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Dichloro(l-histidine)copper(II) crystal ([Cu(l-His)Cl 2 ] complex) was obtained by the slow evaporation method and characterized concerning its thermal stability, phase transformations, and electronic and vibrational properties. X-ray diffraction (XRPD) confirmed that this complex crystallizes with an orthorhombic structure ( P 2 1 2 1 2 1 space group). Thermal analyses (TG and DTA) demonstrate stability from ambient temperature up to 460 K, followed by a phase transition from the orthorhombic structure to the amorphous form around 465 K, as confirmed by temperature-dependent XRPD studies. The active modes in Fourier transform infrared (FT-IR) and Raman spectroscopy spectra were suitably assigned via density functional theory (DFT) calculations. Additionally, Hirshfeld surface analysis uncovered the prominence of Cl···H, O···H, and H···H interactions as the primary intermolecular forces within the crystal structure. The antimicrobial activity of the [Cu(l-His)Cl 2 ] complex was investigated, demonstrating significant efficacy against Gram-positive bacteria ( Staphylococcus aureus ), Gram-negative bacteria ( Pseudomonas aeruginosa ), and fungi ( Candida albicans ). The minimum inhibitory concentration and cell viability tests showed that the complex inhibits the growth of S. aureus bacteria at a concentration of 1.5 μM without causing damage to the human cell line. The pharmacokinetic parameters corroborate the other tested parameters and highlight the [Cu(l-His)Cl 2 ] complex as a promising alternative for future clinical trials and medicinal applications. The alignment of the pharmacokinetic parameters with other tested criteria highlights the potential of the [Cu(l-His)Cl 2 ] complex as a promising candidate for future clinical studies., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Mounting evidence suggests that the phytocannabinoid cannabidiol (CBD) holds promise as an antidepressant agent in conditions underlined by inflammation. Full-spectrum CBD extracts might provide greater behavioral efficacy than CBD-only isolates and might require lower doses to achieve the same outcomes due to the presence of other cannabinoids, terpenes, and flavonoids. However, investigations in this area remain limited. Methods: We evaluated the behavioral response to the administration for 7 days of 15 and 30 mg/kg of a CBD isolate and a full-spectrum CBD product in a rat model of subchronic lipopolysaccharide (LPS, 0.5 mg/kg/day/7 days, intraperitoneal)-induced depressive-like and sickness behavior. The forced swim test was used to assess depressive-like behavior, the open field test (OFT) to assess locomotion, and the elevated plus maze to assess anxiety-like behavior. Results: The full-spectrum CBD extract at both doses, but not the CBD isolate, reversed the LPS-induced depressive-like behavior in the forced swim test. Moreover, the full-spectrum CBD extract at the higher dose but not the CBD isolate restored the subchronic LPS-induced hypolocomotion in the OFT. Repeated administration of both formulations elicited an anxiogenic-like trend in the elevated plus maze. Conclusion: Full-spectrum CBD products might have greater therapeutic efficacy in resolving inflammation-induced depressive and sickness behavior compared to a CBD-only isolate.

Research Background: In a country where millions of people have nutritional needs, innovative ways of producing food from commonly wasted agro-industrial by-products, can be an important alternative for the production of fermented beverages. In light of this, the aim of this study is to evaluate the potential of fruit by-products from acerola, guava and tamarind for the production of fermented beverages., Experimental Approach: Physicochemical and microbiological parameters, total antioxidant capacity and fermentation kinetics were investigated during the first (at 0, 48, 72, 96 and 168 h) and second fermentation (at 0 and 24 h). The acid profile of fermented beverages was determined by chromatography, and the sensory profile was determined by consumer acceptance test., Results and Conclusions: Physicochemical parameters of all formulations complied with current legislation and were of satisfactory microbiological quality. The reslts of fermentation kinetics showed that both pH and soluble solids content decreased - with an average final pH of 3.12, 2.85 and 2.78 for the acerola, guava and tamarind formulations, respectively - while acidity increased with final values of 0.94, 0.75 and 1 % for the same formulations. Of all formulations, tamarind had the highest total soluble solids content (8.17 g/100 g), and acerola had the highest antioxidant potential determined as Trolox equivalents ((20.0±0.8) μM/g). Organic acids were found in all samples, with mainly glucuronic acid detected in the kombucha beverages. All formulations showed satisfactory sensory acceptability, although the results were better for guava. The fruit by-products can be used as raw materials for the development of alternative kombucha beverages., Novelty and Scientific Contribution: As consumers are increasingly selective in their food choices, the development of food products with high nutritional value has increased significantly in recent years. New types of fermentable beverages such as kombucha - using tropical fruit by-products to enhance their chemical composition, sensory properties and nutritional value - have created new opportunities for beverage consumption and offer greater health benefits than the traditional version, where only Camellia sinensis is used. The promotion of these co-products and their respective beverages is an excellent opportunity for sustainability and their commercialisation., Competing Interests: CONFLICT OF INTEREST There is no conflict of interest., (Authors.)

Background: 123 Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity., Methods and Results: Prospectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from 123 iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) 123 iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P <0.001), and correlated negatively with diffuse fibrosis assessed by ECV ( R =-0.34, P <0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, P <0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); ( R =-0.41, P <0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels., Conclusions: Abnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.

Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide's low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management.

Background: Alarms alert healthcare professionals of deviations from normal/physiologic status. However, alarm fatigue may occur when their high pitch and diversity overwhelm clinicians, possibly leading to alarms being disabled, paused, and/or ignored. We aimed to determine whether a staff educational program on customizing alarm settings of bedside monitors may decrease inconsistent alarms in the Post-Anesthesia Care Unit (PACU)., Methods: This is a prospective, analytic, quantitative, pragmatic, open-label, single-arm study. The outcome was evaluated on PACU admission before (P1) and after (P2) the implementation of the educational program. The heart rate, blood pressure, and oxygen saturation alarms were selected for clinical consistency., Results: A total of 260 patients were included and 344 clinical alarms collected, with 270 (78.4%) before (P1), and 74 (21.6%) after (P2) the intervention. Among the 270 alarms in P1, 45.2% were inconsistent (i.e., false alarms), compared to 9.4% of the 74 in P2. Patients with consistent alarms occurred in 30% in the P1 and 27% in the P2 (p = 0.08). Patients with inconsistent alarms occurred in 25.4% in the P1 and in 3.8% in the P2. Ignored consistent alarms were reduced from 21.5% to 2.6% (p = 0.004) in the P2 group. The educational program was a protective factor for the inconsistent clinical alarm (OR = 0.11 [95% CI 0.04-0.3]; p < 0.001) after adjustments for age, gender, and ASA physical status., Conclusion: Customizing alarm settings on PACU admission proved to be a protective factor against inconsistent alarm notifications of multiparametric monitors., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Anestesiologia. Published by Elsevier España S.L.U. All rights reserved.)

Background and Aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF  ≥  45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling., Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system)., Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r =  - 0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r =  - 0.29, p = 0.04) and intracellular water lifetime ( τ ic ) (r =  - 0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r =  - 0.63, p < 0.01)., Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Otavio R Coelho-Filho reports financial support was provided by State of Sao Paulo Research Foundation. Otavio R Coelho-Filho reports was provided by. Otavio R Coelho-Filho reports a relationship with 10.13039/100004325AstraZeneca Pharmaceuticals LP that includes: funding grants and speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100002429Amgen Inc that includes: funding grants. Otavio R Coelho-Filho reports a relationship with 10.13039/100004319Pfizer Inc that includes: funding grants and speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100004336Novartis AG that includes: speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100004326Bayer AG that includes: speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100001003Boehringer Ingelheim Ltd that includes: speaking and lecture fees. Otavio R Coelho-Filho reports a relationship with 10.13039/100007723Takeda Pharmaceutical Company Limited that includes: funding grants and speaking and lecture fees. Tomas G Neilan reports a relationship with H3 Biomedicine Inc that includes: funding grants. Tomas G Neilan reports a relationship with 10.13039/100002429Amgen Inc that includes: funding grants. Tomas G Neilan reports a relationship with 10.13039/100006483AbbVie Inc that includes: funding grants. Tomas G Neilan reports a relationship with 10.13039/100004325AstraZeneca that includes: funding grants. T.G.N. has received support from 10.13039/100004325AstraZeneca, Bristol Myer Squibb, 10.13039/100006483AbbVie, 10.13039/100002429Amgen, and H3 Biomedicine. O.R.C.F. has received research grants and/or speaking honoraria from 10.13039/100002429Amgen, 10.13039/100004325AstraZeneca, 10.13039/100004326Bayer, 10.13039/100001003Boehringer Ingelheim, 10.13039/100004336Novartis, 10.13039/100007723Takeda, and 10.13039/100004319Pfizer. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

The most widely accepted and used type of digital pathology (DP) is whole-slide imaging (WSI). The USFDA granted two WSI system approvals for primary diagnosis, the first in 2017. In Latin America, DP has the potential to reshape healthcare by enhancing diagnostic capabilities through artificial intelligence (AI) and standardizing pathology reports. Yet, we must tackle regulatory hurdles, training, resource availability, and unique challenges to the region. Collectively addressing these hurdles can enable the region to harness DP's advantages-enhancing disease diagnosis, medical research, and healthcare accessibility for its population. Americas Health Foundation assembled a panel of Latin American pathologists who are experts in DP to assess the hurdles to implementing it into pathologists' workflows in the region and provide recommendations for overcoming them. Some key steps recommended include creating a Latin American Society of Digital Pathology to provide continuing education, developing AI models trained on the Latin American population, establishing national regulatory frameworks for protecting the data, and standardizing formats for DP images to ensure that pathologists can collaborate and validate specimens across the various DP platforms., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Renata Coudry, Emilio Assis, Fernando Frasetto, Angela Jansen, Leonard da Silva, Rafael Parra-Medina, Mauro Saieg reports financial support was provided by Americas Health Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.

The objective of this study was to purify sodium maltobionate using Zymomonas mobilis cells immobilized in situ on flexible polyurethane (PU) and convert it into maltobionic acid for further evaluation of bioactivity (iron chelating ability, antibacterial potential and cytoprotection) and incorporation into films based on cassava starch, chitosan, and cellulose acetate. Sodium maltobionate exhibited a purity of 98.1% and demonstrated an iron chelating ability of approximately 50% at concentrations ranging from 15 to 20 mg mL -1 . Maltobionic acid displayed minimal inhibitory concentrations (MIC) of 8.5, 10.5, 8.0, and 8.0 mg mL -1 for Salmonella enterica serovar Choleraesuis, Escherichia coli , Staphylococcus aureus , and Listeria monocytogenes , respectively. Maltobionic acid did not exhibit cytotoxicity in HEK-293 cells at concentrations up to 500 µg mL -1 . Films incorporating 7.5% maltobionic acid into cassava starch and chitosan demonstrated inhibition of microbial growth, with halo sizes ranging from 15.67 to 22.33 mm. These films had a thickness of 0.17 and 0.13 mm, water solubility of 62.68% and 78.85%, and oil solubility of 6.23% and 11.91%, respectively. The cellulose acetate film exhibited a non-uniform visual appearance due to the low solubility of maltobionic acid in acetone. Mechanical and optical properties were enhanced with the addition of maltobionic acid to chitosan and cassava films. The chitosan film with 7.5% maltobionic acid demonstrated higher tensile strength (30.3 MPa) and elongation at break (9.0%). In contrast, the cassava starch film exhibited a high elastic modulus (1.7). Overall, maltobionic acid, with its antibacterial activity, holds promise for applications in active films suitable for food packaging., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03879-3., Competing Interests: Conflict of interestThe authors have no relevant financial or nonfinancial interests to disclose., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Plectranthus barbatus , popularly known as Brazilian boldo, is used in Brazilian folk medicine to treat cardiovascular disorders including hypertension. This study investigated the chemical profile by UFLC-DAD-MS and the relaxant effect by using an isolated organ bath of the hydroethanolic extract of P. barbatus (HEPB) leaves on the aorta of spontaneously hypertensive rats (SHR). A total of nineteen compounds were annotated from HEPB, and the main metabolite classes found were flavonoids, diterpenoids, cinnamic acid derivatives, and organic acids. The HEPB promoted an endothelium-dependent vasodilator effect (~100%; EC50 ~347.10  μ g/mL). Incubation of L-NAME (a nonselective nitric oxide synthase inhibitor; EC50 ~417.20  μ g/mL), ODQ (a selective inhibitor of the soluble guanylate cyclase enzyme; EC50 ~426.00  μ g/mL), propranolol (a nonselective α -adrenergic receptor antagonist; EC50 ~448.90  μ g/mL), or indomethacin (a nonselective cyclooxygenase enzyme inhibitor; EC50 ~398.70  μ g/mL) could not significantly affect the relaxation evoked by HEPB. However, in the presence of atropine (a nonselective muscarinic receptor antagonist), there was a slight reduction in its vasorelaxant effect (EC50 ~476.40  μ g/mL). The addition of tetraethylammonium (a blocker of Ca 2+ -activated K + channels; EC50 ~611.60  μ g/mL) or 4-aminopyridine (a voltage-dependent K + channel blocker; EC50 ~380.50  μ g/mL) significantly reduced the relaxation effect of the extract without the interference of glibenclamide (an ATP-sensitive K + channel blocker; EC50 ~344.60  μ g/mL) or barium chloride (an influx rectifying K + channel blocker; EC50 ~360.80  μ g/mL). The extract inhibited the contractile response against phenylephrine, CaCl 2 , KCl, or caffeine, similar to the results obtained with nifedipine (voltage-dependent calcium channel blocker). Together, the HEPB showed a vasorelaxant effect on the thoracic aorta of SHR, exclusively dependent on the endothelium with the participation of muscarinic receptors and K + and Ca 2+ channels., Competing Interests: The authors declare no conflicts of interest to disclose., (Copyright © 2023 Jeniffer Cristóvão Moser et al.)

Aim: X-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked ( PHEX ) gene. The main purpose of this study is to identify the presence of a genotype-phenotype correlation in a cohort of XLH patients., Methods: This is a retrospective study including patients diagnosed with hypophosphatemic rickets, confirmed by clinical, radiological, and laboratory findings. Medical records were reviewed for phenotypic analyses. Genomic DNA was extracted from the peripheral blood lymphocytes, and PHEX sequencing was performed by exomic NGS sequencing. The Wilcoxon rank-sum test and the two-tailed Fisher's exact test were employed for the statistical analyses of this study., Results: A total of 41 patients were included in this study, and 63.41% (26/41) of the patients were female. The mutation analyses identified 29.27% missense variants and 29.72% nonsense variants, most of them were considered deleterious (66.41%). Six novel deleterious variants in the PHEX gene were detected in seven patients. The median concentrations of pretreatment serum calcium, phosphorus, and parathyroid hormone (PTH) were not significantly different among patients with different genotypes. An orthopedic surgery due to bone deformity was required in 57.69%., Conclusions: Our analysis did not identify any specific genotype as a predictor. No significant genotype-phenotype correlation was found, suggesting that the recognition of subjacent pathogenic mutation in the PHEX gene may have limited prognostic value. Despite this finding, genetic testing may be useful for identifying affected individuals early and providing appropriate treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Borghi, Silva, Bispo and Longui.)

Background: The diagnosis of Cushing's syndrome is challenging; however, through the clinical picture and the search for secondary causes of osteoporosis, it was possible to reach the diagnosis of the case reported. There was an independent, symptomatic ACTH hypercortisolism manifested by typical phenotypic changes, severe secondary osteoporosis and arterial hypertension in a young patient., Case Presentation: A 20-year-old Brazilian man with low back pain for 8 months. Radiographs showed fragility fractures in the thoracolumbar spine, and bone densitometry showed osteoporosis, especially when evaluating the Z Score (- 5.6 in the lumbar spine). On physical examination, there were wide violaceous streaks on the upper limbs and abdomen, plethora and fat increase in the temporal facial region, hump, ecchymosis on limbs, hypotrophy of arms and thighs, central obesity and kyphoscoliosis. His blood pressure was 150 × 90 mmHg. Cortisol after 1 mg of dexamethasone (24.1 µg/dL) and after Liddle 1 (28 µg/dL) were not suppressed, despite normal cortisoluria. Tomography showed bilateral adrenal nodules with more severe characteristics. Unfortunately, through the catheterization of adrenal veins, it was not possible to differentiate the nodules due to the achievement of cortisol levels that exceeded the upper limit of the dilution method. Among the hypotheses for the differential diagnosis of bilateral adrenal hyperplasia are primary bilateral macronodular adrenal hyperplasia, McCune-Albright syndrome and isolated bilateral primary pigmented nodular hyperplasia or associated with Carney's complex. In this case, primary pigmented nodular hyperplasia or carcinoma became important etiological hypotheses when comparing the epidemiology in a young man and the clinical-laboratory-imaging findings of the differential diagnoses. After 6 months of drug inhibition of steroidogenesis, blood pressure control and anti-osteoporotic therapy, the levels and deleterious metabolic effects of hypercortisolism, which could also impair adrenalectomy in the short and long term, were reduced. Left adrenalectomy was chosen, given the possibility of malignancy in a young patient and to avoid unnecessary definitive surgical adrenal insufficiency if the adrenalectomy was bilateral. Anatomopathology of the left gland revealed expansion of the zona fasciculate with multiple nonencapsulated nodules., Conclusion: The early identification of Cushing's syndrome, with measures based on the assessment of risks and benefits, remains the best way to prevent its progression and reduce the morbidity of the condition. Despite the unavailability of genetic analysis for a precise etiological definition, it is possible to take efficient measures to avoid future damage., (© 2023. The Author(s).)

A leading theory for ovarian carcinogenesis proposes that inflammation associated with incessant ovulation is a driver of oncogenesis. Consistent with this theory, nonsteroidal anti-inflammatory drugs (NSAIDs) exert promising chemopreventive activity for ovarian cancer. Unfortunately, toxicity is associated with long-term use of NSAIDs due to their cyclooxygenase (COX) inhibitory activity. Previous studies suggest the antineoplastic activity of NSAIDs is COX independent, and rather may be exerted through phosphodiesterase (PDE) inhibition. PDEs represent a unique chemopreventive target for ovarian cancer given that ovulation is regulated by cyclic nucleotide signaling. Here we evaluate PDE10A as a novel therapeutic target for ovarian cancer. Analysis of The Cancer Genome Atlas (TCGA) ovarian tumors revealed PDE10A overexpression was associated with significantly worse overall survival for patients. PDE10A expression also positively correlated with the upregulation of oncogenic and inflammatory signaling pathways. Using small molecule inhibitors, Pf-2545920 and a novel NSAID-derived PDE10A inhibitor, MCI-030, we show that PDE10A inhibition leads to decreased ovarian cancer cell growth and induces cell cycle arrest and apoptosis. We demonstrate these pro-apoptotic properties occur through PKA and PKG signaling by using specific inhibitors to block their activity. PDE10A genetic knockout in ovarian cancer cells through CRISP/Cas9 editing lead to decreased cell proliferation, colony formation, migration and invasion, and in vivo tumor growth. We also demonstrate that PDE10A inhibition leads to decreased Wnt-induced β-catenin nuclear translocation, as well as decreased EGF-mediated activation of RAS/MAPK and AKT pathways in ovarian cancer cells. These findings implicate PDE10A as novel target for ovarian cancer chemoprevention and treatment., (© 2022. The Author(s).)

This study reports curcumin as an efficient photolarvicide against Aedes aegypti larvae under natural light illumination. Larval mortality and pupal formation were monitored daily for 21 days under simulated field conditions. In a sucrose-containing formulation, a lethal time 50 (LT50) of 3 days was found using curcumin at 4.6 mg L -1 . This formulation promoted no larval toxicity in the absence of illumination, and sucrose alone did not induce larval phototoxicity. The photodegradation byproducts (intermediates) of curcumin were determined and the photodegradation mechanisms proposed. Intermediates with m/z 194, 278, and 370 were found and characterized using LC-MS. The ecotoxicity of the byproducts on non-target organisms ( Daphnia , fish, and green algae) indicates that the intermediates do not exhibit any destructive potential for aquatic organisms. The results of photodegradation and ecotoxicity suggest that curcumin is environmentally safe for non-target organisms and, therefore, can be considered for population control of Ae . aegypti .

Several market sectors are attracted by the potential of unmanned aerial vehicles (UAVs), such as delivery, agriculture, and cinema, among others. UAVs are becoming part of Internet of Things (IoT) networks in the development of autonomous and scalable solutions. However, these vehicles are gradually becoming attractive targets for cyberattacks. This study proposes the development of an efficient platform based on the Message Queuing Telemetry Transport (MQTT) protocol for UAV control and Denial-of-Service (DoS) detection embedded in the UAV system. For the efficiency test, latency, network and memory consumption on the platform were measured, in addition to the correlation between payload and delay time. The results of efficiency tests were collected for the three levels of quality of service (QoS). A strong correlation greater than 90% was found between delay and data size for all QoS levels, showing almost a linear proportion. In DoS detection, the best results were a true positive rate (TPR) of 0.97 with 16 features from the AWID2 dataset using LightGBM with Bayesian optimization and data balancing. Unlike other studies, the built platform shows efficiency for UAV control and guarantees security in the communication with the broker and in the Wi-Fi UAV network.

Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, responsible for an atypical pneumonia that can progress to acute lung injury. MicroRNAs are small non-coding RNAs that control specific genes and pathways. This study evaluated the association between circulating miRNAs and lung injury associated with COVID-19. Methods: We evaluated lung injury by computed tomography at hospital admission and discharge and the serum expression of 754 miRNAs using the TaqMan OpenArray after hospital discharge in 27 patients with COVID-19. In addition, miR-150-3p was validated by qRT-PCR on serum samples collected at admission and after hospital discharge. Results: OpenArray analysis revealed that seven miRNAs were differentially expressed between groups of patients without radiological lung improvement compared to those with lung improvement at hospital discharge, with three miRNAs being upregulated (miR-548c-3p, miR-212-3p, and miR-548a-3p) and four downregulated (miR-191-5p, miR-151a-3p, miR-92a-3p, and miR-150-3p). Bioinformatics analysis revealed that five of these miRNAs had binding sites in the SARS-CoV-2 genome. Validation of miR-150-3p by qRT-PCR confirmed the OpenArray results. Conclusions: The present study shows the potential association between the serum expression of seven miRNAs and lung injury in patients with COVID-19. Furthermore, increased expression of miR-150 was associated with pulmonary improvement at hospital discharge.

Background: Chronic Chagas cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR)., Methods: We performed a prospective observational cohort of patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τ ic , a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τ ic with CV death., Results: A total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = -0.51; P = 0.0015). τ ic decreased linearly with NYHA class ( P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (r = 0.47; P = 0.004). Over a median follow-up of 734 days (range: 6-2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (heart rate [HR] = 1.3; 95% CI = [1.0, 1.8]; P = 0.028) and ECV (HR = 3.4 for 0.1 change, 95% CI = [1.1, 11.0], P = 0.039) were simultaneously associated with CV death., Conclusion: In patients with intermediate-to-high-risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events., Competing Interests: TN has received support from Astra Zeneca, Bristol Myer Squibb, AbbVie, Amgen, and H3 Biomedicine. ORCF has received research grants and/or speaking honoraria from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Novartis, Takeda, and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nardi Gemme, Silva, Martins, da Silva, Paim, Sposito, Nadruz, Fernandes, San Juan Dertkigil, da Silva Wanderley, de Almeida, Metze, Neilan, Jerosch-Herold and Coelho-Filho.)

COVID-19-related in-hospital mortality has been reported at 30.7-47.3% in Brazil, however studies assessing exclusively private hospitals are lacking. This is important because of significant differences existing between the Brazilian private and public healthcare systems. We aimed to determine the COVID-19-related in-hospital mortality and associated risk factors in a Brazilian private network from March/2020 to March/2021. Data were extracted from institutional database and analyzed using Cox regression model. Length of hospitalization and death-related factors were modeled based on available independent variables. In total, 38,937 COVID-19 patients were hospitalized of whom 3058 (7.8%) died. Admission to the intensive care unit occurred in 62.5% of cases, and 11.5% and 3.8% required mechanical ventilation (MV) and renal replacement therapy (RRT), respectively. In the adjusted model, age ≥ 61 years-old, comorbidities, and the need for MV and/or RRT were significantly associated with increased mortality (p < 0.05). Obesity and hypertension were associated with the need for MV and RRT (p < 0.05)., (© 2022. The Author(s).)

Objective: The focus of this study was to evaluate the gastric healing effect of lupeol stearate (LS) and its ability to minimize ulcer recurrence in rodents., Methods: To evaluate the gastric healing properties of LS, rats were subjected to 80% acetic acid-induced ulcer model and treated with vehicle, LS (1 mg/kg, p.o.), or omeprazole (20 mg/kg, p.o.), twice daily by seven days. The gastric ulcers were evaluated macroscopically, histologically, and biochemically. To evaluate the effects of LS in gastric ulcer recurrence, mice were ulcerated with 10% acetic acid and treated with vehicle, LS (1 mg/kg, p.o.), or ranitidine (100 mg/kg, p.o.), twice a day for ten days. Then, ulcer recurrence in these animals was induced by IL-1 β at five days after the treatment period., Results: The oral treatment with LS accelerated gastric healing by 63% in rats compared to the vehicle group, evidenced by histological improvement and increased gastric mucin levels. Moreover, the gastric healing effects of LS in rats were accompanied by an elevation in glutathione S-transferase activity and a reduction in myeloperoxidase activity. Furthermore, the LS treatment reduced the recurred lesions in mice., Conclusions: The oral treatment of LS accelerates gastric healing in rats by favoring mucus production and reducing neutrophil migration, and it also can reduce ulcer recurrence. These data highlighted this compound as promising for developing new pharmacological strategies for the management of gastric ulcer., Competing Interests: The authors have no conflicts of interest., (Copyright © 2022 Lincon Bordignon Somensi et al.)

Background: The preventive role of muscular strength on diminishing neuroinflammation is yet unknown. In this study, the role of the prophylactic muscular strength exercise was investigated in order to verify whether it would diminish cognitive alterations and modify the antioxidant intracellular scenery in an animal neuroinflammatory model in of the CA1 region of the hippocampus., Methods: The animals received muscular strength training (SE) three times a week for eight weeks. Subsequently, the stereotaxic surgery was performed with an intra-hippocampal infusion of either saline solution (SAL) or lipopolysaccharide (LPS). Next, we performed the behavioral tests: object recognition and social recognition. Then, the animals were euthanized, and their hippocampus and prefrontal cortex were collected. In another moment, we performed the dosage of the antioxidant activity and histological analysis., Results: The results showed that the muscular strength exercises could show a beneficial prophylactic effect in the cognitive deficiencies caused by acute neuroinflammation. Regarding oxidative stress, there was an increase in catalase enzyme activity (CAT) in the group (SE + LPS) compared to the control groups (p < 0.05). As for the cognitive alterations, there were found in the (SE + LPS) group, diminishing the mnemonic hazard of the discriminative and social memories compared to the control groups (p < 0.05)., Conclusion: We concluded, therefore, that the exercise performed prophylactically presents a protective effect capable of minimizing such mnemonic deficits and increasing catalase enzyme activity in rats that suffered a local neuroinflammatory process in the hippocampus., (© 2022. The Author(s).)

The hydroalcoholic extract of B. dracunculifolia (HEBD) and its major compound p-coumaric acid were evaluated against the severity of intestinal inflammation and behavioral changes like depressive and anxious behavior in colitis mice. Colitis was induced in Swiss mice by oral dextran sulfate sodium (DSS) administration for five days. The mice received vehicle (10 ml/kg), HEBD (3, 30, or 300 mg/kg), or p-coumaric acid (15 mg/kg) orally, once a day for twelve days. Behavioral tests were performed on the 11 th and 12 th days after the beginning of the treatments. Moreover, the colon, cortex, and hippocampus were collected to analyze oxidative and inflammatory parameters. The treatment with HEBD (300 mg/Kg), but not p-coumaric acid, showed decreased disease activity index (DAI) values compared to the vehicle group and partially preserved the villi architecture and mucin levels. Furthermore, the HEBD increased the antioxidant defenses in the colon and hippocampus and reduced the myeloperoxidase activity and IL-6 levels in the colon from colitis mice. Colitis mice treated with HEBD did not show depressive-like behavior in the tail suspension test. HEBD reduced colon inflammation, while it maintains antioxidant defenses and mucin levels in this tissue. It may reduce neuropsychiatric comorbidities associated with colitis through its antioxidant effects., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Tauani Caroline Santos França et al.)

A double-channel transmission line impedance model was applied to the study of supercapacitors to investigate the charge transport characteristics in the ionic and electronic conductors forming the electrode/solution interface. The macro homogeneous description of two closely mixed phases (Paasch-Micka-Gersdorf model) was applied to study the influence of disordered materials on the charge transport anomalies during the interfacial charge-discharge process. Different ex situ techniques were used to characterize the electrode materials used in electrical double-layer (EDLC) and pseudocapacitor (PC) devices. Two time constants in the impedance model were adequate to represent the charge transport in the different phases. The interfacial impedance considering frequency dispersion and blocked charge transfer conditions adequately described the charge storage at the interface. Deviations from the normal (Fickian) transport involving the ionic and electronic charge carriers were identified by the dispersive parameters (e.g., n and s exponents) used in the impedance model. The ionic and electronic transports were affected when the carbon-based electrical double-layer capacitor was converted into a composite with strong pseudocapacitive characteristics after the decoration process using NiO. The overall capacitance increased from 2.62 F g -1 to 536 F g -1 after the decoration. For the first time, the charge transport anomalies were unequivocally identified in porous materials used in supercapacitors with the impedance technique.

Boldine, 2,9-dihydroxy-1,10-dimethoxyaporphine, is the main alkaloid found in the leaves and bark of Peumus boldus Molina. In recent years, boldine has demonstrated several pharmacological properties that benefit endothelial function, blood pressure control, and reduce damage in kidney diseases. However, the renal vasodilator effects and mechanisms remain unknown. Herein, perfused rat kidneys were used to study the ability of boldine to induce vasodilation of renal arteries. For that, left kidney preparations with and without functional endothelium were contracted with phenylephrine and received 10-300 nmol boldine injections. The preparations were then perfused for 15 min with phenylephrine plus L-NAME, indomethacin, KCl, tetraethylammonium, glibenclamide, apamin, charybdotoxin, or iberiotoxin. In 30, 100, and 300 nmol doses, boldine induced a dose-and endothelium-dependent relaxing effect on the renal vascular bed. No vasodilator effects were observed in preparations lacking functional endothelium. While the inhibition of the cyclooxygenase enzyme through the addition of indomethacin did not cause any change in the vasodilating action of boldine, the nonselective nitric oxide synthase inhibitor L-NAME fully precluded the vasodilatory action of boldine at all doses tested. The perfusion with KCl or tetraethylammonium (nonselective K + channels blocker) also abolished the vasodilatory effect of boldine, indicating the participation of K + channels in the renal action of boldine. The perfusion with glibenclamide (selective ATP-sensitive K + channels blocker), iberiotoxin (selective high-conductance Ca 2+ -activated K + channel blocker), and charybdotoxin (selective high- and intermediate-conductance Ca 2+ -activated K + channel blocker) did not modify the vasodilatory action of boldine. On the other hand, the perfusion with apamin (selective small-conductance Ca 2+ -activated K + channel blocker) completely prevented the vasodilatory action of boldine at all doses tested. Together, the present study showed the renal vasodilatory properties of boldine, an effect dependent on the generation of nitric oxide and the opening of a small-conductance Ca 2+ -activated K + channel., Competing Interests: The authors declare that they have no conflicts of interest to disclose., (Copyright © 2022 Priscila de Souza et al.)

The studies published on the South Korean response to COVID-19 point to different reasons for the country's success. No reviews were identified on South Korea from January 2020 to April 2021 or that analyzed the pandemic's recrudescence. Aimed at better systematization of South Korea's success in controlling the epidemic, we conducted an integrative review to analyze that country´s experience with the COVID-19 pandemic, seeking to identify the relationship between the measures adopted, the health system's characteristics, and evolution of the selected indicators. Various databases were used, beside epidemiological bulletins and press conferences of the Korea Centers for Disease Control and Prevention (KCDC). We also analyzed reports by the World Health Organization (WHO) and the European Observatory on Health Systems and Policies. The study's results allow identifying a set of lessons based on the South Korean experience with control and management of the disease. The response by South Korea was successful, due to action in the control of risks and harms, action on social determinants to mitigate the socioeconomic effects of the health crisis, prior experience with other respiratory disease epidemics, and effective national coordination.

The identification of fish species using traditional methods is generally based only on morphological characteristics and these methods are currently under review. This kind of identification of hybrid fishes solely based on their morphologies may be unreliable, especially when the samples include juveniles and post-F1 lineage fishes. Therefore, in the present study, we used molecular markers to accurately identify the fish species of economic interest that are used as materials in the projects developed in research institutions. We evaluated six lots of fishes sampled from different research centers, containing a total of 84 specimens acquired from private fish farms that were considered to be the representatives of pure species. Genetic analyses of all the specimens revealed that, globally, 22 samples (26.2%) were interspecific hybrids, while 20 (90.9%) samples were surprisingly characterized as post-F1 hybrids. This result confirms that hybrids are sold in markets without adequate labeling and also indicates the lack of proper control of the commercialization and management of stocks and products in fish farms. In addition, we determined that molecular diagnosis was an extremely effective and necessary method to test the reliability of biological materials currently used in scientific research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Deoclécio da Silva, do Prado, Hashimoto, Senhorini, Foresti and Porto-Foresti.)

Background: Venous thromboembolism (VTE) is a major cause of perioperative morbimortality. Despite significant efforts to advance evidence-based practice, prevention rates remain inadequate in many centres., Objective: To evaluate the effectiveness of different strategies aimed at improving adherence to adequate VTE prophylaxis in surgical patients at high risk of VTE., Method: Before and after intervention study conducted at a tertiary hospital. Adherence to adequate VTE prophylaxis was compared according to three strategies consecutively implemented from January 2019 to December 2020. A dedicated hospitalist physician alone (strategy A) or in conjunction with a nurse (strategy B) overlooked the postoperative period to ensure adherence and correct inadequacies. Finally, a multidisciplinary team approach (strategy C) focused on promoting adequate VTE prophylaxis across multiple stages of care-from the operating room (ie, preoperative team-based checklist) to collaboration with clinical pharmacists in the postoperative period-was implemented., Results: We analysed 2074 surgical patients: 783 from January to June 2019 (strategy A), 669 from July 2019 to May 2020 (strategy B), and 622 from June to December 2020 (strategy C). VTE prophylaxis adherence rates for strategies (A), (B) and (C) were (median (25th-75th percentile)) 43.29% (31.82-51.69), 50% (42.57-55.80) and 92.31% (91.38-93.51), respectively (p<0.001; C>A=B). There was a significant reduction in non-compliance on all analysed criteria (risk stratification (A (25.5%), B (22%), C (6%)), medical documentation (A (68%), B (55.2%) C (9%)) and medical prescription (A (51.85%), B (48%), C (6.10%)) after implementation of strategy C (p<0.05). Additionally, a significant increase in compliance with adequate dosage, dosing interval and scheduling of the prophylactic regimen was observed., Conclusion: Perioperative VTE prophylaxis strategies that relied exclusively on physicians and/or nurses were associated with suboptimal execution and prevention. A multidisciplinary team-based approach that covers multiple stages of patient care significantly increased adherence to adequate VTE prophylaxis in surgical patients at high risk of developing perioperative VTE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this paper, we describe a case series of four patients who were admitted with emergencies related to aortic aneurysms over a 3-day period and were treated with endovascular repair. The first patient was an 81-year-old female with a history of abdominal pain and a ruptured aortic aneurysm diagnosed by AngioCT-scan. The second patient was a 63-year-old male with a history of oral digestive bleeding and an AngioCT-scan showing an aortoenteric fistula. The third patient was a 77-year-old female with sudden-onset abdominal pain and ruptured right common iliac aneurysm. The fourth patient presented with abdominal pain and an AngioCT-scan showed aortic rupture. All four patients were discharged with no major complications or surgical mortality. These case series show that despite the Covid-19 pandemic situation, since elective surgeries decreased, vascular emergencies have increased., Competing Interests: No conflicts of interest declared concerning the publication of this article., (Copyright© 2021 The authors.)

Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.

Objective: To analyze association between social position and access to health services., Methods: This was a cross-sectional study carried out in primary health care centers in Salvador, Bahia, Brazil, where a project for improving accessibility was implemented. Pearson's chi-square test and logistic regression were used., Results: 467 users took part in the study, 75.6% had not finished high school; 78.7% had <2 minimum wages; 51.8% had intermediate/qualified occupations. Low income was associated with starting to queue at the health care center the night before or before 8 a.m. (odds ratio = 2.09 - 95%CI 1.13;3.87) and spending more time scheduling an appointment (odds ratio = 2.13 - 95%CI 1.05;4.31). Having an elementary occupation was associated with face-to-face appointment scheduling (odds ratio = 1.68 - 95%CI 1.14;2.45). Education and social trajectory showed no significant association with use of health services., Conclusion: Social inequalities in access to health services remained after the intervention to improve accessibility.

Programmed death ligand-1 (PD-L1) inhibitors are currently under investigation as a potential treatment option for ovarian cancer. Although this therapy has shown promise, its efficacy is highly variable among patients. Evidence suggests that genomic instability influences the expression of PD-L1, but little is known about this relationship in ovarian cancer. To examine the relationship between PD-L1 expression and genomic instability, we measured DNA damage using Repair Assisted Damage Detection (RADD). We then correlated the presence of persistent DNA damage in the ovarian tumor with protein expression of PD-L1 using immunohistochemistry. Ovarian tumors showed a high prevalence of oxidative DNA damage. As the level of oxidative DNA damage increased, we saw a significant correlation with PD-L1 expression. The highest correlation between DNA damage and PD-L1 expression was observed for mucinous ovarian tumors (r = 0.82), but a strong correlation was also observed for high grade serous and endometrioid tumors (r = 0.67 and 0.69, respectively). These findings link genomic instability to PD-L1 protein expression in ovarian cancer and suggest that persistent DNA damage can be used as a potential biomarker for patient selection for immunotherapy treatment.

Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin, Tax) was identified as a gastroprotective compound and a gastroadhesive formulation was recently developed to prolong its residence time and release in the stomach. So, the gastric healing effectiveness of Tax and gastro-mucoadhesive microparticles containing Tax (MPTax) against the acetic acid induced-gastric ulcer in rats was investigated in this study. Moreover, the interactions between Tax and H + /K + -ATPase were investigated in silico, and its anti- H. pylori activity was determined in vitro. The oral treatment with MPTax (81.37 mg/kg, containing 12.29% of Tax) twice a day for seven days reduced the ulcer area by 63%, compared to vehicle-treated group (Veh: 91.9 ± 10.3 mm 2 ). Tax (10 mg/kg, p.o) reduced the ulcer by 40% but with a p = 0.07 versus Veh group. Histological analysis confirmed these effects. Tax and MPTax increased the gastric mucin amount, reduced the myeloperoxidase activity, and increased the glutathione reduced content at ulcer site. However, only MPTax decreased the lipoperoxide accumulation at ulcer site. Besides, Tax and MPTax normalize the catalase and glutathione S-transferase activity. Tax showed reversible interaction with H + /K + -ATPase in silico and its anti-H. pylori effects was confirmed (MIC = 625 μg/mL). These results suggest that the antiulcer property of Tax involves the strengthening of the gastric protective factors in parallel to its inhibitory interaction with H + /K + -ATPase and H. pylori. Considering that ulcer healing action displayed by Tax was favored by gastroadhesive microparticles, this approach seems to be promising for its oral delivery to treat acid-peptic diseases., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: The aim of this study was to evaluate the frequency and median time for the development of metastases and prognosis by metastatic site after the diagnosis of non-small-cell lung cancer (NSCLC). Patients & methods: This cohort study was conducted with 1096 patients diagnosed with NSCLC between 2006 and 2014. Results: The most prevalent site of NSCLC metastases was the respiratory system. The nervous and adrenal systems presented the longest median time for the development of metastases. The 6-month survival varied from 68.2% for liver to 79.9% for the nervous system. Bone metastases were associated with a higher risk of death. Conclusion: The respiratory system was the most prevalent site of metastases. OS and risk of death varied according to the metastatic site.

Background: Orotracheal intubation (OTI) can result in aerosolisation leading to an increased risk of infection for healthcare providers, a key concern during the COVID-19 pandemic., Objective: This study aimed to evaluate the OTI time and success rate of two aerosol-mitigating strategies under direct laryngoscopy and videolaryngoscopy performed by anaesthesiologists, intensive care physicians and emergency physicians who were voluntarily recruited for OTI in an airway simulation model., Methodology: The outcomes were successful OTI, degree of airway visualisation and time required for OTI. Not using a stylet during OTI reduced the success rate among non-anaesthesiologists and increased the time required for intubation, regardless of the laryngoscopy device used., Results: Success rates were similar among physicians from different specialties during OTI using videolaryngoscopy with a stylet. The time required for successful OTI by intensive care and emergency physicians using videolaryngoscopy with a stylet was longer compared with anaesthesiologists using the same technique. Videolaryngoscopy increased the time required for OTI among intensive care physicians compared with direct laryngoscopy. The aerosol-mitigating strategy under direct laryngoscopy with stylet did not increase the time required for intubation, nor did it interfere with OTI success, regardless of the specialty of the performing physician., Conclusions: The use of a stylet within the endotracheal tube, especially for non-anaesthesiologists, had an impact on OTI success rates and decreased procedural time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Wolbachia is an endosymbiotic bacterium that naturally infects several arthropods and nematode species. Wolbachia gained particular attention due to its impact on their host fitness and the capacity of specific Wolbachia strains in reducing pathogen vector and agricultural pest populations and pathogens transmission. Despite the success of mosquito/pathogen control programs using Wolbachia -infected mosquito release, little is known about the abundance and distribution of Wolbachia in most mosquito species, a crucial knowledge for planning and deployment of mosquito control programs and that can further improve our basic biology understanding of Wolbachia and host relationships. In this systematic review, Wolbachia was detected in only 30% of the mosquito species investigated. Fourteen percent of the species were considered positive by some studies and negative by others in different geographical regions, suggesting a variable infection rate and/or limitations of the Wolbachia detection methods employed. Eighty-three percent of the studies screened Wolbachia with only one technique. Our findings highlight that the assessment of Wolbachia using a single approach limited the inference of true Wolbachia infection in most of the studied species and that researchers should carefully choose complementary methodologies and consider different Wolbachia -mosquito population dynamics that may be a source of bias to ascertain the correct infectious status of the host species.

This study evaluated the gastric healing activity of eugenol, the main bioactive compound from clove (Syzygium aromaticun) essential oil. Five groups of female Wistar rats were submitted to acetic acid-induced ulcer model and treated with Vehicle (1 mL/kg, p.o.), eugenol (1, 10 or 100 mg/kg, p.o) or omeprazole (20 mg/kg, p.o), twice a day, by seven or fourteen days. Macroscopic, microscopic and biochemical analyses were performed in the ulcerated site. Eugenol (1 mg/kg, p.o) administered by 7 or 14 days accelerated the gastric healing process by 33% and 52%, respectively. The healing actions of eugenol were accompanied by the rescue on the histological architecture and the normalization of the superoxide dismutase and catalase activity. Moreover, eugenol (1 mg/kg, p.o) reduced the gastric mucosal myeloperoxidase activity and increased the mucin secretion. In contrast, eugenol at a dose of 100 mg/kg administered by 7 days enhanced 49% the ulcerated area, but at 10 mg/kg did not change the ulcer area after 7 or 14 days of treatment. Thus, despite the undesirable results due to the worsening of the gastric lesion with the use of eugenol in high doses, the antiulcer potential of this compound is evident and manageable in an adequate dose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

It is common to find in the literature different values for the working voltage window (WVW) range for aqueous-based supercapacitors. In many cases, even with the best intentions of the widening the operating voltage window, the measured current using the cyclic voltammetry (CV) technique includes a significant contribution from the irreversible Faradaic reactions involved in the water-splitting process, masked by fast scan rates. Sometimes even using low scan rates is hard to determine precisely the correct WVW of the aqueous-based electrochemical capacitor. In this sense, we discuss here the best practices to determine the WVW for capacitive current in an absence of water splitting using complementary techniques such as CV, chronoamperometry (CA), and the electrochemical impedance spectroscopy (EIS). To accomplish this end, we prepare and present a model system composed of multiwalled carbon nanotubes buckypaper electrodes housed in the symmetric coin cell and soaked with an aqueous-based electrolyte. The system electrochemical characteristics are carefully evaluated during the progressive enlargement of the cell voltage window. The presence of residual Faradaic current is verified in the transients from the CA study, as well as the impedance changes revealed by EIS as a function of the applied voltage, is discussed. We verify that an apparent voltage window of 2.0 V determined using the CV technique is drastically decreased to 1.2 V after a close inspection of the CA findings used to discriminate the presence of a parasitic Faradaic process. Some orientations are presented to instigate the establishment in the literature of some good scientific practices concerned with the reliable characterization of supercapacitors.

Natural products have been recognized as important bioactive compounds on the basis of their wide biological properties. Here we investigated the antitumor effect and molecular mechanisms of the diterpene Fruticuline A (fruti) from Salvia lachnostachys, in human cancer cell lineages and Solid Ehrlich Carcinoma in mice. Fruti reduced MCF-7 and HepG2 proliferation by the reduction of Cyclin D1 levels and decreased NF-κB gene levels in both cell types. Furthermore, fruti also induced apoptosis in HepG2 cells, reduced Bcl-2 gene expression and induced necroptosis by increasing Ripk in MCF-7 cells. In mice, fruti prevented tumor development and reduced Cyclin D1, Bcl-2 and Rela gene levels, and reduced the p-NF-κB/NF-κB ratio in tumor tissue. Furthermore, fruti induced necrosis and apoptosis, increased N-acetyl-β-D-glucosaminidase and TNF-α levels and reduced IL-10 and Vegf levels in tumor tissue. Collectively, fruti exerts antitumor effects through the inhibition of the NF-κB pathway, reducing Cyclin D1 and Bcl-2 levels. In vitro the apoptosis and necroptosis pathways are involved in the cellular death, whereas in vivo, cells undergo necrosis by increased tumor inflammation and reduction of angiogenesis. Thus, fruticuline A acts in tumor cells by multiple mechanisms and represents a promising molecule for drug development in cancer treatment.

Boldine is the main alkaloid of Peumus boldus Molina, widely used in the traditional medicine for the treatment of digestive disorders. It is a compound with excellent antioxidant and anti-inflammatory properties already described. Despite the widespread use of P. boldus for digestive disorders treatment, the gastroprotective effect of Boldine remains unknown. Considering the need for new approaches to treat gastric ulcers with fewer side effects than current therapy, this study aimed to investigate the gastroprotective effect of Boldine in mice, as well as the mechanisms underlying this effect. The gastroprotective effect of Boldine was evaluated on gastric ulcer induced by 60% ethanol/0.3 M HCl or indomethacin (100 mg/kg) in mice. Histological analysis and the mucin-like glycoprotein content were evaluated in ethanol-ulcerated tissue, as well as, oxidative stress and inflammatory parameters. The mechanisms involved in the effect of Boldine were evaluated by pretreating mice with NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), l-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p.). In addition, the in vitro effect of Boldine on H + /K + -ATPase activity was determined. Boldine was able to protect gastric mucosa against the damage induced by ethanol/HCl and indomethacin, as evidenced by reduced lesion area and histological analysis. Moreover, the alkaloid reduced oxidative stress and inflammatory mediators in ethanol-ulcerated tissue, beyond has increased mucin-like glycoprotein amount. Finally, Boldine effect is dependent on non-protein sulfhydryl groups and prostanoids but does not involve the inhibition of H+/K + -ATPase activity, being a promising natural resource for gastric ulcer treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To analyse the use of polymyxins for the treatment of ventilator-associated pneumonia (VAP) at a teaching hospital where carbapenem-resistant gram-negative bacteria are endemic., Patients and Methods: This was a historical cohort study of patients receiving polymyxins to treat VAP in ICUs at a public university hospital in southern Brazil between January 1, 2017 and January 31, 2018., Results: During the study period, 179 cases of VAP were treated with polymyxins. Of the 179 patients, 158 (88.3%) were classified as having chronic critical illness. Death occurred in 145 cases (81.0%). Multivariate analysis showed that the factors independently associated with mortality were the presence of comorbidities (P<0.001) and the SOFA score of the day of polymyxin prescription (P<0.001). Being a burn patient was a protective factor for mortality (P<0.001). Analysis of the 14-day survival probability showed that mortality was higher among the patients who had sepsis or septic shock at the time of polymyxin prescription (P = 0.028 and P<0.001, respectively). Acinetobacter baumannii was identified as the etiological agent of VAP in 121 cases (67.6%). In our cohort, polymyxin consumption and the incidence density of VAP were quite high., Conclusions: In our study, comprised primarily of chronically critically ill patients, there was a high prevalence of VAP caused by multidrug-resistant bacteria, consistent with healthcare-associated infections in low- and middle-income countries. Presence of comorbidities and the SOFA score at the time of polymyxin prescription were predictors of mortality in this cohort. Despite aggressive antimicrobial treatment, mortality was high, stressing the need for antibiotic stewardship., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Intestinal mucositis refers to mucosal damage caused by cancer treatment, and irinotecan is one of the agents most associated with this condition. Focusing on the development of alternatives to prevent this important adverse effect, we evaluated the activity of the flavonoid luteolin, which has never been tested for this purpose despite its biological potential., Experimental Approach: The effects of luteolin were examined on irinotecan-induced intestinal mucositis in mice. Clinical signs were evaluated. Moreover, histological, oxidative, and inflammatory parameters were analysed, as well as the possible interference of luteolin in the anti-tumour activity of irinotecan., Key Results: Luteolin (30 mg·kg -1 ; p.o. or i.p.) prevented irinotecan-induced intestinal damage by reducing weight loss and diarrhoea score and attenuating the shortening of the duodenum and colon. Histological analysis confirmed that luteolin (p.o.) prevented villous shortening, vacuolization, and apoptosis of cells and preserved mucin production in the duodenum and colon. Moreover, luteolin treatment mitigated irinotecan-induced oxidative stress, by reducing the levels of ROS and LOOH and augmenting endogenous antioxidants, and inflammation by decreasing MPO enzymic activity, TNF, IL-1β, and IL-6 levels and increasing IL-4 and IL-10. Disruption of the tight junctions ZO-1 and occludin was also prevented by luteolin treatment. Importantly, luteolin did not interfere with the anti-tumour activity of irinotecan., Conclusion and Implications: Luteolin prevents intestinal mucositis induced by irinotecan and therefore could be a potential adjunct in anti-tumour therapy to control this adverse effect, increasing treatment adherence and consequently the chances of cancer remission., (© 2020 The British Pharmacological Society.)

Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5) and Lupeol caprylate (6) were obtained reacting 1 with an adequate carboxylic acid. Swiss mice were treated with vehicle, carbenoxolone or Lupeol esters before administration of ethanol/HCl or indomethacin. Additionally, the involvement of nitric oxide (NO), sulfhydryl compounds (NP-SH), α-2 adrenergic receptors (α2-AR) and prostaglandins (PGE) in antiulcer effects was investigated using appropriate inhibitors or antagonist. Oxidative and inflammatory parameters were measured after euthanasia and anti-secretory effects was evaluated in pylorus-ligated rats. Ethanol/HCl ulcerated the gastric mucosa by 64.45 ± 6.58 mm 2 , which the oral treatment with 1, 4 and 6 (10 mg/kg), and 3 and 5 (30 mg/kg) reduced the lesion area. Interestingly, 2 reduced the gastric ulcer by oral route in a potent and dose-dependent manner (ED 50  = 0.40 mg/kg), which was accompanied by the increase in reduced glutathione levels and by the reduction of lipids peroxidation and myeloperoxidase and superoxide dismutase activities. Moreover, 2 (0.1 mg/kg) also prevented the ulcerogenesis by intraperitoneal route. The participation of NO, NP-SH, α2-AR and PGE in 2-mediated gastroprotection was confirmed. In indomethacin-induced ulcer, 2 (1 mg/kg, p.o) also reduced the ulcer area and increased the PGE 2 levels. However, 2 did not alter the gastric acid secretion. Therefore, these findings indicate that the obtention of 2 potentiated the antiulcer activity of 1 and that this compound can elicit gastroprotective action due a diversified mode of action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Magnetic silver nanoparticles (MNPAg) are interesting nanotechnology materials with borderless environmental science, that can be used to disinfect water contaminated with pathogenic bacteria. The use of MNPAg leads to increased risk of nanomaterial contamination in the environment, especially natural water sources, with harmful effects on the ecosystem. This study investigating survival and enzyme activity of magnetic O-carboxymethylchitosan loaded silver nanoparticle on Artemia salina. The results showed that mortality increased with increasing concentrations of MNPAg. O-Carboxymethylchitosan loaded silver nanoparticles were found to be more toxic, with a LC 50 of 902.1 mg/L for γ-Fe 2 O 3 /Ag without reducing agent. Accumulation of silver on Artemia salina depends on the type of nanoparticle. Accumulation of nanoparticle containing polymers (carboxymethylchitosan/γ-Fe 2 O 3 /Ag without reducing agent, carboxymethylchitosan/γ-Fe 2 O 3 /Ag reduced with sucrose and carboxymethylchitosan/γ-Fe 2 O 3 /Ag reduced with NaBH 4 ) were found to be higher than γ-Fe 2 O 3 /Ag reduced with NaBH 4 , γ-Fe 2 O 3 /Ag reduced with sucrose and γ-Fe 2 O 3 /Ag without reducing agent under the same experimental conditions. The antioxidant enzyme (CAT, SOD and GST) activities increased slightly following exposure, indicating that the toxic effects are related to oxidative stress. The combined results so far indicate that MNPA does not have the potential to affect aquatic organisms when released into the ecosystem., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study aimed to verify the effect of methanolic extract, fractions, and phenolic compounds of Eugenia mattosii D. Legrand leaves on the aorta relaxation. Isometric tensions were measured on the aorta of normotensive (NTR) and spontaneously hypertensive rats (SHR). The results showed that both methanolic extracts of leaves and stems, as well as, fractions obtained from leaves were able to induce a concentration-dependent relaxation in both endothelium-intact and -denuded aortas. The methanolic extract of leaves (ME-leaves) was the most effective since the maximal relaxation (≈ 83%) obtained was at the concentration of 300 μg/mL. As the endothelium-dependent relaxation was more significant, we investigated the mechanisms by which ME-leaves induced this effect. After the pretreatment with LNAME, ME-leaves-induced relaxation was decreased in the aorta of NTR and SHR. However, the pretreatment with methylene blue only reduced the relaxation in the aorta of NTR. Furthermore, pretreatment with ME-leaves decreased phenylephrine-induced contraction in preparation Ca 2+ -free only in aortic rings from NTR. This study also reveals that both compounds, cryptostrobin isolated from chloroform fraction and catechin from the ethyl acetate fraction induced a marked relaxation in endotheliumintact aortic rings of NTR. In conclusion, ME-leaves induces relaxation in the rat aorta involves the modulation of NO/cGMP dependent signaling pathway, this mechanism may at least, in part, explain the endothelium-dependent relaxation. Furthermore, cryptostrobin and catechin also induced relaxation, which may contribute synergistically to the vasorelaxation effect of the ME-leaves., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© King Abdulaziz City for Science and Technology 2019.)