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The contribution of Eucalyptus globulus plantations to timber production for pulp, paper and energy production may be hampered by climate change. It is expected that Eucalyptus productivity may be affected through drought stress and changes to both pathogen distribution/pathogenicity and host–pathogen interactions. The impact of the fungal pathogen Neofusicoccum kwambonambiense on E. globulus, causing cankers and dieback, is well known but the impact of drought on disease development is still understudied. Our aim was to study the effect of drought on N. kwambonambiense infection by inoculating E. globulus plants under well‐watered conditions or with water limitation. Non‐infected plants for both water regimes were also analysed. Morphophysiological, biochemical and hormonal parameters were assessed 65 days post‐inoculation. Inoculation under conditions of water stress decreased water potential and photosynthetic efficiency and increased abscisic acid, jasmonic acid and lipid peroxidation. Water‐stressed infected plants also showed higher fungal colonization and external lesion length in comparison with well‐watered inoculated plants. Our results indicate that drought increased E. globulus predisposition to N. kwambonambiense infection and may also have promoted a change in the lifestyle of the fungus. Identifying host–pathogen interaction responses under different stress conditions is necessary to provide knowledge for decision‐making in the management of forest systems in general and of Eucalyptus production in particular. [ABSTRACT FROM AUTHOR]

Obesity over‐activates the classical arm of the renin‐angiotensin system (RAS), impairing skeletal muscle remodeling. We aimed to compare the effect of exercise training and enalapril, an angiotensin‐converting enzyme inhibitor, on RAS modulation in the skeletal muscle of obese animals. Thus, we divided C57BL/6 mice into two groups: standard chow (SC) and high‐fat (HF) diet for 16 weeks. At the eighth week, the HF‐fed animals were divided into four subgroups—sedentary (HF), treated with enalapril (HF‐E), exercise training protocol (HF‐T), and combined interventions (HF‐ET). After 8 weeks of treatment, we evaluated body mass and index (BMI), body composition, exercise capacity, muscle morphology, and skeletal muscle molecular markers. All interventions resulted in lower BMI and attenuation of overactivation in the classical arm, while favoring the B2R in the bradykinin receptors profile. This was associated with reduced apoptosis markers in obese skeletal muscles. The HF‐T group showed an increase in muscle mass and expression of biosynthesis markers and a reduction in expression of degradation markers and muscle fiber atrophy due to obesity. These findings suggest that the combination intervention did not have a synergistic effect against obesity‐induced muscle remodeling. Additionally, the use of enalapril impaired muscle's physiological adaptations to exercise training. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has been associated with lifestyle changes, reduced access to care and potential impacts on medication self-management. Our main objectives are to evaluate the impact of the pandemic on patient adherence and access to care and long-term medications and determine its association with sociodemographic and clinical factors. This study is part of the Specchio-COVID-19 longitudinal cohort study in Geneva, Switzerland, conducted through an online questionnaire. Among the 982 participants (median age: 56; 61% female), 827 took long-term medications. There were 76 reported changes in medication dosages, of which 24 (31%) were without a physician's recommendation, and 51 delays in initiation or premature medication interruptions, of which 24 (47%) were without a physician's recommendation. Only 1% (9/827) of participants faced medication access issues. Participants taking a respiratory medication had a four-times greater odds of reporting more regular medication (OR = 4.27; CI 95%: 2.11–8.63) intake, whereas each year increase in age was significantly associated with 6% fewer relative risks of discontinuation (OR = 0.94; CI 95%: 0.91–0.97) and 3% fewer relative risks of changes in medication dosage (OR = 0.97; CI 95%: 0.95–1.00). Despite the limited impact of the pandemic on adherence and access to medications, our results emphasize the need for understanding patient challenges when self-managing their long-term medication, notably during public health crises. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship between vitamin D status and hypertriglyceridemic‐waist (HTW) phenotype and cardiometabolic markers in individuals with type 2 diabetes mellitus (T2DM) living in regions with high solar incidence (10° south). Methods: An observational, cross‐sectional study, with 122 individuals with T2DM, of both sexes, aged between 19 and 59 years, residing in Sergipe/Brazil. Measurements included serum 25‐hydroxyvitamin D (25[OH]D), glucose, insulin, total cholesterol, LDL‐c, HDL‐c, triacylglycerols, blood pressure, body mass index, %body fat, and waist circumference. Participants were classified by the presence or absence of the HTW phenotype, according to increased waist circumference and triacylglycerols concentrations. Logistic and linear regression models were applied to verify the association among the concentration of 25(OH)D, HTW phenotype, and lipid profile variables. Results: Triacylglycerols concentrations (p =.013) and %body fat (p =.011) were higher in women with serum 25(OH)D insufficient/deficient than in those with adequate 25(OH)D levels. Individuals with serum 25(OH)D insufficiency/deficiency were 2.595 times more likely to present the HTW phenotype than those with adequate 25(OH)D levels (p =.021). Additionally, a negative association was observed between the concentration of 25(OH)D and total cholesterol (Beta = −0.204, p =.049). Conclusion: Insufficiency/deficiency of serum 25(OH)D in individuals with T2DM increases the chances of developing the HTW phenotype. [ABSTRACT FROM AUTHOR]

The aim of this work was a complete thermodynamic study on the partitioning of Remazol Yellow l, Remazol Brilliant Blue, and Remazol Red dyes in isopropyl alcohol + sodium phosphate + water aqueous two‐phase systems at different temperatures. The free energy change of transfer, enthalpy change of transfer, and entropy change of transfer were evaluated. The effects of the structure of the dye, tie line length, and temperature on the partitioning were studied. The results indicate that these aqueous two‐phase systems have high capacity to extract the dyes from aqueous matrices to the organic phase of these systems and are an interesting alternative to effluent treatment process. [ABSTRACT FROM AUTHOR]

The C–S cross‐coupling reaction is a very efficient and powerful tool for constructing C–S bonds. Despite the well‐reported C–S cross‐coupling protocols using aryl halides, this reaction using sp2‐hybridized nonaromatic halides is still challenging. Herein, we report light‐assisted C–S cross‐coupling between thiols and 5‐chlorobenzofurazan under blue LED irradiation. We used a new nickel catalyst to synthesize 11 unpublished compounds. Furthermore, we assessed the mechanism and the influence of light irradiation on this reaction and proposed a plausible mechanism that is mediated by the excited state of the nickel catalyst promoted by irradiation with blue light and the C–S coupling product formed. Notably, C–S cross‐coupling under light irradiation was performed for the first time using a nickel catalyst in the absence of an external photocatalyst. We demonstrated that because nickel has a low energy barrier for oxidative addition, this protocol proceeded efficiently using chlorine as a leaving group, and the excited state of the nickel catalyst promoted reductive elimination with a lower energy barrier. It is important to mention that the procedure was tolerated by many functional groups within the thiol, affording a greater than 99% yield after reacting for 6 h. [ABSTRACT FROM AUTHOR]

Exercise training improves physical capacity in patients with heart failure with reduced ejection fraction (HFrEF), but the mechanisms involved in this response is not fully understood. The aim of this study was to determine if physical capacity increase in patients HFrEF is associated with muscle sympathetic nerve activity (MSNA) reduction and muscle blood flow (MBF) increase. The study included 124 patients from a 17-year database, divided according to exercise training status: 1) exercise-trained (ET, n = 83) and 2) untrained (UNT, n = 41). MSNA and MBF were obtained using microneurography and venous occlusion plethysmography, respectively. Physical capacity was evaluated by cardiopulmonary exercise test. Moderate aerobic exercise was performed 3 times/wk. for 4 months. Exercise training increased peak oxygen consumption (V̇O 2 , 16.1 ± 0.4 vs 18.9 ± 0.5 mL·kg−1·min−1, P < 0.001), LVEF (28 ± 1 vs 30 ± 1%, P = 0.027), MBF (1.57 ± 0.06 vs 2.05 ± 0.09 mL.min−1.100 ml−1, P < 0.001) and muscle vascular conductance (MVC, 1.82 ± 0.07 vs 2.45 ± 0.11 units, P < 0.001). Exercise training significantly decreased MSNA (45 ± 1 vs 32 ± 1 bursts/min, P < 0.001). The logistic regression analyses showed that MSNA [(OR) 0.921, 95% CI 0.883–0.962, P < 0.001] was independently associated with peak V̇O 2. The increase in physical capacity provoked by aerobic exercise in patients with HFrEF is associated with the improvement in MSNA. • There is a link between physical capacity and muscle sympathetic nerve activity. • Physical capacity depends on sympathetic-mediated skeletal myopathy amelioration. • The muscle sympathetic nerve activity reduction may contribute to the improvement in prognosis in patients with heart failure. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects million women worldwide, presenting a complex pathophysiology that has not been fully elucidated yet. Recently, it has been suggested that PCOS triggers the endoplasmic reticulum (ER) stress, thus being associated with unfolded protein response (UPR) activation. Indeed, the UPR response has been associated with several pathological conditions, including in the reproductive system. Several studies demonstrated that ovarian UPR markers are upregulated in PCOS, being associated with worst ovarian outcomes, and this was ameliorated by ER stress inhibition. In this review, we aim to summarize the main findings from previous studies covering this topic, in an attempt to clarify the potential role of ER stress and the UPR response in the pathophysiology of PCOS. [ABSTRACT FROM AUTHOR]

Purpose - To analyze the possible association between non-financial risk disclosure and the (in) existence of reputation in the most prominent Brazilian publicly traded companies considering the legitimacy theory. Design/methodology/approach - The sample assembles 118 corporations listed on B3 and 345 reference forms from 2006 to 2018. In the analysis of corporate reputation, the presence or absence on ISE and, or ICO2 from B3 was considered. For non-financial risk disclosure, a factor checklist containing 31 risks was taken, categorized under operational, damage, integrity, and strategic risks, from the analysis of Reference Forms. A tree regression, a multiple correspondence analysis, and a T-test of the difference between means were used for data analysis. Findings - There is scientific evidence that the companies with reputations demonstrate non-financial risk disclosure superior to the others. This behavior is confirmed in the subcategories of integrity and strategic risks. Moreover, risk factors in the subcategory of integrity risks were crucial to non-financial risk disclosure. Originality/value - This research paves the way to deepen the early debate surrounding risk disclosure and corporate reputation, especially regarding the quality of non-financial risk disclosure. [ABSTRACT FROM AUTHOR]

Systemic bacteria such as Xylella fastidiosa can be vertically transmitted by using diseased propagative material during nursery tree production. We tested the hypothesis that X. fastidiosa is not transmitted by symptomless olive tree sprouts. In addition, we investigated the distribution of bacteria in olive plants (different parts of canopy and root system) with initial leaf scorch symptoms and with symptoms spread throughout the canopy. In both studies, the presence of bacteria was tested by quantitative real‐time PCR (qPCR). For the first hypothesis, sprouts from a symptomless olive tree were rooted and checked for X. fastidiosa infection 32 months later. A total of 57.7% (41 of 71) of rooted seedlings were positive for X. fastidiosa (Ct from 24.25 to 31.82) but only one plant had scorched leaves. Regarding the distribution of the bacteria in the diseased plants, results based on qPCR showed that X. fastidiosa was systemically distributed through the olive plant canopy (30% to 77% of sampled tissues, with Ct values from 19.56 to 31.59). Samples from trees showing symptoms of olive quick decline syndrome (OQDS), taken 3 m above the lateral branch with symptoms, were positive for the presence of X. fastidiosa, as was the root system. The results demonstrate that vegetative material from olive plants used for rooting must be carefully selected for the absence of X. fastidiosa. Also, based on the qPCR‐positive results, pruning may have a limited effect on eliminating the bacteria from diseased plants, even from the ones showing few OQDS symptoms. [ABSTRACT FROM AUTHOR]

An efficient and unprecedented S-glycosylation reaction of benzo-2,1,3-thiadiazole at the C-5-position using a Pd-G3 Xantphos palladacycle precatalyst has been described. This methodology showed a high functional group tolerance to the electrophilic partner and can be successfully applied to a variety of β-mono- and di-thiosugar derivatives. A series of thioglycoside derivatives from benzo-2,1,3-thiadiazole were prepared in good to excellent yields under mild and operationally simple reaction conditions. [ABSTRACT FROM AUTHOR]

Trials regarding physical exercise in dermatomyositis (DM) and polymyositis (PM) are heterogeneous. We aimed to summarize and critically analyze the available evidence to support the hypothesis that exercise is safe and improves strength and aerobic capacity. We performed a systematic review of clinical trials regarding physical exercise in dermatomyositis and polymyositis, without time restriction. We included studies from MEDLINE, EMBASE, SciELO, and Web of Science, published in English, Portuguese, or Spanish, and reporting outcomes related to safety, muscle performance, or aerobic capacity. The certainty of evidence was evaluated in accordance with the GRADE methodology. Meta-analysis was carried using pooled standardized mean differences (SMD) with 95% confidence interval as effect measure. We included 19 studies and 298 patients. The certainty of evidence was downgraded due to unbalanced confounding variables. The meta-analysis demonstrated improvements in strength (SMD [95% CI] = 0.61 [0.37–0.85], P <.00001) and aerobic capacity (SMD [95% CI] = 0.82 [0.29–1.34], P =.002), with no difference in creatine phosphokinase levels (SMD [95% CI] = − 0.23 [− 0.5–0.03], P =.08) after the interventions. No exacerbation was reported, and results were favorable in all stages of disease and ages, but might be different in the future with new classification criteria for PM and the inclusion of other idiopathic inflammatory myopathies. Novel approaches such as blood flow restriction training and aquatic plyometric exercises were promising. Physical exercise in DM/PM patients of all ages is probably safe and moderately improves muscle strength and aerobic capacity. [ABSTRACT FROM AUTHOR]

Drug design is an important area of study for pharmaceutical businesses. However, low efficacy, off-target delivery, time consumption, and high cost are challenges and can create barriers that impact this process. Deep Learning models are emerging as a promising solution to perform de novo drug design, i.e., to generate drug-like molecules tailored to specific needs. However, stereochemistry was not explicitly considered in the generated molecules, which is inevitable in targeted-oriented molecules. This paper proposes a framework based on Feedback Generative Adversarial Network (GAN) that includes optimization strategy by incorporating Encoder–Decoder, GAN, and Predictor deep models interconnected with a feedback loop. The Encoder–Decoder converts the string notations of molecules into latent space vectors, effectively creating a new type of molecular representation. At the same time, the GAN can learn and replicate the training data distribution and, therefore, generate new compounds. The feedback loop is designed to incorporate and evaluate the generated molecules according to the multiobjective desired property at every epoch of training to ensure a steady shift of the generated distribution towards the space of the targeted properties. Moreover, to develop a more precise set of molecules, we also incorporate a multiobjective optimization selection technique based on a non-dominated sorting genetic algorithm. The results demonstrate that the proposed framework can generate realistic, novel molecules that span the chemical space. The proposed Encoder–Decoder model correctly reconstructs 99% of the datasets, including stereochemical information. The model's ability to find uncharted regions of the chemical space was successfully shown by optimizing the unbiased GAN to generate molecules with a high binding affinity to the Kappa Opioid and Adenosine A 2 a receptor. Furthermore, the generated compounds exhibit high internal and external diversity levels 0.88 and 0.94, respectively, and uniqueness. [ABSTRACT FROM AUTHOR]

Drug design is an important area of study for pharmaceutical businesses. However, low efficacy, off-target delivery, time consumption, and high cost are challenges and can create barriers that impact this process. Deep Learning models are emerging as a promising solution to perform de novo drug design, i.e., to generate drug-like molecules tailored to specific needs. However, stereochemistry was not explicitly considered in the generated molecules, which is inevitable in targeted-oriented molecules. This paper proposes a framework based on Feedback Generative Adversarial Network (GAN) that includes optimization strategy by incorporating Encoder–Decoder, GAN, and Predictor deep models interconnected with a feedback loop. The Encoder–Decoder converts the string notations of molecules into latent space vectors, effectively creating a new type of molecular representation. At the same time, the GAN can learn and replicate the training data distribution and, therefore, generate new compounds. The feedback loop is designed to incorporate and evaluate the generated molecules according to the multiobjective desired property at every epoch of training to ensure a steady shift of the generated distribution towards the space of the targeted properties. Moreover, to develop a more precise set of molecules, we also incorporate a multiobjective optimization selection technique based on a non-dominated sorting genetic algorithm. The results demonstrate that the proposed framework can generate realistic, novel molecules that span the chemical space. The proposed Encoder–Decoder model correctly reconstructs 99% of the datasets, including stereochemical information. The model's ability to find uncharted regions of the chemical space was successfully shown by optimizing the unbiased GAN to generate molecules with a high binding affinity to the Kappa Opioid and Adenosine A 2 a receptor. Furthermore, the generated compounds exhibit high internal and external diversity levels 0.88 and 0.94, respectively, and uniqueness. [ABSTRACT FROM AUTHOR]

This article describes the motivation, design, and evaluation of the VisVisual toolkit to engage students in learning essential visualization concepts, algorithms, and techniques. The toolkit includes four independent components: 1) VolumeVisual, 2) FlowVisual, 3) GraphVisual, and 4) TreeVisual, covering scalar and vector data visualization in scientific visualization and graph and tree layouts in information visualization. Complementary to the toolkit design is resource development, aiming to help instructors integrate VisVisual into their curriculum. [ABSTRACT FROM AUTHOR]

• Distyly of Rourea chrysomalla is characterized for the first time. • Antisepalous and antipetalous stamens contribute differently to inaccuracy between the morphs. • Lower stigma and anther are more reciprocal among themselves. • Pollen size and shape differ between S-styled and L-styled morph flowers. • Pollen production differs between morphs, but not between the types of anthers in the flowers. Rourea chrysomalla is a rare and endemic plant species from the Brazilian Cerrado, presumably threatened and lacking records within conservation units. In this study, we recorded and characterized, for the first time, the floral and pollen dimorphism, as well as the reciprocity of sexual organs among different morphs of R. chrysomalla. For this purpose, fertile individuals were observed over three years in two natural populations and supplemented by herbarium data. This species is distylous and distinctly exhibits two types of flowers, each characterized by stamens arranged in two whorls of unequal lengths: L-styled and S-styled morphs, both occuring in similar proportions in the two populations. Cross-pollination among anthers of any stamen whorl in L-styled flowers and stigmas in S-styled flowers is more precise in the two morphs, while anthers in S-styled flowers are less reciprocal with the stigmas in L-styled flowers. S-styled flowers exhibit larger pollen grains compared to L-styled flowers, with no differences between the two whorls of stamens. The balanced proportion of floral morphs provides equal opportunities for pollen donation and reception, and reciprocity between morphs is essential for the conservation of R. chrysomalla due to its limited distribution and low population density in the central Brazilian savanna. [ABSTRACT FROM AUTHOR]

Drug design is an important area of study for pharmaceutical businesses. However, low efficacy, off-target delivery, time consumption, and high cost are challenges and can create barriers that impact this process. Deep Learning models are emerging as a promising solution to perform de novo drug design, i.e., to generate drug-like molecules tailored to specific needs. However, stereochemistry was not explicitly considered in the generated molecules, which is inevitable in targeted-oriented molecules. This paper proposes a framework based on Feedback Generative Adversarial Network (GAN) that includes optimization strategy by incorporating Encoder–Decoder, GAN, and Predictor deep models interconnected with a feedback loop. The Encoder–Decoder converts the string notations of molecules into latent space vectors, effectively creating a new type of molecular representation. At the same time, the GAN can learn and replicate the training data distribution and, therefore, generate new compounds. The feedback loop is designed to incorporate and evaluate the generated molecules according to the multiobjective desired property at every epoch of training to ensure a steady shift of the generated distribution towards the space of the targeted properties. Moreover, to develop a more precise set of molecules, we also incorporate a multiobjective optimization selection technique based on a non-dominated sorting genetic algorithm. The results demonstrate that the proposed framework can generate realistic, novel molecules that span the chemical space. The proposed Encoder–Decoder model correctly reconstructs 99% of the datasets, including stereochemical information. The model's ability to find uncharted regions of the chemical space was successfully shown by optimizing the unbiased GAN to generate molecules with a high binding affinity to the Kappa Opioid and Adenosine A 2 a receptor. Furthermore, the generated compounds exhibit high internal and external diversity levels 0.88 and 0.94, respectively, and uniqueness. [ABSTRACT FROM AUTHOR]

Banisteriopsis caapi is used to prepare the psychoactive beverage ayahuasca, and both have therapeutic potential for the treatment of many central nervous system (CNS) conditions. This study aimed to isolate new bioactive compounds from B. caapi extract and evaluate their biological activity, and that of the known β-carboline components of the plant (harmine, harmaline, and tetrahydroharmine), in BV-2 microglial cells, the in vivo activation of which is implicated in the physiopathology of CNS disorders. B. caapi extract was fractionated using semipreparative liquid chromatography (HPLC-DAD) and the exact masses ([M + H]+m/z) of the compounds in the 5 isolated fractions were determined by high-resolution LC-MS/MS: F1 (174.0918 and 233.1289), F2 (353.1722), F3 (304.3001), F4 (188.1081), and F5 (205.0785). Harmine (75.5–302 µM) significantly decreased cell viability after 2 h of treatment and increased the number of necrotic cells and production of reactive oxygen species at equal or lower concentrations after 24 h. F4 did not impact viability but was also cytotoxic after 24 h. Most treatments reduced proinflammatory cytokine production (IL-2, IL-6, IL-17, and/or TNF), especially harmaline and F5 at 2.5 µM and higher concentrations, tetrahydroharmine (9.3 µM and higher), and F5 (10.7 µM and higher). The results suggest that the compounds found in B. caapi extract have anti-inflammatory potential that could be explored for the development of treatments for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The present study evaluated the effect of blue, red, and white light on the expression of four carotenogenic genes (psy, lyc, bkt, and crtr-r); one gene related to nitrogen metabolism (glb- 1), and another gene related to the absorption of blue light (phot). In addition, both promoter and light–oxygen–voltage (LOV) domain from phot gene were analyzed. Haematococcus pluvialis was grown in 7 followed by 5 days, with complete medium and under stress (nitrogen starvation and different light incidence), respectively. The results support the response to light of phot gene by both gene expression and functional response. Additionally, changes in astaxanthin synthesis and macromolecule accumulation were also observed. Blue and red lights were able to over-regulate all genes within 96 h, including the phot gene. Astaxanthin concentration increased under all conditions. Growth under blue light led to a two- and eightfold increase in astaxanthin content in comparison to growth under red light and white light, respectively. The biomass biochemical composition was evaluated on the 5th day of growth under stress, and the highest protein content was measured in the white light growth. Red light led to the highest biomass carbohydrate content. In sum, the biomass composition and productivity of H. pluvialis varied as a function of light color (wavelength), with the highest protein and astaxanthin productivity observed under white and blue lights, respectively, and the highest carbohydrates and chlorophyll productivity under red light. No variations in lipid productivity were observed in any of the treatments. [ABSTRACT FROM AUTHOR]

Rhenium nanoparticles (Re NPs) supported on Norit (activated carbon—C) and graphene (G) were prepared by a solvothermal method under microwave irradiation (MW). The synthesised heterogeneous catalysts were characterised and tested as reduction and oxidation catalysts, highlighting their dual catalytic behaviour. In the first case, they were used, for the first time, to reduce 4-nitrophenol, in aqueous medium, under MW irradiation. Re catalysts were easily recovered by centrifugation and recycled up to six times without significant activity loss. However, the same Re catalysts in MW-assisted oxidation of 1-phenylethanol with no added solvent experienced a significant loss of activity when recycled. The higher activity of the rhenium nanoparticles supported on graphene (Re/G) catalyst in both reactions was assigned to the higher dispersion and smaller particle size of Re NPs when graphene is the support. [ABSTRACT FROM AUTHOR]

The authors examine the impact of countertransference in two clinical cases of transgender patients treated by two cisgender analysts who are accustomed to receiving nonconforming gender patients in France and Brazil. The context is that of contemporary views of transphobic countertransference reactions, specifically the work of Griffin Hansbury, who describes these reactions in terms of "unthinkable anxieties." Like other theorists with expanding notions of countertransference, the authors view transphobia in analysis as an "instrument of research" and consider how taking responsibility for the transference is particularly relevant in respect to clinical cases that also reflect societal changes. Following the authors' case presentations, they identify four different fantasies and countertransferential reactions that sprang from their efforts to be safe analysts or, in other words, analysts concerned about the perpetuation of discrimination, violence, and oppression that may have guided their work. [ABSTRACT FROM AUTHOR]

A new and effective palladium catalyst supported on a magnesium organosilicate for application in the Heck reaction is presented. A group of compounds comprising 22 examples were synthesized in moderate to high yields (up to 99%) within a short time. The palladium supported on magnesium organosilicate catalyst was characterized as an amorphous solid by SEM, containing around 33% of palladium inside the solid, and even with this low quantity of palladium, the catalyst was very efficient in the Heck reaction. Besides, based on the Scherrer equation, the crystallite size of the synthesized palladium nanoparticles was ultrasmall (around 1.3 nm). This strategy is a simple and efficient route for the formation of C–C bonds via the Heck cross-coupling reaction. [ABSTRACT FROM AUTHOR]

The palladium-catalyzed Suzuki–Miyaura cross-coupling reaction is one of the most important and efficient reactions to prepare a variety of organic compounds, including biaryls. Despite the overwhelming number of reports related to this topic, some methodological difficulties persist in terms of catalyst handling, recovery, and reuse, as well as the reaction media. This work reports the rational design of new, efficient, cost-effective, and reusable palladium catalysts supported on synthetic talc for the Suzuki–Miyaura reaction. From the results, key points were identified: both designed catalysts accelerated the reaction in EtOH and an open-flask setup, affording moderate to excellent yields within a short time (e.g., 30 min) even for deactivated aryl halides; the protocol can be applied to a great number of both cross-coupling partners, showing an excellent functional group tolerance; the catalysts can be recovered and reused without significant loss of activity. This protocol was used for the synthesis of a precursor of angiotensin II inhibitors such as valsartan, losartan, irbesartan, and telmisartan. [ABSTRACT FROM AUTHOR]

Data visualization is hard to master because of the inherent complexities that characterize the challenge of facilitating understanding. Competence with data visualization is gaining in recognition as an essential capability and thus fostering the necessary skills is paramount to prepare students for their future professional activity in this field; yet, it is a challenge for educators to design programs that cover all facets. This article presents a framework that profiles the range of different capability "ingredients" which form the recipe of expertise in data visualization, from the point of view of an experienced practitioner. [ABSTRACT FROM AUTHOR]

For the past ten years, psychologists and psychoanalysts in France have been asked whether or not the clinical setting should be presented as a safe space for populations facing specific systemic discriminations, such as LGBTQI+ persons. This discussion illustrates the complex relationship between psychoanalysis and gender studies in France today. An analysis of the context in which the demand for a safe psychoanalyst appears and a discussion on the specificity of the use of language in clinical work bring elements for an answer. [ABSTRACT FROM AUTHOR]

Overactivation of the classical arm of the renin-angiotensin (Ang) system (RAS) occurs during inflammation, oxidative stress and obesity-induced cardiomyopathy. The activation of the protective arm of RAS may act to counterbalance the deleterious effects of the classical RAS. Although aerobic exercise training (AET) shifts the balance of the RAS towards the protective arm, little is known about the molecular adaptations to different volumes of AET. The aim of this study was to evaluate the impact of AET volume on the modulation of RAS, as well as on cardiac biomarkers of oxidative stress and inflammation, in a diet-induced obesity model. Male Wistar rats were fed either control (CON) or high fat (HF) diet for 32 weeks. At week 20, HF group was subdivided into sedentary, low (LEV, 150 min/week) or high (HEV, 300 min/week) exercise volume. After 12 weeks of exercise, body mass gain, systolic blood pressure and heart rate were evaluated, as well as RAS, oxidative stress and inflammation in the heart. Body mass gain, systolic blood pressure and heart rate were higher in HF group when compared with SC group. Both trained groups restored systolic blood pressure and heart rate, but only HEV reduced body mass gain. Regarding the cardiac RAS, the HF group exhibited favoring of the classical arm and both trained groups shifted the balance towards the counterregulatory protective arm. The HF group had higher B1R expression and lower B2R expression than the control group, and B2R expression was reverted in both trained groups. The HF group also presented oxidative stress. The LEV and HEV groups improved the cardiac redox status by reducing Nox 2 and nitrotyrosine expression, but only the LEV group was able to increase the antioxidant defense by increasing Nrf2 signaling. While the HF group presented higher TNF-α, IL-6 and NFκB expression, and lower IL-10 expression, than the SC group, both training protocols improved the inflammatory profile. Although both trained groups improved the deleterious changes related to obesity cardiomyopathy, it is clear that the molecular mechanisms differ between them. Our results suggest that different exercise volumes might reach different molecular targets, and this could be a relevant factor when using exercise to manage obesity. • Obesity increased cardiac inflammation, oxidative stress and ACE/AT1R activation. • 12 weeks of two different exercise volume protocols were tested for its benefits on the heart. • Both training volumes reduced Nox2 expression, nitrosative damage, and inflammation. • Increased Nrf2 signaling was observed with 150 min, but not 300 min of weekly exercise. • Higher exercise volume favored the alternative arm of renin angiotensin system. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN), a senescence‐associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated with age‐dependent hepatosteatosis. Thus, we investigated the role of OPN in the age‐related hepatosteatosis. For this, human serum samples, animal models of aging, and cell lines in which senescence was induced were used. Metabolic fluxes, lipid, and protein concentration were determined. Among individuals with a normal liver, we observed a positive correlation between serum OPN levels and increasing age. This correlation with age, however, was absent in patients with NAFLD. In wild‐type (WT) mice, serum and liver OPN were increased at 10 months old (m) along with liver p53 levels and remained elevated at 20m. Markers of liver senescence increased in association with synthesis and concentration of triglycerides (TG) in 10m OPN‐deficient (KO) hepatocytes when compared to WT hepatocytes. These changes in senescence and lipid metabolism in 10m OPN‐KO mice liver were associated with the decrease of 78 kDa glucose‐regulated protein (GRP78), induction of ER stress, and the increase in fatty acid synthase and CD36 levels. OPN deficiency in senescent cells also diminished GRP78, the accumulation of intracellular TG, and the increase in CD36 levels. In 20m mice, OPN loss led to increased liver fibrosis. Finally, we showed that OPN expression in vitro and in vivo was regulated by p53. In conclusion, OPN deficiency leads to earlier cellular senescence, ER stress, and TG accumulation during aging. The p53‐OPN axis is required to inhibit the onset of age‐related hepatosteatosis. [ABSTRACT FROM AUTHOR]

Functionalization of 2,1,3‐benzothiadiazole (BTD) with thiols at C‐5 position remains low explored. Moreover, the arylthiol‐substitutions at this position are also unexplored and can not be found by a SN2 or SN1 reaction. In this sense, herein we present a new palladium‐catalyzed methodology for a wide variety of unpublished 5‐arylsulfanyl‐benzo‐2,1,3‐thiadiazole derivatives synthesis with moderate to high yields using a low catalytic loading of Pd(L‐Pro)2 as low‐coast, and efficient catalyst in low reaction time. Besides, we concluded that the pKa of thiol species has an important role in this catalysis, mainly in the CMD like catalytic cyclo process, which strongly interferes in the reaction yields. Furthermore, arylsulfanyl‐benzo‐2,1,3‐thiadiazoles derivatives have been assessed (in vitro) as potential acetylcholinesterase inhibitors. [ABSTRACT FROM AUTHOR]

Plants are valuable sources of pharmacologically active substances against many diseases, including cancer. The extracts of Sapindus saponaria L. contain saponins which concentration can be measured and correlated with their pharmacological activity. Numerous studies have been published on the in vitro cytotoxic action of extracts of S. saponaria L. against cell lines of different types of tumors. The saponins of other plants are used as components of adjuvants for vaccines. Our objectives were to evaluate different parts of the plant S. saponaria L., as a source of saponins by measuring the hemolytic activity of aqueous extracts of fruits, seeds and stems and to explore their in vitro antiproliferative potential in the cell line of human prostate cancer PC3. The quantitative determination of saponins in the extracts was carried out using the modified Pape W. technique that measures the hemolytic potential in red blood cells. The concentration of hemoglobin released by lysis of erythrocytes was measured spectrophotometrically. The effect of the extracts, rich in saponins, on the viability of the human tumor line of prostate cancer PC3, was determined by the High Cell Density Test. The concentration of saponins in terms of µg/ml of extract was: 757.0 ± 1.34 in the fruits, reaching the highest values; 173.0 ± 1.11 in seeds and 30.5 ± 0.13 in stems. The extracts of the three sources studied had a marked cytotoxic-antiproliferative effect against the human tumor line PC3. The inhibition of cell proliferation was similar to that shown by the positive control, paclitaxel. Very low concentrations of the extract (0.01 µg/mL) exerted antiproliferative action. It is possible to conclude that fruits, seeds and stems of Sapindus saponaria L. are good sources of saponins and that their extracts can stop the proliferation of the tumor cell line PC3, even at low levels of concentration and hemolytic potential. Analysing together that saponins themselves are important substances as vaccine adjuvants and that they show an antitumor potential, the authors believe that the plant Sapindus saponaria L. has a potential antitumor effect to take into account. [ABSTRACT FROM AUTHOR]

Wolfram Syndrome consists of a neurodegenerative pathology of genetic character, also known by the acronym DIDMOAD that translates the main findings of this disease, Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness. The article report the case of a patient diagnosed clinically with this syndrome in a general ophthalmology out patient clinic. Considering that patients with this genetic alteration have more than one cranial nerve affected by the disease and clinical history without meningitis or other neurological alterations, one has to think about rare alterations, as is the case with this syndrome. From the diagnosis, the WRUS questionnaire was applied in consultation, which all owed the comparation of the patient with concepts obtained internationally available in the literature. [ABSTRACT FROM AUTHOR]

The meiotic recombination checkpoint blocks meiotic cell cycle progression in response to synapsis and/or recombination defects to prevent aberrant chromosome segregation. The evolutionarily conserved budding yeast Pch2TRIP13 AAA+ ATPase participates in this pathway by supporting phosphorylation of the Hop1HORMAD adaptor at T318. In the wild type, Pch2 localizes to synapsed chromosomes and to the unsynapsed rDNA region (nucleolus), excluding Hop1. In contrast, in synaptonemal complex (SC)–defective zip1Δ mutants, which undergo checkpoint activation, Pch2 is detected only on the nucleolus. Alterations in some epigenetic marks that lead to Pch2 dispersion from the nucleolus suppress zip1Δ-induced checkpoint arrest. These observations have led to the notion that Pch2 nucleolar localization could be important for the meiotic recombination checkpoint. Here we investigate how Pch2 chromosomal distribution impacts checkpoint function. We have generated and characterized several mutations that alter Pch2 localization pattern resulting in aberrant Hop1 distribution and compromised meiotic checkpoint response. Besides the AAA+ signature, we have identified a basic motif in the extended N-terminal domain critical for Pch2's checkpoint function and localization. We have also examined the functional relevance of the described Orc1-Pch2 interaction. Both proteins colocalize in the rDNA, and Orc1 depletion during meiotic prophase prevents Pch2 targeting to the rDNA allowing unwanted Hop1 accumulation on this region. However, Pch2 association with SC components remains intact in the absence of Orc1. We finally show that checkpoint activation is not affected by the lack of Orc1 demonstrating that, in contrast to previous hypotheses, nucleolar localization of Pch2 is actually dispensable for the meiotic checkpoint. [ABSTRACT FROM AUTHOR]

This study investigated the impact of an attachment-based intervention on care workers’ reflexive functioning (RF), analyzing 212 professionals in a randomized control trial. The study employed a multi-group latent difference score model to investigate changes in professionals’ certainty (i.e., hypermentalizing) while controlling for attachment-related anxiety and avoidance at T0. Furthermore, it examined whether these changes predicted the professionals’ ability to foster children’s autonomy. Results showed reduced hypermentalizing in the experimental group over time, correlating with higher levels of children’s autonomous/secure support. The role of RF processes in enhancing professionals’ capabilities to support the autonomy of children will be discussed. [ABSTRACT FROM AUTHOR]

According to the attachment theory, the establishment of emotional bonds with significant figures is an important process in human development throughout life. The quality of the relationships between adolescents and their caregivers in residential care (RC) may act as a protective factor for internal reorganisation and the development of emotional regulation skills. The present study aims to analyse the effect of insecure attachment orientation and the quality of relationships developed with caregivers in RC settings and adolescent emotion regulation. It also aims to assess the mediating role of emotion regulation in the association between attachment and the quality of the relationship with caregivers. The sample consisted of 249 adolescents, aged between 12 and 18 years old, living in RC facilities in Porto (Portugal). The results suggest that perceived insecurity of attachment to significant figures has a negative effect on emotional regulation and on the quality of the relationship with caregivers. We also found a negative mediating effect of the differentiating emotions dimension on the association between attachment and the quality of the relationship with caregivers. It is relevant to highlight the importance of close affective relationships in developing adolescents' ability to regulate their emotions and particularly the impact of caregivers and their work in residential care. [ABSTRACT FROM AUTHOR]

Abstract New adjuvant formulations, based on proteoliposomes <40 nm and cochleates <100 nm, without Al(OH) 3 adjuvant, were evaluated regarding their ability to generate Th1 immune response through a Delayed -Type Hypersensitivity Test, at the mouse model, by using a Neisseria meningitidis B protein complex as antigen. The formulations were administered by intramuscular (IM) (2 inoculations - at baseline and after 14 days) and intranasal (IN) (3 inoculations at 7 days) immunization pathways. All IM immunized groups were able to induce similar response to these formulations as well as to VA-MENGOC-BC® vaccine - containing Al(OH) 3 adjuvant (used as positive control of the trial). In all groups, the induced inflammation (IP) rate was statistically higher than in the negative control group (CN) (p < 0.05). Immunogenicity, measured by HSR and CD4+ lymphocyte increase was equivalent to the control vaccine and most important, granuloma reactogenicity at the site of injection was eliminated, fact demonstrated by histological study. All groups of animals immunized by IN route showed HSR reactions and statistically significant differences with respect to the CN group. However, IP values were lower, with statistical differences (p < 0.05) for the same adjuvant formulation IM administered, except the AIF2-nCh formulation that generated statistically similar induction (p > 0.05) by both immunization pathways, suggesting it to be the best candidate for the next IN trial. Proteoliposome and cochleate formulations tested were able to mount potent Th-1 immune response, equivalent to the original vaccine formulation, with the advantage of less reactogenicity in the site of the injection, caused by the toxicity of Al(OH) 3 adjuvant gel. Graphical abstract Unlabelled Image Highlights • New adjuvant formulations based on proteoliposomes <40 nm and cochleates <100 nm • Neisseria meningitidis B. capacity to generate immune response type Th1 • Hindlimb inflation in mice determined after intramuscular/intranasal inoculation. • TCD4+ lymphocytes increase indicates cell activation in immune response. • The new formulations stimulate an immune response according to HSR response. [ABSTRACT FROM AUTHOR]

Leishmaniasis is an infectious disease caused by a protozoan belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and patient's health condition. The outcomes can range from single cutaneous lesions to lethal visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and, in some cases, the second-line drug, amphotericin B, is used. Beside the toxicity of both classes of drugs, in some areas of the world, parasites are resistant to antimonial. These detrimental features make fundamental the discovery and characterization of new drugs or plant extracts with leishmanicidal effects. Brazil is a well-known country for its biodiversity. Additionally, the common knowledge inherited for generations in small villages makes Brazil a source of new information and resources for the discovery and development of new drugs. Based on ethnopharmacology, elderlies were interviewed about plants they commonly used for skin diseases and infections. Five native plants from Atlantic forest were indicated; EtOH and n-hexane extracts were prepared with the vegetative organs of the plants and assayed against promastigote and amastigote forms of L. (L.) amazonensis. The major molecules of each extract were detected using qualitative nuclear magnetic resonance. Among all tested extracts, the n-hexane extract from the leave of Eugenia uniflora (Myrtaceae), enriched in myricitrin and quercitrin flavonoids, was the most effective against L. (L.) amazonensis amastigotes. This data supports the ethnopharmacology approach as a successful tool for the discovery of new drugs with leishmanicidal effects. [ABSTRACT FROM AUTHOR]

The changes and transformations in the different areas of knowledge have been happening in an evident way, demanding from the information professional new functions and professional activities in the labor market. Among the fields of action, the health area is highlighted as a scientific field that requires informational subsidies for health care and for directing the clinical team in the diagnosis of patients and in decision-making. Therefore, the objective of the research is to address how information management, considered an essential activity of the information professional, can contribute to the activities and decision processes in the context of the health area. For this, a review of the literature on the topics addressed was carried out in order to draw up bibliographical discussions of the study. The discussions demonstrate that once contemporary organizations recognize the value of information within the organizational context, move away from theory and actually accept and apply these scenarios, the so-called information and knowledge society can develop and give a further step towards its evolution. As final considerations, it is justified that the information professional becomes a fundamental element in the health area, capable of causing, through the insertion and maintenance of Information Management, internal improvements in the activities and decision-making of health organizations, which also reflect in the increase of the quality of the services provided to the community. [ABSTRACT FROM AUTHOR]

The conditions imposed by the Covid-19 outbreaks forced residential care (RC) facilities to experience new challenges and to adopt new practices. The aim of the current study is to analyze how RC facilities have experienced and managed confinement during the 1st wave of the pandemic. A thematic analysis of 20 semi-structured interviews were conducted with professionals responsible for managing crisis in RC facilities. The main implications of the confinement measures on RC dynamics and relations were organized in three major themes: Chaos, novelty and organization; reinventing normalization and deconfinement. The pandemic exposes the structural weaknesses of RC, namely mobility of human resources, scarcity of supportive networks, and fragilities in providing comprehensive and integrative care. These factors need to be considered when addressing risk/vulnerability and discussing best practices and policies on child/youth welfare domain. Future studies should explore representations of important key actors as youth, families and other professionals from youth care. [ABSTRACT FROM AUTHOR]

Abstract We regard high degree stop-loss transforms as iterated equilibrium distributions to establish comparison criteria with respect to star-shape and convex transform orders. As an application, we derive monotonicity properties for exceedance probabilities, providing information on how likely these distributions are to be far from the extreme values of their support. [ABSTRACT FROM AUTHOR]

Introduction: The early diagnosis of hearing loss is essential to obtain better results in therapy. The use of ASSR with NB-chirp stimulus presents a reduction in the time taken to perform the exam. Objective: To analyze the findings of the Electrophysiological and Electroacoustic assessment in children under six months of age. Methodology: This is an observational, cross-sectional study with a qualitative approach. The sample was collected at the Audiology Outpatient Clinic, and arranged in a table containing data referring to the results obtained in 34 children aged 1 to 5 months. The children underwent the examination of OEA, BERA and ASSR. Results: All thirty-four children underwent OEA and BERA with results within normality bilaterally. From this sample, the mothers of twelve children authorized the performance of the ASSR, with results within the normality bilaterally, with an average recording time of two and a half minutes, proving to be a quick and practical test to perform in clinical practice, allowing recording from low to high. Conclusion: The use of electrophysiological tests in clinical practice are important in this population under six months of age for audiological diagnosis. The ASSR with NB-Chirp stimulus has demonstrated to be fast and effective for use in clinical routine, making it possible to evaluate the frequencies bilaterally, reducing the test execution time in relation to the battery of diagnosis and bringing important information about the responses in the severe regions, which are not registered by the BERA. [ABSTRACT FROM AUTHOR]

Abstract: A simple, efficient and green methodology for the C−S cross‐coupling reaction using Pd(L‐Pro)2 as a heterogeneous catalyst was developed involving aryl iodides, thiols, green‐solvent and a low catalytic loading of palladium prolinate. In addition, the catalyst turned out to be recyclable and the products were obtained in good to excellent yields. [ABSTRACT FROM AUTHOR]

This paper sets out a brief history of the Portuguese villancicos and discusses the poetic-musical genre fashionable in the seventeenth and eighteenth centuries, associated with certain feasts. It can be considered that the villancico formed part of a performance, and was frequently used to transmit religious messages. A comparison is drawn between the Vilancicos de Corpus Christi de 1647 and other villancicos which form part of the Barbosa Machado Collection. This paper focuses on the Corpus Christi villancicos, the only existing Portuguese villancicos written for this festival. They simultaneously celebrate the Eucharist, the Portuguese Restoration in 1640 and D. João IV being saved from an attack in 1646. [ABSTRACT FROM AUTHOR]

The composition of lignocellulosic materials used as enzyme inducers have different effects on enzyme production by fungal cultures. This work reports a comparative study of different cultivation systems for the production of xylanase and β-glucosidase by the fungus Aspergillus fumigatus SCB4 during solid-state fermentation (SSF), using sugarcane bagasse (SCB) or commercial substrates (Kraft pulp and Avicel). SCB was submitted to chemical pretreatments with H 2 O 2 , NaOH and ethanol (organosolv) and pretreated SCB samples were subsequently employed for the synthesis of enzymes. Pretreatments were efficient in the lignin reduction. Among them, the alkaline pretreatment was the most efficient with a reduction of 81.9% of lignin content in NaOH pretreated SCB in comparison to untreated SCB. In NaOH alkali-pretreated SCB, the fibers structure were also more efficiently altered with disrupted arranges and increased porosity. Despite the structural advantages obtained after pretreatments, the enzymatic biosynthesis was favored in cultivations using untreated SCB and commercial substrates as carbon sources. For β-glucosidase, it was noted a peak of production of 30.52 U/g after 96 h of SSF using untreated SCB as substrate. For xylanase, the maximum activity was detected using Kraft pulp (1878.76 U/g of substrate) after 120 h of SSF, probably due to the high concentration of hemicelluloses (19.52%) and low quantity of lignin (1.3%) in this material. Fermentations with untreated SCB also showed high xylanase activities (1647.20 U/g after the same period of incubation). This minor enzymatic biosynthesis after SSF using pretreated SCB might be due to the presence of some inhibitors produced after pretreatments which could be restricting fungal growth and consequently, the production of enzymes. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress poses a new pathological mechanism for metabolic-associated fatty liver disease (MAFLD). MAFLD treatment has encompassed renin-angiotensin system (RAS) blockers and aerobic exercise training, but their association with hepatic ER stress is not well known. Therefore, we aimed to compare the effects of hepatic RAS modulation by enalapril and/or aerobic exercise training over ER stress in MAFLD caused by a diet-induced obesity model. C57BL/6 mice were fed a standard-chow (CON, n = 10) or a high-fat (HF, n = 40) diet for 8 weeks. HF group was then randomly divided into: HF (n = 10), HF + Enalapril (EN, n = 10), HF + Aerobic exercise training (AET, n = 10), and HF + Enalapril+Aerobic exercise training (EN + AET, n = 10) for 8 more weeks. Body mass (BM) and glucose profile were evaluated. In the liver, ACE and ACE2 activity, morphology, lipid profile, and protein expression of ER stress and metabolic markers were assessed. Both enalapril and aerobic exercise training provided comparable efficacy in improving diet-induced MAFLD through modulation of RAS and ER stress, but the latter was more efficient in improving ER stress, liver damage and metabolism. This is the first study to evaluate pharmacological (enalapril) and non-pharmacological (aerobic exercise training) RAS modulators associated with ER stress in a diet-induced MAFLD model. HF diet led to favoring of the RAS classical arm and increased ER stress through higher expression of the eIF2α pathway. These results could be related to HF diet-associated insulin resistance and upregulation of gluconeogenesis enzymes PEPCK and G6Pase, as well as lipid accumulation through increased lipogenic transcription factor SREBP1c and lower PPARα levels. Enalapril treatment, aerobic exercise training, and the combination of both interventions were able to favor the RAS counterregulatory arm, improve ER stress and decrease lipid accumulation. All interventions were also able to improve insulin resistance, although aerobic exercise training showed more efficiency, reverting glucose intolerance and decreasing the expression of PEPCK. Aerobic exercise training was also the only intervention able to reduce binucleation of hepatocytes and the association with enalapril treatment reverted the increase in hepatocytes with two or more nuclei, which could be suggestive of liver damage associated with the pharmacological treatment. [Display omitted] • Enalapril and aerobic exercise training decrease ACE/ACE2 ratio in obese mice. • RAS counterregulatory arm could be associated to decreased ER stress markers in MAFLD. • Aerobic exercise training better improved liver ER stress markers, metabolism and damage. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress poses a new pathological mechanism for metabolic-associated fatty liver disease (MAFLD). MAFLD treatment has encompassed renin-angiotensin system (RAS) blockers and aerobic exercise training, but their association with hepatic ER stress is not well known. Therefore, we aimed to compare the effects of hepatic RAS modulation by enalapril and/or aerobic exercise training over ER stress in MAFLD caused by a diet-induced obesity model. C57BL/6 mice were fed a standard-chow (CON, n = 10) or a high-fat (HF, n = 40) diet for 8 weeks. HF group was then randomly divided into: HF (n = 10), HF + Enalapril (EN, n = 10), HF + Aerobic exercise training (AET, n = 10), and HF + Enalapril+Aerobic exercise training (EN + AET, n = 10) for 8 more weeks. Body mass (BM) and glucose profile were evaluated. In the liver, ACE and ACE2 activity, morphology, lipid profile, and protein expression of ER stress and metabolic markers were assessed. Both enalapril and aerobic exercise training provided comparable efficacy in improving diet-induced MAFLD through modulation of RAS and ER stress, but the latter was more efficient in improving ER stress, liver damage and metabolism. This is the first study to evaluate pharmacological (enalapril) and non-pharmacological (aerobic exercise training) RAS modulators associated with ER stress in a diet-induced MAFLD model. HF diet led to favoring of the RAS classical arm and increased ER stress through higher expression of the eIF2α pathway. These results could be related to HF diet-associated insulin resistance and upregulation of gluconeogenesis enzymes PEPCK and G6Pase, as well as lipid accumulation through increased lipogenic transcription factor SREBP1c and lower PPARα levels. Enalapril treatment, aerobic exercise training, and the combination of both interventions were able to favor the RAS counterregulatory arm, improve ER stress and decrease lipid accumulation. All interventions were also able to improve insulin resistance, although aerobic exercise training showed more efficiency, reverting glucose intolerance and decreasing the expression of PEPCK. Aerobic exercise training was also the only intervention able to reduce binucleation of hepatocytes and the association with enalapril treatment reverted the increase in hepatocytes with two or more nuclei, which could be suggestive of liver damage associated with the pharmacological treatment. [Display omitted] • Enalapril and aerobic exercise training decrease ACE/ACE2 ratio in obese mice. • RAS counterregulatory arm could be associated to decreased ER stress markers in MAFLD. • Aerobic exercise training better improved liver ER stress markers, metabolism and damage. [ABSTRACT FROM AUTHOR]

Affiliation The affiliation "Universidade de Coimbra, CQC-IMS, Department of Chemistry, 3004-535 Coimbra, Portugal" was missing from Dr. Brito. The correct author name is: Rui M. M. Brito. Author name The incorrect author name is: Rui Brito. [Extracted from the article]

In an effort to develop visualization analysis and design skills in master's level information visualization students, the authors use a well-known analytical usability evaluation method, heuristic evaluation, with different sets of heuristics to teach students to analyze visualization applications. The proposed approach, used for three consecutive years, has successfully stimulated critical analysis and discussion sessions as well as helped raise students' awareness concerning the benefit of using systematic analysis methods and the strategies and guidelines that should be used to design visualization applications. [ABSTRACT FROM AUTHOR]