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Background: Inflammation has been proposed as a crucial player in neurodegeneration, including Frontotemporal Dementia (FTD). A few studies on sporadic FTD lead to inconclusive results, whereas large studies on genetic FTD are lacking. The aim of this study is to determine cytokine and chemokine plasma circulating levels in a large cohort of genetic FTD, collected within the GENetic Frontotemporal dementia Initiative (GENFI)., Methods: Mesoscale technology was used to analyse levels of 30 inflammatory factors in 434 plasma samples, including 94 Symptomatic Mutation carriers [(SMC); 15 with mutations in Microtubule Associated Protein Tau (MAPT) 34 in Progranulin (GRN) and 45 in Chromosome 9 Open Reading Frame (C9ORF)72], 168 Presymptomatic Mutation Carriers (PMC; 34 MAPT, 70 GRN and 64 C9ORF72) and 173 Non-carrier Controls (NC)]., Results: The following cytokines were significantly upregulated (P<0.05) in MAPT and GRN SMC versus NC: Tumor Necrosis Factor (TNF)α, Interleukin (IL)-7, IL-15, IL-16, IL-17A. Moreover, only in GRN SMC, additional factors were upregulated, including: IL-1β, IL-6, IL-10, IL-12/IL-23p40, eotaxin, eotaxin-3, Interferon γ-induced Protein (IP-10), Monocyte Chemotactic Protein (MCP)4. On the contrary, IL-1α levels were decreased in SMC compared with NC. Significantly decreased levels of this cytokine were also found in PMC, independent of the type of mutation. In SMC, no correlations between disease duration and cytokine and chemokine levels were found. Considering NfL and GFAP levels, as expected, significant increases were observed in SMC as compared to NC. These differences in mean values remain significant even when stratifying symptomatic patients by the mutated gene (P<0.0001). Considering instead the levels of NfL, GFAP, and the altered inflammatory molecules, no significant correlations emerged., Conclusion: We showed that inflammatory proteins are upregulated in MAPT and GRN SMC, with some specific factors altered in GRN only, whereas no changes were seen in C9ORF72 carriers. Notably, only IL-1α levels were decreased in both SMC and PMC, independent of the type of causal mutation, suggesting common modifications occurring in the preclinical phase of the disease., 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 Elsevier Inc. All rights reserved.)

The glymphatic system (GS) is a whole-brain perivascular network, consisting of three compartments: the periarterial and perivenous spaces and the interposed brain parenchyma. GS dysfunction has been implicated in neurodegenerative diseases, particularly Alzheimer's disease (AD). So far, comprehensive research on GS in humans has been limited by the absence of easily accessible biomarkers. Recently, promising non-invasive methods based on magnetic resonance imaging (MRI) along with aquaporin-4 (AQP4) quantification in the cerebrospinal fluid (CSF) were introduced for an indirect assessment of each of the three GS compartments. We recruited 111 consecutive subjects presenting with symptoms suggestive of degenerative cognitive decline, who underwent 3 T MRI scanning including multi-shell diffusion-weighted images. Forty nine out of 111 also underwent CSF examination with quantification of CSF-AQP4. CSF-AQP4 levels and MRI measures-including perivascular spaces (PVS) counts and volume fraction (PVSVF), white matter free water fraction (FW-WM) and mean kurtosis (MK-WM), diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) (mean, left and right)-were compared among patients with AD (n = 47) and other neurodegenerative diseases (nAD = 24), patients with stable mild cognitive impairment (MCI = 17) and cognitively unimpaired (CU = 23) elderly people. Two runs of analysis were conducted, the first including all patients; the second after dividing both nAD and AD patients into two subgroups based on gray matter atrophy as a proxy of disease stage. Age, sex, years of education, and scanning time were included as confounding factors in the analyses. Considering the whole cohort, patients with AD showed significantly higher levels of CSF-AQP4 (exp(b) = 2.05, p = .005) and FW-WM FW-WM (exp(b) = 1.06, p = .043) than CU. AQP4 levels were also significantly higher in nAD in respect to CU (exp(b) = 2.98, p < .001). CSF-AQP4 and FW-WM were significantly higher in both less atrophic AD (exp(b) = 2.20, p = .006; exp(b) = 1.08, p = .019, respectively) and nAD patients (exp(b) = 2.66, p = .002; exp(b) = 1.10, p = .019, respectively) compared to CU subjects. Higher total (exp(b) = 1.59, p = .013) and centrum semiovale PVS counts (exp(b) = 1.89, p = .016), total (exp(b) = 1.50, p = .036) and WM PVSVF (exp(b) = 1.89, p = .005) together with lower MK-WM (exp(b) = 0.94, p = .006), mean and left ALPS (exp(b) = 0.91, p = .043; exp(b) = 0.88, p = .010 respectively) were observed in more atrophic AD patients in respect to CU. In addition, more atrophic nAD patients exhibited higher levels of AQP4 (exp(b) = 3.39, p = .002) than CU. Our results indicate significant changes in putative MRI biomarkers of GS and CSF-AQP4 levels in AD and in other neurodegenerative dementias, suggesting a close interaction between glymphatic dysfunction and neurodegeneration, particularly in the case of AD. However, the usefulness of some of these biomarkers as indirect and standalone indices of glymphatic activity may be hindered by their dependence on disease stage and structural brain damage., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and are implicated in neurodegenerative diseases, including frontotemporal dementia (FTD). However, their expression patterns and potential as biomarkers in genetic FTD involving Chromosome 9 Open Reading Frame (C9ORF72), Microtubule Associated Protein Tau (MAPT), and Progranulin (GRN) genes are not well understood., Objective: This study aimed to profile the expression levels of lncRNAs in peripheral blood mononuclear cells collected within the GENetic Frontotemporal dementia Initiative (GENFI)., Methods: Fifty-three lncRNAs were analyzed with the OpenArray Custom panel, in 131 patients with mutations in C9ORF72, MAPT, and GRN, including 68 symptomatic mutation carriers (SMC) and 63 presymptomatic mutation carriers (PMC), compared with 40 non-carrier controls (NC)., Results: Thirty-eight lncRNAs were detectable; the relative expression of NEAT1 and NORAD was significantly higher in C9ORF72 SMC as compared with NC. GAS5 expression was instead significantly lower in the GRN group versus NC. MAPT carriers showed no significant deregulations. No significant differences were observed in PMC. Disease duration did not correlate with lncRNA expression., Conclusions: NEAT1 and NORAD are upregulated in C9ORF72 SMC and GAS5 levels are downregulated in GRN SMC, underlining lncRNAs' relevance in FTD and their potential for biomarker development. Further validation and mechanistic studies are crucial for clinical implications.

Background: Perivascular spaces (PVS) are fluid-filled compartments that dilate in response to many different conditions. A high burden of enlarged PVS (EPVS) in the centrum semiovale (CSO) has been linked to neurodegeneration. Moreover, an increase in cerebrospinal fluid (CSF) levels of aquaporin-4 (AQP4), a water channel expressed on PVS-bounding astrocytes, has been described in patients with neurodegenerative dementia. Our aim was to investigate the relationship between neurodegenerative diseases and two putative glymphatic system biomarkers: AQP4 and EPVS., Methods: We included 70 individuals, 54 patients with neurodegenerative diseases and 16 subjects with non-degenerative conditions. EPVS were visually quantified on MRI-scans applying Paradise's scale. All subjects underwent lumbar puncture for the measurement of AQP4 levels in the cerebrospinal fluid (CSF). CSF levels of amyloid-β-1-42, phosphorylated and total tau (tTau) were also measured. Linear regression analyses were adjusted for age, sex, education and disease duration, after excluding outliers., Results: Cerebrospinal fluid (CSF)-AQP4 levels were independent predictors of total (β = 0.28, standard error [SE] = 0.08, p = 0.001), basal ganglia (β = 0.20, SE = 0.08, p = 0.009) and centrum semiovale EPVS (β = 0.37, SE = 0.12, p = 0.003). tTau levels predicted CSO-EPVS (β = 0.30, SE = 0.15, p = 0.046). Moreover, increased levels of AQP4 were strongly associated with higher levels of tTau in the CSF (β = 0.35, SE = 0.13, p = 0.008)., Conclusion: We provide evidence that CSO-EPVS and CSF-AQP4 might be clinically meaningful biomarkers of glymphatic dysfunction and associated neurodegeneration., 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., (Copyright © 2023 Sacchi, Arcaro, Carandini, Pietroboni, Fumagalli, Fenoglio, Serpente, Sorrentino, Visconte, Pintus, Conte, Contarino, Scarpini, Triulzi, Galimberti and Arighi.)

Background: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment., Objective: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance., Design: RCT with parallel and balanced large groups., Setting: Academic university hospital and Olympic gyms., Subjects: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity., Methods: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of "life movements", strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales., Results: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046)., Conclusion: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes. Clinical Trials Registration No : NCT03858114., (© 2021 Carta et al.)

Background: Aging is marked by a progressive rise in chronic diseases with an impact on social and healthcare costs. Physical activity (PA) may soothe the inconveniences related to chronic diseases, has positive effects on the quality of life and biological rhythms, and can prevent the decline in motor functions and the consequent falls, which are associated with early death and disability in older adults., Methods: We randomized 120 over-65 males and females into groups of similar size and timing and will give each either moderate physical activity or cultural and recreational activities. Being younger than 65 years, inability to participate in physical activity for any medical reason, and involvement in a massive program of physical exercise are the exclusion criteria. The primary outcome measures are: quality of life, walking speed, and postural sway. Participants are tested at baseline, post-treatment, and 6-month (24 weeks) and 12-month (48 weeks) follow-ups., Discussion: This study aims at improving the quality of life, wellness, and cognitive functioning in the elderly through a low-cost affordable program of moderate physical activity. Given the growing aging of the world population and the social and economic burden of disability in the elderly, our results might have a major impact on future practices., Trial Registration: ClinicalTrials.gov NCT03858114 . Registered on 28 February 2019.

Objective: Current nosology redefined agoraphobia as an autonomous diagnosis distinct from panic disorder. We investigated the lifetime prevalence of agoraphobia, its association with other mental disorders, and its impact on the health-related quality of life (HR-QoL)., Methods: Community survey in 2,338 randomly selected adult subjects. Participants were interviewed with the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), administered by clinicians. The diagnoses were based on the ICD-10 criteria. The Short-Form Health Survey (SF-12) was used to quantify HR-QoL., Results: In the sample, 35 subjects met the criteria for agoraphobia (1.5%), with greater prevalence among women (2.0%) than men (0.9%): odds ratio (OR) 2.23; 95% CI: 1.0-5-2. Agoraphobia was more often seen among those with (n=26; 1.1%) than without (n=9; 0.4%) panic disorder: OR=8.3; 2.9-24.4. Co-morbidity with other mental disorders was substantial. The mean score of SF-12 in people with agoraphobia was 35.2±7.8, with similar levels of HR-QoL in people with (35.3±7.9) or without (34.8±7.3) panic disorder: ANOVA: F(1;33)=0.0; p=1.00., Conclusion: One out of seventy people may suffer from agoraphobia in their lifetime. The attributable burden in terms of HR-QoL is substantial and comparable to the one observed for chronic mental disorders such as major depression, post-traumatic stress disorder, or obsessive-compulsive disorder.

Aim: To explore the prevalence of Aberrant Salience (AS, an alleged experiential feature of psychosis-proneness) in Italian young people and corroborate the transcultural validity of the Aberrant Salience Inventory (ASI)., Methods: Young adults attending an Italian university (n = 649) underwent serial evaluations with the ASI together with psychometric proxies for help seeking General Health Questionnaire and attenuated positive and negative symptoms Schizotypal Personality Questionnaire (SPQ). The distribution of ASI scores was explored with latent class analysis (LCA)., Results: Reliability of the Italian version of the ASI (I-ASI) was acceptable for all subscales (ordinal alpha >.70). Concurrent validity was in the expected direction, with higher correlations with measures of attenuated positive symptoms vs negative symptoms of psychosis (Steigers' z test, P < .005 in all comparisons). LCA identified three classes, with 217 (33.4%) participants in the "high aberrant salience" class. Gender and age were not related to class membership. Compared to the baseline class, SPQ scores in the schizotypy range were more likely in the "high aberrant salience" class (OR = 39.1; 95%confidence interval: 5.30-288.1)., Conclusion: AS is a relatively common experience among Italian young people. The study also confirmed the validity of field-testing ASI as a tool for the real-world characterization of people with vulnerability to psychosis, such as symptomatic help seekers with clinical high-risk states., (© 2017 John Wiley & Sons Australia, Ltd.)

Agriculture and intensive farming methods are the greatest cause of nitrogen pollution. In particular, nitrification (the conversion of ammonia to nitrate) plays a role in global climate changes, affecting the bio-availability of nitrogen in soil and contributing to eutrophication. In this paper, the Rhodotorula diobovata DSBCA06 was investigated for growth kinetics on nitrite, nitrate, or ammonia as the sole nitrogen sources (10 mM). Complete nitrite removal was observed in 48 h up to 10 mM initial nitrite. Nitrogen was almost completely assimilated as organic matter (up to 90% using higher nitrite concentrations). The strain tolerates and efficiently assimilates nitrite at concentrations (up to 20 mM) higher than those previously reported in literature for other yeasts. The best growth conditions (50 mM buffer potassium phosphate pH 7, 20 g/L glucose as the sole carbon source, and 10 mM nitrite) were determined. In the perspective of applications in inorganic nitrogen removal, other metabolic features relevant for process optimization were also evaluated, including renewable sources and heavy metal tolerance. Molasses, corn, and soybean oils were good substrates, and cadmium and lead were well tolerated. Scale-up tests also revealed promising features for large-scale applications. Overall, presented results suggest applicability of nitrogen assimilation by Rhodotorula diobovata DSBCA06 as an innovative tool for bioremediation and treatment of wastewater effluents.

Introduction: The aim of this study was to carry out a 2-year follow-up of refugees in a camp in Burkina Faso who had been interviewed previously. We also aimed to verify whether the general conditions in which they lived (e.g., protection by international organizations and the conclusion of negotiations and new hope of returning to Mali and reunification with surviving family members) would affect their mental health state., Methods: This is a cross-sectional study repeated over time on a cohort of refugees. People living in the Subgandé camp who had participated in the first survey in 2012 were identified using informational chains and approached for follow-up. Those who agreed were interviewed using the Short Screening Scale for post-traumatic stress disorder (PTSD) and the K6 scale, French versions, to measure general psychopathology and the level of impairment., Results: The second survey shows a dramatic decrease in psychopathological symptoms (positivity at K6 scale). Improvement was also conspicuous in the frequency of people with stress symptoms (positivity at Short Screening Scale for PTSD and simultaneous positivity to K6 scale). The frequency of people screened positive at the Short Screening Scale for PTSD had also decreased, but the level of improvement was not pronounced., Conclusion: Our findings confirm that when physical conditions improve, psychological symptoms can also improve. Although in the studied sample psychological factors, such as the hope of returning to their own land and thus the possibility of maintaining ethnic cohesion, may have played a role, future research carried out with a proper methodology and sufficient resources to identify protective factors is needed.

Background: Research literature suggests that burnout, depression, and a low mental quality of life (QOL) are common among health care workers. Economic crisis might have increased the burden of burnout, depression and low QOL in health care workers., Objectives: To identify depression risk, burnout levels, and quality of life in a sample of workers of an Italian university hospital., Method: Cross sectional study with comparison with two community surveys database results (n = 2000 and 1500, respectively). Overall, 522 workers accepted to take part in the study, representing a 78% response rate (out of 669 individuals)., Results: The frequency of positivity at the screener for Major Depressive Disorder among health care workers was more than double than that in the standardized community sample (33.3% vs 14.1%, p<0.0001). All professionals, except the administrative staff and technicians ( i.e. those who do not have contact with patients), showed a statistically higher frequency of positivity for depressive episodes compared to the controls. Among the medical staff, the highest risk was found in the surgeon units, while the lowest one was in the laboratories. Surgeons also were those most exposed to high risk of burnout, as measured by the Maslach Burnout Inventory., Conclusion: Since burnout is linked to patient safety and quality of patient care, and contribute to medical errors, dedicated interventions aimed at reducing poor mental health and low quality of life in medical staff are indicated.

Dendrimeric peptides make a versatile group of bioactive peptidomimetics and a potential new class of antimicrobial agents to tackle the pressing threat of multi-drug resistant pathogens. These are branched supramolecular assemblies where multiple copies of the bioactive unit are linked to a central core. Beyond their antimicrobial activity, dendrimeric peptides could also be designed to functionalize the surface of nanoparticles or materials for other medical uses. Despite these properties, however, little is known about the structure-function relationship of such compounds, which is key to unveil the fundamental physico-chemical parameters and design analogues with desired attributes. To close this gap, we focused on a semi-synthetic, two-branched peptide, SB056, endowed with remarkable activity against both Gram-positive and Gram-negative bacteria and limited cytotoxicity. SB056 can be considered the smallest prototypical dendrimeric peptide, with the core restricted to a single lysine residue and only two copies of the same highly cationic 10-mer polypeptide; an octanamide tail is present at the C-terminus. Combining NMR and Molecular Dynamics simulations, we have determined the 3D structure of two analogues. Fluorescence spectroscopy was applied to investigate the water-bilayer partition in the presence of vesicles of variable charge. Vesicle leakage assays were also performed and the experimental data were analyzed by applying an iterative Monte Carlo scheme to estimate the minimum number of bound peptides needed to achieve the release. We unveiled a singular beta hairpin-type structure determined by the peptide chains only, with the octanamide tail available for further functionalization to add new potential properties without affecting the structure.

Aims: Using data from a population survey in two communities in the region of Sardinia, Italy, we examined the association between illness definition and attribution of personal characteristics to people with alcoholism., Methods: Quota samples, stratified by gender and age, were drawn from the general population (males: 48%; mean age 48±18; range: 15-90). A fully-structured interview was conducted face-to-face with 404 respondents. The assessment of the public view of 'alcoholics' was measured by their reactions to stimulus words rated on bipolar scales, and defined with adjectives with opposite meanings at each end., Results: 322 participants (80%) rated the 'alcoholic' as 'ill'. The definition of the 'alcoholic' as being ill showed a statistically higher odd of stigma across all the dimensions of personal attributes., Conclusions: The expectation that people adopting the illness model would tend to blame less those afflicted for their condition and, consequently, stigmatize them less, was not confirmed., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Peptide-based antibiotics might help containing the rising tide of antimicrobial resistance. We developed SB056, a semi-synthetic peptide with a dimeric dendrimer scaffold, active against both Gram-negative and Gram-positive bacteria. Being the mechanism of SB056 attributed to disruption of bacterial membranes, we enhanced the amphiphilic profile of the original, empirically derived sequence [WKKIRVRLSA-NH2] by interchanging the first two residues [KWKIRVRLSA-NH2], and explored the effects of this modification on the interaction of peptide, both in linear and dimeric forms, with model membranes and on antimicrobial activity. Results obtained against Escherichia coli and Staphylococcus aureus planktonic strains, with or without salts at physiological concentrations, confirmed the added value of dendrimeric structure over the linear one, especially at physiological ionic strength, and the impact of the higher amphipathicity obtained through sequence modification on enhancing peptide performances. SB056 peptides also displayed intriguing antibiofilm properties. Staphylococcus epidermidis was the most susceptible strain in sessile form, notably to optimized linear analog lin-SB056-1 and the wild-type dendrimer den-SB056. Membrane affinity of all peptides increased with the percentage of negatively charged lipids and was less influenced by the presence of salt in the case of dendrimeric peptides. The analog lin-SB056-1 displayed the highest overall affinity, even for zwitterionic PC bilayers. Thus, in addition to electrostatics, distribution of charged/polar and hydrophobic residues along the sequence might have a significant role in driving peptide-lipid interaction. Supporting this view, dendrimeric analog den-SB056-1 retained greater membrane affinity in the presence of salt than den-SB056, despite the fact that they bear exactly the same net positive charge.

Background: Cytinus is an endophytic parasitic plant occurring in South Africa, Madagascar, and in the Mediterranean region. We have extracted the inflorescences (the only visible part of the plant, emerging from the host roots at the time of blossom) of Cytinus hypocistis collected in Sardinia, Italy, and explored the antimicrobial, antioxidant, anti-tyrosinase, and cytotoxic activities of the extracts., Methods: Extracts from C. hypocistis were prepared using increasing polarity solvents: cyclohexane, ethanol, and water. Phenolic composition were determined through spectrophotometric assays, and antioxidant activity with both electron-transfer and hydrogen-atom assays. Nine different bacterial strains, including clinical isolate methicillin-resistant Staphylococcus aureus, were used in agar diffusion method. Cytotoxicity was tested using against the B16F10 melanoma cell line., Results: While cyclohexane extracts where biologically inactive, ethanolic and aqueous extracts displayed an intriguing activity against several Gram-positive bacterial strains, including methicillin-resistant S. aureus, and against the Gram-negative Acinetobacter baumanii. Compared to the conventional antibiotics like cloxacillin, ampicillin, and oxytetracycline, C. hypocistis extracts were less active in absolute terms, but displayed a wider spectrum (notably, cloxacillin and ampicillin were inactive against methicillin-resistant S. aureus). The ethanolic extract of C. hypocistis was found to be particularly rich in polyphenols, in most part hydrolysable tannins. The antioxidant activity of extracts, tested with several methodologies, resulted to be particularly high in the case of ethanolic extracts, in accordance with the composition in phenolics. In detail, ethanol extracts presented about a twofold higher activity than the water sample when tested through the oxygen radical absorbance capacity-pyrogallol red (ORAC-PYR) assay. Cytotoxicity analysis against the B16F10 melanoma cell line showed that both extracts have not significant cytotoxic effect, even at the highest dose (1000 µg/mL). Tests showed that ethanolic extracts also had the greatest tyrosinase inhibition activity, indicating that C. hypocistis-derived substances could find application in food formulations as anti-browning agents., Conclusions: Overall, these results point to the need of further studies on C. hypocistis extracts, aimed at isolating and fully characterizing its biologically active compounds.

Background: The purpose was to determine if brain damage in Wilson's disease (WD) is different in comorbid bipolar spectrum disorders (BDs), comorbid major depressive disorder (MDD) or without any mood disorders., Methods: An observational study was conducted on consecutive patients from a center for WD care. The study sample was divided by psychiatric assessment into WD without any mood disorders, WD with BDs and WD with MDD negative at Mood Disorder Questionnaire (MDQ)., Results: Thirty-eight WD patients were recruited (53.2% females): 21 without mood disorders (55.2%), 9 with comorbid BDs (26.7%) and 8 with MDD without MDQ+ (21.1%). The BDs showed a higher frequency of brain damage, reaching statistically significant differences in the basal ganglia (P<.001), in the overall brain (P<.003) and at the limit in the white matter (P<.05)., Conclusions: In WD, comorbidity with BDs is associated with earlier evidence of brain damage, especially in the basal ganglia. The results confirm the importance of screening and early diagnosis of BDs in WD. Future follow-up studies on large samples are required to confirm if detection of BDs may be an early marker of brain damage and if a good therapeutic response in BDs may improve the prognosis of WD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The school setting may be the optimal context for early screening of and intervention on child mental health problems, because of its large reach and intertwinement with various participants (child, teacher, parent, other community services). But this setting also exposes children to the risk of stigma, peer rejection and social exclusion. This systematic literature review investigates the efficacy of mental health interventions addressed to children and adolescents in school settings, and it evaluates which programs explicitly take into account social inclusion indicators., Method: Only randomized controlled trials conducted on clinical populations of students and carried out in school settings were selected: 27 studies overall. Most studies applied group Cognitive Behavioural Therapy or Interpersonal Psychotherapy., Results: Findings were suggestive of the effectiveness of school-based intervention programs in reducing symptoms of most mental disorders. Some evidence was found about the idea that effective studies on clinical populations may promote the social inclusion of children with an ongoing mental disorder and avoid the risk of being highly stigmatized., Conclusion: School programs are still needed that implement standardized models with verifiable and evidence-based practices involving the whole school community.

Sparse evidence of a co-aggregation of the risk of schizophrenia and bipolar disorder provides support for a shared but nonspecific genetic etiology of bipolar disorder and schizophrenia. Temperaments are conceptualized as trait sub-syndromic conditions of major pathologies. This study set out to test the hypothesis of a continuum between schizotypy and affective temperaments versus the alternative hypothesis of their independence based on a cross-sectional, survey design involving 649 (males: 47%) college students. The short 39-item TEMPS-A and the SPQ were used as measures of the affective temperaments and of schizotypy, respectively. Confirmatory factor analyses were applied to a unidimensional model, to a standard correlate traits model, to second-order representations of a common latent structure, and to a bifactor model. Confirmatory bifactor modeling provided evidence against a complete independence of the dimensions subsumed by the affective and the schizotypal traits. The best solution distinguished between two sub-domains grouping positive symptoms and negative symptoms as measured by the SPQ subscales, and a sub-domain related to the affective temperaments as measured by the TEMPS-A. Limitations due to the use of subscales from two different tools should be taken into account., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

SB056 is a novel semi-synthetic antimicrobial peptide with a dimeric dendrimer scaffold. Active against both Gram-negative and -positive bacteria, its mechanism has been attributed to a disruption of bacterial membranes. The branched peptide was shown to assume a β-stranded conformation in a lipidic environment. Here, we report on a rational modification of the original, empirically derived linear peptide sequence [WKKIRVRLSA-NH2, SB056-lin]. We interchanged the first two residues [KWKIRVRLSA-NH2, β-SB056-lin] to enhance the amphipathic profile, in the hope that a more regular β-strand would lead to a better antimicrobial performance. MIC values confirmed that an enhanced amphiphilic profile indeed significantly increases activity against both Gram-positive and -negative strains. The membrane binding affinity of both peptides, measured by tryptophan fluorescence, increased with an increasing ratio of negatively charged/zwitterionic lipids. Remarkably, β-SB056-lin showed considerable binding even to purely zwitterionic membranes, unlike the original sequence, indicating that besides electrostatic attraction also the amphipathicity of the peptide structure plays a fundamental role in binding, by stabilizing the bound state. Synchrotron radiation circular dichroism and solid-state 19F-NMR were used to characterize and compare the conformation and mobility of the membrane bound peptides. Both SB056-lin and β-SB056-lin adopt a β-stranded conformation upon binding POPC vesicles, but the former maintains an intrinsic structural disorder that also affects its aggregation tendency. Upon introducing some anionic POPG into the POPC matrix, the sequence-optimized β-SB056-lin forms well-ordered β-strands once electro-neutrality is approached, and it aggregates into more extended β-sheets as the concentration of anionic lipids in the bilayer is raised. The enhanced antimicrobial activity of the analogue correlates with the formation of these extended β-sheets, which also leads to a dramatic alteration of membrane integrity as shown by 31P-NMR. These findings are generally relevant for the design and optimization of other membrane-active antimicrobial peptides that can fold into amphipathic β-strands.

Background: Public beliefs about appropriate treatment impact, help-seeking and treatment adherence., Aim: To determine the recommendations of the Sardinian public for the treatment of depression., Methods: In 2012, a population-based survey was conducted by phone in Sardinia (N = 1,200). In the context of a fully structured interview, respondents were presented with a vignette depicting a case of depression. Subsequently, they were asked about their treatment recommendations. The results are contrasted with findings from a similar survey which had been conducted in Vienna 3 years before., Results: In Sardinia as in Vienna, psychotherapy was the uncontested favorite, while antidepressant medication was recommended by relatively few respondents. In Sardinia, there were also no marked differences between urban and rural areas with regard to these two treatments. However, between Sardinia and Vienna, as well as within Sardinia, great differences were found with regard to autogenic training and 'alternative' methods like homeopathic medicines and acupuncture., Conclusion: Cross-cultural comparisons may help better understand treatment preferences of the public. In Sardinia, as in Vienna, there seems to be a need for improving the public's knowledge about the appropriate treatment of depression., (© The Author(s) 2013.)

Introduction: Abnormalities in biological rhythms (BR) may have a role in the pathophysiology of Bipolar Disorders (BD). The objective of this study is to validate the Italian version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), a useful tool in studying BR, and measure its accuracy in discriminating BD., Methods: 44 outpatients with DSM-IV-TR diagnosis of BD and 38 controls balanced for sex and age were consecutively recruited. The discriminant validity of BRIAN for the screening of BD and its test re-test reliability in two evaluations were assessed., Results: BD patients scored 22.22±11.19 in BRIAN against 7.13±5.6 of the control group (P<0.0001). BRIAN showed a good accuracy to screen between BD non-BD at cutoff 16, a sensitivity was 68.2 and specificity was 92.5. The test-retest stability measured using Pearson's coefficient found very high r values for each section and the total score, thus indicating a correlation at the two times of statistical significance in all measures. Cohen's Kappa varied from 0.47 in the sociality section to 0.80 in the sleep section, with a total K mean of 0.65., Conclusion: The results show that the Italian version of BRIAN has good discriminant validity in detecting BD from healthy controls and shows good test-retest reliability. The study suggests the possibility of developing mixed screening tools by introducing items on dysregulation of biological rhythms to the usual measures of mood.

Background: This survey followed a cohort of patients with chronic psychosis recruited from five catchment areas (DSMs) of the Sardinian community mental health services. The objective was to examine whether the amount of resources in the different sites may be a determinant of the outcomes., Methods: Naturalistic follow-up study on 309 consecutive users with diagnosis of schizophrenic disorder, schizoaffective disorder, bipolar affective disorder with psychotic symptoms (DSM-IV TR) of five Sardinian community mental health services. Mental state and clinical symptoms along with functioning were assessed using semi-structured clinical interviews (ANTAS), Clinical Global Impression Severity Scale (CGI-S), Global Assessment of Functioning Scale (GAF) and Health of the Nation Outcome Scales (HONOS). Assessments were conducted at the beginning of the study and after one year., Results: The proportion of professionals working in all DSMs participating in the study was found lower than the national Italian standard (0.7 vs. 1.0 per 1,500 inhabitants). Follow-up revealed significant differences between DSMs in the improvement of the Honos scores (F = 5.932, p = 0.000). These differences correlate with the improvement of resources in terms of number of professionals during, and one year prior, to the trial., Conclusions: The study shows that mental health services provided in the public sector in Sardinia are still very resource-poor, at least in terms of human resources. Our findings suggest that mental health service resources influence outcomes as regards the social functioning of users. We urge policy makers to take these observations into account when planning future services.

Background: The Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Autoquestionnaire (TEMPS-A) is a widely used self-reported tool aimed at measuring the affective temperaments that define the bipolar spectrum, with cyclothymic, depressive, irritable, hyperthymic, and anxious subscales. Confirmatory factor analysis (CFA) was rarely used to confirm the expected five-factor model. Measurement invariance was never tested., Methods: Cross-sectional, survey design involving 649 Italian college students (males: 47%). The short 39-item TEMPS-A and the 12-item General Health Questionnaire (GHQ-12) were used as measures of the affective temperaments and of psychological distress, respectively. CFA was applied to the TEMPS-A. Measurement invariance by gender, age and levels of psychological distress on the GHQ-12 was calculated with the establishment of subsequent equivalence constraints in the model parameters across groups., Results: The expected five-factor model had the best fit for all CFA indexes. Configural, metric and scalar invariance of the five-factor model of the TEMPS-A was proved across gender, age and levels of psychological distress of the participants. The hyperthymic temperament subscale has low or no links with the other affective temperament subscales, which were interrelated with medium to large effect sizes., Limitations: College students might be not representative of the general population. No information on the clinical status of the students was available beyond self-report data., Conclusion: The study proved the measurement invariance of the (short) TEMPS-A, which is a pre-requisite to compare groups or individuals in cross-sectional and longitudinal surveys. Generalizability cannot be assumed without replication of the findings in clinical samples., (© 2013 Elsevier B.V. All rights reserved.)

Background: The aim of the study was to examine the efficacy of a vocational training program on renewable energy sources in reducing disabilities of people with chronic psychosis (CP). The innovative element was that the project could produce major advantages regarding the economic needs of the whole area involved., Methods: Experimental Cohort, 26 subjects with CP (EC); Control Cohort1, 130 subjects with CP following pharmacotherapy plus other rehabilitation activities (CIC); Control Cohort2, 101 subjects with CP following the usual treatment (pharmacotherapy) (CUC). Study tool: Health of the Nation Outcome Scales (HoNOS). Assessment made at the start of the study (T0) and after three months (T1). Statistical analysis made by MANOVA., Results: Improvement in HoNOS total score in both groups (F=7.574, p=0.000) with non-significant differences between groups over time (F=1.336, p=0.252) was found comparing EC vs. CIC. Greater improvement in EC vs. CIC was shown in the HoNOS "impairment" scale (F=4.910, p=0.028). EC vs. CUC: both groups improved in HoNOS total score (F=9.440, p=0.000) but the improvement was greater in EC (F = 2.273, P=0.048)., Conclusions: Work inclusion, as well as other rehabilitation treatments, reduces the social needs of people with chronic psychosis. Work inclusion in a project with real relevance for the area where these people live, produces more improvement of cognitive, physical and somatic disabilities, probably related to a better outcome in self-efficacy.

Ferula communis (L.), a plant belonging to Apiaceae, is widely present in Sardinia, Italy. Currently, interest in F. communis focuses on the presence of two chemotypes in the wild. One chemotype is poisonous to animals, whereas the other chemotype is non-poisonous. Polyphenol oxidase (PPO) has been extracted and partially purified from the two chemotypes of F. communis. The biochemical characterization of the enzymes showed significant differences. In particular, while the two PPOs were not able to use 6- and 7-hydroxycoumarin as substrates, they showed distinct specificity for 6,7- and 7,8-dihydroxycoumarin. Significant differences in the enzyme behavior towards common PPO inhibitors were also observed. In addition, activation energy and activation energy for denaturation were determined, showing significant differences between FP-PPO and FNP-PPO, particularly for denaturation kinetics. The possible roles of the two PPOs in determining differences in composition and toxicity of the two F. communis chemotypes are also discussed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Synthetic dyes represent a broad and heterogeneous class of durable pollutants, that are released in large amounts by the textile industry. The ability of two immobilized metalloporphines (structurally emulating the ligninolytic peroxidases) to bleach six chosen dyes (alizarin red S, phenosafranine, xylenol orange, methylene blue, methyl green, and methyl orange) was compared to enzymatic catalysts. To achieve a green and sustainable process, very mild conditions were chosen., Results: IPS/MnTSPP was the most promising biomimetic catalyst as it was able to effectively and quickly bleach all tested dyes. Biomimetic catalysis was fully characterized: maximum activity was centered at neutral pH, in the absence of any organic solvent, using hydrogen peroxide as the oxidant. The immobilized metalloporphine kept a large part of its activity during multi-cycle use; however, well-known redox mediators were not able to increase its catalytic activity. IPS/MnTSPP was also more promising for use in industrial applications than its enzymatic counterparts (lignin peroxidase, laccase, manganese peroxidase, and horseradish peroxidase)., Conclusions: On the whole, the conditions were very mild (standard pressure, room temperature and neutral pH, using no organic solvents, and the most environmental-friendly oxidant) and a significant bleaching and partial mineralization of the dyes was achieved in approximately 1 h. Therefore, the process was consistent with large-scale applications. The biomimetic catalyst also had more promising features than the enzymatic catalysts.

Background: Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the main functioning problems experienced by psychiatric patients, specifically bipolar patients. It includes 24 items assessing impairment or disability in six domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time. The aim of this study is to measure the validity and reliability of the Italian version of this instrument., Methods: Twenty-four patients with DSM-IV TR bipolar disorder and 20 healthy controls were recruited and evaluated in three private clinics in Cagliari (Sardinia, Italy). The psychometric properties of FAST (feasibility, internal consistency, concurrent validity, discriminant validity (patients vs controls and eutimic patients vs manic and depressed), and test-retest reliability were analyzed., Results: The internal consistency obtained was very high with a Cronbach's alpha of 0.955. A highly significant negative correlation with GAF was obtained (r = -0.9; p < 0.001) pointing to a reasonable degree of concurrent validity. FAST show a good test-retest reliability between two independent evaluation differing of one week (mean K =0.73). The total FAST scores were lower in controls as compared with Bipolar Patients and in Euthimic patients compared with Depressed or Manic., Conclusion: The Italian version of the FAST showed similar psychometrics properties as far as regard internal consistency and discriminant validity of the original version and show a good test retest reliability measure by means of K statistics.

The Kirkwood high-dose interferon-alpha2b adjuvant therapy in high-risk-of-recurrence melanoma patients (stage IIb-III) demonstrated a benefit in terms of disease-free survival (DFS) (three trials out of three) and overall survival (OS) (two trials out of three). These important and exclusive results match with a grade 3-4 toxicity in about 75% of patients. This problem is the most limiting of this treatment. The aim of the study was to check these results and the feasibility of this treatment using the original Kirkwood schedule of 52 weeks, with appropriate dose modification, until unacceptable toxicity or progression of disease. From 23rd February 1998 until 29th July 2002, 26 patients were treated (mean age 45 years; range 25-70) with high-dose interferon-alpha2b adjuvant therapy. All patients were evaluated for toxicity, whilst 24 out of 26 (92%) were evaluated for OS and DFS. All patients were in stage IIB/III of the new American Joint Committee on Cancer (AJCC) classification. The sentinel node biopsy was performed in 19 out of 26 (73.1%) patients (clinical N0). At 31st December 2002, 20 out of 26 (77%) were still alive, whilst four (15%) had died and two (8%) were lost to follow-up. Of the patients still alive, 14 (70%) were disease free. The patients lost to follow-up refused to continue therapy for toxicity related treatment: one of them was disease free, whereas one was relapsed. There were 11 observed relapses (44%). The DFS ranged from 2 to 27 months. Among the patients, the maximal DFS is, at the time of writing, 59 months. The DFS mean is 29 months, the median is 19 months. The OS calculation will be performed at the end of 5 years observation. Now our attention is on therapy tolerability. In 18 patients out of 26 (69%) we noted at least one grade 3-4 toxicity, in accordance with literature data. The most common toxicities were haematological, hepatic, fever and asthenia. Overall, only two grade 4 events (one hepatic and one haematological) were reported. Grade 3 toxicity was hepatic in 23% of patients and haematological in 50%. Grade 2 toxicity was hepatic in 19%, haematological in 27% and fever in 50%. Grade 1 toxicities were hepatic, haematological and fever in 15, 15 and 35% of patients, respectively. Asthenia was severe in 54%, mild in 31% and not found in 15%. In 39, 4 and 15%, respectively, we have reported no hepatic, haematological or fever events. Less common toxicities were nausea, diarrhoea, headache, arthralgia, alopecia and one case of hypothyroidism. As a result of these reported toxicities, of 23 patients evaluable with regard to the protocol, 12 underwent dose reductions, six suspended treatment for disease progression, eight delayed treatment for toxicity, two interrupted treatment indefinitely for unacceptable toxicity or refused treatment, two refused to continue, two patients had no delay in treatment and three did not receive any delay or dose reduction. Of three patients still in therapy, just one has so far received a delay in treatment. Overall, only four patients (17%) interrupted therapy for toxicity related events, whereas 83% continued with the expected program: 52 weeks of therapy with appropriate dose modifications.

Spigelian hernia repair techniques use prostheses both in the traditional and the videolaparoscopic approach; only in selected cases direct suturing of the parietal defect is performed. The aim of this study is to describe a technique that uses a device proposed specifically for inguinal hernias, but which has not yet been described in the literature, namely the Prolene Hernia System (P.H.S.). Our personal experience consists of 7 cases (5 females and 2 males; mean age: 58 years) operated on from January 2002 to May 2003. Four patients were operated on in the ordinary hospitalisation regime with selective spinal anaesthesia and three patients were treated in the day surgery setting with local anaesthesia. With this technique, the underlay patch is positioned in an adequately prepared preperitoneal space and the onlay patch above the internal oblique muscle, while the connector acts as a plug positioned in the parietal defect. The method has proved simple, safe, and fast. It causes minimal discomfort to the patient in terms of postoperative pain and allows rapid rehabilitation. Moreover, it can also be performed in the day surgery setting. The authors conclude that the P.H.S. Spigelian hernia repair technique is a valid alternative to any of the other methods used to date.

Seventy-nine arteriovenous fistulas for periodic hemodialysis were created in 62 uremic patients: 64 primary vascular accesses and 15 salvage operations for malfunctioning fistulas. Sixty-three distal and 1 proximal arteriovenous fistulas between the radial artery and the cephalic vein, were created as primary vascular access. The utilization time of the primary arteriovenous fistulas was longer than 5 years in 34%, 3-4 years in 25% and 0-2 years in 41% of cases. Eleven fistulas evidenced thrombosis: a salvage operation (resection-anastomosis) was possible for 9 (89%). A salvage operation was possible for 100% of poor flow fistulas. The utilization's time of the salvage fistulas is longer than 5 years in 15%, 3-4 years in 15% and 0-2 years in 70% of cases.

The Authors report their clinical experience in superior mesenteric artery embolism: 10 arterial embolisms (71%) collected from a series of 14 obstructions of the superior mesenteric artery. The main interval from the beginning of the symptomatology to hospital admission was 48 h. Laparotomy was performed in all ten patients; gangrenous bowel was resected in 2 and 2 had an embolectomy of the superior mesenteric artery without intestinal resection. The remaining 6 patients had laparotomy alone and died. The Authors emphasize the difficulty in recognizing the disease at an early stage and suggest to contemplate in patients at risk with a persistent abdominal pain, the possibility of a superior mesenteric artery embolism.

Clinical follow-up of 71 patients subjected to major amputation of the lower extremities for atherosclerotic arteriopathy has been analysed for the purpose of ascertaining real possibilities of functional recovery and quality of life. Research results show that only a small number of patients (38%) can achieve an acceptable quality of life. The reasons have been identified in the objective difficulty of adequate physical and psychotherapeutic rehabilitation owing to structural shortcomings or the presence of associated pathology or the advance in the basic condition which does not permit application or frustrates results.

In arteriosclerotic obstruction of the main tibial arteries, the tibial collateral vessels are usually patent, and about 70% of these arteries are potentially suitable for surgical revascularization. The present study aimed at investigating the practical feasibility of a selective revascularization procedure on these tibial muscular arteries (ultraperipheral revascularization). Six lower limbs amputated at thigh level for arteriosclerotic gangrene with complete obstruction of the main tibial arteries, were studied: the tibial collateral muscular vessels showed patency in 65% of cases. The authors propose a surgical technique for the revascularization of these peripheral vessels with the use of a vascular prosthesis. The "post-operative" angiographic studies showed that revascularization of these peripheral muscular arteries was possible.

The authors report a clinical experience on 37 internal carotid endarterectomies of 33 patients classified as: group A (asymptomatic patients); 4 patients (13%), group B (RIA); 9 patients (27%), group C (stabilized neurological lesions); 19 patients (56%), group D (acute cerebral ischemia): 1 patient (3%). Sixteen thromboendarterectomies (43%) were carried on for the prophylaxis of neurological lesions, 20 (54%) to increase and balance the cerebral blood flow in patients with stable neurological lesions, 1 (3%) for acute cerebral ischemia. The overall operative mortality was 6%, the operative morbidity was 22%. The clinical follow-up concerned 26 patients: the overall mortality was 19%: in survivors the late results were excellent. The rate of postoperative stenosis was 18%: 80% of these arteries had been treated without a patch angioplasty.

The Authors report a 68% overall success rate in a three years follow-up study of 45 "complementary" profundoplasties. The key factors with a significant prognostic effect on the clinical surgical results are the early postoperative increase of the resting ankle pressure index (I.W.) and the angiographic preoperative patency of the tibial arteries. An early postoperative increase of I.W. has been always associated with good results whereas an unchanged postoperative I.W. has always been associated with poor results; an angiographic tibial run-off (one or two or three patient tibial arteries) has been associated with significant better clinical results (p less than 0.001).

One hundred-eighty-one patients who underwent major surgical procedures were retrospectively considered to value the incidence of gastrointestinal bleeding. Upper-gastrointestinal-tract bleeding occurred in only one patient (0.5%). The Authors suggest that only critically ill patients require prophylactic use of cimetidine.

Iatrogenic pathology due to treatment with steroid drugs used by systemic route is well known. On the contrary iatrogenic pathology due to topical use of these drugs is rarely reported. Two cases of abuse of 9-alpha- fluor-prednisolone and kanamycin administered by endonasal route are reported. The same treatment has been carried out in patients and rabbits. Clinical and bio-humoral data in patients and anatomo-pathological findings in rabbits are reported. The risks, sometimes underestimated, of an overdose of corticosteroid and antibiotic drugs used by endonasal route are pointed out.

The records of 93 patients who underwent surgery for solitary thyroid nodule were reviewed. It is emphasized no findings or diagnostic studies currently available which are sufficiently specific to differentiate benign from malignant lesions. All solitary nodules should be removed by excision of the involved thyroid lobe followed pathological examination: operative complications are rare.