Mesenchymal neoplasms with NTRK and other kinase gene alterations

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.     

Comparison of multiple methods of assessing parental emotion language discourse and their effects on Preschooler’s emotion understanding

The current study explored the influence of three methods of parental emotion discourse (structured story-telling, reminiscing, and picture book) and their relation to preschoolers’ emotion understanding. Thirty-seven families participated in the study. Analyses showed that the structured story-telling method produced more emotion words, was high in unique emotion words, and was high for both emotion labelling and explanations. All three methods showed some potential to predict preschooler’s emotion understanding. Structured story-telling was best at predicting role-taking, while reminiscing and the picture book both were better at predicting situation knowledge. Additional studies are needed to further explore the influence of different methods of assessing emotion discourse to enhance validity and reliability of research in this field.     

Nidogen 1 regulates proliferation and migration/invasion in murine claudin-low mammary tumor cells

Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.     

A Tool to Assess Patient and Surrogate Knowledge About the POLST (Physician Orders for Life-Sustaining Treatment) Program

ContextIt is especially important that patients are well informed when making high-stakes, preference-sensitive decisions like those on the Physician Orders for Life-Sustaining Treatment (POLST) form. However, there is currently no way to easily evaluate whether patients understand key concepts when making these important decisions.ObjectivesTo develop a POLST knowledge survey.MethodsExpert (n = 62) ratings of key POLST facts were used to select items for a POLST knowledge survey. The survey was administered to nursing facility residents (n = 97) and surrogate decision-makers (n = 112). A subset (n = 135) were re-administered the survey after a standardized advance care planning discussion to assess the scale's responsiveness to change.ResultsThe 19-item survey demonstrated adequate reliability (α = 0.72.). Residents' scores (x = 11.4, standard deviation 3.3) were significantly lower than surrogate scores (x = 14.7, standard deviation 2.5) (P < 0.001). Scores for both groups increased significantly after administration of a standardized advance care planning discussion (P < 0.001). Although being a surrogate, age, race, education, cognitive functioning, and health literacy were significantly associated with higher POLST Knowledge Survey scores in univariate analyses, only being a surrogate (P < 0.001) and being white (P = 0.028) remained significantly associated with higher scores in multivariate analyses.ConclusionThe 19-item POLST Knowledge Survey demonstrated adequate reliability and responsiveness to change. Findings suggest the survey could be used to identify knowledge deficits and provide targeted education to ensure adequate understanding of key clinical decisions when completing POLST.     

An Evolutionary Perspective on Appearance Enhancement Behavior

Researchers have highlighted numerous sociocultural factors that have been shown to underpin human appearance enhancement practices, including the influence of peers, family, the media, and sexual objectification. Fewer scholars have approached appearance enhancement from an evolutionary perspective or considered how sociocultural factors interact with evolved psychology to produce appearance enhancement behavior. Following others, we argue that evidence from the field of evolutionary psychology can complement existing sociocultural models by yielding unique insight into the historical and cross-cultural ubiquity of competition over aspects of physical appearance to embody what is desired by potential mates. An evolutionary lens can help to make sense of reliable sex and individual differences that impact appearance enhancement, as well as the context-dependent nature of putative adaptations that function to increase physical attractiveness. In the current review, appearance enhancement is described as a self-promotion strategy used to enhance reproductive success by rendering oneself more attractive than rivals to mates, thereby increasing one’s mate value. The varied ways in which humans enhance their appearance are described, as well as the divergent tactics used by women and men to augment their appearance, which correspond to the preferences of opposite-sex mates in a heterosexual context. Evolutionarily relevant individual differences and contextual factors that vary predictably with appearance enhancement behavior are also discussed. The complementarity of sociocultural and evolutionary perspectives is emphasized and recommended avenues for future interdisciplinary research are provided for scholars interested in studying appearance enhancement behavior.

     

Yakima Valley Farm Workers Clinic oral health transformation project

The Yakima Valley Farm Workers Clinic (YVFWC) is one of the largest community health centers in the country with clinics throughout south-central Washington and northern Oregon. Its dental program consists of 14 dental clinics providing general and specialty services to the low-income populations it serves. Modeling itself after the YVFWC medical managed care program; the Dental program recently added value-based metrics to its dental practice after Oregon offered a value-based dental reimbursement plan in 2019. This is the first-step YVFWC's dental program that has taken to prepare for value-based reimbursement and transform its dental practice in order to reduce the disease burden in its patient population. The purpose of this article is to describe the processes YVFWC undertook to prepare itself for the new reimbursement model, which included the development of metrics, a metric validation process, a clinical dashboard, and a method for improving metrics. It also outlines its medical/dental integration improvement brought about by embedding hygienists into the medical primary care teams.     

Atypical cutaneous γδ T cell proliferation with morphologic features of lymphoma but with clinical features and course of PLEVA or lymphomatoid papulosis

Reactive lymphoid infiltrates of the skin composed predominantly of gamma‐delta (γδ) T cells are not well described in the literature. Herein we report a case of an otherwise healthy 4‐year‐old male who presented with a waxing and waning papular rash characterized by small, discrete crusted papules spread across his trunk, face and extremities. Clinical evaluation revealed no evidence of systemic disease. Microscopic examination revealed a dermal, perivascular infiltrate of highly atypical lymphocytes with a γδ T cell phenotype, worrisome for primary cutaneous γδ T cell lymphoma. The clinical course, however, was that of a reactive condition and prompted consideration of a diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP). In many ways, this case defies current classification schemes and seems to expand the spectrum of reactive γδ T cell infiltrates of the skin.