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Adriana Aparecida Siviero-Miachon,1,2 Angela Maria Spinola-Castro,1,2 Maria Lucia de Martino Lee,2 Carlos Manoel de Castro Monteiro,3 Antonio Carlos de Camargo Carvalho,4 Antonio Ramos Calixto,5 Bruno Geloneze,5 Gil Guerra-Junior6 1Division of Pediatric Endocrinology, Department of Pediatrics, Federal University of Sao Paulo (UNIFESP/EPM), 2Pediatric Oncology Institute – IOP/GRAACC, Federal University of Sao Paulo (UNIFESP/EPM), 3Private Office, Castro Monteiro, Sao Paulo, 4Division of Cardiology, Federal University of Sao Paulo (UNIFESP/EPM), 5Laboratory of Investigation on Metabolism and Diabetes (LIMED), Faculty of Medical Sciences, State University of Campinas (UNICAMP), 6Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Brazil Purpose: The aim of this study was to evaluate the relationship between body composition, metabolic profile, adipokines, and carotid intima-media thickness (cIMT) in young survivors of childhood acute lymphocytic leukemia (ALL). Patients and methods: This cross-sectional study compared 55 ALL survivors, of chronological age between 15 years and 24 years, assigned into two groups according to the exposure to cranial radiation therapy (CRT; 25 irradiated and 30 nonirradiated) with 24 leukemia-free controls, and assessed body fat mass (dual-energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, blood pressure (BP), adipokines, and cIMT by a multiple regression analysis. Results: Treatment with CRT had an effect on all of the variables derived from the computed tomography scan: visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (P

Ana Carolina Proença da Fonseca,1,2 Gabriella de Medeiros Abreu,2 Lohanna Palhinha,1 Verônica Marques Zembrzuski,2 Mario Campos Junior,2 João Regis Ivar Carneiro,3 José Firmino Nogueira Neto,4 Fernanda Cristina C Mattos Magno,5 Eliane Lopes Rosado,5 Clarissa Menezes Maya-Monteiro,1 Giselda Maria Kalil de Cabello,2 Pedro Hernán Cabello,2,6 Patricia Torres Bozza1 1Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 3Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 4Department of Pathology and Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brazil; 5Institute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 6Human Genetics Laboratory, Grande Rio University, Rio de Janeiro, BrazilCorrespondence: Ana Carolina Proença da FonsecaHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 4365 Brasil Avenue, Leônidas Deane Building – Office 611/615, Rio de Janeiro, RJ 21040-360, BrazilTel +552138658192Fax +552138658239Email ana.proenca@ioc.fiocruz.brBackground: Brain-derived neurotrophic factor (BDNF) is a pro-survival factor in the brain that also regulates energy balance. BDNF loss-of-function point mutations are responsible for haploinsufficiency, causing severe early-onset obesity. Up to date, only a few studies have sequenced this gene to search for rare mutations related to obesity. In this study, we aimed to investigate the prevalence of BDNF variants in a cohort of adults with severe obesity from Brazil.Material and Methods: This study comprised 201 adults with severe obesity (BMI ≥ 35.0 kg/m2) with onset during childhood- or adolescence/youth. As controls, 73 subjects with normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2) were selected. The exclusion criteria were pregnancy, lactation, the use of medication to lose or gain weight, and the presence of symptoms suggestive of syndromic obesity (only for the case group). The coding region of the BDNF gene was screened by Sanger sequencing. Demographic, anthropometric, and blood pressure parameters were obtained from the participants as well as serum hormone and cytokines concentrations and biochemical values.Results: As a result, three missense variants [p.(Thr2Ile), p.(Val66Met), and p.(Arg209Gln)] and four synonymous variants (p.Leu107=, p.Thr149=, p.Ala150=, and p.Ser213=) were identified. The p.(Arg209Gln) was predicted as pathogenic by all in silico algorithms used and was not observed in the control group. The individuals carrying the p.(Val66Met) mutated allele had higher waist circumference, HDL-cholesterol and MCP1 levels, and reduced risk of developing metabolic syndrome.Conclusion: We observed that the common BDNF p.(Val66Met) variant has influenced waist circumference, HDL-cholesterol, and MCP1 levels. This polymorphism has also a protective effect on metabolic syndrome susceptibility. Additionally, we described for the first time a rare potentially pathogenic BDNF variant in a Brazilian patient with severe obesity and childhood-onset.Keywords: BDNF, severe obesity, rare mutation, early-onset obesity, metabolic syndrome

Objective: Chronic inflammation's role in the pathogenesis, development, and rupture of vascular malformations is undebated. Advanced magnetic resonance imaging techniques with vessel wall studies, specifically Black Blood (bbMRI), may offer insights into vascular wall instability and predict rupture. This case series aims to assess bbMRI as a predictive diagnostic tool for brain arteriovenous malformations (bAVMs) rupture, suggesting early treatment., Material and Methods: A prospective study included demographic, clinical, and neuroimaging data from a consecutive series of patients with ruptured or unruptured bAVMs, regardless of age or gender, between October 2018 and March 2024. All patients underwent MRI brain resonance with Black Blood study. Those with impaired renal function were excluded. Statistical analyses tested sample homogeneity. Univariate and multivariate logistical regressions assessed bbMRI as a rupture predictor for bAVMs, with a p-value set at < 0.05., Results: Ninety patients were retrieved: 64 with unruptured and 26 with ruptured bAVMs. The mean age was 31.9 years, and 55 were female. Admission symptoms were headache, neurological deficits, and seizure in 49, 21, and 19 cases, respectively. bbMRI showed wall enhancement in 56 cases, with 19 in the ruptured and 37 unruptured groups. Univariate and multivariate analyses revealed a significant correlation between bbMRI wall enhancement and bAVM rupture (p:0.033; p:0.047)., Conclusion: bbMRI may be a useful and feasible diagnostic implement to determine vessel inflammation and the bAVMs prone to rupture. Additional studies are needed to confirm the positive bbMRI as a predictive factor for bAVMs rupture., Competing Interests: Declarations Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Federal University of São Paulo (No. 2936701). Consent to participate Informed consente was obtained from all individual participants included in the study. Consent to publish The authors affirm that human research participants provided informed consente for publication of the images in Figs. 1 and 2, 3 A, 3B, 3 C, 4 A, 4B and 4 C. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ethnopharmacological Relevance: Acmella oleracea (L.) R. K. Jansen, commonly referred to as "Jambu", is a valuable medicinal plant native to the Amazon regions. Inflorescences of A. oleracea is utilized as local anesthetic properties and for its insecticidal, antiparasitic, and anthelmintic attributes., Aims of This Study: This study aimed to evaluate the in vitro and in vivo antiparasitic properties of A. oleracea extract and spilanthol (SPL) against Schistosoma mansoni., Materials and Methods: The ethanolic extract of A. oleracea inflorescences (AoE) was prepared, analyzed by HPLC-DAD, and characterized by UHPLC-HRMS/MS. SPL was isolated from AoE by chromatographic fractionation. The antischistosomal properties of AoE and SPL were evaluated in vitro against adult schistosomes and in preclinical assays using murine models of patent S. mansoni infection., Results: Through UHPLC-HRMS/MS analysis, 14 alkamides were annotated in AoE. HPLC-DAD analysis of AoE revealed a peak with a substantial relative area of ∼85%, which was isolated and identified as SPL. AoE and SPL caused mortality of adult schistosomes ex vivo, showing EC 50 values of 32.6 μg/mL and 27.8 μM, respectively, without affected Vero cells or Caenorhabditis elegans. In preclinical studies, the oral administration (400 mg/kg) of AoE and SPL resulted in significant reductions in worm burden of 28% and ∼42%, respectively. Additionally, SPL exhibits remarkable effects on oogram, decreasing egg burden and the number of immature eggs by over 80%, while also promoting significant reductions in hepato- and splenomegaly., Conclusions: The research underscores the antischistosomal activity of A. oleracea highlighting the potential of SPL as a lead for the development of new schistosomicidal drugs and encouraging further studies to validate the traditional anthelmintic use of A. oleracea inflorescences., 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 © 2024 Elsevier B.V. All rights reserved.)

A single dose of standard yellow fever (YF) vaccine is considered to provide life-long protection. In this study, we evaluate the seropositivity conferred by lower doses 10 years post-vaccination. In 2009, Bio-Manguinhos/Fiocruz performed a dose-response study with the 17DD yellow fever vaccine, administering the vaccine in the usual mean dose of 27.476 IU and in decreasing doses (10.447 IU, 3.013 IU, 587 IU, 158 IU and 31 IU), with the usual volume and route (0,5 ml subcutaneous). The decreasing doses were obtained by dilution in the laboratory of the manufacturer and the lots in test had standard quality control and were produced by good manufacturing practices (GMP). Around 30 days after the vaccination, doses down to 587 IU had similar immunogenicity and the 158 IU and 31 IU were inferior to the full dose. The seropositivity was maintained for 10 months, except on the 31 IU group. Eight years after, 85 % of 318 participants evaluated in a follow-up, maintained seropositivity that was similar across groups. Consistently, antibody titers in the reduced-dose groups were also comparable to those of the full-dose group. The current study, 10 years later, showed similarity between the vaccine groups (six arms who received the YF vaccine in decreasing doses: 27.476 IU, 10.447 IU, 3.013 IU, 587 IU, 158 IU, 31 IU) both in relation of seropositivity and in the evaluation of the geometric mean titers. The seropositivity rates across subgroups were 83,1%, 90 %, 87 %, 93 %, 83,8% and 85 %, correspondingly. These findings provides further support to the long-term immunogenicity of lower doses. Clinical trial registry: NCT04416477., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: This study aimed to assess the antimicrobial potential of Bp1-AdE, produced by Bacillus pumilus 64-1, and to investigate its mode of action against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA)., Methods and Results: Bp-1AdE, derived from sponge-associated B. pumilus, exhibited bactericidal activity at 1 550 µg ml-1 against S. aureus ATCC29213 and MRSA strains. Light and fluorescence microscopy revealed drastic cell lysis of S. aureus treated with Bp-1AdE. Scanning and transmission electron microscopy suggested that Bp-1AdE disrupts the cytoplasmic membrane. Toxicity assays showed that Bp-1AdE was non-toxic to Tenebrio molitor larvae. Liquid chromatography-mass spectrometry and Global Natural Product Social spectral libraries identified four substances within Bp-1AdE, including aliphatic alcohols [3,4-dipentylhexane-2,5-diol and 1,1'-(4,5-dibutyl-3,6-dimethylcyclohexane-1,2-diyl)bis(ethan-1-one)] and terpenoids (cholic acid and canrenone)., Conclusions: Bp-1AdE demonstrated selective toxicity and bactericidal activity, highlighting its potential for controlling infections caused by multidrug-resistant S. aureus strains., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Introduction: In adult horses, the development and evaluation of enteral electrolyte solutions containing sodium acetate for correcting hyperchloremic metabolic acidosis are still lacking, although these electrolyte and acid-base imbalances are commonly observed. The objective of this study was to evaluate the alkalinizing effect of two enteral electrolyte solutions containing different concentrations of acetate, administered via nasogastric tube in continuous flow, in adult horses with experimental hyperchloremic metabolic acidosis., Methods: Six mares aged between 3 and 10 years were used in a 6×2 crossover design, with each animal receiving both treatments. The horses were subjected to a protocol to induce hyperchloremic metabolic acidosis. They then received one of two treatments: HighAcetate (81.4 mmol/L) and LowAcetate (22.7 mmol/L) at an infusion rate of 15 mL/kg/h for 12 h. Plasma, serum, and urinary biochemical assessments; hematocrit; urinary volume, pH, and specific gravity; and blood gas analysis were measured at the following time points: T-12 h (beginning of the 12-h fast), T0h (end of fasting and beginning of the acidosis induction phase), every 2 h during the hyperchloremic metabolic acidosis induction phase (T i 2h and T i 4h), every 2 h during the 12-h enteral hydration phase (T t 2h, T t 4h, Tt6h, T t 8h, T t 10h, and T t 12h), with one sample taken at T24h (24 h after the start of acidosis induction) and another at T36h (36 h after the start of acidosis induction). Data were analyzed using descriptive statistics and analysis of variance based on a factorial design of repeated measures, with Tukey's post-hoc test or the Kruskal-Wallis test with Dunn's post-hoc test for non-parametric tests., Results: At the end of the induction phase, the animals developed moderate to severe hyperchloremic metabolic acidosis. The HighAcetate solution effectively corrected electrolyte and acid-base imbalances before the end of the treatment phase (Tt12h), while the LowAcetate solution was not effective in correcting those changes., Conclusion: The HighAcetate (81.4 mmol/L) solution is deemed an effective and safe alternative for the treatment of hyperchloremic metabolic acidosis in horses., 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 © 2024 Monteiro, Costa, Ermita, Júnior, Mattos, Mansur, dos Santos, Alves, Mafort, Fidélis, Avanza, Teixeira, Viana and Filho.)

Background: In response to the coronavirus disease 2019 (Covid-19) pandemic, Brazil authorised the Astra Zeneca/Fiocruz vaccine in January 2021. As the Delta variant emerged in May 2021, interval between vaccine doses was adjusted. By September 2021, the Brazilian National Immunisation Program recommended a booster dose for individuals over 70, and later expanded the recommendation to all adults., Objectives: Assess the equivalence of IgG antibody response against the Covid-19 S protein before and approximately 28 days after the third dose of a Covid-19 recombinant vaccine. Two groups received initial two doses with intervals of eight and 12 weeks., Methods: This is a phase IV clinical study, uncontrolled, non-randomised. The study proposes calculating the ratio of geometric means titres (GMT) 28 days after the third dose, with a target ratio of confidence interval (CI) between 0.77 and 1.3., Findings: In the primary endpoint, there was no equivalence between the eight- and 12-week intervals with a slight variation favouring the eight-week group. Post-third dose, both groups showed increases titres at 28 days, three months, six months and 12 months. Both groups responded similarly to Delta and Omicron BA.1, with a more significant increase for Delta., Main Conclusions: The study showed strong and consistent immune response in all age groups receiving the Covid-19 recombinant vaccine. Third dose elicited an increase in GMT by at least three times aligned with Ministry of Health strategies emphasising Bio-Manguinhos crucial role in pandemic control in the country.

Isolated 17,20-lyase deficiency (ILD) is a partial form of 17α-hydroxylase/17,20-lyase deficiency that typically presents with infertility and lack of pubertal development. Successful live births have been achieved using assisted reproductive techniques. We present a case of spontaneous pregnancy in an 18-year-old female with ILD without reproduction treatments or glucocorticoid use. She presented to our clinic with absence of pubarche and oligomenorrhea and had typical external genitalia and complete breast development. Follicular phase progesterone and estradiol were within reference values, and androgen levels were undetectable. Corticosterone was increased, and cortisol responded partially to the ACTH-stimulation test. This profile raised a suspicion for ILD, which was confirmed by the finding of the homozygous p.R347H variant in the CYP17A1 gene. Sex steroid replacement and glucocorticoid use during stress were prescribed. She returned 2 years later 20 weeks pregnant. Her gestation was uneventful, and a full-term healthy male was born. This phenomenon could be partially explained by sufficient estrogen synthesis via residual 17,20-lyase enzymatic activity. Intermittent estradiol use may have favored uterine development and fine-tuned the pituitary-gonadal axis rhythm. Normal progesterone levels may have permitted an adequate endometrial "implantation window" without glucocorticoid use. Finally, elevated corticosterone may have compensated for the partial cortisol deficiency., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

A three-dimensional (3D) cell culture can more precisely mimic tissues architecture and functionality, being a promising alternative model to study disease pathophysiology and drug screening. Chagas disease (CD) is a neglected parasitosis that affects 7 million people worldwide. Trypanosoma cruzi's ( T. cruzi ) mechanisms of invasion/persistence continue to be elucidated. Benznidazole (BZ) and Nifurtimox (NF) are trypanocidal drugs with few effects on the clinical manifestations of the chronic disease. Chronic Chagas cardiomyopathy (CCC) is the main manifestation of CD due to its frequency and severity. The development of fibrosis and hypertrophy in cardiac tissue can lead to heart failure and sudden death. Thus, there is an urgent need for novel therapeutic options. Our group has more than fifteen years of expertise using 3D primary cardiac cell cultures, being the first to reproduce fibrosis and hypertrophy induced by T. cruzi infection in vitro. These primary cardiac spheroids exhibit morphological and functional characteristics that are similar to heart tissue, making them an interesting model for studying CD cardiac fibrosis. Here, we aim to demonstrate that our primary cardiac spheroids are great preclinical models which can be used to develop new insights into CD cardiac fibrosis, presenting advances already achieved in the field, including disease modeling and drug screening.

Background: Image and Performance-Enhancing Drugs (IPEDs) can enhance mental and physical capabilities and impact one's overall health. Initially confined in sport environments, IPEDs use has become increasingly widespread in a high-performing society. The present study was aimed at profiling IPEDs use during the COVID-19 lockdown among an international sample of young adults., Methods: A cross-sectional observational study was carried out in eight countries (United Kingdom, Italy, Lithuania, Hungary, Portugal, Spain, Brazil, and Japan) between April and May 2020. The survey questionnaire included validated measurements such as Exercise Addiction Inventory (EAI), Appearance Anxiety Inventory (AAI), and Self-Compassion Scale (SCS) as well as questions about the type of IPEDs, purchasing methods and socio-demographic information., Results: A total of 736 IPEDs users were included in the survey. Their mean age was 33.05 years (± SD  = 10.06), and 64.2% were female participants. Overall, 6.8% were found at risk of exercise addiction (EAI >24), 27.6% presented high levels of appearance anxiety, and 24.9% revealed low levels of emotional regulation's self-compassion. Most participants (55.6%) purchased IPEDs through pharmacies/specialized shops, while 41.3% purchased IPEDs on the Internet. Online IPEDs buyers were mainly men who had higher scores on the Exercise Addiction Inventory. One or more IPEDs classifiable as "potentially risky" were used by 66.3% of the sample. Users of "potentially risky IPEDs" were younger and primarily men. They showed higher scores both on the Exercise Addiction Inventory and Appearance Anxiety Inventory., Conclusion: This study profiled users of IPEDs when the most restrictive COVID-19 lockdown policies were implemented in all the participating countries. More targeted post-COVID 19 prevention strategies should be implemented according to the emerged socio-demographic and psychopathological traits and cross-cultural differences emerged. Longitudinal studies will also be needed to determine the long-term effect of the COVID-19 lockdown on IPEDs consumption., 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 © 2024 De Luca, Di Carlo, Burkauskas, Dores, Carvalho, Gómez-Martínez, Szabo, Fujiwara, Barbosa, Di Nicola, Mazza, Sani, Luciani, Pettorruso, di Giannantonio, Cataldo, Esposito, Martinotti, Zandonai, Rabin and Corazza.)

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.

Introduction: Obesity is a multifactorial disease associated with the development of many comorbidities. This disease is associated with several metabolic alterations; however, it has been shown that some individuals with obesity do not exhibit metabolic syndrome. Adipose tissue neutralizes the detrimental effects of circulating fatty acids, ectopic deposition, and inflammation, among others, through its esterification into neutral lipids that are stored in the adipocyte. However, when the adipocyte is overloaded, i.e., its expansion capacity is exceeded, this protection is lost, resulting in fatty acid toxicity with ectopic fat accumulation in peripheral tissues and inflammation. In this line, this study aimed to investigate whether polymorphisms in genes that control adipose tissue fat storage capacity are potential biomarkers for severe obesity susceptibility and also metabolic complications., Methods: This study enrolled 305 individuals with severe obesity (cases, BMI≥35 kg/m 2 ) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9 kg/m 2 ). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in DBC1 (rs17060940), SIRT1 (rs7895833 and rs1467568), UCP2 (rs660339), PPARG (rs1801282) and ADRB2 (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan ® assays., Results: Our findings indicated that SIRT1 rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. SIRT1 rs1467568 and UCP2 rs660339 were associated with anthropometric traits. SIRT1 rs1467568 G allele was related to lower medians of body adipose index and hip circumference, while the UCP2 rs660339 AA genotype was associate with increased body mass index. Additionally, DBC1 rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, SIRT1 rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with Peroxisome Proliferator-Activated Receptor Gama and ADRB2 polymorphisms., Discussion/conclusion: This study revealed that SIRT1 rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. UCP2 rs660339 and DBC1 rs17060940 also showed a significant role in obesity related-traits., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 da Fonseca, Assis, Salum, Palhinha, Abreu, Zembrzuski, Campos Junior, Nogueira-Neto, Cambraia, Souza Junior, Maya-Monteiro, Cabello, Bozza and Carneiro.)

Amblyomma sculptum is a species of tick in the family Ixodidae, with equids and capybaras among its preferred hosts. In this study, the acaricidal activity of the essential oil (EO) from Piper aduncum and its main component, Dillapiole, were evaluated against larvae of A. sculptum to establish lethal concentration values and assess the effects of these compounds on tick enzymes. Dillapiole exhibited slightly greater activity (LC 50 = 3.38 mg/mL; 95% CI = 3.24 to 3.54) than P. aduncum EO (LC 50 = 3.49 mg/mL; 95% CI = 3.36 to 3.62) against ticks. The activities of α-esterase (α-EST), β-esterase (β-EST), and glutathione-S-transferase (GST) enzymes in A. sculptum larvae treated with Dillapiole showed a significant increase compared to the control at all concentrations (LC 5 , LC 25 , LC 50 and LC 75 ), similar results were obtained with P. aduncum EO, except for α-EST, which did not differ from the control at the highest concentration (LC 75 ). The results of the acetylcholinesterase (AChE) activity show an increase in enzyme activity at the two lower concentrations (LC 5 and LC 25 ) and a reduction in activity at the two higher, lethal concentrations (LC 50 and LC 75 ) compared to the control. These results suggest potential mechanisms of action for these natural acaricides and can provide guidance for the future development of potential plant-derived formulations.

Background: Brain tissue-derived extracellular vesicles (bdEVs) act locally in the central nervous system (CNS) and may indicate molecular mechanisms in human immunodeficiency virus (HIV) CNS pathology. Using brain homogenate (BH) and bdEVs from a simian immunodeficiency virus (SIV) model of HIV disease, we identified RNA networks in SIV infection and neuroinflammation., Methods: Postmortem occipital cortex samples were obtained from uninfected controls and SIV-infected subjects (acute and chronic phases with or without CNS pathology [SIV encephalitis]). bdEVs were separated and characterized per international consensus guidelines. RNAs from bdEVs and BH were sequenced and quantitative polymerase chain reaction (qPCR)-amplified to detect levels of small RNAs (sRNAs, including microRNAs [miRNAs]) and longer RNAs including messenger RNAs (mRNAs) and circular RNAs (circRNAs)., Results: Dysregulated RNAs in BH and bdEVs were identified in acute and chronic infection with pathology groups, including mRNAs, miRNAs, and circRNAs. Most dysregulated mRNAs in bdEVs reflected dysregulation in source BH. These mRNAs are disproportionately involved in inflammation and immune responses. Based on target prediction, several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in sRNA levels in bdEVs during SIV infection., Conclusions: RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study aimed to compare the antimicrobial action, cytotoxicity, cleaning ability, and erosion of dentine of hypochlorous acid (HClO) obtained from an electrolytic device at two different concentrations (Dentaqua) and three concentrations of sodium hypochlorite (NaOCl)., Methods: Microbiological test-The root canals of sixty single-rooted extracted human teeth were inoculated with Enterococcus faecalis and divided into 6 groups (n = 10), according to decontamination protocol: DW (control); 1% NaOCl; 2.5% NaOCl; 5.25% NaOCl; 250 ppm HClO and 500 ppm HClO. The colony-forming units were counted to evaluate the decontamination potential of each group, calculating the reduction in bacterial percentage. Cytotoxicity test-Cytotoxicity was evaluated after inoculation of the same tested protocols in fibroblastic cells for 3 min, calculating the cell viability percentages. Specifical statistical analysis was performed (α = 5%). Cleaning ability and erosion-Fifty-six single-rooted bovine lower incisors were divided into seven groups of 8 roots each, being the test groups 1% NaOCl; 2.5% NaOCl; 5,25% NaOCl; 250 ppm HClO and 500 ppm HClO, and a negative and positive control. Negative control was not contaminated, and the other groups were inoculated with Enterococcus faecalis. SEM images were ranked as from the cleanest to the least clean. Erosion was also assessed, being ranked from the least to the most eroded dentine., Results: The highest bacterial reduction was observed in experimental groups, with no statistical differences between them (p > 0.05). The highest number of viable cells was observed in control group, followed by 250 ppm HClO and 500 ppm HClO groups, with statistical differences between them (p < 0.05). 1% NaOCl; 2.5% NaOCl; 5.25% NaOCl and 500 ppm HClO displayed the cleanest areas. All sodium hypochlorite groups displayed erosion with higher ranks with greater concentration, while hypochlorous acid did not display any erosion regardless the concentration., Conclusions: It is possible to conclude that HClO obtained from an electrolytic device presented high antimicrobial activity and low cytotoxicity in both tested concentrations. 500 ppm HClO did not display erosion and showed great cleaning ability., Clinical Relevance: The use of 500 ppm hypochlorous acid may reduce unfavorable behavior of sodium hypochlorite whilst maintaining its antimicrobial action., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individuals display more pronounced physiological and cognitive abnormalities than PWS T2, yet the exact neuropathological mechanisms behind these differences remain unclear. Our study employed postmortem hypothalamic tissues from PWS T1 and T2 individuals, conducting transcriptomic analyses and cell-specific protein profiling in white matter, neurons, and glial cells to unravel the cellular and molecular basis of phenotypic severity in PWS sub-genotypes. In PWS T1, key pathways for cell structure, integrity, and neuronal communication are notably diminished, while glymphatic system activity is heightened compared to PWS T2. The microglial defect in PWS T1 appears to stem from gene haploinsufficiency, as global and myeloid-specific Cyfip1 haploinsufficiency in murine models demonstrated. Our findings emphasize microglial phagolysosome dysfunction and altered neural communication as crucial contributors to the severity of PWS T1's phenotype., (© 2024. The Author(s).)

Background: In 2022, fluralaner was launched on the market for use in the control of the cattle tick Rhipicephalus microplus after showing 100% efficacy in registration trials against the causative agents of cattle tick fever (TFAs). The aim of the present study was to determine whether a strategic control regimen against R. microplus using fluralaner (FLU) in Holstein calves grazing in a tropical region would alter the enzootic stability status of cattle tick fever, triggering outbreaks in these animals up to 22 months age., Methods: In this study, a group of calves treated with FLU was compared with a control group treated with the regimen currently being used on the farm, which consisted of the fipronil + fluazuron formulation (FIFLUA). In the first experiment, the efficacy of the FIFLUA pour-on formulation was evaluated in a field study. In the second experiment, which lasted 550 days, two experimental groups (n = 30/group) of Holstein calves naturally infested with R. microplus were analyzed. Calves aged 4 to 10 months received either a specific treatment regimen with FLU (experimental group) or FIFLUA (control group). During this period, tick counts, animal weight measurement, feces collection (to determine eggs and oocysts per gram of feces), tick fever monitoring, blood smears (to ascertain enzootic stability of the herd), PCR testing for TFAs and serology (indirect enzyme-linked immunosorbent assay [iELISA]) were performed. All calves were evaluated for signs of tick fever between ages 11 and 22 months., Results: FIFLUA showed an acaricidal efficacy of > 90% from post-treatment days 14 to 35. Regarding treatments against the TFAs, the average number of treatments was similar between groups, but animals treated with FLU had a smaller reduction in packed cell volume on some of the evaluation dates of the second and third treatment against TFAs. In calves aged 10 months in the FLU group, B. bovis was not detected by PCR (0/15 samples), 40% of the samples had antibody titers and 33% (10/30) of the samples had positive blood smears. Regarding B. bigemina, > 86% of the samples in both groups tested positive for B. bigemina DNA and antibodies; there was no difference in the antibody titers between the groups. There were no clinical cases of cattle tick fever in calves aged 11 to 22 months., Conclusions: In comparison with the control treatment, the strategic control regimen against R. microplus with FLU that was implemented in the present study did not negatively affect the enzootic stability status of A. marginale and B. bigemina in the herd up to 22 months of age. The enzootic stability status of B. bovis was not reached by either group. These results likely represent a characteristic of the local tick population, so further studies should be performed., (© 2024. The Author(s).)

Inadequate disposal of hazardous waste results risks to the environment and human health. Although the use of hazardous waste in new processes and/or products has received limited attention in the literature, there is still significant potential to be investigated. Reducing the usage of natural resources and waste management are important for sustainable practices during concrete production. This study investigated the mechanical and leaching behavior of paint booth waste (PBW) as a partial substitute (10, 20, 30 and 40%) of coarse aggregate in concrete mixtures for the manufacture of interlocking blocks. A sample of PBW used in this research differs from those in the literature due to its granulometry characterized by aggregates of different sizes. Concrete consistency, compressive strength, water absorption, X-ray diffraction, scanning electron microscopy, and leaching tests were carried out. The PBW did not influence the consistency in the fresh state of the concrete. The blocks with smaller substitutions (10 and 20%) presented denser structures and with greater strengths, surpassing 35 MPa after 28 days. Higher levels of PBW resulted in more porous concrete blocks with greater water absorption. The concrete-PBW mixtures showed no metal toxicity, i.e., the incorporation of this waste in the construction material avoided metal leaching. Concrete blocks with up to 20% PBW demonstrated satisfactory mechanical and environmental performance., (© 2024. The Author(s).)

Aim: To develop nanoemulsions (NEs) loading amphotericin B (AmB) and to evaluate the influence of different excipients on the stability and the supramolecular organization, retention and toxicity of AmB. Materials & methods: The NEs were developed from different oils, surfactants, external media and anionic lipids (disteaoryl phosphatidylglycerol [DSPG] and dioleoyl phosphatidylglycerol [DOPG]). Their impact on the size, pH, zeta potential, AmB encapsulation efficiency, AmB retention and hemolytic potential of the NEs was evaluated. Results & conclusion: The use of soybean oil (lipid matrix), Span 80 (surfactant), phosphate buffer (external phase) and DSPG or DOPG (hydrophobic ion pair) provided better NE stability, higher AmB retention within the NEs and a safer formulation profile in hemolysis tests.

Background: The use of a reliable remote cognitive screening test for older adults is crucial for the diagnosis of cognitive impairment. This study aimed to translate and validate the audiovisual Montreal Cognitive Assessment (MoCA)for older adults in Brazil., Methods: One hundred and fourteen older adults were recruited from the community and demographic, functional, mood, and cognitive data were collected. Participants were classified into two groups: cognitively healthy or mild cognitive impairment (MCI). Statistical analyses were performed in order to assess the validity of the test and the cutoff score., Results: The psychometric properties of the audiovisual MoCA showed good convergent validity. The audiovisual MoCA was represented as a unifactorial adjusted model, the composite reliability value was acceptable and a cutoff point of ≥23 reached adequate sensitivity and specificity at 0.77 and 0.92, respectively., Conclusions: The translated audiovisual MoCA is a valid and reliable cognitive screening test that can be administered remotely in older adults in Brazil. The test demonstrated a great ability to discriminate older adults with MCI from cognitively healthy adults. Future studies should focus on validating the audiovisual MoCA using other target population groups in order to expand the use of this remote screening test., (© 2023. The Author(s).)

Introduction: The aim of this study was to assess the effectiveness of filling removal material from the apical third of curved mesial root canals of mandibular molars. Reciprocating instrumentation followed by additional rotary instrumentation with instruments made of alloys with different heat treatments was evaluated., Materials and Methods: Thirty-six mesial roots of mandibular molars were divided into two groups: Group Class IV consisted of 16 roots with two independent canals, and Group Class II consisted of 20 roots with two canals that merged into one at their apical level. Each of these two groups were further divided into two subgroups, according to the additional rotary instrument used after the reciprocating instrumentation: Group RH and Group RM for Hyflex and Mtwo, respectively. After each procedural step, the roots were scanned by micro-tomography. After each step of filling removal, the Wilcoxon matched pair test and the Mann-Whitney test were used for the evaluation between groups. The significance level adopted was 5%., Results: Significant differences were observed between groups with different Class II and Class IV anatomies, regarding filling removal after Reciproc ( P <0.05). After the use of an additional rotary instrumentation, no differences were observed between the two groups ( P >0.05)., Conclusions: In the apical third of mesial roots of mandibular molars with Class II anatomy, an additional rotary instrumentation was shown to be necessary for improving the removal of filling material after using the single-file reciprocating instrumentation technique., Competing Interests: None.

To investigate the effect of ELVAX polymer subgingival implants incorporated with echistatin peptide on incisor reimplanted tooth in rats. Forty-two male Wistars rats were divided into two groups: echistatin-treated rats (E) and control rats (C). The animals had their right maxillary incisors extracted and treated according to the International Association of Dental Traumatology replantation protocol. The extra-alveolar dry period was 30 and 60 min, and the post-surgical experimental periods were 15, 60, and 90 days. The samples were stained with H&E and analyzed for the presence of an inflammatory response, incidence of resorptions, and dental ankylosis. Results were statistically analyzed (p < 0.05). The presence of inflammatory resorption was significantly higher in group C at 30 and 60 min extra-alveolar time, in the 15-day postoperative period as compared with the E group (p < 0.05). Dental ankylosis was significantly more prevalent in group E in 30 min extra-alveolar time and 15 days postoperative period (p < 0.05). However, in 60 min extra-alveolar time and 60 days postoperative period, dental ankylosis was more prevalent in C group (p < 0.05). The use of ELVAX subgingival implants with echistatin demonstrated therapeutic potential in preventing the experimental resorption process after replantation of maxillary incisors in rats., (© 2023. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Background: Growing evidence demonstrates the role of the striatal dopamine system in the regulation of glucose metabolism. Treatment with dopamine antagonists is associated with insulin resistance and hyperglycemia, while dopamine agonists are used in treatment of type 2 diabetes. The mechanism underlying striatal dopamine effects in glucose metabolism, however is not fully understood. Here, we provide mechanistic insights into the role of nucleus accumbens shell (sNAc) dopaminergic signaling in systemic glucose metabolism., Methods: Endogenous glucose production (EGP), blood glucose and mRNA expression in the lateral hypothalamic area (LHA) in male Wistar rats were measured following infusion of vanoxerine (VNX, dopamine reuptake inhibitor) in the sNAc. Thereafter, we analyzed projections from sNAc Drd1-expressing neurons to LHA using D1-Cre male Long-Evans rats, Cre-dependent viral tracers and fluorescence immunohistochemistry. Brain slice electrophysiology in adult mice was used to study spontaneous excitatory postsynaptic currents of sNAc Drd1-expressing neurons following VNX application. Finally, we assessed whether GABAergic LHA activity and hepatic vagal innervation were required for the effect of sNAc-VNX on glucose metabolism by combining infusion of sNAc-VNX with LHA-bicuculline, performing vagal recordings and combining infusion of sNAc-VNX with hepatic vagal denervation., Results: VNX infusion in the sNAc strongly decreased endogenous glucose production, prevented glucose increases over time, reduced Slc17A6 and Hcrt mRNA in LHA, and increased vagal activity. Furthermore, sNAc Drd1-expressing neurons increased spontaneous firing following VNX application, and viral tracing of sNAc Drd1-expressing neurons revealed direct projections to LHA with on average 67 % of orexin cells directly targeted by sNAc Drd1-expressing neurons. Importantly, the sNAc-VNX-induced effect on glucose metabolism was dependent on GABAergic signaling in the LHA and on intact hepatic vagal innervation., Conclusions: We show that sNAc dopaminergic signaling modulates hepatic glucose metabolism through GABAergic inputs to glutamatergic LHA cells and hepatic vagal innervation. This demonstrates that striatal control of glucose metabolism involves a dopaminergic sNAc-LHA-liver axis and provides a potential explanation for the effects of dopamine agonists and antagonists on glucose metabolism., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Amblyomma sculptum is a species of public health interest because it is associated with the transmission of the bacteria that causes Brazilian Spotted Fever (BSF). The use of repellents on humans is a prophylactic measure widely used to provide protection against a series of arthropod vectors, including mosquitoes and ticks. However, in Brazil, the effectiveness of commercial repellents against A. sculptum is little known. Therefore, it is necessary to carry out specific studies to evaluate the repellency of these commercial products, registered for use against mosquitoes, against the star tick. The main goal of the present work was to evaluate the effectiveness of six commercial repellents against A. sculptum . Unfed nymphs, aged between two and eight weeks, were tested against products based on DEET (OFF! ® and Repelex ® ), Icaridin (Exposis ® and SBP ® ), and IR3535 (Johnsons and Henlau). Three bioassays were conducted to evaluate tick behavior: (i) filter paper, (ii) fingertip, and (iii) field. All bases tested showed high repellent activity, differing significantly ( p < 0.05) from the control. It was observed the formulation with DEET resulted in the best results in the filter paper bioassay. In the fingertip bioassay, the DEET base repelled a greater number of ticks compared to Icaridin. In the field bioassay, there was no significant difference between the Icaridin base and DEET, and both formulations differed from the control ( p < 0.05). The six formulations tested showed significant percentages of repellency against ticks; however, for the fingertip and field bioassays, the products OFF! ® , Repelex ® , and Exposis ® were tested as they showed better performance in the filter paper test. OFF! ® showed the best percentage of repellency (100%), followed by Repelex ® (96.8%), and Exposis ® (93.1%), considering the two-hour period of the bioassay-field-test. Proving the effectiveness of repellents on the market against A. sculptum presented in this study is crucial, since this is the main ectoparasite of humans that can transmit Rickettsia rickettsii when infected. The effectiveness of commercial insect repellents against other tick species that parasitize humans can also be explored.

Background & Aims: Lipid droplet (LD) accumulation in cells and tissues is understood to be an evolutionarily conserved tissue tolerance mechanism to prevent lipotoxicity caused by excess lipids; however, the presence of excess LDs has been associated with numerous diseases. Sepsis triggers the reprogramming of lipid metabolism and LD accumulation in cells and tissues, including the liver. The functions and consequences of sepsis-triggered liver LD accumulation are not well known., Methods: Experimental sepsis was induced by CLP (caecal ligation and puncture) in mice. Markers of hepatic steatosis, liver injury, hepatic oxidative stress, and inflammation were analysed using a combination of functional, imaging, lipidomic, protein expression and immune-enzymatic assays. To prevent LD formation, mice were treated orally with A922500, a pharmacological inhibitor of DGAT1., Results: We identified that liver LD overload correlates with liver injury and sepsis severity. Moreover, the progression of steatosis from 24 h to 48 h post-CLP occurs in parallel with increased cytokine expression, inflammatory cell recruitment and oxidative stress. Lipidomic analysis of purified LDs demonstrated that sepsis leads LDs to harbour increased amounts of unsaturated fatty acids, mostly 18:1 and 18:2. An increased content of lipoperoxides within LDs was also observed. Conversely, the impairment of LD formation by inhibition of the DGAT1 enzyme reduces levels of hepatic inflammation and lipid peroxidation markers and ameliorates sepsis-induced liver injury., Conclusions: Our results indicate that sepsis triggers lipid metabolism alterations that culminate in increased liver LD accumulation. Increased LDs are associated with disease severity and liver injury. Moreover, inhibition of LD accumulation decreased the production of inflammatory mediators and lipid peroxidation while improving tissue function, suggesting that LDs contribute to the pathogenesis of liver injury triggered by sepsis., Impact and Implications: Sepsis is a complex life-threatening syndrome caused by dysregulated inflammatory and metabolic host responses to infection. The observation that lipid droplets may contribute to sepsis-associated organ injury by amplifying lipid peroxidation and inflammation provides a rationale for therapeutically targeting lipid droplets and lipid metabolism in sepsis., Competing Interests: The authors declare no competing interests. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Lipids perform a series of cellular functions, establishing cell and organelles' boundaries, organizing signaling platforms, and creating compartments where specific reactions occur. Moreover, lipids store energy and act as secondary messengers whose distribution is tightly regulated. Disruption of lipid metabolism is associated with many diseases, including those caused by viruses. In this scenario, lipids can favor virus replication and are not solely used as pathogens' energy source. In contrast, cells can counteract viruses using lipids as weapons. In this review, we discuss the available data on how coronaviruses profit from cellular lipid compartments and why targeting lipid metabolism may be a powerful strategy to fight these cellular parasites. We also provide a formidable collection of data on the pharmacological approaches targeting lipid metabolism to impair and treat coronavirus infection., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Cesar-Silva, Pereira-Dutra, Giannini, Maya-Monteiro and de Almeida.)

The gastropod Pseudosuccinea columella participates in the dissemination of Fasciola hepatica in the environment, acting as the main intermediate host of this parasite in Brazil. The present study sought to elucidate the possible pathogenic effects of the entomopathogenic nematode (EPN) Heterorhabditis bacteriophora on P. columella, by evaluating the influence of infection on alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as the concentrations of total protein, uric acid, and urea in the snail's hemolymph. For this, the snails were exposed to EPNs for 24 and 48 h, and for each exposure time, 20 snails were dissected after 7, 14 and 21 days for hemolymph collection. The primary findings suggest a significant proteolysis alongside elevated levels of uric acid and urea in P. columella infected individuals. These findings reveal that H. bacteriophora HP88 infection induced serious changes in the snail's metabolism, triggering important deleterious effects., 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 © 2023 Elsevier B.V. All rights reserved.)

Currently, biofilm-forming bacteria are difficult to treat by conventional antibiotic therapy and are, thus, becoming a clinical and epidemiological problem worldwide. Medicinal plants have been identified as novel alternative treatments due to their therapeutic and antimicrobial effects. In this context, the present study aimed to determine the total phenolic content, antioxidant capacity, and antimicrobial and anti-biofilm potential of nine extracts of Hymenaea courbaril (Fabaceae), popularly known as Jatobá. Furthermore, extracts that exhibited biofilm inhibitory activity against S. aureus (ATCC 25923) were selected for UPLC-HRMS/MS chemical analysis. Our results showed a high total phenolic content, mainly in the stem bark extract, and that the plant is rich in compounds with antioxidant activity. In the anti-biofilm analysis, leaf extracts stood out in comparison with chloramphenicol, with inhibition percentages of 78.29% and 78.85%, respectively. Through chemical analysis by UPLC-HRMS/MS, chrysoeriol-7- O -neohesperidoside, isorhamnetin-3- O -glucoside, and 3,7-di- O -methylquercetin were annotated for the first time in the leaves of H. courbaril . Therefore, these results showed the potential use of H. courbaril as an antioxidant and point to its use in antimicrobial therapy with an anti-biofilm effect.

Introduction: The clinical prognosis of the HER2-overexpressing (HER2-OE) subtype of breast cancer (BC) is influenced by the immune infiltrate of the tumor. Specifically, monocytic cells, which are promoters of pro-tumoral immunosuppression, and NK cells, whose basal cytotoxic function may be enhanced with therapeutic antibodies. One of the standards of care for HER2 + BC patients includes the combination of the anti-HER2 antibodies trastuzumab and pertuzumab. This dual combination was a breakthrough against trastuzumab resistance; however, this regimen does not yield complete clinical benefit for a large fraction of patients. Further therapy refinement is still hampered by the lack of knowledge on the immune mechanism of action of this antibody-based dual HER2 blockade., Methods: To explore how the dual antibody challenge influences the phenotype and function of immune cells infiltrating the HER2-OE BC microenvironment, we developed in vitro 3D heterotypic cell models of this subtype. The models comprised aggregates of HER2 + BC cell lines and human peripheral blood mononuclear cells. Cells were co-encapsulated in a chemically inert alginate hydrogel and maintained in agitation-based culture system for up to 7 days., Results: The 3D models of the HER2-OE immune microenvironment retained original BC molecular features; the preservation of the NK cell compartment was achieved upon optimization of culture time and cytokine supplementation. Challenging the models with the standard-of-care combination of trastuzumab and pertuzumab resulted in enhanced immune cytotoxicity compared with trastuzumab alone. Features of the response to therapy within the immune tumor microenvironment were recapitulated, including induction of an immune effector state with NK cell activation, enhanced cell apoptosis and decline of immunosuppressive PD-L1 + immune cells., Conclusions: This work presents a unique human 3D model for the study of immune effects of anti-HER2 biologicals, which can be used to test novel therapy regimens and improve anti-tumor immune function., 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 © 2023 Batalha, Gomes and Brito.)

Ethnopharmacological Relevance: Roots of Pothomorphe umbellata (L.) Miq. are used in traditional medicine of Africa and South America for the treatment of malaria and helminthiasis. However, neither P. umbellata nor its isolated compounds have been evaluated against Schistosoma species., Aims of This Study: To investigate the antischistosomal effects of P. umbellata root extracts and the isolated compound 4-nerolidylcatechol (4-NC) against Schistosoma mansoni ex vivo and in murine models of schistosomiasis., Materials and Methods: The crude hydroalcoholic (PuE) and hexane (PuH) extracts of P. umbellata roots were prepared and initially submitted to an ex vivo phenotypic screening against adult S. mansoni. PuH was analyzed by HPLC-DAD, characterized by UHPLC-HRMS/MS, and submitted to chromatographic fractionation, leading to the isolation of 4-NC. The anthelmintic properties of 4-NC were assayed ex vivo against adult schistosomes and in murine models of schistosomiasis for both patent and prepatent S. mansoni infections. Praziquantel (PZQ) was used as a reference compound., Results: PuE (EC 50 : 18.7 μg/mL) and PuH (EC 50 : 9.2 μg/mL) kill adult schistosomes ex vivo. The UHPLC-HRMS/MS analysis of PuH, the most active extract, revealed the presence of 4-NC, peltatol A, and peltatol B or C. After isolation from PuH, 4-NC presented remarkable in vitro schistosomicidal activity with EC 50 of 2.9 μM (0.91 μg/mL) and a selectivity index higher than 68 against Vero mammalian cells, without affecting viability of nematode Caenorhabditis elegans. In patent S. mansoni infection, the oral treatment with 4-NC decreased worm burden and egg production in 52.1% and 52.3%, respectively, also reducing splenomegaly and hepatomegaly. 4-NC, unlike PZQ, showed in vivo efficacy against juvenile S. mansoni, decreasing worm burden in 52.4%., Conclusions: This study demonstrates that P. umbellata roots possess antischistosomal activity, giving support for the medicinal use of this plant against parasites. 4-NC was identified from P. umbellata roots as one of the effective in vitro and in vivo antischistosomal compound and as a potential lead for the development of novel anthelmintics., 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 © 2023 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the effectiveness of the experimental formulation containing chlamydospores of Duddingtonia flagrans and Pochonia chlamydosporia fungi, against Moniezia expansa . Two experiments were carried out. The first experiment evaluated the in vitro efficacy using 1 g of the experimental formulation (V1) added to 100 M. expansa eggs and the control (V2) (without the fungal formulation). Intact eggs or eggs with alterations were counted in order to evaluate their effectiveness. The second experiment evaluated the action of the fungal formulation on M. expansa eggs after passing through the gastrointestinal tract of goats. Three groups were identified as B1, B2, and B3, which received 1.0, 1.5 g of experimental fungal formulation, and placebo, respectively. In experiment 1, all the eggs in V1 were subjected to the predatory action of fungi, while in V2, the eggs remained intact. In experiment 2, the reduction of eggs in groups B1 and B2 were 49% and 57% 24 h after ingestion, 60% and 63% 48 h after, and 48% and 58% 72 h after. The predatory capacity against M. expansa eggs shown in the tests demonstrated that experimental fungal formulation has the potential to be used on integrated helminth control programs.

Objectives: To test and validate a new protocol for in vitro contamination of dentinal tubules using Fusobacterium nucleatum ( F. nucleatum ) by confocal laser scanning microscopy (CLSM), in addition to evaluating the effectiveness of conventional endodontic irrigants such as sodium hypochlorite (NaOCl) and chlorhexidine (CLX) on this biofilm., Material and Methods: Thirty lower premolars were contaminated with F. nucleatum (ATCC 51190) for 7 days under anaerobic conditions using the proposed new model . The specimens were divided into a control group and experimental groups, according to the irrigants: NaOCl 2.5% and CLX 2%. Then, the samples were submitted for analysis by CLSM and the LIVE/DEAD technique to quantify bacterial viability. Data normality was verified by the Shapiro-Wilk test. Intragroup and intergroup comparisons were performed using the Kruskal-Wallis test, followed by Dunn's post-test., Results: The CLSM images obtained demonstrated the effectiveness of the proposed new contamination protocol, with a high percentage of viable bacteria in relation to the treated groups (p < 0.05). Lower viability values were observed for the 2.5% NaOCl group., Conclusion: The new contamination protocol resulted in a high and homogeneous percentage of viable bacteria in the dentinal tubules in all specimens evaluated. Both irrigating solutions proved to be effective in reducing the intratubular microbiota, especially 2.5% NaOCl., Competing Interests: The authors have no competing of interest to declare., (© 2023 The Authors.)

Background: Equid herpesvirus (EHV) commonly affects horses causing neurologic and respiratory symptoms beside spontaneous abortions, meaning huge economic losses for equine industry worldwide. In foals, the virus can facilitate secondary infections by Rhodococcus equi, important in morbidity and mortality in equines. A total of five genotypes of EHV were previously described in Brazil including EHV-1, EHV-2, EHV-3, EHV-4, and EHV-5. EHV-2 genotype had only been previously described in Brazil in asymptomatic animals. We report the investigation of the dead of 11 foals in Middle-west region of Brazil showing respiratory and neurological symptoms, as well as several abortions in mares from the same farm., Methods: Clinical and laboratory exams were performed in this case study. Lung, whole blood, serum, and plasma samples were analyzed by necroscopic and histopathologic techniques followed by molecular assays (conventional and qPCR and Sanger sequencing)., Results and Conclusion: Laboratory exams revealed neutrophilia leukocytosis. Necroscopic and histopathologic findings were suppurative bronchopneumonia and ulcerative enteritis. Molecular assays point to the absence of the bacteria Rhodococcus equi and other viruses (including other EHV). The presence of EHV-2 DNA was confirmed by sequencing in serum sample from one foal. This is the first confirmed outbreak of EHV-2 causing disease in Brazilian horses with confirmed presence of the virus, and which highlight the important role of EHV-2 in equine respiratory disease and spontaneous abortions in equid in Brazil., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Vasculitis is a complication of several infectious diseases affecting the central nervous system, which may result in ischemic and/or hemorrhagic stroke, transient ischemic attack, and aneurysm formation. The infectious agent may directly infect the endothelium, causing vasculitis, or indirectly affect the vessel wall through an immunological mechanism. The clinical manifestations of these complications usually overlap with those of non-infectious vascular diseases, making diagnosis challenging. Intracranial vessel wall magnetic resonance imaging (VWI) enables the evaluation of the vessel wall and the diseases that affect it, providing diagnostic data beyond luminal changes and enabling the identification of inflammatory changes in cerebral vasculitis. This technique demonstrates concentric vessel wall thickening and gadolinium enhancement, associated or not with adjacent brain parenchymal enhancement, in patients with vasculitis of any origin. It permits the detection of early alterations, even before a stenosis occurs. In this article, we review the intracranial vessel wall imaging features of infectious vasculitis of bacterial, viral, and fungal etiologies., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: This randomized clinical trial aimed to compare postoperative pain after the use of 2different irrigation activation techniques: passive ultrasonic irrigation and the EasyClean device., Methods: Sixty-six single-rooted teeth diagnosed with asymptomatic pulp necrosis and apical periodontitis were randomly assigned to 2experimental groups (n = 33), which differed in the irrigation activation technique. Postoperative pain levels were assessed after 24, 48, and 72 hours using a verbal rating scale; the ibuprofen intake amount was recorded at the same time intervals. Data were analyzed using Student's t-test, Mann-Whitney U and Fisher's exact tests, with a significance level of 5%., Results: Postoperative pain levels and analgesic intake frequency were not significantly different across the 2irrigation activation techniques (P > .05). The frequencies obtained in relation to the prevalence of postoperative pain were 3.1-25.8% for all participants of the 2studied groups., Conclusion: The irrigation activation techniques of passive ultrasonic irrigation and the EasyClean device were found to be equivalent in terms of postoperative pain and analgesic intake., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: The eradication of C. albicans is difficult due to the organization of the yeast in biofilms. Photodynamic therapy (PDT) has been proposed as an alternative to antifungals. Phenothiazinium dyes, e.g. methylene blue (MB), have been proposed as photosensitizing agents (PS), and their association with sodium dodecyl sulfate (SDS) has recently been shown to improve the effectiveness of PDT in planktonic culture. In this sense, the objective of this work was to evaluate the effect of PDT with phenothiazinium dyes associated to SDS in biofilms at the different stages of growth., Methods: Experiments were carried out to evaluate the effects of PDT on biofilm formation and on established biofilms of C. albicans ATCC 10231. Samples were exposed to PS 50 mg/L (MB, Azure A - AA, Azure B - AB and dimethyl methylene blue - DMMB) dissolved in water or 0.25% SDS, for 5 min in the dark. After irradiation at 660 nm, 37.3mW/cm 2 for 27 min, 60.4J/cm 2 colony forming units count assay (CFU/mL) was performed. One or two irradiations were applied. Statistical methods were used to assess effectiveness., Results: PSs showed low toxicity in the dark. An application of PDT irradiation was not able to reduce the CFU/mL both in mature biofilms (24h) and in biofilms in the dispersion phase (48h), only in the adherence phase did PDT prevent the formation of biofilms. With two successive applications of PDT irradiation in the dispersion phase, PDT with MB, AA, and DMMB completely inactivated C. albicans. The similar was not observed with mature biofilms., Conclusions: Different stages of biofilm growth respond differently to PDT, with the greatest inhibitory effect found in the adhesion stage. Mature and dispersed biofilms are less susceptible to PDT. The use of two successive applications of PDT with PSs associated with SDS may be a useful approach to inactivate C. albicans biofilms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The growth of resistant microorganisms has been a challenge for health systems. Antimicrobial Photodynamic Therapy (aPDT) has gained attention due to its effects on resistant strains. Recently, it was shown that the association of methylene blue (MB) and sodium dodecyl sulfate (SDS) are an effective strategy to increase the effect of aPDT; however, it is unknown which are the best light parameters (such as irradiance and radiant exposure, RE), to reach the most effective protocols. This work aimed to evaluate the light parameters, irradiance, and radiant exposure, in aPDT with MB when conveyed in water compared to MB associated with SDS., Methods: Tests were carried out to quantify the colony-forming units (CFU) of ATCC 10,231 strain of Candida albicans when using MB in different media and with different light parameters: Control (water), SDS (0.25%), MB (20 mg/mL), and the MB/SDS at irradiances of 3.7; 11.2; 18.6, and 26.1 mW/cm 2 and varied irradiation times to reach radiant exposures of 4.4; 17.8; 26.7, and 44 J/cm²., Results: The results showed that aPDT with MB/SDS had a higher antimicrobial effect than MB when conveyed in water. Furthermore, for the highest irradiance studied (26.1 mW/cm 2 ), CFU decreases exponentially with increasing RE from 4.4 up to 44 J/cm 2 . Similarly, at a fixed RE, the higher the irradiance used, the higher the antimicrobial effect was observed, except for the lowest RE studied (4.4 J/cm 2 )., Conclusions: aPDT with MB/SDS had a greater antimicrobial action at the lower light parameters when compared to MB conveyed in water. The authors suggest the use of RE above 18 J/cm 2 and irradiance above 26 mW/cm 2 since at the mentioned parameters the increase in its value caused a greater antimicrobial effect., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Irrigation solutions might affect dentin surface characteristics and, consequently, endodontic sealers adhesion. This study analyzed the effect of different final irrigation protocols on push-out bond strength (BS) of AH Plus to dentin seven days and 20 months after obturation. Scanning electron micrographs were obtained from the dentin surface of one sample/group after final irrigation. Canals of bovine incisors were instrumented and received final irrigation with (n=21): G1 - 2.5% sodium hypochlorite (NaOCl) + distilled water; G2 - 2.5% NaOCl + 17% EDTA; G3 - 2.5% NaOCl + 17% EDTA + 2.5% NaOCl; G4 - 2.5% NaOCl + 17% EDTA + 2% chlorhexidine (CHX); G5 - mixture 5% NaOCl + 18% etidronate (HEDP); and G6 - mixture 5% NaOCl + 10% tetrasodium EDTA (Na4EDTA). After irrigation, one root/group was split and images were obtained by scanning electron microscopy (SEM). The other 20 roots/group were filled with only AH Plus sealer. Three slices/root were used for push-out assessment seven days and 20 months after obturation. One-way analysis of variance and Tukey (α<0.05) were used to compare the results among experimental groups, and unpaired t-test (α<0.05) was used to compare the results of the same group over time. The photomicrographs showed that, excepting G1, all groups completely removed the smear layer from the samples. In G2 and G4, the opening of the dentin tubules enlarged. In G3, erosion was observed in the peritubular and intertubular dentin. Values of the BS in the seven days were G2=G3=G4=G5>G6=G1 and in the 20 months were G3=G5>G6=G4>G1=G2. G3, G5, and G6 presented values of BS in 20 months similar to the values of seven days (P>0.05). The final irrigation protocols tested produced dentin surfaces with different characteristics. Only G3 and G5 presented high BS values that were stable over time.

Background: Currently, most Pulmonary Rehabilitation (PR) programs work with conventional physical training, using resources that are not available in public health in Brazil. Multicomponent physical training is a strategy that uses few resources and can reach a larger portion of the population., Objective: To investigate the effectiveness and safety of multicomponent physical training on physical-functional performance in patients with COPD., Design: Protocol for a randomized clinical trial with 2 groups in parallel (1:1)., Setting: University-based, outpatient, physiotherapy clinic., Participants: 64 patients aged ⩾50 years, clinical-functional diagnosis of COPD, GOLD II and III criteria will participate in the study., Intervention: Participants will be randomly allocated into 2 groups: Multicomponent Physical Training-MPT (n = 32): aerobic, strength, balance and flexibility exercises performed in a circuit training format, or Conventional Physical Training-CPT (n = 32): aerobic and strength training. The interventions will be carried out twice a week, for 8 weeks and supervised by the same physiotherapist., Measurements: The 3 primary outcomes are the 6-Minute Walk Test (6MWT), the 6-Minute Step Test (6MST) and VO 2 consumption as measured during the 6MWT. Secondary outcomes will be exercise capacity, level of physical activity in daily life, peripheral muscle strength, functional status, dyspnea, fatigue and quality of life. Safety will be assessed by recording adverse effects. These outcomes will be evaluated before and after the intervention and the evaluator will be blind., Limitations: It will not be possible to perform the blinding of the physiotherapist who will supervise the interventions., Conclusions: This study is expected to demonstrate that MPT using simple resources is an effective and safe intervention for the improvement of the aforementioned outcomes and, in addition, to broaden the horizon of research in relation to new methods of physical rehabilitation for patients with COPD., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The dietary exposure of six food azo-colours was assessed in a sample of pre-schoolers from Guaratuba-Paraná, Brazil. Consumption data of 323 children aged 2 to 5 years was collected through 3-day food records. Dietary exposure, is expressed by milligrams of food colour by kilogram of body weight per day, as compared to the Acceptable Daily Intake (ADI). Three exposure scenarios were developed to account for uncertainties around consumption estimates. Intakes of Amaranth (INS 123) described in means, 50th and 95th percentiles exceeded ADI levels in the two most conservative scenarios, with the highest percentiles exceeding about four times the ADI. High intakes of Sunset Yellow FCF (INS 110) were also observed, of up to 85% of the ADI in the worst-case scenario. Findings suggest high exposure levels to azo-dyes in the survey population, with children likely exceeding the ADI for Amaranth (INS 123) and concerns for Sunset Yellow FCF (INS 110). Major food contributors were beverages (juice powders and soft drinks), dairy and sweets. Further studies on dietary exposure assessment are needed at the national level. The authors highlight the need of controlling the use of such additives through national policies that are aligned with the consumption patterns observed in the country.

Background: Studies show an increase in hemorrhagic risk related to selective serotonin-reuptake inhibitors (SSRIs) alone, but also in association with vitamin K antagonists (VKAs). Non-VKA anticoagulants (NOACs) can be a good substitute to VKAs, but the correlation between them and SSRIs is not well studied. Therefore, we conducted a systematic review to evaluate the risk of major bleeding associated with concomitant use of SSRIs and NOACs., Methods: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PubMed databases were searched, in September 2022, for longitudinal studies evaluating SSRIs' impact on hemorrhagic risk in anticoagulated patients taking NOACs compared with a control group taking non-SSRI medication instead or no antidepressants at all. The outcome of interest was major bleeding. The quality of the included studies was assessed using the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled RRs with 95% confidence intervals (CIs), and heterogeneity was evaluated using the I2 statistic., Results: Eight studies were included in the meta-analysis. From a population of 279,540 anticoagulated patients taking NOACs, the ones taking SSRIs concomitantly were associated with a higher risk of major bleeding (relative risk, 1.33; 95% CI, 1.06-1.66; I2 = 60%). However, the subgroup analysis of cohort studies did not achieve statistical significance (relative risk, 1.05; 95% CI, 0.94-1.66)., Conclusions: The findings show that SSRIs are associated with a greater hemorrhagic risk in patients anticoagulated with NOACs; however, our confidence is reduced because of nonstatistically significant results from more robust studies, as cohort studies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Polymyxin-carbapenem-resistant Klebsiella pneumoniae (PCR-Kp) with pan (PDR)- or extensively drug-resistant phenotypes has been increasingly described worldwide. Here, we report a PCR-Kp outbreak causing untreatable infections descriptively correlated with bacterial genomes. Hospital-wide surveillance of PCR-Kp was initiated in December-2014, after the first detection of a K. pneumoniae phenotype initially classified as PDR, recovered from close spatiotemporal cases of a sentinel hospital in Rio de Janeiro. Whole-genome sequencing of clinical PCR-Kp was performed to investigate similarities and dissimilarities in phylogeny, resistance and virulence genes, plasmid structures and genetic polymorphisms. A target phenotypic profile was detected in 10% (12/117) of the tested K. pneumoniae complex bacteria recovered from patients (8.5%, 8/94) who had epidemiological links and were involved in intractable infections and death, with combined therapeutic drugs failing to meet synergy. Two resistant bacterial clades belong to the same transmission cluster (ST437) or might have different sources (ST11). The severity of infection was likely related to patients' comorbidities, lack of antimicrobial therapy and predicted bacterial genes related to high resistance, survival, and proliferation. This report contributes to the actual knowledge about the natural history of PCR-Kp infection, while reporting from a time when there were no licensed drugs in the world to treat some of these infections. More studies comparing clinical findings with bacterial genetic markers during clonal spread are needed., (© 2023. The Author(s).)

Objectives: Latent infection by HIV hinders viral eradication despite effective antiretroviral treatment (ART). Among proposed contributors to viral latency are cellular small RNAs that have also been proposed to shuttle between cells in extracellular vesicles. Thus, we profiled extracellular vesicle small RNAs during different infection phases to understand the potential relationship between these extracellular vesicle associated small RNAs and viral infection., Design: A well characterized simian immunodeficiency virus (SIV)/macaque model of HIV was used to profile extracellular vesicle enriched blood plasma fractions harvested during preinfection, acute infection, latent infection/ART treatment, and rebound after ART interruption., Methods: Measurement of extracellular vesicle concentration, size distribution, and morphology was complemented with qPCR array for small RNA expression, followed by individual qPCR validations. Iodixanol density gradients were used to separate extracellular vesicle subtypes and virions., Results: Plasma extracellular vesicle particle counts correlated with viral load and peaked during acute infection. However, SIV gag RNA detection showed that virions did not fully explain this peak. Extracellular vesicle microRNAs miR-181a, miR-342-3p, and miR-29a decreased with SIV infection and remained downregulated in latency. Interestingly, small nuclear RNA U6 had a tight association with viral load peak., Conclusion: This study is the first to monitor how extracellular vesicle concentration and extracellular vesicle small RNA expression change dynamically in acute viral infection, latency, and rebound in a carefully controlled animal model. These changes may also reveal regulatory roles in retroviral infection and latency., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Large language models (LLMs) have promised a revolution in answering complex questions using the ChatGPT model. Its application in chemistry is still in its infancy. This viewpoint addresses the question of how well ChatGPT understands chemistry by posing five simple tasks in different subareas of chemistry.