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Cortical organoids derived from human induced pluripotent stem cells (hiPSCs) represent a powerful in vitro experimental system to investigate human brain development and disease, often inaccessible to direct experimentation. However, despite steady progress in organoid technology, several limitations remain, including high cost and variability, use of hiPSCs derived from tissues harvested invasively, unexplored three-dimensional (3D) structural features and neuronal connectivity. Here, using a cost-effective and reproducible protocol as well as conventional two-dimensional (2D) immunostaining, we show that cortical organoids generated from hiPSCs obtained by reprogramming stem cells from human exfoliated deciduous teeth (SHED) recapitulate key aspects of human corticogenesis, such as polarized organization of neural progenitor zones with the presence of outer radial glial stem cells, and differentiation of superficial- and deep-layer cortical neurons and glial cells. We also show that 3D bioprinting and magnetic resonance imaging of intact cortical organoids are alternative and complementary approaches to unravel critical features of the 3D architecture of organoids. Finally, extracellular electrical recordings in whole organoids showed functional neuronal networks. Together, our findings suggest that SHED-derived cortical organoids constitute an attractive model of human neurodevelopment, and support the notion that a combination of 2D and 3D techniques to analyze organoid structure and function may help improve this promising technology.

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Ruthenium complexes with facially coordinating tripodal phosphine ligands are privileged catalysts for a broad range of (de-)hydrogenation-based transformations. Among these, C-O bond hydrogenolysis holds potential for the depolymerisation of both the biopolymer lignin and epoxy resins applied in wind turbine blades, aircrafts and more. However, this methodology is poorly understood in mechanistic terms. Here, we present a detailed investigation on the triphos-Ru catalysed C-O bond scission on a molecular level. A combination of experimental, spectroscopical and theoretical studies elucidates the reactivity of the ruthenium trimethylenemethane precatalyst, revealing the key roles of ruthenium phenolates in both catalyst activation as well as the catalytic cycle itself. Furthermore, a Ru(0)/Ru(II) oxidative addition into the C-O bond is disclosed, with a triphos-Ru(0) dihydrogen complex as entry point. With the molecular nature of the operating triphos-Ru species and the thermodynamics and kinetics of the catalysis unravelled, improvements of established methods as well as design of related transformations may become possible.

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The effect of electromyographic (EMG) activity on agonist muscles during exercises performed on stable and unstable surfaces remains uncertain. We aimed to review the literature regarding the comparison of the EMG activity of the agonist muscles of exercises performed on stable and unstable surfaces. Eighty-six studies that evaluated the EMG activity of 1783 individuals during exercises for the lower limbs, upper limbs, and core were included. The EMG activities of the pectoralis major (SMD = 0.28 [95% CI 0.09, 0.47]) and triceps brachii muscles (SMD = 0.45 [95% CI 0.25, 0.66]) were significantly increased when the unstable device was added to the exercise. Likewise, the EMG activity of all core muscles showed a significant increase with the unstable surface during the exercises, such as the rectus abdominis (SMD = 0.51 [95% CI 0.37, 0.66]), external oblique (SMD = 0.44 [95% CI 0.28, 0.61]), internal oblique (SMD = 1.04 [95% CI 0.02, 2.07]), erector spinae (SMD = 0.37 [95% CI 0.04, 0.71]), and lumbar multifidus (SMD = 0.35 [95% CI 0.08, 0.61]). However, the lower limb muscles did not show greater EMG activity during the exercise with unstable surfaces compared to the stable surface. In conclusion, unstable conditions increase the EMG activity of some upper limb and core muscles compared to a stable surface.

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Carbon isotope labelling of bioactive molecules is essential for accessing the pharmacokinetic and pharmacodynamic properties of new drug entities. Aryl carboxylic acids represent an important class of structural motifs ubiquitous in pharmaceutically active molecules and are ideal targets for the installation of a radioactive tag employing isotopically labelled CO2. However, direct isotope incorporation via the reported catalytic reductive carboxylation (CRC) of aryl electrophiles relies on excess CO2, which is incompatible with carbon-14 isotope incorporation. Furthermore, the application of some CRC reactions for late-stage carboxylation is limited because of the low tolerance of molecular complexity by the catalysts. Herein, we report the development of a practical and affordable Pd-catalysed electrocarboxylation setup. This approach enables the use of near-stoichiometric 14CO2 generated from the primary carbon-14 source Ba14CO3, facilitating late-stage and single-step carbon-14 labelling of pharmaceuticals and representative precursors. The proposed isotope-labelling protocol holds significant promise for immediate impact on drug development programmes.

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Ascorbic acid (AA) may contribute to restoring hemostatic balance after mental stress (MS) in overweight/obese adults. We aimed to determine the effects of AA administration on hemostatic responses to MS in overweight/obese men. Fourteen overweight/obesity men (27 ± 7 years; BMI: 29.7 ± 2.6 kg m-2) performed the Stroop color-word stress task for 5 min after non-simultaneous infusion of placebo (PL, 0.9% NaCl) and AA (3 g). Blood was collected at baseline, during MS, and 60 min after MS to measure: activated partial thromboplastin time, prothrombin time, and fibrinogen concentration, by coagulometer; platelet-derived microvesicles (PMV, mv/µL), by flow cytometry; nitrite (µM), by chemiluminescence. In PL session, MS led to decreases in PTs (stress, p = 0.03; 60 min, p < 0.001), PT-INR (stress, p < 0.001; 60 min, p < 0.01), aPTTs (60 min, p = 0.03), aPTT ratio (60 min, p = 0.04) and fibrinogen (60 min, p = 0.04), while increased PT activity (60 min, p = 0.01) when compared to baseline. Furthermore, AA increased PTs (60 min, p < 0.001), PT-INR (60 min, p = 0.03) and decreased PT activity (60 min, p < 0.001) and fibrinogen (stress, p = 0.04) when compared to PL. Nitrite was increased in response to stress during AA session (p < 0.001 vs PL). There was no difference in PMV. Ascorbic acid prevented the impaired hemostatic profile and improved nitrite response to stress in the overweight and obese adults.

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BACKGROUND: Shoulder pain affects millions of workers worldwide and is considered one of the leading causes of absenteeism and presenteeism. Therefore, using exercises in the work environment emerges as a strategy to prevent or reduce shoulder pain. OBJECTIVE: The objective of this study was to evaluate the effects of a workplace-based exercise program on shoulder pain and function in fruit workers. METHODS: This was an 8-week parallel two-arm randomized controlled trial. Forty-four fruit workers who reported chronic shoulder pain were randomized to an Experimental Group (EG) or Control Group (CG). The EG was submitted to a program of resistance and stretching exercises for eight weeks, twice a week. The CG received a booklet with muscle stretching and mobility exercises. The primary outcome was shoulder pain intensity; the secondary outcomes were Shoulder Pain and Disability Index (SPADI) and perceived global effect. RESULTS: Both groups showed reductions in pain intensity EG: 4.26 (95% CI 2.78-5.74) and CG: 3.74 (95% CI 1.98-5.50) points. The SPADI results showed an average reduction of 17.76 (CI 95% 3.10-32.43) for the EG and 18.39 (CI 95% 3.66-33.13) for the CG. The mean value of the perceived global effect for the CG was 3.45±2.01, and for the EG, the mean was 4.13±1.24. No differences were observed between groups in any outcome analyzed. CONCLUSION: Both groups showed significant changes in the analyzed outcomes. However, the workplace-based exercise program was not superior to the exercise booklet.

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BACKGROUND: Low back pain is prevalent in workers' health and functional performance. OBJECTIVE: To evaluate the effects of a physical exercise program on low back pain and disability in fruit workers. METHODS: This randomized controlled trial assigned 44 workers (37 ± 9 years) to two groups. The experimental group consisted of 10 men and 12 women with an average age of 38 (± 9) years, and the control group consisted of 8 men and 14 women with an average age of 36 (± 10) years. The experimental group (EG) performed a program of strength and flexibility exercises for eight weeks, twice a week. The control group (CG) received minimal care, with a booklet with guidelines for performing exercises. The primary outcomes included changes in perceived disability and the intensity of pain evaluated by the Rolland-Morris questionnaire and the Numerical Pain Scale, respectively. All outcomes were measured at baseline and after eight weeks of intervention. RESULTS: A significant difference was observed in the within-group analysis, with a mean reduction in pain intensity in the EG and CG of -4.55 (95%CI -7.01 to -2.09) and -3.81 (95%CI 1.72-5.90), respectively. For disability, a reduction of -4.45 (95% CI -8.89 to -0.02) was observed in the EG and of -4.43 (-7.38 to -1.48) in the CG. There were no significant differences in the between-groups analysis. CONCLUSIONS: The exercise program was not superior to using the educational booklet. However, both interventions showed substantial decreases in pain and disability levels.

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The year 2019 brought three such impacts of high socio-environmental proportions in Brazil: the dam collapse in Brumadinho, oil spills on the coast, and fires in the Amazon. We investigated the Brazilian population's perceptions of the country's overall environmental situation, the degree to which Brazilians felt affected by these impacts considering personal and social factors, and the entities they held responsible for these disasters. Through Facebook's social media networks, we disseminated structured online surveys for Brazilian citizens above 18 years. Educational background explained how much the 775 respondents felt affected by the three evaluated events. Age was an explanatory factor for the degree to which the respondents felt affected by the dam collapse, and proximity to the disasters, while income levels were for the dam collapse and the fires in the Amazon. The government, criminal activity, and private companies were considered to be the main responsible for these three impacts. This perception reflects the series of changes in the country's environmental laws and protections that threaten biodiversity and the environment.

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Poly(ethylene terephthalate) polyester represents the most common class of thermoplastic polymers widely used in the textile, bottling, and packaging industries. Terephthalic acid and ethylene glycol, both of petrochemical origin, are polymerized to yield the polyester. However, an earlier report suggests that polymerization of methoxyterephthalic acid with ethylene glycol provides a methoxy-polyester with similar properties. Currently, there are no established biobased synthetic routes toward the methoxyterephthalic acid monomer. Here, we show a viable route to the dicarboxylic acid from various tree species involving three catalytic steps. We demonstrate that sawdust can be converted to valuable aryl nitrile intermediates through hydrogenolysis, followed by an efficient fluorosulfation-catalytic cyanation sequence (>90%) and then converted to methoxyterephthalic acid by hydrolysis and oxidation. A preliminary polymerization result indicates a methoxy-polyester with acceptable thermal properties.

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Over the last two decades, with the advent of continuous flow technologies, continuous processes have emerged as a major area in organic synthesis. In this context, continuous flow processes have been increasing in the preparation of Active Pharmaceutical Ingredients (APIs) and fine chemicals, such as complex synthetic intermediates, agrochemicals, and fragrances. Thus, the development of multi-step protocols has attracted special interest from the academic and industrial chemistry communities. In addition to the beneficial aspects intrinsically associated with continuous processes (e.g., waste reduction, optimal heat transfer, improved safety, and the possibility to work under harsh reaction conditions and with more dangerous reagents), these protocols also allow a rapid increase in molecular complexity. Moreover, in telescoped multi-step processes, isolation and purification steps are generally avoided or, if necessary, carried out in-line, presenting an important economy of time, solvents, reagents, and labor. Last, important synthetic strategies such as photochemical and electrochemical reactions are compatible with flow processes and are delivering relevant advances to the synthetic approaches. In this review, a general overview of the fundamentals of continuous flow processes is presented. Recent examples of multi-step continuous processes for the preparation of fine chemicals, including telescoped and end-to-end processes, are discussed, pointing out the possible advantages and/or limitations of each of these methodologies.

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Fibre-reinforced epoxy composites are well established in regard to load-bearing applications in the aerospace, automotive and wind power industries, owing to their light weight and high durability. These composites are based on thermoset resins embedding glass or carbon fibres1. In lieu of viable recycling strategies, end-of-use composite-based structures such as wind turbine blades are commonly landfilled1-4. Because of the negative environmental impact of plastic waste5,6, the need for circular economies of plastics has become more pressing7,8. However, recycling thermoset plastics is no trivial matter1-4. Here we report a transition-metal-catalysed protocol for recovery of the polymer building block bisphenol A and intact fibres from epoxy composites. A Ru-catalysed, dehydrogenation/bond, cleavage/reduction cascade disconnects the C(alkyl)-O bonds of the most common linkages of the polymer. We showcase the application of this methodology to relevant unmodified amine-cured epoxy resins as well as commercial composites, including the shell of a wind turbine blade. Our results demonstrate that chemical recycling approaches for thermoset epoxy resins and composites are achievable.

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INTRODUÇÃO: Capacidade intrínseca (CI) é um construto que engloba capacidades físicas e mentais para o autocuidado e envelhecimento saudável. A compreensão do papel potencial do treinamento resistido, com e sem instabilidade, para promover o CI precisa ser esclarecida. OBJETIVO: Avaliar o impacto do treinamento de força sobre os níveis de capacidade intrínseca em idosos com queixas cognitivas. MÉTODOS: Idosos com queixas cognitivas (n=67) foram aleatoriamente designados para 12 semanas de TF tradicional (n=23), TF com dispositivos de instabilidade (TFI) (n=22) ou controle (n=22). Ambos os grupos de treinamento realizaram três séries de 10- 15 repetições. O grupo TFI realizou exercícios utilizando dispositivos de instabilidade. O grupo controle recebeu aulas semanais de educação em saúde. Os domínios da CI foram de mobilidade e velocidade da marcha (locomotora), função global e executiva (cognitivo), força de preensão e teste de caminhada de seis minutos (vitalidade), e sintomas depressivos e autoeficácia (psicológicos) por meio de escores-z compostos. Calculamos os níveis globais de CI pela soma de cada pontuação composta. RESULTADOS: Diferença significativa intragrupo nos níveis gerais de CI (∆TFI = +1.69, ∆TF = +1.30) e seus respectivos domínios (Locomoção: ∆TFI = +2.32, ∆TF = +3.21; Cognição: ∆TFI = +2.31; Vitalidade: ∆TFI = +1.23, ∆TF = +1.42; e Psicológico: ∆TFI = -0.65, ∆TF = -0.62). Contudo, não houve diferenças entre os grupos. Análise de sensibilidade mesclando os grupos de treinamento revelou diferença significativa para o domínio locomotor após 12 semanas (+1.97, p=0.045). CONCLUSÃO: Treinamento de força com e sem dispositivos de instabilidade não melhorou os níveis de CI em idosos com queixas cognitivas.

INTRODUCTION: Intrinsic capacity (IC) is a construct that encompasses physical and mental capacities important for self-care and healthy aging. Understanding the potential role of resistance training with and without instability to promote IC needs to be clarified. OBJECTIVE: To assess the impact of resistance training on intrinsic capacity levels in older adults with cognitive complaints. METHODS: Older adults with cognitive complaints (n=67) were randomly assigned to either 12 weeks of traditional RE (n=23), RE with instability devices (REI) (n=22), or control (n=22). Both training groups performed three sets of 10-15 repetitions. REI group performed each exercise using instability devices. The control group received weekly health education classes. IC domains were analyzed using mobility and gait velocity (locomotor), global and executive functioning (cognitive), grip strength and six-minute walking test (vitality), and depressive symptoms and self-efficacy (psychological) through z-composite scores. We computed global levels of IC by the sum of each composite score. RESULTS: A significant within-group difference (improvement) in overall levels of IC (∆REI = +1.69, ∆RE = +1.30) and all their domains (Locomotion: ∆REI = +2.32, ∆RE = +3.21; Cognition: ∆REI = +2.31; Vitality: ∆REI = +1.23, ∆RE = +1.42; and Psychological: ∆REI = -0.65, ∆RE = -0.62). However, no between-group differences were observed at the completion of the trial. Sensitivity analysis merging training groups revealed a between-group difference for the locomotor domain (+1.97, p=0.045). CONCLUSION: Resistance training with and without instability devices did not improve IC levels among older adults with cognitive complaints.

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The main goal was to determine the impact of mental stress (MS) on blood flow regulation in overweight/obese men. Fourteen overweight/obese men (27 ± 7 years; 29.8 ± 2.6 kg/m2 ) participated in two randomized experimental sessions with oral administration of the AT1R blocker Olmesartan (40 mg; AT1RB) or placebo (PL). After 2 h, a 5-min acute MS session (Stroop Color Word Test) was administered. Blood flow was assessed at baseline and during the first 3 min of MS by vascular ultrasound in the brachial artery. Blood was collected before (baseline) and during mental stress (MS) for measurement of nitrite (chemiluminescence) and endothelin-1 (ELISA kit). The AT1R blocker was able to reverse the MS responses observed in the placebo session for retrograde flow (p < 0.01), retrograde SR (p < 0.01) and oscillatory shear index (p = 0.01). Regarding vasoactive substances, no differences were observed in ET-1 (p > 0.05) responses to MS between experimental sessions. However, for nitrite responses, the administration of the AT1R blocker was able to increase circulating levels of NO (p = 0.03) Blockade of AT1R appears to prevent the decrease in endothelial function by reducing low shear stress and maintaining the vasoactive substances balance after MS in overweight/obese men.

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BACKGROUND: Fruitculture workers are exposed to shoulder pain disorders due to long working times in overhead activities. OBJECTIVE: This study aims to analyze the association between the time of physical work and leisure activities over the perception of shoulder pain intensity in fruit growing workers. METHODS: This is a descriptive and correlational cross-sectional study. The sample consisted of 180 fruit-growing workers. Multivariable logistic regression was used, with an estimate of the Odds Ratio (OR) and 95% confidence intervals. The dependent variable: Numeric Pain Rating Scale (NPRS) (0-10 points), was categorized as low and high, with cutoff points of NPRS > 3 and NPRS > 4, and was associated with the independent variables (level of physical activity, personal, labour and psychosocial). RESULTS: Workers which are insufficiently active in leisure time are more likely to report high-intensity shoulder pain, NPRS > 3 (OR: 2.39; p = 0.049) and NPRS > 4 (OR: 2.85; p = 0.036). In addition, working time in overhead activities is a risk factor for high-intensity pain for NPRS > 3 and NPRS > 4 (OR = 1.01; p < 0.001). Underweight and normal-weight workers were less likely to report shoulder pain in NPRS > 3 (OR = 0.35; p = 0.020) and in NPRS > 4 (OR = 0.20; p = 0.001). CONCLUSION: Fruit-growing workers had a high prevalence of severe shoulder pain. In addition, workers who are insufficiently active at leisure, overweight and obese are more likely to report severe pain. It was observed that overhead tasks increase the chances of reporting high-intensity shoulder pain among workers.

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BACKGROUND: Scapular dyskinesis has been associated with shoulder dysfunctions, and changes in electromyographic (EMG) activity have been reported during the execution of some exercises. OBJECTIVE: To compare upper limb muscles EMG of asymptomatic subjects with and without scapular dyskinesis during bench-press and dumbbell fly exercise performed on different surface stability conditions. METHODS: Twenty-eight physically active men were allocated into two groups: Control group (n= 14) and Dyskinesis group (n= 14). The participants performed six repetitions lasting three seconds of the bench press and dumbbell fly exercises with 50% of one-repetition maximum (1RM) on a bench and a Swiss ball. The EMG activity of the pectoralis major, serratus anterior, upper and lower trapezius, anterior deltoid, biceps and triceps muscles were recorded. RESULTS: No differences were found between groups, regardless of exercise or surface type. Inserting the unstable surface in the supine exercise promoted a slight increase in upper trapezius EMG activity for the control [4.32 (95% CI: 1.04 to 7.60)] and dyskinesis [3.30 (95% CI: 0.34 to 6.27)] groups. CONCLUSIONS: There is no difference in upper limb muscle EMG activity between subjects with and without scapular dyskinesis. In addition, inserting unstable surfaces did not modify EMG activity.

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Theoretical calculations, associated with control experiments, were carried out to gain insights into the mechanism and origin of enantioselectivity in the phosphoric-acid-catalyzed dynamic kinetic resolution of azlactones. The results revealed a Münchnone intermediate as the key species involved in the isomerization of azlactone rings. The developed model was successfully employed in the comprehension and prediction of enantioselectivity under diverse of reaction conditions, including alcoholysis and aminolysis protocols.

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The main objective of this study is to update the evidence related to the effectiveness of exercise and ergonomic interventions in the perception of shoulder pain intensity in workers considering the shoulder pain intensity and the minimum clinically important change in the analysis. The bibliographic search was conducted in seven databases (Cochrane, EMBASE, SciELO, PubMed, PEDro, Web of Science and Scopus) from March to April 2019. The study selection included randomized controlled trials (RCTs) involving workers with shoulder pain who underwent physical exercises, ergonomics, and combined interventions. To analyze the RCTs, the intensity of pain was divided into two subgroups < 3 and ≥ 3 (0-10 points scale). A total of 27 RCTs were included in the qualitative synthesis considering the perception scales of shoulder pain intensity and the PEDro scale score of assessment of RCTs quality and risk of bias. Within these, seven RCTs were included in the quantitative synthesis. The overall effectiveness of interventions was calculated using a meta-analysis method, and the associated measurement used as a mean difference. The meta-analysis revealed that exercise interventions in workers with shoulder pain > 3 presented a minimally clincially important difference (MCID), but with no difference in workers with pain < 3. The interventions with exercise in workers with pain ≥ 3 at baseline reported a beneficial effect in reducing shoulder pain intensity, and a MCID. However, there was no significant difference for workers with pain < 3 and the effects of ergonomic interventions are still uncertain to reduce shoulder pain in workers.

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A novel electron-donor-acceptor (EDA) complex-enabled flow photochemical hydrotrifluoromethylation of unsaturated ß-keto esters is described. The developed protocol has an easy experimental procedure and does not require the use of transition-metal-based photocatalysts, allowing the isolation of 14 new compounds in up to 86% yield. Control experiments and computational studies revealed that the reaction proceeds through a Michael-type 1,4-addition of a trifluoromethyl radical, followed by a proton transfer step. Furthermore, the reaction could be scaled up to 1 mmol, and the final product could be employed in the preparation of an isoxazolone and a pyrazolone as trifluoro-substituted heterocycles.

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A novel methodology for the 1,1-dichlorocyclopropanation of dicarbonyl conjugated olefins was described. The developed protocol is simple and uses readily accessible starting materials, allowing the isolation of the desired adducts in moderate to excellent yields (up to 99 %). Furthermore, the reaction tolerated scale up to the gram scale; thus highlighting the synthetic potential of this transformation. Control experiments and DFT studies revealed that the reaction proceeded through a Michael-initiated ring-closure process, in which reaction temperature played a crucial role. Finally, these gem-dichlorocyclopropanes were also employed in the preparation of a trisubstituted naphthyl derivative and a diastereoselective reduction was also demonstrated.

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The theoretical-guided evaluation of the Steglich rearrangement of azlactones and isoxazolones allowed the determination of the reactivity patterns in these heterocycles, including the factors that drive the regioselectivity toward both possible sites. These results allowed the first experimental report on the regioselective Steglich rearrangement of isoxazolones, affording the nitrogen- or carbon-acyloxy adducts.