Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVE: Summarize the evidence on drug therapies for obstructive sleep apnea. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis. RESULTS: 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]. CONCLUSION: The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed. PROSPERO REGISTRATION NUMBER: CRD42022362639.

Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis

Abstract Objective Summarize the evidence on drug therapies for obstructive sleep apnea. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis. Results 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]. Conclusion The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed. PROSPERO registration number CRD42022362639.

Clinical-epidemiological profile of confirmed cases of osteoarticular tuberculosis.

Introduction: tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. The incidence of TB has increased since the 1980s. Given the increasing prevalence of TB worldwide, osteoarticular TB (OATB) is a significant health problem. Methods: retrospective study of a case series of hospitalized patients with confirmed OATB by culture or histopathological examination who were seen at a reference orthopedic hospital in São Paulo, Brazil, from 2014 to 2019. Results: thirty patients with confirmed bone and joint TB were seen from 2014 to 2019. The main sites of OATB were the spine (83.3 %) and the appendicular skeleton (26.7 %). Indication of surgical treatment was significantly related to the need for hospitalization ( p = 0.009 ) and the increased length of hospital stay ( p = 0.005 ). Presence of sequelae at the end of treatment was correlated with the presence of motor deficit at the time of OATB diagnosis ( p = 0.035 ) as well as with initial presence of functional limitation ( p = 0.025 ) and with high value of C-reactive protein at the end of treatment ( p = 0.037 ). Conclusions: the delay in the onset of clinical and laboratory signs of cases of osteoarticular infections hinders the early diagnosis and treatment of the disease, resulting in major complications sometimes requiring surgical treatment and consequently leading to a prolonged hospital stay, evidence of high inflammatory activities, and the presence of neurological deficits.

Bivariate GWAS reveals pleiotropic regions among feed efficiency and beef quality-related traits in Nelore cattle.

Feed-efficient cattle selection is among the most leading solutions to reduce cost for beef cattle production. However, technical difficulties in measuring feed efficiency traits had limited the application in livestock. Here, we performed a Bivariate Genome-Wide Association Study (Bi-GWAS) and presented candidate biological mechanisms underlying the association between feed efficiency and meat quality traits in a half-sibling design with 353 Nelore steers derived from 34 unrelated sires. A total of 13 Quantitative Trait Loci (QTL) were found explaining part of the phenotypic variations. An important transcription factor of adipogenesis in cattle, the TAL1 (rs133408775) gene located on BTA3 was associated with intramuscular fat and average daily gain (IMF-ADG), and a region located on BTA20, close to CD180 and MAST4 genes, both related to fat accumulation. We observed a low positive genetic correlation between IMF-ADG (r = 0.30 ± 0.0686), indicating that it may respond to selection in the same direction. Our findings contributed to clarifying the pleiotropic modulation of the complex traits, indicating new QTLs for bovine genetic improvement.

Rumen and fecal microbiomes are related to diet and production traits in Bos indicus beef cattle.

Background: Ruminants harbor a complex microbial community within their gastrointestinal tract, which plays major roles in their health and physiology. Brazil is one of the largest producers of beef in the world and more than 90% of the beef cattle herds are composed of pure and crossbred Nelore (Bos indicus). Despite its importance to the Brazilian economy and human feeding, few studies have characterized the Nelore microbiome. Therefore, using shotgun metagenomics, we investigated the impact of diet on the composition and functionality of the Nelore microbiome, and explored the associations between specific microbial taxa and their functionality with feed efficiency and methane emission. Results: The ruminal microbiome exhibited significantly higher microbial diversity, distinctive taxonomic profile and variations in microbial functionality compared to the fecal microbiome, highlighting the distinct contributions of the microbiomes of these environments. Animals subjected to different dietary treatments exhibited significant differences in their microbiomes' archaeal diversity and in the abundance of 89 genera, as well as in the functions associated with the metabolism of components of each diet. Moreover, depending on the diet, feed-efficient animals and low methane emitters displayed higher microbial diversity in their fecal microbiome. Multiple genera were associated with an increase or decrease of the phenotypes. Upon analyzing the functions attributed to these taxa, we observed significant differences on the ruminal taxa associated with feed efficient and inefficient cattle. The ruminal taxa that characterized feed efficient cattle stood out for having significantly more functions related to carbohydrate metabolism, such as monosaccharides, di-/oligosaccharides and amino acids. The taxa associated with methane emission had functions associated with methanogenesis and the production of substrates that may influence methane production, such as hydrogen and formate. Conclusion: Our findings highlight the significant role of diet in shaping Nelore microbiomes and how its composition and functionality may affect production traits such as feed efficiency and methane emission. These insights provide valuable support for the implementation of novel feeding and biotechnological strategies.

COVID-19 and isolation: Risks and implications in the scenario of new variants.

With the emergence of new variants of SARS-CoV-2, questions about transmissibility, vaccine efficacy, and impact on mortality are important to support decision-making in public health measures. Modifications related to transmissibility combined with the fact that much of the population has already been partially exposed to infection and/or vaccination, have stimulated recommendations to reduce the isolation period for COVID-19. However, these new guidelines have raised questions about their effectiveness in reducing contamination and minimizing impact in work environments. Therefore, a collaborative task force was developed to review the subject in a non-systematic manner, answering questions about SARS-CoV-2 variants, COVID-19 vaccines, isolation/quarantine periods, testing to end the isolation period, and the use of masks as mitigation procedures. Overall, COVID-19 vaccines are effective in preventing severe illness and death but are less effective in preventing infection in the case of the Omicron variant. Any strategy that is adopted to reduce the isolation period should take into consideration the epidemiological situation of the geographical region, individual clinical characteristics, and mask for source control. The use of tests for isolation withdrawal should be evaluated with caution, due to results depending on various conditions and may not be reliable.

Prune homolog 2 with BCH domain (PRUNE2) gene expression is associated with feed efficiency-related traits in Nelore steers.

Animal feeding is a critical factor in increasing producer profitability. Improving feed efficiency can help reduce feeding costs and reduce the environmental impact of beef production. Candidate genes previously identified for this trait in differential gene expression studies (e.g., case-control studies) have not examined continuous gene-phenotype variation, which is a limitation. The aim of this study was to investigate the association between the expression of five candidate genes in the liver, measured by quantitative real-time PCR and feed-related traits. We adopted a linear mixed model to associate liver gene expression from 52 Nelore steers with the following production traits: average daily gain (ADG), body weight (BW), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency (FE), Kleiber index (KI), metabolic body weight (MBW), residual feed intake (RFI), and relative growth ratio (RGR). The total expression of the prune homolog 2 (PRUNE2) gene was significantly associated with DMI, FCR, FE, and RFI (P < 0.05). Furthermore, we have identified a new transcript of PRUNE2 (TCONS_00027692, GenBank MZ041267) that was inversely correlated with FCR and FE (P < 0.05), in contrast to the originally identified PRUNE2 transcript. The cytochrome P450 subfamily 2B (CYP2B6), early growth response protein 1 (EGR1), collagen type I alpha 1 chain (COL1A1), and connective tissue growth factor (CTGF) genes were not associated with any feed efficiency-related traits (P > 0.05). The findings reported herein suggest that PRUNE2 expression levels affects feed efficiency-related traits variation in Nelore steers.

Stool and Ruminal Microbiome Components Associated With Methane Emission and Feed Efficiency in Nelore Beef Cattle.

Background: The impact of extreme changes in weather patterns on the economy and human welfare is one of the biggest challenges our civilization faces. From anthropogenic contributions to climate change, reducing the impact of farming activities is a priority since it is responsible for up to 18% of global greenhouse gas emissions. To this end, we tested whether ruminal and stool microbiome components could be used as biomarkers for methane emission and feed efficiency in bovine by studying 52 Brazilian Nelore bulls belonging to two feed intervention treatment groups, that is, conventional and by-product-based diets. Results: We identified a total of 5,693 amplicon sequence variants (ASVs) in the Nelore bulls' microbiomes. A Differential abundance analysis with the ANCOM approach identified 30 bacterial and 15 archaeal ASVs as differentially abundant (DA) among treatment groups. An association analysis using Maaslin2 software and a linear mixed model indicated that bacterial ASVs are linked to the host's residual methane emission (RCH4) and residual feed intake (RFI) phenotype variation, suggesting their potential as targets for interventions or biomarkers. Conclusion: The feed composition induced significant differences in both abundance and richness of ruminal and stool microbial populations in ruminants of the Nelore breed. The industrial by-product-based dietary treatment applied to our experimental groups influenced the microbiome diversity of bacteria and archaea but not of protozoa. ASVs were associated with RCH4 emission and RFI in ruminal and stool microbiomes. While ruminal ASVs were expected to influence CH4 emission and RFI, the relationship of stool taxa, such as Alistipes and Rikenellaceae (gut group RC9), with these traits was not reported before and might be associated with host health due to their link to anti-inflammatory compounds. Overall, the ASVs associated here have the potential to be used as biomarkers for these complex phenotypes.

DNA methylation may affect beef tenderness through signal transduction in Bos indicus.

BACKGROUND: Beef tenderness is a complex trait of economic importance for the beef industry. Understanding the epigenetic mechanisms underlying this trait may help improve the accuracy of breeding programs. However, little is known about epigenetic effects on Bos taurus muscle and their implications in tenderness, and no studies have been conducted in Bos indicus. RESULTS: Comparing methylation profile of Bos indicus skeletal muscle with contrasting beef tenderness at 14 days after slaughter, we identified differentially methylated cytosines and regions associated with this trait. Interestingly, muscle that became tender beef had higher levels of hypermethylation compared to the tough group. Enrichment analysis of predicted target genes suggested that differences in methylation between tender and tough beef may affect signal transduction pathways, among which G protein signaling was a key pathway. In addition, different methylation levels were found associated with expression levels of GNAS, PDE4B, EPCAM and EBF3 genes. The differentially methylated elements correlated with EBF3 and GNAS genes overlapped CpG islands and regulatory elements. GNAS, a complex imprinted gene, has a key role on G protein signaling pathways. Moreover, both G protein signaling pathway and the EBF3 gene regulate muscle homeostasis, relaxation, and muscle cell-specificity. CONCLUSIONS: We present differentially methylated loci that may be of interest to decipher the epigenetic mechanisms affecting tenderness. Supported by the previous knowledge about regulatory elements and gene function, the methylation data suggests EBF3 and GNAS as potential candidate genes and G protein signaling as potential candidate pathway associated with beef tenderness via methylation.

Impacts of Consumption of Ultra-Processed Foods on the Maternal-Child Health: A Systematic Review.

Background and Aims: Changes in eating patterns have been leading to an increase in the consumption of ultra-processed foods (UPF), negatively impacting the quality of the diet and generating risk of harm to the health of the adult population, however, there is no systematized evidence of the impact of UPF in maternal-child health. Thus, in this study we aimed to evaluated the association between UPF consumption and health outcomes in the maternal-child population. Methods: Systematic review registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021236633), conducted according to the PRISMA diagram in the following databases: PubMed, Medline, Scopus, Web of Science, Scielo, and CAPES thesis and dissertation directory. We included original cross-sectional, case-control and cohort studies in any language. Eligibility criteria were (a) food consumption assessment by the NOVA classification, (b) health outcome (nutritional or diseases), and (c) maternal-child population (pregnant, lactating women and infants/children). All data were analyzed and extracted to a spreadsheet structured by two independent reviewers. We evaluated the methodological quality of the studies included using the Newcastle-Otawa Scale and RoB 2. Results: Searches retrieved 7,801 studies and 15 contemplated the eligibility criteria. Most studies included were cohort studies (n = 8, 53%), had children as their population (n = 9, 60%) and only one study evaluated UPF consumption in infants and lactating women. Panoramically, we observed that a higher participation of UPF in children's diet has been associated with different maternal-child outcomes, such as increase of weight gain, adiposity measures, overweight, early weaning, lower diet quality, metabolic alterations, diseases, and consumption of plastic originated from packaging. Only one of the studies included did not present high methodological quality. Conclusion: Despite the limited literature on UPF consumption and health outcomes in the maternal-child population, the highest UPF consumption negatively impacted nutrition and disease development indicators in pregnant, lactating women and children. Considering the expressive participation of these foods in the diet, other studies should be conducted to further investigate the impact of UPF consumption on different health indicators, especially in the lactation phase for this was the one to present the most important knowledge gap. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021236633], identifier [CRD42021236633].

Orthopedic infections due to Trichosporon species: Case series and literature review.

Reports of orthopedic fungal infections caused by Trichosporon species are extremely scarce, thus we aimed to describe a case series and review the cases published in the literature. Patients were retrospectively included if a previous culture of bone, joint, or soft tissues had resulted positive for Trichosporon species along with a clinical diagnosis of an orthopedic infection. Eight patients were included with diverse orthopedic conditions, most of them cases of osteomyelitis. The main isolated species was Trichosporon asahii. All patients were treated with antifungals, mainly voriconazole, and surgical management, resulting in high rates of clinical improvement and low associated mortality.

Reports of orthopedic infections caused by Trichosporon species are scarce. We described a case series of orthopedic infections caused by Trichosporon species and reviewed the previous published cases in the literature. We observed a high rate of clinical improvement and a low associated mortality.

COVID-19 and isolation: Risks and implications in the scenario of new variants

Abstract With the emergence of new variants of SARS-CoV-2, questions about transmissibility, vaccine efficacy, and impact on mortality are important to support decision-making in public health measures. Modifications related to transmissibility combined with the fact that much of the population has already been partially exposed to infection and/or vaccination, have stimulated recommendations to reduce the isolation period for COVID-19. However, these new guidelines have raised questions about their effectiveness in reducing contamination and minimizing impact in work environments. Therefore, a collaborative task force was developed to review the subject in a non-systematic manner, answering questions about SARS-CoV-2 variants, COVID-19 vaccines, isolation/quarantine periods, testing to end the isolation period, and the use of masks as mitigation procedures. Overall, COVID-19 vaccines are effective in preventing severe illness and death but are less effective in preventing infection in the case of the Omicron variant. Any strategy that is adopted to reduce the isolation period should take into consideration the epidemiological situation of the geographical region, individual clinical characteristics, and mask for source control. The use of tests for isolation withdrawal should be evaluated with caution, due to results depending on various conditions and may not be reliable.

Microcurrent stimulates cell proliferation and modulates cytokine release in fibroblast cells.

AIMS: To analyse the effects of microcurrent on L929 fibroblast cell culture. METHODS: Cells were cultivated in six-well plates at densities of 5×104, 1×105, 3×105 and 5×105 cells/well to determine the best plating density. Subsequently, two methods of current application were tested: with a paper cone coupled to the electrode (M1) and with the electrode directly inside the well (M2). Then, streams of 60µA (G60), 100µA (G100), 500µA (G500) and 900µA (G900) were applied to the cells (n=3) once a day for three minutes, for a period of one (T1), two (T2) and three days (T3). The MTT assay method was used to evaluate cell proliferation. For the quantification of the inflammatory markers by flow cytometry, the group and time that presented the best results were selected. RESULTS: The ideal plating density was established as 1x105 cells/well and M2 as the best application method. An increase in cell viability was observed at all intensities from T1 to T2, but with no significant differences. From T2 to T3, there was a decrease in viability in all groups, with a significant difference only in G500 (p<0.05). Flow cytometry was performed in the GC and G900 groups at T2. It was possible to observe an increase of 0.56pg/ml in Interleukin (IL)-17 and a decrease of 5.45pg/ml in IL-2. CONCLUSION: This study showed that two applications of microcurrent increases cell proliferation and modulates the inflammatory response, aiding tissue regeneration and playing a key role in rehabilitation.

First complete genome sequence and molecular characterization of Canine morbillivirus isolated in Central Brazil.

The Brazilian regions are still highly endemic areas for Canine morbillivirus [canine distemper virus (CDV)]. However, little is known regarding the genetic variability of the strain circulating in several Brazilian regions. Here, we report the first full-length genome and molecular characterization of CDV isolated from domestic dogs in the Brazilian Center-West region. Sequence alignment and phylogenetic analyses based on deduced amino acid and nucleotide sequences showed that the isolated strain is characterized as the South America-I/Europe genotype. However, it segregates into a CDV subgenotype branch. Interestingly, both H and F proteins have a gain of a potential N-glycosylation sites compared to the Onderstepoort vaccine strain. Therefore, this study provides a reference to further understand the epidemic and molecular characteristics of the CDV in Brazil.

Bioactive glass S53P4 to fill-up large cavitary bone defect after acute and chronic osteomyelitis treated with antibiotic-loaded cement beads: A prospective case series with a minimum 2-year follow-up.

INTRODUCTION: Bioactive glass S53P4 (BAG-S53P4) has been used in the treatment of osteomyelitis with excellent results. The aim of this study was to evaluate the clinical and radiographic results of patients treated with use of antibiotic-loaded cement beads, followed by bone defects filling using bioglass. METHODS: We treated a prospective series of patients presenting with acute or chronic osteomyelitis of a long bone of the upper or lower limb. The first-stage procedure involved debridement and filling of cavitary defects with antibiotic-loaded polymethylmethacrylate (PMMA) beads. When signs of infection subsided, the defects were filled with BAG-S53P4. The main outcomes assessed were the reinfection rate, need for reoperation, radiographic and functional evaluations (DASH and Lysholm scores). RESULTS: Ten patients were included, aged between 4 and 66 years (mean 25.4 years). The source of infection was hematogenic in five cases and post-traumatic in the other five. Hematogenic infections required two debridements before filling with bioglass, whereas post-traumatic cases required only one. The time between the first debridement and the application of bioglass varied from 1 to 63 weeks (average of 17 weeks). All patients showed a favorable evolution after bioglass procedure, with no need for reoperation or relevant wound problems. The radiographic evaluation showed partial incorporation of the material and adequate bone formation, and functional scores were satisfactory in all cases. CONCLUSION: The treatment of osteomyelitis with surgical debridement and PMMA beads, followed by filling of bone defect with BAG-S53P4, was effective in all patients evaluated, with adequate infectious control and bone regeneration. No cases required reoperation after bioglass implantation. Patients with hematogenous osteomyelitis required a greater number of debridements before filling with bioglass.

Continuous glucose monitoring in obese pregnant women with no hyperglycemia on glucose tolerance test.

OBJECTIVE: The objective of the present study was to compare 24-hour glycemic levels between obese pregnant women with normal glucose tolerance and non-obese pregnant women. METHODS: In the present observational, longitudinal study, continuous glucose monitoring was performed in obese pregnant women with normal oral glucose tolerance test with 75 g of glucose between the 24th and the 28th gestational weeks. The control group (CG) consisted of pregnant women with normal weight who were selected by matching the maternal age and parity with the same characteristics of the obese group (OG). Glucose measurements were obtained during 72 hours. RESULTS: Both the groups were balanced in terms of baseline characteristics (age: 33.5 [28.7-36.0] vs. 32.0 [26.0-34.5] years, p = 0.5 and length of pregnancy: 25.0 [24.0-25.0] vs. 25.5 [24.0-28.0] weeks, p = 0.6 in the CG and in the OG, respectively). Pre-breakfast glycemic levels were 77.77 ± 10.55 mg/dL in the CG and 82.02 ± 11.06 mg/dL in the OG (p<0.01). Glycemic levels at 2 hours after breakfast were 87.31 ± 13.10 mg/dL in the CG and 93.48 ± 18.74 mg/dL in the OG (p<0.001). Daytime blood glucose levels were 87.6 ± 15.4 vs. 93.1 ± 18.3 mg/dL (p<0.001) and nighttime blood glucose levels were 79.3 ± 15.8 vs. 84.7 ± 16.3 mg/dL (p<0.001) in the CG and in the OG, respectively. The 24-hour, daytime, and nighttime values of the area under the curve were higher in the OG when compared with the CG (85.1 ± 0.16 vs. 87.9 ± 0.12, 65.6 ± 0.14 vs. 67.5 ± 0.10, 19.5 ± 0.07 vs. 20.4 ± 0.05, respectively; p<0.001). CONCLUSION: The results of the present study showed that obesity in pregnancy was associated with higher glycemic levels even in the presence of normal findings on glucose tolerance test.

Psoroptes ovis mange in a dog in Brazil.

Psoroptes ovis (Acari: Psoroptidae, Hering, 1838) is an ectoparasite that poses a high risk to herd animals and causes a severe dermal disease called psoroptic mange. This work aimed to report P. ovis parasitism in a dog. A male Pinscher that lives in rural areas and had free access to sheep farming showed hair loss in the dorsal region and mild itching. Dermatological examination demonstrated irregular alopecia, scabs, dry desquamation and erythema around the dorsal region of the thorax and pelvis. Hemogram has shown mild eosinophilia and the fungal culture was negative. In skin scrapings, P. ovis was observed, and its morphological characteristics were recorded. Treatment with ivermectin (0.5 mg/kg) was initiated orally once weekly for six weeks and amitraz for environmental control shown positive results. The diagnosis of psoroptic mange in dogs was performed based on morphological characterization of mite and the report of sheep contact. This is the first report of the occurrence of P. ovis in dog.

Exercise-Induced Modulation of Angiotensin II Responses in Femoral Veins From 2-Kidney-1-Clip Hypertensive Rats.

The present study investigated the angiotensin II (Ang II) responses in rat femoral veins taken from 2-kidney-1clip (2K1C) hypertensive rats at 4 weeks after clipping, as well as the effects of exercise on these responses. In this manner, femoral veins taken from 2K1C rats kept at rest or exposed to acute exercise or to exercise training were challenged with Ang II or endothelin-1 (ET-1) in organ bath. Simultaneously, the presence of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined in these preparations by western blotting. In these experiments, femoral veins exhibited subdued Ang II responses. However, after nitric oxide (NO) synthesis blockade, the responses were higher in the femoral veins taken from animals kept at rest [0.137(0.049-0.245); n = 10] than those obtained in trained animals kept at rest [0.008(0.001-0.041); n = 10] or studied after a single bout of exercise [0.001(0.001-0.054); n = 11]. In preparations in which, in addition to NO synthesis, both the local production of prostanoids and the action of ET-1 on type A (ETA) or B (ETB) receptors were inhibited, the differences induced by exercise were no longer observed. In addition, neither ET-1 responses nor the presence of COX-1 and COX-2 in these preparations were modified by the employed exercise protocols. In conclusion, NO maintains Ang II responses reduced in femoral veins of 2K1C animals at rest. However, vasodilator prostanoids as well as other relaxing mechanisms, activated by ETB stimulation, are mobilized by exercise to cooperate with NO in order to maintain controlled Ang II responses in femoral veins.

Multi-Omics Approach Reveals miR-SNPs Affecting Muscle Fatty Acids Profile in Nelore Cattle.

MicroRNAs (miRNAs) are key regulators of gene expression, potentially affecting several biological processes, whose function can be altered by sequence variation. Hence, the integration of single nucleotide polymorphisms (SNP) and miRNAs can explain individual differences in economic traits. To provide new insights into the effects of SNPs on miRNAs and their related target genes, we carried out a multi-omic analysis to identify SNPs in miRNA mature sequences (miR-SNPs) associated with fatty acid (FA) composition in the Nelore cattle. As a result, we identified 3 miR-SNPs in different miRNAs (bta-miR-2419-3p, bta-miR-193a-2, and bta-miR-1291) significantly associated with FA traits (p-value < 0.02, Bonferroni corrected). Among these, the rs110817643C>T, located in the seed sequence of the bta-miR-1291, was associated with different ω6 FAs, polyunsaturated FA, and polyunsaturated:saturated FA ratios. Concerning the other two miR-SNPs, the rs43400521T>C (located in the bta-miR-2419-3p) was associated with C12:0 and C18:1 cis-11 FA, whereas the rs516857374A>G (located in the bta-miR-193a-2) was associated with C18:3 ω6 and ratio of ω6/ω3 traits. Additionally, to identify potential biomarkers for FA composition, we described target genes affected by these miR-SNPs at the mRNA or protein level. Our multi-omics analysis outlines the effects of genetic polymorphism on miRNA, and it highlights miR-SNPs and target candidate genes that control beef fatty acid composition.