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Objectives A study was performed on the effects of stimulation at Zusanli-point (ST.36) by electroacupuncture (EA) at two frequencies on the bioavailability of 99mTc-sodium pertechnetate (Na99mTcO4) in rats. Methods Forty Wistar rats were divided into four groups: untreated control, treated by manual acupuncture at ST.36 bilaterally, treated by EA at 2 Hz at ST.36 bilaterally, and the same site at 100 Hz bilaterally. Na99mTcO4(7.4 MBq) was administrated via the ocular-plexus and, 20 minutes before sacrifice, blood was withdrawn for radiolabeling assay (BRL). In the bioavailability analysis, organs and tissues were isolated, their radioactivity determined, and the percentage of injected dose per gram of organ or tissue (%ID/g) and the %ID were calculated for each organ or tissue (%ID/ot). For BRL, the plasma and blood cells isolated, and the fractions also precipitated with 5% trichloroacetic acid to separate the soluble and insoluble fractions; these were assessed as percentage of injected dose (%ID) in blood (%ID/b). Results The results showed significant differences in the %ID/g in some organs and tissues in comparison with controls; lung (p = 0.0013), spleen (p = 0.0085), pancreas (p = 0.0167), liver (p = 0.0003), stomach (p<0.0001), small-intestine (p = 0.0181), large-intestine (p = 0.04099), urinary-bladder (p = 0.0271), thyroid (p< 0.0001), muscle (p = 0.0187); %ID/ot in spleen (p = 0.0349); and %ID/b in blood sample (p = 0.0235). In the blood labeling analyses, EA in either frequency significantly increased insoluble fraction/blood cells (p < 0.0001). Conclusions These findings suggested that acupuncture procedures at ST.36 could modulate responses in some organs, tissues, and blood in rats. Further rigorous experimental studies to examine the effectiveness in either acupuncture therapy need to be pursued. [ABSTRACT FROM AUTHOR]

The control of microbiologically influenced corrosion (MIC) challenges the oil exploration sector. The MIC results from electrochemical reactions facilitated by microorganisms such as sulfate-reducing bacteria (SRB), which adhere to the surface of the ducts forming biofilms. SRB uses sulfate as the final electron acceptor, resulting in hydrogen sulfide as the final product, a highly reactive corrosive, and toxic compound. Due to the high diversity of the SRB group, this study evaluated the effect of an Escherichia coli phage, with biofilm degrading enzymes, in preventing biofilm formation by microbial consortium P48SEP and reducing H 2 S production in a complex SRB community. Three phage concentrations were evaluated (10 4 , 10 8 and 10 12 UFP/ml). High and medium phage concentrations prevented biofilm development, as evidenced by scanning electron microscopy, chemical analysis, and cell counts. In addition, the virus altered the expression pattern of some bacterial genes and the relative abundance of proteins related to biofilm formation and cell stress response. Using a complex culture formed mainly by SRB, it was possible to observe the bacterial growth, H 2 S, and metabolic activity reduction after the phage was added. This study shows for the first time the ability of an E. coli -infecting phage to prevent the biofilm formation of an SRB consortium and infect and replicate at high concentrations on the non-specific host. This new finding turns the use of non-specific phages a promising alternative for the control of biocorrosion in oil and gas installations, on the other side, alert to the use of large concentration of phages and the influence on bacterial groups with geological importance, opening a research field in phage biology., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

This study aimed to analyze the association between sociodemographic factors, maternal and neonatal characteristics and the time taken to introduce complementary feeding in low birthweight and preterm newborns. This is a prospective cohort study of 79 preterm newborns weighing less than or equal to 1,800g. Data were collected at the time of hospital discharge and at the 6th, 9th ,and 12th months of corrected gestational age (CGA), using a structured questionnaire to analyze the time taken to introduce complementary feeding and the texture of the foods introduced. Furthermore, the Survey of Well-being of Young Children (SWYC-BR) was used to assess the risk of developmental delay. Cox proportional hazards regression was used to analyze the variables. The introduction of complementary feeding was assessed in preterm newborns based on the median age of introduction of liquid foods (3.50; IQR: 2.50-5.00), followed by solid (4.70; IQR: 3.20-5.20) and soft foods (5.00; IQR: 4.50-5.50). There was also an association with gestational age (RR = 1.25; 95%CI: 1.02-1.52) throughout the process of food introduction. For solid and soft foods, those with the longest length of stay (RR = 1.03; 95%CI: 1.10-1.05) and on mixed breastfeeding (RR = 2.97; 95%CI: 1.24-7.09) delayed the introduction of complementary feeding the longest. For liquid foods, less severe preterm newborns (Score for Neonatal Acute Physiology and Perinatal Extension - SNAPPE II [RR = 0.96; 95%CI: 0.94-0.98]) and mothers who were breastfeeding at hospital discharge (RR = 11.49; 95%CI: 1.57-84.10) delayed the introduction of complementary feeding. Guidelines are needed to better advise professionals and parents and/or guardians on the ideal time to introduce feeding.

Objective: To evaluate the association between the inflammatory potential of the diet measured by the energy-adjusted diet inflammatory index (E-DII) and inflammatory markers in adolescents., Methods: This cross-sectional study was conducted among 518 adolescents aged 18 and 19 years from São Luís, Maranhão, Brazil in 2016. A semiquantitative food frequency questionnaire (FFQ) was used to assess dietary intake from which E-DII scores were calculated to determine the inflammatory potential of the diet. The associations between E-DII and inflammatory markers (hs-CRP, IL-6, IL-4, TNF-α, and IFNγ) were analyzed using multivariable linear regression. The variables included in the adjusted model were identified using the directed acyclic graph., Results: The diet of these adolescents was mostly pro-inflammatory; mean E-DII score was 1.71 and ranged from -2.44 to 5.58. Higher E-DII scores were positively associated with higher levels of IFNγ in the adjusted analysis (Adjusted Coef.: 1.19; 95%CI: 0.36-12.04). We observed no associations between E-DII and other inflammatory markers (hs-CRP, IL-6, IL-4, TNF-α). Study results indicate that E-DII is useful in evaluating the inflammatory potential of the diet of Brazilian adolescents., Conclusions: Cross-sectionally E-DII scores were positively associated with IFNγ concentrations. Future research should examine the association between changes in E-DII scores and levels of inflammatory markers longitudinally.

Bacteria of the species Oceanotoga teriensis belong to the family Petrotogaceae , are Gram-negative bacilli, are moderately thermophilic and are included in the group of thiosulfate-reducing bacteria, being capable of significantly accelerating corrosion in metallic structures. However, no in-depth study on the genome, antibiotic resistance and mobile elements has been carried out so far. In this work, the isolation, phenotypic and genotypic characterization of the multi-resistant O. teriensis UFV&#95;LIMV02 strain was carried out, from water samples from an offshore oil extraction platform in Rio de Janeiro (Brazil). We determined that the isolate has a genome of 2 812 778 bp in size, with 26 % GC content, organized into 34 contigs. Genomic annotation using Rapid Annotation using Subsystem Technology revealed the presence of genes related to resistance to antibiotics and heavy metals. By evaluating the antimicrobial resistance of the isolate using the disc diffusion technique, resistance was verified for the classes of antibiotics, beta-lactams, fluoroquinolones, aminoglycosides, sulfonamides, lincosamides and rifamycins, a total of 14 antibiotics. The search for genomic islands, prophages and defence systems against phage infection revealed the presence of five genomic islands in its genome, containing genes related to resistance to heavy metals and antibiotics, most of which are efflux pumps and several transposases. No prophage was found in its genome; however, nine different defence systems against phage infection were detected. When analysing the clustered regularly interspaced short palindromic repeat (CRISPR) systems, four CRISPR arrays, classified as types I-B and III-B, with 272 spacers, can provide the strain with immunity to different mobile genetic elements and bacteriophage infection. The results found in this study show that the isolate UFV&#95;LIVM02 is an environmental bacterium, resistant to different classes of antibiotics, and that the proteins encoded by the predicted genomic islands may be associated with the development of greater resistance to antibiotics and heavy metals. They provide evidence that environmental bacteria found in offshore oil exploration residues may pose a risk for the spread of antibiotic resistance genes. More comprehensive studies on the microbial community present in oil waste are needed to assess the risks of horizontal gene transfer., Competing Interests: The authors declare that there are no conflicts of interests., (Copyright © 2024 The Authors.)

α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension.

Differently from immunocompromised patients, very little information is available in the literature regarding the clinical presentation, epidemiology, and outcomes of histoplasmosis in non-immunosuppressed individuals living in endemic areas. This retrospective case series study was carried out by reviewing the medical records of non-immunocompromised patients with histoplasmosis, residents in a hyperendemic area in northeastern Brazil, between 2011 and 2022. Thirty HIV-negative patients were identified with histoplasmosis, and 19 cases met the inclusion criteria: three had acute, five subacute and one chronic pulmonary forms; two with mediastinal picture and eight had disseminated disease (two with severe symptoms). The median age of our sample was 32.7 years old [interquartile range: 24-45]. Most of the patients were male (male-to-female ratio = 15:4) and resided in the state capital (n = 9). The majority had a previous history of exposure to well-known risk factors for Histoplasma infection. Pulmonary nodules were observed in all subacute form, two patients (acute and subacute forms) were initially treated empirically for pulmonary tuberculosis; one death was registered in the subacute form. The chronic pulmonary form of histoplasmosis was diagnosed in one patient only after the symptoms persisted despite specific treatment. The primary clinical manifestations of the moderate form of DH were enlarged lymph nodes, with histopathology being the main diagnostic method. The cases were detected as isolated occurrences and not as an outbreak, suggesting that exposure to Histoplasma can be more widespread than presumed. Despite the self-limiting nature of the disease, death can occur even in previously heathy patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Microwave-assisted extraction of mucilage from juá was investigated using response surface methodology. The optimal conditions for extraction were a power of 300 W, an extraction time of 240 s, a pH of 8.0, and a water/sample ratio of 1/6, which achieved a 26.43% yield. The monosaccharide composition and antioxidant activity of the mucilage from juá fruits from different regions of Caatinga were investigated. The fruits from Agreste Paraibano showed the highest mucilage extraction yield (18.64%) compared to that of fruits from Mata Paraibana (MP) (12.37%), Borborema (BB) (11.47%), and Sertão Paraibano (8.31%) (p < 0.05). Glucose (32.8%-50.8%) and arabinose (19.3%-32.9%) were the main monosaccharides found in juá mucilage. The mucilage from fruits in the MP presented the highest antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity assays. Our results demonstrated the potential for the future exploration and application of juá mucilage in the food industry. PRACTICAL APPLICATION: Juá (Ziziphus joazeiro Mart.) mucilage contains phenolic compounds and antioxidant activity, and its extraction by MAE is efficient, as it contributed to a higher yield., (© 2024 Institute of Food Technologists.)

Whopping cough (or Pertussis) is an acute infectious respiratory disease caused by Bordetella pertussis bacteria. The disease is highly transmissible and can be fatal in children under two years old. Since the introduction of vaccine immunization in 1940, Pertussis incidence decreased worldwide. In Brazil, the immunization was introduced in 1977 using the whole cell (wP) vaccine. Despite the high vaccination coverage, an unexpected increase in the number of observed Pertussis cases was observed in 2012. In this year, 2257 cases were reported exceeding the average incidence rate of <1000 cases per year until 2010. This outbreak reached a peak level in 2014 and ended in 2018 according to the Brazilian National Surveillance System (SINAN). To understand the relationship between the outbreak and the vaccination, bacterial isolates (n = 136) from the Brazilian Midwest region obtained during the outbreak were submitted to genotyping of two vaccine loci: ptxP and fim3. Most of isolates (102) were obtained from nursing children (29 days to 2 years old). Genotyping of 94 isolates revealed that fim3-24/ptxP-3 was the most prevalent genotype (68%) associated with the outbreak peak. Two additional genotypes were also observed: fim3-1/ptxP-3 (15%) and fim3-3/ptxP-3 (17%). Conversely, the fim3-1/ptxP-2 genotype, which is harbored by the strain used in the wP vaccine (Bp137), was not observed. These results showed that B. pertussis circulating strains in the outbreak analyzed were different from the strain used for Pertussis immunization in Brazil. These observations provide insights that could be used to target vaccination programs to prevent future whooping cough outbreaks in Brazil., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: To compare children's stereometric optic disc parameters and inner retinal thickness measured by optical coherence tomography (OCT) in two different moments in life in the same children and to establish a correlation between the optic nerve head (ONH) area and the difference of these parameters in the two observations., Methods: In this observational cohort, children were evaluated on two occasions: at 6.7 ± 1.6 and 13.2 ± 0.7 years of age. Cup volume, neuroretinal rim (NRR) area, average cup-to-disc ratio, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell inner plexiform layer (GCIPL) were measured by the Cirrus HD-OCT (Carl Zeiss Meditec AG)., Results: A total of 175 children were included, 89 boys (50.9%) and 86 girls (49.1%). There was a significant decrease of the NRR area ( P < .001) and increase of the cup volume ( P < .001) on the second observation. The pRNFL thickness and GCIPL thickness also decreased ( P < .001 and P = .002, respectively). There was a positive correlation between the ONH area and the difference of the cup volume ( P = .047; r = 0.102) and a negative correlation with the difference of the NRR area ( P < .001; r = 0.237)., Conclusions: During childhood, there is an increase of the cup volume, a decrease of the NRR area, and a decrease of inner retinal layer thickness (more significant in the superior and inferior quadrants) measured by OCT. This study demonstrates that in children with large discs the enlargement of the cup and decrease of the NRR is more evident. Considering these changes, the physiological enlargement of the cup in a child with a large disc can be misinterpreted as the development of a glaucomatous lesion. [ J Pediatr Ophthalmol Strabismus . 20XX;X(X):XXX-XXX.] .

Natural fiber reinforcements have the potential to enhance mechanical properties, thereby improving performance and durability in various applications. In this study, we comprehensively evaluated the impact of environmental degradation over 120 days on reprocessed polypropylene (PP) reinforced with corn husk fiber (CHF) composites. The manufactured systems underwent rigorous analysis using various techniques, including Fourier transform infrared spectroscopy, thermogravimetric analysis, optical microscopy, scanning electron microscopy, and tensile testing. These analyses revealed that climatic conditions significantly influenced ( p < 0.05) the mechanical properties of all systems. Photodegradation led to surface morphological changes and chemical structures. Regardless, adding CHF filler proved a key factor, as it allowed for less susceptibility to environmental degradation than the reprocessed matrix. These findings, therefore, provide robust evidence supporting the feasibility of using CHF composites for manufacturing agricultural containers.

Interactions between multiple genes and environmental factors could be related to the pathogenesis of type 1 diabetes (T1D). The Brazilian population results from different historical miscegenation events, resulting in a highly diverse genetic pool. This study aimed to analyze the mtDNA of patients with T1D and to investigate whether there is a relationship between maternal ancestry, self-reported color and the presence of T1D. The mtDNA control region of 204 patients with T1D residing in three geographic regions of Brazil was sequenced following the International Society for Forensic Genetics (ISFG) recommendations. We obtained a frequency of Native American matrilineal origin (43.6%), African origin (38.2%), and European origin (18.1%). For self-declared color, 42.6% of the patients with diabetes reported that they were White, 50.9% were Brown, and 5.4% were Black. Finally, when we compared the self-declaration data with maternal ancestral origin, we found that for the self-declared White group, there was a greater percentage of haplogroups of Native American origin (50.6%); for the self-declared Black group, there was a greater percentage of African haplogroups (90.9%); and for the Brown group, there was a similar percentage of Native American and African haplogroups (42.3% and 45.2%, respectively). The Brazilian population with diabetic has a maternal heritage of more than 80% Native American and African origin, corroborating the country's colonization history., (© 2024. The Author(s).)

PD-1 blockade unleashes potent antitumor activity in CD8 + T cells but can also promote immunosuppressive T regulatory (Treg) cells, which may worsen the response to immunotherapy. Tumor-Treg inhibition is a promising strategy to improve the efficacy of checkpoint blockade immunotherapy; however, our understanding of the mechanisms supporting tumor-Tregs during PD-1 immunotherapy is incomplete. Here, we show that PD-1 blockade increases tumor-Tregs in mouse models of melanoma and metastatic melanoma patients. Mechanistically, Treg accumulation is not caused by Treg-intrinsic inhibition of PD-1 signaling but depends on an indirect effect of activated CD8 + T cells. CD8 + T cells produce IL-2 and colocalize with Tregs in mouse and human melanomas. IL-2 upregulates the anti-apoptotic protein ICOS on tumor-Tregs, promoting their accumulation. Inhibition of ICOS signaling before PD-1 immunotherapy improves control over immunogenic melanoma. Thus, interrupting the intratumor CD8 + T cell:Treg crosstalk represents a strategy to enhance the therapeutic efficacy of PD-1 immunotherapy., Competing Interests: Declaration of interests T.R.M. is a founder and shareholder in Monopteros Therapeutics, Inc. This commercial relationship is unrelated to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Statement of Problem: Knowledge on the biomechanical behavior of glass-ceramics, their survival rate over time, and their potential failures is essential for decision-making in clinical practice. Systematic reviews and meta-analysis of their survival rates and irreparable failures are lacking., Purpose: The purpose of this systematic review and meta-analysis was to evaluate the survival rates and irreparable failures of various monolithic glass-ceramic dental restorations to help determine biomechanical indications., Material and Methods: A comprehensive literature search was conducted across the PubMed, Scopus, Web of Science, and EMBASE databases based on the population, intervention, comparison, and outcome (PICO) question, risk of bias assessment, data extraction, subgroup analysis, and meta-analysis. Both randomized and nonrandomized clinical trials that reported survival rate and irreparable failure were screened. The risk, with a 95% confidence interval, was calculated by using the Mantel-Haenszel method., Results: A total of 46 articles met the inclusion criteria: 8 for laminate veneers, 20 for partial coverage restorations, 11 for single crowns, and 6 for fixed partial dentures, encompassing 1715 participants rehabilitated with 4209 restorations. The estimated cumulative survival rate for partial coverage restorations was 90% over an average span of 6.2 years, with an irreparable failure occurrence of n=5.9. Laminate veneers had a survival rate of 90.2% over 6.5 years, with an irreparable failure occurrence of n=8.2. Single crowns had a survival rate of 96% over 4.6 years and an irreparable failure of n=2.7. Conversely, fixed partial dentures had a survival rate of 76.1% over 6.5 years with an irreparable failure of n=5.2., Conclusions: Glass-ceramic materials demonstrate relatively high survival rates, indicating that they provide a safe and reliable option for partial coverage restorations, laminate veneers, and single crowns. However, fixed partial dentures had a higher proportion of irreparable failures and a lower survival rate, and caution is required., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

This study investigated the effect of the serine protease on metabolizable energy and amino acids' digestibility of different soybean meal for broilers. A total of 684 broilers chickens form 14 to 23 d age were distributed with nineteen treatments, six replicates, and six birds per replicate. Nine samples of soybean meal from different regions in Brazil were used, with some samples supplemented with the protease enzyme and others without addition. Apparent and corrected-for-nitrogen-balance metabolizable energy were evaluated, as well as the coefficients of amino acid digestibility. All collected data were submitted to ANOVA at a significance level of 5% and Tukey's test was applied. The results showed that the addition of the protease enzyme significantly increased the values of AME and AMEn in all soybean meal samples. The soybean meal of different origins has significant variations in AME and AMEn. The addition of the protease improved the digestibility of essential amino acids compared to soybean meal without enzyme addition. These results indicate that supplementation with serine protease can improve the metabolizable energy and amino acid digestibility of soybean meal from different regions in the diet of broilers, potentially being an effective strategy to enhance nutrient utilization and animal performance.

The iconic mountains of the Pantepui biogeographical region host many early-diverging endemic animal and plant lineages, concurring with Conan Doyle's novel about an ancient "Lost World". While this is the case of several frog lineages, others appear to have more recent origins, adding to the controversy around the diversification processes in this region. Due to its remoteness, Pantepui is challenging for biological surveys, and only a glimpse of its biodiversity has been described, which hampers comprehensive evolutionary studies in many groups. During a recent expedition to the Neblina massif on the Brazil-Venezuela border, we sampled two new frog species that could not be assigned to any known genus. Here, we perform phylogenetic analyses of mitogenomic and nuclear loci to infer the evolutionary relationships of the new taxa and support their description. We find that both species represent single lineages deeply nested within Brachycephaloidea, a major Neotropical clade of direct-developing frogs. Both species diverged >45 Ma from their closest relatives: the first is sister to all other Brachycephaloidea except for Ceuthomantis, another Pantepui endemic, and the second is sister to Brachycephalidae, endemic to the Brazilian Atlantic Forest. In addition to these considerable phylogenetic and biogeographic divergences, external morphology and osteological features support the proposition of two new family and genus-level taxa to accommodate these new branches of the amphibian tree of life. These findings add to other recently described ancient vertebrate lineages from the Neblina massif, providing a bewildering reminder that our perception of the Pantepui's biodiversity remains vastly incomplete. It also provides insights into how these mountains acted as "museums" during the diversification of Brachycephaloidea and of Neotropical biotas more broadly, in line with the influential "Plateau theory". Finally, these discoveries point at the yet unknown branches of the tree of life that may go extinct, due to global climate change and zoonotic diseases, before we even learn about their existence, amphibians living at higher elevations being particularly at risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effect of two finishing techniques, glazing or polishing, in comparison with the as-cut condition, on the biaxial-flexural-strength (BFS) of a zirconia-reinforced lithium silicate ceramic (ZLS). Cylinders were milled from CAD/CAM blocks and sliced to obtain disc-shaped specimens (ISO6872:2015). Polished and glazed specimens were processed following the manufacturer's instructions. Thirty-three specimens were obtained for each condition and microstructural and BFS/fractographic characterizations were performed. BFS and roughness data were analyzed using Weibull statistics and ANOVA one-way with Tukey post-hoc test, respectively. While a rougher surface was observed for as-cut specimens, smoother surfaces were observed for polished and glazed ZLS at microscopical evaluation and confirmed through surface-roughness evaluation. X-ray spectra depicted a glass phase for all groups and characteristic metasilicate, lithium disilicate, and lithium phosphate peaks for the as-cut and polished specimens. Glazed specimens showed higher characteristic strength than polished and as-cut specimens, which did not differ significantly. While higher Weibull-modulus was observed for the polished than for the as-cut specimens, no statistically significant differences were noted between glazed and polished, and between glazed and as-cut specimens. ZLS presents higher strength when glazed, and polishing increases the structural reliability of the material relative to the as-cut condition. Both finishing techniques reduced surface roughness similarly., (© 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Background: Paracoccidioidomycosis is a neglected tropical disease caused by fungi of the genus Paracoccidioides. A wide range of symptoms is related to the disease; however, lungs and skin are the sites predominantly affected. The disease is mostly seen in people living in rural areas in Latin America., Case Report: We present a pediatric case of severe disseminated paracoccidioidomycosis that slowly responded to the antifungal treatment. Within three months, symptoms evolved into hepatosplenomegaly, necrotic cervical and abdominal lymph nodes, and splenic abscess. Clinical response to amphotericin B deoxycholate and itraconazole was slow, resulting in pleural and peritoneal cavity effusions, heart failure and shock. Amphotericin B deoxycholate was replaced by the liposomal formulation, with no response. Subsequently, prednisone was added to the treatment, which led to improvement in the clinical response. Serological Paracoccidioides antibody titers were atypical, with very low titers in the critical phase and significant increase during the convalescence phase. The infection was finally cleared up with amphotericin B deoxycholate, liposomal amphotericin B and the use of corticosteroids. Paracoccidioidomycosis serology was non-reactive two years post-discharge., Conclusions: Due to the intense inflammatory response triggered by Paracoccidioides cells, giving low-dose prednisone for a short period of time modulated the inflammatory response and supported antifungal treatment., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Gallic acid (GA) is a powerful antioxidant extracted from plants of the Brazilian Cerrado. Oxidative stress plays an important role in the occurrence of radiation-induced osteonecrosis in patients treated for head and neck cancer. There is a need to develop research aimed at developing complementary therapies to prevent or reverse bone damage. The aim of the present study was to investigate the effect of GA in preosteoblasts exposed to therapeutic ionizing radiation. MC3T3-E1 preosteoblast cells were treated with 10 µM GA and exposed to 6 Gy ionizing radiation. We performed in vitro assays of cell proliferation, oxidative stress analysis by detection of reactive oxygen species, and alkaline phosphatase assay. GA at lower concentrations was able to significantly increase proliferation and inhibit radiation-induced generation of reactive oxygen species in osteoblast precursor cells, despite ionizing radiation-induced injury. Furthermore, GA significantly increased alkaline phosphatase at a dose of 6 Gy. The findings suggested that GA could attenuate ionizing radiation-induced injuries in osteoblast precursor cells. Moreover, in vivo studies are needed to better investigate the role of GA in osteonecrosis, especially in cancer patients undergoing radiotherapy or taking antiresorptive drugs., (© The Author(s).)

Margarine exhibits significant variations in composition, allowing it to cater to diverse consumer segments. This study aimed to characterize the physical and sensory attributes of margarine samples available in the Brazilian market. Twelve commercial samples from six different brands, encompassing 30% to 80% of lipid contents, were subjected to instrumental texture analysis and affective assessment. A total of 112 consumers participated in acceptance tests and Check-All-That-Apply (CATA) evaluations, while another group of 62 subjects performed Projective Mapping. Samples with lipid percentages exceeding 70% achieved the highest average acceptance scores for taste and overall impression. The brand with the lowest lipid content (30%) exhibited a stronger association with negative attributes, including rancid flavor and aroma, bitterness, and metallic flavor, resulting in lower average scores for aroma, flavor, texture, and overall impression. However, these scores were not statistically different from samples with 50% and 60% lipid content. Reducing lipid levels in fat-based products such as margarine poses a challenge to food manufacturers, as consumers generally perceive higher lipid percentages as indicative of superior flavor quality.

The peroneus longus tendon seems a viable graft option for knee ligament reconstructions, with adequate biomechanical properties and low morbidity after harvesting. The objective of this article is to describe a combined anterior cruciate ligament and anterolateral ligament reconstruction technique using a single peroneus longus tendon graft harvested from the infra malleolar region to ensure sufficient length., (© 2023 The Authors.)

Bioactive glasses (BGs) can potentially be applied in biomedicine, mainly for bone repair and replacement, given their unique ability to connect to natural bone tissue and stimulate bone regeneration. Since their discovery, several glass compositions have been developed to improve the properties and clinical abilities of traditional bioactive glass. Different inorganic ions, such as strontium (Sr 2+ ), have been incorporated in BG due to their ability to perform therapeutic functions. Sr 2+ has been gaining prominence due to its ability to stimulate osteogenesis, providing an appropriate environment to improve bone regeneration, in addition to its antibacterial potential. However, as there are still points in the literature that are not well consolidated, such as the influence of ionic concentrations and the BG production technique, this review aims to collect information on the state of the art of the biological behavior of BGs containing Sr 2+ . It also aims to gather data on different types of BGs doped with different concentrations of Sr 2+ , and to highlight the manufacturing techniques used in order to analyze the influence of the incorporation of this ion for bone regeneration purposes.

Staphylococcus aureus is one of the most relevant mastitis pathogens in dairy cattle, and the acquisition of antimicrobial resistance genes presents a significant health issue in both veterinary and human fields. Among the different strategies to tackle S. aureus infection in livestock, bacteriophages have been thoroughly investigated in the last decades; however, few specimens of the so-called jumbo phages capable of infecting S. aureus have been described. Herein, we report the biological, genomic, and structural proteomic features of the jumbo phage vB&#95;SauM-UFV&#95;DC4 (DC4). DC4 exhibited a remarkable killing activity against S. aureus isolated from the veterinary environment and stability at alkaline conditions (pH 4 to 12). The complete genome of DC4 is 263,185 bp (GC content: 25%), encodes 263 predicted CDSs (80% without an assigned function), 1 tRNA (Phe-tRNA), multisubunit RNA polymerase, and an RNA-dependent DNA polymerase. Moreover, comparative analysis revealed that DC4 can be considered a new viral species belonging to a new genus DC4 and showed a similar set of lytic proteins and depolymerase activity with closely related jumbo phages. The characterization of a new S. aureus jumbo phage increases our understanding of the diversity of this group and provides insights into the biotechnological potential of these viruses. KEY POINTS: • vB&#95;SauM-UFV&#95;DC4 is a new viral species belonging to a new genus within the class Caudoviricetes. • vB&#95;SauM-UFV&#95;DC4 carries a set of RNA polymerase subunits and an RNA-directed DNA polymerase. • vB&#95;SauM-UFV&#95;DC4 and closely related jumbo phages showed a similar set of lytic proteins., (© 2023. The Author(s).)

Objective: The aim of the study was to evaluate the effect of the addition of 10% nanohydroxyapatite in an experimental resin infiltrant on color stability and mineral loss., Material and Methods: Bovine enamel blocks were randomized into five groups (n = 27/group): SE (sound enamel); ICL (initial caries lesion); I (Icon®); E (experimental infiltrant); EH (experimental infiltrant containing 10% nanohydroxyapatite). Color evaluation (n = 15) was performed and CIEL*a*b* values were obtained at points T 0 (baseline), T 1 (14 days immersed on coffee solution), and T 2 (28 days immersed) and data were calculated ∆E 00 , ∆W ID , ∆L*, ∆a*, and ∆b*. Cross-sectional microhardness (n = 12) was performed and lesion area (∆S) was calculated. Images were obtained with polarized light optical microscopy at 40 × magnification (n = 5)., Results: In color stability results, there was significant difference between time (14 and 28 days); ICL demonstrated significant difference among treated groups in all measures (∆L*, ∆a*, ∆b*, ∆E 00 , ∆W ID ) regardless of time; I and E demonstrated similar behavior on those measures and EH differed from I in ∆L*. For ∆S, ICL group showed a significant difference compared to I and EH groups, but did not differ from E., Conclusion: The nanohydroxyapatite incorporation suggested an effective mineral recovery on initial caries lesion in depth; however, it showed high color variation, such as Icon. In terms of ∆S, I and EH had lower mineral loss, suggesting a reinforcement on initial caries lesion., Clinical Relevance: Commercial and experimental infiltrants containing nanohydroxyapatite present low color stability and might reinforce mineral in initial caries lesion., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the gastrointestinal tract. The etiology is not fully understood, but environmental, microbial, and immunologic factors, as well as a genetic predisposition, play a role. UC is characterized by episodes of abdominal pain, diarrhea, bloody stools, weight loss, severe colonic inflammation, and ulceration. Despite the increase in the frequency of UC and the deterioration of the quality of life, there are still patients who do not respond well to available treatment options. Against this background, natural products such as polysaccharides are becoming increasingly important as they protect the intestinal mucosa, promote wound healing, relieve inflammation and pain, and restore intestinal motility. In this study, we investigated the effect of a polysaccharide isolated from the biomass of Campomanesia adamantium and Campomanesia pubescens (here referred to as CPW) in an experimental model of acute and chronic ulcerative colitis induced by dextran sulfate sodium (DSS). CPW reversed weight loss, increased disease activity index (DAI), bloody diarrhea, and colon shortening. In addition, CPW reduced visceral mechanical hypersensitivity, controlled oxidative stress and inflammation, and protected the mucosal barrier. CPW is not absorbed in the intestine, does not inhibit cytochrome P450 proteins, and does not exhibit AMES toxicity. These results suggest that CPW attenuates DSS-induced acute and chronic colitis in mice and may be a potential alternative treatment for UC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

COVID-19 vaccination during pregnancy is safe and effective in reducing the risk of complications. However, the uptake is still below targets worldwide. This study aimed to explore the factors associated with COVID-19 vaccination uptake among pregnant women since data on this topic is scarce in low-to-middle-income countries. A retrospective cohort study included linked data on COVID-19 vaccination and pregnant women who delivered a singleton live birth from August 1, 2021, to July 31, 2022, in Rio de Janeiro City, Brazil. Multiple logistic regression was performed to identify factors associated with vaccination during pregnancy, applying a hierarchical model and describing odds ratio with 95% confidence intervals. Of 65,304 pregnant women included in the study, 53.0% (95% CI, 52-53%) received at least one dose of COVID-19 vaccine during pregnancy. Higher uptake was observed among women aged older than 34 (aOR 1.21, 95%CI 1.15-1.28), black (aOR 1.10, 1.04-1.16), or parda/brown skin colour (aOR 1.05, 1.01-1.09), with less than eight years of education (aOR 1.09, 1.02-1.17), living without a partner (aOR 2.24, 2.16-2.34), more than six antenatal care appointments (aOR 1.92, 1.75-2.09), and having a previous child loss (OR 1.06, 1.02-1.11). These results highlight the need for targeted educational campaigns, trustful communication, and accessibility strategies for specific populations to improve vaccination uptake during pregnancy., (© 2023. Springer Nature Limited.)

The study investigates the effect of organizational citizenship behavior (OCB) on well-being at work. The study further examines the moderating role of people and task-focused leadership styles between OCB on well-being at work. Individual-directed organizational citizenship behaviors (OCBI) and organizational-directed organizational citizenship behaviors (OCBO) will also be analyzed. A quantitative study was conducted and convenient sampling was adopted in selecting respondent workers ( n = 200) in different Portuguese organizations. The results show that OCBs positively and significantly influence well-being at work. The strength of individual-directed organizational citizenship behaviors (OCBI) on well-being at work is stronger than that of organization-directed organizational citizenship behaviors (OCBO). Contrary to expectations, the relationship between leadership styles and well-being was not statistically significant, offering possibilities for discussion regarding the central importance usually attributed to leadership in the organizational context. However, leadership styles have a moderating effect between OCB and well-being at work, except when the employee adopts OCBO and the leadership style is people-oriented. The present study is innovative because it positions OCB as an antecedent in the relationship with well-being at work and investigates the moderating role of leadership styles in the relationship between organizational citizenship behavior and well-being., Competing Interests: The authors declare no conflicts of interest.

Aim: COVID-19 is an inflammatory disease and its prognosis is associated with cardiovascular risk, which can be associated with changes in lipoprotein metabolism. The single nucleotide polymorphism (SNP) rs187238 of Interleukin (IL)-18 is extensively reported in association with worsening inflammatory and cardiovascular disease (CVD). This study evaluated the association of IL-18 levels and its SNP rs187238 with lipoprotein profile changes in COVID-19 outpatients., Methods: Observational, analytical, cross-sectional study that evaluated 250 patients with respiratory syndrome, 36% (n = 90) with COVID-19. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), apolipoproteins A-I and B (Apo A-I and Apo B) and IL-18 levels were determined. Polymorphism genotyping was done by real-time polymerase chain reaction (qPCR). The significance level was p < 0.05., Results: Patients with COVID-19 showed a reduction in TC and HDL-c, without difference in IL-18. HDL-c and LDL-c had a high frequency outside the reference values. There was a negative correlation of IL-18 with HDL-c and a positive correlation with Apo B/Apo A-I ratio. The frequencies of the C (wild) and G (polymorphic) alleles between patients with and without COVID-19 followed the Hardy-Weinberg equilibrium. However, COVID-19 was associated with reduced HDL-c and Apo A-I values in patients with the CC genotype., Conclusion: IL-18 levels and its SNP rs187238 were associated with decreased HDL-c and Apo A-I in COVID-19 outpatients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive form of cancer unresponsive to androgen deprivation therapy (ADT) that spreads quickly to other organs. Despite reduced androgen levels after ADT, mCRPC development and lethality continues to be conducted by the androgen receptor (AR) axis. The maintenance of AR signaling in mCRPC is a result of AR alterations, androgen intratumoral production, and the action of regulatory elements, such as noncoding RNAs (ncRNAs). ncRNAs are key elements in cancer signaling, acting in tumor growth, metabolic reprogramming, and tumor progression. In prostate cancer (PCa), the ncRNAs have been reported to be associated with AR expression, PCa proliferation, and castration resistance. In this study, we aimed to reconstruct the lncRNA-centered regulatory network of mCRPC and identify the lncRNAs which act as master regulators (MRs)., Methods: We used publicly available RNA-sequencing to infer the regulatory network of lncRNAs in mCRPC. Five gene signatures were employed to conduct the master regulator analysis. Inferred MRs were then subjected to functional enrichment and symbolic regression modeling. The latter approach was applied to identify the lncRNAs with greater predictive capacity and potential as a biomarker in mCRPC., Results: We identified 31 lncRNAs involved in cellular proliferation, tumor metabolism, and invasion-metastasis cascade. SNHG18 and HELLPAR were the highlights of our results. SNHG18 was downregulated in mCRPC and enriched to metastasis signatures. It accurately distinguished both mCRPC and primary CRPC from normal tissue and was associated with epithelial-mesenchymal transition (EMT) and cell-matrix adhesion pathways. HELLPAR consistently distinguished mCRPC from primary CRPC and normal tissue using only its expression., Conclusion: Our results contribute to understanding the regulatory behavior of lncRNAs in mCRPC and indicate SNHG18 and HELLPAR as master regulators and potential new diagnostic targets in this tumor., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The virulence of Cryptococcus spp. is modulated in the natural environment through interaction with abiotic and biotic factors, and this can occasionally have implications for the progression of cryptococcosis in mammals. Hence, we evaluated whether the prior interaction of highly virulent Cryptococcus gattii strain R265 with Acanthamoeba castellanii influenced the progression of cryptococcosis. The influence of the capsule on endocytosis was evaluated using amoeba and yeast morphometrics. Mice were intratracheally infected with yeast re-isolated from the amoeba (Interaction), yeast without prior contact with the amoeba (Non-Interaction), or sterile phosphate-buffered saline (SHAM). Morbidity signs and symptoms were monitored during the survival curve, while cytokine and fungal burden measurements and histopathological analysis were performed on the 10th day post infection. Morbidity and mortality parameters in experimental cryptococcosis were influenced by the prior interaction of yeast with amoeba, which led to phenotypic changes in the cryptococcal cells, polysaccharide secretion, and their tolerance to oxidative stress. Our results suggest that a prior yeast-amoeba interaction modulates yeast virulence, which is associated with a greater tolerance to oxidative stress related to the exo-polysaccharide content and influences the progression of cryptococcal infection., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Proteus mirabilis is an opportunistic pathogen and is responsible for more than 40% of all cases of catheter-associated urinary tract infections (CAUTIs). Healthcare-associated infections have been aggravated by the constant emergence of antibiotic-resistant bacterial strains. Because of this, the use of phages to combat bacterial infections gained renewed interest. In this study, we describe the biological and genomic features of two P. mirabilis phages, named BigMira and MidiMira. These phages belong to the Acadevirus genus (family Autographiviridae ). BigMira and MidiMira are highly similar, differing only in four missense mutations in their phage tail fiber. These mutations are sufficient to impact the phages' depolymerase activity. Subsequently, the comparative genomic analysis of ten clinical P. mirabilis strains revealed differences in their antibiotic resistance profiles and lipopolysaccharide locus, with the latter potentially explaining the host range data of the phages. The massive presence of antimicrobial resistance genes, especially in the phages' isolation strain P. mirabilis MCS, highlights the challenges in treating infections caused by multidrug-resistant bacteria. The findings reinforce BigMira and MidiMira phages as candidates for phage therapy purposes.

Gastric cancer (GC) is a highly prevalent and deadly malignant neoplasm worldwide. Currently, long non-coding RNAs (lncRNAs) have recently been identified as crucial regulators implicated in GC development and progression. Dysregulated expression of lncRNAs is commonly associated with enhanced tumor migration, invasiveness, and therapy resistance, highlighting their potential as promising targets for clinical applications. This review offers a comprehensive historical overview of lncRNAs in GC, describes the molecular mechanisms, and discusses the prospects and challenges of establishing lncRNAs as precision biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Silva, Teixeira, Mourão, Ferraz, Moreira, Assumpção and Calcagno.)

Paracoccidioidomycosis (PCM) is a infection caused by the thermodimorphic fungus Paracoccidioides spp. (P. lutzii and, mainly, P. brasiliensis ). This infection predominantly affects rural male workers aged between 30 and 50 years old who deal with soil on daily activities. Clinically, the disease is classified as acute/subacute phase, which evolves rapidly, secondary to dissemination of the fungus through to the phagocytic-mononuclear system, leading to fever, weight loss, and anorexia, associated with hepatosplenomegaly and lymphadenopathy, which can be complicated with suppuration and fistulization; and chronic phase, which corresponds to 74% to 95% of symptomatic cases, with a common pulmonary involvement. Central nervous system involvement is almost always a characteristic of the chronic form. Inhalation is the most common route of primary infection, usually affecting the lungs, forming the primary complex. From the primary complex, hematogenic dissemination can occur to any organ, including the brain and spinal cord. Although PCM of the central nervous system diagnosis is usually based on histopathological analysis and the imaging features are not specific for PCM, computed tomography and magnetic resonance imaging can demonstrate evidences of granuloma, abscess, meningitis, or a combination of these lesions, contributing to a preoperative diagnosis, especially when considered in conjunction with epidemiology. In this article, we review the pathophysiology, clinical manifestations and imaging aspects of neuro-PCM., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Costa et al.)

Older runners (OR) are increasing their participation in races. Aging may impact the adopted running pattern. Hence, the analysis of stiffness and the inter-joint lower limb coordination in the sagittal plane could contribute to investigating this impact. This study aimed to compare the vertical stiffness (K vert ) and the inter-joint lower limb coordination in the sagittal plane between younger runners (YR) and OR. This cross-sectional study recruited 15 YR males and 15 OR males. The pelvis and lower limb motions were assessed while running on a treadmill at self-selected (range OR: 1.94-3.75 m.s -1 , YR: 2.08-4.17 m.s -1 ) and fixed speeds (3.33 m.s -1 ). Hip-ankle, knee-ankle, and hip-knee coupling angle (CA) and its variability (CAV) were extracted using the vector coding method. Mann-Whitney U tests compared K vert between groups at each running speed. Watson's U 2 tests compared the mean CA between groups in three intervals of the contact phase at each running speed. Statistical Parametric Mapping independent t-test compared the CAV curve between groups at each running speed. OR showed greater K vert than YR at both speeds. Hip-ankle CA pattern differed between groups during the early stance at both speed conditions. OR showed in-phase, distal dominancy in hip-ankle CA, whereas YR showed anti-phase, proximal dominancy. Knee-ankle CA was distinct only at self-selected speed, in which OR showed in-phase, proximal dominancy, while YR exhibited anti-phase, proximal dominancy. CAV did not differ between groups. The findings showed that OR adopted a stiffer pattern characterized by distinct inter-joint lower limb CA, at early stance, during self-selected and fixed speeds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study is to compare feeding practices of low birthweight (LBW) infants, according to type of care received during and after hospital discharge: Kangaroo Care (KC) and Conventional Care (CC)., Methods: Prospective cohort study was conducted at a university hospital (Brazil) between 2019 and 2021. The sample consisted of 65 LBW infants (weight ≤ 1800 g)-46 in KC and 19 in CC. KC includes breastfeeding (BF) guidance and support to parents at hospital and after discharge. Data collection was performed at hospital discharge, and at the 4th and 6th month of corrected gestational age (CGA). Consumption of 27 foods was analyzed in the last 2 periods of the follow-up and expressed in relative frequency. Three indicators were analyzed: exclusive breastfeeding (EBF), mixed BF, and introduction of liquid and solid foods., Results: Groups had similar health characteristics, except for the weight at hospital discharge and the Score for Neonatal Acute Physiology - Perinatal (SNAPPE II) score that were lower in KC group. We found higher frequency of EBF among KC at hospital discharge (CC = 5.3% vs KC = 47.8%; P = 0.001). The higher frequency of mixed BF was observed in KC at 4 months of CGA (CC = 5.6% vs KC = 35.0%; P = 0.023), and at 6 months of CGA (CC = 0.0% vs KC = 24.4%; P = 0.048). Consumption of solid foods (4th month of CGA = 25.9%, 6th month of CGA = 91.2%) and liquids (4th month of CGA = 77.6%, 6th month of CGA = 89.5%) were similar between groups., Conclusions: In KC, SNAPPE II scores were lower and frequency of EBF was higher at hospital discharge and frequency of mixed BF was higher over 6 months. Early supply of infant formula, liquid and solid foods were similar in both groups., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

The objective of this article is to develop and validate a KAP (knowledge, attitude, and practice) instrument for caregivers of children up to 36 months of age monitored by the Family Health Strategy. This methodological study was conducted in three stages: an integrative review, preparation of the initial version, and content validation by 29 judges. The instrument was validated for content and appearance. The Content Validity Index (CVI) and the FINN and Gwe-AC1 coefficients were calculated to assess inter-judge agreement. The overall CVI values of the 39-item instrument were: Clarity (0.91) and Relevance (0.95). The final version was obtained through 19 knowledge, 10 attitude, and 10 practice questions on caries, diet, oral hygiene, fluoride, breastfeeding, artificial feeding, milk teeth, and the need to take the baby to the dentist. The instrument produced can be used because it has the potential for use depending on the more global assessment of its psychometric properties.

Hydroxyapatite (HA) from bovine bones has been used as a biomaterial in dentistry due to its biocompatibility and bioactivity. However, dense HA bioceramics still present inadequate properties for applications that require high mechanical performance, such as infrastructure. Microstructural reinforcements and control of ceramic processing steps are methods to improve these shortcomings. The present study assessed the effects of polyvinyl butyral (PVB) addition in combination with two sintering methodologies (2-step and conventional), on the mechanical properties of polycrystalline bovine HA bioceramics. The samples were divided into four groups (with 15 samples per group): conventional sintering with binder (HBC) and without binder (HWC) and 2-step sintering with (HB2) and without binder (HW2). HA was extracted from bovine bones, turned into nanoparticles in a ball mill, and subjected to uniaxial and isostatic pressing into discs, according to ISO 6872 standards. All groups were characterized by x-ray diffractometry (XRD), differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and relative density. Besides, mechanical analyses (biaxial flexural strength (BFS) and modulus of elasticity) were also performed. The characterization results demonstrated that adding agglutinants or the sintering method did not affect HA's chemical and structural characteristics. Even so, the HWC group showed the highest mechanical values for BFS and modulus of elasticity being 109.0 (98.0; 117.0) MPa and 105.17 ± 14.65 GPa, respectively. The HA ceramics submitted to conventional sintering and without the addition of binders achieved better mechanical properties than the other groups. The impacts of each variable were discussed and correlated to the final microstructures and mechanical properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Medullary thyroid carcinoma (MTC) arises from parafollicular cells in the thyroid gland, and although rare, it represents an aggressive type of thyroid cancer. MTC is recognized for its low mutational burden, with point mutations in RET or RAS genes being the most common oncogenic events. MTC can be resistant to cytotoxic chemotherapy, and multitarget kinase inhibitors (MKIs) have been considered a treatment option. They act by inhibiting the activities of specific tyrosine kinase receptors involved in tumor growth and angiogenesis. Several tyrosine kinase inhibitors are approved in the treatment of advanced MTC, including vandetanib and cabozantinib. However, due to the significant number of adverse events, debatable efficiency and resistance, there is a need for novel RET-specific TKIs. Newer RET-specific TKIs are expected to overcome previous limitations and improve patient outcomes. Herein, we aim to review MTC signaling pathways, the most recent options for treatment and the applications for personalized medicine.

The first objective of this study was to develop a thermal stress index for sheep based on environmental and animal data collected in a climate chamber under various environmental conditions. The second objective was to compare published indices of thermal comfort and the proposed index, testing them with the data from this study, with the objective of pointing out the most adequate index to be used by breeders when choosing management procedures. A total of 3024 data were obtained for the physiological variables of the sheep exposed to the eight thermal conditions in the climatic chamber and in ambient condition, kept three days in each thermal condition. A principal component analysis summarized the measurements of physiological variables into only one variable (y1). Using SigmaPlot software, multiple regression of y1 with the environmental variables and their combinations produced a number of indices. The equation chosen was the heat stress index for sheep, TSI = 24.153 - (0.0523*A T ) + (0.746*B GT ) + (4.104*Vp), with R 2  = 0.668. The correlations presented high values, where these correlation values were assumed to indicate the efficiency of each index as indicators of the animals' response to the environment. Thus, it was assumed that the TSI presents a high efficiency., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The interplay of positive and negative interactions between drug-sensitive and resistant cells influences the effectiveness of treatment in heterogeneous cancer cell populations. Here, we study interactions between estrogen receptor-positive breast cancer cell lineages that are sensitive and resistant to ribociclib-induced cyclin-dependent kinase 4 and 6 (CDK4/6) inhibition. In mono- and coculture, we find that sensitive cells grow and compete more effectively in the absence of treatment. During treatment with ribociclib, sensitive cells survive and proliferate better when grown together with resistant cells than when grown in monoculture, termed facilitation in ecology. Molecular, protein, and genomic analyses show that resistant cells increase metabolism and production of estradiol, a highly active estrogen metabolite, and increase estrogen signaling in sensitive cells to promote facilitation in coculture. Adding estradiol in monoculture provides sensitive cells with increased resistance to therapy and cancels facilitation in coculture. Under partial inhibition of estrogen signaling through low-dose endocrine therapy, estradiol supplied by resistant cells facilitates sensitive cell growth. However, a more complete blockade of estrogen signaling, through higher-dose endocrine therapy, diminished the facilitative growth of sensitive cells. Mathematical modeling quantifies the strength of competition and facilitation during CDK4/6 inhibition and predicts that blocking facilitation has the potential to control both resistant and sensitive cancer cell populations and inhibit the emergence of a refractory population during cell cycle therapy., (© 2023. The Author(s).)

The acute toxicity and hypokinetic activity induced by menthofuran on the gastrointestinal tract of rodents were investigated in the present study. An absence of acute toxicity was observed. Menthofuran delayed gastric emptying at oral doses of 25, 50, and 100 mg/kg in the experimental model of phenol red, as well as it reduced the intestinal transit at oral doses of 50 and 100 mg/kg. Interestingly, a scopolamine-similar hypokinetic effect was observed for menthofuran. In the experimental model of castor oil-induced intestinal hypermotility, menthofuran (50 and 100 mg/kg) reduced the number of loose stools as observed for the normal group. Additionally, menthofuran induced a marked concentration-dependent relaxation in rat ileum segments precontracted with KCl (EC 50  = 0.059 ± 0.008  μ g/mL) or carbachol (EC 50  = 0.068 ± 0.007  μ g/mL). These results suggest the possible decrease of calcium influx underlying the effects of menthofuran on the gastrointestinal tract, which opens the door for further study regarding this potential application for the treatment of gastrointestinal disorders, noting possible limitations of its use due to adverse effects in children., Competing Interests: The authors declare that there are no conflicts of interests regarding the publication of this paper., (Copyright © 2023 Railson de Sousa Santos et al.)

Atrx loss was recently ascertained as insufficient to drive pancreatic neuroendocrine tumour (PanNET) formation in mice islets. We have identified a preponderant role of Atrx in the endocrine dysfunction in a Rip-Cre;Atrx KO genetically engineered mouse model (GEMM). To validate the impact of a different Cre -driver line, we used similar methodologies and characterised the Pdx1-Cre;Atrx KO ( P.Atrx KO ) GEMM to search for PanNET formation and endocrine fitness disruption for a period of up to 24 months. Male and female mice presented different phenotypes. Compared to P.Atrx WT , P.Atrx HOM males were heavier during the entire study period, hyperglycaemic between 3 and 12 mo., and glucose intolerant only from 6 mo.; in contrast, P.Atrx HOM females started exhibiting increased weight gains later (after 6 mo.), but diabetes or glucose intolerance was detected by 3 mo. Overall, all studied mice were overweight or obese from early ages, which challenged the histopathological evaluation of the pancreas and liver, especially after 12 mo. Noteworthily, losing Atrx predisposed mice to an increase in intrapancreatic fatty infiltration (FI), peripancreatic fat deposition, and macrovesicular steatosis. As expected, no animal developed PanNETs. An obese diabetic GEMM of disrupted Atrx is presented as potentially useful for metabolic studies and as a putative candidate for inserting additional tumourigenic genetic events.

Excess adipose tissue is associated with basic tastes perception change, which can negatively affect food choices. However, the effect of overweight and obesity on sensory perception is not clearly explained in the literature yielding heterogeneous results. The present investigation aimed to investigate the temporal dominance of sweet taste according to body mass index (BMI) classification in adults during the ingestion of five passion fruit nectar samples prepared with different sucrose concentrations. The temporal dominance of sensations methodology was applied, which allowed the representation of the stimuli assessed in dominance curves, considering a significant difference in Fisher's exact test (p ≤ 0.05). The attributes evaluated were sweet taste, bitter taste, acidic taste, astringency, passion fruit flavor, metallic taste, or none of the previous options. The sensory analysis was performed with the participation of ninety adult consumers, divided into three groups: EG = eutrophic, WG = overweight, and OG = obesity group, according to the BMI classification. Between the groups a difference in the perception of the attribute "sweet taste" was observed: The EG demonstrated perception of the stimulus in food samples at lower sucrose concentrations, whereas WG and OG showed a higher rate of sweet taste dominance in the food samples with higher concentration of sucrose. Overweight and obese individuals have a lower sensory perception of sweet taste and require a greater amount of sucrose to producing sensory dominance of the attribute "sweet taste" when compared to eutrophic individuals. PRACTICAL APPLICATION: Overweight and obese individuals may experience taste perception in foods in a different way. This study investigated the dominance of sweet taste perception in a fruit beverage by adults with adequate weight and overweight. The results of the tests support the hypothesis that obese and nonobese individuals differ in the sweet taste perception, which can help to understand which factors are involved in sensory perception and food consumption, in addition to providing subsidies for the nonalcoholic beverage industry to elaborate products with new alternatives for concentration and/or replacement of sucrose., (© 2023 Institute of Food Technologists.)

Morphological studies on the oropharyngeal cavity of turtles are an interesting tool in understanding evolutionary processes associated with feeding habits. There is paucity of morphological information on the oropharyngeal cavity of the Trachemys adiutrix turtle. Thus, the aim of this study was to describe the tongue and palate morphology of T. adiutrix to establish a standard model for the species, providing information that may improve knowledge on the species feeding habits. Gross dissection, light microscopy and scanning electron microscopy assessments of 11 specimens were carried out. The tongue of T. adiutrix is triangular with a slightly rounded apex and broad base and lingual papillae widely distributed throughout the entire dorsal surface. The palate is composed of bony structures, displaying a triangular apex with one pair of choanae and palatine raphe that begin in the middle region, dividing the two openings. The body was elongated and smooth. The root was wrinkled and opened into the oesophagus. The tongue was lined by non-keratinized stratified squamous epithelium, rich in mucous cells and a large number of different-shaped papillae and taste buds. The palate was mainly lined by a pseudostratified cylindrical ciliated epithelium rich in mucous cells. In conclusion, the tongue and palate characteristics of T. adiutrix include evidence that these animals are semiaquatic, displaying morphological characteristics associated with aquatic and terrestrial trophic ecology, similar to that observed in other semiaquatic and terrestrial chelonian species., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), naturally abundant in fish oil (FO), are known for their anti-inflammatory and potential antioxidant properties. The aim in this article is to evaluate the effect of the infusion of a parenteral FO-containing lipid emulsion on markers of liver lipid peroxidation and oxidative stress in rats undergoing central venous catheterization (CVC)., Methods: After 5-day acclimatization, adult Lewis rats (n = 42) receiving a 20-g/day AIN-93M oral diet were randomly subdivided into four groups: (1) basal control (BC) (n = 6), without CVC or LE infusion; (2) SHAM (n = 12), with CVC but without LE infusion; (3) soybean oil (SO)/medium-chain triglyceride (MCT) (n = 12), with CVC and receiving LE without FO (4.3 g/kg fat); and (4) SO/MCT/FO (n = 12), with CVC and receiving LE containing 10% FO (4.3 g/kg fat). Animals from the BC group were euthanized immediately after acclimatization. The remaining groups of animals were euthanized after 48 or 72 h of surgical follow-up to assess profiles of liver and plasma fatty acids by gas chromatography, liver gene transcription factor Nrf2, F2-isoprostane lipid peroxidation biomarker, and the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) by enzyme-linked immunosorbent assay. R program (version 3.2.2) was utilized for data analysis., Results: Compared with the other groups, liver EPA and DHA levels were higher in the SO/MCT/FO group, which also showed the highest liver Nrf2, GPx, SOD, and CAT levels and lower liver F2-isoprostane (P < 0.05)., Conclusion: Experimental delivery of FO via EPA and DHA sources in a parenteral LE was associated with a liver antioxidant effect., (© 2023 American Society for Parenteral and Enteral Nutrition.)