for the liquid-biopsy-based diagnosis of pancreatic ductal adenocarcinoma (PDAC). EVs, including exosomes of 50-150 nm in size, are emerging as a promising candidate for liquid biopsy because nature portfolio | reporting summary

Training in front of mirrors is common, yet little is known about how the use of mirrors effects muscle force production. Accordingly, we investigated how performing in front of a mirror influences performance in single and multi-joint tasks, and compared the mirror condition to the established performance effects of internal focus (IF) and external focus (EF) instructions in a two part experiment. In the single-joint experiment 28 resistance-trained participants (14 males and 14 females) completed two elbow flexion maximal voluntary isometric contractions under four conditions: mirror, IF, EF and neutral instructions. During these trials, surface EMG activity of the biceps and triceps were recorded. In the multi-joint experiment the same participants performed counter-movement jumps on a force plate under the same four conditions. Single-joint experiment: EF led to greater normalized force production compared to all conditions (P≤0.02, effect-size range [ES] = 0.46–1.31). No differences were observed between neutral and mirror conditions (P = 0.15, ES = 0.15), but both were greater than IF (P<0.01, ES = 0.79–1.84). Surface EMG activity was comparable across conditions (P≥0.1, ES = 0.10–0.21). Multi-joint experiment: Despite no statistical difference (P = 0.10), a moderate effect size was observed for jump height whereby EF was greater than IF (ES = 0.51). No differences were observed between neutral and mirror conditions (ES = 0.01), but both were greater than IF (ES = 0.20–22). The mirror condition led to superior performance compared to IF, inferior performance compared to EF, and was equal to a neutral condition in both tasks. These results provide novel and practical evidence concerning mirror training during resistance type training.

Data defining the optimal management of abdominal compartment syndrome resulting from acute pancreatitis are lacking. We investigated the outcomes of patients with acute pancreatitis who underwent surgery for treatment of abdominal compartment syndrome at a tertiary referral center. An electronic database was searched to identify patients with acute pancreatitis who underwent laparotomy between January 1, 2000, and December 31, 2009, for treatment of abdominal compartment syndrome. Twelve patients underwent decompressive laparotomy for abdominal compartment syndrome. The median interval between onset of pancreatitis and laparotomy was 4.5 days. Nine patients underwent a laparotomy within seven days of onset of pancreatitis. As a result of cardiopulmonary instability, four decompressive laparotomies were performed in the intensive care unit. In 11 patients, cardiopulmonary improvement was observed. Statistically significant improvements were seen across multiple physiologic parameters. Despite this initial improvement, six patients (50%) died from multisystem organ failure. Two patients survived without need for pancreatic débridement. Abdominal compartment syndrome is an uncommon but likely underrecognized and highly lethal complication of acute pancreatitis that should be considered in patients who become critically ill early in the course of their pancreatitis. Prompt recognition and decompressive laparotomy may rescue some of these patients and does not mandate future débridement.

Full cervical immobilization is a myth. It would seem logical to match the level-specific efficacy of the device to the level of injury. Data are provided for the Aspen collar.