Maherjones3244

OBJECTIVE The diagnostic approach for patients presenting to EDs with headaches suspicious for subarachnoid haemorrhage (SAH) remains challenging. Modern third-generation computed tomography (CT) has been shown to be extremely sensitive in identifying SAH and may eliminate the need for lumbar puncture (LP) which is an invasive, time-consuming procedure with limited accuracy and complications. The aim of this study is to assess the utility of LP in patients being evaluated for possible SAH in the ED after a negative non-contrast CT scan of the brain, as well as addressing the knowledge gap in regard to rational diagnostics among clinicians. METHODS We conducted a retrospective data analysis of patients being evaluated for possible SAH between June 2013 and June 2018 across three EDs in Victoria, Australia. A diagnosis of SAH was defined by SAH on CT or an abnormal cerebrospinal fluid result in conjunction with positive results on cerebral angiography. A follow-up period of 6 months was chosen. RESULTS A total of 4407 patients met inclusion criteria; 397 (9%) patients were diagnosed with SAH on CT. A total of 388 patients underwent LP and 778 were admitted to hospital for further investigations and management. A total of 2613 patients discharged from ED without LP remained well at 6 months from their initial presentation, but 230 cases were lost to follow up. One patient died from haemorrhagic stroke during his third hospitalisation. A single patient demonstrated a true positive LP after a normal CT brain. CONCLUSION LP is not required in all patients with suspected SAH who have a negative CT scan. There are defining patient characteristics that can be used to risk stratify patients and may eliminate the need for LP. © 2020 Australasian College for Emergency Medicine.As the hydrogen has been increasingly considered as promising sustainable energy supply, the electrochemical water overall splitting driven by highly efficient non-noble metal electrocatalysts has aroused extensive attention. Transition metal phosphides (TMPs) have demonstrated remarkable electrocatalytic performance including high activity and robust durability towards hydrogen evolution reaction (HER) in acidic and alkaline as well as neutral electrolytes. In this review, up-to-date progress of TMPs-based HER electrocatalysts is summarized. The diversified synthesis strategies of TMPs are presented, and the reaction mechanisms of HER as well as the contribution of phosphorus in TMPs to HER activity are briefly clarified. The multiscale approaches for promoting the activity and stability of TMPs-based catalysts are elaborately discussed with respect to the intrinsic electronic structure, hybrids, microstructure and working electrode interface. In the end, some crucial issues and future perspectives of TMPs are pointed out. These modulated approaches and challenges are also instructive for constructing other high-activity energy-related electrocatalysts. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Recently, 2D transition metal dichalcogenides (TMDs) have become intriguing materials in the versatile field of photonics and optoelectronics because of their strong light-matter interaction that stems from the atomic layer thickness, broadband optical response, controllable optoelectronic properties, and high nonlinearity, as well as compatibility. Nevertheless, the low optical cross-section of 2D-TMDs inhibits the light-matter interaction, resulting in lower quantum yield. Therefore, hybridizing the 2D-TMDs with plasmonic nanomaterials has become one of the promising strategies to boost the optical absorption of thin 2D-TMDs. Acetyl-CoA carboxylase inhibitor The appeal of plasmonics is based on their capability to localize and enhance the electromagnetic field and increase the optical path length of light by scattering and injecting hot electrons to TMDs. In this regard, recent achievements with respect to hybridization of the plasmonic effect in 2D-TMDs systems and its augmented optical and optoelectronic properties are reviewed. The phenomenon of plasmon-enhanced interaction in 2D-TMDs is briefly described and state-of-the-art hybrid device applications are comprehensively discussed. Finally, an outlook on future applications of these hybrid devices is provided. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The number of publications applying nonlinear mixed-effect (NLME) modeling has increased yearly since its first appearance in 1979. Here, we evaluated articles that have used NLME modeling, were published in journals that attract a broader audience, and we discussed the standard of presentation of these to stimulate target audience-specific improvements for increased impact in the future. © 2020 The Authors. CPT Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.The ubiquitin conjugating enzyme E2 N (UBE2N) has been reported to be involved in the tumorigenesis of several tumors, but its function in cervical carcinoma has not been investigated yet. In the present study, UBE2N was found elevated in cervical carcinoma, and patients with high UBE2N had a shorter overall survival than patients with low expression. Additionally, knockdown of UBE2N decreased the activation of MEK1/2 and p38 in cervical carcinoma cells, and UBE2N knockdown also markedly inhibited cervical carcinoma cell growth. Our further studies found that microRNA-590-3p (miR-590-3p) was significantly decreased in cervical carcinoma, and patients with high miR-590-3p had a longer overall survival than patients with low expression. Moreover, miR-590-3p expression was found negatively correlated with UBE2N expression in cervical carcinoma, and our further studies showed that miR-590-3p targeted UBE2N and inhibited its expression in cervical carcinoma. Overexpression of miR-590-3p could inhibit cervical carcinoma cell growth, but enhanced UBE2N could rescue miR-590-3p-induced cell growth inhibition in cervical carcinoma. This study indicated that targeting miR-590-3p/UBE2N axis could be a potential strategy for the treatment of cervical carcinoma. © 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.Levocetirizine is classified as a second-generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single-center, single-dose, open-label, randomized, 2-way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate-release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study. © 2020 GlaxoSmithKline. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.It remains a challenge to rational design of a new metal organic framework (MOF) as highly efficient direct catalysts for the oxygen evolution reaction (OER). Herein, we developed a simple and effective method to explore a new pillared-layered MOF with syringic acid as a promising OER catalyst. The isostructural mono, heterobimetallic MOF and N, S co-doped MOF by mixing thiourea  were quickly synthesized in a high yield under solvothermal condition. Moreover, the optimized N,S co-doped MOF exhibits the lowest overpotential of 254 mV at 10 mA cm-2 on a glass carbon electrode and a small Tafel slope of 50 mV dec-1, especially, this catalyst also possesses long-term electrochemical durability for at least 16 hrs. According to the characterization, the incorporation of N and S atoms into this heterobimetallic CoFe-MOF could modify its pore structure, tune the electronic structure, accordingly, improve the mass and electron transportation, and facilitate the formation of active species, as a consequence, the improved activity of this new N, S co-doped MOF for OER might mainly be ascribed to higher electrochemical activation to lead to the active species via the in-situ surface modification during OER process. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Genetic alterations in multiple cell signaling pathways are involved in the molecular pathogenesis of thyroid cancer. Oncogene mutation testing and gene-expression profiling are routinely used for the preoperative risk management of adult thyroid nodules. In this study, we evaluated the potential value of miRNA biomarkers for the classification of pediatric thyroid lesions. PROCEDURE Double-blind case-control study with 113 resected pediatric lesions 66 malignant and 47 benign. Quantitative and qualitative molecular data generated with a 10-miRNA expression panel (ThyraMIR) and a next-generation sequencing oncogene panel (ThyGeNEXT) were compared with clinicopathological parameters. RESULTS miRNAs were differentially expressed in benign versus malignant tumors with distinct expression patterns in different histopathology categories. The 10-miRNA classifier identified 39 (59%) malignant lesions with 100% specificity. A positive classifier score was associated with lymph node metastasis, extrathyroidal extension and intrathyroidal spread. Genetic alterations associated with increased risk for malignancy were detected in 35 (53%) malignant cases, 20 positive for point mutations in BRAF, HRAS, KRAS, NRAS, PIK3CA, or TERT and 15 positive for gene rearrangements involving ALK, NTRK3, PPARG, or RET. The 10-miRNA classifier correctly identified 11 mutation-negative malignant cases. The performance of the combined molecular test was 70% sensitivity and 96% specificity with an area under the curve of 0.924. CONCLUSIONS These data suggest that the regulatory miRNA pathways underlying thyroid tumorigenesis are similar in adults and children. miRNA expression can identify malignant lesions with high specificity, augment the diagnostic yield of mutation testing, and improve the molecular classification of pediatric thyroid nodules. © 2020 Wiley Periodicals, Inc.Monoclonal antibodies (mAbs) against B cell antigens are extensively used in the treatment of rheumatoid arthritis (RA). The B cell depletion therapy prevents RA symptoms and/or alleviates existing inflammation. The previously established two-step drug-free macromolecular therapeutics (DFMT) is applied in the treatment of collagen-induced rheumatoid arthritis in a collagen-induced rheumatoid arthritis mouse model. DFMT is a B cell depletion strategy utilizing Fab' fragment of anti-CD20 mAb for biorecognition and receptor crosslinking to induce B cell apoptosis. DFMT is composed from two nanoconjugates 1) bispecific engager, Fab'-MORF1 (anti-CD20 Fab' fragment conjugated with morpholino oligonucleotide MORF1), and 2) a crosslinking (effector) component P-(MORF2)X (N-(2-hydroxypropyl)methacrylamide copolymer grafted with multiple copies of complementary morpholino oligonucleotide MORF2). The absence of Fc fragment has the potential to avoid development of resistance and infusion-related reactions. DFMT produces B cell depletion, keeps the RA score low for more than 100 days, and shows minimal cartilage and bone erosion and inflammatory cell infiltration.