Assessment and Treatment of Combat-Related Posttraumatic Stress Disorder: Results from STRONG STAR and the Consortium to Alleviate PTSD

Extensive research has been conducted since 11 September 2001 to develop and evaluate evidence-based treatments for combat-related posttraumatic stress disorder (PTSD) in active duty United States military personnel treated in the combat theater and in garrison. This chapter reviews the results of 20 PTSD clinical trials funded by the United States Department of Defense and Department of Veterans Affairs on the treatment of combat-related PTSD. All of the studies were conducted under the leadership and management of two research consortia: the South Texas Research Organizational Network Guiding Studies on Trauma and Resilience (STRONG STAR) Consortium and the Consortium to Alleviate PTSD

Effects of a Brief E-Learning Resource on Sexual Attitudes and Beliefs of Healthcare Professionals Working in Prostate Cancer Care: A Pilot Study

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)Sexual issues and treatment side effects are not routinely discussed with men receiving treatment for prostate cancer, and support to address these concerns is not consistent across settings. This study evaluates a brief e-learning resource designed to improve sexual wellbeing support and examine its effects on healthcare professionals’ sexual attitudes and beliefs. Healthcare professionals (n = 44) completed an online questionnaire at baseline which included a modified 12-item sexual attitudes and beliefs survey (SABS). Follow-up questionnaires were completed immediately after the e-learning and at 4 weeks. Data were analysed using one-way, repeat measures ANOVAs to assess change in attitudes and beliefs over time. Significant improvements were observed at follow-up for a number of survey statements including ‘knowledge and understanding’, ‘confidence in discussing sexual wellbeing’ and the extent to which participants felt ‘equipped with the language to initiate conversations’. The resource was seen as concise, relevant to practice and as providing useful information on potential side effects of treatment. In brief, e-learning has potential to address barriers to sexual wellbeing communication and promote delivery of support for prostate cancer survivors. Practical methods and resources should be included with these interventions to support implementation of learning and long-term changes in clinical behaviour.Peer reviewe

The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury

Background & Aims: In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration; however, the mechanism of activation in chronic liver injury is poorly understood. This study aimed to characterise Hh pathway activation upon thioacetamide (TAA)- induced chronic liver injury in vivo by defining Hh-responsive cells, namely cells harbouring Pc and Pc-localised SMO. Methods: C57BL/6 mice (wild-type or Ptc1+/_) were TAA-treated. Liver injury and Hh ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI manipulation and SMO dependent/ independent activation of GLI-mediated transcriptional response in Pc-positive (Pc+) cells were studied in vitro. Results: In vivo, Hh activation was progressively induced following TAA. At the epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands. Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2+. Pc+ cells increased following TAA, but only EpCAM+/GLI2+ progenitors were Pc+/SMO+. In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in Pc+ progenitors, whilst increased proliferation occurred with hGli1 overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO. Ptc1+/_ mice exhibited increased progenitor, myofibroblast and fibrosis responses. Conclusions: In chronic liver injury, Pc+ progenitors receive Hh ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc_/GLI2+ cells. Increased fibrosis in Hh gain-of-function mice likely occurs by primary progenitor expansion/proliferation and secondary fibrotic myofibroblast expansion, in close contact with progenitors

Challenges and support needs of parents and children when a parent is at end of life: A systematic review

Background: Preparing children for the death of a parent is challenging. Parents are often uncertain if and how to communicate and support their children. Many parents feel it is protecting their children by not telling them about the prognosis. Children less prepared for parental death from a terminal illness are more susceptive to later adversities. To facilitate coping and moderate for such adversities, there is a need to gain insight and understand the experience and challenges confronted by families. Aim: This review synthesised evidence on the experiences of parents and children when a parent is at end of life to discern their challenges, support needs and factors that facilitated good practice. Design: Mixed-methods systematic review. Data sources: Four electronic databases (CINAHL, PubMed, PsycINFO and Ovid MEDLINE) using MeSH terms and word searches in October 2018. Studies were not limited by year of publication, language or country. Grey literature searches were also completed on Google Scholar and OpenGrey. Results: In all, 7829 records were identified; 27 qualitative and 0 quantitative studies met the inclusion criteria. Eight descriptive themes were identified, further categorised into two broad themes: (1) barriers and facilitators in sharing the news that a parent is dying and (2) strategies to manage the changing situation. Conclusion: Lack of understanding in relation to the parent’s prognosis, denial and feeling ill-equipped were suggested as barriers for parents to share the news with their children. Engagement with social networks, including extended family relatives and peers, and maintaining routines such as attending school were suggested supportive by parents and children. Findings are limited primarily to White, middle-class two-parent families. A number of areas for future research are identified.</p

Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 -/- mouse model.

BACKGROUND: Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 -/- mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development. RESULTS: Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred. CONCLUSION: In Mdr2 -/- mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development