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In this study, lead (Pb), cadmium (Cd), and total mercury (Hg) concentrations in European squids (Loligo vulgaris) and flying squids (Todarodes sagittatus) from the northern Adriatic Sea (Italy) were analyzed. The risk of the Italian population being exposed to potentially hazardous metal concentrations through the consumption of these products was also assessed. Compared to European squids, flying squids showed three times higher total Hg concentrations and one hundred times higher Cd concentrations to the point that more than 6 and 25% of the samples exceeded the maximum Hg and Cd limits established by the current legislation. From the evaluation of dietary exposure levels, it emerged that the consumption of flying squids was associated with the highest Pb intake by children and, consequently, with the lower margin of exposure values in relation to the risk of neurotoxicity (margin of exposure=33). Consumption of flying squids, especially by children, was also associated with higher intakes of Cd, inorganic, and methyl-Hg, which, respectively, accounted for 156, 113, and 23% of the tolerable weekly intakes established for these contaminants at European level. The obtained results raise concern and it may be necessary to provide specific dietary advice on the moderate dietary consumption of some cephalopod species, especially to the youngest and most vulnerable segment of the population. However, besides the highly conservative deterministic method adopted in this study, a refined consumer exposure assessment should be performed through the probabilistic methodology, which is more suitable to represent the real exposure scenario.

Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder that impacts the dopaminergic neurons of the substantia nigra, leading to motor and non-motor symptoms, as well as changes in activities of daily living (ADL) and quality of life (QoL). Aquatic physical exercises and dual-task physical exercises have been used to manage PD symptoms. The aim of this study was to investigate the effects of a dual-task aquatic exercise program on the ADL, motor symptoms, and QoL of individuals with PD. Methods: A randomized controlled trial with a parallel group design was employed, and participants were randomized into 2 groups: a control group and an experimental group. The intervention was a 10-week program consisting of twice-weekly 40-minute aquatic dual-task exercises. Pre-intervention evaluations of ADL, motor function, and QoL were conducted at baseline (AS1), immediately after the intervention (AS2), and 3 months post-intervention (follow-up—AS3). The Unified Parkinson’s Disease Rating Scale (UPDRS) II and III sections and the Parkinson’s Disease Questionnaire 39 (PDQ-39) were utilized for outcome measures. Results: A total of 25 individuals completed the study. The experimental group showed significant improvements in both the UPDRS II (ADL) and III (motor function) sections ( P ’s

Background and Objectives. A relatively small number of studies have investigated the characteristics, comorbidities and laboratory measures associated with prognosis in patients with COVID-19, admitted to Internal Medicine Units (IMU) in Italy. Therefore, we performed a retrospective multicentre study to identify baseline features, predisposing to severe disease and poor outcomes, in adult individuals with SARS-CoV-2 infection, hospitalized in 5 IMUs in the Emilia-Romagna region (Italy). Materials and Methods. We included 129 consecutive patients (male 75, median age 68 years) from 1st March 2020 to 31st October 2021. Patients’ baseline characteristics, comorbidities, laboratory measures, and outcomes were collected. Results. At admission, the factors significantly associated with a higher risk of in-hospital mortality included: age (median 68 vs. 83 years in survived vs. dead patients, P=0.000), diabetes [Odds Ratio (OR) 4.00, P=0.016], chronic obstructive pulmonary disease (OR 4.60, P=0.022), cancer (OR 5.81, P=0.021), acute- (OR 9.88, P=0.000) and chronic-renal failure (OR 6.76, P=0.004). During the study period, 16 individuals died (12.4%), all over 70 years old. In deceased vs. non-deceased patients were detected: i) more elevated white blood cells and neutrophils-counts and lower lymphocytes count; ii) higher levels of total/direct bilirubin, creatinine, C-reactive-protein, lactate-dehydrogenase, ferritin, but only a slight Interleukin-6 increase; iii) a trend of lower vitamin D values. Conclusions. We proposed a new I index, a modified form of the Age-Adjusted Charlson Comorbidity Index, by considering pO2/FiO2 ratio, to better characterize the severity of COVID-19. Furthermore, we critically discuss our results with the current assumption which considers COVID-19 as a pathological condition associated with cytokine storm.

We assessed the effect of 28-homocatasterone on xylem functionality and its relationship with blossom end rot (BER) occurrence and the quality of 'BRS Montese' tomatoes. Tomato plants were cultivated in a protected environment, with a semi-hydroponic system. During full flowering, open flowers were selected, marked, and pollinated. After two days, the flowers received the application of 28-homocatasterone at a concentration of 10-6 M or deionized water (control). Treatments were reapplied weekly up to 24 days after the first application (DAFA). At 24 DAFA, fruits were harvested and evaluated for fresh mass, texture (skin rupture and pulp penetration forces), skin color, xylem functionality, membrane permeability, apoplastic calcium concentration, and BER incidence. The application of 28-homocatasterone at 10-6 M did not increase the fresh mass nor change the fruits' texture attributes. However, 28-homocatasterone increased or kept xylem functionality, which was assicated with increased apoplastic calcium concentration and reduced BER occurrence in 'BRS Montese' tomatoes. Thus, the application of 10-6 M catasterone could be an alternative for BER control in tomatoes.

Mutations in the ceruloplasmin (CP) gene are responsible for the rare genetic disease aceruloplasminemia characterized by iron accumulation in different organs, including the brain. We previously reported that administration of purified CP in the CP-deficient (cpKO) mouse model of the disease, was therapeutically effective. Here we evaluated the bioavailability of the therapeutic protein in different organs of the cpKO mouse. The distribution of administered radiolabelled-[64Cu]-CP was assessed in brain and peripheral tissues in vivo and ex vivo. The uptake of [64Cu]-CP in cpKO mice varied according to animal sex and age, with a higher accumulation in the cerebellum and liver of males at 6 months of age, while higher levels were observed in the same organs in females at 10 months. Sex-specific variations in the uptake of radiolabelled-CP were genotype-associated, by comparison with wild type mice. Based on these findings, we assessed sex effects on the therapeutic efficacy of the CP-replacement therapy previously performed. Multivariate analysis confirmed that the therapeutic effect was present for both sexes, and this was more pronounced in males than females. Therefore, sex-related variation in CP tissue bioavailability point to the possibility of sex-specific therapeutic regimens in the design of future CP-replacement therapies for aceruloplasminemia. Sex-related variation in 64Cu-ceruloplasmin tissue bioavailability in the mouse model of the disease for aceruloplasminemia point to the possibility of sex-specific therapeutic regimens in the design of future enzyme replacement therapies for this disease. [ABSTRACT FROM AUTHOR]

The application of quantum‐based NMR methods for the structural elucidation of natural and unnatural products has grown significantly. However, accurately calculating the conformational landscape of flexible molecules with intricate intramolecular hydrogen bonding (IHB) networks continues to be a major challenge. In this work, we thoroughly studied the effect of entropic contributions (trough Gibbs free energies calculations) in the DP4+ performance. Our results show that to solve biased systems with strong IHB interactions requires computing the Boltzmann contributions using Gibbs free energies computed with at least triple‐ξ basis set and SMD solvation model. In response to this finding, we have updated our DP4+App, a user‐friendly Python applet that automates the entire process of calculating DP4+ probabilities. In the new version, the program allows for calculating of conformational contributions at any selected theory level, using either SCF or Gibbs free energies. [ABSTRACT FROM AUTHOR]

Background: Postoperative physiotherapy is a cornerstone of Enhanced Recovery After Surgery (ERAS) programs, especially following lung resection. Despite its importance, the literature lacks clear recommendations and guidelines, particularly regarding the role of incentive spirometry (IS). This study aims to determine whether incentive spirometry offers additional benefits over early ambulation alone in patients undergoing lung resection for primary lung cancer. Methods: We conducted a retrospective case–control study at the European Institute of Oncology (IEO) involving patients who underwent lung resection from June 2020 to June 2022. Patients were divided into two cohorts: early ambulation alone (control group) and early ambulation with IS (IS group). The primary endpoint was the rate of postoperative pulmonary complications. Secondary endpoints included length of hospital stay and time to chest drain removal. A propensity score-matched analysis was performed based on age, sex, and BMI. Data were compared using Chi-squared and Student's t-tests as appropriate. Results: A total of 304 patients were included, with 153 in the intervention group and 151 in the control group. After propensity-score matching, 52 patients from each cohort were compared. No significant differences were found between the groups regarding postoperative oxygen requirement, fever, atelectasis, residual pleural space, need for bronchoscopy toilette, and re-hospitalization rate. IS group showed trends toward shorter hospital stays and lower time to chest drain removal, though without reaching statistical significance. Conclusions: IS did not significantly improve postoperative outcomes compared to early ambulation alone in patients undergoing lung resection for primary lung cancer. More extensive, prospective, randomized trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

A growing literature explores the phenomenon of simultaneous cooperating and competing firms. Mostly in strategic management, this literature primarily focused upon large firms. The dynamics of coopetition in small firms, including new and micro-firms, however, remains under-explored raising questions about how they both engage with and manage this complex paradoxical relationship. Shifting the focus in coopetition research to small firms is vital as despite many noted benefits, evidence suggests that liabilities of newness and smallness affect engagement in cooperative relationships. Due to the specificities of small firms, it remains unlikely that the knowledge derived from their larger counterparts will adequately reflect the drivers and mechanisms of small firm coopetition. How does coopetition unfold in the small firm sector? How do challenges and specificities of small firms influence principles and mechanisms identified by the literature on large firm coopetition? To analyse such issues, in this annual review article, we evaluate the emerging body of research on small firm coopetition. Connecting coopetition strategy with small firms and entrepreneurship, we provide a comprehensive review of this emerging literature drawing from which, we then formulate future research needs and directions. [ABSTRACT FROM AUTHOR]

The increasingly aging workforce is bringing particular attention to senior individuals in production sectors. While the interest in Virtual Reality (VR) applications for industrial robotics grows, the question of whether and how senior workers can withstand VR-based repetitive tasks arises. We here aimed to answer such questions by systematically assessing young and senior users' experiential, behavioural, and cognitive factors during simulated robotic teleoperations in VR. Two control systems for VR telerobotics, button- and action-based controls, were employed. Human performance, vigilance, and workload were measured through self-reports and a VR-integrated eye-tracker. Additionally, age-dependent differences in individual cultural and experiential factors were explored via self-report measures. Despite being slower and experiencing increased fatigue under specific conditions, as suggested by the eye-tracking measures, senior users demonstrated comparable precision in operating the robotic arm to their younger counterparts. Notably, both age groups reported similar levels of perceived fatigue. The paper provides an in-depth analysis of the advantages and challenges of adopting advanced telerobotics control systems across different age groups, consistently emphasising the human-centered dimension. [ABSTRACT FROM AUTHOR]

This is the first study to assess the physicochemical and biological compatibility of herbicides used in corn crops with entomopathogenic fungi used in the management of Dalbulus maidis in Brazil. The biological index was employed to ascertain the in vitro compatibility of the herbicides with pure spores (not formulated) of tested fungal isolates (Esalq-1296 of Cordyceps javanica and IBCB66 and Simbi BB15 of Beauveria bassiana). The results indicated a significant interaction between herbicides and fungal isolates when colony diameter and colony-forming units (CFU) were considered. Furthermore, changes in physicochemical characteristics were observed in some mixtures of herbicides and mycoinsecticides tested. The number of CFU was significantly reduced as the exposure time increased in the mixtures containing all the herbicides tested. In general, the Esalq-1296 isolate of C. javanica, formulated in a suspension concentrate (Octane®), proved to be more sensitive to the herbicides studied. In vivo bioassays demonstrated that, despite the synergistic effect of the binary mixtures of herbicides and mycoinsecticides on D. maidis mortality, the presence of the herbicide in the mixtures prevented the extrusion of entomopathogens from cadavers; therefore, caution is recommended when combining mycoinsecticides and post-emergent herbicides in tank mixtures aiming to manage D. maidis. [ABSTRACT FROM AUTHOR]

Background: The genetic determinants of peripartum depression (PPD) are not fully understood. Using a multi-polygenic score approach, we characterized the relationship between genome-wide information and the history of PPD in patients with mood disorders, with the hypothesis that multiple polygenic risk scores (PRSs) could potentially influence the development of PPD. Methods: We calculated 341 PRSs for 178 parous mood disorder inpatients affected by major depressive disorder (MDD) or bipolar disorder (BD) with (n = 62) and without (n = 116) a history of PPD. We used partial least squares regression in a novel machine learning pipeline to rank PRSs based on their contribution to the prediction of PPD, in the whole sample and separately in the two diagnostic groups. Results: The PLS linear regression in the whole sample defined a model explaining 27.12% of the variance in the presence of PPD history, 56.73% of variance among MDD, and 42.96% of variance in BD. Our findings highlight that multiple genetic factors related to circadian rhythms, inflammation, and psychiatric diagnoses are top contributors to the prediction of PPD. Specifically, in MDD, the top contributing PRS was monocyte count, while in BD, it was chronotype, with PRSs for inflammation and psychiatric diagnoses significantly contributing to both groups. Conclusions: These results confirm previous literature about the immune system dysregulation in postpartum mood disorders, and shed light on which genetic factors are involved in the pathophysiology of PPD. [ABSTRACT FROM AUTHOR]

Background Anhedonic features within major depressive disorder (MDD) have been associated with worse course and outcome and may predict nonresponse to treatment. However, a detailed clinical profile of anhedonia in MDD is still lacking. Materials and Methods One thousand two hundred ninety-four patients with MDD were selected from the cross-sectional European multicenter Group for the Study of Resistant Depression study. Anhedonia was assessed through the Montgomery–Åsberg Depression Rating Scale anhedonia item "inability to feel." Clinical and demographic features were then analyzed. Results The presence of anhedonia related to a distinct demographical (living alone) and clinical profile (thyroid diseases, diabetes, suicide risk, high number of previous depressive episodes, more severe MDD, and more frequent inpatient status). Furthermore, anhedonia was associated with nonresponse to treatment and treatment resistance, even after adjusting for confounding variables. Conclusions Our findings support the role of anhedonia as a modulating feature of MDD, being associated with a more severe depression profile. Moreover, anhedonic features are independent predictors of poor treatment response. [ABSTRACT FROM AUTHOR]

This review emphasizes the recent ongoing shift in the wood coating industry towards bio-based resources and circular economy principles, promoting eco-friendly alternatives. In addressing wood’s vulnerabilities, this study investigates the use of natural compounds and biopolymers to enhance wood coatings. These materials contribute to protective matrices that safeguard wood surfaces against diverse challenges. Essential oils, vegetable oils, and bio-based polymers are explored for their potential in crafting eco-friendly and durable coating matrices. Furthermore, this review covers efforts to counter weathering and biological decay through the application of various natural compounds and extracts. It evaluates the effectiveness of different bio-based alternatives to traditional chemical preservatives and highlights promising candidates. This review also delves into the incorporation of sustainable pigments and dyes into wood coatings to enhance both protective and aesthetic qualities. Innovative pigments are able to provide visually appealing solutions in line with sustainability principles. As the wood coating industry embraces bio-based resources and the circular economy, researchers are actively developing protective solutions that encompass the coating matrix, preservatives, bio-based fillers, and natural-pigment dyes. This review showcases the continuous efforts of academia and industry to enhance wood coatings’ effectiveness, durability, and sustainability, while maintaining their aesthetic appeal.

Objective: The aim of this cross-sectional study was to evaluate the neurological/psychomotor development of children aged 0-5 years attending Child Education Centers in Brazil. Method: This developmental assessment included a screening test to identify which variables could be associated with risks for developmental delays. A total of 444 children were evaluated using the Denver II, which examines the personal-social, language, fine motor-adaptive, and gross motor domains. To demonstrate associations between variables, the chi-square test for k-proportions was used, followed by a logistic regression model. Results: The evaluation indicated a risk for developmental delay in 45.9% of the children, with the personal-social and language domains being the most affected. The influence of the school environment and age group on child development was noted. Conclusions: These data are of great importance in that they serve to provide a basis for the identification and monitoring of the achievements of children.

Abstract Background SARS-CoV-2 infection in the pediatric age group has a milder course than in adults, but in some cases even children may present with severe forms or develop long-term consequences. The aim of this study was to analyze the clinical features, long-term effects, lifestyle changes and psychological effects of SARS-CoV-2 infection in a pediatric sample of the Italian population. Methods We conducted a telephone survey among 3075 children infected with SARS-CoV-2 in the Latina Local Health Authority. Outcomes included: clinical features of infection, long-term symptoms, lifestyle changes and emotional symptoms during the illness. The information obtained was automatically linked to a spreadsheet and analyzed. Results One thousand four hundred thirteen children agreed to participate in the study; the mean age was 112.8 ± 21.9 months. Children were infected mainly inside familial clusters (59.6%; n = 842); 99% (n = 1399) of children were asymptomatic or exhibited mild symptoms. 20% (n = 259) of children experienced long-term symptoms; risk factors were: older age, higher body mass index and longer duration of infection. Throughout the period of infection, children spent most of the time on devices like tv-video, social media and mobile phone for non-educational activities. 58.8% (n = 620) of parents expressed a negative opinion about distance learning. Finally, we observed that 49,6% (n = 532) of children experienced psychological symptoms during quarantine period. Conclusion Despite a lower susceptibility to COVID-19 in children, it is important to keep the focus high in children, both because of the possible long symptoms after infection and the impact on a children’s mental and physical health due to pandemic. We believe that the return to school or other extracurricular activities are important to correct some of the risk factors for the long COVID syndrome, as obesity, and to limit the cultural damage generated by distance learning and psychological effects related to restrictive measures.

The macroscopic properties of composite materials depend on the microscopic properties of the constituents and the geometric arrangement of their phases. Therefore, it is essential to predict heterogeneous materials’ mechanical properties by simulating microstructural finite element models. The present article aims to analyze particle reinforced composites composed of spherical alumina inclusions surrounded by a glass matrix using a tridimensional representative volume element. Herein, microstructures are artificially created considering a regular or random arrangement of the inclusions. Two materials systems previously studied in the literature were analyzed. The discretization of the models was performed to have periodic mesh, thus enabling the use of periodic boundary conditions. A finite element model is created using Abaqus software. Numerical results show that the macroscopic properties can be estimated with high accuracy for the temperature where linear matrix behavior stands. The predictions were compared to experimental data from the literature. The models with a regular arrangement of inclusions show a difference inferior to 10%, while random arrangements show a difference inferior to 3.9%. The developed numerical algorithms can be modified to include new features, such as other dispersed phase arrangements or nonlinear material behavior.

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Chondrocalcinosis (CC) is the one of the most common crystal pyrophosphate disease associated arthritis in the elderly. It has been shown to coexist with seronegative and seropositive rheumatoid arthritis (RA), yet mostly with seronegative RA. Among the localisation of CC, the deposition in the ligaments surrounding the odontoid process may remain asymptomatic for years or may lead to and acute severe symptomatology, which may mimic several clinical illnesses among which meningitis (fever, severe pain, acute phase reactants). This is called the ‘crowned dens syndrome (CDS)’, which has been reported to represent an important percentage of acute neck pain needing hospital admission in neurosurgery units. In this case, the rapid demonstration of ‘crowned dens’ through CT scan may allow to avoid lumbar puncture and cerebrospinal fluid examination. The coexistence of RA and CDS is very rare, and rarely reported in the literature, yet it may represent a clinical challenge. We describe here one case that while on therapy with methotrexate (MTX) and naproxen (NPX) had an acute neck pain, and peripheral arthritis flare, that responded well to colchicine given along with MTX and NPX.

Background: Androgen receptor signaling inhibitors (ARSis) abiraterone acetate (AA) plus prednisone and enzalutamide (Enza), are currently the most administered first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). AA and Enza have shown similar overall survival (OS) benefits and there is no consensus upon the best option for mCRPC first-line treatment. Volume of disease may represent a useful biomarker to predict response to therapy in such patients. Objectives: In this study, we seek to evaluate the impact of volume of disease on patients treated with first-line AA versus Enza for mCRPC. Design and methods: We retrospectively evaluated a cohort of consecutive patients with mCRPC categorized by volume of disease [high volume (HV) or low volume (LV) per E3805 criteria] at ARSi onset and treatment type (AA or Enza), assessing OS and radiographic progression-free survival (rPFS), from therapy start, as co-primary endpoints. Results: Of the 420 patients selected, 170 (40.5%) had LV and received AA (LV/AA), 76 (18.1%) LV and had Enza (LV/Enza), 124 (29.5%) HV and were given AA (HV/AA), and 50 (11.9%) HV and received Enza (HV/Enza). Among patients with LV, OS was significantly longer when treated with Enza [57.2 months; 95% confidence interval (CI): 52.1–62.2 months] versus AA (51.6 months; 95% CI, 42.6–60.6 months; p = 0.003). Consistently, those with LV receiving Enza showed increased rPFS (40.3 months; 95 CI, 25.0–55.7 months) than those having AA (22.0 months; 95% CI, 18.1–26.0 months; p = 0.004). No significant difference in OS or rPFS was observed in those with HV treated with AA versus Enza ( p = 0.51 and p = 0.73, respectively). In multivariate analysis of patients with LV, treatment with Enza was independently associated with better prognosis than AA. Conclusion: Within the intrinsic limitations of a retrospective design and small population, our report suggests that volume of disease could be a useful predictive biomarker for patients starting first-line ARSi for mCRPC.

Introduction About 60% of bipolar disorder (BD) cases are initially misdiagnosed as major depressive disorder (MDD), preventing BD patients from receiving appropriate treatment. An urgency exists to identify reliable biomarkers for improving differential diagnosis (DD). Machine learning methods may help translate current knowledge on biomarkers of mood disorders into clinical practice by providing individual-level classification. No study so far has combined biological data with clinical data to provide a multifactorial predictive model for DD. Objectives Define a predictive algorithm for BD and MDD by integrating structural neuroimaging and inflammatory data with neuropsychological measures (NM). Two different algorithms were compared: multiple kernel learning (MKL) and elastic net regularized logistic regression (EN). Methods In a sample of 141 subjects (70 MDD; 71 BD), two different models were implemented for each algorithm: 1) structural neuroimaging measures only (i.e. voxel-based morphometry (VBM), white matter fractional anisotropy (FA), and mean diffusivity (MD)); 2) VBM, FA, and MD combined with NM. In a subsample of 71 subjects (36 BD; 38 MDD), two similar models were implemented: 1) VBM, FA, and, MD combined with only NM; 2) VBM, FA, and MD combined with NM and peripheral inflammatory markers. Finally, the best model was selected for comparison with healthy controls (HC). Results Overall, the EN model based on all the modalities achieved the highest accuracy (AUC = 90.2%), outperforming MKL (AUC=85%). EN correctly classified BD and MDD with a diagnostic accuracy of 78.3%, sensitivity of 75%, and specificity of 81.6%. The most significant predictors of BD (variable inclusion probability (VIP) > 80%) were the parahippocampal cingulate, interleukin 9, chemokine CCL5, posterior thalamic radiation, and internal capsule, whereas MDD was best predicted by chemokine CCL23, the anterior cerebellum, and the sagittal stratum. In contrast, NM did not help to differentiate between MDD and BD. However, they help to distinguish patients from HC. Psychomotor coordination and speed of information processing discriminated between MDD and HC (VIP>90%), whereas fluency, working memory, and executive functions differentiated between BD and HC (VIP>80%). Conclusions In summary, BD was predicted by a strong proinflammatory profile, whereas MDD was identified by structural neuroimaging data. A multimodal approach offers additional instruments to improve personalized diagnosis in clinical practice and enhance the ability to make DD. Disclosure of Interest None Declared

Introduction One of the main obstacles in providing effective treatments for major depressive disorder (MDD) is clinical heterogeneity, whose neurobiological correlates are not clearly defined. A biologically meaningful stratification of depressed patients is needed to promote tailored diagnostic procedures. Objectives Using structural data, we performed an unsupervised clustering to define clinically meaningful clusters of depressed patients. Methods T1-weighted and diffusion tensor images were obtained from 102 MDD patients. In 64 patients, clinical symptoms, number of stressful life events, severity and exposure to adverse childhood experiences were evaluated using the Beck Depression Inventory (BDI), Schedule of Recent Experiences (SRE), Risky Family Questionnaire (RFQ), and Childhood Trauma Questionnaire (CTQ). Clustering analyses were performed with extracted tract-based fractional anisotropy (TBSS, FSL), cortical thickness, surface area, and regional measures of grey matter volumes (CAT12). Gaussian mixture model was implemented for clustering, considering Support Vector Machine (SVM) as classifier. A 10x2 repeated cross-validation with grid search was performed for hyperparameters tuning and clusters’ stability. The optimal number of clusters was determined by normalized stability, Akaike and Bayesian information criterion. Analyses were adjusted for total intracranial volume, age, and sex. The clinical relevance of the identified clusters was assessed through MANOVA, considering domains of clinical scales as dependent variables and clusters’ labels as fixed factors. Discriminant analysis was subsequently performed to assess the discriminative power of these variables. Results Cross-validated clustering approach identified 2 highly stable clusters (normalized stability=0.316, AIC=-80292.48, BIC=351329.16). MANOVA showed a significant between-clusters difference in clinical scales scores (p=0.038). Discriminant analysis distinguished the two clusters with an accuracy of 78.1%, with BDI behavioural and CTQ minimisation/denial domains showing the highest discriminant values (0.325 and 0.313). Conclusions Our results defined two biologically informed clusters of MDD patients associated with childhood trauma and specific clinical profiles, which may assist in targeting effective interventions and treatments. Disclosure of Interest None Declared

Introduction In recent years much focus has been put on the role of immune/inflammatory alterations in affecting Major Depression (MDD) development and antidepressant efficacy. Neutrophil-to-lymphocyte ratio (NLR) is an inexpensive inflammatory marker shown to be elevated in depressed patients, with large population studies reporting this effect only in women. However, its relation to treatment response is much less clear. Reduced hippocampal volumes (HV) are among the few consistent brain structural predictors of poor treatment response, and they have been shown to be influenced by inflammatory status. Objectives To investigate the effect of NLR on treatment response in MDD patients, testing a possible moderating role of sex. To investigate the effect of NLR on HV and test a possible mediating role of the latter in the relation between NLR and treatment response. Methods Our study was performed on a sample of 120 MDD inpatients suffering from a non psychotic depressive episode (F=78; M=42). Depression severity was assessed via the Hamilton Depression Rating Scale (HDRS), both at admission and discharge; as a measure of treatment response, delta HDRS was calculated subtracting the two scores. NLR was calculated for each subject. Patients underwent 3T MRI acquisition and bilateral HV were estimated. Results We found a significant moderating effect of sex on the relationship between NLR and Delta HDRS (p < 0.001): a negative relation was found in women (p < 0.001) and a positive one in men (p = 0.042). NLR was found to negatively affect left HV in the whole sample (p = 0.027) and in women (p = 0.038). A positive effect on Delta HDRS was found for both left (p = 0.038) and right (p = 0.027) HV. Finally, we found a significant indirect effect of NLR values on Delta HDRS through left HV in women (95% BCa CI [- 0.948, -0.017]); the direct effect of NLR on Delta HDRS also remained significant (p = 0.002). Conclusions Sex was found to moderate the relation between NLR and treatment response. The detrimental effect in women is in line with previous reports linking inflammation to hampered antidepressant effect; the positive one in men is more surprising: however, the only studies to date on the effect of NLR on antidepressant efficacy report a positive effect in patients with psychotic depression. In women we found NLR to affect treatment response partially through its effect on left HV, providing a possible, albeit incomplete, mechanistic explanation of the effect of inflammatory status on antidepressant efficacy. Disclosure of Interest None Declared

Introduction Major depressive disorder (MDD) is largely considered the most prevalent psychiatric disorder worldwide. Despite its domineering presence, effective treatment for many individuals remains elusive. Investigation into relevant biological markers, specifically neuroimaging correlates, of MDD and treatment response have gained traction in recent years; however, findings are still inconsistent. Objectives In this study, we aimed to investigate the resting state functional connectivity patterns associated with treatment response in MDD inpatients in a real world setting. Methods Forty-three inpatients suffering from a major depressive episode were recruited from the psychiatric ward at IRCCS San Raffaele Hospital in Milan, Italy. Symptom severity was assessed via the 21-item Hamilton Depression Rating Scale (HDRS). The percentage of decrease in HDRS scores from admission to discharge was then calculated with the formula [(HDRS admission – HDRS discharge) * 100] / HDRS admission. All patients underwent a 3T MRI scan within one week of admission to acquire resting-state fMRI images, which included 200 sequential T2*-weighted volumes. Images were preprocessed using the CONN toolbox, running within Statistical Parametric Mapping (SPM 12). Preprocessing was performed according to a standard pipeline. A voxel-wise metric, intrinsic connectivity contrast (ICC), was implemented to explore the global resting state functional connectivity (rs-FC) patterns associated with treatment response. ICC-derived maps were then entered in the second-level analyses to examine the effect of the percentage of HDRS decrease, including age, sex, admission HDRS score, duration of hospitalization, and antidepressant dose equivalents as nuisance covariates. Results We found that the percentage of HDRS decrease after treatment predicted rs-FC. ICC analysis identified 2 clusters where changes in HDRS scores were significantly associated with rs-FC, with increased connectivity in the supramarginal gyrus (pFDR = 0.002) and decreased connectivity in the amygdala and parahippocampal gyrus (pFDR = 0.047). Conclusions Our results suggest that altered connectivity of the supramarginal gyrus, amygdala and parahippocampal gyrus is related to antidepressant treatment response. Given that these brain areas are implicated in emotional processing and mood, it is conceivable that a better integrity of brain connectivity may facilitate treatment response in major depression. Disclosure of Interest None Declared

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder of lymphocyte homeostasis classically due to mutation of FAS, FASL, and CASP10 genes (ALPS-FAS/CASP10). Despite recent progress, about one-third of ALPS patients does not carry classical mutations and still remains gene orphan (ALPS-U, undetermined genetic defects). The aims of the present study were to compare the clinical and immunological features of ALPS-FAS/CASP10 versus those of ALPS-U affected subjects and to deepen the genetic characteristics of this latter group. Demographical, anamnestic, biochemical data were retrieved from medical record of 46 ALPS subjects. An enlarged panel of genes (next-generation sequencing) was applied to the ALPS-U group. ALPS-U subjects showed a more complex phenotype if compared to ALPS-FAS/CASP10 group, characterized by multiorgan involvement (P = 0.001) and positivity of autoimmune markers (P = 0.02). Multilineage cytopenia was present in both groups without differences with the exception of lymphocytopenia and autoimmune neutropenia that were more frequent in ALPS-U than in the ALPS-FAS/CASP10 group (P = 0.01 and P = 0.04). First- and second-line treatments were able to control the symptoms in 100% of the ALPS-FAS/CASP10 patients, while 63% of ALPS-U needed >2 lines of treatment and remission in some cases was obtained only after target therapy. In the ALPS-U group, we found in 14 of 28 (50%) patients 19 variants; of these, 4 of 19 (21%) were known as pathogenic and 8 of 19 (42%) as likely pathogenic. A characteristic flow cytometry panel including CD3CD4-CD8-+TCRαβ+, CD3+CD25+/CD3HLADR+, TCR αβ+ B220+, and CD19+CD27+ identified the ALPS-FAS/CASP10 group. ALPS-U seems to represent a distinct entity from ALPS-FAS/CASP10; this is relevant for management and tailored treatments whenever available.