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Contents The main objective of this study was to determine if administration of meloxicam, a cyclooxygenase (COX) two inhibitor, to heifers in which embryo transfer (ET) is more difficult and requires a greater manipulation of the tract, would be beneficial. Nulliparous recipient heifers were divided in two groups: CON (n = 102), in which animals received 10 ml of saline IM (the same volume of meloxicam) and MEL (n = 105) animals that were treated with meloxicam. According to the degree in passing the catheter, recipients from both groups were classified as Grade I, easy (< 60 s), and Grade II (more than 80 s), difficult. Immediately after embryo transfer, MEL recipients received an injection of 200 mg of meloxicam (10 ml).There was no difference in the pregnancy rates on Day 35 considering animals which presented Grade I cervix independently whether the treatment was performed or not (p = 0.22). There was a statistical difference in the pregnancy rates (p < 0.01) between both groups (49.0% and 66.7% for CON and MEL, respectively) when cervical grade was not considered, on Day 35. Considering the animals that presented Grade II cervix, the pregnancy rate was higher for MEL (21.15% and 78.84%, respectively) in both examinations (p < 0.01).The authors concluded that meloxicam had a positive influence on general pregnancy rate of treated heifers in comparison to non-treated heifers. It was also observed that pregnancy rate was not influenced by meloxicam administration in Grade I heifers. Treatment increased the pregnancy rate of Grade II heifers. [ABSTRACT FROM AUTHOR]

STATEMENT OF PROBLEM.: Unresolved controversy exists concerning the preferred cavity design and restorative technique used to restore endodontically treated maxillary premolars to minimize strain and improve stress distribution under occlusal load. PURPOSE.: The purpose of this study was to analyze the influence of cavity design and restorative material on strain measurement and stress distribution in maxillary premolars under occlusal loading conditions, and correlate these influences with the failure modes analyzed in Part I. MATERIAL AND METHODS.: For the strain gauge test, 21 additional specimens were prepared as described in Part 1 of this study (n=3). Two strain gauges were fixed on the buccal (B) and palatal (P) cusps of each specimen with cyanoacrylate adhesive. The specimens were submitted to continuous axial compression loading at a speed of 0.5 mm/min, using a 6-mm sphere, to a maximum limit of 150 N in a universal testing machine. Total strain values were obtained by combining the B and P cusp strain values. These values were submitted to 2-way ANOVA and the Dunnet test (alpha=.05). For finite element analyses, 7 numerical 2-D models were generated: MODd, direct mesio-occlusal-distal preparation; MODi, indirect mesio-occlusal-distal preparation; AM, MODd restored with amalgam; CR, MODd restored with composite resin; LPR, MODi restored with laboratory-processed composite resin; and LGC, MODi restored with leucite-reinforced glass ceramic; each corresponding to 1 of the experimental groups tested in Part I of this study. The models were analyzed with finite element software, using the von Mises criteria for stress distribution analysis. RESULTS.: With the strain gauge test, MODd, MODi, and AM groups showed significantly higher strain values than the CR, LPR, and LGC. Finite element analyses revealed that tooth structure removal and the type of restorative material altered the stress distribution pattern. The MODd, MODi, AM, and LPR models showed higher stress concentration within the tooth structure. CONCLUSIONS.: The specimens with adhesive restorations were shown to behave in a manner similar to the biomechanical behavior of healthy teeth, while the behavior of those restored with amalgam restorations was more like that observed for teeth with nonrestored cavity preparations. These results directly correlate with the fracture mode results obtained in Part I of this study. (J Prosthet Dent 2008;99:114-122). [ABSTRACT FROM AUTHOR]

STATEMENT OF PROBLEM: Unresolved controversy exists concerning the preferred cavity design and restorative technique used to restore endodontically treated maxillary premolars to improve their resistance to fracture under occlusal load. PURPOSE: The purpose of this study was to evaluate the fracture resistance, stress distribution, and cusp deformation of endodontically treated human maxillary premolars restored with different materials. The study is divided into 2 parts. In Part I, fracture resistance and fracture mode were determined. MATERIAL AND METHODS: Seventy noncarious human maxillary premolars were selected and divided into 7 groups (n=10). The control group, ST, consisted of sound unprepared teeth. Teeth in the other 6 groups were endodontically treated and each received 1 of 2 cavity preparation designs: MODd, direct mesio-occlusal-distal preparation; MODi, indirect mesio-occlusal-distal preparation. Teeth were restored with 4 types of material: AM, MODd restored with amalgam; CR, MODd restored with composite resin; LPR, MODi restored with laboratory-processed composite resin; and LGC, MODi restored with leucite-reinforced glass ceramic. The fracture resistance (N) was assessed under compressive load in a universal testing machine. The data were analyzed by 1-way ANOVA and the Tukey HSD test (alpha =.05). Fracture modes were recorded based on the degree of tooth structure involvement and restoration damage. RESULTS: Statistical analysis showed that the ST group presented the highest fracture resistance values. The restored groups showed significantly higher fracture resistance values compared to the nonrestored groups. The groups restored with adhesive techniques (LPR, CR, and LGC) presented significantly higher fracture resistance values than the group restored with the nonadhesive technique (AM) (P<.001). The catastrophic fractures were prevalent in MODd, MODi, AM, and LPR groups, and less severe fractures were found in ST and LGC groups. For the CR group, there was no prevalent fracture mode. CONCLUSIONS: Teeth with the greatest amount of remaining tooth structure and those restored using adhesive technology showed higher fracture resistance values. There was great variation in the type of fracture among groups. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the presence of beta-lactams resistance genes and the clonal relationship of clinical isolates of Enterobacterales obtained from patients with and without COVID-19, in a hospital in northeastern Brazil., Methods and Results: The study analyzed 45 carbapenem-resistant clinical isolates using enterobacterial repetitive intergenic consensus (ERIC-PCR), PCR, and amplicon sequencing to detect resistance genes (blaKPC, blaGES, blaNDM, blaVIM, and blaIMP). The main species were Klebsiella pneumoniae, Serratia marcescens, and Proteus mirabilis. Detected genes included blaNDM (46.66%), blaKPC (35.55%), and both (17.79%). ERIC-PCR showed multiclonal dissemination and high genetic variability. The main resistance gene was blaNDM, including blaNDM-5 and blaNDM-7., Conclusions: The presence of Enterobacterales carrying blaKPC and blaNDM in this study, particularly K. pneumoniae, in infections and colonizations of patients with COVID-19 and non-COVID-19, highlights genetic variability and resistance to carbapenems observed in multiple species of this order., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Aims: To investigate the genetic profile and characterize antimicrobial resistance, including the main β-lactam antibiotic resistance genes, in Acinetobacterbaumannii isolates from a tertiary hospital in Recife-PE, Brazil, in the post-COVID-19 pandemic period., Methods and Results: Acinetobacter baumannii isolates were collected between 2023 and 2024 from diverse clinical samples. Antimicrobial resistance testing followed standardized protocols, with β-lactamase-encoding genes detected via PCR and sequencing. Investigation into ISAba1 upstream of blaOXA-carbapenemase and blaADC genes was also conducted. Genetic diversity was assessed through ERIC-PCR. Among the 78 A. baumannii, widespread resistance to multiple antimicrobials was evident. Various acquired β-lactamase-encoding genes (blaOXA-23,-24,-58,-143, blaVIM, and blaNDM) were detected. Furthermore, this is the first report of blaVIM-2 in A. baumannii isolates harboring either the blaOXA-23-like or the blaOXA-143 gene in Brazil. Molecular typing revealed a high genetic heterogeneity among the isolates, and multi-clonal dissemination., Conclusion: The accumulation of genetic resistance determinants underscores the necessity for stringent infection control measures and robust antimicrobial stewardship programs to curb multidrug-resistant strains., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

CASZ1 is a conserved transcription factor involved in neural development, blood vessel assembly and heart morphogenesis. CASZ1 has been implicated in cancer, either suppressing or promoting tumor development depending on the tissue. However, the impact of CASZ1 on hematological tumors remains unknown. Here, we show that the T-cell oncogenic transcription factor TAL1 is a direct positive regulator of CASZ1, that T-cell acute lymphoblastic leukemia (T-ALL) samples at diagnosis overexpress CASZ1b isoform, and that CASZ1b expression in patient samples correlates with PI3K-AKT-mTOR signaling pathway activation. In agreement, overexpression of CASZ1b in both Ba/F3 and T-ALL cells leads to the activation of PI3K signaling pathway, which is required for CASZ1b-mediated transformation of Ba/F3 cells in vitro and malignant expansion in vivo. We further demonstrate that CASZ1b cooperates with activated NOTCH1 to promote T-ALL development in zebrafish, and that CASZ1b protects human T-ALL cells from serum deprivation and treatment with chemotherapeutic drugs. Taken together, our studies indicate that CASZ1b is a TAL1-regulated gene that promotes T-ALL development and resistance to chemotherapy.

Aims: Investigated and compared the occurrence of virulence genes fimH, mrkD, irp2, entB, cps, rmpA, and wabG, resistance genes blaKPC and blaNDM, and the genetic variability and clonal relationship of 29 Klebsiella pneumoniae clinical isolates of patients with and without COVID-19, from a hospital in Brazil., Methods and Results: All isolates were resistant to beta-lactams. The genes were investigated by PCR, and for molecular typing, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and MLST were used. The detection of blaNDM was greater (n = 23) when compared to that of blaKPC (n = 14). The virulence genes that most occurred were fimH, entB, cps, and wabG, which are responsible for adhesins, siderophore enterobactin, capsule, and lipopolysaccharides, respectively. Among the isolates, 21 distinct genetic profiles were found by ERIC-PCR, with multiclonal dissemination. Four isolates belonged to the ST11 clone., Conclusions: The occurrence of the ST11 is worrying as it is a high-risk clone involved in the dissemination of virulent strains throughout the world., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Understanding the molecular and cellular processes involved in lung epithelial regeneration may fuel the development of therapeutic approaches for lung diseases. We combine mouse models allowing diphtheria toxin-mediated damage of specific epithelial cell types and parallel GFP-labeling of functionally dividing cells with single-cell transcriptomics to characterize the regeneration of the distal lung. We uncover cell types, including Krt13 + basal and Krt15 + club cells, detect an intermediate cell state between basal and goblet cells, reveal goblet cells as actively dividing progenitor cells, and provide evidence that adventitial fibroblasts act as supporting cells in epithelial regeneration. We also show that diphtheria toxin-expressing cells can persist in the lung, express specific inflammatory factors, and transcriptionally resemble a previously undescribed population in the lungs of COVID-19 patients. Our study provides a comprehensive single-cell atlas of the distal lung that characterizes early transcriptional and cellular responses to concise epithelial injury, encompassing proliferation, differentiation, and cell-to-cell interactions., (© 2024. The Author(s).)

The behavior of organic UV filters in aquatic ecosystems and living organisms raises concern. For the first time, biochemical biomarkers were evaluated in the liver and brain of juvenile Oreochromis niloticus exposed to 0.001 and 0.5 mg L -1 of a benzophenone-3 (BP-3), octyl methoxycinnamate (EHMC), and octocrylene (OC) mixture for 29 days. Before the exposure, the stability of these UV filters was investigated using liquid chromatography. The experiment with aeration in the aquarium showed a high percentage of concentration reduction (%) after 24 h: 62 ± 2 for BP-3, 96 ± 6 for EHMC, and 88 ± 2 for OC versus 5 ± 4 for BP-3, 8 ± 7 for EHMC, and 2 ± 3 for OC when without aeration. These results defined the bioassay protocol. The stability of the filters concentrations after being stored in PET flasks and subjected to freezing and thawing cycles was also verified. In PET bottles, the BP-3, EHMC, and OC presented concentration reductions of 8 ± 1, 28 ± 7 and 25 ± 5 respectively, after 96 h storage and four freezing cycles. In falcon tubes the concentration reductions observed were 47 ± 2 for BP-3, >95 ± 1 for EHMC and 86 ± 2 for OC after 48 h and two cycles. The 29 days of sub-chronic exposure indicated the occurrence of oxidative stress through the enhanced lipid peroxidation (LPO) levels for the groups exposed to both bioassay concentrations. The catalase (CAT), glutathione-S-transferase (GST), and acetylcholinesterase (AChE) activities did not show significant alterations. The genetic adverse effects were analyzed in erythrocytes of fish exposed to 0.001 mg L -1 of the mixture by comet and micronucleus biomarkers and no significant damage was observed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This study aimed to evaluate the effects of the repeated administration of tramadol subcutaneously on postoperative analgesia, liver, kidneys, and oxidative status in the postoperative period of cats undergoing ovariohysterectomy. Thirty-seven cats were randomly assigned to 5 groups, according to the postoperative analgesic treatment: NaCl 0.9%, GC; tramadol at 2 mg/kg, T2B (q12h) and T2T (q8h); or 4 mg/kg, T4B (q12h) and T4T (q8h). Oxidative status was assessed at baseline, 12 hours and 24 hours after the final administration of tramadol by the activity of superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), butyrylcholinesterase (BuChE), and lipoperoxidation (MDA). Total blood count, serum biochemistry and urinalysis were compared between baseline and 12 hours posttramadol. Postoperative pain was evaluated by applying the Glasgow Feline Composite Measure Pain Scale at baseline, 3 (T3), 6 (T6), 8 (T8), 12 (T12), 24 (T24) e 36 (T36) hours after extubation. No side effects were observed. Tramadol increased SOD activity while CAT varied among groups in all time points but not over time. MDA levels increased from baseline to 12 hours in all groups but T4T. MPO activity decreased from baseline to 24 hours in some groups, including GC. Creatinine and phosphatase alkaline decreased in T2T, T4B, and T4T at 12 hours. Higher pain scores were observed from T3 to T8, except for GC. Rescue analgesia was administered only at T3. No difference in pain scores was observed from T8 onwards. Based on the findings, it is suggested that tramadol at 2 mg/kg every 8 hours is recommended for postoperative analgesia of cats undergoing ovariohysterectomy., Competing Interests: Declaration of Competing Interest None of the authors of this article has a financial or personal relationship with other people or organizations that may influence the content of the article, declaring any potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The respiratory system is a vital component of our body, essential for both oxygen uptake and immune defense. Knowledge of cellular composition and function in different parts of the respiratory tract provides the basis for a better understanding of the pathological processes involved in various diseases such as chronic respiratory diseases and cancer. Single-cell RNA sequencing (scRNA-seq) is a proficient approach for the identification and transcriptional characterization of cellular phenotypes. Although the mouse is an essential tool for the study of lung development, regeneration, and disease, a scRNA-seq mouse atlas of the lung in which all epithelial cell types are included and annotated systematically is lacking. Here, we established a single-cell transcriptome landscape of the mouse lower respiratory tract by performing a meta-analysis of seven different studies in which mouse lungs and trachea were analyzed by droplet and/or plate-based scRNA-seq technologies. We provide information on the best markers for each epithelial cell type, propose surface markers for the isolation of viable cells, harmonized the annotation of cell types, and compare the mouse single-cell transcriptomes with human scRNA-seq data of the lung., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

To evaluate the feasibility of using a milled polyetheretherketone (PEEK) post and core in endodontically treated teeth with or without a ferrule. Sixty bovine tooth roots were endodontically treated followed by cementation of intraradicular retainers (IR), according to each experimental group: a) non-ferrule glass fiber post (f0FP); b) 2-mm-ferrule glass fiber post (f2FP); c) non-ferrule resized glass fiber post (f0PR); d) 2-mm-ferrule resized glass fiber post (f2PR); e) non-ferrule PEEK post and core (f0PPC); and f) 2-mm-ferrule PEEK post and core (f2PPC). Metal crowns were made and cemented. A periodontal ligament was simulated using polyether. A force was applied to the palatine portion of each sample at 45°, until fracture. Fracture resistance data were submitted to two-way ANOVA and Tukey's test (α = 0.05). Three-dimensional digital models were developed to calculate the tensions formed in the root using finite element analysis. Models of glass fiber posts and PEEK posts and cores were evaluated with or without a ferrule. The results were analyzed by the Mohr-Coulomb criterion. The type of IR was not influenced by fracture strength (p = 0.243). There were significant statistical differences among the remaining factors. Ferrule groups had greater fracture resistance, and the failure mode of teeth with a ferrule was more catastrophic than the non-ferrule group. A ferrule increases fracture resistance and influences failure mode; the PEEK post and core did not modify the biomechanics of endodontically treated teeth, and resembled the glass fiber post results. The crack initiation point differed between the ferrule and non-ferrule groups.

Objectives: This study aimed to evaluate the effect of 0.15% sodium hyaluronate (SH) on tear film breakup time (TFBT) in healthy anesthetized cats., Procedures: Forty cats undergoing elective surgery were enrolled. TFBT was assessed before anesthesia to obtain baseline values. As a preanesthetic medication, cats received midazolam, tramadol, and cetamine combined in the same syringe. For anesthetic induction and maintenance, propofol and isoflurane were used. After a 15 min stabilization period to achieve the surgical anesthetic plane, one eye was treated with one drop of SH, while the other eye received saline and served as a control. TFBT was measured at the end of the general anesthesia (T40) and 35 (T75) and 80 min (T120) after the termination of the anesthesia. TFBT values were compared between the control and SH-treated eyes; both values were also compared with the baseline values (p < .05)., Results: In the control eyes, TFBT significantly decreased from baseline at all time points (p < .001), while in SH-treated eyes, TFBT significantly increased from baseline only at T40 (p < .0001). In SH-treated eyes, TFBT was significantly higher than that in the control eyes at all time points (p < .001)., Conclusions: In healthy cats, TFBT decreases significantly after 40 min of general anesthesia, and one drop of 0.15% sodium hyaluronate was able to maintain the stability of the tear film for up to 75 min in treated eyes. However, the isolated effect of each drug used in our anesthetic protocol on TFBT should be executed in further studies., (© 2022 American College of Veterinary Ophthalmologists.)

Mayaro virus (MAYV, Togaviridae) and Oropouche orthobunyavirus (OROV, Peribunyaviridae) are emerging enzootic arboviruses in Latin America. Outbreaks of febrile illness associated with MAYV and OROV have been reported among humans mainly in the northern region of Brazil since the 1980s, and recent data suggest these viruses have circulated also in more populated areas of western Brazil. MAYV shares mosquito vectors with yellow fever virus and it has been historically detected during yellow fever epidemics. Aiming to investigate the transmission of OROV and MAYV at the human-animal interface during a yellow fever, chikungunya and Zika outbreaks in Brazil, we conducted a retrospective molecular investigation in 810 wild and domestic animals, 106 febrile patients, and 22.931 vectors collected from 2016 to 2018 in Cuiaba and Campo Grande metropolitan regions, western Brazil. All samples tested negative for OROV and MAYV RNA by RT-qPCR. Findings presented here suggest no active circulation of MAYV and OROV in the sampled hosts. Active surveillance and retrospective investigations are instrumental approaches for the detection of cryptic and subclinical activity of enzootic arboviruses and together serve as a warning system to implement appropriate actions to prevent outbreaks., Competing Interests: The authors declare no conflict of interest., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The objective of this study was to determine the effect of early lactation body condition (BC) loss in multiparous dairy cows on serum lipids and the effect of these changes on oocyte and cumulus cell transcriptomes. Body condition loss in dairy cattle after parturition is associated with reduced fertility and increased pregnancy loss. The complex interplay between BC, nutrition, dry matter intake, milk production, and time of calving has presented a barrier to understanding mechanisms leading to reduced fertility. We identified cows that lost BC (L group; n = 10) or maintained or gained BC (M/G group; n = 8) during the first 27 to 33 d in milk and investigated changes in serum fatty acids and oocyte and cumulus cell transcriptomes at 75 to 81 d in milk. The L group had increased serum levels of nonesterified fatty acids and mead acid, and reduced serum levels of petroselaidic acid and behenic acid. Transcriptome analyses revealed 38 differentially expressed genes (DEG) in oocytes and 71 DEG in cumulus cells of L (n = 3) compared with M/G group (n = 3). Network analysis connected serum fatty acid changes to downstream effects including reduced inflammatory response and mitochondrial membrane depolarization, increased production of reactive oxygen species, and functions related to fatty acid metabolism and cytoplasmic organization in oocytes. These effects were associated with predicted effects on signaling in oocytes through calcium, insulin, O-GlcNAcase (OGA), fibroblast growth factor receptor 4 (FGF4R), peroxisome proliferator activated receptor gamma coactivator 1 α (PPARGC1A), and phospholipase D2 (PLD2) pathways, with a connection to the cumulus cell via calcium signaling. These results connect BC loss following parturition to changes in serum lipid levels, and changes potentially affecting oocyte quality; thus, these results provide new insight into mechanism of reduced fertility., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

This in vitro study evaluated color change, mineral content, and morphology of enamel, pH and cytotoxicity of experimental bleaching agents containing 35% hydrogen peroxide (HP), titanium tetrafluoride (TiF4), Natrosol, and Chemygel. Sixty enamel/dentin blocks were randomly treated with (n = 10) HP; HP+Natrosol+Chemygel with different TiF4 concentrations: 0.05 g HPT0.5, 0.1 g HPT1, 0.2 g HPT2, 0.3 g HPT3, 0.4 g HPT4. Bleaching was performed in three sessions (3 × 15 min application). Color change (CIELab-ΔEab, CIEDE2000-ΔE00, ΔWID) and Knoop microhardness (KHN) were evaluated. Enamel morphology and composition were observed under scanning electron microscopy and energy-dispersive spectrometry (EDS), respectively. Cell viability of keratinocyte cells was evaluated using MTT assay. Data were analyzed by one-way ANOVA and LSD and Tukey tests, and two-way repeated measures ANOVA and Bonferroni (α = 5%). The pH and EDS were analyzed descriptively. Lightness-L* increased, and a* and b* parameters decreased, except for HPT3 and HPT4 (b*). HPT0.5, HPT1, and HPT2 exhibited ΔEab and ΔWID similar to HP. ΔE00 did not present statistical difference. HP, HPT0.5, and HPT1 promoted higher KHN. HPT0.5 exhibited no changes on enamel surface. Keratinocyte cells were viable when treated with T0.5, and weak viable for T1. Experimental agents exhibited acidic pH and Ti elements. HPT0.5 exhibited bleaching efficacy, maintained KHN without enamel alterations, and did not increase cytotoxicity.

This study describes the synthesis of a new bioadsorbent with zwitterionic characteristics and its successful application for removal of a cationic dye (crystal violet, CV) and an anionic dye (orange II, OII) from single component aqueous systems. The new bi-functionalized cellulose derivative (MC3) was produced by chemical modification of cellulose with succinic anhydride and choline chloride to introduce carboxylic and quaternary ammonium functional groups on the cellulose surface. MC3 was characterized by several wet chemical and spectroscopic methods. The effects of solution pH, contact time, and initial solute concentration on removal of CV and OII by MC3 were investigated. Studies of the desorption and re-adsorption of the dyes were also carried out. The isotherms for adsorption of CV and OII on MC3 were satisfactorily fitted using the Konda and Langmuir models. MC3 showed experimental maximum adsorption capacities of 2403 mg g -1 for CV and 201 mg g -1 for OII. The desorption and re-adsorption results showed that MC3 could be reused in successive adsorption cycles, which is essential for minimizing process costs and waste generation. The findings showed that MC3 is a versatile biosorbent capable of efficiently removing both cationic and anionic dyes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Commitment to the CD4+ or CD8+ T cell lineages is linked to the acquisition of a functional program broadly defined by helper and cytotoxic properties, respectively. The mechanisms underlying these processes in the human thymus remain largely unclear. Moreover, recent thymic emigrants are thought to have some degree of plasticity, which may be important for the shaping of the immune system and adjustment to specific peripheral needs. We show here that IL-4 induces proliferation-independent de novo synthesis of CD8αβ in human CD4 single-positive (SP) thymocytes, generating a stable CD8SP population that features a diverse TCRαβ repertoire, CD4 expression shut-down and ThPOK downregulation. IL-4 also promotes an innate-like program in both CD4SP and CD8SP thymocytes, characterized by Eomes upregulation in the absence of T-bet, in line with its recognized role in the generation of thymic innate-like CD8+ T cells. The clinical relevance of these findings is further supported by the profile of IL-4 production and IL-4 receptor expression that we identified in the human thymus. Importantly, human cord blood CD4+ T cells preserve the ability to generate Eomes+ CD8+ T cells in the presence of IL-4, with implications in neonatal immunity. Our results support a role for IL-4 in the dynamic regulation of human thymocyte plasticity and identify novel strategies to modulate immune responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nunes-Cabaço, Ramalho-dos-Santos, Pires, Martins, Barata and Sousa.)

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction, and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously downregulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in upregulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are upregulated in response to SHH signaling. This analysis uncovers opposing trans-regulatory inputs from SHH- and SMAD4-mediated BMP signal transduction on anterior and posterior gene expression during the digit patterning and outgrowth in early limb buds., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Total intravenous anesthesia (TIVA) has been gaining ground in the routine of small animals. This study aimed to evaluate the hemodynamic effects produced by continuous infusion of propofol isolated or associated with ketamine, S-ketamine, or remifentanil in dogs submitted to video laparoscopic ovariectomy. Thirty-two female dogs were randomly assigned to 4 groups (n = 8): G,1 propofol (0.6 mg/kg/min); G2. ketamine (2 mg/kg followed by 100 µg/kg/min) and propofol (0.4 mg/kg/min); G3, S-ketamine (1 mg/kg followed by 50 µg/kg/min) and propofol (0.4 mg/kg/min); and G4, remifentanil (1 µg/kg followed by 0.2 µg/kg/min) and propofol (0.4 mg/kg/min). All dogs were submitted to the same pre-anesthetic protocol with acepromazine (0.1 mg/kg) and meperidine (4 mg/kg) intramuscularly, followed by anesthetic induction with propofol (4 mg/kg). All animals were mechanically ventilated. Heart rate (HR), respiratory rate (f), SpO 2 , systolic, diastolic and mean arterial blood pressures (SAP, DAP and MAP, respectively), EtCO 2 , cardiac output (CO), blood glucose and rectal temperature were evaluated in 7 time-points (M0-M7). HR increased throughout the anesthesia in all groups, except for G4, which showed inferior values. In all groups, EtCO 2 increased from M1 to M7. SAP was higher in G1 in relation to G2 in M2 and M3, and G4 in all time points. G4 also obtained the lower values for DAP and MAP, although not inferior to 60 mmHg. CO was unchanged through time and among groups. No groups had hyperglycemia, although glucose levels varied with time. It was concluded that all TIVA protocols showed satisfactory results and hemodynamic stability., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The intensive use of the antihypertensive losartan potassium (LOS) has culminated in its high occurrence in aquatic environments. However, insufficient studies had investigated its effects in non-target organisms. In this study, ecotoxicity of LOS was assessed in aquatic organisms from distinct trophic levels (Desmodesmus subspicatus, Daphnia magna, and Astyanax altiparanae). Genotoxicity was assessed by the comet assay in D. magna and A. altiparanae, and biochemical biomarkers for the fish. LOS was more toxic to D. subspicatus (EC 50(72h) = 27.93 mg L -1 ) than D. magna (EC 50 = 303.69 mg L -1 ). Subsequently, this drug showed to induce more DNA damage in D. magna than A. altiparanae, when exposed to 2.5 mg L -1 . No significant stress responses were observed by the fish biomarkers, suggesting that higher trophic levels organisms are more tolerant to LOS toxicity. LOS showed relatively low toxic potential for a short period of exposure, but with different patterns of toxicity for the organisms from distinct trophic levels, contributing to further risk assessment of LOS., (Copyright © 2021. Published by Elsevier B.V.)

Background: Considering the new SARS-CoV-2 pandemic and the potential scarcity of material resources, the reuse of personal protective equipment such as filtering facepiece respirators (FFRs) for N95 filtering or higher is being discussed, mainly regarding the effectiveness and safety of cleaning, disinfection and sterilization processes., Aim: To analyze the available evidence in the literature on the safety in processing FFRs., Methods: A systematic review conducted by searching for studies in the following databases: PubMed, CINAHL, LILACS, CENTRAL, EMBASE, Web of Science, and Scopus., Results: Forty studies were included in this review. The disinfectant/sterilizing agents most frequently tested at different concentrations and exposure periods were ultraviolet irradiation, vaporized hydrogen peroxide and steam sterilization. Microbial reduction was assessed in 21 (52.5%) studies. The only disinfectants/sterilizers that did not caused degradation of the material-integrity were alcohol, electric cooker, ethylene oxide, and peracetic acid fogging. Exposure to ultraviolet irradiation or microwave generated-steam resulted in a nonsignificant reduction in filter performance., Conclusion: There is a complex relationship between the FFR raw materials and the cycle conditions of the decontamination methods, evidencing the need for validating FFRs by models and manufacturers, as well as the process. Some methods may require additional tests to demonstrate the safety of FFRs for use due to toxicity., (Copyright © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Helicobacter pylori is a spiral-shaped bacterium, which plays a role in the aetiology of gastric diseases in humans. Non- H . pylori Helicobacter (NHPH) species naturally colonise the stomach of animals and also induce gastric lesions in humans, highlighting their zoonotic importance. We evaluated the gastric bacterial colonisation density and gastric lesions and sought to identify the main phylogenetic groups of the Helicobacter spp. obtained from dogs in the central region of Rio Grande do Sul, Brazil, with this study aiming to investigate the occurrence of Helicobacter spp. in saliva and gastric samples from these dogs. This study included 35 dogs and used analysis such as cytology, histopathology, PCR, rapid urease testing, and phylogenetic analysis. Of the dogs, 94.3% were positive for Helicobacter spp., and these bacteria were present in the stomach of 32 dogs and saliva of eight. Respectively, eight, 15, and nine dogs had mild, moderate, and severe colonisation. Lymphocytic-plasmacytic infiltrate was the main gastric lesion. However, the presence of Helicobacter and the density appeared to be unrelated to the gastric lesions. The samples possessed a high nucleotide identity with remarkably similar sequences among some of the species of NHPH such as H . heilmannii s.s. , H . salomonis , H. felis, and H. bizzozeronii. The saliva of domestic dogs, even of those who appear clinically healthy, can cause Helicobacter infection in humans and other animals, with, in these dogs, increased density, occurrence rate, and predominance of NHPH of zoonotic importance being found in the stomach with a lower occurrence of Helicobacter spp. in the saliva., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Daniel D. Guerra Segundo et al.)

Although banished in some countries, triclosan (TCS) and triclocarban (TCC) have been detected in surface waters in concentrations ranging from ng L -1 to μg L -1 and have shown to affect non-target organisms posing risk to aquatic ecosystems. However, the majority of the studies consider higher levels of these chemicals and single exposure effects to investigate their potential risks, rather than using environmentally relevant concentrations and their binary mixture. In this study, the toxicity of TCS and TCC, and their binary mixture was assessed in catfish embryos (Rhamdia quelen, a south American native species) exposed to environmental concentrations during 96 h. Organisms were evaluated through the endpoints of developmental abnormalities (spine, fin, facial/cranial and thorax), biochemical biomarkers related to oxidative stress responses: catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) activities, protein carbonylation (PCO) and neurotoxicity by acetylcholinesterase activity (AChE). The data showed that TCS caused fin abnormalities, decrease of SOD activity and increase of AChE activity in the catfish embryos of 96hpf. On the other hand, TCC and the binary mixture showed a higher abnormality index for the 96hpf embryos, and an induction of CAT and GST activities for the mixture treatment. The results obtained were able to show potential, but not severe, toxicity of TCS and TCC even in low concentrations and a short period of exposure. The relevance of studies approaching real scenarios of exposure should be reinforced, considering environmental concentrations of chemicals, interactions of contaminants in complex mixtures and the use of a native species such as R. quelen exposed during initial stages of development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Of all cyanobacteria, Microcystis aeruginosa is the most commonly found species in bloom episodes all over the world. This species is known to produce cyanopeptides with hepatotoxic effects, namely microcystins (MCs). In this regard, Advanced Oxidation Processes (AOPs) have been widely studied for cyanotoxin degradation, but very few studies focused on cyanobacteria inactivation combined with toxin removal. To our knowledge, this is the first report of the photo-Fenton process application focusing on M. aeruginosa inactivation and microcystin-LR (MC-LR) degradation. This research work aimed to evaluate the photo-Fenton process under three different conditions with regard to Fe2+/H2O2 ratios (0.6/10, 5/50, and 20/100 mg L-1) at the initial near-neutral pH. Process efficiency was measured by immediate cell density reduction, growth inhibition, effect on MC-LR concentrations, and scanning electron microscopy (SEM) to analyze any alterations in cell morphology. Growth inhibition test (GIT) results pointed to cell inactivation under all conditions tested, and MC-LR concentrations were reduced below WHO's maximum limit at medium and higher concentrations of reagents. The possible mechanisms of cell inactivation by oxidative species are discussed.

Objectives: The aim of this study was to evaluate the effects of dipyrone and tramadol, used for 5 days, on postoperative pain, hematological and biochemical parameters, and oxidative markers on erythrocytes., Methods: Twenty-eight healthy cats underwent ovariohysterectomy and were randomly allocated to four groups (each n = 7), according to the postoperative treatment administered intravenously: control (saline 1 ml q8h), DIP1 (dipyrone 25 mg/kg q24h), DIP2 (dipyrone 25 mg/kg q12h) and DIP3 (dipyrone 25 mg/kg q8h). All animals received tramadol (2 mg/kg q8h). Pain was assessed by visual analog (VAS), multidimensional UNESP and Glasgow pain scales for cats preoperatively and at 3, 6, 12, 24, 36 and 48 h after extubation. Venous blood was collected daily for 5 days, and on day 10, to perform a complete blood count (CBC) and determine the percentage of Heinz bodies (HBs). Serum biochemistry was evaluated preoperatively and on days 5 and 10; superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and lipoperoxidation were evaluated preoperatively and on days 3, 5 and 10., Results: Control cats had higher pain scores than DIP3 cats by UNESP ( P = 0.0065), and DIP2 ( P = 0.0035) and DIP3 cats ( P = 0.0108) by VAS 3 h postoperatively. Rescue analgesia was required by two animals in the control group and one each in the DIP1 and DIP2 groups. There was no difference in SOD or CAT among groups. On day 5, MPO was more active in DIP2 than in DIP3 cats ( P = 0.0274). No difference in lipoperoxidation among treatment and control cats was found. CBC remained constant and without statistical difference among groups. Control, DIP2 and DIP3 cats presented a similar percentage of HBs on day 10. Biochemical variables were similar among groups and times., Conclusions and Relevance: The administration of dipyrone in cats, when used in combination with tramadol, did not ensure better analgesia than tramadol alone. Dipyrone did not significantly affect biochemical variables and oxidative markers, despite minimal, clinically irrelevant, hematological differences between groups.

Purpose: To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease., Experimental Design: Tumor-infiltrating lymphocytes (TIL) were quantified by semiautomated whole-slide analysis in brain metastases from 81 lung adenocarcinomas. Multi-color staining enabled phenotyping of TILs (CD3, CD8, and FOXP3) on a single-cell resolution. Molecular determinants of the extent of TILs in brain metastases were analyzed by transcriptomics in a subset of 63 patients. Findings in lung adenocarcinoma brain metastases were related to published multi-omic primary lung adenocarcinoma The Cancer Genome Atlas data ( n = 230) and single-cell RNA-sequencing (scRNA-seq) data ( n = 52,698)., Results: TIL numbers within tumor islands was an independent prognostic marker in patients with lung adenocarcinoma brain metastases. Comparative transcriptomics revealed that expression of three surfactant metabolism-related genes ( SFTPA1, SFTPB , and NAPSA ) was closely associated with TIL numbers. Their expression was not only prognostic in brain metastasis but also in primary lung adenocarcinoma. Correlation with scRNA-seq data revealed that brain metastases with high expression of surfactant genes might originate from tumor cells resembling alveolar type 2 cells. Methylome-based estimation of immune cell fractions in primary lung adenocarcinoma confirmed a positive association between lymphocyte infiltration and surfactant expression. Tumors with a high surfactant expression displayed a transcriptomic profile of an inflammatory microenvironment., Conclusions: The expression of surfactant metabolism-related genes ( SFTPA1, SFTPB , and NAPSA ) defines an inflamed subtype of lung adenocarcinoma brain metastases characterized by high abundance of TILs in close vicinity to tumor cells, a prolonged survival, and a tumor microenvironment which might be more accessible to immunotherapeutic approaches., (©2020 American Association for Cancer Research.)

Introduction: Ketamine (KET) is an anesthetic agent widely used in human and veterinary medicine. According to studies, KET is associated to direct neutorotoxic damages due to its capacity to induce oxidative stress. Because of the free radical generation in the organism and its relation with diseases' development, there is a growing interest to study antioxidant molecules, such as gallic acid (GA), a natural phenolic compound., Aim: Evaluate the GA antioxidant potential for the prevention of oxidative damage in the brain and liver tissue of rats exposed to acute KET administration., Material and Methods: 32 Wistar male rats received GA (by gavage, 13.5 mg/kg) for three consecutive days, 24 h after the last GA dose, animals were anesthetized with KET (50 mg/kg, i.m.). All animals were euthanized by decapitation 60 min after KET administration. The liver, brain cortex and hippocampus were removed and homogenized for biochemical analysis., Results: In brain cortex, KET increased reactive species (RS) generation, protein carbonyls (PC) levels and reduced non-protein thiols (NPSH) levels, while GA pre-treatment reduced PC and increased NPSH levels. KET increased PC and decreased NPSH levels in the hippocampus, and GA reduced PC and NPSH levels. In the liver, no difference was observed in the RS generation, while KET induced and increase of PC levels and decreased NPSH levels, while GA pre-treatment prevented it., Conclusion: GA administration can prevent oxidative damage caused by acute KET administration and minimize its noxious effects. Further studies are needed to evidence GA antioxidant properties regarding KET chronic use., (Copyright © 2019. Published by Elsevier B.V.)

The urokinase plasminogen activator system (uPAS) has been poorly investigated in veterinary oncology. The aim of this study was to determine uPA serum concentrations in healthy and oncologic cats to understand the potential value of uPA as a cancer biomarker. Serum samples were collected from 19 healthy cats and 18 cats with spontaneous malignant neoplasms and uPA was measured through a specific enzyme-linked immunosorbent assay kit. The differences between uPA values and their relation with intrinsic factors and clinicopathological parameters were analyzed using an analysis of variance (ANOVA) and independent t -test. The average serum concentration of uPA in cancerous cats (0.54 ± 0.22 ng/mL) differed from that of healthy cats (1.10 ± 1.16 ng/mL) but was not significantly influenced by cats' clinicopathological parameters or by the presence of metastases. This study describes, for the first time, the serum concentrations of uPA in cats and proposes directions for future studies to uncover the relevance of uPAS in feline carcinogenesis., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Objective: To compare technical feasibility, surgical time, surgical complications, and postoperative pain in ovariectomy (OVE) by hybrid and total natural orifice transluminal endoscopic surgery (NOTES)., Study Design: Prospective randomized clinical trial., Animals: Sixteen healthy and sexually intact bitches., Methods: Dogs were randomly assigned to the hybrid NOTES group (HNG; n = 8) and the total NOTES group (TNG; n = 8) to compare surgical time, pain scores and complications. Pain was assessed by using the visual analog scale (VAS) and the Melbourne pain scale (MPS)., Results: Surgical time did not differ between the experimental groups (HNG = 46.3 ± 18.5 minutes, TNG = 54.6 ± 31.1 minutes). Exteriorization of the ovaries through the vaginal wound was the major difficulty. Complications were minor in both groups and occurred intraoperatively only in the HNG, and in both groups post operatively. No dogs required rescue analgesia in the intraoperative or postoperative period. There were no differences in VAS or MPS scores between the groups for any surgical times except for the VAS assessment at 72 hours after extubation (HNG = 1.1 ± 0.3, TNG = 0.7 ± 0.4, P = .0221)., Conclusion: Both NOTES techniques were comparable for canine OVE, with no requirement for additional analgesia in the postoperative periods. It was not possible to determine whether there was a clear advantage of one technique rather than the other., Clinical Significance: The minimally invasive techniques proposed for laparoscopic OVE are feasible for dogs with low pain scores and low rates of complications for both groups., (© 2018 The American College of Veterinary Surgeons.)

The purpose of this study was to compare the linear polymerization shrinkage of different restorative resin-based composites (RBCs) using fiber Bragg grating (FBG) sensors. Five RBCs were evaluated: Zirconfill ® (ZFL); Aura Bulk-Fill (ABF); Tetric ® N-Ceram Bulk-Fill (TBF); Filtek TM Bulk-Fill (FBF); and Admira Fusion-Ormocer ® (ADF). Ten samples per resin were produced in standardized custom-made half-gutter silicone molds. Two optical FBG sensors were used to assess temperature and polymerization shrinkage. Light curing was performed for 40 s and polymerization shrinkage was evaluated at 5, 10, 40, 60, 150, and 300 s. Statistical analysis was accomplished for normal distribution (Shapiro-Wilk, p > 0.05). Two-way repeated measures ANOVA with Greenhouse-Geisser correction followed by Bonferroni's post-hoc test was used to analyze the linear shrinkage data ( p < 0.05). ZFL showed the highest linear shrinkage and ADF the lowest. Shrinkage increased for all RBCs until 300 s, where significant differences were found between ADF and all other resins ( p < 0.05). Among bulk-fill RBCs, TBF showed the lowest shrinkage value, but not statistically different from FBF. The ADF presented lower linear shrinkage than all other RBCs, and restorative bulk-fill composites exhibited an intermediate behavior.

This study evaluated the variability of the peripheral perfusion index (PI) in 22 anaesthetised female dogs undergoing elective ovariohysterectomy and examined the relationship between peripheral PI and heart rate, blood pressure, blood pH, end tidal CO 2 (EtCO 2 ), O 2 saturation (SpO 2 ), core-peripheral temperature gradient (ΔTc-p), partial pressure of CO 2 (PCO 2 ), and concentrations of glucose, cortisol, lactate and bicarbonate (HCO 3 - ). Blood pH, lactate and glucose concentrations were determined 15, 30, 45min into the ovariohysterectomy procedure and after extubation. Cortisol concentrations were assessed before anaesthesia and after extubation. Other variables were recorded at every 5min throughout the ovariohysterectomy procedure. Hyperglycaemia was observed in 59% of bitches during surgery, but serum cortisol concentrations remained unchanged. Most measures of perfusion (ΔTc-p, pH, PCO 2 , EtCO 2 , SpO 2 ) and heart rate remained unchanged throughout anaesthesia and did not correlate with peripheral PI. Mean arterial pressure increased during the ovariohysterectomy procedure, while peripheral PI decreased, resulting in negative correlations between these variables at 30 and 45min. Lactate concentrations decreased from baseline to the time of measurement post-extubation. Peripheral PI gradually decreased during the ovariohysterectomy procedure, probably reflecting vasoconstriction induced by nociceptive stimuli. Using lactate concentrations as the reference standard for peripheral perfusion, low peripheral PI in healthy bitches undergoing ovariohysterectomy might not represent peripheral hypoperfusion., (Copyright © 2018 Elsevier Ltd. All rights reserved.)