KGaA, Weinheim.Biallelic mutations in ECHS1, encoding the mitochondrial enoyl-CoA hydratase, have been associated with mitochondrial encephalopathies with basal ganglia involvement. Here, we describe a novel clinical presentation consisting of dystonia-ataxia syndrome with hearing loss and a peculiar torsional nystagmus observed in two adult siblings. The presence of a 0.9-ppm peak at MR spectroscopy analysis suggested the accumulation of branched-chain amino acids. Exome sequencing in index probands identified two ECHS1 mutations, one of which was novel (p.V82L). ECHS1 protein levels and residual activities were reduced in patients’ fibroblasts. This paper expands the phenotypic spectrum observed in patients with impaired valine catabolism. © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.PURPOSE To develop and validate the operational definition (ODs) for each defining characteristic (DC) contained in the Nursing Diagnosis (ND) “insomnia” (00095) in the occupational health context. METHODS Methodological study carried out in two stages, including a consensus of experts to develop the ODs (Stage 1) and an online Delphi panel, performed in two rounds, to validate them (Stage 2). FINDINGS The 15 ODs proposed in Stage 1 were narrowed down to six validated ODs in the first round (diagnostic content validity index [DCVI] = 0.80-0.89). In the second round, five ODs were validated (DCVI = 0.80-0.94). Finally, the remaining four ODs were validated by the general consensus of experts. CONCLUSIONS The ODs were validated, although there remains some doubt as to whether some of the DCs can be applied to the field of occupational health. IMPLICATIONS FOR NURSING PRACTICE The ODs developed and validated could improve the diagnostic accuracy of the ND “insomnia” (00095) in the context of occupational health. © 2020 NANDA International, Inc.Despite impressive clinical benefit obtained with anti-HER2-targeted therapies, in advances stages, especially in the metastatic setting, HER2-positive tumors remain incurable. Therefore, it is important to develop novel strategies to fight these tumors, especially when they become resistant to available therapies. We show here that the anti-HER3 antibody-drug conjugate EV20/MMAF exerted potent anti-tumoral properties against several models of primary resistance and secondary resistance to common anti-HER2 available therapies, including trastuzumab, lapatinib, neratinib, and trastuzumab-emtansine. HER3 was expressed in these HER2+ breast cancer cells and knockdown experiments demonstrated that HER3 expression was required for the action of EV20/MMAF. In mice injected with trastuzumab-resistant HER2+ cells, a single dose of EV20/MMAF caused complete and long-lasting tumor regression. Mechanistically, EV20/MMAF bound to cell surface HER3 and became internalized to the lysosomes. Treatment with EV20/MMAF caused cell cycle arrest in mitosis and promoted cell death through mitotic catastrophe. These findings encourage the clinical testing of EV20/MMAF for several indications in the HER2+ cancer clinic, including situations in which HER2+ tumors become refractory to approved anti-HER2 therapies. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.OBJECTIVES First-line treatment for patients with neurogenic detrusor overactivity (NDO) is anticholinergic or beta-3 agonist medication. The addition of a secondary medication in patients with NDO may avoid progression to third- and fourth-line therapies. We aim to identify patterns of medication use for patients with neurogenic lower urinary tract dysfunction (NLUTD) using a national database. METHODS The National Ambulatory Medical Care Survey (NAMCS) database was queried for a sample of ambulatory patient visits from 2003 to 2015. Outpatient visits were included for all patients aged 18 years or older diagnosed with NLUTD. Dual therapy was defined as prescription of two anticholinergics or one anticholinergic + beta-3 agonist on the same visit. Visits in which medications were prescribed were analyzed with descriptive statistics. RESULTS Out of a weighted sample of 5 391 680 patient visits with a primary diagnosis of NLUTD, 1 602 705 (30%) were prescribed medical therapy. Of included patients prescribed NDO medications, the majority were white (80%), located in the Northeast (71%), and of a mean age of 51 ± 3. Of these patients, at least 93% of patients were prescribed anticholinergics, and 37% were prescribed dual therapy. Patients 65 years and older were more likely to initiate a new NDO medication at their visit (43%) than patients under 65 (7%). CONCLUSIONS This is the first study to analyze the use of medical therapy for NLUTD in a large outpatient setting. Selleckchem E-7386 Further prospective evaluation of patient satisfaction and efficacy of both single anticholinergic medication and dual therapy is needed. © 2020 John Wiley & Sons Australia, Ltd.Virus-like nanoparticles (VLPs) have been used as an attractive means in cancer immunotherapy because of their unique intrinsic immunostimulatory properties. However, for treating metastatic tumors in the peritoneal cavity, such as ovarian cancer, multiple injections of therapy are needed due to the large peritoneal space and fast excretion of therapy. Here, it is reported on the development of active VLP delivery vehicles for the treatment of peritoneal ovarian tumors using biocompatible Qβ VLPs-loaded Mg-based micromotors. The autonomous propulsion of such Qβ VLPs-loaded Mg-micromotors in the peritoneal fluid enables active delivery of intact immunostimulatory Qβ VLPs to the peritoneal space of ovarian tumor bearing mice, greatly enhancing the local distribution and retention of Qβ VLPs. Such improved distribution and longer retention time of Qβ in the peritoneal cavity leads to enhanced immunostimulation and therefore increased survival rate of tumor-bearing mice compared to a passive Qβ treatment. For clinical translation, the active delivery of VLPs holds great promise for tumor immunotherapy toward the treatment of different types of primary and metastatic tumors in the peritoneal cavity. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.