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10 páginas, 4 figuras, 1 tabla. ; Primary aldosteronism (PA) is a disease characterized by high aldosterone levels caused by benign adrenal tumors being the most frequent cause of secondary hypertension. Aldosterone plays vital physiological roles through the mineralocorticoid receptor (MR) but in certain cell types, it can also activate the glucocorticoid (GC) receptor (GR). Both MR and GR are structurally and functionally related and belong to the same family of ligand-dependent transcription factors that recognize identical GC regulatory elements (GREs) on their target genes. GCs play key roles in skin pathophysiology acting through both GR and MR; however, the effects of aldosterone and the potential association of PA and skin disease were not previously addressed. Skin samples from PA revealed histopathological alterations relative to control subjects, featuring epidermal hyperplasia, impaired differentiation, and increased dermal infiltrates, correlating with increased NF-κB signaling and up-regulation of TNF-A and IL-6 cytokines. PA skin samples also showed significantly higher expression of MR, GR, and HSD11B2. In cultured keratinocytes, aldosterone treatment increased GRE transcriptional activity which was significantly inhibited by co-treatment with GR- and MR-antagonists. This study demonstrates that high levels of aldosterone in PA patients correlate with skin anomalies and inflammatory features associated with abnormal GR/MR activation in epidermal keratinocytes. ; This work was supported by grant SAF2014-59474-R (MINECO, Spanish Government). J. Boix and J. Bigas are recipients of FPI fellowships of MINECO. We thank COST ADMIRE BM-1301 and NURCAMEIN (SAF2015-71878-REDT) for support for dissemination. We thank Jose Nieto for assistance with histopathological work. We are indebted to the patients and healthcare professionals that collaborated in this study. ; Peer reviewed

Background: Paclitaxel is a microtubule-stabilizing chemotherapeutic agent. Despite its widespread use, it damages healthy tissues such as skin. The goal of this study was to prove that the real impact of paclitaxel-induced skin toxicity could be underestimated because the adverse events might appear asymptomatic. Methods: Gynecological cancer patients were recruited. Skin parameters measurements were taken after three and six paclitaxel cycles. Measurements were conducted using specific probes which measure hydration, transepidermal water loss (TEWL), sebum, elasticity and firmness, erythema, roughness, smoothness, skin thickness, and desquamation levels. Further, a 3D epidermis model was incubated with paclitaxel to analyze gene and protein expression of aquaporin 3, collagen type 1, elastin, and fibronectin. Results: Paclitaxel induced alterations in the skin parameters with no visible clinical manifestations. Gynecological cancer patients under paclitaxel treatment had a decrease in hydration, TEWL, sebum, elasticity, and thickness of the skin, while erythema, roughness, and desquamation were increased. The molecular markers, related to hydration and the support of the skin layers, and analyzed in the 3D epidermis model, were decreased. Conclusions: Results suggest that paclitaxel modifies gene and protein expression of skin-related molecular markers, and impairs different physical, physiological, and biomechanical properties of the skin of cancer patients at a subclinical level. ; This work was supported by the grants PID2020-114871RB-I00 (JC), European Regional Development Fund (FEDER), and Instituto de Salud Carlos III, PI20/01363 (JM), CIBERES (CB06/06/0027) from the Spanish Government, and by research grants from the Regional Government Prometeo 2017/023/UV (JC), from "Generalitat Valenciana". Funding entities did not contribute to the study design or data collection, analysis, and interpretation, or to the writing of the manuscript.

Cover -- Title page -- Copyright page -- Contents -- Acknowledgements -- Overture -- 1 -- 2 -- 3 -- 4 -- I A Time to Come without Past or Future -- 1 -- 2 -- 3 -- 4 -- 5 -- 6 -- II From Ontology to Technology -- 1 -- Illogical Technology -- 2 -- Automation, Alteration -- 3 -- From Ontology to Technology -- Coda -- III Juan Manuel Garrido Not the Universal, but the Unknown -- 1 -- Life as the Production of Knowledge -- 2 -- Carelessness of the Self -- 3 -- The Sharing of the Unknown -- IV Right Here in the Present -- 1 -- 2 -- 3 -- 4 -- 5 -- 6 -- V The Accident and the Season -- 1 -- 2 -- 3 -- 4 -- 5 -- VI Jean-Christophe Bailly Havâ / Zamân -- VII The Fragile Skin of the World -- 1 -- 2 -- 3 -- 4 -- 5 -- 6 -- VIII Taking on Board (Of the World and of Singularity) -- Notes -- Overture -- I A Time to Come without Past or Future -- II From Ontology to Technology -- III Juan Manuel Garrido: Not the Universal, but the Unknown -- IV Right Here in the Present -- V The Accident and the Season -- VI Jean-Christophe Bailly: Havâ / Zamân -- VII The Fragile Skin of the World -- VIII Taking on Board (Of the World and of Singularity) -- EULA.

The goal of this work is to report the main dermatological alterations occurring during pregnancy and actual cosmetic protocols available and recommended for safe use. Throughout pregnancy, woman's body undergoes many transformations such as hormonal changes and weight gain. These alterations can result in undesirable skin aspects that end up affecting the future mother's life. The main complaints of pregnant women involve melasma advent, varicose veins, edema, and natural skin aging. Even if most of the time is recommended to wait for the birth to use cosmetics, there are some alternatives to prevent and to treat these alterations during pregnancy. For all these cases, there is a need to update information about safety and efficacy of new actives and technologies in cosmetic products. The purpose of this study was to conduct a literature review about the main skin alterations during pregnancy and actual recommended treatments, according to the current legislation.

Athletes and certain occupations (e.g., military, firefighters) must navigate unique heat challenges as they perform physical tasks during prolonged heat stress, at times while wearing protective clothing that hinders heat dissipation. Such environments and activities elicit physiological adjustments that prioritize thermoregulatory skin perfusion at the expense of arterial blood pressure and may result in decreases in cerebral blood flow. High levels of skin blood flow combined with an upright body position augment venous pooling and transcapillary fluid shifts in the lower extremities. Combined with sweat-driven reductions in plasma volume, these cardiovascular alterations result in levels of cardiac output that do not meet requirements for brain blood flow, which can lead to orthostatic intolerance and occasionally syncope. Skin surface cooling countermeasures appear to be a promising means of improving orthostatic tolerance via autonomic mechanisms. Increases in transduction of sympathetic activity into vascular resistance, and an increased baroreflex set-point have been shown to be induced by surface cooling implemented after passive heating and other arterial pressure challenges. Considering the further contribution of exercise thermogenesis to orthostatic intolerance risk, our goal in this review is to provide an overview of post-exercise cooling strategies as they are capable of improving autonomic control of the circulation to optimize orthostatic tolerance. We aim to synthesize both basic and applied physiology knowledge available regarding real-world application of cooling strategies to reduce the likelihood of experiencing symptomatic orthostatic intolerance after exercise in the heat.

Allergic skin diseases caused by low molecular weight chemical compounds are a major health concern among the general population, especially in certain occupational groups. To limit exposure to such compounds, it is important that thorough risk assessments are performed before products reach the consumer market. Traditionally, such risk assessments have been based on animal tests, but due to several factors, including legislations and ethical concerns, the use of animal testing has become increasingly unjustifiable. In this context, one focus in predictive toxicology has been the development of alternative methods to replace animal experiments. Although several alternative methods have been validated for regulatory decision making, they lack certain endpoints for complete risk assessments, and molecular mechanisms underlying skin sensitization are still not entirely understood. The work described in this thesis aims at increasing our knowledge about the mechanisms in dendritic cell activation in response to skin sensitizers and to further develop a dendritic cell-based in vitro assay.In Paper I, we investigated the microRNA regulation in response to stimulation of a DC model with structurally similar rubber sensitizers. The changes triggered by the rubber sensitizers in both mRNA and microRNA expression suggest a chemical-specific regulation, despite the structural similarity of the rubber sensitizers. In Paper II, the skin sensitizing properties of herbicidal formulations are investigated. Here, we predicted the herbicide glyphosate as a non-sensitizer, while the co-formulant polyethylated tallow amine and two glyphosate-based formulations were predicted as sensitizers. Additionally, we also investigated the proteomic alterations in response to these chemicals and formulations, and identified cellular responses associated with the differentially expressed proteins. In the last two papers, Paper III and Paper IV, we present additional applications for the in vitro assay setup used in this thesis. In Paper III, we identified a biomarker signature for the prediction of skin sensitizer potency, demonstrating a balanced accuracy of 78% targeting three potency classes, i.e., 1A (strong sensitizers), 1B (weak sensitizers) and no cat (non-sensitizers). In Paper IV, we applied a statistical method, the conformal prediction framework, to investigate the predictive boundaries of the in vitro assay, and concluded, based on 70 chemicals, that the assay can be applied to a large chemical space.In conclusion, the work presented here can contribute to a better understanding of the mechanisms underlying the immunological response to skin sensitizing chemicals, which together with state-of-the-art predictive assays could be used for improved risk assessment of chemical compounds and to develop tools for prevention and treatment of allergic skin diseases.

AbstractIn Colombia, glyphosate (GP) is used to control weeds, with Roundup Active® being the most widely used. This use has affected aquatic ecosystems, causing malformations in amphibians. The Savannah frog (D. molitor) is a tropical frog inhabiting the mountain of Colombia. In the present study, we determined the effect of sublethal concentrations of GP (Roundup Active®) on the skin of D. molitor. Twenty-four tadpoles were exposed to concentrations of GP (T1: 0, T2: 1.4, T3: 3.6, and T4: 5.6 a.e mg/L) during 31 days. In 10 individuals per treatment, two skin regions were evaluated: dorsal cranial and caudal ventral to determine histopathological alterations. Morphometric analysis of the layers of the skin was performed: epidermis, dermis, and hypodermis-muscular. T1 did not present histopathological alterations. Since T2 was identified, glandular cell hyperplasia and hypertrophy increased melanophores and melanin accumulations in the highest concentrations of GP. The ultrastructure revealed an increase in excretory glands in the dermis. In the other layers, an increase of melanophores and melanocyte clusters was observed accompanied by vacuolization of basal cells. The morphometry showed an increase in the thickness of the dermis in the dorso-cranial region in T2 compared to the other treatments, while the ventral caudal region exhibited a variation in the thickness of the dermis from T2 and a decrease in T4. Despite evaluating sublethal concentrations, the skin of D. molitor tadpoles presents histopathological, ultrastructural, and morphometric alterations that could affect the survival of the species in the natural environment.

Surfactant-based skin care products can induce minimal to severer alterations of the human stratum corneum (SC). These changes can be conveniently assessed using electrometric devices. Four different surfactant-based solutions were applied to the forearms of 10 healthy volunteers following a soap chamber test method. The 2-day patch testing was followed by a 2-week follow-up. Clinical and instrumental assessments were performed at 7 time points. Data generated by the Corneometer^® CM820, the Dermalab Moisture Module^® and the Nova Dermal Phase Meter^® (DPM) 9003 were compared. The significant differences between the product aggressiveness to the SC were similarly disclosed by the Corneometer and the Dermalab Moisture Module. The ranking of product aggressiveness given by the 3 devices 5 days after patch removal was similar to that given by the clinical assessment of erythema. A high level of correlation was found between the values yielded by the immediate and continuous mode assessments using the Dermalab Moisture Module with the pin probe, while the correlation was weaker with the Nova DPM. This finding may be related to the fact that the Nova DPM is influenced by the accumulation of the transepidermal water loss in the continuous mode assessment while there is no significant occlusion effect of the Dermalab Moisture pin probe that is more representative of the initial level of SC hydration. In conclusion, the Corneometer and the Dermalab Moisture Module respond similarly to changes in the SC content. This finding is different from some previous reports.

Forensic science transforms criminal investigations by resolving previously unsolvable cases and bringing an increased sense of justice to communities. This application of scientific disciplines to legal questions aids investigators in solving crimes. While many sciences can be utilized—such as physics (pattern evidence), chemistry (toxicology), or biology (cause of death), to name a few—two aspects of scientific advancement have played an outsized role in responding to crime. Trace evidence analysis—specifically, deoxyribonucleic acid (DNA) analysis—is an essential component to an effective and accurate criminal justice system. DNA evidence has emerged as a powerful tool to identify perpetrators of unspeakable crimes and to exonerate innocent individuals accused of similarly heinous actions. However, a different method of examining traditional trace evidence has quietly grown somewhat unnoticed. The emergence of so-called "touch-DNA" evidence and chemical analysis of skin traces represents powerful, novel uses of trace evidence that have significant implications for personal privacy. Furthermore, these abilities are developing within an outdated DNA jurisprudence that is wholly inadequate to protect individual privacy and facilitate the legitimate government interest in accurately investigating crime. Just as beeper and antiquated cellphone jurisprudence was an inadequate framework for the issues arising from smartphones or GPS tracking, DNA jurisprudence has failed to keep pace with modern uses of DNA. This article addresses touch DNA, chemical analysis of skin traces, and their implications for crime scene investigation, arguing that changes in how trace evidence is analyzed require alterations in the law's approach to its use. Discussing the history of traditional DNA analysis, the article also examines the emergence of touch DNA and related technologies and how they differ from traditional DNA analysis. It analyzes new risks of these new technologies, specifically to suspects and victims of crime. Finally, it proposes a legal framework to address these privacy threats - drawing a distinction between the collection of DNA and cellular materials for identification purposes and a subsequent examination of these materials for other information about the source. The framework adopted by the Supreme Court for cell phone examination in Riley v. California, required a more specific level of suspicion to examine the contents of a cell phone than to obtain it incident to arrest. This article advocates utilizing this framework in the collection and examination of the even more personal information contained within DNA and cellular evidence. Specifically, it distinguishes between collecting the evidence and routinely testing it for identity and the more invasive examination of the evidence for additional personal information about the source. Before searching this deeply into this evidence for any information beyond identification, the government must establish a higher level of suspicion and obtain a warrant.