Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.     

Determinantes sociales de la salud de distintos niveles por género: educación y hogar en España

Objective

To explore from a gender perspective the association with subjective health of the interaction between education and household arrangements within the framework of social determinants of health placed at the micro and mezzo levels.

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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Cardiopulmonary exercise testing for personalized job reintegration after acute cardiovascular attacks: a pilot cross-sectional study

Background:Cardiovascular diseases (CVD), particularly the ischemic heart disease, are a growing public health issue. In addition, the return to work after an acute cardiovascular attack represents a complex challenge.Objectives:To evaluate utility and safety of cardiopulmonary exercise testing (CPET), particularly performed “on site”, to promote a return to work in line with the residual working capacity.Methods:Fifty-nine workers affected by a major cardiovascular event, aged 18-63 years, have been enrolled between 2015 and 2018. All the patients underwent a CPET in outpatient clinic. Eleven workers also underwent the “on site” CPET, recorded during their working activities.Results:Outpatient clinic CPET outcomes (i.e. normal, mild impairment or moderate/severe impairment of cardiopulmonary function) were associated with the subjective perception of workers’ health status after returning to work. The “on site” CPET was found to be safe and reliable to promote a personalized return to work of patients. In 7 out of 11 patients, the values of O₂ consumption (VO₂) during the working activity were higher than 40% of VO₂ max as obtained from laboratory CPET.Conclusions:This study provides evidence for safety and usefulness of “on site” CPET for a personalized statement of fitness for work. This may facilitate the job retention of patients characterized by a high risk of unnecessary job loss. The use of CPET represents a first step of energy expenditure evaluation associated with specific working tasks.Key words: Acute coronary syndrome, cardiopulmonary exercise testing, return to work     

Critical study of hair growth analysis with computer-assisted methods

BACKGROUND: Computer-assisted image analysis has been proposed for human hair growth studies. METHODS: The performances of Trichoscan, a commercially available automated system combining epiluminiscence microscopy with digital image analysis, developed for office-based hair growth measurements, have been evaluated comparatively on the same skin sites using standardized photographic equipment and calibrated processing for contrast-enhanced phototrichogram (CE-PTG) analysis. This reference method has been validated with scalp biopsies and histological examination of serial sectioning. RESULTS: Besides edge effects, hair fibres escaped the Trichoscan analysis for various reasons including, but not limited to, thickness, pigmentation, closeness and crossing. CONCLUSION: Most of these problems have been identified in the late 1980s and remain largely unsolved by the processing software that was evaluated in 2004. Therefore claims promoting the Trichoscan method for accurate hair measurements in clinical trials on scalp and body hair are not supported by the present investigation. The speed at which the analysis is performed is outweighed by the errors in signal detection. Therefore we suggest that improvements must be clearly documented before Trichoscan is established for quantified diagnostic purposes and detailed hair cycle monitoring during hair trials.