Hydroxychloroquine is associated with lower seroconversion upon 17DD-Yellow fever primovaccination in patients with primary Sjögren's syndrome.

The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren's syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.

High viral suppression rates among PLHIV on dolutegravir who had an initial episode of viral non-suppression in Uganda September 2020-July 2021.

BACKGROUND: In 2019, WHO recommended dolutegravir (DTG) as a backbone for first- and second-line antiretroviral therapy (ART) regimens for people living with HIV (PLHIV). According to the 2018 Uganda's HIV treatment guidelines, patients with viral non-suppression (≥1,000 copies/mL) should receive intensive adherence counseling (IAC) with repeat viral load (VL) within 6 months. This analysis focused on the prevalence and factors associated with viral suppression following IAC among PLHIV on DTG-based regimens (DBRs) with an initial episode of viral non-suppression (VNS) in Uganda. METHODS: We conducted a retrospective analysis for PLHIV on DBRs with an initial episode of VNS (≥1,000 copies/mL) in Uganda during October 2019-September 2020 who had a follow up VL test result during September 2020-July 2021. Data were abstracted from the Central Public Health Laboratory (CPHL) database, including patient demographics and VL results. Viral non-suppression (VNS) was defined as a VL test result of ≥1,000 copies/mL. We characterized PLHIV on DBRs and used logistic regression models to determine factors associated with VL suppression after an initial episode of VNS. RESULTS: A total of 564 PLHIV on DBRs with an initial episode of VNS were followed up and 43 were excluded due to missing data. Of the 521, 220 (42.2%) were children (<15 years) and 231 (44.3%) were female. Median age was 28 years (interquartile range [IQR]: 12-43 years), and median duration on DBRs was 12 months (IQR: 6-15 months). Overall, 80.8% (421/521) PLHIV had a suppressed viral load at first follow up testing (children = 74.5% [164/220]; adults = 85.4% [257/301]). Children with initial VL results ≥5,000 copies/mL were less likely to achieve viral suppression at follow up testing compared to those with <5,000 copies/mL (AOR: 0.38; 95% CI: 0.20-0.71; p = 0.002). CONCLUSIONS: In a programmatic setting, most adults and children suppressed following an initial episode of VNS on DBRs. High rates of suppression after VNS suggest adherence challenges, rather than drug resistance. Continuation of DBRs should be considered before regimen switch.

Amantadine mitigates the cytotoxic and genotoxic effects of doxorubicin in SH-SY5Y cells and reduces its mutagenicity.

Amantadine (AMA) is a useful drug in neuronal disorders, but few studies have been performed to access its toxicological profile. Conversely, doxorubicin (Dox) is a well-known antineoplastic drug that has shown neurotoxic effects leading to cognitive impairment. The aims of this study are to evaluate the cytotoxic, genotoxic, and mutagenic effects of AMA, as well as its possible protective actions against deleterious effects of Dox. The Salmonella/microsome assay was performed to assess mutagenicity while cytotoxicity and genotoxicity were evaluated in SH-SY5Y cells using MTT and comet assays. Possible modulating effects of AMA on the cytotoxicity, genotoxicity, and mutagenicity induced by Dox were evaluated through cotreatment procedures. Amantadine did not induce mutations in the Salmonella/microsome assay and decreased Dox-induced mutagenicity in the TA98 strain. AMA reduced cell viability and induced DNA damage in SH-SY5Y cells. In cotreatment with Dox, AMA attenuated the cytotoxicity of Dox and showed an antigenotoxic effect. In conclusion, AMA does not induce gene mutations, although it has shown a genotoxic effect. Furthermore, AMA decreases frameshift mutations induced by Dox as well as the cytotoxic and genotoxic effects of Dox in SH-SY5Y cells, suggesting that AMA can interfere with Dox mutagenic activity and attenuate its neurotoxic effects.

Toxoplasma gondii infection and high levels of IgE are associated to erythema nodosum leprosy (ENL).

Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease may evolve for inflammatory reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), the major cause of irreversible neuropathy in leprosy, which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. Leprosy remains persistently endemic in our region where it predominantly affects lowest socioeconomic conditions people, as Toxoplasma gondii infection in the municipality studied. Previously, we have shown T. gondii coinfection as a risk marker for leprosy, mainly in its severe form. This present study assessed whether T. gondii infection is also a risk factor for leprosy reactions and the predictive value of immunoglobulin production prior to development of leprosy reactions. Patients with leprosy (n = 180), co-infected or not with T. gondii, had their serum investigated for levels of IgA, IgE, IgG1, IgG2, IgG3 and IgG4 anti-PGL-1 by ELISA prior to development of leprosy reactions. The serologic prevalence for T. gondii infection was 87.7% in leprosy reaction patients reaching 90.9% in those with ENL. The leprosy reaction risk increased in T. gondii seropositive individuals was two-fold ([OR] = 2.366; 95% confidence interval [CI 95%]: 1.024-5.469) higher than those seronegative, and considering the risk of ENL, this increase was even more evident (OR = 6.753; 95% CI: 1.050-72.85) in coinfected individuals. When evaluated the prediction of anti-PGL-1 immunoglobulin levels for development of leprosy reactions in patients coinfected or not with T. gondii, only the increase IgE levels were associated to occurrence of reactional episodes of leprosy, specifically ENL type, in patients coinfected with T. gondii, compared to those not coinfected or no reaction. Thus, the immunomodulation in co-parasitism T. gondii-M. leprae suggest increased levels of IgE as a biomarker for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.

The Influence of Probiotic Lactobacilli on COVID-19 and the Microbiota.

This comprehensive review explores the potential of using lactobacilli as a probiotic in the management of COVID-19. Our findings suggest that lactobacilli show promise in reducing the risk of death, gastrointestinal and overall symptoms, and respiratory failure, as well as in lowering cytokines and inflammatory markers associated with the disease. The molecular mechanisms by which lactobacilli protect against COVID-19 and other viral infections may be related to the reduction in inflammation, modulation of the immune response, and direct interaction with viruses to produce antiviral substances. However, the selected studies demonstrate the presence of mixed findings for various clinical, biochemical, hematological, and immunological parameters, which may be attributed to methodological differences among studies. We highlight the importance of clearly describing randomization processes to minimize bias and caution against small sample sizes and inappropriate statistical tests that could lead to errors. This review offers valuable insights into the therapeutic potential of lactobacilli in the context of COVID-19 and identifies avenues for further research and applications. These findings hold promise for the development of novel approaches to managing COVID-19 and warrant further investigation into the potential benefits of lactobacilli in combating the disease.

Genotoxic and antiproliferative properties of Endopleura uchi bark aqueous extract.

The bark extract from Endopleura uchi has been widely used in traditional medicine to treat gynecological-related disorders, diabetes, and dyslipidemias albeit without scientific proof. In addition, E. uchi bark extract safety, especially regarding mutagenic activities, is not known. The aim of this study was to determine the chemical composition, antitumor, and toxicological parameters attributed to an E. uchi bark aqueous extract. The phytochemical constitution was assessed by colorimetric and chromatographic analyzes. The antiproliferative effect was determined using sulforhodamine B (SRB) assay using 4 cancer cell lines. Cytotoxic and genotoxic activities were assessed utilizing MTT and comet assays, respectively, while mutagenicity was determined through micronucleus and Salmonella/microsome assays. The chromatographic analysis detected predominantly the presence of gallic acid and isoquercitrin. The antiproliferative effect was more pronounced in human colon adenocarcinoma (HT-29) and human breast cancer (MCF-7) cell lines. In the MTT assay, the extract presented an IC50 = 39.1 µg/ml and exhibited genotoxic (comet assay) and mutagenic (micronucleus test) activities at 20 and 40 µg/ml in mouse fibroblast cell line (L929) and mutagenicity in the TA102 and TA97a strains in the absence of S9 mix. Data demonstrated that E. uchi bark possesses bioactive compounds which exert cytotoxic and genotoxic effects that might be associated with its antitumor potential. Therefore, E. uchi bark aqueous extract consumption needs to be approached with caution in therapeutic applications.

Using active learning strategies during a quality improvement collaborative: exploring educational games to enhance learning among healthcare professionals.

BACKGROUND: The Breakthrough Series model uses learning sessions (LS) to promote education, professional development and quality improvement (QI) in healthcare. Staff divergences regarding prior knowledge, previous experience, preferences and motivations make selecting which pedagogic strategies to use in LS a challenge. AIM: We aimed to assess new active-learning strategies: two educational games, a card game and an escape room-type game, for training in healthcare-associated infection prevention. METHODS: This descriptive case study evaluated the performance of educational strategies during a Collaborative to reduce healthcare-associated infections in Brazilian intensive care units (ICUs). A post-intervention survey was voluntarily offered to all participants in LS activities. RESULTS: Seven regional 2-day LS were held between October and December 2022 (six for adult ICUs and one for paediatric/neonatal ICUs). Of 194 institutions participating in a nationwide QI initiative, 193 (99.4%) participated in these activities, totalling 850 healthcare professionals. From these, 641 participants responded to the survey (75.4%). The post-intervention survey showed that the participants responded positively to the educational activities. CONCLUSION: The participants perceived the various pedagogical strategies positively, which shows the value of a broad and diverse educational approach, customised to local settings and including game-based activities, to enhance learning among healthcare professionals.

Comparison of ruminal microbiota, IL-1ß gene variation, and tick incidence between Holstein × Gyr and Holstein heifers in grazing system.

Introduction: The variation in bacterial communities among breeds has been previously reported and may be one of the reasons why Holstein × Gyr dairy heifers have better development in grazing systems in tropical conditions. This study aimed to explore the ruminal microbiota composition, the IL-1ß gene variation, tick incidence, and blood parameters of Holstein × Gyr (½ Holstein × ½ Gyr) and Holstein heifers grazing intensely managed Guinea grass (Panicum maximum Jacq. cv. Mombaça). Methods: Sixteen heifers were divided into two groups consisting of 8 Holstein × Gyr and 8 Holstein heifers. The experimental period was comprised of 3 periods of 21 days. Ruminal samples were taken via the stomach tube technique. The sequencing of the V4 hypervariable region of the 16S rRNA gene was performed using the Illumina MiSeq platform. Counting and collection of ticks were conducted each 21 days. Blood and skeletal muscle tissue biopsies were performed at the end of the experiment. Results: Firmicutes were the most abundant phyla present in both breed rumen samples and Bacteroidota showed differences in relative abundance between breed groups, with greater values for Holstein heifers (p < 0.05 with FDR correction). The 10 most abundant unique OTUs identified in each breed included several OTUs of the genus Prevotella. Holstein heifers had a greater tick count and weight (9.8 ticks/animal and 1.6 g/animal, respectively) than Holstein × Gyr (2.56 ticks/animal and 0.4 g/animal, respectively). We found nucleotide substitutions in the IL-1ß gene that might be related to adaptation and resistance phenotypes to tick infestation in Holstein × Gyr heifers. Blood concentrations of urea, albumin, insulin-like growth factor 1, triiodothyronine, and thyroxine were greater in Holstein × Gyr than in Holstein heifers. Conclusion: Adaptations in Holstein × Gyr heifers such as ruminal microbiota, tick resistance, nucleotide substitutions in IL-1ß gene, and hormone concentration suggest a better energy metabolism and thermoregulation resulting in better performance in tropical grazing systems.

Intestinal microbial diversity of swines fed with different sources of lithium.

A drug that is widely used in the treatment of psychiatric disorder is lithium (Li) salts. The people who make therapeutic use of this drug develop a series of side effects. Through metataxonomic data, this study assessed the impacts of lithium, as Li carbonate or Li-enriched mushrooms, on the microbial composition of the ileum, colon, and feces of piglets. Employing Bray-Curtis metric, no differences were observed among the treatments evaluated. Nevertheless, the alpha diversity indices showed differences in the Simpson, Shannon, and Chao-1 indices in the colon and Chao-1 in the feces in the diets with Li compared with the diets without Li. The taxa with the highest relative abundance varied among the ileum, colon, and feces, with a predominance of the phyla Firmicutes, Bacteroidota, and Proteobacteria in diets with Li. Many groups of microorganisms that are important for the health of the host (e.g., Lactobacillus, Ruminococcaceae, Enterorhabdus, Muribaculaceae, and Coprococcus) had their relative abundance increased in animals that received diets with the recommended dose of lithium. Furthermore, there was an increase in the abundance of Prevotellaceae and Bacteroidales (in the diet with Li-enriched mushroom) and Clostridia, Ruminococcus, Burkholderia, and Bacteroidales (diets with Li carbonate) at the recommended dosages. This is the first study to show the effects of Li carbonate and Li-enriched mushrooms on the intestinal microbiota of piglets. Thus, the effects of lithium on the body may be related to its ability to change the composition of the intestinal microbiota. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03938-3.

Prevalence and characteristics of ESBL-producing Escherichia coli in clinically healthy pigs: implications for antibiotic resistance spread in livestock.

AIM: This study aimed to compare and characterize the resistance profile and the presence of extended-spectrum beta-lactamase (ESBL) related genes in Escherichia coli isolated from healthy finishing pigs fed with or without antibiotics in their diets. METHODS AND RESULTS: A total of 27 ceftiofur-resistant E. coli isolates were obtained from 96 healthy pigs. The antibiotic resistance profile was tested, and all 27 isolates were classified as multidrug-resistant (MDR). A high proportion of isolates were resistant to cephalosporins, ampicillin, ciprofloxacin, and tetracyclines. The ESBL production was observed in 85% of isolates by double-disc synergy test. The MDR-E. coli isolates harbored ESBL genes, such as blaTEM, blaCTX-M-1, blaCTX-M-2, and blaCTX-M-8,25. In addition, other antibiotics resistance genes (ARGs) were also detected, such as sul2, ant(3″)-I, tetA, and mcr-1. The mobilization of the blaCTX-M gene was confirmed for nine E. coli isolates by conjugation assays. The presence of blaCTX-M on mobile genetic elements in these isolates was demonstrated by Southern blot hybridization, and the resistance to cephalosporins was confirmed in the transconjugants. Our results indicate the prevalence of CTX-M-producing E. coli strains harboring mobile genetic elements in the normal microbiota of healthy pigs. CONCLUSIONS: These findings highlight the significance of ESBL genes as a global health concern in livestock and the potential spread of antimicrobial resistance to other members of the gastrointestinal tract microbiota.

Physical activity of adolescents and the urban environment of Brazilian capitals: National School Health Survey, 2015.

This study aimed to evaluate the practice of physical activity (PA) among adolescents and its association with characteristics of the urban environment of Brazilian capitals. Study with adolescents from the 26 Brazilian capitals and the Federal District participating in the National School Health Survey, 2015 edition. The association between regular practice of PA (≥300 minutes/week) and the dimensions of urban well-being (urban mobility, urban environmental conditions, urban housing conditions, urban collective services, and urban infrastructure) was examined using multilevel logistic regression. A total of 50,904 adolescents were evaluated, among which 20.7% were active. It was observed in the multiple model that adolescents who live in capitals with better urban environmental conditions, such as the presence of tree coverage, less open sewage, and less accumulated garbage around the houses, are more likely to be active (OR = 1.06; 95% CI:1.01;1.12). Adolescents who live in cities with less urban disorder are more likely to be active.

Developing and validating a 2D digital version of the Brazilian Children's anxiety questionnaire.

PURPOSE: This study aims to transpose the printed Brazilian Children's Anxiety Questionnaire (CAQ BR) into a 2D digital format, validate it with nurses and hospitalized children, and analyze the association between the printed and 2D digital format versions. DESIGN AND METHOD: This is a descriptive and multicentric study, conducted from 2021 to 2022 on working in pediatric care at two hospitals in Brazil. The nurses analyzed the printed and digital instruments and subsequently applied them to a child and proposed suggestions. A cutoff score of 0.80 on the content validity index was used; items that scored an average lower than the CVI in the study were adequate. Eighty children responded to the questionnaires sequentially according to the randomization table. A 90% agreement rate was used. RESULTS: The digital instrument was validated in content by 51 experts, with a CVI of 0.95. Face validation data for 80 children (mean age = 7.9 years) shows a 90% agreement rate. The intraclass correlation index for the general score was 0.87 and 95% CI (0.79-0.91), which shows good stability of the children's responses in both questionnaires. In addition, 59% (n = 47) of the children reported a preference for the digital questionnaire. CONCLUSIONS: The digital CAQ BR can be used as an audiovisual instrument by nurses when implementing the systematization of nursing care in pediatrics. PRACTICAL IMPLICATIONS: The digital 2D version was successfully applied and can be used in hospitals to measure children's self-reported anxiety.

Alpha1- and Beta-norepinephrinergic receptors of dorsomedial and ventromedial hypothalamic nuclei modulate panic attack-like defensive behaviour elicited by diencephalic GABAergic neurotransmission disinhibition.

Gamma-aminobutyric acid (GABA) disinhibition in medial hypothalamus (MH) nuclei of rats elicits some defensive reactions that are considered panic attack-like behaviours. Recent evidence showed that the norepinephrine-mediated system modulates fear-related defensive behaviours organised by MH neurons at least in part via noradrenergic receptors recruitment on midbrain tegmentum. However, it is unknown whether noradrenergic receptors of the MH also modulate the panic attack-like reactions. The aim of this work was to investigate the distribution of noradrenergic receptors in MH, and the effects of either α1-, α2- or ß-noradrenergic receptors blockade in the MH on defensive behaviours elaborated by hypothalamic nuclei. Defensive behaviours were evaluated after the microinjection of the selective GABAA receptor antagonist bicuculline into the MH that was preceded by microinjection of either WB4101, RX821002, propranolol (α1-, α2- and ß-noradrenergic receptor selective antagonists, respectively), or physiological saline into the MH of male Wistar rats. The α1-, α2- and ß-noradrenergic receptors were found in neuronal perikarya of all MH nuclei, and the α2-noradrenergic receptor were also found on glial cells mainly situated in the ventrolateral division of the ventromedial hypothalamic nucleus. The α1- and ß-noradrenergic receptors blockade in the MH decreased defensive attention and escape reactions elicited by the intra-MH microinjections of bicuculline. These findings suggest that, despite the profuse distributions of α1-, α2- and ß-noradrenergic receptors in the MH, both α1- and ß-noradrenergic receptor- rather than α2-noradrenergic receptor-signalling in MH are critical for the neuromodulation of panic-like behaviour.

Is Galleria mellonella model a good alternative to study virulence in Staphylococcus aureus from bovine mastitis?

Staphylococcus aureus is one of the agents of bovine mastitis of hardest control due to a complex pathogenesis comprising a variety of virulence factors, which ensures its persistence in the mammary gland, causing significant health and economic losses. Therefore, understanding the pathogenesis of this agent is imperative. Galleria mellonella has stood out as an invertebrate animal model for the study of infectious diseases that affect several hosts. This work aimed to evaluate G. mellonella larvae as an experimental model for the study of virulence phenotypes in an S. aureus population isolated from bovine mastitis. Thirty genetically divergent S. aureus strains were chosen based on PFGE analysis. After experimental infection, larvae survival rates, bacterial growth in hemolymph, melanization intensity of the dorsal vessel, and histological characteristics of the infected tissues were evaluated. The G. mellonella model showed a clear diversity in the S. aureus pathogenicity pattern, allowing the differentiation of strains with virulence phenotypes ranging from high to low degrees. Histological analysis confirmed that the strains tested were capable of inducing the formation of nodules and melanization spots in the dorsal vessels of the larvae in different magnitudes. The strains 16S-717, 19C-828, and 31S-1443 presented the highest virulence intensity among the bacteria tested and will be used further for the generation of S. aureus mutant populations to prospect genetic targets aimed to develop control strategies of bovine mastitis. Altogether, our results suggest that G. mellonella is an attractive and low-cost animal model for characterizing virulence phenotypes of large S. aureus populations.

A combined experimental-molecular modeling study of crown ether europium complexes: Effects of the coordinated anion on structural and luminescence properties.

It is reported the synthesis, characterization by elemental analysis, thermogravimetry; electronic absorption, infrared, excitation, and emission spectroscopies of the [Eu(12C4)(phen)2(X)n]X2 complexes, where 12C4 = 12-crown-4, phen = 1,10-phenanthroline, and X  = F-, Cl-, Br-, SCN-, ClO4-, and NO3-. It is verified that the polarizability of the anion X- exerts remarkable effects on the emission process. As a general trend, lower wavenumbers for the 7F0→5L6, 7F0→5D2 and 7F0→5D1 transitions are associated with the anions with higher volumes and, consequently, higher polarizability. The molecular modeling results performed with quantum methods (RHF and DFT) suggest some relationships between the calculated structures, electronic, and luminescence properties with the presence of the LMCT (ligand-to-metal charge transfer) states, which explains the differences in the emission spectra of these complexes due to the coordinated anion.

Comparative toxicity of coal and coal ash: Assessing biological impacts and potential mechanisms through in vitro and in vivo testing.

BACKGROUND: Coal and coal ash present inorganic elements associated with negative impacts on environment and human health. The objective of this study was to compare the toxicity of coal and coal ash from a power plant, assess their inorganic components, and investigate the biological impacts and potential mechanisms through in vitro and in vivo testing. METHODS: Particle-Induced X-ray Emission method was used to quantify inorganic elements and the toxicity was evaluated in Caenorhabditis elegans and Daphnia magna in acute and chronic procedures. The genotoxic potential was assessed using alkaline and FPG-modified Comet assay in HepG2 cells and mutagenicity was evaluated using Salmonella/microsome assay in TA97a, TA100, and TA102 strains. RESULTS: Inorganic elements such as aluminum (Al) and chromium (Cr) were detected at higher concentrations in coal ash compared to coal. These elements were found to be associated with increased toxicity of coal ash in both Caenorhabditis elegans and Daphnia magna. Coal and coal ash did not induce gene mutations, but showed genotoxic effects in HepG2 cells, which were increased using the FPG enzyme, indicating DNA oxidative damage. CONCLUSIONS: The combined findings from bioassays using C. elegans and D. magna support the higher toxicity of coal ash, which can be attributed to its elevated levels of inorganic elements. The genotoxicity observed in HepG2 cells confirms these results. This study highlights the need for continuous monitoring in areas affected by environmental degradation caused by coal power plants. Additionally, the analysis reveals significantly higher concentrations of various inorganic elements in coal ash compared to coal, providing insight into the specific elemental composition contributing to its increased toxicity.

Antimicrobial Resistance Profiles of Multidrug-Resistant Enterobacteria Isolated from Feces of Weaned Piglets.

Nosocomial infections caused by multidrug-resistant enterobacteria have become a major challenge in global public health. Previous studies have indicated that use of antibiotics in livestock production chains is linked to the rising threat of antibiotic resistance in humans. In this study, we aimed to evaluate the distribution of genes encoding resistance to tetracycline, ß-lactams, and colistin in multidrug-resistant enterobacteria isolated from feces of weaned pigs. Ninety-four enterobacteria isolates were submitted to antibiotic susceptibility test by minimum inhibitory concentration (MIC). In addition, we performed conjugation experiments to verify if plasmid-bearing isolates containing the mcr-1 gene could transfer their resistance determinant to a colistin-sensitive recipient strain. Our results demonstrated a positive association between the detection of antibiotic resistance genes in enterobacteria and the phenotypic resistance profiles of the bacterial isolates. At least one of the extended-spectrum ß-lactamases (ESBL) genes (blaCTX-M, blaTEM, or bla SHV) and tetA was found among most bacterial genera analyzed. In addition, results revealed that the mcr-1 gene can be transferred from E. coli UFV-627 isolate to an F- recipient (Escherichia coli K12) by conjugation. Our findings support the hypothesis that swine represents an important reservoir of antibiotic resistance genes and suggest that horizontal transfer mechanisms (e.g., conjugation) may mediate the spread of these genes in the swine gastrointestinal tract.

Toxicological assessment of minoxidil: A drug with therapeutic potential besides alopecia.

Minoxidil is regularly prescribed for alopecia, and its therapeutic potential has expanded in recent times. However, few studies have been conducted to evaluate its toxicity, and controversial findings regarding its mutagenic activities remain unsolved. This study aimed to access cytotoxic, genotoxic, and mutagenic properties of minoxidil using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, comet assay, and micronucleus test in mouse fibroblast (L929) cells and its point mutation induction potential in the Salmonella/microsome assay. Furthermore, an in vivo toxicity assessment was conducted in Caenorhabditis elegans. Minoxidil showed cytotoxicity at 2.0 mg/mL in MTT assay. Genotoxicity was observed after 3 h treatment in L929 cells using comet assay. No mutagenic effect was observed in both the micronucleus test and the Salmonella/microsome assay. The lethal dose 50 in C. elegans was determined to be 1.75 mg/mL, and a delay in body development was detected at all concentrations. In conclusion, minoxidil induces DNA damage only in early treatment, implying that this DNA damage may be repairable. This observation corroborates the absence of mutagenic activities observed in L929 cells and Salmonella typhimurium strains. However, the toxicity of minoxidil was evident in both C. elegans and L929 cells, underscoring the need for caution in its use.

Evaluation of the Neuroprotective Effect of Organic Selenium Compounds: An in Vitro Model of Alzheimer's Disease.

Selenium (Se) is an essential trace element for human health and plays an important role in the development and maintenance of central nervous system functions. Se deficiency has been associated with cognitive decline and increased oxidative stress. The increase in oxidative stress is one of the hypotheses for the emergence and worsening of neurodegenerative diseases, such as Alzheimer's disease (AD). To investigate the neuroprotective effects of organic Se compounds in human neuroblastoma cells (SH-SY5Y) differentiated into cholinergic neurons-like. The SH-SY5Y cells were differentiated into cholinergic neuron-like with retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). AD was mimicked exposing the cells to okadaic acid (OA) and beta-amyloid protein (Aß). The neuroprotective effect of organic Se compounds, selenomethionine (SeMet) and Ebselen, was evaluated through cell viability tests, acetylcholinesterase and antioxidant enzyme activities, and detection of reactive oxygen species (ROS). None of the SeMet concentrations tested protected against the toxic effect of OA + Aß. On the other hand, previous exposure to 0.1 and 1 µM Ebselen protected cells from the toxic effect of OA + Aß. Cell differentiation induced by RA and BDNF exposure was effective, showing characteristics of neuronal cells, and pointing to a promising model of AD. Ebselen showed a protective effect, but more studies are needed to identify the mechanism of action.

Cranial anatomical structures with high sexual dimorphism in metric and morphological evaluation: A systematic review.

The mastoid process has attracted the attention of several researchers due to its protected position at the base of the skull and the fact that it is relatively compact, in addition to being highly resistant and dimorphic, considered as a gold standard anatomical structure in the determination of the sexual dimorphism of skulls. However, intrinsic and extrinsic factors may influence this anatomical structure over time, providing contradictory and ambiguous data. Therefore, other anatomical structures need to be evaluated concurrently with the mastoid process to provide better accuracy and reliability of skull sexual dimorphism data. Thus, the objective of this systematic review was to evaluate the degree of reliability of the mastoid process to determine sexual dimorphism compared to other dimorphic structures, since there are still no systematic reviews on the subject in the literature. This review follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was recorded in the Prospective International Systematic Reviews Registry (PROSPERO) (CRD 42023395167 Systematic Registry) (CRD420223). The inclusion criteria for selecting the studies were based on the PICO question: "Are skull anatomical structures reliable as alternatives to determine sexual dimorphism compared to the mastoid process?". A literature search for studies was performed in the MEDLINE Scopus, Web of Science, LILACS, and Cochrane Library databases. The Kappa agreement presented an approval level of (k = 0.93). This systematic review analyzed 13 ex-vivo studies published between 2008 and 2023. The risk of bias was considered low in 12 of the studies, and high in 1 study. Based on the findings, it can be concluded that even with the limitations of this systematic review, quantitative and qualitative analyses are essential in sexual identification of human skulls, and different anatomical structures can be used as references in addition to the mastoid process, with high reliability and precision, among them the; glabella, frontal profile, superciliary arch, bizygomatic width, maximum cranial length, and nasal height.