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Claudia Carmassi,1 Virginia Pedrinelli,1,2 Corinna Antonini,1 Valerio Dell’Oste,1,2 Davide Gravina,1 Benedetta Nardi,1 Carlo Antonio Bertelloni,1 Gabriele Massimetti,1 Joaquín Nieto-Munuera,3 Liliana Dell’Osso1 1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy; 3Department of Psychiatry and Social Psychology, University of Murcia, Murcia, SpainCorrespondence: Virginia Pedrinelli, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, Pisa, 56100, Italy, Tel +39 050 2219760, Fax +39 050 2219787, Email virginiapedrinelli@gmail.comBackground: The present study aimed at reporting about the validity and reliability of the Spanish version of the Trauma and Loss Spectrum-Self Report (TALS-SR), an instrument based on a multidimensional approach to Post-Traumatic Stress Disorder (PTSD) and Prolonged Grief Disorder (PGD), including a range of threatening or traumatic experiences and significant losses, besides the spectrum of peri-traumatic stress reactions and post-traumatic stress symptoms that may occur.Methods: A sample of 87 Health Care Workers (HCWs) employed in the COVID-19 Emergency Department at the Virgen de la Arrixaca and Reina Sofia Hospitals (Murcia, Spain) during the pandemic, was consecutively recruited and fulfilled the TALS-SR. Assessments also included the Impact of Event Scale-Revised (IES-R), to examine post-traumatic stress symptoms and probable PTSD. Nineteen HCWs fulfilled the TALS-SR again after three weeks from baseline for test–retest reliability.Results: This study provides evidence of good internal consistency and test–retest reliability of the Spanish version of the TALS-SR. Strong support for the internal validity structure was obtained, with positive and significant correlations between the five symptomatologic domains and the symptomatologic total score. Significant and good correlations between the TALS-SR symptomatologic domains and the IES-R total and single domains’ scores were found. The Questionnaire also demonstrated to discriminate between subjects with and without PTSD, with subjects with PTSD showing significantly higher mean scores in each domain of the TALS-SR.Conclusion: This study validates the Spanish version of TALS-SR, providing a useful instrument for a spectrum approach to PTSD and confirms the potential utility of this psychometric tool in both clinical practice and research settings.Keywords: mental health, stress disorders, traumatic, PTSD, psychological distress, health personnel, psychological tests

Liliana Dell’Osso,1 Ivan M Cremone,1 Barbara Carpita,1 Valerio Dell’Oste,1 Dario Muti,1 Gabriele Massimetti,1 Stefano Barlati,2 Antonio Vita,2 Andrea Fagiolini,3,4 Claudia Carmassi,1 Camilla Gesi11Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 3Department of Mental Health, University of Siena, Siena, Italy; 4Department of Molecular Medicine, University of Siena, Siena, ItalyBackground: The interrelationship between mood disorders and borderline personality disorder (BPD) has been long debated in the literature. Increasing attention has also been paid to the relationship between posttraumatic stress disorder (PTSD) and BPD, as well as to the role of rumination in the development and severity of BPD. This study aims to evaluate the association of rumination, PTSD, and mood spectrum among patients with BPD with or without comorbid mood disorders.Methods: Fifty patients with BPD and 69 healthy controls were assessed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders 5, MoodSpectrum Self-Report (MOODS-SR), and Ruminative Response Scale (RRS).Results: The BPD group was split into subjects with BPD+ mood disorder (MD) or BPD only) . PTSD-criteria fulfillment, MOODS, and RRS scores were significantly higher in both BPD subgroups than in controls, while BPD+MD patients scored significantly higher than the BPD-only group. RRS scores and PTSD-criteria fulfillment were significantly related to the presence of both BPD and BPD+MD, with no effect of MOODS-SR scores.Conclusion: Our findings confirm the presence of a relationship between BPD and the PTSD spectrum, highlighting also a possible role of rumination in BPD psychopathology. Rumination and PTSD symptoms seem to prevail in the effect of mood spectrum in predicting BPD.Keywords: ruminative thinking, borderline personality disorder, post-traumatic stress disorder, mood disorders

Claudia Carmassi,1 Valerio Dell’Oste,1 Diana Ceresoli,1 Stefano Moscardini,2 Enrico Bianchi,3 Roberto Landi,4 Gabriele Massimetti,1 Cristiana Nisita,1 Liliana Dell’Osso1 1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2General Medicine Outpatient Clinic, ASL 5 Tuscany, Pisa, Italy; 3General Medicine Outpatient Clinic, ASL 6 Tuscany, Livorno, Italy; 4General Medicine Outpatient Clinic, ASL 2 Tuscany, Lucca, Italy Background: Frequent attenders (FAs), defined as patients reporting a disproportionate number of visits to general practitioners (GPs), may represent up to one-third of GP patients responsible for a high burden of care not always justified by the severity of the medical condition. The aim of this study was to explore sociodemographic and clinical characteristics of FAs of GP in Italy with particular attention to functional impairment. Methods: A total sample of 75 FAs (defined as individuals who had consulted GPs 15 times or more during 2015) of GPs of three primary care centers (Pisa, Livorno, and Lucca) in Italy were enrolled and assessed by sociodemographic scale, Structured Clinical Interview for DSM-5 (SCID-5), global functioning (Global Assessment of Functioning [GAF]), illness behavior and perceived health (Illness Behavior Inventory), and somatic comorbidity (Cumulative Illness Rating Scale). Results: Most of the sample were females, middle aged, married, or cohabiting, with low levels of education. One-third of FAs was low functioning (LF; GAF score

Introduction: Patients with Post-traumatic stress disorder (PTSD) or mood disorders, as depression, often showed dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, resulting in increased levels of pro-inflammatory cytokines and heightened activity of the immune system that may cause alterations in the structure and function of brain regions through direct neurotoxic effects, oxidative stress, changes in levels of neurotransmitters and decreasing some neurotrophins. Among the most studied pro-inflammatory cytokines in this field there are Intereleukine-6 (IL-6) and Interleukine-1β (IL-1β); however, scant and conflicting data are currently available in the literature about their use as potential biomarkers, and even less on possible comparisons in PTSD and depression. Objectives: The aim of the present study was to evaluate circulating levels of IL-6 and IL-1β in patients with PTSD and to compare them with those of subjects with depression and healthy controls. Methods: A sample of 45 subjects, including 15 subjects diagnosed with PTSD (PTSD group), 15 with depression (DEP group), and 15 healthy controls (HC group) were recruited at the Psychiatric Clinic of the Department of Clinical and Experimental Medicine, University of Pisa. HC group included subjects recruited on a voluntary basis. The psychiatric diagnosis was assessed by the Structured Clinical Interview for DSM-5-Clinician Version (SCID-5-CV), the Impact of Event Scale-Revised (IES-R) and the Trauma and Loss Spectrum-Self Report lifetime version (TALS-SR). A peripheral venous blood sample was collected to perform the biochemical assays. The analyses of IL-6 and IL-1β were performed with a dedicated enzyme-linked immunosorbent assay (ELISAs) achieved at the Laboratory of Biochemistry of the Department of Pharmacy, University of Pisa. Results: No statistically significant gender or age differences emerged in the three groups. There were no statistically significant differences in IL-1β levels among the three groups. Conversely, the PTSD group showed higher levels of IL-6 compared to the DEP and to the HC ones, with a statistically significant difference in the post-hoc analysis among the PTSD and DEP groups with respect to the HC one (p<0.05). Conclusions: Our results suggest the key role of a chronic low-grade inflammatory state in PTSD and in depression, probably related to a dysregulation in HPA axis and cortisol release, with an increase in proinflammatory cytokines including IL-6 that seemed to be more pronounced in PTSD. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Recent data showed a high risk for Problematic Use of the Internet (PUI) in patients with mood disorders, especially Bipolar Disorder (BD). Despite traumatic exposure and Post-Traumatic Stress Disorder (PTSD) have been shown to be associated with alcohol and substance use disorder, as well as behavioral addictions such as gambling disorder among patients with BD, little is known about the possible correlations with PUI. Objectives: The aim of this study was to examine the relationships between PUI and lifetime trauma exposure, besides Post-Traumatic Stress Spectrum symptoms, in a sample of inpatients with BD consecutively hospitalized at the Psychiatric Clinic of the University of Pisa. Methods: 113 inpatients with BD completed the Adult Autism Spectrum (AdAS Spectrum), that includes item 66 to assess putative PUI, and the Trauma and Loss Spectrum Self-Report (TALS-SR), to explore lifetime Post-Traumatic Stress Spectrum symptoms. Results: 21.2% of the sample reported a putative PUI with significantly higher TALS-SR total scores with respect to patients with BD without PUI. The former also reported significantly high scores in some of the TALS-SR domains: Potentially Traumatic Events, Re-experiencing, Maladaptive Coping and Arousal. Furthermore, a positive association emerged between Potentially Traumatic Events and Arousal TALS-SR domains scores and putative PUI. Conclusions: This study reveals a significant association between PUI and lifetime trauma exposure as well as Post-Traumatic Stress Spectrum symptoms in patients with BD, suggesting the need for accurate evaluation of these subjects and possible targeted treatment. [ABSTRACT FROM AUTHOR]

Introduction: Emerging evidence suggests how individuals with Gambling Disorder (GD) may show an increased risk for suicide and suicidal ideation compared with the general population. Objectives: The aim of this study was to first explore the relationship between GD and suicidality in a sample of patients attending a specific program for GD in the Center for pathological addictions (SerD). Methods: A sample of 36 patients with GD attending the SerD in Lucca (Italy) completed the Columbia-Suicide Severity Rating Scale (C-SSRS) to assess suicidal ideation and behavior. Results:Most of the patientsweremales (33, 89,2%), with a mean age (±SD) of 50,6 ± years. A 40.5% of the total sample met at least one C-SSRS item of suicidal ideation at admission and 13.5% of suicidal behavior. Those who had at least one C-SSRS suicidal ideation item had an intensity of ideation mean score of 11.5 / 25 points. Conclusions: This study corroborates the need for careful investigation and specific prevention of suicidal ideation and attempts in patients with a behavioural addiction, such as GD. [ABSTRACT FROM AUTHOR]

Protein expression is regulated through multiple mechanisms, including post-translational modifications (PTMs), which can alter protein structure, stability, localization, and function. Among these, citrullination stands out due to its ability to convert arginine residues into citrulline, altering protein charge and mass. This modification is catalyzed by calcium-dependent protein arginine deiminases (PADs), enzymes implicated in various inflammatory diseases. We have recently shown that human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) exploit these enzymes to enhance their replication capabilities. Although the role of PADs in HCMV and HSV-1 infections is well documented, their involvement in HSV-2 infection has not yet been thoroughly investigated. Here, we demonstrate that HSV-2 manipulates the overall protein citrullination profile by activating three PAD isoforms: PAD2, PAD3, and PAD4. However, as previously observed during HSV-1 infection, PAD3 is the most significantly upregulated isoform, both at the mRNA and protein levels. Consistently, we demonstrate that inhibiting PAD3, either through the specific inhibitor CAY10727 or via CRISPR/Cas9-mediated gene silencing, markedly reduces HSV-2 replication and viral protein expression. Lastly, we show that CAY10727 displays an IC50 value of 0.3 μM, which is extremely close to what was previously observed for HSV-1. Overall, our findings highlight the crucial role of PAD3 in the life cycle of HSV-2 and suggest that the targeted inhibition of PAD3 may represent a promising approach for treating HSV-2 infections, especially in cases resistant to existing antiviral therapies.

Objective: Healthcare workers (HCWs) were considered a population at risk for developing psychiatric symptoms during the COVID-19 pandemic, such as anxiety, depression, and post-traumatic stress disorder (PTSD). Peritraumatic distress is associated with post-traumatic psychopathological symptoms; however, little is known about how it may affect functioning. The study aimed at evaluating the level of peritraumatic distress in a sample of HCWs during the first wave of the COVID-19 pandemic and at examining the relationship between peritraumatic distress, mental health symptoms, and functioning impairment., Methods: A sample of 554 frontline HCWs were consecutively enrolled in major university hospitals and community services in Italy. The PDI, IES-R, PHQ-9, and GAD-7 were used to assess peritraumatic distress, symptoms of PTSD, depression, and anxiety, respectively, and the WSAS to investigate functioning impairment. PDI scores were higher among females, community services, physicians, and nurses. Furthermore, the PDI correlated significantly with the GAD-7, PHQ-9, IES-R, and WSAS., Results: In a mediation analysis, the direct effect of PDI on WSAS and the indirect effects through the PHQ-9 and IES-R were statistically significant (P < .001)., Conclusion: Peritraumatic distress reported by HCWs was associated with symptoms of PTSD, depression, and anxiety, but the association with reduced functioning may be only partially mediated through symptoms of depression and PTSD.

Background: Cariprazine, a third-generation antipsychotic (TGAs), has demonstrated efficacy in the treatment of schizophrenia with good tolerability profile. Actual real-world literature data are lacking, particularly when exploring its efficacy in the long term. The present study examined the effects of cariprazine treatment on specific psychopathological domains with a particular focus on outcomes and side effects in real-life experience, after a long-term treatment., Methods: The present 12-month longitudinal naturalistic study included a sample of subjects with a DSM-5-TR diagnosis of schizophrenia, recruited in the outpatients' psychiatric services of university and community hospitals in Italy, naturally treated with cariprazine. The assessments included: a sociodemographic data sheet, the Structured Clinical Interview for the DSM-5 (SCID-5), the Positive and Negative Symptom Scale (PANSS) and the St. Hans Rating Scale (SHRS). The PANSS was also administered after 6 (T1) and 12 (T2) months of treatment with cariprazine while the SHRS at T1., Results: The total sample consisted of 31 patients, 15 males and 16 females. A significant decrease of the PANSS' subscales, Marder factors and total mean scores emerged at both T1 and T2 with respect to T0. Extrapyramidal symptoms occurred in a minority of patients and in mild or mild/moderate forms: no patient showed moderate forms of psychic/motor akathisia or dystonia, three subjects showed moderate parkinsonism., Conclusions: This study confirms a good efficacy profile of cariprazine in both positive and negative symptoms in patients with Schizophrenia, combined with a good tolerability profile in extrapyramidal symptoms., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Carmassi, Dell’Oste, Fantasia, Bordacchini, Bertelloni, Scarpellini and Pedrinelli.)

The growing prevalence of bacterial and viral infections, highlighted by the recent COVID-19 pandemic, urgently calls for new antimicrobial strategies. To this end, we have synthesized and characterized a novel fatty acid epoxy-ester plasticizer for polymers, named GDE. GDE is not only sustainable and user-friendly but also demonstrates superior plasticizing properties, while its epoxy components improve the heat stability of PVC-based matrices. A key feature of GDE is its ability to confer antimicrobial properties to surfaces. Indeed, upon contact, this material can effectively kill enveloped viruses, such as herpes simplex virus type 1 (HSV-1) and the β-coronavirus prototype HCoV-OC43, but it is ineffective against nonenveloped viruses like human adenovirus (HAdV). Further analysis using transmission electron microscopy (TEM) on HSV-1 virions exposed to GDE showed significant structural damage, indicating that GDE can interfere with the viral envelope, potentially causing leakage. Moreover, GDE demonstrates antibacterial activity, albeit to a lesser extent, against notorious pathogens such as Staphylococcus aureus and Escherichia coli . Overall, this newly developed plasticizer shows significant potential as an antimicrobial agent suitable for use in both community and healthcare settings to curb the spread of infections caused by microorganisms contaminating physical surfaces.

Post-traumatic stress disorder (PTSD) is a highly disabling mental disorder arising after traumatism exposure, often revealing critical and complex courses when comorbidity with bipolar disorder (BD) occurs. To search for PTSD or depression biomarkers that would help clinicians define BD presentations, this study aimed at preliminarily evaluating circulating brain-derived-neurotrophic factor (BDNF) levels in BD subjects with PTSD or experiencing a major depressive episode versus controls. Two bloodstream BDNF components were specifically investigated, the storage (intraplatelet) and the released (plasma) ones, both as adaptogenic/repair signals during neuroendocrine stress response dynamics. Bipolar patients with PTSD ( n = 20) or in a major depressive episode ( n = 20) were rigorously recruited together with unrelated healthy controls ( n = 24) and subsequently examined by psychiatric questionnaires and blood samplings. Platelet-poor plasma (PPP) and intraplatelet (PLT) BDNF were measured by ELISA assays. The results showed markedly higher intraplatelet vs. plasma BDNF, confirming platelets' role in neurotrophin transport/storage. No between-group PPP-BDNF difference was reported, whereas PLT-BDNF was significantly reduced in depressed BD patients. PLT-BDNF negatively correlated with mood scores but not with PTSD items like PPP-BDNF, which instead displayed opposite correlation trends with depression and manic severity. Present findings highlight PLT-BDNF as more reliable at detecting depression than PTSD in BD, encouraging further study into BDNF variability contextually with immune-inflammatory parameters in wider cohorts of differentially symptomatic bipolar patients.

Citrullination is an emerging post-translational modification catalyzed by peptidyl-arginine deiminases (PADs) that convert peptidyl-arginine into peptidyl-citrulline. In humans, the PAD family consists of five isozymes (PADs 1-4, 6) involved in multiple diseases, including cancer. Given that high-risk (hr) human papillomaviruses (HPVs) are the etiological agents of cervical cancer, in this study, we sought to determine whether PAD-mediated protein citrullination would play a functional role in the HPV-driven transformation of epithelial cells. Here we show that both total protein citrullination and PAD4 expression levels are significantly associated with cervical cancer progression. Specifically, epithelial immunostaining for PAD4 revealed an increasingly higher histoscore from low-grade (CIN1) to high-grade (CIN2, CIN3) cervical intraepithelial neoplasia, and invasive squamous cell carcinoma (SCC) lesions, raising the attractive possibility that PAD4 may be used as tumor staging markers. Furthermore, taking advantage of the epidermoid cervical cancer cell line CaSki, which harbors multiple copies of the integrated HPV16 genome, we show that the expression of E6 and E7 HPV oncoproteins is impaired by treatment with the pharmacological pan-PAD inhibitor BB-Cl-amidine. Consistently, p53 and p21, two targets of HPV oncoproteins, are upregulated by the PAD inhibitor, which undergoes cell growth arrest and apoptosis. Altogether, these findings highlight a novel mechanism by which hrHPVs alter host regulatory pathways involved in cell cycle and survival to gain viral fitness, raising the possibility that PADs may represent an attractive target for developing novel host-targeting antivirals effective in preventing cervical cancer progression., 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 © 2024 Albano, Biolatti, Mazibrada, Pasquero, Gugliesi, Lo Cigno, Calati, Bajetto, Riva, Griffante, Landolfo, Gariglio, De Andrea and Dell’Oste.)

The rise of drug resistance to antivirals poses a significant global concern for public health; therefore, there is a pressing need to identify novel compounds that can effectively counteract strains resistant to current antiviral treatments. In light of this, researchers have been exploring new approaches, including the investigation of natural compounds as alternative sources for developing potent antiviral therapies. Thus, this work aimed to evaluate the antiviral properties of the organic-soluble fraction of a root exudate derived from the tomato plant Solanum lycopersicum in the context of herpesvirus infections. Our findings demonstrated that a root exudate from Solanum lycopersicum exhibits remarkable efficacy against prominent members of the family Herpesviridae , specifically herpes simplex virus type 1 (HSV-1) (EC 50 25.57 µg/mL, SI > 15.64) and human cytomegalovirus (HCMV) (EC 50 9.17 µg/mL, SI 32.28) by inhibiting a molecular event during the herpesvirus replication phase. Moreover, the phytochemical fingerprint of the Solanum lycopersicum root exudate was characterized through mass spectrometry. Overall, these data have unveiled a novel natural product with antiherpetic activity, presenting a promising and valuable alternative to existing drugs.

Emotional dysregulation (ED) has recently been conceptualized as a transnosographic entity in major mental disorders, and increasing evidence has suggested association between ED and post-traumatic stress symptoms (PTSS), though the nature of this association is unclear. The aim of the present review was to examine the possible interplay between ED and trauma exposure in the literature, as well as a possible role for the comorbidity of PTSD or PTSS in adolescents and young adults. In particular, we explored whether ED may represent a risk factor for PTSD or, conversely, a consequence of traumatic exposure. This systematic review was conducted according to PRISMA 2020 guidelines in three databases (PubMed, Scopus, and Embase). The 34 studies included showed a wide heterogeneity in terms of the populations selected and outcomes examined. Most studies used the Difficulties in Emotion Regulation Scale (DERS) and examined the relationship between ED, trauma, and psychopathological manifestations after the occurrence of trauma, with a focus on child abuse. Although current data in the literature are heterogeneous and inconclusive, this research highlights the role of ED as a mechanism that may mediate vulnerability to PTSD, but also as a predictor of severity and maintenance of typical, atypical, or associated PTSD symptoms, suggesting prevention programs for PTSD and other mental disorders should support the development of emotion regulation strategies.

Herpes simplex virus 1 (HSV-1) is a neurotropic virus that remains latent in neuronal cell bodies but reactivates throughout an individual's life, causing severe adverse reactions, such as herpes simplex encephalitis (HSE). Recently, it has also been implicated in the etiology of Alzheimer's disease (AD). The absence of an effective vaccine and the emergence of numerous drug-resistant variants have called for the development of new antiviral agents that can tackle HSV-1 infection. Host-targeting antivirals (HTAs) have recently emerged as promising antiviral compounds that act on host-cell factors essential for viral replication. Here we show that a new class of HTAs targeting peptidylarginine deiminases (PADs), a family of calcium-dependent enzymes catalyzing protein citrullination, exhibits a marked inhibitory activity against HSV-1. Furthermore, we show that HSV-1 infection leads to enhanced protein citrullination through transcriptional activation of three PAD isoforms: PAD2, PAD3, and PAD4. Interestingly, PAD3-depletion by specific drugs or siRNAs dramatically inhibits HSV-1 replication. Finally, an analysis of the citrullinome reveals significant changes in the deimination levels of both cellular and viral proteins, with the interferon (IFN)-inducible proteins IFIT1 and IFIT2 being among the most heavily deiminated ones. As genetic depletion of IFIT1 and IFIT2 strongly enhances HSV-1 growth, we propose that viral-induced citrullination of IFIT1 and 2 is a highly efficient HSV-1 evasion mechanism from host antiviral resistance. Overall, our findings point to a crucial role of citrullination in subverting cellular responses to viral infection and demonstrate that PAD inhibitors efficiently suppress HSV-1 infection in vitro, which may provide the rationale for their repurposing as HSV-1 antiviral drugs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pasquero 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.)

Objective: Although the association between chronotype and mood disorders has been consistently reported, conversely, attempts to measure the association between chronotype and anxiety symptoms have generated inconsistent results. We aimed at evaluating whether chronotype (assessed through subjective and objective measures) is associated with lifetime mood and panic-agoraphobic spectrum symptoms in healthy controls (HCs) and in patients with bipolar disorder (BD)., Methods: Overall, 173 subjects, patients with BD in euthymic phase ( n =  76) and HC ( n =  97), were evaluated through the reduced Morningness-Eveningness Questionnaire (rMEQ), actigraphy monitoring and mood and panic-agoraphobic spectrum self-report (MOODS-SR and PAS-SR). The discrepancy between objective (actigraphic-based) versus subjective (rMEQ-based) circadian typology was estimated through the Circadian Classification Discrepancy Index (CCDI)., Results: rMEQ-based evening chronotype (ET) was associated with higher scores in MOODS-SR depressive and rhythmicity and vegetative functions domains in HC and BD.Both ET and morning chronotypes (MT) were associated with higher PAS-SR scores in BD only. Actigraphic-based MT was associated with higher MOODS-SR depressive scores in HC. Likewise, the discrepancy between actigraphic-based and rMEQ-based circadian typology was associated with depressive symptoms in HC only., Conclusion: Self-reported ET was consistently associated with mood symptoms, while associations with panic-agoraphobic symptoms only emerged in BD and involved both extreme chronotypes. The discrepancy between the preferred circadian typology (rMEQ-based) and the actual one (actigraphic-based) could contribute to depressive symptoms in HC. These results pave the way for interventional studies targeting circadian typology in an attempt to prevent or treat mental health disorders.

The APOBEC3 family of DNA cytosine deaminases comprises an important arm of the innate antiviral defense system. The gamma-herpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus and the alpha-herpesviruses herpes simplex virus (HSV)-1 and HSV-2 have evolved an efficient mechanism to avoid APOBEC3 restriction by directly binding to APOBEC3B and facilitating its exclusion from the nuclear compartment. The only viral protein required for APOBEC3B relocalization is the large subunit of the ribonucleotide reductase (RNR). Here, we ask whether this APOBEC3B relocalization mechanism is conserved with the beta-herpesvirus human cytomegalovirus (HCMV). Although HCMV infection causes APOBEC3B relocalization from the nucleus to the cytoplasm in multiple cell types, the viral RNR (UL45) is not required. APOBEC3B relocalization occurs rapidly following infection suggesting the involvement of an immediate early or early (IE/E) viral protein. In support of this possibility, genetic (IE1 mutant) and pharmacologic (cycloheximide) strategies that prevent the expression of IE/E viral proteins also block APOBEC3B relocalization. In comparison, the treatment of infected cells with phosphonoacetic acid, which interferes with viral late protein expression, still permits A3B relocalization. These results combine to indicate that the beta-herpesvirus HCMV uses an RNR-independent, yet phenotypically similar, molecular mechanism to antagonize APOBEC3B. IMPORTANCE Human cytomegalovirus (HCMV) infections can range from asymptomatic to severe, particularly in neonates and immunocompromised patients. HCMV has evolved strategies to overcome host-encoded antiviral defenses to achieve lytic viral DNA replication and dissemination and, under some conditions, latency and long-term persistence. Here, we show that HCMV infection causes the antiviral factor, APOBEC3B, to relocalize from the nuclear compartment to the cytoplasm. This overall strategy resembles that used by related herpesviruses. However, the HCMV relocalization mechanism utilizes a different viral factor(s) and available evidence suggests the involvement of at least one protein expressed at the early stages of infection. This knowledge is important because a greater understanding of this mechanism could lead to novel antiviral strategies that enable APOBEC3B to naturally restrict HCMV infection., Competing Interests: The authors declare no conflict of interest.

Increasing interest is being paid on full-threshold and sub-threshold autism spectrum conditions among adults. Sub-threshold autistic traits (AT) seem to be distributed in a continuum from the clinical to the general population, being particularly higher among subjects with other psychiatric disorders. The aim of the present study was to evaluate the distribution of AT in a sample of subjects with different psychiatric conditions by means of a cluster analysis on the basis of the score reported to the AdAS Spectrum instrument. A total of 738 subjects recruited by seven Italian Universities were divided in 5 groups depending on the clinical diagnosis: Autism spectrum disorder (ASD), subthreshold ASD symptoms (partial ASD), Bipolar disorder (BD), Feeding and eating disorders (FED), and controls (CTLs). All subjects were assessed with the AdAS Spectrum. The cluster analysis identified 3 clusters: the high, medium and low autism clusters. The Restricted interests and rumination domain reported the highest influence in forming the clusters. The high, medium and low autism clusters were respectively more represented in the ASD, partial ASD and CTL groups. The clusters were represented intermediately in the FED and BD groups, confirming the presence of intermediate levels of AT in these clinical populations., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 Elsevier B.V. All rights reserved.)

The current SARS-CoV-2 pandemic and the likelihood that new coronavirus strains will emerge in the immediate future point out the urgent need to identify new pan-coronavirus inhibitors. Strigolactones (SLs) are a class of plant hormones with multifaceted activities whose roles in plant-related fields have been extensively explored. Recently, we proved that SLs also exert antiviral activity toward herpesviruses, such as human cytomegalovirus (HCMV). Here we show that the synthetic SLs TH-EGO and EDOT-EGO impair β-coronavirus replication including SARS-CoV-2 and the common cold human coronavirus HCoV-OC43. Interestingly, in silico simulations suggest the binding of SLs in the SARS-CoV-2 main protease (M pro ) active site, and this was further confirmed by an in vitro activity assay. Overall, our results highlight the potential efficacy of SLs as broad-spectrum antivirals against β-coronaviruses, which may provide the rationale for repurposing this class of hormones for the treatment of COVID-19 patients.