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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

The current COVID-19 pandemic has highlighted the relevance of aerosol-based infections. This work describes a laser device able to rapidly sterilize aerosol containing infectious viruses and bacteria, including Legionella pneumophila and SARS-CoV-2, when aerosolized by a novel system able to mimic droplet formation during human speech. This is a major advantage over existing devices that either purify incoming air through filters or sterilize solid surfaces, which are not major transmission routes. [Display omitted] The current COVID-19 pandemic has highlighted the importance of aerosol-based transmission of human pathogens; this therefore calls for novel medical devices which are able to sterilize contaminated aerosols. Here we describe a new laser device able to sterilize droplets containing either viruses or bacteria. Using engineered viral particles, we determined the 10,600 nm wavelength as the most efficient and exploitable laser source to be manufactured in a commercial device. Given the lack of existing working models to reproduce a human aerosol containing living microbial particles, we developed a new system mimicking human droplet formation and preserving bacterial and viral viability. This evidenced the efficacy of 10,600 nm laser light to kill two aerosol transmitted human pathogens, Legionella pneumophila and SARS-CoV-2. The minimal exposure time of <15 ms was required for the inactivation of over 99% pathogens in the aerosol; this is a key element in the design of a device that is safe and can be used in preventing inter-individual transmission. This represents a major advantage over existing devices, which mainly aim at either purifying incoming air by filters or sterilizing solid surfaces, which are not the major transmission routes for airborne communicable diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nanoscale manipulations of the extracellular microenvironment are increasingly attracting attention in tissue engineering. Here, combining microscopy, biological, and single-cell electrophysiological methodologies, we demonstrate that neonatal rat ventricular myocytes cultured on substrates of multiwall carbon nanotubes interact with carbon nanotubes by forming tight contacts and show increased viability and proliferation. Furthermore, we observed changes in the electrophysiological properties of cardiomyocytes, suggesting that carbon nanotubes are able to promote cardiomyocyte maturation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Evidence suggests that psychiatric patients are at an increased vascular risk. In this exploratory pilot study, we hypothesized that low levels of the soluble receptor for advanced glycation endproducts (sRAGE) might be found in psychiatric patients due to its association with atherothrombosis. We recruited 74 patients with different psychiatric disorders (39 schizophrenia, 10 major depression, 13 bipolar disorder and 12 personality disorder) and 74 healthy controls. Serum levels of sRAGE were determined by enzyme-linked immunosorbant assay. In univariate analysis, serum sRAGE levels of the patient groups with schizophrenia, major depression and bipolar disorder were significantly lower than that of the control group. The median sRAGE levels of these diagnostic groups were comparable with those reported in patients with prior atherothrombotic events. After allowance for potential confounders, the odds of reduced sRAGE remained independently associated with schizophrenia and major depression. Although subject to future confirmation, our findings suggest that the reduced serum sRAGE may contribute to increased cardiovascular risk in schizophrenia and major depression. [ABSTRACT FROM AUTHOR]

Background: Limited research has been done on depression and quality of life in long-term survival after heart transplantation. The aim of the present study was to investigate the role of age on depression and quality of life in a sample of long-term heart transplant recipients. Methods: We investigated 137 consecutive patients recruited in a single center who were still alive at more than 10 years after transplantation. Quality of life and depression were rated with the Medical Outcome Study Short Form (SF-36) and the Beck Depression Inventory (BDI), respectively. Sociodemographic, clinical, affective, and quality of life data for long-term survival patients stratified by current age younger than 70 years (young) and 70 years or older (old) were compared using Fisher’s exact tests and Student’s t-tests. Results: The SF-36 Mental Component Summary did not significantly differ between the young subjects (48.75 ± 10.2) compared with old (48.47 ± 10.1; p = 0.897). By contrast, the SF-36 Physical Component Summary was higher in younger subjects (46.88 ± 10.2 vs 40.81 ± 10.6, p = 0.008). According to BDI, 37.4% of the young group and 13.3% of the old group scored above the selected threshold of 10 (p = 0.014). Conclusions: In the light of our findings, older age does not seem to negatively affect the mental component of quality of life in the long term after heart transplantation, but it does on the physical component, as expected. On the other hand, it may be even associated with a lower prevalence of depressive symptoms more than 10 years after surgery. Hence, age per se does not represent a major limiting factor when considering candidates for this procedure, at least with regard to the issue of psychologic distress. [Copyright &y& Elsevier]

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 < 0.001) were predictors of high BDI scores. 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. [Copyright &y& Elsevier]

• Cyberbullying represents a public health problem with serious implications for adolescents' mental health • Male gender and older age (>15 years) are discriminating factors for both Cybervictimization and Cyberbullying behaviors • Mood states are specific predictors of high risk of cyberbullying and cybervictimization behavior 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It is widely accepted that the pathological state of cells is characterized by a modification of mechanical properties, affecting cellular shape and viscoelasticity as well as adhesion behaviour and motility. Thus, assessing these parameters could represent an interesting tool to monitor disease development and progression, but also the effects of drug treatments. Since biomechanical properties of cells are strongly related to cytoskeletal architecture, in this work we extensively studied the effects of selective impairments of actin microfilaments and microtubules on HeLa cells through force-deformation curves and stress relaxation tests with atomic force microscopy. Confocal microscopy was also used to display the effects of the used drugs on the cytoskeletal structure. In synergy with the aforementioned methods, stress relaxation data were used to assess the storage and loss moduli, as a complementary way to describe the influence of cytoskeletal components on cellular viscoelasticity. Our results indicate that F-actin and microtubules play a complementary role in the cell stiffness and viscoelasticity, and both are fundamental for the adhesion properties. Our data support also the application of biomechanics as a tool to study diseases and their treatments. [ABSTRACT FROM AUTHOR]

Background: Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer’s disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD. Methods: We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent. Results: After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24–6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34–1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001). Conclusion: Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Abstract: Objective: High levels of neuroticism and low self-esteem are markers for vulnerability to depression, a condition associated with a higher risk of arrhythmias. The question as to whether these depression-related personality domains are related to cardiac repolarization (duration of QT interval) in apparently healthy men has been addressed in this study. Methods: Participants were 658 clinically healthy males who underwent a health screening programme. QT interval duration was determined in the resting 12-lead electrocardiogram using an automated analysis program. Neuroticism was assessed by the short-scale Eysenck Personality Questionnaire and self-esteem by the Rosenberg self-esteem scale. Results: Heart-rate corrected QT interval {QTc, formula of Bazett [Bazett HC. An analysis of time relations of electrocardiograms. Heart 1920;7:353–370]} progressively increased across quartiles of neuroticism ratings. By contrast, no differences in QTc were observed across different degrees of self-esteem. A multivariate regression analysis showed that neuroticism was a statistically significant, independent predictor of QTc duration. Conclusion: After adjustment for potential confounders, neuroticism scores independently predicted QT interval duration in apparently healthy men. These findings highlight the possibility that higher arrhythmic risk could be present not only in patients with clinical depression but also in depression-prone, otherwise healthy individuals. [Copyright &y& Elsevier]

Abstract: Dipeptidyl peptidase IV (DPPIV or CD26) is an ubiquitously expressed protease that could play a role in the pathogenesis of anxiety in view of its capacity to cleave several behaviourally active neuropeptides. Hereto we sought to determine the relationship between phobic anxiety, as measured by the Crown–Crisp index, and circulating levels of soluble CD26 (sCD26) in a large cohort of 1017 Italian women participating in a general health survey. The association between sCD26 levels and phobic anxiety was tested using simple correlation analysis, linear regression and multivariate logistic regression analysis. A highly significant inverse association was found between sCD26 concentrations and anxiety scores both in simple correlation and linear regression analysis. Compared with subjects in the first tertile of sCD26 levels, the age-adjusted odds ratio for scoring ≥6 compared to scoring 0 or 1 was 0.31 (95% CI: 0.18–0.74) for the second and 0.47 (95% CI: 0.34–0.63) for the third tertile. Altogether, our data suggest that reduced plasma sCD26 concentrations could be a marker of high levels of phobic anxiety in women. [Copyright &y& Elsevier]

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 analysis (BIVA), in patients affected by systemic amyloid light-chain (AL) amyloidosis. Methods: One hundred-twenty seven consecutive newly diagnosed, treatment-naïve patients with histologically confirmed AL amyloidosis were enrolled. Nutritional assessment including BIVA-derived PhA was performed before treatment initiation. Results: PhA was associated with unintentional weight loss, caloric intake and the physical component of quality of life (QoL). After a median follow-up of 16.3 months (25th–75th percentile: 8.4–28.9 months), 49 (38.6%) subjects had died. At multivariable Cox proportional hazard analysis, PhA ≤4.3 independently predicted survival (HR = 2.26 [95%CI, 1.04–4.89]; p =.038]) after controlling for hydration status, haematologic response to treatment and modified Mayo Clinic cardiac stage. There was no effect modification of PhA on mortality by cardiac stage (P for interaction = 0.61). Conclusions: In AL amyloidosis, BIVA-derived PhA is associated with the common parameters implied in malnutrition assessment and QoL, and adjusted for hydration independently predicts survival. Due to its feasibility, BIVA should be systematically considered for the nutritional and clinical assessment of AL patients, in whom nutritional intervention trials are warranted. [ABSTRACT FROM AUTHOR]

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. • Defense mechanisms are recognized as subjective reactions in response to all experiences and moods that generate conflict or stress, as a way of removing the stressors or reducing their impact. • 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, and neurotic factor) can be an effective way to search for predictive indices of a good quality of life and adherence to treatments. [ABSTRACT FROM AUTHOR]

Living kidney donation is a complex emotional experience for donor candidates and recipients. The international literature underlines the importance of the type of donor-recipient bond to understand specific problems of donor candidates and optimize psychosocial evaluation and support for these patients. The aim of our study was to analyze the emotional experience of donating in the living couple according to the type of donor-recipient bond (parental/nonparental) and the possible presence of psychopathologic symptoms in the couples pretransplantation and post-transplantation. Thirty donor-recipient couples (8 nonparental, emotionally linked couples [husband-wife or wife-husband], 22 genetically linked parental couples [16 parent-son or parent-daughter, 6 siblings]), recruited at the Organ Transplant Unit (University Hospital of Catania), were evaluated with a questionnaire (prepared ad hoc by the authors) to investigate the experience of donation in the couple and the aspects of the donor-recipient relationship in pre- and post-transplantation, and with the SCL-90-R to study the couples' possible psychopathologic variables before the donation and in the follow-up 24 months post-transplant. The authors have seen in their study how, in particular, the parent-child bond complicates the donation process, especially when the sons are young subjects. The "mental distress" that emerged and the "unpredictability" of behaviors of these subjects makes the adaptation process more complicated with difficulty in accepting the organ received. It is certainly necessary for transplant psychiatrists and psychologists to keep them "hooked" and work with them to increase awareness and therefore clarity of their behaviors. • Living kidney donation is a complex emotional experience, for donor candidates and recipients. • The international literature shows the importance of the type of donor-recipient bond to understand specific problems of donor candidates and optimize psychosocial evaluation and support for these patients. • The psychosocial assessment of pretransplant donors and recipients is an opportunity to identify potential ambivalences and pave the way toward resolving the conflicts that have emerged to achieve good therapeutic adherence and better survival of the graft. [ABSTRACT FROM AUTHOR]

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. 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. • This research has shown that the spontaneous graphic production of transplant 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. • The association between the time post transplant and the intrapsychic dimension of paranoia was significant (P <.001). • This result could be connected to the fact that the more years after the transplant, the more the recipients feel the "threat" of possible organ loss and the inevitable resumption of the dialysis treatment. [ABSTRACT FROM AUTHOR]

Objectives: The oral carcinoma is a widespread pathology and still presents poor prognosis. Among the available procedures for its early detection, Narrow Band Imaging technique allows to assess potential vascular network abnormalities. The reliability of this technique in the detection of dysplastic and neoplastic oral lesions was evaluated in a preclinical and clinical study.Materials and Methods: In the preclinical study, a chemical oral carcinogen was administered to 50 mice to induct both dysplastic and neoplastic oral lesions. In the clinical study 91 patients, bearing suspicious premalignant and malignant oral lesions, have been included. Images of animals' and patients' lesions were acquired under white and Narrow Band Imaging light prior to biopsy. Two expert raters examined the images and classified lesions, which were eventually compared to the histological diagnosis. The diagnostic performance included sensitivity, specificity, positive likelihood ratio, positive and negative predictive values, accuracy, percentages and degree of agreement between raters' evaluation and the histological report.Results: In the preclinical study sensitivity ranged from 0.57 to 1, specificity from 0.85 to 0.99, positive likelihood ratio from 6.54 to 65.04, positive predictive values from 0.32 to 0.96, negative predictive values from 0.91 to 1 and accuracy from 0.86 to 0.98. In the clinical study sensitivity ranged from 0.63 to 0.99, specificity from 0.89 to 1, positive likelihood ratio from 8.45 to 61.47, positive predictive values from 0.59 to 0.96, negative predictive values from 0.78 to 1 and accuracy from 0.82 to 0.99.Conclusion: Narrow Band Imaging is an accurate technique, which holds a great potential for tumour angiogenesis evaluation and for the subsequent early detection of suspicious premalignant and malignant oral lesions. [ABSTRACT FROM AUTHOR]

Background and Objectives: 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. Methods: 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. Results: 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. Conclusion: Our study suggests that rs8076005 in the SLC6A4 gene may be a modulator of antidepressant response, especially when pharmacological treatment is used. [ABSTRACT FROM AUTHOR]

Conclusion: The study suggests that Mozart therapy could be a valid alternative to the common sound therapy methods in tinnitus patients. Objectives: The aim of the study was to evaluate the presence of the Mozart effect as indexed by a variation in tinnitus intensity and tolerability. Method: Sixty-two individuals aged between 22 and 78 years, reporting tinnitus for at least 1 year, were enrolled for the study. All patients attended a 1 h cognitive behavioral counseling session and listened to Mozart's sonata k448 for 1 h per day for a month. Afterwards patients listened to Beethoven's Für Elise sonata for 1 h per day for a month. To evaluate the general stress level, the impact of tinnitus on patients' quality of life, and the intensity of tinnitus, patients were invited to participate in three tests: the Measure du Stress Psychologique (MSP) questionnaire, the Tinnitus Handicap Inventory (THI), and a 0 to 10 visual analog scale (VAS). Results: For all the parameters investigated, MSP, THI, and intensity, there was a general significant improvement between the pre- and post-listening evaluation. A significant improvement, as regards THI and intensity, could already be appreciated after a single exposure to Mozart's sonata. [ABSTRACT FROM AUTHOR]

Abstract: LRTI are among the most common diseases in developed countries, including chronic obstructive pulmonary disease (COPD), one of the most frequent conditions. Their treatment in general practice is often unsuccessful and this increases hospital admissions. We know, bacterial infections in the elderly show a higher morbidity and mortality, either for more severe symptoms, than in younger adults, or because the causing agent often remains unknown. The need for a quick initiation of ABT often requires to chose on empirical grounds. To date there are no official guidelines for empirical ABT of COPD exacerbations, but only heterogeneous and often conflicting recommendations exist. The aim of our study was to identify a tool to guide the choice of the most effective empirical ABT when symptoms are acute and bacteriological tests cannot be performed. We used an ANN to study 117 patients aged between 55 and 97 years (mean 81.5±8.7 years) (±S.D.), admitted with a diagnosis of pneumonia, COPD exacerbation or pneumonia with respiratory failure. We registered symptoms at onset and some individual variables such as age, sex, risk factors, comorbidity, current drug therapies. Then the ANN was applied to choose ABT in 20 patients versus 20 subjects whose therapy was chosen by the physicians, comparing these groups for therapy''s efficacy, mean durations of therapy and hospitalization (H). In the learning phase, the ANN could predict the resolution index 99.05% of the time (i.e., 104 times) with a ±S.D.=0.23. After the training, during the test phase, the network predicted the resolution index 91.67% of the time (i.e., 11 times) with a ±S.D.=0.54, thus proving the validity of the relations identified during the learning phase. Preliminary results of the application of our tool, show the ANN allowed us to greatly reduce the duration of the ABT and subsequently of the H. Based on preliminary results, we assume that the use of ANN can make a valuable contribution in the choice of empirical ABT in the course of acute lung diseases in elderly. [Copyright &y& Elsevier]

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-βand 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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which addresses research indicating that music by the late composer Wolfgang Amadeus Mozart can play an important role in the rehabilitation of elderly adult patients with mild cognitive impairments, and it mentions spatial task performance and brain plasticity.

Abstract: 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. [Copyright &y& Elsevier]

Abstract: The zinc metalloenzyme glyoxalase I (GLO1) is thought to play a role in anxiety disorders because a reduced brain expression of GLO1 has been associated with increased anxiety-behaviours in mice. Recently, a functional Ala111Glu polymorphism in GLO1 has been shown to result in a reduced enzyme activity. The present study tested the hypothesis that this common genetic variant could confer susceptibility to panic disorder using an Italian population sample of 162 panic disorder patients and 288 matched controls. Statistical analysis failed to show association with the overall diagnosis of the disease. However, a weak but significant association was demonstrated between this polymorphism and panic disorder without agoraphobia. While our data suggest that this polymorphism is unlikely to have a major function in the pathogenesis of panic disorder, it could play a role in the subgroup of patients without agoraphobic avoidance. [Copyright &y& Elsevier]

Ankrd2 may be a link between the sarcomere and the nucleus; a similar role has recently been proposed for CARP that has a high level of structural and functional conservation with Ankrd2. Both Ankrd2 and CARP are involved in striated muscle hypertrophy. The mechanism by which muscle stretch is sensed and signals are transduced is still unknown; however, Ankrd2 and CARP could play similar roles in pathways leading to hypertrophy, the triggering mechanisms being heart pressure overload monitored by CARP and mechanical stretch in skeletal muscle monitored by Ankrd2. Recently Ankrd2 and CARP have been proposed as members of a family of muscle ankyrin repeat proteins (MARPs) that form a complex with titin, myopalladin and calpain protease p94, involved in signaling and regulation of gene expression in response to muscle stress. Here, we show that Ankrd2 is able to interact with the Z-disc protein telethonin as well as being able to interact with three transcription factors: YB-1, PML and p53. Ankrd2 binding to the ubiquitous transcription factor YB-1 can be demonstrated both in vitro and in vivo; this is not very surprising, since a similar interaction was previously described for CARP. However, the interactions with PML and p53 are unexpected new findings, with interesting implications in the Ankrd2 signaling cascade. Ankrd2 co-localizes with the transcriptional co-activator and co-repressor PML in nuclear bodies (NBs) in human myoblasts as detected by confocal immunofluorescence. Interestingly, we show that Ankrd2 not only binds the tumor suppressor protein p53 both in vitro and in vivo but also enhances the up-regulation of the p21WAFI/CIPI promoter by p53. Therefore, our findings strengthen the hypothesis that Ankrd2 may be involved in sensing stress signals and linking these to muscle gene regulation. [Copyright &y& Elsevier]

Background: Mutations in genes encoding intercalated disk/desmosome proteins, such as plakophilin 2 (PKP2), cause arrhythmogenic cardiomyopathy (ACM). Desmosomes are responsible for myocyte–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-α1 (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Poor adherence to pharmacotherapy negatively affects the course and the outcome of schizophreniaspectrum psychoses, enhancing the risk of relapse. Falloon and coworkers developed a Psychoeducation Program aimed at improving communication and problem-solving abilities in patients and their families. This study set out to evaluate changes in adherence to pharmacotherapy in patients diagnosed with schizophrenia-spectrum psychoses, by comparing one group exposed to the Falloon Psychoeducation Program (FPP) with another group exposed to family supportive therapy with generic information on the disorders.Methods: 340 patients diagnosed with schizophrenia and related disorders according to standardized criteria from 10 participating units distributed throughout the Italian National Health System (NHS), will be enrolled with 1:1 allocation by the method of blocks of randomized permutations. Patients will be reassessed at 6, 12 and 18 months after start of treatment (duration: 6 months).The primary objective is to evaluate changes in adherence to pharmacotherapy after psychoeducation. Adherence will be assessed at three-month intervals by measuring blood levels of the primary prescribed drug using high pressure liquid chromatography, and via the Medication Adherence Questionnaire and a modified version of the Adherence Interview. Secondary objectives are changes in the frequency of relapse and readmission, as the main indicator of the course of the disorder.Enrolled patients will be allocated to the FPP (yes/no) randomly, 1:1, in a procedure controlled by the coordinating unit; codes will be masked until the conclusion of the protocol (or the occurrence of a severe negative event). The raters will be blind to treatment allocation and will be tested for blinding after treatment completion. Intention-to-treat will be applied in considering the primary and secondary outcomes. Multiple imputations will be applied to integrate the missing data. The study started recruitment in February 2013; the total duration of the study is 27 months.Discussion: If the psychoeducation program proves effective in improving adherence to pharmacotherapy and in reducing relapse and readmissions, its application could be proposed as a standard adjunctive psychosocial treatment within the Italian NHS.Trial Registration: Protocol Registration System of ClinicalTrials.gov NCT01433094; registered on 20 August 2011; first patient was randomized on 12 February 2013. [ABSTRACT FROM AUTHOR]