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The purpose of this pilot study was to examine the effectiveness of a 6-week workplace mindfulness- and self-compassion-based intervention (MSCBI) on perceived stress, burnout, immune functioning (assessed with the biomarker Immunoglobulin A), self-compassion, and experiential avoidance compared to a Workplace Stress Management Intervention. Both interventions were contextual, i.e., they were carried out in the workplace setting and during working hours. We followed a randomised controlled trial study design. The total sample was composed of 24 employees of an automotive company. One-way analyses of covariance between groups revealed significant differences in post-intervention levels of perceived stress, salivary Immunoglobulin A (sIgA), emotional exhaustion, self-compassion, and experiential avoidance, after adjusting for pre-test scores. The results of this study have several implications. Firstly, it confirms that MSCBIs might be more effective than regular psychoeducational interventions for work-related stress and burnout treatment. Secondly, sIgA can be used to assess immune function state changes when MSCBIs are carried out. Furthermore, these results indicate that it is feasible to carry out MSCBIs within companies and during working hours, and that these interventions can help effectively manage stress and burnout associated with the work environment.

The mental health of university students is a public health concern, as psychopathology has significantly risen among this population. Mindfulness-based programs may support their mental health, though more research is needed. We used a two-armed pilot randomized controlled trial to study the feasibility, preliminary effectiveness, and potential mechanisms of a brief 6-week instructor-led mindfulness- and compassion-based program (MCBP for University Life) on perceived stress and psychological distress. Thirty undergraduate psychology students participated (15 in the intervention group, and 15 as wait-list controls). Those in the intervention arm engaged well with the course and formal at-home practice, attending at least five sessions and meditating between 4-6 days per week. Significant improvements in perceived stress, psychological distress, mindfulness skills, decentering, self-compassion, and experiential avoidance were found at the end of the intervention, while the wait-list group remained unchanged. There were significant differences between the two groups in those variables at post-test, favoring the intervention arm with major effects. Reductions in stress were mediated by improvements in mindfulness skills, decentering, and self-compassion; meanwhile reductions in psychological distress were mediated by improvements in decentering. These results suggest that this intervention might be feasible and effective for university students, but more high-quality research is needed.

The adipokine Neuregulin 4 (Nrg4) protects against obesity-induced insulin resistance. Here, we analyze how the downregulation of Nrg4 influences insulin action and the underlying mechanisms in adipocytes. Validated shRNA lentiviral vectors were used to generate scramble (Scr) and Nrg4 knockdown (KD) 3T3-L1 adipocytes. Adipogenesis was unaffected in Nrg4 KD adipocytes, but there was a complete impairment of the insulin-induced 2-deoxyglucose uptake, which was likely the result of reduced insulin receptor and Glut4 protein. Downregulation of Nrg4 enhanced the expression of proinflammatory cytokines. Anti-inflammatory agents recovered the insulin receptor, but not Glut4, content. Proteins enriched in Glut4 storage vesicles such as the insulin-responsive aminopeptidase (IRAP) and Syntaxin-6 as well as TBC1D4, a protein involved in the intracellular retention of Glut4 vesicles, also decreased by Nrg4 KD. Insulin failed to reduce autophagy in Nrg4 KD adipocytes, observed by a minor effect on mTOR phosphorylation, at the time that proteins involved in autophagy such as LC3-II, Rab11, and Clathrin were markedly upregulated. The lysosomal activity inhibitor bafilomycin A1 restored Glut4, IRAP, Syntaxin-6, and TBC1D4 content to those found in control adipocytes. Our study reveals that Nrg4 preserves the insulin responsiveness by preventing inflammation and, in turn, benefits the insulin regulation of autophagy.

D-amino acid oxidase (DAAO) is an enzyme that catalyzes the oxidation of D-amino acids generating H 2 O 2 . The enzymatic chimera formed by DAAO bound to the choline-binding domain of N-acetylmuramoyl-L-alanine amidase (CLytA) induces cytotoxicity in several pancreatic and colorectal carcinoma and glioblastoma cell models. In the current work, we determined whether the effect of CLytA-DAAO immobilized in magnetic nanoparticles, gold nanoparticles, and alginate capsules offered some advantages as compared to the free CLytA-DAAO. Results indicate that the immobilization of CLytA-DAAO in magnetic nanoparticles increases the stability of the enzyme, extending its time of action. Besides, we compared the effect induced by CLytA-DAAO with the direct addition of hydrogen peroxide, demonstrating that the progressive generation of reactive oxygen species by CLytA-DAAO is more effective in inducing cytotoxicity than the direct addition of H 2 O 2 . Furthermore, a pilot study has been initiated in biopsies obtained from pancreatic and colorectal carcinoma and glioblastoma patients to evaluate the expression of the main genes involved in resistance to CLytA-DAAO cytotoxicity. Based on our findings, we propose that CLytA-DAAO immobilized in magnetic nanoparticles could be effective in a high percentage of patients and, therefore, be used as an anti-cancer therapy for pancreatic and colorectal carcinoma and glioblastoma.

The combination of the choline binding domain of the amidase N-acetylmuramoyl-L-alanine (CLytA)-D-amino acid oxidase (DAAO) (CLytA-DAAO) and D-Alanine induces cell death in several pancreatic and colorectal carcinoma and glioblastoma cell lines. In glioblastoma cell lines, CLytA-DAAO-induced cell death was inhibited by a pan-caspase inhibitor, suggesting a classical apoptotic cell death. Meanwhile, the cell death induced in pancreatic and colon carcinoma cell lines is some type of programmed necrosis. In this article, we studied the mechanisms that trigger CLytA-DAAO-induced cell death in pancreatic and colorectal carcinoma and glioblastoma cell lines and we acquire a further insight into the necrotic cell death induced in pancreatic and colorectal carcinoma cell lines. We have analyzed the intracellular calcium mobilization, mitochondrial membrane potential, PARP-1 participation and AIF translocation. Although the mitochondrial membrane depolarization plays a crucial role, our results suggest that CLytA-DAAO-induced cell death is context dependent. We have previously detected pancreatic and colorectal carcinoma cell lines (Hs766T and HT-29, respectively) that were resistant to CLytA-DAAO-induced cell death. In this study, we have examined the putative mechanism underlying the resistance in these cell lines, evaluating both detoxification mechanisms and the inflammatory and survival responses. Overall, our results provide a better understanding on the cell death mechanism induced by CLytA-DAAO, a promising therapy against cancer.

Achievement emotions that the university student experiences in the learning process can be significant in facilitating or interfering with learning. The present research looked for linear and predictive relations between university students' achievement emotions, coping strategies, and engagement-burnout, in three different learning situations (classroom, study time, and testing). Hypotheses were identified for a possible model that would analyze the two facets of perfectionism based on these relations. In the case of perfectionistic strivings, the test hypothesis was that positive emotions would predispose the use of problem-focused coping strategies and an emotional state of engagement; in the case of perfectionistic concerns, however, negative emotions would predispose the use of emotion-focused strategies and a state of burnout. A total of 654 university students participated in the study, using an online tool to complete validated questionnaires on the three study variables. All students provided informed consent and corresponding permissions. Given the ex-post facto linear design, the predictions could be verified for each situation by means of logistic regression analyses and Structural Equations Models (SEM). Empirical results lent support, in varying degree, to the proposed theoretical relations. The testing situation was of particular interest. We discuss implications for perfectionism research and for the practice of prevention, education and health care in the university setting.

D-amino acid oxidase (DAAO) catalyzes the oxidation of D-amino acids generating hydrogen peroxide, a potential producer of reactive oxygen species. In this study, we used a CLytA-DAAO chimera, both free and bound to magnetic nanoparticles, against colon carcinoma, pancreatic adenocarcinoma, and glioblastoma cell lines. We found that the enzyme induces cell death in most of the cell lines tested and its efficiency increases significantly when it is immobilized in nanoparticles. We also tested this enzyme therapy in non-tumor cells, and we found that there is not cell death induction, or it is significantly lower than in tumor cells. The mechanism triggering cell death is apparently a classical apoptosis pathway in the glioblastoma cell lines, while in colon and pancreatic carcinoma cell lines, CLytA-DAAO-induced cell death is a necrosis. Our results constitute a proof of concept that an enzymatic therapy, based on magnetic nanoparticles-delivering CLytA-DAAO, could constitute a useful therapy against cancer and besides it could be used as an enhancer of other treatments such as epigenetic therapy, radiotherapy, and treatments based on DNA repair., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.