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In the recent 2022 monkeypox (Mpox) global outbreak, cases have been mostly documented among men who have sex with men. Proctitis was reported in almost 14% of cases. In this study, four Mpox-confirmed cases requiring hospitalizations for severe proctitis were characterized by clinical, virological, microbiological, endoscopic, and histological aspects. The study showed the presence of lymphofollicular lesions associated with Mpox virus rectal infection for the first time.

Inositol is a natural sugar-like compound, commonly present in many plants and foods. It is involved in several biochemical pathways, most of them controlling vital cellular mechanisms, such as cell development, signaling and nuclear processes, metabolic and endocrine modulation, cell growth, signal transduction, etc. In this narrative review, we focused on the role of inositol in human brain physiology and pathology, with the aim of providing an update on both potential applications and current limits in its use in psychiatric disorders. Overall, imaging and biomolecular studies have shown the role of inositol levels in the pathogenesis of mood disorders. However, when administered as monotherapy or in addition to conventional drugs, inositol did not seem to influence clinical outcomes in both mood and psychotic disorders. Conversely, more encouraging results have emerged for the treatment of panic disorders. We concluded that, despite its multifaceted neurobiological activities and some positive findings, to date, data on the efficacy of inositol in the treatment of psychiatric disorders are still controversial, partly due to the heterogeneity of supporting studies. Therefore, systematic use of inositol in routine clinical practice cannot be recommended yet, although further basic and translational research should be encouraged.

Abstract Objective Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add‐on treatment. Methods We performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add‐on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency, and adverse events were recorded at 3, 6, and 12 months after PER introduction. Subanalyses by early or late use of PER and by concomitant ASM were also conducted. Results Five hundred and three patients were included (age 36.5 ± 19.9 years). Eighty‐one percent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the subanalyses, although patients who used PER as early add‐on, as compared with late add‐on, more often reached early seizure freedom at 3‐month follow‐up (66% vs 53%, P = .05). Treatment‐emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. Significance This study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real‐life conditions. We provide robust data about its effectiveness as only add‐on treatment even in patients with a long‐standing history of epilepsy and previously treated with many ASMs.

Introduction People with mental disorders may present impairments in cognitive and metacognitive functions. Self-reflection is the ability to reflect on oneself (specifically on one’s behavior, emotions, and thoughts) and insight is the awareness of one’s internal experience. Mindwandering (MW) is defined as the tendency to divert attention from current reality without a clearly defined intention. It can be spontaneous or deliberate. Several studies have investigated these alterations in patients with schizophrenia (SZ), while less is known for people with substance use disorder (SUD). Objectives The aim of the present study was to explore self-reflection, insight and MW in a group of patients with SZ and SUD. Methods The Self-reflection and Insight Scale (SRIS) and the spontaneous (MW-S) and deliberate (MW-D) mindwandering scales were administered to 25 patients with SZ, 21 patients with SUD, and 21 healthy controls (HC). Linear regressions were performed to evaluate the associations between the variables under study. Results Preliminary data showed that SZ and SUD patients presented lower SRIS and MW values than HC. Examining MW in detail, participants with SZ reported higher scores at than MW-D, while in people with SUD, MW-D scores were higher than MW-S scores. Linear regressions revealed that MW-D was negatively associated with self-reflection in SUD; moreover, insight scores were negatively associated with MW-S in SZ. Conclusions Our preliminary results confirm the importance of acting on the elements of metacognition in patients with mental disorders to improve the general outcome of the disease. A comprehensive therapeutic approach should include psychotherapeutic and social interventions aimed at increasing attention and introspection. Disclosure of Interest None Declared

Abstract Objectives Treatment persistence refers to the act of continuing a treatment as prescribed and reflects the patient's or doctor's judgment about efficacy, tolerability, and acceptability. In patients with schizophrenia, antipsychotic persistence is often poor, because of issues such as lack or loss of efficacy, side effects, and poor adherence, which is often related to the degree to which patients find the medication and overall intervention to be helpful, tolerable, fair, reasonable, appropriate, and consistent with expectations of treatment. Despite the poor antipsychotic persistence that has been reported to date in patients with schizophrenia, we previously observed a relatively high (86%) 6 months persistence with aripiprazole once-monthly (AOM) in a group of patients with schizophrenia, treated in the real world Italian clinical practice. The present study explores the longer term persistence with AOM, over a mean follow-up period of 48 months. Methods This was a multicenter, retrospective, non-interventional follow-up study, aimed at evaluating the longer term persistence with AOM in a group of patients with schizophrenia who had already shown persistence over a period of at least 6 months. The study included 161 individuals who had participated in our previous study, where 86% of participating individuals had shown persistence with AOM for at least 6 months. Non-persistence was defined as discontinuing the medication for any reason. Baseline demographic and clinical characteristics of patients who continued AOM were then compared to those of patients who discontinued the medication. Results Study subjects were predominantly male (64.4%) and their mean age was 39.7 (SD: 12.24). Treatment persistence with AOM was 69.6% and 112 out of 161 patients were still receiving AOM treatment at the last follow-up visit. The mean duration of AOM treatment until the last recorded observation was 55.87 months (median 56.17, SD6.23) for the 112 persistent patients and 32.23 (median 28.68.SD 15.09) months for the 49 non-persistent individuals. The mean observation period for all patients (persistent and non-persistent) was 48.78 months (median 52.54, SD 14.64). For non-persistent subjects, the observation period ended with the discontinuation of AOM. Subjects treated with AOM at 400 mg presented a 69.6% lower risk of all-cause treatment discontinuation when compared with patients treated with 300 mg (HR: 0.314; 95% confidence interval [CI] 0.162–0.608; P = 0.001). The main reasons for discontinuation were lack of efficacy (30.6%), patient/caregiver choice (18.4%), physician’s choice (16.3%), non-adherence (12.2%) and inconvenience (6.1%). Only 3 patients (6.1%) discontinued AOM for tolerability issues. Conclusions In subjects with schizophrenia, who had already shown a 6 months persistence with AOM, a high number of patients (69.6%) continued to be persistent over a 4-year follow-up period. This may reflect a favourable profile of efficacy, tolerability, and acceptability. Larger and prospective studies are warranted to confirm our observations.

ABSTRACT Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in children. AFM outbreaks have been associated with increased circulation and genetic diversity of EV-D68 since 2014, although the virus was discovered in the 1960s. The mechanisms by which EV-D68 targets the central nervous system are unknown. Since enteroviruses are human pathogens that do not routinely infect other animal species, establishment of a human model of the central nervous system is essential for understanding pathogenesis. Here, we describe two human spinal cord organoid (hSCO)-based models for EV-D68 infection derived from induced, pluripotent stem cell (iPSC) lines. One hSCO model consists primarily of spinal motor neurons, while the another model comprises multiple neuronal cell lineages, including motor neurons, interneurons, and glial cells. These hSCOs can be productively infected with contemporary strains, but not a historic strain, of EV-D68 and produce extracellular virus for at least 2 weeks without appreciable cytopathic effect. By comparison, infection with hSCO with another enterovirus, echovirus 11, causes significant structural destruction and apoptosis. Together, these findings suggest that EV-D68 infection is not the sole mediator of neuronal cell death in the spinal cord in those with AFM and that secondary injury from the immune response likely contributes to pathogenesis. IMPORTANCE AFM is a rare condition that causes significant morbidity in affected children, often contributing to life-long sequelae. It is unknown how EV-D68 causes paralysis in children, and effective therapeutic and preventative strategies are not available. Mice are not native hosts for EV-D68, and thus, existing mouse models use immunosuppressed or neonatal mice, mouse-adapted viruses, or intracranial inoculations. To complement existing models, we report two hSCO models for EV-D68 infection. These three-dimensional, multicellular models comprised human cells and include multiple neural lineages, including motor neurons, interneurons, and glial cells. These new hSCO models for EV-D68 infection will contribute to understanding how EV-D68 damages the human spinal cord, which could lead to new therapeutic and prophylactic strategies for this virus.

BackgroundINPLASY® is an international platform for registering systematic reviews and meta-analysis protocols that was launched in March 2020. INPLASY® provides an online database in which the protocols are maintained as permanent public records and can be accessed on its website (www.inplasy.com).MethodsWe described the database features and registered information of all records published since the launch of the registry on March 31, 2023. Additionally, we analyzed the website statistics dataset to explore user experience and promote data transparency.ResultsFour thousand six hundred fifty-eight records were registered in INPLASY®, and more than 94% of the protocols were published within 24 h. Most of the submissions were from China, followed by Portugal, Taiwan, Malaysia, and Brazil. The INPLASY® website received 386,395 page views from 64,568 visitors during the first three years. The accesses were obtained from 170 countries. Most of the accesses were from China, followed by the US, the UK, and Portugal. The review status “completed and published” was observed in 898 protocols, and these studies were published in 372 different scientific peer-reviewed journals. The features of INPLASY® include the following: (i) INPLASY® identifier, a unique protocol number; (ii) the digital object identifier (DOI) number, the URL of the protocol linked to a specific DOI; (iii) ORCID update, INPLASY® automatically updates authors' ORCID page, including their protocol; and (iv) search tools, the protocols are freely accessible on www.inplasy.com.ConclusionsINPLASY® has several practical and useful features that should be considered when planning the registration of a systematic review protocol. Furthermore, the sharp increase in the number of protocols registered in INPLASY® in the first three years and the database statistics demonstrate that INPLASY® has become an important source of systematic review protocols. Therefore, authors should access INPLASY® before planning a future review study to avoid unintended duplication of efforts and to obtain timely registration.

Long coronavirus disease 19 (COVID-19) is an emerging multifaceted illness with the pathological hallmarks of chronic inflammation and neuropsychiatric symptoms. These pathologies have also been implicated in developing suicidal behaviors and suicidal ideation (SI). However, research addressing suicide risk in long COVID-19 is limited. In this prospective study, we aim to characterize SI development among long-COVID-19 patients and to determine the predictive power of inflammatory markers and long-COVID-19 symptoms—including those of psychiatric origin—for SI. During this prospective, longitudinal, multicenter study, healthy subjects and long-COVID-19 patients will be recruited from the University Hospital of Geneva, Switzerland, the University of Genova, the University of Rome “La Sapienza”, and the University of San Francisco. Study participants will undergo a series of clinic visits over a follow-up period of 1 year for SI assessment. Baseline and SI-onset levels of inflammatory mediators in plasma samples, along with 12 long-COVID-19 features (post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal disturbance, palpitations, changes in sexual desire/capacity, loss/change of smell/taste, thirst, chronic cough, chest pain, and abnormal movements) will be collected for SI risk analysis. The proposed enrollment period is from 15 January 2024 to 15 January 2026 with targeted recruitment of 100 participants for each study group. The anticipated findings of this study are expected to provide important insights into suicide risk among long-COVID-19 patients and determine whether inflammation and psychiatric comorbidities are involved in the development of SI in these subjects. This could pave the way to more effective evidence-based suicide prevention approaches to address this emerging public health concern.

A chronotype is generally defined as the variability of the phase angle of entrainment, while the latter reflects the relationship between the timing of a certain rhythm (e.g., the sleep–wake cycle) and the timing of an external temporal cue. Individuals can be placed on a spectrum from “morning types” (M types) to “evening types” (E types). E-chronotype has been proposed as a transdiagnostic risk factor for psychiatric conditions, and it has been associated with psychopathological dimensions. Eveningness seems to be correlated with both suicidal ideation (SI) and suicidal behavior (SB) through several possible mediating factors. Immunological alterations have also been linked to later chronotypes and SI/SB. This narrative review aims to summarize the evidence supporting the possible association between chronotypes and suicide and the eventual mediating role of neuroinflammation and several psychopathological dimensions. A search of the literature (2003–2023) was conducted using various databases: PUBMED, EMBASE, Scopus, UpToDate, PsycINFO, and Cochrane Library. English-language articles were collected and screened for eligibility. Despite the apparent absence of a direct correlation between E-chronotype and suicidality, E-chronotype promotes a chain of effects that could be involved in an increased risk of SB, in which with neuroinflammation possibly plays an intriguing role and some psychopathological dimensions may stand out.

Sexual dysfunctions are common side effects reported by patients during antidepressant treatment. When they occur, patients often discontinue psychopharmacological therapy, with a negative impact on the underlying psychiatric disease. Recently, great attention has been paid to the use of nutraceuticals in the management of psychiatric disorders, although a systematic review on their effects as a treatment option for antidepressant-induced sexual dysfunctions (AISD) is lacking. Here, we conducted a systematic search in the following databases: MEDLINE (through PubMed), EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and Web of Science. We searched eligible studies among parallel or crossover randomized controlled trials (RCTs) in adult populations. After this process, a total of 10 articles that evaluated the effect of six different nutraceuticals versus placebo were included: Maca Root, S-adenosyl-L-methionine (SAMe), Rosa Damascena, Ginkgo Biloba, Saffron, and Yohimbine. Overall, a high dose of Maca Root and the use of SAMe or Saffron may improve AISD. Additionally, the administration of Rosa Damascena seemed to be more effective in men than in women, whereas no evidence of effects emerged for Gingko Biloba and Yohimbine. Given the mixed results still available, future RCTs should consider larger samples and confounding factors, such as depressive status and individual vulnerability.

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

Introduction Language is usually considered the social vehicle of thought in intersubjective communications. However, the relationship between language and high-order cognition seems to evade this canonical and unidirectional description (ie, the notion of language as a simple means of thought communication). In recent years, clinical high at-risk mental state (CHARMS) criteria (evolved from the Ultra-High-Risk paradigm) and the introduction of the Clinical Staging system have been proposed to address the dynamicity of early psychopathology. At the same time, natural language processing (NLP) techniques have greatly evolved and have been successfully applied to investigate different neuropsychiatric conditions. The combination of at-risk mental state paradigm, clinical staging system and automated NLP methods, the latter applied on spoken language transcripts, could represent a useful and convenient approach to the problem of early psychopathological distress within a transdiagnostic risk paradigm.Methods and analysis Help-seeking young people presenting psychological distress (CHARMS+/− and Clinical Stage 1a or 1b; target sample size for both groups n=90) will be assessed through several psychometric tools and multiple speech analyses during an observational period of 1-year, in the context of an Italian multicentric study. Subjects will be enrolled in different contexts: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa—IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Mental Health Department—territorial mental services (ASL 3—Genoa), Genoa, Italy; and Mental Health Department—territorial mental services (AUSL—Piacenza), Piacenza, Italy. The conversion rate to full-blown psychopathology (CS 2) will be evaluated over 2 years of clinical observation, to further confirm the predictive and discriminative value of CHARMS criteria and to verify the possibility of enriching them with several linguistic features, derived from a fine-grained automated linguistic analysis of speech.Ethics and dissemination The methodology described in this study adheres to ethical principles as formulated in the Declaration of Helsinki and is compatible with International Conference on Harmonization (ICH)-good clinical practice. The research protocol was reviewed and approved by two different ethics committees (CER Liguria approval code: 591/2020—id.10993; Comitato Etico dell’Area Vasta Emilia Nord approval code: 2022/0071963). Participants will provide their written informed consent prior to study enrolment and parental consent will be needed in the case of participants aged less than 18 years old. Experimental results will be carefully shared through publication in peer-reviewed journals, to ensure proper data reproducibility.Trial registration number DOI:10.17605/OSF.IO/BQZTN.

Summary: We report the follow-up laboratory investigation of three MPXV cases infected in May-June 2022 from diagnosis to disease resolution, monitoring viral shedding in different body fluids and antibody kinetics. Out of 138 non-lesion samples, viral DNA was found in 92.3% saliva, 85.7% semen, 86.2% oropharyngeal swabs, 51.7% plasma, 46.1% stool, and 9.5% urine samples. Viral load quantified by digital PCR widely varied, but tend to be higher in oropharyngeal swabs, saliva, and stool. Replication competent virus was recovered from four out of seventeen samples, including 1 saliva, 1 oropharyngeal swabs, 1 semen, and 1 stool. The analysis of the antibody kinetics revealed that IgM, IgA, and IgG antibodies were detected within two weeks post-symptoms onset for all three patients, with IgG detected early on at day 4-8 and IgM and IgA showing lower titers along the time frame of the study. Antibody levels increased during the second week of illness with IgG reaching high titers.