RESUMEN
BACKGROUND: Dermoscopy is known to increase the diagnostic accuracy of pigmented skin lesions (PSLs) when used by trained professionals. The effect of dermoscopy training on the diagnostic ability of dermal therapists (DTs) has not been studied so far. OBJECTIVES: This study aimed to investigate whether DTs, in comparison with general practitioners (GPs), benefited from a training programme including dermoscopy, in both their ability to differentiate between different forms of PSL and to assign the correct therapeutic strategy. METHODS: In total, 24 DTs and 96 GPs attended a training programme on PSLs. Diagnostic skills as well as therapeutic strategy were assessed, prior to the training (pretest) and after the training (post-test) using clinical images alone, as well as after the addition of dermatoscopic images (integrated post-test). Bayesian hypothesis testing was used to determine statistical significance of differences between pretest, post-test and integrated post-test scores. RESULTS: Both the DTs and the GPs demonstrated benefit from the training: at the integrated post-test, the median proportion of correctly diagnosed PSLs was 73% (range 30-90) for GPs and 63% (range 27-80) for DTs. A statistically significant difference between pretest results and integrated test results was seen, with a Bayes factor > 100. At 12 percentage points higher, the GPs outperformed DTs in the accuracy of detecting PSLs. CONCLUSIONS: The study shows that a training programme focusing on PSLs while including dermoscopy positively impacts detection of PSLs by DTs and GPs. This training programme could form an integral part of the training of DTs in screening procedures, although additional research is needed.
Asunto(s)
Competencia Clínica , Dermoscopía , Médicos Generales , Dermoscopía/educación , Dermoscopía/métodos , Humanos , Médicos Generales/educación , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/diagnóstico por imagen , Femenino , Masculino , Dermatólogos/educación , Dermatólogos/estadística & datos numéricos , Educación Médica Continua/métodos , AdultoRESUMEN
The development of lymphoid organs depends on cross talk between hematopoietic cells and mesenchymal stromal cells and on vascularization of the lymphoid primordia. These processes are orchestrated by cytokines, chemokines, and angiogenic factors that require tight spatiotemporal regulation. Heparan sulfate (HS) proteoglycans are molecules designed to specifically bind and regulate the bioactivity of soluble protein ligands. Their binding capacity and specificity are controlled by modification of the HS side chain by HS-modifying enzymes. Although HS proteoglycans have been implicated in the morphogenesis of several organ systems, their role in controlling lymphoid organ development has thus far remained unexplored. In this study, we report that modification of HS by the HS-modifying enzyme glucuronyl C5-epimerase (Glce), which controls HS chain flexibility, is required for proper lymphoid organ development. Glce(-/-) mice show a strongly reduced size of the fetal spleen as well as a spectrum of defects in thymus and lymph node development, ranging from dislocation to complete absence of the organ anlage. Once established, however, the Glce(-/-) primordia recruited lymphocytes and developed normal architectural features. Furthermore, Glce(-/-) lymph node anlagen transplanted into wild-type recipient mice allowed undisturbed lymphocyte maturation. Our results indicate that modification of HS by Glce is required for controlling the activity of molecules that are instructive for early lymphoid tissue morphogenesis but may be dispensable at later developmental stages and for lymphocyte maturation and differentiation.
Asunto(s)
Carbohidrato Epimerasas/inmunología , Proteoglicanos de Heparán Sulfato/metabolismo , Tejido Linfoide/embriología , Tejido Linfoide/enzimología , Organogénesis/inmunología , Animales , Carbohidrato Epimerasas/deficiencia , Separación Celular , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Proteoglicanos de Heparán Sulfato/inmunología , Ratones , Ratones NoqueadosRESUMEN
For the formation of lymph nodes and Peyer's patches, lymphoid tissue inducer (LTi) cells are crucial in triggering stromal cells to recruit and retain hematopoietic cells. Although LTi cells have been observed in fetal spleen, not much is known about fetal spleen development and the role of LTi cells in this process. Here, we show that LTi cells collect in a periarteriolar manner in fetal spleen at the periphery of the white pulp anlagen. Expression of the homeostatic chemokines can be detected in stromal and endothelial cells, suggesting that LTi cells are attracted by these chemokines. As lymphotoxin (LT)alpha1beta2 can be detected on B cells but not LTi cells in neonatal spleen, starting at 4 days after birth, the earliest formation of the white pulp in fetal spleen occurs in a LTalpha1beta2-independent manner. The postnatal development of the splenic white pulp, involving the influx of T cells, depends on LTalpha1beta2 expressed by B cells.
Asunto(s)
Heterotrímero de Linfotoxina alfa1 y beta2/metabolismo , Bazo/citología , Bazo/embriología , Animales , Animales Recién Nacidos , Humanos , Ratones , Ratones Endogámicos C57BL , Células del Estroma/citologíaRESUMEN
The recognition that lymphocytes existed in different varieties and that lymphoid organs were important for their differentiation greatly influenced immunological research. The growing awareness that started in the mid-fifties of the previous century has shifted the emphasis of immunology from a molecular, mostly serological science to the cell-oriented modern immunology of today. Matters such as hematopoietic differentiation, cell-cell interaction, cellular activation, as well as migratory behavior of hematopoietic cells received much attention and deepened our insight in the immune system. The relatively recent generation of mutant mice lacking lymphoid organs prompted the realization that the organogenesis of lymphoid organs could be dissected at the cellular and molecular level. Now we can distinguish several phases of development for lymphoid organs, and can assign molecules and cells to be essentially involved in these phases. Future research will identify additional molecules and cells required for the formation of the various lymphoid organs, because the picture is not complete yet.
Asunto(s)
Diferenciación Celular/inmunología , Tejido Linfoide/citología , Tejido Linfoide/embriología , Organogénesis/inmunología , Animales , Humanos , Ratones , Ratones MutantesRESUMEN
During murine embryogenesis, the formation of Peyer's patches (PPs) is initiated by CD45(+)CD4(+)CD3(-) lymphoid tissue inducers that trigger adhesion molecule expression and specific chemokine production from an organizing stromal cell population through ligation of the lymphotoxin-beta receptor. However, the steps involved in the development of lymph nodes (LNs) are less clear than those of PPs, and the characteristics of the organizing cells within the LN anlagen have yet to be documented. In this study, we show for the first time that the early anlage is bordered by an endothelial layer that retains a mixed lymphatic and blood vascular phenotype up to embryonic day 16.5. This in turn encompasses CD45(+)CD4(+)CD3(-) cells interspersed with ICAM-1/VCAM-1/mucosal addressin cell adhesion molecule-1, lymphotoxin-beta receptor-positive, chemokine-producing cells analogous to the organizing population previously observed in PPs. Moreover, these LN organizers also express the TNF family member, TRANCE. Lastly, we show that the ICAM-1/VCAM-1/mucosal addressin cell adhesion molecule-1 cells present in peripheral and mesenteric LN form two discrete populations expressing either intermediate or high levels of these adhesion molecules but that the former population is specifically reduced in PLN. These findings provide a possible explanation for the well-known differences in developmental requirements for nodes at peripheral or mesenteric locations.