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. 相似文献
It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing. 相似文献
ABSTRACTClose observation of the interactions between a traumatised mother and her infant son provides information on the modes of transmission of psychic trauma in the mother–infant dyad. Following the presentation of a current literature review on the theme, the subject of “radioactive residue” and counter-transference in the transmission of psychic trauma from mother to infant will be illustrated through a clinical case study that focuses on a Haitian mother and her two-year-old infant son who has been referred to a “transitional care nursery” in urban Paris. The encounter with this mother–infant dyad is analysed through observing the quality of the interactions that take place between the mother and infant in order to determine how a particularly traumatic narrative impacts the mother–infant relationship, in addition to relations with the clinician. Mother and infant respond to one another through the emission and reception of “radioactive residues” as hypothesized by Gampel. This clinical case study shows that there is a need to consider transcultural factors and collective experience and history when analysing traumatic events. Additionally, the case study shows that counter-transference can be an effective clinical tool for gaining access to an infant's experience as the recipient of a traumatic narrative. 相似文献
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.
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. 相似文献