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Elena Campione,1 Evelin Jasmine Paternò,2 Eleonora Candi,3,4 Mattia Falconi,5 Gaetana Costanza,2 Laura Diluvio,1 Alessandro Terrinoni,4 Luca Bianchi,1 Augusto Orlandi2,6,7 1Department of Dermatology, 2Department of Biomedicine and Prevention, 3Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, 4Biochemistry Laboratory IDI-IRCCS, Faculty of Medicine, University of Rome “Tor Vergata”, 5Department of Biology, University of Rome “Tor Vergata”, 6Institute of Anatomic Pathology, University of Rome “Tor Vergata”, 7Tor Vergata University-Policlinic of Rome, Rome, Italy Abstract: Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclooxygenases-1 and -2 (COX-1 and 2), downregulates the production of prostaglandins (PGs) and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action of PXM on the pathogenesis of nonmelanoma skin cancer, analyzing and evaluating binding modes and energies between COX-1 or COX-2 and PXM by protein–ligand molecular docking. Our clinical experience about the local use of PXM on actinic keratoses and field cancerization is also reported, confirming its efficacy as target therapy. Keywords: COXs inhibitor, actinic keratosis, tumor progression, binding mode

Abstract Background Non-suicidal self-injury (NSSI) is a common concern among hospitalized adolescents, and can have significant implications for short and long-term prognosis. Little research has been devoted on how personality features in severely ill adolescents interact with NSSI and "attitude toward life and death" as a dimension of suicidality. Developing more specific assessment methodologies for adolescents who engage in self-harm without suicidal intent is relevant given the recent proposal of a non-suicidal self-injury (NSSI) disorder and may be useful in predicting risk in psychiatrically impaired subjects. Methods Consecutively hospitalized adolescents in a psychiatric unit (N = 52; 71% females; age 12-19 years), reporting at least one recent episode of self-harm according to the Deliberate Self-harm Inventory, were administered the Structured Clinical Interview for DSM Mental Disorders and Personality Disorders (SCID I and II), the Children's Depression Inventory and the Multi-Attitude Suicide Tendency Scale (MAST). Results Mean age onset of NSSI in the sample was 12.3 years. All patients showed "repetitive" NSSI (high frequency of self-harm), covering different modalities. Results revealed that 63.5% of adolescents met criteria for Borderline Personality Disorder (BPD) and that the rest of the sample also met criteria for personality disorders with dysregulated traits. History of suicide attempts was present in 46.1% of cases. Elevated depressive traits were found in 53.8%. Results show a statistically significant negative correlation between the score on the "Attraction to Life" subscale of the MAST and the frequency and diversification of self-harming behaviors. Conclusions Most adolescent inpatients with NSSI met criteria for emotionally dysregulated personality disorders, and showed a reduced "attraction to life" disposition and significant depressive symptoms. This peculiar psychopathological configuration must be addressed in the treatment of adolescent inpatients engaging in NSSI and taken into account for the prevention of suicidal behavior in self-injuring adolescents who do not exhibit an explicit intent to die.

Leiomyomas are smooth muscle-derived benign neoplasms that can affect all organs, most frequently in the uterus. Fumarate hydratase gene (FH) mutation is characterised by an autosomal dominant disease with increased occurrence of renal tumours, but also by cutaneous (CLs) and uterine leiomyomas (ULs). So far, an increased occurrence of skin tumours in non-mutated patients with ULs has not been verified. To this aim, a case-group of women who were FH non-mutated patients surgically treated for ULs (n = 34) was compared with a control-group (n = 37) of consecutive age-matched healthy women. The occurrence of skin neoplasms, including CLs and dermatofibromas (DFs), was evaluated. Moreover, the microscopic features of FH non-mutated skin tumours were compared with those of an age-matched population group (n = 70) who presented, in their clinical history, only one type of skin tumour and no ULs. Immunohistochemical and in vitro studies analysed TGFβ and vitamin D receptor expression. FH non-mutated patients with ULs displayed a higher occurrence of CLs and DFs (p < 0.03 and p < 0.001), but not of other types of skin tumours. Immunohistochemistry revealed a lower vitamin D receptor (VDR) expression in CLs and DFs from the ULs group compared with those from the population group (p < 0.01), but a similar distribution of TGFβ-receptors and SMAD3. In vitro studies documented that TGFβ-1 treatment and vitamin D3 have opposite effects on α-SMA, TGFβR2 and VDR expression on dermal fibroblast and leiomyoma cell cultures. This unreported increased occurrence of CLs and DFs in FH non-mutated patients with symptomatic ULs with vitamin D deficiency suggests a potential pathogenetic role of vitamin D bioavailability also for CLs and DFs.

Abstract Background Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. Methods An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. Results Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. Conclusions This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient’s SOFA score could identify patients at low risk where outpatient treatment may be safe.

Background: Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well as a major contributor to gut enteropathy and stunting. There are currently no licensed vaccines for shigellosis but it has been estimated that an effective vaccine could avert 590,000 deaths over a 20-year period. A challenge to effective Shigella vaccine development has been the low immunogenicity and protective efficacy of candidate Shigella vaccines in infants and young children. Additionally, a new vaccine might be less immunogenic in a highly endemic setting compared to a low endemic setting ("vaccine hyporesponsiveness"). The use of a potent adjuvant enhancing both mucosal and systemic immunity might overcome these problems. InvaplexAR-Detox is an injectable Shigella vaccine that uses a novel combination of conserved invasion plasmid antigen proteins and a serotype-specific bacterial lipopolysaccharide attenuated for safe intramuscular administration. The adjuvant dmLT has been shown to enhance Shigella immune responses in mice, has safely been administered intramuscularly, and was shown to enhance immune responses in healthy volunteers when given in combination with other antigens in phase I trials. This article describes the protocol of a study that will be the first to assess the safety, tolerability, and immunogenicity of InvaplexAR-Detox co-administered with dmLT in healthy adults in low-endemic and high-endemic settings. Methods: In a multi-center, randomized, double-blind, and placebo-controlled dose-escalation phase Ia/b trial, the safety, tolerability, and immunogenicity of three intramuscular vaccinations administered 4 weeks apart with 2.5 µg or 10 µg of InvaplexAR-Detox vaccine, alone or in combination with 0.1 µg of the dmLT adjuvant, will first be assessed in a total of 50 healthy Dutch adults (phase Ia) and subsequently in 35 healthy Zambian adults (phase Ib) aged 18–50 years. The primary outcome is safety, and secondary outcomes are humoral and cellular immune responses to the adjuvanted or non-adjuvanted vaccine. Discussion: This trial is part of the ShigaPlexIM project that aims to advance the early clinical development of an injectable Shigella vaccine and to make the vaccine available for late-stage clinical development. This trial addresses the issue of hyporesponsiveness in an early stage of clinical development by testing the vaccine and adjuvant in an endemic setting (Zambia) after the first-in-human administration and the dose-escalation has proven safe and tolerable in a low-endemic setting (Netherlands). Besides strengthening the vaccine pipeline against a major diarrheal disease, another goal of the ShigaPlexIM project is to stimulate capacity building and strengthen global North-South relations in clinical research. Trial registration: EU CT number: 2023-506394-35-02, ClinicalTrials.gov identifier: NCT05961059. [ABSTRACT FROM AUTHOR]

Hydrofluorocarbons (HFCs) are widely used in refrigeration, air conditioning, heat pumps (RACHP), and various other applications such as aerosols, fire extinguishers, foams, and solvents. Initially, HFCs were adopted as the primary substitutes for ozone-depleting substances (ODSs) regulated under the Montreal Protocol. However, many HFCs are potent greenhouse gases, and as such subject to a global phasedown under the provisions of the Kigali Amendment to the Montreal Protocol. Managing the refrigerant bank of ODSs and HFCs throughout the equipment's lifecycle—referred to as Lifecycle Refrigerant Management (LRM)—presents a significant challenge but also a significant climate action opportunity. LRM includes the leak prevention, recovery, recycling, reclamation, and destruction (RRRD) of refrigerants. This study employed the GAINS modeling framework to assess the ozone and climate benefits of LRM. The findings indicated that implementing robust LRM practices during the use and end-of-life stages of RACHP equipment could reduce ODS emissions by approximately 5 kt ODP (Ozone Depletion Potential) between 2025 and 2040, and HFC and hydrochlorofluorocarbon (HCFC) emissions by about 39 Gt CO2e between 2025 and 2050. The implementation of robust LRM measures in conjunction with the ongoing phasedown of HFCs under the Kigali Amendment can yield substantial additional climate benefits beyond those anticipated from the HFC phasedown alone. [ABSTRACT FROM AUTHOR]

Background: Cognitive functions represent foundational factors for mental health and quality of life (QoL). In Tourette syndrome (TS), psychiatric comorbidities are common and have been inconsistently reported to affect the cognition and QoL of patients, while the role of tic disorder duration has not been yet explored. Methods: To examine how comorbidities and TS duration may influence cognition and QoL, N = 80 children with TS (6–16 years) were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Standardized questionnaires were used to assess the presence and severity of TS main comorbidities and QoL. Data were interpreted using linear correlations, regression, and mediation analysis. Results: Depression and attention-deficit/hyperactivity disorder (ADHD) symptoms accounted for poorer cognitive performance. Anxiety oppositely predicted better cognitive performance, while no significant role for obsessive compulsive disorder (OCD) was observed. Disease duration was associated with lower total IQ, verbal reasoning, and working memory abilities. Depression, anxiety, and TS duration also deeply influenced QoL measures. Conclusions: TS common comorbidities have a differential impact on the cognitive abilities of children and adolescents, which translates into a complex influence on their perceived QoL. A longer clinical history of tics was related to worse cognitive outcomes, which prompts further consideration of disease duration in both clinical and research settings involving children and adolescents.

Background: It has been reported that mid-regional proadrenomedullin (MR-proADM) could be considered a useful tool to stratify the mortality risk in COVID-19 patients upon admission to the emergency department (ED). During the COVID-19 outbreak, computed tomography (CT) scans were widely used for their excellent sensitivity in diagnosing pneumonia associated with SARS-CoV-2 infection. However, the possible role of CT score in the risk stratification of COVID-19 patients upon admission to the ED is still unclear. Aim: The main objective of this study was to assess if the association of the CT findings alone or together with MR-proADM results could ameliorate the prediction of in-hospital mortality of COVID-19 patients at the triage. Moreover, the hypothesis that CT score and MR-proADM levels together could play a key role in predicting the correct clinical setting for these patients was also evaluated. Methods: Epidemiological, demographic, clinical, laboratory, and outcome data were assessed and analyzed from 265 consecutive patients admitted to the triage of the ED with a SARS-CoV-2 infection. Results and conclusions: The accuracy results by AUROC analysis and statistical analysis demonstrated that CT score is particularly effective, when utilized together with the MR-proADM level, in the risk stratification of COVID-19 patients admitted to the ED, thus helping the decision-making process of emergency physicians and optimizing the hospital resources.

Infectious diseases such as HIV and HBV are a global concern for their impact in terms of public health and costs for national health services. A central role in contrasting the spread of the infections is represented by timely diagnosis. The speed of detection depends on several factors including the type of test used. Antibody response to hepatitis B surface antigens (anti-HBs) is an important serological marker used for HBV-infection detection. The aim of this study was to compare the performance of the Abbott system and of the new analyser Mindray 1200i in the detection of HBV- and HIV-infections. Clinical serum samples were collected from patients randomly selected from PTV University Hospital of University of Rome “Tor Vergata” and tested for HBV and HIV antibodies. Samples were evaluated by Mindray Cl 1200i CLIA screening tests for HBV and HIV and the results were compared with the Abbott Architect analytical system, the routine instrument of the hospital clinical biochemistry laboratory. Precision study, linearity, and carryover were performed on the results obtained. The agreement between the results of the Abbott and Mindray CLIA ranged from 99% to 100% and the discrepancy rate from 0% to 1%. The measurements demonstrated that the Mindray CL-1200i platform offers high-level performance with accurate and consistent test results and could represent a valuable tool if implemented in routine analysis.

Recensione di Luppi, F. (2018). Fathers and Sons at the Abbey Theatre (1904-1938). A New Perspective on the Study of Irish Drama. Irvine-Boca Raton (FL): Brown Walker Press, 246 pp.

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a significant impact on global health, with severe cases often characterized by a worsening cytokine storm. Since it has been described that the NF-κB signaling pathway, regulated by microRNAs, could play a pivotal role in the inflammatory response, in this study, the role of miR-9 in modulating NF-κB signaling and inflammatory cytokine expression in COVID-19 patients was investigated. This observational retrospective single-center study included 41 COVID-19 patients and 20 healthy controls. Serum samples were analyzed for miR-9, NF-κB, and IκBα expression levels using RT-PCR. The expression levels and production of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α were measured using RT-PCR and ELISA. Statistical analyses, including correlation and regression, were conducted to explore relationships between these variables. COVID-19 patients, particularly non-survivors, exhibited significantly higher miR-9 and NF-κB levels compared to controls. A strong positive correlation was found between miR-9 and NF-κB expression (r = 0.813, p < 0.001). NF-κB levels were significantly correlated with IL-6 (r = 0.971, p < 0.001), IL-1β (r = 0.968, p < 0.001), and TNF-α (r = 0.968, p < 0.001). Our findings indicate that miR-9 regulates NF-κB signaling and inflammation in COVID-19. Elevated miR-9 levels in non-survivors suggest its potential as a severity biomarker. While COVID-19 cases have decreased, targeting miR-9 and NF-κB could improve outcomes for other inflammatory conditions, including autoimmune diseases, highlighting the need for continued research in this area. [ABSTRACT FROM AUTHOR]

Introduction Non-suicidal self-injury (NSSI) is a clinical condition defined as intentional, self-inflicted act causing pain or superficial damage without suicidal intents (12-35% of the adolescent community). Several findings show a high correlation between NSSI and impairments in the impulsivity control. Objectives The goal of our study is to evaluate the role of impulsivity in NSSI adolescents, relatively to the inhibitory control, in order to investigate if it can represent a neurocognitive risk factor underlying maladaptive behaviours and which psychopathological dimensions can be associated with this neurobiological process. Methods 30 NNSI inpatients (age range: 12 to 18 years), drug-free, were compared with an age-matched control group, using two behavioural paradigms for the study of inhibitory control: the Stop Signal task and the emotive go/Nogo. Psychopathological traits were evaluated by self-report questionnaires for impulsivity dimensions, suicidality and self-injurious acts. Statistical analyses were performed with SPSS program (p =0.05). Results NSSI patients did not present impairments in the global inhibitory control but they had longer movement times in both paradigms and faster reaction times in the Go/no-go behavioural paradigm. Therefore, NSSI patients tended to be impulsive at an early stage of movement (rapid TR) and have to slow down in a second phase (TM slow) in order to have time to rework the cognitive processes underlying movement. Conclusions The impulsivity dimension is a complex construct that involves multiple interconnected factors. The study of neuro-cognitive and psychopathological aspects and how they are interconnected is necessary to draw new perspectives on the etiopathogenesis of NNSI.

Introduction The COVID-19 social lockdown imposed important limitation to non-emergency health care services in Italy, between March and May 2020, with many difficulties in the mental health assistance of those chronic conditions needing a continuative therapeutic support. Objectives Our study aimed to describe how therapeutic activities have been carried on by remote services in two Adolescent Psychiatric Day Hospital Units (Rome and Turin) and the outcome of these assistance interventions in youths with subacute psychopathology. Methods The patient cohort includes 162 adolescents (12-19 years old; QI>70) DH outpatients presenting a complete clinical and neuropsychiatric assessment before the lockdown. During the several phases of COVID-19 quarantine all patients were monitored and supported by telemedicine interventions. All data were recorded and standardized every 15 days: symptom severity was rated by global severity (CGI-S) and stress level by self-reported measures of stress (IES-R). Results Among patients, CGI score remained stable, IES-R score declined over time: higher IES-R score was significantly associated with female gender and but no differences was observed related with the primary diagnosis. 5 patients presented a clinical acute state needing a hospitalization. The rate of hospitalization was not significantly different compared with the rate observed in the same period of 2019. Conclusions In youth with psychopathological conditions, remote assistance for psychiatric cares resulted effective and it was associated with a clinical stability with decreasing stress levels. Disclosure No significant relationships.

Introduction Anorexia Nervosa (AN) and Avoidant/Restrictive Food Intake Disorder (ARFID) are two primary restrictive eating disorders described in DSM-5, characterized both of them by insufficient food intake. This behavior In ARFID is not driven by weight and shape concerns that tipify AN. While there are several studies that highlight the presence of mentalizing difficulties in AN, there are still no data about mentalizing profile in ARFID. Objectives The aim of this study was to better characterize the mentalizing profile of AN and ARFID children and adolescent. Methods Two groups of AN or ARFID outpatients (15+15), aged 6 to 18 years, were assessed by Alexythimia Questionnaire for Children (AQC) and Toronto Alexythimia Scale-20 (TAS-20) to evaluate alexythimia; by Interpersonal Reactivity Index (IRI) and Basic Empathy Scale (BES) to assess empathy; by NEPSY-II social perception subtests to evaluate Theory of Mind and Emotion recognition. Exclusion criteria were the presence of intellectual disability, pervasive developmental disorders and binge eating behavior (eating disorder other than AN or ARFID). Results Preliminary results showed different mentalizing profiles between ARFID and AN patients, with differences in the score for affective empathy, lower in ARFID than in AN patients while the score for alexythimia traits resulted higher in AN population. Conclusions By our results, mentalization impairment appeared trans-diagnostic across several eating disorders. This first result should be further improved to better analyze this construct in order to develop effective clinical intervention to improve the subject’s affective regulation. Disclosure No significant relationships.

Introduction Non-suicidal self-injury (NSSI) has been proposed as diagnostic entity and was added in the section 3 of the DSM 5. However, little is known about the long-term course of the disorder: NSSI and suicide attempt (SA) often lie on a continuum of self-harm, but it’s still unclear if they represent two different nosografical entities. Both these groups are commonly enclosed in the term of Deliberate self-harm (DSH), also including self-harm with suicidal intent conditions. Objectives This study aims to explore differences between two clinical samples (NSSI and SA) to highlight the possible connection between these two categories, to better understand the risk of progression from NNSI into suicidal intent conditions. Methods 102 inpatients with DSH (62 NNSI; 40 SA; age range: 12 to 18 years) were assessed by self-report questionnaires: the Deliberate Self-Harm Inventory (DSHI) and the Repetitive Non-suicidal Self-Injury Questionnaire (R-NSSI-Q) to explore the severity and repetitiveness of self-injurious behaviors and by the Beck Hopelessness Scale (BHS) and Multi-Attitude Suicide Tendency scale (MAST), as indirect measures of suicidal risk. Results Preliminary results showed that inpatients with NSSI (62) presented high scores of indirect suicide risk, similar to SA sample (40). Conclusions This result highlights the possibility to consider NSSI and SA in a continuum of psychopathology and that repetitive self-harm even in the absence of clear suicidal intentions represent a significant risk factor in the development of suicidality in adolescence. Disclosure No significant relationships.

Introduction Anorexia Nervosa (AN) is an eating disorder characterized by low body weight, fear of gaining weight and distorted perception of body. Patients have rigidity, repetition of thoughts, alterations in decision-making skills and poor ability to provide new solutions. Avoidant/Restrictive Food Intake Disorder (ARFID) is a new eating disorder characterized by the absence of distress about body shape or fear of weight gain. Studies on neurocognitive aspects are few and no effective treatments are known. Objectives The aim of our study was to further investigate the executive functions’ domains in AN and ARFID children and adolescents, to provide possible distinct neurocognitive traits in these patients. Methods AN or ARFID patients (15 + 15; range 6-18 years), were assessed by neuropsychological tools, such as: Wechsler Intelligence Scale to measure I.Q. profile, NEPSY-II to explore attention and executive functions, Tower of London test to detect planning and problem solving abilities, the Bells Test to evaluate visual selective and focused attention, the Wisconsing Card Sorting Test (WCST) for assessment of flexibility and directing behaviors by achieving a goal and the Rey-Osterrieth complex figure test (ROCF) to assess visual-spatial abilities. Results Patients with ARFID presented impairments in several executive functions domains, with difficulties in the impulse inhibition, in the sustained attention and in visual-spatial skills. Finally, in their anamnesis a higher comorbidity with neurodevelopmental disorders such as specific learning disorder has been underlined. Conclusions The identification of specific deficit in neuropsychological profile of ARFID patients could be a rehabilitation target, together with standardized treatment.

Introduction Triple Network Model (TNM), which considers the dynamic interaction between Default Mode (DMN), Salience (SN), and Central Executive (CEN) networks, explains clinical features in mental disorders from a neurophysiological perspective. Some studies highlight the increased connectivity in TNM in adults with Borderline Personality Disorder (BPD), but little is known about adolescents. Objectives The aim of our preliminary study was to investigate TN functional connectivity (FC) in BPD adolescents with a history of traumatic experiences, and its correlation with dissociative symptoms. Methods 15 BPD adolescents (DSM-5 criteria) with early traumatic experiences were compared to 15 healthy controls, matched for sex and age. Dissociation Questionnaire (DIS-Q) was administered. Eyes-closed resting-state (RS) EEG recordings were performed (19 electrodes; 10- 20 system) and analyzed using Exact Low-Resolution Electromagnetic Tomography software (eLORETA). FC was computed for all frequency bands and 9 Regions of Interest for TNM. Results BPD adolescents showed a hyper-connection between CEN and DMN [dorso-lateral prefrontal cortex (dlPFC) and posterior cingulate cortex (PCC); PCC and left posterior parietal cortex (PPC)] and within the CEN (left and right PPC). The strength of PCC-dlPFC and left-right PPC connections was correlated with dissociative symptoms severity. Conclusions FC alterations can already be identified in BPD adolescents, supporting the need for early diagnosis. Normally DMN and CEN show opposite functioning. In our BPD adolescents, the absence of this “anti-correlation” reflects the typical confusion between internal and external mental states, which clarify their difficulties in metacognition or mentalization. Moreover, in dissociative symptoms, two CEN nodes are also involved, not only DMN as previously described. Disclosure No significant relationships.

In the past two pandemic years, Emergency Departments (ED) have been overrun with COVID-19-suspicious patients. Some data on the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to assess the potential role of the new biomarker mid-regional proadrenomedullin (MR-proADM) in stratifying the in-hospital mortality risk of COVID-19 patients at the triage. A further goal of the present study is to evaluate whether MR-proADM together with other biochemical markers could play a key role in assessing the correct care level of these patients. Data from 321 consecutive patients admitted to the triage of the ED with a COVID-19 infection were analyzed. Epidemiological; demographic; clinical; laboratory; and outcome data were assessed. All the biomarkers analyzed showed an important role in predicting mortality. In particular, an increase of MR-proADM level at ED admission was independently associated with a threefold higher risk of IMV. MR-proADM showed greater ROC curves and AUC when compared to other laboratory biomarkers for the primary endpoint such as in-hospital mortality, except for CRP. This study shows that MR-proADM seems to be particularly effective for early predicting mortality and the need of ventilation in COVID-19 patients admitted to the ED.

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the "toolbox" to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets. [ABSTRACT FROM AUTHOR]

Cholera toxin (CT) is widely used as an effective adjuvant in experimental immunology for inducing mucosal immune responses; yet its mechanisms of adjuvant action remain incompletely defined. Here, we demonstrate that mice lacking NFκB, compared to wild-type (WT) mice, had a 90% reduction in their systemic and mucosal immune responses to oral immunization with a model protein antigen [Ovalbumin (OVA)] given together with CT. Further, NFκB−/− mouse dendritic cells (DCs) stimulated in vitro with CT showed reduced expression of MHCII and co-stimulatory molecules, such as CD80 and CD86, as well as of IL-1β, and other pro-inflammatory cytokines compared to WT DCs. Using a human monocyte cell line THP1 with an NFκB activation reporter system, we show that CT induced NFκB signaling in human monocytes, and that inhibition of the cyclic AMP—protein kinase A (cAMP-PKA) pathway abrogated the activation and nuclear translocation of NFκB. In a human monocyte-CD4+ T cell co-culture system we further show that the strong Th17 response induced by CT treatment of monocytes was abolished by blocking the classical but not the alternative NFκB signaling pathway of monocytes. Our results indicate that activation of classical (canonical) NFκB pathway signaling in antigen-presenting cells (APCs) by CT is important for CT's adjuvant enhancement of Th17 responses. Similar findings were obtained using the almost completely detoxified mmCT mutant protein as adjuvant. Altogether, our results demonstrate that activation of the classical NFκB signal transduction pathway in APCs is important for the adjuvant action of both CT and mmCT.

Ichthyoses are genetically determined cornification disorders of the epidermis characterized by the presence of different degrees of scaling, hyperkeratosis, and erythroderma often associated with palmoplantar keratoderma. Different classifications of these diseases have been proposed, often based upon the involved genes and/or the clinical presentation. The clinical features of these diseases present some overlap of phenotypes among distinct genetic entities, depending mainly on the penetrance of mutations. In this study, using a clinical, genetic, and molecular approach, we analyzed a family with two affected members who had clinical and histological features resembling erythrokeratodermia variabilis (EKV) or a type of erythrodermic hyperkeratosis with palmoplantar keratoderma. Despite of the clinical presentation, we demonstrated that the affected patients were genetically double heterozygous for two different mutations in the ABCA12 gene, known to be responsible for harlequin ichthyosis. To explain the mild phenotype of our patients, we performed a molecular characterization of the skin. In the upper layers of the epidermis, the results showed a patchy presence of the glucosyl-ceramides (GlcCer), which is the lipid transported by ABCA12, fundamental in contributing to skin impermeability. Indeed, the two mutations detected do not completely abolish ABCA12 activity, indicating that the mild phenotype is due to a partial loss of function of the enzyme, thus giving rise to an intermediate phenotype resembling EKVP, due to a partial depletion of GlcCer deposition. [ABSTRACT FROM AUTHOR]

Background: It has been reported that mid-regional proadrenomedullin (MR-proADM) could be considered a useful tool to stratify the mortality risk in COVID-19 patients upon admission to the emergency department (ED). During the COVID-19 outbreak, computed tomography (CT) scans were widely used for their excellent sensitivity in diagnosing pneumonia associated with SARS-CoV-2 infection. However, the possible role of CT score in the risk stratification of COVID-19 patients upon admission to the ED is still unclear. Aim: The main objective of this study was to assess if the association of the CT findings alone or together with MR-proADM results could ameliorate the prediction of in-hospital mortality of COVID-19 patients at the triage. Moreover, the hypothesis that CT score and MR-proADM levels together could play a key role in predicting the correct clinical setting for these patients was also evaluated. Methods: Epidemiological, demographic, clinical, laboratory, and outcome data were assessed and analyzed from 265 consecutive patients admitted to the triage of the ED with a SARS-CoV-2 infection. Results and conclusions: The accuracy results by AUROC analysis and statistical analysis demonstrated that CT score is particularly effective, when utilized together with the MR-proADM level, in the risk stratification of COVID-19 patients admitted to the ED, thus helping the decision-making process of emergency physicians and optimizing the hospital resources. [ABSTRACT FROM AUTHOR]

Aim: Concerns have been raised about possible neuropsychiatric sequelae of COVID-19. The objective of this study was to examine the plausibility of long-term mental health consequences of COVID-19 by assessing a sample of children after the resolution of the acute SARS-CoV-2 infection. Method: As part of a systematic follow-up assessment of pediatric patients with COVID-19 conducted at two university children's hospitals, 50 children (56% males) aged 8 to 17 years (median 11.5), 26% with previous multisystem inflammatory syndrome in children (MIS-C), without a prior history of neuropsychiatric disorders, received a battery of clinical neuropsychiatric and neuropsychological rating scales that included the Pediatric Migraine Disability Assessment (PedMIDAS), Sleep Disturbance Scale for Children (SDSC), Multidimensional Anxiety Scale for Children (MASC-2), Child Depression Inventory (CDI-2), Child Behavior Checklist (CBCL), and the NEPSY II (Neuropsychological Assessment, Second Edition). The assessments were conducted between 1 and 18 months (median 8 months) after the acute infection. Results: The CBCL internalizing symptoms score was in the clinical range for 40% of the participants (vs. a population expected rate of about 10%, p < 0.001). A sleep disturbance was detected in 28%, clinically significant anxiety in 48%, and depressive symptoms in 16%. The NEPSY II scores showed impairment in attention and other executive functions in 52%, and memory deficits in 40% of the children. Conclusions: These data from direct assessment of a sample of children who had SARS-CoV-2 infection show higher than expected rates of neuropsychiatric symptoms, thus supporting the possibility that COVID-19 may have mental health sequelae long after the resolution of the acute infection. [ABSTRACT FROM AUTHOR]