Oakley and colleagues (2021) suggest that a classic scale - HGSHSA, aiming to measure hypnotic suggestibility - can be used to measure direct verbal suggestibility (DVS). According to the authors, DVS is a trait that can be measured both with and without hypnosis. I find this initiative highly welcome. However, I wish to give several examples why it is time to develop entirely new scales instead. Rather than trying to explain more phenomena with a single scale or concept, researchers should take a cue from research that points to a far more nuanced picture of suggestibility than a construct like DVS allows. There may be no single, unified phenomenon that can be measured with a single scale. The old, time-tested scales should be treated neither as sacred nor final. https://www.selleckchem.com/products/Naphazoline-hydrochloride-Naphcon.html They require up-to-date, critical analysis of what exactly they measure, with an eye to how they can be further improved.In this pilot study, we carried out metabolic profiling of patients with rheumatoid arthritis (RA) starting therapy with biological disease-modifying antirheumatic drugs (bDMARDs). The main aim of the study was to assess the occurring metabolic changes associated with therapy success and metabolic pathways involved. In particular, the potential of the metabolomics profiles was evaluated as therapeutically valuable prognostic indicators of the effectiveness of bDMARD treatment to identify responders versus non-responders prior to implementing treatment. Plasma metabolomic profiles of twenty-five patients with RA prior bDMARD treatment and after three months of therapy were obtained by 1H NMR, liquid chromatography - mass spectrometry, and gas chromatography - mass spectrometry and evaluated by statistical and multivariate analyses. In the group of responders, significant differences in their metabolic patterns were seen after three months of the bDMARD therapy compared with profiles prior to treatment. We identified 24 metabolites that differed significantly between these two-time points mainly belonging to amino acid metabolism, peptides, lipids, cofactors, and vitamins and xenobiotics. Eleven metabolites differentiated responders versus non-responders before treatment. Additionally, N-acetylglucosamine and N-acetylgalactosamine (GlycA) and N-acetylneuraminic acid (GlycB) persisted significant in comparison responders to non-responders after three months of therapy. Moreover, those two metabolites indicated prediction of response potential by results of receiver-operating characteristic (ROC) curve analysis. The applied analysis provides novel insights into the metabolic pathways involved in RA patient's response to bDMARD and therapy effectiveness. GlycA and GlycB are promising biomarkers to identify responding patients prior onset of bDMARD therapy.Signaling via TNF-R1 mediates pleiotropic biological outcomes ranging from inflammation and proliferation to cell death. Previous reports demonstrated that pro-survival signaling emanates from membrane resident TNF-R1 complexes (complex I) while only internalized TNF-R1 complexes are capable for DISC formation (complex II) and thus, apoptosis induction. Internalized TNF-R1 containing endosomes undergo intracellular maturation towards lysosomes, resulting in activation and release of Cathepsin D (CtsD) into the cytoplasm. We recently revealed HSP90 as target for proteolytic cleavage by CtsD, resulting in cell death amplification. In this study, we show that extrinsic cell death activation via TNF or TRAIL results in HSP90β degradation. Co-incubation of cells with either TNF or TRAIL in combination with the HSP90β inhibitor KUNB105 but not HSP90α selective inhibition promotes apoptosis induction. In an attempt to reveal further downstream targets of combined TNF-R1 or TRAIL-R1/-R2 activation with HSP90β inhibition, we identify HIF1α and validate its ligandinhibitor triggered degradation. Together, these findings suggest that selective inhibition of HSP90 isoforms together with death ligand stimulation may provide novel strategies for therapy of inflammatory diseases or cancer, in future.Given the rapid growth of artificial intelligence (AI) applications in radiotherapy and the related transformations toward the data-driven healthcare domain, this article summarizes the need and usage of the FAIR (Findable, Accessible, Interoperable, Reusable) data principles in radiotherapy. This work introduces the FAIR data concept, presents practical and relevant use cases and the future role of the different parties involved. The goal of this article is to provide guidance and potential applications of FAIR to various radiotherapy stakeholders, focusing on the central role of medical physicists.Parent-child synchrony-parent-child interaction patterns characterized by contingent social responding, mutual responsivity, and co-regulation-has been robustly associated with adaptive child outcomes. Synchrony has been investigated in both behavioral and biological frameworks. While it has been demonstrated that adversity can influence behavioral parent-child synchrony, the neural mechanisms by which this disruption occurs are understudied. The current study examined the association between adversity, parent-child behavioral synchrony, and parent-child neural synchrony across lateral prefrontal cortical regions using functional near-infrared spectroscopy hyperscanning during a parent-child interaction task that included a mild stress induction followed by a recovery period. Participants included 115 children (ages 4-5) and their primary caregivers. Parent-child behavioral synchrony was quantified as the amount time the dyad was synchronous (e.g., reciprocal communication, coordinated behaviors) during the interaction task. Parent-child neural synchrony was examined as the hemodynamic concordance between parent and child lateral PFC activation. Adversity was examined across two, empirically-derived domains sociodemographic risk (e.g., family income) and familial risk (e.g., household chaos). Adversity, across domains, was associated with decreased parent-child behavioral synchrony across task conditions. Sociodemographic risk was associated with decreased parent-child neural synchrony in the context of experimentally-induced stress. These findings link adversity to decreased parent-child behavioral and neural synchrony.
Oakley and colleagues (2021) suggest that a classic scale - HGSHSA, aiming to measure hypnotic suggestibility - can be used to measure direct verbal suggestibility (DVS). According to the authors, DVS is a trait that can be measured both with and without hypnosis. I find this initiative highly welcome. However, I wish to give several examples why it is time to develop entirely new scales instead. Rather than trying to explain more phenomena with a single scale or concept, researchers should take a cue from research that points to a far more nuanced picture of suggestibility than a construct like DVS allows. There may be no single, unified phenomenon that can be measured with a single scale. The old, time-tested scales should be treated neither as sacred nor final. https://www.selleckchem.com/products/Naphazoline-hydrochloride-Naphcon.html They require up-to-date, critical analysis of what exactly they measure, with an eye to how they can be further improved.In this pilot study, we carried out metabolic profiling of patients with rheumatoid arthritis (RA) starting therapy with biological disease-modifying antirheumatic drugs (bDMARDs). The main aim of the study was to assess the occurring metabolic changes associated with therapy success and metabolic pathways involved. In particular, the potential of the metabolomics profiles was evaluated as therapeutically valuable prognostic indicators of the effectiveness of bDMARD treatment to identify responders versus non-responders prior to implementing treatment. Plasma metabolomic profiles of twenty-five patients with RA prior bDMARD treatment and after three months of therapy were obtained by 1H NMR, liquid chromatography - mass spectrometry, and gas chromatography - mass spectrometry and evaluated by statistical and multivariate analyses. In the group of responders, significant differences in their metabolic patterns were seen after three months of the bDMARD therapy compared with profiles prior to treatment. We identified 24 metabolites that differed significantly between these two-time points mainly belonging to amino acid metabolism, peptides, lipids, cofactors, and vitamins and xenobiotics. Eleven metabolites differentiated responders versus non-responders before treatment. Additionally, N-acetylglucosamine and N-acetylgalactosamine (GlycA) and N-acetylneuraminic acid (GlycB) persisted significant in comparison responders to non-responders after three months of therapy. Moreover, those two metabolites indicated prediction of response potential by results of receiver-operating characteristic (ROC) curve analysis. The applied analysis provides novel insights into the metabolic pathways involved in RA patient's response to bDMARD and therapy effectiveness. GlycA and GlycB are promising biomarkers to identify responding patients prior onset of bDMARD therapy.Signaling via TNF-R1 mediates pleiotropic biological outcomes ranging from inflammation and proliferation to cell death. Previous reports demonstrated that pro-survival signaling emanates from membrane resident TNF-R1 complexes (complex I) while only internalized TNF-R1 complexes are capable for DISC formation (complex II) and thus, apoptosis induction. Internalized TNF-R1 containing endosomes undergo intracellular maturation towards lysosomes, resulting in activation and release of Cathepsin D (CtsD) into the cytoplasm. We recently revealed HSP90 as target for proteolytic cleavage by CtsD, resulting in cell death amplification. In this study, we show that extrinsic cell death activation via TNF or TRAIL results in HSP90β degradation. Co-incubation of cells with either TNF or TRAIL in combination with the HSP90β inhibitor KUNB105 but not HSP90α selective inhibition promotes apoptosis induction. In an attempt to reveal further downstream targets of combined TNF-R1 or TRAIL-R1/-R2 activation with HSP90β inhibition, we identify HIF1α and validate its ligandinhibitor triggered degradation. Together, these findings suggest that selective inhibition of HSP90 isoforms together with death ligand stimulation may provide novel strategies for therapy of inflammatory diseases or cancer, in future.Given the rapid growth of artificial intelligence (AI) applications in radiotherapy and the related transformations toward the data-driven healthcare domain, this article summarizes the need and usage of the FAIR (Findable, Accessible, Interoperable, Reusable) data principles in radiotherapy. This work introduces the FAIR data concept, presents practical and relevant use cases and the future role of the different parties involved. The goal of this article is to provide guidance and potential applications of FAIR to various radiotherapy stakeholders, focusing on the central role of medical physicists.Parent-child synchrony-parent-child interaction patterns characterized by contingent social responding, mutual responsivity, and co-regulation-has been robustly associated with adaptive child outcomes. Synchrony has been investigated in both behavioral and biological frameworks. While it has been demonstrated that adversity can influence behavioral parent-child synchrony, the neural mechanisms by which this disruption occurs are understudied. The current study examined the association between adversity, parent-child behavioral synchrony, and parent-child neural synchrony across lateral prefrontal cortical regions using functional near-infrared spectroscopy hyperscanning during a parent-child interaction task that included a mild stress induction followed by a recovery period. Participants included 115 children (ages 4-5) and their primary caregivers. Parent-child behavioral synchrony was quantified as the amount time the dyad was synchronous (e.g., reciprocal communication, coordinated behaviors) during the interaction task. Parent-child neural synchrony was examined as the hemodynamic concordance between parent and child lateral PFC activation. Adversity was examined across two, empirically-derived domains sociodemographic risk (e.g., family income) and familial risk (e.g., household chaos). Adversity, across domains, was associated with decreased parent-child behavioral synchrony across task conditions. Sociodemographic risk was associated with decreased parent-child neural synchrony in the context of experimentally-induced stress. These findings link adversity to decreased parent-child behavioral and neural synchrony.
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