Evaluation of the Synovial Effects of Biological and Targeted Synthetic DMARDs in Patients with Psoriatic Arthritis: A Systematic Literature Review and Meta-Analysis

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD -0.85 [95% CI -1.23; -0.47]) and CD68+ macrophages (sublining, sl) (SMD -0.74 [-1.16; -0.32]) in synovial biopsies from patients treated for 4-12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature

Awareness of health risks related to body art practices among youth in Naples, Italy: a descriptive convenience sample study

<p>Abstract</p> <p>Background</p> <p>Body art practices have emerged as common activities among youth, yet few studies have investigated awareness in different age groups of possible health complications associated with piercing and tattooing.</p> <p>Methods</p> <p>We investigated perceptions of and knowledge about health risks. To highlight differences among age groups, we gathered data from students at high schools and universities in the province of Naples.</p> <p>Results</p> <p>Of 9,322 adolescents, 31.3% were pierced and 11.3% were tattooed. Of 3,610 undergraduates, 33% were pierced and 24.5% were tattooed (p < 0.05). A higher number of females were pierced in both samples, but there were no gender differences among tattooed students. Among high school students, 79.4% knew about infectious risks and 46% about non-infectious risks; the respective numbers among university students were 87.2% and 59.1%. Only 3.5% of students in high school and 15% of university undergraduates acknowledged the risk of viral disease transmission; 2% and 3% knew about allergic risks. Among adolescents and young adults, 6.9% and 15.3%, respectively, provided signed informed consent; the former were less knowledgeable about health risks (24.7% vs. 57.1%) (p < 0.05). Seventy-three percent of the high school students and 33.5% of the university students had body art done at unauthorized facilities. Approximately 7% of both samples reported complications from their purchased body art.</p> <p>Conclusions</p> <p>Results indicate a need for adequate information on health risks associated with body art among students in Naples, mainly among high school students. Therefore, adolescents should be targeted for public health education programs.</p

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

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

Emerging role of PML in the modulation of NLRP3-mediated inflammatory responses

Promyelocytic leukemia protein (PML) is a moonlighting protein that, in addition to playing a well-recognized role in controlling gene expression in the nucleus, acts at the ER-mitochondria interfaces, at the so-called mitochondria-associated membranes (MAMs) where controls mitochondrial metabolism and cell death processes, as apoptosis and autophagy, through the regulation of Ca2+ transfer to mitochondria. MAMs were identified as platforms for inflammatory signaling, regulated by NLRP3 inflammasome. In resting conditions, the NLRP3 localizes at the ER, whereas in response to danger signals, both NLRP3 and its adaptor ASC relocate to MAMs, driving inflammasome assembly. Here, we provide evidence that PML and NLRP3 together with P2X7R form a trimeric complex at MAMs that modulates inflammasome responses and IL-1 release. In particular, we demonstrated that loss of PML promotes the release of a cytokines storm NLRP3-related in response to stress conditions due to the increased relocation of P2X7R at MAMs. Moreover, the increased amount of IL-1β released in the tumor microenvironment (TME) in hosts lacking PML producing a permissive environment for tumor growth. Pharmacological inhibition of NLRP3 or of its activator P2X7R reduces IL-1 release and slows down tumor growth in a PML-deficient background. Our data revealed a new function of PML at the ER/MAM regions in regulating P2X7/NLRP3 axis and inflammation responses. Radiotherapy (RT) is one of the most widely employed cancer therapies, with about half of all cancer patients undergoing irradiation during their disease. However, RT is associated with long-term cardiovascular complications such as atherosclerosis. We demonstrated that traditional fractionated low doses of RT strongly stimulate NLRP3 inflammasome through hypersecretion of IL-1 in a PML-deficient background. In addition, we revealed that the enhanced release of IL-1 is the main actor of endothelial dysfunction, the early stage of atherosclerosis. According to our results, RT could induce a sustained NLRP3-mediated inflammation in the absence of PML, resulting in the overproduction of pro-inflammatory cytokines which trigger the activation of endothelial adhesion markers and lead to endothelial dysfunction. Modulating the impact of RT on the immune system and in NLRP3-mediated inflammation could define new RT protocols and improve cancer patients’ survival ratePromyelocytic leukemia protein (PML) è una proteina che, oltre a svolgere un ruolo ben riconosciuto nel controllo dell'espressione genica nel nucleo, agisce anche a livello delle cosiddette membrane associate ai mitocondri (MAMs). In questo compartimento cellulare, PML controlla il metabolismo mitocondriale e i processi di morte cellulare, come l'apoptosi e l'autofagia, attraverso la regolazione del trasporto di Ca2+ ai mitocondri. Le MAMs svolgono una funzione importante nei meccanismi di segnalazione infiammatoria mediati dall’inflammasoma NLRP3. In condizioni di riposo, NLRP3 si localizza a livello del reticolo endoplasmatico (ER), mentre in risposta a stimoli, sia NLRP3 che il suo adattatore ASC traslocano nelle MAMs, guidando l'assemblaggio dell'inflammasoma. Abbiamo dimostrato che a livello delle MAMs, PML, NLRP3 e P2X7R formano un complesso trimerico che modula le risposte dell'inflammasoma e il rilascio di IL-1. In particolare, abbiamo dimostrato che, in risposta a condizioni di stress, la mancanza di PML promuove la traslocazione di P2X7R nelle MAMs e, di conseguenza, il rilascio di citochine correlate all’attivazione del NLRP3. Inoltre, alti livelli di IL-1β nel microambiente tumorale (TME) privo di PML, generano un ambiente permissivo per la crescita accelerata del tumore. L'inibizione farmacologica di NLRP3 o del suo attivatore P2X7R è in grado di ridurre il rilascio di IL-1β e di rallentare la crescita tumorale. I nostri dati hanno rivelato una nuova funzione di PML nelle regioni ER/MAMs nella regolazione dell'asse P2X7/NLRP3 e delle risposte infiammatorie. La radioterapia (RT) è una delle terapie antitumorali più utilizzate, oltre il 50% di tutti i pazienti oncologici ricevono irradiazioni durante il corso della loro malattia. Tuttavia, la RT è associata a complicazioni cardiovascolari a lungo termine, come l'aterosclerosi. Abbiamo dimostrato che la RT tradizionale, frazionata a basse dosi, stimola fortemente l'inflammasoma NLRP3 portando all'ipersecrezione di IL-1β in un contesto in cui PML è assente. Inoltre, abbiamo rivelato che l'aumento del rilascio di IL-1β è il principale responsabile della disfunzione endoteliale, lo stadio iniziale dell'aterosclerosi. Secondo i nostri risultati, la RT sembra indurre un'infiammazione sostenuta mediata da NLRP3 in assenza di PML, con conseguente iperproduzione di citochine pro-infiammatorie che innescano l'attivazione dei marcatori di adesione endoteliale e portano alla disfunzione endoteliale. Modulando l'impatto della RT sul sistema immunitario e sull'infiammazione NLRP3-mediata si potrebbero definire nuovi protocolli di RT e migliorare il tasso di sopravvivenza dei pazienti oncologici

Using the Adolescent Time Inventory-Time Attitudes (ATI-TA) to assess time attitudes in Italian adolescents and young adults: Psychometric properties and validity

Time attitudes (TA) are evaluative feelings toward the past, present and future. Given the role of TA in psychological and behavioral outcomes, the aim of this study was to analyze the adequacy of the Adolescent Time Inventory—Time Attitudes (ATI-TA) scale among adolescents and young adults in Italy. The scale was administered to 638 students in order to test its psychometric properties and validity. The analyses confirmed the adequacy of the six-factor model and the reliability of the subscales. Additionally, the measurement invariance of the scale across genders and age groups (between adolescents up to the age of 18, and young adults above 18) was demonstrated. Specifically, gender invariance reached the level of equivalence of error variances/covariances, and the same level was partially reached for invariance across age groups. Evidence of the validity of the scale was also provided by obtaining significant correlations between the subscales, and self-esteem and strategic learning. Taken together, these results support the suitability of the ATI-TA to be used for research and clinical purposes

Measuring Test Anxiety with an invariant measure across genders: The case of the German Test Anxiety Inventory

Since test performance is increasingly relevant in educational and occupational circles, the assessment of test anxiety-the phenomenological, physiological, and behavioral responses to the negative consequences that often emerge in evaluative situations-has become increasingly important to scholars and practitioners. One of the most widely employed scales to measure test anxiety in adolescents is the German Test Anxiety Inventory (in German: Prufungsangstfragebogen, PAF). The current study investigated the psychometric properties of the PAF when administered to Italian students. Our research found evidence of validity, supported the five-factor structure, and demonstrated the test's good internal consistency. Moreover, the invariance of the dimensional structure across genders was examined. Overall, this study provides evidence for the reliability and validity of the PAF among Italian students

An Updated Understanding of the Role of YAP in Driving Oncogenic Responses

Yes-associated protein (YAP) has emerged as a key component in cancer signaling and is considered a potent oncogene. As such, nuclear YAP participates in complex and only partially understood molecular cascades that are responsible for the oncogenic response by regulating multiple processes, including cell transformation, tumor growth, migration, and metastasis, and by acting as an important mediator of immune and cancer cell interactions. YAP is finely regulated at multiple levels, and its localization in cells in terms of cytoplasm–nucleus shuttling (and vice versa) sheds light on interesting novel anticancer treatment opportunities and putative unconventional functions of the protein when retained in the cytosol. This review aims to summarize and present the state of the art knowledge about the role of YAP in cancer signaling, first focusing on how YAP differs from WW domain-containing transcription regulator 1 (WWTR1, also named as TAZ) and which upstream factors regulate it; then, this review focuses on the role of YAP in different cancer stages and in the crosstalk between immune and cancer cells as well as growing translational strategies derived from its inhibitory and synergistic effects with existing chemo-, immuno- and radiotherapies

Il fenomeno della Change Blindness nella Malattia di Parkinson

La malattia di Parkinson (MP) è una malattia neurodegenerativa con un’incidenza annuale tra i 10-20 casi su 100000. La sintomatologia è costituita da sintomi motori e da un’ampia costellazione di sintomi non motori tra cui compromissione a vario grado di specifici domini cognitivi compreso il dominio attentivo. In particolare è riportata una difficoltà nell’attenzione focalizzata e nelle strategie di ricerca visiva. Il presente studio si propone di valutare, in un compito attenzionale di ricerca visiva (Flicker Task), la natura del fenomeno di Change Blindness (difficoltà a rilevare dei cambiamenti nella scena visiva) nella MP, considerando anche l’influenza della valenza emotiva degli stimoli. Hanno partecipato 20 pazienti con MP (13M,7F;anni:64.55±7.93), selezionati presso l’ambulatorio dedicato del DAI Neuroscienze e Salute Mentale del Policlinico Umberto I di Roma, e 20 controlli sani appaiati per genere ed età(13M,7F;anni:64.3±6.89). A tutti è stato somministrato l’Attention Network Test-Vigilance e il Flicker Task, che prevedeva l’identificazione di una piccola differenza tra due immagini (identiche in tutto, meno che in un particolare) che si alternavano rapidamente, intervallate da uno schermo grigio. I cambiamenti potevano essere d’interesse Centrale (CE) o Marginale (MA) Le immagini avevano una valenza emotiva Positiva, Negativa o Neutra. I livelli di Vigilanza dei due gruppi non sono risultati significativamente differenti (F1.37=3.66, p=0.06). Le ANOVA effettuate sui Tempi di Risposta (TR) al Flicker Task hanno evidenziato un effetto del Gruppo (F1.38=47.46, p<0.0001, ηp2=0.55), con TR più lenti nei pazienti rispetto ai controlli, e un’interazione Gruppo x Tipo di Cambiamento (F1.38=47.19, p<0.0001, ηp2=0.55). I pazienti presentavano TR maggiori dei controlli sia nelle prove CE (PD=18205 ms vs Controlli=10185 ms), sia nelle prove MA (PD=104883 ms vs Controlli=48019 ms). L’ANOVA condotta sul punteggio di bias attenzionale (TR prove emotive (Negative/Positive) – TR prove neutre) ha evidenziato un’interazione Gruppo x Valenza (F1.38=4.68, p<0.04, ηp2=0.11) indicando nei pazienti un bias attenzionale maggiore per le immagini Negative rispetto alle Positive (F1.38=22.40, p<0.0001, ηp2=0.37). Questa differenza non è emersa nel gruppo di controllo (F<1). L’introduzione di QI e Trattamento Farmacologico in un’analisi della covarianza ha confermato i risultati precedenti. I risultati dello studio evidenziano che i pazienti con MP, indipendentemente dai livelli di QI e dalla terapia farmacologica, mostrano maggiori difficoltà nella detezione del cambiamento, in particolare quello marginale. Questi risultati suggerirebbero che i pazienti con MP presentano delle difficoltà attenzionali soprattutto quando il carico cognitivo richiesto dal compito è elevato e implica processi volontari dell’attenzione. L’assenza di differenze significative tra i due gruppi nei livelli di Vigilanza escluderebbe la possibile influenza del rallentamento motorio tipico del MP. Inoltre, i pazienti hanno impiegato più tempo nel rispondere alle prove a valenza negativa (difficoltà a disancorare l’attenzione), mentre la detezione del cambiamento è risultata rapida per gli stimoli a valenza positiva (ancoraggio attenzionale). Tale differenza non è emersa nel gruppo di controllo. Si potrebbe dunque suggerire che la componente emotiva potrebbe influenzare le prestazioni nei compiti ad alto carico cognitivo nei pazienti con MP. Questo studio è stato il primo ad aver valutato il fenomeno del change blindness in un gruppo di pazienti affetti da MP, permettendo di evidenziare alcuni tra i fattori che influenzano le loro difficoltà attentive. Sarebbe opportuno confermare tali risultati su un gruppo più numeroso di pazienti, considerando anche i diversi livelli di gravità della MP