An n-of-one RCT for intravenous immunoglobulin G for inflammation in hereditary neuropathy with liability to pressure palsy (HNPP).

Paroxysmal Cerebral Disorder

mlplasmids : a user-friendly tool to predict plasmid- and chromosome-derived sequences for single species

Assembly of bacterial short-read whole-genome sequencing data frequently results in hundreds of contigs for which the origin, plasmid or chromosome, is unclear. Complete genomes resolved by long-read sequencing can be used to generate and label short-read contigs. These were used to train several popular machine learning methods to classify the origin of contigs from Enterococcus faecium, Klebsiella pneumoniae and Escherichia colt using pentamer frequencies. We selected support-vector machine (SVM) models as the best classifier for all three bacterial species (Fl-score E. faecium=0.92, F1-score K. pneumoniae=0.90, F1-score E. coli=0.76), which outperformed other existing plasmid prediction tools using a benchmarking set of isolates. We demonstrated the scalability of our models by accurately predicting the plasmidome of a large collection of 1644 E. faecium isolates and illustrate its applicability by predicting the location of antibiotic-resistance genes in all three species. The SVM classifiers are publicly available as an R package and graphical-user interface called 'mlplasmids'. We anticipate that this tool may significantly facilitate research on the dissemination of plasmids encoding antibiotic resistance and/or contributing to host adaptation.Peer reviewe

A translational rat model for ex vivo lung perfusion of pre-injured lungs after brain death

The process of brain death (BD) detrimentally affects donor lung quality. Ex vivo lung perfusion (EVLP) is a technique originally designed to evaluate marginal donor lungs. Nowadays, its potential as a treatment platform to repair damaged donor lungs is increasingly studied in experimental models. Rat models for EVLP have been described in literature before, yet the pathophysiology of BD was not included in these protocols and prolonged perfusion over 3 hours without anti-inflammatory additives was not achieved. We aimed to establish a model for prolonged EVLP of rat lungs from brain-dead donors, to provide a reliable platform for future experimental studies. Rat lungs were randomly assigned to one of four experimental groups (n = 7/group): 1) healthy, directly procured lungs, 2) lungs procured from rats subjected to 3 hours of BD and 1 hour cold storage (CS), 3) healthy, directly procured lungs subjected to 6 hours EVLP and 4), lungs procured from rats subjected to 3 hours of BD, 1 hour CS and 6 hours EVLP. Lungs from brain-dead rats showed deteriorated ventilation parameters and augmented lung damage when compared to healthy controls, in accordance with the pathophysiology of BD. Subsequent ex vivo perfusion for 6 hours was achieved, both for lungs of healthy donor rats as for pre-injured donor lungs from brain-dead rats. The worsened quality of lungs from brain-dead donors was evident during EVLP as well, as corroborated by deteriorated ventilation performance, increased lactate production and augmented inflammatory status during EVLP. In conclusion, we established a stable model for prolonged EVLP of pre-injured lungs from brain-dead donor rats. In this report we describe tips and pitfalls in the establishment of the rat EVLP model, to enhance reproducibility by other researchers

Chronic kidney disease after lung transplantation in a changing era

Lung transplant (LTx) physicians are responsible for highly complex post-LTx care, including monitoring of kidney function and responding to kidney function loss. Better survival of the LTx population and changing patient characteristics, including older age and increased comorbidity, result in growing numbers of LTx patients with chronic kidney disease (CKD). CKD after LTx is correlated with worse survival, decreased quality of life and high costs. Challenges lie in different aspects of post-LTx renal care. First, serum creatinine form the basis for estimating renal function, under the assumption that patients have stable muscle mass. Low or changes in muscle mass is frequent in the LTx population and may lead to misclassification of CKD. Second, standardizing post-LTx monitoring of kidney function and renal care might contribute to slow down CKD progression. Third, new treatment options for CKD risk factors, such as diabetes mellitus, proteinuria and heart failure, have entered clinical practice. These new treatments have not been studied in LTx yet but are of interest for future use. In this review we will address the difficult aspects of post-LTx renal care and evaluate new and promising future approaches to slow down CKD progression.</p

Waiting List Dynamics and Lung Transplantation Outcomes After Introduction of the Lung Allocation Score in The Netherlands

The Netherlands was the third country to adopt the lung allocation score (LAS) for national allocation of donor lungs in April 2014. Evaluations of the introduction of the LAS in the United States and Germany showed mainly beneficial effects, including increased survival after transplantation. Methods: Data for transplant candidates from 2010 to 2019 were retrieved from the Dutch Transplant Foundation database. Diagnosis categories and outcomes were compared between the periods before and after the introduction of the LAS. Time-dependent Cox regression and Fine-Gray analyses were performed to compare the chance for transplantation before and after introduction of the LAS. Results: The cohort comprised 1276 patients. After introduction of the LAS, the annual number of transplantations and waiting list mortality did not change. The proportion of patients on the waiting list and transplanted patients with pulmonary fibrosis increased (25%-37%, P < 0.001; 22%-39%, P < 0.001). The chance of transplantation increased significantly for patients with pulmonary fibrosis after introduction of the LAS (hazard ratio 1.9 [95% confidence interval 1.4-2.9]). Patients who died on the waiting list had an increased LAS compared to the time of placement on the waiting list, reflecting clinical deterioration. This was not the case in patients with chronic obstructive pulmonary disease (P < 0.001). Overall survival was similar after introduction of the LAS (5-y survival 68%, compared to 74% [P = 0.171]). Conclusions: After the introduction of the LAS in The Netherlands, an increased proportion of transplantations was performed for patients with pulmonary fibrosis. Overall survival after transplantation did not change

Generic nano-imprint process for fabrication of nanowire arrays

A generic process has been developed to grow nearly defect free arrays of (heterostructured) InP and GaP nanowires. Soft nanoimprint lithography has been used to pattern gold particle arrays on full 2 inch substrates. After lift-off organic residues remain on the surface, which induce the growth of additional undesired nanowires. We show that cleaning of the samples before growth with piranha solution in combination with a thermal anneal at 550 C for InP and 700 C for GaP results in uniform nanowire arrays with 1% variation in nanowire length, and without undesired extra nanowires. Our chemical cleaning procedure is applicable to other lithographic techniques such as e-beam lithography, and therefore represents a generic process.Comment: 12 pages, 4 figures, 2 table

Crossing barriers:a multidisciplinary approach to children and adults with young-onset movement disorders

Abstract Background Diagnosis of less common young-onset movement disorders is often challenging, requiring a broad spectrum of skills of clinicians regarding phenotyping, normal and abnormal development and the wide range of possible acquired and genetic etiologies. This complexity often leads to considerable diagnostic delays, paralleled by uncertainty for patients and their families. Therefore, we hypothesized that these patients might benefit from a multidisciplinary approach. We report on the first 100 young-onset movement disorders patients who visited our multidisciplinary outpatient clinic. Methods Clinical data were obtained from the medical records of patients with disease-onset before age 18 years. We investigated whether the multidisciplinary team, consisting of a movement disorder specialist, pediatric neurologist, pediatrician for inborn errors of metabolism and clinical geneticist, revised the movement disorder classification, etiological diagnosis, and/or treatment. Results The 100 referred patients (56 males) had a mean age of 12.5 ± 6.3 years and mean disease duration of 9.2 ± 6.3 years. Movement disorder classification was revised in 58/100 patients. Particularly dystonia and myoclonus were recognized frequently and supported by neurophysiological testing in 24/29 patients. Etiological diagnoses were made in 24/71 (34%) formerly undiagnosed patients, predominantly in the genetic domain. Treatment strategy was adjusted in 60 patients, of whom 43 (72%) reported a subjective positive effect. Conclusions This exploratory study demonstrates that a dedicated tertiary multidisciplinary approach to complex young-onset movement disorders may facilitate phenotyping and improve recognition of rare disorders, with a high diagnostic yield and minimal diagnostic delay. Future studies are needed to investigate the cost-benefit ratio of a multidisciplinary approach in comparison to regular subspecialty care