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Accurate evaluation of the mitral valve (MV) apparatus is essential for understanding the mechanisms of MV disease across various clinical scenarios. The mitral annulus (MA) is a complex and crucial structure that supports MV function; however, conventional imaging techniques have limitations in fully capturing the entirety of the MA. Moreover, recognizing annular changes might aid in identifying patients who may benefit from advanced cardiac imaging and interventions. Multimodality cardiovascular imaging plays a major role in the diagnosis, prognosis, and management of MV disease. Transthoracic echocardiography is the first-line modality for evaluation of the MA, but it has limitations. Cardiac MRI (CMR) has emerged as a robust imaging modality for assessing annular changes, with distinct advantages over other imaging techniques, including accurate flow and volumetric quantification and assessment of variations in the measurements and shape of the MA during the cardiac cycle. Mitral annular disjunction (MAD) is defined as atrial displacement of the hinge point of the MV annulus away from the ventricular myocardium, a condition that is now more frequently diagnosed and studied owing to recent technical advances in cardiac imaging. However, several unresolved issues regarding MAD, such as the functional significance of pathologic disjunction and how this disjunction advances in the clinical course, require further investigation. The authors review the role of CMR in the assessment of MA disease, with a focus on MAD and its functional implications in MV prolapse and mitral regurgitation. ©RSNA, 2024 Supplemental material is available for this article. See the invited commentary by Stojanovska and Fujikura in this issue.
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Imagen por Resonancia Magnética , Válvula Mitral , Humanos , Válvula Mitral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagenRESUMEN
Beef cattle breeding programs offer genetic evaluations and consulting services on animal breeding practices to help breeders improve the genetic merit of their herds. Some breeders are more willing to apply best practices and technologies than others. Consequently, the average genetic merit and genetic trends differ across herds. We benchmarked some parameters of an average herd (AVE) and the corresponding parameters of herds with higher genetic merit (TOP), both participating in a commercial Nellore breeding program. Expected progeny differences (EPD) for growth, reproductive and carcass traits and a selection index (SI) of animals born from 2005 to 2019 on 128 farms located in Brazil, Bolivia and Paraguay were used to compute the AVE parameters. The 20 herds with higher mean SI of animals born in the last five birth seasons were classified as TOP herds. The mean SI and EPD of animals born in the last five seasons in the TOP herds were, respectively, 89% and 79% to 206% higher (p ≤ 0.001) than those of animals from the AVE herd. Genetic trends over the entire period were also higher (50% for SI and 31% to 88% separately for each trait, p ≤ 0.006) in the TOP herds compared to the AVE herd. Although the difference in the numbers of cows, bulls and calves between the TOP and AVE herds did not reach statistical significance (p = 0.175, p = 0.273 and p = 0.061, respectively), the numbers of progeny per cow and per bull were 21% (p = 0.012) and 26% (p = 0.047) higher in the TOP herds, respectively. Multiple ovulation and embryo transfer and in vitro fertilization and embryo transfer (MOET/IVF) accounted for a higher percentage of births in the TOP herds compared to AVE (24.6% vs. 12.5%, p = 0.002). The generation interval was 17% shorter (p < 0.001) in the TOP herds compared to AVE. The average inbreeding coefficient of animals from the TOP herds (1.08 ± 0.52%) did not differ (p = 0.78) from that of AVE animals (1.26 ± 0.96%). In general, AVE herds are evolving in the desirable direction but differences in genetic merit between AVE and TOP herds are increasing over time. The more frequent use of MOET/IVF, a lower cow-to-bull ratio, and a larger family size (progeny per cow or per bull) can help achieve larger selection differentials and increase genetic trends and average genetic merits of TOP herds compared to AVE herds.
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Benchmarking , Reproducción , Embarazo , Femenino , Bovinos/genética , Animales , Masculino , Reproducción/genética , Parto , Endogamia , Fenotipo , Industria LecheraRESUMEN
Zilpaterol and clenbuterol are two ß-adrenergic agonist drugs used in animal production. Both drugs have anabolic effects with advantages on carcass yield. Meanwhile, zilpaterol is approved for animal feed in authorized countries. Clenbuterol is a banned substance due to the risk of toxicity; however, it is still being used in unknown dose levels in many farm species. Therefore, the use and abuse of these substances should be closely monitored, considering the clenbuterol ability and the not proved yet of zilpaterol to produce reactive oxygen and nitrogen species. Regarding glutathione which is the main intracellular antioxidant plays detoxification functions on liver metabolism; in this work, it is our interest to know the capacity of chitosan-glutathione nanoparticles (CS/GSH-NP) as a complementary source of exogenous GSH to modify the oxide-reduction status on bovine precision-cut liver slice cultures (PCLS) exposed to clenbuterol and zilpaterol. A single drug assay was performed in first instance by adding clenbuterol, zilpaterol, chitosan nanoparticles (CS-NP), and CS/GSH-NP. Then combinate drug assay was carried out by testing clenbuterol and zilpaterol combined with CS-NP or CS/GSH-NP. The results showed that both ß-adrenergic agonists modify in a dose-dependent manner in oxide-reduction response through ROS generation. The activity or content of glutathione peroxidase activity, intracellular GSH, gamma glutamyl-transpeptidase, aspartate aminotrasnferase and alanine aminotrasnferase were modified. The exogenous GSH delivered by nanoparticles could be used to modulate these markers.
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Quitosano , Clenbuterol , Nanopartículas , Agonistas Adrenérgicos beta , Animales , Antioxidantes , Bovinos , Quitosano/toxicidad , Clenbuterol/toxicidad , Glutatión , Hígado , Nanopartículas/toxicidad , Óxidos , Compuestos de TrimetilsililoRESUMEN
Epiphytic lichens, collected from 119 sampling sites grown over "Roistonea Royal Palm" trees, were used to assess the spatial distribution pattern of lead (Pb) and identify possible pollution sources in Havana (Cuba). Lead concentrations in lichens and topsoils were determined by flame atomic absorption spectrophotometry and inductively coupled plasma (ICP) atomic emission spectrometry, respectively, while Pb in crude oils and gasoline samples were measured by ICP-time of flight mass spectrometry (ICP-ToF-MS). Lead isotopic ratios measurements for lichens, soils, and crude oils were obtained by ICP-ToF-MS. We found that enrichment factors (EF) reflected a moderate contamination for 71% of the samples (EF > 10). The 206Pb/207Pb ratio values for lichens ranged from 1.17 to 1.20 and were a mixture of natural radiogenic and industrial activities (e.g., crude oils and fire plants). The low concentration of Pb found in gasoline (<7.0 µg L-1) confirms the official statement that leaded gasoline is no longer used in Cuba.
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Monitoreo del Ambiente/métodos , Contaminación Ambiental/análisis , Plomo/análisis , Líquenes/química , Cuba , Gasolina/análisis , Isótopos/análisis , Suelo/química , Espectrofotometría Atómica/métodos , ÁrbolesRESUMEN
BACKGROUND: Nelore is the major beef cattle breed in Brazil with more than 130 million heads. Genome-wide association studies (GWAS) are often used to associate markers and genomic regions to growth and meat quality traits that can be used to assist selection programs. An alternative methodology to traditional GWAS that involves the construction of gene network interactions, derived from results of several GWAS is the AWM (Association Weight Matrices)/PCIT (Partial Correlation and Information Theory). With the aim of evaluating the genetic architecture of Brazilian Nelore cattle, we used high-density SNP genotyping data (~770,000 SNP) from 780 Nelore animals comprising 34 half-sibling families derived from highly disseminated and unrelated sires from across Brazil. The AWM/PCIT methodology was employed to evaluate the genes that participate in a series of eight phenotypes related to growth and meat quality obtained from this Nelore sample. RESULTS: Our results indicate a lack of structuring between the individuals studied since principal component analyses were not able to differentiate families by its sires or by its ancestral lineages. The application of the AWM/PCIT methodology revealed a trio of transcription factors (comprising VDR, LHX9 and ZEB1) which in combination connected 66 genes through 359 edges and whose biological functions were inspected, some revealing to participate in biological growth processes in literature searches. CONCLUSIONS: The diversity of the Nelore sample studied is not high enough to differentiate among families neither by sires nor by using the available ancestral lineage information. The gene networks constructed from the AWM/PCIT methodology were a useful alternative in characterizing genes and gene networks that were allegedly influential in growth and meat quality traits in Nelore cattle.
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Bovinos/crecimiento & desarrollo , Bovinos/genética , Redes Reguladoras de Genes , Carne Roja , Animales , Brasil , Estudios de Asociación Genética , Pleiotropía Genética , Genotipo , Desequilibrio de Ligamiento , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genéticaRESUMEN
Aging populations are increasing worldwide and strategies to minimize the impact of falls on older people need to be examined. Falls in hospitals are common and current hospital technological implementations use localized sensors on beds and chairs to alert caregivers of unsupervised patient ambulations; however, such systems have high false alarm rates. We investigate the recognition of bed and chair exits in real-time using a wireless wearable sensor worn by healthy older volunteers. Fourteen healthy older participants joined in supervised trials. They wore a batteryless, lightweight and wireless sensor over their attire and performed a set of broadly scripted activities. We developed a movement monitoring approach for the recognition of bed and chair exits based on a machine learning activity predictor. We investigated the effectiveness of our approach in generating bed and chair exit alerts in two possible clinical deployments (Room 1 and Room 2). The system obtained recall results above 93% (Room 2) and 94% (Room 1) for bed and chair exits, respectively. Precision was >78% and 67%, respectively, while F-score was >84% and 77% for bed and chair exits, respectively. This system has potential for real-time monitoring but further research in the final target population of older people is necessary.
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Accidentes por Caídas/prevención & control , Técnicas Biosensibles/métodos , Monitoreo Fisiológico/métodos , Tecnología Inalámbrica/instrumentación , Anciano , Anciano de 80 o más Años , Técnicas Biosensibles/instrumentación , Suministros de Energía Eléctrica , Femenino , Hospitales , Humanos , Masculino , Monitoreo Fisiológico/instrumentación , Movimiento/fisiologíaRESUMEN
In order to analyze the effects of extrusion temperature (T: 164, 182, 200 °C) and grits moisture content (g/100 g sample) (%M: 14, 16.5, 19) on textural and physicochemical properties of red sorghum extrudates, whole grain flour was extruded according to a factorial experimental design. The higher values for specific mechanical energy consumption (1006.98 J/g) and expansion (3.36) were obtained at 164 °C-14%M and for sensorial hardness at 164 °C-19%M. While for specific volume, the highest value (10.41 cm³/g) was obtained at 200 °C-14%M. Water solubility and water absorption were directly related with T and inversely with M. Microscopic observation of the samples indicates that the greatest cooking degree was obtained at 200 °C-4%M and the lowest at 164 °C-19%M. Extrusion at 182 °C-14%M allows obtaining an expanded product with good properties. Proximal composition did not show statistically significant differences with raw sample. Extruded sample showed a 25.4% reduction of available lysine and a 31% increase in protein digestibility.
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Fibras de la Dieta/análisis , Harina/análisis , Manipulación de Alimentos , Semillas/química , Sorghum/química , Argentina , Fenómenos Químicos , Culinaria , Fibras de la Dieta/metabolismo , Proteínas en la Dieta/análisis , Proteínas en la Dieta/química , Proteínas en la Dieta/metabolismo , Digestión , Dureza , Calor/efectos adversos , Humanos , Hierro de la Dieta/análisis , Hierro de la Dieta/metabolismo , Lisina/análisis , Lisina/metabolismo , Valor Nutritivo , Proteínas de Plantas/análisis , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Semillas/ultraestructura , Sensación , Solubilidad , Sorghum/ultraestructura , Almidón/análisis , Almidón/química , Almidón/metabolismo , Almidón/ultraestructura , Agua/análisis , Zinc/análisis , Zinc/metabolismoRESUMEN
Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175â mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed. Conclusion: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).
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PURPOSE: As the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access. METHODS: Sixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed. RESULTS: Latin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent. CONCLUSION: Despite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , América Latina/epidemiología , ConsensoRESUMEN
Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3'-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed: (1) To evaluate biochemical parameters in blood (2) to determine the tissue oxidative stress by biomarkers as TBARS and glutathione peroxidase activity, and (3) to evaluate anatomopathological changes in organs such as the brain, liver, kidney, and lung after oral administration of n-hexane extract of Ac and D and N. D and N were administrated following the OECD guides for acute oral toxicity evaluation (Guide 420). Fifty Wistar rats were distributed into ten groups as follows: Group 1 (G1): 4 mg/Kg; G2: 40 mg/Kg; G3: 240 mg/Kg; G4: 1600 mg/Kg of n-hexane extract of Ac. G5: 2 mg/Kg; G6: 20 mg/Kg; G7: 120 mg/Kg; G8: 800 mg/Kg of D and N, G9: water and G10: polyvinylpyrrolidone at 2000 mg/Kg. At 14 days, the rats were euthanized, and the blood, liver, brain, kidney, and lung were taken for biochemical analysis, anatomopathological changes, and TBARS and GSH evaluation. Glucose, cholesterol, and phosphorus were altered. Histopathological analysis showed multifocal neuronal degeneration in the brain (G2). The kidney and lungs had changes in G7. The GSH and TBARS increased in G6 and G7. The TBARS activity was higher in G1 and G2. In conclusion, extract and D and N of Ac did not have damage at therapeutic doses. D, N, and n-hexane extract of A. cina do not cause histopathological damage at pharmaceutical doses. Still, the brain, kidney, and liver are related to biochemical parameters at higher doses. However, compounds are proposed as antioxidant agents.
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Biomarcadores , Estrés Oxidativo , Extractos Vegetales , Ratas Wistar , Animales , Estrés Oxidativo/efectos de los fármacos , Ratas , Extractos Vegetales/farmacología , Extractos Vegetales/química , Masculino , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Encéfalo/patología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Glutatión Peroxidasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Comparisons of duration of response (DoR) and duration of clinical benefit (DoCB) within clinical trials are prone to biases. To address these biases, we used new methodology to prospectively analyze expected DoR and expected DoCB. Objective response rate and clinical benefit rate were calculated for fulvestrant 500 and 250 mg, and used to calculate expected DoR and expected DoCB for each dose group. The ratios for expected DoR and expected DoCB (expected DoR500/expected DoR250 and expected DoCB500/expected DoCB250) were then calculated, thereby allowing statistical comparisons of these endpoints between each arm of the COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) trial. Expected DoRs for fulvestrant 500 and 250 mg were 3.2 and 3.6 months, respectively. The expected DoR ratio between fulvestrant 500 and 250 mg was not statistically significant (0.89; 95 % CI, 0.48-1.67, P = 0.724). The expected DoCBs for fulvestrant 500 and 250 mg were 9.8 and 7.2 months, respectively. The expected DoCB ratio showed that the expected DoCB for fulvestrant 500 mg was significantly improved compared with the expected DoCB for fulvestrant 250 mg (1.36; 95 % CI, 1.07-1.73, P = 0.013). Analysis of the expected DoR and expected DoCB showed fulvestrant 500 mg significantly increased expected DoCB compared with fulvestrant 250 mg in the CONFIRM trial.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Estradiol/análogos & derivados , Antineoplásicos Hormonales/administración & dosificación , Estradiol/administración & dosificación , Estradiol/uso terapéutico , Femenino , Fulvestrant , Humanos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Genoma Bacteriano/genética , Secuencia de Bases , Genómica , Grupos de Población , Infecciones por Helicobacter/microbiologíaRESUMEN
We conducted a global-scale study to identify H. pylori antimicrobial-resistant genes (ARG), address their global distribution, and understand their effect on the antimicrobial resistance (AMR) phenotypes of the clinical isolates. We identified ARG using several well-known tools against extensive bacterial ARG databases, then analyzed their correlation with clinical antibiogram data from dozens of patients across countries. This revealed that combining multiple tools and databases, followed by manual selection of ARG from the annotation results, produces more conclusive results than using a single tool or database alone. After curation, the results showed that H. pylori has 42 ARG against 11 different antibiotic classes (16 genes related to single antibiotic class resistance and 26 genes related to multidrug resistance). Further analysis revealed that H. pylori naturally harbors ARG in the core genome, called the 'Set of ARG commonly found in the Core Genome of H. pylori (ARG-CORE)', while ARG-ACC-the ARG in the accessory genome-are exclusive to particular strains. In addition, we detected 29 genes of potential efflux pump-related AMR that were mostly categorized as ARG-CORE. The ARG distribution appears to be almost similar either by geographical or H. pylori populations perspective; however, some ARG had a unique distribution since they tend to be found only in a particular region or population. Finally, we demonstrated that the presence of ARG may not directly correlate with the sensitive/resistance phenotype of clinical patient isolates but may influence the minimum inhibitory concentration phenotype.
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Due to cartilage's limited capacity for regeneration, numerous studies have been conducted to find new drugs that modify osteoarthrosis's progression. Some evidence showed the capability of chitosan nanoparticles with glutathione (Np-GSH) to regulate the oxide-redox status in vitro in human chondrocytes. This work aimed to evaluate the capacity of Np-GSH in vivo, using Wistar rats with induced surgical osteoarthritis. Radiographic, biochemical (GSH and TBARS quantification), histopathological, and immunohistochemical (Col-2 and MMP-13) analyses were performed to evaluate the progress of the osteoarthritic lesions after the administration of a single dose of Np-GSH. According to the results obtained, the GSH contained in the NPs could be vectored to chondrocytes and used by the cell to modulate the oxidative state reduction, decreasing the production of ROS and free radicals induced by agents oxidizing xenobiotics, increasing GSH levels, as well as the activity of GPx, and decreasing lipid peroxidation. These results are significant since the synthesis of GSH develops exclusively in the cell cytoplasm, and its quantity under an oxidation-reduction imbalance may be defective. Therefore, the results allow us to consider these nanostructures as a helpful study tool to reduce the damage associated with oxidative stress in various diseases such as osteoarthritis.
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PURPOSE: Predictive biomarkers for capecitabine benefit in triple-negative breast cancer (TNBC) have been recently proposed using samples from phase III clinical trials, including non-basal phenotype and biomarkers related to angiogenesis, stroma, and capecitabine activation genes. We aimed to validate these findings on the larger phase III GEICAM/CIBOMA clinical trial. EXPERIMENTAL DESIGN: Tumor tissues from patients with TNBC randomized to standard (neo)adjuvant chemotherapy followed by capecitabine versus observation were analyzed using a 164-gene NanoString custom nCounter codeset measuring mRNA expression. A prespecified statistical plan sought to verify the predictive capacity of PAM50 non-basal molecular subtype and tested the hypotheses that breast tumors with increased expression of (meta)genes for cytotoxic cells, mast cells, endothelial cells, PDL2, and 38 individual genes benefit from adjuvant capecitabine for distant recurrence-free survival (DRFS; primary endpoint) and overall survival. RESULTS: Of the 876 women enrolled in the GEICAM/CIBOMA trial, 658 (75%) were evaluable for analysis (337 with capecitabine and 321 without). Of these cases, 553 (84%) were profiled as PAM50 basal-like whereas 105 (16%) were PAM50 non-basal. Non-basal subtype was the most significant predictor for capecitabine benefit [HRcapecitabine, 0.19; 95% confidence interval (CI), 0.07-0.54; P < 0.001] when compared with PAM50 basal-like (HRcapecitabine, 0.9; 95% CI, 0.63-1.28; P = 0.55; Pinteraction<0.001, adjusted P value = 0.01). Analysis of biological processes related to PAM50 non-basal subtype revealed its enrichment for mast cells, extracellular matrix, angiogenesis, and features of mesenchymal stem-like TNBC subtype. CONCLUSIONS: In this prespecified correlative analysis of the GEICAM/CIBOMA trial, PAM50 non-basal status identified patients with early-stage TNBC most likely to benefit from capecitabine.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Capecitabina/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Células Endoteliales/patología , Adyuvantes Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
The infectious prion protein PrP(Sc) is encoded by the PRNP gene. In cattle, insertion/deletion (indel) polymorphisms are among the changes that occur in this gene, the most studied of which are within intron 1 (12 bp) and the promoter region (23 bp). Sequence variants in this gene may affect the formation of PrP(Sc). In the present study, nucleotide variability in specific regions of the PRNP gene in Caracu cattle free of bovine spongiform encephalopathy was investigated to determine the genotypic profile of each animal within the group. Caracu cattle exhibited high allele frequency for the two polymorphic regions studied, 12ins (70 %) and 23ins (72.5 %), genotype frequencies of 50 % for 12ins/ins and 50 % for 23ins/del, and a high frequency of the 12ins-23ins haplotype (57.5 %). Of the 40 animals sampled, 15 had the 12ins-23ins/12ins-23ins diplotype.
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Encefalopatía Espongiforme Bovina/genética , Mutación INDEL , Intrones , Polimorfismo Genético , Priones/genética , Regiones Promotoras Genéticas , Animales , Secuencia de Bases , Bovinos , Cromosomas de los Mamíferos/genética , Análisis Mutacional de ADN , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Heterocigoto , Desequilibrio de Ligamiento , Datos de Secuencia Molecular , Priones/patogenicidadRESUMEN
Cardioneural ablation is a novel treatment for functional bradycardia. However, the risk of acute complications is still unknown. The aim of this case report is to describe acute occlusion of the sinus node artery after cardiac denervation procedures in 2 patients and to encourage measures to prevent it, such as evaluating the aortic angulation in older patients before the procedure and by monitoring signs of sinus failure during ablation in patients with electroanatomical maps showing a constricted aspect of the right atrium. (Level of Difficulty: Advanced.).
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Helicobacter pylori have coevolved with mankind since its origins, adapting to different human groups. In America, H. pylori has evolved into several subpopulations. We analysed the genome of 154 Colombian strains along with 1,091 strains from worldwide populations to discern the ancestry and adaption to Colombian people. Population structure and ancestry was inferred with FineStructure and ChromoPainter. Phylogenetic relationship and the relative effect of recombination were analysing the core SNPs. Also, a Fst index was calculated to identify the gene variants with the strongest fixation in the Colombian subpopulations compared to their parent population hspSWEurope. FineStructure allowed the identification of two Colombian subpopulations, the previously described hspSWEuropeColombia and a novel subpopulation named hspColombia, that included three subgroups following their geographic origin. Colombian subpopulations represent an admixture of European, African and Indigenous ancestry; although some genomes showed a high proportion of self identity, suggesting an advanced adaption to these mestizo Colombian groups. We found that recombination is more important that punctual mutations in H. pylori genome diversity, 13.9 more important in hspSWEurope, 12.5 in hspSWEColombia and 10.5 in hspColombia, reflecting the divergence of these subpopulations. Fst analysis identified 82 SNPs fixed in 26 genes of the hspColombia subpopulation that encode for outer membrane and central metabolism proteins. Strongest fixation indexes were identified in genes encoding HofC, HopE, FrpB-4 and Sialidase A. These findings demonstrate that H. pylori has evolved in Colombia to give rise to subpopulations with a self identity ancestry, reflected in allele changes on genes encoding for outer membrane proteins.
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Helicobacter pylori , Alelos , Colombia , Helicobacter pylori/genética , Humanos , Filogenia , Recombinación GenéticaRESUMEN
Hibiscus sabdariffa L. (HSL) has high amounts of antioxidants and many beneficial effects in several pathologies. However, few studies describe the possible harmful effects of high concentrations of HSL. Here we evaluate the effect of excessive and chronic consumption of infusions with different percentages of HSL on some oxidative stress markers in serum, and the possible association with inflammation and increased systolic blood pressure (SBP), in healthy rats. A total of 32 male Wistar rats were used to form 4 groups with 8 animals each. Group 1 control (drinking tap water), group 2, 3 and 4, drinking water supplemented with 15, 30 and 60 g/L of HSL calyxes respectively. SBP was evaluated and determinations in serum of the NO3-/NO2- ratio, glutathione (GSH), total antioxidant capacity (TAC), selenium (Se), TNF-α, IL-1α/IL-1F1, IL-1ß, IL-10, extracellular superoxide dismutase (EcSOD), thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities, were evaluated. The SBP (p = 0.01), GPx activity, GSH, TAC, Se, TNF-α and EcSOD activities (p ≤ 0.001) and IL-1α/IL-1F1, IL-1ß, TrxR and NO3-/NO2- (p ≤ 0.05), were increased but IL-10 (p < 0.001) was decreased in rats that consumed the 3 and 6% HSL infusions. The excessive and chronic consumption of HSL may increase the TAC that could lead to a proinflammatory state which is associated with hypertension.
Asunto(s)
Hibiscus , Extractos Vegetales , Animales , Antioxidantes/farmacología , Presión Sanguínea , Glutatión , Glutatión Peroxidasa , Hibiscus/química , Inflamación , Interleucina-10 , Masculino , Dióxido de Nitrógeno , Extractos Vegetales/efectos adversos , Ratas , Ratas Wistar , Selenio , Superóxido Dismutasa , Reductasa de Tiorredoxina-Disulfuro , Factor de Necrosis Tumoral alfaRESUMEN
This study aimed to evaluate whether aluminum chloride (AlCl3) causes hematological changes in the peripheral blood of Sprague-Dawley (SD) rats. Five groups of female SD rats were intragastrically administered with 4 different concentrations of AlCl3 for 5 days a week for a total of 90 days. The aluminum concentration was determined via graphite furnace atomic absorption spectroscopy. Analysis of serum iron-kinetic profiles, blood cytometry outcomes, and blood smears of the blood samples. Scanning electron microscopy (SEM) and Raman spectroscopy were used to search for structural and ultrastructural changes, respectively. Blood aluminum concentration ranged 12.38-16.24 µg/L with no significant difference between experimental treatments. At the AlCl3 concentration of 40 mg Al/kg bw of rats/day, the mean ferritin value in the serum iron kinetic profile was 29.81±6.1 ng/mL, and this value showed a significant difference between experimental treatments. Blood cytometry revealed that there were 6.45-7.11×106 cells/µL erythrocytes, 8.91-9.32×103 cells/µL leukocytes, and 477.2-736.3×103 cells/µL platelets along with a hemoglobin of 37.38-41.93 g/dL and hematocrit level of 37.38-41.93%; the experimental treatments showed no significant differences. Erythrocyte structural analysis using SEM showed no differences between experimental treatments, whereas ultrastructural evaluation using Raman spectroscopy made it possible to identify the following bands: 741, 1123, 1350, 1578, and 1618 cm-1, which were respectively associated with the following vibrational modes and compounds: vibration of the tryptophan ring, asymmetric C-O-C stretching of glucose, C-H curve of tryptophan, C=C stretching of the heme group, and C-N stretching of the heme group, with no significant differences between experimental treatments. Therefore, AlCl3 administration does not induce ultrastructural changes in the erythrocyte membrane. This study revealed that serum ferritin concentration was the only parameter affected by AlCl3 exposure at 40 mg of Al/kg bw of rats/day.