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This software demonstration presents the possibilities for the construction, administration, and evaluation of criterion- referenced, computerized adaptive and nonadaptive tests with the R-based open-source KAT-HS app. This app enables users to apply the continuous item calibration strategy of Fink, Born, Spoden, and Frey (2018).
Background: Treatment of first-time shoulder dislocation (FSD) is a topic of debate. After high rates of recurrent instability after nonoperative management were reported in the literature, primary repair of FSD significantly increased. At the same time, new concepts were proposed that had promising results for immobilization in external rotation (ER) and abduction (ABD). Purpose: The aim of this study was to evaluate the recurrence rates (primary outcome) and clinical outcomes (secondary outcome parameters) of immobilization in ER+ABD versus arthroscopic primary stabilization after FSD. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In a multicenter randomized controlled trial, patients with FSD were randomized to either treatment with immobilization in 60° of ER plus 30° of ABD (group 1) or surgical treatment with arthroscopic Bankart repair (group 2). Clinical evaluation was performed 1, 3, and 6 weeks as well as 6, 12, and 24 months postoperatively or after reduction, including range of motion, instability testing, subjective shoulder value, Constant-Murley score, Rowe score, and Western Ontario Shoulder Instability Index. Recurrent instability events were prospectively recorded. Results: Between 2011 and 2017, a total of 112 patients were included in this study. Of these, 60 patients were allocated to group 1 and 52 to group 2. At the 24-month follow-up, 91 patients (81.3%) were available for clinical examination. The recurrence rate was 19.1% in group 1 and 2.3% in group 2 (P = .016). No significant differences were found between groups regarding clinical shoulder scores (P > .05). Due to noncompliance with the immobilization treatment protocol, 4 patients (6.7%) were excluded. Conclusion: Immobilization in ER+ABD versus primary arthroscopic shoulder stabilization for the treatment of FSD showed no differences in clinical shoulder scores. However, recurrent instability was significantly higher after nonoperative treatment.
Feasibility of present-centered therapy for prolonged grief disorder: results of a pilot study
(2021)
Present-centered therapy (PCT) was originally developed as a strong comparator for the non-specific effects of psychotherapy in the treatment of posttraumatic stress disorder. PCT qualifies as a not strictly supportive treatment as it is structured and homework is assigned between sessions. It does not focus on cognitive restructuring or exposure. A growing body of literature supports its beneficial effects. For example, it demonstrated only slightly inferior effect sizes and lower dropout rates compared to that of trauma-focused cognitive behavioral therapy in several trials with patients suffering from posttraumatic stress disorder. The current study is the first to evaluate the feasibility and the treatment effects of PCT in adults with prolonged grief disorder (PGD). Meta-analyses on psychotherapy for PGD have yielded moderate effect sizes. N = 20 individuals suffering from PGD were treated with PCT by novice therapists as part of a preparation phase for an upcoming RCT in an outpatient setting. Treatment consisted of 20–24 sessions á 50 min. All outcomes were assessed before treatment, at post-treatment, and at the 3-month follow-up. The primary outcome, PGD symptom severity, was assessed using the Interview for Prolonged Grief-13. Secondary outcomes were self-reported PGD severity, depression, general psychological distress, and somatic symptom severity. Furthermore, therapists evaluated their experiences with their first PCT patient and the treatment manual. In intent-to-treat analyses of all patients we found a significant decrease in interview-based PGD symptom severity at post-treatment (d = 1.26). Decreases were maintained up to the 3-month follow-up assessment (d = 1.25). There were also significant decreases in self-reported PGD symptoms, depression, and general psychological distress. No changes were observed for somatic symptoms. The completion rate was 85%. Therapists deemed PCT to be a learnable treatment program that can be adapted to the patient's individual needs. The preliminary results of PCT as a treatment for PGD demonstrate large effects and indicate good feasibility in outpatient settings. The treatment effects were larger than those reported in meta-analyses. Thus, PCT is a promising treatment for PGD. Possible future research directions are discussed.
Background: Gan–Dou–Fu–Mu decoction (GDFMD) improves liver fibrosis in experimental and clinical studies including those on toxic mouse model of Wilson disease (Model). However, the mechanisms underlying the effect of GDFMD have not been characterized. Herein, we deciphered the potential therapeutic targets of GDFMD using transcriptome analysis.
Methods: We constructed a tx-j Wilson disease (WD) mouse model, and assessed the effect of GDFMD on the liver of model mice by hematoxylin and eosin, Masson, and immunohistochemical staining. Subsequently, we identified differentially expressed genes (DEGs) that were upregulated in the Model (Model vs. control) and those that were downregulated upon GDFMD treatment (compared to the Model) using RNA-sequencing (RNA-Seq). Biological functions and signaling pathways in which the DEGs were involved were determined by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. A protein–protein interaction (PPI) network was constructed using the STRING database, and the modules were identified using MCODE plugin with the Cytoscape software. Several genes identified in the RNA-Seq analysis were validated by real-time quantitative PCR. Results: Total of 2124 DEGs were screened through the Model vs. control and Model vs. GDFMD comparisons, and dozens of GO and KEGG pathway terms modulated by GDFMD were identified. Dozens of pathways involved in metabolism (including metabolic processes for organic acids, carboxylic acids, monocarboxylic acids, lipids, fatty acids, cellular lipids, steroids, alcohols, eicosanoids, long-chain fatty acids), immune and inflammatory response (such as complement and coagulation cascades, cytokine–cytokine receptor interaction, inflammatory mediator regulation of TRP channels, antigen processing and presentation, T-cell receptor signaling pathway), liver fibrosis (such as ECM-receptor interactions), and cell death (PI3K-Akt signaling pathway, apoptosis, TGF-beta signaling pathway, etc.) were identified as potential targets of GDFMD in the Model. Some hub genes and four modules were identified in the PPI network. The results of real-time quantitative PCR analysis were consistent with those of RNA-Seq analysis. Conclusions: We performed gene expression profiling of GDFMD-treated WD model mice using RNA-Seq analysis and found the genes, pathways, and processes effected by the treatment. Our study provides a theoretical basis to prevent liver fibrosis resulting from WD using GDFMD.
Working memory capacity (WMC) and fluid intelligence (Gf) are highly correlated, but what accounts for this relationship remains elusive. Process-overlap theory (POT) proposes that the positive manifold is mainly caused by the overlap of domain-general executive processes which are involved in a battery of mental tests. Thus, executive processes are proposed to explain the relationship between WMC and Gf. The current study aims to (1) achieve a relatively purified representation of the core executive processes including shifting and inhibition by a novel approach combining experimental manipulations and fixed-links modeling, and (2) to explore whether these executive processes account for the overlap between WMC and Gf. To these ends, we reanalyzed data of 215 university students who completed measures of WMC, Gf, and executive processes. Results showed that the model with a common factor, as well as shifting and inhibition factors, provided the best fit to the data of the executive function (EF) task. These components explained around 88% of the variance shared by WMC and Gf. However, it was the common EF factor, rather than inhibition and shifting, that played a major part in explaining the common variance. These results do not support POT as underlying the relationship between WMC and Gf.
Simple Summary: Mutations in RAS-family genes frequently cause different types of human cancers. Inhibitors of the MEK (mitogen-activated protein kinase) and ERK (extracellular signal-regulated kinase) protein kinases that function downstream of RAS proteins have shown some clinical benefits when used for the treatment of these cancers, but drug resistance frequently emerges. Here we show that combined treatment with MEK and ERK inhibitors blocks the emergence of resistance to either drug alone. However, if cancer cells have already developed resistance to MEK inhibitors or to ERK inhibitors, the combined therapy is frequently ineffective. These findings imply that these inhibitors should be used together for cancer therapy. We also show that drug resistance involves complex patterns of rewiring of cellular kinase signaling networks that do not overlap between each different cancer cell line. Nonetheless, we show that MAP4K4 is required for efficient cell proliferation in several different MEK/ERK inhibitor resistant cancer cell lines, uncovering a potential new therapeutic target.
Abstract: Oncogenic mutations in RAS family genes arise frequently in metastatic human cancers. Here we developed new mouse and cellular models of oncogenic HrasG12V-driven undifferentiated pleomorphic sarcoma metastasis and of KrasG12D-driven pancreatic ductal adenocarcinoma metastasis. Through analyses of these cells and of human oncogenic KRAS-, NRAS- and BRAF-driven cancer cell lines we identified that resistance to single MEK inhibitor and ERK inhibitor treatments arise rapidly but combination therapy completely blocks the emergence of resistance. The prior evolution of resistance to either single agent frequently leads to resistance to dual treatment. Dual MEK inhibitor plus ERK inhibitor therapy shows anti-tumor efficacy in an HrasG12V-driven autochthonous sarcoma model but features of drug resistance in vivo were also evident. Array-based kinome activity profiling revealed an absence of common patterns of signaling rewiring in single or double MEK and ERK inhibitor resistant cells, showing that the development of resistance to downstream signaling inhibition in oncogenic RAS-driven tumors represents a heterogeneous process. Nonetheless, in some single and double MEK and ERK inhibitor resistant cell lines we identified newly acquired drug sensitivities. These may represent additional therapeutic targets in oncogenic RAS-driven tumors and provide general proof-of-principle that therapeutic vulnerabilities of drug resistant cells can be identified.
Neurogenic/neuropathic bowel dysfunction (NBD) is common in children who are affected by congenital and acquired neurological disease, and negatively impacts quality of life. In the past, NBD received less attention than neurogenic bladder, generally being considered only in spina bifida (the most common cause of pediatric NBD). Many methods of conservative and medical management of NBD are reported, including relatively recently Transanal Irrigation (TAI). Based on the literature and personal experience, an expert group (pediatric urologists/surgeons/gastroenterologists with specific experience in NBD) focused on NBD in children and adolescents. A statement document was created using a modified Delphi method. The range of causes of pediatric NBD are discussed in this paper. The various therapeutic approaches are presented to improve clinical management. The population of children and adolescents with NBD is increasing, due both to the higher survival rate and better diagnosis. While NBD is relatively predictable in producing either constipation or fecal incontinence, or both, its various effects on each patient will depend on a wide range of underlying causes and accompanying comorbidities. For this reason, management of NBD should be tailored individually with a combined multidisciplinary therapy appropriate for the status of the affected child and caregivers.
Analysing causality among oil prices and, in general, among financial and economic variables is of central relevance in applied economics studies. The recent contribution of Lu et al. (2014) proposes a novel test for causality— the DCC-MGARCH Hong test. We show that the critical values of the test statistic must be evaluated through simulations, thereby challenging the evidence in papers adopting the DCC-MGARCH Hong test. We also note that rolling Hong tests represent a more viable solution in the presence of short-lived causality periods.