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.     

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.     

Racial matching and adolescent self-disclosure of substance use and mental health symptoms

Obtaining accurate assessment data from adolescents in treatment aids clinical decision making and facilitates more accurate outcome evaluations. However, findings could be biased due to underreported substance use and mental health symptoms. This article compares self-reports of youth in non-White matched client–assessor dyads and those in nonmatched dyads. There were no differences on self-reported substance use, but matched youth reported significantly fewer attention deficit/hyperactivity disorder symptoms versus the comparison group. One possible reason for these findings is the effect of in-group stereotype threat. Future studies should examine the potential effect that in-group stereotyping and perceived racism have on the therapeutic relationship.     

Serological Responses of Raccoons and Striped Skunks to Ontario Rabies Vaccine Bait in West Virginia during 2012–2016

Since the 1990s, oral rabies vaccination (ORV) has been used successfully to halt the westward spread of the raccoon rabies virus (RV) variant from the eastern continental USA. Elimination of raccoon RV from the eastern USA has proven challenging across targeted raccoon (Procyon lotor) and striped skunk (Mephitis mephitis) populations impacted by raccoon RV. Field trial evaluations of the Ontario Rabies Vaccine Bait (ONRAB) were initiated to expand ORV products available to meet the rabies management goal of raccoon RV elimination. This study describes the continuation of a 2011 trial in West Virginia. Our objective was to evaluate raccoon and skunk response to ORV occurring in West Virginia for an additional two years (2012–2013) at 75 baits/km² followed by three years (2014–2016) of evaluation at 300 baits/km². We measured the change in rabies virus-neutralizing antibody (RVNA) seroprevalence in targeted wildlife populations by comparing levels pre- and post-ORV during each year of study. The increase in bait density from 75/km² to 300/km² corresponded to an increase in average post-ORV seroprevalence for raccoon and skunk populations. Raccoon population RVNA levels increased from 53% (300/565, 95% CI: 50–57%) to 82.0% (596/727, 95% CI: 79–85%) during this study, and skunk population RVNA levels increased from 11% (8/72, 95% CI: 6–20%) to 39% (51/130, 95% CI: 31–48%). The RVNA seroprevalence pre-ORV demonstrated an increasing trend across study years for both bait densities and species, indicating that multiple years of ORV may be necessary to achieve and maintain RVNA seroprevalence in target wildlife populations for the control and elimination of raccoon RV in the eastern USA.     

Central nervous system and peripheral cell labeling by vascular endothelial cadherin-driven lineage tracing in adult mice

Understanding the contribution of endothelial cells to the progenitor pools of adult tissues has the potential to inform therapies for human disease.To address whether endothelial cells transdifferentiate into non-vascular cell types,we performed cell lineage tracing analysis using transgenic mice engineered to express a fluorescent marker following activation by tamoxifen in vascular endothelial cadherin promoter-expressing cells(VEcad-CreERT2;B6 Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze).Activation of target-cell labeling following 1.5 months of ad libitum feeding with tamoxifen-laden chow in 4–5 month-old mice resulted in the tracing of central nervous system and peripheral cells that include:cerebellar granule neurons,ependymal cells,skeletal myocytes,pancreatic beta cells,pancreatic acinar cells,tubular cells in the renal cortex,duodenal crypt cells,ileal crypt cells,and hair follicle stem cells.As Nestin expression has been reported in a subset of endothelial cells,Nes-CreERT2 mice were also utilized in these conditions.The tracing of cells in adult Nes-CreERT2 mice revealed the labeling of canonical progeny cell types such as hippocampal and olfactory granule neurons as well as ependymal cells.Interestingly,Nestin tracing also labeled skeletal myocytes,ileal crypt cells,and sparsely marked cerebellar granule neurons.Our findings provide support for endothelial cells as active contributors to adult tissue progenitor pools.This information could be of particular significance for the intravenous delivery of therapeutics to downstream endothelial-derived cellular targets.The animal experiments were approved by the Boise State University Institute Animal Care and Use Committee(approval No.006-AC15-018)on October 31,2018.