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1.
J Physiol ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39057844

RESUMO

Renal ischaemia and reperfusion (I/R) is caused by a sudden temporary impairment of the blood flow. I/R is a prevalent cause of acute kidney injury. As nitric oxide generated by inducible nitric oxide synthase (iNOS) has detrimental effects during I/R, the pharmacological blockade of iNOS has been proposed as a potential strategy to prevent I/R injury. The aim of this study was to improve the understanding of 1400W (an iNOS inhibitor) on renal I/R as a pharmacological strategy against kidney disease. BALB/c mice received 30 min of bilateral ischaemia, followed by 48 h or 28 days of reperfusion. Vehicle or 1400W (10 mg/kg) was administered 30 min before inducing ischaemia. We found that after 48 h of reperfusion 1400W decreased the serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin and proliferating cell nuclear antigen 3 in the I/R animals. Unexpectedly, we observed mRNA upregulation of genes involved in kidney injury, cell-cycle arrest, inflammation, mesenchymal transition and endothelial activation in the renal medulla of sham animals treated with 1400W. We also explored if 1400W promoted chronic kidney dysfunction 28 days after I/R and did not find significant alterations in renal function, fibrosis, blood pressure or mortality. The results provide evidence that 1400W may have adverse effects in the renal medulla. Importantly, our data point to 1400W-induced endothelial dysfunction, establishing therapeutic limitations for its use. KEY POINTS: Acute kidney injury is a global health problem associated with high morbidity and mortality. The pharmacological blockade of inducible nitric oxide synthase (iNOS) has been proposed as a potential strategy to prevent AKI induced by ischaemia and reperfusion (I/R). Our main finding is that 1400W, a selective and irreversible iNOS inhibitor with low toxicity that is proposed as a therapeutic strategy to prevent kidney I/R injury, produces aberrant gene expression in the medulla associated to tissue injury, cell cycle arrest, inflammation, mesenchymal transition and endothelial activation. The negative effect of 1400W observed in the renal medulla at 48 h from drug administration, is transient as it did not translate into a chronic kidney disease condition.

2.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732154

RESUMO

The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196 for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.


Assuntos
Biomarcadores , Doenças Cardiovasculares , Vesículas Extracelulares , Proteínas de Choque Térmico HSP47 , Miócitos Cardíacos , Humanos , Vesículas Extracelulares/metabolismo , Biomarcadores/sangue , Masculino , Doenças Cardiovasculares/metabolismo , Feminino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Pessoa de Meia-Idade , Animais , Proteínas de Choque Térmico HSP47/metabolismo , Ratos , Canal de Potássio ERG1/metabolismo , Idoso , Adulto , Canais de Potássio Éter-A-Go-Go/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/sangue
3.
Rev Med Chil ; 151(5): 551-559, 2023 May.
Artigo em Espanhol | MEDLINE | ID: mdl-38687536

RESUMO

PURPOSE OF THE STUDY: To know the experience of first-year medical students at Universidad Austral de Chile regarding virtual Problem-Based learning (PBL) tutorials carried out by peer tutors during the second semester of 2021. METHODS: Quantitative and qualitative research, transversal, descriptive. The non-probabilistic sample consisted of 45 medical students who participated in virtual PBL tutorials with peer tutors. Data collection through an anonymous and voluntary opinion survey comprised two areas: methodology and role of the tutor, considering open questions related to facilitating and hindering aspects. Quantitative data analysis was performed using descriptive statistics with frequency measurements. The qualitative ones with progressive reduction. Study approved by the Scientific Ethics Committee, Valdivia Health Service. RESULTS: There is a high degree of satisfaction in all three areas. Both in the qualitative and quantitative results, the participants positively value the performance of the peer tutor, highlighting empathy, commitment, trust, facilitation, feedback, and a good learning environment, allowing collaborative learning. Unlike the quantitative, the qualitative is more frequently identified as hindering factors, poor internet connection, excessive curricular load, and lack of knowledge about the methodology by the tutor. CONCLUSIONS: Although the preparation of peer tutors for PBL tutorials is essential, it is even more critical in virtual mode since they face challenges such as managing virtual platforms and achieving effective communication that allows learning collaboratively.


Assuntos
COVID-19 , Educação de Graduação em Medicina , Grupo Associado , Aprendizagem Baseada em Problemas , Estudantes de Medicina , Humanos , Chile , Estudantes de Medicina/psicologia , Aprendizagem Baseada em Problemas/métodos , COVID-19/prevenção & controle , Masculino , Feminino , Educação de Graduação em Medicina/métodos , Estudos Transversais , Pesquisa Qualitativa , Pandemias , Adulto Jovem , Inquéritos e Questionários , Adulto
4.
J Exp Bot ; 73(15): 5322-5335, 2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-35383379

RESUMO

High-throughput phenotyping is an emerging approach in plant science, but thus far only a few applications have been made in horticultural crop breeding. Remote sensing of leaf or canopy spectral reflectance can help breeders rapidly measure traits, increase selection accuracy, and thereby improve response to selection. In the present study, we evaluated the integration of spectral analysis of canopy reflectance and genomic information for the prediction of strawberry (Fragaria × ananassa) powdery mildew disease. Two multi-parental breeding populations of strawberry comprising a total of 340 and 464 pedigree-connected seedlings were evaluated in two separate seasons. A single-trait Bayesian prediction method using 1001 spectral wavebands in the ultraviolet-visible-near infrared region (350-1350 nm wavelength) combined with 8552 single nucleotide polymorphism markers showed up to 2-fold increase in predictive ability over models using markers alone. The integration of high-throughput phenotyping was further validated independently across years/trials with improved response to selection of up to 90%. We also conducted Bayesian multi-trait analysis using the estimated vegetative indices as secondary traits. Three vegetative indices (Datt3, REP_Li, and Vogelmann2) had high genetic correlations (rA) with powdery mildew visual ratings with average rA values of 0.76, 0.71, and 0.71, respectively. Increasing training population sizes by incorporating individuals with only vegetative index information yielded substantial increases in predictive ability. These results strongly indicate the use of vegetative indices as secondary traits for indirect selection. Overall, combining spectrometry and genome-wide prediction improved selection accuracy and response to selection for powdery mildew resistance, demonstrating the power of an integrated phenomics-genomics approach in strawberry breeding.


Assuntos
Fragaria , Teorema de Bayes , Fragaria/genética , Fenótipo , Melhoramento Vegetal , Análise Espectral
5.
Molecules ; 27(2)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35056877

RESUMO

Palm kernel cake (PKC) is an abundant side stream that can only be added to non-ruminant feed in small concentrations due to its content of antinutritional factors, mainly galactomannan, which cannot be digested by non-ruminants. ß-mannanases can be added to partially hydrolyze galactomannan to form mannose oligosaccharides, which are known to be prebiotic. We here investigate the action of a ß-mannanase from B. subtilis on PKC by colorimetry, NMR and fluorescence microscopy. The amount of mannan oligosaccharides in solution was significantly increased by the ß-mannanase and their degree of polymerization (DP) was significantly reduced. There was a dose-response behavior in that larger ß-mannanase concentrations increased the amount of soluble mannose oligosaccharides while reducing their average DP. Using confocal immunofluorescence microscopy, solubilization of galactomannan in PKC was clearly visualized. Images show a clear disruption of the cellulose and galactomannan structures of the PKC cell walls. We thus show in this study that using commercial dosages of ß-mannanase on PKC can lead to formation of prebiotic compounds. Thus, this study suggests that utilization of PKC in poultry feed formulation might be increased by addition of a ß-mannanase and would improve the return on investment.


Assuntos
beta-Manosidase
6.
J Gen Intern Med ; 36(10): 3080-3087, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34379281

RESUMO

BACKGROUND: Age is a risk factor for COVID severity. Most studies performed in hospitalized patients with SARS-CoV2 infection have shown an over-representation of older patients and consequently few have properly defined COVID-19 in younger patients who require hospital admission. The aim of the present study was to analyze the clinical characteristics and risk factors for the development of respiratory failure among young (18 to 50 years) hospitalized patients with COVID-19. METHODS: This retrospective nationwide cohort study included hospitalized patients from 18 to 50 years old with confirmed COVID-19 between March 1, 2020, and July 2, 2020. All patient data were obtained from the SEMI-COVID Registry. Respiratory failure was defined as the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) ≤200 mmHg or the need for mechanical ventilation and/or high-flow nasal cannula or the presence of acute respiratory distress syndrome. RESULTS: During the recruitment period, 15,034 patients were included in the SEMI-COVID-19 Registry, of whom 2327 (15.4%) were younger than 50 years. Respiratory failure developed in 343 (14.7%), while mortality occurred in 2.3%. Patients with respiratory failure showed a higher incidence of major adverse cardiac events (44 (13%) vs 14 (0.8%), p<0.001), venous thrombosis (23 (6.7%) vs 14 (0.8%), p<0.001), mortality (43 (12.5%) vs 7 (0.4%), p<0.001), and longer hospital stay (15 (9-24) vs 6 (4-9), p<0.001), than the remaining patients. In multivariate analysis, variables associated with the development of respiratory failure were obesity (odds ratio (OR), 2.42; 95% confidence interval (95% CI), 1.71 to 3.43; p<0.0001), alcohol abuse (OR, 2.40; 95% CI, 1.26 to 4.58; p=0.0076), sleep apnea syndrome (SAHS) (OR, 2.22; 95% CI, 1.07 to 3.43; p=0.032), Charlson index ≥1 (OR, 1.77; 95% CI, 1.25 to 2.52; p=0.0013), fever (OR, 1.58; 95% CI, 1.13 to 2.22; p=0.0075), lymphocytes ≤1100 cells/µL (OR, 1.67; 95% CI, 1.18 to 2.37; p=0.0033), LDH >320 U/I (OR, 1.69; 95% CI, 1.18 to 2.42; p=0.0039), AST >35 mg/dL (OR, 1.74; 95% CI, 1.2 to 2.52; p=0.003), sodium <135 mmol/L (OR, 2.32; 95% CI, 1.24 to 4.33; p=0.0079), and C-reactive protein >8 mg/dL (OR, 2.42; 95% CI, 1.72 to 3.41; p<0.0001). CONCLUSIONS: Young patients with COVID-19 requiring hospital admission showed a notable incidence of respiratory failure. Obesity, SAHS, alcohol abuse, and certain laboratory parameters were independently associated with the development of this complication. Patients who suffered respiratory failure had a higher mortality and a higher incidence of major cardiac events, venous thrombosis, and hospital stay.


Assuntos
COVID-19 , Insuficiência Respiratória , Adolescente , Adulto , Estudos de Coortes , Hospitais , Humanos , Pessoa de Meia-Idade , RNA Viral , Sistema de Registros , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Espanha/epidemiologia , Adulto Jovem
7.
Arch Anim Nutr ; 74(2): 138-149, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31899960

RESUMO

The apparent total tract digestibility (ATTD) of nutrients can be assessed by total collection of faeces (TC), which is the reference method, or by the indicator method (IM). Little information is available on proper faecal sampling methodologies for IM in canines to obtain results comparable to TC. The objective of this study was to determine the minimum number of sub-samples required for the IM to make it comparable with TC. A total of 11 adult male dogs were individually housed in metabolism cages. Dogs had access to a grass yard to facilitate defaecation. Faecal sub-samples (1/day) were taken from the daily faecal output to prepare the pooled samples for IM, obtaining cumulative sample combinations of 3 (IM3), 4 (IM4), 5 (IM5), 6 (IM6) and 7 d (IM7). Digestibility of dry matter, gross energy, crude protein and crude fibre was similar between TC and IM5, IM6 and IM7 (p > 0.05). The IM7 presented the greatest statistical similarity with TC. Nevertheless, IM was not a good predictor of crude fibre digestibility. In conclusion, IM can replace the TC method in dogs to evaluate ATTD of several nutritional fractions as long as the composite sample is collected during seven consecutive days. For estimation of fibre digestibility by IM, longer collection periods are probably required.


Assuntos
Ciências da Nutrição Animal/métodos , Digestão , Nutrientes/metabolismo , Fisiologia/métodos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Cães , Fezes , Masculino
10.
Int J Urol ; 24(12): 826-832, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28901582

RESUMO

OBJECTIVES: To assess the level of agreement between digital rectal examination findings of two urologists and its effect on risk prediction using the digital rectal examination-based Rotterdam Prostate Cancer Risk Calculator. METHODS: The study sample consisted of a prospective cohort of asymptomatic unscreened men with prostate-specific antigen ≤50.0 ng/mL and transrectal ultrasound volume ≤110 mL who underwent transrectal ultrasound-guided prostate biopsy. Both urologists' digital rectal examination findings were graded normal or abnormal (nodularity and/or induration), and volume classified as 25, 40 or 60 mL, according to the risk calculator algorithm. Interrater agreement analysis using Cohen's kappa (κ) statistic was carried out to determine consistency of digital rectal examination outcome and volume assessment. Receiver operating characteristic curve analysis and calibration plots were constructed to determine the effect of interrater differences. Decision curve analysis was applied to evaluate the clinical usefulness of the model. RESULTS: Of the 241 men included in the study, 41% (n = 98) had prostate cancer (81 were clinically significant, i.e. Gleason ≥3 + 4). There was substantial agreement in the digital rectal examination (abnormal/normal; κ = 0.78; P < 0.001) and volume estimation (κ = 0.79; P < 0.001). Receiver operating characteristic analyses showed good discrimination (0.75-0.78) and were comparable for both urologists. In the high-risk cohort, at a probability threshold of 25%, the risk calculator reduced the prostate biopsy rate by 9%, without missing cancers. CONCLUSIONS: Slight differences in digital rectal examination findings seem to have very limited impact on the performance of the Rotterdam Prostate Cancer Risk Calculator. Therefore, this can be considered a useful prostate biopsy outcome prediction tool.


Assuntos
Exame Retal Digital/estatística & dados numéricos , Detecção Precoce de Câncer , Variações Dependentes do Observador , Neoplasias da Próstata/diagnóstico , Idoso , Área Sob a Curva , Biópsia/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Valor Preditivo dos Testes , Estudos Prospectivos , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Curva ROC , Medição de Risco , Ultrassonografia
11.
J Food Sci Technol ; 54(11): 3744-3751, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29051671

RESUMO

Abalone (Haliotis spp.) is an exotic seafood product recognized as a protein source of high biological value. Traditional methods used to preserve foods such as drying technology can affect their nutritional quality (protein quality and digestibility). A 28-day rat feeding study was conducted to evaluate the effects of the drying process assisted by high-pressure impregnation (HPI) (350, 450, and 500 MPa × 5 min) on chemical proximate and amino acid compositions and nutritional parameters, such as protein efficiency ratio (PER), true digestibility (TD), net protein ratio, and protein digestibility corrected amino acid score (PDCAAS) of dried abalone. The HPI-assisted drying process ensured excellent protein quality based on PER values, regardless of the pressure level. At 350 and 500 MPa, the HPI-assisted drying process had no negative effect on TD and PDCAAS then, based on nutritional parameters analysed, we recommend HPI-assisted drying process at 350 MPa × 5 min as the best process condition to dry abalone. Variations in nutritional parameters compared to casein protein were observed; nevertheless, the high protein quality and digestibility of HPI-assisted dried abalones were maintained to satisfy the metabolic demands of human beings.

12.
BMC Plant Biol ; 14: 77, 2014 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-24666927

RESUMO

BACKGROUND: The main bottleneck to elevate jatropha (Jatropha curcas L.) from a wild species to a profitable biodiesel crop is the low genetic and phenotypic variation found in different regions of the world, hampering efficient plant breeding for productivity traits. In this study, 182 accessions from Asia (91), Africa (35), South America (9) and Central America (47) were evaluated at genetic and phenotypic level to find genetic variation and important traits for oilseed production. RESULTS: Genetic variation was assessed with SSR (Simple Sequence Repeat), TRAP (Target Region Amplification Polymorphism) and AFLP (Amplified fragment length polymorphism) techniques. Phenotypic variation included seed morphological characteristics, seed oil content and fatty acid composition and early growth traits. Jaccard's similarity and cluster analysis by UPGM (Unweighted Paired Group Method) with arithmetic mean and PCA (Principle Component Analysis) indicated higher variability in Central American accessions compared to Asian, African and South American accessions. Polymorphism Information Content (PIC) values ranged from 0 to 0.65. In the set of Central American accessions. PIC values were higher than in other regions. Accessions from the Central American population contain alleles that were not found in the accessions from other populations. Analysis of Molecular Variance (AMOVA; P < 0.0001) indicated high genetic variation within regions (81.7%) and low variation across regions (18.3%). A high level of genetic variation was found on early growth traits and on components of the relative growth rate (specific leaf area, leaf weight, leaf weight ratio and net assimilation rate) as indicated by significant differences between accessions and by the high heritability values (50-88%). The fatty acid composition of jatropha oil significantly differed (P < 0.05) between regions. CONCLUSIONS: The pool of Central American accessions showed very large genetic variation as assessed by DNA-marker variation compared to accessions from other regions. Central American accessions also showed the highest phenotypic variation and should be considered as the most important source for plant breeding. Some variation in early growth traits was found within a group of accessions from Asia and Africa, while these accessions did not differ in a single DNA-marker, possibly indicating epigenetic variation.


Assuntos
Jatropha/genética , África , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Ásia , Biodiversidade , Análise por Conglomerados , Jatropha/classificação , Repetições de Microssatélites/genética , Filogenia , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , América do Sul
13.
Food Res Int ; 179: 114035, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342515

RESUMO

This study evaluated the influence of starch-protein interactions on the chemical properties and digestibility of a 3D-printed gel based on salmon by-product protein. Changes in the starch-protein interactions of the stable cornstarch (CS, 15%) and salmon protein isolate (SPI, 4%-12%) printable gels during the in vitro gastrointestinal digestion process were studied by principal component analysis. Protein-rich printed gels increased resistant starch content by 18.05%. Changes in chemical properties and the starch-protein concentration of the gels during the digestion process were highly correlated. The CS-SPI gels in the gastric and intestinal phases exhibited lower α-helix/ß-sheet ratio and fluorescence intensity values, whereas surface hydrophobicity increased. This resulted in more ordered structures with a high level of molecular interaction that inhibited enzymatic hydrolysis. This study provides crucial information about the transformations of starch-protein interactions during the digestibility of 3D-printed food matrices as an alternative source of nutrients with a high nutritional quality.


Assuntos
Salmão , Amido , Animais , Amido/química , Salmão/metabolismo , Proteínas/química , Géis/química , Alimentos Marinhos/análise , Impressão Tridimensional
14.
Vaccines (Basel) ; 12(2)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38400131

RESUMO

Maintaining respiratory tract health is crucial for layers, impacting gut health, laying performance, and egg quality. Viral diseases and standard vaccinations can compromise tracheal epithelium function, leading to oxidative stress. This study assessed the impact of a blend of feed additives, predominantly lysozyme (L), essential oils (EO), and vitamins (VIT) (referred to as L + EO + VIT), on young layers during an oral vaccination schedule. The supplementation significantly enhanced antibody titers for Newcastle Disease Virus (NDV) and Infectious Bronchitis Virus (IBV) after vaccination, trachea functionality and intestinal health in the jejunum, increased egg production, and exhibited a trend toward higher egg weight. Although feed intake showed no significant difference, egg quality remained consistent across experimental groups. Moreover, L + EO + VIT supplementation elevated total phenolic content in eggs, improving oxidative stability in both fresh and stored eggs, particularly under iron-induced oxidation. Notably, it substantially reduced yolk lipid peroxidation and albumen protein carbonyls. In conclusion, water supplementation with L + EO + VIT may enhance humoral immune response to IBV and NDV, positively impacting hen productivity. These findings indicate improved tracheal function and enhanced oxidative stability, emphasizing the potential of this blend in promoting overall health and performance in layers.

15.
Biomolecules ; 14(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38927060

RESUMO

Plasmacytoid dendritic cells (pDCs) are vital players in antiviral immune responses because of their high levels of IFN-α secretion. However, this attribute has also implicated them as critical factors behind the immunopathogenesis of inflammatory diseases, and no currently available therapy can efficiently inhibit pDCs' aberrant activation. Mesenchymal stromal cells (MSCs) possess stromal immunomodulatory functionality, regulating immune cell activation through several mechanisms, including the adenosinergic (CD39/CD73/adenosine) pathway. The IFN-γ preconditioning of bone marrow MSCs improves their inhibitory properties for therapy applications; however, isolating human gingival tissue-derived MSCs (hGMSCs) is more accessible. These cells have shown better immunomodulatory effects, yet the outcome of IFN-γ preconditioning and its impact on the adenosinergic pathway has not been evaluated. This study first validated the immunoregulatory properties of primary-cultured hGMSCs, and the results showed that IFN-γ preconditioning strengthens CD39/CD73 coexpression, adenosine production, and the regulatory properties of hGMSC, which were confirmed by describing for the first time their ability to reduce pDC activation and their IFN-α secretion and to increase the frequency of CD73+ pDC. In addition, when CD73's enzymatic activity was neutralized in hGMSCs, adenosine production and the IFN-γ preconditioning effect were restrained. This evidence might be applied to design hGMSCs- and adenosine-based immunotherapeutic strategies for treating inflammatory disorders that are associated with pDC overactivation.


Assuntos
5'-Nucleotidase , Adenosina , Células Dendríticas , Gengiva , Interferon gama , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/citologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Adenosina/metabolismo , Interferon gama/metabolismo , Gengiva/citologia , 5'-Nucleotidase/metabolismo , Células Cultivadas , Apirase/metabolismo , Proteínas Ligadas por GPI
16.
Anemia ; 2024: 4940760, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716363

RESUMO

Sickle cell anemia has been classified as a noninfectious neglected tropical disease and, although not exclusively, affects African descendants more frequently. This study aimed to detect asymptomatic sickle cell hemoglobin carriers (HbAS) in marginalized and vulnerable populations during a public health screening in African descendants from Oaxaca, Mexico, and to validate an amplification refractory mutation system (ARMS)-PCR methodology to detect fetal-hemoglobin (HbF)-regulating genetic variants in BCL11A toward affordable routine association of single nucleotide variants (SNVs) with HbF concentrations. To this aim, hemoglobin variants were detected by acidic citrate agar and alkaline cellulose acetate electrophoreses. SNVs in the hemoglobin subunit beta gene (HBB) were identified by the ß-globin mutation detection assay (ß-GMDA) and ARMS-PCR, respectively, and validated by Sanger sequencing. The association between genotypes and HbF concentrations was evaluated using Spearman's correlation coefficient. The results obtained during a directed screening in 140 self-identified African descendants revealed 42 HbS-carriers (30%), of which 39 showed normal total hemoglobin concentrations (92.8%), only 3 presented anemia (7.2%), and 9 showed quantifiable HbF concentration (21.4%). As validated by Sanger sequencing, the designed ARMS-PCR efficiently detected homozygous and heterozygous variants in BCL11A. In a cohort of 42 heterozygous (HbAS) and 27 healthy (HbAA) individuals from the same population, only one SNV (rs766432) showed statistically significant association with increasing HbF concentration, and two new unrelated homozygous silent variants were identified. This study reveals the need to raise coverage of HbS screening in vulnerable populations and shows a feasible low-cost ARMS-PCR methodology to determine the presence of SNVs in quantitative trait loci affecting HbF.

17.
Bioorg Med Chem Lett ; 23(12): 3576-9, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23659860

RESUMO

Aromatic oligovalent glycosyl disulfides and some diglycosyl disulfides were tested against three different Trypanosoma cruzi strains. Di-(ß-D-galactopyranosyl-dithiomethylene) benzenes 2b and 4b proved to be the most active derivatives against all three strains of cell culture-derived trypomastigotes with IC50 values ranging from 4 to 11 µM at 37 °C. The inhibitory activities were maintained, although somewhat lowered, at a temperature of 4 °C as well. Three further derivatives displayed similar activities against at least one of the three strains. Low cytotoxicities of the active compounds, tested on confluent HeLa, Vero and peritoneal macrophage cell cultures, resulted in significantly higher selectivity indices (SI) than that of the reference drug benznidazole. Remarkably, several molecules of the tested panel strongly inhibited the parasite release from T. cruzi infected HeLa cell cultures suggesting an effect against the intracellular development of T. cruzi amastigotes as well.


Assuntos
Antiprotozoários/farmacologia , Dissulfetos/farmacologia , Glicosídeos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Derivados de Benzeno/farmacologia , Doença de Chagas/tratamento farmacológico , Chlorocebus aethiops , Dissulfetos/química , Glicosídeos/química , Células HeLa , Humanos , Trypanosoma cruzi/crescimento & desenvolvimento , Células Vero
18.
Rev Esc Enferm USP ; 57: e20220319, 2023.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37184235

RESUMO

OBJECTIVE: To know emotional exhaustion in nursing students from four universities. METHOD: Cross-sectional, correlational study, carried out in Chile and Spain (2017-2018), with 1,368 students answering a self-applied instrument (sociodemographic/academic variables and the Emotional Exhaustion scale). Analysis with Stata 15, according to variables: Chi2 tests, Wilcoxon rank sum test (Mann Whitney U test), analysis of variance and multiple regression; confidence level 95% and significance 5% (p < 0.05). Approved by the Ethics Committee, Universidad de Girona. RESULTS: Academic variables and perceived stress with Quite Much/Much classification: Exams, Problem-Based Learning, Laboratory/Simulation. Statistically significant differences in emotional exhaustion, according to sex, dependent people, workers, commuting time >30 minutes. Greater emotional exhaustion when taking courses for the second time and in academic activities where they declare perceived stress as Quite Much/Much (p < 0.005). CONCLUSION: All students present mean level of emotional exhaustion (>26 and <37 points). The variables sex and having dependents are relevant aspects. Stress perceived by methodologies is significantly related to levels of emotional exhaustion.


Assuntos
Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Estudos Transversais , Inquéritos e Questionários , Emoções , Análise Multivariada
19.
Gels ; 9(9)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37754446

RESUMO

This study aimed to optimize the 3D printing parameters of salmon gelatin gels (SGG) using artificial neural networks with the genetic algorithm (ANN-GA) and response surface methodology (RSM). In addition, the influence of the optimal parameters obtained using the two different methodologies was evaluated for the physicochemical and digestibility properties of the printed SGG (PSGG). The ANN-GA had a better fit (R2 = 99.98%) with the experimental conditions of the 3D printing process than the RSM (R2 = 93.99%). The extrusion speed was the most influential parameter according to both methodologies. The optimal values of the printing parameters for the SGG were 0.70 mm for the nozzle diameter, 0.5 mm for the nozzle height, and 24 mm/s for the extrusion speed. Gel thermal properties showed that the optimal 3D printing conditions affected denaturation temperature and enthalpy, improving digestibility from 46.93% (SGG) to 51.52% (PSGG). The secondary gel structures showed that the ß-turn structure was the most resistant to enzymatic hydrolysis, while the intermolecular ß-sheet was the most labile. This study validated two optimization methodologies to achieve optimal 3D printing parameters of salmon gelatin gels, with improved physicochemical and digestibility properties for use as transporters to incorporate high value nutrients to the body.

20.
Sci Rep ; 13(1): 22129, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092821

RESUMO

The emergence of large language models (LLM) with remarkable performance such as ChatGPT and GPT-4, has led to an unprecedented uptake in the population. One of their most promising and studied applications concerns education due to their ability to understand and generate human-like text, creating a multitude of opportunities for enhancing educational practices and outcomes. The objective of this study is twofold: to assess the accuracy of ChatGPT/GPT-4 in answering rheumatology questions from the access exam to specialized medical training in Spain (MIR), and to evaluate the medical reasoning followed by these LLM to answer those questions. A dataset, RheumaMIR, of 145 rheumatology-related questions, extracted from the exams held between 2010 and 2023, was created for that purpose, used as a prompt for the LLM, and was publicly distributed. Six rheumatologists with clinical and teaching experience evaluated the clinical reasoning of the chatbots using a 5-point Likert scale and their degree of agreement was analyzed. The association between variables that could influence the models' accuracy (i.e., year of the exam question, disease addressed, type of question and genre) was studied. ChatGPT demonstrated a high level of performance in both accuracy, 66.43%, and clinical reasoning, median (Q1-Q3), 4.5 (2.33-4.67). However, GPT-4 showed better performance with an accuracy score of 93.71% and a median clinical reasoning value of 4.67 (4.5-4.83). These findings suggest that LLM may serve as valuable tools in rheumatology education, aiding in exam preparation and supplementing traditional teaching methods.


Assuntos
Reumatologia , Humanos , Escolaridade , Transporte Biológico , Hidrolases , Idioma
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