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Purpose: Tissue inadequacy and operational challenges may limit lung cancer comprehensive biomarker testing. Here, we describe the initial implementation of a tailored tissue molecular journey at Oncoclínicas Precision Medicine Laboratory in Brazil, which includes fast-track (FT) non-next-generation sequencing (NGS) assays combined with a broad NGS panel., Methods: From 2021 to 2023, all nonsquamous lung cancer samples eligible for the patient support program "Lung Mapping Consortium" at Oncoclínicas & Co were evaluated using the FT panel (immunohistochemistry for PD-L1 and anaplastic lymphoma kinase [ALK], polymerase chain reaction for EGFR and BRAF , and fluorescence in situ hybridization for ROS1 ) plus a broad DNA and RNA sequencing panel of 180 genes (custom ARCHER panel)., Results: From 1,272 samples received by the laboratory, 3% had no tissue for any molecular testing, 20% was not eligible for broad NGS panel as per pathologist assessment (tumor purity and quantity), additional 12% did not reach presequencing analytical thresholds (nucleic acid quantity and/or quality), and 3% had postsequencing failure. Most frequent alterations were KRAS mutations (28.4%, KRAS G12C 9.7%), EGFR mutations (23.6%, exon20 insertions 2.9%), ALK fusions (6.4%), MET exon 14 skipping (4.4%), ERBB2 mutations (3.4%), ROS1 fusions (3.1%), and BRAF V600E (1.9%). In 35% of the samples, FT non-NGS tests were the only molecular diagnostics: EGFR mutations (14%), ALK fusions (4.4%), ROS1 fusions (1.8%), and BRAF V600E (0.7%). Overall, high PD-L1 expression (≥50%) was found in 12.3%., Conclusion: This study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of EGFR mutations, ALK fusions, and MET exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.

HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1 , an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 da Silva Costa, Ito, da Cruz, De Souza, Rios, Bertozzo, Camargo, Viturino, Lanaro, de Albuquerque, do Canto, Saad, Ospina-Prieto, Ozelo, Costa and de Melo.)

Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aims to evaluate the effects of increasing tannin levels from Mimosa tenuiflora hay on the intake, digestibility, and balance of nitrogen (N), water, and energy in hair lambs. Thirty-two Santa Ines lambs, at an average age of 150 days and body weight of 26.75 ± 2.29 kg, were randomly assigned to four treatments in a completely randomized design. The treatments consisted of four diets: a control diet, tannin-free, and three diets with increasing levels of total tannin, 26.2, 52.4, and 78.6 g tannin/kg dry matter (DM). Including the total tannins in the lambs' diet led to a quadratic increase in the intake of nutrients, N-retention (g/day), water intake, water absorption and retention, energy intake, and energy excretion in feces and gases. However, the digestibility of crude protein, neutral and acid detergent fibers, and total carbohydrates decreased. It was observed that there is a correlation between the variable nutrient digestibility and N-ingested and the N-absorbed, N-urinary, and N-retained. However, the N-excreted in feces did not correlate with any of the variables studied. It is recommended to include 33 g/kg DM of total natural tannins from Mimosa tenuiflora hay in the diet of hair lambs, as it improves intake, energy balance, dietary N, and body water composition while reducing the excretion of N-urinary and gas emissions to the environment.

SARS-CoV-2 genome surveillance is important for monitoring risk groups and health workers as well as data on new cases and mortality rate due to COVID-19. We characterized the circulation of SARS-CoV-2 variants from May 2021 to April 2022 in the state of Santa Catarina, southern Brazil, and evaluated the similarity between variants present in the population and healthcare workers (HCW). A total of 5291 sequenced genomes demonstrated the circulation of 55 strains and four variants of concern (Alpha, Delta, Gamma and Omicron-sublineages BA.1 and BA.2). The number of cases was relatively low in May 2021, but the number of deaths was higher with the Gamma variant. There was a significant increase in both numbers between December 2021 and February 2022, peaking in mid-January 2022, when the Omicron variant dominated. After May 2021, two distinct variant groups (Delta and Omicron) were observed, equally distributed among the five Santa Catarina mesoregions. Moreover, from November 2021 to February 2022, similar variant profiles between HCW and the general population were observed, and a quicker shift from Delta to Omicron in HCW than in the general population. This demonstrates the importance of HCW as a sentinel group for monitoring disease trends in the general population.

The aim of this study was to investigate the association between healthy food outlet proximity, metabolic syndrome (MS), and two of its components, waist circumference (WC) and systolic blood pressure (SBP), in older adults (63-107 years old, median age 73 years) living in Florianópolis, South Brazil in 2013-2014. This is a cross-sectional analysis of the second wave of the EpiFloripa Aging Cohort Study. Individual-level data on MS, WC, SBP, and socio-demographic and health-related characteristics were collected from face to face interviews. The healthy food environment was assessed via the number and types of establishments present. The residences of older adult participants were georeferenced using Geographical Information System (GIS) software. The number of each type of food establishment in a 500 m buffer around the each residence was determined. Multivariate linear regression was used to test association between food outlet proximity and continuous outcomes (SBP and WC), and multiple logistic regression was used to examine the relations between the predictor variables and the dichotomous outcome of MS (yes/no). The study revealed that greater frequency of supermarkets and restaurants in the neighborhood was associated with a lower likelihood of having MS. WC was lower in individuals living in places with greater availability of greengrocers' shops and restaurants. The results demonstrated that the number of establishments in a neighborhood is associated with cardiometabolic outcomes, and the likelihood of MS and increased WC is lower for older adults who live in neighborhoods with more access to establishments that sell foundational components of a healthy diet., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Souza, Quialheiro, Correa, Rech, Giehl and d’Orsi.)

Purpose: Glaucoma is the world's leading cause of irreversible blindness, with primary open-angle glaucoma (POAG) being the most prevalent subtype. In recent years, there have been advances in knowledge about the genetics involved in POAG, but genetic studies in admixed populations, such as Brazilians, are still rare. This study aimed to evaluate the association of single nucleotide variants (SNV) of the ABCA1 (rs2472493) and GAS7 (rs9913911) genes with POAG in a sample of the Brazilian population. Furthermore, the study aimed to evaluate the relationship between these SNVs and the need for surgical intervention in glaucoma control., Methods: A cross-sectional association study with 1,009 subjects (505 patients with POAG and 504 controls) was performed. Participants underwent a comprehensive ocular examination, including the need for surgical procedures for intraocular pressure control. Genotyping of SNVs was performed using the TaqMan genotyping assay., Results: SNV rs9913911 of GAS7 was found to be associated with POAG in the presence of the risk allele A (p = 0.0004) and the AA genotype (p = 0.002). There was no association between SNV rs2472493 of ABCA1 for either the allele risk or genotypes. However, the combination of these variants showed an additive effect on the risk for POAG: ABCA1 (GG) + GAS7 (AA; p = 0.02), ABCA1 (GG) + GAS7 (AG; p = 0.003), and ABCA1 (AG) + GAS7 (AG; p = 0.004). Also, POAG patients carrying the AA genotype of the GAS7 gene required antiglaucomatous surgery more frequently than those without the AA genotype (p = 0.01)., Conclusions: In a Brazilian population sample, there was an association identified between SNV rs9913911 ( GAS7 ) and the risk of POAG, and an additive effect was found when GAS7 was combined with SNV rs2472493 ( ABCA1 ). There was an association between SNV rs9913911 ( GAS7 ) and the risk for antiglaucomatous surgery., (Copyright © 2022 Molecular Vision.)

In freshwater environments the rotifer group may be divided into microphagous and raptorial species regarding their feeding patterns, and such guilds differently interact with other community components. Here, we analyzed the influence of cladocerans, cyclopoid nauplii, temperature, food resources and an exotic species on rotifer guilds, based on weekly samplings for 1 year. We have identified rotifer species and their trophi types in order to separate them into the raptorial and microphagous functional groups. The ratio raptorial:microphagous rotifers (Guild ratio, GR) was used in interaction analyses with cladocerans, nauplii, temperature, food resources and the exotic species Kellicottia bostoniensis. Correlations between total rotifers and food (phytoplankton carbon) and temperature were negative and significant, therefore, these factors did not lead to the increase of rotifer community. On the other hand, microphagous rotifers had opposing relation to cladoceran densities, as GR values showed that they became predominant when cladoceran populations declined. The use of density-based GR was adequate, with similar results compared to biomass-based studies regarding interactions with other organisms. Furthermore, we have found no invasive characteristics for the exotic microphagous rotifer, Kellicottia bostoniensis, and it seems to be outcompeted by the native microphagous species.

The objective of this study was to evaluate the physiological responses, ethology, and ingestive behavior of female Morada Nova sheep kept in a thermoneutral environment, after thermal stress and after consuming water with different levels of salinity. Thirty-six Morada Nova females with a mean age of 10.0 ± 2.0 months and a mean weight of 25.0 ± 3.0 kg were evaluated and distributed in a climatic chamber. The experimental design was completely randomized, with a factorial scheme of 2 (air temperature (AT)) × 3 (salinity levels (SLs)) and six replications. The sheep's physiological responses, ethology (day/night), and ingestive behavior were evaluated while they were subjected to ATs of 26.0 and 32.0 °C and SLs of 3.0, 6.0, and 9.0 dS/m. With elevation in AT, the animals experienced increased (P < 0.05) rectal temperatures (RTs), respiratory rates (RFs), and surface temperatures (STs) and exhibited reduced (P < 0.05) heart rates (HRs). When consuming water with an SL of 9.0 dS/m, a HR reduction (P < 0.05) was observed. Sleep behavior increased (P < 0.05) with the increase in SL during the day. Sleeping and drinking behaviors increased (P < 0.05), and the time of inactivity was reduced (P < 0.05) during the nocturnal period with increased SLs. With increased SLs, sheep consumed more water (P < 0.05) and reduced (P < 0.05) the number of regurgitated ruminal boluses per day (NRBD). Under the conditions of thermal stress (32.0 °C), sheep need to make physiological adjustments to maintain homeothermy. Water consumption of SLs up to 9.0 dS/m causes a higher state of dormancy in female Morada Nova sheep.

β-defensins are capable of creating pores in the bacterial membrane. In this study, we aim to determine the structure of 3 different sheep β-defensin 2 (SBD-2) sequences by molecular modeling. A herd of 47 sheep from the Centre for Ovine and Caprine Research of Pará was selected for this investigation. The AA, AG, and GG alleles were found on β-defensin sequences. We used homology modeling and molecular dynamic simulations to generate 3D models of peptides and they were successfully validated. The proteins are structurally very similar to classic defensins composed of 3 β-sheets and 3 disulfide bonds. Variations in the organization of the tertiary structure and distribution of charged residues were found between AA, AG, and GG alleles. In this study, we were able to characterize and show the structure of 3 SBD-2 gene variants for the first time in Amazonian sheep. Results demonstrated that these variants are similar in structures to classic β-defensins, but contain more positives charges, which may indicate an increase in efficacy.

This article reviews the literature, organizes the major findings, and generates the best evidence-based recommendations on nutrition therapy for head trauma patients. Despite recent advances in head trauma diagnosis and therapy, the mortality associated with this condition remains high. Few therapeutic interventions have been proven to effectively improve this condition. Head trauma causes multiple metabolic and electrolytic disorders; it is characterized by a hypermetabolic state that is associated with intensive catabolism, leading to specific nutritional needs. The current literature lacks specific guidelines for nutrition therapy in severe head trauma patients, although a substantial amount of data has been reported and relevant issues are currently being studied; these data may allow better nutrition therapy guidelines for these patients. In addition to a well-trained multi-disciplinary team, the following recommendations appear to improve outcomes: introducing nutrition therapy early; preferred enteral administration; appropriate energy intake; formulations that are tailored to specific patients, including appropriate nutrients; and strict electrolytic and metabolic monitoring. Understanding the pathophysiology and the consequences of therapy is fundamental.