The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.

PTPRK is a receptor tyrosine phosphatase that is linked to the regulation of growth factor signalling and tumour suppression. It is stabilized at the plasma membrane by trans homophilic interactions upon cell-cell contact. PTPRK regulates cell-cell adhesion but is also reported to regulate numerous cancer-associated signalling pathways. However, the signalling mechanism of PTPRK remains to be determined. Here, we find that PTPRK regulates cell adhesion signalling, suppresses invasion and promotes collective, directed migration in colorectal cancer cells. In vivo, PTPRK supports recovery from inflammation-induced colitis. In addition, we confirm that PTPRK functions as a tumour suppressor in the mouse colon and in colorectal cancer xenografts. PTPRK regulates growth factor and adhesion signalling, and suppresses epithelial to mesenchymal transition (EMT). Contrary to the prevailing notion that PTPRK directly dephosphorylates EGFR, we find that PTPRK regulation of both EGFR and EMT is independent of its catalytic function. This suggests that additional adaptor and scaffold functions are important features of PTPRK signalling.

Robot-Assisted Pelvic Dissection for Enlarged Lymph Nodes in Melanoma Improves Recovery with Equivalent Oncological Outcomes to Open Pelvic Dissection.

BACKGROUND: Robot-assisted pelvic lymph node dissection (rPLND) has been reported in heterogenous groups of patients with melanoma, including macroscopic or at-high-risk-for microscopic metastasis. With changing indications for surgery in melanoma, and availability of effective systemic therapies, pelvic dissection is now performed for clinically detected bulky lymph node metastasis followed by adjuvant drug therapy. rPLND has not been compared with open pelvic lymph node dissection (oPLND) for modern practice. METHODS: All patients undergoing pelvic node dissection for macroscopic melanoma at a single institution were reviewed as a cohort, observational study. RESULTS: Twenty-two pelvic lymph node dissections were identified (8 oPLND; 14 rPLND). The number of pelvic lymph nodes removed was similar (median oPLND 6.5 (interquartile range [IQR] 6.0-12.5] versus rPLND 6.0 [3.75-9.0]), with frequent matted nodes (11/22, 50.0%). Operative time (median oPLND 130 min [IQR 95.5-182] versus rPLND 126 min [IQR 97.8-160]) and complications (Clavien-Dindo scale) were similar. Length of hospital stay (median 5.34 days (IQR 3.77-6.94) versus 1.98 days (IQR 1.39-3.50) and time to postoperative adjuvant therapy (median 11.6 weeks [IQR 10.6-18.5] versus 7.71 weeks [IQR 6.29-10.4]) were shorter in the rPLND group. No differences in pelvic lymph node recurrence (p = 0.984), distant metastatic recurrence (p = 0.678), or melanoma-specific survival (p = 0.655) were seen (median follow-up 21.1 months [rPLND] and 25.7 months [oPLND]). CONCLUSIONS: rPLND is an effective way to remove bulky pelvic lymph nodes in melanoma, with a shorter recovery and reduced interval to initiating adjuvant therapy compared with oPLND. This group of patients may especially benefit from neoadjuvant systemic approaches to management.

Adult Day Services for People With Intellectual and Developmental Disabilities: A Scoping Review.

BACKGROUND: Adult day services (ADS) are therapeutic, social, and health-related activities that keep people in their homes, rather than institutional settings. While there is a growing body of literature on ADS for older adults, there is far less information available about ADS for younger adults with intellectual and/or developmental disabilities (IDDs). METHOD: Researchers conducted a scoping review of 6 databases (892 total articles). RESULTS: After applying inclusion and exclusion criteria, 74 full articles were reviewed, with 10 articles meeting study requirements. The research team found the literature is limited to simple descriptive reports or interventions that use ADS as a platform. CONCLUSIONS: Simply put, we know very little about the services provided to younger adults with IDD in ADS. Implications for future research are discussed, including the need to catalog the services offered in ADS for younger adults with IDD and to evaluate their impact on participant well-being.

A Qualitative Examination of a Reminiscence Intervention for Older Adults Using Three-Dimensional (3D) Printed Objects.

Reminiscence has been found to be an effective therapy for older adults and researchers and practitioners have identified a range of benefits, from cognitive stimulation to the reconciliation of past experiences. In this qualitative study, the authors explore the experiences of older adults engaged in a technology-enhanced form of reminiscence therapy (RT) using three-dimensional (3D) printed objects from peoples' past. Content analysis of individual interviews with seven participants (n = 7) revealed three themes: (1) positive experiences with the RT intervention; (2) reflections on the use of 3D printed objects; and (3) the development of relationships between participants and researchers. These findings suggest that RT using 3D printed objects can be effective, but only if objects are accurate and if it suits participants' personalities. Researchers and practitioners may find that the use of 3D printed objects can enhance their RT interventions and thereby enrich the lives of older adults.

Dysregulation of extracellular matrix and Lysyl Oxidase in Ehlers-Danlos syndrome type IV skin fibroblasts.

BACKGROUND: Ehlers-Danlos syndrome Type IV (aka Vascular Ehlers Danlos, or vEDS) is a dominantly inherited mutation in the Collagen 3A1 gene (COL3A1). The disease is characterized by tissue friability and age-related susceptibility to arterial aneurysm, dissection and rupture as well as uterine and bowl tears. These clinical manifestations result in major surgical intervention and decreased life expectancy. Understanding how mutations in COL3A1 impact the structure and function of the extracellular matrix (ECM) is important to managing the disease and finding treatments. RESULTS: Skin fibroblasts from vEDS subjects heterozygous for the p.G588S pathogenic variant in the COL3A1 gene and a normal individual were cultured and studied. Proteomics analysis identified dozens of upregulated proteins related to extracellular matrix dysregulation that is characteristic of fibrosis. Gene expression libraries from cultured primary fibroblasts were screened for messenger RNA (mRNA) markers of ECM degradation. The proteomics and targeted gene expression array results were largely consistent with dysregulation of the extracellular matrix in vEDS. The data show upregulation of multiple Collagen proteins and genes, other ECM components, and enzymes related to ECM processing and turn-over. vEDS fibroblasts expressed significantly more cross linked C-Telopeptide of Collagen III (CTXIII) than normal fibroblasts, indicative of Collagen III degradation and turn-over. Further, the expression and activity of Lysyl Oxidase (LOX), an enzyme that initiates covalent cross-linking of soluble collagen and elastin into protease resistant fibers, is elevated in vEDS fibroblasts compared to normal fibroblasts. CONCLUSION: Together, these findings suggest dysregulated ECM deposition and processing, reminiscent of a state of fibrosis. Therapeutics that target the dysregulated ECM proteins or help replace damaged tissue may improve clinical outcomes.

Healthy Aging and Older Adults with Autism: A Scoping Review.

BACKGROUND AND OBJECTIVES: Autism Spectrum Disorder (ASD) is a lifelong diagnosis. While several studies have examined the effects of autism throughout childhood, few have considered older adulthood and the difference between the allistic (i.e., persons who are not autistic) population and autistic older adults. In literature regarding healthy aging, there is sparse evidence regarding the intersections of older adulthood and autism. The purpose of this scoping review was to examine the state of literature regarding autistic older adults and the domains of healthy aging, utilizing the framework conceived by Arksey and O'Malley (2005). RESEARCH DESIGN AND METHODS: To identify the research question, we took the following steps: identify the relevant studies; select studies; chart the data; and collate, summarize, and report the results. The specific domains of healthy aging considered include physical health, mobility, mental health, cognition and memory, and social connectedness. RESULTS: A total of 35 articles were selected for final review. Fifty-seven percent of these studies considered only one domain of healthy aging, 23% studied two domains, while 14% measured three domains and 6% assessed four domains. No study considered all five domains. Of the five domains considered for this scoping review, mental health and cognition and memory were the most represented domains in the studies. DISCUSSION AND IMPLICATIONS: Overall, healthy aging among autistic older adults is largely understudied. More research is needed to better identify and tailor interventions and services for autistic older adults and their families to support healthy aging.

Qualitative Analysis of Implementation Factors of an Embedded Caregiver Support Intervention into Adult Day Services.

Background: Adult day services (ADS) are an important and often underutilized support resource for older adults. For persons living with dementia (PLWD), ADS is an optimal access point to not only receive therapeutic and rehabilitative activities, but as a vehicle for respite/relief for dementia caregivers. Yet, there is currently a lack of research on integrating caregiver interventions into home and community-based services such as ADS. Objective: This paper reports on qualitative findings from the Improving Outcomes for Family Caregivers of Older Adults with Complex Conditions: The Adult Day Plus (ADS Plus) Program Trial. Methods: Drawing from semi-structured interviews conducted with family caregivers and ADS site staff, we conducted a thematic analysis to examine the implementation process of ADS Plus. Results: Themes address the relational nature of the intervention, learning, influence of the administrative infrastructure, and receptivity of ADS Plus. Conclusions: Our analysis determined that implementation of ADS Plus was feasible and accepted by site staff and dementia caregivers but also calls for additional evaluation of embedded caregiver support interventions across different contexts (e.g., staff size, limited technology environments) to further identify and test implementation mechanisms across settings.