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Anthropogenic activities often lead to changes in the distribution and behavior of wild species. The mere presence of humans and free-roaming domestic cats ( Felis catus ) can affect wildlife communities; however, responses to these disturbances might not be ubiquitous and may vary with local conditions. We investigated European pine marten's ( Martes martes ) distribution on Elba Island, Italy, where the species is the only wild carnivore. In this system, pine martens act as the top predator, and human presence is mostly driven by seasonal tourism. We evaluated (1) pine marten's occurrence in relation to vegetation type and elevation and the potential effects of proximity to settlements, (2) whether pine marten's distribution was associated with the co-occurrence of humans and domestic cats, and, if so, (3) whether these co-occurrence patterns were associated with proximity to anthropogenic infrastructures. Additionally, we explored similarities in activity patterns between pine marten and the other two species. We collected camera-trap data at 77 locations throughout Elba Island in February-July 2020. Using single-season multistate occupancy models, we found evidence that pine martens' occupancy was generally high across all vegetation types and elevation, and proximity to settlements was only weakly associated with the species occurrence. Contrary to expectations, we found no evidence of an association between pine martens' distribution and the presence of either humans or free-roaming domestic cats on Elba Island. Opposing activity patterns might have facilitated pine martens' co-existence with humans, with pine martens being active at ground level almost exclusively during nighttime. On the contrary, cats and pine martens showed similar activity patterns, and further studies are needed to define the co-existence mechanisms. These findings have important management implications and suggest that response to direct and indirect anthropogenic pressures can be highly context-dependent and mediated by the availability of resources and competition mechanisms., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

The Well-being Numerical Rating Scales (WB-NRSs) can be used to assess rapidly and accurately different types of well-being. However, the spiritual well-being scale showed slightly weaker psychometric properties. This study aimed to further investigate its suitability in measuring spiritual well-being. Participants ( N  = 270, age: M  = 32.98; SD = 15.64; 67% females) were administered a questionnaire including spiritual well-being, gratitude, compassionate love, and personality traits measures. A network analysis (based on correlations) was used to display graphically the pattern of relationships among the measured constructs (i.e. the nomological net). Results provided evidence that the scale measures spiritual well-being as defined in the literature, that is, a component distinct from faith and compassionate love, but connected to meaning in life, quality of relationships, personality traits, and gratitude. These findings confirm the WB-NRSs is a psychometrically sound and easy-to-use tool with clear benefits for both research and clinical assessment., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

Background and Objective: This cross-sectional study aimed to provide a scale to assess different aspects of the will based on Roberto Assagioli's theory., Methods and Results: The scale development followed three steps. Step 1 focused on operationalizing the construct and developing the items. It was carried out through several phases of item generation and refinement, resulting in a pool of 38 items. At Step 2 we tested the psychometric properties of the initial 38-item scale with the goal of excluding the items that weakened the structural validity and reliability of the scale. Descriptive, internal consistency, and exploratory factor analyses statistics were computed on a large sample (Sample 1: N = 587; age: M = 21.55, SD = 4.14, 66% female) and they led to a five-dimension model (Strong, Skillful, Good toward Self and Other, and Transpersonal Will) and the exclusion of 15 items. Analyses conducted at Step 3 on a different sample (Sample 2: N = 683; age: M = 34.09, SD = 16.27, 54% female) allowed for further refinement of the scale. Confirmatory factor analysis conducted on the resulting 19-item scale showed a good fit for the five-factor model (χ2 (142) = 507.63, p< .001, TLI = .91; CFI = .93; RMSEA = .06 [90%CI: .06‒.07]), and evidence of its invariance across genders and ages was provided. Reliability indices (internal consistency and intraclass correlation coefficients) were adequate (ranging from .66 to .83) and correlations with measures of related constructs supported the external validity of the scale., Conclusion: This study provides researchers, therapists, and counselors with an efficient measurement tool to assess Assagioli's construct of will., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bonacchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The wood mouse Apodemus sylvaticus is common in woodlands and open areas of the Western Palearctic. Despite extensive research, little is known about its population ecology in fields in the Mediterranean area, where the climate involves great seasonal changes in environmental features. Here, we investigated wood mice seasonal fluctuations in the number of captures and population structure by sampling long-fallow fields and woodlands, i.e., oak forest and conifer plantation, in a heterogeneous landscape of central Italy. Mice were live-trapped every two months for three years (23.814 trap-days). The number of captures, mice body weight, and proportion of adult, residents and breeding individuals were analyzed. Mice dynamics changed across seasons and habitats. In fields, we recorded more captures, more reproductive individuals, and fewer non-adults and resident individuals in the warmer months compared to the colder months; mice were heavier in warmer months. During the cold season, the captures and adult proportion in fields were lower than in resource-rich woodlands. Breeding and non-resident mice were more abundant in fields than in woodlands in warmer months. Overall, the seasonal demographic variations we recorded provide evidence that fields can represent a suboptimal habitat in Mediterranean heterogeneous landscapes, acting nonetheless as a source of food resources, cover, and mates for mice in spring-summer.

Patients with chronic liver disease face debilitating complications in their daily living and constantly report several types of unmet needs, but there is a paucity of validated questionnaires to assess these needs. In this study, we present the development of the Needs Evaluation Questionnaire for Liver Diseases (NEQ-LD) for the assessment of unmet needs in patients with chronic liver disease. Two hundred eighty-six outpatients with chronic liver diseases from a single tertiary referral center completed the NEQ-LD and related validity measures. Item response theory analyses were performed and demonstrated the strong psychometric properties of the questionnaire. Differential item functioning analyses showed that the scale functions equally across groups differing for age, sex, and presence of cirrhosis, suggesting the large applicability of the NEQ-LD for the assessment of unmet needs and between-group comparisons. Criterion validity measures provided evidence that unmet needs were positively associated with measures of depression and anxiety and negatively associated with measures of subjective well-being and physical and mental health. Unmet needs were expressed by a high percentage of patients, especially in the areas of information and dialogue with clinicians. One third of the sample reported material needs. Most of the items describing unmet needs were reported more frequently by patients with cirrhosis. Conclusion: We developed a reliable, valid, and largely employable instrument that can promote patient-centered care and facilitate support services in Hepatology., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic., Methods: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t-tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis., Results: We analysed data from 511 patients observing significant associations between quality of life's physical score and both age and adherence to Mediterranean diet (p < .01). A significant negative correlation was observed between mental score and the sedentary activity (p < .05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors., Conclusions: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

The assessment of well-being remains an important topic for many disciplines including medical, psychological, social, educational, and economic fields. The present study assesses the reliability and validity of a five-item instrument for evaluating physical, psychological, spiritual, relational, and general well-being. This measure uniquely utilizes a segmented numeric version of the visual analog scale in which a respondent selects a whole number that best reflects the intensity of the investigated characteristic. In study one, 939 clinical (i.e., diagnosed with cancer and liver disease with cirrhosis) and non-clinical (i.e., undergraduate students and their family and acquaintances) participants between the ages of 18 to 87 years (M = 47.20 years, SD = 19.62, 54% males) were recruited. Results showed items have strong discriminant ability and the spread of threshold parameters attests to the appropriateness of the response categories. Moreover, convergent and discriminant validity were found with other self-report measures (e.g., depression, anxiety, optimism, well-being) and the measure showed responsiveness to two separate interventions for clinical populations. In study two, 287 Canadian (ages ranged from 18 to 30 years; M = 20.78, SD = 3.32; 23% males) and 342 Italian undergraduate psychology students (age ranged from 18 to 29 years, M = 21.21 years, SD = 1.73, 38% males) were recruited to complete self-report questionnaires. IRT-based differential item functioning analyses provided evidence that the item properties were similar for the Italian and English versions of the scale. Additionally, the validity results obtained in study one were replicated and similar relationships between criterion variables were found when comparing the Italian- and the English-speaking samples. Overall, the current study provides evidence that the Italian and English versions of the WB-NRSs offer added value in research focused on well-being and in assessing well-being changes prompted by intervention programs., Competing Interests: The authors have declared that no competing interests exist.

The present study aims to develop and validate an Italian version of the Brief Self-Control Scale (BSCS). A large sample of Italian-speaking participants (N = 1139) completed the BSCS and measures of personality and individual dispositions. A clinical sample (N = 217) was administered the Italian version and an English-speaking sample (N = 274) completed the original version to test measurement invariance. Using confirmatory factor analysis, the best fit was observed for a shortened two-factor model (i.e., impulse control and self-discipline). Metric invariance across languages and partial strong invariance across genders, ages, and clinical status were demonstrated. Internal consistency and test-retest reliability for the total scale were adequate, and validity was established based on its correlations with related constructs and confirming that males and young individuals are more likely to have lower self-control. Results support the use of the shortened BSCS version to assess self-control in Italian-speaking individuals., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Although an optimal goal remains the routine assessment of unmet needs of all patients with cancer, particular attention should be paid to those groups of patients with characteristics known to be more frequently associated with unmet needs in general or with specific areas of need. This report aims to describe the sociodemographic, clinical, and psychological characteristics associated with higher unmet needs in Italian cancer patients., Methods: A total of 835 cancer patients from different care settings (ward, day hospital, follow-up ambulatory, rehabilitation unit, and palliative care) filled out the Needs Evaluation Questionnaire (NEQ), the Psychological Distress Inventory, and the Sense of Coherence Scale. Association of NEQ scores with the clinical and demographic variables were tested using analysis of variance., Results: Higher NEQ total score was associated with lower educational level, inpatient care setting, radiotherapy treatment, psychological distress, and lower resilience trait sense of coherence. Different predictors were identified for different areas of unmet needs. Care setting, psychological distress, and resilience trait were the strongest indicators of unmet needs in every area: information/communication, assistance/care, material needs, relational needs, and psychoemotional support., Conclusions: Clinicians should consider that inpatients with a high distress and a low resilience trait sense of coherence represent a group of cancer patients to be investigated with particular attention regarding unmet needs.

ABSTRACTObjective:The present study intended to evaluate the impact of a standardized format-called the "Music Givers," based on a single session of music intervention followed by a buffet-on the psychological burden and well-being of hospitalized cancer patients., Method: The Distress Thermometer (DT), the Hospital Anxiety and Depression Scale (HADS), and self-reported visual analogue scales (score range = 1-10) to assess pain, fatigue, and five areas of well-being (i.e., physical, psychological, relational, spiritual, and overall well-being) were administered to 242 cancer patients upon admission to and at discharge from the hospital. Among them, 103 were hospitalized during which time a live concert took place (intervention group), whereas 139 patients were hospitalized when it did not (control group)., Results: Compared to the control group, patients in the intervention group demonstrated less distress at discharge according to the DT (adjusted estimate of difference = -0.8, p = 0.001), lower HADS-Anxiety (-1.7, p &lt; 0.001) and HADS-Depression scores (-1.3, p = 0.001), and higher scores on all the well-being scales, with the exception of spiritual well-being. In addition, no between-group differences were found in terms of pain and fatigue scores at discharge., Significance of Results: The one-session format of the Music Givers intervention is an effective, standardized, easy-to-replicate, and low-cost intervention that reduces psychological burden and improves the well-being of hospitalized cancer patients. Listening to live music and the opportunity to establish better relationships between patients and staff could explain these results.

Purpose: Assessing patients' unmet supportive care needs is essential in order to prioritize areas of cancer care that require improvement. The aim of the present cross-sectional study was to compare the unmet needs of cancer patients in different stages of the disease and care process (diagnosis, treatments following diagnosis, follow-up and/or rehabilitation, relapse/recurrence, progression of the disease, and palliative care)., Methods: The research focused on patients from 7 oncology units of the same geographic region (Tuscany, a region of central Italy) in the same period of time regardless of primary tumor site. A total of 752 patients filled in the Needs Evaluation Questionnaire and the Psychological Distress Inventory., Results: We observed high rates of cancer patients who expressed unmet needs, especially in the areas of information and relational and material needs. The multiple regression models showed a direct correlation between psychological distress and extent of unmet needs. Individual unmet needs had significantly different entities at diverse phases., Conclusions: The present study confirmed the dynamic nature of needs of cancer patients, highlighting some critical aspects in different stages of the care process on which to concentrate attention and resources and suggesting the usefulness of periodic and repeated assessments of principal needs.

In Italy a new experience of music medicine called "The Music Givers" is spreading among Oncology Units; it aims to organise weekly live concerts (length 45-60 min) followed by a buffet. Purpose of the present study is to evaluate the effect of the format of The Music Givers on cancer in-patients' anxiety. State-Trait Anxiety Inventory (STAI-Y) was administered to 111 in-patients before and after the concerts. After the concerts we observed a 3.87 point decrease in state anxiety (p < .001) and statistically significant differences in most of the domains assessed by STAI-Y. These results invite a reflection on the importance of offering to inpatients events such as live music concerts, in order to improve their psychological condition during hospitalisation., (© 2016 John Wiley & Sons Ltd.)

Objective: The main aim of this study was to provide evidence of the broad employability of the NEQ with patients of different gender and age with cancer in different phases of the disease and care process, using an Item Response Theory (IRT) approach and investigating Differential Item Functioning (DIF)., Methods: The NEQ was completed by 762 patients visiting, consecutively, outpatient clinics or admitted to oncology wards. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. The properties of the questionnaire were analyzed by applying IRT to test how well each item of the scale concurs in measuring unmet needs, how reliable the whole scale is, and whether the scale was metrically invariant across gender, age, and phase of the disease., Results: Results showed that the NEQ performed well in measuring unmet needs and measurement equivalence of the scale across gender, age, and phase of the disease was verified., Conclusions: The current study supports the utility and broad employability of the NEQ, thus providing empirical evidence that it is psychometrically sound and metrically equivalent across different groups of cancer patients. As such, the scale could be an effective tool when planning psychosocial interventions to improve the care process and patients' quality of life.

Purpose: The Needs Evaluation Questionnaire (NEQ) is a self-administered instrument with 23 dichotomous items that is used both in oncology clinical practice and in research. It was originally developed for use in setting of hospitalization. The aim of the present study was to assess the factor structure of the NEQ in an outpatient oncology sample and to compare the unmet needs of inpatients and outpatients in the Italian context., Methods: In 6 Italian oncology departments, 783 patients completed the NEQ. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. There were 195 inpatients and 588 outpatients total., Results: Confirmatory factor analysis (CFA) showed that, with outpatients, the NEQ retained the distribution of the items in five main areas previously described with inpatients. Cancer outpatients expressed high percentages of unmet needs primarily concerning "material needs" and "needs for psycho-emotional support." Our survey also suggested that, in addition to the 23 original items, four new items could be tested for specific use with outpatients., Conclusions: Our findings highlight the importance of establishing routine assessment of unmet needs also in clinical oncology settings different from wards-such as day hospitals, ambulatory rehabilitation, or follow-up ambulatory care-where, at least in the Italian context, the rate of unmet needs is currently considerably high. The NEQ could be an effective tool for this assessment.

Objective: Although many studies indicate that the use of complementary and alternative medicine by cancer patients is common and widespread, few studies have focused on unmet needs of patients using complementary therapies (CTs). The aim of the present study was to evaluate, through a quantitative approach, possible associations between the use of CTs and the presence of specific unmet needs in cancer patients., Methods: In six Italian oncology departments, 783 patients were interviewed about CTs use and completed the Needs Evaluation Questionnaire. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process., Results: At the time of the survey, 38.3% of patients were using one or more types of CTs. According to Needs Evaluation Questionnaire, the use of CTs was associated (p < .05) with the need to be more involved in therapeutic choices (40% vs. 31.7%), the need to have a better dialogue with clinicians (44.4% vs. 37.2%), and the need to have more economic-insurance information in relation to their illness (46.1% vs. 36.4%). Statistical significance was confirmed with multivariable analysis for the last two items, whereas three more needs were associated with the use of CTs after adjustment: to receive more explanation on treatments (46.8% vs. 41.0%), to receive more comprehensible information (38% vs. 31.9%), and to receive more attention from nurses (16% vs. 12.1%)., Conclusions: Our study shows interesting differences regarding perceived needs between cancer patients who use and who do not use CTs. Unmet needs that are more expressed in CTs users should be known and, when possible, could be taken into account to improve both psychosocial interventions in the context of conventional care process and the quality of the relationship between patient and medical and nursing staff., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Dying at home and dying at the preferred place of death are advocated to be desirable outcomes of palliative care. More insight is needed in their usefulness as quality indicators. Our objective is to describe whether "the percentage of patients dying at home" and "the percentage of patients who died in their place of preference" are feasible and informative quality indicators., Methods and Findings: A mortality follow-back study was conducted, based on data recorded by representative GP networks regarding home-dwelling patients who died non-suddenly in Belgium (n = 1036), The Netherlands (n = 512), Italy (n = 1639) or Spain (n = 565). "The percentage of patients dying at home" ranged between 35.3% (Belgium) and 50.6% (The Netherlands) in the four countries, while "the percentage of patients dying at their preferred place of death" ranged between 67.8% (Italy) and 86.0% (Spain). Both indicators were strongly associated with palliative care provision by the GP (odds ratios of 1.55-13.23 and 2.30-6.63, respectively). The quality indicator concerning the preferred place of death offers a broader view than the indicator concerning home deaths, as it takes into account all preferences met in all locations. However, GPs did not know the preferences for place of death in 39.6% (The Netherlands) to 70.3% (Italy), whereas the actual place of death was known in almost all cases., Conclusion: GPs know their patients' actual place of death, making the percentage of home deaths a feasible indicator for collection by GPs. However, patients' preferred place of death was often unknown to the GP. We therefore recommend using information from relatives as long as information from GPs on the preferred place of death is lacking. Timely communication about the place where patients want to be cared for at the end of life remains a challenge for GPs.

Context: In Italy, data regarding the use of complementary therapies (CTs) among patients with cancer are sparse and discordant., Objectives: The present study aimed to investigate the demographic and psychological characteristics of Italian cancer patients who use CTs and the perceived benefit of users., Methods: Eight hundred three patients from six Italian oncology departments were interviewed about CT use and completed two questionnaires to explore psychological distress and the resilience trait called sense of coherence (SOC). Patients included in the study had different primary tumor sites and were in different phases of the disease and care process., Results: At the time of measurement, 37.9% of patients were using one or more types of CTs. The most commonly used CTs were diets and dietary supplements (27.5%), herbs (10.8%), homeopathy (6.4%), and mind-body therapies (5.5%). The Italian context is characterized by a high percentage of patients who informed their physicians about CT use (66.3%) and who experienced benefits (89.6%); 75.2% of the patients had used CTs in the past. Multivariate analysis revealed that young, female patients, who previously used complementary and alternative medicine in the past, appear more likely to use at least one type of CT in the present. Predictors of the use of CTs varied according to the type of CT. Among psychological factors, SOC was positively associated with both past and present CT use., Conclusion: Overall prevalence of CTs among Italian cancer patients is high and is in accordance with the European average. In addition to clinical and sociodemographic factors, the resilience trait SOC also was associated with CT use., (Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

The accuracy of the Life Orientation Test-Revised (LOT-R) in measuring dispositional optimism was investigated applying item response theory (IRT). The study was conducted on a sample of 484 university students (62% males, M age = 22.79 years, SD = 5.63). After testing the 1-factor structure of the scale, IRT was applied to evaluate the functioning of the LOT-R along the pessimism-optimism continuum. Item parameter estimates and the test information function showed that each item and the global scale satisfactorily measured the latent trait. Referring to the IRT estimated trait levels, the validity of the LOT-R was studied examining the relationships between dispositional optimism and psychological well-being, sense of mastery, and sense of coherence. Overall findings based on IRT analyses provide evidence of the accuracy of the LOT-R and suggest possible modifications of the scale to improve the assessment of dispositional optimism.

Background: There is an increase in the attention to factors influencing the quality of life of cancer patients. The aim of the present study was to evaluate temperament and character traits related to health-related quality of life (HRQoL) in patients with cancer., Methods: Two hundred and three inpatients from three Italian oncology departments filled in the Temperament Character Inventory (TCI-140) based on Cloninger's personality model, the SF-36 questionnaire assessing HRQoL, and the Hospital Anxiety and Depression Scale (HADS). Eighty percent of patients were undergoing chemotherapy., Results: Lower levels of harm avoidance and higher levels of self-directedness were significantly correlated with a better HRQoL. Regression analysis controlling for psychopathology (anxiety and depression symptoms) showed that the influence of temperament and character traits on quality of life seemed to add little to the influence of psychopathology., Conclusions: The present study demonstrates the existence of some relations between HRQoL and temperament and character traits assessed using the TCI-140 questionnaire. However, among the psychological factors, psychopathology seems to retain more influence on HRQoL of cancer patients.

Background and Aim: Spiritual life can be defined as the search for personal contact with the transcendent. Careful assessment of spiritual life can help to value its importance to cancer patients from the moment of their diagnosis., Methods: This is a cross-sectional study. Two hundred fifty-seven patients undergoing cancer treatment filled in the validated Italian version of the Systems of Belief Inventory (SBI-15R). Patients were also asked to attribute themselves to one of the following, mutually exclusive categories: believer and churchgoer, believer but no churchgoer, and non-believer., Results: Five patients did not report their religious stance and were therefore excluded from the analysis. Of the remaining 252 patients, 49% declared to be believers and churchgoers, 43% believers but not churchgoers, and 8% non-believers. Of the 20 cancer patients who declared not to have a religious faith, 7 patients agreed with the statement that they felt certain that God exists in some form, and 4 had experienced peace of mind through prayer and meditation. Almost all of the patients who declared to have a religious faith and to be churchgoers explicitly affirmed to have been helped by prayer and meditation in coping with their illness. Among believer churchgoers, only 30% declared to seek out the religious or spiritual community when they needed help., Conclusions: A large proportion of cancer patients find themselves involved with the search for a personal contact with the transcendent, also beyond any specific religious affiliation. These spiritual issues may be important even when they are not expressed as participation in religious rituals or adherence to specific religious beliefs. On the other hand, participation in religious rituals often implies the need for a personal spiritual life, both through those rituals and beyond them, as through personal prayer and meditation. These results ask for more attention on the part of professionals towards spiritual resources among cancer patients. It might be appropriate to look systematically for these resources from the moment of the diagnosis, through the sensitive administration of an easy and valid assessment tool like the SBI-15R.

A fully automated, non invasive, rapid and high-throughput method for the direct determination of sarcosine and N-ethylglycine in urine and urinary sediments using hexyl chloroformate derivatization followed by direct immersion solid-phase micro extraction and fast gas chromatography-mass spectrometric analysis was developed and validated. The use of a new ionic liquid narrow bore column, as well as the automation and miniaturization of the preparation procedure by a customized configuration of the utilized XYZ robotic system, allowed a friendly use of the GC apparatus achieving a quantitation limit of 0.06 μg L(-1) for sarcosine, good repeatability with CV always lower than 7% and reduced analysis times useful for point-of-care testing. The method was then applied for the analysis of 56 samples of urine and urinary sediments in healthy subjects, in those with benign prostatic hypertrophy and in patients with clinically localized prostate cancer. The results obtained showed that the medians of sarcosine/creatinine in urine were 103, 137 and 267 μg g(-1) respectively, thus assessing the potential use of sarcosine as urinary biomarker for prostate cancer detection. The highest values of sensitivity (79%) and specificity (87%) were obtained in correspondence of a cut-off value of 179 μg sarcosine(g creatinine)(-1), thus by using this cut-off threshold, sarcosine was significantly associated with the presence of cancer (p<0.0001). Finally, ROC analyses proved that the discrimination between clinically localized prostate cancer and patients without evidence of tumor is significantly correlated with sarcosine., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Observation and characterization of environmental pollution, focussing on Volatile Organic Compounds (VOCs), in a high-risk industrial area, are particularly important in order to provide indications on a safe level of exposure, indicate eventual priorities and advise on policy interventions. The aim of this study is to use the Solid Phase Micro Extraction (SPME) method to measure VOCs, directly coupled with atmospheric measurements taken on a small aircraft environmental platform, to evaluate and locate the presence of VOC emission sources in the Marghera industrial area. Lab analysis of collected SPME fibres and subsequent analysis of mass spectrum and chromatograms in Scan Mode allowed the detection of a wide range of VOCs. The combination of this information during the monitoring campaign allowed a model (Gaussian Plume) to be implemented that estimates the localization of emission sources on the ground., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The evaluation of psychological distress in cancer patients recently entered oncologic clinical practice. The objective of this study was to evaluate the role of clinical interview within psycho-oncologic assessment., Methods: Questionnaires assessing distress (PDI), psychopathology (MHQ, HADS) and needs (NEQ) and a subsequent clinical interview were proposed to 320 consecutive inpatients from the Oncology Department of Careggi Hospital in Florence., Results: The clinical interview made it possible to evaluate a significant percentage of patients (30%) who did not fill in questionnaires and to detect the presence of distress in 39 (13.7%) patients who would not have received a diagnosis in a protocol for the assessment of distress based only on questionnaires. It also provided the possibility to ask for help or to receive clinical support to a high percentage of patients (44.1%) who had not requested to speak to a psychologist through the questionnaires (NEQ). Moreover, 25% of patients who received prolonged clinical support had a low score in tests detecting distress, indicating that the opportunity for therapeutic support can emerge during a clinical interview, also in the absence of relevant symptoms detected by questionnaires., Conclusions: The use of more than one questionnaire in the assessment of distress and psychopathology is associated with reduced compliance and redundant information. On the other hand, clinical interview has a pivotal role in clinical evaluation and access to psychological support. We conclude that optimal efficacy of programs assessing distress in cancer patients is reached when a single questionnaire evaluating distress is associated with a clinical interview., (Copyright © 2010 John Wiley & Sons, Ltd.)

The present research is focused on automation, miniaturization, and system interaction with high throughput for multiple and specific Direct Immersion-Solid Phase Microextraction/Fast Gas Chromatography analysis of the urinary ketones. The specific Mass Spectrometry instrumentation, capable of supporting such the automated changeover from Negative Chemical to Electron Ionization mode, as well as the automation of the preparation procedure by new device called MultiFiber Exchange, through change of the fibers, allowed a friendly use of mass spectrometry apparatus with a number of advantages including reduced analyst time and greater reproducibility (2.01-5.32%). The detection limits for the seven ketones were less than 0.004 mg/L. For an innovative powerful meaning in high-throughput routine, the generality of the structurally informative Mass Spectrometry fragmentation patterns together with the chromatographic separation and software automation are also investigated.

The liver represents a site of expression of neurotrophins and their receptors. We have characterized the expression and intracellular localization of the nerve growth factor (NGF) receptor, Trk-A, in liver cells in vivo and in vitro. In both normal and fibrotic liver tissue, Trk-A immunostaining was present in different cell types, including parenchymal cells and cells of the inflammatory infiltrate. In hepatocytes and activated stellate cells (HSC), Trk-A showed a predominant nuclear localization, both in the presence and absence of injury. In cultured HSC, Trk-A was found to be functional, because exposure of the cells to recombinant NGF resulted in stimulation of cell migration and activation of intracellular signaling pathways, including Ras-ERK and PI3K/Akt. Remarkably, in cultured HSC, Trk-A staining was found constitutively in the nucleus. In these cells, Trk-A could be stained only by antibodies directed against the intracellular domain but not by those recognizing the extracellular portion of Trk-A suggesting that the intracellular portion of the receptor is the major determinant of nuclear Trk-A staining. In contrast to HSC, freshly isolated hepatocytes did not show any nuclear localization of the intracellular portion of Trk-A. In pheocromocytoma cells, nuclear staining for Trk-A was not present in conditions of serum deprivation, but could be induced by exposure to NGF or to a mixture of soluble mediators. We conclude that nuclear localization of the intracellular domain of Trk-A is observed constitutively in liver cells such as HSC, while in other cell types it could be induced in response to soluble factors.

Background and Aims: Myofibroblast-like cells, originating from activation of hepatic stellate cells (HSC/MFs), play a key role in liver fibrosis, a potentially reversible process that may rely on induction of HSC/MFs apoptosis. While this possibility has been shown in cultured rat HSC, very limited data are currently available for human HSC/MFs., Methods: Cultured human HSC/MFs were exposed to several proapoptotic stimuli, including those known to induce apoptosis in rat HSC/MFs, and induction of cell death and related mechanisms were investigated using morphology, molecular biology, and biochemical techniques., Results: In this study we report that fully activated human HSC/MFs did not undergo spontaneous apoptosis and survived to prolonged serum deprivation, Fas activation, or exposure to nerve growth factor, tumour necrosis factor alpha (TNF-alpha), oxidative stress mediators, doxorubicin, and etoposide. Induction of caspase dependent, mitochondria driven apoptosis in HSC/MFs was observed only when protein synthesis or transcription were inhibited. Importantly, the process of HSC activation was accompanied by changes in expression of a set of genes involved in apoptosis control. In particular, activated human HSC/MFs in culture overexpressed Bcl-2. The role of Bcl-2 was crucial as Bcl-2 silenced cells became susceptible to TNF-alpha induced apoptosis. Finally, Bcl-2 was markedly expressed in HSC/MFs present in liver tissue obtained from patients with hepatitis C virus related cirrhosis., Conclusions: Human activated HSC/MFs are resistant to most proapoptotic stimuli due to Bcl-2 overexpression and this feature may play a key role in the progression of fibrosis in chronic liver diseases.

Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO was associated with a dose-dependent increase in cell migration and chemoinvasion through Matrigel-coated filters. A checkerboard analysis showed that the effects of TPO on cell migration were dependent on both chemotaxis and chemokinesis. Exposure of HepG2 cells to TPO resulted in the activation of different members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated with increased activation of nuclear factor-kappaB. With the use of specific inhibitors, tyrosine phosphorylation and activation of PI3K were found to be required for the induction of migration in response to TPO. We conclude that TPO exerts biological actions on cultured hepatoblastoma cells via activation of c-Mpl and its downstream signaling.

Hepatic stellate cells (HSC) coordinate the liver wound-healing response through secretion of several cytokines and chemokines, including CCL2 (formerly known as monocyte chemoattractant protein-1). In this study, we evaluated the role of different proteins of the MAPK family (ERK, p38(MAPK), and JNK) in the regulation of CCL2 expression by HSC, as an index of their proinflammatory activity. Several mediators activated all three MAPK, including TNF, IL-1, and PDGF. To assess the relative role of the different MAPKs, specific pharmacological inhibitors were used; namely, SB203580 (p38(MAPK)), SP600125 (JNK), and PD98059 (MEK/ERK). The efficacy and specificity of the different inhibitors in our cellular system were verified analyzing the enzymatic activity of the different MAPKs using in vitro kinase assays and/or testing the inhibition of phosphorylation of downstream substrates. SB203580 and SP600125 dose-dependently inhibited CCL2 secretion and gene expression induced by IL-1 or TNF. In contrast, inhibition of ERK did not affect the upregulation of CCL2 induced by the two cytokines. Finally, activin A was also found to stimulate CCL2 expression and to activate ERK, JNK, p38, and their downstream targets. Unlike in cells exposed to proinflammatory cytokines, all three MAPKs were required to induce CCL2 secretion in response to activin. We conclude that members of the MAPK family differentially regulate cytokine-induced chemokine expression in human HSC.

Background and Aims: The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation. We investigated the expression of CCL21 and CCR7 in chronic hepatitis C. The effects of CCL21 on hepatic stellate cells (HSCs) were also studied., Methods: Expression of CCL21 was assessed by in situ hybridization and immunohistochemistry. CCR7 on T cells was analyzed by flow cytometry. Cultured human HSCs were studied in their activated phenotype., Results: In patients with chronic hepatitis C, expression of CCL21 and CCR7 was up-regulated. CCL21 was detected in the portal tracts and around inflammatory lymphoid follicles, in proximity to T lymphocytes and dendritic cells, which contributed to expression of this chemokine. Expression of CCR7 was also increased in patients with primary biliary cirrhosis. Intrahepatic CD8(+) T lymphocytes isolated from patients with chronic hepatitis C had a significantly higher percentage of positivity for CCR7 than those from healthy controls, and the expression of CCR7 was associated with that of CXCR3. Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model. Exposure of HSCs to CCL21 triggered several signaling pathways, including extracellular signal-regulated kinase, Akt, and nuclear factor kappaB, resulting in induction of proinflammatory genes., Conclusions: Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs.

Background/aims: Little is known about the role of fractalkine (CX3CL1) in the liver. The aim of this study was to investigate the expression patterns of fractalkine and its receptor CX3CR1 in normal human liver and in conditions of injury., Methods: Distribution and expression of fractalkine and its receptor were investigated using immunohistochemistry, in situ hybridization, flow cytometry and reverse transcriptase-polymerase chain reaction. In vitro experiments were conducted in HepG2 cells., Results: Both fractalkine and CX3CR1 were up-regulated during chronic injury, in areas of portal and lobular inflammation. In severe acute hepatitis, fractalkine and CX3CR1 were expressed at high levels not only in areas of inflammation but also in regenerating epithelial cells within bile duct-like structures, which showed co-expression of fractalkine and cytokeratin-7 or CX3CR1. The human hepatocarcinoma cell line HepG2 expressed fractalkine at the gene and protein level, and HepG2-conditioned medium was chemotactic for cells overexpressing CX3CR1. Transcripts for CX3CR1 were detected in HepG2, and exposure of these cells to recombinant fractalkine induced cell migration., Conclusions: This study shows that the fractalkine system is up-regulated during liver damage, and suggests that fractalkine may play a role in the recruitment and adhesion of inflammatory cells and in the biology of liver epithelial cells.

Hepatic stellate cells (HSC) and glomerular mesangial cells (MC) are tissue-specific pericytes involved in tissue repair, a process that is regulated by members of the chemokine family. In this study, we explored the signal transduction pathways activated by the chemokine receptor CXCR3 in vascular pericytes. In HSC, interaction of CXCR3 with its ligands resulted in increased chemotaxis and activation of the Ras/ERK cascade. Activation of CXCR3 also stimulated Src phosphorylation and kinase activity and increased the activity of phosphatidylinositol 3-kinase and its downstream pathway, Akt. The increase in ERK activity was inhibited by genistein and PP1, but not by wortmannin, indicating that Src activation is necessary for the activation of the Ras/ERK pathway by CXCR3. Inhibition of ERK activation resulted in a decreased chemotactic and mitogenic effect of CXCR3 ligands. In MC, which respond to CXCR3 ligands with increased DNA synthesis, CXCR3 activation resulted in a biphasic stimulation of ERK activation, a pattern similar to the one observed in HSC exposed to platelet-derived growth factor, indicating that this type of response is related to the stimulation of cell proliferation. These data characterize CXCR3 signaling in pericytes and clarify the relevance of downstream pathways in the modulation of different biologic responses.

Activated hepatic stellate cells (HSC) regulate the liver "wound-healing" response through expression of chemokines, including monocyte chemoattractant protein-1 (MCP-1), which participate in the formation of the inflammatory infiltrate during liver injury. Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid into prostaglandins, which may contribute to the inflammatory response. In this study, we investigated the effects of COX inhibitors on the expression of MCP-1 in cultured HSC. Pretreatment of HSC with nonspecific COX inhibitors such as indomethacin or ibuprofen markedly reduced the expression of MCP-1 caused by exposure to tumor necrosis factor alpha (TNF-alpha) or interleukin-1alpha (IL-1alpha). NS-398, a specific COX-2 inhibitor, also resulted in a dose-dependent inhibition of MCP-1 gene and protein expression. These effects were dependent on reduced MCP-1 transcription, as established using a reporter plasmid. In contrast, the up-regulation of MCP-1 expression caused by interferon gamma (IFN-gamma) was not sensitive to COX inhibitors. Quiescent HSC did not show detectable expression of COX-2, which became evident after activation in culture, and while TNF-alpha and IL-1alpha markedly increased the expression of COX-2, IFN-gamma did not have any effects. Pretreatment of HSC with the stable cyclic adenosine monophosphate (cAMP) analog, 8-bromo cAMP, reverted the effects of the COX-2 inhibitor, but not of a nuclear factor-kappaB (NF-kappaB) inhibitor, demonstrating that prostaglandins modulate MCP-1 expression via production of cAMP. On the other hand, the action of NF-kappaB inhibitors was negligible in IFN-gamma-stimulated cells. These findings indicate that cross-talk between cytokines and a prostaglandin-cAMP pathway differentially regulates the proinflammatory potential of HSC, contributing to the modulation of liver tissue inflammation.

Background & Aims: Proliferation and migration of hepatic stellate cells (HSCs) and expression of chemokines are involved in the pathogenesis of liver inflammation and fibrogenesis. Peroxisome proliferator-activated receptor (PPAR)-gamma is a receptor transcription factor that controls growth and differentiation in different tissues. We explored the effects of PPAR-gamma agonists on the biological actions of cultured human HSCs., Methods: HSCs were isolated from normal human liver tissue and used in their myofibroblast-like phenotype or immediately after isolation. Activation of PPAR-gamma was induced with 15-deoxy-Delta(12, 14)-prostaglandin J(2) or with troglitazone., Results: PPAR-gamma agonists dose-dependently inhibited HSC proliferation and chemotaxis induced by platelet-derived growth factor. This effect was independent of changes in postreceptor signaling or expression of c-fos and c-myc and was associated with inhibition of cell cycle progression beyond the G(1) phase. Activation of PPAR-gamma also resulted in a complete inhibition of the expression of monocyte chemotactic protein 1 at the gene and protein levels. Comparison of quiescent and culture-activated HSCs revealed a marked decrease in PPAR-gamma expression in activated cells., Conclusions: Activation of PPAR-gamma modulates profibrogenic and proinflammatory actions in HSCs. Reduced PPAR-gamma expression may contribute to confer an activated phenotype to HSCs.