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Abstract This is an overview of recent advances on predominant polarity conceptualization in bipolar disorder (BD). Current evidence on its operationalized definitions, possible contextualization within the affective spectrum, along with its epidemiological impact, and treatment implications, are summarized. Predominant polarity identifies three subgroups of patients with BD according to their mood recurrencies: (i) those with depressive or (ii) manic predominance as well as (iii) patients without any preponderance (‘nuclear’ type). A predominant polarity can be identified in approximately half of patients, with similar rates for depressive and manic predominance. Different factors may influence the predominant polarity, including affective temperaments. More generally, affective disorders should be considered as existing on a spectrum ranging from depressive to manic features, also accounting for disorders with ‘ultrapredominant’ polarity, i.e., unipolar depression and mania. While mixed findings emerge on its utility in clinical practice, it is likely that the construct of predominant polarity, in place of conventional differentiation between BD-I and BD-II, may be useful to clarify the natural history of the disorder and select the most appropriate interventions. The conceptualization of predominant polarity seems to reconcile previous theoretical views of both BD and affective spectrum into a novel perspective. It may provide useful information to clinicians for the early identification of possible trajectories of BD and thus guide them when selecting interventions for maintenance treatment. However, further research is needed to clarify the specific role of predominant polarity as a key determinant of BD course, outcome, and treatment response.

Background Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder. Aims We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder. Method The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates. Results We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = −3.19, 95% CI: −5.30 to −1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = −1.57, 95% CI: −2.88 to −0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP (P < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP (P < 0.05). No differences were estimated for other variables. Conclusions Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.

Alteration in the gut microbiome in human patients with chronic liver disease is a well-known pathophysiological mechanism. Therefore, it represents both a diagnostic and therapeutical target. Intestinal dysbiosis has also been identified in dogs with chronic liver disease, but clinical trials evaluating the effectiveness of synbiotic administration are lacking. Thirty-two dogs with chronic hepatobiliary disease were equally randomized into two groups: one treated with a synbiotic complex for 4–6 weeks (TG) and one untreated control group (CG). All dogs underwent clinical evaluation, complete anamnesis, bloodwork, abdominal ultrasound, fecal bile acids, and gut microbiome evaluation at T0–T1 (after 4–6 weeks). Treated dogs showed a significant reduction in ALT activity (p = 0.007) and clinical resolution of gastrointestinal signs (p = 0.026) compared to control dogs. The synbiotic treatment resulted in a lower increase in Enterobacteriaceae and Lachnospiraceae compared to the control group but did not affect the overall richness and number of bacterial species. No significant changes in fecal bile acids profile were detected with synbiotic administration. Further studies are needed to better evaluate the effectiveness of synbiotic administration in these patients and the metabolic pathways involved in determining the clinical and biochemical improvement.

Objective: Evidence on the relationship between depression and clinical dimensions of schizophrenia remains limited. This cross-sectional study investigated the association between depression and Positive and Negative Syndrome Scale (PANSS) dimensions in people with schizophrenia spectrum disorders. Methods: Trained assessors administered the PANSS to measure symptoms of schizophrenia and the Calgary Depression Scale for Schizophrenia to measure depression. The association of depression with overall PANSS score and related dimensions was investigated in multiple logistic regression analyses. Results: We included 231 inpatients with schizophrenia spectrum disorders (mean age: 42.4 (SD: 12.9) years; men: 58.9%; mean overall PANSS score: 82.5 (SD: 20.1); drug-free or naïve: 39.3%), including 78 (33.8%) with clinically significant depressive symptoms. Depression was associated with higher overall (regression coefficient, SE: 0.029, 0.008; p < 0.001) and general psychopathology (regression coefficient, SE: 0.118, 0.023; p < 0.001) PANSS scores. We found an inverse relationship between depression and positive symptoms (regression coefficient, SE: -0.088, 0.028; p = 0.002). No association between depression and negative symptoms was found. Conclusion: Despite some limitations, our study shows that people affected by schizophrenia spectrum disorders with depression are likely to show more overall and general psychopathology symptoms but lower positive symptoms. Additional studies are needed to explore the generalizability of our findings.

Summary: Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01–2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the “2016 Call for Independent Drug Research”.

Preliminary evidence shows that the kynurenine pathway (KP) may be altered in attention-deficit/hyperactivity disorder (ADHD). We thus conducted a systematic review and meta-analysis exploring the peripheral blood concentrations of tryptophan catabolites (TRYCATs) in people with ADHD. We searched the main electronic databases up to 7th December 2023. Standardised mean differences (SMDs) with 95% confidence intervals (95%CIs) were used to compare TRYCAT concentrations between participants with ADHD and healthy controls (HCs). We included eight studies. Random-effects meta-analyses found higher kynurenine (SMD = 0.56; 95%CI: 0.04 to 1.08; p = 0.033; I2 = 90.3%) and lower kynurenic acid (SMD = −0.33; 95%CI: −0.49 to −0.17; p < 0.001; I2 = 0%) concentrations in people with ADHD compared to HCs. Additional analyses on drug-free children with ADHD showed higher tryptophan (SMD = 0.31; 95%CI: 0.11 to 0.50; p = 0.002; I2 = 0%) and kynurenine (SMD = 0.74; 95%CI: 0.30 to 1.17; p < 0.001; I2 = 76.5%), as well as lower kynurenic acid (SMD = −0.37; 95%CI: −0.59 to −0.15; p < 0.001; I2 = 0%) blood levels, as compared to HCs. Despite some limitations, our work provides preliminary evidence on KP alterations in ADHD that may suggest decreased neuroprotection. Further research is needed to clarify the role of the KP in ADHD.

Abstract Introduction Information on the off–label use of Long–Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on– vs off–label LAIs and predictors of off–label First– or Second–Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off– or on–label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off–label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on– and off–label use. Approximately 1 in 4 patients received an off–label prescription. In the off–label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off–label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co–morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns.

Clinical trials and real-world data have shown that long-acting injectable antipsychotics (LAIs) might be an effective therapeutic option also for people with bipolar disorder (BD). However, complementing evidence from mirror-image studies investigating LAIs in BD is scattered and has not been systematically evaluated so far. We thus performed a review of observational mirror-image studies testing the effectiveness of LAI treatment on clinical outcomes in people with BD. Embase, MEDLINE, and PsycInfo electronic databases were systematically searched (via Ovid) up to November 2022. We included six mirror-image studies that compared relevant clinical outcomes between the 12-months after (post-treatment period) and the 12-months before (pre-treatment period) the initiation of a LAI treatment in adults with BD. We found that LAI treatment is associated with a significant reduction in days spent in hospital and number of hospitalizations. Moreover, LAI treatment seems to be associated with a significant decrease in the proportion of individuals with at least one hospital admission, even though data on this outcome were reported by just two studies. In addition, studies consistently estimated a significant reduction of hypo-/manic relapses after LAI treatment initiation, while the effect of LAIs for depressive episodes is less clear. Finally, LAI treatment initiation was associated with a lower number of emergency department visits in the year after LAI initiation. The findings of this review seem to suggest that the use of LAIs is an effective strategy to improve major clinical outcomes in people with BD. Nonetheless, additional research, based on standardized assessments of prevalent polarity and relapses, is needed to identify the clinical characteristics of individuals with BD who are most likely to benefit from a LAI treatment.

In 2020, the Global Cancer Observatory estimated the incidence of colorectal cancer (CRC) at around 10.7% coupled with a mortality rate of 9.5%. The explanation for these values lies in the tumor microenvironment consisting of the extracellular matrix and cancer-associated fibroblasts (CAFs). Fibroblast activation protein (FAP) offers a promising target for cancer therapy since its functions contribute to tumor progression. Immunohistochemistry examination of FAP, fibronectin ED-B, and CXCR4 in primary tumors and their respective synchronous and/or metachronous metastases along with semiquantitative analysis have been carried out on histological samples of 50 patients diagnosed with metastatic CRC. The intensity of FAP, articulated by both “Intensity %” and “Intensity score”, is lower in the first metastasis compared to the primary tumor with a statistically significant correlation. No significant correlations have been observed regarding fibronectin ED-B and CXCR4. Tumors that produce FAP have an ambivalent relationship with this protein. At first, they exploit FAP, but later they reduce its expressiveness. Although our study has not directly included FAP-Inhibitor (FAPI) PET/CT, the considerable expression of FAP reveals its potential as a diagnostic and therapeutic tool worthy of further investigation. This dynamic relationship between cancer and FAP has substantial diagnostic and therapeutic implications.

Abstract Background The role of image-derived biomarkers in recurrent oligometastatic Prostate Cancer (PCa) is unexplored. This paper aimed to evaluate [18F]FMCH PET/CT radiomic analysis in patients with recurrent PCa after primary radical therapy. Specifically, we tested intra-patient lesions similarity in oligometastatic and plurimetastatic PCa, comparing the two most used definitions of oligometastatic disease. Methods PCa patients eligible for [18F]FMCH PET/CT presenting biochemical failure after first-line curative treatments were invited to participate in this prospective observational trial. PET/CT images of 92 patients were visually and quantitatively analyzed. Each patient was classified as oligometastatic or plurimetastatic according to the total number of detected lesions (up to 3 and up to 5 or > 3 and > 5, respectively). Univariate and intra-patient lesions' similarity analysis were performed. Results [18F]FMCH PET/CT identified 370 lesions, anatomically classified as regional lymph nodes and distant metastases. Thirty-eight and 54 patients were designed oligometastatic and plurimetastatic, respectively, using a 3-lesion threshold. The number of oligometastic scaled up to 60 patients (thus 32 plurimetastatic patients) with a 5-lesion threshold. Similarity analysis showed high lesions' heterogeneity. Grouping patients according to the number of metastases, patients with oligometastatic PCa defined with a 5-lesion threshold presented lesions heterogeneity comparable to plurimetastic patients. Lesions within patients having a limited tumor burden as defined by three lesions were characterized by less heterogeneity. Conclusions We found a comparable heterogeneity between patients with up to five lesions and plurimetastic patients, while patients with up to three lesions were less heterogeneous than plurimetastatic patients, featuring different cells phenotypes in the two groups. Our results supported the use of a 3-lesion threshold to define oligometastatic PCa.

Abstract Artificial intelligence (AI) refers to a field of computer science aimed to perform tasks typically requiring human intelligence. Currently, AI is recognized in the broader technology radar within the five key technologies which emerge for their wide-ranging applications and impact in communities, companies, business, and value chain framework alike. However, AI in medical imaging is at an early phase of development, and there are still hurdles to take related to reliability, user confidence, and adoption. The present narrative review aimed to provide an overview on AI-based approaches (distributed learning, statistical learning, computer-aided diagnosis and detection systems, fully automated image analysis tool, natural language processing) in oncological hybrid medical imaging with respect to clinical tasks (detection, contouring and segmentation, prediction of histology and tumor stage, prediction of mutational status and molecular therapies targets, prediction of treatment response, and outcome). Particularly, AI-based approaches have been briefly described according to their purpose and, finally lung cancer—being one of the most extensively malignancy studied by hybrid medical imaging—has been used as illustrative scenario. Finally, we discussed clinical challenges and open issues including ethics, validation strategies, effective data-sharing methods, regulatory hurdles, educational resources, and strategy to facilitate the interaction among different stakeholders. Some of the major changes in medical imaging will come from the application of AI to workflow and protocols, eventually resulting in improved patient management and quality of life. Overall, several time-consuming tasks could be automatized. Machine learning algorithms and neural networks will permit sophisticated analysis resulting not only in major improvements in disease characterization through imaging, but also in the integration of multiple-omics data (i.e., derived from pathology, genomic, proteomics, and demographics) for multi-dimensional disease featuring. Nevertheless, to accelerate the transition of the theory to practice a sustainable development plan considering the multi-dimensional interactions between professionals, technology, industry, markets, policy, culture, and civil society directed by a mindset which will allow talents to thrive is necessary.

Abstract Introduction Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues cannot be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action. Based on studies to date, it may have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance and does not alter cardiovascular and endocrine parameters. The present study aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression. The rate of participants withdrawing from treatment due to adverse events after 6 months of follow up will be the primary outcome. Methods and analysis This is a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial funded by the Italian Medicines Agency (AIFA - Agenzia Italiana del Farmaco). Thirteen Italian Community Psychiatric Services will consecutively enrol elderly participants suffering from an episode of major depression over a period of 12 months. Participants will be assessed at baseline and after 1, 3 and 6 months of follow up. At each time point, the following validated rating scales will be administered: Montgomery–Åsberg Depression Rating Scale (MADRS), Antidepressant Side-Effect Checklist (ASEC), EuroQual 5 Dimensions (EQ-5D), Short Blessed Test (SBT), and Charlson Age-Comorbidity Index (CACI). Outcome assessors and the statistician will be masked to treatment allocation. A total of 358 participants (179 in each group) will be enrolled. Ethics and dissemination This study will fully adhere to the ICH E6 Guideline for Good Clinical Practice. Participants’ data will be managed and safeguarded according to the European Data Protection Regulation 2016/679. An external Ethical Advisory Board will help guarantee high ethical standards. Trial registration Clinicaltrials.gov: NCT03779789 , Registered on 19 December 2018. Submitted on 19 December. EudraCT number: 2018–001444-66. Trial status Protocol version 1.5; 09/06/2018. Recruitment started In February 2019 and it is ongoing. It is expected to end approximately on 30 September 2021.

Abstract Background Lower levels of tryptophan (TRP) have been identified in people with inflammatory bowel disease and in dogs with protein-losing enteropathy (PLE). No data on serum amino acids (AAs) but some on plasma in canine immunosuppressant-responsive enteropathy (IRE) are available. The aim of this study is to compare serum AAs between healthy and IRE dogs, considering clinicopathological variables and follow-up. Results Twenty-six healthy control dogs (CD) and 51 IRE dogs were included. IRE was diagnosed after the exclusion of extra-intestinal diseases and food and antibiotic responsive enteropathies. The canine chronic enteropathy clinical activity index (CCECAI) was assessed at presentation and during the clinical follow-up. In CD and IRE dogs, 19 different serum AAs were measured. IRE dogs were classified into responders, partial responders and non-responders, based on CCECAI after 1 month, and divided into PLE and non-PLE, based on albumin level. IRE dogs showed lower L-Tyrosine (TYR), L-Phenylalanine (PHE) and TRP (p

AbstractBackgroundThe balance between neurotoxic and neuroprotective effects of kynurenine pathway (KP) components has been recently proposed as a key element in the pathophysiology of bipolar disorder (BD) and related mood episodes. This comprehensive overview explored the link of KP with symptom severity and other clinical features of BD.MethodsWe searched Medline, Embase, and PsycInfo electronic databases for studies assessing the association of peripheral and/or central concentrations of KP metabolites with putative clinical features, including symptom severity and other clinical domains in BD.ResultsWe included the findings of 13 observational studies investigating the possible variations of KP metabolites according to symptom severity, psychotic features, suicidal behaviors, and sleep disturbances in BD. Studies testing the relationship between KP metabolites and depression severity generated mixed and inconsistent findings. No statistically significant correlations with manic symptoms were found. Moreover, heterogeneous variations of the KP across different clinical domains were shown. Few available studies found (a) higher levels of cerebrospinal fluid kynurenic acid and lower of plasma quinolinic acid in BD with psychotic features, (b) lower central and peripheral picolinic acid levels in BD with suicide attempts, and (c) no significant correlations between KP metabolites and BD-related sleep disturbances.ConclusionsAn imbalance of KP metabolism toward the neurotoxic branches is likely to occur in people with BD, though evidence on variations according to specific clinical features of BD is less clear. Additional research is needed to clarify the role of KP in the etiopathogenesis of BD and related clinical features.

Advanced image analysis, including radiomics, has recently acquired recognition as a source of biomarkers, although there are some technical and methodological challenges to face for its application in the clinic. Among others, proper phenotyping of metastatic or systemic disease where multiple lesions coexist is an issue, since each lesion contributes to characterization of the disease. Therefore, the radiomic profile of each lesion should be modeled into a more complex architecture able to reproduce each “unit” (lesion) as a part of the “entire” (patient). This work aimed to characterize intra-tumor heterogeneity underpinning metastatic prostate cancer using an exhaustive innovative approach which consist of a i) feature transformation method to build an agnostic (i.e., irrespective of pre-existence knowledge, experience, and expertise) radiomic profile of lesions extracted from [18F]FMCH PET/CT, ii) qualitative assessment of intra-tumor heterogeneity of patients, iii) quantitative representation of the intra-tumor heterogeneity of patients in terms of the relationship between their lesions’ profiles, to be associated with prognostic factors. We confirmed that metastatic prostate cancer patients encompassed lesions with different radiomic profiles that exhibited intra-tumor radiomic heterogeneity and that the presence of many radiomic profiles within the same patient impacted the outcome.

Purpose: This study aimed to assess the diagnostic performances of multimodal imaging [i.e., white blood cell single-photon emission computed tomography/CT (99mTc-HMPAO-WBC SPECT/CT) and 18-fluoride-fluorodeoxyglucose positron emission tomography/CT ([18F]FDG PET/CT)] in patients with suspected infection after the Bentall procedure, proposing new specific diagnostic criteria for the diagnosis.Methods: Between January 2009 and December 2019, we selected within a cardiovascular infections registry, 76 surgically treated patients (27 women and 49 men, median 66 years, and range 29–83 years). All the patients underwent molecular imaging for a suspected infection after the replacement of the aortic valve and ascending aorta according to the Bentall procedure. We analyzed 98 scans including 49 99mTc-WBC and 49 [18F]FDG PET/CT. A total of 22 patients with very early/early suspected infection (

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time.Methods: The STAR Network “Depot Study” was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS ≥ 41).Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions—conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently—showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline.Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders.

Background: The aim of this study was to evaluate the effectiveness of positron emission tomography/computed tomography with [18F]-fludeoxyglucose (FDG-PET/CT) and radiomics analysis in detecting differences between the native aorta and the abdominal aortic allograft after the total eradication of infection in patients undergoing infected graft removal and in situ reconstruction with cryopreserved allografts. Methods: Between January 2008 and December 2018, 56 vascular reconstructions with allografts have been performed at our department. The present series included 12 patients undergoing abdominal aortic in situ reconstruction with cryopreserved allografts. During the follow-up, all patients underwent a total-body [18F]FDG PET/CT with subsequent radiomics analysis. In all patients, a comparative analysis between the data extracted from native aorta and cryopreserved graft for each patient was performed. Results: All patients were male with a mean age of 72.8 years (range 63–84). Mean duration of follow-up was 51.3 months (range 3–120). During the follow-up, 2 patients (16.7%) needed a redo allograft-related surgical intervention. Overall, the rate of allograft dilatation was 33.3%. No patient had a redo infection during the follow-up. Radiomics analysis showed a different signature of implanted allograft and native aorta. Comparative analysis between the native aortas and cryopreserved allografts (dilated or not) showed several statistical differences for many texture features. Conclusions: The higher metabolic activity of allografts could indicate a state of immune-mediated degeneration. This theory should be proven with prospective, multicentric studies with larger sample sizes.

Attention deficit/hyperactivity disorder (ADHD) is associated with poor academic performance also among university students. This relationship may be made more complex by comorbid conditions. The aim of this study was to evaluate the mediating role of anxiety and depressive symptoms in the relationship between ADHD and academic performance. Data were drawn from the CAMPUS study (registration number: 0058642/21), an ongoing survey on university students’ mental health. Using a logit model, mediation analyses were carried out to test whether the relationship between ADHD symptoms (assessed by ASRS-5) and academic performance might be mediated by depressive (assessed by PHQ-9) and anxiety (assessed by GAD-7) symptoms. Our results showed that worse academic performance is associated with ADHD symptoms (p < 0.001). However, about 24% of the overall association between ADHD symptoms and academic performance was mediated by depressive symptoms (indirect effect: 0.065, 95%CI 0.022; 0.100), whereas the contribution of anxiety symptoms to the model was not significant. Along with the association between ADHD symptoms and poor academic performance, our findings highlight the key mediating role of depressive symptoms, which may be targeted with tailored support, ultimately improving both the academic performance and the well-being of university students with ADHD.

In humans, chronic liver disease may cause alterations in amino acids (AAs) metabolism, with serum branched-chain AAs (BCAAs) decreasing and aromatic AAs (AAAs) increasing. A reduced Fischer ratio (BCAAs/AAAs) has been found to be associated with hepatic fibrosis and is useful for assessing prognosis in human patients. In veterinary medicine, few studies have been performed, and in contrast to human patients, dogs with different kinds of hepatopathy tend to show both increased AAAs and BCAAs. In dogs, the association between histological scores and serum AAs has not been previously investigated. The aim of this study was to evaluate serum AAs in dogs with chronic hepatitis (CH) compared with a healthy control group (C) and, among CH dogs, in relation to their histological fibrosis and necroinflammatory activity scores. Leftover serum samples of 16 dogs with histological CH and 25 healthy dogs were employed. Serum AAs were measured by high performance liquid chromatography. Proline and the AAAs phenylalaine and tyrosine progressively increased with the histological severity. In contrast, cysteine, tryptophan and BCAA isoleucine progressively reduced. Lysine and the BCAAs leucine and valine showed a non-linear trend with the histological findings. The BCAAs/AAAs ratio was significatively reduced if higher grades of liver fibrosis were present.

Introduction: Studies have shown that the Ki-67 index is a valuable biomarker for the diagnosis, and classification of gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). We re-evaluated the expression of Ki-67 based on the intensity of the stain, basing our hypothesis on the fact that the Ki-67 protein is continuously degraded. Background: The aim was to evaluate whether a new scoring method would be more effective in classifying NETs by reducing staining heterogeneity. Methods: Patients with GEP-NET (n = 87) were analyzed. The classification difference between the two methods was determined. Results: The classification changed significantly when the Ki-67 semiquantal index was used. The percentage of G1 patients increased from 18.4% to 60.9%, while the G2 patients decreased from 66.7% to 29.9% and the G3 patients also decreased from 14.9% to 9.2%. Moreover, it was found that the traditional Ki-67 was not significantly related to the overall survival (OS), whereas the semiquantal Ki-67 was significantly related to the OS. Conclusions: The new quantification was a better predictor of OS and of tumor classification. Therefore, it could be used both as a marker of proliferation and as a tool to map tumor dynamics that can influence the diagnosis and guide the choice of therapy.

FAP-targeted radiopharmaceuticals represent a breakthrough in cancer imaging and a viable option for therapeutic applications. OncoFAP is an ultra-high-affinity ligand of FAP with a dissociation constant of 680 pM. OncoFAP has been recently discovered and clinically validated for PET imaging procedures in patients with solid malignancies. While more and more clinical validation is becoming available, the need for scalable and robust procedures for the preparation of this new class of radiopharmaceuticals continues to increase. In this article, we present the development of automated radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging and therapy. A new series of [68Ga]Ga-OncoFAP, [177Lu]Lu-OncoFAP and [18F]AlF-OncoFAP was produced with high radiochemical yields. Chemical and biochemical characterization after radiolabeling confirmed its excellent stability, retention of high affinity for FAP and absence of radiolysis by-products. The in vivo biodistribution of [18F]AlF-NOTA-OncoFAP, a candidate for PET imaging procedures in patients, was assessed in mice bearing FAP-positive solid tumors. The product showed rapid accumulation in solid tumors, with an average of 6.6% ID/g one hour after systemic administration and excellent tumor-to-healthy organs ratio. We have developed simple, quick, safe and robust synthetic procedures for the preparation of theranostic OncoFAP-compounds based on Gallium-68, Lutetium-177 and Fluorine-18 using the commercially available FASTlab synthesis module.

Abnormalities of serum amino acid profile, mostly characterized by a reduction in essential amino acids (EAAs) and an increase in non-essential amino acids (NEAAs), have been documented in human chronic kidney diseases (CKD). Amino acid disorders have been associated with CKD complications, such as metabolic acidosis and malnutrition. The aim of the present study was to evaluate EAAs and NEAAs in dogs affected by CKD at different IRIS stages, with particular reference to calcium–phosphate abnormalities, metabolic acidosis, and protein-energy wasting syndrome (PEW). Serum EAAs (L-histidine, L-isoleucine, L-leucine, L-lysine, methionine, L-phenylalanine, L-threonine, tryptophan, L-valine, and L-arginine) and serum NEAAs (L-alanine, L-aspartic acid, L-cysteine, L-glutamic acid, glycine, proline, L-serine, and L-tyrosine) were analyzed with HPLC in a group of dogs with CKD (n = 62), and in a group of healthy dogs (n = 25). CKD dogs showed significantly lower serum levels of histidine (p < 0.000), isoleucine (p < 0.000), tryptophan (p < 0.000), alanine (p = 0.013), cysteine (p < 0.000), and serine (p = 0.002), and significantly higher levels of proline (p < 0.000), leucine (p = 0.001), lysine (p < 0.000), valine (p < 0.000), arginine (p = 0.002), glutamic acid (p = 0.002), and glycine (p = 0.010) compared to healthy dogs. Dogs with abnormal calcium x phosphate values showed significantly higher levels of cysteine (p = 0.003), and lower levels of tryptophan (p = 0.025) compared to CKD dogs with normal CaxP. Dogs with metabolic acidosis showed significantly higher levels of phenylalanine (p = 0.035) and leucine (p = 0.034) compared to CKD dogs without metabolic acidosis. Dogs with PEW showed significantly lower levels for most of amino acids. In PEW dogs, the median distribution of both EAAs (p = 0.000) and NEAAs (p = 0.001) was significantly lower. The serum pattern of both EAAs and NEAAs was significantly different in CKD dogs compared to healthy dogs, although no association with the progression of the IRIS stage was found.

Personalized approaches in psychiatry, albeit being extensively explored in the literature since the early 2010s [...]

Aim: to exploit tissue-specific interactions among thymic epithelial tumor (TETs) cells and extra-domain B fibronectin (ED-B FN). Material and methods: The stromal pattern of ED-B FN expression was investigated through tumor specimen collection and molecular profiling in 11 patients with recurrent TETs enrolled in prospective theragnostic phase I/II trials with Radretumab, an ED-B FN specific recombinant human antibody. Radretumab radioimmunotherapy (R-RIT) was offered to patients who exhibited the target expression. Experiments included immunochemical analysis (ICH), cell cultures, immunophenotypic analysis, Western blot, slot-blot assay, and quantitative RT-PCR of two primary thymoma cultures we obtained from patients’ samples and in the Ty82 cell line. Results: The in vivo scintigraphic demonstration of ED-B FN expression resulted in R-RIT eligibility in 8/11 patients, of which seven were treated. The best observed response was disease stabilization (n = 5/7) with a duration of 4.3 months (range 3–5 months). IHC data confirmed high ED-B FN expression in the peripherical microenvironment rather than in the center of the tumor, which was more abundant in B3 thymomas. Further, there was a predominant expression of ED-B FN by the stromal cells of the thymoma microenvironment rather than the epithelial cells. Conclusions: Our data support the hypothesis that thymomas induce stromal cells to shift FN production to the ED-B subtype, likely representing a favorable hallmark for tumor progression and metastasis. Collectively, results derived from clinical experience and molecular insights of the in vitro experiments suggested that R-RIT inefficacy is unlikely related to low target expression in TET, being the mechanism of R-RIT resistance eventually related to patients’ susceptibility (i.e., inherent characteristics), the pattern expression of the target (i.e., at periphery), the biological characteristics of the tumor (i.e., aggressive and resistant phenotypes), and/or to format of the target agent (i.e., 131I-L19-SIP).

Cerenkov luminescence imaging (CLI) has been recently proposed as a method to visualize surgical margins in the operating theater, immediately after resection, to allow refining surgery in a single procedure. Our group is preparing a pilot clinical study to evaluate the impact of CLI during hepatic metastasectomy, using 18F-FDG and 68Ga-DOTATOC. Currently, we are optimizing the clinical protocol in terms of patient inclusion criteria, activity to inject, maximum allowed delay for imaging, and radiation monitoring. This paper describes a preliminary study we have performed to define the clinical protocol. The study is composed of two branches: 1) an in-vitro study to predict the typical signals and optical attenuation in the liver with 18F and 68Ga, 2) an analysis of clinical PET/CT data to determine typical values of relevant parameters, such as uptake and lesion dimension. The combined information by these two branches gives us an indication of the feasibility of CLI for margin assessment in liver metastasectomy. For 68Ga, we obtained detection limits ranging from 0.55 to 3.5 kBq/cc, to be compared with minimum and mean clinical uptakes of 1.6 and 7 kBq/cc, respectively. For 18F, the detection limits ranged from 12 to 145 kBq/cc, and the minimum and mean clinical uptakes were 5 and 11 kBq/cc, respectively. From these values, we expect CLI with 68Ga to be able to detect surgical margins in most patients, while with 18F the activities to inject for sufficient signal-to-noise ratio should be larger than standards, or the time delay between injection and imaging largely reduced. The results reported here can be useful also more in general, for studies dedicated to other CLI applications in the liver.

AbstractBackgroundThe fight against the COVID-19 pandemic seems to encompass a social media debate, possibly resulting in emotional contagion and the need for novel surveillance approaches. In the current study, we aimed to examine the flow and content of tweets, exploring the role of COVID-19 key events on the popular Twitter platform.MethodsUsing representative freely available data, we performed a focused, social media-based analysis to capture COVID-19 discussions on Twitter, considering sentiment and longitudinal trends between January 19 and March 3, 2020. Different populations of users were considered. Core discussions were explored measuring tweets’ sentiment, by both computing a polarity compound score with 95% Confidence Interval and using a transformer-based model, pretrained on a large corpus of COVID-19-related Tweets. Context-dependent meaning and emotion-specific features were considered.ResultsWe gathered 3,308,476 tweets written in English. Since the first World Health Organization report (January 21), negative sentiment proportion of tweets gradually increased as expected, with amplifications following key events. Sentiment scores were increasingly negative among most active users. Tweets content and flow revealed an ongoing scenario in which the global emergency seems difficult to be emotionally managed, as shown by sentiment trajectories.ConclusionsIntegrating social media like Twitter as essential surveillance tools in the management of the pandemic and its waves might actually represent a novel preventive approach to hinder emotional contagion, disseminating reliable information and nurturing trust. There is the need to monitor and sustain healthy behaviors as well as community supports also via social media-based preventive interventions.

Background: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients. Methods: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient’s attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence. Results: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness). Conclusion: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient’s engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies.

Attention Deficit-Hyperactivity disorder (ADHD) may influence rates of Alcohol Use Disorder (AUD) among individuals suffering from Bipolar Disorder (BD). The aim of this systematic review and meta-analysis was to estimate the strength and consistency of the potential association between ADHD and AUD in BD. We searched main electronic databases for studies indexed up to November 2020. We included observational studies investigating the association between ADHD and AUD among individuals with BD. The association between ADHD and AUD was estimated using odds ratios (ORs) with 95% Confidence Intervals (CIs). Eleven studies, involving 2734 individuals with BD (516 with ADHD), were included in the meta-analysis. Individuals with both BD and ADHD had higher rates of AUD as compared with subjects with BD only (34.0% vs. 18.3%). The estimated OR of AUD for ADHD was 2.50 (95% CI: 1.91 to 3.27; I2 = 13.0%). Study-level characteristics did not influence the effect size. No risk of publication bias was estimated. Despite some limitations, this meta-analysis estimated an association between ADHD and AUD among individuals suffering from BD. At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship.

This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments.

BackgroundThe management of mentally ill offenders in the community is one of the great challenges imposed on community psychiatry.AimThe aim of this study was to analyze the association between sociodemographic, clinical, and psychosocial factors and violent behavior in a sample of outpatients with severe mental disorders.MethodThis was a prospective cohort study with a baseline cross-sectional design used to provide a detailed analysis of patients' profiles, followed by a longitudinal design to measure aggressive and violent behavior during a 1-year follow-up. Patients with severe mental disorders, with or without a history of violence, were enrolled in four Italian Departments of Mental Health and underwent a comprehensive multidimensional assessment.ResultsThe sample included 247 outpatients, for a total of 126 cases and 121 controls. Compared to controls, patients with a history of violence had a greater frequency of lifetime domestic violence, a greater lifetime propensity to misuse substances, and a higher number of compulsory admissions. The forthnightly monitoring during the 1-year follow-up did show statistically significant differences in aggressive and violent behavior rates between the two groups. Verbal aggression was significantly associated with aggression against objects and physical aggression. Moreover, outpatients with an history of violence showed statistically significant higher MOAS scores compared to both residential patients with an history of violence, assessed in the first wave of this project, and all controls.ConclusionsPatients with a history of violence had specific characteristics and showed a greater occurrence of additional community violence during a 1-year observation period. Our results may assist clinicians in implementing standardized methods of patient assessment and violence monitoring in outpatient mental health services and may prompt improved collaboration between different community services.

Background: Post-stroke depression (PSD) is a common and serious complication after stroke. In this systematic review and meta-analysis, we evaluated the association between early PSD and mortality, considering depressive symptoms occurring within the first 3 months after the neurological event.Methods: This meta-analysis was conducted following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and based on studies indexed till May 2018 in PubMed and Web of Science databases. The relative risk (RR) for mortality in individuals with PSD, as compared with non-depressed ones, was estimated. Findings were pooled according to a random-effects model. Meta-regression and subgroup analyses were carried out.Results: We included seven studies, accounting for 119,075 individuals, of whom 17,609 suffering from an early PSD. We found higher rates of mortality in subjects with PSD as compared with non-depressed ones (RR = 1.50; 95%CI: 1.28 to 1.75; p < 0.001). Heterogeneity across studies was moderate (I2 = 50.7%). Subgroup analysis showed a slightly higher effect of PSD on short-term mortality (RR = 1.70; p < 0.001), as compared with long-term one (RR = 1.35; p = 0.01). According to relevant meta-regression analyses, the estimate was influenced by sample proportion of men (p = 0.043).Conclusions: Despite some limitations, our study shows the negative impact of early PSD on survival rates. Mechanisms underlying this association still need to be elucidated and several interpretations can be hypothesized. Future research should test if an early management of depression may increase life expectancy after stroke.

Although cannabis’ major psychoactive component, Δ-9-tetrahydrocannabinol (THC), has been linked to both earlier onset and poorer outcomes of psychotic disorders, Cannabidiol (CBD) seems to have different pharmacological mechanisms and potential therapeutic properties. However, no clinical study has investigated CBD for the treatment of co-occurring psychotic and cannabis use disorders so far, even though its utility seems grounded in a plausible biological basis. The aim of this work is thus to provide an overview of available clinical studies evaluating the efficacy of CBD for psychotic symptoms induced by THC, schizophrenia, and cannabis use disorders. After searching for relevant studies in PubMed, Cochrane Library, and ClinicalTrials.gov, we included 10 clinical studies. Available evidence suggests that CBD may attenuate both psychotic-like symptoms induced by THC in healthy volunteers and positive symptoms in individuals with schizophrenia. In addition, preliminary data on the efficacy of CBD for cannabis use disorders show mixed findings. Evidence from ongoing clinical studies will provide insight into the possible role of CBD for treating psychotic and cannabis use disorders.

Background and objectives: Readmissions of youths hospitalized for a severe mental disorder are common events and bear a remarkable human, social, and economic burden. The current study aimed at evaluating predictors of 1-year rehospitalization in a sample of adolescents and young adults with severe mental disorders. Materials and Methods: Data for ≤25-year-old inpatients with a severe mental disorder and consecutively admitted between 1 January 2016 and 30 June 2019 were collected. Subjects were retrospectively assessed over a follow-up period of one year after the index discharge to track readmissions—i.e., the primary outcome variable. Standard descriptive statistics were used. The association between variables and 1-year rehospitalization was estimated using the univariate Cox proportional hazards regression model. We then carried out a multivariable Cox regression model, also estimating the covariate-adjusted survivor function. Hazard ratios (HRs) with related 95% confidence intervals (95% CIs) were provided. Results: The final sample included 125 individuals. The multivariable Cox regression model estimated that co-occurring substance use disorders (HR = 2.14; 95% CI: 1.08 to 4.26; p = 0.029) and being admitted for a suicide attempt (HR = 2.49; 95% CI: 1.13 to 5.49; p = 0.024) were both significant predictors of 1-year rehospitalization. Conclusions: Our study showed that comorbid substance use disorders and being admitted for a suicide attempt were predictors of early readmission in youths with severe mental disorders. Although their generalizability is limited, our findings could contribute to improve the quality of young patients’ mental health care by identifying vulnerable subjects who may benefit from tailored interventions to prevent rehospitalizations.

It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. The purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. Treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. In this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine- and ATP-mediated signaling at P1 and P2 receptors, respectively. Furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. In particular, A2A and P2X7 receptors have been identified as potential targets for depression treatment. Preclinical studies highlight that both selective A2A and P2X7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. Consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. In particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. Although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.

BACKGROUND:For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. METHODS:The STAR Network "Depot" Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. RESULTS:Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. DISCUSSION:LAIs' prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs.

Carboxymethylcellulose (CMC) is a well-known pharmaceutical polymer, recently gaining attention in the field of nanomedicine, especially as a polyelectrolyte agent for the formation of complexes with oppositely charged macromolecules. Here, we report on the application of pH-sensitive pharmaceutical grade CMC-based nanoparticles (NP) for white blood cells (WBC) PET imaging. In this context and as an alternative to 99mTc-HMPAO SPECT labeling, the use of 68Ga3+ as PET radionuclide was investigated since, at early time points, it could provide the greater spatial resolution and patient convenience of PET tomography over SPECT clinical practices. Two operator-friendly kit-type formulations were compared, with the intention of radiolabeling within a short time (10 min), under mild conditions (physiological pH, room temperature) and in agreement with the actual clinically applied guidelines. NP were labeled by directly using 68Ga3+ eluted in HCL 0.05 N, from hospital suited 68Ge/68Ga generator and in absence of chelator. The first kit type approach involved the application of 68Ga3+ as an ionotropic gelation agent for in-situ forming NP. The second kit type approach concerned the re-hydration of a proper freeze-dried injectable NP powder. pH-sensitive NP with 250 nm average diameter and 80% labeling efficacy were obtained. The NP dispersant medium, including a cryoprotective agent, was modulated in order to optimize the Zeta potential value (−18 mV), minimize the NP interaction with serum proteins and guarantee a physiological environment for WBC during NP incubation. Time-dependent WBC radiolabeling was correlated to NP uptake by using both confocal and FT-IR microscopies. The ready to use lyophilized NP formulation approach appears promising as a straightforward 68Ga-WBC labeling tool for PET imaging applications.

LBS avanzati su dispositivi PDA

LBS avanzati su dispositivi PDA II° parte

Background. Depression after stroke may have great burden on the likelihood of functional recovery and long-term outcomes. Objective. To estimate the association between depression after stroke and subsequent mortality. Methods. A systematic search of articles using PubMed and Web of Science databases was performed. Odds ratios (ORs) and hazard ratios (HRs) were used as association measures for pooled analyses, based on random-effects models. Results. Thirteen studies, involving 59,598 subjects suffering from stroke (6,052 with and 53,546 without depression), had data suitable for meta-analysis. The pooled OR for mortality at followup in people suffering from depression after stroke was 1.22 (1.02–1.47). Subgroups analyses highlighted that only studies with medium-term followup (2–5 years) showed a statistically significant association between depression and risk of death. Four studies had data suitable for further analysis of pooled HR. The meta-analysis revealed a HR for mortality of 1.52 (1.02–2.26) among people with depression after stroke. Conclusions. Despite some limitations, this paper confirms the potential role of depression on post stroke mortality. The relationship between depression and mortality after stroke seems to be related to the followup duration. Further research is needed to clarify the nature of the association between depression after stroke and mortality.

La crescente comunità di escursionisti si trova ciclicamente a dover affrontare il dilemma di quale percorso scegliere per la “prossima” escursione ricorrendo al Web per la ricerca di siti dedicati allo scopo, in apprezzabile aumento, ma non ancora consolidati nel supporto da offrire agli utenti nella fase in cui devono prendere la decisione di quale percorso sia più idoneo per loro. Il presente articolo propone una soluzione originale su questa delicata questione A GIS solution for the choiceof hiking trails The growing community of hikers is periodically faced with the dilemma of which path to choose for the "next" tour. The use of the Web to search sites for hiking, in noticeable increase, must be supported to better provide info to users, in the phase in which they must make the decision on which path is most suitable for them. This ar-ticle proposes an original solution to this sensitive issue.

Gi4DM - Geomatics for crisis management The recent disasters in Haiti, Chile, L'Aquila and Madeira underlined the importance of reliable geospatial datasets, used to better manage and organize rescue measures. The Gi4DM Conference, held in Turin last february, aimed at providing a scientific framework to all researchers and organizations that are envolved in the aftermath of these events.

ESRI EMEA User Conference 2010 The ESRI EMEA User Conference is held every two years, and after London 2008, '2010 edition was held in Rome Oct. 26 to 28. 1500 participants from 75 countries have created one of the most important events of the GIS in which they were submitted more than 150 projects.

Semantic enrichment of alpine tourism Ontological enrichment from semantic Web finds its own achievement in tourism information, mostly those related to alpine world. Moreover, information systems and trails become straightforward and user-centric when tourist doesn’t need to learn concepts and meanings from maps. Broad boundaries patterns accomplish this semantic refinement in order to worth both geographic appeal and routes safety, making sense of avalanche awareness risk.

Avalanche risk management and XML applications The most powerful tool for early warning and mitigating the risk of an avalanche has arisen in the last few years. A standard application model has been already accepted at Open Geospatial Consortium. When CAAML, as model for structured electronic exchange of avalanche related information, will become also standard at European community, public avalanche bulletins and professional network observations could be shared at regional and national level among organizations promoting safety services and avalanche awareness such as AINEVA and METEOMONT. This system will create a common platform for professional and public information exchanges that will open doors to a wide array of opportunities for data sharing, viewing and analyzing based on WFS/WMS services.

ArcGis 9.3 and spatial databases: application sceneries The latest news from ESRI suggests that it will soon be possible to link to the PostgreSQL database. This resulted in a collaboration between the PostGis geometry model with SDOGEOMETRY - the oracle database - a hierarchial and spatial design database. This had a direct impact on the PMI review and the business models of local governments. ArcSde would be replaced by Zig-Gis 2.0 providing greater offerings to the GIS community. Harnessing this system will take advantage of human resources to aid in the design of potent conceptual data models. Further funds are still required to promote the product under a prominent license.

Geospatial solutions: the pedestrian systems Investigating alongside Decision Support System simulation based models are centric. Even though Geographic Information Systems do not get in touch with Agent Based Models sooner, geospatial simulations provide several enhancements in emergency evacuation scenarios. In a small scale pedestrian movement modelling which depicts crowd behaviour and gathering as well as ingress and egress situations from large venue where panic usually rises. Crowd managers can be supported in their decisions by running the same model against different conditions such as spatial constraints to take a turn for the better and avoid congestions as well crushing and trampling phenomena.

Le emergenze risultano caratterizzate da comportamenti macroscopici stabili generati da interazioni locali di entità individuali. In base a tale definizione, si evince come tali situazioni non possano essere razionalizzate come parti di un sistema. Un ingorgo, per esempio, si forma spesso nella direzione di marcia opposta a quella di un incidente stradale. Le caratteristiche delle situazioni d’emergenza le rendono difficili da comprendere e da prevedere così come per le loro conseguenze, molto lontane dalle aspettative che solitamente si fanno al riguardo.