Analysis and imaging of biocidal agrochemicals using ToF-SIMS

ToF-SIMS has been increasingly widely used in recent years to look at biological matrices, in particular for biomedical research, although there is still a lot of development needed to maximise the value of this technique in the life sciences. The main issue for biological matrices is the complexity of the mass spectra and therefore the difficulty to specifically and precisely detect analytes in the biological sample. Here we evaluated the use of ToF-SIMS in the agrochemical field, which remains a largely unexplored area for this technique. We profiled a large number of biocidal active ingredients (herbicides, fungicides, and insecticides); we then selected fludioxonil, a halogenated fungicide, as a model compound for more detailed study, including the effect of co-occurring biomolecules on detection limits. There was a wide range of sensitivity of the ToF-SIMS for the different active ingredient compounds, but fludioxonil was readily detected in real-world samples (wheat seeds coated with a commercial formulation). Fludioxonil did not penetrate the seed to any great depth, but was largely restricted to a layer coating the seed surface. ToF-SIMS has clear potential as a tool for not only detecting biocides in biological samples, but also mapping their distribution

Agile six sigma in healthcare: Case study at santobono pediatric hospital

Healthcare is one of the most complex systems to manage. In recent years, the control of processes and the modelling of public administrations have been considered some of the main areas of interest in management. In particular, one of the most problematic issues is the management of waiting lists and the consequent absenteeism of patients. Patient no-shows imply a loss of time and resources, and in this paper, the strategy of overbooking is analysed as a solution. Here, a real waiting list process is simulated with discrete event simulation (DES) software, and the activities performed by hospital staff are reproduced. The methodology employed combines agile manufacturing and Six Sigma, focusing on a paediatric public hospital pavilion. Different scenarios show that the overbooking strategy is effective in ensuring fairness of access to services. Indeed, all patients respect the times dictated by the waiting list, without “favouritism”, which is guaranteed by the logic of replacement. In a comparison between a real sample of bookings and a simulated sample designed to improve no-shows, no statistically significant difference is found. This model will allow health managers to provide patients with faster service and to better manage their resources. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

The Show Must Go On: A Snapshot of Italian Academic Working Life during Mandatory Work from Home through the Results of a National Survey

During the COVID-19 pandemic, universities worldwide have provided continuity to research and teaching through mandatory work from home. Taking into account the specificities of the Italian academic environment and using the Job Demand-Resource-Recovery model, the present study provides, through an online survey, for the first time a description of the experiences of a large sample of academics (N = 2365) and technical and administrative staff (N = 4086) working in Italian universities. The study analyzes the main differences between genders, roles or work areas, in terms of some job demands, recovery experiences, and outcomes, all important dimensions to achieve goals 3, 4, and 5 of the 2030 Agenda for Sustainable Development. The results support the reflections on gender equality measures in universities and provide a general framework useful for further in-depth analysis and development of measures in order to improve well-being (SDG 3), quality of education (SDG 4), and gender equality (SDG 5)

Combining Thermal Desorption with Selected Ion Flow Tube Mass Spectrometry for Analyses of Breath Volatile Organic Compounds

Supporting Information is available online at: https://pubs.acs.org/doi/10.1021/acs.analchem.3c04286 .An instrument integrating thermal desorption (TD) to selected ion flow tube mass spectrometry (SIFT-MS) is presented, and its application to analyze volatile organic compounds (VOCs) in human breath is demonstrated for the first time. The rationale behind this development is the need to analyze breath samples in large-scale multicenter clinical projects involving thousands of patients recruited in different hospitals. Following adapted guidelines for validating analytical techniques, we developed and validated a targeted analytical method for 21 compounds of diverse chemical class, chosen for their clinical and biological relevance. Validation has been carried out by two independent laboratories, using calibration standards and real breath samples from healthy volunteers. The merging of SIFT-MS and TD integrates the rapid analytical capabilities of SIFT-MS with the capacity to collect breath samples across multiple hospitals. Thanks to these features, the novel instrument has the potential to be easily employed in clinical practice.This project was supported by Royal Society of Chemistry through the Research Fund. This research was also supported by Wellcome Trust, Surgery and Cancer Department, Imperial College London and NIHR London In Vitro Diagnostics Co-operative

A New Academic Quality at Work Tool (AQ@workT) to Assess the Quality of Life at Work in the Italian Academic Context

The present study provides evidence for a valid and reliable tool, the Academic Quality at Work Tool (AQ@workT), to investigate the quality of life at work in academics within the Italian university sector. The AQ@workT was developed by the QoL@Work research team, namely a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The tool is grounded in the job demands-resources model and its psychometric properties were assessed in three studies comprising a wide sample of lecturers, researchers, and professors: a pilot study (N = 120), a calibration study (N = 1084), and a validation study (N = 1481). Reliability and content, construct, and nomological validity were supported, as well as measurement invariance across work role (researchers, associate professors, and full professors) and gender. Evidence from the present study shows that the AQ@workT represents a useful and reliable tool to assist university management to enhance quality of life, to manage work-related stress, and to mitigate the potential for harm to academics, particularly during a pandemic. Future studies, such as longitudinal tests of the AQ@workT, should test predictive validity among the variables in the tool

Factor Structure and Measurement Invariance of the Spanish Burnout Inventory Among Professionals Across 17 Countries and Regions

Studies on the prevalence of burnout in professionals in service organizations who work in direct contact with the clients or users of the organization have concluded that burnout is a serious health disorder that has increased due to the COVID-19 pandemic. A significant advantage of the Spanish Burnout Inventory (SBI) over other instruments is that it provides a broader conceptualization of burnout by including feelings of guilt as a dimension of burnout to explain its development. However, the measurement invariance of the SBI across countries has not been investigated. The purpose of this study was to test the measurement invariance of the SBI among professionals across 17 countries and regions in Europe, Latin America, and Asia, and in different languages. All the countries showed a good fit to the four-factor model, except the Indian sample, which was excluded from the measurement invariance study. Using the alignment method, it was possible to verify the scalar measurement invariance of the four SBI factors across 15 countries and one Spanish region (16 samples). The comparison of estimated latent means indicates that France is the country with the lowest scores on the Enthusiasm factor and the highest scores on the negative factors (Exhaustion, Indolence, and Guilt). In contrast, the Andean countries, Colombia, Peru, and Ecuador, show the highest latent means on the Enthusiasm factor and the lowest means on the negative factors. These results support the validity of the SBI in the countries and regions in Europe and Latin America included in this study

A Mitochondrial Kinase Complex Is Essential to Mediate an ERK1/2-Dependent Phosphorylation of a Key Regulatory Protein in Steroid Biosynthesis

ERK1/2 is known to be involved in hormone-stimulated steroid synthesis, but its exact roles and the underlying mechanisms remain elusive. Both ERK1/2 phosphorylation and steroidogenesis may be triggered by cAMP/cAMP-dependent protein kinase (PKA)-dependent and-independent mechanisms; however, ERK1/2 activation by cAMP results in a maximal steroidogenic rate, whereas canonical activation by epidermal growth factor (EGF) does not. We demonstrate herein by Western blot analysis and confocal studies that temporal mitochondrial ERK1/2 activation is obligatory for PKA-mediated steroidogenesis in the Leydig-transformed MA-10 cell line. PKA activity leads to the phosphorylation of a constitutive mitochondrial MEK1/2 pool with a lower effect in cytosolic MEKs, while EGF allows predominant cytosolic MEK activation and nuclear pERK1/2 localization. These results would explain why PKA favors a more durable ERK1/2 activation in mitochondria than does EGF. By means of ex vivo experiments, we showed that mitochondrial maximal steroidogenesis occurred as a result of the mutual action of steroidogenic acute regulatory (StAR) protein –a key regulatory component in steroid biosynthesis-, active ERK1/2 and PKA. Our results indicate that there is an interaction between mitochondrial StAR and ERK1/2, involving a D domain with sequential basic-hydrophobic motifs similar to ERK substrates. As a result of this binding and only in the presence of cholesterol, ERK1/2 phosphorylates StAR at Ser232. Directed mutagenesis of Ser232 to a non-phosphorylable amino acid such as Ala (StAR S232A) inhibited in vitro StAR phosphorylation by active ERK1/2. Transient transfection of MA-10 cells with StAR S232A markedly reduced the yield of progesterone production. In summary, here we show that StAR is a novel substrate of ERK1/2, and that mitochondrial ERK1/2 is part of a multimeric protein kinase complex that regulates cholesterol transport. The role of MAPKs in mitochondrial function is underlined

Capacidade Funcional: estudo prospectivo em idosos residentes em uma instituição de longa permanência

The Short Physical Performance Balance - SPPB has been largely used in researches related to the effects of aging, as a practical and efficient instrument to estimate the physical conditions and screening of elderly people with future disability risk. The SPPB estimates the performance of lower limbs in three aspects: muscle strength, gait and balance, all recognized as fundamental to achieve good quality of life, being accepted as universal indicators to value the health conditions of the elderly. PURPOSE: Analyze the SPPB effectiveness to detect functional capacity changes among institutionalized elderly patients and how it is influenced by cognitive, clinical and global functional variables. METHODS: a prospective study, involving 30 residents of a philanthropic long-term care facility in São Paulo (17 women and 13 men), with ages above 60 years old (43% older than 80 years old) and an average of seven years of residence. After 18 months, these old people were reevaluated and data were compared. RESULTS: Considering the evaluated elderly who had good performance (17%), all of them showed up loss of strength during the research. It was observed that there was an improvement of 16% and 1%, respectively, in the balance and in gait, respectively. There was one or more falls in 47% of them. Comparing the Katz's Index of Independency in the Daily Living, the SPPB was more sensitive to the functional decline, indicating 39%, as compared to the 14% of the loss indentified by Katz. CONCLUSIONS: the data confirm the previous studies, which indicate the functional capacity decline of institutionalized elderly and for the SPPB applicability in the routine of functional attendance of this population.A Short Physical Performance Balance - SPPB vem sendo utilizada largamente em pesquisas sobre o envelhecimento, como instrumento prático e eficaz na avaliação do desempenho físico e rastreamento de idosos com riscos futuros de incapacidades. Ela avalia o desempenho de membros inferiores em três aspectos: força muscular, marcha e equilíbrio, reconhecidos como componentes fundamentais para a qualidade de vida, sendo aceitos como indicadores universais do estado de saúde em idosos. OBJETIVO: Analisar a eficácia da SPPB em detectar alterações na capacidade funcional do idoso institucionalizado e como esta é influenciada pelas variáveis cognitivas, clínicas e funcionais globais. METODOLOGIA: estudo prospectivo do qual participaram 30 residentes de uma instituição de longa permanência, filantrópica, em São Paulo (17 mulheres e 13 homens), com idades acima de 60 anos ou mais (43% maiores de 80 anos) e média de sete anos de residência. Após 18 meses, estes idosos foram reavaliados e os dados, comparados. RESULTADOS: Dos idosos avaliados que obtiveram bom desempenho (17%), todos apresentaram perda de força ao longo do seguimento. Quanto ao equilíbrio e marcha, notou-se melhora de 16% e 1%, respectivamente. Apresentaram uma ou mais quedas, 47% dos sujeitos. Quando comparada com o Índex de Independência nas Atividades de Vida Diária de Katz, a SPPB se mostrou mais sensível em relação ao declínio funcional, apontando 39% em comparação aos 14% de perda identificada pelo Katz. CONCLUSÃO: os dados corroboram estudos anteriores, que apontam para o declínio da capacidade funcional de idosos institucionalizados e para a aplicabilidade da SPPB na rotina de acompanhamento funcional dessa população.Universidade Federal de São Paulo (UNIFESP) Curso de Especialização em Reabilitação GerontológicaLar Escola São Francisco Centro de Reabilitação Setor de Reabilitação GerontológicaUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasUNIFESP, Curso de Especialização em Reabilitação GerontológicaSciEL

Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice