The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

Linguistic profile automated characterisation in pluripotential clinical high-risk mental state (CHARMS) conditions: methodology of a multicentre observational study

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

Thymopentin down-regulates both activity and expression of iNOS in blood cells of Sézary syndrome patients

While thymopentin has been used for many years in the experimental treatment of Sézary syndrome (SS), a rare and very aggressive lymphoma, its mechanism of action is still not known. Herein we show that this peptide acts as an inhibitor of isolated iNOS and nNOS isoforms, and reduces iNOS protein/mRNA levels and iNOS activity in blood cells obtained from both healthy donors and SS patients. Similar results were obtained with TPN-2, the N(ω)-nitro analogue of the Arg-Lys motif present in thymopentin. Additional investigations are necessary to confirm the role and the relative importance of the two mechanisms of iNOS down-regulation in the therapeutic action of these peptides against SS

mTOR Activation by PI3K/Akt and ERK Signaling in Short ELF-EMF Exposed Human Keratinocytes

<div><p>Several reports suggest that ELF-EMF exposures interact with biological processes including promotion of cell proliferation. However, the molecular mechanisms by which ELF-EMF controls cell growth are not completely understood. The present study aimed to investigate the effect of ELF-EMF on keratinocytes proliferation and molecular mechanisms involved. Effect of ELF-EMF (50 Hz, 1 mT) on HaCaT cell cycle and cells growth and viability was monitored by FACS analysis and BrdU assay. Gene expression profile by microarray and qRT-PCR validation was performed in HaCaT cells exposed or not to ELF-EMF. mTOR, Akt and MAPKs expressions were evaluated by Western blot analysis. In HaCaT cells, short ELF-EMF exposure modulates distinct patterns of gene expression involved in cell proliferation and in the cell cycle. mTOR activation resulted the main molecular target of ELF-EMF on HaCaT cells. Our data showed the increase of the canonical pathway of mTOR regulation (PI3K/Akt) and activation of ERK signaling pathways. Our results indicate that ELF-EMF selectively modulated the expression of multiple genes related to pivotal biological processes and functions that play a key role in physio-pathological mechanisms such as wound healing.</p></div

Effect of ELF-EMF exposure on AKT and MAPK activity.

<p>A. Representative image of immunoblotting for p-ERK, p-JNK, p-p38 and p-AKT of gels using three separate pools of protein extracted from HaCaT cells time-course exposed to ELF-EMF. B. Averaged band density of p-ERK, p-JNK, p-p38-immunoreactive and p-AKT is expressed as relative expression in both exposed and non-exposed to ELF-EMF (mean±SD; ^#<i>p<0</i>.<i>05 vs</i> time related non-exposed cells).</p

Effects of pharmacological inhibitors on HaCaT cells proliferation.

<p>Proliferative rate of HaCaT cells assed by BrdU incorporation assay, after 24 h of incubation in non-exposed and exposed to ELF-EMF only for the first hour. Cells were pre-treated or not with selective inhibitor of ERK kinase activity (PD980559, 1 μM), PI3K (Ly294002, 1 μM), JNK Inhibitor II (20 μM) for 30 min. Each bar represents the mean±SD of three independent experiments performed in triplicate.</p

Cell cycle analysis.

<p>Flow cytometry cell cycle analysis of HaCaT cells exposed to ELF-EMF (1 mT, 50 Hz) for 1 and 24 h, using PI (40 μg/ml) as probe. Percentage of fluorescent cells for G0/G1, S and G2/M phases were reported in the bottom panel. Mean±SD of three analyses is reported. *<i>p<0</i>.<i>05 vs</i> non-exposed cells. </p

Effects of pharmacological inhibitors on mTOR activation.

<p>A. Representative image of immunoblotting for p-mTOR in HaCaT cell non-exposed or exposed for 1 and 3 h to ELF-EMF and treated or not with 20 nM Rapamycin. Data are reported as relative expression of p-mTOR <i>vs</i> un-phosphorilated form (mean±SD, n = 3). ^*<i>p<0</i>.<i>05</i> treated cells <i>vs</i> cells no-treated with Rapamycin (lef). Proliferative rate of HaCaT cells assed by BrdU incorporation assay, after 24 h of incubation in non-exposed and exposed to ELF-EMF only for the first hour, and treated or not with 20 nM Rapamycin. Each bar represents the mean±SEM of three independent experiments performed in triplicate. ^*<i>p<0</i>.<i>05</i> treated cells <i>vs</i> cells no-treated with Rapamycin (right). B. Representative image of immunoblotting for p-mTOR in HaCaT cell non-exposed or exposed for 1 and 3 h to ELF-EMF and pre-treated or not with selective inhibitor of PI3K (Ly294002, 1 μM) and selective inhibitor of ERK kinase activity (PD980559, 1 μM). Data are reported as relative expression of p-mTOR <i>vs</i> un-phosphorilated form (mean±SD, n = 6). ^#<i>p<0</i>.<i>05</i> treated cells <i>vs</i> cells no-treated with selective inhibitors.</p

Efficacy of Secukinumab in Psoriasis: Post Hoc Gender-Wise Analysis of the SUPREME Study

Purpose: Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24.Patients and Methods: The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test.Results: Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5; P<0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%; P=0.0779) and 24 (83.2% vs 79.7%; P=0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (-10.9 vs -8.1, respectively, in females vs males; P=0.0004).Conclusion: In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender