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Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first-line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7x10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression.

Calmodulinopathies are caused by mutations in calmodulin (CaM), and result in debilitating cardiac arrythmias such as long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). In addition, many patients exhibit neurological comorbidities, including developmental delay and autism spectrum disorder. Until now, most work into these mutations has focused on cardiac effects, identifying impairment of Ca 2+ /CaM-dependent inactivation (CDI) of Ca V 1.2 channels as a major pathogenic mechanism. However, the impact of these mutations on neurological function has yet to be fully explored. CaM regulation of voltage-gated calcium channels (VGCCs) is a critical element of neuronal function, implicating multiple VGCC subtypes in the neurological pathogenesis of calmodulinopathies. Here, we explore the potential for pathological CaM variants to impair the Ca 2+ /CaM-dependent regulation of Ca V 1.3 and Ca V 2.1, both essential for neuronal function. We find that mutations in CaM can impair the CDI of Ca V 1.3 and reduce the Ca 2+ -dependent facilitation (CDF) of Ca V 2.1 channels. We find that mutations associated with significant neurological symptoms exhibit marked effects on Ca V 1.3 CDI, with overlapping but distinct impacts on Ca V 2.1 CDF. Moreover, while the majority of CaM variants demonstrated the ability to bind the IQ region of each channel, distinct differences were noted between Ca V 1.3 and Ca V 2.1, demonstrating distinct CaM interactions across the two channel subtypes. Further, C-domain CaM variants display a reduced ability to sense Ca 2+ when in complex with the Ca V IQ domains, explaining the Ca 2+ /CaM regulation deficits. Overall, these results support the possibility that disrupted Ca 2+ /CaM regulation of VGCCs may contribute to neurological pathogenesis of calmodulinopathies.

Mutations in the small, calcium-sensing, protein calmodulin cause cardiac arrhythmia and can ultimately prove lethal. Here, we report the impact of the G113R variant on the structure and dynamics of the calmodulin molecule, both in the presence and in the absence of calcium. We show that the mutation introduces minor changes into the structure of calmodulin and that it changes the thermostability and thus the degree of foldedness at human body temperature. The mutation also severely impacts the intramolecular mobility of calmodulin, especially in the apo form. Glycine 113 acts as an alpha-helical C-capping residue in both apo/ - and Ca 2+ /calmodulin, but its exchange to arginine has very different effects on the apo and Ca 2+ forms. The majority of arrhythmogenic calmodulin variants identified affects residues in the Ca 2+ coordinating loops of the two C-domain EF-Hands, causing a 'direct impact on Ca 2+ binding'. However, G113R lies outside a Ca 2+ coordinating loop and acts differently and more similar to the previously characterized arrhythmogenic N53I. Therefore, we suggest that altered apo/CaM dynamics may be a novel general disease mechanism, defining low-calcium target affinity - or Ca 2+ binding kinetics - critical for timely coordination of essential ion-channels in the excitation-contraction cycle., Competing Interests: Declaration of Competing Interest MTO acted as expert witness for the defense in the 2022/2023 Inquiry into the convictions of Kathlen Megan Folbigg (https://2022folbigginquiry.dcj.nsw.gov.au/). CVH, NMP and HI are employees of private companies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This pre-post intervention study investigated the effectiveness of the Patient Care Board (PCB) as a tool to increase the participation of patients and relatives during hospital ward rounds., Methods: Using The Activity Barometer (TAB), we rated 121 video-recorded rounds to compare participation before and after implementing the PCB into clinical practice. Associations between scores for the extent to which patients ask questions or express preferences and concerns were tested with multiple linear regression., Results: TAB-scores tended to be higher after implementing the PCB, especially for the relatives. However, no significant differences were found. The greatest impact on participation was time spent on rounds (p < 0.001). Preparing questions in advance of the round, as well as using anatomical drawings for explanations, increased patient participation (p = 0.041, 0.024). Furthermore, the implementation of the PCB led to higher nurse attendance (p = 0.003)., Conclusion: Although we found tendencies towards higher participation, the study could not confirm a significant impact of the overall intervention., Innovation: Our results suggest that further research is needed, to ensure a higher degree of preparation among the patients, better opportunities for relatives to participate as well as integration of visual information in the rounds., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: We hypothesized that health care providers would behave in a more patient-centered manner after the implementation of communication skills training, without causing the consultation to last longer., Methods: This study was part of the large-scale implementation of a communication skills training program called "Clear-Cut Communication With Patients" at Lillebaelt Hospital in Denmark. Audio recordings from real-life consultations were collected in a pre-post design, with health care providers' participation in communication skills training as the intervention. The training was based on the Calgary-Cambridge Guide, and audio recordings were rated using the Observation Scheme-12., Results: Health care providers improved their communication behavior in favor of being more patient-centered. Results were tested using a mixed-effect model and showed significant differences between pre- and postintervention assessments, with a coefficient of 1.3 (95% Cl: 0.35-2.3; P=0.01) for the overall score. The consultations did not last longer after the training., Conclusions: Health care providers improved their communication in patient consultations after the implementation of a large-scale patient-centered communication skills training program based on the Calgary-Cambridge Guide. This did not affect the length of the consultations., Competing Interests: Conflicts of Interest None., (© 2021 Aurora Health Care, Inc.)

Background: The aim of the study was to confirm the validity and reliability of the Observation Scheme-12, a measurement tool for rating clinical communication skills., Methods: The study is a sub-study of an intervention study using audio recordings to assess the outcome of communication skills training. This paper describes the methods used to validate the assessment tool Observation Scheme-12 by operationalizing the crude 5-point scale into specific elements described in a codebook. Reliability was tested by calculating the intraclass correlation coefficients for interrater and intrarater reliability., Results: The validation of the Observation Scheme-12 produced a rating tool with 12 items. Each item has 0 to 5 described micro-skills. For each item, the codebook described the criteria for delivering a rating from 0 to 4 depending on how successful the different micro-skills (or number of used jargon words) was accomplished. Testing reliability for the overall score intraclass correlation coefficients was 0.74 for interrater reliability and 0.86 for intrarater reliability. An intraclass correlation coefficient greater than 0.5 was observed for 10 of 12 items., Conclusion: The development of a codebook as a supplement to the assessment tool Observation Scheme-12 enables an objective rating of audiotaped clinical communication with acceptable reliability. The Observation Scheme-12 can be used to assess communication skills based on the Calgary-Cambridge Guide.

Objective: To translate and cultural adapt the 14-item Communication Assessment Tool (CAT) into Norwegian and Danish, making them as similar as possible., Design: This was a translation and validation study including individual interviews for content and face validity and a patient survey for internal consistency and floor-ceiling effect., Setting: Outpatient clinic at the Department of Internal Medicine, Lillebaelt Hospital, Denmark and a Norwegian general practice., Participants: Ten patients were included for individual interviews and 440 participants completed the survey., Main Outcome Measure: Translation and validation of the CAT., Results: Despite minor differences in the use of words in the translated versions of CAT, the final versions were very similar. Based on the content and face validation and after agreement with the developers, it was decided to include a 'non-applicable' answering option, not a part of the original version. The use of 'non-applicable' for each item ranged from 0% to 30% in Norway and from 0% to 6.1% in Denmark. The overall CAT score, i.e. items rated excellent, were 55.5% in Norway and 50.3% in Denmark. For each item, the CAT score ranged between 31.3% and 69.8% in Norway and 33.7% and 57.4% in Denmark., Conclusion: The translated and validated CAT can be used to measure patients' perspectives on clinicians' communication skills in Denmark and Norway., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)