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Objectives: Despite its seeming relevance, limited information exists about antibiotic sinus tissue penetration and how it is affected by inflammation. Thus the reason for the present investigation.Study Design: A randomized, open, multiple-dose, pharmacological study, employing cefuroxime axetil, an approved oral antimicrobial for the treatment of acute bacterial rhinosinusitis, was developed.Methods: Twenty subjects, selected for surgery because of chronic rhinosinusitis, were randomly allocated to receive either a short (3-8 d) or a long (9-14 d) preoperative treatment regime with 500 mg cefuroxime axetil BID, the last dosage being taken 3 to 4 hours before surgery. At the operation, tissue samples were collected at specific sinonasal sites for both pharmacological determination of antibiotic levels and histopathological assessment of the degree of inflammation. The blood levels of the drug were simultaneously assayed.Results: Cefuroxime kinetic behavior on chronically inflamed mucosa was shown to be, for the most part, dependent on the blood levels, regardless of the inflammatory state. Distribution was even throughout the different sinus cavities, and the tissue levels were still, 3 to 4 hours after dosing, above the reported minimum inhibitory concentration (MIC) values for some of the most prevalent sinus pathogens. The extended treatment course did not seem to add any extra histopathological or pharmacological benefit.Conclusions: Cefuroxime penetrates adequately and uniformly into chronically inflamed sinus mucosa, apparently unaffected by the degree of inflammation, in a way not dissimilar to its pharmacokinetic behavior in the normal state. Persistent MIC levels for common pathogens still warrant antimicrobial efficacy for a significant period of time after dosing. [ABSTRACT FROM AUTHOR]

This study aimed to perform in vitro antiparasitic and antimicrobial tests with the essential oil (EO) of Schinus terebinthifolius against of fish and shrimp. The chemical composition of the EO of S. terebinthifolius was determined by gas chromatography. For the antiparasitic test, the protozoan Epistylis sp. obtained from parasitized Oreochromis niloticus was used, and exposed to different concentrations of EO (2%, 1%, 0.5%, 0.25%), and control with 1% grain alcohol. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) test with EO of S. terebinthifolius evaluated the antimicrobial potential, with serial dilutions starting at 2% and control with 1% grain alcohol, using the strains of Aeromonas hydrophila (2.2 × 10 8  CFU mL -1 ), Edwardsiella tarda, Vibrio parahaemolyticus, V. harveyi, and V. alginolyticus (2.0 × 10 8  CFU mL -1 ). Chemical analysis revealed that the major EO compounds of S. terebinthifolius were δ-3-Carene (56.00%) and α-Pinene (16.89%). In the antiparasitic test, the concentration of 2% EO showed 100% efficacy against Epistylis sp. within 5 min. In the antimicrobial tests, the concentration of 2% EO was effective against all bacteria tested. The EO of S. terebinthifolius demonstrated antiparasitic and antimicrobial activity at a concentration of 2%, standing out as an alternative to conventional antibiotics., (© 2024 John Wiley & Sons Ltd.)

This study investigated the in vitro antimicrobial and anthelmintic effect of copper nanoparticles (CuNPs) against the bacterium Aeromonas hydrophila, the monogeneans Dactylogyrus minutus, Dactylogyrus extensus, Gyrodactylus cyprini, and the cestode Schyzocotyle acheilognathi, as well as their toxicity to Cyprinus carpio Koi. In the antimicrobial in vitro test, the inhibition zone method and minimum inhibitory concentration (MIC) were performed. In order to determine the time and efficacy of monogenean parasite mortality, the parasites were exposed to CuNP concentrations of 20, 50, 100, 150, 200, and 300 mg L -1 , and a control group with tank water and one with copper sulphate pentahydrate (CuSO 4 . 5 H 2 O) at a concentration of 0.3 mg L -1 , performed in triplicate. The parasites were observed every 10 min for 300 min, and mortality was recorded. For the cestodes, parasites were immersed in CuNP concentrations of 50, 100, 150, and 300 mg L -1 . At the end of the in vitro tests, the anthelmintic efficacy of each treatment was calculated. To assess the tolerance and toxicity in fish, they were exposed to CuNP concentrations of 0.6, 1.25, 2.5, 5, 10, 20, and 50 mg L -1 for 12 h. The MIC demonstrated that CuNPs effectively inhibited the growth of A. hydrophila up to a dilution of 12,500 mg L -1 and showed an inhibition zone of 14.0 ± 1.6 mm for CuNPs. The results of anthelmintic activity showed a dose-dependent effect of concentration for both groups of parasites, with the most effective concentration being 300 mg L -1 in 120 min. In the toxicity test, the carps showed tolerance to lower concentrations. The study indicated that CuNPs were effective against the studied pathogens. However, it proved to be toxic to fish at high concentrations. The use of low concentrations is recommended still requires further investigation., (© 2024 John Wiley & Sons Ltd.)

The objective of this study was to evaluate the effect of dietary supplementation with Citrus sinensis (L.) Osbeck essential oil on the growth, immune system, and resistance to Aeromonas hydrophila infection in Colossoma macropomum fingerlings. The experiment was conducted with five treatments (control diet, Tween80 diet, and diets supplemented with 200, 400, and 800 mg L -1 of C. sinensis essential oil) with four replicates. At the end of the experimental period, growth parameters were measured, and blood samples were collected for thrombogram, leukogram, and phagocytic activity analysis. A bacterial challenge with A. hydrophila was conducted for 96 h. C. macropomum fingerlings that were fed with 400 and 800 mg L -1 of C. sinensis essential oil had the highest growth parameters, with final weights of 533.18 ± 2.03 mg and 531.91 ± 2.67 mg, respectively, and an increase in the number of thrombocytes, lymphocytes, monocytes, and neutrophils, as well as higher phagocytosis rates compared to the control group. Regarding the challenge, fish in the 400 and 800 mg L -1 treatments also exhibited the lowest cumulative mortality rate (26.66% ± 3.33%). Therefore, supplementation with C. sinensis essential oil promotes growth, improves health, and enhances resistance to A. hydrophila in C. macropomum fingerlings., (© 2024 John Wiley & Sons Ltd.)

Objectives: To evaluate the short and long-term effects of anodal tDCS (a-tDCS) targeting the left temporoparietal area (LTA) on tinnitus severity, annoyance, and loudness., Methods: This is a double-blind, randomized, sham-controlled, and parallel-group clinical trial. A total of 42 individuals with tinnitus were randomized to a-tDCS (n = 24) or sham tDCS (n = 18). The a-tDCS group received tDCS over the LTA during five consecutive day sessions (2 mA, 20 min). The sham group received a placebo current with the same characteristics as the a-tDCS group. Participants were assessed at baseline, after the fifth session, and at the 30-day follow-up, using hearing assessments and symptom questionnaires., Results: There was no effect of comparison between groups or interaction effect (time x group) in all hearing assessments and symptom questionnaires. There was only a main effect of time for Tinnitus Handicap Inventory - THI [F(1.642, 45.988) = 5.128; p = 0.014; η 2 = 0.155]. Bonferroni post hoc showed that there was a significant difference in THI in the sham group between pre and post-treatment [CI (0.107, 14.643; p = 0.046)]. However, there was no difference between pre-treatment and follow-up THI, or between post-treatment and follow-up THI. There was no treatment effect on tinnitus severity (assessed by Tinnitus Functional Inventory - TFI), tinnitus annoyance or loudness (assessed by Visual Analogue Scale - VAS), or tinnitus pitch, loudness or minimum masking level (assessed by tinnitometry)., Conclusion: Five consecutive sessions of a-tDCS targeting LTA do not improve tinnitus severity, annoyance, and loudness. Future studies should investigate if other tDCS protocols are effective or a combination of tDCS with other forms of treatment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Anxiety disorder is one of the most well-characterized behavioral disorders in individuals subjected to acute or chronic stress. However, few studies have demonstrated how different types of stressors can modulate the neurochemical alterations involved in the generation of anxiety. In this study, we hypothesize that subjects exposed to different aversive stimuli (mechanical, chemical, and spatial restriction) present varied intensities of anxiety-like responses associated with distinct patterns of gamma-aminobutyric acid (GABA) and glutamate release in the brain. Adult zebrafish, Danio rerio ( n  = 60), were randomly divided into four experimental groups; control, acute restraint stress (ARS), conspecific alarm substance (CAS), and chasing with net (CN). After the stress protocols, the animals were individually transferred to a novel tank diving test for behavioral analysis. Subsequently, their brains were collected and subjected to GABA and glutamate release assay for quantification by HPLC. Our behavioral results showed that all aversive stimuli were capable of inducing anxiety-like behavior. However, the impact of anxiogenic behavior was more prominent in the CN and CAS groups when compared to ARS. This phenomenon was evident in all analyzed behavioral parameters (time on top, freezing, mean speed, maximum speed, and erratic swimming). Our data also showed that all aversive stimuli significantly decreased GABA release compared to the control group. Only animals exposed to CN and CAS presented an increase in extracellular glutamate levels. Different acute stressors induced different levels of anxiety-like behavior in zebrafish as well as specific alterations in GABAergic and glutamatergic release in the brain. These results demonstrate the complexity of anxiety disorders, highlighting that both behavioral and neurochemical responses are highly context-dependent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martins, Pinheiro, Saito, Lima, Leão, Batista, Passos, Gouveia, Oliveira and Herculano.)

The study aimed to evaluate the in vitro anthelminthic and antimicrobial activity of silver nanoparticles (AgNPs) against Dactylogyrus minutus and Aeromonas hydrophila, pathogens of Cyprinus carpio Koi. Gill arches of the fish were removed and placed into six-well plates containing 10 mL of tank water with varying concentrations of AgNPs: 100, 400, 500, 600, and 800 mg/L, along with control groups using tank water and distilled water. Each group was tested in triplicate. Parasites were observed every 10 min for 300 min (5 h) using a stereomicroscope, and mortality rates were recorded. Anthelminthic efficacy was calculated at the end of the tests. For the in vitro antimicrobial test, the Minimum Inhibitory Concentration (MIC) of AgNPs was determined by adding 100 μL of Poor Broth (PB) culture medium to all 96 wells of a microplate. The first well was filled with 100 μL of AgNPs, followed by serial dilutions (1:2 ratio). Subsequently, 50 μL of A. hydrophila (1 × 10 7  CFU/mL) was added to all wells and incubated for 24 h at 28 °C. Results showed that 800 mg/L of AgNPs achieved 87% anthelminthic efficacy within 300 min, while 100 mg/L achieved 47% efficacy. The MIC showed bacterial growth inhibition at 125 mg/mL. Despite the 87% efficacy against parasites within 300 min, AgNPs did not reach 100% efficacy quickly, limiting their potential use in ornamental fish farming. Further studies are needed to assess the toxicity of AgNPs in fish., 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.)

In the aquaculture industry, biocides are routinely used to treat parasitosis in fish, and researchers are continually developing sustainable alternatives that can replace these harsh chemicals. In this context, the objective of this study was to evaluate the effectiveness of a new natural compound, BiokosTM, for the treatment against Epistylis sp. in Carassius auratus fish. The infestation was identified by the presence of whitish plaques on the integument of five animals, and the diagnosis was confirmed through skin scrapings. BiokosTM is a lipopeptide derived from the bacteria Pseudomonas that can destroy the functionality of the cell membrane of ciliated protozoa. The action of BiokosTM does not harm animals and the environment because the compound degrades into amino acids and fatty acids within days. A 0.15 m3 (150 L) aquarium was treated with an Ich-AwayTM water conditioner manufactured by the Danish company Sundew ApS, which has BiokosTM as the active ingredient. Six tablets were added to the water daily for two days, and new skin scrapings were performed. The fish were clinically well and no longer possessed lesions or parasites. The results obtained indicate that BiokosTM can be an innovative and more sustainable alternative for controlling epistyliasis in ornamental fish.

Morphine is a widely used opioid for the treatment of pain. Differences in drug transporter expression and activity may contribute to variability in morphine pharmacokinetics and response. Using appropriate mouse models, we investigated the impact of the efflux transporters ABCB1 and ABCG2 and the OATP uptake transporters on the pharmacokinetics of morphine, morphine-3-glucuronide (M3G), and M6G. Upon subcutaneous administration of morphine, its plasma exposure in Abcb1a/1b -/- ;Abcg2 -/-- , Abcb1a/1b -/- ;Abcg2 -/- ;Oatp1a/1b -/- ;Oatp2b1 -/- (Bab12), and Oatp1a/1b -/- ;Oatp2b1 -/- mice was similar to that found in wild-type mice. Forty minutes after dosing, morphine brain accumulation increased by 2-fold when mouse (m)Abcb1 and mAbcg2 were ablated. Relative recovery of morphine in small intestinal content was significantly reduced in all the knockout strains. In the absence of mOatp1a/1b and mOatp2b1, plasma levels of M3G were markedly increased, suggesting a lower elimination rate. Moreover, Oatp-deficient mice displayed reduced hepatic and intestinal M3G accumulation. Mouse Oatps similarly affected plasma and tissue disposition of subcutaneously administered M6G. Human OATP1B1/1B3 transporters modestly contribute to the liver accumulation of M6G. In summary, mAbcb1, in combination with mAbcg2, limits morphine brain penetration and its net intestinal absorption. Variation in ABCB1 activity due to genetic polymorphisms/mutations and/or environmental factors might, therefore, partially affect morphine tissue exposure in patients. The ablation of mOatp1a/1b increases plasma exposure and decreases the liver and small intestinal disposition of M3G and M6G. Since the contribution of human OATP1B1/1B3 to M6G liver uptake was quite modest, the risks of undesirable drug interactions or interindividual variation related to OATP activity are likely negligible., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Margarida L. F. Martins reports financial support was partly provided by Di-AcetylM BV (Amsterdam, the Netherlands). J.H. Beijnen is the CEO of Di-AcetylM BV. The funding agency had no involvement in any stage of the scientific process. Alfred H. Schinkel's research group receives revenue from the commercial distribution of some of the mouse strains used in this study. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Creating molecules capable of inhibiting ice recrystallization is an active research area aiming to improve the freeze-thaw characteristics of foods and biomedical materials. Peptide mixtures have shown promise in preventing freezing-induced damage, but less is known about the relationship between their amino acid compositions and ice recrystallization inhibition (IRI) activities. In this article, we used Ni 2+ immobilized metal affinity chromatography (IMAC) to fractionate pulse protein hydrolysates, created by Alcalase and trypsin, into mixtures lacking and enriched in His, and Cys residues. The aim of this study was to fractionate pulse protein hydrolysates based on their amino acid compositions and evaluate their resulting physicochemical and IRI characteristics. Ni 2+ IMAC fractionation induced IRI activity in all of the evaluated soy, chickpea, and pea protein hydrolysates regardless of their amino acid composition. Ni 2+ IMAC fractionation produced chemically distinct fractions of peptides, differing by their molecular weights, amino acid composition, and IRI activities. The resulting peptide mixtures' molecular weight, amino acid composition, secondary structure, and sodium ion levels were found to have no correlation with their IRI activities. Thus, we demonstrate for the first time the ability of Ni 2+ IMAC fractionation to induce IRI activity in hydrolyzed pulse proteins., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024. Published by Elsevier Ltd.)

Developing better energy storage devices depends on comprehending the underlying mechanisms involved in charge storage. With the continuous conception of new electrolytes, this task becomes progressively more urgent and complex. An example is the utilization of co-solvated concentrated solutions. While these show promising electrochemical responses, their dynamic properties (especially under confinement) and their relationships with performance are not fully understood. Here, we combined modified step potential electrochemical spectroscopy and quasielastic neutron scattering to investigate systems composed of activated mesoporous carbon (AMC) and concentrated solutions of lithium bis(trifluoromethanesulfonyl)imide in acetonitrile co-solvated with either toluene or acetone. We report that acetone does not impair surface-controlled mechanisms, contrary to the case with toluene, which competes with charged species to populate the AMC's pores without contributing to charge storage. In turn, toluene promotes a greater overall capacitance owing to Faradaic processes, which may be related to changes in the solvation structures under confinement.

Objective: To analyze, through a systematic review, the effectiveness of educational tools (ETs) in Oral Health Programs (OHPs) for pregnant women in improving their oral status and that of their babies., Method: Searches were carried out in 5 electronic databases. Randomized (RCTs) and non-randomized clinical trials (CTs) were selected that included pregnant women exposed or not to ETs in OHPs, whose oral health status, in the pre- or postnatal period, or of their babies were verified. The types of ETs, outcomes, and results were extracted. Bias risk was assessed by ROBINS-I and RoB 2.0; and the certainty of the evidence (CE) by GRADE., Results: A total of nine studies were included. Most used more than one ET (n = 8), with verbal guidance used in all (n = 9). Mothers showed a reduction in biofilm (n = 3), caries (n = 4) and periodontitis (n = 4). All studies with babies (n = 3) were successful in preventing caries. RCTs (n = 3) were classified as low risk of bias (n = 1), with concerns (n = 1) and high risk of bias (n = 1). CTs (n = 6) presented risk of bias as low (n = 2), serious (n = 1) and critical (n = 3). Studies about caries in babies showed high CE, and those who evaluated caries and periodontal parameters/biofilm in the mother had moderate and low CE, respectively., Conclusion: ETs as a strategy of OHPs for pregnant women can be effective in preventing caries in themselves and in their babies. However, despite the improvement of the mothers' oral hygiene and gingival condition, the CE was low considering this parameter., (© 2024. The Author(s), under exclusive licence to British Dental Association.)

The study evaluated dietary supplementation with a feed additive composed of multi-strain Bacillus for Nile tilapia Oreochromis niloticus. In vitro and in vivo assays employing culture-based microbiological methods and metagenomics were performed. Additionally, the study assessed the haemato-immunology, intestinal microbiome, and growth performance of the animals. For this, 30 juvenile Nile tilapia were used in the in vitro assay and 180 (60 + 120) in the in vivo assays. In the in vitro assay, we found evidence of adhesion of the probiotic bacteria to the intestinal mucus of fish, corroborated in the 15-day in vivo assay, in which the count of B. licheniformis was significantly higher in fish fed with probiotic when compared to fish of the control group. Furthermore, in the 50-day in vivo trial, a metagenomic analysis provided evidence for the modulation of the intestine microbiome of Nile tilapia by dietary supplementation of the probiotic. In addition, there was an increase in species richness, higher abundance of potentially probiotic autochthonous species and a lower abundance of Aeromonas sp. when the animals were fed the supplemented diet. Finally, no significant differences were observed in growth performance and haemato-immunological analyses, suggesting no harm to fish health when the product was supplemented for 15 and 50 days. The in vitro results indicate that the multi-strain probiotics were able to adhere to the intestinal mucus of Nile tilapia. Additionally, a modulation of the intestinal microbiome was evidenced in the in vivo assay., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This study evaluated the supplementation of iron and copper nanoparticles in channel catfish diets and their influences on growth and health. A comparative feeding trial was carried out for 9 weeks to evaluate combinations of iron and copper nanoparticles: only iron nanoparticles (IronNP), only copper nanoparticles (CopperNP), CopperNP + IronNP, and a control diet supplemented with inorganic iron and copper (FeSO 4 and CuSO 4 ). After a 9-week feeding trial, growth performance, hematological parameters, whole-body proximate composition, and intestinal microbiota were evaluated, and fish were subjected to a bacterial challenge against Edwardsiella ictaluri to evaluate the contribution of the experimental treatments to fish health status. No statistical differences were detected for catfish fed the various diets in terms of production performance or survival after bacterial challenge. The hematocrit and RBC counts from fish fed the diet containing copper nanoparticles were significantly lower than the control group. A higher relative abundance of gram-positive bacteria was found in the digesta of catfish fed diets containing copper nanoparticles. Furthermore, in the context of hematology, iron nanoparticles did not impact the blood parameters of channel catfish; however, reduced hematocrits were observed in fish fed the copper nanoparticle diet, which lacked supplemental dietary iron, thus reinforcing the importance of dietary iron to catfish hematopoiesis. Nonetheless, additional studies are needed to investigate the effects of dietary copper nanoparticle supplementation in catfish diets to better illuminate its effects on the intestinal microbiota., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In this study, we analyzed the hematoimmunological effects of dietary supplementation with immunomodulators (β-glucans + nucleotides) and different levels of vitamins on Nile tilapia ( Oreochromis niloticus ) after exposure to physical stress. The following four diet treatments were used: diets with indicated vitamin levels (Vitind), diets with Vitind + immunomodulator (Vitind + Immune), diets with high vitamin content (Vithigh), and those with Vithigh + immunomodulator (Vithigh + Immune). The experiment included 560 fish in 28 tanks (20 fish tank -1 ), with seven replicates per treatment. After 60 days of supplementation, the water temperature was set at 20 °C, and complete biometrics were performed. The animals were then subjected to physical stress with temperature oscillations of 20 ºC to 30 ºC/30 ºC to 20 ºC/20 ºC to 30 ºC. Hematoimmunological data from 140 animals were collected post-stress. Antimicrobial titer and total plasma protein levels were significantly higher in fish not receiving immunomodulator-supplemented diets (2.88 ± 0.43 log2 and 26.81 ± 4.01 mg∙mL -1 , respectively) than in those that did. Conversely, the agglutination titer increased in fish fed with lower vitamin levels (3.33 ± 0.66 log2) compared to those with higher vitamin levels. Increased immunoglobulin levels were observed in fish fed diets co-supplemented with vitamins and immunomodulators, revealing an interaction between immunomodulators and dietary vitamin levels. In summary, the inclusion of immunomodulators in the diet enhanced the animals' resistance to physical stress and improved hematoimmunological parameters. Additionally, a high vitamin content in the diet did not modulate the immune responses in the animals., Competing Interests: Conflict of interests: DSC, ILP, SAPD, LC, PBM, LVPR, MCML, TAS, EY, UPP, JLPM and MLM – No conflict of interest

Objectives: This case series aims to evaluate the long-term outcomes of congenital cytomegalovirus (CMV) infection in a population treated with valaciclovir during pregnancy. The study focuses on assessing the prevalence of long-term sequelae in infants with confirmed CMV fetal infection., Methods: A retrospective analysis was conducted on 33 pregnancies corresponding to 34 fetus with confirmed CMV congenital infection. They were followed from November 2004 to December 2020. Valaciclovir treatment was initiated after confirmation of fetal infection, and fetal outcomes were monitored through serial ultrasounds, neurosonography, and fetal magnetic resonance imaging (MRI). Postnatal assessments included: PCR confirmation, symptoms evaluation at birth, and long-term follow-up protocols for visual, auditory, and neurodevelopmental assessment., Results: Therapy was started at a median gestational age of 24 weeks. Of the 34 newborns 79.4 % were asymptomatic at birth. Median follow-up time was 6 years and 32.35 % developed long-term sequelae. Neurosensorial hearing loss (SNHL) was the predominant sequelae. In the cases which developed sequelae 54.5 % had imaging findings, and all with major findings developed long-term sequelae., Conclusions: In our treated population we had a higher asymptomatic rate at birth comparing with a non-treated population, similar to those found in previous studies. We had a long-term sequelae rate of 32.35 %, similar to recent studies on non-treated population, although we registered a slightly lower rate of SNHL. A larger multicenter studies with a longer follow-up time, where treatment is started in the first trimester, is of the utmost importance, so we can truly understand the correlation between these imaging findings, therapy and long-term sequelae., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Zinc is one of the essential microelements for the metabolism of animals. Zinc nanoparticles may have higher bioavailability due to their low specific surface area, facilitating absorption by fish. The present study aimed to evaluate the effects of supplementation with different zinc-based products on the growth and health of Nile tilapia Oreochromis niloticus. Zinc, in different sizes (nanoparticles or bulk) and forms (inorganic or organic), were used as a supplement in the tilapia diet at a dose of 15 mg kg feed -1 for 60 days. At the end of the feeding trial, production performance, hemato-immunological parameters, activity of antioxidant system enzymes, exposure to Streptococcus agalactiae and zinc concentration in the muscle were examined. After the bacterial challenge, the mean corpuscular hemoglobin concentration (MCHC) significantly increased in the fish treated with organic zinc, inorganic nano zinc, and organic nano zinc, while in the control group (inorganic zinc), MCHC remained unchanged. Regarding defense cells, dietary inorganic nano zinc increased the number of basophils (1.50 ± 1.10) compared to organic zinc (0.80 ± 0.90). Lymphocyte count increased after the challenge only in the organic zinc treatments (bulk and nanoparticles). Neutrophils decreased in the control (inorganic zinc) (2.20 ± 1.70) and inorganic nano zinc (2.60 ± 2.70) treatments after the challenge. When compared before and after the bacterial challenge, the plasma antimicrobial titer significantly increased after the bacterial challenge in all treatments. No significant differences were observed for total proteins, enzymes (SOD and CAT), cumulative survival and zinc deposition on fillet. In conclusion, organic zinc in nanoparticles or bulk size increased Nile tilapia innate defense during bacterial infection. However, the other parameters evaluated were not affected by zinc particle size or form (organic or inorganic), indicating that further evaluations should be conducted with organic zinc in nanoparticles or bulk size in the tilapia diet., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A silent spread of human T cell lymphotropic virus type 1 (HTLV-1) has been occurring for thousands of years, with a high prevalence in some regions due to the sexual and vertical transmission and formation of family clusters. The time from HTLV-1 infection until the onset of virus-associated diseases is extremely long, approximately one to three decades. In this study, we evaluated intrafamilial HTLV-1 transmission and associated diseases in 1,204 individuals enrolled and followed up by the GIPH cohort between 1997 and 2017. The family groups ( n  = 43) were composed of 279 individuals who were tested for HTLV-1/human T cell lymphotropic virus type 2 (HTLV-2) and were classified as two groups according to the index case: blood donor (blood donors referred to the GIPH cohort) and nondonor (individuals referred to the GIPH cohort by other health services). The observed rates of HTLV-1 transmission and associated diseases among the relatives were high. Of 236 family members and sexual partners tested for HTLV, 104 (44.1%) were confirmed as having HTLV infection, with 36.7% of relatives whose index case was blood donors and 56.9% of relatives with nondonor index cases. At least one case of HTLV-1-associated myelopathy was observed in 42.9% of the families with intrafamilial transmission of HTLV-1. Brazil is an endemic area for HTLV-1/2 and has implemented mandatory universal screening of blood donors for HTLV-1/2 since 1993. However, the lack of public health services offer diagnosis for HTLV to the general population and pregnant women in the country makes it difficult to identify infected people, and contributes to the silent spread of the virus.

This study evaluated the growth performance and parasite load of angelfish juveniles Pterophyllum scalare kept at different stocking densities using two rearing systems. The experiment was conducted in a factorial design (4x2) with four stocking densities (0.1, 0.4, 0.7, and 1.0 g/L), two type of aquarium tanks (glass and ceramic aquariums), and four replicates. The experiment lasted 60 days using 148 juvenile fish (3.05 ± 0.09 g) randomly placed in 32 aquariums (50 L) equipped with filters and aeration. All fish received two meals a day ad libitum (8:00 and 16:00). Water quality parameters such as temperature, dissolved oxygen, pH, and total ammonia were measured. At the end of the experiment, all fish were measured and weighed to determine growth performance and then subjected to parasitological analysis. The data were analyzed with a two-way ANOVA with post-hoc Tukey test (p<0.05). No effects on growth performance at different stocking densities were observed. However, there was an increase in Capillaria pterophylli infestation in the high stocking density within ceramic aquariums. Thus, this study recommends the use of 1.0 g/L for the intensive aquaculture system of freshwater angelfish, and applying cleaning management to avoid parasite infestation, particularly in ceramic aquariums.

Objective: This study aimed to survey the practice of palliative sedation in Portugal, where data on this subject were lacking. Methods: This was a prospective multicentric study that included all patients admitted to each team that agreed to participate. Patients were followed until death, discharge, or after 3 months of follow-up. Results: The study included 8 teams: 4 as palliative care units (PCU), 1 as a hospital palliative care team (HPCT), 2 as home care (HC), and 1 as HPCT and HC. Of the 361 patients enrolled, 52% were male, the median age was 76 years, and 285 (79%) had cancer. Continuous sedation was undergone by 49 (14%) patients: 26 (53%) were male, and the median age was 76. Most patients, 46 (94%), had an oncological diagnosis. Only in a minority of cases, the family, 16 (33%), or the patient, 5 (10%), participated in the decision to sedate. Delirium was the most frequent symptom leading to sedation. The medication most used was midazolam (65%). In the multivariable analysis, only age and the combined score were independently associated with sedation; patients <76 years and those with higher levels of suffering had a higher probability of being sedated. Conclusions: The practice of continuous palliative sedation in Portugal is within the range reported in other studies. One particularly relevant point was the low participation of patients and their families in the decision-making process. Each team must have a deep discussion on this aspect., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intravenously administered chemotherapeutic cabazitaxel is used for palliative treatment of prostate cancer. An oral formulation would be more patient-friendly and reduce the need for hospitalization. We therefore study determinants of the oral pharmacokinetics of cabazitaxel in a ritonavir-boosted setting, which reduces the CYP3A-mediated first-pass metabolism of cabazitaxel. We here assessed the role of organic anion-transporting polypeptides (OATPs) in the disposition of orally boosted cabazitaxel and its active metabolites, using the Oatp1a/b-knockout and the OATP1B1/1B3-transgenic mice. These transporters may substantially affect plasma clearance and hepatic and intestinal drug disposition. The pharmacokinetics of cabazitaxel and DM2 were not significantly affected by Oatp1a/b and OATP1B1/1B3 activity. In contrast, the plasma AUC 0-120 min of DM1 in Oatp1a/b -/- was 1.9-fold ( p < 0.05) higher than that in wild-type mice, and that of docetaxel was 2.4-fold ( p < 0.05) higher. We further observed impaired hepatic uptake and intestinal disposition for DM1 and docetaxel in the Oatp-ablated strains. None of these parameters showed rescue by the OATP1B1 or -1B3 transporters in the humanized mouse strains, suggesting a minimal role of OATP1B1/1B3. Ritonavir itself was also a potent substrate for mOatp1a/b, showing a 2.9-fold ( p < 0.0001) increased plasma AUC 0-120 min and 3.5-fold ( p < 0.0001) decreased liver-to-plasma ratio in Oatp1a/b -/- compared to those in wild-type mice. Furthermore, we observed the tight binding of cabazitaxel and its active metabolites, including docetaxel, to plasma carboxylesterase (Ces1c) in mice, which may complicate the interpretation of pharmacokinetic and pharmacodynamic mouse studies. Collectively, these results will help to further optimize (pre)clinical research into the safety and efficacy of orally applied cabazitaxel.

Background and Objectives: Serological HTLV-1/2 screening is mandatory for blood donor candidates in Brazil. Our objective was to analyse HTLV test results in blood donors submitted for screening and confirmatory assays in a Brazilian blood bank., Materials and Methods: Retrospective analysis (2017-2022) results of chemiluminescence immunoassays and confirmatory tests for HTLV-1/2 in reactive donors were performed. During the analysed period, three sets of assays were used: (1) Architect rHTLV-I/II + HTLV Blot 2.4 (Western blot [WB]); (2) Alinity s HTLV I/II Reagent Kit + INNO-line immunoassay (LIA) HTLV I/II Score (LIA); (3) Alinity + WB., Results: The analysed period comprised a total of 1,557,333 donations. The mean percentage of HTLV reactive donors using the Architect assay was 0.14%. With the change to the Alinity assay, that percentage dropped 2.3-fold (0.06%). The reactivity rate in the confirmatory tests (1064 samples) ranged from 13.5% to 30.2%, whereas 58.3%-85.9% of samples were non-reactive. The highest rates of positive (30.2%) and indeterminate (11.5%) results were seen using LIA. Considering all analysed samples, those with signal/cut-off ratio (S/CO) >50 were positive in confirmatory tests (positive predictive value, PPV = 100%), whereas samples with S/CO ≤6 are very unlikely to be truly positive (PPV = 0)., Conclusion: The use of the Alinity assay reduced the frequency of false-positive results. Confirmatory tests are important to identify true HTLV infection in blood donors, because more than 58% of initially reactive individuals are confirmed as seronegative. Categorizing S/CO values is useful for assessing the likelihood of true HTLV-1/2 infection., (© 2024 International Society of Blood Transfusion.)

The nutritional quality of food can affect the health of animals. This study examined the effects of dietary supplementation with Lippia sidoides essential oil (LSEO) on the physiology of Danio rerio. Four hundred fourty-eight fish were divided into 28 tanks and subjected to different dietary treatments: a control group with no supplementation, a group with grain alcohol supplementation and five groups with LSEO at concentrations of 0.25%, 0.50%, 0.75%, 1.00% and 1.25%. After 15 days, histological and enzymatic analyses were conducted. The 0.25% LSEO group exhibited lower glutathione peroxidase and catalase activity compared to the 1.00% group. Additionally, fish in the 0.25% LSEO group showed improved liver, kidney and splenic integrity indices. These findings support the inclusion of 0.25% LSEO in the diet of D. rerio, suggesting potential benefits for fish physiology and encouraging further research on phytotherapeutics in fish diets., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

The study evaluated the effects of dietary supplementation with Lippia sidoides essential oil on the microbiota and intestinal morphology of Danio rerio . For this, 448 fish were randomly distributed in 28 tanks divided into a control group fed a commercial diet without supplementation, a group fed a commercial diet containing grain alcohol and five groups fed a commercial diet containing essential oil of L. sidoides (LSEO) at concentrations of 0.25%, 0.50%, 0.75%, 1.00% and 1.25%. After the period of dietary supplementation, biological materials were collected for microbiological and histological analyses. There were no significant differences regarding the microbiological count between the groups. Diversity of the microbiome was higher in 0.25% group than in control group. LSEO inhibited the growth of potentially pathogenic bacteria. Fish fed LSEO 0.25% showed greater intestinal histomorphometric indices. The inclusion of LSEO at 0.25% in the diet of D. rerio provided improvements in fish microbiota and intestine integrity., Competing Interests: Conflict of interests: The authors have no financial or nonfinancial competing interests to disclose.

The translocated intimin receptor (Tir) is an essential type III secretion system (T3SS) effector of attaching and effacing pathogens contributing to the global foodborne disease burden. Tir acts as a cell-surface receptor in host cells, rewiring intracellular processes by targeting multiple host proteins. We investigated the molecular basis for Tir's binding diversity in signalling, finding that Tir is a disordered protein with host-like binding motifs. Unexpectedly, also are several other T3SS effectors. By an integrative approach, we reveal that Tir dimerises via an antiparallel OB-fold within a highly disordered N-terminal cytosolic domain. Also, it has a long disordered C-terminal cytosolic domain partially structured at host-like motifs that bind lipids. Membrane affinity depends on lipid composition and phosphorylation, highlighting a previously unrecognised host interaction impacting Tir-induced actin polymerisation and cell death. Furthermore, multi-site tyrosine phosphorylation enables Tir to engage host SH2 domains in a multivalent fuzzy complex, consistent with Tir's scaffolding role and binding promiscuity. Our findings provide insights into the intracellular Tir domains, highlighting the ability of T3SS effectors to exploit host-like protein disorder as a strategy for host evasion., (© 2024. The Author(s).)

Objective: To assess the in-vitro effect of single applications of CPP-ACP pastes and different fluoridated solutions on the prevention of dental caries around orthodontic brackets., Material and Methods: Tooth/bracket sets (n=65) were immersed in artificial saliva (1h at 37ºC) and randomly subjected to single applications (100µL; 1min) of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP emulsion), CPP-ACP with fluoride (CPP-ACPF emulsion), solutions of titanium tetrafluoride (TiF4) or sodium fluoride (NaF), or no treatment (CG). Multispecies biofilm (5 x 105 CFU/mL) was formed in the presence of 2% sucrose. After 24 h, the pH and the concentration of total soluble fluoride (TSF) were analyzed by culture medium. The presence of active white spot lesions (WSL) evaluated by macroscopic examination and the percent surface mineral loss (%SML) were analyzed. Also, the topography of enamel was detected by analysis of scanning electron microscopy (SEM). The data was assessed by chi-square, Kruskal-Wallis, and Mann-Whitney tests (p < 0.05)., Results: Fluoride-containing compounds led to a smaller pH reduction than did CPP-ACP and CG (p<0.05). There was difference in TSF between the groups (p<0.05), denoted as TiF4> NaF > CPP-ACPF > CPP-ACP > CG. Regarding the presence of WSL and %SML, the NaF group obtained lower values (p<0.05), while TiF4 and CPP-ACPF were similar (p>0.05). SEM demonstrated that fluoride-free groups had a larger surface dissolution., Conclusion: Fluoridated groups including solutions and CPP-ACPF were more effective than CPP-ACP in reducing enamel demineralization around orthodontic brackets after a single application.

Molecular analysis of blood groups is important in transfusion medicine, allowing the prediction of red blood cell (RBC) antigens. Many blood banks use single nucleotide variant (SNV) based methods for blood group analysis. While this is a well-established approach, it is limited to the polymorphisms included in genotyping panels. Thus, variants that alter antigenic expression may be ignored, resulting in incorrect prediction of phenotypes. The popularization of next-generation sequencing (NGS) has led to its application in transfusion medicine, including for RBC antigens determination. The present review/meta-analysis aimed to evaluate the applicability of the NGS for the prediction of RBC antigens. A systematic review was conducted following a comprehensive literature search in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies were selected based on predefined criteria and evaluated using Strengthening the Reporting of Observational studies in Epidemiology guidelines. The characteristics and results of the studies were extracted and meta-analysis was performed to verify the agreement between results from standard molecular methods and NGS. Kell (rs8176058), Duffy (rs2814778, rs12078), or Kidd (rs1085396) alleles were selected as a model for comparisons. Additionally, results are presented for other blood group systems. Of the 864 eligible studies identified, 10 met the inclusion criteria and were selected for meta-analysis. The pooled concordance proportion for NGS compared to other methods ranged from 0.982 to 0.994. The sequencing depth coverage was identified as crucial parameters for the reliability of the results. Some studies reported difficulty in analyzing more complex systems, such as Rh and MNS, requiring the adoption of specific strategies. NGS is a technology capable of predicting blood group phenotypes and has many strengths such as the possibility of simultaneously analyzing hundred individuals and gene regions, and the ability to provide comprehensive genetic analysis, which is useful in the description of new alleles and a better understanding of the genetic basis of blood groups. The implementation of NGS in the routine of blood banks depends on several factors such as cost reduction, the availability of widely validated panels, the establishment of clear quality parameters and access to bioinformatics analysis tools that are easy to access and operate., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In Brazil, studies evaluating the concentration of trace metals in fish farms are scarce. Therefore, studies investigating the presence and levels of these metals in aquatic biota, particularly in fish tissues, are crucial for developing appropriate strategies to mitigate the impact of possible toxic metals. Herein, we investigated the levels of trace metals (Cr, Mn, Co, Ni, Cu, Zn, Al, Ag, Cd, Pb, Fe, Na, Mg, Ca, K, and Ba) in water, feed, and sediment, as well as the bioconcentration and bioaccumulation factors in tambaqui muscles (Colossoma macropomum). For this purpose, eight commercial fish farms, which are also engaged in other agricultural activities, were selected. Fe, Zn, Mg, and Cr concentration in tambaqui muscles exceeded the limits set by the Brazilian regulations for daily consumption by adults. Mn, Zn, Al, Pb, Fe, Na, Cu, Co, Ag, Cd, and Ba levels were substantially higher in the liver tissue of tambaquis than those in the muscle tissue. The most prevalent metals found in the feed were Ca, K, Na, Mg, and Fe. However, the levels of Cr and Cd in the sediment, as well as Pb, Mn, Cu, and Fe in the water, exceeded the maximum limits allowed by the Brazilian legislation. The highest bioconcentration factors were observed for the metals, Na, Zn, and K, with concentrations up to 4.74, 12.61, and 72.08 times, respectively, higher in tambaqui muscle compared to those in water. The bioaccumulation factors for Ca, Zn, Mg, Na, and K were 2.90, 6.96, 21.21, 212.33, and 492.02 times, respectively, higher in the muscle tissue than those in the sediment values in fishponds across all fish farms. Therefore, our findings suggest that tambaquis have a remarkable ability to bioaccumulate trace metals, particularly the essential ones, and can be categorized as a bioindicator species for environmental quality. Furthermore, we observed that, although water exhibits the highest prevalence and diversity of elements above the values recommended by the Brazilian legislation, sediment is the primary source of trace metal contamination for tambaquis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the effects of supplementation with whey protein combined with vitamins C and E on inflammatory markers in hemodialysis (HD) patients., Design and Methods: This was a pioneer, randomized and double-blinded study. Patients were randomized into two groups and stratified by HD frequency. The supplementation group received 20 g of whey protein, 250 mg of vitamin C, and 600 IU of vitamin E; the placebo group, 20 g of rice flour, and microcrystalline cellulose capsules. The interventions were given after HD, 3 times a week, for 8 weeks. The inflammatory markers were assessed: interleukin (IL) IL-12p70, IL-10, IL-6, IL-8, and tumor necrosis factor alpha. For statistical analysis, the χ2 test, Student's t-test, Mann-Whitney test, analysis of variance for repeated two-way measurements, paired t test, and Wilcoxon test were performed. P < .05 was considered statistically significant., Results: Twenty-three patients completed the study. No significant differences were found in inflammatory markers when comparing the groups postintervention. In the intragroup was a decrease in IL-10 in the supplementation group after 8 weeks (P = .0382). IL-6 tended to decrease by 810.95% in the supplementation group and increased by 732.8% (nonsignificant) in the placebo group., Conclusion: Whey protein combined with vitamins C and E significantly reduced IL-10 in the supplementation group and could be beneficial to reduce IL-6 in HD patients. Future studies are suggested with a larger sample size, different supplementation doses, and longer interventions., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load., Methods: We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4 + and T CD8 + ) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen., Results: T CD4 + and T CD8 + lymphocytes cells stimulated by HBZ-peptides (HBZ 42-50 and HBZ 157-176 ) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8 + cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44 +High /CD62L -Low ), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8 + T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA., Conclusions: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine., (© 2023. The Author(s).)

This work considers the problem of segmenting heart sounds into their fundamental components. We unify statistical and data-driven solutions by introducing Markov-based Neural Networks (MNNs), a hybrid end-to-end framework that exploits Markov models as statistical inductive biases for an Artificial Neural Network (ANN) discriminator. We show that an MNN leveraging a simple one-dimensional Convolutional ANN significantly outperforms two recent purely data-driven solutions for this task in two publicly available datasets: PhysioNet 2016 (Sensitivity: 0.947 ±0.02; Positive Predictive Value : 0.937 ±0.025) and the CirCor DigiScope 2022 (Sensitivity: 0.950 ±0.008; Positive Predictive Value: 0.943 ±0.012). We also propose a novel gradient-based unsupervised learning algorithm that effectively makes the MNN adaptive to unseen datum sampled from unknown distributions. We perform a cross dataset analysis and show that an MNN pre-trained in the CirCor DigiScope 2022 can benefit from an average improvement of 3.90% Positive Predictive Value on unseen observations from the PhysioNet 2016 dataset using this method.

Background & Purpose: Heroin (diacetylmorphine; diamorphine) is a highly addictive opioid prodrug. Heroin prescription is possible in some countries for chronic, treatment-refractory opioid-dependent patients and as a potent analgesic for specific indications. We aimed to study the pharmacokinetic interactions of heroin and its main pharmacodynamically active metabolites, 6-monoacetylmorphine (6-MAM) and morphine, with the multidrug efflux transporters P-glycoprotein/ABCB1 and BCRP/ABCG2 using wild-type, Abcb1a/1b and Abcb1a/1b;Abcg2 knockout mice., Methods & Results: Upon subcutaneous (s.c.) heroin administration, its blood levels decreased quickly, making it challenging to detect heroin even shortly after dosing. 6-MAM was the predominant active metabolite present in blood and most tissues. At 10 and 30 min after heroin administration, 6-MAM and morphine brain accumulation were increased about 2-fold when mouse (m)Abcb1a/1b and mAbcg2 were ablated. Fifteen minutes after direct s.c. administration of an equimolar dose of 6-MAM, we observed good intrinsic brain penetration of 6-MAM in wild-type mice. Still, mAbcb1 limited brain accumulation of 6-MAM and morphine without affecting their blood exposure, and possibly mediated their direct intestinal excretion. A minor contribution of mAbcg2 to these effects could not be excluded., Conclusions: We show that mAbcb1a/1b can limit 6-MAM and morphine brain exposure. Pharmacodynamic behavioral/postural observations, while non-quantitative, supported moderately increased brain levels of 6-MAM and morphine in the knockout mouse strains. Variation in ABCB1 activity due to genetic polymorphisms or environmental factors (e.g., drug interactions) might affect 6-MAM/morphine exposure in individuals, but only to a limited extent., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Porous carbons are the active materials of choice for supercapacitor applications because of their power capability, long-term cycle stability, and wide operating temperatures. However, the development of carbon active materials with improved physicochemical and electrochemical properties is generally carried out via time-consuming and cost-ineffective experimental processes. In this regard, machine-learning technology provides a data-driven approach to examine previously reported research works to find the critical features for developing ideal carbon materials for supercapacitors. Here, we report the design of a machine-learning-derived activation strategy that uses sodium amide and cross-linked polymer precursors to synthesize highly porous carbons (i.e., with specific surface areas > 4000 m 2 /g). Tuning the pore size and oxygen content of the carbonaceous materials, we report a highly porous carbon-base electrode with 0.7 mg/cm 2 of electrode mass loading that exhibits a high specific capacitance of 610 F/g in 1 M H 2 SO 4 . This result approaches the specific capacitance of a porous carbon electrode predicted by the machine learning approach. We also investigate the charge storage mechanism and electrolyte transport properties via step potential electrochemical spectroscopy and quasielastic neutron scattering measurements., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Gastric Intestinal Metaplasia (GIM) is one of the precancerous conditions in the gastric carcinogenesis cascade and its optical diagnosis during endoscopic screening is challenging even for seasoned endoscopists. Several solutions leveraging pre-trained deep neural networks (DNNs) have been recently proposed in order to assist human diagnosis. In this paper, we present a comparative study of these architectures in a new dataset containing GIM and non-GIM Narrow-band imaging still frames. We find that the surveyed DNNs perform remarkably well on average, but still measure sizeable inter-fold variability during cross-validation. An additional ad-hoc analysis suggests that these baseline architectures may not perform equally well at all scales when diagnosing GIM.Clinical relevance- Enhanching a clinician's ability to detect and localize intestinal metaplasia can be a crucial tool for gastric cancer management policies.

The use of nanoparticles as chemotherapeutic carriers has been suggested as a way to overcome a range of side effects associated with classical cancer treatment such as poor selectivity and tumor resurgence. Obtaining precise control of the size and shape of therapeutic nanoparticles is crucial to optimize the targeting of tumor sites. In this work, it is shown that a previously developed system of polypeptide encapsulating individual DNA molecules, that forms rod-shaped nanoparticles of precisely controlled aspect ratio, can be loaded with the DNA-intercalating chemotherapeutic drug doxorubicin (DOX). It is characterized the size and shape of the DOX loaded-Virus-Like DNA Particles (DOX-VLDP) and shown that in this system the DOX payload does not leak out. Through in vitro cell studies, it is shown that DOX-VLDP is internalized by melanoma tumor cells (B16F10 cells) in a delayed and endocytosis-dependent way culminating in increased cytotoxicity and selectivity to tumor cells in comparison with free DOX. In addition, it is found that DOX-VLDP trigger apoptosis and autophagy pathways in treated cells. Taken together, the data on the DOX-VLDP nanoparticles shows that they kill cancer cells differently from free DOX., (© 2023 Wiley-VCH GmbH.)

The aim of this study was to observe how abiotic and biotic factors in a tropical region influence the rate of monogenean parasitism in Nile tilapia ( Oreochromis niloticus ) that are farmed in net cages. A total of 240 sexually reversed fish were analyzed, and 20 from each culture stage were collected during each sampling month. Overall, 60 fish were sampled in April (autumn), 60 in August (winter), 60 in November (spring), and 60 in February (summer). Fish were collected from a commercial fish farm located in Capivara Reservoir in the lower Paranapanema River region of Paraná, Brazil. In total, 3290 monogenean parasites were collected from fish gills of the following species: Cichlidogyrushalli , C. thurstonae , Scutogyruslongicornis , C. cirratus , C. sclerosus , and C. tilapiae . Higher parasitological indices were observed in colder seasons with lower precipitation. Autumn had the highest parasitic infection values compared to the other seasons. The occurrence of monogenean parasites showed a negative correlation with season, in contrast to the culture stage, in which there was a positive correlation. These results may provide a means for establishing adequate fish farm management to predict periods of high monogenean infestation.

To assess the in vitro and in situ effect of experimental combined fluoride and calcium nanocomposite solutions on dental caries prevention. Nanocompound mesoporous silica (MS) with calcium (Ca) and sodium fluoride (NaF) - (MSCaNaF); MS with NaF (MSNaF), NaF solution (positive control), and deionized water (negative control - CG) were studied. The specimens (n=130) were submitted in vitro to a multispecies biofilm in the presence of 2% sucrose. After 24 h and 48 h, the culture medium pH, the percent of surface mineral loss (%SML), and lesion depth (ΔZ) were analyzed. In the in situ study, 10 volunteers participated in four phases of 7-days each. The products were applied on the specimens (n=240) before 20% sucrose solution drips. The polysaccharides (SEPS and IEPS), %SML and roughness (Sa) were evaluated. There was an in vitro decrease in pH values in 24h and 48h, compared to baseline. The MSCaNaF and MSNaF groups obtained lower values of %SML and ΔZ (p < 0.05) than CG and NaF after 24h and were similar to NaF after 48h (p<0.05). In situ results showed similar SEPS and IEPS among all groups after 48h. An after 7-days, the nanocomposites had similar values (p>0.05), while NaF was similar to CG (p>0.05). After 48h, the MSCaNaF and MSNaF reduced the %SML (p<0.05). After 7-days, both experimental nanocomposites were similar to NaF (p>0.05). Regarding Sa, MSCaNaF was better than NaF for both periods (p<0.05). The nanocomposites controlled the in vitro and in situ enamel demineralization, mainly in the initial periods.

This study aimed to search parasites in 333 ornamental fish from five Brazilian states (Ceará, Minas Gerais, São Paulo, Paraná and Santa Catarina). Fish were sent from eight farms located in the municipalities of Fortaleza, Patrocínio do Muriaé, São Francisco do Glória, Cascavel, Timbó, Iguape, Jacareí and Mairinque. All fish received anesthesia earlier to euthanasia procedures. After the search for parasites, it was verified that 70.6% (235/333) of fishes were infected by at least one type of parasite, being 12 types of parasites identified: monogeneans, digenean metacercariae, cestodes, nematodes, Lernaea cyprinacea, trichodinids, Piscinoodinium pillulare, Ichthyophthirius multifiliis, diplomonad flagellates, Ichthyobodo sp., Chilodonella sp., and Tetrahymena sp. The proportion of infected fishes among the farms is compared through statistical tests, besides, animal handling adopted in each farm is also discussed. The importance of ensuring fish health in order to make the ornamental freshwater fish industry economically viable and reduce losses in production is highlighted.