The resuscitation of severely injured bleeding patients has evolved into a multi-modal strategy termed damage control resuscitation (DCR). This guideline evaluates several aspects of DCR including ...the role of massive transfusion (MT) protocols, the optimal target ratio of plasma (PLAS) and platelets (PLT) to red blood cells (RBC) during DCR, and the role of recombinant activated factor VII (rVIIa) and tranexamic acid (TXA).
Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, a subcommittee of the Practice Management Guidelines (PMG) Section of EAST conducted a systematic review using MEDLINE and EMBASE. Articles in English from1985 through 2015 were considered in evaluating four PICO questions relevant to DCR.
A total of 37 studies were identified for analysis, of which 31 met criteria for quantitative meta-analysis. In these studies, mortality decreased with use of an MT/DCR protocol vs. no protocol (OR 0.61, 95% CI 0.43-0.87, p = 0.006) and with a high ratio of PLAS:RBC and PLT:RBC (relatively more PLAS and PLT) vs. a low ratio (OR 0.60, 95% CI 0.46-0.77, p < 0.0001; OR 0.44, 95% CI 0.28-0.71, p = 0.0003). Mortality and blood product use were no different with either rVIIa vs. no rVIIa or with TXA vs. no TXA.
DCR can significantly improve outcomes in severely injured bleeding patients. After a review of the best available evidence, we recommend the use of a MT/DCR protocol in hospitals that manage such patients and recommend that the protocol target a high ratio of PLAS and PLT to RBC. This is best achieved by transfusing equal amounts of RBC, PLAS, and PLT during the early, empiric phase of resuscitation. We cannot recommend for or against the use of rVIIa based on the available evidence. Finally, we conditionally recommend the in-hospital use of TXA early in the management of severely injured bleeding patients.
Paraneoplastic syndromes are rare but possible manifestations of colorectal cancer. We present THE CASE of a 51-year-old female diagnosed with cT3N2 rectal adenocarcinoma who developed back pain and ...progressive muscle weakness during preoperative treatment. She had a rapid worsening in mobility and was ultimately ambulating with a wheelchair, despite physical therapy and conservative treatments. Extensive laboratory workup including onconeural antibodies was negative and her lower extremity electromyogram was suggestive of a subacute demyelinating lumbosacral plexopathy. After multidisciplinary discussion, the decision was made to proceed with curative resection. She had significant improvement in her weakness following resection, suggesting a paraneoplastic etiology. One year after resection, she remains free of disease and is ambulating comfortably. Onconeural antibodies can be a helpful diagnostic tool, but their absence does not rule out paraneoplastic disease. A high index of suspicion is necessary when assessing patients with atypical symptoms, particularly with the rise of colorectal cancer in young adults.
Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip ...genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Since its first identification in the 1950s as a regulator of cell division, cytokinin has been linked to many physiological processes in plants, spanning growth and development and various responses ...to the environment. Studies from the last two and one-half decades have revealed the pathways underlying the biosynthesis and metabolism of cytokinin and have elucidated the mechanisms of its perception and signaling, which reflects an ancient signaling system evolved from two-component elements in bacteria. Mutants in the genes encoding elements involved in these processes have helped refine our understanding of cytokinin functions in plants. Further, recent advances have provided insight into the mechanisms of intracellular and long-distance cytokinin transport and the identification of several proteins that operate downstream of cytokinin signaling. Here, we review these processes through a historical lens, providing an overview of cytokinin metabolism, transport, signaling, and functions in higher plants.
Background. Data on integrase inhibitor resistance come primarily from clinical trials and in vitro studies. We examined results of all clinically indicated integrase genotypic resistance tests ...(GRTs) performed at a US national referral lab from 2009 through 2012. Methods. Integrase sequences and demographic data were compiled with paired protease–reverse transcriptase (PR-RT) GRT results, when available. Analyses utilized the Stanford HIV Drug Resistance Database. "Major" integrase mutations included T66AIK, E92QV, F121Y, Y143CHR, S147G, Q148HKR, and N155H; multiple accessory mutations were also assessed. Results. Among 3294 sequences from 3012 patients, 471 patients had viruses with ≥1 raltegravir or elvitegravir resistance mutation (15.6%). Q148 and N155 pathways were equally represented (both n = 197); 84 had Y143 mutations. Q148 rarely occurred without accessory mutations (n = 3). Among 224 patients with serial integrase GRTs, 22 with baseline wild-type acquired a major mutation, after a median 224 days between tests (interquartile range, 148– 335 days). Major mutations were observed to persist up to 462 days. Most (62%) had paired PR-RT results. Patients with integrase-resistant viruses were older and more likely to have PR-RT mutations (both P < .001). Among those with PR-RT data, 42 patients had 4-class resistance (2.3%). Sex, geographic region, and test year were not associated with integrase resistance. High-level dolutegravir resistance was predicted in 12% of patients with raltegravir- or elvitegravir-resistant viruses (2% of all patients). Conclusions. Approximately 1 in 6 US patients undergoing integrase GRT for clinical decision making harbors significant resistance, with Q148 and N155 pathways equally common. Dolutegravir is likely to have full or partial activity against most variants observed.
Electron-beam-induced damages in methylammonium lead triiodide (MAPbI3) perovskite thin films were studied by cathodoluminescence (CL) spectroscopy. We find that high-energy electron beams can ...significantly alter perovskite properties through two distinct mechanisms: (1) defect formation caused by irradiation damage and (2) phase transformation induced by electron-beam heating. The former mechanism causes quenching and broadening of the excitonic peaks in CL spectra, whereas the latter results in new peaks with higher emission photon energy. The electron-beam damage strongly depends on the electron-beam irradiation conditions. Although CL is a powerful technique for investigating the electronic properties of perovskite materials, irradiation conditions should be carefully controlled to avoid any significant beam damage. In general, reducing acceleration voltage and probing current, coupled with low-temperature cooling, is more favorable for CL characterization and potentially for other scanning electron-beam-based techniques as well. We have also shown that the stability of perovskite materials under electron-beam irradiation can be improved by reducing defects in the original thin films. In addition, we investigated effects of electron-beam irradiation on formamidinium lead triiodide (FAPbI3) and CsPbI3 thin films. FAPbI3 shows similar behavior as MAPbI3, whereas CsPbI3 displays higher resistance to electron-beam damage than its organic–inorganic hybrid counterparts. Using CsPbI3 as a model material, we observed nonuniform luminescence in different grains of perovskite thin films. We also discovered that black-to-yellow phase transformation of CsPbI3 tends to start from the junctions at grain boundaries.
PURPOSE OF REVIEWDrug checking services invite drug consumers to anonymously submit drug samples for chemical analysis and provide feedback of results. Drugs are tested for strength/dose and/or ...presence of adulterants. Drug checking appears to be more common in recent years in response to increases in fentanyl-related deaths and the proliferation of new psychoactive substances (NPS). We aim to provide information regarding the current state of drug checking in relation to analysis methods, adulteration rates, and behavioral responses to results.
RECENT FINDINGSVarious technologies are being used to detect the presence of fentanyl, its analogs, and other NPS in drug samples. Proxy drug checking, which we define as biospecimen testing for drug exposure postconsumption, is also becoming common. However, there appears to a dichotomy between research focusing on populations at high risk for fentanyl exposure and to exposure to NPS such as synthetic cathinones.
SUMMARYDrug checking research and services largely focus on opioid consumers and nightclub and dance festival attendees, but more focus may be needed on the general population. Drug checking results can inform surveillance efforts, and more research is needed to overcome barriers to drug checking and to focus on whether test results indeed affect behavior change.
BACKGROUND:Enhanced recovery pathways (ERPs) have been shown to aid in patient recovery and improve outcomes in many surgical settings. At present, there is limited data available regarding the use ...and feasibility of ERPs for patients undergoing microsurgical breast reconstruction. We sought to assess patient outcomes before and after the introduction of an ERP that was adopted by multiple surgeons at a single cancer center.
METHODS:A multidisciplinary ERP was developed for patients undergoing deep inferior epigastric perforator (DIEP) or muscle-sparing free transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction. Core elements of the ERP included substituting intravenous patient-controlled analgesia with a multimodal pain regimen consisting of intravenous ketorolac and transversus abdominis plane blocks with liposomal bupivacaine, as well as the use of intraoperative goal-directed fluid management. Patients who underwent surgery between April and August 2015 using the ERP were compared with a historical control cohort. The primary endpoints were hospital length of stay (LOS) and total postoperative opioid consumption.
RESULTS:In total, 91 consecutive patients were analyzed (ERP, 42; pre-ERP, 49). Mean hospital LOS was significantly shorter in the ERP group than in the pre-ERP group (4.0 vs. 5.0 days; p<0.0001). Total postoperative morphine equivalent consumption was also lower in the ERP group (46.0 vs. 70.5 mg; p=0.003). There was no difference in the incidence of 30-day complications between the groups (p=0.6).
CONCLUSIONS:The adoption of an ERP for DIEP and TRAM flap reconstruction by multiple surgeons significantly decreased opioid consumption and reduced LOS by 1 day.
The gaseous phytohormone ethylene C ₂H ₄ mediates numerous aspects of growth and development. Genetic analysis has identified a number of critical elements in ethylene signaling, but how these ...elements interact biochemically to transduce the signal from the ethylene receptor complex at the endoplasmic reticulum (ER) membrane to transcription factors in the nucleus is unknown. To close this gap in our understanding of the ethylene signaling pathway, the challenge has been to identify the target of the CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) Raf-like protein kinase, as well as the molecular events surrounding ETHYLENE-INSENSITIVE2 (EIN2), an ER membrane-localized Nramp homolog that positively regulates ethylene responses. Here we demonstrate that CTR1 interacts with and directly phosphorylates the cytosolic C-terminal domain of EIN2. Mutations that block the EIN2 phosphorylation sites result in constitutive nuclear localization of the EIN2 C terminus, concomitant with constitutive activation of ethylene responses in Arabidopsis . Our results suggest that phosphorylation of EIN2 by CTR1 prevents EIN2 from signaling in the absence of ethylene, whereas inhibition of CTR1 upon ethylene perception is a signal for cleavage and nuclear localization of the EIN2 C terminus, allowing the ethylene signal to reach the downstream transcription factors. These findings significantly advance our understanding of the mechanisms underlying ethylene signal transduction.
The problem of communicating over the additive white Gaussian noise (AWGN) channel with lattice codes is addressed in this paper. Theoretically, Voronoi constellations have proved to yield very ...powerful lattice codes when the fine/coding lattice is AWGN-good and the coarse/shaping lattice has an optimal shaping gain. However, achieving Shannon capacity with these premises and practically implementable encoding algorithms is in general not an easy task. In this paper, a new way to encode and demap Construction-A Voronoi lattice codes is presented. As a meaningful application of this scheme, the second part of the paper is focused on Leech constellations of lowdensity Construction-A (LDA) lattices: LDA Voronoi lattice codes are presented whose numerically measured waterfall region is situated at less than 0.8 dB from Shannon capacity. These LDA lattice codes are based on dual-diagonal nonbinary low-density parity-check codes. With this choice, encoding, iterative decoding, and demapping have all linear complexity in the block length.
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