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Epstein-Barr virus (EBV) uses latency programs to colonize the memory B-cell reservoir, and each program is associated with human malignancies. However, knowledge remains incomplete of epigenetic mechanisms that maintain the highly restricted latency I program, present in memory and Burkitt lymphoma cells, in which EBNA1 is the only EBV-encoded protein expressed. Given increasing appreciation that higher order chromatin architecture is an important determinant of viral and host gene expression, we investigated roles of Wings Apart-Like Protein Homolog (WAPL), a host factor that unloads cohesin to control DNA loop size and that was discovered as an EBNA2-associated protein. WAPL knockout (KO) in Burkitt cells de-repressed LMP1 and LMP2A expression, but not other EBV oncogenes, to yield a viral program reminiscent of EBV latency II, which is rarely observed in B-cells. WAPL KO also increased LMP1/2A levels in latency III lymphoblastoid cells. WAPL KO altered EBV genome architecture, triggering formation of DNA loops between the LMP promoter region and the EBV origins of lytic replication (oriLyt). Hi-C analysis further demonstrated that WAPL KO reprogrammed EBV genomic DNA looping. LMP1 and LMP2A de-repression correlated with decreased histone repressive marks at their promoters. We propose that EBV coopts WAPL to negatively regulate latent membrane protein expression to maintain Burkitt latency I., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Murray-Nerger 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 health benefits of nut consumption have been extensively demonstrated in observational studies and intervention trials. Besides the high nutritional value, countless evidences show that incorporating nuts into the diet may contribute to health promotion and prevention of certain diseases. Such benefits have been mostly and certainly attributed not only to their richness in healthy lipids (plentiful in unsaturated fatty acids), but also to the presence of a vast array of phytochemicals, such as polar lipids, squalene, phytosterols, tocochromanols, and polyphenolic compounds. Thus, many nut chemical compounds apply well to the designation "nutraceuticals," a broad umbrella term used to describe any food component that, in addition to the basic nutritional value, can contribute extra health benefits. This contribution analyses the general chemical profile of groundnut and common tree nuts (almond, walnut, cashew, hazelnut, pistachio, macadamia, pecan), focusing on lipid components and phytochemicals, with a view on their bioactive properties. Relevant scientific literature linking consumption of nuts, and/or some of their components, with ameliorative and/or preventive effects on selected diseases - such as cancer, cardiovascular, metabolic, and neurodegenerative pathologies - was also reviewed. In addition, the bioactive properties were analyzed in the light of known mechanistic frameworks.

Epstein-Barr virus (EBV) uses latency programs to colonize the memory B-cell reservoir, and each program is associated with human malignancies. However, knowledge remains incomplete of epigenetic mechanisms that maintain the highly restricted latency I program, present in memory and Burkitt lymphoma cells, in which EBNA1 is the only EBV-encoded protein expressed. Given increasing appreciation that higher order chromatin architecture is an important determinant of viral and host gene expression, we investigated roles of Wings Apart-Like Protein Homolog (WAPL), a host factor that unloads cohesins to control DNA loop size and that was discovered as an EBNA2-associated protein. WAPL knockout (KO) in Burkitt cells de-repressed LMP1 and LMP2A expression but not other EBV oncogenes to yield a viral program reminiscent of EBV latency II, which is rarely observed in B-cells. WAPL KO also increased LMP1/2A levels in latency III lymphoblastoid cells. WAPL KO altered EBV genome architecture, triggering formation of DNA loops between the LMP promoter region and the EBV origins of lytic replication (oriLyt). Hi-C analysis further demonstrated that WAPL KO reprograms EBV genomic DNA looping. LMP1 and LMP2A de-repression correlated with decreased histone repressive marks at their promoters. We propose that EBV coopts WAPL to negatively regulate latent membrane protein expression to maintain Burkitt latency I., Author Summary: EBV is a highly prevalent herpesvirus etiologically linked to multiple lymphomas, gastric and nasopharyngeal carcinomas, and multiple sclerosis. EBV persists in the human host in B-cells that express a series of latency programs, each of which is observed in a distinct type of human lymphoma. The most restricted form of EBV latency, called latency I, is observed in memory cells and in most Burkitt lymphomas. In this state, EBNA1 is the only EBV-encoded protein expressed to facilitate infected cell immunoevasion. However, epigenetic mechanisms that repress expression of the other eight EBV-encoded latency proteins remain to be fully elucidated. We hypothesized that the host factor WAPL might have a role in restriction of EBV genes, as it is a major regulator of long-range DNA interactions by negatively regulating cohesin proteins that stabilize DNA loops, and WAPL was found in a yeast 2-hybrid screen for EBNA2-interacting host factors. Using CRISPR together with Hi-ChIP and Hi-C DNA architecture analyses, we uncovered WAPL roles in suppressing expression of LMP1 and LMP2A, which mimic signaling by CD40 and B-cell immunoglobulin receptors, respectively. These proteins are expressed together with EBNA1 in the latency II program. We demonstrate that WAPL KO changes EBV genomic architecture, including allowing the formation of DNA loops between the oriLyt enhancers and the LMP promoter regions. Collectively, our study suggests that WAPL reinforces Burkitt latency I by preventing the formation of DNA loops that may instead support the latency II program.

Purpose: The aim of the present study, conducted by a working group of the Italian Association of Medical Physics (AIFM), was to define typical z-resolution values for different digital breast tomosynthesis (DBT) models to be used as a reference for quality control (QC). Currently, there are no typical values published in internationally agreed QC protocols., Methods: To characterize the z-resolution of the DBT models, the full width at half maximum (FWHM) of the artifact spread function (ASF), a technical parameter that quantifies the signal intensity of a detail along reconstructed planes, was analyzed. Five different commercial phantoms, CIRS Model 011, CIRS Model 015, Modular DBT phantom, Pixmam 3-D, and Tomophan, were evaluated on reconstructed DBT images and 82 DBT systems (6 vendors, 9 models) in use at 39 centers in Italy were involved., Results: The ASF was found to be dependent on the detail size, the DBT angular acquisition range, the reconstruction algorithm and applied image processing. In particular, a progressively greater signal spread was observed as the detail size increased and the acquisition angle decreased. However, a clear correlation between signal spread and angular range width was not observed due to the different signal reconstruction and image processing strategies implemented in the algorithms developed by the vendors studied., Conclusions: The analysis led to the identification of typical z-resolution values for different DBT model-phantom configurations that could be used as a reference during a QC program., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Epstein-Barr virus (EBV) establishes lifelong asymptomatic infection by replication of its chromatinized episomes with the host genome. EBV exhibits different latency-associated transcriptional repertoires, each with distinct three-dimensional structures. CTCF, Cohesin and PARP1 are involved in maintaining viral latency and establishing episome architecture. Epstein-Barr virus-associated gastric cancer (EBVaGC) represents 1.3-30.9% of all gastric cancers globally. EBV-positive gastric cancers exhibit an intermediate viral transcription profile known as 'Latency II', expressing specific viral genes and noncoding RNAs. In this study, we investigated the impact of PARP1 inhibition on CTCF/Cohesin binding in Type II latency. We observed destabilization of the binding of both factors, leading to a disrupted three-dimensional architecture of the episomes and an altered viral gene expression. Despite sharing the same CTCF binding profile, Type I, II and III latencies exhibit different 3D structures that correlate with variations in viral gene expression. Additionally, our analysis of H3K27ac-enriched interactions revealed differences between Type II latency episomes and a link to cellular transformation through docking of the EBV genome at specific sites of the Human genome, thus promoting oncogene expression. Overall, this work provides insights into the role of PARP1 in maintaining active latency and novel mechanisms of EBV-induced cellular transformation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Importance: Epstein-Barr virus (EBV) latency is controlled by epigenetic silencing by DNA methylation [5-methyl cytosine (5mC)], histone modifications, and chromatin looping. However, how they dictate the transcriptional program in EBV-associated gastric cancers remains incompletely understood. EBV-associated gastric cancer displays a 5mC hypermethylated phenotype. A potential treatment for this cancer subtype is the DNA hypomethylating agent, which induces EBV lytic reactivation and targets hypermethylation of the cellular DNA. In this study, we identified a heterogeneous pool of EBV epialleles within two tumor-derived gastric cancer cell lines that are disrupted with a hypomethylating agent. Stochastic DNA methylation patterning at critical regulatory regions may be an underlying mechanism for spontaneous reactivation. Our results highlight the critical role of epigenetic modulation on EBV latency and life cycle, which is maintained through the interaction between 5mC and the host protein CCCTC-binding factor., Competing Interests: P.M.L. is a founder and advisor to Vironika, LLC.

PARP1 has been shown to regulate EBV latency. However, the therapeutic effect of PARP1 inhibitors on EBV+ lymphomagenesis has not yet been explored. Here, we show that PARPi BMN-673 has a potent anti-tumor effect on EBV-driven LCL in a mouse xenograft model. We found that PARP1 inhibition induces a dramatic transcriptional reprogramming of LCLs driven largely by the reduction of the MYC oncogene expression and dysregulation of MYC targets, both in vivo and in vitro . PARP1 inhibition also reduced the expression of viral oncoprotein EBNA2, which we previously demonstrated depends on PARP1 for activation of MYC. Further, we show that PARP1 inhibition blocks the chromatin association of MYC, EBNA2, and tumor suppressor p53. Overall, our study strengthens the central role of PARP1 in EBV malignant transformation and identifies the EBNA2/MYC pathway as a target of PARP1 inhibitors and its utility for the treatment of EBNA2-driven EBV-associated cancers., Competing Interests: Competing Interest Statement: P.M.L. is a founder and consultant for Vironika, LLC.

Introduction: Disorganization is a crucial domain in affective psychoses. However, it has received poor research attention, especially at the illness onset. The aims of this study were: (a) to monitor the longitudinal course of disorganization in young people with first episode affective psychosis (FEAP) across 2 years of follow-up, and (b) to investigate any relevant correlation of disorganized symptoms with psychopathology, functioning and the specific treatment elements of an "Early Intervention in Psychosis" (EIP) protocol along the follow-up period., Materials and Methods: Seventy-five FEAP participants (aged 12-35 years) completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). Spearman's rank correlation coefficients were calculated., Results: During the follow-up, disorganized symptoms showed significant enduring positive correlations with PANSS items representing delusional thought content and uncooperativeness, as well as a persistent negative association with the GAF score. Across the 2-year follow-up period, FEAP individuals also had a relevant reduction in disorganization levels. This symptom decrease was specifically related with the combination of antipsychotic medication with the specific psychosocial components of our EIP intervention offered to FEAP patients during the first 12 months of treatment., Conclusions: Disorganization is relevant in FEAP subjects already at their enrollment in specialized EIP protocols. However, it decreases over time, together with the delivery of specific, combined (person-tailored) EIP interventions., (Copyright © 2021 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)

Epstein-Barr Virus (EBV) is a human gamma-herpesvirus that is widespread worldwide. To this day, about 200,000 cancer cases per year are attributed to EBV infection. EBV is capable of infecting both B cells and epithelial cells. Upon entry, viral DNA reaches the nucleus and undergoes a process of circularization and chromatinization and establishes a latent lifelong infection in host cells. There are different types of latency all characterized by different expressions of latent viral genes correlated with a different three-dimensional architecture of the viral genome. There are multiple factors involved in the regulation and maintenance of this three-dimensional organization, such as CTCF, PARP1, MYC and Nuclear Lamina, emphasizing its central role in latency maintenance.

Purpose: To fully characterize the flat panel detector of the new Sphinx Compact device with scanned proton and carbon ion beams., Materials and Methods: The Sphinx Compact is designed for daily QA in particle therapy. We tested its repeatability and dose rate dependence as well as its proportionality with an increasing number of particles and potential quenching effect. Potential radiation damage was evaluated. Finally, we compared the spot characterization (position and profile FWHM) with our radiochromic EBT3 film baseline., Results: The detector showed a repeatability of 1.7% and 0.9% for single spots of protons and carbon ions, respectively, while for small scanned fields it was inferior to 0.2% for both particles. The response was independent from the dose rate (difference from nominal value < 1.5%). We observed an under-response due to quenching effect for both particles, mostly for carbon ions. No radiation damage effects were observed after two months of weekly use and approximately 1350 Gy delivered to the detector. Good agreement was found between the Sphinx and EBT3 films for the spot position (central-axis deviation within 1 mm). The spot size measured with the Sphinx was larger compared to films. For protons, the average and maximum differences over different energies were 0.4 mm (3%) and 1 mm (7%); for carbon ions they were 0.2 mm (4%) and 0.4 mm (6%)., Conclusions: Despite the quenching effect the Sphinx Compact fulfills the requirements needed for constancy checks and could represent a time-saving tool for daily QA in scanned particle beams., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

A major concern for olive cultivation in many extra-Mediterranean regions is the adaptation of recently introduced cultivars to environmental conditions different from those prevailing in the original area, such as the Mediterranean basin. Some of these cultivars can easily adapt their physiological and biochemical parameters in new agro-environments, whereas others show unbalanced values of oleic acid content. The objective of this study was to evaluate the effects of the thermal regime during oil synthesis on the expression of fatty acid desaturase genes and on the unsaturated fatty acid contents at the field level. Two cultivars (Arbequina and Coratina) were included in the analysis over a wide latitudinal gradient in Argentina. The results suggest that the thermal regime exerts a regulatory effect at the transcriptional level on both OeSAD2 and OeFAD2-2 genes and that this regulation is cultivar-dependent. It was also observed that the accumulated thermal time affects gene expression and the contents of oleic and linoleic acids in cv. Arbequina more than in Coratina. The fatty acid composition of cv. Arbequina is more influenced by the temperature regime than Coratina, suggesting its greater plasticity. Overall, findings from this study may drive future strategies for olive spreading towards areas with different or extreme thermal regimes serve as guidance for the evaluation olive varietal patrimony.

Aim: Negative symptoms (NS) severely affect daily functioning already at the psychosis onset. However, most studies investigating beneficial effects of specific treatments for NS mainly included individuals with prolonged psychotic disorders. Furthermore, evidence on psychosocial rehabilitation for NS in early psychosis is still relatively poor. The aims of this study therefore were (A) to longitudinally examine NS stability in people with first episode psychosis (FEP) along a 2-year follow-up period, and (B) to overtime explore any relevant association of NS levels with the specific intervention components of an 'early intervention in psychosis' (EIP) protocol during the follow-up., Methods: At baseline, 266 FEP subjects (aged 12-35 years) completed the positive and negative syndrome scale (PANSS). Multiple linear regression analyses were then performed., Results: Along the follow-up, FEP participants had a relevant improvement in NS levels. This was specifically predicted by the total number of case management sessions offered within our 2-year EIP protocol, as well as by shorter duration of untreated psychosis at entry and by longitudinal reduction in PANSS depressive and positive symptom dimension levels. No association with antipsychotic medication was found., Conclusions: NS are clinically relevant in FEP, already at the recruitment time in specialized EIP services. However, their severity appears to improve over time together with the delivery of patient-tailored, integrated EIP case management., (© 2022 John Wiley & Sons Australia, Ltd.)

Purpose: Persistent Negative Symptoms (PNS) affect real-world functioning already at the onset of schizophrenia. Longitudinal studies on beneficial effects of psychosocial treatments for PNS in First Episode Schizophrenia (FES) are still relatively scarce. The aim of the current study was to evaluate the longitudinal persistence of PNS in young FES individuals treated according to the multimodal "Early Intervention in Psychosis" (EIP) program over a 2-year follow-up period., Materials and Methods: 133 FES subjects (aged 12-35 years) were recruited within the Italian EIP program and completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). In accordance with the PNS criteria, we dichotomized FES individuals with and without PNS. In the FES group with PNS, a multiple linear regression analysis was conducted to examine relevant associations between longitudinal PNS levels and the specialized treatment components of our EIP protocol., Results: Twenty (15%) FES participants met the PNS criteria. At baseline, PNS levels had relevant positive correlations with functioning decline and PANSS total score. At the end, the 2-years follow-up period, FES subjects with PNS showed a significant decrease in PNS levels. In our linear regression analysis, this reduction was associated with a higher number of individual psychotherapy and case management sessions delivered during our follow-up (together with a shorter DUP [Duration of Untreated Psychosis])., Conclusions: PNS are clinically relevant in a minority of FES individuals. Our results suggest that patient-tailored psychosocial interventions can reduce clinical severity of PNS over a 2-year period.

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam's Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors contributed to the article and approved the submitted version., (Copyright © 2022 Moglioni, Kraan, Baroni, Battistoni, Belcari, Berti, Carra, Cerello, Ciocca, De Gregorio, De Simoni, Del Sarto, Donetti, Dong, Embriaco, Fantacci, Ferrero, Fiorina, Fischetti, Franciosini, Giraudo, Laruina, Maestri, Magi, Magro, Malekzadeh, Marafini, Mattei, Mazzoni, Mereu, Mirandola, Morrocchi, Muraro, Orlandi, Patera, Pennazio, Pullia, Retico, Rivetti, Da Rocha Rolo, Rosso, Sarti, Schiavi, Sciubba, Sportelli, Tampellini, Toppi, Traini, Trigilio, Valle, Valvo, Vischioni, Vitolo, Wheadon and Bisogni.)

Purpose: Routine Outcome Monitoring (ROM) is still poorly implemented in the routine forensic psychiatric practice. As reliable ROM instruments are lacking, the aims of this research was to assess the psychometric properties of the Parma Scale (Pr-Scale) and its sensitivity to measure scores' longitudinal changes., Methods: Interrater and test-retest reliability, internal consistency and concurrent validity were investigated in offenders with mental disorder. Scores' longitudinal changeability was examined after a 3-month period using the Wilcoxon test for repeated measure., Results: Sixty male adult patients were recruited in this study. Our findings showed good to excellent interrater and test-retest reliability, concurrent validity and internal consistency for the Pr-Scale. Pr-Scale scores also display a moderate to large changeability over time., Conclusions: Our results support the clinical use of the Pr-Scale in forensic psychiatric settings as reliable ROM instrument., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Peanuts contain a diverse and vast array of phenolic compounds having important biological properties. They are allocated mostly in the seed coat (skin), an industrial waste with minor and undervalued applications. In the last few years, a considerable amount of scientific knowledge about extraction, composition, bioactivities and health benefits of peanut skin phenolics has been generated. The present review was focused on four main aspects: a) extraction methods and technologies for obtaining peanut skin phenolics with an emphasis on green-solvent extraction processes; b) variations in chemical profiles including those due to genetic variability, extraction methodologies and process-related issues; c) bioactive properties, especially antioxidant activities in food and biological systems; d) update of promising food applications. The revision was also aimed at identifying areas where knowledge is insufficient and to set priorities for further research., (Copyright © 2022. Published by Elsevier Ltd.)

Negative symptoms (NS) severely interfere with real-world performance, already at the onset of schizophrenia and in "clinical high risk" mental states. However, most of the empirical studies specifically examining treatment effectiveness on NS included patients with stable, prolonged schizophrenia. Moreover, research on psychosocial interventions for NS in early schizophrenia is still relatively scarce. Thus, the aims of this study were (1) to longitudinally monitor the NS stability in young individuals with First Episode Schizophrenia (FES) across a 2-year follow-up period, and (2) to investigate any significant association of NS with functioning, other aspects of FES psychopathology and the specific treatment component effects on NS of an "Early Intervention in Psychosis" (EIP) program during the 2 years of follow-up. At entry, 159 FES participants (aged 12-35 years) completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). Spearman's correlations and multiple linear regression analyses were performed. NS had relevant enduring associations with PANSS disorganization scores and GAF functioning decline. Across the follow-up, FES individuals showed a significant improvement in NS levels. This was specifically associated with the number of individual psychotherapy and intensive case management sessions provided during the 2 years of our EIP program, as well as with the antipsychotic dosage at entry. NS are clinically relevant in FES, already at the enrollment in specialized EIP services. However, their clinical severity seems to decrease over time, together with the delivery of specific, patient-tailored EIP interventions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: To compare different stereotactic body techniques-intensity-modulated radiotherapy with photons and protons, applied to radiotherapy of prostatic cancer-with simultaneous integrated boost (SIB) on the dominant intraprostatic lesion (DIL)., Methods: Ten patients were selected for this planning study. Dosimetric results were compared between volumetric modulated arc therapy, intensity-modulated radiation therapy (IMRT), and intensity-modulated proton therapy both with two (IMPT 2F) and five fields (IMPT 5F) planning while applying the prescription schemes of 7.25 Gy/fraction to the prostate gland and 7.5 Gy/fraction to the DIL in 5 fractions., Results: Comparison of the coverages of the planning target volumes showed that small differences exist. The IMPT-2F-5F techniques allowed higher doses in the targets; conformal indexes resulted similar; homogeneity was better in the photon techniques (2%-5%). Regarding the organs at risk, all the techniques were able to maintain the dose well below the prescribed constraints: in the rectum, the IMPT-2F-5F and IMRT were more efficient in lowering the intermediate doses; in the bladder, the median dose was significantly better in the case of IMPT (2F-5F). In the urethra, the best sparing was achieved only by IMPT-5F., Conclusions: Stereotactic radiotherapy with SIB for localized prostate cancer is feasible with all the investigated techniques. Concerning IMPT, the two-beam technique does not seem to have a greater advantage compared to the standard techniques; the 5-beam technique seems more promising also accounting for the range uncertainty.

Introduction: Suicidal thinking is relevant in patients with First Episode Psychosis (FEP). However, longitudinal studies specifically examining treatment response for suicidal ideation in FEP are still relatively scarce, especially with long-term design and in real-world clinical settings. The aims of this research were (A) to longitudinally assess suicidal thoughts in people with FEP along a 2-year follow-up period and (B) to overtime investigate any significant association of suicidal ideation levels with the specific treatment components of an 'Early Intervention in Psychosis' (EIP) protocol along the 2 years of follow-up., Methods: At entry, 232 FEP participants (aged 12-35 years) completed the Brief Psychiatric Rating Scale (BPRS), including a 'Suicidality' item subscore. Multiple linear regression analysis was then performed., Results: Across the follow-up, FEP subjects showed a relevant decrease in suicidal thinking levels overtime. This was specifically predicted by the total number of individual psychotherapy sessions offered within the 2-year EIP protocol and antidepressant dose (at least as regards the first year of our intervention)., Conclusion: Suicidal ideation is clinically relevant in FEP but seems to improve overtime together with the provision of specific, patient-tailored and integrated EIP treatments, especially individual psychotherapy., (© 2021 John Wiley & Sons, Ltd.)

Background: Tocopherols and sterols are minor components of virgin olive oils that contribute to oil quality. Based on observations at different geographical locations, it has been suggested that environmental temperature during fruit growth affects tocopherol and sterol oil concentrations in olive fruit. However, controlled experiments have not been conducted to directly assess their responses to temperature. In this study, a manipulative experiment using open-top chambers (OTCs) was performed in the field to evaluate the responses of these oil components to a moderate air temperature increase during oil accumulation in young trees of two olive cultivars (Arbequina, Coratina). The two temperature levels in the OTCs were a control about 1 °C above ambient temperature (T0) and a heated treatment (T+) with a target temperature of 4 °C above T0., Results: Total tocopherol and sterol oil concentrations in olive fruit were generally higher in the T+ temperature treatment than in the control at the end of the oil accumulation period. The increase in total tocopherols in T+ appeared to be related to a decrease in fruit oil concentration with heating. Individual sterols showed both significant increases and decreases due to T+, and some differences in response occurred between the two cultivars., Conclusion: These findings provide evidence that growth temperature affects tocopherol and sterol oil concentrations in olive fruit at the end of the oil accumulation period. Cultivars should be carefully chosen for new olive-growing regions, and the results could be relevant for global warming scenarios in existing growing regions. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Aim: Disorganization has been considered as a clinical domain close to the core of psychosis. However, it has received poor attention, especially at the illness onset. Moreover, most of the studies examining disorganized symptoms have been conducted in patients with chronic psychosis and research in the early stages of illness is still relatively scarce. Thus, the aims of this study were (a) to longitudinally monitor the stability of disorganization in patients with first episode psychosis (FEP) across a 1-year follow-up period, and (b) to investigate any relevant association of disorganized symptoms with functioning, psychopathology and the specific treatment components of an 'early intervention in psychosis' (EIP) program along the 1 year of follow-up., Methods: At baseline, 312 FEP participants (aged 12-35 years) completed the positive and negative syndrome scale (PANSS) and the global assessment of functioning (GAF). Spearman's correlations and multiple linear regression analysis were used., Results: At baseline, disorganization showed significant associations with all PANSS subscores, and a relevant negative correlation with GAF score. Across the follow-up, FEP individuals showed a significant improvement in disorganization severity. This decrease was specifically related to both baseline antipsychotic dosage and the number of individual cognitive-behavioural therapy sessions offered across the 1-year follow-up period., Conclusions: Disorganization is clinically relevant in FEP patients, already ate the enrollment in an EIP program. However, it tends to improve over time together with the delivery of specialized, person-tailored FEP interventions within a specific EIP protocol., (© 2021 John Wiley & Sons Australia, Ltd.)

Purpose: Recently two instruments were developed to address the study of the cognitive biases in schizophrenia spectrum disorders (SSD): the Cognitive Biases Questionnaire for Psychosis (CBQ-P) and the Davos Assessment of Cognitive Biases Scale (DACOBS). Aim of this study was to validate the Italian version of the DACOBS., Methods: We investigated factor structure, reliability, discriminative and convergent validity of the instrument by comparing to the CBQ-P in an Italian sample of 102 patients diagnosed with SSD and 330 healthy controls (HC), matched by age, education and gender., Results: The second-order seven-factor solution provided the best results among the four models tested. Reliability proved to be very satisfactory, with ω coefficient ranged from 0.75 for Jumping to conclusions to 0.89 for Safety Behavior. The Italian version of DACOBS could discriminate psychosis from HC (Wilks' Lambda=0.64, F=34.284, p<0.001; h2=0.364). All seven DACOBS subscales were significantly correlated with the CBQ-P subscales (total sample: r=0.331-0.707; SSD group: r=0.424-0.735; HC group: r=0.177-0.460)., Conclusions: The Italian version of DACOBS is a valid instrument for measuring cognitive biases for patients with psychosis, confirming previous results regarding the psychometric properties of the tool.

The Epstein Barr virus (EBV) infects almost 95% of the population worldwide. While typically asymptomatic, EBV latent infection is associated with several malignancies of epithelial and lymphoid origin in immunocompromised individuals. In latently infected cells, the EBV genome persists as a chromatinized episome that expresses a limited set of viral genes in different patterns, referred to as latency types, which coincide with varying stages of infection and various malignancies. We have previously demonstrated that latency types correlate with differences in the composition and structure of the EBV episome. Several cellular factors, including the nuclear lamina, regulate chromatin composition and architecture. While the interaction of the viral genome with the nuclear lamina has been studied in the context of EBV lytic reactivation, the role of the nuclear lamina in controlling EBV latency has not been investigated. Here, we report that the nuclear lamina is an essential epigenetic regulator of the EBV episome. We observed that in B cells, EBV infection affects the composition of the nuclear lamina by inducing the expression of lamin A/C, but only in EBV+ cells expressing the Type III latency program. Using ChIP-Seq, we determined that lamin B1 and lamin A/C bind the EBV genome, and their binding correlates with deposition of the histone repressive mark H3K9me2. By RNA-Seq, we observed that knock-out of lamin A/C in B cells alters EBV gene expression. Our data indicate that the interaction between lamins and the EBV episome contributes to the epigenetic control of viral gene expression during latency, suggesting a restrictive function of the nuclear lamina as part of the host response against viral DNA entry into the nucleus., Competing Interests: The authors have declared that no competing interests exist.

The aim of this work was the investigation of the ion recombination and polarity factors (k sat ad k pol ) for a PTW Advanced Markus ionization chamber exposed to proton and carbon ion beams at the Centro Nazionale di Adroterapia Oncologica. Measurements with protons were specifically dedicated for ocular treatments, in the low energy range and for small, collimated scanning fields. For both protons and carbon ions, several measurements were performed by delivering a 2D single energy layer of 3x3 cm 2 and homogeneous, biologically-optimized SOBPs. Data were collected at different depths in water, by varying the voltage values of the ionization chamber and for two different dose rates (the nominal one and one reduced to 20% of it). The k sat -values were determined from extrapolation of the saturation curves. Furthermore k pol -values were calculated using the recommendations from the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice. Results showed that the Advanced Markus performs optimally in this clinical scenario characterized by small treatment volumes and high dose gradients although for both particle types, but particularly for carbon ions, a charge multiplication effect up to 1.7% occurs at voltage higher than 150 V. For protons, both the ion recombination and polarity corrections were always smaller than 0.3%, for all the analysed cases and adopted dose rates, so not affecting the dosimetric measurements for clinical routine. For carbon ions the polarity effect can be neglected while ion recombination has to be carefully calculated and cannot be neglected since corrections even higher than 1% can be found, especially at high LET measuring points., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: The peanut skin (PS) is considered as an industrial waste with undervalued applications. Although several studies report potent antioxidant capacities of PS phenolics, the effectiveness in highly unsaturated lipid systems has not yet been evaluated. The objectives of the present study were two-fold: (i) to characterize a PS phenolic extract (PSE) obtained by means of a green technology and (ii) to evaluate its antioxidant efficacy on pure chia oil and chia oil in water (O/W) acid emulsion., Results: PSE was composed mainly of monomeric and condensed flavonoids (procyanidin and proanthocyanidin oligomers). PSE displayed strong antioxidant properties as measured by different reducing power and radical scavenging capacities [IC 50  = 0.36 μg dry extract (DE) mL -1 for ferric reducing antioxidant power; IC 50  = 4.96 μg DE mL -1 for 2,2-diphenyl-1-picrylhydrazyl (DPPH) • ; IC 50  = 6.01 μg DE mL -1 for 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) •+ ; IC 50  = 2.62 μg DE mL -1 for HO • ]. It also showed high antioxidant efficacy when tested in pure chia oil under accelerated oxidation conditions (Rancimat, 100 °C). When added to the O/W emulsions maintained at 40 °C for 15 days, the PSE was more effective than a synthetic antioxidant (tert-butylhydroquinone) with respect to minimizing the formation and degradation of lipid hydroperoxides., Conclusions: The antioxidant efficacy of PSE was primarily attributed to the abundance of compounds with a high number of phenolic-OH groups. Because they were found to cover a relatively wide range of partition coefficients, the antioxidant properties could be also enhanced by effect of both interfacial and solubility phenomena. All of these features allow the potential use of PSE as a natural antioxidant in different types of foods, including acid emulsion systems. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Aim: Recently, there has been increasing interest in providing Personal Health Budgets (PHBs) to patients with severe mental illness. However, information on implementing PHB initiatives is still limited. Aim of this observational study was to evaluate the applicability of a PHB intervention model in a sample of Italian adults with first-episode psychosis (FEP) across a 2-year follow-up period., Methods: Participants (n = 104; 18-50 years) were recruited within the 'Parma-Early Psychosis' program and completed the brief psychiatric rating scale (BPRS), the health of nation outcome scale (HoNOS) and the global assessment of functioning (GAF). Mixed-design analysis of variance (ANOVA) and Kaplan-Maier survival analysis (as drop-out measure) were performed., Results: A significant effect of time on all BPRS, HoNOS and GAF scores along the follow-up was observed in both the FEP subgroups (i.e., with [n = 49] and without [n = 55] PHB intervention). Mixed-design ANOVA results showed a significant 'time x group' interaction effects on BPRS 'Disorganization', HoNOS 'Psychiatric Symptoms' and GAF scores in FEP participants with PHB. Kaplan-Meyer survival analysis showed a longer survival mean for FEP patients with PHB., Conclusions: Our results support the applicability of a PHB model within an 'Early Intervention in Psychosis' program in public community mental health services., (© 2021 John Wiley & Sons Australia, Ltd.)

Purpose: To generate virtual 4DCT from 4DMRI with field of view (FOV) extended to the entire involved patient anatomy, in order to evaluate its use in carbon ion radiation therapy (CIRT) of the abdominal site in a clinical scenario., Materials and Methods: The virtual 4DCT was generated by deforming a reference CT in order to (1) match the anatomy depicted in the 4DMRI within its FOV, by calculating deformation fields with deformable image registration to describe inter-fractional and breathing motion, and (2) obtain physically plausible deformation outside of the 4DMRI FOV, by propagating and modulating the previously obtained deformation fields. The implemented method was validated on a digital anthropomorphic phantom, for which a ground truth (GT) 4DCT was available. A CIRT treatment plan was optimized at the end-exhale reference CT and the RBE-weighted dose distribution was recalculated on both the virtual and GT 4DCTs. The method estimation error was quantified by comparing the virtual and GT 4DCTs and the corresponding recomputed doses. The method was then evaluated on 8 patients with pancreas or liver tumors treated with CIRT using respiratory gating at end-exhale. The clinical treatment plans adopted at the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy) were considered and the dose distribution was recomputed on all respiratory phases of the planning and virtual 4DCTs. By comparing the two datasets and the corresponding dose distributions, the geometrical and dosimetric impact of organ motion was assessed., Results: For the phantom, the error outside of the 4DMRI FOV was up to 4.5mm, but it remained sub-millimetric in correspondence to the target within the 4DMRI FOV. Although the impact of motion on the target D 95% resulted in variations ranging from 22% to 90% between the planned dose and the doses recomputed on the GT 4DCT phases, the corresponding estimation error was ≤2.2%. In the patient cases, the variation of the baseline tumor position between the planning and the virtual end-exhale CTs presented a median (interquartile range) value of 6.0 (4.9) mm. For baseline variations larger than 5mm, the tumor D 95% variation between the plan and the dose recomputed on the end-exhale virtual CT resulted larger than 10%. Median variations higher than 10% in the target D 95% and gastro-intestinal OARs D 2% were quantified at the end-inhale, whereas close to the end-exhale phase, limited variations of relevant dose metrics were found for both tumor and OARs., Conclusions: The negligible impact of the geometrical inaccuracy in the estimated anatomy outside of the 4DMRI FOV on the overall dosimetric accuracy suggests the feasibility of virtual 4DCT with extended FOV in CIRT of the abdominal site. In the analyzed patient group, inter-fractional variations such as baseline variation and breathing variability were quantified, demonstrating the method capability to support treatment planning in gated CIRT of the abdominal site., (Copyright © 2020. Published by Elsevier GmbH.)

Purpose/background: Although the prevalence of mental disorders in prisoners is known to be higher than in the general population, less is known about the antipsychotic (AP) prescribing rate in jail. The aim of this research was to investigate prevalence and appropriateness of AP prescription in an Italian prison to expand our understanding on this crucial area of clinical-forensic practice., Methods/procedures: A cross-sectional (census day) design was used among male adults in the Parma Penitentiary Institutes (PPI). Sociodemographic, clinical and prescription data were collected from the PPI electronic clinical database management system. The AP prescribing appropriateness was examined in accordance with the therapeutic indications included in the Italian National Formulary. A descriptive statistical analysis was performed., Findings/results: A total of 98 (14.1%) of 696 PPI prisoners were taking AP medications. Moreover, 90 (91.8%) of the 98 PPI participants were also taking other psychotropic medications concurrently. Quetiapine and olanzapine were the most common prescribed APs. Antipsychotic medications were most likely to be prescribed for off-label indications (74.4%). Less than one fifth of all AP prescriptions were for psychotic disorders., Implications/conclusions: Antipsychotic medications are widely used in prison, often together with other psychotropic drugs. Considering their common adverse effects, it is crucial to longitudinally monitor their potential risk of metabolic, cardiovascular, and extrapyramidal symptoms and signs, as well as their early risk of mortality. Given the high prevalence of AP off-label prescription, the rationale for AP prescribing should be clearly documented and regularly reviewed within the prison by mental health professionals., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: In-beam positron emission tomography (PET) is one of the modalities that can be used for in vivo noninvasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy-to-interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in-beam PET monitoring images that can be used to locate, quantify, and visualize regions with possible morphological changes occurring over the course of treatment., Methods: We selected a patient treated for squamous cell carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel-wise two-tailed statistical tests of the simulated PET images, resembling the voxel-based morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change., Results: The VBM resembling method has been successfully applied to the simulated in-beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify interfractional morphological changes and to visualize them superimposed on the computed tomography (CT) scan. In particular, the characteristic color patterns resulting from the two-tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment., Conclusions: The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal interfractional morphological changes in patients, occurring over the course of treatment. Based on simulated in-beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments., (© 2021 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Mental health interventions for Italian prisoners with mental disorders remain a problematic issue, despite radical changes in general psychiatric care and a 2008 major government reform transferring mental health care in prison to the National Health Service. The aim of this study is to describe the mental health intervention model implemented since January 2020 for prisoners allocated in the Parma Penitentiary Institutes (PPI). This approach is specifically based on specialized, "person-centered" and "person-tailored" therapeutic-rehabilitation plans in line with psychiatric treatments usually provided in community mental health-care centers of the Parma Department of Mental Health., Design/methodology/approach: All the processes and procedures included in the PPI intervention model were first carefully illustrated, paying special attention to the service for newly admitted prisoners and each typology of specialized therapeutic-rehabilitation treatment potentially provided. Additionally, a preliminary descriptive process analysis of the first six months of clinical activity was also performed., Findings: Since January 2020, 178 individuals entered the PPI service for newly admitted prisoners. In total, 83 (46.7%) of them were engaged in the services of the PPI mental health-care team (35 with pathological addiction and 48 with mental disorders): 56 prisoners were offered an integrated mental health intervention and 27 exclusively an individual psychological or psychiatric treatment., Originality/value: The results support the potential applicability of an integrated mental health intervention in prison, planning a person-tailored rehabilitation in close collaboration with the prisoners, their families and the local mental health/social services., (© Emerald Publishing Limited.)

Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and aim - Evidence on discrete dimensions underlining negative symptoms in First Episode Affective Psychosis (FEAP) may be useful for their treatment strategy, but is still relatively scarce. Aim of this study was to examine the negative symptom configuration in patients with FEAP using both exploratory and confirmatory factor analysis methods on the Positive And Negative Syndrome Scale (PANSS). Methods - Seventy-eight participants, aged 13-35 years, completed the PANSS within the "Parma Early Psychosis" (Pr-EP) program, a specialized protocol of early detection and intervention in psychosis implemented since January 2013 in all public adolescent and adult mental health services of the Parma Department of Mental Health (Northern Italy). Results - A 3-factor model (i.e. "Alogia", "Social Withdrawal" and "Motor/Affective Expression Poverty" domains) was identified. As an alternative, a 2-factor solution previously proposed in patients with first episode schizophrenia (always within the Pr-EP program) also showed good fit indices in our FEAP sample. Conclusions - Our results suggest the crucial importance of identifying discrete negative symptom domains already at the onset of affective psychosis in order to implement specific early intervention strategies aiming to improve prognosis and long-term outcomes also in this young FEAP help-seeking population.

Objective: Disorganization is a core dimension of schizophrenia, yet it is relatively under-investigated compared to positive and negative ones, especially at the illness onset. Indeed, most of the empirical studies investigating the disorganized domain included patients with prolonged schizophrenia. Therefore, the aims of this research were (1) to monitor the longitudinal stability of disorganized symptoms in young patients with First Episode Schizophrenia (FES) along a 2-year follow-up period, and (2) to examine any significant association of disorganization with functioning, psychopathology and the specific treatment components of an "Early Intervention in Psychosis" (EIP) program across the 2 years of follow-up., Methods: At baseline, 159 FES individuals (aged 12-35 years) completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). Spearman's correlation coefficients and multiple linear regression analysis were carried out., Results: During the follow-up period, disorganization had relevant enduring positive associations with PANSS negative symptoms, lack of judgment/insight and positive symptoms representing delusional thought contents, as well as significant enduring negative correlation with GAF scores. Along the 2 years of follow-up, FES patients also showed a relevant improvement in disorganization symptoms. This reduction was specifically associated with the number of individual psychotherapy sessions provided during the first year of treatment., Conclusion: Disorganization is a prominent clinical feature in FES at the recruitment in specialized EIP services, but its temporal trajectory reveals a decrease over time, together with the delivery of specific, patient-tailored EIP interventions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Dosiomics is a texture analysis method to produce dose features that encode the spatial 3D distribution of radiotherapy dose. Dosiomic studies, in a multicentre setting, require assessing the features' stability to dose calculation settings and the features' capability in distinguishing different dose distributions. Dose distributions were generated by eight Italian centres on a shared image dataset acquired on a dedicated phantom. Treatment planning protocols, in terms of planning target volume coverage and dose-volume constraints to the organs at risk, were shared among the centres to produce comparable dose distributions for measuring reproducibility/stability and sensitivity of dosiomic features. In addition, coefficient of variation (CV) was employed to evaluate the dosiomic features' variation. We extracted 38,160 features from 30 different dose distributions from six regions of interest, grouped by four features' families. A selected group of features (CV < 3 for the reproducibility/stability studies, CV > 1 for the sensitivity studies) were identified to support future multicentre studies, assuring both stable features when dose distributions variation is minimal and sensitive features when dose distribution variations need to be clearly identified. Dosiomic is a promising tool that could support multicentre studies, especially for predictive models, and encode the spatial and statistical characteristics of the 3D dose distribution.

Disturbances of conscious awareness, or self-disorders, are a defining feature of schizophrenia. These include symptoms such as delusions of control, i.e. the belief that one's actions are controlled by an external agent. Models of self-disorders point at altered neural mechanisms of source monitoring, i.e. the ability of the brain to discriminate self-generated stimuli from those driven by the environment. However, evidence supporting this putative relationship is currently lacking. We performed electroencephalography (EEG) during self-paced, brisk right fist closures in ten (M = 9; F = 1) patients with Early-Course Schizophrenia (ECSCZ) and age and gender-matched healthy volunteers. We measured the Readiness Potential (RP), i.e. an EEG feature preceding self-generated movements, and movement-related EEG spectral changes. Self-disorders in ECSCZ were assessed with the Examination of Anomalous Self-Experience (EASE). Patients showed a markedly reduced RP and altered post-movement Event-Related Synchronization (ERS) in the beta frequency band (14-24 Hz) compared to healthy controls. Importantly, smaller RP and weaker ERS were associated with higher EASE scores in ECSCZ. Our data suggest that disturbances of neural correlates preceding and following self-initiated movements may reflect the severity of self-disorders in patients suffering from ECSCZ. These findings point towards deficits in basic mechanisms of sensorimotor integration as a substrate for self-disorders., (© 2021. The Author(s).)

Background - Interventions for inmates with Pathological Addiction (PA) still remain a problematic issue in Italian prisons, despite a 1999 major government reform transferring PA care in prison to the National Health Service. Aim of this research was to describe the integrated intervention model implemented for prisoners with PA in the Parma Penitentiary Institutes from January 2020 to June 2020. This specific approach is based on "person-tailored" therapeutic-rehabilitation programs in line with local community PA services. Methods - All the procedures were first carefully illustrated, especially the service for newly admitted inmates and the specialized rehabilitation treatments provided. A process analysis on the first six months of clinical activity was then performed. Results - Since January 2020, 178 subjects entered the service for newly admitted inmates: 55 (30.9%) were taken in charge for a PA. Conclusions - Our results support the feasibility of an integrated intervention model for PA in Italian prisons, based on specialized psychiatric treatments planned and provided in collaboration with inmates and their community health and social services.

Objective: Personal Health Budget has been provided to consumers with severe mental illness within a policy shift toward a person-tailored mental healthcare treatment based on individual unmet needs. Evidence of beneficial effects of Personal Health Budget is still scarce. The aim of this study was to provide preliminary data on clinical and social benefits of adding Personal Health Budget to a standard pharmacotherapy in patients with severe mental illness across a 24-month follow-up period., Methods: Participants ( n  = 137) were individuals with severe mental illness, aged 18-50 years, recruited in one of the adult mental health services of the Parma Department of Mental Health. They completed the Global Assessment of Functioning scale, the Health of the Nation Outcome Scale and the Brief Psychiatric Rating Scale. This age range was chosen to limit Personal Health Budget interventions to adults with a non-prolonged illness duration. Friedman's test for repeated measure was used to assess the longitudinal stability of functioning and clinical parameters. A linear regression analysis was also performed., Results: A significant decrease in all Global Assessment of Functioning scale, Health of the Nation Outcome Scale and Brief Psychiatric Rating Scale scores along the 24 months of follow-up was observed. Regression analysis results specifically showed a relevant association between a Personal Health Budget multiaxial intervention and the longitudinal reduction in Brief Psychiatric Rating Scale 'Negative Symptoms' and Health of the Nation Outcome Scale 'Social Problems' subscores., Conclusion: Our findings support the useful implementation of a Health of the Nation Outcome Scale approach for severe mental illness patients within the Italian mental health service network.

Background: Although depression has frequently been associated with Internet Gaming Disorder (IGD), its epidemiological impact on this emerging condition has not been systematically assessed. In this study, we aimed to synthesize the available evidence focusing on depression and depressive symptoms in individuals with IGD., Methods: We searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey, and ProQuest up to March 2020 for observational studies focusing on depression-related outcomes in IGD. We conducted random-effects meta-analyses on 1) rate of comorbid depression in IGD; 2) severity of depressive symptoms in IGD participants without depression., Results: We identified 92 studies from 25 different countries including 15,148 participants. 21 studies (n = 5025 participants) provided data for the first analysis, resulting in a pooled event rate of depression of 0.32 (95% Confidence Interval 0.21-0.43). The pooled Beck Depression Inventory scores in individuals without depression were suggestive of mild severity (13 studies, n = 508; 10.3, 95% Confidence Interval 8.3-12.4)., Limitations: The considerable inconsistency of methods employed across studies limits the transferability of these findings to clinical practice., Conclusions: The prevalence of depression in individuals with IGD varied considerably across studies, affecting approximately one out of three participants overall. Furthermore, a globally major severity of depressive symptoms was found in those without a clinical diagnosis of depression, compared to the general population. These findings confirm a relevant impact of mood disturbances in IGD., Registration Detail: PROSPERO (CRD42018100823)., (Copyright © 2021. Published by Elsevier B.V.)

The identification of discrete dimensions underlining negative symptoms in First Episode Psychosis (FEP) may be useful in the treatment strategy for such severe symptomatology. Aim of this research was to investigate the negative symptom configuration in FEP patients and to compare the emerging factor solutions between individuals with and without Schizophrenia Spectrum Disorders (non-SSD vs SSD). Two-hundred-seventy-four participants (144 non-SSD and 130 SSD), aged 13-35 years, completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). Confirmatory and exploratory factor analyses were then performed to examine PANSS negative symptom configuration in both SSD and non-SSD samples. In SSD, a 3-factor model solution (i.e. "Experiential Deficits", "Volition/Empathy Deficits" and "Motor/Affective Expression Deficits" domains) was identified. A different 2-factor configuration (with "Social/Communicative Withdrawal" and "Motor/Affective/Motivational Deficits" dimensions) was more appropriate in non-SSD. In conclusion, our results show differences in negative symptom factor models between non-SSD and SSD. Thus, a different specificity and significance of negative symptom solutions in FEP populations with diagnoses other than schizophrenia (compared to those with SSD) must be realistically considered., (Copyright © 2020. Published by Elsevier B.V.)

Background: The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT)., Methods: We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes., Results: After a median follow-up of 44 (range, 6-87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients., Conclusions: Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC., Key Points: • Proton and carbon ion therapy are effective and safe in skull base chordoma.• Prognostic factors are GTV, organs at risk compression, and dose coverage.• Dual particle therapy and customized strategy was adopted., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Stearoyl-ACP desaturases (SADs) and fatty acid desaturases (FADs) play a critical role in plant lipid metabolism and also affect oil fatty acid composition introducing double bonds into the hydrocarbon chains to produce unsaturated fatty acids. In the present study, the genomic sequences of three SAD and three FAD candidate genes were characterized in olive and their expression was evaluated in different plant tissues. OeSAD genes corresponded to olive SAD1 and SAD2 and to a newly identified OeSAD4, sharing the conserved protein structure with other plant species. On the other hand, the full-length genomic sequences of two microsomal OeFAD genes (FAD2-1 and FAD2-2) and the plastidial FAD6, were released. When the level of expression was tested on different tissues of cv. Leccino, OeSAD1 and OeSAD2 were mainly expressed in the fruits, while OeFAD genes showed the lowest expression in this tissue. The mRNA profiling of all genes was directly studied in fruits of Leccino and Coratina cultivars during fruit development. In both genotypes, the expression level of OeSAD1 and OeSAD2 had the highest value during and after the pit-hardening period, when oil accumulation in fruit mesocarp is intensively increasing. Furthermore, the expression level of both OeFAD2 genes, which were the main candidates for oleic acid desaturation, were almost negligible during fruit ripening. These results have made possible to define candidate genes of the machinery regulation of fatty acid composition in olive oil, providing information on their sequence, gene structure and chromosomal location.

Purpose: To investigate the impact of four-dimensional robust optimization (4DRO) on dose delivered to lung cancer patients in pencil beam scanning proton therapy., Methods and Materials: 2 strategies were compared for 20 lung cancer patients, using a different number of breathing phases of the reconstructed 4D computed tomography (CT) included in the plan optimization problem. In the restricted approach combined with gating, only 3 phases close to reference end-exhale were considered instead of the whole breathing cycle. The prescribed dose was 60 Gy(RBE) in 10 fractions. Target coverage (D98%) and dose to healthy tissues were evaluated using Wilcoxon signed-rank test. To assess the robustness against interfractional anatomical and respiratory variations, the optimized plans were recalculated on re-evaluation 4DCTs. To compare the sensitivity of both strategies to interplay effects, we implemented an end-to-end test with a home-made heterogeneous moving phantom and ionization chambers measurements. Robustly optimized plans with prescription doses of 6 Gy(RBE) were delivered in different dynamic conditions., Results: Both 4D robustly optimized plans reached the same target coverage (p = 0.56), while a statistically significant decrease of the homolateral lung dose was observed using the restricted approach (p < 0.0001). Plan recalculations within 15 days from the treatment simulation showed the same robustness of target D98% against interfractional variations (p = 0.48), with an average decrease of approximately 3 Gy(RBE). Phantom measurements confirmed the delivery accuracy of the restricted approach (mean dose deviations <5%). Higher deviations were found for ungated full 4DRO and larger motion amplitude., Conclusion: The restricted approach combined with gating improved normal tissue sparing and was shown to be more robust to single fraction deliveries and large motion amplitude., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nuts contain a vast array of phenolic compounds having important biological properties. They include substances allocated into the five major groups named phenolic acids, flavonoids, tannins, phenolic lignans, and stilbene derivatives. The complexity in composition does not allow for setting a universal extraction procedure suitable for extraction of all nut phenolics. The use of non-conventional extraction techniques, such as those based on microwave, ultrasound, and compressed fluids, combined with generally recognized as safe solvents is gaining major interest. With regard to the latter, ethanol, water, and ethanol-water mixtures have proven to be effective as extracting solvents and allow for clean, safe, and low-cost extraction operations. In recent years, there has been an increasing interest in biological properties of natural phenolic compounds, especially on their role in the prevention of several diseases in which oxidative stress reactions are involved. This review provides an updated and comprehensive overview on nut phenolic extraction and their chemical profiles and bioactive properties.

Olive is a long-living perennial species with a wide geographical distribution, showing a large genetic and phenotypic variation in its growing area. There is an urgent need to uncover how olive phenotypic traits and plasticity can change regardless of the genetic background. A two-year study was conducted, based on the analysis of fruit and oil traits of 113 cultivars from five germplasm collections established in Mediterranean Basin countries and Argentina. Fruit and oil traits plasticity, broad-sense heritability and genotype by environment interaction were estimated. From variance and heritability analyses, it was shown that fruit fresh weight was mainly under genetic control, whereas oleic/(palmitic + linoleic) acids ratio was regulated by the environment and genotype by environment interaction had the major effect on oil content. Among the studied cultivars, different level of stability was observed, which allowed ranking the cultivars based on their plasticity for oil traits. High thermal amplitude, the difference of low and high year values of temperature, negatively affected the oil content and the oleic acid percentage. Information derived from this work will help to direct the selection of cultivars with the highest global fitness averaged over the environments rather than the highest fitness in each environment separately.

Purpose: Beam energy validation is a fundamental aspect of the routine quality assurance (QA) protocol of a particle therapy facility. A multilayer ionization chamber (MLIC) detector provides the optimal tradeoff between achieving accuracy in particle range determination and saving operational time in measurements and analysis procedures. We propose the characterization of a commercial MLIC as a suitable QA tool for a clinical environment with proton and carbon-ion scanning beams., Materials and Methods: Commercial MLIC Giraffe (IBA Dosimetry, Schwarzenbruck, Germany) was primarily evaluated in terms of short-term and long-term stability, linearity with dose, and dose-rate independence. Accuracy was tested by analyzing range of integrated depth-dose curves for a set of representative energies against reference acquisitions in water for proton and carbon ion beams; in addition, 2 modulated proton spread-out Bragg peaks were also measured. Possible methods to increase the native spatial resolution of the detector were also investigated., Results: Measurements showed a high repeatability: mean relative standard deviation was within 0.5% for all channels and both particle types. The long-term stability of the gain calibration showed discrepancies less than 1% at different times. The detector response was linear with dose ( R 2 > 0.99) and independent on the dose rate. Measurements of integrated depth-dose curve ranges revealed a mean deviation from reference measurements in water of 0.1 ± 0.3 mm for protons with a maximum difference of 0.4 mm and 0.2 ± 0.6 mm with maximum difference of 0.85 mm for carbon ion beams. For the 2 modulated proton spread-out Bragg peaks, measured differences in distal dose falloff were ≤0.5 mm against calculated values., Conclusions: The detector is stable, linearly responding with dose, precise, and easy to handle for QA beam energy checks of proton and carbon ion beams., Competing Interests: Conflicts of Interest: Michele Togno, PhD, and Sara La Civita, MS, were employed full time with IBA Dosimetry (Schwarzenbruck, Germany) at the time of this study. The authors have no additional conflicts to disclose., (© Copyright 2019 The Author(s).)

Olive seeds, a potential food by-product from both table olive and olive oil industries, were examined for their overall proximate composition, oil, protein, mineral and phenolic components. Proximate analysis indicates that olive seeds are an unusually rich source of total dietary fibre (≅ 47% dry weight basis, DWB), as well as lipids (≅ 30%) and proteins (≅ 17%). Oil composition shows high levels of oleic (≅ 62% of total fatty acids) and linoleic (≅ 24%) acids, moderate concentrations of tocopherols (≅ 460 mg/kg) and squalene (≅ 194 mg/kg), and relatively high amounts of several sterols and non-steroidal triterpenoids. Olive seed proteins are a rich source of essential amino acids (about 46% of the total AA content). Olive seeds also contain significant amounts of some essential macro-elements (K, Ca, Mg, Na, P) and micro-elements (Zn, Mn, Cu). Phenolic compounds are present at relatively high quantities (≅ 2.8 mg/g seed, DWB); the most abundant belong to the group of secoiridoid compounds (elenolic acid derivatives) including oleuropein and structurally related substances (demethyloleuropein and ligstroside), and nüzhenide derivatives. Based on the general nutritional profile and nutraceutical components, olive seeds have value-added potential as a source of edible oil, proteins or meal serving as feed supplements.

A process to obtain phenolic compounds with antioxidant properties from pistachio nuts using water/ethanol mixture under high temperature and pressure conditions was carried out. To optimize extraction conditions and antioxidant activity of bioactive compounds, theoretical models were scanned against experimental data. Phenolic profile was dominated by several flavonoids and gallic acid derivatives. A fitted model for phenolic compounds extraction presented a maximum predicted value under the following conditions: 220 °C extraction temperature, 6.5 MPa pressure, and 50% ethanol. Beneath these conditions, phenolic extracts gave the highest radical scavenging capacity, similar to that reached by using commercial antioxidants. A mathematical model, namely two-site desorption kinetic model, showed to be suitable for the description of extraction kinetics under the optimal operation conditions. Overall, the process described in this study shows a potential alternative method for extraction of pistachio bioactive compounds. PRACTICAL APPLICATION: Pistachio nuts are known to contain a vast array of phenolic and polyphenolic substances having strong antioxidant properties. Currently, the use of natural antioxidants in the food industry has increased, in consequence there is a growing interest in improving the extraction processes using GRAS (general recognize as safe) solvents. This study describes a safe, inexpensive, and short-time method (subcritical fluid extraction) to obtain antioxidant extracts from defatted pistachio nuts. This type of process may be adapted toward applications at industrial scale., (© 2019 Institute of Food Technologists®.)

Within the dosimetric characterization of particle beams, laterally-integrated depth-dose-distributions (IDDs) are measured and provided to the treatment planning system (TPS) for beam modeling or used as a benchmark for Monte Carlo (MC) simulations. The purpose of this work is the evaluation, in terms of ion recombination and polarity effect, of the dosimetric correction to be applied to proton and carbon ion curves as a function of linear energy transfer (LET). LET was calculated with a MC code for selected IDDs. Several regions of Bragg peak (BP) curve were investigated. The charge was measured with the plane-parallel BP-ionization chamber mounted in the Peakfinder as a field detector, by delivering a fixed number of particles at the maximum flux. The dose rate dependence was evaluated for different flux levels. The chamber was connected to an electrometer and exposed to un-scanned pencil beams. For each measurement the chamber was supplied with {±400, +200, +100} V. Recombination and polarity correction factors were then calculated as a function of depth and LET in water. Three energies representative of the clinical range were investigated for both particle types. The corrected IDDs (IDD k s) were then compared against MC. Recombination correction factors were LET and energy dependent, ranging from 1.000 to 1.040 (±0.5%) for carbon ions, while nearly negligible for protons. Moreover, no corrections need to be applied due to polarity effect being  <0.5% along the whole IDDs for both particle types. IDD k s showed a better agreement than uncorrected curves when compared to MC, with a reduction of the mean absolute variation from 1.2% to 0.9%. The aforementioned correction factors were estimated and applied along the IDDs, showing an improved agreement against MC. Results confirmed that corrections are not negligible for carbon ions, particularly around the BP region.

To estimate the impact of dose calculation approaches adopted in different treatment planning systems (TPSs) on proton therapy dose delivered with pencil beam scanning (PBS). Treatment plans for six regular volumes in water and 15 clinical cases were optimized with Syngo-VC13 and exported for forward recalculation with Raystation-V7.0 pencil beam (RS-PBA) and Monte Carlo (RS-MC) algorithms and with the independent Fluka-MC engine. To verify clinical consistency between the two TPS dosimetric outcomes, the average percentage variations of clinical target volume (CTV) D 98% , D 50% and D 2% , adopted for plan prescription and evaluation, were considered. Ionization chamber measurements served as a further reference for comparison in homogeneous conditions. CTV dose volume histogram (DVH) analysis and gamma evaluation with 3 mm-3% agreement criteria quantified the dose deviation of TPS calculation algorithms, in heterogeneous conditions, against the Fluka-MC code. CTV D 50% , representing the plan dose prescription goal, was higher on average over H&N cases of (3.9  ±  0.9)% and (2.3  ±  0.6)% as calculated with RS-PBA and RS-MC, respectively, compared to Syngo. For tumors located in the pelvis district, average D 50% variations of (1.6  ±  0.7)% and (1.2  ±  0.7)% were found. Syngo underestimated target near maximum doses with respect to all computation systems. Calculation accuracy in heterogeneous conditions of RS-PBA H&N plans resulted poor when a range shifter was required. Target DVH and γ-analysis showed excellent agreement between RS-MC and Fluka-MC, with γ-pass rates  >98% for all patient groups. Different TPS dose calculation approaches mainly affected dose delivered in H&N proton treatments, while minor deviations were found for pelvic tumors. RS-MC proved to be the most accurate TPS dose calculation algorithm when compared to an independent MC simulation code.