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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.

An efficient manufacturing of colorimetric nonwoven indicators represents a promising alternative to enable applications of such materials in food quality monitoring. The objective of this study is to use the solution blow spinning technique (SBS) to rapidly produce colorimetric nonwoven indicators based on polycaprolactone, incorporating natural or synthetic pH indicators to detect volatile amines, bacterial growth and monitor pH. Produced via the SBS method, these indicators were characterized aiming their physical, mechanical, thermal, and spectroscopic properties, evaluating their efficacy in detecting amines, monitoring bacterial growth, and pH, as well as assessing color stability during storage. The thermal stability and mechanical properties of the nonwovens practically always increased with the incorporation of natural and synthetic indicators. When exposed to volatile amines, the nonwoven indicators, particularly those embedded with bromophenol blue, displayed remarkable color change abilities in the presence of five volatile amines. These smart nonwovens in direct contact with E. coli K-12 or its volatiles in 24 h changed their color perceptible to the naked eye. The nanofiber nonwovens displayed visible color changes (ΔE ≥ 3) in response to buffer solutions (pH between 3 and 10). The smart nonwovens rapidly produced by the solution blow spinning method prove to be a promising tool for real-time monitoring of food freshness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chitin-derived furans offer a sustainable alternative feedstock for nitrogen appended aromatic compounds. Herein, we address the challenge of using chitin-derived furans, 3-acetamido-5-acetylfuran (3A5AF) and 3-acetamido-5-furfural aldehyde (3A5F), to favour the formation of exo Diels-Alder adducts and 4-acetylaminophthalimides respectively, using a mechanochemical ball-milling technique. Mechanochemical activation is explored through the synthesis of 7-oxa-norbornene backbones with novel substitution pattern from 3A5AF in yields up to 77 % and improved exo:endo selectivity compared to solution-phase reactions. The synthesis of 4-acetylaminophthalimides from 3A5F in yields up to 79 % is also showcased from hydrazone derivatives., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Background: Premature loss of primary teeth presents a significant challenge in oral health, with conflicting views on using space maintainers., Aim: To assess mandibular arch space changes associated with premature lower primary molar (PM) loss with or without a space maintainer., Design: A randomized clinical trial with children (6-9 years old) with premature loss of a lower PM divided into two groups: control group (CG), without a space maintainer, and intervention group (IG), with a space maintainer. Dental casts were measured at baseline, 3 months, and 6 months. Linear distance; intercanine width and length; and arch width, length, and perimeter were measured. ANOVA and t-test were applied (p = .05)., Results: Twenty-six patients (mean: 7.3 years; standard deviation [SD]: 0.92) were included: 14 in CG and 12 in IG. CG had a greater space loss (-0.9 mm; SD: 0.45) than IG (-0.4 mm; SD: 0.61) at 3 months (p < .05). No difference between the groups was observed after 6 months (p = .610). CG decreases space at 6 months, especially with the first permanent molars without intercuspation (-2 mm; SD: 0.71; p = .007)., Conclusion: Premature lower PM loss resulted in reduced arch space loss after 6 months, regardless of a space maintainer use. CG showed more loss of space when the first permanent molars lacked intercuspal relationship., (© 2024 BSPD, IAPD and John Wiley & Sons Ltd.)

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.)

Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals that exhibit exceptional chemical and thermal stability. However, their resistance to degradation has led to their widespread environmental contamination. PFAS also negatively affect the environment and other organisms, highlighting the need for effective remediation methods to mitigate their presence and prevent further contamination. Computational chemistry methods, such as Density Functional Theory (DFT) and Molecular Dynamics (MD) offer valuable tools for studying PFAS and simulating their interactions with other molecules. This review explores how computational chemistry methods contribute to understanding and tackling PFAS in the environment. PFAS have been extensively studied using DFT and MD, each method offering unique advantages and computational limitations. MD simulates large macromolecules systems however it lacks the ability model chemical reactions, while DFT provides molecular insights however at a high computational cost. The integration of DFT with MD shows promise in predicting PFAS behavior in different environments. This work summarizes reported studies on PFAS compounds, focusing on adsorption, destruction, and bioaccumulation, highlighting contributions of computational methods while discussing the need for continued research. The findings emphasize the importance of computational chemistry in addressing PFAS contamination, guiding risk assessments, and informing future research and innovations in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

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

Background: Primary open-angle glaucoma (POAG), the world's main cause of irreversible blindness, is an asymptomatic and neurodegenerative disease of multifactorial etiology with ethnic and geographic disparities. Multiethnic genome-wide association studies (GWAS) identified single nucleotide variants (SNVs) in ATXN2, FOXC1 , and TXNRD2 loci as risk factors for POAG pathophysiology and/or endophenotypes. The aim of this case-control study was to investigate the association of the variants rs7137828 ( ATXN2 ), rs2745572 ( FOXC1 ), and rs35934224 ( TXNRD2 ), as risk factors for POAG development, additionally to rs7137828 association with glaucoma clinical parameters in a Brazilian cohort from the Southeast and South regions., Methods: This investigation comprised 506 cases and 501 controls. Variants rs2745572 and rs35934224 were genotyped through TaqMan® assays and validated by Sanger sequencing. Variant rs7137828 was genotyped exclusively by Sanger sequencing., Results: The primary research outcome revealed that the variant rs7137828 ( ATXN2 ) was associated with an increased risk for the development of POAG in the presence of the TT genotype compared to the CC genotype ( p  = 0.006; Odds Ratio [OR] = 1.717; Confidence Interval [CI] 95% = 1.169-2.535). There was no significant association of rs2745572 and rs35934224 genotypes with POAG. The CT genotype of the rs7137828 was associated with the vertical cup-to-disk ratio (VCDR) ( p  = .023) but not with the age at diagnosis or the mean deviation., Conclusion: Our data indicate the rs7137828 associated with increased risk for the development of POAG and VCDR in a Brazilian cohort. If validated in additional populations, these findings may enable the development of relevant strategies for early diagnosis of glaucoma in the future.

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 systematic review and meta-analysis was to assess whether the presence of inferior third molars during sagittal split mandibular ramus osteotomy increases the risk of intraoperative and postoperative complications. The PRISMA protocol was followed in this study, and the review was registered in the PROSPERO database (CRD42020147642). A search was conducted in the MEDLINE (PubMed), Web of Science, Cochrane Central, and Scopus databases on November 1, 2021. Nineteen articles were included, and the variables analysed were unfavourable fractures, infection, neurosensory disturbance, removal of osteosynthesis material, and duration of surgery. Meta-analyses were performed for the variables unfavourable fractures (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.58-1.57, P = 0.84), infection (RR 0.75, 95% CI 0.48-1.18, P = 0.21), and neurosensory disturbance (RR 1.55, 95% CI 0.61-3.91, P = 0.35); no statistically significant difference in the risk of these variables was found between the groups with and without third molars. The third molars did not increase the need to remove fixation material, but increased the surgery time. The presence of the third molar during sagittal split mandibular ramus osteotomy appears not to increase the risk of intraoperative and postoperative complications. The results presented here must be interpreted with caution due to the heterogeneity presented by the observational studies included., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

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.)

This study aimed to investigate the effect of beta-casein genotypes (A1A2 and A2A2) in three different thermal comfort conditions on the adaptability of Sindhi cows and as a tool for selecting thermotolerant cattle. Twelve Sindhi cows were used in a completely randomized design in a 2 × 3 factorial arrangement, with six replicates, with two genotypes, and three thermal comfort conditions. The climatic variables were recorded, while black globe temperature, humidity index, and radiant heat load were calculated. We measured respiratory rate, surface temperature, and rectal temperature while the heat tolerance coefficient was calculated. Genotype had no significant effect (p > 0.05) on any of the parameters measured. However, there was a thermal comfort condition effect (p < 0.05) on rectal temperature, surface temperature, and thermal gradients. The respiratory rate and heat tolerance coefficient were not significantly affected (p > 0.05). Therefore, although the results indicate substantial adaptability of Sindhi cows under any thermal conditions, the tested genotypes should not be used as a tool for selecting thermotolerant Sindhi cows., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

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.

Conservation practices in the tropics often rely on the data available for a few, better-known species and the adoption of an appropriate spatial scale. By defining a set of landscape units that account for critical aspects of the focal species, the information available on these conservation targets can support regional conservation policies. Here, we define and classify adjacent landscapes, termed planning units, to orientate management decisions within and among these landscapes, which are occupied by an endangered flagship primate species (Coimbra-Filho's titi monkey, Callicebus coimbrai) from eastern Brazil. We use landscape boundaries (highways and river systems), and a high-resolution map of forest remnants to identify continuous and manageable landscapes. We employed functional landscape metrics based on the species' dispersal ability and home range size to characterize and classify these landscapes. We classified planning units by scoring them according to a suite of selected metrics through a Principal Component Analysis. We propose 31 planning units, containing one to six C. coimbrai populations, most with low values of habitat availability, functional connectivity and carrying capacity, and a high degree of degradation. Due to this poor landscape configuration, basic management practices are recommendable. However, additional aspects of the landscapes and the populations they contain (e.g., matrix type and genetic variability) should improve the scheme, which will require a closer integration of research aims with socio-political strategies. Even so, our scheme should prove useful for the combination of information on conservation targets (i.e., focal species) with management strategies on an administrative scale., (© 2017 Wiley Periodicals, Inc.)

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

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.