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BACKGROUND Creutzfeldt-Jakob disease (CJD) is an uncommon, invariably fatal, neurodegenerative disorder that presents as progressive dementia with concurrent motor symptoms and myoclonia. The pathophysiology involves prion protein misfolding and spreading in a self-catalyzed manner. It has been shown to be transmissible through tissue transplants. Variant CJD (vCJD), a subtype of the disease is also transmissible through transfusion of blood products. This study aims to corroborate the scarce data that suggest that sporadic CJD (sCJD) is not transmitted via blood transfusion. METHODS AND STUDY DESIGN A retrospective cohort study was performed, using data from the bi-national Scandinavian Donations and Transfusions (SCANDAT2) database containing data on blood donors, donations, transfusions, and transfused patients in Sweden and Denmark since 1968 and 1982, respectively. Mortality and medical data were collected from nationwide health care and population registries. Donors with subsequent CJD were identified, as well as recipients of blood products from these donors. A second analysis was performed, screening for clustering of CJD cases from donors without a CJD diagnosis. RESULTS We identified 39 donors with a subsequent diagnosis of sCJD. No cases of CJD occurred among the 883 recipients of blood products from these donors. A total of 89 CJD cases were identified among recipients of transfusions. No clustering of cases from the same donor occurred. DISCUSSION Using data from a large, bi-national database of transfused patients, we find no evidence of sCJD transmission. Our data adds to the growing body of evidence indicating that sCJD is not transfusion transmitted. © 2020 AABB.Xylem hydraulic failure is a major driver of tree death during drought. However, to better understand mortality risk in trees, especially during hot-drought events, more information is required on both rates of residual water-loss from small branches (gres ) after stomatal closure, as well as the phase transition temperature (Tp ), beyond which gres significantly increases. Here, we describe and test a novel low-cost tool, the DroughtBox, for phenotyping gres and Tp across species. The system consists of a programmable climatically controlled chamber in which branches dehydrate and changes in the mass recorded. Test measurements show that the DroughtBox maintains stable temperature and relative humidity across a range of set points, a prerequisite for getting accurate gres and Tp values. Among a study group of four conifer and one angiosperm species, we observed a range of gres (0.44-1.64 mmol H2 O m-2 s-1 ) and Tp (39.4-43.8°C) values. Furthermore, the measured time to hydraulic failure varied between two conifers species and was shortened in both species following a heatwave event. The DroughtBox is a reliable and customizable tool for phenotyping gres and Tp , as well as for testing models of time to hydraulic failure that will improve our ability to assess climate change impacts on plants. © 2020 John Wiley &amp; Sons Ltd.Lonicera japonica is a wide-spread member of the Caprifoliaceae (honeysuckle) family utilized in traditional medical practices. This twining vine honeysuckle is also a much-sought ornamental, in part due to its dynamic flower coloration, which changes from white to gold during development. The molecular mechanism underlying dynamic flower coloration in L. japonica was elucidated by integrating whole genome sequencing, transcriptomic analysis, and biochemical assays. Here, we report a chromosome-level genome assembly of L. japonica, comprising nine pseudo-chromosomes with a total size of 843.2 Mb. [https://www.selleckchem.com/products/en4.html selleck kinase inhibitor] We also provide evidence for a whole genome duplication event in the lineage leading to L. japonica, which occurred after its divergence from Dipsacales and Asterales. Moreover, gene expression analysis not only revealed correlated expression of the relevant biosynthetic genes with carotenoid accumulation, but also suggested a role for carotenoid degradation in L. japonica's dynamic flower coloration. The variation of flower color is consistent with not only the observed carotenoid accumulation pattern, but also with the release of volatile apocarotenoids that presumably serve as pollinator attractants. Beyond novel insights into the evolution and dynamics of flower coloration, the high-quality L. japonica genome sequence also provides a foundation for molecular breeding to improve desired characteristics. This article is protected by copyright. All rights reserved.KEY POINTS The neural strategies behind the control of force during muscle pain are not well understood as previous research has been limited in assessing pain responses during low-force contractions only. Here we compared, for the first time, the behaviour of motor units recruited at low and high forces in response to pain. The results showed that motor units activated at low forces were inhibited while those recruited at higher forces increased their activity in response to pain. When analysing lower and higher-threshold motor unit behaviour at high forces we observed differential changes in discharge rate and recruitment threshold across the motor unit pool. These adjustments allow the exertion of high forces in acute painful conditions but could eventually lead to greater fatigue and stress of the muscle tissue. ABSTRACT During low force contractions, motor unit (MU) discharge rates decrease when muscle pain is induced by injecting nociceptive substances into the muscle. Despite this consistent observatioults show that there is a differential adjustment between low-and high-threshold motor units during painful conditions. An increase in excitatory drive to high threshold motor units is likely required to compensate for the inhibitory influence of nociceptive afferent inputs on low-threshold motor units. These differential mechanisms allow the force output to be maintained during acute pain but this strategy could lead to increased muscle fatigue and symptom aggravation in the long term. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.PURPOSE To create a dose response model that predicts lung ventilation change following radiation therapy, and examine the effects of out-of-phase ventilation. METHODS The dose response model was built using 27 human subjects who underwent radiation therapy (RT) from an IRB-approved trial. For each 4DCT, two ventilation maps were created by calculating the N-phase local expansion ratio (LERN ) using most or all breathing phases and the 2-phase LER (LER2 ) using only the end inspiration and end expiration breathing phases. A polynomial regression model was created using the LERN ventilation maps pre-RT and post-RT and dose distributions for each subject, and cross-validated with a leave-one-out method. Further validation of the model was performed using 15 additional human subjects using common statistical operating characteristics and gamma pass rates. RESULTS For voxels receiving 20 Gy or greater, there was a significant increase from 52% to 59% (p=0.03) in the gamma pass rates of the LERN model predicted post-RT Jacobian maps to the actual post-RT Jacobian maps, relative to the LER2 model. Additionally, accuracy significantly increased (p=0.03) from 68% to 75% using the LERN model, relative to the LER2 model. CONCLUSIONS The LERN model was significantly more accurate than the LER2 model at predicting post-RT ventilation maps. More accurate post-RT ventilation maps will aid in producing a higher quality functional avoidance treatment plan, allowing for potentially better normal tissue sparing. This article is protected by copyright. All rights reserved.Patients with lysine-related inborn errors of metabolism (pyridoxine-dependent epilepsy [PDE] and glutaric aciduria type 1 [GA1]), follow a lysine-restricted diet with arginine-fortified lysine-free amino acid formula and additional oral arginine supplementation as a newer therapy for PDE. The rationale of arginine supplementation is based on arginine's ability to compete with lysine transport across cell membranes via shared transporter systems. Adequate doses of arginine required to competitively inhibit enteral lysine uptake has not been studied in humans This proof-of-concept study investigates the effect of incremental enteral arginine doses on whole-body lysine oxidation using an in vivo stable isotope tracer, L-[1-13 C] lysine, in healthy humans. Five healthy men completed six study days each consuming one dose of l-arginine HCl per study day; range = 50-600 mg/kg/d. Lysine intake was at DRI (30 mg/kg/d). Breath samples were analysed for L-[1-13 C] lysine oxidation to 13 CO2 using an isotope ratio mass spectrometer. Plasma amino acid concentrations were analysed using an amino acid analyser. Increasing doses of l-arginine HCl caused a linear decrease in whole-body lysine oxidation. Plasma arginine concentration increased, and plasma lysine concentration decreased below normal range with high arginine intakes. We provide the first empirical evidence of arginine-lysine antagonism in response to increasing oral arginine doses. Results suggest 300-600 mg/kg/d of l-arginine HCl and lysine intake restricted to DRI is needed to reduce enteral lysine uptake and systemic lysine oxidation. This could potentially lead to a recommended dose for arginine in lysine-related inborn errors of metabolism. © 2020 SSIEM.in English, Spanish ANTECEDENTES Los ensayos controlados con placebo juegan un papel importante en la evaluación de las intervenciones sanitarias. Sin embargo, pueden ser difíciles de diseñar e implementar en el caso de intervenciones invasivas, incluida la cirugía. Se necesita un conocimiento profundo de los componentes de la intervención terapéutica (para determinar qué se debe y qué no se debe administrar como parte del placebo). También se precisa de una evaluación del riesgo para los pacientes y de las estrategias para garantizar que el placebo imite el tratamiento de forma efectiva. Hasta la fecha no existen guías para el diseño de intervenciones invasivas con placebo. Este estudio tuvo como objetivo desarrollar un marco para optimizar el diseño y la práctica de intervenciones invasivas con placebo dentro en los ensayos clínicos aleatorizados (ECA). MÉTODOS Utilizando la literatura publicada, se desarrolló un marco preliminar para i) ampliar el alcance de los modelos existentes para facilitar la deconstión de intervenciones sanitarias.BACKGROUND Endometrial hyperplasia is a precursor to endometrioid adenocarcinoma (EMC), the most common uterine cancer. The likelihood of progression to carcinoma may be evaluated by histologic subclassification of endometrial hyperplasia, although these subclasses are subjective and only modestly reproducible among pathologists. Patient care would be improved by a more objective test to predict the risk of cancer progression. METHODS Next-generation sequencing was performed on archived endometrial biopsy specimens from a retrospective cohort of women with endometrial hyperplasia. Cases were considered to be either progressing if the patient subsequently developed EMC or resolving if the patient had a subsequent negative tissue sampling or no cancer during medium-term follow-up (32 patients 15 progressing and 17 resolving). Somatic mutations in endometrial hyperplasia were assessed for enrichment in progressing cases versus resolving cases, with an emphasis on genes commonly mutated in EMC. RESULTS Several mutations were more common in progressing hyperplasia than resolving hyperplasia, although significant overlap was observed between progressing and resolving cases.