Mitochondrial Transfer Between Mesenchymal Stem Cells and Cancer Cells.

Mitochondrial transfer (MT) is a biological process that allows a donor cell to horizontally share its own mitochondria with a recipient cell. Mitochondria are highly dynamic membrane-bound sub-cellular organelles prominently involved in the regulation of the cell energy balance, calcium homeostasis, and apoptotic machinery activation. They physiologically undergo fusion and fission processes in response to the cell requirement, with a continuous morphological re-arrangement. This structural and functional plasticity is at the basis of the MT, described in tissue regeneration, cardiac and neurological diseases, as well as in cancer. Here, the MT has been observed in the tumor micro-environment (TME) from the adipose-derived stem cells (ASCs) to the cancer cells, eventually reverting the lack of the mitochondria respiration function, or enhancing their motility and drug resistance. In this chapter, we outline some key protocols for evaluating this exciting phenomenon of MT. These methodological and technical approaches are very important, considering all the limitations that scientists constantly face, especially in this field of the research.

Cancer Stem Cells: Detection and Characterization from Solid Tumors.

Cancer stem cells (CSCs) have emerged as an attractive research interest due to their prominent role in development of the tumors. CSCs are rare dormant cells that can self-renew and maintain tumor development and heterogeneity. A better understanding of CSCs can improve tumor classification and contribute toward the development of novel therapeutic approaches to fight cancer. Hence, it is of immense importance to comprehend the basic function of CSCs in tumor formation, which can only be possible by devising perfected methodologies to isolate, detect, and characterize them. In this chapter, we outline the key protocols to culture, identify, and isolate CSCs from solid tumors to further advance basic and clinical investigation related to CSCs and their role in tumor biology.

When does shared decision making is adopted in psychiatric clinical practice? Results from a European multicentric study.

To identify factors associated with the use of shared decision making in routine mental health care in a large multicenter European study. Data have been collected within the study "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR), which is a naturalistic, longitudinal, observational study carried out in six European countries. Patients with a severe mental illness attending outpatient units and their treating clinicians have been recruited. Clinicians' Clinical Decision Making (CDM) styles have been explored through the Clinical Decision Making Style Scale. Patients' clinical and social outcomes have been assessed through validated assessment instruments. The sample consisted of 588 patients and 213 professionals. Professionals were mainly psychiatrists (35.7%), nurses (21.6%), support workers, social workers or occupational therapists (24.9%), psychologists (9.9%) or trainees in psychiatry (4.7%). In the majority of cases, clinicians adopted a shared CDM style. Shared CDM was more frequently adopted with patients with psychotic disorders, with a better quality of life and social functioning. At multivariate analyses, the likelihood of adopting shared decision making increased in patients with higher levels of interpersonal relationships' skills (p < 0.05) and global functioning (p < 0.01). On the contrary, being a trainee in psychiatry reduced the likelihood of adopting shared CDM (p < 0.008). Shared decision making has been adopted mainly when patients have a better functioning and less severe clinical symptomatology and by less trained clinicians, differently from national and international recommendations. More efforts should be made to implement interventions to promote shared CDM, with a specific focus for trainees in psychiatry.

Corrigendum to: Phosphonium Salt Displays Cytotoxic Effects Against Human Cancer Cell Lines.

Due to an oversight one of the author's name was published wrong in the article entitled "Phosphonium Salt Displays Cytotoxic Effects Against Human Cancer Cell Lines" in "Anti-Cancer Agents in Medicinal Chemistry, 2015, Vol. 17, No. 13. pp. 1796."The correct names of all authors are given below:Dhanyalayam D, Palma G, Cappello AR, Mariconda A, Sinicropi MS, Giordano F, Del Vecchio V, Ramunno A, Arra C, Longo P, Saturnino C.

Participation in medical decision-making across Europe: An international longitudinal multicenter study.

BACKGROUND: The purpose of this paper was to examine national differences in the desire to participate in decision-making of people with severe mental illness in six European countries. METHODS: The data was taken from a European longitudinal observational study (CEDAR; ISRCTN75841675). A sample of 514 patients with severe mental illness from the study centers in Ulm, Germany, London, England, Naples, Italy, Debrecen, Hungary, Aalborg, Denmark and Zurich, Switzerland were assessed as to desire to participate in medical decision-making. Associations between desire for participation in decision-making and center location were analyzed with generalized estimating equations. RESULTS: We found large cross-national differences in patients' desire to participate in decision-making, with the center explaining 47.2% of total variance in the desire for participation (P<0.001). Averaged over time and independent of patient characteristics, London (mean=2.27), Ulm (mean=2.13) and Zurich (mean=2.14) showed significantly higher scores in desire for participation, followed by Aalborg (mean=1.97), where scores were in turn significantly higher than in Debrecen (mean=1.56). The lowest scores were reported in Naples (mean=1.14). Over time, the desire for participation in decision-making increased significantly in Zurich (b=0.23) and decreased in Naples (b=-0.14). In all other centers, values remained stable. CONCLUSIONS: This study demonstrates that patients' desire for participation in decision-making varies by location. We suggest that more research attention be focused on identifying specific cultural and social factors in each country to further explain observed differences across Europe.

Psychometric validation of the Italian version of the Reported and Intended Behaviour Scale (RIBS).

BACKGROUND: Many instruments have been developed and validated to assess the stigma associated with mental disorders and its various domains across different populations. To our knowledge, the Reported and Intended Behaviour Scale (RIBS) is the only validated questionnaire to analyse the presence of reported and intended stigmatising/discriminatory behaviours towards people with mental health problems in the general population. The aims of the study presented herein are to translate and validate the RIBS in Italian language and to adapt it to the Italian socio-cultural background (RIBS-I). METHOD: The RIBS considers reported and intended behaviours across four different domains: (1) living with, (2) working with, (3) living nearby and (4) continuing a relationship with someone with a mental health problem. The validation process included four phases: (1) translation/back translation of the questionnaire from English to Italian and vice versa; (2,3) face validity and reliability of RIBS-I; (4) description of model fit through confirmatory factor analysis. The questionnaire was administered to a sample of the general public via distribution in public places such as shopping centres, markets, squares, cinemas and other gathering places. Questionnaires were administered by trained mental health professionals. RESULTS: A total of 447 lay respondents were recruited. The mean age was 38.08 (s.d. = ±14.74) years. Fifty-seven per cent of the sample (n = 257) were female. The Cronbach alpha of RIBS-I was 0.83. All indices of model fit were above the reference values: Goodness of Fit Index (GFI) = 0.987 (GFI > 0.9); Adjusted Goodness of Fit Index (AGFI) = 0.975 (AGFI > 0.9); Comparative Fit Index (CFI) = 0.994 (CFI > 0.9); and Root-Mean-Square Error of Approximation (RMSEA) = 0.023 (RMSEA < 0.05). The χ 2 = 23.60 (df = 19; p = 0.21) and χ 2/df = 1.24 supported the model. CONCLUSIONS: The RIBS-I demonstrated good psychometric properties and it can be considered a useful tool to: (1) assess stigmatising (actual or potential) behaviours in the general population; (2) test the efficacy of anti-stigma campaigns and actions; (3) design further studies to better understand the relationship between the three different components of stigmatisation: knowledge, attitudes and behaviours.

Perceived insecurity, mental health and urbanization: Results from a multicentric study.

AIMS: This article aims to (1) explore the levels of perceived insecurity in a sample of patients with mood or anxiety disorders and (2) assess whether living in 'big cities' can influence the levels of patients' perceived insecurity and social contacts compared to living in a non-urbanized context. METHODS: A total of 24 Italian mental health centers (MHCs) have been invited to participate. Twenty patients consecutively accessing the MHC have been recruited. All patients have been assessed using validated assessment tools. RESULTS: The sample consisted of 426 patients, mostly female, with a mean age of 45 years. Globally, 52.2% of patients had a diagnosis of mood disorders, and 37.8% had anxiety disorders. Half of the sample declared that the main feeling toward life is uncertainty; higher levels of pessimistic views toward life have been detected in patients living in urban areas. A positive association between negative attitudes toward life and higher levels of depressive and anxiety symptoms, poor social functioning and higher levels of perceived psychological distress has been found. CONCLUSION: Our findings confirm the presence of a common sense of perceived uncertainty among our sample. Such attitude toward life can have a detrimental impact on patients' psychological and physical well-being, contributing to high levels of distress.

Feasibility of a psychoeducational family intervention for people with bipolar I disorder and their relatives: Results from an Italian real-world multicentre study.

BACKGROUND: Despite several guidelines recommend the use of psychoeducational family interventions (PFIs) as add-on in the treatment of patients with bipolar I disorder, their implementation on a large scale remains limited. The aim of the present study is to identify obstacles for the feasibility of PFIs in routine care. METHODS: This was a multicentre, real-world, controlled, outpatient trial, carried out in 11 randomly recruited Italian mental health centres. Two mental health professionals from each center attended a modular training course on PFI and provided the intervention. Difficulties and benefits experienced by mental health professionals in implementing the intervention were assessed through the Family Intervention Schedule (FIS-R), which was administered six times. RESULTS: Sixteen out of the 22 recruited professionals completed the training and administered the PFI to 70 patients with bipolar I disorder and their relatives. The retention rate of families receiving the intervention was 93%. Mental health professionals reported high levels of organizational difficulties, several benefits in their daily clinical work and low levels of intervention-related difficulties. The most important organizational obstacles were related to the need to integrate the intervention with other work responsibilities and to the lack of time to carry out the intervention. These difficulties did not decrease over time. Intervention-related difficulties were rated as less problematic since the first time assessment and tended to improve over time. LIMITATIONS: Low number of recruited professionals; use of a not previously validated assessment instrument. CONCLUSIONS: PFIs are feasible in routine care for the treatment of patients with bipolar I disorder and their relatives, and main obstacles are related to the organization/structure of mental health centres, and not to the characteristics of the intervention itself.

Empowerment and satisfaction in a multinational study of routine clinical practice.

OBJECTIVE: Decision-making between mental health clinicians and patients is under-researched. We tested whether mental health patients are more satisfied with a decision made (i) using their preferred decision-making style and (ii) with a clinician with the same decision-making style preference. METHOD: As part of the CEDAR Study (ISRCTN75841675), a convenience sample of 445 patients with severe mental illness from six European countries were assessed for desired clinical decision-making style (rated by patients and paired clinicians), decision-specific experienced style and satisfaction. RESULTS: Patients who experienced more involvement in decision-making than they desired rated higher satisfaction (OR=2.47, P=0.005, 95% CI 1.32-4.63). Decisions made with clinicians whose decision-making style preference was for more active involvement than the patient preference were rated with higher satisfaction (OR=3.17, P=0.003, 95% CI 1.48-6.82). CONCLUSION: More active involvement in decision-making than the patient stated as desired was associated with higher satisfaction. A clinical orientation towards empowering, rather than shared, decision-making may maximise satisfaction.

Risk of burnout among early career mental health professionals.

Burnout is a stress-related syndrome that often affects mental health professionals (MHPs) and may have serious consequences on personal well-being as well as on the quality of provided psychiatric care. Established literature shows a high risk to develop burnout among MHPs. Few data are available on the incidence and on the clinical implications of the burnout syndrome in the early phases of MHP professional career. We confirmed the presence of burnout among early career MHPs: early career psychiatrists showed a lower sense of personal accomplishment, while non-medical MHPs tended to have more depersonalization and suffered from higher levels of depression. Specific programmes to identify the presence of the burnout syndrome and to cope with it should be taught within mental health training curricula. Burnout is a stress-related syndrome that often affects professionals working in emotionally loaded and highly interpersonal environments. Mental health professionals (MHPs) are long known to be at high risk to develop the burnout syndrome, but this has rarely been investigated in professionals in an early phase of career. The aim of the present study was to evaluate the presence of the burnout syndrome and of depressive symptoms among early career psychiatrists and 'non-medical' MHPs. One hundred MHPs (including 50 psychiatrists and 50 non-medical MHPs) were screened for the presence of burnout and depression, with the Maslach Burnout Inventory and the Beck Depression Inventory - revised, respectively. The relationships of burnout with socio-demographical and professional characteristics were also explored. We confirmed the presence of burnout among both groups of early career MHPs, but psychiatrists had a significantly higher degree of emotional exhaustion and a lower sense of personal accomplishment, while non-medical MHPs adopted more frequently depersonalization as a coping strategy and had higher scores for depression, which is associated with higher level of burnout. The risk of developing burnout should be properly addressed in training curricula and strategies to overcome it should be systematically taught, in order to promote personal well-being and efficient team work in mental health settings.

Patient characteristics and symptoms associated with perceived coercion during hospital treatment.

OBJECTIVE: Large numbers of psychiatric patients either are involuntarily admitted to hospital treatment or feel coerced despite a legally voluntary admission. For ethical and clinical reasons, their perceived coercion should be reduced as far as possible. There is however limited evidence on patient characteristics associated with perceived coercion during hospital treatment. This study aimed to identify i) sociodemographic and clinical characteristics associated with perceived coercion at admission and ii) changes in symptoms and global functioning associated with changes in perceived coercion over time. METHOD: Three thousand and ninety three in-patients who were involuntarily admitted or felt coerced to hospital treatment despite a legally voluntary admission were recruited in the European evaluation of coercion in psychiatry and harmonization of best clinical practice - EUNOMIA project in 11 European countries. Perceived coercion, global functioning and symptoms were assessed after admission and at a 3-month follow-up. RESULTS: Involuntary admission, female gender, poorer global functioning and more positive symptoms were associated with higher levels of perceived coercion at admission. Perceived coercion significantly decreased over time, and the improvements in global functioning and positive symptoms were associated with reduction in perceived coercion. CONCLUSION: Female patients perceive more coercion in psychiatric hospital treatment. Effective treatment for positive symptoms and improving patients' global functioning may lead to a reduction in perceived coercion.

How to improve clinical practice on involuntary hospital admissions of psychiatric patients: suggestions from the EUNOMIA study.

Number and procedures of involuntary hospital admissions vary in Europe according to the different socio-cultural contexts. The European Commission has funded the EUNOMIA study in 12 European countries in order to develop European recommendations for good clinical practice in involuntary hospital admissions. The recommendations have been developed with the direct and active involvement of national leaders and key professionals, who worked out national recommendations, subsequently summarized into a European document, through the use of specific categories. The need for standardizing the involuntary hospital admission has been highlighted by all centers. In the final recommendations, it has been stressed the need to: providing information to patients about the reasons for hospitalization and its presumable duration; protecting patients' rights during hospitalization; encouraging the involvement of family members; improving the communication between community and hospital teams; organizing meetings, seminars and focus-groups with users; developing training courses for involved professionals on the management of aggressive behaviors, clinical aspects of major mental disorders, the legal and administrative aspects of involuntary hospital admissions, on communication skills. The results showed the huge variation of involuntary hospital admissions in Europe and the importance of developing guidelines on this procedure.

Molecular characterisation of a field strain of bubaline herpesvirus isolated from buffaloes (Bubalus bubalis) after pharmacological reactivation.

Two healthy buffaloes (Bubalus bubalis) in a herd which had not been vaccinated against infectious bovine rhinotracheitis (IBR), were selected for their seropositivity for anti-bovine herpesvirus type 1 (BoHV-1) glycoprotein E antibodies, and injected intramuscularly daily with dexamethasone for five consecutive days (day 1 to day 5) to reactivate any latent herpesvirus. Blood samples and nasal and vaginal swabs were collected daily from day 5 to day 15 from each buffalo for virological examination. All the vaginal swabs and blood samples were negative, but 13 of the 22 nasal swabs were positive; a cytopathic effect was observed in primary cultures of bovine fetal lung cells, and the viral isolates were identified as a herpesvirus by PCR. The viral strains were characterised by the sequence analysis of the genes coding for glycoproteins D and B, and the gene sequences were then used for phylogenetic analysis. The isolates from both buffaloes appeared identical at the level of the two genes, and were more closely related to bovine herpesvirus type 5 than to BoHV-1.

Use of long-range repetitive element polymorphism-PCR to differentiate Bacillus anthracis strains.

The genome of Bacillus anthracis is extremely monomorphic, and thus individual strains have often proven to be recalcitrant to differentiation at the molecular level. Long-range repetitive element polymorphism-PCR (LR REP-PCR) was used to differentiate various B. anthracis strains. A single PCR primer derived from a repetitive DNA element was able to amplify variable segments of a bacterial genome as large as 10 kb. We were able to characterize five genetically distinct groups by examining 105 B. anthracis strains of diverse geographical origins. All B. anthracis strains produced fingerprints comprising seven to eight bands, referred to as "skeleton" bands, while one to three "diagnostic" bands differentiated between B. anthracis strains. LR REP-PCR fingerprints of B. anthracis strains showed very little in common with those of other closely related species such as B. cereus, B. thuringiensis, and B. mycoides, suggesting relative heterogeneity among the non-B. anthracis strains. Fingerprints from transitional non-B. anthracis strains, which possessed the B. anthracis chromosomal marker Ba813, scarcely resembled those observed for any of the five distinct B. anthracis groups that we have identified. The LR REP-PCR method described in this report provides a simple means of differentiating B. anthracis strains.

DNA fingerprinting of Candida rugosa via repetitive sequence-based PCR.

A repetitive sequence-based PCR (rep-PCR) technique was developed to characterize the genotypic relatedness among Candida rugosa isolates. Two repetitive sequences, viz., Care-2 and Com29 from Candida albicans, were used to design primers Ca-21, Ca-22, and Com-21, respectively. When used alone or in combination, these primers generated discriminatory fingerprints by amplifying the adjacent variable regions of the genome. Twenty-three isolates from burn patients, eight from other human sources, and four C. rugosa isolates pathogenic in animals were placed into nine fingerprinting groups. Different primers placed these isolates into identical groups, indicating that rep-PCR is a specific and reproducible technique for molecular characterization of C. rugosa. Moreover, these primers unequivocally discriminated among other important Candida species such as C. albicans, C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, C. kefyr, and C. lusitaniae. These data confirm the conservation of repetitive sequences in Candida species. Because of its ease and sensitivity, rep-PCR offers a relatively rapid and discriminatory method for molecular typing of C. rugosa in outbreaks.

Molecular genotyping of methicillin-resistant Staphylococcus aureus via fluorophore-enhanced repetitive-sequence PCR.

Methicillin resistance in Staphylococcus aureus is a frequent cause of nosocomial and community-acquired infections. Accurate, rapid epidemiologic typing is crucial to the identification of the source and spread of infectious disease and could provide detailed information on the generation of methicillin-resistant S. aureus (MRSA) strains. The high degree of genetic relatedness of MRSA strains has precluded the use of more conventional methods of genetic fingerprinting. A rapid DNA fingerprinting method that exploits PCR amplification from a DNA repeat sequence in MRSA is described. The random chromosomal distribution of this repeat sequence provides an ideal target for detecting DNA fragment patterns specific to individual MRSA strains. Two PCR fingerprinting methods which use an oligonucleotide primer based on a repetitive sequence found in Mycoplasma pneumoniae are presented. The repetitive element sequence-based PCR (rep-PCR) and fluorophore-enhanced rep-PCR (FERP) can identify epidemic strains among background MRSA. The combination of oligonucleotide primers labeled with different fluorescent dyes allowed simultaneous FERP fingerprinting and mecA gene detection. Eight different fingerprint patterns were observed in MRSA strains collected from different sources. These techniques provide a rapid discriminatory means of molecular epidemiologic typing of MRSA involved in nosocomial infections.