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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

Obesity is increasingly prevalent among adolescents. Clinical and research data support the use of bariatric surgery (BS) as a treatment option for severely obese adolescents, with good results in terms of weight loss, improvement or resolution of comorbidities, and compliance to follow up. Nevertheless, concerns still remain, with significant disparities among countries and ethical concerns mainly raised by performing an irreversible and invasive procedure in adolescence, with potential life-long alterations. In this context, the purpose of this narrative review was to discuss the main current ethical challenges in performing BS in adolescence and to inform appropriate clinical management in the field. The core ethical principles of autonomy, beneficence, nonmaleficence, and justice were revised in terms of patient-centered healthcare through the lens of psychosocial implications. The review concludes with a discussion regarding the potential directives for future research for effective, patient-centered, and ethical management of obesity in the adolescent population.

Obesity is a major worldwide health problem, causing an ongoing and decades-long pandemic, which the WHO has termed the “global obesity epidemic”, concurrent with the COVID-19 pandemic [...]

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...

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.

The term Samaritan is used to indicate the choice of a living donor to offer its own organ to save the life of a patient with whom it has no parental or affective relation (article 1, Law of 26 June 1967). It is a gesture of great solidarity, one that promotes life. The purpose of this study has been to analyze a case of potential Samaritan donation. The investigation consisted of six interviews, on a bi-weekly basis, for a total duration of three months. The clinical interviews allowed us to delve deeper into the motivations for the donation. The following tests were administered: the Rorschach projective test, the Millon Clinical Multiaxial Inventory Personality Test (MCMI-III) and the Symptom Checklist-90-Revised (SCL-90-R). Some issues regarding age, self-confidence, emotional difficulties and maladjustment to social environment emerged. The analysis of the test results confirmed the "negative" indices that led the authors to decide against the psychological-psychiatric suitability for the Samaritan donation. The Samaritan donation is a rare and precious donation and understanding in depth the motivations behind this choice is extremely important. The choice to donate, even if freely made, must not make one forget their responsibility towards themselves and towards the integrity of their own body.

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.

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.

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.