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Background: For investigating the individual-environment interplay and individual differences in response to environmental exposures as captured by models of environmental sensitivity including Diathesis-stress, Differential Susceptibility, and Vantage Sensitivity, over the last few years, a series of statistical guidelines have been proposed. However, available solutions suffer of computational problems especially relevant when sample size is not sufficiently large, a common condition in observational and clinical studies., Method: In the current contribution, we propose a Bayesian solution for estimating interaction parameters via Monte Carlo Markov Chains (MCMC), adapting Widaman et al. (Psychological Methods, 17, 2012, 615) Nonlinear Least Squares (NLS) approach., Results: Findings from an applied exemplification and a simulation study showed that with relatively big samples both MCMC and NLS estimates converged on the same results. Conversely, MCMC clearly outperformed NLS, resolving estimation problems and providing more accurate estimates, particularly with small samples and greater residual variance., Conclusions: As the body of research exploring the interplay between individual and environmental variables grows, enabling predictions regarding the form of interaction and the extent of effects, the Bayesian approach could emerge as a feasible and readily applicable solution to numerous computational challenges inherent in existing frequentist methods. This approach holds promise for enhancing the trustworthiness of research outcomes, thereby impacting clinical and applied understanding., (© 2024 Association for Child and Adolescent Mental Health.)

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor outcomes in Parkinson's disease (PD) but may have adverse long-term effects on specific cognitive domains. The aim of this study was to investigate the association between total electrical energy (TEED) delivered by DBS and postoperative changes in verbal fluency., Methods: Seventeen PD patients undergoing bilateral STN-DBS were assessed with the Alternate Verbal Fluency Battery (AVFB), which includes phonemic (PVF), semantic (SVF), and alternate verbal fluency (AVF) tests, before surgery (T0) and after 6 (T1) and 12 months (T2). Bilateral TEED and average TEEDM were recorded at T1 and T2. For each AVFB measurement, changes from T0 to T1 (Δ-01) and from T0 to T2 (Δ-02) were calculated., Results: At T1, PVF ( p = 0.007) and SVF scores ( p = 0.003) decreased significantly. TEED measures at T1 and T2 were unrelated to Δ-01 and Δ-02 scores, respectively. However, an inverse, marginally significant association was detected between the TEEDM and Δ-01 scores for the AVF ( p = 0.041, against an α adjusted = 0.025)., Conclusions: In conclusion, the present reports provide preliminary evidence that TEED may not be responsible or only slightly responsible for the decline in VF performance after STN-DBS in PD.

The common bean ( Phaseolus vulgaris L.) is one of the oldest food crops in the world. In this study, the ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-MS/MS) technique was used to characterize the polar lipid composition and polyphenolic fraction of five bean varieties commonly consumed in Italy: Cannellino (PVCA), Controne (PVCO), Borlotti (PVBO), Stregoni (PVST), and Vellutina (PVVE). Lipid content represents a minor fraction of the whole metabolome in dry beans, and little is known about their polar lipids, which could be potentially bioactive components. Thirty-three compounds were detected through UHPLC-MS/MS, including oxylipins, phospholipids, N-acyl glycerolipids, and several fatty acids. The dichloromethane extracts were subjected to principal component analysis (PCA), with the results showing greater differentiation for the Borlotti variety. Moreover, 27 components belonging to different polyphenol classes, such as phenolic acids, flavonoids, catechins, anthocyanins and their glycosides, and some saponins, were identified in the hydroalcoholic seed extracts. In addition, the mineral content of the beans was determined. Considering the high number of compounds in the five apolar seed extracts, all samples were examined to determine their in vitro inhibitory activity against the enzyme cyclooxygenase-2 (COX-2), which is inducible in inflammatory cells and mediates inflammatory responses. Only PVCO showed the best inhibition of the COX-2 enzyme with an IC 50 = 31.15 ± 2.16 µg/mL. In light of these results, the potential anti-inflammatory properties of PVCO were evaluated in the LPS-stimulated murine macrophage cell line J774A.1. Herein, we demonstrate, for the first time, that PVCO at 30 µg/mL can significantly reduce the release of TNF-α, with a less significant anti-inflammatory effect being observed in terms of IL-6 release.

School teachers are among workers most exposed to stress and burnout-a relevant occupational phenomenon leading to psychological and economic costs. The Environmental Sensitivity individual trait-as captured by the psychological marker of sensory processing sensitivity (SPS)-has been found to have a relevant role in stress and emotional exhaustion at work. Yet, little is still known about heightened SPS in the educational field and on underlying mechanisms occurring in the relationship between SPS, stress and burnout. The current work aimed to explore the association between SPS and burnout among teachers as well as the moderating role of perceived stress and school climate in this association. One hundred and ninety eight teachers (44.3 years; SD = 9.7, 94% F) reported on their levels of SPS, occupational burnout, perceived stress and school climate quality. In line with a vulnerability effect, we found heightened SPS largely associated with burnout. This was particularly evident in a context of high-perceived stress, suggesting that teachers high on SPS may experience more challenges in the face of elevated stress with the need of more support. When exposed to positive and supportive school climate, highly sensitive teachers showed a decrease in burnout, suggesting high SPS as a valuable strength for benefiting from positive experiences. Findings have the potential to inform the customisation of support programs, assisting both schools and work agencies in increasing their awareness of the role of individual differences in responding to both work-demand-related stress and to positive work environments., (© 2024 The Author(s). Stress and Health published by John Wiley & Sons Ltd.)

Background: Depression presents with altered energy regulation and neural plasticity. Previous electroencephalography (EEG) studies showed that practice in learning tasks increases power in beta range (13-30 Hz) in healthy subjects but not in those with impaired plasticity. Here, we ascertain whether depression presents with alterations of spectral activity and connectivity before and after a learning task., Methods: We used publicly available resting-state EEG recordings (64 electrodes) from 122 subjects. Based on Beck Depression Inventory (BDI) scores, they were assigned to either a high BDI (hBDI, BDI > 13, N = 46) or a control (CTL, BDI < 7, N = 75) group. We analyzed spectral activity, theta-beta, and theta-gamma phase-amplitude coupling (PAC) of EEG recorded at rest before and after a learning task., Results: At baseline, compared to CTL, hBDI exhibited greater power in beta over fronto-parietal regions and in gamma over the right parieto-occipital area. At post task, power increased in all frequency ranges only in CTL. Theta-beta and theta-gamma PAC were greater in hBDI at baseline but not after the task., Conclusions: The lack of substantial post-task growth of beta power in depressed subjects likely represents power saturation due to greater baseline values. We speculate that inhibitory/excitatory imbalance, altered plasticity mechanisms, and energy dysregulation present in depression may contribute to this phenomenon.

Introduction: Mother-infant attunement is fundamental to supporting infant socio-emotional development. Based on the assumption that we connect better with others if we are aware of and connected with our own experience, mindfulness could affect the maternal ability to attune to the infant. However, little is known about this topic in the first year of life. Study 1 aimed to investigate the role of maternal dispositional mindfulness and mindful parenting in mother-infant physiological and behavioral attunement at 3 months of age. Study 2 aimed to explore the effect of a mindfulness-based intervention not specific to parenting experience on mother-infant behavioral and physiological attunement and on maternal wellbeing at 9 months of age., Methods: In Study 1, mother-infant ( n  = 67) behavioral and physiological attunement (i.e., co-regulation and RSA) were collected simultaneously each 20 s during face-to-face interaction. Mothers completed questionnaires about their dispositional mindfulness and mindful parenting. In Study 2, mother-infant dyads were randomly divided into a control ( n  = 20) and an intervention group ( n  = 29). The intervention group attended a 5-week mindfulness-based intervention. At T1 and T2, the same procedure described in Study 1 was applied and mothers reported about their wellbeing., Results: Results showed that maternal mindfulness was associated with high physiological and behavioral attunement at 3 months and with more positive maternal behaviors and less stress at 9 months. Analysis evidenced a slight improvement in the intervention group in maternal dispositional mindfulness and a reduction in parenting stress at T2., Discussion: Findings from both studies suggested that maternal mindfulness could represent a protective factor that could support mothers in fostering better dyadic interactions with their infants. The implementation of mindfulness-based interventions for mothers could have preventive and clinical implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Passaquindici, Pastore, Nardozza, Lionetti, D’Urso, Palumbo, Fasolo and Spinelli.)

Background: The consensus in scientific literature is that each child undergoes a unique linguistic development path, albeit with shared developmental stages. Some children excel or lag behind their peers in language skills. Consequently, a key challenge in language acquisition research is pinpointing factors influencing individual differences in language development., Methods: We observed children longitudinally from 3 to 24 months of life to explore early predictors of vocabulary size. Based on the productive vocabulary size of children at 24 months, 30 children met our sample selection criteria: 10 late talkers and 10 early talkers, and we compared them with 10 typical talkers. We evaluated interactive behaviors at 3, 6, 9 and 12 months, considering vocal production, gaze at mother's face, and gestural production during mother-child interactions, and we considered mothers' report of children's actions and gestures and receptive-vocabulary size at 15 and 18 months., Results: Results indicated early precursors of language outcome at 24 months identifiable as early as 3 months in vocal productions, 6 months for gaze at mother's face and 12 months for gestural productions., Conclusions: Our research highlights both theoretical and practical implications. Theoretically, identifying the early indicators of belonging to the group of late or early talkers underscores the significant role of this developmental period for future studies. On a practical note, our findings emphasize the crucial need for early investigations to identify predictors of vocabulary development before the typical age at which lexical delay is identified., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Logrieco MG et al.)

A significant amount of European basic and clinical neuroscience research includes the use of transcranial magnetic stimulation (TMS) and low intensity transcranial electrical stimulation (tES), mainly transcranial direct current stimulation (tDCS). Two recent changes in the EU regulations, the introduction of the Medical Device Regulation (MDR) (2017/745) and the Annex XVI have caused significant problems and confusions in the brain stimulation field. The negative consequences of the MDR for non-invasive brain stimulation (NIBS) have been largely overlooked and until today, have not been consequently addressed by National Competent Authorities, local ethical committees, politicians and by the scientific communities. In addition, a rushed bureaucratic decision led to seemingly wrong classification of NIBS products without an intended medical purpose into the same risk group III as invasive stimulators. Overregulation is detrimental for any research and for future developments, therefore researchers, clinicians, industry, patient representatives and an ethicist were invited to contribute to this document with the aim of starting a constructive dialogue and enacting positive changes in the regulatory environment., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

This research focuses on the target deconvolution of the natural compound myrianthic acid, a triterpenoid characterized by an ursane skeleton isolated from the roots of Myrianthus arboreus and from Oenothera maritima Nutt. (Onagraceae), using MS-based chemical proteomic techniques. Application of drug affinity responsive target stability (DARTS) and targeted-limited proteolysis coupled to mass spectrometry (t-LiP-MS) led to the identification of the enzyme fatty acid synthase (FAS) as an interesting macromolecular counterpart of myrianthic acid. This result, confirmed by comparison with the natural ursolic acid, was thoroughly investigated and validated in silico by molecular docking, which gave a precise picture of the interactions in the MA/FAS complex. Moreover, biological assays showcased the inhibitory activity of myrianthic acid against the FAS enzyme, most likely related to its antiproliferative activity towards tumor cells. Given the significance of FAS in specific pathologies, especially cancer, the myrianthic acid structural moieties could serve as a promising reference point to start the potential development of innovative approaches in therapy.

Background: The literature supports the role of parental dispositional mindfulness on parent-child relationship quality. However, little is known about the connection between these two aspects., Objective: The aim of this study was to investigate whether emotion regulation during parenting, that is, the ability to control negative emotions, mediated the association between parental dispositional mindfulness and parent-child relationship quality. The study also explored the moderation role of child age on the association between parental dispositional mindfulness and parent's ability to control negative emotions during parenting., Methods: Participants were 635 mothers of children aged between 12 months and 5 years. Mothers completed self-report questionnaires to measure maternal dispositional mindfulness, mother-child relationship quality and maternal control of negative emotions during parenting., Results: Results showed that maternal ability to control negative emotions during parenting partially mediated the association between maternal dispositional mindfulness and mother-child relationship quality. Moreover, the moderation role of child age indicated that the association between maternal dispositional mindfulness and maternal ability to control negative emotions during parenting was stronger for older children's mothers., Conclusion: Dispositional mindfulness has a protective role for the quality of parenting and the mother-child relationship. Theoretical and practical implications are discussed., (© 2024 John Wiley & Sons Ltd.)

Obsessive-compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insights of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas the severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need for additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and an extraordinary supply of essential resources.

Adaptive functioning constitutes a fundamental aspect of the phenotype associated with autism spectrum disorder (ASD) in preschool-aged children, exerting a significant influence on both the child and the family's overall quality of life. The aim of this study was to investigate the predictors of the adaptive functioning domains in preschool-age children with ASD at two time points, providing a snapshot of this fundamental developmental step. Methods: Ninety-five children with ASD ( M = 3.89, SD = 1.13) were included in the study and longitudinal data (the mean length of the longitudinal data collection was 1 year) on ASD features such as social communication and social interaction, repetitive and restricted behavior, cognitive level, and adaptive functioning were collected. We considered autistic features, cognitive level, and sociodemographic factors as possible predictors of the different adaptive functioning domains one year later. Results: Data obtained showed a worsening of the ASD features and adaptive functioning after one year. Furthermore, the severity of repetitive and restricted behavior predicted adaptive functioning, especially in the social and practical domains of the child, one year later. This prediction was observed alongside the child's cognitive level. Conclusions: The study identifies some potential predictive factors of specific adaptive functioning domains in preschoolers with ASD. Considering how critical adaptive functioning is for the well-being of both the child and their family, it becomes imperative to design early-stage interventions focused on nurturing adaptive skills in children with ASD.

Introduction: As captured by the individual trait of Sensory Processing Sensitivity (SPS), highly sensitive children perceive, process, and responds more strongly to stimuli. This increased sensitivity may make more demanding the process of regulating and managing emotions. Yet, developmental psychology literature also showed that other variables, as those related to the rearing environment, are likely to contribute to the process of regulating emotions. With the current contribution, we aim to bridge two lines of research, that of attachment studies and that of SPS, by investigating the additive and interactive contribution of SPS and internal working models of attachment representations on emotion regulation competencies in school-aged children., Method: Participants were N  = 118 Italian children (mean age: 6.5, SD = 0.58 years, and 51.8% female) with their mothers. Children's positive attachment representations were rated observationally through the Manchester Child Attachment Story Task procedure during an individual session at school. Mothers reported on children SPS trait and emotion regulation competencies completing the Highly Sensitive Child Scale-parent report and the Emotion Regulation Checklist. We performed and compared a series of main and interaction effect models., Results: SPS was not directly associated with emotion regulation but it was significantly associated with positive attachment representations in predicting emotion regulation. Highly sensitive children showed poorer emotion regulation when the internalized representations were low in maternal warmth and responsiveness. When driven by sensitive and empathic attachment representation, highly sensitive children showed better emotion regulation than less-sensitive peers, suggesting a for better and for worse effect., Discussion: Highly sensitive children are not only more vulnerable to adversities but also show better emotion regulation competencies when supported by positive internal working models of attachment relationships. Overall, findings shed light on the link between SPS and attachment and suggest that working for promoting secure attachment relationships in parent-child dyads may promote better emotion regulation competences, particularly in highly sensitive children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sperati, Acevedo, Dellagiulia, Fasolo, Spinelli, D’Urso and Lionetti.)

The present study aims to explore the forms of psychological parental control that are interconnected with dysfunctional emotional states (i.e., anxiety and depression), and how these internalizing problems may manifest as distorted behaviors (i.e., vigorexic and orthorexic behaviors) during adolescence. Participants included 403 Italian adolescent athletes (231 boys and 172 girls) aged 14 to 18 years. The participants completed self-report questionnaires designed to assess psychological parental control oriented towards dependence and achievement, anxiety and depression, and vigorexia and orthorexia. The results highlight how both forms of psychological parental control predict anxiety and depression. Furthermore, anxiety was found to be linked to both vigorexic and orthorexic behaviors, while depression is connected only to vigorexia. This study delves into the intricacies of parental influence on adolescents, revealing that both dependency-oriented and success-oriented psychological parental control have notable implications for the mental well-being of adolescents. The findings underscore the interconnectedness of these factors, demonstrating that anxiety can set off a chain reaction, leading to engagement in vigorexic and orthorexic behaviors. On the other hand, depression appears to be uniquely associated with vigorexia. These insights contribute to our understanding of the complex dynamics between parental control and adolescent mental health. The implications of this research extend to both theoretical frameworks and practical interventions, emphasizing the need for a nuanced approach to supporting adolescents in navigating these challenges.

Mycalin A (MA) is a polybrominated C-15 acetogenin isolated from the marine sponge Mycale rotalis . Since this substance displays a strong antiproliferative bioactivity towards some tumour cells, we have now directed our studies towards the elucidation of the MA interactome through functional proteomic approaches, (DARTS and t-LIP-MS). DARTS experiments were performed on Hela cell lysates with the purpose of identifying MA main target protein(s); t-LiP-MS was then applied for an in-depth investigation of the MA-target protein interaction. Both these techniques exploit limited proteolysis coupled with MS analysis. To corroborate LiP data, molecular docking studies were performed on the complexes. Finally, biological and SPR analysis were conducted to explore the effect of the binding. Mortalin (GRP75) was identified as the MA's main interactor. This protein belongs to the Hsp70 family and has garnered significant attention due to its involvement in certain forms of cancer. Specifically, its overexpression in cancer cells appears to hinder the pro-apoptotic function of p53, one of its client proteins, because it becomes sequestered in the cytoplasm. Our research, therefore, has been focused on the possibility that MA might prevent this sequestration, promoting the re-localization of p53 to the nucleus and facilitating the apoptosis of tumor cells.

Human milk is the gold standard for infant nutrition, but when it is not available or insufficient to satisfy the needs of the infant, formula milk is proposed as an effective substitute. A prospective observational cohort study was conducted on late preterm infants fed with breast and two different formula milks. On this basis, they were divided into three groups: group FMPB (fed with formula + postbiotic), group FM (fed with standard formula), and group BM (breastfed). Stool samples for a metabolomic study were collected at T0 (5-7 days after birth), T1 (30 days of life), and T2 (90 days of life), giving rise to 74 samples analyzed via liquid chromatography coupled with high-resolution mass spectrometry. The T0, T1, and T2 LC-MS raw data were processed for Partial Least Square Discriminant Analysis (PLS-DA), followed by a statistical analysis. This preliminary study highlighted a good overlapping between the fecal metabolome of breast and substitute feeding systems, confirming the efficacy of the formula preparations as breast milk substitutes. Moreover, several similarities were also detected between the FMPB and BM metabolome, highlighting that the addition of a postbiotic to standard formula milk could be more effective and considered a better alternative to breast milk.

The metabolite fingerprinting of four Italian commercial bean seed cultivars, i.e., Phaseolus Cannellino (PCANN), Controne (PCON), Vellutina (PVEL), and Occhio Nero (PON), were investigated by Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate data analysis. The hydroalcoholic and organic extract analysis disclosed more than 32 metabolites from various classes, i.e., carbohydrates, amino acids, organic acids, nucleosides, alkaloids, and fatty acids. PVEL, PCON, and PCANN varieties displayed similar chemical profiles, albeit with somewhat different quantitative results. The PON metabolite composition was slightly different from the others; it lacked GABA and pipecolic acid, featured a higher percentage of malic acid than the other samples, and showed quantitative variations of several metabolites. The lipophilic extracts from all four cultivars demonstrated the presence of omega-3 and omega-6 unsaturated fatty acids. After the determination of the total phenolic, flavonoids, and condensed tannins content, in vitro antioxidant activity was then assessed using the DPPH scavenging activity, the ABTS scavenging assay, and ferric-reducing antioxidant power (FRAP). Compared to non-dark seeds (PCON, PCANN), brown seeds (PVEL, PON) featured a higher antioxidant capacity. Lastly, only PON extract showed in vitro antifungal activity against the sclerotia growth of S. rolfsii , by inhibiting halo growth by 75%.

Mass spectrometry-based chemical proteomic approaches using limited proteolysis have become a powerful tool for the identification and analysis of the interactions between a small molecule (SM) and its protein target(s). Gracilioether A (GeA) is a polyketide isolated from a marine sponge, for which we aimed to trace the interactome using this strategy. DARTS (Drug Affinity Responsive Target Stability) and t-LiP-MS (targeted-Limited Proteolysis-Mass Spectrometry) represented the main techniques used in this study. DARTS was applied on HeLa cell lysate for the identification of the GeA target proteins, and t-LiP-MS was employed to investigate the protein's regions involved in the binding with GeA. The results were complemented through the use of binding studies using Surface Plasmon Resonance (SPR) and in silico molecular docking experiments. Ubiquitin carboxyl-terminal hydrolase 5 (USP5) was identified as a promising target of GeA, and the interaction profile of the USP5-GeA complex was explained. USP5 is an enzyme involved in the pathway of protein metabolism through the disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. This activity is connected to different cellular functions concerning the maintenance of chromatin structure and receptors and the degradation of abnormal proteins and cancerogenic progression. On this basis, this structural information opens the way to following studies focused on the definition of the biological potential of Gracilioether A and the rational development of novel USP5 inhibitors based on a new structural skeleton., Competing Interests: The authors declare no conflicts of interest.

Satureja bachtiarica is an endemic plant from the Lamiaceae family, growing in the Zagros mountain range in Iran. Even if S. bachtiarica is reported to possess many biological activities, little is known about its chemical composition. For this reason, in the present research, a phytochemical investigation of this species was carried out. To have a preliminary metabolite profile of S. bachtiarica , the n -BuOH extract was analyzed using LC-ESI/LTQOrbitrap/MS/MS in negative ion mode, allowing the identification of specialized metabolites belonging to flavonoid, monoterpene, indol, phenylpropanoid, phenolic, lignan, coumarin, biphenyl, and triterpene classes. The LC-MS/MS analysis guided the isolation of compounds, and their structures were characterized using spectroscopic methods including 1D- and 2D-NMR experiments and HRMS n analysis. In this way, a compound never reported before belonging to the biphenyl class was identified. Total flavonoid content of the extract along with the antioxidant activity were assessed. Based on the traditional uses of S. bachtiarica suggesting potential antibacterial properties, an evaluation of the biofilm inhibitory activity of the extract and isolated compounds against mature biofilms of Acinetobacter baumannii , Escherichia coli , Listeria monocytogenes , Pseudomonas aeruginosa , and Staphylococcus aureus , as well as their influence on the metabolism of sessile bacterial cells, was conducted. The results evidenced that some compounds including parmentin B, biphenyls, and 1-(1H-indole-3-carboxylate)-β-D-glucopyranoside might inhibit some changes occurring in the bacterial cells, which increases their virulence. In particular, biphenyl derivatives at a concentration of 80 μg/mL were capable of limiting remarkably the mature biofilms of A. baumannii and L. monocytogenes remarkably at a percentage ranging between 52.76% and 75.02%, and they reached an inhibition percentage of 69.28 % against E. coli . Biphenyl derivatives were also effective in exerting an inhibitory action against the mature biofilm of P. aeruginosa (inhibition ranging from 59.38% to 81.08%) and Staphylococcus aureus (inhibition percentage reached 82.94%). Of note, the biphenyl derivatives resulted in being capable of acting on the metabolism of the cells within the biofilm of all five pathogens.

The application of metabolomics to the study of plants is growing because of the current development of analytical techniques. The most commonly used analytical technology driving plant metabolomics studies is Mass Spectrometry (MS) coupled to liquid chromatography (LC). In recent years, Nuclear Magnetic Resonance (NMR) spectroscopy, not requiring a previous chromatographic separation, has been receiving growing attention for metabolite fingerprinting of natural extracts. Herein, an integrated LC-MS and 1 H NMR metabolomic approach provided a comprehensive phytochemical characterization of Symphytum anatolicum whole plant, taking into account both primary and specialized metabolites. Moreover, the NMR analyses provided direct quantitative information. Species belonging to the Symphytum genus, known as comfrey, have shown several biological activities including anti-inflammatory, analgesic, hepatoprotective, antifungal, and antibacterial. The LC-MS profile showed the presence of 21 main specialized metabolites, belonging to the classes of flavonoids, phenylpropanoids, salvianols, and oxylipins. The 1 H NMR spectrum revealed the occurrence of metabolites including organic acids, phenolics, flavonoids, sugars, and amino acids. A quantitative analysis of these metabolites was performed and their concentration was obtained with respect to the known concentration of TSP, by means of the software package Chenomx which allows quantification of individual components in the NMR spectra. Furthermore, the phenolic content, antioxidant activity, glucosidase, and tyrosinase inhibitory activity of S. anatolicum extract were evaluated. The resulting bioactivity profile suggests how S. anatolicum represents a source of metabolites with health-promoting activity.

Background: This study seeks to further our understanding of the factors associated with adolescent athletes and disordered eating, by expanding current research into a less-explored eating disorder known as orthorexia. Aim: The aim of the study is to explore the impact of parents' relationships and emotional regulation on the orthorexia nervosa (ON) tendencies of adolescent athletes. Methods: The participants were 303 adolescents, ranging from 15 to 17 years old, of which 139 participated in competitive sport, and 164 did not. Three self-report questionnaires were administered to assess orthorexia (ORTO-15), relationship with parents (Inventory of Parent and Peer Attachment) and emotion regulation (Emotion Regulation Questionnaire). Results: The results highlight that those who practice sports report higher levels of orthorexia, inadequate relationships with parents, as well as greater emotional regulation difficulties. Furthermore, inadequate parents' relationship predicts orthorexia while expressive emotional regulation mediates this relationship. Conclusion: These findings highlight how ON tendencies in athletes are linked to poor management of emotions combined with inadequate relationships with parents in terms of communication and affection. Implications for practice and support for athletes are discussed.

Almost 25% of schizophrenia patients suffer from obsessive-compulsive symptoms (OCS) considered a transdiagnostic clinical continuum. The presence of symptoms pertaining to both schizophrenia and obsessive-compulsive disorder (OCD) may complicate pharmacological treatment and could contribute to lack or poor response to the therapy. Despite the clinical relevance, no reviews have been recently published on the possible neurobiological underpinnings of this comorbidity, which is still unclear. An integrative view exploring this topic should take into account the following aspects: (i) the implication for glutamate, dopamine, and serotonin neurotransmission as demonstrated by genetic findings; (ii) the growing neuroimaging evidence of the common brain regions and dysfunctional circuits involved in both diseases; (iii) the pharmacological modulation of dopaminergic, serotoninergic, and glutamatergic systems as current therapeutic strategies in schizophrenia OCS; (iv) the recent discovery of midbrain dopamine neurons and dopamine D1- and D2-like receptors as orchestrating hubs in repetitive and psychotic behaviors; (v) the contribution of N-methyl-D-aspartate receptor subunits to both psychosis and OCD neurobiology. Finally, we discuss the potential role of the postsynaptic density as a structural and functional hub for multiple molecular signaling both in schizophrenia and OCD pathophysiology.

One of the most important purposes of the modern industry is a sustainable production, considering the minimization of the energy and of the raw materials used, together with the reduction of polluting emissions. In this context, Friction Stir Extrusion stands out, since it allows to obtain extrusions starting from metal scraps deriving from traditional mechanical machining processes (e.g., chips deriving from cutting operations), heated only by the friction generated between the scraps and the tool, so avoiding the material melting phase. Given the complexity of this new kind of process, the objective of this research is the study of the bonding conditions considering both the heat and the stresses generated during the process under different working parameters, namely tool rotational and descent speeds. As a result, the combined approach involving the Finite Element Analysis and the Piwnik and Plata criterion proves to be a valid tool for forecasting if bonding phenomenon occurs and how it is influenced by the process parameters. The results have also demonstrated that it is possible to achieve completely massive pieces between 500 rpm and 1200 rpm, but at different tool descent speeds. Specifically, up to 1.2 mm/s for 500 rpm and just over 2 mm/s for 1200 rpm.

Background: Symptoms of obsessive-compulsive disorder (OCD) have been reported to increase during the COVID-19 lockdowns because of the hygiene requirements related to the pandemic. Patients with adjustment disorder (AD) may, in turn, represent a vulnerable population for identifiable stressors. In this study, we aimed at assessing potential symptoms changes in OCD patients during the lockdown in comparison with AD patients as well as versus healthy controls (HC)., Methods: During the COVID-related lockdown, we enrolled 65 patients and 29 HC. Participants were tested with four clinical rating scales (Yale-Brown obsessive-compulsive scale and Brown Assessment of Beliefs Scale for OCD patients; Beck Depression Inventory-II and State-Trait Anxiety Inventory-Y for each group) that had been also administered just before the Italian lockdown., Results: Our results showed that during the lockdown: (i) the symptoms of depression and anxiety increased in all groups, but this increase was most pronounced in HC ( p  < 0.001); (ii) OCD symptoms severity did not increase, but the insight worsened ( p  = 0.028); (iii) the proportion of OCD patients showing hygiene-related symptoms increased ( p  = 0.031 for obsessions of contamination), whereas that of patients with checking-related symptoms decreased., Conclusions: The lockdown-induced psychological distress apparently changed the characteristics and the pattern of OCD symptoms expression but not their overall severity. This evidence confirms the heterogeneity and changing nature of OCD symptoms, strongly depending on the environmental circumstances.

The study investigated the emergence of toddlers' regulatory strategies in aversive contexts. Forty-two toddlers were observed at 24 and 30 months of age using two paradigms designed to elicit fear and anger. We examined toddlers' use of regulatory strategies at these two stages of life regarding the frequency of self-versus other-oriented strategies and of reactive versus more controlled behaviors. Results showed that the type and level of control of strategies used in toddlerhood in managing negative emotions depend on emotion (e.g., fear versus anger) and age. Toddlers used self-oriented strategies to regulate fear and other-oriented strategies to regulate anger. To manage fear, when toddlers got older, they increased the use of reactive strategies (i.e., releasing tension) and decreased the use of more purposeful strategies (i.e., dealing with the aversive stimulus). In contrast, to regulate anger, toddlers utilized an intermediate level of control (i.e., drawing the mother's attention to themselves) and increased the use of this strategy with age. In addition, toddlers were able to select appropriate strategies for different stressors, and they increased with age the ability to adapt the strategies to the environmental conditions. Theoretical and practical implications are discussed.

The COVID-19 pandemic and the associated restrictions caused great psychological suffering to the general population and psychiatric patients. We aimed to explore the course of depression and anxiety symptoms in obsessive compulsive disorder (OCD) patients, adjustment disorder (AD) patients, and participants without psychiatric disorders (control group, CG) across the different phases of the pandemic: the first lockdown, a temporary interruption of restrictions, and the second lockdown. Out of the 158 patients screened, we enrolled 46 OCD and 19 AD patients as well as 29 CG participants. The Beck Depression Inventory-II and the State-Trait Anxiety Inventory-Y were administered to all participants at each time point. The results showed different symptom severities among the groups throughout the whole study, with OCD patients always scoring higher than AD patients and the CG, and the AD patients always scoring higher than the CG. The symptom course within each group was different. OCD patients' symptoms sharply worsened during the first lockdown and then remained stable irrespective of the subsequent pandemic phases. In the AD and CG groups, symptoms waxed and waned following the fluctuations of the restriction provisions, with a complete return to the baseline when the restrictions were stopped only in the CG. These findings suggest that the influence of the pandemic and of the associated restrictions on depression and anxiety manifestations may vary depending on the particular pre-existing mental health status.

The multidomain ribosomal protein bS1 is the biggest and the most flexible and dynamic protein in the 30S small subunit. Despite being essential for mRNA recruitment and its primary role in the accommodation of the start codon within the decoding centre, there has not yet been a high-resolution description of its structure. Here, we present a 3D atomic model of OB1 and OB2, bS1's first two N-terminal domains, bound to an elongation-competent 70S ribosome. Our structure reveals that, as previously reported, bS1 is anchored both by a π-stacking to the 30S subunit and via a salt bridge with the Zn2+ pocket of bS1. These contacts are further stabilized by other interactions with additional residues on OB1. Our model also shows a new conformation of OB2, interacting with the Shine-Dalgarno portion of the mRNA. This study confirms that OB1 plays an anchoring role, but also highlights a novel function for OB2, which is directly involved in the modulation and support of mRNA binding and accommodation on the ribosome., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Indoor farming of basil ( Ocimum basilicum L.) under artificial lighting to support year-round produce demand is an area of increasing interest. Literature data indicate that diverse light regimes differently affect downstream metabolic pathways which influence basil growth, development and metabolism. In this study, basil was grown from seedlings to fully developed plants in a microcosm, an innovative device aimed at growing plants indoor as in natural conditions. Specifically, the effects of white (W) and blue-red (BR) light under a photosynthetic photon flux density of 255 μmol m -2 s -1 on plant growth, photochemistry, soluble nutrient concentration and secondary metabolism were investigated. Plants grew taller (41.8 ± 5.0 vs. 28.4 ± 2.5 cm) and produced greater biomass (150.3 ± 24.2/14.7 ± 2.0 g vs. 116.2 ± 28.3/12.3 ± 2.5 g fresh/dry biomass) under W light compared to BR light. The two lighting conditions differently influenced the soluble nutrient concentration and the translocation rate. No photosynthetic stress was observed under the two lighting regimes, but leaves grown under W light displayed higher levels of maximum quantum yield of PSII and electron transport rate. Sharp differences in metabolic patterns under the two lighting regimes were detected with higher concentrations of phenolic compounds under the BR light.

Despite multiple available treatments for bipolar depression (BD), many patients face sub-optimal responses. Transcranial direct current stimulation (tDCS) has been advocated in the management of different conditions, including BD, especially in treatment-resistant cases. The optimal dose and timing of tDCS, the mutual influence with other concurrently administered interventions, long-term efficacy, overall safety, and biological underpinnings nonetheless deserve additional assessment. The present study appraised the existing clinical evidence about tDCS for bipolar depression, delving into the putative biological underpinnings with a special emphasis on cellular and molecular levels, with the ultimate goal of providing a translational perspective on the matter. Two separate systematic reviews across the PubMed database since inception up to August 8 th 2022 were performed, with fourteen clinical and nineteen neurobiological eligible studies. The included clinical studies encompass 207 bipolar depression patients overall and consistently document the efficacy of tDCS, with a reduction in depression scores after treatment ranging from 18% to 92%. The RCT with the largest sample clearly showed a significant superiority of active stimulation over sham. Mild-to-moderate and transient adverse effects are attributed to tDCS across these studies. The review of neurobiological literature indicates that several molecular mechanisms may account for the antidepressant effect of tDCS in BD patients, including the action on calcium homeostasis in glial cells, the enhancement of LTP, the regulation of neurotrophic factors and inflammatory mediators, and the modulation of the expression of plasticity-related genes. To the best of our knowledge, this is the first study on the matter to concurrently provide a synthesis of the clinical evidence and an in-depth appraisal of the putative biological underpinnings, providing consistent support for the efficacy, safety, and tolerability of tDCS., Competing Interests: Declaration of Competing Interest GDU, ET, AB, MP, BDO, GDL, AM, GM, MF, FI have no interest to declare; AdB has received research support from Janssen, Lundbeck, and Otsuka and lecture fees for educational meeting from Chiesi, Lundbeck, Roche, Sunovion, Vitria, Recordati, Angelini and Takeda; he has served on advisory boards for Eli Lilly, Jansen, Lundbeck, Otsuka, Roche, and Takeda, Chiesi, Recordati, Angelini, Vitria., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The arrest of protein synthesis caused when ribosomes stall on an mRNA lacking a stop codon is a deadly risk for all cells. In bacteria, this situation is remedied by the trans-translation quality control system. Trans-translation occurs because of the synergistic action of two main partners, transfer-messenger RNA (tmRNA) and small protein B (SmpB). These act in complex to monitor protein synthesis, intervening when necessary to rescue stalled ribosomes. During this process, incomplete nascent peptides are tagged for destruction, problematic mRNAs are degraded and the previously stalled ribosomes are recycled. In this 'Structural Snapshot' article, we describe the mechanism at the molecular level, a view updated after the most recent structural studies using cryo-electron microscopy., (© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

School engagement in adolescence is often associated with better academic performance at school, but what are the longitudinal associations between school engagement and adult educational and employment status? The current study explored these longitudinal associations using data spanning 40-years of life, from the 1970 British Cohort Study. School engagement at age 16-years was used to predict highest educational level at age 34-years, and socioeconomic status and income at ages 34- and 46-years, controlling for childhood socioeconomic status, cognitive ability, gender, and ethnic minority status, collected at ages 5- or 10-years. The 13,135 individuals in the sample were born in 1970, were mainly White (96%), and were identified at age 5-years as being 48% female. Longitudinal structural equation models revealed that adolescent school engagement had a persistent, positive impact on adult educational and employment outcomes after individual differences were controlled for. The results are interpreted using the perspective that school engagement can channel resources which are important for later educational and occupational success. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The global spread of COVID-19 and the declaration of the pandemic status made by the World Health Organization (WHO) led to the establishment of mass vaccination campaigns. The challenges posed by the request to immunise the entire population necessitated the set-up of new vaccination sites, named Mass Vaccination Centres (MVCs), capable of handling large numbers of patients rapidly and safely. The present study focused on the evolution of MVC performances, in terms of the maximum number of vaccinated patients and primary resource utilisation ratio, while involving statistics belonging to the patient dimension. The research involved the creation of a digital model of the MVC, using the Discrete-Event Simulation (DES) software (FlexSim Healthcare), and consequent what-if analyses. The results were derived from the study of an existing facility, located within a sports centre in the province of Bergamo (Italy) and operating with an advanced MVC organisational model, in compliance with the national anti-SARS-CoV-2 legislation. The research provided additional evidence on innovative MVC organisational models, identifying an optimal MVC configuration. Besides, the obtained results remain relevant for countries where a significant portion of the population has not yet addressed the emergency, either for upcoming vaccination treatments. Furthermore, the methodology adopted in the present article proved to be a valuable resource in the analysis of the healthcare processes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Among the environmental factors, seasonality is the one which most affects the metabolome of a plant. Depending on the harvest season, the plant may have a variable content of certain metabolites and thus may have different biological properties. Foeniculum vulgare is an annual plant whose cultivation creates large amounts of waste rich in bioactive compounds. The present investigation was performed with the aim of determining the amount of biologically active compounds in F. vulgare wastes obtained from varieties of different seasonality. Ten polyphenolic compounds were quantified in the little stems and leaves of Tiziano, Pegaso, and Preludio cultivars by ultra performance liquid chromatography (UPLC) hyphenated to QTRAP mass spectrometry by using the MRM (multiple reaction monitoring) method. The antioxidant activity of hydroalcoholic extracts was then evaluated using TEAC and DPPH spectrophotometric assays, followed by a multivariate statistical analysis to determine the correlation between metabolite expression and antioxidant activity. The Preludio variety, grown in summer, showed a higher content of bioactive compounds, which guarantees it a better antioxidant power; kaempferol 3-O-glucuronide, quercetin 3-O-glucuronide, and quercetin 3-O-glucoside are the polyphenolic compounds that could be mainly responsible for the antioxidant effect of fennel. The PLS chemometric model, which correlated quantitative data obtained by a sensitive and selective LC-ESI-QTrap-MS/MS analysis of antioxidant activity, resulted in a selective tool to detect the compounds responsible for the activity shown by the extracts in chemical tests.

Myrtle liqueur production generates high amounts of by-products that can be employed for the extraction of bioactive compounds. Bio-based, non-toxic and biodegradable solvents (ethyl acetate and 2-methyltetrahydrofuran), and a mechanical extraction were applied to myrtle seeds, by-products of the liqueur production, to extract oils rich in phenolic compounds. The oils obtained were characterized for yield, peroxide value (PV), lipid composition, and total phenolic concentration (TPC). The phenolic profile of the oils, determined by LC-MS, the antioxidant activity, and the oxidative stability were also analyzed. A validated UHPLC-ESI-QTRAP-MS/MS analytical method in multiple reaction monitoring (MRM) mode was applied to quantify myricetin and its main derivatives in myrtle oils. The results pointed out clear differences among extraction methods on myricetin concentration. The oxidative stability of myrtle oils was studied with electron paramagnetic resonance (EPR) spectroscopy highlighting the effect of the extraction method on the oxidation status of the oils and the role of phenolic compounds in the evolution of radical species over time. A principal component analysis applied to LC-MS data highlighted strong differences among phenolic profiles of the oils and highlighted the role of myricetin in the oxidative stability of myrtle oils. Myrtle oil, obtained from the by-products of myrtle liqueur processing industry, extracted with sustainable and green methods might have potential application in food or cosmetic industries.

Scabiosa atropurpurea L. subsp. maritima (L.) Arc. (Caprifoliaceae) is a plant widely distributed in the Mediterranean region and represented by 32 taxa in the flora of Turkey. In the present study, an in-depth phytochemical investigation of S. atropurpurea methanol extract of the whole plant was carried out using a combination of LC-ESI-FT-MS and NMR analysis. This approach allowed the isolation and structural elucidation of 28 compounds: 17 iridoids, 7 flavonoids, and 4 phenolic acids. Among these compounds, three previously unreported iridoids named secologanin-methyl-hemiacetal, atropurpurin A, and atropurpurin B were identified. The methanol extract of S. atropurpurea was assayed for its antioxidant and antihyperglycemic activity, showing a potent α-glucosidase inhibitory activity (IC 50  = 100 μg/mL), higher than that exerted by acarbose (IC 50  = 196 μg/mL), used as the positive control. Thus, the most abundant iridoids were selected to be tested for their antihyperglycemic activity, and molecular docking experiments were carried out to assess the possibility for selected compounds to form complexes with α-glucosidase enzyme active site., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Few longitudinal studies have so far investigated the impact of sustained COVID-19 among people with pre-existing psychiatric disorders. We conducted a prospective study involving people with serious mental illness (n = 114) and healthy controls (n = 41) to assess changes in the Perceived Stress Scale, Generalized Anxiety Disorder Scale, Patient Health Questionnaire, and Specific Psychotic Experiences Questionnaire scores 18 months after the COVID-19 pandemic outset. Subjects underwent interviews with a mental health professional in April 2020 and at the end of the local third wave (October 2021). A significant increase in perceived stress was found in healthy controls, especially females. Psychiatric patients showed a significant worsening of anxiety symptoms compared to baseline records (t = -2.3, p = 0.036). Patients who rejected vaccination had significantly higher paranoia scores compared to those willing to get vaccinated (U = 649.5, z = -2.02, p = 0.04). These findings indicate that COVID-19's sustained emergency may cause enduring consequences on mental health, soliciting further investigations., (© 2022 The Authors. Journal of Community Psychology published by Wiley Periodicals LLC.)

Introduction: The uterine caesarean scar defect, also known as uterine niche or isthmocele, is an irregularity in the anterior uterine wall at the site of a previous cesarean section scar. It is associated with obstetrical complications such as caesarean scar, ectopic pregnancy, uterine rupture, and the placenta accreta spectrum. Women with cesarean scar defects are frequently asymptomatic but may also experience abnormal vaginal bleeding, chronic pelvic pain, and infertility., Methods: This systematic review aims to determine the best hysterotomy closure technique to prevent subsequent development of uterine scar defects. An electronic search in Medline, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov was performed from January 2001 until December 2020 for studies evaluating hysterotomy closure techniques., Results: Our systematic search strategy identified 1,781 titles. Six studies fulfilled inclusion criteria and were included in the final analysis. The results supported the superiority of the double-layer closure over the single-layer closure., Conclusions: Hysterotomy closure with continuous running sutures in two layers represents a suitable option to prevent cesarean scar defect formation. Particularly, the first layer should include the decidua and the second layer should overlap the first., (© 2023 S. Karger AG, Basel.)

Radiation therapy has become the standard of care in the treatment of canine intranasal neoplasia, but because of the poor prognosis associated with stage IV nasal tumours and the proximity of the brain to the irradiation target, few data regarding the treatment of very advanced neoplasms are available. The aim of this pilot study was to evaluate the feasibility, safety and effectiveness of a combined treatment composed of definitive high-dose hypofractionated volumetric modulated arc radiotherapy on tumours with concurrent treatment of regional lymph nodes if positive or as prophylaxis, carboplatin radio-sensitising, and adjuvant metronomic chemotherapy for stage IV canine nasal tumours with intracranial extension. A pilot observational study was conducted in 7 dogs. Magnetic resonance imaging follow-up examinations revealed complete responses in 5 dogs and partial responses in 2. The median overall survival time, evaluated via Kaplan-Meier survival analysis, was 310 days with a 95% confidence interval of 210-400 days, whereas the median progression-free survival was 240 days with a 95% confidence interval of 190-290 days. Despite the proximity of highly sensitive organs at risk, no grade III or IV toxicities were observed, and volumetric modulated arc radiotherapy seemed to be a feasible treatment option for stage IV canine nasal tumours where conformal 3D radiotherapy has proven to give higher doses with severe damage to the surrounding unaffected tissues. Further studies are needed on the role of the sphenoid bone microscopic infiltration and regional lymph node involvement. The absence of severe toxicity could also lead to a dose escalation study and chemotherapy scheme., (Copyright © 2022. Published by Elsevier Inc.)

Parkinson’s disease (PD) patients may experience neuropsychiatric symptoms, including depression, anxiety, sleep disturbances, psychosis, as well as behavioral and cognitive symptoms during all the different stages of the illness. Deep Brain Stimulation (DBS) therapy has proven to be successful in controlling the motor symptoms of PD and its possible correlation with the occurrence or worsening of neuropsychiatric symptoms has been reported. We aimed to assess the neuropsychiatric symptoms of 14 PD patients before and after one year of Subthalamic Nucleus (STN)-DBS and to correlate the possible changes to the lead placement and to the total electrical energy delivered. We assessed PD motor symptoms, depression, anxiety, apathy, impulsivity, and suicidality using clinician- and/or self-administered rating scales and correlated the results to the lead position using the Medtronic SuretuneTM software and to the total electrical energy delivered (TEED). At the 12-month follow-up, the patients showed a significant improvement in PD symptoms on the UPDRS (Unified Parkinson’s disease Rating Scale) (−38.5%; p < 0.001) and in anxiety on the Hamilton Anxiety Rating Scale (HAM-A) (−29%; p = 0.041), with the most significant reduction in the physiological anxiety subscore (−36.26%; p < 0.001). A mild worsening of impulsivity was detected on the Barratt Impulsiveness Scale (BIS-11) (+9%; p = 0.048), with the greatest increase in the attentional impulsiveness subscore (+13.60%; p = 0.050). No statistically significant differences were found for the other scales. No correlation was found between TEED and scales’ scores, while the positioning of the stimulating electrodes in the different portions of the STN was shown to considerably influence the outcome, with more anterior and/or medial lead position negatively influencing psychiatric symptoms.

Uterine smooth muscle tumors of uncertain malignant potential (STUMP) represent a group of rare uterine smooth muscle tumors not diagnosed unequivocally as benign or malignant. To data, diagnostic criteria, malignant potential, surgical management, and follow-up of these neoplasms remain controversial. Considering that STUMP and leiomyoma are not significantly different in terms of clinical presentation and preoperative sonographic characteristics, it might be difficult to distinguish between the two affections prior to pathological confirmation at surgery. All cases should be managed by multidisciplinary tumor teams and patients' follow-up should comprise consultation with a gynecologic oncologist and a close surveillance because of the possibility of recurrence or metastasis. We present the case of a 32-year-old nulliparous woman admitted to our gynecology clinic. She was asymptomatic and only complained an increase in abdominal volume started during the past 6 months. A transabdominal and transvaginal pelvic ultrasound revealed a large heterogeneous tumor mass measuring 190×163 mm, color score 2, expanded in the left iliac fossa, suspected for benign uterine myoma. Subsequent magnetic resonance imaging confirmed a large pelvic-abdominal tumor located near the left posterior-lateral uterine wall with areas of necrosis, suggestive of subserosal leiomyoma with cystic degeneration. The patient underwent a median longitudinal laparotomy for excision of the pelvic mass. The patient was normally discharged five days after surgery in good health conditions. The final histological examination was compatible with STUMP. At present, the patient has had no relapses or metastases and she is undergoing follow-up.

Gliomas are the second-most-common primary brain tumors in dogs. Surgery and radiotherapy are established treatment approaches with similar median survival time, whereas conventional chemotherapy is burdened by severe adverse effects. Spinal and leptomeningeal spread of gliomas have been described following radiotherapy treatment alone. The purpose of this study was to evaluate the outcome for four dogs with primary high-grade gliomas in the forebrain without evidence, at diagnosis, of neoplastic invasion along the spinal cord, that were treated with concomitant chemotherapy (temozolomide) and hypofractionated volumetric-modulated arc radiotherapy (VMAT-RT). Temozolomide was selected for its radiosensitive properties, and radiotherapy dose protocols of 37 Gy in 7 fractions or 42 Gy in 10 fractions were used. After an initial complete or partial response, tumors recurred across the cranial-spinal pathway. Post-mortem macroscopic examinations confirmed swollen spinal cord and hyperemic meningeal sleeve, with nodular lesions on the meningeal surface. Microscopically, infiltration of the spinal cord and meninges by neoplastic cells (with features of oligodendrogliomas) were observed. This work seems to suggest that the entire central nervous system should be investigated in diagnostic examinations of canine gliomas. Dose-escalation trials and/or spinal cord prophylaxis treatment could also be evaluated to prevent tumor progression.

The aim of this study is to investigate the role played by mindfulness in the relationship between cognitive styles and gambling disorders in a sample of female young adults. Participants in this study (125 women; M age  = 18.64 years; SD = 1.7) were recruited in betting or bingo halls. They completed the South Oaks Gambling Screen, the Child and Adolescent Mindfulness Measure, and Sternberg's questionnaire on thinking styles. The results from the mediation analyses revealed that the executive thinking style increases gambling and that the deficit in mindfulness ability mediates this relationship. Theoretical and clinical implications are discussed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease., Methods: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks. The primary end point was the change from baseline to week 52 in the sum of scores on parts I, II, and III of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 236, with higher scores indicating greater impairment). Secondary end points included the dopamine transporter levels in the putamen of the hemisphere ipsilateral to the clinically more affected side of the body, as measured by 123 I-ioflupane single-photon-emission computed tomography (SPECT)., Results: A total of 316 participants were enrolled; 105 were assigned to receive placebo, 105 to receive 1500 mg of prasinezumab, and 106 to receive 4500 mg of prasinezumab. The baseline mean MDS-UPDRS scores were 32.0 in the placebo group, 31.5 in the 1500-mg group, and 30.8 in the 4500-mg group, and mean (±SE) changes from baseline to 52 weeks were 9.4±1.2 in the placebo group, 7.4±1.2 in the 1500-mg group (difference vs. placebo, -2.0; 80% confidence interval [CI], -4.2 to 0.2; P = 0.24), and 8.8±1.2 in the 4500-mg group (difference vs. placebo, -0.6; 80% CI, -2.8 to 1.6; P = 0.72). There was no substantial difference between the active-treatment groups and the placebo group in dopamine transporter levels on SPECT. The results for most clinical secondary end points were similar in the active-treatment groups and the placebo group. Serious adverse events occurred in 6.7% of the participants in the 1500-mg group and in 7.5% of those in the 4500-mg group; infusion reactions occurred in 19.0% and 34.0%, respectively., Conclusions: Prasinezumab therapy had no meaningful effect on global or imaging measures of Parkinson's disease progression as compared with placebo and was associated with infusion reactions. (Funded by F. Hoffmann-La Roche and Prothena Biosciences; PASADENA ClinicalTrials.gov number, NCT03100149.)., (Copyright © 2022 Massachusetts Medical Society.)

Foeniculum vulgare is a perennial aromatic plant whose cultivation produces large amounts of waste rich in bioactive compounds with promising anti-inflammatory activities. Nine selected metabolites were quantified through Ultra Performance Liquid Chromatography (UPLC) hyphenated to QTRAP mass spectrometry by using MRM (multiple reaction monitoring) was performed on four parts of fennel: bulb, stem, little stem, and leaf. Analysis revealed significant differences in the amount of quantified metabolites, suggesting that little stem and leaf are the most valuable parts of the waste. Phenolic acids and glycosylated flavonoids were quantified for their known possible anti-inflammatory activities; in fact, due to this reason their ability to inhibit COX-1 and COX-2 isoforms was evaluated through a fluorometric assay, resulting in specific inhibitors of COX-2 at certain concentrations. In conclusion, as the leaf of fennel may be beneficial to human health, clinical studies should include it in nutraceuticals or functional foods for human consumption.

Depressive disorders are one of the leading causes of disability worldwide. Transcranial direct current stimulation (tDCS) is a safe, simple, non-invasive brain stimulation technique showing considerable effectiveness in improving depressive symptoms. Most studies to date have applied anodal tDCS to the left dorsolateral prefrontal cortex (DLPFC), in line with the hypothesis that depressed patients exhibit relative hypoactivity in the left DLPFC compared to the right. Considering the emerging role of the cerebellum in emotional processes, we aimed to study the effect of combining bilateral cerebellar tDCS with the commonly used bifrontal stimulation in patients with severe depression. This open-label pilot study entailed the simultaneous administration of bilateral cerebellar (anode over the left cerebellum, cathode over the right cerebellum) and bilateral frontal (anode over the left DLPFC, cathode over the right DLPFC) tDCS to patients ( N = 12) with treatment-resistant depression. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory-II (BDI-II) were selected as outcome measures. Electric fields distribution originating from this novel electrode montage was obtained by a computational method applied to a realistic human head model. We observed a 30% reduction of both clinician-rated and self-reported severity of depressive symptoms after only five days (10 sessions) of treatment. Younger age was associated with greater clinical improvement. Adverse events were similar to those of the conventional electrodes montage. The modelling studies demonstrated that the electric fields generated by each pair of electrodes are primarily distributed in the cortical areas under the electrodes. In conclusion, the cerebellum could represent a promising adjunctive target for tDCS interventions in patients with TRD, particularly for younger patients.

Toxins of toxin-antitoxin systems use diverse mechanisms to control bacterial growth. Here, we focus on the deleterious toxin of the atypical tripartite toxin-antitoxin-chaperone (TAC) system of Mycobacterium tuberculosis, whose inhibition requires the concerted action of the antitoxin and its dedicated SecB-like chaperone. We show that the TAC toxin is a bona fide ribonuclease and identify exact cleavage sites in mRNA targets on a transcriptome-wide scale in vivo. mRNA cleavage by the toxin occurs after the second nucleotide of the ribosomal A-site codon during translation, with a strong preference for CCA codons in vivo. Finally, we report the cryo-EM structure of the ribosome-bound TAC toxin in the presence of native M. tuberculosis cspA mRNA, revealing the specific mechanism by which the TAC toxin interacts with the ribosome and the tRNA in the P-site to cleave its mRNA target., (© 2022. The Author(s).)

During the COVID-19 pandemic, an increase in the incidence of psychiatric disorders in the general population and an increase in the severity of symptoms in psychiatric patients have been reported. Anxiety and depression symptoms are the most commonly observed during large-scale dramatic events such as pandemics and wars, especially when these implicate an extended lockdown. The early detection of higher risk clinical and non-clinical individuals would help prevent the new onset and/or deterioration of these symptoms. This in turn would lead to the implementation of public policies aimed at protecting vulnerable populations during these dramatic contingencies, therefore optimising the effectiveness of interventions and saving the resources of national healthcare systems. We used a supervised machine learning method to identify the predictors of the severity of psychiatric symptoms during the Italian lockdown due to the COVID-19 pandemic. Via a case study, we applied this methodology to a small sample of healthy individuals, obsessive-compulsive disorder patients, and adjustment disorder patients. Our preliminary results show that our models were able to predict depression, anxiety, and obsessive-compulsive symptoms during the lockdown with up to 92% accuracy based on demographic and clinical characteristics collected before the pandemic. The presented methodology may be used to predict the psychiatric prognosis of individuals under a large-scale lockdown and thus supporting the related clinical decisions.