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Kidney transplantation (KT) is the preferred treatment for end-stage renal diseases. Human leukocyte antigen G (HLA-G) and programmed death-ligand 1 (PD-L1) have notable clinical and therapeutic significance in transplantation because of their roles in promoting tolerance. This study aimed to assess HLA-G and PD-L1 levels at various stages following KT. A cohort of 12 patients was monitored from the pretransplant phase to 12 months post-surgery. Blood samples were taken at specific intervals: before kidney transplantation (T0), and then on the 7th (T7), 30th (T30), 90th (T90), 180th (T180), and 365th days post transplantation. Renal biopsies were performed in patients with graft dysfunction. Plasma levels of soluble HLA-G (sHLA-G) and PD-L1 were quantified using enzyme-linked immunosorbent assays. Additionally, immunohistochemistry was used to detect the presence of both molecules in biopsy samples. Multivariate analysis indicated that episodes of rejection were correlated with decreased expression of sHLA-G (P < .001) and PD-L1 (P < .001). Over the course of the study, the sHLA-G levels also declined (P < .001). Patients who had been transfused had lower PD-L1 levels (P = .03). Furthermore, kidney recipients from related live donors had increased HLA-G expression (P < .001). Our findings suggest that diminished HLA-G and PD-L1 levels correlate with an increased risk of graft rejection. Notably, HLA-G expression significantly decrease after the third-month posttransplantation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The muscle phenotype of fish is regulated by numerous factors that, although widely explored, still need to be fully understood. In this context, several studies aimed to unravel how internal and external stimuli affect the muscle growth of these vertebrates. The pacu (Piaractus mesopotamicus) is a species of indeterminate muscular growth that quickly reaches high body weight. For this reason, it adds great importance to the productive sector, along with other round fish. In this context, we aimed to compile studies on fish biology and skeletal muscle growth, focusing on studies by our research group that used pacu as an experimental model along with other species. Based on these studies, new muscle phenotype regulators were identified and explored in vivo, in vitro, and in silico studies, which strongly contribute to advances in understanding muscle growth mechanisms with future applications in the productive sector., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Genomic selection (GS) experiments in forest trees have largely reported estimates of predictive abilities from cross-validation among individuals in the same breeding generation. In such conditions, no effects of recombination, selection, drift, and environmental changes are accounted for. Here, we assessed the effectively realized predictive ability (RPA) for volume growth at harvest age by GS across generations in an operational reciprocal recurrent selection (RRS) program of hybrid Eucalyptus ., Methods: Genomic best linear unbiased prediction with additive (GBLUP&#95;G), additive plus dominance (GBLUP&#95;G+D), and additive single-step (HBLUP) models were trained with different combinations of growth data of hybrids and pure species individuals ( N = 17,462) of the G 1 generation, 1,944 of which were genotyped with ~16,000 SNPs from SNP arrays. The hybrid G 2 progeny trial (HPT267) was the GS target, with 1,400 selection candidates, 197 of which were genotyped still at the seedling stage, and genomically predicted for their breeding and genotypic values at the operational harvest age (6 years). Seedlings were then grown to harvest and measured, and their pedigree-based breeding and genotypic values were compared to their originally predicted genomic counterparts., Results: Genomic RPAs ≥0.80 were obtained as the genetic relatedness between G 1 and G 2 increased, especially when the direct parents of selection candidates were used in training. GBLUP&#95;G+D reached RPAs ≥0.70 only when hybrid or pure species data of G 1 were included in training. HBLUP was only marginally better than GBLUP. Correlations ≥0.80 were obtained between pedigree and genomic individual ranks. Rank coincidence of the top 2.5% selections was the highest for GBLUP&#95;G (45% to 60%) compared to GBLUP&#95;G+D. To advance the pure species RRS populations, GS models were best when trained on pure species than hybrid data, and HBLUP yielded ~20% higher predictive abilities than GBLUP, but was not better than ABLUP for ungenotyped trees., Discussion: We demonstrate that genomic data effectively enable accurate ranking of eucalypt hybrid seedlings for their yet-to-be observed volume growth at harvest age. Our results support a two-stage GS approach involving family selection by average genomic breeding value, followed by within-top-families individual GS, significantly increasing selection intensity, optimizing genotyping costs, and accelerating RRS breeding., 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 Simiqueli, Resende, Takahashi, de Sousa and Grattapaglia.)

Rhipicephalus microplus (Ixodidae, canestrini, 1888) is an invasive ectoparasite of cattle which causes high economic losses in emerging countries such as Brazil. Phytochemical compounds have been tested as an alternative to synthetic acaricides due to potentially lower mammalian toxicity. This study evaluated the acaricidal activity against R. microplus of the 2-methoxy-clovan-9-ol rich fraction obtained from Eugenia copacabanensis Kiaersk.leaves, a little known Myrtaceae species from the Brazilian Atlantic Forest. This fraction was obtained by maceration with methanol, partition with n-hexane and purification by normal-phase column chromatography. GC-MS, 1 H and 13 C NMR and IR analysis contributed to the identification of a major compound as the sesquiterpene 2-methoxy-clovan-9-ol, reported for the first time for the Myrtaceae family. The fraction was tested against R. microplus unfed larvae and engorged females and a 93% larval mortality was observed at the concentration of 50 mg mL -1 . Lower concentrations of the solution tested demonstrated a significant difference in egg mass weight, hatching and control percentage. Experiments with 50.0 mg mL -1 showed significative results, with lower concentration and maximum efficacy for both assays. The IC 50 values for unfed larvae and engorged females were 21.76 and 11.13 mg mL -1 , respectively. These results were similar to those obtained in other studies with isolated botanical compounds and essential oils. The lower IC 50 for engorged females than for unfed R. microplus larvae had also been described for other plant materials, including plants from the same Myrtaceae family. The present result suggested different mechanisms of action of the compound on the reproductive biology of engorged females, improving its effect against egg viability. These results are important for tick control, suggesting that 2-methoxy-clovan-9-ol could be a potential natural acaricidal product against both R. microplus unfed larvae and engorged females., Competing Interests: Declaration of competing interest All authors declare that there is no financial interest to report this manuscript or conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To evaluate the phytochemical composition and effects of the baru peel and pulp (BPP) and the partially defatted baru nut (DBN) on the growth and metabolism of probiotics., Methods and Results: The proximate composition, including dietary fibers, and polyphenol profile were determined in the BPP and DBN, and the prebiotic activity was evaluated on the growth and metabolism of the Lactobacillus and Bifidobacterium strains. BPP and DBN have a high content of insoluble fibers and phenolic compounds, mainly flavonoids and phenolic acids. Moreover, DBN stands out for its high content of proteins and lipids. BPP and DBN stimulated the growth and metabolism of Bifidobacterium animalis subsp. lactis BB-12, Lactobacillus acidophilus LA-05, and Lacticaseibacillus casei L-26., Conclusions: Baru by-products have potential prebiotic properties to be confirmed in preclinical and clinical studies, and to be explored as an ingredient in new health-promoting foods., Impact Statement: Agro-industrial baru wastes, the peel plus pulp and the partially defatted nut, are sources of health-promoting compounds and stimulate the growth and metabolism of probiotics, indicating prebiotic properties., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: Pathogen infections have been associated with autoimmunity, which in turn has been implicated in the pathogenesis of vitiligo. However, the association between pathogen infections and vitiligo remains elusive., Aims: This study aimed to assess the proportion of individuals who tested positive for specific IgG antibodies against selected pathogens in patients with vitiligo and control subjects., Materials and Methods: Plasma from 51 patients with vitiligo and 51 age- and gender-matched controls were tested for anti- Toxoplasma gondii (T. gondii) IgG, anti-herpes simplex types 1 and 2 (HSV-1/2) IgG, anti-cytomegalovirus (CMV) IgG and anti-hepatitis C virus IgG., Results: Among all participants ( n = 102), 63%, 84% and 87% tested positive for anti- T. gondii , anti-HSV-1/2 and anti-CMV IgG antibodies, respectively. Anti-hepatitis C virus IgG was negative in all samples tested. Positive anti- T. gondii IgG was detected in plasma samples of 39 (78%) patients with vitiligo and 25 (49%) controls (odds ratio [OR] 3.68, 95% confidence interval [CI] 1.55-8.76, P = 0.0036). Anti-HSV-1/2 IgG was detected in samples of 47 (92%) patients with vitiligo and 38 (76%) controls (OR 3.71, 95% CI 1.11-12.44, P = 0.031). Differences in frequencies of positive results for anti- T. gondii IgG and anti-HSV-1/2 IgG were only significant in samples from female patients with vitiligo when compared with controls ( P = 0.036 and 0.024, respectively). Anti-CMV IgG was detected in samples from 46 patients with vitiligo (90%) and 41 (84%) controls ( P = 0.384)., Conclusions: T. gondii IgG and HSV-1/2 IgG were significantly more frequent in patients with vitiligo, especially in women, when compared with age- and gender-matched controls. Since T. gondii and HSV-1/2 infections can trigger autoimmune events, past exposure to these pathogens may be a risk factor for the development of vitiligo., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Dermatology.)

Introduction: Cytokine levels are related to the aethiopathogenia of acute apical abscesses (AAA); however, the specific cytokine profiles in these cases are unclear. This study aimed to investigate the changes in systemic cytokine levels in patients with AAA and trismus onset, postantibiotic treatment, and postroot canal disinfection., Methods: In total, 46 AAA patients with trismus and 32 control subjects were included. After seven days of antibiotic therapy, root canal disinfection was performed in the AAA patients. The serum levels of cytokines were evaluated at basal, seven, and 14 days after endodontic treatment. Quantification of cytokines from T helper (Th) 1, Th2, Th17, and regulatory T cells profiles was determined using the BioPlex MagPix system, and the obtained data were analyzed using SPSS statistical software (P < .05)., Results: AAA patients showed higher tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6, and IL-10 levels than control subjects, at basal measurement (P < .05); there were similar levels of interferon gamma, IL-1β, IL-4, and IL-17 between groups (P > .05). IL-6 and IL-10 levels decreased after antibiotic treatment (P < .05), which was also associated with clinical improvement in patients with AAA and trismus. Patients with AAA had a positive correlation with higher serum levels of IL-6 and IL-10. In addition, TNF-α levels decreased only after antibiotic and endodontic treatment., Conclusions: In conclusion, patients with AAA had increased systemic serum levels of TNF-α, IL-6, and IL-10. Moreover, increased levels of IL-6 and IL-10 are associated with acute inflammatory symptoms. However, IL-6 and IL-10 levels decreased after antibiotic treatment, while TNF-α levels decreased after antibiotic and endodontic treatment., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To conduct a systematic review to summarize the results of studies on this subject and to identify whether single nucleotide polymorphisms (SNPs) are good prognostic markers for body weight trajectory after bariatric surgery., Recent Findings: A considerable number of events can influence the body weight trajectory after bariatric surgery, and in the post-genomic era, genetic factors have been explored. This study is registered with PROSPERO (CRD42021240903). SNPs positively associated with poor weight loss after bariatric surgery were rs17702901, rs9939609, rs1360780, rs1126535, rs1137101, rs17782313, rs490683, and rs659366. Alternatively, SNPs rs2229616, rs5282087, rs490683, rs9819506, rs4771122, rs9939609, rs4846567, rs9930506, rs3813929, rs738409, rs696217, rs660339, rs659366, rs6265, rs1801260, and rs2419621 predicted a higher weight loss after bariatric surgery. Six studies performed with a genetic risk score (GRS) model presented significant associations between GRS and outcomes following bariatric surgery. This systematic review shows that, different SNPs and genetic models could be good predictors for body weight trajectory after bariatric surgery. Based on the results of the selected studies for this Systematic Review is possible to select SNPs and metabolic pathways of interest for the GRS construction to predict the outcome of bariatric surgery to be applied in future studies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Like other phthalates, diethyl phthalate (DEP) is considered as a contaminant of emerging concern (CEC) due to its ease in migrating from a package to water and food, and hence contaminate consumers, being metabolized and excreted in the urine. Its presence has a negative impact on aquatic ecosystems, especially with respect to disruption of the endocrine system and to reproductive disorders in humans. It mainly enters water bodies via sewage effluents from effluent treatment plants, due to its incomplete or inefficient removal. The objective of this work was to evaluate the toxicity of DEP at different trophic levels and to analyze data on the incidence and concentration of DEP according to its solubility. The concentrations ranged from 12.5 mg L -1 to 500 mg L -1 considering the response for toxicity at each trophic level and to determine the lethal concentration in 50% of the following organisms (LC 50 ) (in mg L -1 ): Lactuca sativa seeds, Artemia salina Leach nauplii and Zebrafish embryo larval stage ( Danio rerio ), being 41,057.58 after 120 h; 401.77 after 48 h; and 470 after 96 h of exposure, respectively. As expected, higher organisms were more affected even at low concentrations, which shows the anthropological contribution of CECs to water bodies., 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., (© 2023 Published by Elsevier Ltd.)

Background: Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd., Materials and Methods: We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software., Results: We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%)., Conclusions: In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data Sharing Data sharing is not applicable to this article as no new data were created or analyzed in this study., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The female prostate is associated with the urogenital system and presents homology in morphological terms with the male prostate. Due to its responsiveness to endogenous hormones, this gland is under a constant risk of developing prostatic pathologies and neoplasia when exposed to certain exogenous compounds. Bisphenol A (BPA) is an endocrine disruptor found in different plastic and resin products. Studies have emphasized the effects of perinatal exposure to this compound on different hormone-responsive organs. However, there have been few studies highlighting the influence on female prostate morphology of perinatal exposure to BPA. The objective of this study was to describe the histopathological alterations caused by perinatal exposure to BPA (50 µg/kg) and 17-β estradiol (E2) (35 µg/kg) in the prostate of adult female gerbils. The results showed that E2 and BPA induced proliferative lesions in the female prostate and acted along similar pathways by modulating steroid receptors in the epithelium. BPA was also found to be a pro-inflammatory and pro-angiogenic agent. The impacts of both agents were marked in the prostatic stroma. An increase in the thickness of the smooth muscle layer and a decrease in AR expression were observed, but no alterations in the expression of ERα and ERβ, leading to estrogenic sensitivity of the prostate. However, a peculiar response of the female prostate was to diminish the collagen frequency under BPA exposure correlated to smooth muscle layer. These data therefore indicate the development of features related to estrogenic and non-estrogenic tissue repercussions by BPA perinatally exposure in gerbil female prostate., 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 orchid genus Brachystele Schltr. (Orchidoideae, Cranichideae, Spiranthinae) comprises 20 species distributed from Mexico to Argentina, with 10 species found in Brazil. Anatomical studies of Orchidoideae Lindl. have been scarce, and the anatomy and histochemistry of Brachystele are still largely unknown. In this study, we conducted a characterization of the vegetative organs of B. guayanensis (Lindl.) Schltr. using standard anatomical and histochemical microtechniques. In this study, we provide the first information about the anatomy and histochemistry of Brachystele . The studied species was observed to display anatomical characters commonly found in the vegetative organs of representatives of the Cranichideae tribe (e.g., uniseriate epidermis; homogeneous mesophyll with 6-11 layers; rhizomes with rings of fibers; vascular bundles in the form of "^" or "v"; fleshy roots with uniseriate velamen, simple trichomes, and spiranthosomes). Others can be interpreted as adaptive strategies conditioned by the environment and their terrestrial life form (e.g., cuticle thickness; amphistomatic leaves; roots with reduced velamen compared to the cortex (18-20 layers); and raphides). In this study, cataphylls, and the presence of spiranthosomes in leaves, including stomatal guard cells, as well as alkaloids in these structures, are anatomically described for the first time in Orchidaceae. The presence of hyphae and pelotons in the stem of B. guayanensis is described for the first time in Cranichideae. Histochemical tests confirmed the presence of lignin, proteins, and alkaloids, the lipidic nature of the cuticle, starch grains stored in spiranthosomes, and the composition of the raphides. Alkaloids were observed in abundance, particularly in the roots, suggesting a potential role in defense against pathogens and herbivores, as well as potential medicinal activities, as seen in phylogenetically related groups to Brachystele .

miRNAs, a class of small non-coding RNAs, play a role in post-transcriptional gene expression. Therefore, this study aimed to conduct a systematic review of miRNAs associated with GDM to build a panel of miRNAs. A bibliographic search was carried out in the PubMed/Medline, Virtual Health Library (VHL), Web of Science, and EMBASE databases, selecting observational studies in English without time restriction. The protocol was registered on the PROSPERO platform (number CRD42021291791). Fifty-five studies were included in this systematic review, and 82 altered miRNAs in GDM were identified. In addition, four miRNAs were most frequently dysregulated in GDM (mir-16-5p, mir-20a-5p, mir-222-3p, and mir-330-3p). The dysregulation of these miRNAs is associated with the mechanisms of cell cycle homeostasis, growth, and proliferation of pancreatic β cells, glucose uptake and metabolism, insulin secretion, and resistance. On the other hand, identifying miRNAs associated with GDM and elucidating its main mechanisms can assist in the characterization and definition of potential biomarkers for the diagnosis and treatment of GDM.

The increase in the preference for vegan and vegetarian diets is directly related to changing eating habits and the need for plant-based alternatives to animal-based products, which are better for health, due to the high content of essential amino acids and lipid profile rich in polyunsaturated fatty acids, and have lower environmental impacts. In this scenario, there is a growing demand for plant-based foods, making it necessary to find new plant-based ingredients for application in foods and beverages. Flaxseed, chia seed, and Barbados gooseberry contain mucilage, a component with potential application in plant-based products. These hydrocolloids can be used as gelling agents, texture modifiers, stabilizers, and emulsifiers in solid and semi-solid foods. This review presents the extraction, characterization, and application of flaxseed, chia seed, and Barbados gooseberry mucilage for use in plant-based foods. It was found that mucilage composition varies due to the extraction method used, extraction conditions, and geographic location of the seed or leaf. However, applications in plant-based foods are currently limited, mainly focused on applying chia mucilage in bakery products and packaging. Research on applying flaxseed and Barbados gooseberry mucilage to plant-based products is limited, though it has been shown to have potential applications in packaging. Mucilage may also increase the nutritional profile of the product and provide better technological, functional, and sensory characteristics. Therefore, because of mucilage's excellent functional and technological properties, it is a promising candidate to act as an ingredient in plant-based food products., 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.)

Background: The unilateral Seated Shot-Put Test (USSPT) is an easy to apply, inexpensive tool that can be used to assess shoulder performance unilaterally. Two different positions of execution have been described in previous studies, however, differences regarding reference values and psychometric properties were not assessed., Purpose: To investigate the performance, test-retest reliability and measurement error of the USSPT according to different positions of execution (floor versus chair) in overhead athletes. The hypothesis was that both positions would present similar values, good to excellent test-retest reliability and clinically acceptable measures., Study Design: Test-retest reliability., Methods: Forty-four overhead athletes performed the USSPT on the floor (USSPT-F) and on a chair (USSPT-C). Normative values were established according to gender, age, and dominance. Test-retest reliability was determined using Intraclass Correlation Coefficient and measurement error through Standard Error of Measurement, Smallest Detectable Change, as well as Bland and Altman plots., Results: Reference values for both positions were provided. Women performed better on the USSPT-C than USSPT-F. Excellent test-retest reliability 0.97 (0.89 - 0.99) for dominant side and 0.95 (0.80 - 0.98) for non-dominant side was found for the USSPT-F. Moderate to excellent reliability 0.91 (0.67 - 0.98) for dominant side and 0.74 (0.01 - 0.93) for non-dominant side was found for the USSPT-C. Presence of systematic error (14.76 cm) was found only for USSPT-C dominant (p=0.011)., Conclusion: Differences were found only for women with better performance on the USSPT-C. The USSPT-F presented higher reliability values. Both tests presented clinically acceptable measures. Presence of systematic error was found only in the USSPT-C., Level of Evidence: 3., Competing Interests: The authors report no conflicts of interest.

Rotavirus (RV) and Norovirus (NV) are the main viral etiologic agents of acute gastroenteritis (AG), a serious pediatric condition associated with significant death rates and long-term complications. Anti-RV vaccination has been proved efficient in the reduction of severe AG worldwide, however, the available vaccines are all attenuated and have suboptimal efficiencies in developing countries, where AG leads to substantial disease burden. On the other hand, no NV vaccine has been licensed so far. Therefore, we used immunoinformatics tools to develop a multi-epitope vaccine (ChRNV22) to prevent severe AG by RV and NV. Epitopes were predicted against 17 prevalent genotypes of four structural proteins (NV's VP1, RV's VP4, VP6 and VP7), and then assembled in a chimeric protein, with two small adjuvant sequences (tetanus toxin P2 epitope and a conserved sequence of RV's enterotoxin, NSP4). Simulations of the immune response and interactions with immune receptors indicated the immunogenic properties of ChRNV22, including a Th1-biased response. In silico search for putative host-homologous, allergenic and toxic regions also indicated the vaccine safety. In summary, we developed a multi-epitope vaccine against different NV and RV genotypes that seems promising for the prevention of severe AG, which will be further assessed by in vivo tests., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Helioswilton Sales-Campos reports financial support was provided by Fundação de Amparo à Pesquisa (FUNAPE). Amanda de Oliveira Matos reports financial support was provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Pedro Henrique dos Santos Dantas reports financial support was provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-β1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-β1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile., (© 2023 International Federation for Cell Biology.)

The ovaries regulate fertility and hormonal control in females, and aging is a crucial factor in this process, when ovarian function is drastically impacted. Exogenous endocrine disruptors may accelerate this process, acting as the main agents in decreased female fertility and hormonal imbalance, since they impact different features related to reproduction. In the present study, we demonstrate the implications of exposure of adult mothers to the endocrine disruptor bisphenol A (BPA) during pregnancy and lactation on their ovarian function during the transition to later in life (aging). The follicle population of BPA exposed ovaries showed impairment in the development of follicles to the mature stages, with growing follicles being halted in the early stages. Atretic and early-atretic follicles were also enhanced. Expression of estrogen and androgen receptors in the follicle population demonstrated impairment in signaling function: ERβ was highly expressed in follicles from BPA exposed females, which also showed a higher incidence of early atresia of developed follicles. ERβ1 wild-type isoform was also enhanced in BPA-exposed ovaries, compared to its variant isoforms. In addition, steroidogenesis was targeted by BPA exposure: aromatase and 17-β-HSD were reduced, whereas 5-α reductase was enhanced. This modulation was reflected in serum levels of estradiol and testosterone, which decreased in BPA-exposed females. Imbalances in steroidogenesis impair the development of follicles and play an important role in follicular atresia. Our study demonstrated that BPA exposure in two windows of susceptibility - gestation and lactation - had implications during aging, enhancing perimenopausal and infertile features., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Salivary gland tumors (SGT) are a diverse group of uncommon neoplasms that are rare in pediatric patients. This study aimed to characterize the clinicopathological profile of pediatric patients affected by SGT from a large case series derived from an international group of academic centers., Study Design: A retrospective analysis of pediatric patients with SGT (0-19 years old) diagnosed between 2000 and 2021 from Brazil, South Africa, and the United Kingdom was performed. SPSS Statistics for Windows was used for a quantitative analysis of the data, with a descriptive analysis of the clinicopathological characteristics and the association between clinical variables and diagnoses., Results: A total of 203 cases of epithelial SGT were included. Females were slightly more commonly (56.5%), with a mean age of 14.1 years. The palate was the most common site (43.5%), followed by the parotid gland (29%), lip (10%), and submandibular gland (7.5%). The predominant clinical presentation was a flesh-colored, smooth, and painless nodule. Pleomorphic adenoma (PA) was the most frequently diagnosed SGT (58.6%), followed by mucoepidermoid carcinoma (MEC) (26.6%). Surgery (90.8%) was the favored treatment option., Conclusions: Benign SGT in pediatric patients are more commonly benign than malignant tumors. Clinicians should keep PA and MEC in mind when assessing nodular lesions of possible salivary gland origin in pediatric patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interest or any commercial associations., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) is an incurable primary brain tumor with a poor prognosis. Resection, radiation therapy, and temozolomide (TMZ) are insufficient to increase survival, making the treatment limited. Thus, the search for more effective and specific treatments is essential, making plants a promising source for elucidating new anti-glioblastoma compounds. Accordingly, this study investigated the effects of four fractions of hexane and ethyl acetate extract of Annona coriacea Mart., enriched with acetogenins, against GBM cell lines. All four fractions were selectively cytotoxic to GBM cells when compared to TMZ. Moreover, A. coriacea fractions delayed cell migration; reduced cytoplasmic projections, the metalloproteinase 2 (MMP-2) activity; and induced morphological changes characteristic of necroptosis, possibly correlated with the increase in receptor-interacting protein kinase 1 and 3 (RIP-1 and RIP-3), apoptosis-inducing factor (AIF), and the non-activation of cleaved caspase 8. The present findings reinforce that fractions of A. coriacea Mart. should be considered for more studies focusing treatment of GBM.

Background: As of September 2022, nearly 1.3 billion doses of COVID-19 vaccine products have been administered in Latin America and the Caribbean, where 27% of global COVID-19 deaths have occurred. This study aimed to estimate the effectiveness of COVID-19 vaccines against lab-confirmed COVID-19 related hospitalizations and deaths among adults in Argentina, Brazil, Chile, and Colombia., Methods: Using a test-negative case control design, we evaluated the effectiveness of a primary vaccination series considering six COVID-19 vaccine products (Sputnik V, mRNA-1273, CoronaVac, ChAdOx1, BNT162b2, Ad26.COV2.S) against lab-confirmed COVID-19 hospitalizations and deaths among 83,708 hospitalized adults from February-December, 2021. Data from hospitalization records, COVID surveillance, and vaccination registries were used. Vaccine effectiveness was estimated using logistic regression ((1-OR) x 100)., Findings: The average age of participants was 56.7 (SD = 17.5), and 45,894 (54.8%) were male. Adjusted VE (aVE) estimates for full vaccination against hospitalization were 82% for mRNA-1273 (95% confidence interval (CI) = -30 to 98%), 76% (71%-81%) for BNT162b2, 65% (61-68%) for ChAdOx1, 57% (10-79%) for Sputnik V, 53% (50-56%) for CoronaVac, and 46% (23-62%) for Ad26.COV2.S. Estimates, particularly for CoronaVac, varied by variant. Decreasing aVE was estimated as age increased, particularly for CoronaVac and ChAdOx1. aVE estimates against death were generally higher, with 100% (CI not estimated) for mRNA-1273, 82% (69-90%) for BNT162b2, 73% (69-77%) for ChAdOx1, 65% (60-67%) for CoronaVac, 38% (-75 to 78%) for Sputnik V, 6% (-58 to 44%) for Ad26.COV2.S., Interpretation: Primary series vaccination with available COVID-19 vaccine products was effective against COVID-19 hospitalization and mortality. Effectiveness varied by product and declined with increasing age., Funding: This study was funded by the Pan-American Health Organization (PAHO, World Health Organization (WHO)). PAHO convened and led the study implementation., Competing Interests: CMT received research suppport fees to support this work. CJ and RK were hired consultant to support study design, implementation, and analysis. CD has received payment or honoraria from Merck, Sanofi, Janssen, Pfizer., (© 2023 Published by Elsevier Ltd.)

Study Design: Retrospective review of multicentric data., Objectives: To estimate the time from initial visit to surgery in adolescent idiopathic scoliosis (AIS) patients and the main reasons for the time to surgery in a multicenter study., Methods: This retrospective study evaluated 509 patients with AIS from 16 hospitals across six Latin American countries. From each hospital's deformity registry, the following patient data were extracted: demographics, main curve Cobb angle, Lenke Classification at the initial visit and time of surgery, time from indication-for-surgery to surgery, curve progression, Risser skeletal-maturity score and causes for surgical cancelation or delay. Surgeons were asked if they needed to change the original surgical plan due to curve progression. Data also were collected on each hospital's waiting list numbers and mean delay to AIS surgery., Results: 66.8% of the patients waited over six months and 33.9% over a year. Waiting time was not impacted by the patient's age when surgery first became indicated ( p  = 0.22) but waiting time did differ between countries ( p  < 0.001) and hospitals ( p  < 0.001). Longer time to surgery was significantly associated with increasing magnitude of the Cobb angle through the second year of waiting ( p  < 0.001). Reported causes for delay were hospital-related (48.4%), economic (47.3%), and logistic (4.2%). Oddly, waiting time for surgery did not correlate with the hospital's reported waiting-list lengths ( p  = 0.57)., Conclusion: Prolonged waits for AIS surgery are common in Latin America, with rare exceptions. At most centers, patients wait over six months, most commonly for economic and hospital-related reasons. Whether this directly impacts surgical outcomes in Latin America still must be studied., 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., (© 2023 The Authors.)

Background: Snakebites represent a significant health problem in tropical countries, with an annual incidence of 2.7 million cases worldwide. The incidence of secondary infections after snake bites is also high and is usually caused by bacteria from the oral cavity of snakes. Morganella morganii has been identified as an important cause of infections and has been guiding antibiotic therapy in several regions of Brazil and the world., Methodology/principal Findings: We performed a retrospective cross-sectional evaluation of snakebites in hospitalized patients between January 2018 and November 2019 and selected those with secondary infection in their medical records. During the period, 326 cases of snakebites were treated, and 155 (47.5%) of them eventually had secondary infections. However, only seven patients underwent culture of soft tissue fragments, in which three cases were negative culture results, while Aeromonas hydrophila was identified in four cases. Of these, 75% were resistant to ampicillin/sulbactam, 50% had intermediate sensitivity to imipenem, and 25% had intermediate sensitivity to piperacillin/tazobactam. Trimethoprim/sulfamethoxazole (TMP-SMX) was not tested on any strain. Of the 155 cases that progressed to secondary infections, 48.4% (75) were empirically treated with amoxicillin/clavulanate, 41.9% (65) with TMP-SMX, and 32 (22%) of these 144 cases required a change to a second regimen, and 10 of these 32 patients required a third therapeutic regimen., Conclusion: Wild animals act as reservoirs of resistant bacteria because their oral cavity favors biofilm formation, which explains the finding of A. hydrophila with a reduced sensitivity profile in this study. This fact is essential for the appropriate choice of empirical antibiotic therapy., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Soares Coriolano Coutinho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diagnosis of Trypanosoma cruzi ( T. cruzi ) infection in the chronic phase of Chagas disease (CD) is performed by serologic testing. Conventional tests are currently used with very good results but require time, laboratory infrastructure, and expertise. Rapid diagnostic tests (RDTs) are an alternative as the results are immediate and do not require specialized knowledge, making them suitable for epidemiologic studies and promising as a screening tool. Nevertheless, few studies conducted comparative evaluations of RDTs to validate the results and assess their performance. In this study, we analyzed four trades of rapid tests (OnSite Chagas Ab Combo Rapid Test-United States, SD Bioline Chagas AB-United States, WL Check Chagas-Argentina, and TR Chagas Bio-Manguinhos-Brazil) using a panel of 190 samples, including sera from 111 infected individuals, most of whom had low T. cruzi antibody levels. An additional 59 samples from uninfected individuals and 20 sera from individuals with other diseases, mainly visceral leishmaniasis, were included. All tests were performed by three independent laboratories in a blinded manner. Results showed differences in sensitivity from 92.8 to 100%, specificity from 78.5 to 92.4%, and accuracy from 90.5 to 95.3% among the four assays. The results presented here show that all four RDTs have high overall diagnostic ability. However, WL Check Chagas and TR Chagas Bio-Manguinhos were considered most suitable for use in screening studies due to their high sensitivity combined with good performance. Although these two RDTs have high sensitivity, a positive result should be confirmed with other tests to confirm or rule out reactivity/positivity, especially considering possible cross-reactivity with individuals with leishmaniasis or toxoplasmosis., Competing Interests: AS and FS are employees of FIOCRUZ and one of the RDTs was produced by a subsidiary of FIOCRUZ (Bio-Manguinhos), but they are not involved in the production of this kit (TR Chagas Bio-Manguinhos). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Iturra, Leony, Medeiros, Souza Filho, Siriano, Tavares, Luquetti, Belo, Sousa and Santos.)

A multi-disciplinary team surveyed ranchers at the Kalunga Historical and Cultural Heritage Site, in the Cerrado region of west central Brazil, to determine impacts promoted by toxic plants on cattle. The expedition to the Kalunga region was carried out by Brazilian and American researchers. Previously selected cattle ranch properties from "Vão das Almas", "Engenho II" and "Vão do Moleque" were visited. Twenty-four interviews were carried out with cattle ranchers and a questionnaire was applied to obtain information about outbreaks of native plant poisoning and their effects on livestock, and the use of local plants in phytotherapy. We classified problematic plants into three distinct categories. First, the toxic plants most cited by residents causing cattle losses were the flowers of Caryocar brasiliense Cambess ("pequi"), the fruits of Terminalia corrugata (Ducke) Gere & Boatwr. (Buchenavia tomentosa Eichler - "mirindiba" or "pau-pilão"), Eugenia dysenterica (Mart.) DC ("cagaita"), and Palicourea marcgravii A. St. Hil ("erva-café" or "cafezinho"). Secondly, other plants considered toxic, but causing less severe losses were Emmotum nitens (Benth.) Miers ("casco d'anta"), Indigofera lespedezioides (Kunth) ("timbozinho"), Ricinus communis L. ("mamona"), Pteridium esculentum (G. Forst.) Cockayne ("samambaia"), Stryphnodendron adstringens (Mart.) Coville ("barbatimão"), and Actinocladum verticillatum (Nees) McClure ex Soderstr. ("cambaúba"). The most important finding was the identification of the C. brasiliense flower as potentially toxic to cattle, which must be subject for future research. Further, we confirmed the toxicity and importance of P. marcgravii, E. dysenterica, and Terminalia corrugata. The survey highlighted phytotherapy plants used by the community, and greatly increased awareness by local livestock producers of poisonous plants for management purposes. We conclude that ethnobotanical knowledge, especially from the traditional community, is essential to understand livestock losses to toxic plants, and should be valued not only for reducing livestock losses, but also for cultural importance to the Kalunga communities in the Cerrado., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Franklin Riet-Correa, co-author of our manuscript is a member of the Editorial Council of Toxicon. The project was approved by the Research Ethics Committee (CEP) of the Federal University of Goiás (UFG), under registration number 3,438,019 and the permission to access genetic heritage (CTA) was registered in the Heritage SisGen under access code A8E13C7., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) assesses posterior-cortical and frontal-subcortical cognitive functioning and distinguishes mild cognitive impairment in Parkinson's disease (PD-MCI); however, it was not evaluated in Brazil., Objectives: To investigate PD-CRS's reliability, validity, normative data, and accuracy for PD-MCI screening in Brazil., Methods: The effects of age, education, and sex on PD-CRS scores were explored. The instrument was tested in 714 individuals (53% female, 21-94 years), with a broad range of education and no neurodegenerative disorder. Trail Making, Consonant Trigrams, Five-Point, and semantic fluency tests were administered for comparison. A second study enrolled patients with PD and intact cognition (n = 44, 59.75 ± 10.79 years) and with PD-MCI (n = 25, 65.76 ± 10.33 years) to investigate criterion validity. PD-CRS subtests were compared with the Cambridge Automated Neuropsychological Battery memory and executive tasks., Results: PD-CRS was unidimensional and reliable (McDonald's ω = 0.83). Using robust multiple regressions, age, and education predicted the total and derived scores in the normative sample. At the 85-point cutoff, PD-MCI was detected with 68% sensitivity and 86% specificity (area under the curve = 0.870). PD-CRS scores strongly correlated with executive and verbal/visual memory tests in both normative and clinical samples., Conclusions: This study investigated the applicability of PD-CRS in the Brazilian context. The scale seems helpful in screening for PD-MCI, with adequate internal consistency and construct validity. The PD-CRS variance is influenced by age and educational level, a critical issue for cognitive testing in countries with educational and cultural heterogeneity., (© 2023 International Parkinson and Movement Disorder Society.)

This work aimed to evaluate poly(pseudo)rotaxanes (PPRs) potential for vaginal antifungal delivery. For this, PPRs containing terbinafine (TB) 2 % were obtained using two small surfactants, Kolliphor® RH40 and Gelucire® 48/16, and different α-cyclodextrin (α-CD) concentrations (5 and 10 %). PPRs were characterized by their physicochemical characteristics, irritation, and mucoadhesion capabilities. Formulations' performance was assessed in a vertical penetration model, which uses ex vivo entire porcine vagina. Conventional penetration experiments with excised vaginal tissue were performed as a control. Results showed all formulations were non-irritant according to the HET-CAM test. Furthermore, PPRs with 10 % αCD showed superior mucoadhesion (p < 0.05). Conventional horizontal penetration studies could not differentiate formulations (p > 0.05). However, PPRs with 10 % αCD presented a better performance in vertical ex vivo studies, achieving higher drug penetration into the vaginal mucosa (p < 0.05), which is probably related to the formulation's prolonged residence time. In addition, the antifungal activity of the formulations was maintained against Candida albicans and C. glabrata cultures. More importantly, the formulation's viscosity and drug delivery control had no negative impact on the antifungal activity. In conclusion, the best performance in a more realistic model evidenced the remarkable potential of PPRs for vaginal drug delivery., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to evaluate modifications in proteoglycan morphology and composition in the prostatic stroma of 18-month-old gerbils after surgical castration, in association or not with an androgenic blockade., Methods: The animals (n = 5) were sorted into groups subjected or not to antiandrogen treatment (flutamide 10 mg/kg/day) administered for the total postsurgery period and euthanized at 7- or 30-day postcastration; the control group consisted of intact animals. Tissue analysis included immunohistochemical assessment (perlecan and chondroitin sulfate) and proteoglycan morphology was analyzed by transmission electron microscopy., Results: Chondroitin sulfate frequency was increased 7 days postcastration with an androgenic blockade. The presence of these carbohydrates was rare after 30 days of androgenic blockade treatment. There was a significant increase in the amount of perlecan in the prostate stroma from groups subjected to castration plus flutamide for 7 or 30 days. Ultrastructural analysis showed that the incidence of areas occupied by proteoglycans and basement membrane was altered by treatment. In addition, androgenic blockade results in changes in the amount, thickness, and morphology of these structures. At 30 days postcastration, with or without flutamide treatment, larger proteoglycans were common., Conclusions: In this study, in particular, the decrease in chondroitin sulfate after the longer period might be understood as a prostatic response to androgenic deprivation, while the high frequency and permanence of perlecan led to the assumption that its modulation could be androgen-independent. Length and form alterations in proteoglycans as well as associations among them and with the basement membrane were dynamic events in the prostate microenvironment., (© 2022 Wiley Periodicals LLC.)

Little knowledge is available in literature regarding the chemical composition and health-promoting effects of baru (Dipteryx alata Vog.) pulp, a by-product usually discarded by the agro-industry during the processing of baru fruit. This study evaluated the chemical composition of baru pulp and investigated its prebiotic activity on distinct probiotic strains and human colonic microbiota with in vitro assays. Baru pulp had high contents of insoluble dietary fibers and phenolic compounds (mainly hesperidin). Baru pulp stimulated the growth and metabolism of the probiotics Bifidobacterium animalis subsp. lactis BB-12, Lactobacillus acidophilus LA-05, and Lacticaseibacillus casei L-26. In addition, digested baru pulp induced significant benefits on the human colonic microbiota, increasing the relative abundance of Lactobacillus-Enterococcus, Bifidobacterium, and Bacteroides-Prevotella, as well as the production of lactate, acetate, propionate, and butyrate. The results show that baru pulp has potential prebiotic properties to be explored in the formulation of new health-promoting foods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to compare different materials' effects on alveolar ridge preservation of postextraction sockets in anterior maxilla., Materials and Method: In this prospective, single center, randomized, controlled clinical trial, healthy patients who needed one single anterior maxillary tooth extraction (including bicuspids) were selected. After a minimally traumatic extraction without complications, 44 patients were randomly allocated into 4 groups: 1) natural socket healing (blood clot), 2) xenograft and gingival free graft, 3) dense polytetrafluoroethylene membrane, and 4) platelet rich fibrin plugs. Alveolar ridge height and width loss were evaluated in cone beam computed tomography (CBCT) and in dental casts at 3 moments: 1) preoperative (T1), 2) 7 days postoperative (T2), and 3) 120 days postoperative (T3). Height and width alveolar ridge loss detected in CBCT and in dental casts were compared among the groups (two-way analysis of variance [ANOVA]; P < .05)., Results: Forty patients (24 women and 16 men) ranging from 25 to 70 years old (mean of 42 years old) participated in this study. Group 2 showed the least alveolar ridge height loss results in CBCT (9.8 ± 1.9% at T3) and dental cast analysis (1.0 ± 0.2 mm). Groups 2 (12.7 ± 4.7% at T3) and 3 (15.4 ± 2.7% at T3) showed the least alveolar ridge width loss measured in CBCT compared with groups 1 and 4, but the difference between groups 2 and 3 were not statistically significant (P = .968). Group 3 (0.9 ± 0.2 mm) and group 2 (1.0 ± 0.2 mm) showed the least width loss compared with groups 1 and 4 in dental cast analysis. Again, the difference between groups 3 and 2 was not statistically significant (P = 1.000)., Conclusion: In postextraction sockets of the anterior maxilla and bicuspid region, group 2 (xenogenous bone graft with free gingival graft) and group 3 (dense polytetrafluoroethylene) obtained the best results in alveolar preservation, with group 2 being more indicated when the vertical alveolar ridge preservation is mandatory., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Imidazo[1,2 -a ]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.

The deforestation of tropical forests raises environmental concerns worldwide. Removing the pristine forest impacts the soil, consequently affecting the environmental services it provides. Within this context, the main goal of this study was to determine how the conversion of the tropical rainforest to pasture affects soil fertility across an extended range of soil heterogeneity, including different soil types. We sampled 13 sites, among forests, recent pastures (≤7-year-old), and old pastures (≥10-year-old), on Acrisols, Ferralsols, Plinthosols, and Luvisols, across a ± 800 km geographical range in the Western Brazilian Amazon. Soils were classified taxonomically, and their superficial layer's chemical and physical properties (0-10 cm) were analyzed. Furthermore, we tested the sensibility of Actinobacteria and Proteobacteria to detect changes in these soil properties based on their ecological habitat. An inter-regional gradient of soil fertility was observed, and the sampling sites were clustered mostly by soil type and associated land use than by spatial distance. The Sum of bases, Ca + Mg, base saturation, Al saturation, and pH were consistently affected by land use, increasing after conversion to pasture, at different degrees and with a more pronounced effect on oxidic soils. The Sum of bases was the only property that increased significantly among the study sites (R adj = 0.860, p < 0.001), being able to detect the effect of anthropic land use on a larger coverage of soil types. Finally, the Actinobacteria:Proteobacteria ratio was also sensitive to the impact of forest-to-pasture conversion, with a higher ratio observed in pasture systems, and it was positively correlated with soil pH (rho = 0.469, p < 0.001). Our results consistently show that the forest-to-pasture conversion leads to strong alterations in the soil environment, with varying intensities depending on soil type., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Pain management is challenging in neonatal care. We aimed to compare the effects of gentle touch and sucrose on pain relief during suctioning in premature newborns (PTNB). This crossover randomized clinical trial enrolled PTNBs with low birth weight, hemodynamically stable, and requiring suctioning during hospitalization in the neonatal intensive care unit. PTNBs underwent three different suctioning procedures. The first was performed without intervention (baseline). Right after, PTNBs were randomly allocated (sucrose and gentle touch or vice versa) to the next two suctioning procedures. Two validated scales assessed pain: the Neonatal Infant Pain Scale (NIPS) and the Premature Infant Pain Profile-Revised (PIPP-R). We evaluated 50 PTNBs (mean of 28 weeks) with a mean low birth weight of 1050 g; most were under continuous positive airway pressure 37 (74%) and mechanical ventilation 41 (82%). Gentle touch was efficacious for pain relief since NIPS (p = 0.010) compared to baseline. Sucrose was also effective in reducing pain NIPS and PIPP-R (p < 0.001). Although the two interventions reduced pain, no difference was observed between gentle touch and sucrose.

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is highly virulent and causes coronavirus disease 2019 (COVID-19), resulting in high morbidity and mortality mainly associated with pulmonary complications. Because this virus is highly transmissible, it was quickly spread globally, resulting in COVID-19 being declared as a pandemic. This study aimed to analyze the prevalence of mortality and the factors related to mortality due to COVID-19 in patients with severe acute respiratory syndrome (SARS) at a university hospital in the Central—West region of Brazil. This retrospective cross-sectional study was based on an analysis of the medical records of patients with SARS aged >18 years and admitted to an intensive care unit due to COVID-19 with the requirement of invasive mechanical ventilation. Hospital death was considered as an outcome variable in this study. Moreover, demographic and lifestyle-related variables as well as the therapeutic measures used during the hospital stay were recorded and correlated with the death outcome. After excluding 188 medical records, 397 were analyzed. Most of the participants were men (59.7%), and the mortality rate in patients with SARS due to COVID-19 was 46.1%. Multiple regression analysis indicated that the independent factors associated with mortality in patients with SARS due to COVID-19 were the age of >60 years (p < 0.001) and the use of azithromycin (p = 0.012). Protective factors for mortality were considered as not having the following diseases: hyperthyroidism, asthma, hepatic inheritance, and not being a smoker. The mortality rate in patients with SARS due to COVID-19 was associated with older age and the use of azithromycin., Competing Interests: The authors declare no conflict of interest.

The use of benzodiazepines (BZDs) during pregnancy, especially alprazolam, is common and its impact on the fetal neural tissue is not known. In this sense, the present study aimed to investigate the effects of prenatal treatment with alprazolam on the cerebellum of Wistar rat pups. Thirty animals (24 females and six males, CEUA protocol 014/17) were separated into pairs for copulation. Females were divided into three groups: Control (CT), treatment 1 (T1, 1.25 mg per animal), and treatment 2, which is an overdose (T2, 30 mg per animal). Alprazolam was administered 10 days before copulation and throughout pregnancy. We evaluated the number and weight of pups and the macroscopic changes in the brain. Eight neonates (n = 8) from each group were used in the following analyses: Cellular and chromatin density, gliosis, synaptic density, inflammation, and oxidative stress. The results showed no significant differences regarding the number of pups, body weight, and macroscopic changes. The morphological study focused on the external granular layer (EGL) that is presented only in the immature cerebellum. Here, we detected more cells after alprazolam treatment; the T2 group showed large nuclei and some pyknotic nuclei; also, both treated groups presented an increase in the euchromatin density compared with the control. The molecular and biochemical analyses used the total protein extract of the entire cerebellum and showed an increased expression of Iba-1 and NF-κBp65 but without indication of inflammation or degeneration in the T1 group. Overdose of alprazolam presented an increased level of oxidative degradation of lipids. The treatment with alprazolam during pregnancy involved cellular and molecular changes in the immature cerebellum., (© 2022 International Society for Developmental Neuroscience.)

The objective of this study was to analyze the indicators of access and use of health services in people with diabetes mellitus. This study used data from the National Health Survey, conducted in Brazil in 2013. The National Health Survey was carried out with adults aged 18 years or older residing in permanent private households in Brazil. Indicators from 492 individuals with self-reported diabetes mellitus living in the Central-West region of the country were analyzed. Item response theory was used to estimate the score for access to and use of health services. Multiple linear regression was used to analyze factors associated with scores of access and use of health services by people with diabetes mellitus. The mean score of access estimated by the item response theory and use estimated was 51.4, with the lowest score of zero (lowest access and use) and the highest 100 (highest access and use). Among the indicators analyzed, 74.6% reported having received medical care in the last 12 months and 46.4% reported that the last visit occurred in primary care. Only 18.9% had their feet examined and 29.3% underwent eye examinations. Individuals of mixed-race/skin color and those residing outside capital and metropolitan regions had lower access and use scores when compared to white individuals and residents of state capitals, respectively. The study shows several gaps in the indicators of access and use of health services by people with diabetes. People of mixed race/skin color and residents outside the capitals and metropolitan regions had lower scores for access and use, suggesting the need to increase health care in these groups.

Introduction: Brazil experienced moments of collapse in its health system throughout 2021, driven by the emergence of variants of concern (VOC) combined with an inefficient initial vaccination strategy against Covid-19., Objectives: To support decision-makers in formulating COVID-19 immunization policy in the context of limited vaccine availability and evolving variants over time, we evaluate optimal strategies for Covid-19 vaccination in Brazil in 2021, when vaccination was rolled out during Gamma variant predominance., Methods: Using a discrete-time epidemic model we estimate Covid-19 deaths averted, considering the currently Covid-19 vaccine products and doses available in Brazil; vaccine coverage by target population; and vaccine effectiveness estimates. We evaluated a 5-month time horizon, from early August to the end of December 2021. Optimal vaccination strategies compared the outcomes in terms of averted deaths when varying dose intervals from 8 to 12 weeks, and choosing the minimum coverage levels per age group required prior to expanding vaccination to younger target populations. We also estimated dose availability required over time to allow the implementation of optimal strategies., Results: To maximize the number of averted deaths, vaccine coverage of at least 80 % should be reached in older age groups before starting vaccination into subsequent younger age groups. When evaluating varying dose intervals for AZD1222, reducing the dose interval from 12 to 8 weeks for the primary schedule would result in fewer COVID-19 deaths, but this can only be implemented if accompanied by an increase in vaccine supply of at least 50 % over the coming six-months in Brazil., Conclusion: Covid-19 immunization strategies should be tailored to local vaccine product availability and supply over time, circulating variants of concern, and vaccine coverage in target population groups. Modelling can provide valuable and timely evidence to support the implementation of vaccination strategies considering the local context, yet following international and regional technical evidence-based guidance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We estimated the impact of sarcopenia parameters on mortality risk and assessed its prevalence and associated factors in the older adults according to the European Working Group on Sarcopenia in Older People's 2010 (EWGSOP1) and 2018 (EWGSOP2) criteria. This was a 10-year follow-up cohort study. Low muscle mass (MM) was defined as low skeletal muscle mass index (SMI) using dual-energy X-ray absorptiometry (DXA), and low calf circumference (CC). Cox regression and the Kaplan-Meier method were performed. The prevalence of sarcopenia and associated factors were influenced by the MM measurement method and diagnostic criteria used [6.8% (SMI and EWGSOP2), 12.8% (CC and EWGSOP2; and SMI and EWGSOP1) and 17.4% (CC and EWGSOP1)]. While a low BMI was associated with sarcopenia regardless of the sarcopenia definitions, diabetes, and high TGs were associated with sarcopenia only when using the EWGSOP1 criteria. Low SMI increased mortality risk (EWGSOP1: HR = 2.01, 95% CI 1.03-3.92; EWGSOP2: HR = 2.07, 95% CI 1.05-4.06). The prevalence of sarcopenia was higher according to EWGSOP1 than EWGSOP2. A low BMI, diabetes, and high TGs were associated with sarcopenia. A low SMI doubled the risk of mortality in community-dwelling older adults., (© 2022. The Author(s).)

To identify how variables such as exercise condition, supplementation strategy, participant characteristics and demographics, and practices that control oral microbiota diversity could modify the effect of inorganic nitrate ingestion (as nitrate salt supplements, beetroot juice, and nitrate-rich vegetables) on exercise performance, we conducted a systematic review with meta-analysis. Studies were identified in PubMed, Embase, and Cochrane databases. Eligibility criteria included randomized controlled trials assessing the effect of inorganic nitrate on exercise performance in healthy adults. To assess the variation in effect size, we used meta-regression models for continuous variables and subgroup analysis for categorical variables. A total of 123 studies were included in this meta-analysis, comprising 1705 participants. Nitrate was effective for improving exercise performance (standardized mean difference [SMD]: 0.101; 95% CI: 0.051, 0.151, P <0.001, I2 = 0%), although nitrate salts supplementation was not as effective (P = 0.629) as ingestion via beetroot juice (P <0.001) or a high-nitrate diet (P = 0.005). Practices that control oral microbiota diversity influenced the nitrate effect, with practices harmful to oral bacteria decreasing the ergogenic effect of nitrate. The ingestion of nitrate was most effective for exercise lasting between 2 and 10 min (P <0.001). An inverse dose-response relation between the fraction of inspired oxygen and the effect size (coefficient: -0.045, 95% CI: -0.085, -0.005, P = 0.028) suggests that nitrate was more effective in increasingly hypoxic conditions. There was a dose-response relation for acute administration (P = 0.049). The most effective acute dose was between 5 and 14.9 mmol provided ≥150 min prior to exercise (P <0.001). An inverse dose-response for protocols ≥2 d was observed (P = 0.025), with the optimal dose between 5 and 9.9 mmol·d-1 (P <0.001). Nitrate, via beetroot juice or a high-nitrate diet, improved exercise performance, in particular, in sessions lasting between 2 and 10 min. Ingestion of 5-14.9 mmol⋅d-1 taken ≥150 min prior to exercise appears optimal for performance gains and athletes should be aware that practices controlling oral microbiota diversity may decrease the effect of nitrate., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Modified release systems depend on the selection of an appropriate agent capable of controlling the release of the drug, sustaining the therapeutic action over time, and/or releasing the drug at the level of a particular tissue or target organ. Polyethylene glycol 4000 (PEG 4000) is commonly employed in drug release formulations while polymethyl methacrylate (PMMA) is non-toxic and has a good solubility in organic solvents. This study aimed at the incorporation of ketoconazole in PMMA-g-PEG 4000 and its derivatives, thus evaluating its release profile and anti- Candida albicans and cytotoxic activities. Ketoconazole was characterized and incorporated into the copolymers. The ketoconazole incorporated in the copolymer and its derivatives showed an immediate release profile. All copolymers with ketoconazole showed activity against Candida albicans and were non-toxic to human cells in the entire concentration tested.

In Nellore beef cattle, studies addressing genetic correlations between ultrasound marbling content and other economically important traits are still incipient. Therefore, this work aimed to estimate heritability and genetic correlations between ultrasound marbling content in the longissimus dorsi muscle (MARB) and growth, reproductive, feed efficiency, and carcass-related traits in a Nellore beef cattle population from Brazil. Phenotypic records of 614,395 Nellore animals were used and included adjusted weight at 210 (W210) and 450 (W450) days of age, adult cow weight (AW), early heifer pregnancy (EH), stayability (STAY), adjusted scrotal circumference at 365 days of age (SC365), ribeye area (REA), subcutaneous backfat thickness (BF), rump fat thickness (RF), and marbling (MARB). The genetic parameters for all traits but EH and STAY were estimated considering a linear animal model, whereas for those two nonlinear traits, a threshold animal model was used. The direct and correlated response to selection for MARB versus the other traits, and the relative efficiency of selection, were also calculated. The heritability estimate for MARB was 0.31 and for the other conventional evaluated traits was low to moderate, with values ranging from 0.14 to 0.41. The genetic correlations between MARB and growth, reproductive, feed efficiency, and carcass-related trait were very low, with values close to zero, with similar correlated responses. The MARB displayed adequate genetic variability to respond to selection and crossbreeding programs looking forward to higher meat quality and differential market standards for the Nellore beef. The selection for growth, reproductive, feed efficiency, and carcass-related traits would not affect MARB in Nellore beef cattle and vice versa. Therefore, this trait should be included as a selection criterion in the Nellore breeding program., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

This article presents a systematic review of the literature concerning scientific publications on wrist wearables that can help to identify stress levels. The study is part of a research project aimed at modeling a stress surveillance system and providing coping recommendations. The investigation followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In total, 38 articles were selected for full reading, and 10 articles were selected owing to their alignment with the study proposal. The types of technologies used in the research stand out amongst our main results after analyzing the articles. It is noteworthy that stress assessments are still based on standardized questionnaires, completed by the participants. The main biomarkers collected by the devices used in the selected works included: heart rate variation, cortisol analysis, skin conductance, body temperature, and blood volume at the wrist. This study concludes that developing a wrist wearable for stress identification using physiological and chemical sensors is challenging but possible and applicable.

Background: Leprosy is caused by Mycobacterium leprae and Mycobacterium lepromatosis. Most of the affected population lives in low-income countries and may take up to 10 years to show any clinical signs, which is how physicians diagnose it. However, due to progressive cell damage, early diagnosis is very important. The best way to confirm leprosy is through bacilloscopic, which only confirms the diagnosis and has low accuracy or PCR, that requires specialized operators and is expensive. Since the bacteria are fastidious and do not grow in any culture media, therefore, diagnosing leprosy in the lab is still a challenge. In this concern, a recombinant multi-epitope protein can be a beneficial strategy in the management of the diagnosis, as diverse immunogenic epitopes are precisely selected to detect specific antibodies. Therefore, the purposes of the present study were to select immunogenic epitopes from different relevant proteins, with immunogenic properties, and then to construct a recombinant multi-epitope protein that accuses the presence of the antibodies in the early stages of the disease, making it more than appropriate to be applied as a diagnostic tool., Results: We selected 22 common proteins from both species and, using bioinformatics tools, predicted B and T cell epitopes. After multiple filtering and analyzing, we ended up with 29 epitopes {MHC-I (total 18) and MHC-II (total 11)} from 10 proteins, which were then merged into one construct. Its secondary and tertiary structures were also predicted and refined to comprise the amino acid residues in the best conformation possible. The multi-epitope protein construct was stable, non-host homologous, non-allergic, non-toxic, and elicit humoral and cellular responses. It has conformational B cell epitopes and potential to elicit IFN-γ, IL-4, and IL-10 secretion., Conclusions: This novel recombinant multi-epitope protein constructed using the common epitopes from M. leprae and M. lepromatosis has a huge immunological potential, is stable, and can be lyophilized to be used in ELISA plates or even in biosensors, which are user-friendly diagnosis tools, facilitating translation into human sample tests., (© 2022. The Author(s).)

Background: Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease that affects motor neurons and promotes progressive muscle atrophy. Vascular Endothelial Growth Factor A (VEGF-A) plays multiple roles in the central nervous systems (CNS). The purpose of this study was to evaluate the association between single nucleotide polymorphism (SNP) VEGF-A rs28357093 and ALS., Methods and Results: This case-control study was conducted in 101 ALS patients and 119 healthy individuals. Genotyping was performed by Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP). The statistical analysis was carried out using the RStudio® and SNPStats© software's. Analysis of genetic inheritance models was performed by logistic regression. Our findings demonstrated a strong association between VEGF- A rs28357093 and ALS in all genetic inheritance models, with a 9-fold increased risk for A/C - C/C genotypes (95%CI = 3.70-21.88; p < 0.001)., Conclusions: The mutant allele was more frequent in ALS patients (p < 0.001) and this finding could be associated with ALS risk. This first study from the Brazilian central population was conducted to provide new insight into the pathogenesis of ALS., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

This study outlines the profile of research productivity grant holders of the Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq (National Council for Scientific and Technological Development)] in the field of pediatric dentistry. A cross-sectional study with data collected from the Brazilian academic curriculum vitae database. The eligibility criterion was being a research productivity grant holder in pediatric dentistry from 2018 to 2020. In the period of interest, 215 individuals were research productivity grant holders in the field of dentistry, 33 of whom had graduate degrees (specialization, master's or doctorate) in pediatric dentistry. The period of scientific production and work concluded of advising of scientific initiation, master, doctoral and post-doctoral degrees was 2010 to 2020. Descriptive analysis was performed and the Kruskal-Wallis test was used to analyze associations (5% significance level) between productivity grant level (2, 1D, 1C, 1B or 1A) and year of obtainment of the doctoral degree. The VOSviewer (version 1.6.17) was used to present graphically the interinstitutional collaborations. The sample was composed of Level 2 researchers (66.7%), women (66.7%), researchers linked to institutions in the southeastern region of Brazil (81.8%), with a doctoral degree concluded prior to 2002 (51.5%), began working as a professor at a higher education institution prior to 2007 (78.8%) and the title of full professor (45.5%). No significant association was found between productivity grant level and year of conclusion of the doctoral degree (p = 0.10). Median (interquartile range) of scientific articles was 119 (37-312). The prevalence of citations (57.52%) and JCR articles (62.76%) was higher among female researchers. In conclusion, CNPq research productivity grant holders in pediatric dentistry are essentially represented by females from the southeast region of the country (UFMG and USP). However, males have proportionally greater productivity.

Background and Aim: A photosensitizer (PS) delivery and comprehensive tumor targeting platform was developed that is centered on the photosensitization of key pharmacological targets in solid tumors (cancer cells, tumor vascular endothelium, and cellular and non-cellular components of the tumor microenvironment) before photodynamic therapy (PDT). Interstitially targeted liposomes (ITLs) encapsulating zinc phthalocyanine (ZnPC) and aluminum phthalocyanine (AlPC) were formulated for passive targeting of the tumor microenvironment. In previous work it was established that the PEGylated ITLs were taken up by cultured cholangiocarcinoma cells. The aim of this study was to verify previous results in cancer cells and to determine whether the ITLs can also be used to photosensitize cells in the tumor microenvironment and vasculature. Following positive results, rudimentary in vitro and in vivo experiments were performed with ZnPC-ITLs and AlPC-ITLs as well as their water-soluble tetrasulfonated derivatives (ZnPCS4 and AlPCS4) to assemble a research dossier and bring this platform closer to clinical transition., Methods: Flow cytometry and confocal microscopy were employed to determine ITL uptake and PS distribution in cholangiocarcinoma (SK-ChA-1) cells, endothelial cells (HUVECs), fibroblasts (NIH-3T3), and macrophages (RAW 264.7). Uptake of ITLs by endothelial cells was verified under flow conditions in a flow chamber. Dark toxicity and PDT efficacy were determined by cell viability assays, while the mode of cell death and cell cycle arrest were assayed by flow cytometry. In vivo systemic toxicity was assessed in zebrafish and chicken embryos, whereas skin phototoxicity was determined in BALB/c nude mice. A PDT efficacy pilot was conducted in BALB/c nude mice bearing human triple-negative breast cancer (MDA-MB-231) xenografts., Results: The key findings were that (1) photodynamically active PSs (i.e., all except ZnPCS4) were able to effectively photosensitize cancer cells and non-cancerous cells; (2) following PDT, photodynamically active PSs were highly toxic-to-potent as per anti-cancer compound classification; (3) the photodynamically active PSs did not elicit notable systemic toxicity in zebrafish and chicken embryos; (4) ITL-delivered ZnPC and ZnPCS4 were associated with skin phototoxicity, while the aluminum-containing PSs did not exert detectable skin phototoxicity; and (5) ITL-delivered ZnPC and AlPC were equally effective in their tumor-killing capacity in human tumor breast cancer xenografts and superior to other non-phthalocyanine PSs when appraised on a per mole administered dose basis., Conclusions: AlPC(S4) are the safest and most effective PSs to integrate into the comprehensive tumor targeting and PS delivery platform. Pending further in vivo validation, these third-generation PSs may be used for multi-compartmental tumor photosensitization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Little is known about the impact of low muscle mass (MM) assessed by calf circumference (CC), arm circumference (AC), arm muscle circumference (AMC), and corrected arm muscle circumference (CAMC)-on mortality risk later in life. We aimed to investigate the impact of low MM assessed by CC, AC, AMC and, CAMC on all-cause, cardiovascular, and cancer mortality risk., Methods: Data came from 418 older adults who participated in a 10-year follow-up prospective cohort study. Low MM was defined as a CC < 33 cm for women and < 34 cm for men and by the lowest tertile of AC, AMC, and CAMC stratified by sex. The log rank test, Kaplan-Meier curves, and Cox regression were used., Results: There were 147 deaths: 49 related to CVD and 22 to cancer. A small CC (HR = 1.57, 95% CI, 1.12-2.20), AMC (HR = 1.61, 95% CI, 1.13-2.30) and CAMC (HR = 1.45, 95% CI, 1.03-2.04) were associated with all-cause mortality. A small CAMC was a protective factor for CVD mortality (HR = 0.46, 95% CI, 0.22-0.98). In the Kaplan-Meier analysis, older adults with LMM presented low all-cause mortality survival, with AC (p < 0.05), AMC (p < 0.005), CAMC (p < 0.002), and CC (p < 0.001). Cancer mortality was associated with low CAMC (p < 0.020)., Conclusions: Low MM assessed by anthropometric measures (AC, AMC, CAMC and CC) increased the all-cause mortality risk. A small CAMC decreased the CVD mortality., Competing Interests: The authors have declared that no competing interests exist.