Evidence has been presented that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) may provide a relatively simple way to identify apparently healthy insulin-resistant persons with increased cardiometabolic risk ( 1, 2 ). However, there is evidence that the actual values of the ratio that best identifi es such individuals will vary as a function of racial/ethnic background ( 3-7 ). More recently, it has also been shown that the most useful TG/ HDL-C cut-point to identify cardiometabolic risk is not the same in men and women ( 2 ). However, there is essentially no information as to whether age also modifi es the ability of the TG/HDL-C ratio to identify apparently healthy individuals with increased cardiometabolic risk. The primary goal of this analysis was to address this issue, and it is based on data obtained in an apparently healthy population of young men and women, mean age of 19 years. Second, since the diagnostic category of the metabolic syndrome (MetS) is commonly used to identify cardiometabolic risk in apparently healthy individuals ( 3, 8 ), our second goal was to compare these two approaches to identify insulin resistance (IR) and associated cardiometabolic risk in a population of young adults . In support of this effort is the recent observation that the plasma concentration ratio of TG/HDL-C was an independent determinant of arterial stiffness in adolescents and young adults ( 9 ). SUBJECTS AND METHODSThis study presents results obtained from an epidemiological study from which data of a different nature have been published previously ( 10 ).Abstract Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17-24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identifi ed as being IR. The MetS identifi ed fewer individuals as being IR, but their risk profi le was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profi le. The TG/HDL-C ratio identifi ed a somewhat greater number of "high risk" subjects, whereas the MetS found a group whose risk profi le was somewhat magnifi ed. These fi ndings suggest that the TG/ HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk.
BackgroundWhen mosquitoes infected with DENV are feeding, the proboscis must traverse the epidermis several times (“probing”) before reaching a blood vessel in the dermis. During this process, the salivary glands release the virus, which is likely to interact first with cells of the various epidermal and dermal layers, cells which could be physiologically relevant to DENV infection and replication in humans. However, important questions are whether more abundant non-hematopoietic cells such as fibroblasts become infected, and whether they play any role in antiviral innate immunity in the very early stages of infection, or even if they might be used by DENV as primary replication cells.Methodology/Principal FindingsFibroblasts freshly released from healthy skin and infected 12 hours after their isolation show a positive signal for DENV. In addition, when primary skin fibroblast cultures were established and subsequently infected, we showed DENV-2 antigen-positive intracellular signal at 24 hours and 48 hours post-infection. Moreover, the fibroblasts showed productive infection in a conventional plaque assay. The skin fibroblasts infected with DENV-2 underwent potent signaling through both TLR3 and RIG- 1, but not Mda5, triggering up-regulation of IFNβ, TNFα, defensin 5 (HB5) and β defensin 2 (HβD2). In addition, DENV infected fibroblasts showed increased nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3), but not interferon regulatory factor 7 (IRF7), when compared with mock-infected fibroblasts.Conclusions/SignificanceIn this work, we demonstrated the high susceptibility to DENV infection by primary fibroblasts from normal human skin, both in situ and in vitro. Our results suggest that these cells may contribute to the pro-inflammatory and anti-viral microenvironment in the early stages of interaction with DENV-2. Furthermore, the data suggest that fibroblast may also be used as a primary site of DENV replication and provide viral particles that may contribute to subsequent viral dissemination.
Summary Dendritic cells (DC) are often arranged in planar layers in tissues with high antigenic exposure, such as skin and mucosae. Providing an en face view, this arrangement optimizes in situ analysis regarding morphology (even of individual dendrites), topographic distribution (regular/clustered) and quantification. The few reports on human genital DC usually utilize single markers and conventional sections, restricting immunolabelling only to cell parts sectioned by the cut. To better assess DC in situ, we labelled epithelial sheets, prepared from fresh cervix biopsies, with antibodies to major histocompatibility complex (MHC)‐CII, CD1a and Langerin, revealing (with each of these markers) a dense DC network in a planar‐like, regular distribution. Using the hybrid capture system to detect the high‐risk mucotropic human papilloma virus (HPV) group, 16 positive and five negative women were studied and the results were compared between these groups. DC frequency per area was substantially reduced (to ≈ 50% for the three markers) in samples from all HPV‐infected patients compared with samples from controls. Unlike HPV– samples, Langerin+ DC in HPV+ cervix exhibited a highly accentuated dendritic appearance. We believe this to be the first study using these three DC‐restricted markers (Langerin, CD1a and MHC‐CII) in cervical epithelial sheets from high‐risk HPV+ donors and also the first study to demonstrate the morphological and quantitative changes triggered by high‐risk HPV infection. Cervical DC reduction in early, premalignant high‐risk HPV infection might represent viral subversion strategies interfering with efficient antigen handling by the immune system's peripheral sentinels, the DC, perhaps hampering appropriate recruitment and subsequent development of effector (cytotoxic) T cells.
Hypohidrotic Ectodermal Dysplasia (HED) is a genetic human disorder which affects structures of ectodermal origin. Although there are autosomal recessive and dominant forms, X-linked (XL) is the most frequent form of the disease. This XL-HED phenotype is associated with mutations in the gene encoding the transmembrane protein ectodysplasin-1 (EDA1), a member of the TNFα-related signaling pathway. The proteins from this pathway are involved in signal transduction from ectoderm to mesenchyme leading to the development of ectoderm-derived structures in the fetus such as hair, teeth, skin, nails, and eccrine sweat glands. The aim of this review was to update the main clinical characteristics of HED regarding to recent molecular advances in the comprehension of all the possible genes involved in this group of disorders since it is known that Eda-A1-Edar signaling has multiple roles in ectodermal organ development, regulating their initiation, morphogenesis, and differentiation steps. The knowledge of the biological mechanisms that generate HED is needed for both a better detection of possible cases and for the design of efficient prevention and treatment approaches.
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