ABSTRACT
Post-traumatic stress disorder (PTSD) is associated with osteopenia, osteoporosis and increased fracture risk in the clinical population. Yet, the development of preclinical models to study PTSD-induced bone loss remains limited. In this study, we present a previously unreported model of PTSD in adult female C57BL/6 mice, by employing inescapable foot shock and social isolation, that demonstrates high face and construct validity. A subset of mice exposed to this paradigm (i.e. PTSD mice) display long-term alterations in behavioral and inflammatory indices. Using three-dimensional morphometric calculations, cyclic reference point indentation (cRPI) testing and histological analyses, we find that PTSD mice exhibit loss of trabecular bone, altered bone material quality, and aberrant changes in bone tissue architecture and cellular activity. This adult murine model of PTSD exhibits clinically relevant changes in bone physiology and provides a valuable tool for investigating the cellular and molecular mechanisms underlying PTSD-induced bone loss.
Subject(s)
Stress Disorders, Post-Traumatic , Female , Mice , Animals , Stress Disorders, Post-Traumatic/complications , Mice, Inbred C57BL , Phenotype , Bone and Bones , Disease Models, AnimalABSTRACT
BACKGROUND: Research is essential for gathering evidence to inform best practice and clinical decision making, for developing and testing new treatments and services in palliative and end-of-life care (PEoLC). The participation of patients, carers and family members is essential, however, personal and ethical concerns are often cited by professionals as barriers to recruitment. There is evidence that patients and family members can benefit from participation in PEoLC research. AIM: To synthesise the evidence regarding patients', family members' and carers' experiences of participating in PEoLC research. To identify recommendations for enhancing the experience of participants. DESIGN: A qualitative rapid review and thematic synthesis. DATA SOURCES: MEDLINE, PsycINFO and PubMed were searched from 2010 to 2020. Studies reporting patients', family members' or carers' experiences of participating in PEoLC research were included. RESULTS: 4 studies were included and 7 themes identified relating to the benefits of, and barriers to, participation in PEoLC research. Both altruistic and personal benefits of participation were reported. Barriers (negative aspects) to participation included feeling overwhelmed, practical issues, reminders of being a patient, not seeing the research as relevant to them and unmet needs. CONCLUSIONS: A number of benefits (positive aspects) surround participation in PEoLC research. However, several barriers (negative aspects) can prevent or discourage participation. This review has identified recommendations for research teams to enhance the experience, and number of people who those participating in research in this field.
Subject(s)
Hospice Care , Palliative Medicine , Terminal Care , Humans , Family , Caregivers , Qualitative ResearchABSTRACT
Src homology-2 domain-containing phosphatase 2 (SHP2) is a ubiquitously expressed phosphatase that is vital for skeletal development and maintenance of chondrocytes, osteoblasts, and osteoclasts. Study of SHP2 function in small animal models has led to insights in phenotypes observed in SHP2-mutant human disease, such as Noonan syndrome. In recent years, allosteric SHP2 inhibitors have been developed to specifically target the protein in neoplastic processes. These inhibitors are highly specific and have great potential for disease modulation in cancer and other pathologies, including bone disorders. In this review, we discuss the importance of SHP2 and related signaling pathways (e.g., Ras/MEK/ERK, JAK/STAT, PI3K/Akt) in skeletal development. We review rodent models of pathologic processes caused by germline mutations that activate SHP2 enzymatic activity, with a focus on the skeletal phenotype seen in these patients. Finally, we discuss SHP2 inhibitors in development and their potential for disease modulation in these genetic diseases, particularly as it relates to the skeleton.
