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Elaine A Leite,1,2 Cristina M Souza,3 Álvaro D Carvalho-Júnior,1,2 Luiz GV Coelho,4 Ângela MQ Lana,5 Geovanni D Cassali,3 Mônica C Oliveira11Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Departamento de Farmácia, Faculdade de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil; 3Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 4Departamento de Clínica Médica, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 5Departamento de Zootecnia, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilAbstract: Cisplatin (CDDP) is one of the most effective and potent anticancer drugs used as first-line chemotherapy against several solid tumors. However, the severe side effects and its tendency to provoke chemoresistance often limit CDDP therapy. To avoid these inconveniences, the present study's research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). The present study aimed to evaluate the antitumor effect and toxicity of SpHL-CDDP, as compared with that of free CDDP, and long-circulating and non-pH-sensitive liposomes containing CDDP (NSpHL-CDDP), after their intravenous administration in solid Ehrlich tumor-bearing mice. Antitumor activity was evaluated by analysis of tumor volume and growth inhibition ratio, serum vascular endothelial growth factor (VEGF) levels, and histomorphometric and immunohistochemical studies. Body weight variation and the histological examination of bone marrow and kidneys were used as toxicity indicators. A significant reduction in the tumor volume and a higher tumor growth inhibition ratio was observed after SpHL-CDDP treatment, compared with free CDDP and NSpHL-CDDP treatments. In addition, complete remission of the tumor was detected in 18.2% of the mice treated with SpHL-CDDP (16 mg/kg). As such, the administration of SpHL-CDDP, as compared with free CDDP and NSpHL-CDDP, led to a decrease in the area of necrosis and in the percentage of positive CDC 47 tumor cells. A significant reduction in the VEGF serum level was also observed after SpHL-CDDP treatment, as compared with free-CDDP treatment. SpHL-CDDP administered in a two-fold higher dose than that of free CDDP presented a loss in body weight and changes in the hematopoietic tissue morphology, which proved to be similar to that of free CDDP. No changes could be verified in the renal tissue after any formulations containing CDDP had been administered. These findings showed that SpHL-CDDP allowed for the administration of higher doses of CDDP, significantly improving its antitumor effect.Keywords: antitumor effect, toxicity, angiogenesis, Ehrlich tumor

Forest degradation in the Brazilian Amazon due to selective logging and forest fires may greatly increase the human footprint beyond outright deforestation. We demonstrate a method to quantify annual deforestation and degradation simultaneously across the entire region for the years 2000-2010 using high-resolution Landsat satellite imagery. Combining spectral mixture analysis, normalized difference fraction index, and knowledge-based decision tree classification, we mapped and assessed the accuracy to quantify forest (0.97), deforestation (0.85) and forest degradation (0.82) with an overall accuracy of 0.92. We show that 169,074 km2 of Amazonian forest was converted to human-dominated land uses, such as agriculture, from 2000 to 2010. In that same time frame, an additional 50,815 km2 of forest was directly altered by timber harvesting and/or fire, equivalent to 30% of the area converted by deforestation. While average annual outright deforestation declined by 46% between the first and second halves of the study period, annual forest degradation increased by 20%. Existing operational monitoring systems (PRODES: Monitoramento da Florestal Amazônica Brasileira por Satélite) report deforestation area to within 2% of our results, but do not account for the extensive forest degradation occurring throughout the region due to selective logging and forest fire. Annual monitoring of forest degradation across tropical forests is critical for developing land management policies as well as the monitoring of carbon stocks/emissions and protected areas.. © 2013 by the authors.

Bassam Felipe Mogharbel,1 Julio Cesar Francisco,1 Ana Carolina Irioda,1 Dilcele Silva Moreira Dziedzic,1 Priscila Elias Ferreira,1 Daiany de Souza,1 Carolina Maria Costa de Oliveira Souza,1 Nelson Bergonse Neto,2 Luiz Cesar Guarita-Souza,2 Celia Regina Cavichiolo Franco,3 Celso Vataru Nakamura,4 Vanessa Kaplum,4 Letícia Mazzarino,5 Elenara Lemos-Senna,6 Redouane Borsali,7 Paula A Soto,8 Patricia Setton-Avruj,8 Eltyeb Abdelwahid,9 Katherine Athayde Teixeira de Carvalho1 1Cell Therapy and Biotechnology in Regenerative Medicine Department, Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research and Pequeno Príncipe Faculty, Curitiba, Paraná, Brazil; 2Institute of Biological and Health Sciences, Pontifical Catholic University of Paraná (PUCPR), Centro de Ciências Biológicas e da Saúde (CCBS), Curitiba, Brazil; 3Cell Biology Department, Federal University of Paraná, Curitiba, Paraná, Brazil; 4Department of Pharmaceutical Sciences, Universidade Estadual de Maringá, Maringá, Paraná, Brazil; 5Department of Pharmaceutical Sciences, NanoBioMat Laboratory, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil; 6Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil; 7Centre de Recherches sur les Macromolécules Végétales (CERMAV), Centre National de la Recherche Scientifique (CNRS), University Grenoble Alpes, F-38000, Grenoble, France; 8Instituto de Química y Físicoquímica Biológica (IQUIFIB), Departament of Química Biológica, Facultad de Farmacia y Bíoquímica, Universidad de Buenos Aires (UBA) Consejo nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentine; 9Feinberg School of Medicine, Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, Il, USA Background: Posttransplant cell tracking, via stem cell labeling, is a crucial strategy for monitoring and maximizing benefits of cell-based therapies. The structures and functionalities of polysaccharides, proteins, and lipids allow their utilization in nanotechnology systems. Materials and methods: In the present study, we analyzed the potential benefit of curcumin-loaded nanoparticles (NPC) using Vero cells (in vitro) and NPC-labeled adipose-derived mesenchymal stem cells (NPC-ADMSCs) (in vivo) in myocardial infarction and sciatic nerve crush preclinical models. Thereafter, transplantation, histological examination, real time imaging, and assessment of tissue regeneration were done. Results: Transplanted NPC-ADMSCs were clearly identified and revealed potential benefit when used in cell tracking. Conclusion: This approach may have broad applications in modeling labeled transplanted cells and in developing improved stem cell therapeutic strategies. Keywords: mesenchymal stem cells, transplantation, cell marking, myocardium infarction, sciatic nerve crush

Background and Objective: Chronic kidney disease (CKD) is a complex disorder, which results in several complications involving disturbance of mineral metabolism. Periodontal disease is an infectious disease that appears to be an important cause of systemic inflammation in CKD patients. Periodontal disease is characterized by clinical attachment loss (CAL) caused by alveolar bone resorption around teeth, which may lead to tooth loss. Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. Polymorphisms are the main source of genetic variation, and single nucleotide polymorphisms (SNPs) have been reported as major modulators of disease susceptibility. The aim of this study was to investigate the association of a polymorphism located at position -223 in the untranslated region of the OPG gene, previously known as -950, with susceptibility to CKD and periodontal disease. Material and Methods: A sample of 224 subjects without and with CKD (in hemodialysis) was divided into groups with and without periodontal disease. The OPG polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Results: No association was found between the studied OPG polymorphism and susceptibility to CKD or periodontal disease. Conclusion: It was concluded that polymorphism OPG-223 (C/T) was not associated with CKD and periodontal disease in a Brazilian population. Studies on other polymorphisms in this and other genes of the host response could help to clarify the involvement of bone metabolism mediators in the susceptibility to CKD and periodontal disease. [ABSTRACT FROM AUTHOR]

ETHNOPHARMACOLOGICAL RELEVANCE: Validate the popular use of Plectranthus grandis in gastric disorders through the active components. AIMS: Isolation of barbatusin (BB) and 3beta-hydroxy-3-deoxibarbatusin (BBOH), diterpenes from Plectranthus grandis, and evaluation of their gastroprotective effect and possible mechanisms of action. MATERIALS AND METHODS: Isolation and chemical characterization of diterpenes from Plectranthus grandis by chromatographic and spectroscopic methods and evaluation of gastroprotective action of the diterpenes through ethanol-induced gastric injury in mice model. It was evaluated the effect of capsazepine, indomethacin and the role of nitric oxide and K(ATP-) channels on the gastroprotective effect of BBOH and BB. Additionally it was measured the concentrations of gastric mucus, non-proteic-sulfhydryl groups and total thiobarbituric acid-reactive substances. RESULTS: Orally administered BBOH and BB at doses of 5 and 10mg/kg, markedly reduced the gastric lesions by 59 and 96%, and 32 and 76%, respectively, with superior results as compared to N-acetylcysteine (150 mg/kg, i.p.), reference compound that caused 85% lesion suppression. Although BBOH presented a higher gastroprotection than BB they act by similar mechanisms in relation to N-acetylcysteine, and prevent the depletion of gastric mucus, gastric mucosal non-proteic-sulfhydryl groups as well as the increase in thiobarbituric acid-reactive species. Moreover, the gastroprotective effect of BB was effectively blocked in mice pretreated with TRPV1 antagonist capsazepine, by the non-selective cyclooxygenase inhibitor indomethacin, or by the nitric oxide synthase inhibitor L-NAME but not by K(+)(ATP) channel inhibitor glibenclamide. In contrast, the gastroprotective effect of BBOH was blocked only by indomethacin and glibenclamide pretreatments. CONCLUSION: The protective role for BBOH and BB affording gastroprotection against gastric damage induced by ethanol indicates that these compounds contribute for the activity of Plectranthus species. The different modes of action are probably related to differences in their chemical structure. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa, an opportunistic pathogen often found in Healthcare-associated infections (HAI), has shown increased resistance to carbapenems (imipenem, meropenem, doripenem), the primary treatment options. We've seen a rise in carbapenemase-producing P. aeruginosa in Brazil, including NDM-producers. This study characterises an isolate carrying bla NDM-1 from a patient's skin fragment in a Brazilian hospital. The whole genomic sequence (WGS) of P. aeruginosa CCBH26428 was extracted and sequenced using Illumina and minION platforms. The assembly used MinION results mapped with Illumina reads, and annotation was performed by the RAST server. Resistance genes and clonality were identified using the CABGen platform. Additional information was carried out by manual annotation using Geneious software and BLAST tool. The genomic analysis revealed a genome of 6.995.008 bp and G+C 65.9 %. P. aeruginosa CCBH26428 belongs to ST2407. The bla NDM gene, associated with ISAba125, was found in a 63.862 pb genomic region flanked by IS26 insertion sequences. This region also contained the repA of the plasmid incompatibility group IncC2 and other resistance genes, suggesting it is a possible "translocation unit". Additionally, 17 resistance genes, mutations in OprD and GyrA, and several virulence genes were detected, potentially exacerbating the infection. This study is report a WGS analysis of P. aeruginosa carrying bla NDM-1 in Brazil, highlighting the role of IS26 in the acquisition and spread of resistance genes between plasmids and chromosomes., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: An in-depth evaluation of the published evidence is needed on self-medication, specifically the evidence focusing on vulnerable groups, such as pregnant women. This scoping review aims to provide an overview of the differences in self-medication prevalence and study characteristics among different groups, while identifying gaps in the literature., Methods: A literature search was performed in PubMed and Web of Science, including articles published in the last 10 years for the pregnant women group (PWG) and the general population group (GPG). Data on study design, self-medication prevalence, medications used, and other variables were collected, tabulated, and summarized., Results: From 2888 screened articles, 75 were considered including 108,559 individuals. The self-medication (SM) in the PWG ranged from 2.6 to 72.4% and most studies had an SM prevalence between 21 and 50% and in the GPG, 32 from 50 studies had a SM prevalence higher than 50%. The reviewed studies varied considerably in methodology, requiring careful interpretation. While most of the studies assessed self-medication during the entire pregnancy, self-medication definition was often inconsistent between studies. Acetaminophen was the most used medication and headache was the most frequent symptom leading to self-medication initiation in the PWG., Conclusions: Self-medication among pregnant women showed a lower prevalence when compared to the general population. The medications used and symptoms reported were similar between groups. However, methodological differences must be carefully considered. Pregnant women should carefully follow their physicians' advice before initiating self-medication to avoid preventable maternal and fetal adverse effects., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Objective: To develop and validate a mobile application prototype for nursing shift handover in a hospital inpatient unit., Methods: A methodological study of technological production, carried out from April 2020 to January 2022, for mobile application construction and validity through the Design Thinking methodology. The study involved the stages of prototype development and validity by experts., Results: The application for mobile nursing shift handover obtained a usability score of 79 points and a content validity coefficient of 0.7., Conclusions: The instrument obtained an excellent assessment according to usability and agreement among experts. However, future studies are needed to implement this technology in order to assess effectiveness, time optimization and failures during communication.

Purpose: To investigate the association of SOX2 polymorphisms with oral leukoplakia with dysplasia (OLD) and compare it with the immunohistochemical expression of SOX-2., Methods: The samples comprised 64 patients with oral leukoplakia and 20 with normal oral mucosa who were subjected to SOX2 polymorphism rs77677339 genotyping by real-time polymerase chain reaction and immunohistochemistry for SOX-2 (basal epithelium expression, suprabasal and total; nuclear area and intensity). Statistical tests included the Chi-square and Fisher's exact tests., Results: No significant difference was observed in genotype distribution between the OLD and control groups. The GG genotype (96.9%) was observed in the OLD group and 100% in the control group. The GA genotype was not observed in the control group. Statistical comparisons between the immunohistochemistry and genetic results were not statistically significant. No association was identified between rs77677339 and immunohistochemistry in OLD; however, the presence of allele A in heterozygotes with OLD suggests that this allele may serve as a risk marker., Conclusion: The variant rs77677339 is localized in a region that contains different micro-RNA-binding sites, which can lead to changes in gene expression, contributing to OLD development through unclear molecular mechanisms. This study presents the preliminary results for this single nucleotide polymorphism in the literature., Competing Interests: DECLARATIONS OF INTEREST The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

A feature of Candida tropicalis is its ability to undergo phenotypic switching that can affect antifungal sensitivity and virulence traits. Here, we investigated the effect of switching on alterations at the cellular structure level of C. tropicalis morphotypes and whether exposure to fluconazole (FLC) in vitro could be associated with these alterations in a morphotype-dependent manner. Candida tropicalis morphotypes included clinical isolate (Parental) and two switch strains (Crepe variant and revertant of Crepe-RC). The minimum inhibitory concentration (MIC50) of fluconazole was determined according to EUCAST. Cell wall porosity, quantification of cell wall components, cell size/complexity, and expression of ERG11 and CDR1 genes in morphotypes pre- and post-exposure to fluconazole were determined. Crepe and RC showed an eightfold higher MIC50 (1 µg/ml) than the Parental (0.125 µg/ml). Exposure to FLC resulted in twofold higher MIC50 for Parental and RC. The Crepe variant exhibited a fourfold higher expression of ERG11, and the RC showed 10-fold higher expression of CDR1 than the clinical isolate. Switch strains showed reduced cell wall porosity compared to Parental, and exposure to FLC resulted in a significant reduction in the porosity of Parental and RC cells. Furthermore, phenotypic switching affected cell wall β-1,3-glucan and chitin contents in a morphotype-dependent manner. Our findings indicate that switching affects cellular structure in C. tropicalis and the occurrence of differential alterations between the clinical isolate and its switched states in response to fluconazole exposure., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Fungal lipolytic enzymes play crucial roles in various lipid bio-industry processes. Here, we elucidated the biochemical and structural characteristics of an unexplored fungal lipolytic enzyme (TaLip) from Thermoascus aurantiacus var. levisporus, a strain renowned for its significant industrial relevance in carbohydrate-active enzyme production. TaLip belongs to a poorly understood phylogenetic branch within the class 3 lipase family and prefers to hydrolyze mainly short-chain esters. Nonetheless, it also displays activity against natural long-chain triacylglycerols. Furthermore, our analyses revealed that the surfactant sodium dodecyl sulfate (SDS) enhances the hydrolytic activity of TaLip on pNP butyrate by up to 5.0-fold. Biophysical studies suggest that interactions with SDS may prevent TaLip aggregation, thereby preserving the integrity and stability of its monomeric form and improving its performance. These findings highlight the resilience of TaLip as a lipolytic enzyme capable of functioning in tandem with surfactants, offering an intriguing enzymatic model for further exploration of surfactant tolerance and activation in biotechnological applications., 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 Inc. All rights reserved.)

Background: Resistant infectious diseases caused by gram-negative bacteria are among the most serious worldwide health problems. Antimicrobial peptides (AMPs) have been explored as promising antibacterial, antibiofilm, and anti-infective candidates to address these health challenges., Major Conclusions: Here we report the potent antibacterial effect of the peptide PaDBS1R6 on clinical bacterial isolates and identify an immunomodulatory peptide fragment incorporated within it. PaDBS1R6 was evaluated against Acinetobacter baumannii and Escherichia coli clinical isolates and had minimal inhibitory concentration (MIC) values from 8 to 32 μmol L -1 . It had a rapid bactericidal effect, with eradication showing within 3 min of incubation, depending on the bacterial strain tested. In addition, PaDBS1R6 inhibited biofilm formation for A. baumannii and E. coli and was non-toxic toward healthy mammalian cells. These findings are explained by the preference of PaDBS1R6 for anionic membranes over neutral membranes, as assessed by surface plasmon resonance assays and molecular dynamics simulations. Considering its potent antibacterial activity, PaDBS1R6 was used as a template for sliding-window fr agmentation studies (window size = 10 residues). Among the sliding-window fragments, PaDBS1R6F8, PaDBS1R6F9, and PaDBS1R6F10 were ineffective against any of the bacterial strains tested. Additional biological assays were conducted, including nitric oxide (NO) modulation and wound scratch assays, and the R6F8 peptide fragment was found to be active in modulating NO levels, as well as having strong wound healing properties., General Significance: This study proposes a new concept whereby peptides with different biological properties can be derived by the screening of fragments from within potent AMPs., 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. Published by Elsevier B.V.)

Purpose: To analyze the influence of temperature on the flow/texture of different foods, immediately after preparation and after one hour, and 2) To compare the influence of varying the cook in food preparation, in relation to food flow., Methods: This is a quantitative and experimental study. The IDDSI standardized flow test was used to evaluate the remaining volume in the syringe and the levels of foods (porridge, smoothie, liquid soup, and pureed light soup) prepared by different cooks, in triplicate, at time zero (T0) and after one hour (T1)., Results: Differences in temperature were observed in all foods at T0 and T1 (p < 0.05). The IDDSI level changed only in porridge, from level 3 to 4 (p = 0.043). Modifications were observed in the preparation by different cooks for smoothie, on the 2nd and 3rd day (p = 0.049), from level 3 to 4 of IDDSI. In porridge, on the 1st and 3rd day (p = 0.048) and 2nd and 3rd day (p = 0.048), with a change from level 4 to 3 of IDDSI., Conclusion: The temperature of all foods differed within the one-hour interval, with modifications in the flow test and in the IDDSI levels, from level 3 to 4, only for porridge. Different cooks prepared the smoothie and porridge with different characteristics, resulting in changes from level 3 to 4 in both foods.

The COVID-19 pandemic created global disruption in health professions education and healthcare practice, necessitating an abrupt move to digital delivery. A longitudinal survey was conducted to track the evolution of global responses to the pandemic. During the initial stages, educational and health institutions were forced to adapt quickly without careful consideration of optimal pedagogy, practices, and effectiveness of implemented approaches. In this paper, we report the results of Phase 3 of the global survey that was distributed between November 2021 and February 2022 through InterprofessionalResearch.Global (IPR.Global). The Phase 3 qualitative survey received 27 responses, representing 25 institutions from 13 countries in 6 regions. Using inductive thematic analysis, the data analysis resulted in three emerging themes: Impact of the pandemic on the delivery of interprofessional education and collaborative practice (IPECP); Impact of the pandemic on the healthcare system (team, population/client health, clients); and Sustainability and innovation. This study highlights the evolving nature of health education and collaborative practices in response to the COVID-19 pandemic. IPECP educators need to be resilient and deal with the complexities of face-to-face and digital learning delivery. Preparing for emerging forms of teamwork is essential for new work contexts and optimal health services.

Enterobacter cloacae complex isolates have been reported as an important nosocomial multidrug resistance pathogen. In the present study, we investigated antimicrobial susceptibility and the colistin-resistance rates, their genetic determinants and clonality among clinical E. cloacae complex isolates from different Brazilian states. For this, an initial screening was carried out on 94 clinical isolates of E. clocacae complex received between 2016 and 2018 by LAPIH-FIOCRUZ, using EMB plates containing 4 μg/mL of colistin, followed MIC determination, resulting in the selection of 26 colistin-resistant isolates from the complex. The presence of carbapenemases encoding genes (bla KPC , bla NDM and bla OXA-48 ), plasmidial genes for resistance to polymyxins (mcr1-9) and mutations in chromosomal genes (pmrA, pmrB, phoP and phoQ) described as associated with resistance to polymyxin were screened by PCR and DNA sequencing. Finally, the hsp60 gene was sequenced to identify species of the E. cloacae complex and genetic diversity was evaluated by PFGE and MLST. The results have shown that among 94 E. cloacae complex isolates, 19 (20.2%) were colistin-resistant. The resistant strains exhibited MIC ranging from 4 to 128 µg / mL and E. hormaechei subsp. steigerwaltii was the prevalent species in the complex (31,6%), followed by E. cloacae subsp. cloacae (26,3%). The antimicrobials with the highest susceptibility rate were gentamicin (21%) and tigecycline (26%). Carbapenemases encoding genes (bla KPC n = 5, bla NDM n = 1) were detected in 6 isolates and mcr-9 in one. Among the modifications found in PmrA, PmrB, PhoP e PhoQ (two-component regulatory system), only the S175I substitution in PmrB found in E. cloacae subsp cloacae isolates were considered deleterious (according to the prediction of PROVEAN). By PFGE, 13 profiles were found among E. cloacae complex isolates, with EcD the most frequent. Furthermore, by MLST 10 ST's, and 1 new ST, were identified in E. cloacae. In conclusion, no prevalence of clones or association among carbapenemase production and polymyxin resistance was found between the E. cloacae. Thereby, the results suggest that the increased polymyxin-resistance is related to the selective pressure exerted by the indiscriminate use in hospitals. Lastly, this study highlights the urgent need to elucidate the mechanism involved in the resistance to polymyxin in the E. cloacae complex and the development of measures to control and prevent infections caused by these multiresistant bacteria., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Introduction: Acinetobacter baumannii contributes significantly to the global issue of multidrug-resistant (MDR) nosocomial infections. Often, these strains demonstrate resistance to carbapenems (MDR-CRAB), the first-line treatment for infections instigated by MDR A. baumannii . Our study focused on the antimicrobial susceptibility and genomic sequences related to plasmids from 12 clinical isolates of A. baumannii that carry both the blaOXA-58 and bla NDM-1 carbapenemase genes., Methods: Whole-genome sequencing with long-read technology was employed for the characterization of an A. baumannii plasmid that harbors the bla OXA-58 and blaNDM-1 genes. The location of the bla OXA-58 and bla NDM-1 genes was confirmed through Southern blot hybridization assays. Antimicrobial susceptibility tests were conducted, and molecular characterization was performed using PCR and PFGE., Results: Multilocus Sequence Typing analysis revealed considerable genetic diversity among bla OXA-58 and bla NDM-1 positive strains in Brazil. It was confirmed that these genes were located on a plasmid larger than 300 kb in isolates from the same hospital, which also carry other antimicrobial resistance genes. Different genetic contexts were observed for the co-occurrence of these carbapenemase-encoding genes in Brazilian strains., Discussion: The propagation of bla OXA-58 and bla NDM-1 genes on the same plasmid, which also carries other resistance determinants, could potentially lead to the emergence of bacterial strains resistant to multiple classes of antimicrobials. Therefore, the characterization of these strains is of paramount importance for monitoring resistance evolution, curbing their rapid global dissemination, averting outbreaks, and optimizing therapy., Competing Interests: AS was employed by Laboratório Reunidos Ltda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodrigues, Silveira, Pribul, Karam, Picão, Kraychete, Pereira, de Lima, de Souza, Leão, Marques, Rocha-de-Souza and Carvalho-Assef.)

The increasing resistance to polymyxins in Acinetobacter baumannii has made it even more urgent to develop new treatments. Anti-virulence compounds have been researched as a new solution. Here, we evaluated the modification of virulence features of A. baumannii after acquiring resistance to polymyxin B. The results showed lineages attaining unstable resistance to polymyxin B, except for Ab7 (A. baumannii polymyxin B resistant lineage), which showed stable resistance without an associated fitness cost. Analysis of virulence by a murine sepsis model indicated diminished virulence in Ab7 (A. baumannii polymyxin B resistant lineage) compared with Ab0 (A. baumannii polymyxin B susceptible lineage). Similarly, downregulation of virulence genes was observed by qPCR at 1 and 3 h of growth. However, an increase in bauE, abaI, and pgAB expression was observed after 6 h of growth. Comparison analysis of Ab0, Ab7, and Pseudomonas aeruginosa suggested no biofilm formation by Ab7. In general, although a decrease in virulence was observed in Ab7 when compared with Ab0, some virulence feature that enables infection could be maintained. In light of this, virulence genes bauE, abaI, and pgAB showed a potential relevance in the maintenance of virulence in polymyxin B-resistant strains, making them promising anti-virulence targets., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Bovine mastitis is a mammary gland inflammation that can occur due to infectious pathogens, Staphylococcus aureus and Escherichia coli , which are, respectively, the most prevalent Gram-positive and Gram-negative bacteria associated with this disease. Currently, antibiotic treatment has become more complicated due to the presence of resistant pathogens. This review, therefore, aims to identify the most common resistance genes reported for these strains in the last four years. During the review, it was noted that bla Z , bla SHV, bla TEM , and bla ampC are the most reported genes for S. aureus and E. coli, associated with drug inactivation, mainly β-lactamases. They are characterized by generating bacterial resistance to β-lactam antibiotics, the most common treatment in animal and human bacterial treatments (penicillins and cephalosporins, among others). Genes associated with efflux systems were also present in the two strains and included norA, tetA, tetC , and tetK , which generate resistance to macrolide and tetracycline antibiotics. Additionally, the effects of spreading resistance between animals and humans through direct contact (such as consumption of contaminated milk) or indirect contact (through environmental contamination) has been deeply discussed, emphasizing the importance of having adequate sanitation and antibiotic control and administration protocols.

Cannabis sativa is a plant of the Cannabaceae family, whose molecular composition is known for its vast pharmacological properties. Cannabinoids are the molecules responsible for Cannabis sativa potential effects, especially tetrahydrocannabinol and cannabidiol. Scientific development has shown interest in the potential of cannabidiol in various health conditions, as it has demonstrated lower adverse events and great pharmacological potential, especially when administered topically. The present study aims to carry out a scoping review, focusing on the use of cannabidiol, in vivo models, for topical administration. Thus, the methodological approach used by the Joanna Briggs Institute was applied, and the studies were selected based on previously established inclusion criteria. Even though more information regarding the dose to achieve pharmacological potential is still needed, cannabidiol demonstrated potential in treating and preventing different conditions, such as glaucoma, atopic dermatitis, epidermolysis bullosa, and pyoderma gangrenosum.

Bovine mastitis is a frequent infection in lactating cattle, causing great economic losses. Staphylococcus aureus represents the main etiological agent, which causes recurrent and persistent intramammary infections because conventional antibiotics are ineffective against it. Mastoparan-like peptides are multifunctional molecules with broad antimicrobial potential, constituting an attractive alternative. Nevertheless, their toxicity to host cells has hindered their therapeutic application. Previously, our group engineered three mastoparan-L analogs, namely mastoparan-MO, mastoparan-R1, and [I 5 , R 8 ] MP, to improve cell selectivity and potential. Here, we were interested in comparing the antibacterial efficacy of mastoparan-L and its analogs against bovine mastitis isolates of S. aureus strains, making a correlation with the physicochemical properties and structural arrangement changes promoted by the sequence modifications. As a result, the analog's hemolytic and/or antimicrobial activity was balanced. All the peptides displayed α-helical folding in hydrophobic and membrane-mimetic environments, as determined by circular dichroism. The peptide [I 5 , R 8 ] MP stood out for its enhanced selectivity and antibacterial features related to mastoparan-L and the other derivatives. Biophysical approaches revealed that [I 5 , R 8 ] MP rapidly depolarizes the bacterial membrane of S. aureus , causing cell death by subsequent membrane disruption. Our results demonstrated that the [I 5 , R 8 ] MP peptide could be a starting point for the development of peptide-based drugs for the treatment of bovine mastitis, with the advantage of no residue in milk, which would help reduce the use of classical antibiotics.IMPORTANCE Staphylococcus aureus is a leading cause of mastitis, the world's most important dairy cattle disease. The multidrug resistance and zoonotic potential of S. aureus , besides the likelihood of antibiotic residues in milk, are of critical concern to public and animal health. Antimicrobial peptides offer a novel antimicrobial strategy. Here, we demonstrate that [I 5 , R 8 ] MP is a potent and selective peptide, which acts on S. aureus by targeting the bacterial membrane. Therefore, understanding the physicochemical determinants and the modes of action of this class of antimicrobials opens novel prospects for peptide development with enhanced activities in the bovine mastitis context., Competing Interests: The authors declare no conflict of interest.

This short report is based on the 2022 Global IPE Situational Analysis Results e-Book that is available at https://interprofessionalresearch.global/. As an up-to-date global environmental scan of interprofessional education (IPE), this cross-sectional study investigated institutional, administrative, and system-level processes that support IPE program development and implementation globally. Conducted by InterprofessionalResearch.Global (IPR.Global), the survey included 17 quantitative questions that were analyzed at global and regional levels. Three open-text questions were thematically analyzed. In total, 152 institutions from six regions worldwide contributed to this study. Results revealed that only 51.97% of all responding institutions have an established IPE program, with Canada and the USA having the highest (84%) and Africa (26%) having the lowest numbers. Globally, 37.33% of respondents reported no formal leadership positions and 41.33% reported the absence of a designated IPE Director or Coordinator. In addition, IPE funding varies considerably across the world, with 32.65% of institutions reporting no financial support. Over 48.22% of respondents indicated their institutions are rarely or not involved in IPE-related scholarly work or research. The open-text analysis revealed that supportive senior leadership, a culture of collaboration, and recognition of IPE as a strategic direction and/or priority at the institutional level, could foster the successful implementation of IPE. On the other hand, inadequate administrative support, lack of funding, poor attitudes regarding IPE, and limited dedicated time for research, seemed to impair successful implementation of scholarly activities in the field.

Background: The synthetic antimicrobial peptide, PaDBS1R1, has been reported as a powerful anti-Klebsiella pneumoniae antimicrobial. However, there is only scarce knowledge about whether K. pneumoniae could develop resistance against PaDBS1R1 and which resistance mechanisms could be involved., Objectives: Identify via label-free shotgun proteomics the K. pneumoniae resistance mechanisms developed against PaDBS1R1., Methods: An adaptive laboratory evolution experiment was performed to obtain a PaDBS1R1-resistant K. pneumoniae lineage. Antimicrobial susceptibility was determined through microdilution assay. Modifications in protein abundances between the resistant and sensitive lineages were measured via label-free quantitative shotgun proteomics. Enriched Gene Ontology terms and KEGG pathways were identified through over-representation analysis. Data are available via ProteomeXchange with identifier PXD033020., Results: K. pneumoniae ATCC 13883 parental strain challenged with increased subinhibitory PaDBS1R1 concentrations allowed the PaDBS1R1-resistant K. pneumoniae lineage to emerge. Proteome comparisons between PaDBS1R1-resistant K. pneumoniae and PaDBS1R1-sensitive K. pneumoniae under PaDBS1R1-induced stress conditions enabled the identification and quantification of 1702 proteins, out of which 201 were differentially abundant proteins (DAPs). The profiled DAPs comprised 103 up-regulated proteins (adjusted P value < 0.05, fold change ≥ 2) and 98 down-regulated proteins (adjusted P value < 0.05, fold change ≤ 0.5). The enrichment analysis suggests that PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery could be relevant resistance mechanisms against PaDBS1R1., Conclusions: Based on experimental evolution and a label-free quantitative shotgun proteomic approach, we showed that K. pneumoniae developed resistance against PaDBS1R1, whereas PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery appear to be relevant resistance mechanisms against PaDBS1R1., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

State-of-the-art cloud computing platforms such as Google Earth Engine (GEE) enable regional-to-global land cover and land cover change mapping with machine learning algorithms. However, collection of high-quality training data, which is necessary for accurate land cover mapping, remains costly and labor-intensive. To address this need, we created a global database of nearly 2 million training units spanning the period from 1984 to 2020 for seven primary and nine secondary land cover classes. Our training data collection approach leveraged GEE and machine learning algorithms to ensure data quality and biogeographic representation. We sampled the spectral-temporal feature space from Landsat imagery to efficiently allocate training data across global ecoregions and incorporated publicly available and collaborator-provided datasets to our database. To reflect the underlying regional class distribution and post-disturbance landscapes, we strategically augmented the database. We used a machine learning-based cross-validation procedure to remove potentially mis-labeled training units. Our training database is relevant for a wide array of studies such as land cover change, agriculture, forestry, hydrology, urban development, among many others., (© 2023. The Author(s).)

Objective: To develop and validate a prototype of a mobile application shift handover between nurses in the emergency room using a severity scale., Method: This is a technological tool carried out at the Universidade Estadual de Maringá using design thinking, divided into four phases: discovering, defining, developing, and delivering. To structure the information, a checklist was used based on the Situation Background Assessment Recommendation, and to categorize patients in terms of severity, the National Early Warning Score was used. The validation of the sample was carried out by 10 nurses, specialized in the field of urgency and emergency, using the System Usability Scale questionnaire to assess usability. The content validity coefficient was used for analysis., Results: The application scored 75.75 in usability and had a content validity coefficient of 0.8., Conclusion: The prototype obtained an excellent evaluation of usability and agreement between evaluators. Future studies are needed for implementation in practice, evaluating the practicality, applicability, efficiency and time savings in shift information transfer.

Objective: To evaluate the etiology of and factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients., Methods: This was a single-center case-control study conducted between December of 2017 and March of 2020 at a referral center for kidney transplantation in the city of Belo Horizonte, Brazil. The case:control ratio was 1:1.8. Cases included kidney or kidney-pancreas transplant recipients hospitalized with pulmonary infection. Controls included kidney or kidney-pancreas transplant recipients without pulmonary infection and matched to cases for sex, age group, and donor type (living or deceased)., Results: A total of 197 patients were included in the study. Of those, 70 were cases and 127 were controls. The mean age was 55 years (for cases) and 53 years (for controls), with a predominance of males. Corticosteroid use, bronchiectasis, and being overweight were associated with pulmonary infection risk in the multivariate logistic regression model. The most common etiologic agent of infection was cytomegalovirus (in 14.3% of the cases), followed by Mycobacterium tuberculosis (in 10%), Histoplasma capsulatum (in 7.1%), and Pseudomonas aeruginosa (in 7.1%)., Conclusions: Corticosteroid use, bronchiectasis, and being overweight appear to be risk factors for pulmonary infection in kidney/kidney-pancreas transplant recipients, endemic mycoses being prevalent in this population. Appropriate planning and follow-up play an important role in identifying kidney and kidney-pancreas transplant recipients at risk of pulmonary infection.

Currently, obesity is considered a global public health problem. It is the main risk factor for noncommunicable diseases and reproductive complications, such as recurrent miscarriage (RM). RM affects approximately 1% of couples of reproductive age, and recent studies suggest that its prevalence is increasing. Immunological abnormalities may be responsible for a significant number of cases of unexplained RM. Obesity is recognized as a chronic low-grade inflammatory condition. The accumulation of fat in obese adipose tissue promotes changes in the local and systemic immune response. Adipokines, exosomes, micro-RNAs, lipids, and other factors released or secreted by adipose tissue are responsible for the interconnection between obesity and the immune system. Obesity-induced dysregulation of the innate and acquired immune response is also involved in the immunopathology of pregnancy loss in patients with unexplained RM. Therefore, understanding the communication pathways between maternal adipose tissue and the immune response in women living with obesity and RM is an important objective. Thus, diagnostic tools and new immunomodulatory therapies may be proposed for the management of patients with concurrent obesity and RM., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objective: Candida tropicalis is among the most prevalent human pathogenic yeast species. Switch states of C. tropicalis differ in virulence traits. Here, we evaluate the effect of phenotypic switching on phagocytosis and yeast-hyphae transition in C. tropicalis., Methods: C. tropicalis morphotypes included a clinical strain and two switch strains (rough variant and rough revertant). In vitro, phagocytosis assay was performed using peritoneal macrophages and hemocytes. The proportion of hyphal cells was ascertained by scoring morphology using optical microscopy. Expression of the WOR1 (White-opaque regulator 1) and EFG1 (Enhanced filamentous growth protein 1) was determined by quantitative PCR., Results: The rough variant was more resistant to in vitro phagocytosis by peritoneal macrophages than that observed for the clinical strain, while hemocytes phagocytosed clinical and rough variant to the same extent. The rough revertant was more phagocytosed than the clinical strain by both phagocytes. During co-incubation with phagocytic cells, the clinical strain of C. tropicalis exists mainly as blastoconidia. The co-culture of the rough variant with macrophages resulted in a higher percentage of hyphae than blastoconidia cells, while in co-culture with hemocytes, no differences were observed between the percentage of hyphae and blastoconidia. The expression levels of WOR1 in the rough variant co-cultured with phagocytes were significantly higher than they were in the clinical strain., Conclusions: Differences on phagocytosis and hyphal growth between switch states cells of C. tropicalis co-cultured with phagocytic cells were observed. The pronounced hyphal growth may affect the complex host-pathogen relationship and favor the pathogen to escape phagocytosis. The pleiotropic effects of phenotypic switching suggest that this event may contribute to the success of infection associated with C. tropicalis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. The authors alone are responsible for the content and the writing of the paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Carbapenemase production is a global public health threat. Antimicrobial resistance (AMR) data analysis is critical to public health policy. Here we analyzed carbapenemase detection trends using the AMR Brazilian Surveillance Network., Methods: Carbapenemase detection data from Brazilian hospitals included in the public laboratory information system dataset were evaluated. The detection rate (DR) was defined as carbapenemase detected by gene tested per isolate per year. The temporal trends were estimated using the Prais-Winsten regression model. The impact of COVID-19 on carbapenemase genes in Brazil was determined for the period 2015-2022. Detection pre- (October 2017 to March 2020) and post-pandemic onset (April 2020 to September 2022) was compared using the χ2 test. Analyses were performed with Stata 17.0 (StataCorp, College Station, TX)., Results: 83 282 blaKPC and 86 038 blaNDM were tested for all microorganisms. Enterobacterales DR for blaKPC and blaNDM was 68.6% (41 301/60 205) and 14.4% (8377/58 172), respectively. P. aeruginosa DR for blaNDM was 2.5% (313/12 528). An annual percent increase for blaNDM of 41.1% was observed, and a decrease for blaKPC of -4.0% in Enterobacterales, and an annual increase for blaNDM of 71.6% and for blaKPC of 22.2% in P. aeruginosa. From 2020 to 2022, overall increases of 65.2% for Enterobacterales, 77.7% for ABC, and 61.3% for P. aeruginosa were observed in the total isolates., Conclusions: This study shows the strengths of the AMR Brazilian Surveillance Network with robust data related to carbapenemases in Brazil and the impact of COVID-19 with a change in carbapenemase profiles with blaNDM rising over the years., Competing Interests: Potential conflicts of interest. B. R. S. K., I. C. D. O. S., C. M. R. D. S., and A. P. D. C. A. report funding from the CDC, Brazilian Ministry of Health, Agência Nacional de Vigilância Sanitária (ANVISA), and Fundação Oswaldo Cruz; payments to their laboratory (LAPIH) from the CDC, ANVISA, Fundação Oswaldo Cruz, and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. M. P. reports funding support from the Instituto Oswaldo Cruz, Coordenação Geral de Laboratórios de Saúde Publica do Ministério da Saúde, and the CDC; payment for a training lecture from Pfizer; and holding an unpaid position on the Brazilian Committee on Antimicrobial Susceptibility Testing. A. L. D. A. reports funding from the Instituto Oswaldo Cruz Brasilia and Coordenação Geral de Laboratórios de Saúde Publica do Ministério da Saúde. R. T. D. S. P. reports funding from the Instituto Oswaldo Cruz, Coordenação Geral de Laboratórios de Saúde Publica do Ministério da Saúde, Agência Nacional de Vigilância Sanitária, and the CDC and participation on a data and safety monitoring or advisory board for Global Leaders Group and the World Health Organization Global AMR research agenda in human health. All other authors report no potential 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.)

Bacterial nasal colonization is common in many mammals and Staphylococcus represents the main pathogen isolated. Staphylococcus nasal carriage in humans constitutes a risk factor for Staphylococcus infections pointing out the need for animal experimentation for nasal colonization studies, especially for vaccine development. A limitation in addressing this hypothesis has been a lack of appropriate animal model. Murine models do not mimic human nasal colonization studies. Non-human primates (NHP) remain the best classical models for nasal colonization studies. In this study, we analyzed nasal colonization between two species of Old World monkeys (cynomolgus and rhesus) and a New World monkey (squirrel monkey) from breeding colony at Fiocruz (Brazil). Sixty male and female NHP with the average age of 1-21 years old, comprising twenty animals of each species, were analyzed. Nine different Staphylococcus species (S. aureus, S. cohnii, S. saprophyticus, S. haemolyticus, S. xylosus, S. warneri, S. nepalensis, S. simiae, and S. kloosi) were identified by MALDI-TOF and 16S rRNA gene sequence analyses. Antibiotic resistance was not detected among the isolated bacterial population. S. aureus was the main isolate (19 strains), present in all species, predominant in cynomolgus monkeys (9/20) and squirrel monkeys (7/20). spa typing was used to examine the clonal structure and genetic profile of Staphylococcus aureus isolates. Eight (8) spa types were identified among the S. aureus strains. A major cluster was identified, corresponding to a new spa type t20455, and no spa types found in this study were seen before in Brazil., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Candida tropicalis  is among the most important  Candida  species in terms of epidemiology, virulence and resistance. Considering the increase in C. tropicalis incidence and high rates of mortality associated with this species, knowledge of its adhesion and biofilm formation abilities is needed. These traits determine the persistence and survival of yeast on different indwelling medical devices and host sites. C. tropicalis is among the most adherent Candida species, and it has been described as a strong biofilm producer. Environmental factors, phenotypic switching and quorum sensing molecules can affect adhesion and biofilm growth. C. tropicalis can form sexual biofilms, which are promoted by mating pheromones. C. tropicalis biofilms are regulated by a wide and complex network of genes and signaling pathways that are currently poorly understood. Morphological studies showed improved biofilm architecture, which was related to the expression of several hypha-specific genes. Based on recent updates, research is still needed to increase our knowledge on the genetic network of adhesion and biofilm formation by C. tropicalis , as well as the protein diversity that mediates interactions with inert materials and biological surfaces. Here, we have reviewed the main aspects related to adhesion and biofilm formation in C. tropicalis and summarized current knowledge on the significance of these virulence factors in this opportunistic species., Competing Interests: The authors declare that there are no conflicts of interest.

COVID-19 remains a global pandemic of an unprecedented magnitude with millions of people now developing "COVID lung fibrosis." Single-cell transcriptomics of lungs of patients with long COVID revealed a unique immune signature demonstrating the upregulation of key proinflammatory and innate immune effector genes CD47, IL-6, and JUN. We modeled the transition to lung fibrosis after COVID and profiled the immune response with single-cell mass cytometry in JUN mice. These studies revealed that COVID mediated chronic immune activation reminiscent to long COVID in humans. It was characterized by increased CD47, IL-6, and phospho-JUN (pJUN) expression which correlated with disease severity and pathogenic fibroblast populations. When we subsequently treated a humanized COVID lung fibrosis model by combined blockade of inflammation and fibrosis, we not only ameliorated fibrosis but also restored innate immune equilibrium indicating possible implications for clinical management of COVID lung fibrosis in patients.

Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. Although the main mechanism of carbapenem-resistance in Pseudomonas aeruginosa is the loss of OprD porin, carbapenemases continue to be a problem worldwide. The aim of this study was to evaluate the performance of phenotypic tests (Carba NP, Blue Carba, and mCIM/eCIM) for detection of carbapenemase-producing Pseudomonas spp. in Brazil. One hundred twenty-seven Pseudomonas spp. clinical isolates from different Brazilian states were submitted to phenotypic and molecular carbapenemase detection. A total of 90 carbapenemase-producing P. aeruginosa and 5 Pseudomonas putida (35, bla VIM-2 ; 17, bla SPM-1 ; 2, bla IMP-10 ; 1, bla VIM-24 ; 1, bla NDM-1 ; 39, bla KPC-2 ). The phenotypic Carba NP, Blue Carba, and mCIM/eCIM showed sensitivity of 94.7%, 93.6%, and 93.6%, and specificity of 90.6%, 100%, and 96.8%, respectively. However, only the Carba NP presented the highest sensitivity and showed the ability in differentiating the carbapenemases between class A and class B using EDTA. Blue Carba failed to detect most of the class B carbapenemases, having the worst performance using EDTA. Our results show changes in the epidemiology of the spread of carbapenemases and the importance of their detection by phenotypic and genotypic tests. Such, it is essential to use analytical tools that faithfully detect bacterial resistance in vitro in a simple, sensitive, rapid, and cost-effective way. Much effort must be done to improve the current tests and for the development of new ones., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Pseudomonas aeruginosa and species of Acinetobacter calcoaceticus-baumanii complex are multiresistant intrahospital opportunistic pathogens, able to acquire carbapenemases and produce outbreaks with high morbidity and mortality. Pseudomonas putida has also emerged with similar characteristics. The aim of this research was to characterize the Metallo-β-lactamases (MBLs) detected by surveillance in Paraguay in the first 5 years of their circulation in hospitals. The coexistence of KPC and OXA-type carbapenemases was also investigated. 70 MBL-producing strains from inpatients were detected from clinical samples and rectal swab from 11 hospitals. The strains were identified by manual, automated, and molecular methods. Antimicrobial susceptibility was studied by Kirby-Bauer and automated methods, while colistin susceptibility was determined by broth macrodilution. MBLs were investigated by synergy with EDTA against carbapenems and PCR, and their variants by sequencing. KPC and OXA-carbapenemases were investigated by PCR. Clonality was studied by pulsed-field gel electrophoresis (PFGE). The results demonstrated the circulation of bla VIM-2 (60%), bla NDM-1 (36%), and bla IMP-18 (4%). The MBL-producing species were P. putida (45.7%), P. aeruginosa (17.2%), A. baumannii (24.3%), A. pittii (5.7%), A. nosocomialis, (4.3%) A. haemolyticus (1.4%), and A. bereziniae (1.4%). PFGE analysis showed one dominant clone for A. baumannii, a predominant clone for half of the strains of P. aeruginosa, and a polyclonal spread for P. putida. In the first 5 years of circulation in Paraguay, MBLs were disseminated as unique variants per genotype, appeared only in Pseudomonas spp. and Acinetobacter spp., probably through horizontal transmission between species and vertical by some successful clones., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Bacterial resistance is a threat to health worldwide, mainly due to reduced effective treatment. In this context, the search for strategies to control such infections and suppress antimicrobial resistance is necessary. One of the strategies that has been used is combination therapy. In the present work, we investigated the in vitro efficacy of the antimicrobials diminazene aceturate (DA), chloramphenicol (CHL), and streptomycin (STP) alone and in combination against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus clinical isolates. DA was capable of inhibiting all strains with MIC of 25-400 μg mL-1, while STP and CHL showed antibacterial activity with minimum inhibitory concentration (MICs) of ≤3.12-400 μg mL-1. The combination of aceturate with STP showed synergism toward almost all Gram-negative bacteria, with fractional inhibitory concentration index (FICIs) of 0.09-0.37. In addition, for CHL and aceturate, synergisms for Gram-negative and -positive strains were observed. A time-kill assay against E. coli revealed that the aceturate and STP combination can inhibit bacterial growth in a shorter time when compared with single antibiotics. In addition, antimicrobials did not show hemolytic activity even at the highest concentrations used. Therefore, the antimicrobial combinations presented in this work showed important results, demonstrating that combined therapy can be used as an alternative strategy for pathogen control., (© The Author(s) 2022. Published by Oxford University Press on behalf of Applied Microbiology International.)

Introduction: Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates. Considering that there are relatively few approved medications available for combating fungal diseases and no vaccine formulation commercially available, multiple groups are searching for new antifungal drugs, examining drugs for repurposing and developing antifungal vaccines, in order to control deaths, sequels, and the spread of these complex infections., Areas Covered: This review provides a summary of advances in fungal vaccine studies and the different approaches under development, such as subunit vaccines, whole organism vaccines, and DNA vaccines, as well as studies that optimize the use of adjuvants. We conducted a literature search of the PubMed with terms: fungal vaccines and genus of fungal pathogens (Cryptococcus spp. Candida spp. Coccidioides spp. Aspergillus spp. Sporothrix spp. Histoplasma spp. Paracoccidioides spp. Pneumocystis spp. and the Mucorales order), a total of 177 articles were collected from database., Expert Opinion: Problems regarding the immune response development in an immunocompromised organism, the similarity between fungal and mammalian cells, and the lack of attention by health organizations to fungal infections are closely related to the fact that, at present, there are no fungal vaccines available for clinical use.

Background: Phenotypic switching generates fungal colonies with altered morphology and allows pathogens to adapt to changing environments., Objective: This study investigated the structure and genetic factors of switched morphotypes colonies in Candida tropicalis., Methods: Morphotypes of C. tropicalis comprised the clinical strain 49.07 that exhibited smooth colony phenotype and switched (crepe and rough) morphotypes that showed colonies with marked structural variations, including wrinkled surface, depressions areas, and irregular edges (structured morphology). The morphotypes were analyzed for the presence and distribution of the extracellular matrix (ECM) at the ultrastructural level-SEM. The composition of the ECM and the percentage of hyphae in colonies were evaluated. The expression of EFG1 (Enhanced filamentous growth protein 1), WOR1 (White-opaque regulator 1), and BCR1 (Biofilm and cell wall regulator 1) in the morphotypes was measured by RT-qPCR., Results: Colonies of the switched variants exhibited distinct arrangements of ECM compared to the smooth phenotype (clinical strain). In addition, rough variant colonies showed higher amounts of total carbohydrates and proteins in ECM (p < 0.05). Switched (crepe and rough) colonies exhibited a higher percentage of hyphae throughout their development (p < 0.05). The mRNA expression levels of EFG1, WOR1, and BCR1 in the rough morphotype were significantly higher than they were in the smooth morphotype. In addition, there was a positive correlation between the expression of these genes and filamentation (hyphae formation) of the rough morphotype (r 2  > 0.9472, p < 0.05)., Conclusion: Structural variations in switched morphotypes colonies of C. tropicalis seem to be associated with increased hyphae growth and the amount and distribution of ECM. Switched colonies have distinct expressions of the EFG1, WOR1, and BCR1 master regulators genes., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Gestational diabetes mellitus (GDM) has an impact on maternal health; however, there is no consensus about the diagnostic criterion and frequency of disease. The objective of this study was to estimate the prevalence of GDM and to evaluate the clinical characteristics of normoglycemic pregnant women and of those diagnosed with gestational diabetes mellitus, based on each criterion., Methods: Prospective cohort study. Third-trimester pregnant women participated, with the occurrence of GDM being verified, according to two different diagnostic criteria. Prevalence was estimated in each category, and the prevalence ratios (PR) and 95% confidence intervals were adjusted using Poisson Regression., Results: A total of 8.7% of women were diagnosed with GDM (glycemia ≥95) and 8% had glycemic levels ≥92mg/dL according to IADPSG diagnosis. Factors related to the disease were the same, although the magnitude of the associations differed according to the diagnosis criteria. Pre-gestational obesity (PR 3.59 CI 1.28-10,07), previous diseases (PR 3.03 CI 1.15-7.94), and excessive weight gain (PR 4.71 CI 1.80-12.33) were factors related to total GDM, plus low nutritional knowledge (PR 3.17 CI 1.10-9.11). Regardless of the diagnostic criterion, women with GDM were at higher risk of intercurrences during pregnancy., Conclusion: Nutritional knowledge and status were associated with GDM occurrence, independently of the diagnosis criteria. The adoption of the glycemic cutoff point of ≥ 92mg/dL indicated an important portion of the population without a diagnosis, suggesting that this cutoff point, more sensitive, should be used in order to guide women and minimize untoward outcomes., 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 © 2022. Published by Elsevier Ltd.)

The International Dysphagia Diet Standardization Initiative (IDDSI) flow test is useful for the global standardization of food consistencies of dysphagia patients. In clinical practice, different compositions of food thickeners are commonly used, directly influencing viscosity parameters and swallowing physiology. We aimed to compare the IDDSI thickness levels, remaining volume in the syringe (RVS), and viscosity parameters of three different food thickeners. As a secondary objective, we compared the cost of preparing 100 mL of thickened drinks using the studied thickeners. Thickeners A (xanthan gum), B (corn starch, tara gum, xanthan gum, and guar gum), and C (corn starch) were prepared in increasing concentrations from 1 to 7 g/100 mL and were assayed in quintuplicate using the IDDSI flow test. Thickeners A, B, and C presented statistically different results for the IDDSI levels, RVS, and viscosity parameters at all concentrations. Thickener A reached higher levels in the IDDSI framework, RVS, and viscosity parameters compared with thickeners B and C. A large range of RVS was observed at different concentrations for thickener B compared with C. Regarding viscosity, thickeners B and C, with corn starch in their composition, showed exponential behavior as concentrations increased, while thickener A presented a linear trend. The thickener composition was significantly influenced by IDDSI classification, RVS, and viscosity parameters. The study shows that xanthan gum thickeners present less variability in IDDSI, RVS, and viscosity compared with starch-based thickeners., Competing Interests: Conflict of interestThe authors declare that they do not have any conflict of interest., (© Association of Food Scientists & Technologists (India) 2022.)

The high rates of carbapenem resistance among Brazilian Pseudomonas aeruginosa isolates are mainly associated with the clone ST277 producing the carbapenemase SPM-1. Here, the complete genetic composition of a IncP plasmid harboring bla KPC-2 in isolates of this endemic clone carrying chromosomal bla SPM-1 was described using whole genome sequencing. These results confirm the association of these two carbapenemases in ST277 and also describe the genetic composition of a novel bla KPC-2 -plasmid. Considering the fact that this association occurs in a high-risk clone, monitoring the dissemination of this plasmid should be a public health concern., (Copyright © 2022. Published by Elsevier B.V.)