Spatially Resolved Investigation of Herbicide-Safener Interaction in Maize (Zea mays L.) by MALDI-Imaging Mass Spectrometry.

Monitoring agrochemical distribution within plant tissues delivers significant insights into the adsorption, distribution, metabolism, and elimination of agrochemicals. Detection and imaging of the safener cyprosulfamide (CSA) and the herbicide thiencarbazone-methyl (TCM) after micro-droplet application on the surface of maize leaves (Zea mays L.) have been achieved using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). The agrochemicals were deposited onto the adaxial surface of maize leaves on growing plants, and their uptake, distribution, and metabolism were investigated at four timepoints (3 h, 24 h, 4 days, and 7 days) to assess the influence of CSA treatment on TCM metabolism. MALDI MSI visualized significant changes for the metabolism of TCM after 24 h. Although TCM metabolism was detected neither in the control without the safener nor in the approach with CSA on the second leaf, the co-application on the same leaf showed significant metabolism of the herbicide by detecting the metabolite N-demethylated TCM. These findings suggest that safener protection against herbicide injury is a rapid process in which CSA and TCM need to be present in the same tissues. This study showcases the use of MALDI MSI to visualize and analyze indirect interactions of two substances in planta.

Perceptions, emotional reactions and needs of adolescent psychiatric inpatients during the COVID-19 pandemic: a qualitative analysis of in-depth interviews.

BACKGROUND: The new coronavirus pandemic (COVID-19) has been accompanied by severe psychological pressure on the entire population. However, little is known about how this pandemic could affect the more vulnerable population with severe mental illness. AIMS: To explore adolescent psychiatric inpatients' perceptions, emotional reactions and needs during the first wave of the COVID-19 pandemic. METHODS: Individual in-depth interviews were conducted with nine psychiatric inpatients aged 12-17 years. Through open-ended questions, interviewers initiated five themes: (a) knowledge about coronavirus pandemic, (b) changes in everyday routine due to the pandemic, (c) adolescents' feelings about the pandemic, (d) adolescents' positive thoughts and behaviors, and (e) how the social environment can help adolescents deal with the pandemic-related situation. A thematic analysis was conducted using line-by-line open coding. RESULTS: Regarding their knowledge of the impact of the current pandemic, almost all adolescents focused on information about the nature of coronavirus and on existing crisis management practices. Almost all patients identified predominantly negative changes due to the quarantine state, including restrictions on both social life and personal freedom as well as excessive contact with family members during home isolation. As far as their emotions were concerned, adolescents did acknowledge anxiety about self-harm and harming their loved ones as well as mood swings within the family nucleus; anxiety was also manifested about the unknown and the management of the pandemic in other countries. Avoidance of thought rumination about the coronavirus and its consequences, positive thinking and looking towards the future were reported as constructive strategies for coping with challenging emotions. Additionally, a sense of belongingness seems to have been playing a pivotal role in the adolescents coping strategies. Trust in the authorities and the community was another quite noteworthy point that emerged during the interviews. Lastly, our findings indicated adolescents' benefit from receiving balanced health messaging coupled with balanced thinking within their social and family environment. CONCLUSIONS: Enhanced comprehension of possible mediating psychological pathways is needed to help clinicians, researchers, and decision-makers to avert the deterioration of mental disorders and overall functioning, as well as additional stress-related disorders.

Toward an accurate estimation of wall shear stress from 4D flow magnetic resonance downstream of a severe stenosis.

PURPOSE: First, to investigate the agreement between velocity, velocity gradient, and Reynolds stress obtained from four-dimensional flow magnetic resonance (4D flow MRI) measurements and direct numerical simulation (DNS). Second, to propose and optimize based on DNS, 2 alternative methods for the accurate estimation of wall shear stress (WSS) when the resolution of the flow measurements is limited. Thirdly, to validate the 2 methods based on 4D flow MRI data. METHODS: In vitro 4D MRI has been conducted in a realistic rigid stenosed aorta model under a constant flow rate of 12 L/min. A DNS of transitional stenotic flow has been performed using the same geometry and boundary conditions. RESULTS: Time-averaged velocity and Reynolds stresses are in good agreement between in vitro 4D MRI data and DNS (errors between 2% and 8% of the reference downsampled data). WSS estimation based on the 2 proposed methods applied to MRI data provide good agreement with DNS for slice-averaged values (maximum error is less than 15% of the mean reference WSS for the first method and 25% for the second method). The performance of both models is not strongly sensitive to spatial resolution up to 1.5 mm voxel size. While the performance of model 1 deteriorates appreciably at low signal-to-noise ratios, model 2 remains robust. CONCLUSIONS: The 2 methods for WSS magnitude give an overall better agreement than the standard approach used in the literature based on direct calculation of the velocity gradient close to the wall (relative error of 84%).

Sleep problems in children and adolescents following traumatic life events.

Rates of childhood trauma exposure are extremely high, with approximately 70% of children and adolescents experiencing at least one traumatic event. Among the most common non-specific consequences of stress and trauma are disruptions of sleep. Sleep problems, such as shorter sleep duration, difficulty falling asleep, frequent awakenings, nightmares, sleepless nights, and early-morning wakefulness appear to have a higher prevalence among children and adolescents following traumatic events. This review will illustrate the role of sleep problems in traumatized children and adolescents, and emphasize the need to consider a wide range of etiological mechanisms for these symptoms. However, the relationship of trauma exposure to sleep problems among children and adolescents needs further investigation in future research. Moreover, in view of the adverse consequences of long-term disrupted sleep on mental health outcomes following trauma, the need to effectively address sleep disturbances in traumatized children and adolescents is crucial.

Mental health promotion and prevention interventions in families with parental depression: A randomized controlled trial.

BACKGROUND: The transgenerational transmission of affective disorders calls for integrating promotion of child development in the services offered to families with parental depression. The main objective of the present research was to examine the effectiveness and differences in the impact of two relevant interventions in Greece. METHODS: Thirty families of depressed patients were randomly assigned to the six-to-eight session Family Talk Intervention group and 32 families were included in the lower intensity parent-only two-to-three session Let's Talk about the Children group. Depressed parents and the eldest of their children were assessed prior to the interventions and 4, 10, and 18 months following baseline assessment. RESULTS: In both groups there were significant improvements in parent's depression, anxiety, perceived social support, parenting and family functioning, as well as improvements in child's depression, anxiety, and child emotional/behavioral problems. Child's prosocial behavior, perceived social support, and health-related quality of life were significantly improved in both groups. All positive effects were evident four months following baseline assessment and could be still documented at 1.5-year follow-up. Mixed linear models showed that family functioning and parenting to a lesser extent were associated with the greatest changes in children's psychosocial outcomes in both interventions.. LIMITATIONS: The lack of data regarding parents that refused to receive the interventions may limit generalizability of results. A further limitation is the lack of a no-intervention control group. CONCLUSIONS: The study offers a preliminary evidence base for integrating preventive interventions for child mental health in routine clinical practice with adult depressed patients.

A Novel Estimation Approach of Pressure Gradient and Haemodynamic Stresses as Indicators of Pathological Aortic Flow Using Subvoxel Modelling.

OBJECTIVE: The flow downstream from aortic stenoses is characterised by the onset of shear-induced turbulence that leads to irreversible pressure losses. These extra losses represent an increased resistance that impacts cardiac efficiency. A novel approach is suggested in this study to accurately evaluate the pressure gradient profile along the aorta centreline using modelling of haemodynamic stress at scales that are smaller than the typical resolution achieved in experiments. METHODS: We use benchmark data obtained from direct numerical simulation (DNS) along with results from in silico and in vitro three-dimensional particle tracking velocimetry (3D-PTV) at three voxel sizes, namely 750  µm, 1 mm and 1.5 mm. A differential equation is derived for the pressure gradient, and the subvoxel-scale (SVS) stresses are closed using the Smagorinsky and a new refined model. Model constants are optimised using DNS and in silico PTV data and validated based on pulsatile in vitro 3D-PTV data and pressure catheter measurements. RESULTS: The Smagorinsky-based model was found to be more accurate for SVS stress estimation but also more sensitive to errors especially at lower resolution, whereas the new model was found to more accurately estimate the projected pressure gradient even for larger voxel size of 1.5 mm albeit at the cost of increased sensitivity at this voxel size. A comparison with other methods in the literature shows that the new approach applied to in vitro PTV measurements estimates the irreversible pressure drop by decreasing the errors by at least 20%. CONCLUSION: Our novel approach based on the modelling of subvoxel stress offers a validated and more accurate way to estimate pressure gradient, irreversible pressure loss and SVS stress. SIGNIFICANCE: We anticipate that the approach may potentially be applied to image-based in vivo, in vitro 4D flow data or in silico data with limited spatial resolution to assess pressure loss and SVS stresses in disturbed aortic blood flow.

What Can Machine Learning Approaches in Genomics Tell Us about the Molecular Basis of Amyotrophic Lateral Sclerosis?

Amyotrophic Lateral Sclerosis (ALS) is the most common late-onset motor neuron disorder, but our current knowledge of the molecular mechanisms and pathways underlying this disease remain elusive. This review (1) systematically identifies machine learning studies aimed at the understanding of the genetic architecture of ALS, (2) outlines the main challenges faced and compares the different approaches that have been used to confront them, and (3) compares the experimental designs and results produced by those approaches and describes their reproducibility in terms of biological results and the performances of the machine learning models. The majority of the collected studies incorporated prior knowledge of ALS into their feature selection approaches, and trained their machine learning models using genomic data combined with other types of mined knowledge including functional associations, protein-protein interactions, disease/tissue-specific information, epigenetic data, and known ALS phenotype-genotype associations. The importance of incorporating gene-gene interactions and cis-regulatory elements into the experimental design of future ALS machine learning studies is highlighted. Lastly, it is suggested that future advances in the genomic and machine learning fields will bring about a better understanding of ALS genetic architecture, and enable improved personalized approaches to this and other devastating and complex diseases.

Safening activity and metabolism of the safener cyprosulfamide in maize and wheat.

BACKGROUND: Safeners extend the application of existing herbicides by selectively enhancing tolerance in large-grained cereal crops. While their activity is linked to enhanced herbicide metabolism, their exact mode of action and reasons for their crop specificity have yet to be determined. In this study, we investigated the selectivity of the recently developed sulfonamide safener cyprosulfamide (CSA) in maize (Zea mays L.) and wheat (Triticum aestivum), focusing on its uptake, distribution and metabolism in the two species. RESULTS: CSA protected maize, but not wheat, from injury by thiencarbazone-methyl (TCM). This correlated with the selective enhanced detoxification of the herbicide in maize. CSA underwent more rapid metabolism in maize than in wheat, with the formation of a specific hydroxylated metabolite correlating with safening. Studies with the nsf1 mutant sweetcorn line showed that the hydroxylation of CSA was partly mediated by the cytochrome P450 CYP81A9. However, primary metabolites of CSA were chemically synthesised and tested for their ability to safen TCM in maize but when tested were inactive as safeners. CONCLUSION: The results of this study suggest that the protection against TCM injury by CSA is linked to enhanced herbicide metabolism. This selective activity is due to the specific recognition of parent CSA in maize but not in wheat. Subsequent rapid oxidative metabolism of CSA led to its inactivation, demonstrating that cytochrome P450s regulate the activity of safeners as well as herbicides. © 2020 Society of Chemical Industry.

Machine Learning Guided Atom Mapping of Metabolic Reactions.

Atom mapping of a chemical reaction is a mapping between the atoms in the reactant molecules and the atoms in the product molecules. It encodes the underlying reaction mechanism and, as such, constitutes essential information in computational studies in drug design. Various techniques have been investigated for the automatic computation of the atom mapping of a chemical reaction, approaching the problem as a graph matching problem. The graph abstraction of the chemical problem, though, eliminates crucial chemical information. There have been efforts for enhancing the graph representation by introducing the bond stabilities as edge weights, as they are estimated based on experimental evidence. Here, we present a fully automated optimization-based approach, named AMLGAM (Automated Machine Learning Guided Atom Mapping), that uses machine learning techniques for the estimation of the bond stabilities based on the chemical environment of each bond. The optimization method finds the reaction mechanism which favors the breakage/formation of the less stable bonds. We evaluated our method on a manually curated data set of 382 chemical reactions and ran our method on a much larger and diverse data set of 7400 chemical reactions. We show that the proposed method improves the accuracy over existing techniques based on results published by earlier studies on a common data set and is capable of handling unbalanced reactions.

The synergy of the refugee crisis and the financial crisis in Greece: Impact on mental health.

BACKGROUND: The current global financial crisis that started in 2008 resulted in a significant decline in global trade, slowing/reversing economic growth worldwide, and a dramatic increase in public sector debt. At the same time, the global migrant/refugee crisis has reached extreme rates, with millions of people being forced to abandon their homes and communities because of war, political violence or related threats. There is a broad consensus about the deleterious consequences of these crises on psychological well-being, depression, anxiety disorders, insomnia, alcohol abuse and suicidal behavior. Although the separate consequences of economic recession and immigration are extensively discussed in previous research, we know very little about the processes through which the intersection of economic crisis and migrant crisis contributes to the vulnerabilities of natives and migrants during these crises. Of particular concern is the status of children, adolescents and their families, who constitute one of the most vulnerable groups in society. AIM: To discuss the contexts that economic and migrant crises shape and suggest possible effects of this intersection on mental health risks, especially among children, adolescents and their families, through reflecting on the recent experience in Greece. METHOD: Review of the literature and critical analysis of the effects of the confluent crises. CONCLUSION: The interactive effects of these two crises need further exploration. Novel and diverse models of psychological understanding need to be developed in order to manage the effects of the confluent crises. The role of mental health professionals is crucial in this respect, offering culturally flexible, accommodating and empathetic approaches, allowing healing and acceptance in the face of adversity.

Stressful life events and psychosocial correlates of pediatric inflammatory bowel disease activity.

AIM: To investigate the association of psychiatric and psychosocial correlates with inflammatory bowel disease (IBD) activity in children and adolescents. METHODS: A total of 85 pediatric IBD patients (in remission or active state of the disease) and their parents completed a series of questionnaires and semi-structured interviews measuring life events, depression, anxiety, family dysfunction, and parent mental health. Differences between the remission and the IBD active group and the association of any significant variable with the disease activity state were examined. RESULTS: Parents of children being in active state of the disease reported more life events (P = 0.005) and stressful life events (P = 0.048) during the past year and more mental health symptoms (P < 0.001), while the children themselves reported higher levels of anxiety symptoms (P = 0.017) compared to the remission group. In the logistic regression multivariate analysis, the only predictor which had a significant positive effect on the probability of the patients being in active state was parent mental health symptoms (OR = 4.8; 95%CI: 1.2-25.8). CONCLUSION: Life events, child anxiety and parent mental health symptoms may be important correlates of pediatric IBD activity and targets of thorough assessment and treatment.

Psychiatric reform in Greece: an overview.

Leros became infamous worldwide in the 1980s because of a scandal in its mental institution, the Leros asylum. The scandal provoked universal outrage and the international pressure triggered the Greek mental health reform. Under the reform projects Leros I and Leros II (1990-1994), numerous interventions took place in the Leros asylum as part of deinstitutionalisation. Following that, the Psychargos programme advanced developments for community-based services. Deinstitutionalisation and development of community mental health services have advanced significantly since the 1980s. However, this reform is still incomplete, given that sectorisation, adequate primary care policies, inter-sectoral coordination and specialised services are under-developed. This problematic situation is further complicated by the severe impact of the current financial crisis.

Psychosocial distress and functioning of Greek youth with cystic fibrosis: a cross-sectional study.

BACKGROUND: To assess psychosocial functioning and distress of children and adolescents with cystic fibrosis compared to healthy controls. METHODS: Thirty-six patients with cystic fibrosis aged 8-18 years (24 boys, mean age ± SD: 11.5 ± 2.6 years) and 31 sex- and age-matched healthy control subjects (18 boys, mean age ± SD: 12 ± 2.5 years) were enrolled in the study. In order to assess the self-esteem, social adjustment, and family functioning of these young people, the Culture-free Self-esteem Inventory, the Social Adjustment Scale-Self-Report, and the Family Assessment Device were administered. Emotional/ behavioral problems were assessed through the Youth Self Report and the Child Behavior Checklist given to both the subjects and their parents. RESULTS: No significant differences were found for self-esteem between the two study groups. Regarding social adjustment, children with cystic fibrosis reported significantly worse friendship and overall adjustment (P < 0.05). Moreover, no difference was found in the levels of family functioning between the two groups. No significant differences between the groups were found in emotional/ behavioral problems from the self-reports. On the contrary, parents of children with cystic fibrosis reported significantly higher levels of withdrawal/ depression, thought problems, and delinquent behavior (P ≤ 0.01) as compared to controls. CONCLUSIONS: Children and adolescents with cystic fibrosis appear to be a psychosocially vulnerable group. A biopsychosocial approach should emphasize the assessment and treatment of the psychosocial distress of these patients alongside multiple somatic treatments.