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.

Toward hyperuniform disordered plasmonic nanostructures for reproducible surface-enhanced Raman spectroscopy.

We report on the self-assembling of clusters of gold-nanoparticles (Au-NPs) directed by the phase separation of poly(styrene)-b-poly(methylmethacrylate) (PS-b-PMMA) block-copolymer (BCP) on indium tin oxide coated glass, which induces the onset of vertical lamellar domains. After thermal evaporation of gold on BCP, Au-NPs of 4 nm are selectively included into PS-nanodomains by thermal annealing, and then clustered with large density of hot spots (> 10(4) µm(2)) in a random two-dimensional pattern. The resulting nanostructure exhibits near-hyperuniform long-range correlations. The consequent large degree of homogeneity of this isotropic plasmonic pattern gives rise to a highly reproducible Surface-Enhanced Raman Scattering (SERS) enhancement factor over the centimeter scale (std. dev. ∼ 10% over 0.25 cm(2)). We also discuss the application of a static electric field for modulating the BCP host morphology. The electric field induces an alignment of Au-NP clusters into ordered linear chains, exhibiting a stronger SERS activity, but reduced SERS spatial reproducibility.

Rest perfusion abnormalities in hypertrophic cardiomyopathy: correlation with myocardial fibrosis and risk factors for sudden cardiac death.

AIM: To measure the prevalence of abnormal rest perfusion in a population of consecutive patients with known hypertrophic cardiomyopathy (HCM) referred for cardiovascular MRI (CMR), and to assess any associations between abnormal rest perfusion and the presence, pattern, and severity of myocardial scar and the presence of risk factors for sudden death. MATERIALS AND METHODS: Eighty consecutive patients with known HCM referred for CMR underwent functional imaging, rest first-pass perfusion, and late gadolinium enhancement (LGE). RESULTS: Thirty percent of the patients had abnormal rest perfusion, all of them corresponding to areas of mid-myocardial LGE and to a higher degree of segmental hypertrophy. Rest perfusion abnormalities correlated with more extensive and confluent LGE. The subgroup of patients with myocardial fibrosis and rest perfusion abnormalities (fibrosis+/perfusion+) had more than twice the incidence of episodes of non-sustained ventricular tachycardia on Holter monitoring in comparison to patients with myocardial fibrosis and normal rest perfusion (fibrosis+/perfusion-) and patients with no fibrosis and normal rest perfusion (fibrosis-/perfusion-). CONCLUSIONS: First-pass perfusion CMR identifies abnormal rest perfusion in a significant proportion of patients with HCM. These abnormalities are associated with the presence and distribution of myocardial scar and the degree of hypertrophy. Rest perfusion abnormalities identify patients with increased incidence of episodes of non-sustained ventricular tachycardia on Holter monitoring, independently from the presence of myocardial fibrosis.

Tyrosine phosphorylation of estradiol receptor by Src regulates its hormone-dependent nuclear export and cell cycle progression in breast cancer cells.

We report that in breast cancer cells, tyrosine phosphorylation of the estradiol receptor alpha (ERalpha) by Src regulates cytoplasmic localization of the receptor and DNA synthesis. Inhibition of Src or use of a peptide mimicking the ERalpha p-Tyr537 sequence abolishes ERalpha tyrosine phosphorylation and traps the receptor in nuclei of estradiol-treated MCF-7 cells. An ERalpha mutant carrying a mutation of Tyr537 to phenylalanine (ER537F) persistently localizes in nuclei of various cell types. In contrast with ERalpha wt, ER537F does not associate with Ran and its interaction with Crm1 is insensitive to estradiol. Thus, independently of estradiol, ER537F is retained in nuclei, where it entangles FKHR-driving cell cycle arrest. Chromatin immunoprecipitation analysis reveals that overexpression of ER537F in breast cancer cells enhances FKHR interaction with cyclin D1 promoter. This mutant also counteracts cell transformation by the activated forms of Src or PI3-K. In conclusion, in addition to regulating receptor localization, ERalpha phosphorylation by Src is required for hormone responsiveness of DNA synthesis in breast cancer cells.

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.

Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptor α and ß.

Raloxifene (RAL), a selective estrogen receptor (ER) modulator (SERM) seems to induce apoptosis in both androgen-dependent and -independent prostate cell (PC) lines via activation of ERß and an antagonistic effect on ERα. In this study, we evaluated the effects of RAL on epithelial PC growth using the two following in vitro models: the androgen-dependent cell line EPN which expressed both ERs; and a stabilized epithelial cell line derived from a prostate cancer specimen (CPEC), which expressed low levels of ERß and lacked ERα. In EPN cells, there was an increase in the pre-G1 apoptotic peak and a reduction in the S phase of the cell cycle with G0/G1 arrest after E2 or RAL treatment; bcl-2 mRNA and Bcl-2 protein levels were significantly reduced, while activated caspase-3 and Par-4 levels increased significantly after either E2 or RAL treatment; in addition, c-myc transcript was inhibited after 10(-6) M RAL treatment. A dose-dependent increase of metallothionein II gene RNA level was also induced by RAL in EPN. In CPEC, there was only a weak apoptotic peak associated with caspase-3 activation and Par-4 increase after either E2 or RAL treatment; while c-myc transcript level increased. RAL induced a rapid but transient phosphorylation of ERK 1/2 in EPN cells but generated a sustained effect in CPEC. These findings suggest that RAL effects on PC growth control in vitro are cell-specific, depending on ERß or ERß/ERα relative expression levels. Moreover, this study demonstrated that RAL affected both transcriptional regulation and non-genomic signals, which resulted in the modulation of multiple signaling pathways of apoptosis and of cell cycle progression.

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.

[The IPSEMA initiative on health and safety at the maritime work place]. / Iniziative dell'IPSEMA in materia di salute e sicurezza nei luoghi di lavoro marittimo.

IPSEMA, founded in 1994 on former Casse Marittime institute, provides insurance to maritime workers from work injuries and occupational disease. According to current law IPSEMA, together with INAIL and ISPESL is engaged in the field of workplace safety and health, and in its promotion. For this purpose, IPSEMA is involved in injuries and diseases monitoring and in technical education. Recently ISPEMA has published "Quaderni di Formazione per la Sicurezza a Bordo delle Navi" and the research results on physical agent-based dams realized together with INSEAN. IPSEMA is now involved, with INMP institute, in "Salute in Mare" project in order to realize an information campaign on sea workers' self-health and health education.

Long-term physical training allows high exercise performance in moderate chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is a major health problem, because of its prevalence, morbidity and mortality. As a result of symptoms such as cough and dyspnea patients with COPD suffer from exercise limitation and reduced health related quality of life. The present paper reports the case of a 67-year old ex-smoker patient with COPD, who had exercised regularly since when he was young, and maintained a better exercise capacity than healthy people of the same age, despite a forced expiratory volume in 1 second of the 60% of the predicted normal value. This case suggests that regular physical exercise in COPD patients may prevent the loss of exercise capacity despite significant airway obstruction.

Prediction of the health effects of polychlorinated biphenyls (PCBs) and their metabolites using quantitative structure-activity relationship (QSAR).

Polychlorinated biphenyls (PCBs) are a group of 209 persistent environmental contaminants that are slightly different but structurally related. PCBs are known to induce a variety of health effects and often have been toxicologically tested as complex commercial mixtures (Aroclors) but environmental exposure occurs separately to a small number of specific congeners. Recently, the Third National Report on Human Exposures to Environmental Chemicals, an assessment of exposure data of the National Health and Nutrition Examination Survey (NHANES), identified 35 individual PCB congeners in the U.S. population. These types of findings necessitate the toxicity evaluation of individual congeners but adequate toxicity data for most individual PCB congeners are not available. Due to this, a quantitative structure-activity relationship (QSAR) approach was used to assess the potential mutagenesis and carcinogenesis of individual congeners and their possible metabolites. The predictions were analyzed to define the underlying generalizations between the parent PCBs, their metabolites, and some important toxicological endpoints. This analysis reveals that (1) mono and di-chlorinated PCBs and their metabolites can be potential mutagens; (2) PCB benzoquinone metabolites could be carcinogenic but the weight of evidence is poor. These results support the hypothesis that environmental exposure to some PCBs and/or their metabolites could produce mutagenicity and/or carcinogenicity. Hence, these data should be considered as priority toxicological testing data needs. As with all computational toxicology analytical findings, these conclusions must yield to empirical data as they become available.

Toxicity assessment of unintentional exposure to multiple chemicals.

Typically exposure to environmental chemicals is unintentional, and often the exposure is to chemical mixtures, either simultaneously or sequentially. When exposure occurs, in public health practice, it is prudent to ascertain if thresholds for harmful health effects are exceeded, whether by individual chemicals or by chemicals in combination. Three alternative approaches are available for assessing the toxicity of chemical mixtures. Each approach, however, has shortcomings. As the procedures of each approach are described in this paper, at various steps research needs are identified. Recently, reliance has increased on computational toxicology methods for predicting toxicological effects when data are limited. Advances in molecular biology, identification of biomarkers, and availability of accurate and sensitive methods allow us to more precisely define the relationships between multiple chemical exposures and health effects, both qualitatively and quantitatively. Key research needs are best fulfilled through collaborative research. It is through such collaborations that resources are most effectively leveraged to further develop and apply toxicity assessment methods that advance public health practices in vulnerable communities.

[Surgical treatment of sinus pilonidalis by Dufourmentel's flap technique]. / Il trattamento chirurgico del sinus pilonidalis con trasposizione di lembo secondo Dufourmentel.

The present study reports the results of surgical treatment of 175 consecutive chronic pilonidalis sinus cases by excision alone, excision and primary closure, excision and Dufourmentel's flap technique. The analysis of hospital stay , average recovery time, patient compliance and percentages of failures and recurrences enables us to state that Dufourmentel's technique is the best choice, allowing fast recovery with minimal discomfort and lower rate of recurrence. Moreover the good compliance of the technique and the use of recently introduced more effective local anaesthetics have allowed us to plan the treatment in a day-surgery setting with good clinical results.

Combination of all-trans-retinoic acid and gemtuzumab ozogamicin in an elderly patient with acute promyelocytic leukemia and severe cardiac failure.

All-trans-retinoic acid (ATRA) combined with anthracyclines is currently the standard treatment for acute promyelocytic leukemia (APL). In elderly patients the presence of comorbidities, such as cardiomyopathy or different organ failures, often represents an absolute contraindication to standard chemotherapy. In this particular setting of patients, alternative front-line approaches are needed. Here we report the use of gemtuzumab ozogamicin as consolidation therapy in a 68-year-old patient not eligible for standard dose anthracycline due to severe cardiac failure and chronic anticoagulant therapy, affected by low-risk APL. Induction therapy was started with ATRA alone, at a dose of 45 mg/m2 for 80 days. The patient obtained a complete hematological and molecular remission. At day +170 the patient was treated with 6 mg/m2 gemtuzumab ozogamicin monthly for two months (2 total doses) as a consolidation therapy and then started a maintenance program with ATRA 45 mg/m2 for 15 days every three months, for a total time of two years. No adverse events were observed in every phase of treatment and the patient is still in complete continuous hematological and molecular remission 29 months from diagnosis. This approach represents an intriguing therapeutic option to be investigated in randomized studies in low- and intermediate-risk elderly patients (older than 65 years), aiming to minimize or to eliminate standard chemotherapy in advantage of new non-conventional agents, including ATO.

Implications of chemical mixtures in public health practice.

The Agency for Toxic Substances and Disease Registry (ATSDR) is a federal public health agency that investigates and strives to prevent human health problems produced by exposure to toxic chemicals and their mixtures in the environment. Most human exposures involving toxic chemicals or mixtures are thought to originate from environmental and occupational sources; however, concurrent exposures are also likely from other sources, such as prescription and nonprescription drugs, indoor air pollutants, alcohol, and tobacco smoke. Thus, in evaluating the potential hazard following exposure to environmental mixtures, ATSDR not only considers the inherent joint toxicity of the mixture but also the influence of environmental, demographic, occupational, and lifestyle factors. To foster these goals, ATSDR has pursued a Mixtures Research and Assessment Program that consists of three component efforts: trend analysis, joint toxicity assessment, and experimental testing. Through trend analysis, ATSDR sets priorities for environmental mixtures of concern for which joint toxicity assessments are conducted as needed. If data are not available to conduct appropriate assessments, a research agenda is pursued through established extramural mechanisms. Ultimately, the data generated are used to support ATSDR's work at sites involving exposure to chemical mixtures. This pragmatic approach allows testable hypotheses or research needs to be identified and resolved and enhances our understanding of the mechanisms of joint toxicity. Several collaborative and cooperative efforts with national and international organizations such as the Toxicology and Nutrition Office, the Netherlands, and the Department of Energy are being pursued as part of these activities. ATSDR also develops guidance manuals to consistently and accurately apply current methodologies for the joint toxicity assessment of chemicals. Further, expert panels often are assembled to resolve outstanding scientific issues or obtain expert advice on pertinent issues. Recently, the need for studies on chemical mixtures has been proposed as one of the six priority areas the agency identified in its agenda for public health environmental research. This has been reinforced through the agency's close work with communities whose leaders have spoken passionately about their concern for information on exposures to chemical mixtures. The five other priority research areas the agency identified are exposure, susceptible populations, communities and tribal involvement, evaluation/surveillance of health effects, and health promotion/prevention.

Development of a model based on body composition to predict drug kinetics-1 evaluation in healthy volunteers.

A kinetic model for widely used drugs, based on body composition analysis, was developed and evaluated in young and elderly healthy individuals. Body composition was studied by body impedance analysis (BIA). Antipyrine, amlodipine, digoxin and tobramycin kinetics, liver microsomal activity enzyme (lidocaine/MEGX test), and appropriate clinical and laboratory tests were carried out. Major variables (V(d), AUC, t(1/2), C(max), Cl) for these drugs were calculated, and the possible relationships with the other clinical and biochemical data were analyzed by the Pearson's moment correlation, forecasting models being then obtained by a multiple linear regression method. Major kinetic parameters, particularly for the mixed elimination drugs (liver/renal), i.e. digoxin and amlodipine, proved to be well correlated to data collected during the study, in particular with body structure parameters. Results were less satisfactory in the case of the mainly renally handled tobramycin. Mathematical models to forecast the kinetic behaviors of the three chosen drugs, using readily accessible data, showed both in the young and the elder, as well as in the whole examined population, very satisfactory correlations in the case of digoxin (R(2) ranging from 0.89 to 0.85) and amlodipine (R(2) between 0.81 and 0.91), less satisfactory (with a wide range of R(2), from 0.65 to 0.94), in the case of tobramycin.

Development of a model based on body composition to predict drug kinetics; II. Application of the model to the use of digoxin in elderlies.

The applicability of a kinetic model for the prediction of steady-state blood levels, based on body composition as assessed by bioelectric impedance analysis (BIA), was applied to a population of elderly patients, candidates for digoxin therapy. Elderlies, all >70 years of age, underwent standard laboratory and clinical evaluation but no further characterization of liver or renal function. These 72 patients were given 0.125 mg digoxin for 5 days, in order to reach steady-state levels. Treatment was then interrupted and samples were collected 2 and 48 h after the last administration. Plasma digoxin levels were determined both by the immunochemical method with TDX and according to the BIA method described in the accompanying paper. Plasma levels calculated and measured in 2 h samples did not differ statistically, but levels were about 15% higher in the directly measured samples. There was a similar underestimation, i.e. about 15%, for the 48 h calculated levels. However, only approximately 5% of the levels were outside of the 95% confidence intervals as determined from the directly measured levels. These findings indicate that digoxin levels, calculated based on a BIA evaluation, may be sufficiently reliable, in the majority of patients, to allow direct determination of the more appropriate doses of digoxin.

The puzzle-feeder as feeding enrichment for common marmosets (Callithrix jacchus): a pilot study.

The use of a puzzle-feeder, as feeding enrichment, was investigated in three families of captive common marmosets (Callithrix jacchus). The study was carried out as a simultaneous choice test between two cages: one contained the puzzle-feeder, the other contained the usual food dishes, but otherwise both were arranged similarly. The monkeys were allowed to choose whether to feed from the usual dishes, or from the puzzle-feeder which required more effort. They were observed for two sessions in which they were differently motivated to feed. The enriched cage was always visited first, the marmosets managed to extract food from the puzzle-feeder, and spent more time eating from the puzzle-feeder when less hungry. These data contribute to a wider understanding on the use, and the effects, of feeding enrichments with different captive non-human primates.