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1.
Article in English | MEDLINE | ID: mdl-36673981

ABSTRACT

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.


Subject(s)
Bariatric Surgery , Obesity, Morbid , Adolescent , Humans , Obesity, Morbid/surgery , Obesity/epidemiology , Comorbidity , Weight Loss
2.
Article in English | MEDLINE | ID: mdl-36554394

ABSTRACT

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 [...].


Subject(s)
Bariatric Surgery , COVID-19 , Obesity, Morbid , Humans , Quality of Life/psychology , Pandemics , COVID-19/epidemiology , Bariatric Surgery/psychology , Obesity/epidemiology , Obesity/psychology
3.
Sci Transl Med ; 14(660): eabo0699, 2022 08 31.
Article in English | MEDLINE | ID: mdl-36044596

ABSTRACT

Therapies for patients with myocardial infarction and heart failure are urgently needed, in light of the breadth of these conditions and lack of curative treatments. To systematically identify previously unidentified cardioactive biologicals in an unbiased manner in vivo, we developed cardiac FunSel, a method for the systematic, functional selection of effective factors using a library of 1198 barcoded adeno-associated virus (AAV) vectors encoding for the mouse secretome. By pooled vector injection into the heart, this library was screened to functionally select for factors that confer cardioprotection against myocardial infarction. After two rounds of iterative selection in mice, cardiac FunSel identified three proteins [chordin-like 1 (Chrdl1), family with sequence similarity 3 member C (Fam3c), and Fam3b] that preserve cardiomyocyte viability, sustain cardiac function, and prevent pathological remodeling. In particular, Chrdl1 exerted its protective activity by binding and inhibiting extracellular bone morphogenetic protein 4 (BMP4), which resulted in protection against cardiomyocyte death and induction of autophagy in cardiomyocytes after myocardial infarction. Chrdl1 also inhibited fibrosis and maladaptive cardiac remodeling by binding transforming growth factor-ß (TGF-ß) and preventing cardiac fibroblast differentiation into myofibroblasts. Production of secreted and circulating Chrdl1, Fam3c, and Fam3b from the liver also protected the heart from myocardial infarction, thus supporting the use of the three proteins as recombinant factors. Together, these findings disclose a powerful method for the in vivo, unbiased selection of tissue-protective factors and describe potential cardiac therapeutics.


Subject(s)
Heart Failure , Myocardial Infarction , Secretome , Animals , Cytokines/metabolism , Dependovirus/genetics , Disease Models, Animal , Eye Proteins/metabolism , Fibrosis , Heart Failure/drug therapy , Heart Failure/metabolism , Mice , Mice, Inbred C57BL , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Myocytes, Cardiac/metabolism , Myofibroblasts/pathology , Neoplasm Proteins/metabolism , Nerve Tissue Proteins/metabolism , Ventricular Remodeling
4.
Environ Int ; 164: 107272, 2022 06.
Article in English | MEDLINE | ID: mdl-35526297

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Aerosols , Humans , Lasers , Pandemics , Sterilization
5.
Nat Commun ; 13(1): 81, 2022 01 10.
Article in English | MEDLINE | ID: mdl-35013172

ABSTRACT

Despite the high prevalence of ischemic heart diseases worldwide, no antibody-based treatment currently exists. Starting from the evidence that a specific isoform of the Bone Morphogenetic Protein 1 (BMP1.3) is particularly elevated in both patients and animal models of myocardial infarction, here we assess whether its inhibition by a specific monoclonal antibody reduces cardiac fibrosis. We find that this treatment reduces collagen deposition and cross-linking, paralleled by enhanced cardiomyocyte survival, both in vivo and in primary cultures of cardiac cells. Mechanistically, we show that the anti-BMP1.3 monoclonal antibody inhibits Transforming Growth Factor ß pathway, thus reducing myofibroblast activation and inducing cardioprotection through BMP5. Collectively, these data support the therapeutic use of anti-BMP1.3 antibodies to prevent cardiomyocyte apoptosis, reduce collagen deposition and preserve cardiac function after ischemia.


Subject(s)
Antibodies, Monoclonal/pharmacology , Bone Morphogenetic Protein 1/genetics , Cardiotonic Agents/pharmacology , Cicatrix/genetics , Endomyocardial Fibrosis/genetics , Myocardial Infarction/genetics , Animals , Bone Morphogenetic Protein 1/antagonists & inhibitors , Bone Morphogenetic Protein 1/metabolism , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolism , Bone Morphogenetic Protein 5/genetics , Bone Morphogenetic Protein 5/metabolism , Case-Control Studies , Cell Survival/drug effects , Cicatrix/etiology , Cicatrix/metabolism , Cicatrix/prevention & control , Disease Models, Animal , Endomyocardial Fibrosis/etiology , Endomyocardial Fibrosis/metabolism , Endomyocardial Fibrosis/prevention & control , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression Regulation , Humans , Mice , Mice, Inbred C57BL , Myocardial Infarction/complications , Myocardial Infarction/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Primary Cell Culture , Protein Isoforms/genetics , Protein Isoforms/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Troponin T/genetics , Troponin T/metabolism
6.
Children (Basel) ; 8(3)2021 Mar 08.
Article in English | MEDLINE | ID: mdl-33800320

ABSTRACT

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.

7.
Psychiatry Res ; 300: 113908, 2021 06.
Article in English | MEDLINE | ID: mdl-33836473

ABSTRACT

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.


Subject(s)
Bullying , Crime Victims , Cyberbullying , Adolescent , Aged , Aggression , Female , Humans , Internet , Male , Peer Group
8.
G Ital Nefrol ; 38(1)2021 Feb 16.
Article in English | MEDLINE | ID: mdl-33599427

ABSTRACT

Background: Living donor kidney transplantation (LDKT) is the treatment of choice for end stage renal disease. LDKT involves complex psychosocial issues, which remain partially unexplored. Methods: The study involved all potential living donors and recipient pairs consecutively referred for psychosocial evaluation from the nephrologist. Clinical and sociodemographic variables including prior psychiatric history, previous and current use of psychopharmacological therapy, motivation and information about the transplant procedure were collected. Study participants completed the Symptom Checklist-90-R (SCL-90-R) to assess psychopathological distress. Results: Fifty-three donor/recipient pairs underwent psychiatric and psychological evaluation. Seven subjects (13%) in the recipient group and 13 subjects (25%) in the donor group reported a history of psychological distress and/or psychiatric conditions. A psychiatric diagnosis was confirmed in 4 recipients (7.5% of the study sample, including autism spectrum disorder, histrionic personality disorder, and anxiety-depressive disorders) and 5 donors (9%, including narcissistic personality disorder in one case and anxiety-depressive disorders). SCL-90-R GSI mean scores were 0.3 ±0.3 and 0.2 ±0.2 for the recipient and donor groups, respectively. Overall, 8 couples (15%) suspended the living donation pathway before transplantation. Four couples were excluded for a new onset medical condition. The psychological and psychiatric evaluation excluded one candidate. One couple dropped out before completing the scheduled exams. One recipient refused to undergo crossover renal transplantation, while 1 donor candidate withdrew her consent for transplantation at the end of the evaluation process. Conclusions: Limited but significant psychopathological distress in donors and recipients supports the usefulness of psychiatric and psychological competencies within the transplant team.


Subject(s)
Autism Spectrum Disorder , Kidney Failure, Chronic , Kidney Transplantation , Depression , Female , Humans , Kidney Failure, Chronic/surgery , Living Donors
9.
Article in English | MEDLINE | ID: mdl-33172015

ABSTRACT

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.


Subject(s)
Behavior, Addictive/epidemiology , Internet Addiction Disorder , Psychopathology , Video Games , Adolescent , Adult , Female , Humans , Internet , Italy/epidemiology , Male , Young Adult
11.
Transplant Proc ; 52(5): 1539-1543, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32387079

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Kidney Transplantation/psychology , Living Donors/psychology , Parent-Child Relations , Parents/psychology , Transplant Recipients/psychology , Adult , Child , Emotions , Female , Hospitals, University , Humans , Male , Middle Aged , Postoperative Period , Preoperative Period , Surveys and Questionnaires
12.
Transplant Proc ; 52(5): 1570-1576, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32229045

ABSTRACT

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.


Subject(s)
Adaptation, Psychological , Defense Mechanisms , Kidney Transplantation/psychology , Quality of Life , Adult , Anxiety , Emotions , Female , Humans , Male , Middle Aged , Self Concept , Surveys and Questionnaires
13.
Front Psychiatry ; 11: 106, 2020.
Article in English | MEDLINE | ID: mdl-32194453

ABSTRACT

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.

14.
Amyloid ; 27(3): 168-173, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32212933

ABSTRACT

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.


Subject(s)
Electric Impedance/therapeutic use , Heart/physiopathology , Immunoglobulin Light Chains/genetics , Immunoglobulin Light-chain Amyloidosis/therapy , Adult , Aged , Female , Heart/radiation effects , Humans , Immunoglobulin Light-chain Amyloidosis/pathology , Kaplan-Meier Estimate , Male , Malnutrition/diagnosis , Prognosis , Proportional Hazards Models , Prospective Studies , Quality of Life
15.
J Cancer Educ ; 35(5): 1041-1045, 2020 10.
Article in English | MEDLINE | ID: mdl-31786799

ABSTRACT

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.


Subject(s)
Breast Neoplasms/psychology , Intimate Partner Violence/psychology , Intimate Partner Violence/statistics & numerical data , Mastectomy/psychology , Spouses/psychology , Stress, Psychological , Breast Neoplasms/surgery , Female , Humans , Middle Aged
16.
Cells ; 8(12)2019 12 14.
Article in English | MEDLINE | ID: mdl-31847412

ABSTRACT

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.


Subject(s)
MicroRNAs/genetics , Myocytes, Cardiac/metabolism , Plakophilins/genetics , Animals , Cell Adhesion/genetics , Cell Adhesion/physiology , Cell Line , Cell Plasticity , Cytoskeleton/metabolism , Desmosomes/metabolism , Mice , Myocardium/metabolism , Plakophilins/metabolism
17.
Transplant Proc ; 51(9): 2931-2935, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31607624

ABSTRACT

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.


Subject(s)
Kidney Transplantation/psychology , Nonverbal Communication , Psychological Tests , Psychopathology/instrumentation , Transplant Recipients/psychology , Adult , Female , Humans , Male , Middle Aged , Quality of Life
18.
NPJ Biofilms Microbiomes ; 5(1): 29, 2019.
Article in English | MEDLINE | ID: mdl-31602310

ABSTRACT

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.


Subject(s)
Biofilms/growth & development , Biofilms/radiation effects , Lasers , Light , Oxidative Stress , Pseudomonas aeruginosa/growth & development , Pseudomonas aeruginosa/radiation effects , Animals , Cell Line , Culture Media , Disease Models, Animal , Humans , Mice, Inbred C57BL , Models, Biological , Pseudomonas Infections/therapy , Radiotherapy/methods , Treatment Outcome , Wound Infection/therapy
19.
G Ital Nefrol ; 36(3)2019 Jun 11.
Article in Italian | MEDLINE | ID: mdl-31251004

ABSTRACT

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.


Subject(s)
Living Donors/psychology , Personality , Humans , Personality Tests
20.
JCI Insight ; 4(8)2019 04 18.
Article in English | MEDLINE | ID: mdl-30996132

ABSTRACT

Fibrosis is a hallmark in the pathogenesis of various diseases, with very limited therapeutic solutions. A key event in the fibrotic process is the expression of contractile proteins, including α-smooth muscle actin (αSMA) by fibroblasts, which become myofibroblasts. Here, we report the results of a high-throughput screening of a library of approved drugs that led to the discovery of haloperidol, a common antipsychotic drug, as a potent inhibitor of myofibroblast activation. We show that haloperidol exerts its antifibrotic effect on primary murine and human fibroblasts by binding to sigma receptor 1, independent from the canonical transforming growth factor-ß signaling pathway. Its mechanism of action involves the modulation of intracellular calcium, with moderate induction of endoplasmic reticulum stress response, which in turn abrogates Notch1 signaling and the consequent expression of its targets, including αSMA. Importantly, haloperidol also reduced the fibrotic burden in 3 different animal models of lung, cardiac, and tumor-associated fibrosis, thus supporting the repurposing of this drug for the treatment of fibrotic conditions.


Subject(s)
Fibrosis/drug therapy , Haloperidol/pharmacology , Myofibroblasts/drug effects , Receptors, sigma/metabolism , Actins/metabolism , Animals , Calcium/metabolism , Cell Differentiation/drug effects , Cells, Cultured , Disease Models, Animal , Drug Repositioning , Endoplasmic Reticulum Stress/drug effects , Fibrosis/pathology , Haloperidol/therapeutic use , Humans , Intravital Microscopy/methods , Lung/cytology , Lung/pathology , Mice , Myocardium/cytology , Myocardium/pathology , Myofibroblasts/pathology , Optical Imaging/methods , Primary Cell Culture , RNA Interference , RNA, Small Interfering/metabolism , Receptor, Notch1/metabolism , Receptors, sigma/genetics , Signal Transduction/drug effects , Signal Transduction/genetics , Sigma-1 Receptor
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