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BackgroundAlthough observational studies have already shown promising results of flourishing, a broader concept of health based on positive psychology, there is still a gap in the literature regarding studies that combine different topics of flourishing in a single intervention.ObjectivesTo develop a comprehensive and integrate intervention based on positive psychology gathering different topics of flourishing to improve mental health outcomes in individuals with depressive symptoms.MethodsThe following steps were performed: (1) a comprehensive literature review; (2) the designing of a 12-session group intervention based on the values, virtues, and topics of flourishing; (3) assessment of the rationale, coherence, and feasibility by a panel of healthcare professionals answering semi-structured questions, and (4) application of an e-Delphi technique including mental health experts to reach a consensus of at least 80% for each item of the protocol.ResultsA total of 25 experts participated in the study, 8 in the panel with semi-structured questions and 17 in the e-Delphi technique. A three-round e-Delphi technique was required to reach a consensus for all items. In the first round, a consensus was reached for 86.2% of the items. The remaining items (13.8%) were either excluded or reformulated. In the second round, a consensus was not obtained on one item, which was reformulated and approved in the third round. Qualitative analyses of the open questions were performed and suggestions for the protocol were considered. The final version of the intervention was composed of 12 weekly group sessions with 90-min each. The topics included in the intervention were physical and mental health, virtues and character strengths, love, gratitude, kindness, volunteering, happiness, social support, family, friends and community, forgiveness, compassion, resilience, spirituality, purpose and meaning of life, imagining the “best possible future,” and flourishing.ConclusionThe flourishing intervention was successfully developed using an e-Delphi technique. The intervention is ready to be tested in an experimental study to verify its feasibility and effectiveness.

Background: Several instruments that measure spirituality present overlaps with positive emotions, impacting the interpretation of their findings. In order to minimize these problems, we aimed to develop, assess the reliability and validate a new scale to evaluate spirituality.Methods: The instrument was designed using a theoretical framework minimizing tautological issues (i.e., Koenig’s framework), a qualitative study investigating the definitions of spirituality, the development of the first version of instrument by experts’ meetings and a qualitative cognitive debriefing. Then, the instrument was examined for its content validity by a multidisciplinary group of judges and was pilot-tested in two different groups – less religious (medical students – n = 85) and more religious (practicing religious members – n = 85). Finally, psychometric properties and validity were assessed.Results: The developed Attitudes Related to Spirituality Scale (ARES) is a self-report 11-item instrument using five-level Likert items. ARES presented appropriate psychometric properties revealing excellent internal consistency (alpha = 0.98) and temporal stability (ICC = 0.98). Likewise, ARES was strongly correlated with other validated R/S instruments (i.e., Duke Religion Index and Brief Multidimensional Measure of Religiousness/Spirituality) and was able to discriminate higher and lower religious groups. In the exploratory factor analysis, a unidimensional structure of the scale was described. Fit indices for the scale demonstrated good fit in the unidimensional model.Conclusion: The ARES is a reliable, valid and stable one-dimension instrument that is appropriate for use in the Portuguese-speaking population.Descriptors: Spirituality; Scale; Factorial Analysis; Instrument; Measure; Psychometrics.

The induction of autophagy, the catabolic pathway by which damaged or unnecessary cellular components are subjected to lysosome-mediated degradation and recycling, is impaired in Collagen VI (COL6) null mice and COL6-related myopathies. This autophagic impairment causes an accumulation of dysfunctional mitochondria, which in turn leads to myofiber degeneration. Our previous work showed that reactivation of autophagy in COL6-related myopathies is beneficial for muscle structure and function both in the animal model and in patients. Here we show that pterostilbene (Pt)—a non-toxic polyphenol, chemically similar to resveratrol but with a higher bioavailability and metabolic stability—strongly promotes in vivo autophagic flux in the skeletal muscle of both wild-type and COL6 null mice. Reactivation of autophagy in COL6-deficient muscles was also paralleled by several beneficial effects, including significantly decreased incidence of spontaneous apoptosis, recovery of ultrastructural defects and muscle remodeling. These findings point at Pt as an effective autophagy-inducing nutraceutical for skeletal muscle with great potential in counteracting the major pathogenic hallmarks of COL6-related myopathies, a valuable feature that may be also beneficial in other muscle pathologies characterized by defective regulation of the autophagic machinery.

The aim of this study is the analysis and characterization of a hydrolyzed keratin-based biomaterial and its processing using electrospinning technology to develop in vitro tissue models. This biomaterial, extracted from poultry feathers, was mixed with type A porcine gelatin and cross-linked with γ-glycidyloxy-propyl-trimethoxy-silane (GPTMS) to be casted initially in the form of film and characterized in terms of swelling, contact angle, mechanical properties, and surface charge density. After these chemical-physical characterizations, electrospun nanofibers structures were manufactured and their mechanical properties were evaluated. Finally, cell response was analyzed by testing the efficacy of keratin-based structures in sustaining cell vitality and proliferation over 4 days of human epithelial, rat neuronal and human primary skin fibroblast cells.

Collagen VI (ColVI) is an abundant and distinctive extracellular matrix protein secreted by fibroblasts in different tissues. Human diseases linked to mutations on ColVI genes are primarily affecting skeletal muscle due to non-cell autonomous myofiber defects. To date, it is not known whether and how fibroblast homeostasis is affected by ColVI deficiency, a critical missing information as this may strengthen the use of patients’ fibroblasts for preclinical purposes. Here, we established primary and immortalized fibroblast cultures from ColVI null (Col6a1-/-) mice, the animal model of ColVI-related diseases. We found that, under nutrient-stringent condition, lack of ColVI affects fibroblast survival, leading to increased apoptosis. Moreover, Col6a1-/- fibroblasts display defects in the autophagy/lysosome machinery, with impaired clearance of autophagosomes and failure of Parkin-dependent mitophagy. Col6a1-/- fibroblasts also show an increased activation of the Akt/mTOR pathway, compatible with the autophagy impairment, and adhesion onto purified ColVI elicits a major effect on the autophagic flux. Our findings reveal that ColVI ablation in fibroblasts impacts on autophagy regulation and cell survival, thus pointing at the new concept that this cell type may contribute to the pathological features of ColVI-related diseases.

Collagen VI is an extracellular matrix (ECM) protein playing a key role in skeletal muscles and whose deficiency leads to connective tissue diseases in humans and in animal models. However, most studies have been focused on skeletal muscle features. We performed an extensive proteomic profiling in two skeletal muscles (diaphragm and gastrocnemius) of wild-type and collagen VI null (Col6a1−/−) mice at different ages, from 6- (adult) to 12- (aged) month-old to 24 (old) month-old. While in wild-type animals the number of proteins and the level of modification occurring during aging were comparable in the two analyzed muscles, Col6a1−/− mice displayed a number of muscle-type specific variations. In particular, gastrocnemius displayed a limited number of dysregulated proteins in adult mice, while in aged muscles the modifications were more pronounced in terms of number and level. In diaphragm, the differences displayed by 6-month-old Col6a1−/− mice were more pronounced compared to wild-type mice and persisted at 12 months of age. In adult Col6a1−/− mice, the major variations were found in the enzymes belonging to the glycolytic pathway and the tricarboxylic acid (TCA) cycle, as well as in autophagy-related proteins. When compared to wild-type animals Col6a1−/− mice displayed a general metabolic rewiring which was particularly prominent the diaphragm at 6 months of age. Comparison of the proteomic features and the molecular analysis of metabolic and autophagic pathways in adult and aged Col6a1−/− diaphragm indicated that the effects of aging, culminating in lipotoxicity and autophagic impairment, were already present at 6 months of age. Conversely, the effects of aging in Col6a1−/− gastrocnemius were similar but delayed becoming apparent at 12 months of age. A similar metabolic rewiring and autophagic impairment was found in the diaphragm of 24-month-old wild-type mice, confirming that fatty acid synthase (FASN) increment and decreased microtubule-associated proteins 1A/1B light chain 3B (LC3B) lipidation are hallmarks of the aging process. Altogether these data indicate that the diaphragm of Col6a1−/− animal model can be considered as a model of early skeletal muscle aging.

Mutations of genes encoding for collagen VI cause various muscle diseases in humans, including Bethlem myopathy and Ullrich congenital muscular dystrophy. Collagen VI null (Col6a1–/–) mice are affected by a myopathic phenotype with mitochondrial dysfunction, spontaneous apoptosis of muscle fibers and defective autophagy. Moreover, Col6a1–/– mice display impaired muscle regeneration and defective self-renewal of satellite cells after injury. Treatment with cyclosporin A (CsA) is effective in normalizing the mitochondrial, apoptotic and autophagic defects of myofibers in Col6a1–/– mice. A pilot clinical trial with CsA in Ullrich patients suggested that CsA may increase the number of regenerating myofibers. Here we report the effects of CsA administration at 5 mg/kg body weight every 12 hr in Col6a1–/– mice on muscle regeneration under physiological conditions and after cardiotoxin (CdTx)-induced muscle injury. Our findings indicate that CsA influences satellite cell activity and triggers the formation of regenerating fibers in Col6a1–/– mice. Data obtained on injured muscles show that under appropriate administration regimens CsA is able to stimulate myogenesis in Col6a1–/– mice by significantly increasing the number of myogenin (MyoG)-positive cells and of regenerating myofibers at the early stages of muscle regeneration. CsA is also able to ameliorate muscle regeneration of Col6a1–/– mice subjected to multiple CdTx injuries, with a concurrent maintenance of the satellite cell pool. Our data show that CsA is beneficial for muscle regeneration in Col6a1–/– mice.