Substrate Stiffness Modulates Gene Expression and Phenotype in Neonatal Cardiomyocytes In Vitro

Biomaterials to be used as cell delivery systems for cardiac tissue engineering should be able to comply with cardiac muscle contractile activity, while favoring cell survival and neo-angiogenesis in a hostile environment. Biocompatible synthetic materials can be tailored to mimic cardiac tissue three-dimensional organization in the micro- and nanoscales. Nonetheless, they usually display mechanical properties that are far from those of the native myocardium and thus could affect host cell survival and activity. In the present investigation, inert poly-ɛ-caprolactone planar layers were manufactured to change the surface stiffness (with Young's modulus ranging from 1 to 133 MPa) without changing matrix chemistry. These substrates were challenged with neonatal murine cardiomyocytes to study the possible effect of substrate stiffness on such cell behavior without changing biological cues. Interestingly, softer substrates (0.91±0.08 and 1.53±0.16 MPa) were found to harbor mostly mature cardiomyocytes having assembled sarcomeres, as shown by the expression of alpha actinin and myosin heavy chain in typical striations and the upregulation of sarcomeric actin mRNA. On the other hand, a preferential expression of immature cardiac cell genes (Nkx-2.5) and proteins (GATA-4) in cardiac cells grown onto stiffer materials (49.67±2.56 and 133.23±8.67 MPa) was detected. This result could not be ascribed to significant differences in cell adhesion or proliferation induced by the substrates, but to the stabilization of cardiomyocyte differentiated phenotype induced by softer layers. In fact, cardiac cell electromechanical coupling was shown to be more organized on softer surfaces, as highlighted by connexin 43 distribution. Moreover, a differential regulation of genes involved in extracellular matrix remodeling was detected on soft films (0.91±0.08 MPa) as compared with the stiffest (133.23±8.67 MPa). Finally, the upregulation of a number of genes involved in inflammatory processes was detected when the stiffest polymer is used. These events highlight the differences in cell mechanosensitivity in a heterogeneous cell preparation and are likely to contribute to the differences encountered in cardiac cell phenotype induced by substrate stiffness.Peer reviewe

Clinical utility of the Diagnostic Criteria for Psychosomatic Research for a comprehensive assessment of the elderly

INTRODUCTION: According to the revised version of the Diagnostic Criteria for Psychosomatic Research (DCPR-R), this study explored the prevalence and clinical correlates of DCPR-R psychosomatic syndromes in the elderly and tested whether DCPR-R provide an incremental contribution to the prediction of psychosocial functioning over and above DSM-5. METHOD: One hundred seven elderly subjects were recruited. Participants received a clinical assessment, which included the DCPR-Revised Semi-Structured Interview (DCPR-R SSI), the Structured Clinical Interview for DSM-5-Clinician Version (SCID-5-CV), the Psychological Well-Being (PWB) Scales, the Geriatric Anxiety Scale (GAS) and the Geriatric Depression Scale (GDS). Analyses of covariance (ANCOVA) and hierarchical regression analyses were run. RESULTS: Twenty-two (20.6%) subjects had at least one DSM-5 diagnosis, and 62 (57.9%) reported at least one DCPR-R diagnosis. Subjects with at least one DCPR-R diagnosis showed lower PWB Personal Growth and PWB Purpose in Life than those without DCPR-R diagnoses. When the incremental validity of the DCPR-R was tested using PWB Personal Growth, PWB Purpose in Life, PWB Self-acceptance, GAS Cognitive symptoms and GAS affective symptoms subscales as criterion variable, the DCPR-R increased up to 0.135-0.263 the explained variance. CONCLUSION: The DCPR-R might be implemented together with the DSM-5 to have a comprehensive assessment of elderly subjects

Clinical utility of the Diagnostic Criteria for Psychosomatic Research for a comprehensive assessment of the elderly

INTRODUCTION: According to the revised version of the Diagnostic Criteria for Psychosomatic Research (DCPR-R), this study explored the prevalence and clinical correlates of DCPR-R psychosomatic syndromes in the elderly and tested whether DCPR-R provide an incremental contribution to the prediction of psychosocial functioning over and above DSM-5. METHOD: One hundred seven elderly subjects were recruited. Participants received a clinical assessment, which included the DCPR-Revised Semi-Structured Interview (DCPR-R SSI), the Structured Clinical Interview for DSM-5-Clinician Version (SCID-5-CV), the Psychological Well-Being (PWB) Scales, the Geriatric Anxiety Scale (GAS) and the Geriatric Depression Scale (GDS). Analyses of covariance (ANCOVA) and hierarchical regression analyses were run. RESULTS: Twenty-two (20.6%) subjects had at least one DSM-5 diagnosis, and 62 (57.9%) reported at least one DCPR-R diagnosis. Subjects with at least one DCPR-R diagnosis showed lower PWB Personal Growth and PWB Purpose in Life than those without DCPR-R diagnoses. When the incremental validity of the DCPR-R was tested using PWB Personal Growth, PWB Purpose in Life, PWB Self-acceptance, GAS Cognitive symptoms and GAS affective symptoms subscales as criterion variable, the DCPR-R increased up to 0.135-0.263 the explained variance. CONCLUSION: The DCPR-R might be implemented together with the DSM-5 to have a comprehensive assessment of elderly subjects

iPSC Bioprinting: Where are We at?

Here, we present a concise review of current 3D bioprinting technologies applied to induced pluripotent stem cells (iPSC). iPSC have recently received a great deal of attention from the scientific and clinical communities for their unique properties, which include abundant adult cell sources, ability to indefinitely self-renew and differentiate into any tissue of the body. Bioprinting of iPSC and iPSC derived cells combined with natural or synthetic biomaterials to fabricate tissue mimicked constructs, has emerged as a technology that might revolutionize regenerative medicine and patient-specific treatment. This review covers the advantages and disadvantages of bioprinting techniques, influence of bioprinting parameters and printing condition on cell viability, and commonly used iPSC sources, and bioinks. A clear distinction is made for bioprinting techniques used for iPSC at their undifferentiated stage or when used as adult stem cells or terminally differentiated cells. This review presents state of the art data obtained from major searching engines, including Pubmed/MEDLINE, Google Scholar, and Scopus, concerning iPSC generation, undifferentiated iPSC, iPSC bioprinting, bioprinting techniques, cartilage, bone, heart, neural tissue, skin, and hepatic tissue cells derived from iPSC

Criterion-related validity in a sample of migraine outpatients:the diagnostic criteria for psychosomatic research

OBJECTIVE.: The Diagnostic Criteria for Psychosomatic Research (DCPR) are those of psychosomatic syndromes that did not find room in the classical taxonomy. More recently, the DCPR were updated, called DCPR-revised (DCPR-R). The present study was conducted to test the criterion-related validity of the DCPR-R. METHODS.: Two hundred consecutive subjects were enrolled at the Headache Center of Careggi University Hospital (Italy): 100 subjects had a diagnosis of chronic migraine (CM) and 100 had a diagnosis of episodic migraine (EM). Participants received a clinical assessment, which included the DCPR-revised Semi-Structured Interview (DCPR-R SSI), the Structured Clinical Interview for DSM-5 (SCID-5), and the psychosocial index (PSI). RESULTS.: Forty-seven subjects (23.5%) had at least one DSM-5 diagnosis: major depressive disorder (8.5%; n = 17) and agoraphobia (7.5%; n = 15) were the most frequent. One hundred and ten subjects (55%) reported a DCPR-R diagnosis: allostatic overload (29%; n = 58) and type A behavior (10.5%; n = 21) were the most frequent. When the incremental validity of the DCPR system over the DSM system was tested using PSI subscales as the criterion variable, the DCPR-R increased up to 0.11-0.24 the amount of explained variance. Subjects with at least one DCPR-R diagnosis showed lower PSI well-being scores (p = .001), higher PSI stress scores (p < .001), and higher PSI psychological distress scores (p = .008) than subjects without a DCPR-R diagnosis. CONCLUSION.: The DCPR-R showed a good criterion-related validity in migraine outpatients. Thus, they might be implemented, together with the DSM-5, in the assessment of migraine subjects