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Structural variants (SVs) account for the majority of base pair differences both within and between primate species. However, our understanding of inter- and intra-species SV has been historically hampered by the quality of draft primate genomes and the absence of genome resources for key taxa. Recently, advances in long-read sequencing and genome assembly have begun to radically reshape our understanding of SVs. Two landmark achievements include the publication of a human telomere-to-telomere (T2T) genome as well as the development of the first human pangenome reference. In this review, we first look back to the major works laying the foundation for these projects. We then examine the ways in which T2T genome assemblies and pangenomes are transforming our understanding of and approach to primate SV. Finally, we discuss what the future of primate SV research may look like in the era of T2T genomes and pangenomics.
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Genômica , Primatas , Telômero , Humanos , Animais , Primatas/genética , Telômero/genética , Genômica/métodos , Genoma Humano , Genoma/genética , Evolução Molecular , Variação Estrutural do Genoma/genéticaRESUMO
INTRODUCTION: Several clinical trials have established the efficacy and safety of dupilumab for treating atopic dermatitis (AD). However, literature remains scarce in reporting the long-term effectiveness, safety, and drug survival of dupilumab in real-world settings. This study aimed to describe the latter outcomes of dupilumab in patients with AD. METHODS: This Portuguese, multicentric, observational, retrospective study included consecutive adult patients with AD who initiated dupilumab between January 2019 and September 2023, with a follow-up period up to 30 months. Drug discontinuation and adverse effects data were used to estimate drug survival. Clinical assessments included the Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), and Dermatology Life Quality Index (DLQI). RESULTS: A total of 312 patients were included in the study, with 56.4% being male (median age of 30 years, range 18-83). The 30-month drug survival rate was 82.0%. During the study period, 12.5% of the sample (n = 39 patients) discontinued treatment: 7.3% due to treatment failure, 2.9% due to safety concerns, 1.3% due to complete disease control, 0.6% due to pregnancy, and 0.3% due to lack of compliance. Adverse events not leading to drug discontinuation were noted in 25.6% of the sample (n = 80). Conjunctivitis was the most frequently reported adverse event (17%), followed by facial erythema (9%). At 30 months, the mean EASI decreased significantly from 27.30 ± 11.89 at baseline to 2.92 ± 3.96 (p < 0.001), reflecting an overall improvement of 89.3%. Similarly, pruritus NRS decreased from 7.36 ± 1.90 at baseline to 1.74 ± 2.16 at month 30 (p < 0.001), improving by 76.4%, and mean DLQI changed from 18.0 ± 7.09 at baseline to 2.67 ± 3.95 at month 30 (p < 0.001), decreasing by 85.2%. CONCLUSIONS: This study increases our current understanding of dupilumab in real-world settings, demonstrating its long-term effectiveness and safety in treating AD.
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Water security and industrial wastewater treatment are significant global concerns. One of the main issues with environmental contamination has been the discharge of dye wastewater from the textile and dye industries, contributing to an ever-growing problem with water pollution, poisoning water supplies, and harming the ecosystem. The traditional approach to wastewater treatment has been found to be inefficient, and biosorption techniques and mechanisms have been proven to be a successful replacement for conventional methods. Recent developments have led to the recognition of fibrous materials as an environmentally friendly option with broad application in several industries, including wastewater treatment. This review explores the potential of fibrous materials produced by the electrospinning technique as adsorbents for wastewater treatment, while at the same time, for the removal of adsorbates such as oil, dyes, heavy metals, and other substances, as reported in the literature. Textile wastewater filtering structures, produced by electrospinning, are summarized and the use of synthetic and natural polymers for this purpose is discussed. The limitations of electrospun textile wastewater filtering structures are also mentioned. Electrospun nanofibrous membranes appear to be a very promising route to filter textile wastewater and therefore contribute to water reuse and to reducing the contamination of water courses.
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The adoption of agriculture, first documented ~12,000 years ago in the Fertile Crescent, triggered a rapid shift toward starch-rich diets in human populations. Amylase genes facilitate starch digestion and increased salivary amylase copy number has been observed in some modern human populations with high starch intake, though evidence of recent selection is lacking. Here, using 52 long-read diploid assemblies and short read data from ~5,600 contemporary and ancient humans, we resolve the diversity, evolutionary history, and selective impact of structural variation at the amylase locus. We find that amylase genes have higher copy numbers in populations with agricultural subsistence compared to fishing, hunting, and pastoral groups. We identify 28 distinct amylase structural architectures and demonstrate that nearly identical structures have arisen recurrently on different haplotype backgrounds throughout recent human history. AMY1 and AMY2A genes each exhibit multiple duplications/deletions with mutation rates >10,000-fold the SNP mutation rate, whereas AMY2B gene duplications share a single origin. Using a pangenome graph-based approach to infer structural haplotypes across thousands of humans, we identify extensively duplicated haplotypes present at higher frequencies in modern day populations with traditionally agricultural diets. Leveraging 533 ancient human genomes we find that duplication-containing haplotypes (i.e. haplotypes with more amylase gene copies than the ancestral haplotype) have increased in frequency more than seven-fold over the last 12,000 years providing evidence for recent selection in West Eurasians. Together, our study highlights the potential impacts of the agricultural revolution on human genomes and the importance of long-read sequencing in identifying signatures of selection at structurally complex loci.
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Chest X-ray scans are frequently requested to detect the presence of abnormalities, due to their low-cost and non-invasive nature. The interpretation of these images can be automated to prioritize more urgent exams through deep learning models, but the presence of image artifacts, e.g. lettering, often generates a harmful bias in the classifiers and an increase of false positive results. Consequently, healthcare would benefit from a system that selects the thoracic region of interest prior to deciding whether an image is possibly pathologic. The current work tackles this binary classification exercise, in which an image is either normal or abnormal, using an attention-driven and spatially unsupervised Spatial Transformer Network (STERN), that takes advantage of a novel domain-specific loss to better frame the region of interest. Unlike the state of the art, in which this type of networks is usually employed for image alignment, this work proposes a spatial transformer module that is used specifically for attention, as an alternative to the standard object detection models that typically precede the classifier to crop out the region of interest. In sum, the proposed end-to-end architecture dynamically scales and aligns the input images to maximize the classifier's performance, by selecting the thorax with translation and non-isotropic scaling transformations, and thus eliminating artifacts. Additionally, this paper provides an extensive and objective analysis of the selected regions of interest, by proposing a set of mathematical evaluation metrics. The results indicate that the STERN achieves similar results to using YOLO-cropped images, with reduced computational cost and without the need for localization labels. More specifically, the system is able to distinguish abnormal frontal images from the CheXpert dataset, with a mean AUC of 85.67% - a 2.55% improvement vs. the 0.98% improvement achieved by the YOLO-based counterpart in comparison to a standard baseline classifier. At the same time, the STERN approach requires less than 2/3 of the training parameters, while increasing the inference time per batch in less than 2 ms. Code available via GitHub.
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Artefatos , Tórax , Raios X , Exercício FísicoRESUMO
This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.
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Elucidating the evolutionary process of animal adaptation to deserts is key to understanding adaptive responses to climate change. Here we generated 82 individual whole genomes of four fox species (genus Vulpes) inhabiting the Sahara Desert at different evolutionary times. We show that adaptation of new colonizing species to a hot arid environment has probably been facilitated by introgression and trans-species polymorphisms shared with older desert resident species, including a putatively adaptive 25 Mb genomic region. Scans for signatures of selection implicated genes affecting temperature perception, non-renal water loss and heat production in the recent adaptation of North African red foxes (Vulpes vulpes), after divergence from Eurasian populations approximately 78 thousand years ago. In the extreme desert specialists, Rueppell's fox (V. rueppellii) and fennec (V. zerda), we identified repeated signatures of selection in genes affecting renal water homeostasis supported by gene expression and physiological differences. Our study provides insights into the mechanisms and genetic underpinnings of a natural experiment of repeated adaptation to extreme conditions.
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Adaptação Biológica , Evolução Biológica , Raposas , Animais , Adaptação Biológica/genética , África do Norte , Clima Desértico , Raposas/genética , Genômica , Água , Homeostase/genética , Homeostase/fisiologiaRESUMO
BACKGROUND AND OBJECTIVE: Convolutional neural networks are widely used to detect radiological findings in chest radiographs. Standard architectures are optimized for images of relatively small size (for example, 224 × 224 pixels), which suffices for most application domains. However, in medical imaging, larger inputs are often necessary to analyze disease patterns. A single scan can display multiple types of radiological findings varying greatly in size, and most models do not explicitly account for this. For a given network, whose layers have fixed-size receptive fields, smaller input images result in coarser features, which better characterize larger objects in an image. In contrast, larger inputs result in finer grained features, beneficial for the analysis of smaller objects. By compromising to a single resolution, existing frameworks fail to acknowledge that the ideal input size will not necessarily be the same for classifying every pathology of a scan. The goal of our work is to address this shortcoming by proposing a lightweight framework for multi-scale classification of chest radiographs, where finer and coarser features are combined in a parameter-efficient fashion. METHODS: We experiment on CheXpert, a large chest X-ray database. A lightweight multi-resolution (224 × 224, 448 × 448 and 896 × 896 pixels) network is developed based on a Densenet-121 model where batch normalization layers are replaced with the proposed size-specific batch normalization. Each input size undergoes batch normalization with dedicated scale and shift parameters, while the remaining parameters are shared across sizes. Additional external validation of the proposed approach is performed on the VinDr-CXR data set. RESULTS: The proposed approach (AUC 83.27±0.17, 7.1M parameters) outperforms standard single-scale models (AUC 81.76±0.18, 82.62±0.11 and 82.39±0.13 for input sizes 224 × 224, 448 × 448 and 896 × 896, respectively, 6.9M parameters). It also achieves a performance similar to an ensemble of one individual model per scale (AUC 83.27±0.11, 20.9M parameters), while relying on significantly fewer parameters. The model leverages features of different granularities, resulting in a more accurate classification of all findings, regardless of their size, highlighting the advantages of this approach. CONCLUSIONS: Different chest X-ray findings are better classified at different scales. Our study shows that multi-scale features can be obtained with nearly no additional parameters, boosting performance.
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Aprendizado Profundo , Redes Neurais de Computação , Radiografia , Radiografia Torácica/métodosRESUMO
Twin pregnancy is associated with an increased risk of perinatal and maternal complications, and early establishment of the chorionicity type defines this risk. In monochorionic (MC) pregnancies, the fetuses share the same placental mass and exhibit vascular anastomoses crossing the intertwin membrane, and the combination and pattern of anastomoses determine the primary clinical picture and occurrence of future complications. Twin Anemia-Polycythemia Sequence (TAPS) was first described in 2006 after fetoscopic laser surgery in twin-to-twin transfusion syndrome (TTTS) twins, and in 2007, the first spontaneous cases were reported, recognizing TAPS as an individualized vascular identity in fetofetal transfusion syndromes. There are two types of TAPS: spontaneous (3-5%) and iatrogenic or postlaser (2-16%). TAPS consists of small diameter arteriovenous anastomoses (<1 mm) and low-rate, small-caliber AA anastomoses in the absence of amniotic fluid discordances. There are certain antenatal and postnatal diagnostic criteria, which have progressively evolved over time. New, additional secondary markers have been proposed, and their reliability is being studied. The best screening protocol for TAPS in MC twins is still a matter of debate. This review provides a survey of the relevant literature on the epidemiology, vascular pathophysiology, underlying hemodynamic factors that regulate mismatched vascular connections, and diagnostic criteria of this condition. The aim is to increase awareness and knowledge about this recently identified and frequently unrecognized and misdiagnosed pathology.
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Transfusão Feto-Fetal , Policitemia , Gravidez , Feminino , Humanos , Placenta/patologia , Policitemia/diagnóstico , Policitemia/epidemiologia , Policitemia/etiologia , Reprodutibilidade dos Testes , Transfusão Feto-Fetal/diagnóstico , Transfusão Feto-Fetal/epidemiologia , Transfusão Feto-Fetal/cirurgia , Gravidez de GêmeosRESUMO
Chicks are ideal to follow the development of the intestinal microbiota and to understand how a pathogen perturbs this developing population. Taxonomic/metagenomic analyses captured the development of the chick microbiota in unperturbed chicks and in chicks infected with Salmonella enterica serotype Typhimurium (STm) during development. Taxonomic analysis suggests that colonization by the chicken microbiota takes place in several waves. The cecal microbiota stabilizes at day 12 posthatch with prominent Gammaproteobacteria and Clostridiales. Introduction of S. Typhimurium at day 4 posthatch disrupted the expected waves of intestinal colonization. Taxonomic and metagenomic shotgun sequencing analyses allowed us to identify species present in uninfected chicks. Untargeted metabolomics suggested different metabolic activities in infected chick microbiota. This analysis and gas chromatography-mass spectrometry on ingesta confirmed that lactic acid in cecal content coincides with the stable presence of enterococci in STm-infected chicks. Unique metabolites, including 2-isopropylmalic acid, an intermediate in the biosynthesis of leucine, were present only in the cecal content of STm-infected chicks. The metagenomic data suggested that the microbiota in STm-infected chicks contained a higher abundance of genes, from STm itself, involved in branched-chain amino acid synthesis. We generated an ilvC deletion mutant (STM3909) encoding ketol-acid-reductoisomerase, a gene required for the production of l-isoleucine and l-valine. ΔilvC mutants are disadvantaged for growth during competitive infection with the wild type. Providing the ilvC gene in trans restored the growth of the ΔilvC mutant. Our integrative approach identified biochemical pathways used by STm to establish a colonization niche in the chick intestine during development. IMPORTANCE Chicks are an ideal model to follow the development of the intestinal microbiota and to understand how a pathogen perturbs this developing population. Using taxonomic and metagenomic analyses, we captured the development of chick microbiota to 19 days posthatch in unperturbed chicks and in chicks infected with Salmonella enterica serotype Typhimurium (STm). We show that normal development of the microbiota takes place in waves and is altered in the presence of a pathogen. Metagenomics and metabolomics suggested that branched-chain amino acid biosynthesis is especially important for Salmonella growth in the infected chick intestine. Salmonella mutants unable to make l-isoleucine and l-valine colonize the chick intestine poorly. Restoration of the pathway for biosynthesis of these amino acids restored the colonizing ability of Salmonella. Integration of multiple analyses allowed us to correctly identify biochemical pathways used by Salmonella to establish a niche for colonization in the chick intestine during development.
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Microbiota , Doenças das Aves Domésticas , Salmonelose Animal , Animais , Galinhas/microbiologia , Isoleucina , Salmonella typhimurium/metabolismo , Ceco/microbiologia , Aminoácidos de Cadeia Ramificada/metabolismo , Valina/metabolismo , Salmonelose Animal/microbiologia , Doenças das Aves Domésticas/microbiologiaRESUMO
The reprogramming of cellular metabolism of immune cells is an essential process in the regulation of antifungal immune responses. In particular, glucose metabolism has been shown to be required for protective immunity against infection with Aspergillus fumigatus. However, given the intricate cross talk between multiple metabolic networks and signals, it is likely that cellular metabolic pathways other than glycolysis are also relevant during fungal infection. In this study, we demonstrate that glutamine metabolism is required for the activation of macrophage effector functions against A. fumigatus. Glutamine metabolism was found to be upregulated early after fungal infection and glutamine depletion or the pharmacological inhibition of enzymes involved in its metabolism impaired phagocytosis and the production of both proinflammatory and T-cell-derived cytokines. In an in vivo model, inhibition of glutaminase increased susceptibility to experimental aspergillosis, as revealed by the increased fungal burden and inflammatory pathology, and the defective cytokine production in the lungs. Moreover, genetic variants in glutamine metabolism genes were found to regulate cytokine production in response to A. fumigatus stimulation. Taken together, our results demonstrate that glutamine metabolism represents an important component of the immunometabolic response of macrophages against A. fumigatus both in vitro and in vivo. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. The reprogramming of cellular metabolism is essential for innate immune cells to mount effective antifungal responses. In this study, we report the pivotal contribution of glutaminolysis to the host defense against A. fumigatus. Glutamine metabolism was essential both in vitro as well as in in vivo models of infection, and genetic variants in human glutamine metabolism genes regulated cytokine production in response to fungal stimulation. This work highlights the relevance of glutaminolysis to the pathogenesis of aspergillosis and supports a role for interindividual genetic variation influencing glutamine metabolism in susceptibility to infection.
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Aspergilose , Aspergillus fumigatus , Humanos , Aspergillus fumigatus/genética , Glutamina , Antifúngicos , Aspergilose/microbiologia , Citocinas/metabolismoRESUMO
Tendon and ligament traumatic injuries are among the most common diagnosed musculoskeletal problems. Such injuries limit joint mobility, reduce musculoskeletal performance, and most importantly, lower people's comfort. Currently, there are various treatments that are used to treat this type of injury, from surgical to conservative treatments. However, they're not entirely effective, as reinjures are frequent and, in some cases, fail to re-establish the lost functionality. Tissue engineering (TE) approaches aim to overcome these disadvantages by stimulating the regeneration and formation of artificial structures that resemble the original tissue. Fabrication and design of artificial fibrous scaffolds with tailored mechanical properties are crucial for restoring the mechanical function of the tissues. Recently, polymeric nanofibers produced by wetspinning have been largely investigated to mimic, repair, and replace the damaged tissue. Wetspun fibrous structures are extensively used due to their exceptional properties, such as the ability to mimic the native tissue, their biodegradability and biocompatibility, and good mechanical properties. In this review, the tendon and ligament structure and biomechanics are presented. Then, promising wetspun multifunctional fibrous structures based on biopolymers, more specifically polyhydroxyalkanoates (PHA), polycaprolactone (PCL), and polyethylenes, will be discussed, as well as reinforcing agents such as cellulose nanocrystals (CNC), nanoparticles, and growth factors.
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The knowledge of bacterial species diversity within the female urinary microbiome (FUM) is essential for understanding the role of the FUM in urinary tract health and disease. This study aimed to characterize the bacterial species diversity of the FUM of asymptomatic reproductive-age European women by combining extended culturomics and long-read sequencing of the near-full-length 16S rRNA gene. A total of 297 bacterial species (median of 53 species/sample) were identified, yet only 22% of the species were detected by both culture and sequencing methods. Recently recognized Gardnerella, Lactobacillus, and Limosilactobacillus species and 5 new putative Corynebacterium species were identified by culturomics, while anaerobic species (e.g., 11 Peptoniphilus spp.) were mostly detected by amplicon sequencing. Notably, there was not a single species common to all samples, although members of the genus Lactobacillus were detected in all. Lactobacillus crispatus, Lactobacillus iners, and Lactobacillus mulieris were observed in high relative abundance in several samples, as well as other species (e.g., Streptococcus agalactiae, Fannyhessea vaginae, Gardnerella vaginalis, Gardnerella swidsinskii), while low-abundance members (e.g., Finegoldia magna) were often more prevalent. A moderate correlation (Mantel test; r = 0.5) between community structure types captured by culturomics and amplicon sequencing was observed, highlighting the benefit of combining both methodologies. This study provided a detailed FUM structure at the species level, which is critical to unveil the potential relationship between specific microbiome members and urinary diseases/disorders. Moreover, the different capacity to characterize microbiome profiles of culturomic and amplicon sequencing is described, providing valuable insights for further urinary microbiome studies. IMPORTANCE The bacterial species diversity within the female urinary microbiome (FUM) has been insufficiently characterized. This study demonstrated that complementarity between optimized culture-dependent and -independent approaches is highly beneficial for comprehensive FUM species profiling by detecting higher FUM species diversity than previously reported, including identification of unreported species belonging to the genera Lactobacillus, Limosilactobacillus, and Latilactobacillus and putative novel Corynebacterium species. Although some species were present in high relative abundance, low-abundance members were more prevalent. FUM classification into community structure types demonstrated high interindividual differences in urinary microbiome composition among asymptomatic women. We also report moderate correlation between culture-dependent and -independent derived data-highlighting drawbacks of each methodological approach. Our findings suggest that FUM bacterial diversity reported from previous studies may be underestimated. Finally, our results contribute to the fundamental knowledge of the FUM required for further exploration of the urinary microbiome role in urinary tract diseases.
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Microbiota , Sistema Urinário , Humanos , Feminino , RNA Ribossômico 16S/genética , Sistema Urinário/microbiologia , Gardnerella vaginalis/genética , Bactérias/genética , Corynebacterium/genética , Microbiota/genética , População Europeia , Vagina/microbiologiaRESUMO
Semi-empirical models are used to predict the power spectral density of wall pressure fluctuations in the turbulent boundary layer. Current advancements in power spectral density wall pressure fluctuation prediction have focused on expanding the range of experiments that can be predicted to include adverse pressure gradient flows; however, favorable pressure gradient flows have not received much attention. An experiment was performed to capture the effects of the favorable pressure gradient on the power spectral density. A model was then created to improve upon some of the limitations of existing models. The proposed model improves upon the prediction of the high-frequency roll-off location, incorporates improvements made by past models, and captures the effects of favorable pressure gradients.
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The objective of this study is to assess, in zebrafish, the effects of combining linseed oil (LO) and clove leaf essential oil (CLEO) on the incorporation of fatty acids in the muscle, oxidative markers, lipid peroxidation and expression of the PPAR-α (Peroxisome Proliferator-Activated Receptor-α) and the SREBP-2 (Sterol Regulatory Element Binding Protein-2) genes. Six diets were prepared, containing combinations of LO (3, 6 and 9%) and CLEO (0.5 and 1%): 3% LO + 0.5% CLEO; 3% LO + 1% CLEO; 6% LO + 0.5% CLEO; 6% LO + 1% CLEO; 9% LO + 0.5% CLEO; 9% LO + 1% CLEO. Results showed increase in the incorporation of n-3 fatty acids in the muscle concomitantly with the addition of LO and CLEO. The activities of superoxide dismutase and catalase were reduced and the glutathione content had increased. Lipid peroxidation was lower in the treatment with 1% CLEO, regardless of LO content. The expression of the PPAR-α and the SREBP-2 genes was higher in animals fed 9% LO + 0.5% CLEO. Therefore, for a greater incorporation and protection against the oxidative damages of n-3 fatty acids, a combined use of 9% LO with 0.5% CLEO is recommended for zebrafish.
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Ácidos Graxos Ômega-3 , Óleos Voláteis , Syzygium , Animais , Ácidos Graxos/análise , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/metabolismo , Óleo de Semente do Linho/química , Óleo de Semente do Linho/metabolismo , Óleo de Semente do Linho/farmacologia , Peroxidação de Lipídeos , Fígado/metabolismo , Músculos/metabolismo , Óleos Voláteis/metabolismo , Estresse Oxidativo , PPAR alfa/análise , PPAR alfa/metabolismo , Folhas de Planta/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/análise , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Peixe-Zebra/metabolismoRESUMO
Pyoderma gangrenosum (PG) is a rare chronic neutrophilic dermatosis that can be associated with underlying conditions, such as inflammatory bowel disease and neoplasms, or can be idiopathic. Classically, it presents as painful skin lesions. We present a case of a 54-year-old woman who got a synovial cyst removed from her left hand, which later aggravated into a non-healing wound, and subsequently a painful necrotic ulcer. The histological pattern combined with the clinical features suggested PG. General wound care was performed, associated with topical tacrolimus and oral corticotherapy with a good response. Three similar episodes with lesions scattered over the body followed and required a combination of other pharmacological alternatives. An extensive etiological study was carried out to screen secondary causes without any relevant findings. Therefore, an idiopathic relapsing PG was assumed. PG is poorly understood, underdiagnosed and hard to treat. It has a clear impact on the quality of life of the patient, so high suspicion and timely treatment are essential to minimize complications.
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The evolutionary history of African ungulates has been explained largely in the light of Pleistocene climatic oscillations and the way these influenced the distribution of vegetation types, leading to range expansions and/or isolation in refugia. In contrast, comparatively fewer studies have addressed the continent's environmental heterogeneity and the role played by its geomorphological barriers. In this study, we performed a range-wide analysis of complete mitogenomes of sable antelope (Hippotragus niger) to explore how these different factors may have contributed as drivers of evolution in southcentral Africa. Our results supported two sympatric and deeply divergent mitochondrial lineages in west Tanzanian sables, which can be explained as the result of introgressive hybridization of a mitochondrial ghost lineage from an archaic, as-yet-undefined, congener. Phylogeographical subdivisions into three main lineages suggest that sable diversification may not have been driven solely by climatic events affecting populations differently across a continental scale. Often in interplay with climate, geomorphological features have also clearly shaped the species' patterns of vicariance, where the East Africa Rift System and the Eastern Arc Mountains acted as geological barriers. Subsequent splits among southern populations may be linked to rearrangements in the Zambezi system, possibly framing the most recent time when the river attained its current drainage profile. This work underlines how the use of comprehensive mitogenomic data sets on a model species with a wide geographical distribution can contribute to a much-enhanced understanding of environmental, geomorphological and evolutionary patterns in Africa throughout the Quaternary.
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Antílopes , Mustelidae , Animais , Antílopes/genética , DNA Mitocondrial/genética , Variação Genética/genética , Filogenia , FilogeografiaRESUMO
Metabolic syndrome, especially its component related to dyslipidemia, is related to the development of nonalcoholic fatty liver disease (NAFLD), which is a disease with a significant global prevalence. Supplementation with omega-3 polyunsaturated fatty acids emerged as a complementary therapeutic possibility for dyslipidemia, but its benefits are questioned. This paper aims at evaluating the effects of fish oil supplementation in rats with hypercholesterolemia induced by hypercholesterolemic diet (HD). The study design is based on an experimental model in which the animals were randomly divided into 3 groups: G1 (standard commercial feed + saline solution); G2 (hypercholesterolemic diet + saline solution) and G3 (hypercholesterolemic diet + fish oil) over a period of 16 weeks. Metabolic control parameters and oxidative stress biomarkers were evaluated according to standardized methodologies. The G3 group showed significantly lower values of plasma concentrations of TG, and hepatic myeloperoxidase as well as higher erythrocyte superoxide dismutase activity (p < 0.05). Regarding histopathological analysis, there was lipid accumulation in the liver of animals from group G2; meanwhile, hepatocytes reorganization and expressive reduction of lipid vacuoles and hepatic TG content was observed in group G3. This study demonstrated how fish oil supplementation reduced the plasma concentration and hepatic content of triglycerides, as well as liver tissue damage in histopathological analysis.
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Óleos de Peixe , Hepatopatia Gordurosa não Alcoólica , Animais , Biomarcadores , Suplementos Nutricionais , Óleos de Peixe/farmacologia , Estresse Oxidativo , RatosRESUMO
Atherosclerosis is a cardiovascular disease associated with abnormalities of vascular functions. The consumption of mono- and polyunsaturated fatty acids can be considered a strategy to reduce clinical events related to atherosclerosis. In the present study, we investigated the effects of supplementation with 310 mg of ω-3 PUFAs (2:1 eicosapentaenoic/docosahexaenoic acids) for 56 days on rats with hypercholesterolemia induced by a diet containing cholesterol (0.1%), cholic acid (0.5%), and egg yolk. Serum biochemical parameters were determined by the enzymatic colorimetric method. Assessment of vascular effects was performed by analysis of histological sections of the heart and aortic arch stained with hematoxylin and eosin and vascular reactivity of the aorta artery. We observed that treatment with ω-3 PUFAs did not promote alterations in lipid profile. On the other hand, we documented a favorable reduction in liver biomarkers, as well as contributions to the preservation of heart and aortic arch morphologies. Interestingly, the vascular reactivity of rat thoracic aortic preparations was improved after treatment with ω-3 PUFAs, with a decrease in hyperreactivity to phenylephrine and increased vasorelaxation promoted by acetylcholine. Our findings suggest that the supplementation of hypercholesterolemic rats with ω-3 PUFAs promoted improvement in liver and vascular endothelial function as well as preserving heart and aortic tissue, reinforcing the early health benefits of ω-3 PUFAs in the development of atherosclerotic plaque and further related events.