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xrRNAs from flaviviruses survive in host cells because of their exceptional dichotomic response to the unfolding action of different enzymes. They can be unwound, and hence copied, by replicases, and yet can resist degradation by exonucleases. How the same stretch of xrRNA can encode such diverse responses is an open question. Here, by using atomistic models and translocation simulations, we uncover an elaborate and directional mechanism for how stress propagates when the two xrRNA ends, [Formula see text] and [Formula see text], are driven through a pore. Pulling the [Formula see text] end, as done by replicases, elicits a progressive unfolding; pulling the [Formula see text] end, as done by exonucleases, triggers a counterintuitive molecular tightening. Thus, in what appears to be a remarkable instance of intra-molecular tensegrity, the very pulling of the [Formula see text] end is what boosts resistance to translocation and consequently to degradation. The uncovered mechanistic principle might be co-opted to design molecular meta-materials.

Immediate-release fentanyl is indicated in the treatment of breakthrough pain in cancer patients who already receive opioids as background chronic analgesia. According to an alert issued by the Spanish Agency of Medicines, its consumption under non-authorized conditions has alarmingly increased in recent years, with a greater risk of abuse and dependence. The main objective of this study is to compare the off-label use of immediate-release fentanyl in our hospital during 2014 and 2017.

Retrospective cross-sectional descriptive study in which immediate-release fentanyl prescriptions were compared in adult patients admitted during 2014 and 2017 in a group 5 hospital. Variables were collected by the electronic medical record. The association study between qualitative variables was calculated using the χ

test, and quantitative variables with the t-student test.

In 2014, 0.43 immediate-release fentanyl prescriptions were made in our center for every 100 admissions, and in 2017 0.54/100 admissions. 22.1% (n=34) prescriptions were off-label in 2014, while in 2017 31.8% (n=76) (p=0.034). Both years, the most frequent off-label indications were healing of ulcers and wounds and non-cancer chronic pain.

The use of immediate-release fentanyl in the hospital setting has considerably increased in comparison to 2014, as well as its off-label use.

The use of immediate-release fentanyl in the hospital setting has considerably increased in comparison to 2014, as well as its off-label use.BACKGROUND Contracture is related to modulation of passive stiffness in muscle and tendon after spinal cord injury (SCI). Current clinical assessments of stiffness in muscles and tendons are subjective in patients with spinal cord injury. We proposed a quantitative method to evaluate stiffness of the gastrocnemius and Achilles tendon (AT) with a portable device, the MyotonPRO. The purpose of this study was to investigate the intraoperator and interoperator reliability of the MyotonPRO when used in patients after spinal cord injury. MATERIAL AND METHODS Fourteen patients with SCI participated in this study. Gastrocnemius stiffness and AT stiffness were measured with the MyotonPRO. RESULTS In participants with SCI, the intraclass correlation coefficient (ICC) values for intraoperator and interoperator reliability of stiffness measurements in the gastrocnemius and AT were excellent (all ICC >0.87), with relatively low values for standard error measurement (SEM) and minimal detectable change (MDC). CONCLUSIONS Our findings suggest that use of the MyotonPRO is feasible for evaluating stiffness of the gastrocnemius and AT in the lower limbs of patients with spinal cord injury.BACKGROUND A previous phase 3 clinical trial in de novo adult kidney transplant recipients (NCT01187953) compared the efficacy and safety of once-daily LCP-tacrolimus (LCPT) and twice-daily immediate-release tacrolimus (IR-Tac). However, whether the rate of tacrolimus metabolism affects outcomes between LCPT and IR-Tac was not examined. MATERIAL AND METHODS Patients were initiated on 0.17 mg/kg/day LCPT or 0.1 mg/kg/day IR-Tac, with doses adjusted over time to maintain target therapeutic trough concentrations. This post hoc analysis examined dosing trends, relative efficacy, and safety of LCPT (n=247) and IR-Tac (n=249) in slow, intermediate, and rapid metabolizers as defined by concentration/dose ratios at day 30. RESULTS For all metabolizer subgroups, minimum target tacrolimus trough concentrations were obtained more rapidly with LCPT than with IR-Tac. Slow metabolizers were more likely to exceed target trough concentrations with LCPT, while rapid metabolizers were more likely to fall below target trough concentrations with IR-Tac. Regardless of metabolizer status, significant differences were not detected between LCPT and IR-Tac for treatment failure, death, graft failure, biopsy-proven acute rejection, estimated glomerular filtration rate, or other clinical outcomes. CONCLUSIONS Although within metabolizer subgroups, attainment of target trough concentrations in the first week differed between LCPT and IR-Tac, these results suggest that, regardless of metabolizer phenotype, clinical outcomes do not differ between these formulations when dose adjustments are made.BACKGROUND Diverticulosis and its complication of diverticulitis is a common condition that can be found in up to 35% of the population. find more Giant colonic diverticulum is a rare entity with fewer than 200 cases reported in the scientific literature. Development of a giant diverticulum as a sequelae of laparoscopic washout is an unreported event in current literature. CASE REPORT The patient was a 74-year-old female who had a well-known history of diverticulosis and diverticulitis. She developed perforated sigmoid diverticulitis, underwent laparoscopic washout and recovered without colon resection. Within a year after washout, she developed abdominal distention and bloating, and computed tomography (CT) imaging revealed a giant diverticulum. She went on to undergo surgery for resection of her sigmoid colon, which contained the giant diverticulum. Her recovery was otherwise uneventful. CONCLUSIONS To our knowledge, this is the first case report of giant diverticulum presenting as a complication of abdominal washout for management of acute diverticulitis.

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