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An increasing number of patients experiences prolonged symptoms, whose profile and timeline remain uncertain, a condition that has been defined as post COVID. The majority of recovered hospitalized patients manifests at least one persistent symptom even sixty days after the first clinical manifestation's onset. Particularly, in light of the COVID-19-related symptomatology, it has been hypothesized that SARS-CoV-2 might affect the dopamine pathway. However, no scientific evidence has been produced so far.To this end, human iPSC-derived dopaminergic neurons were infected with EU, Delta and Omicron SARS-CoV-2 variants. The infection with EU and Delta variants, but not with Omicron, results in a reduced intracellular content and extracellular release of dopamine. Indeed, the tyrosine hydroxylase was found to be significantly upregulated at the mRNA level, while being greatly reduced at the protein level. The major downstream synthetic enzyme DOPA-decarboxylase and the dopamine transporter were significantly downregulated both at the mRNA and protein level. Notably, in vitro SARS-CoV-2 infection was also associated with an altered MAP2 and TAU expression and with an increased presence of neuronal stress markers.These preliminary observations suggest that the dopamine metabolism and production are affected by SARS-CoV-2, partially explaining some of the neurological symptoms manifested.

Introduction The closure of forensic psychiatric hospitals and the conversion to a residential model of care based on secure residential units in the community (REMS) has made Italy the first and only country in the world to have followed the principles of the deinstitutionalization movement. Following the reform, several management issues have emerged, such as the creation of long waiting lists for admission to REMS. Improper hospitalization in Acute Psychiatric Units (SPDC) has often been used to address this issue. In addition, the handover of inmates’ care to Mental Health Departments (DSMD’s) has posed further challenges. To date, the field has received little attention from international literature. Objectives Description and analysis of a sample of offender inpatients hospitalized in an acute psychiatric unit. Methods We conducted a retrospective study including male offenders admitted to the SPDC of San Gerardo Hospital (ASST Monza), between January 2007 and September 2022. Data analysis was performed by using SPSS. Results 120 male offenders were included for a total of 204 admissions. 98 offenders (81.7%) were hospitalized once. We observed an absolute (N=1; N=30) and percentage (0.2%;12%) increase in the number of hospitalized offenders per year during the time period under study. Jail was the main provenance in the sample (46.6%), followed by residential care facilities (27%) and the psychiatric observation unit (ROP) of Monza’s jail (10.8%). The two most prevalent diagnoses were personality disorders (37.5%) and psychosis (39.2%). In addition, 66 subjects (55%) had a history of substance abuse. The average duration of hospitalization was 19.45 days; it increased to 77 days for inpatients waiting to be transferred to REMS. Hetero-aggressive behavior as the reason for admission was associated with longer hospitalization (p=0.031), while attempted suicide correlated to shorter hospital stay (p=0.032). Out of the 55 offenders who attempted suicide, 41 came from jail (74.5%). Finally, longer hospitalizations were associated with an increased number of adverse events (p=0.001). Conclusions Psychiatric hospitalizations of offenders have increased over the last years. This population tends to require longer hospital stays (regional average of SPDC hospitalization in Lombardy: 14 days), which are even lengthier for inpatients destined to REMS. Longer hospitalizations exert a large burden on DSMD’s and impact the general health of patients, exposing them to a higher risk of adverse events. Further studies are needed to confirm our findings and to develop better strategies for the management and care of offender patients. Disclosure of Interest None Declared

Introduction Depression is a severe mental disorder with an estimated 3.8% of the population affected, representing a leading cause of disability worldwide. Being linked to reduced quality of life and individual functioning, medical morbidity and mortality, depression has a huge social and economic impact. A wide range of potentially modifiable factors for depression has been identified. Among these, social factors (e.g. support/engagement) appear to play a major role in the emergence and severity of depression. Objectives We aimed at providing a quantitative synthesis of the consistency and magnitude of the association between measures of social connection and depression. Social connection included both quantitative (i.e. existence/absence of social relationships) and functional (i.e. support provided) measures of social relationships, as well as measures focusing on social inequalities related to participation in community spaces/activities (i.e. social discrimination). Methods We searched PubMed, PsycINFO, Cochrane Library and EMBASE. The strength of the association between exposure factors (social measures) and depression was extracted and equivalent odds ratios were computed to compare the strength of the effect sizes among meta-analyses. The quality of each review was assessed using AMSTAR-2. Results As a result of the selection process 47 studies were included in the umbrella review. Social support was found to have a protective role on depression, with an observed moderate/strong effect in peripartum population and a weaker effect in clinical populations (e.g. AIDS/HIV patients). A moderate association between stigma/discrimination and depression emerged in clinical populations (e.g. epilepsy, mental illness, post-stroke), while a weaker effect was found in (ethnic) minorities. There are still few studies quantitatively investigating the link between depression and other social measures (e.g. community connectedness). Conclusions Our findings align with the literature on social connection and mental health, confirming the role of social determinants in the emergence and severity of depression, particularly in the case of vulnerable populations. Social factors emerge as important modifiable targets in the context of depression prevention. Efforts to counteract disconnection at the societal and individual levels and to reduce stigma should be central to an effective depression prevention agenda. Disclosure of Interest None Declared

Introduction Intellectual Developmental Disorder (IDD) is diagnosed with cognitive and adaptive behaviour evaluations. There is increasing evidence of a high prevalence of psychiatric disorders comorbid with IDD. The relationship between specific cognitive dysfunctions and psychiatric vulnerability may provide the basis for a paradigm shift from “intellectually below average IQ” to “neuropsychological characterization”. Objectives 1) reassessing an IDD sample in cognitive profile and psychiatric comorbidities 2) investigating the correlations between specific cognitive dysfunctions and specific psychiatric diagnoses in IDD. Methods 120 individuals with IDD from 3 Italian facilities were consecutively evaluated, one group with mild IDD, using WAIS-IV or Leiter-3, TMT, Stroop and TOL tests, after which a professional caregiver did individual interviews (Vineland Adaptive Behavior Scale-II, SPAIDD-G, and STA-DI) to evaluate the patient adaptive behaviour, psychiatric comorbidities and presence of ASD. The second group (more severe IDD), was evaluated only with professional caregiver assessment tools. Results 90 males and 30 females, mean age 57 years, institutionalized for a mean period of 36.44 years. 52% had no education, 19% a middle school diploma. IDD diagnoses: borderline 3%, mild 16%, moderate 11%, moderate-severe 4%, severe 59%, profound 0%.11% comorbid ASD diagnosis, 29% with ASD after diagnostic re-assessment (STA-DI). 89% physical comorbidities, 58% psychiatric comorbidities, 56% psychoses (Fig. 1). Psychiatric comorbidities re-assessment (SPAIDD-G) identified a significant number of disorders (Fig. 2), despite the medical records showed a low prevalence of psychiatric diagnoses. The consistent quantity of psychotropic drugs prescribed in the sample, possibly reflects the real prevalence of psychopathology. Pearson correlations (p

Introduction According to DSM V, substance-induced psychotic disorder is a mental health condition in which the onset of psychotic symptoms can be traced to the use of a psychotropic substance. The pathogenesis of this disease is still poorly understood; current literature traces its causes back to genetic predisposition and early traumatic events (i.e. child abuse). Objectives The present study aims to identify specific clinical features and biochemical markers which could be addressed as predictors for the long-term prognosis of this disease. Moreover, we aim to identify specific correlations between the clinical phenotype and the underlying substance abuse, in order to allow the early start of a tailored treatment. Methods Between 2020 and 2022 we recruited 218 patients referring to the Policlinico Hospital in Milan and the San Gerardo Hospital in Monza, Italy. All the patients were diagnosed with substance induced psychotic disorder: 31 reported alcohol abuse (14,2%), 71 psichostimulants (32,6%), 116 cannabis, (53,2%). For each patients, we collected demographic data, medical records and a comprehensive psychometric assessment (GAF, PANSS, BPRS, Modified Sad Person Scale-MOAS). Furthermore, we collected a blood sample for dosing Na+, K+, Na+/K+, hemogram with formula and platelets, glucose , urea, creatinine, uric acid, transaminases, γGT, bilirubin, plasma proteins, albumin, LDH, CPK, PCHE, cholesterol, HDL, LDL, Tg, TSH. Results Chi squared test (χ²) has been used to compare qualitative variables between the 3 subgrous (alcohol-, psychostimulants- and cannabis-induced psychotic syndromes) (fig.1). One way ANOVA test has been used to compare quantitative variables between the same 3 subgroups (fig.2). After removing one of the subgropus (alcohol-induced psychotic symptoms), the same analysis have been repeated. Significant variables have been included in a binary logistic regression model in order to confirm their validity as predictors for cannabis- and psychostimulants-induced psychotic disorders (fig 3). Finally we performed Omnibus test and Hosmer-Lemeshow test in order to verify the validity of these regression models. Image: Image 2: Image 3: Conclusions For each considered subgroups, we indentified the following features. Alcohol induced psychotic syndrome: higher age of onset and age of hospital admission, higher cholesterol and hurea levels, , high comorbidity with medical conditions anxiety/depression, low social functioning, higher suicidal risk;, higher hospitalization rate. Cannabis induced psychotic syndrome: higher hemoglobin and albumin levels, more severe psychiatric symtoms (BPRS), higher smoking rates. Psychostimulants induced psychotic syndrome: higher multi-drug abuse risk. We could assume that according to this consideration the treatment protocols for each of these subgroups should be tailored according to their specific features. Disclosure of Interest None Declared

Introduction Bipolar Disorder (BD) is a frequent psychiatric disorder, which can be associated with high disability. Psychotic symptoms occur in more than half of bipolar patients and are associated with an unfavorable course of the disorder (Chakrabarti et al. World J Psychiatry 2022; 12(9) 1204-1232). Objectives The aim of this study is therefore to identify clinical and biological markers able to discriminate between BD patients with (BD-PS) and without lifetime psychotic symptoms (BD-NPS) to facilitate early diagnosis and to implement a target clinical management of these patients. Methods We recruited 665 patients consecutively hospitalized for BD at Fondazione IRCCS Policlinico (Milan) and at San Gerardo Hospital (Monza). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. Patients were assessed by psychometric scales. The two groups (BD-PS and BD-NPS) were compared by t tests for quantitative variables and χ2 tests for qualitative ones. Variables that resulted to be significant in univariate analyses were inserted in binary logistic models with the presence of psychotic symptoms as dependent variable. Results Among the total sample, 64.5% of patients were affected by BD-PS while 35.5% by BD-NPS. The final binary logistic regression model showed that, compared to patients with BD-NPS, those with BD-PS had a longer duration of hospitalization (p=0.007) and were more frequently hospitalized for a manic episode (p=0.001). In addition, subjects with BD-PS had a lower score on the current Global Assessment of Functioning (GAF) (t = 3.157; p = 0.002) and were more frequently males (χ² = 4.061; p = 0.044; OR = 1.399). With regard to biological variables, patients with BD-PS, compared to the counterpart, had a higher Neutrophile to Lymphocyte Ratio (NLR) (t = 2.776; p = 0.006), lower levels of Gamma-Glutamyl Transferase (γGT) (t = 2.249; p = 0.026), higher total bilirubin (t = 2.348; p = 0.019) and creatine phosphokinase (CPK) (t=2.807; p = 0.005), lower total cholesterol (t = 2.369; p = 0.018) and triglycerides (t = 2.554; p = 0.013). Conclusions Our data appear to be in line with the literature, especially with respect to the occurrence of psychotic symptoms mainly in manic episodes and their association with greater clinical severity, longer hospitalization and worse outcome (Altamura et al. Aust N Z J Psychiatry 2019; 53(8) 772-781). From a biological point of view, it seems important to emphasize that patients with lifetime psychotic symptoms presented a higher NLR, revealing more prominent low-grade inflammation in these patients than the counterpart. These data confirm the possibility of using NLR as biomarker of severity in bipolar patients, as proposed previously by other authors (Kulacaoglu et al. Nord J Psychiatry 2022). Future multi-center study have to confirm the results of the present study. Disclosure of Interest None Declared

Metamaterials have enabled the tailored engineering of optical properties. Here, Clericiet al. show that independent interband and intraband nonlinearities in transparent conducting oxides allow dynamic optical control of the real and imaginary parts of the refractive index.

We present a novel class of CMOS-compatible devices aimed to perform the solid-state-biased coherent detection of ultrashort terahertz pulses, i.e., featuring a gap-free bandwidth at least two decades-wide. Such a structure relies on a 1-µm-wide slit aperture located between two parallel aluminum pads, embedded in a 1-µm-thick layer of silicon nitride, and deposited on a quartz substrate. We show that this device can detect ultra-broadband terahertz pulses by employing unprecedented low optical probe energies of only a few tens of nanojoules. This is due to the more than one order of magnitude higher nonlinear coefficient of silicon nitride with respect to silica, the nonlinear material employed in the previous generations. In addition, due to the reduced distance between the aluminum pads, very high static electric fields can be generated within the slit by applying extremely low external bias voltages (in the order of few tens of volts), which strongly enhance the dynamic range of the detected THz waveforms. These results pave the way to the integration of solid-state ultra-broadband detection in compact and miniaturized terahertz systems fed by high repetition-rate laser oscillators and low-noise, low-voltage generators.

The aerosol direct radiative effect (ADRE) affecting the Po Valley and the adjacent North Adriatic Sea is studied using 10-year series of measurements collected at two AERONET sites located in the western part of the Valley (Ispra), and on a platform (AAOT) offshore Venice. This region is characterized by a high, mostly continental, aerosol load with comparable average aerosol optical thickness τa at both locations (0.21 at 500 nm) and more absorbing aerosols at Ispra. A dynamic aerosol model accounting for the changes in scattering phase function with τa is used for radiative transfer calculations, together with boundary conditions representative of terrestrial and marine surfaces. A sensitivity analysis allows the construction of an error budget for the daily ADRE estimates, found to be of the order of 20% and mostly due to uncertainties on aerosol single scattering albedo and τa. The daily radiative efficiencies, normalized by τa at 500 nm, increase from December to June, from −17 to −24 W m−2 τa−1 at top-of-atmosphere (TOA) and −33 to −72 W m−2 τa−1 at surface for the Po Valley, and from −15 to −32 (TOA) and −35 to −65 W m−2 τa−1 (surface) for the AAOT site. The average of log-transformed ADRE for TOA, surface and atmosphere are −5.2, −12.2 and +6.8 W m−2 for the Po Valley case, and −6.5, −13.0 and +6.5 W m−2 for the AAOT site but these values can be much higher for individual days. Concurrent clear-sky days give indications on the regional atmospheric heating spatial gradients. Differences between the atmospheric ADRE at the two locations average 6.3 W m−2 with a gradient positive towards the inner valley in 65% of the cases. This study confirms the importance of duly considering the radiative impact of aerosols on the regional climate.

Nature Communications 8 Article number: 15829 (2017); Published 9 June 2017; Updated 1 August 2017 An incorrect version of the Supplementary Information was inadvertently published with this Article, where the pump wavelengths for panels a and b were interchanged in the figure caption of Supplementary Fig.

Reactive oxygen species (ROS) are mainly produced by microglia and macrophages during inflammation-driven oxidative burst. However, they can in turn affect the reactivity and function of immune cells. For the first time, the relationship between these two key players involved in Multiple Sclerosis (MS) was evaluated at peripheral level. We performed an in-depth immune-phenotypic and functional analysis of MBP (Myelin Basic Protein)-stimulated Peripheral Blood Mononuclear Cells (PBMCs) by flow-cytometry. In addition, blood Coenzyme-Q10 (CoQ10), total, oxidized and reduced forms of glutathione (GSTot, GSSG, GSH), malondialdehyde (MDA), ROS, anti-oxidized-low-density-lipoproteins antibodies (anti-oxLDL), and anti-oxidant-power (PAO) were studied in 31 untreated MS patients (MSnoTP), 23 MS patients (MSTP) treated with Disease Modifying Drugs (DMDs) and 39 matched controls (HC). The focus of our study was the correlation between oxidative stress biomarkers and distribution of immune-phenotypes across the 3 studied groups. In MSnoTP an inverse correlation between MDA and apoptotic cells (CD4+ AnnexinV+TIM3+) was detected (rs= − 0.50, p= 0.01). Ml functional phenotype (CD14+IL6+) and TH17 cells (CD4+IL22+) inversely (rs= − 0.48) and directly (rs= 0.46) correlated (p = 0.01) with Anti-oxLDL antibodies and GSSG, respectively. The latter direct correlation was shown also in MSTP. Notably, in this group, we also detected a direct correlation between CD4+ IL4+ and CD4+ IL25+ (TH2 phenotype) with CoQ10 (rs= 0.54) and GSH (rs= 0.46) (p< 0.03), two crucial anti-oxidants. Again, a direct correlation was found between CD8+ BDNF+ cells (suppressor phenotype) and anti-oxLDL (rs= 0.48, p= 0.03). Surprisingly, we measured an inverse correlation between CD14+ IL10+ cells (M2 immune-regulatory cells) with GSH (rs= − 0.59, p< 0.001). Our findings endorse the idea of a relationship between pro-inflammatory cells and pro-oxidative environment, even at peripheral level. Interestingly, the correlation between CD4+ IL10+cells and a defective anti-oxidant equipment might be regarded as evidence of the involvement of these cells during an inflammatory/oxidative phase that they try to control. The finding of this link only in MSTP patients might suggest that DMDs can provide an alternative way to counteract inflammation, regardless of an absolute increase of these immune-regulatory cells.

Multiple Sclerosis (MS) presents in a variety of clinical forms associated with a diverse grade of neurological impairment, different prognosis and, possibly, multiple pathogenic mechanisms. Thus, whereas relapsing-remitting (RR) MS appears to be largely driven by inflammatory processes, neurodegeneration, partially independent from inflammation, drives primary progressive (PP) and secondary progressive (SP) MS. An extensive analysis of neuroinflammation in the different forms of MS was performed by evaluating immunophenotypic and functional parameters in MBP-stimulated T lymphocytes of 103 MS patients (26 benign (BE) MS, 30 RRMS, 33 SPMS and 14 PPMS) and 40 healthy controls (HC). Results showed that: i) IL-17-producing and RORC/γt-expressing CD4+ T cells (TH17 lymphocytes), as well as IL-6 expressing CD14+ cell were augmented in all patients; ii) IL-22-expressing cells were increased in all forms of MS with the exception of PPMS; iii) TGF-β-expressing B cells were increased only in RRMS; and iv) GATA3-, NFATc-1, IL-13-, and IL-25-expressing cells (TH2 lymphocytes) were augmented in RRMS and BEMS patients alone. Data herein indicate a pivotal pathogenic role of TH17-driven inflammation in all clinical forms of MS and suggest that control over disease (RRMS and BEMS) is associated not with lack of inflammation per se, but rather with the activation of immune-mediated anti-inflammatory mechanisms. These results could help the design of novel diagnostic and therapeutic approaches.

The acquired immunodeflciency syndrome (AIDS) is a clinically multifaceted disease induced by infection with the human immunodeficiency virus (HIV). HIV infection results in a complex pattern of immunologic alterations that leads to the development of AIDS in the majority of HIV seropositive (HIV+) individuals. The reduction in CD4 T lymphocyte counts is the hallmark of HIV infection; nevertheless, long before the reduction in CD4 counts reaches critical levels, a series of profound and complex defects that impair the function of CD4 T lymphocytes can be detected. Thus, HIV infection is characterized by quantitative and qualitative defects affecting CD4 T lymphocytes. It was suggested recently that programmed cell death (PCD) is an important mechanism leading to CD4 depletion in HIV infection, and that susceptibility of peripheral lymphocytes to PCD is differentially regulated by diverse cytokines. Thus, type 1 cytokines would protect CD4 lymphocytes against PCD, whereas type 2 cytokines would not protect against, and could augment, PCD. We suggest that the qualitative alterations of the immune response provoke the CD4 depletion characteristic of HIV disease via type 2 cytokinemediated augmentation of PCD, and are therefore ultimately responsible for the progression of HIV infection. Finally, we summarize recent data showing that three correlates of disease progression: emergence of HIV strains with syncitium-inducing ability (SI), type 1-to-type 2 cytokine shift, and CD4 depletion, are significantly associated, suggesting a complex interconnected virologic-immunologic pathogenesis of HIV infection.