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Liver iron overload was reported in 62% of patients and occurred regardless of transfusion cohort.

Even never transfused patients with PK deficiency had higher rates of select comorbidities and complications than individuals without PK deficiency.

Even never transfused patients with PK deficiency had higher rates of select comorbidities and complications than individuals without PK deficiency.

There is a lack of evidence guiding discontinuation of disease-modifying therapy (DMT) in relapsing multiple sclerosis (RMS). Thus, the objective of this study was to generate and validate a risk score for disease reactivation after DMT discontinuation in RMS.

We drew a generation and validation dataset from two separate prospectively collected observational databases including RMS patients who received interferon-β or glatiramer acetate for ≥12months, then discontinued DMT for ≥6months and had ≥2years of follow-up available. In the generation sample (n=168), regression analysis was performed to identify clinical or magnetic resonance imaging (MRI) variables independently predicting disease reactivation after DMT discontinuation. A predictive score was calculated using the variables included in the multivariable model and applied to the validation sample (n=98).

The variables included in the final model as independent predictors of disease reactivation were age at discontinuation, MRI activity at discontinuation, and duration of clinical stability (all p<0.001). The resulting score was able to robustly identify patients at high (83%-85%), moderate (36%-38%), and low risk (7%) of disease reactivation within 5years after DMT discontinuation in both cohorts.

The composite VIAADISC score is a valuable tool to inform and support patients and neurologists in the process of decision making to discontinue injectable DMTs.

The composite VIAADISC score is a valuable tool to inform and support patients and neurologists in the process of decision making to discontinue injectable DMTs.Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open-label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (11) to receive a single pretransplant intravenous infusion of third-party bone marrow-derived MSC or standard of care alone. The primary endpoint was the safety profile of MSC administration during the 1-year follow-up. In all, 19 patients completed the study, and none of those who received MSC experienced infusion-related complications. The incidence of serious and non-serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56bright NK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC-treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance-associated transcripts in 1-year protocol biopsies were similar in the two groups. In conclusion, pretransplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.gov identifier NCT02260375.

The Tooth Wear Evaluation System (TWES) is a type of tooth wear index. To date, there is the lack of data comparing the reliability of the application of this index on gypsum cast records and digital greyscale intra-oral scan records.

A comparative evaluation between the use of gypsum cast records and digital greyscale intra-oral scan records with the reliability of tooth wear scoring using the TWES amongst a group of patients with tooth wear.

Records for 10 patients with moderate to severe tooth wear (TWES≥2) were randomly selected from a larger clinical trial. TWES grading of the occlusal/incisal, buccal and palatal/lingual surfaces was performed to determine the levels of intra- and interobserver agreement. Intra-observer reproducibility was based on the findings of one examiner only. For the interobserver reproducibility, the findings of two examiners were considered. One set of models/ records were used per patient. (S)-Glutamic acid Cohen’s weighted kappa (κ

) was used to ascertain agreement between and within thg of wearing occlusal/incisal surfaces using gypsum casts. The reliability offered by digital greyscale intra-oral scans for consecutive scoring was in general, inferior.

The TWES can offer a reliable means for the scoring of wearing occlusal/incisal surfaces using gypsum casts. The reliability offered by digital greyscale intra-oral scans for consecutive scoring was in general, inferior.Psychosocial emergency care personnel form an important first responder subgroup, in which trained volunteers provide psychological first aid to accident and trauma survivors, their relatives, eye witnesses, bystanders and first responders themselves. This is the first longitudinal study to assess psychological burden due to secondary traumatisation and relevant resilience factors in psychosocial emergency care personnel. link2 We asked 100 German psychosocial emergency care workers to assess their feeling of preparedness and resilience factors prior training. After training, when participants had worked emergency responses, we assessed secondary traumatisation. Overall, the level of secondary traumatisation was sub-clinical (M = 37.50, SD = 5.35) after training and reported resilience factor levels were high. Three regression analyses were conducted to examine the moderation effect of preparedness on specific expertise (R2 = 0.479, p less then 0.001), performance competence (R2 = 0.419, p = 0.002) and inner attitude (R2 = 0.336, p = 0.002) in regard to the relationship between resilience factors and secondary traumatisation. Feeling prepared and competent for emergency responses were protective factors. Practical implications include the following volunteers should not take part in emergency responses if they are under excessive stress; the volunteers’ resilience factors should be taken into account; emergency response training should promote the feeling of preparedness in specific expertise and performance competence.

The purpose of this study was to quantitatively assess the longitudinal acquisition repeatability of MRI radiomics features in a three-dimensional (3D) T1-weighted (T1W) TSE sequence via a well-controlled prospective phantom study.

Thirty consecutive daily datasets of an ACR-MRI phantom were acquired on two 1.5T MRI simulators using a 3D T1W TSE sequence. Images were blindly segmented by two observers. Post-acquisition processing was minimized but an intensity discretization (fixed bin size of 25). One hundred and one radiomics features (shape n=12; first order n=16; texture n=73) were extracted. Longitudinal repeatability of each feature was evaluated by Pearson correlation and coefficient of variance (CV

). Interobserver feature value agreement was also quantified using intraclass correlation coefficient (ICC) and Bland-Altman analysis. A most repeatable radiomics feature set on both scanners was determined by feature coefficient of variance (CV

<5%), ICC (>0.75), and the ratio of the interobsexhibited heterogeneous longitudinal repeatability, while the shape features were the most repeatable, in this phantom study with a 3D T1W TSE acquisition. The most repeatable radiomics feature set derived in this study should be helpful for the selection of reliable radiomics features in the future clinical use.

Radiomics features exhibited heterogeneous longitudinal repeatability, while the shape features were the most repeatable, in this phantom study with a 3D T1W TSE acquisition. The most repeatable radiomics feature set derived in this study should be helpful for the selection of reliable radiomics features in the future clinical use.We have previously identified receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a direct transcriptional target of TTF-1/NKX2-1, a lineage-survival oncogene in lung adenocarcinoma. ROR1 sustains prosurvival signaling from multiple receptor tyrosine kinases including epidermal growth factor receptor, MET, and insulin-like growth factor 1 receptor in part by maintaining the caveolae structure as a scaffold protein of cavin-1 and caveolin-1. link3 In this study, a high throughput screening of the natural product library containing 2560 compounds was undertaken using a cell-based FluoPPI assay detecting ROR1-cavin-1 interaction. As a result, geldanamycin (GA), a known inhibitor of heat shock protein 90 (HSP90), was identified as a potential inhibitor of ROR1. Geldanamycin, as well as two GA derivatives tested in the clinic, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), decreased ROR1 protein expression. We found that ROR1 physically interacted with HSP90α, but not with other HSP90 paralogs, HSP90β or GRP94. Geldanamycin in turn destabilized and degraded ROR1 protein in a dose- and time-dependent manner through the ubiquitin/proteasome pathway, resulting in a significant suppression of cell proliferation in lung adenocarcinoma cell lines, for which the kinase domain of ROR1, but not its kinase activity or N-glycosylation, was required. Our findings indicate that HSP90 is required to sustain expression of ROR1 crucial for lung adenosarcoma survival, suggesting that inhibition of HSP90 could be a promising therapeutic strategy in ROR1-positive lung adenocarcinoma.

Bleeding phenotypes among individuals with severe factor VIII (FVIII) deficiency are variable, even with routine prophylactic FVIII administration. Activated platelets, in addition to their role in primary hemostasis, play a major role in coagulation by providing a phospholipid surface to which coagulation factors bind.

The aim of this study was to determine whether platelet function is associated with past and/or future bleeding in patients with severe FVIII deficiency on prophylaxis.

Platelet function quantified by platelet surface expression of phosphatidylserine, platelet surface glycoprotein (GP) VI, platelet surface activated GPIIb-IIIa, platelet surface P-selectin, the percentage of coated platelets, and the percentage of platelet-derived microparticles in the presence or absence of in vitro activation by various agonists was assessed in 34 patients.

Decreased platelet surface phosphatidylserine expression (identified by annexin V binding), both in the presence and absence of ADP/thrombin receptor activating peptide, demonstrated a significant association with both prior and subsequent bleeding in any location and specifically with hemarthrosis. No significant difference between patients with and without bleeding was observed in any of the other platelet activity markers.

Decreased platelet surface phosphatidylserine expression measured by annexin V binding predicts increased bleeding in severe FVIII deficient patients on prophylaxis.

Decreased platelet surface phosphatidylserine expression measured by annexin V binding predicts increased bleeding in severe FVIII deficient patients on prophylaxis.