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In this paper, we present the case of a 48-year-old woman diagnosed with early breast cancer. As candidate for mastectomy, she refused immediate reconstruction. She was referred to a psycho-oncologist for further evaluation and support. Psychological sessions helped reveal a history of intimate partner violence and helped clarify the reason for her refusal to undergo immediate reconstruction. Experience with this case highlights the importance of a multidisciplinary practice in which collaboration between surgeons, oncologists, and mental health professionals leads to a more in-depth understanding of the apparently paradoxical behaviors of patients, and to better care for their needs.

Videogames use has constantly increased among children and adolescents, with uncertain consequences on their health. This study aimed to assess the prevalence of videogames use and addiction in a sample of Italian children during the COVID-19 pandemic and their association with anxiety symptoms. One hundred and sixty-two children (M/F:78/84, age range: 8–10 years, average age 9.4 ± 0.7 years) completed the Videogame Addiction Scale for Children (VASC), the Test of Anxiety and Depression (TAD) and the Children’s Anxiety Meter—State (CAM-S). Demographic variables and data on the access to electronic tools and games preferences were also collected. Overall, 96.3% of the study participants stated to have access to one or more device. They reported a low risk of videogame addiction (VASC score (mean ± SD): 46.7 ± 15.4), a moderate level of trait anxiety (TAD score (mean ± SD): 135 ± 16.8) and a low state anxiety (CAM-S score (mean ± SD): 2.2 ± 2.1). Males reported to spend more time on videogames, to perceive higher self-control and to be more influenced by reinforcement mechanisms, females described higher levels of trait anxiety. In the regression analysis, state anxiety was a predictor of videogame use and addiction (p = 0.01). Further research is needed to confirm these data and to maximize the developmentally positive effects of videogames and preventing the negative consequences.

Cyberbullying is an intentional aggressive behavior repeatedly perpetrated by a single person or a group against a peer who can not easily defend, characterized by the use of electronic forms of contact. This phenomenon is a public health concern with serious implications for adolescents’ mental health. We aimed to investigate the role of gender, age, and subjective self perceived mood states in cyberbullying and victimization (being a victim of cyberbullying) behaviors. A total of 554 adolescents (293 males and 261 females, age 15.27; SD = 2.21) completed the Florence Cyber-Bullying Cyber-Victimization Scales (FCBVSs) and the Profile of Mood States (POMS). Older age and male gender were associated to both cyberbullying and victimization.The aggressiveness/anger (A) and confusion/bewilderment (C) factors measured by the POMS were predictors of all types of cyberbulliyng and cybervictimization behaviors; the tension/anxiety (T) factor was a predictor of all cyberbullying behaviors and of the FCBVSs impersonification subscale of cybervictimization. Subjective specific mood states may contribute to both cyberbulliyng and victimization behaviors, suggesting the potential benefit of preventive strategies addressing the recognition and management of mood states in adolescents.

Purpose: This cross-sectional study aimed at comparing the quality of life (Qol), the prevalence of psychiatric diagnosis and pharmacological treatment in 104 candidates to bariatric surgery according to the degree of obesity (class 2 vs. class ≥ 3 obesity). Methods: All surgical candidates underwent a detailed psychiatric interview based on DSM-5 criteria, including sociodemographic, clinical, psychological and psychiatric data. Participants completed the Binge Eating Scale (BES) and the 12-Item Short Form Health Survey (SF-12). Results: Overall, bariatric candidates reported a significant impairment in the physical (PCS 38.8 [95% CI 36.2–41.5]) and mental (MCS 42.2 [95% CI 40.4–43.9]) components of Qol compared to population norms (p < 0.001 for both). Subjects with class 2 obesity scored significantly lower in the MCS compared to those with class 3 (38.7 (8.1) vs. 43.6 (8.4), p = 0.008). No other statistically significant differences were found between the two groups in terms of sociodemographic and clinical variables. Conclusion: These data support the usefulness of Qol assessment in bariatric candidates as a sensible screening parameter, especially in patients with lower BMI, in whom MCS could identify the need for early psychosocial intervention. Level of evidence: Level III,case-control analyticstudy.

Background: The aim of the present prospective study (ClinicalTrials.gov Identifier: NCT02111538) was to assess the prognostic value of phase angle (PhA), derived from bioimpedance vectorial analys...

Kidney transplantation is a serious event that involves profound psychological, relational and social changes both for the patient and his family context. Assessment of personality profile, awareness of disease, family and social support of the patient candidate for kidney transplantation are necessary because factors not adequately considered, can influence the success of the transplant and alter the psychological stability of the patient. The present study aims to provide a systematic review of the literature of the last twelve years (2006-2018), focusing in particular on patient's readiness level and illness management and on possible psychopathology. Sixty-two studies were examined. Based on the Downs and Black checklist, most studies (n = 32) were of high quality; 15 of which related to lifestyle, health education, and therapeutic adherence in post-renal transplantation, 17 studies concerned the possible existence of psychopathology and cognitive impairment of renal deceased transplanted subjects. The literature used has shown that the population of kidney transplant patients is exposed to a high risk of psychiatric disorders with repercussions on the quality of life and the risk of rejection. Therefore, an adequate pre-transplant psychosocial assessment is necessary, which allows a more in-depth knowledge of the candidate to plan coping strategies and possible post-transplant psychotherapy.

Heart failure is a disease of epidemic proportion, and is a leading cause of mortality in the world. Since cardiac myocytes are terminally differentiated cells with minimal intrinsic ability to self-regenerate, cardiac tissue engineering has emerged as one of the most realistic therapeutic strategies for cardiac repair. We have previously proven the ability of carbon nanotube scaffolds to promote cardiomyocytes proliferation, maturation and long-term survival. Here, we tested if 3-dimensional scaffolds of carbon nanotube-based composites can also promote cardiomyocyte growth, electrophysiological maturation, and formation of functional syncytia. To this purpose, we developed an elastomeric scaffold which consists of a microporous and self–standing material made of polydimethylsiloxane (PDMS) containing micrometric cavities, and integrated multi-wall carbon nanotubes (MWCNTs) into the scaffold. We combined microscopy, cell biology and calcium imaging, to investigate whether neonatal rat ventricular myocytes (NRVMs) cultured on the 3D-PDMS+MWCNT acquire a more viable and mature phenotype compared to control. We found that, when cultured in the 3D-PDMS+MWCNTs, NRVMs showed improved viability (p < 0.005 at day3) and more defined and mature sarcomeric phenotype compared to 3D PDMS control. These modifications were associated with an increase of connexin-43 gene expression, gap junction areas (p < 0.005 at day 3), and a more mature electrophysiological phenotype of syncytia and calcium transients. Finally, 3D-PDMS+MWCNT boosted NRVMs proliferation (p < 0.005 at day 3) while hindering cardiac fibroblasts proliferation compared to control PDMS. Thus, 3D-PDMS+MWCNT has the ability to promote viability, proliferation and functional maturation of cardiac myocytes. These properties are essential in cardiac tissue engineering and offer novel perspectives in the development of innovative therapies for cardiac repair.

Prader-Willi syndrome (PWS) is a complex genetic disorder and represents the most common genetic cause of life-threatening obesity in childhood and adolescence. The indication for bariatric surgery in children and adolescents with syndromic obesity is still controversial. This case report deals with the preoperative medical and psychosocial evaluation of a 16-y-old male adolescent with PWS who underwent sleeve gastrectomy. Information on a 6-mo follow-up is also reported. The preoperative body weight was 223 kg (body mass index [BMI] 80.9 kg/m2). Comorbidities included severe obstructive sleep apnea with nocturnal respiratory failure, hypertension, and impaired glucose tolerance. At 2- and 6-mo follow-ups, the percent excess weight loss was 16 (BMI 71.8 kg/m2) and 29.2 (BMI 64.6 kg/m2), respectively. Comorbities did improve. Intellectual disability of genetic origin per se may not represent an absolute contraindication to bariatric surgery if adequate and tailored clinical and psychosocial support is provided.

Rationale: Recent evidence indicates that a few human microRNAs (miRNAs), in particular hsa-miR-199a-3p and hsa-miR-590-3p, stimulate proliferation of cardiomyocytes and, once expressed in the mouse heart using viral vectors, induce cardiac regeneration after myocardial infarction. Viral vectors, however, are not devoid of safety issues and, more notably, drive expression of the encoded miRNAs for indefinite periods of time, which might not be desirable in light of human therapeutic application. Objective: As an alternative to the use of viral vectors, we wanted to assess the efficacy of synthetic miRNA mimics in inducing myocardial repair after single intracardiac injection using synthetic lipid formulations. Methods and Results: We comparatively analyzed the efficacy of different lipid formulations in delivering hsa-miR-199a-3p and hsa-miR-590-3p both in primary neonatal mouse cardiomyocytes and in vivo. We established a transfection protocol allowing persistence of these 2 mimics for at least 12 days after a single intracardiac injection, with minimal dispersion to other organs and long-term preservation of miRNA functional activity, as assessed by monitoring the expression of 2 mRNA targets. Administration of this synthetic formulation immediately after myocardial infarction in mice resulted in marked reduction of infarct size and persistent recovery of cardiac function. Conclusions: A single administration of synthetic miRNA–lipid formulations is sufficient to stimulate cardiac repair and restoration of cardiac function.

Defenses mechanisms are defined as the tools an individual uses to manage instincts, drives, and affects. Transplantation is a stressful event that requires the body to mobilize its internal and external defenses and implement coping and adaptation strategies, which can be essential for overcoming the painful and potentially dangerous environmental, existential, and relational situations that may occur after transplantation. The aim of our study was to analyze the defense styles in 50 kidney transplanted subjects and to correlate the latter with any psychopathology and the quality of life subjectively perceived. The Defense Style Questionnaire was administered to evaluate the defense mechanisms. The Symptom Checklist-90-R (SCL-90-R) was used for the evaluation of any psychopathology. Quality of life was studied using the Complete Form Health Survey (SF-36). The "somatization" (SOM) and "anxiety" (ANX) dimensions of the SCL-90 R correlated significantly with the "reaction formation" (RF) neurotic defense (RF/SOM r = .893; RF/ANX r = .966; P .05). A good perception of one's "general health" (GH) correlated significantly with the "humor" (HU) and "sublimation" (SU) mature defenses (HU/GH r = .681; SU/GH r = .524; P .05). Kidney transplanted subjects are exposed to persistent physical and psychosocial stress and each transplanted subject uses their own defense mechanisms to contain the mental pain and reduce the emotional stress derived from the transplantation experience. Identifying the different kinds of defenses (mature, immature, or neurotic) can be an effective way to search for predictive indices of a good quality of life and adherence to treatments.

Internet addiction is currently considered a worldwide problem, with a possible impact on mental health. This study aimed to investigate the prevalence of internet gaming disorder (IGD) among Italian young adults and to explore its association with psychopathological symptoms. Our sample included 566 young adults (324 males/242 females; age: 22.74 ± 4.83 years). Participants were asked to state their favorite games and complete the following questionnaires: the Internet Gaming Disorder Scale Short Form (IGD9-SF); the APA symptom checklist, based on DSM-5 diagnostic criteria for IGD; the Symptom Checklist-90 Revised (SCL-90 R); and the Social Adaptation Self Evaluation Scale (SASS). Use of video games was common among study participants (95% of the sample). Thirty subjects (5.3% of the sample) matched criteria for a clinical diagnosis of IGD. Data showed a positive correlation between higher use of online games and higher levels of depression (r = 0.501), anxiety (r = 0.361) and psychoticism (r = 0.431), and lower family and extra-family relationships (r = −0.383). At linear regression analysis, somatization (p = 0.002), depression (p = 0.001) and sleep disturbances (p = 0.003) were predictors of IGD diagnosis. IGD was significantly associated to mental health distress. Healthcare professionals should be aware of the problematic consequences of online gaming.

Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression. This striking, unexpected result, was paralleled by the recruitment of immune cells, in particular T lymphocytes and dendritic cells, which secreted type I interferons. Laser light also reduced the number of highly angiogenic macrophages within the tumor mass and promoted vessel normalization, an emerging strategy to control tumor progression. Collectively, these results set photobiomodulation as a safety procedure in oncological patients and open the way to its innovative use for cancer therapy., Highlights • Laser light reduces tumor progression while increasing metabolism of cultured cells • Laser-treated tumors contain mature vessels and less pro-angiogenic macrophages • Tumors treated by photobiomodulation are surrounded by lymphocytes and dendritic cells • Laser light promotes secretion of type I interferons in vitro and in vivo Laser therapy, also named photobiomodulation, is recommended to heal mucositis induced by oncological treatments, raising concerns on its safe use in cancer patients. Ottaviani et al. showed that laser light inhibits tumor progression, induces tumor vessel normalization and stimulates the immune system to produce type I interferons, proving the safety and extending the use of laser-based therapies to cancer.

Transplant recipients have difficulty expressing, identifying, and describing their emotional experiences. The Machover human figure test allows us to bring out the deepest contents of a patient's personality, which are normally hidden and not explained to structured quantitative tests. The study analyzed possible situations of distress and possible symptoms of psychopathology in kidney transplant recipients, emerged from the projective test of the human figure and not easily verbalized to the common standardized tests. The sample included 80 kidney transplant patients (51 men and 29 women; mean age, 47.74 [SD, 12.39] years) during follow-up visits at 12 months after transplant. The Machover test was used to evaluate body image, affective aspects, and personality variables by projective method; the Symptom Checklist-90-R was used for the evaluation of possible psychopathology, and the 36-Item Short Form Health Survey was used for the assessment of perceived quality of life. RESULTS: showed that the more anxiety there is in the human figure test, the less somatization dimensions (ANX/SOM R = -331, P .05), depression (ANX/DEP R = -326, P .05), and the global index of psychic symptomatology (ANX/GSI R = -367, P .05) of the Symptom Checklist-90-R are present. This research has confirmed the hypothesis that the spontaneous graphic production of the recipients, through the projective methods, allows them to identify and deepen their psychological contents and to activate and maintain a good psychophysical balance post transplant.

Resolution of bacterial infections is often hampered by both resistance to conventional antibiotic therapy and hiding of bacterial cells inside biofilms, warranting the development of innovative therapeutic strategies. Here, we report the efficacy of blue laser light in eradicating Pseudomonas aeruginosa cells, grown in planktonic state, agar plates and mature biofilms, both in vitro and in vivo, with minimal toxicity to mammalian cells and tissues. Results obtained using knock-out mutants point to oxidative stress as a relevant mechanism by which blue laser light exerts its anti-microbial effect. Finally, the therapeutic potential is confirmed in a mouse model of skin wound infection. Collectively, these data set blue laser phototherapy as an innovative approach to inhibit bacterial growth and biofilm formation, and thus as a realistic treatment option for superinfected wounds.

Living donor kidney transplantation (LDKT) is the best therapy for patients with chronic renal failure. Its advantages, compared with cadaveric transplantation, include the possibility of avoiding dialysis, the likelihood of best outcome, and donor pool expansion. Careful assessment of potential donors is important to minimize the risks and ensure success. However, the proportion of donors disqualified has been poorly investigated. The aim of this work is to describe our experience and present the main reasons for missed donation.This was a single-center, retrospective study of all potential donors and recipients evaluated for LDKT between January 2008 and December 2017.During the period of study, 81 donor-recipient pairs were evaluated. Of these, 45.7% were disqualified and 37 LDKTs were carried out. LDKT was the first choice in 68% of cases and preemptive in 20%; 60% of transplants were among family members. Sex distribution revealed a prevalence of females in the donor group (69%) and males in the recipient group (70%). The mean living donor age was 53 ± 9.5 years; the mean recipient age was lower in recipients listed in the living transplant program than those listed for cadaver transplantation (45.8 ± 13.4 vs 54.2 ± 11.08; P .0001). Reasons for denial included hypertension (18.9%), deceased donor transplant performed during the study period (16.2%), urologic pathology (13.5%), incompatibility (13.5%), withdrawal of consent by donor or recipient (13.5%), psychological unsuitability (8.1%), donor cancer (5.4%), and reduced renal clearance (2.7%).LDKT is considered an option especially for younger recipients. Of the potential kidney living donors, 45.7% were disqualified during the evaluation, with medical reasons being the primary cause.

Cardiomyocyte proliferation stops at birth when the heart is no longer exposed to maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to promote maternal tolerance towards the fetus. Here, we report a role of Tregs in promoting cardiomyocyte proliferation. Treg-conditioned medium promotes cardiomyocyte proliferation, similar to the serum from pregnant animals. Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte proliferation. Treg depletion after myocardial infarction results in depressed cardiac function, massive inflammation, and scarce collagen deposition. In contrast, Treg injection reduces infarct size, preserves contractility, and increases the number of proliferating cardiomyocytes. The overexpression of six factors secreted by Tregs (Cst7, Tnfsf11, Il33, Fgl2, Matn2, and Igf2) reproduces the therapeutic effect. In conclusion, Tregs promote fetal and maternal cardiomyocyte proliferation in a paracrine manner and improve the outcome of myocardial infarction., Regulatory T cells (Tregs) expand during pregnancy to promote tolerance towards the fetus. Here the authors show that Tregs induce proliferation of fetal and maternal cardiomyocytes during pregnancy and enhance myocardial repair via proliferation-promoting paracrine actions.

Summary Over the last several years, mesenchymal stromal cells (MSCs) have been isolated from different tissues following a variety of different procedures. Here, we comparatively assess the ex vivo and in vivo properties of MSCs isolated from either adipose tissue or bone marrow by different purification protocols. After MSC transplantation into a mouse model of hindlimb ischemia, clinical and histological analysis revealed that bone marrow MSCs purified on adhesive substrates exerted the best therapeutic activity, preserving tissue viability and promoting formation of new arterioles without directly transdifferentiating into vascular cells. In keeping with these observations, these cells abundantly expressed cytokines involved in vessel maturation and cell retention. These findings indicate that the choice of MSC source and purification protocol is critical in determining the therapeutic potential of these cells and warrant the standardization of an optimal MSC isolation procedure in order to select the best conditions to move forward to more effective clinical experimentation., Graphical Abstract, Highlights • MSCs were isolated from various tissues according to different protocols • All MSCs provided a therapeutic benefit in a hindlimb ischemia model • Adhesive MSCs from bone marrow were the most effective in preserving tissue viability • These cells promoted massive vascularization in a paracrine fashion, Zacchigna and colleagues compared the ex vivo and in vivo properties of mesenchymal stromal cells (MSCs) isolated from either adipose tissue or bone marrow by different protocols. Adhesive MSCs from bone marrow exerted the best therapeutic activity in a hindlimb ischemia model, preserving viability and inducing angiogenesis in a paracrine manner. The optimization of a standard MSC isolation procedure is required to improve clinical results.

Background In the context of kidney transplantation (KT), multidisciplinary interventions, including assessment and management of psychosocial aspects, are important to improve transplant's outcome. The aim of this study was to describe a multidisciplinary team approach to KT, with a specific focus on early detection and treatment of psychological distress and psychopathologic conditions in the early phase postsurgery. Methods The multidisciplinary team in kidney transplantation was implemented in January 2016. In this team approach, all transplant recipients are invited to 3 scheduled appointments for a multidisciplinary evaluation at 1, 3, and 6 months posttransplant, including a psychiatric interview, with the aim to assess the patient's adjustment after transplantation and provide support when necessary. Results This pilot study involved all 41 KT recipients consecutively referred for the first multidisciplinary appointment after transplantation. Five subjects (12% of the study sample) presented with a current psychiatric diagnosis. Psychopharmacologic treatment was confirmed or introduced for all these patients. Further psychological support was suggested to 4 other patients (10%). Conclusion KT significantly improves patients' quality of life. However, the percentage of subjects receiving psychopharmacologic treatment and referred for further psychological and psychiatric support (22%) suggests the need for careful monitoring of psychosocial aspects over the long term.

In a tissue continuously challenged by mechanical stresses, such as the skin or the heart, cells perceive information about their microenvironment through several adhesive protein complexes and activate cell-signaling events to maintain tissue cohesion. Consequently, alteration of cell adhesion components leads to aberrant assembly of the associated cytoplasmic scaffolding and signaling pathways, which may reflect changes to the tissue physiology and mechanical resistance. Desmoplakin is an essential component of the cell-cell junction, anchoring the desmosomal protein complex to the intermediate filaments (IFs). Inherited mutations in desmoplakin are associated with both heart and skin disease (cardiocutaneous syndrome). In this study, we investigated the mechanical properties of human keratinocytes harboring a cardiocutaneous-associated homozygous C-terminal truncation in desmoplakin (JD-1) compared to a control keratinocyte line (K1). Using Single Cell Force Spectroscopy (SCFS) AFM-based measurements, JD-1 keratinocytes displayed an overall alteration in morphology, elasticity, adhesion capabilities and viscoelastic properties, highlighting the profound interconnection between the adhesome pathways and the IF scaffold.

Aims Given the clinical impact of LMNA cardiomyopathies, understanding lamin function will fulfill a clinical need and will lead to advancement in the treatment of heart failure. A multidisciplinary approach combining cell biology, atomic force microscopy (AFM), and molecular modeling was used to analyse the biomechanical properties of human lamin A/C gene (LMNA) mutations (E161K, D192G, N195K) using an in vitro neonatal rat ventricular myocyte model. Methods and results The severity of biomechanical defects due to the three LMNA mutations correlated with the severity of the clinical phenotype. AFM and molecular modeling identified distinctive biomechanical and structural changes, with increasing severity from E161K to N195K and D192G, respectively. Additionally, the biomechanical defects were rescued with a p38 MAPK inhibitor. Conclusions AFM and molecular modeling were able to quantify distinct biomechanical and structural defects in LMNA mutations E161K, D192G, and N195K and correlate the defects with clinical phenotypic severity. Improvements in cellular biomechanical phenotype was demonstrated and may represent a mechanism of action for p38 MAPK inhibition therapy that is now being used in human clinical trials to treat laminopathies.

Lung transplantation (LT) increases the life expectancy of patients affected by end stage pulmonary disease; specifically, its ultimate aims are to improve survival and health related quality of life (HRQoL). The aim of the present longitudinal study was to determine the HRQoL trajectory and changes in functional capacity from time of entry in the waiting list for LT to 2 year after LT. The study included sixty-nine outpatients enrolled in a single medical center when they entered the waiting list for LT and who subsequently received it. They were then followed up over 2 years after LT. HRQoL was assessed by the physical and mental component summary (PCS and MCS) scores of the 36-item Short Form Health Survey (SF-36) and Saint George’s Respiratory Questionnaire (SGRQ). Psychological distress was evaluated with the General Health Questionnaire (GHQ), and functional capacity was investigated using the six-minute walk test (6MWT) and forced expiratory volume (FEV1). Patients showed low SF-36 PCS (30.5±7.8) and SGRQ total (61.8±17.5) scores at entry in the waiting list, but exhibited significant changes over time after LT (p

Background: Mutations in genes encoding intercalated disk/desmosome proteins, such as plakophilin 2 (PKP2), cause arrhythmogenic cardiomyopathy (ACM). Desmosomes are responsible for myocyte&ndash, myocyte attachment and maintaining mechanical integrity of the myocardium. Methods: We knocked down Pkp2 in HL-1 mouse atrial cardiomyocytes (HL-1Pkp2-shRNA) and characterized their biomechanical properties. Gene expression was analyzed by RNA-Sequencing, microarray, and qPCR. Immunofluorescence was used to detect changes in cytoskeleton and focal adhesion. Antagomirs were used to knock down expression of selected microRNA (miR) in the rescue experiments. Results: Knockdown of Pkp2 was associated with decreased cardiomyocyte stiffness and work of detachment, and increased plasticity index. Altered mechanical properties were associated with impaired actin cytoskeleton in HL-1Pkp2-shRNA cells. Analysis of differentially expressed genes identified focal adhesion and actin cytoskeleton amongst the most dysregulated pathways, and miR200 family (a, b, and 429) as the most upregulated miRs in HL-1Pkp2-shRNA cells. Knockdown of miR-200b but not miR-200a, miR-429, by sequence-specific shRNAs partially rescued integrin-&alpha, 1 (Itga1) levels, actin organization, cell adhesion (on collagen), and stiffness. Conclusions: PKP2 deficiency alters cardiomyocytes adhesion through a mechanism that involves upregulation of miR-200b and suppression of Itga1 expression. These findings provide new insights into the molecular basis of altered mechanosensing in ACM.

Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.

ObjectiveTo investigate the frequency of psychiatric disorders in subjects wishing to lose weight categorized according to BMI.DesignCross-sectional study.SettingAn academic outpatient clinical nutrition service in Italy.SubjectsA total of 207 subjects (thirty-nine men and 168 women; mean age: 38·7 (sd 14·1) years) consecutively attending the study centre for the first time between January 2003 and December 2006.ResultsIn the entire study group, eighty-three (40 %) subjects had a psychiatric disorder according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision. Eating disorders were the most prevalent psychiatric condition (thirty-six subjects, 17·4 %), followed by mood and anxiety disorders (9·7 % and 8·7 %, respectively). The frequency of psychiatric disorders among different BMI categories was as follows: 75·0 % in underweight, 50·0 % in normal weight, 33·3 % in overweight and 33·3 % in obese subjects.ConclusionsPsychiatric disorders may be frequently found in subjects wishing to lose weight. Our results highlight the importance of psychiatric assessment especially in underweight and normal-weight subjects.

Objective Neurotrophins (NT) are a family of closely related proteins, including brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5). NTs are deemed to regulate several aspects of neuronal survival, development, and function. Although NTs have been associated to a variety of mental disorders, the potential role of NT alterations in hypochondriasis (HC) has never been investigated. Methods In the present study, plasma concentrations of NTs were evaluated in 23 adult patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for HC and 22 healthy controls. Platelet serotonin (5-HT) content was chosen as a measure of serotonergic function. Hypochondriacal symptoms were assessed using the Whiteley Index of Hypochondriasis (WIH). Results Plasma NT-3 level ( P =.004) and platelet 5-HT ( P =.008) were significantly lower in patients with HC compared with controls. Correlation analyses showed that the WIH score was significantly and inversely associated with both NT-3 values ( r =−.60, P =.002) and platelet serotonin content ( r =−.53, P =.009). We used a multivariate regression model to determine independent predictors of the WIH score. After allowance for potential confounders, plasma NT-3 levels remained the unique independent predictor of the WIH ( β =.003, t =−3.5, P =.003). Conclusions Decreased NT-3 concentration, alongside with serotonin dysfunction, may represent a biological correlate of HC.

Few data are available regarding the prevalence of burnout among dialysis health care workers. Aims of the present study were to assess and compare burnout levels in a sample of nurses and physicians working in dialysis units, and to investigate their relationships with quality of life, in a cross-sectional observational study.A total of 344 workers from 10 dialysis centres in Northern Italy completed a battery of questionnaires including the Maslach Burnout Inventory, the MOS-36 Item Short Form Health Survey [SF36: physical (PCS) and mental (MCS) component scores] and the 30-item General Health Questionnaire (GHQ30). Data on social and demographic characteristics and working conditions were also collected. General Estimating Equations models were used for the analysis.Overall, burnout scores were lower than the Italian normative sample, with no significant differences between physicians and nurses. However, 30% of nurses had high emotional exhaustion vs 18% of physicians (adjusted OR 2.38, P = 0.003). Emotional exhaustion was also predicted by number of worked hours and months worked in dialysis in the previous 2 years. Depersonalisation was predicted by male gender and bad relationship with coworkers. Having no children and having a permanent hospital position predicted low personal accomplishment. PCS was lower in nurses (50.0 vs 53.3, P0.001), while no significant difference was found for MCS and GHQ30. Lower PCS was associated with emotional exhaustion (P = 0.007) and GHQ305 with depersonalization (P = 0.032).Although burnout is not a general problem in dialysis health care providers, a subgroup of them may be identified, who would benefit from supportive measures to prevent this condition. Nurses appeared more burned-out in the emotional exhaustion scale than physicians.

Arrhythmogenic cardiomyopathy (AC) is a genetic disease caused by mutations in genes encoding the intercalated disk (ID) proteins. ID is a multiprotein complex providing cell-cell junction and connecting the nucleus to the extracellular matrix, and playing a pivotal role for maintaining the structural integrity of the heart tissue. Mutations in PKP2 encoding plakophilin 2 (PKP2) are the most common causes of AC. The objective of this study was to investigate the biomechanical properties of the PKP2-knock down HL-1 mouse cardiac myocytes (PKP2-KD). PKP2 protein levels were reduced by 66 to 75% upon shRNA-targeting of the Pkp2 mRNA. Nuclear stiffness (Young’s modulus) and the force required to deform the nucleus were assessed by atomic force microscopy (AFM). Nuclear stiffness was decreased significantly (5 times) in PKP2-KD HL-1 myocytes as compared to wild-type (WT) myocytes, indicating an increased elasticity and/or susceptibility of the nucleus to be deformed (2 times). Interestingly, cell adhesion was also reduced (10 times) in the PKP2-KD myocytes, indicating a pivotal role of ID proteins in maintaining cell adhesion and mechanical integrity in cardiomyocytes. In the stress-relaxation test, while the decay time value was comparable between WT and PKP2-KD cells, relaxation force and cell deformation values were decreased 3 and 8 times, respectively, in PKP2-KD HL-1 myocytes, confirming the finding in the Young’s modulus. Moreover, the relaxation test revealed a reduced viscosity, highlighting a compromised cytoskeletal stability induced by the PKP2 deficiency. RNA-Sequencing and Ingenuity Canonical Pathway analysis identified integrin, tight junction, and the canonical Wnt signaling, among the most disturbed pathways in the PKP2-KD HL-1 myocytes. The findings indicate that the deficiency of a component of the ID protein markedly affects the whole-cellular biomechanics, which is expected to affect tissue stability, leading to activation of the mechano-transduction pathways.

Atomic force microscopy (AFM) cell loading/unloading curves were used to provide comprehensive insights into biomechanical behavior of cardiomyocytes carrying the lamin A/C (LMNA) D192G mutation known to cause defective nuclear wall, myopathy and severe cardiomyopathy. Our results suggested that the LMNA D192G mutation increased maximum nuclear deformation load, nuclear stiffness and fragility as compared to controls. Furthermore, there seems to be a connection between this lamin nuclear mutation and cell adhesion behavior since LMNA D192G cardiomyocytes displayed loss of AFM probe-to-cell membrane adhesion. We believe that this loss of adhesion involves the cytoskeletal architecture since our microscopic analyses highlighted that mutant LMNA may also lead to a morphological alteration in the cytoskeleton. Furthermore, chemical disruption of the actin cytoskeleton by cytochalasin D in control cardiomyocytes mirrored the alterations in the mechanical properties seen in mutant cells, suggesting a defect in the connection between the nucleoskeleton, cytoskeleton and cell adhesion molecules in cells expressing the mutant protein. These data add to our understanding of potential mechanisms responsible for this fatal cardiomyopathy and show that the biomechanical effects of mutant lamin extend beyond nuclear mechanics to include interference of whole-cell biomechanical properties.

Objective Despite an improved quality of life, about 33% of heart transplant recipients will develop depressive symptoms post-operatively. To date, no review has explored the efficacy and safety of pharmacologic or psychologic interventions in this patient group. Methods We conducted a comprehensive Medline, EmBase, Psycinfo search for studies of the treatment of depression in heart transplant recipients. Results We identified 34 studies of variable methodologic quality. Selective serotonin re-uptake inhibitors (SSRIs), particularly citalopram and new-generation anti-depressants (mirtazapine), seem to represent the best therapeutic choices for this population. Tricyclic anti-depressants (TCAs), and electroconvulsive therapy (ECT) should be reserved for severe depression unresponsive to other treatments, whereas monoamine oxidase inhibitors (MAOIs) should be avoided. St John's wort, an alternative herbal drug, has been associated with life-threatening immunosuppression. Psychologic therapy offers further advantages after heart transplantation. Conclusions Further well-conducted, randomized, controlled trials are needed to clarify the efficacy and the safety of pharmacologic (SSRIs and atypical anti-depressants) and psychologic interventions in the management of depression after heart transplantation.

In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies. © 2013 Fabbro et al.

Background The purpose of this study was to advance current understanding of factors that influence long-term quality-of-life (QoL) outcomes after heart transplantation, by addressing the influence of depression on perceived health status. Methods Data were collected from all recipients ( n = 137) still alive at >10 years after transplantation. They completed the Short Form Health Survey (SF-36) inventory and the Beck Depression Inventory (BDI) questionnaire, while objective measures of health status were retrieved from medical records. All instruments used had acceptable reliability and validity. Data were analyzed using descriptive statistics, general linear regression models and survival analysis. Results We assessed 137 patients who received transplants between November 1985 and June 1994 in Pavia and have survived 10 to 18 years after transplantation (mean 13.64 years, SD 2.25). They rated their health as good and only the physical QoL (PCS) was impaired when compared with the general population. Thirty-two percent of patients experienced mood depressive symptoms in the long term after transplantation, indicating a low perceived QoL. Higher educational qualification ( p = 0.049), being unemployed and receiving a disability pension ( p = 0.001), high triglycerides levels ( p = 0.020) and lack of physical activity ( p Conclusions Assessment of depression levels and better understanding of risk factors for psychiatric disorders in the long term after transplantation could be of benefit in predicting negative outcomes and allowing future developments in patient management.

Myocardial tissue engineering currently represents one of the most realistic strategies for cardiac repair. We have recently discovered the ability of carbon nanotube scaffolds to promote cell division and maturation in cardiomyocytes. Here, we test the hypothesis that carbon nanotube scaffolds promote cardiomyocyte growth and maturation by altering the gene expression program, implementing the cell electrophysiological properties and improving networking and maturation of functional syncytia. In our study, we combine microscopy, biological and electrophysiological methodologies, and calcium imaging, to verify whether neonatal rat ventricular myocytes cultured on substrates of multiwall carbon nanotubes acquire a physiologically more mature phenotype compared to control (gelatin). We show that the carbon nanotube substrate stimulates the induction of a gene expression profile characteristic of terminal differentiation and physiological growth, with a 2-fold increase of α-myosin heavy chain (P < 0.001) and upregulation of sarcoplasmic reticulum Ca(2+) ATPase 2a. In contrast, markers of pathological hypertrophy remain unchanged (β-myosin heavy chain, skeletal α-actin, atrial natriuretic peptide). These modifications are paralleled by an increase of connexin-43 gene expression, gap junctions and functional syncytia. Moreover, carbon nanotubes appear to exert a protective effect against the pathologic stimulus of phenylephrine. Finally, cardiomyocytes on carbon nanotubes demonstrate a more mature electrophysiological phenotype of syncytia and intracellular calcium signaling. Thus, carbon nanotubes interacting with cardiomyocytes have the ability to promote physiological growth and functional maturation. These properties are unique in the current vexing field of tissue engineering, and offer unprecedented perspectives in the development of innovative therapies for cardiac repair.

Previous investigations suggested that lamin A/C gene (LMNA) mutations, which cause a variety of human diseases including muscular dystrophies and cardiomyopathies, alter the nuclear mechanical properties. We hypothesized that biomechanical changes may extend beyond the nucleus. Combining atomic force microscopy (AFM), molecular and cellular biology, we studied the biomechanical properties of cardiomyocytes expressing the cardiomyopathy LMNA D192G mutation, and attempted rescue through the subsequent introduction of wild-type LMNA. Neonatal rat ventricular myocytes (NRVMs) were infected with adenoviral vectors carrying either human LMNA wild-type or D192G gene. LMNA protein expression was confirmed up to day 6 by western blot. Live-cell AFM force-deformation curves from day 1 through day 6 showed that the nuclei of NRVMs expressing LMNA D192G displayed increased stiffness compared to both uninfected and wild-type expressing cells, with a peak at 48 hours (3-fold increase in nuclear Young modulus, p

AFM was used to collect the whole force-deformation cell curves. They provide both the elasticity and adhesion behavior of mouse primary cardiac fibroblasts. To confirm the hypothesis that a link exists between the membrane receptors and the cytoskeletal filaments causing therefore changing in both elasticity and adhesion behavior, actin-destabilizing Cytochalsin D was administrated to the fibroblasts. From immunofluorescence observation and AFM loading/unloading curves, cytoskeletal reorganization as well as a change in the elasticity and adhesion was indeed observed. Elasticity of control fibroblasts is three times higher than that for fibroblasts treated with 0.5 μM Cytochalasin. Moreover, AFM loading-unloading curves clearly show the different mechanical behavior of the two different cells analyzed: (i) for control cells the AFM cantilever rises during the dwell time while cells with Cytochalasin fail to show such an active resistance; (ii) the maximum force to deform control cells is quite higher and as far as adhesion is concern (iii) the maximum separation force, detachment area and the detachment process time are much larger for control compared to the Cytochalasin treated cells. Therefore, alterations in the cytoskeleton suggest that a link must exist between the membrane receptors and the cytoskeletal filaments beneath the cellular surface and inhibition of actin polymerization has effects on the whole cell mechanical behavior as well as adhesion.

ZASP is a cytoskeletal PDZ-LIM protein predominantly expressed in striated muscle. It forms multiprotein complexes and plays a pivotal role in the structural integrity of sarcomeres. Mutations in the ZASP protein are associated with myofibrillar myopathy, left ventricular non-compaction and dilated cardiomyopathy. The ablation of its murine homologue Cypher results in neonatal lethality. ZASP has several alternatively spliced isoforms, in this paper we clarify the nomenclature of its human isoforms as well as their dynamics and expression pattern in striated muscle. Interaction is demonstrated between ZASP and two new binding partners both of which have roles in signalling, regulation of gene expression and muscle differentiation; the mechanosensing protein Ankrd2 and the tumour suppressor protein p53. These proteins and ZASP form a triple complex that appears to facilitate poly-SUMOylation of p53. We also show the importance of two of its functional domains, the ZM-motif and the PDZ domain. The PDZ domain can bind directly to both Ankrd2 and p53 indicating that there is no competition between it and p53 for the same binding site on Ankrd2. However there is competition for this binding site between p53 and a region of the ZASP protein lacking the PDZ domain, but containing the ZM-motif. ZASP is negative regulator of p53 in transactivation experiments with the p53-responsive promoters, MDM2 and BAX. Mutations in the ZASP ZM-motif induce modification in protein turnover. In fact, two mutants, A165V and A171T, were not able to bind Ankrd2 and bound only poorly to alpha-actinin2. This is important since the A165V mutation is responsible for zaspopathy, a well characterized autosomal dominant distal myopathy. Although the mechanism by which this mutant causes disease is still unknown, this is the first indication of how a ZASP disease associated mutant protein differs from that of the wild type ZASP protein.

Several gene variants have been related to major depressive disorder (MDD) treatment outcomes; however, few studies have investigated a possible different effect on pharmacotherapy and brief psychotherapy response. A total of 137 MDD patients were randomized to either interpersonal counseling (IPC; n = 40) or antidepressant pharmacological treatment (n = 97). Outcomes were remission, response, and symptom improvement at week 8. Five genetic variants were investigated (5HTR2A rs6314, BDNF rs6265, SLC6A4 rs8076005, CREB1 rs2253206, and TPH2 rs11179023) as possible modulators of outcomes. The LC6A4 rs8076005 AA genotype and A allele were associated with response rate in the antidepressant group (p = 0.015 and 0.005, respectively) and in the whole sample (p = 0.03 and 0.02, respectively). In the IPC group a non-significant trend in the same direction was observed. The TPH2 rs11179023 A allele showed a marginal association with symptom improvement in the IPC group only. Other gene variants did not impact on outcomes in any treatment group. Our study suggests that rs8076005 in the SLC6A4 gene may be a modulator of antidepressant response, especially when pharmacological treatment is used.

Objective Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. Methods One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). Results IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. Conclusion Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.

M. Gemma Cherry *, Anne-Linda Frisch , Marij A. Hillen , Valentina Martinelli , Peter F. Pype , Isabelle Scholl , Nete Schwenessen , Kimberly A. Gudzune h Centre for Excellence in Evidence Based Teaching and Learning (CEEBLT), School of Medical Education, University of Liverpool, Liverpool, UK b Institute of Communication and Health (ICH), Department of Communication Sciences, Universita Della Svizzera Italiana, Lugano, Switzerland Department of Medical Psychology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands d Section of Psychiatry, Department of Health Sciences, University of Pavia, Italy Department of General Practice and Primary Health Care, Ghent University, Ghent, Belgium Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany g Steno Health Promotion Center, Patient Education Research Team, Gentofte, Denmark Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Background.This study examined the prevalence of students’ reported experiences of bullying and victimization in primary and secondary schools and their association with levels of perceived stress and cannabis use.Methods.We consecutively enrolled 407 students attending three secondary schools in Pavia (Italy). Bullying and victimization were measured using the retrospective bullying questionnaire (RQB). The 10-item perceived stress scale (PSS-10) was used to assess the degree to which situations in life were perceived as stressful. Data on demographic characteristics and cannabis use in the previous 6 months were also collected.Results.There were 328 victims (80.6%) and 221 bullies (52.1%). The results of the stepwise regression analysis with bullying as the dependent variable were significant with either male sex (R2 = 0.030,p = 0.024) or PSS-10 scores (R2 = 0.056,p = 0.036) in the model. With victimization as the dependent variable, only the PSS-10 scores were retained in the model as an independent predictor variable (R2 = 0.048,p Conclusions.The results from this study indicate that the level of perceived stress has an independent association with both bullying and victimization. Further studies are needed to clarify the psychobiological links between stress, cannabis use and bullying behaviours.

Recent years have witnessed numerous attempts at identifying the biological correlates of impending psychosis. Biochemical markers may theoretically provide a powerful approach to identify at-risk individuals, potentially leading to more effective intervention strategies to treat them. Hopefully, future developments in the field of research biochemistry in patients with at risk mental states or prodromal symptoms will make this approach ideal for screening and monitoring purposes. In this review, we provide an overview of the different biochemical markers which have been recently demonstrated to be altered in the biological fluids of patients with impending psychosis. We will also examine the practical issues that seem to be limiting the effective integration of biomarkers into clinical development.

Background Ankrd2 (also known as Arpp) together with Ankrd1/CARP and DARP are members of the MARP mechanosensing proteins that form a complex with titin (N2A)/calpain 3 protease/myopalladin. In muscle, Ankrd2 is located in the I-band of the sarcomere and moves to the nucleus of adjacent myofibers on muscle injury. In myoblasts it is predominantly in the nucleus and on differentiation shifts from the nucleus to the cytoplasm. In agreement with its role as a sensor it interacts both with sarcomeric proteins and transcription factors. Methodology/Principal Findings Expression profiling of endogenous Ankrd2 silenced in human myotubes was undertaken to elucidate its role as an intermediary in cell signaling pathways. Silencing Ankrd2 expression altered the expression of genes involved in both intercellular communication (cytokine-cytokine receptor interaction, endocytosis, focal adhesion, tight junction, gap junction and regulation of the actin cytoskeleton) and intracellular communication (calcium, insulin, MAPK, p53, TGF-β and Wnt signaling). The significance of Ankrd2 in cell signaling was strengthened by the fact that we were able to show for the first time that Nkx2.5 and p53 are upstream effectors of the Ankrd2 gene and that Ankrd1/CARP, another MARP member, can modulate the transcriptional ability of MyoD on the Ankrd2 promoter. Another novel finding was the interaction between Ankrd2 and proteins with PDZ and SH3 domains, further supporting its role in signaling. It is noteworthy that we demonstrated that transcription factors PAX6, LHX2, NFIL3 and MECP2, were able to bind both the Ankrd2 protein and its promoter indicating the presence of a regulatory feedback loop mechanism. Conclusions/Significance In conclusion we demonstrate that Ankrd2 is a potent regulator in muscle cells affecting a multitude of pathways and processes.