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Abstract Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = −0.34, 95% CI = [−0.660, −0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity.

Objetivo. Determinar el efecto de un tratamiento con metformina (MET) sobre la predisposición adipogénica de células progenitoras de médula ósea (CPMO), adiposidad de la médula ósea y propiedades biomecánicas óseas. Materiales y métodos: 20 ratas Wistar machos adultos jóvenes fueron separados en cuatro grupos, recibiendo en agua de bebida: 100% agua (C); 20% de fructosa (F); metformina 100 mg/kg peso/día (M); o fructosa más metformina (FM). Tras cinco semanas se sacrificaron los animales, se diseccionaron ambos húmeros para obtener CPMO, y ambos fémures para evaluar adiposidad medular (histomorfometría) y propiedades biomecánicas (flexión a 3 puntos). Las CPMO se cultivaron in vitro en medio adipogénico para evaluar expresión de RUNX2, PPAR-γ y RAGE por RT-PCR, actividad de lipasa y acumulación de triglicéridos. Resultados. La dieta rica en fructosa (grupo F) produjo un aumento tanto de triglicéridos in vitro, como de la adiposidad medular in vivo; siendo parcial o totalmente prevenido por un co-tratamiento con metformina (grupo FM). No se observaron diferencias en las pruebas biomecánicas femorales in vivo, ni en actividad de lipasa y relación RUNX2/PPAR-γ in vitro. La DRF aumentó la expresión de RAGE en CPMO, siendo prevenido por co-tratamiento con MET. Conclusiones. El síndrome metabólico inducido por una dieta rica en fructosa aumenta la adiposidad medular femoral y, en parte, la predisposición adipogénica de las CPMO. A su vez, esto puede ser prevenido total o parcialmente por un co-tratamiento oral con MET.

AbstractLong COVID affects approximately 10–20% of COVID-19 patients and has a devastating impact on their quality of life and mental health. This study aimed to evaluate symptoms of psychological distress in people with long COVID and explore whether high levels of self-compassion are associated with low levels of psychological distress. An online cross-sectional survey of people with Long COVID was conducted. In total, 332 respondents participated in the survey. All dimensions of self-compassion were found to be significantly associated with depression, anxiety, and perceived stress, independent of symptom severity. Specifically, self-kindness, common humanity, and mindfulness were strongly negatively associated with distress, whereas self-judgment, isolation, and over-identification were strongly and positively associated with distress. Self-compassion seems to play a role in explaining levels of psychological distress in people with long COVID symptoms. The centrality of self-compassion may lead to the development of effective interventions to help patients with long COVID reduce self-judgmental and self-critical tendencies and improve their psychological well-being.

Objectives Workplace stigmatisation and discrimination are significant barriers to accessing employment opportunities, reintegration and promotion in the workforce for people with mental illnesses in comparison to other disabilities. This paper presents qualitative evidence of anticipated and experienced workplace stigma and discrimination among individuals with major depressive disorder (MDD) in 35 countries, and how these experiences differ across countries based on their Human Development Index (HDI) level.Design Mixed-method cross-sectional survey.Participants, setting and measures The qualitative data were gathered as part of the combined European Union Anti-Stigma Programme European Network and global International Study of Discrimination and Stigma Outcomes for Depression studies examining stigma and discrimination among individuals with MDD across 35 countries. Anticipated and experienced stigma and discrimination were assessed using the Discrimination and Stigma Scale version 12 (DISC-12). This study used responses to the open-ended DISC-12 questions related to employment. Data were analysed using the framework analysis method.Results The framework analysis of qualitative data of 141 participants identified 6 key ‘frames’ exploring (1) participants reported experiences of workplace stigma and discrimination; (2) impact of experienced workplace stigma and discrimination; (3) anticipated workplace stigma and discrimination; (4) ways of coping; (5) positive work experiences and (6) contextualisation of workplace stigma and discrimination. In general, participants from very high HDI countries reported higher levels of anticipated and experienced discrimination than other HDI groups (eg, less understanding and support, being more avoided/shunned, stopping themselves from looking for work because of expectation and fear of discrimination). Furthermore, participants from medium/low HDI countries were more likely to report positive workplace experiences.Conclusions This study makes a significant contribution towards workplace stigma and discrimination among individuals with MDD, still an under-researched mental health diagnosis. These findings illuminate important relationships that may exist between countries/contexts and stigma and discrimination, identifying that individuals from very high HDI countries were more likely to report anticipated and experienced workplace discrimination.

Most clinical isolates of both Staphylococcus aureus and Staphylococcus epidermidis show the capacity to adhere to abiotic surfaces and to develop biofilms resulting in a contribution to chronic human skin infections. Antibiotic resistance and poor biofilm penetration are the main causes of ineffective therapeutic treatment in killing bacteria within biofilms. A possible strategy could be represented by drug delivery systems, such as nanoemulsions (composed of bioactive oil, surfactant and water phase), which are useful for enhancing the drug permeation of a loaded drug inside the biofilm and its activity. Phytochemical characterization of Pistacia lentiscus oil (LO) by direct infusion Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) allowed the identification of bioactive compounds with antimicrobial properties, including fatty acids and phenolic compounds. Several monoterpenes and sesquiterpenes have been also detected and confirmed by gas chromatography–mass spectrometric (GC-MS) analysis, together providing a complete metabolomic profiling of LO. In the present study, a nanoemulsion composed of LO has been employed for improving Levofloxacin water solubility. A deep physical–chemical characterization of the nanoemulsion including hydrodynamic diameter, ζ-potential, morphology, entrapment efficiency, stability release and permeation studies was performed. Additionally, the antimicrobial/antibiofilm activity of these preparations was evaluated against reference and clinical Staphylococcus spp. strains. In comparison to the free-form antibiotic, the loaded NE nanocarriers exhibited enhanced antimicrobial activity against the sessile forms of Staphylococcus spp. strains.

IntroductionEpithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease.Study designRegistry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE.ObjectivesTo improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern.MethodsSettings and participantsIt is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. VariablesFull details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methodsThe data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression.ResultsThe registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual.

We studied the COVID-19 impact in newly-diagnosed breast cancer (7,349 patients in 2019, and 5,563 in 2020). In 2020 there were two diagnostic drops: −37.2% (March–May), −15.8% (October–December). Early-stage at presentation (76.4% vs. 74.4%, p = 0.0013), conserving surgery (71.0% vs. 67.0%, p

Abstract Background Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in ‘real-world’ services. Methods/Design The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers’ patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrolment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms’ severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300. Owing to the implementation of the intervention at the CMHC level, the blinding of patients, clinicians, and raters is not possible, but every effort will be made to preserve the independency of the raters. We expect that this study will generate evidence on the best treatments for FEP, and will identify barriers that may hinder its feasibility in ‘real-world’ clinical settings, patient/family conditions that may render this intervention ineffective or inappropriate, and clinical, psychological, environmental, and service organization predictors of treatment effectiveness, compliance, and service satisfaction. Trial registration ClinicalTrials.gov Identifier NCT01436331

Abstract Background A strong relationship has been observed between comorbidities and the risk of severe/fatal COVID‐19 manifestations, but no score is available to evaluate their association in cancer patients. To make up for this lacuna, we aimed to develop a comorbidity score for cancer patients, based on the Lombardy Region healthcare databases. Methods We used hospital discharge records to identify patients with a new diagnosis of solid cancer between February and December 2019; 61 comorbidities were retrieved within 2 years before cancer diagnosis. This cohort was split into training and validation sets. In the training set, we used a LASSO‐logistic model to identify comorbidities associated with the risk of developing a severe/fatal form of COVID‐19 during the first pandemic wave (March–May 2020). We used a logistic model to estimate comorbidity score weights and then we divided the score into five classes (=5). In the validation set, we assessed score performance by areas under the receiver operating characteristic curve (AUC) and calibration plots. We repeated the process on second pandemic wave (October–December 2020) data. Results We identified 55,425 patients with an incident solid cancer. We selected 21 comorbidities as independent predictors. The first four score classes showed similar probability of experiencing the outcome (0.2% to 0.5%), while the last showed a probability equal to 5.8%. The score performed well in both the first and second pandemic waves: AUC 0.85 and 0.82, respectively. Our results were robust for major cancer sites too (i.e., colorectal, lung, female breast, and prostate). Conclusions We developed a high performance comorbidity score for cancer patients and COVID‐19. Being based on administrative databases, this score will be useful for adjusting for comorbidity confounding in epidemiological studies on COVID‐19 and cancer impact.

Colorectal cancer is very widespread in developed countries. Its diagnosis partly depends on pathologists’ experience and their laboratories’ instrumentation, producing uncertainty in diagnosis. The use of spectroscopic techniques sensitive to the cellular biochemical environment could aid in achieving a reliable diagnosis. So, we used Raman micro-spectroscopy, combined with a spectral analysis by means of machine learning methods, to build classification models, which allow colon cancer to be diagnosed in cell samples, in order to support such methods as complementary tools for achieving a reliable identification of colon cancer. The Raman spectra were analyzed in the 980–1800 cm−1 range by focusing the laser beam onto the nuclei and the cytoplasm regions of single FHC and CaCo-2 cells (modelling healthy and cancerous samples, respectively) grown onto glass coverslips. The comparison of the Raman intensity of several spectral peaks and the Principal Component Analysis highlighted small biochemical differences between healthy and cancerous cells mainly due to the larger relative lipid content in the former cells with respect to the latter ones and to the larger relative amount of nucleic acid components in cancerous cells compared with healthy ones. We considered four classification algorithms (logistic regression, support vector machine, k nearest neighbors, and a neural network) to associate unknown Raman spectra with the cell type to which they belong. The built machine learning methods achieved median values of classification accuracy ranging from 95.5% to 97.1%, sensitivity values ranging from 95.5% to 100%, and specificity values ranging from 93.9% to 97.1%. The same median values of the classification parameters, which were estimated for a testing set including unknown spectra, ranged between 93.1% and 100% for accuracy and between 92.9% and 100% for sensitivity and specificity. A comparison of the four methods pointed out that k nearest neighbors and neural networks better perform the classification of nucleus and cytoplasm spectra, respectively. These findings are a further step towards the perspective of clinical translation of the Raman technique assisted by multivariate analysis as a support method to the standard cytological and immunohistochemical methods for diagnostic purposes.

Abstract Background During the first months of the COVID-19 pandemic, local health authorities in most Italian regions prescribed a reduction of ordinary outpatient and community mental health care. The aim of this study was to assess the impact of the COVID-19 pandemic on access to the emergency departments (ED) for psychiatric consultation in the pandemic years 2020 and 2021 compared to 2019. Methods This is a retrospective study conducted by using routinely collected administrative data of the two EDs of the Verona Academic Hospital Trust (Verona, Italy). All ED psychiatry consultations registered from 01.01.2020 to 31.12.2021 were compared with those registered in the pre-pandemic year (01.01.2019 to 31.12.2019). The association between each recorded characteristic and the year considered was estimated by chi-square or Fisher’s exact test. Results A significant reduction was observed between 2020 and 2019 (-23.3%) and between 2021 and 2019 (-16.3%). This reduction was most evident in the lockdown period of 2020 (-40.3%) and in the phase corresponding to the second and third pandemic waves (-36.1%). In 2021, young adults and people with diagnosis of psychosis showed an increase in requests for psychiatric consultation. Conclusions Fear of contagion may have been an important factor in the overall reduction in psychiatric consultations. However, psychiatric consultations for people with psychosis and for young adults increased. This finding underlines the need for mental health services to implement alternative outreach strategies aimed to support, in times of crisis, these vulnerable segments of the population.

Abstract Background Recent studies have shown that nurses have been more affected by the COVID-19 pandemic than any other group of hospital workers in terms of anxiety, depression, and burnout. Several clinical studies had previously demonstrated the effectiveness of mindfulness and compassion interventions in reducing burnout and emotional distress amongst healthcare professionals. Methods and analysis A parallel-group randomized controlled trial will assess the feasibility, acceptability, and efficacy of a mindfulness and compassion-focused programme on frontline nurses who had been working during the COVID-19 pandemic. Seventy-two participants will be recruited from Verona University Hospital Trust (Veneto Region, north-east Italy) and will be divided equally into an intervention group and a control group. Primary outcome will be assessed using the Emotional Exhaustion subscale of the Maslach Burnout Inventory General Survey (MBI-GS). Secondary outcomes will be measured by the Cynicism and Professional Efficacy subscales of the MBI-GS, the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7), the Insomnia Severity Index (ISI), the Impact of Stressful Events (IES-R), the Perceived Stress Scale (PSS), the Five Facet Mindfulness Questionnaire (FFMQ), and the Forms of Self-Criticising/attacking and Self-Reassuring Scale (FSCRS). Discussion The study aims to fill a gap in the literature and present a scientifically validated intervention for those healthcare professionals most exposed to the stressful conditions of working during the COVID-19 pandemic. Trial registration ClinicalTrials.gov; Identifier: NCT05308537

Since the introduction of Universal Varicella Vaccination (UVV) in the Argentinean National Immunization Program in 2015, a significant decline in the incidence of varicella has been reported. This study aimed to estimate the economic impact of single-dose UVV in Argentina from 2015 to 2019. The economic impact was assessed based on the observed incidence of varicella in the post-UVV period and the number of cases avoided, obtained from a previously published study that used an Autoregressive Integrated Moving Average (ARIMA) model. The weighted average cost per case was calculated using local studies. The post-UVV cost reductions were calculated by multiplying the number of cases avoided from 2015 –2019 by the weighted average cost per case. Data were summarized yearly and by peak (September−November) periods for the target (1−4 years) and overall populations. We estimated avoided costs of United States dollars (USD) $65 million in the target population and $112 million in the overall population over 4 years following UVV introduction. We observed a trend toward greater reductions in costs over time, with substantial differences observed in peak periods. We estimated that the single-dose UVV program considerably reduced the economic burden of varicella in Argentina by avoiding direct and indirect costs associated with varicella management.

IntroductionFunctional neurological disorder (FND) presents motor, sensory, and cognitive symptoms characterized by clinical signs incongruent with known neurological disease. Together with other health professionals, like neurologists, psychiatrists can play an essential role in diagnosing and managing these disorders. Hence, understanding their opinion and clinical experience with FND is of utmost importance to catch potential educational needs and improve healthcare services for patients. This study aims at assessing the knowledge, opinion, and clinical approach of Italian psychiatrists to FND.MethodsMembers of the Italian Society of Psychiatry completed a 14-item web-based survey investigating their approach to FND. Results. Overall, 174 questionnaires were completed. Our main findings suggest that Italian psychiatrists have a psychogenetic conceptualization of FND. “Conversion disorders”, in fact, is the term most frequently used by Italian psychiatrists to refer to FND, thus implying a psychological etiology of these disorders. Congruently with this view, psychotherapy associated with pharmacological therapy is considered the most appropriate treatment by psychiatrists, while physiotherapy is an under-recognized treatment option for FND.DiscussionThe present study highlights that a psychogenetic view of FND dominates among Italian psychiatrists. This could be due to out-of-date knowledge about the pathophysiology of this group of disorders. Promoting education about novel approaches to FND would be of crucial importance to improving care for patients suffering from this condition.

IntroductionComparable indicators on complete cancer prevalence are increasingly needed in Europe to support survivorship care planning. Direct measures can be biased by limited registration time and estimates are needed to recover long term survivors. The completeness index method, based on incidence and survival modelling, is the standard most validated approach.MethodsWithin this framework, we consider two alternative approaches that do not require any direct modelling activity: i) empirical indices derived from long established European registries; ii) pre-calculated indices derived from US-SEER cancer registries. Relying on the EUROCARE-6 study dataset we compare standard vs alternative complete prevalence estimates using data from 62 registries in 27 countries by sex, cancer type and registration time.ResultsFor tumours mostly diagnosed in the elderly the empirical estimates differ little from standard estimates (on average less than 5% after 10-15 years of registration), especially for low prognosis cancers. For early-onset cancers (bone, brain, cervix uteri, testis, Hodgkin disease, soft tissues) the empirical method may produce substantial underestimations of complete prevalence (up to 20%) even when based on 35-year observations. SEER estimates are comparable to the standard ones for most cancers, including many early-onset tumours, even when derived from short time series (10-15 years). Longer observations are however needed when cancer-specific incidence and prognosis differ remarkably between US and European populations (endometrium, thyroid or stomach).DiscussionThese results may facilitate the dissemination of complete prevalence estimates across Europe and help bridge the current information gaps.

Nowadays, the lack of quantitative criteria to resolve the diagnostic heterogeneity of psychotic onsets limits the development of safer and more effective treatments. Therefore, the hypothesis to integrate multimodal data to uncover biological subtypes of psychosis has risen [1,2]. Here we explored the existence of subgroups of patients affected by first episode psychosis (FEP) with a possible immunopathogenic basis.To do this, we designed a computational model that use unsupervised machine learning to cluster a sample of 127 FEP patients and 117 healthy controls (HC), based on the peripheral blood concentrations of 12 immune gene transcripts which demonstrated to classify with high accuracy between FEP patients and healthy subjects in a previous study [3]. To validate the model, we applied a resampling strategy based on the half-splitting of the total sample. Further, we tested the correlation between the subgroups and clinical, neuropsychological and brain structural variables.In both the discovery and validation samples, the model identified a FEP cluster characterized by the high expression of inflammatory and immune-activating genes (IL1b, CCR7 and IL12a) and of a single immune counterregulatory gene (CCR3)[4] and a further cluster consisting of equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). Also, none of the subgroups were related to specific symptoms dimensions or longitudinal diagnosis. FEP patients included in the balanced immune subgroup showed a reduced left hippocampal volume and a left supramarginal and lateroccipital cortexes’ thinning. These correlations seem to support an opposite pattern in the correspondent brain area of the inflammatory subgroup [5].Our results demonstrated the existence of a FEP patients’ subgroup that present a prominent activation of the inflammatory response. This evidence may pave the way to sample stratification in future trials aiming to develop personalized diagnostic tools and therapies targeting specific immunopathogenic pathways of psychosis onsets.

In the present study, we focus on dinuclear cobalt-based CO-RMs with the aim of elucidating their CO release mechanism, as well as to understand how structural changes targeted to modify the electronic properties of these compounds can modulate CO delivery. To this end, we specifically synthesized a set of phenyl-propargyl-based CO-RMs bearing –NO2, –H, and –OCH3 as para-substituents (R) with varying mesomeric influence (M) and different heteroatoms (X = NH, O, or S) linking the propargyl tail and the aromatic ring. The effects of R and X in modulating CO release were assessed by using several experimental and computational techniques to obtain a coherent picture and to shed light on the stability and release properties of Co-based CO-RMs. [ABSTRACT FROM AUTHOR]

People surviving COVID‐19 may experience social stigma related to their condition even after clinical recovery. This study aimed to: (1) investigate COVID‐19‐related experienced discrimination and internalized stigma, and (2) explore their association with symptoms of anxiety, depression, and insomnia. We conducted an online survey of people who survived COVID‐19. Perception of stigma was assessed using the COVID‐19 Experienced Discrimination Scale and the COVID‐19 Internalized Stigma Scale. Depression, anxiety, and insomnia were assessed using, respectively, the Patient Health Questionnaire‐9, the General Anxiety Disorder Scale‐7, and the Insomnia Severity Index. Multivariable logistic regression analyses for each psychopathological domain were performed. A total of 579 participants participated in this study. Overall, 25% reported some degree of experienced discrimination, and 23% reported some degree of internalized stigma. Adjusted odds ratio showed that scoring higher on internalized stigma related significantly to higher symptoms of depression (2.14; 95% confidence interval [CI], 1.35–3.39), anxiety (2.30; 95% CI, 1.48–3.59), and insomnia (2.54; 95% CI, 1.64–3.95), whereas experienced discrimination was associated to anxiety (1.55; 95% CI, 1.06–2.28) and insomnia (1.82; 95% CI, 1.24–2.69). Experiences of social stigmatization are frequent among people surviving COVID‐19 and seem to be associated with levels of psychological disturbances. Further research is required to elucidate the direction of these relationships to implement effective treatment strategies. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings. Study Design We used incidence data in people aged 18–64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group. Study Results Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61–0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55–0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02–2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings. Conclusions Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders. [ABSTRACT FROM AUTHOR]

Colorectal cancer was one of the most frequent causes of death due to cancer in 2020. Current diagnostic methods, based on colonoscopy and histological analysis of biopsy specimens, are partly dependent on the operator’s skills and expertise. In this study, we used Fourier transform infrared (FTIR) spectroscopy and different machine learning algorithms to evaluate the performance of such method as a complementary tool to reliably diagnose colon cancer. We obtained FTIR spectra of FHC and CaCo-2 cell lines originating from healthy and cancerous colon tissue, respectively. The analysis, based on the intensity values of specific spectral structures, suggested differences mainly in the content of lipid and protein components, but it was not reliable enough to be proposed as diagnostic tool. Therefore, we built six machine learning algorithms able to classify the two different cell types: CN2 rule induction, logistic regression, classification tree, support vector machine, k nearest neighbours, and neural network. Such models achieved classification accuracy values ranging from 87% to 100%, sensitivity from 88.1% to 100%, and specificity from 82.9% to 100%. By comparing the experimental data, the neural network resulted to be the model with the best performance parameters, having excellent values of accuracy, sensitivity, and specificity both in the low-wavenumber range (1000–1760 cm−1) and in the high-wavenumber range (2700–3700 cm−1). These results are encouraging for the application of the FTIR technique, assisted by machine learning algorithms, as a complementary diagnostic tool for cancer detection.

Objective Seropositive rheumatoid arthritis (RA) is a chronic autoimmune disease that is rarely “cured.” Human mesenchymal stem cells (hMSCs) are known to reduce inflammation and restore immune homeostasis. However, methods for predicting therapeutic hMSC potency have not been established. The goal of these studies was to use and refine an ex vivo functional assay that determines potency of hMSCs and can then be validated in clinical trials as a potency measure of hMSCs used therapeutically to treat RA. Methods Allogeneic hMSCs were cytokine‐stimulated, and a conditioned medium (CM) was harvested. The CM was tested for the potential to attenuate RA CD4+ T cell proliferation using suppression assays. Indoleamine 2, 3‐dioxygenase (IDO) mRNA, and protein were quantified in hMSCs as a measure to compare hMSCs across (prior) studies. Results To mimic a proinflammatory environment that resembles that in RA, interleukin‐1(IL1β), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) (alone or in combination) were used to precondition hMSCs. Treating hMSCs with a combination of these cytokines generated a CM “secretome” that suppressed T cell proliferation between 70 and 83%. Forty‐eight hours of cytokine preconditioning hMSCs was required to maximize this effect. T cell suppression positively correlated with increases in hMSC cellular IDO mRNA and protein. Conclusion By standardizing assays to measure hMSC effects, their potency on T cell suppression can be quantified. These studies demonstrate that hMSCs can be compared functionally to identify optimal preparation(s) for therapeutic use in RA and that the potency of hMSC‐dependent T cell suppression may differ between hMSC donors. Clinical studies are warranted to validate the hypothesis that ex vivo potency in suppressing T cells will positively correlate with a reduction in RA disease activity and increase in immunological quiescence.

This article discusses advance statements in mental health care, which allow individuals with mental disorders to express their preferences for treatment during mental health crises. Despite the evidence supporting their effectiveness, their implementation in clinical practice remains limited. This article explores variations among advance statements, such as psychiatric advance directives (PADs), joint crisis plans (JCPs) and self-binding directives (SBDs), highlighting their content, development process and legal status. We outline the benefits of advance statements, including empowerment, early intervention, improved therapeutic relationships and reduced compulsory admissions. We then draw attention to the challenges that may contribute to their lack of implementation, including legal complexities, communication issues, cultural factors, potential inequities, healthcare provider knowledge, changing preferences, resource constraints, crisis responses, data privacy, family involvement, and long-term evaluation. In conclusion, advance statements offer significant benefits but require addressing these critical aspects to ensure ethical and effective use. Bridging the evidence-to-practice gap is essential, with a focus on implementation science. Integrating these tools into routine clinical practice can significantly benefit individuals with severe mental disorders and mental health systems.