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Herein we report a study on the sequential substitution of different nucleophiles on cyanuric chloride to obtain potential candidates for metal sensors (5a-c). The set of nucleophiles on the 1,3,5-triazine ring includes a phenolic BODIPY, an aminoalkyl pyridine and aminoalkyl phosphoramidates, each one designed to play a specific role in the final fluoroionophore. Three new triazine triads were synthesized in similar yields: 5a (45%), 5b (43%) and 5c (52%) after a methodical sequential combination of the nucleophiles via thermodependent nucleophilic aromatic substitution of the three chlorine atoms of cyanuric chloride. To ratify the synthetic results we simulated the reaction mechanisms for the different nucleophiles, aiming to address the distinctive orthogonality and temperature control inherent in this process, identifying and providing a sound rationale for any preferential sequence of nucleophiles inserted into the triazine core. According to our experimental and computational analysis (thermo- and kinetic preferences), we have identified the following preferential order for the sequential substitution: p-hydroxybenzaldehyde > 2-(pyridin-2-yl)ethanamine > aminoalkyl phosphoramidate, indicating that all steps follow a single-step process (concerted) in two stages, where nucleophilic addition precedes leaving group dissociation. The Meisenheimer σ-complex was identified as a transition state structure, with insufficient stability to exist as an intermediate. We observed a consistent and progressive increase in barrier height: 2-8 kcal mol-1 for the first step, 9-15 kcal mol-1 for the second step, and >15 kcal mol-1 for the third substitution. These findings align with the experimental observation of thermodependency in the sequential substitution.

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The phytochemical investigation of the leaves and trunk bark of a specimen of Ocotea aciphylla collected in the southern portion of the Amazon forest led to the isolation of an oxabicyclo[3.2.2]nonane-type neolignan and 15 bicyclo[3.2.1]octanoid neolignans, 14 of which are unreported compounds (2-15), including one with an unusual oxidation pattern of the side chain at C-1' and two rare 7.1',8.3'-connected bicyclo[3.2.1]octanoid derivatives. Their structures and relative configurations were determined by extensive spectrometric analysis based on 1D- and 2D-NMR spectroscopy and HRESIMS data, while their absolute configurations were unambiguously assigned using electronic and vibrational circular dichroism data assisted by density functional theory calculations. Additionally, known sesquiterpenes, phenylpropanoids, and phytosterols were also isolated.

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Family history of hypertension is associated with early autonomic dysfunction and increased oxidative stress. These alterations have been found to be reinforced by the overweight factor. Conversely, an active lifestyle is effective in improving the mechanisms regulating blood pressure control. Hence, we ought to investigate the effects of an active lifestyle on the hemodynamic, autonomic and oxidative stress parameters in individuals carrying both family history of hypertension and overweight risk factors. Fifty-six normotensive males were divided into four groups: eutrophic offspring of normotensive parents (EN, n = 12), eutrophic and inactive with hypertensive parents (EH, n = 14), overweight and inactive with hypertensive parents (OH, n = 13), and overweight and physically active with hypertensive parents (OAH, n = 17). Cardiovascular autonomic modulation was assessed by heart rate (HRV) and blood pressure (BPV) variability indexes. Oxidative stress included pro/antioxidant markers and nitrite concentration. Inactive offspring of hypertensive parents (EH and OH) showed higher LFSBP (vs EN), an indicator of sympathetic outflow to the vasculature and reduced anti-oxidant activity (vs EN), while higher pro-oxidant markers were found exclusively in OH (vs EN and EH). Conversely, the OAH group showed bradycardia, higher vagally-mediated HFabs index (vs OH and EN), lower sympathovagal balance (vs OH) and preserved LFSBP. Yet, the OAH showed preserved pro/antioxidant markers and nitrite levels. Our findings indicates that overweight offspring of hypertensive parents with an active lifestyle have improved hemodynamic, cardiac autonomic modulation and oxidative stress parameters compared to their inactive peers.

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Preserving vascular function is crucial for preventing multiorgan failure and death in ischemic and low-pressure states such as trauma/hemorrhagic shock (T/HS). It has recently been reported that inhibiting circulating proteases released from the bowel to the circulation during T/HS may preserve vascular function and improve outcomes following T/HS. This study aimed to evaluate the role of the serine protease inhibitor gabexate mesilate (GM) in preserving vascular function during T/HS when given enterally. We studied the vascular reactivity of mesenteric arteries from male Wistar rats treated with enteral GM (10 mg/kg) (GM-treated, n = 6) or control (Shock-control, n = 6) following (T/HS) using pressure myography. Concentration-response curves of endothelial-dependent and endothelial-independent agonists (e.g., acetylcholine, sodium nitroprusside) ranging from 10-10 to 10-5 M were performed. In a second set of experiments, ex-vivo arteries from healthy rats were perfused with plasma from shocked animals from both groups and vascular performance was similarly measured. Arteries from the GM-treated group demonstrated a preserved concentration-response curve to the α1 adrenergic agonist phenylephrine compared to arteries from Shock-control animals (- logEC50: - 5.73 ± 0.25 vs. - 6.48 ± 0.2, Shock-control vs. GM-treated, p = 0.04). When perfused with plasma from GM-treated rats, healthy arteries exhibited an even greater constriction and sensitivity to phenylephrine (- logEC50: - 6.62 ± 0.21 vs. - 7.13 ± 0.21, Shock-control vs. GM-treated, p = 0.02). Enteral GM also preserved the endothelium-dependent vascular response to agonists following T/HS and limited syndecan-1 shedding as a marker of glycocalyx compromise (41.84 ± 9 vs. 17.63 ± 3.97 ng/mL, Shock-control vs. GM-treated, p = 0.02). Syndecan-1 cleavage was correlated with plasma trypsin-like activity (r2 = 0.9611). Enteral gabexate mesilate was able to maintain vascular function in experimental T/HS, which was reflected by improved hemodynamics (mean arterial pressure 50.39 ± 7.91 vs. 64.95 ± 3.43 mmHg, Shock-control vs. GM treated, p = 0.0001). Enteral serine protease inhibition may be a potential therapeutic intervention in the treatment of T/HS.

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Glanders is a contagious disease of equids caused by the Gram-negative bacterium Burkholderia mallei. In Brazil, the disease is considered to be reemerging and has been expanding, with records of equids with positive serology in most of the federative units. However, there are few reports describing the genotypic detection of the agent. This study demonstrated the detection of B. mallei by species-specific PCR directly from tissues or from bacterial cultures, followed by amplicon sequencing in equids (equines, mules, and asinines) with positive serology for glanders in all five geographic regions of Brazil. The molecular evidence of B. mallei infection in serologically positive equids in this study expands the possibility of strain isolation and the conduction of epidemiological characterizations based on molecular information. The microbiological detection of B. mallei in cultures from nasal and palate swabs, even in equids without clinical manifestations, raises the possibility of environmental elimination of the agent.

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INTRODUCTION: Hereditary angioedema is an autosomal dominant genetic disease, associated with increased levels of bradykinin. It is classified into 3 types according to the C1-INH enzyme. The diagnosis is clinical and laboratory. Its treatment is divided into short- and long-term and crisis prophylaxis. CASE REPORT: 40-year-old female patient who came to the emergency service for labial edema without resolution with corticosteroids. The tests for IgE, C4 and C1 esterase inhibitors had a low result. She currently uses danazol prophylactically and fresh frozen plasma in crises. CONCLUSIONS: Since it is a disease that considerably affects the quality of life, hereditary angioedema must be diagnosed and an effective treatment plan made to prevent or reduce its complications.

INTRODUCCIÓN: El angioedema hereditario es una enfermedad genética autosómica dominante, asociada con aumento de las concentraciones de bradicinina. Se clasifica en tres tipos, de acuerdo con la enzima C1-INH. El diagnóstico se establece por las manifestaciones clínicas y los estudios de laboratorio. El tratamiento consiste profilaxis a corto y largo plazo, y protocolo para el control de las crisis. REPORTE DEL CASO: Paciente femenina de 40 años, que acudió al servicio de Urgencias por edema labial, sin reacción al tratamiento con corticosteroides. Se detectaron concentraciones bajas de IgE, C4 e inhibidores de la esterasa C1. Se estableció el diagnóstico de angioedema hereditario. Actualmente se mantiene en tratamiento profiláctico con danazol y plasma fresco congelado para el control de las crisis. CONCLUSIONES: El angioedema hereditario es una enfermedad que afecta considerablemente la calidad de vida; por tanto, debe diagnosticarse de forma oportuna y establecer un plan de tratamiento eficaz, con la intención de prevenir o reducir las complicaciones.

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The aim of this study was to determine the incidence of infections and cytological abnormalities and to investigate possible predisposing factors such as sociodemographic characteristics, sexual behavioral habits, and gynecological and obstetric backgrounds. Between 2013 and December 2016, a cross-sectional study was conducted among 429 consenting women, from whom cervical samples were tested for the presence of Human papillomavirus (HPV) by polymerase chain reaction (PCR). Susceptibility to HPV infection was assessed by binary logistic regression in light of possible predisposing factors, which were collected using a questionnaire. In our sample population, the prevalence of HPV infection was 49%; high-risk types had a higher prevalence of 89.1%. A larger proportion of HPV-infected women were under 25 years of age, were single, and had monthly incomes up to minimum wage. Multivariate binary logistic regression analysis showed that age younger than 25 years increased the odds of infection fivefold, while a monthly income of one to three minimum wages provided protection against HPV infection, even if the women were married or had a cohabiting partner. In the HPV-positive group, squamous intraepithelial lesions (SIL) occurred more frequently in women who earned up to one minimum wage monthly, but a monthly income of one to three minimum wages protected against the development of SIL. The results suggest that age, marital status, and monthly income are important cofactors for HPV infection and the development of SIL.

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Background: Understanding the correlation between the methods of monitoring surface cleaning and disinfection (SCD) is fundamental for better infection control. Purpose: This study aims to correlate the SCD monitoring methods in a Brazilian pediatric unit. This is an exploratory, longitudinal, and correlational study. Methods: The study was conducted in a pediatric hospitalization unit of a medium-sized hospital from December 2020 to March 2021. Four high-contact surfaces were analyzed before and after the cleaning and disinfection process by means of visual inspection, quantification of adenosine triphosphate (ATP), and colony-forming unit (CFU) count. The study consisted of three stages: stage I involving situational diagnosis of the SCD process; stage II referring to the implementation of the Surface Cleaning and Disinfection Standardization Program (SCDSP); and stage III involving long-term assessment after implementing the program. A total of 192 assessments were performed in each stage, totaling 576 in the three study stages. Conclusions: A significant correlation was found between the ATP quantification methods and microbial count in the bed railing (p = 0.009) and companion's armchair (p = 0.018) surfaces. In both cases, Spearman's correlation coefficients were positive, indicating a positive correlation between ATP and microbial count scores, that is, the higher the ATP values (in RLUs), the greater the microbial counts (in CFUs/cm2). The analysis of the ROC curves suggests that the surfaces presenting ATP below 108 RLUs can be considered approved. The ATP method yielded 78.6% sensitivity; in turn, microbial count presented a sensitivity of 85.7%. It is important to use different methods to monitor the cleaning and disinfection of surfaces, as each one has different sensitivity and specificity.

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The application of the mitigation hierarchy (MH) to mining projects is challenging in situations of locational overlap between endemic flora and mineral deposits. We review flora surveys conducted in connection with the environmental impact assessment of several iron ore mining projects in an area of high degree of endemism in Eastern Amazon to discuss the practical implications of anticipating conservation strategies. Desktop studies and secondary data review were conducted to guide field searches to determine the distribution of endemic flora, resulting in 45 out of 46 endemic plant species having their known distribution extended to new areas. A framework for positioning flora conservation strategies in the MH is presented. Specific habitat requirements and scarce knowledge about endangered and endemic flora species are a conservation obstacle, since essential information to define species conservation strategies may be lacking. We show that anticipating conservation strategies can minimize time-lag uncertainties related to restoration success and biodiversity offsets. The more effort is placed in the preventative steps of the MH, the smaller the time-lag between impact (biodiversity losses) and conservation outcomes (biodiversity gains), decreasing uncertainties and reducing risks to biodiversity.

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4-Quinolones compose a remarkable class of compounds that show various pharmacological applications. In particular, the activities of both (S) and (R) enantiomers of 2-aryl-2,3-dihydro-4(1H)-quinolones have made them an object of befitting interest for asymmetric synthesis. Although readily yielded as a racemic mixture from an one-pot reaction between 2-aminoacetophenone and benzaldehyde, a pathway for the metal-free enantioselective one-pot synthesis of the (S) isomer is not completely clear. In the present work, guided by the burgeoning role of organocatalysis in asymmetric synthesis and recent experimental insight into the most likely reaction mechanism, we report the in silico screening for a roster of MacMillan chiral imidazolidinones through quantum mechanics calculations. Two stereopredictive models yielding similarly high expected ee (up to 97%) were proposed. The role of aromatic interactions for the control of enantioselectivity was systemically studied, as well as the Pro-S si-enantiofacial attack activation energies, which were found to correlate well (R2 = 0.75) with the reported Bürgi-Dunitz angle for the expected intramolecular Mannich reaction mechanism.

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