Identification and validation of N-acetylputrescine in combination with non-canonical clinical features as a Parkinson's disease biomarker panel.

Parkinson's disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group with variable motor and non-motor symptoms with a degree of misdiagnosis. Only 3-25% of sporadic Parkinson's patients present with genetic abnormalities that could represent a risk factor, thus environmental, metabolic, and other unknown causes contribute to the pathogenesis of Parkinson's disease, which highlights the critical need for biomarkers. In the present study, we prospectively collected and analyzed plasma samples from 194 Parkinson's disease patients and 197 age-matched non-diseased controls. N-acetyl putrescine (NAP) in combination with sense of smell (B-SIT), depression/anxiety (HADS), and acting out dreams (RBD1Q) clinical measurements demonstrated combined diagnostic utility. NAP was increased by 28% in Parkinsons disease patients and exhibited an AUC of 0.72 as well as an OR of 4.79. The clinical and NAP panel demonstrated an area under the curve, AUC = 0.9 and an OR of 20.4. The assessed diagnostic panel demonstrates combinatorial utility in diagnosing Parkinson's disease, allowing for an integrated interpretation of disease pathophysiology and highlighting the use of multi-tiered panels in neurological disease diagnosis.

Green Analytical Toxicology procedure for determination of ketamine, its metabolites and analogues in oral fluid samples using dispersive liquid-liquid microextraction (DLLME).

New psychoactive substances (NPS) are often synthesized via small changes in the molecular structure, producing drugs whose effect and potency are not yet fully known. Ketamine is one of the oldest NPS, with therapeutic use in human and veterinary medicine authorized in several countries, being metabolized mainly into norketamine and 6-hydroxy-norketamine. Furthermore, two structural analogues of ketamine have recently been identified, deschloroketamine and 2-fluorodeschloroketamine, marketed as drugs of abuse. To comply with Green Analytical Toxicology (GAT) fundamentals, miniaturized techniques such as dispersive liquid-liquid microextraction (DLLME) were employed to determine toxicants in biological fluids. An analytical method for determining ketamine, its metabolites and its analogues in oral fluid was fully developed and validated by using DLLME and liquid chromatography-tandem mass spectrometry (LC-MS-MS). The extraction parameters were optimized by multivariate analysis, obtaining the best conditions with 200 µL of sample, 100 µL of methanol as dispersive solvent and 50 µL of chloroform as extractor solvent. Linearity was obtained from 10 to 1,000 ng/mL, with limit of detection (LOD) and lower limit of quantification (LLOQ) at 10 ng/mL. Imprecision (% relative standard deviation) and bias (%) were less than 8.2% and 9.5%, respectively. The matrix effect did not exceed 10.6%, and the recovery values varied from 24% to 42%. No matrix interference and good selectivity in the evaluation of 10 different sources of oral fluid and 42 drugs at 500 ng/mL, respectively, were observed. The method was applied in the analysis of 29 authentic oral fluid samples and had its green characteristic evaluated by three different tools: the Green Analytical Procedure Index (GAPI), the Analytical Eco-Scale and the Analytical GREEnness (AGREE) metrics.

Fluoxetine alters rat's milk properties causing impact on offspring's development.

Fluoxetine is an antidepressant used to treat several conditions including postpartum depression. This disease causes cognitive, emotional, behavioral and physical changes, negatively affecting the mother, child and family life. However, fluoxetine is excreted in breast milk, causing short and long-term effects on children who were exposed to the drug during lactation, so studies that seek to uncover the consequences of these effects are needed. Thus, the aim of this study was to evaluate the effects of fluoxetine on the nutritional characteristics of milk and on growth and neurobehavioral development of the offspring on a rat model. Lactating rats were divided into 4 groups: control group and three experimental groups, which were treated with different doses of fluoxetine (1, 10 and 20 mg/kg) during the lactation. Dams body weight and milk properties were measured, as well as offspring's growth and physical and neurobehavioral development. Results showed that the use of fluoxetine during lactation decreased dam's body weight and alters milk's properties, leading to a decrease in offspring's growth until adulthood. Therefore, the use of fluoxetine during lactation needs to be cautiously evaluated, with the benefits to the mothers and the associated risk to the offspring carefully balance.

Germination of Pisum sativum L. Seeds Is Associated with the Alternative Respiratory Pathway.

The alternative oxidase (AOX) is a ubiquinol oxidase with a crucial role in the mitochondrial alternative respiratory pathway, which is associated with various processes in plants. In this study, the activity of AOX in pea seed germination was determined in two pea cultivars, 'Maravilha d'América' (MA) and 'Torta de Quebrar' (TQ), during a germination trial using cytochrome oxidase (COX) and AOX inhibitors [rotenone (RT) and salicylic hydroxamic acid (SHAM), respectively]. Calorespirometry was used to assess respiratory changes during germination. In both cultivars, SHAM had a greater inhibitory effect on germination than RT, demonstrating the involvement of AOX in germination. Although calorespirometry did not provide direct information on the involvement of the alternative pathway in seed germination, this methodology was valuable for distinguishing cultivars. To gain deeper insights into the role of AOX in seed germination, the AOX gene family was characterized, and the gene expression pattern was evaluated. Three PsAOX members were identified-PsAOX1, PsAOX2a and PsAOX2b-and their expression revealed a marked genotype effect. This study emphasizes the importance of AOX in seed germination, contributing to the understanding of the role of the alternative respiratory pathway in plants.

Evaluation of konjac noodle as a microsurgery training model: learning curve analysis.

BACKGROUND: classical models of microsurgical anastomosis training are expensive and have ethical implications. Some alternatives join low cost and easiness to store. However, the translation of knowledge acquired by training in these methods into the traditional ones is not clear. This project aims to assess the feasibility of konjac noodles as a reliable microsurgery-training model. METHODS: 10 neurosurgery residents performed an end-to-end anastomosis in a 2-3mm placenta artery. The anastomoses were evaluated quantitatively, recording time; and qualitatively, applying a validated score (Anastomosis Lapse Index - ALI) by three experienced neurosurgeons and verifying the presence of gross leakage through the infusion of fluorescein. Subsequently, they performed 10 non-consecutive sessions of anastomosis training in the konjac noodle. Eventually, a final anastomosis in the placenta model was performed and the same parameters were scored. RESULTS: we observed a 17min reduction in the mean time to perform the anastomosis in the placenta model after the training in the konjac (p<0.05). There was a non-significant 20% reduction in gross leakage, but the training sessions were not able to consistently improve the ALI score. CONCLUSIONS: we demonstrate a reduction in anastomosis performing time in placental arteries after training sessions in the konjac noodle model, which can be regarded as a feasible low-cost method, particularly useful in centers with surgical microscopes only in the operation room.

Artéria vertebral esquerda anômala ­ relato de caso / Anomalous left vertebral artery ­ case report

Introdução: Os procedimentos cirúrgicos e radiológicos das regiões do tórax e pescoço são frequentes e a identificação precoce de variantes do arco da aorta e especificamente da artéria vertebral ajudam a identificar possíveis obstáculos nesses procedimentos, antes que se tornem um problema. Objetivo: Relatar um caso de variação da artéria vertebral esquerda. Método: Estudo descritivo, retrospectivo de um relato de caso sobre artéria vertebral anômala identificada por meio de uma dissecção de rotina. Resultados: Durante o procedimento se observou que o arco da artéria aorta apresentava um ramo arterial emergindo entre a artéria carótida comum esquerda e a artéria subclávia esquerda. Posteriormente, avançando a dissecção para a região cervical, identificou-se que o ramo variável do arco aórtico se tratava da artéria vertebral esquerda, confirmando seu trajeto pelo forame do processo transverso das vértebras cervicais. Conclusão: Dessa forma, torna-se importante apresentar o presente relato de caso da artéria vertebral anômala, bem como discutir as possíveis implicações cirúrgicas, hemodinâmicas e radiológicas do achado. É fundamental o conhecimento das variações anatômicas da artéria vertebral, as quais, possuem relevância cirúrgica, radiológica e hemodinâmica, já que processos patológicos podem ser observados ou negligenciados por métodos de imagem. Assim, podem-se evitar eventuais lesões iatrogênicas baseadas no conhecimento prévio dessa variação

Introduction: Surgical and radiological procedures of the thorax and neck regions are frequent and early identification of variants of the aortic arch and specifically the vertebral artery help to identify possible obstacles in these procedures, before they become a problem. Objective: To report a case of variation of the left vertebral artery. Methods: Descriptive, retrospective study of a case report on anomalous vertebral artery identified by routine dissection. Results: During the procedure it was observed that the arch of the aortic artery had an arterial branch emerging between the left common carotid artery and the left subclavian artery. Subsequently, advancing the dissection to the cervical region, it was identified that the variable branch of the aortic arch was the left vertebral artery, confirming its path through the foramen of the transverse process of the cervical vertebrae. Conclusion: Thus, it is important to present the present case report of the anomalous vertebral artery, as well as to discuss the possible surgical, hemodynamic and radiological implications of the finding. It is essential to know the anatomical variations of the vertebral artery, which have surgical, radiological and hemodynamic relevance, since pathological processes can be observed or neglected by imaging methods. Thus, one can avoid eventual iatrogenic lesions based on prior knowledge of this variation.

Introducción: Los procedimientos quirúrgicos y radiológicos en las regiones de tórax y cuello son frecuentes y la identificación temprana de variantes del arco aórtico y específicamente de la arteria vertebral ayuda a identificar posibles obstáculos en estos procedimientos, antes de que se conviertan en un problema. Objetivo: Reportar un caso de variación de la arteria vertebral izquierda. Métodos: Estudio descriptivo retrospectivo de un reporte de caso sobre una arteria vertebral anómala identificada a través de una disección de rutina. Resultados: Durante el procedimiento se observó que el arco aórtico presentaba una rama arterial que emergía entre la arteria carótida común izquierda y la arteria subclavia izquierda. Posteriormente, avanzando la disección a la región cervical, se identificó que la rama variable del arco aórtico era la arteria vertebral izquierda, confirmándose su trayecto por el foramen de la apófisis transversa de las vértebras cervicales. Conclusión: Por lo tanto, es importante presentar el presente caso clínico de arteria vertebral anómala, así como discutir las posibles implicaciones quirúrgicas, hemodinámicas y radiológicas del hallazgo. Es fundamental conocer las variaciones anatómicas de la arteria vertebral, las cuales tienen relevancia quirúrgica, radiológica y hemodinámica, ya que los procesos patológicos pueden ser observados o despreciados por métodos de imagen. Así, se pueden evitar posibles lesiones iatrogénicas en base al conocimiento previo de esta variación

Epidemiological model for the construction of scenarios of the dissemination of COVID-19 in Codó-MA / Modelo epidemiológico para construção de cenários da disseminação da COVID-19 em Codó-MA / Modelo epidemiológico para la construcción de escenarios de la diseminación del COVID-19 en Codó-MA

Background and objectives: due to the increase in the number of cases of the new coronavirus in the city of Codó-MA, there was a need to carry out a study on the spread of COVID-19 in the municipality in order to have a better knowledge and understanding of the problem. A study was carried out on the spread of COVID-19 in the city of Codó-MA, comparing the quantitative data on the number of cases in 2020 and 2021 between May and July and using the epidemiological model Susceptible-Infectious-Isolated-Recovered (SIQR). Methods: we collected daily data from the epidemiological bulletins made available by the Municipal Health Department of Codó (SEMUS-Codó), we chose the SIQR compartmental model to carry out the simulations, we assumed hypotheses and estimated the parameters in order to design the scenarios. We simulated scenarios such as social distancing of healthy individuals and social isolation of infected individuals. Results: in early 2020, cases increased more frequently than in early 2021, and approximately 20% of those infected were in social isolation. According to projections, more than 80% of cases of COVID-19 were not accounted for in Codó. In 2021, there was greater underreporting than in 2020, approximately 82% and 85%, respectively. Conclusion: from the results, the authors conclude that the social isolation of those infected is a more efficient method to contain an epidemic than the total blockade of the population and that the high number of underreported cases is because most of these cases are asymptomatic.(AU)

Justificativa e objetivos: devido ao aumento do número de casos do novo coronavírus na cidade de Codó-MA, viu-se a necessidade para fazer um estudo sobre a propagação da COVID-19 no município para a ter melhor conhecimento e entendimento do problema. Foi realizado um estudo sobre a disseminação da COVID-19 na cidade de Codó-MA, sendo comparados os dados quantitativos dos números de casos nos anos de 2020 e 2021 entre os meses de maio e julho e utilizando o modelo epidemiológico Suscetíveis-Infecciosos-Isolados-Recuperados (SIQR). Métodos: coletamos os dados diários dos boletins epidemiológicos disponibilizados pela Secretaria Municipal de Saúde de Codó (SEMUS- Codó), escolhemos o modelo compartimental SIQR para a realização das simulações, supomos hipóteses e estimamos os parâmetros para podermos projetar os cenários. Simulamos cenários, tais como distanciamento social dos indivíduos sadios e isolamento social dos indivíduos infectados. Resultados: no início de 2020, os casos aumentaram com mais frequência do que no início de 2021, e aproximadamente 20% dos infectados estavam em isolamento social. De acordo com as projeções, mais de 80% dos casos de COVID-19 não foram contabilizados em Codó. Em 2021, houve maior subnotificação do que em 2020, aproximadamente 82% e 85%, respectivamente. Conclusão: a partir dos resultados, os autores concluem que o isolamento social dos infectados é um método mais eficiente para conter uma epidemia do que o bloqueio total da população e que o alto número de casos subnotificados são porque a maioria desses casos são assintomáticos.(AU)

Antecedentes y objetivos debido al incremento en el número de casos del nuevo coronavirus en la ciudad de Codó-MA, surgió la necesidad de realizar un estudio sobre la propagación del COVID-19 en el municipio con el fin de tener un mejor conocimiento y comprensión de el problema. Se realizó un estudio sobre la propagación del COVID-19 en la ciudad de Codó-MA, comparando datos cuantitativos del número de casos en 2020 y 2021 entre mayo y julio y utilizando el modelo epidemiológico Susceptible-Infeccioso-Aislado-Recuperado (SIQR). Métodos: recolectamos datos diarios de los boletines epidemiológicos que pone a disposición la Secretaría Municipal de Salud de Codó (SEMUS-Codó), elegimos el modelo compartimental SIQR para realizar las simulaciones, asumimos hipótesis y estimamos los parámetros para poder diseñar los escenarios. Simulamos escenarios como el distanciamiento social de personas sanas y el aislamiento social de personas infectadas. Resultados: a principios de 2020, los casos aumentaron con más frecuencia que a principios de 2021, y aproximadamente el 20% de los infectados se encontraban en aislamiento social. Según proyecciones, en Codó no se contabilizaron más del 80% de los casos de COVID-19. En 2021 hubo mayor subregistro que en 2020, aproximadamente 82% y 85%, respectivamente. Conclusión: de los resultados, los autores concluyen que el aislamiento social de los contagiados es un método más eficiente para contener una epidemia que el bloqueo total de la población y que el alto número de casos subregistrados se debe a que la mayoría de estos casos son asintomáticos.(AU)

Colony Age of Trichoderma azevedoi Alters the Profile of Volatile Organic Compounds and Ability to Suppress Sclerotinia sclerotiorum in Bean Plants.

Common bean (Phaseolus vulgaris L.) is one of the most important crops in human food production. The occurrence of diseases, such as white mold, caused by Sclerotinia sclerotiorum can limit the production of this legume. The use of Trichoderma has become an important strategy in the suppression of this disease. The aim of the present study was to evaluate the effect of volatile organic compounds (VOCs) emitted by Trichoderma azevedoi CEN1241 in five different growth periods on the severity of white mold in common bean. The in vitro assays were carried out in double-plate and split-plate, and the in vivo assays, through the exposure of the mycelia of S. sclerotiorum to the VOCs of T. azevedoi CEN1241 and subsequent inoculation in bean plants. Chemical analysis by gas chromatography coupled to mass spectrometry detected 37 VOCs produced by T. azevedoi CEN1241, covering six major chemical classes. The profile of VOCs produced by T. azevedoi CEN1241 varied according to colony age and was shown to be related to the ability of the biocontrol agent to suppress S. sclerotiorum. T. azevedoi CEN1241 VOCs reduced the size of S. sclerotiorum lesions on bean fragments in vitro and reduced disease severity in a greenhouse. This study demonstrated in a more applied way that the mechanism of antibiosis through the production of volatile compounds exerted by Trichoderma can complement other mechanisms, such as parasitism and competition, thus contributing to a better efficiency in the control of white mold in bean plants.

Evaluation of konjac noodle as a microsurgery training model: learning curve analysis / Avaliação do uso de macarrão japonês para treinamento microcirúrgico: análise objetiva da melhora na performance

ABSTRACT Background: classical models of microsurgical anastomosis training are expensive and have ethical implications. Some alternatives join low cost and easiness to store. However, the translation of knowledge acquired by training in these methods into the traditional ones is not clear. This project aims to assess the feasibility of konjac noodles as a reliable microsurgery-training model. Methods: 10 neurosurgery residents performed an end-to-end anastomosis in a 2-3mm placenta artery. The anastomoses were evaluated quantitatively, recording time; and qualitatively, applying a validated score (Anastomosis Lapse Index - ALI) by three experienced neurosurgeons and verifying the presence of gross leakage through the infusion of fluorescein. Subsequently, they performed 10 non-consecutive sessions of anastomosis training in the konjac noodle. Eventually, a final anastomosis in the placenta model was performed and the same parameters were scored. Results: we observed a 17min reduction in the mean time to perform the anastomosis in the placenta model after the training in the konjac (p<0.05). There was a non-significant 20% reduction in gross leakage, but the training sessions were not able to consistently improve the ALI score. Conclusions: we demonstrate a reduction in anastomosis performing time in placental arteries after training sessions in the konjac noodle model, which can be regarded as a feasible low-cost method, particularly useful in centers with surgical microscopes only in the operation room.

ABSTRACT Introdução: modelos tradicionais de treinamento de anastomose microcirúrgica costumam ter custos elevados e implicações éticas de aquisição e manutenção, buscando-se alternativas que reúnam baixo custo e facilidade de armazenamento. Existem diferentes propostas, porém há poucas evidências de que conhecimentos adquiridos com o treinamento nessas plataformas se traduza em melhora na performance, quando estes são comparados a modelos consagrados. Este projeto objetiva avaliar a viabilidade do macarrão de konjac como modelo confiável de treinamento microcirúrgico. Métodos: 10 residentes de neurocirurgia realizaram uma anastomose término-terminal em artéria placentária humana de 2-3mm. As anastomoses foram avaliadas quantitativamente, registrando-se o tempo de confecção e qualitativamente, aplicando-se um escore validado (Anastomosis Lapse Index - ALI) por neurocirurgiões experientes e verificando-se a presença de vazamento grosseiro através da visualização no modo fluorescente injetando-se fluoresceína. Subsequentemente, realizaram 10 sessões de treinamento não consecutivos de anastomose términoterminal no modelo de konjac. Por fim, uma anastomose final foi realizada no modelo placentário e os mesmo parâmetros reavaliados. Resultados: observamos uma redução de 17 min no tempo médio de confecção da anastomose no modelo de placenta após os treinos no modelo do macarrão (p<0.05). Houve uma redução não significativa de 20% no vazamento grosseiro. As sessões de treino no macarrão não foram capazes de melhorar consistentemente o score ALI. Conclusão: o treinamento em modelo de macarrão konjac é capaz de reduzir o tempo para realização das anastomoses no modelo em placenta humana, mostrando-se alternativa viável de baixo custo e manutenção, útil em serviços que disponham de microscópio apenas no ambiente cirúrgico.

Multiplex CRISPR/Cas9-mediated knockout of the phytoene desaturase gene in Coffea canephora.

Coffea canephora (2n = 2x = 22 chromosomes) is a species with extensive genetic diversity and desirable agronomic traits for coffee breeding programs. However, obtaining a new coffee cultivar through conventional breeding techniques may require more than 30 years of crossing cycles and selection, which hampers the effort of keeping up with market demands and rapidly proposing more resilient to climate change varieties. Although, the application of modern biotechnology tools such as precision genetic engineering technologies may enable a faster cultivar development process. Therefore, we aimed to validate the CRISPR/Cas9 system to generate mutations on a selected genotype of C. canephora, the clone 14. Embryogenic calli and a multiplex binary vector containing two sgRNAs targeting different exons of the CcPDS gene were used. The sgRNAs were under the C. canephora U6 promoter regulation. The target gene encodes phytoene desaturase, an enzyme essential for photosynthesis involved in ß-carotene biosynthesis. Somatic seedlings and embryos with albino, variegated and green phenotypes regenerated after Agrobacterium tumefaciens-mediated genetic transformation were analyzed by verifying the insertion of the Cas9 gene and later by sequencing the sgRNAs target regions in the genome of Robusta modified seedlings. Among them, 77% had the expected mutations, and of which, 50% of them had at least one target with a homozygous mutation. The genotype, temperature of co-cultivation with the bacteria, and light intensity used for subsequent embryo regeneration appeared to strongly influence the successful regeneration of plants with a mutated CcPDS gene in the Coffea genus.

Hypothesis-Agnostic Network-Based Analysis of Real-World Data Suggests Ondansetron is Associated with Lower COVID-19 Any Cause Mortality.

BACKGROUND: The COVID-19 pandemic generated a massive amount of clinical data, which potentially hold yet undiscovered answers related to COVID-19 morbidity, mortality, long-term effects, and therapeutic solutions. OBJECTIVES: The objectives of this study were (1) to identify novel predictors of COVID-19 any cause mortality by employing artificial intelligence analytics on real-world data through a hypothesis-agnostic approach and (2) to determine if these effects are maintained after adjusting for potential confounders and to what degree they are moderated by other variables. METHODS: A Bayesian statistics-based artificial intelligence data analytics tool (bAIcis®) within the Interrogative Biology® platform was used for Bayesian network learning and hypothesis generation to analyze 16,277 PCR+ patients from a database of 279,281 inpatients and outpatients tested for SARS-CoV-2 infection by antigen, antibody, or PCR methods during the first pandemic year in Central Florida. This approach generated Bayesian networks that enabled unbiased identification of significant predictors of any cause mortality for specific COVID-19 patient populations. These findings were further analyzed by logistic regression, regression by least absolute shrinkage and selection operator, and bootstrapping. RESULTS: We found that in the COVID-19 PCR+ patient cohort, early use of the antiemetic agent ondansetron was associated with decreased any cause mortality 30 days post-PCR+ testing in mechanically ventilated patients. CONCLUSIONS: The results demonstrate how a real-world COVID-19-focused data analysis using artificial intelligence can generate unexpected yet valid insights that could possibly support clinical decision making and minimize the future loss of lives and resources.

Development of analytical method for the determination of methylphenidate, the analog ethylphenidate and their metabolite ritalinic acid in oral fluid samples by micro-QuEChERS and liquid chromatography-tandem mass spectrometry.

The aim of this study was to develop a quantitative method for the analysis of methylphenidate, the analog ethylphenidate and their metabolite ritalinic acid in oral fluid, using micro-QuEChERS extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oral fluid samples were collected with Quantisal™ device, extracted by micro-QuEChERS technique and analyzed by LC-MS/MS. The developed method met the validation criteria of Academy Standards Board (ASB) Standard Practices for Method Validation in Forensic Toxicology (Standard 036, 2019) with limits of detection and quantification of 0.5 ng/mL and calibration curve from 0.5 to 50 ng/mL. Within-run imprecision was greater than 18.7% while between-run imprecision was greater than 17.0 % for all analytes. Bias did not vary more than 7.7 %. No evidence of carryover was found. Stability studies presented satisfactory results for 24 h on autosampler (10 °C), after 3 cycles of freeze/thaw, 7 days on freezer (-20 °C) and until 7 days on refrigerator (4 °C) for methylphenidate. The validated method was further successfully applied to the analysis of 5 authentic oral fluid samples collected from volunteers at parties and music festivals from different cities in Brazil. Four samples had positive results for methylphenidate and ritalinic acid, and only one sample was positive for methylphenidate. Ethylphenidate was not detected in the samples. The method showed acceptable analytical performance and is environmentally friendly, requiring reduced use of solvents and reagents, with potential to be applied to clinical and forensic analyses.

Closed doors: Predictors of stress, anxiety, depression, and PTSD during the onset of COVID-19 pandemic in Brazil.

BACKGROUND: The rise in mental health problems in the population directly or indirectly because of the coronavirus disease 2019 (COVID-19) pandemic is a major concern. The aim of this study was to investigate and compare independent predictors of symptoms of stress, anxiety, depression, and posttraumatic stress disorder (PTSD) in Brazilians one month after the implementation of measures of social distancing. METHODS: This cross-sectional study was performed using a web-based survey. The Depression, Anxiety, and Stress Scale (DASS-21) and PTSD Checklist for DSM-5 (PCL-5) were the outcomes. Data were gathered regarding demographics, social distancing, economic problems, exposure to the news of the pandemic, psychiatric history, sleep disturbances, traumatic situations, and substance use. The Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) was also administered. The predictors of the symptoms were investigated using hierarchical multiple linear regression. RESULTS: Of a sample of 3587 participants, approximately two-thirds considered that their mental health worsened after the beginning of the social restriction measures. The most important predictors of the symptoms investigated were the intensity of the distress related to the news of the pandemic, younger age, current psychiatric diagnosis, trouble sleeping, emotional abuse or violence, and economic problems. CONCLUSIONS: These results confirmed the hypothesis that the pandemic impacted the mental health of the population and indicated that the level of distress related to the news was the most important predictor of psychological suffering.

Plasma Metabolite Signature Classifies Male LRRK2 Parkinson's Disease Patients.

Parkinson's disease (PD) is a progressive neurodegenerative disease, causing loss of motor and nonmotor function. Diagnosis is based on clinical symptoms that do not develop until late in the disease progression, at which point the majority of the patients' dopaminergic neurons are already destroyed. While many PD cases are idiopathic, hereditable genetic risks have been identified, including mutations in the gene for LRRK2, a multidomain kinase with roles in autophagy, mitochondrial function, transcription, molecular structural integrity, the endo-lysosomal system, and the immune response. A definitive PD diagnosis can only be made post-mortem, and no noninvasive or blood-based disease biomarkers are currently available. Alterations in metabolites have been identified in PD patients, suggesting that metabolomics may hold promise for PD diagnostic tools. In this study, we sought to identify metabolic markers of PD in plasma. Using a 1H-13C heteronuclear single quantum coherence spectroscopy (HSQC) NMR spectroscopy metabolomics platform coupled with machine learning (ML), we measured plasma metabolites from approximately age/sex-matched PD patients with G2019S LRRK2 mutations and non-PD controls. Based on the differential level of known and unknown metabolites, we were able to build a ML model and develop a Biomarker of Response (BoR) score, which classified male LRRK2 PD patients with 79.7% accuracy, 81.3% sensitivity, and 78.6% specificity. The high accuracy of the BoR score suggests that the metabolomics/ML workflow described here could be further utilized in the development of a confirmatory diagnostic for PD in larger patient cohorts. A diagnostic assay for PD will aid clinicians and their patients to quickly move toward a definitive diagnosis, and ultimately empower future clinical trials and treatment options.

Impact of using cocoa bean shell powder as a substitute for wheat flour on some of chocolate cake properties.

The cocoa bean shell is a residue rich in bioactive compounds and its use as an ingredient in the food industry has been studied. This work had the objective of proposing the elaboration of chocolate cake with substitution of wheat flour by cocoa bean shell powder (CSp). Five formulations with different percentages of CSp were used: 25%, 50%, 75%, 100% and 0% (control). The cakes were evaluated by technological characteristics (volume, texture profile, firmness and colour), antioxidant profile (DPPH, ß-carotene/linoleic acid system, phenolic compounds, anthocyanins and tannins) and sensory tests (TDS and acceptance). The technological characteristics and antioxidant activity of the cakes were influenced by the different concentrations of CSp compared to the control sample. The cakes containing up to 75% CSp presented satisfactory sensory acceptance. Therefore, CSp has been revealed to be a prominent alternative substitute ingredient to be used promisingly in the food industry.

Impact of hemolysis on multi-OMIC pancreatic biomarker discovery to derisk biomarker development in precision medicine studies.

Cancer biomarker discovery is critically dependent on the integrity of biofluid and tissue samples acquired from study participants. Multi-omic profiling of candidate protein, lipid, and metabolite biomarkers is confounded by timing and fasting status of sample collection, participant demographics and treatment exposures of the study population. Contamination by hemoglobin, whether caused by hemolysis during sample preparation or underlying red cell fragility, contributes 0-10 g/L of extraneous protein to plasma, serum, and Buffy coat samples and may interfere with biomarker detection and validation. We analyzed 617 plasma, 701 serum, and 657 buffy coat samples from a 7-year longitudinal multi-omic biomarker discovery program evaluating 400+ participants with or at risk for pancreatic cancer, known as Project Survival. Hemolysis was undetectable in 93.1% of plasma and 95.0% of serum samples, whereas only 37.1% of buffy coat samples were free of contamination by hemoglobin. Regression analysis of multi-omic data demonstrated a statistically significant correlation between hemoglobin concentration and the resulting pattern of analyte detection and concentration. Although hemolysis had the greatest impact on identification and quantitation of the proteome, distinct differentials in metabolomics and lipidomics were also observed and correlated with severity. We conclude that quality control is vital to accurate detection of informative molecular differentials using OMIC technologies and that caution must be exercised to minimize the impact of hemolysis as a factor driving false discovery in large cancer biomarker studies.

Dispersive liquid-liquid microextraction of 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid applied to urine testing.

Aim: THC-COOH is the major metabolite of Δ9-tetrahydrocannabinol commonly tested in urine to determine cannabis intake. In this study, a method based on dispersive liquid-liquid microextraction was developed for testing THC-COOH in urine. Materials & methods: Hydrolyzed urine specimens were extracted via dispersive liquid-liquid microextraction with acetonitrile (disperser solvent) and chloroform (extraction solvent). Derivatization was performed with N,O-Bis(trimethylsilyl)trifluoroacetamide with 1% trichloro(chloromethyl)silane. Analysis was performed by GC-MS/MS. Results: The method showed acceptable linearity (5-500 ng/ml), imprecision (<10.5%) and bias (<4.9%). Limits of detection and quantitation were 1 and 5 ng/ml, respectively. Twenty-four authentic samples were analyzed, with 22 samples being positive for THC-COOH. Conclusion: The proposed method is more environmentally friendly and provided good sensitivity, selectivity and reproducibility.

Tweetable abstract Green analytical toxicology: Dispersive liquid­liquid microextraction applied to the analysis of THC-COOH in urine by GC­MS/MS.

O esporte para o desenvolvimento e a paz nas revistas acadêmicas brasileiras: uma revisão de literatura integrativa / Sport for development and peace in brazilian academic journals: an integrative literature review / El deporte para el desarrollo y la paz en las revistas académicas brasileñas: una revisión de literatura integrativa

Neste artigo, realizamos uma revisão de literatura integrativa através de quatro bases de dados científicas de ampla utilização no meio acadêmico brasileiro, a partir dos descritores: "Esporte e Desenvolvimento Social", "Projeto Social Esportivo" e "Projetos Sociais Esportivos". Encontramos 341 artigos, os quais foram, posteriormente e de acordo com critérios de inclusão/exclusão, reduzidos a 57 trabalhos analisados. Apresentamos aqui resultados referentes às categorias "Campo de atuação", "Ano de publicação", "Revistas" e "Resultados da pesquisa". A metodologia seguiu os passos sugeridos por Whittemore e Knafl (2005): (a) identificação do problema, (b) pesquisa da literatura, (c) avaliação dos dados, (d) análise dos dados e (e) apresentação. Os resultados de nossa pesquisa lidam com variações que consideramos significativas no contexto das categorias eleitas e sugerem interpretações para tais variações. Além disso, por fim, refletimos acerca dos limites de nossa pesquisa e das implicações deste trabalho para investigações futuras. (AU)

In this article, we carry out an integrative literature review in four databases widely used in the Brazilian academic environment, using the descriptors: "Sport and Social Development", "Sport Social Project" and "Sports Social Projects". We found 341 articles, which were, later and according to inclusion/exclusion criteria, reduced to 60 works to be analyzed. Here we present results referring to the categories "Field of action", "Year of publication", "Journals" and "Research results". The methodology followed the steps suggested by Whittemore and Knafl (2005): (a) problem identification, (b) literature search, (c) data evaluation, (d) data analysis and (e) presentation. The results of our research deal with variations that we considered significant in the context of the categories chosen and suggest interpretations for such variations. In addition, finally, we reflect on the limits of our research and the implications of this work for future research. (AU)

En este artículo, realizamos una revisión de literatura integrativa en cuatro bases de datos ampliamente utilizadas en el medio académico brasileño, a partir de los siguientes descriptores: "Deporte y Desarrollo Social", "Proyecto Social Deportivo" y "Proyectos Sociales Deportivos". Encontramos 341 artículos, los cuales fueron, posteriormente y de acuerdo con criterios de inclusión/exclusión, reducidos a 57 trabajos analizados. Presentamos aquí resultados referentes a las categorías "Campo de actuación", "Año de publicación", "Revistas" y "Resultados de la investigación". La metodología siguió los pasos sugeridos por Whittemore y Knafl (2005): (a) identificación del problema, (b) investigación de la literatura, (c) evaluación de los datos, (d) análisis de los datos y (e) presentación. Los resultados de nuestra investigación trabajan con variaciones que consideramos significativas en el contexto de las categorías elegidas y sugieren interpretaciones para tales variaciones. Además, reflexionamos acerca de los límites de nuestra investigación y de las implicaciones de este trabajo para las futuras investigaciones. (AU)

Clinical utility of a serum biomarker panel in distinguishing prostate cancer from benign prostate hyperplasia.

Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which also exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. Herein, we evaluated the utility of FLNA IP-MRM, age, and prostate volume to stratify men with BPH from those with PCa. Diagnostic performance of the biomarker panel was better than PSA alone in discriminating patients with negative biopsy from those with PCa, as well as those who have had multiple prior biopsies (AUC 0.75 and 0.87 compared to AUC of PSA alone 0.55 and 0.57 for patients who have had single compared to multiple negative biopsies, respectively). Of interest, in patients with PCa, the panel demonstrated improved performance than PSA alone in those with Gleason scores of 5-7 (AUC 0.76 vs. 0.56) and Gleason scores of 8-10 (AUC 0.74 vs. 0.47). With Gleason scores (8-10), the negative predictive value of the panel is 0.97, indicating potential to limit false negatives in aggressive cancers. Together, these data demonstrate the ability of the biomarker panel to perform better than PSA alone in men with BPH, thus preventing unnecessary biopsies.