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1.
Int J Mol Sci ; 24(6)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36982461

RESUMO

High-density lipoproteins (HDLs) are known to enhance vascular function through different mechanisms, including the delivery of functional lipids to endothelial cells. Therefore, we hypothesized that omega-3 (n-3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of HDLs would improve the beneficial vascular effects of these lipoproteins. To explore this hypothesis, we performed a placebo-controlled crossover clinical trial in 18 hypertriglyceridemic patients without clinical symptoms of coronary heart disease who received highly purified EPA 460 mg and DHA 380 mg, twice a day for 5 weeks or placebo. After 5 weeks of treatment, patients followed a 4-week washout period before crossover. HDLs were isolated using sequential ultracentrifugation for characterization and determination of fatty acid content. Our results showed that n-3 supplementation induced a significant decrease in body mass index, waist circumference as well as triglycerides and HDL-triglyceride plasma concentrations, whilst HDL-cholesterol and HDL-phospholipids significantly increased. On the other hand, HDL, EPA, and DHA content increased by 131% and 62%, respectively, whereas 3 omega-6 fatty acids significantly decreased in HDL structures. In addition, the EPA-to-arachidonic acid (AA) ratio increased more than twice within HDLs suggesting an improvement in their anti-inflammatory properties. All HDL-fatty acid modifications did not affect the size distribution or the stability of these lipoproteins and were concomitant with a significant increase in endothelial function assessed using a flow-mediated dilatation test (FMD) after n-3 supplementation. However, endothelial function was not improved in vitro using a model of rat aortic rings co-incubated with HDLs before or after treatment with n-3. These results suggest a beneficial effect of n-3 on endothelial function through a mechanism independent of HDL composition. In conclusion, we demonstrated that EPA and DHA supplementation for 5 weeks improved vascular function in hypertriglyceridemic patients, and induced enrichment of HDLs with EPA and DHA to the detriment of some n-6 fatty acids. The significant increase in the EPA-to-AA ratio in HDLs is indicative of a more anti-inflammatory profile of these lipoproteins.


Assuntos
Ácidos Graxos Ômega-3 , Animais , Ratos , Ácido Araquidônico , Estudos Cross-Over , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/farmacologia , Células Endoteliais , Ácidos Graxos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Lipoproteínas , Triglicerídeos , Humanos
2.
Molecules ; 26(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34770839

RESUMO

Studies on polyphenols and flavonoids in natural products reveal benefits in the prevention of multiple diseases. Proper extraction, treatment of extracts, and quantification of polyphenols and flavonoids demand attention from the scientific community in order to report more specific biological action. Total polyphenol content (TPC) and total flavonoid content (TFC) (measured at three different times) of ethanol, methanol and acetone extracts of Mauritia flexuosa (aguaje) and Theobroma grandiflorum (copoazú) fresh pulp, from the Colombian Amazon region, were evaluated with the purpose of focusing in the polyphenol/flavonoid proportion and its effective antioxidant activity. This objective could help to explain specific flavonoid biological action based on higher flavonoid proportion rather than higher total polyphenol content. Differences in extracting solvents resulted in statistically significant different yields; the highest TPC was observed with acetone 70% in Mauritia flexuosa and ethanol 80% for T. grandiflorum. The best flavonoid/polyphenol ratio in M. flexuosa was about 1:2.4 and 1:12.8 in T. grandiflorum and the antioxidant efficacy was proportionally higher for flavonoids extracted from T. grandiflorum. HPLC analysis revealed 54 µg/g of the flavonoid kaempferol in M. Flexuosa and 29 µg/g in T. grandiflorum. Further studies evaluating this proportionality, in seeds or peel of fruits, as well as, other specific biological activities, could help to understand the detailed flavonoid action without focusing on the high total polyphenol content.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Cacau/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Antioxidantes/análise , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Frutas/química , Compostos Fitoquímicos , Extratos Vegetais/química , Polifenóis/química , Solventes , Análise Espectral
3.
Adicciones ; 33(2): 137-148, 2021 Mar 31.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32677693

RESUMO

Nomophobia is a situational phobia leading to a deep, irrational, and disproportionate fear of not being able to use the smartphone. An instrumental study on the Spanish version of the Nomophobia Questionnaire (NMP-Q) was carried out. The objectives were: 1) To analyse its factor structure and reliability; 2) to test for the invariance of sex and age groups, and 3) to obtain specific cut-off points by sex and age non-existent to date. Sampling was incidental and non-probabilistic with 5012 participants (57.9%, females) aged 12-24 years (M = 18.04, SD = 3.3). The confirmatory factor analysis revealed a hierarchical model with four correlated factors explained by a general second-order factor. The internal validity and reliability values of the NMP-Q dimensions are satisfactory, ranging between .78, .85, .86, and .92 (Omega w). A multigroup analysis confirmed the invariance across sex and age groups. Building on the NMP-Q scores, we calculated 3 cut-off points using percentiles 15th, 80th and 95th (unnomophobic, at risk of nomophobia, and nomophobic). Females aged 12-15 years had the highest nomophobic scores. We can conclude that the proposed sex and age cut-off points will allow us to better identify nomophobic problems from a clinical point of view.


La nomofobia es una fobia situacional en la que se experimenta un miedo intenso, irracional y desproporcionado a no poder usar el smartphone. Se realizó un estudio instrumental de la versión española del cuestionario de Nomofobia (NMP-Q) con los objetivos de: 1) analizar su estructura factorial y fiabilidad; 2) analizar su invarianza con relación al sexo y la edad, y 3) obtener puntos de cortes específicos para distintas edades y sexo. El muestreo fue incidental y no probabilístico. Hubo 5012 participantes (57.9%, mujeres) de 12-24 años (M = 18,04, SD = 3,3). El análisis factorial confirmatorio mostró un modelo jerárquico de 4 factores correlacionados y explicados por uno general de segundo orden. Los índices de fiabilidad de las dimensiones del NMP-Q fueron satisfactorios oscilando entre ,78, ,85, ,86 y ,92 (Omega w). Un análisis multigrupo confirmó la invarianza por sexo y edad. A partir de las puntuaciones del NMP-Q se calcularon 3 puntos de corte siguiendo los percentiles 15, 80 y 95 (sin nomofobia, riesgo de nomofobia, y nomofóbico). Las mujeres de 12-15 años tuvieron las puntuaciones más altas en nomofobia. Podemos concluir que el NMP-Q nos permite identificar problemas de nomofobia por sexo y edad desde un punto de vista clínico.


Assuntos
Transtornos Fóbicos , Análise Fatorial , Feminino , Humanos , Masculino , Transtornos Fóbicos/diagnóstico , Reprodutibilidade dos Testes , Smartphone , Inquéritos e Questionários
4.
J Cutan Pathol ; 47(11): 1076-1079, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32761868

RESUMO

Polyarteritis nodosa (PAN) is a necrotizing vasculitis. The clinical manifestations are determined by the location of the compromised arteries. Cutaneous PAN can present as nodular lesions similar to erythema nodosum, palpable purpura, livedo reticularis, and ulceration. It often affects the lower limbs but other anatomical sites can also be involved. However, concomitant facial edema is an extremely rare manifestation. It has been more than 20 years since the last case report describing this unusual presentation of PAN. Furthermore, our patient is the first case presenting with hemifacial edema fluctuating every second or third day due to PAN confirmed by skin biopsy.


Assuntos
Edema/etiologia , Face/patologia , Poliarterite Nodosa/patologia , Dermatopatias/patologia , Humanos , Masculino , Poliarterite Nodosa/complicações , Dermatopatias/etiologia , Adulto Jovem
5.
Fetal Diagn Ther ; 45(3): 168-175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29635237

RESUMO

OBJECTIVE: To assess the added value of maternal serum levels of IL-6 in women with preterm-prelabor rupture of membranes (PPROM) as a non-invasive test for the prediction of histological chorioamnionitis (HCA). METHODS: This was a prospective cohort study of pregnant women between 20 + 0 and 36 + 6 weeks of gestation with a confirmed diagnosis of PPROM. Logistic regression models were created for the prediction of HCA and compared by assessing the improvement in their Naegelkerke R2 as a measure of goodness of fit. Predictive performance of all models was assessed by receiver operating characteristics curve (ROC) analysis and compared by the DeLong method. RESULTS: From 47 women with PPROM, 31 (66%) developed HCA. Maternal serum IL-6 ≥19.5 pg/dL was the best cut-off point for the prediction of HCA (OR = 15; 95% CI: 3.6-61; p < 0.01). A model comprising maternal characteristics and IL-6 ≥19.5 pg/dL showed an area under the curve of 0.85 (95% CI: 0.74-0.95), significantly improving the previous models of IL-6 ≥19.5 pg/dL (R2: 23.3 vs. 34.1%; p = 0.01) or maternal characteristics (R2: 8.4 vs. 34.1%; p < 0.01). CONCLUSIONS: A model comprising maternal serum levels of IL-6 plus maternal characteristics proves to be a good non-invasive predictor of HCA.


Assuntos
Corioamnionite/diagnóstico , Ruptura Prematura de Membranas Fetais/diagnóstico , Interleucina-6/sangue , Adulto , Biomarcadores/sangue , Corioamnionite/sangue , Feminino , Ruptura Prematura de Membranas Fetais/sangue , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos , Adulto Jovem
6.
Scand J Psychol ; 60(2): 160-168, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30690725

RESUMO

This study explores the psychometric properties of the Cyberbullying Triangulation Questionnaire (CTQ), which measures and triangulates the roles of cybervictimization, cyberaggression, and cyberbystanding. The study sample was composed of 5,036 Spanish students with a mean age of 14.19 years (SD = ±1.7; range = 10-23 years). Confirmatory factor analysis of the three correlated-factor model yielded a high goodness of fit. Reliability as measured by Omega coefficients was adequate (>0.94). The measurement model was invariant for the two age groups (10-14 years and 15-23 years). Cybervictimization and cyberaggression correlated with offline victimization and aggression (r = 0.49; p < 0.001; r = 0.57; p < 0.001, respectively). The results show that the most prevalent cyberbystanding subrole was that of the Defender of the Victim (54.6%), and that cyberaggression and cyberbystanding were more prevalent among male adolescents (p < 0.001). The lack of parental control over children's use of the mobile phone was associated with cyberaggression (p < 0.001).


Assuntos
Comportamento do Adolescente/psicologia , Vítimas de Crime/psicologia , Cyberbullying/psicologia , Psicometria/instrumentação , Inquéritos e Questionários/normas , Adolescente , Adulto , Criança , Vítimas de Crime/estatística & dados numéricos , Cyberbullying/estatística & dados numéricos , Feminino , Humanos , Masculino , Prevalência , Psicometria/normas , Reprodutibilidade dos Testes , Fatores Sexuais , Espanha/epidemiologia , Adulto Jovem
7.
Biol Res ; 50(1): 42, 2017 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-29268779

RESUMO

BACKGROUND: Fresh frozen plasma (FFP) administration may increase the risk of nosocomial infections in parallel with the development of immune modulation. This could be driven by soluble mediators, possibly influencing the in vitro activation of human U937 monocyte cells, in a manner dependent on the age of the donors. METHODS: FFP donors were stratified into groups of 19-30 years, 31-40 years or 41-50 years, and U937 cells were cultured with FFP (alone or plus lipopolysaccharide-LPS) for 24 h. Both in FFP and supernatants, TNF, IL-1ß, IL-6, and IL-10 levels were measured by ELISA. Additionally, CD11B, TLR2, and CASP3 gene expression were measured by qtPCR in U937 cells. Total phagocytic activity was also assayed. RESULTS: Elevated IL-10, but low TNF and IL-1ß levels were measured in FFP from individuals aged 19-40 years, whereas in individuals aged 41-50 years FFP were characterized by equalized TNF and IL-10 levels. Elevated IL-6 levels were found in all FFP samples, especially in those from the oldest individuals. FFP stimulation was associated with striking modifications in cytokine production in an age-dependent way. Exposure to FFP attenuates the response to LPS. TLR2 and CD11B expression were enhanced regardless of the age of plasma donors, although CASP3 expression was increased only when FFP from individuals aged 19-40 years were tested. Phagocytosis decreased after exposure to FFP regardless of donor age. CONCLUSION: Our results suggest that soluble mediators in FFP may modulate the functioning of monocytes. Interestingly, this effect appears to be partially influenced by the age of donors.


Assuntos
Doadores de Sangue , Citocinas/imunologia , Monócitos/imunologia , Plasma/imunologia , Células U937/imunologia , Adulto , Fatores Etários , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
8.
Arch Orthop Trauma Surg ; 137(8): 1077-1085, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28555367

RESUMO

INTRODUCTION: Subtrochanteric fractures are more difficult to treat than other proximal femoral fractures. The aim of this study was to report the outcomes for patients with subtrochanteric fractures treated using a cephalomedullary nail following open reduction and cerclage wiring versus closed reduction alone, regarding health-related quality of life (HRQoL) and social function. MATERIALS AND METHODS: We performed a prospective cohort study including patients aged 60 years or older suffering fragility subtrochanteric fractures of the femur treated with cephalomedullary nails, with a minimum 2-year follow-up. We defined two treatment groups: one treated with closed reduction manoeuvres (60 patients), and another treated with open reduction and cerclage wiring (30 patients). The outcomes were mortality, orthopaedic complications (reoperation and no-union), social function (Jensen Index), and HRQoL (EQ-5D index score). RESULTS: There were no differences regarding sex, age, side affected, type of implant, anaesthetic risk, 1-year mortality, and orthopaedic complications. Surgical time was longer in the cerclage wire group, but length of stay was 2 days shorter for the cerclage group and reduction was better. Patients treated with cerclage wiring had significantly better EQ-ED at 12 months (0.66 ± 0.22 points vs. 0.78 ± 0.15 points); and social status at 12 and 18 months (2.77 ± 1.00 points vs. 2.10 ± 1.22 points). CONCLUSIONS: Better reduction is achieved when using cerclage wires for fragility subtrochanteric fractures. These fractures had a negative effect on quality of life and social function, but better outcomes were observed in the cerclage group.


Assuntos
Fios Ortopédicos , Redução Fechada , Fixação Intramedular de Fraturas , Fraturas do Quadril/cirurgia , Redução Aberta , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Fios Ortopédicos/efeitos adversos , Fios Ortopédicos/estatística & dados numéricos , Redução Fechada/efeitos adversos , Redução Fechada/estatística & dados numéricos , Feminino , Fixação Intramedular de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/métodos , Fixação Intramedular de Fraturas/estatística & dados numéricos , Humanos , Masculino , Redução Aberta/efeitos adversos , Redução Aberta/estatística & dados numéricos , Estudos Prospectivos
9.
Actas Esp Psiquiatr ; 45(4): 137-44, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28745386

RESUMO

INTRODUCTION: Nomophobia is the fear of being out of mobile phone contact. People suffering from this anxiety disorder have feelings of stress and nervousness when access to their mobiles or computers is not possible. This work is an adaptation and validation study of the Spanish version of the Nomophobia Questionnaire (NMP-Q). METHODOLOGY: The study included 306 students (46.1% males and 53.9% females) with ages ranging 13 to 19 years (Md=15.41±1.22). RESULTS: Exploratory factor analysis revealed four dimensions that accounted for 64.4% of total variance. The ordinal α-value was 0.95, ranging from 0.75 to 0.92 across factors. Measure of stability was calculated by the testretest method (r=0.823). Indicators of convergence with the Spanish versions of the “Mobile Phone Problem Use Scale” (r=0.654) and the “Generalized Problematic Internet Use Scale” (r=0.531) were identified. Problematic mobile phone use patterns were examined taking the 15P, 80P and 95P percentiles as cut-off points. Scores of 39, 87 and 116 on NMP-Q corresponded to occasional, at-risk and problematic users, respectively. CONCLUSIONS: Psychometric analysis shows that the Spanish version of the NMP-Q is a valid and reliable tool for the study of nomophobia.


Assuntos
Telefone Celular , Transtornos Fóbicos/diagnóstico , Autorrelato , Adolescente , Feminino , Humanos , Masculino , Traduções , Adulto Jovem
10.
Clin Case Rep ; 12(5): e8854, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38689688

RESUMO

Crusted scabies is a severe form of scabies infestation caused by the ectoparasite Sarcoptes scabiei. Risk factors include immunosuppression, neuropathies, and psychiatric disorders. Its management poses important challenges due to its contagius nature. Here we present a case or Acute Generalized Exanthematous Pustulosis secondary to Ivermectin therapy in a patient with crusted scabies.

11.
Behav Sci (Basel) ; 14(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39062435

RESUMO

This study analyzes the perception and usage of ChatGPT based on the technology acceptance model (TAM). Conducting reticular analysis of coincidences (RAC) on a convenience survey among university students in the social sciences, this research delves into the perception and utilization of this artificial intelligence tool. The analysis considers variables such as gender, academic year, prior experience with ChatGPT, and the training provided by university faculty. The networks created with the statistical tool "CARING" highlight the role of perceived utility, credibility, and prior experience in shaping attitudes and behaviors toward this emerging technology. Previous experience, familiarity with video games, and programming knowledge were related to more favorable attitudes towards ChatGPT. Students who received specific training showed lower confidence in the tool. These findings underscore the importance of implementing training strategies that raise awareness among students about both the potential strengths and weaknesses of artificial intelligence in educational contexts.

12.
Biomol Biomed ; 24(2): 302-314, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-37688493

RESUMO

Marfan syndrome (MFS) is a multisystem genetic disorder with over 3000 mutations described in the fibrillin 1 (FBN1) gene. Like MFS, other connective tissue disorders also require a deeper understanding of the phenotype-genotype relationship due to the complexity of the clinical presentation, where diagnostic criteria often overlap. Our objective was to identify mutations in patients with connective tissue disorders using a genetic multipanel and to analyze the genotype-phenotype associations in a cohort of Mexican patients. We recruited 136 patients with MFS and related syndromes from the National Institute of Cardiology. Mutations were identified using next-generation sequencing (NGS). To examine the correlation between mutation severity and severe cardiovascular conditions, we focused on patients who had undergone Bentall-de Bono surgery or aortic valve repair. The genetic data obtained allowed us to reclassify the initial clinical diagnosis across various types of connective tissue disorders. The transforming growth factor beta receptor 2 (TGFBR2) rs79375991 mutation was found in 10 out of 16 (63%) Loeys-Dietz patients. We observed a high prevalence (65%) of more severe mutations, such as frameshift indels and stop codons, among patients requiring invasive treatments like aortic valve-sparing surgery, Bentall and de Bono procedures, or aortic valve replacement due to severe cardiovascular injury. Although our study did not achieve precise phenotype-genotype correlations, it underscores the importance of a multigenetic panel evaluation. This could pave the way for a more comprehensive diagnostic approach and inform medical and surgical treatment decision-making.


Assuntos
Doenças Cardiovasculares , Doenças do Tecido Conjuntivo , Síndrome de Marfan , Humanos , Síndrome de Marfan/diagnóstico , Receptores de Fatores de Crescimento Transformadores beta/genética , Proteínas Serina-Treonina Quinases/genética , Fibrilina-1/genética , Tecido Conjuntivo
13.
Biochim Biophys Acta ; 1823(10): 1756-66, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22796641

RESUMO

XAB1/Gpn1 is a GTPase that associates with RNA polymerase II (RNAPII) in a GTP-dependent manner. Although XAB1/Gpn1 is essential for nuclear accumulation of RNAPII, the underlying mechanism is not known. A XAB1/Gpn1-EYFP fluorescent protein, like endogenous XAB1/Gpn1, localized to the cytoplasm but it rapidly accumulated in the cell nucleus in the presence of leptomycin B, a chemical inhibitor of the nuclear transport receptor Crm1. Crm1 recognizes short peptides in substrate proteins called nuclear export sequences (NES). Here, we employed site-directed mutagenesis and fluorescence microscopy to assess the functionality of all six putative NESs in XAB1/Gpn1. Mutating five of the six putative NESs did not alter the cytoplasmic localization of XAB1/Gpn1-EYFP. However, a V302A/L304A double mutant XAB1/Gpn1-EYFP protein was clearly accumulated in the cell nucleus, indicating the disruption of a functional NES. This functional XAB1/Gpn1 NES displays all features present in most common and potent NESs, including, in addition to Φ1-Φ4, a critical fifth hydrophobic amino acid Φ0. Therefore, in human Gpn1 this NES spans amino acids 292-LERLRKDMGSVAL-304. XAB1/Gpn1 NES is remarkably conserved during evolution. XAB1/Gpn1 NES was sufficient for nuclear export activity, as it caused a complete exclusion of EYFP from the cell nucleus. Molecular modeling of XAB1/Gpn1 provided a mechanistic reason for NES selection, as functionality correlated with accessibility, and it also suggested a mechanism for NES inhibition by intramolecular masking. In conclusion, we have identified a highly active, evolutionarily conserved NES in XAB1/Gpn1 that is critical for nucleo-cytoplasmic shuttling and steady-state cytoplasmic localization of XAB1/Gpn1.


Assuntos
Núcleo Celular/enzimologia , Sinais de Exportação Nuclear , RNA Polimerase II/metabolismo , Transporte Ativo do Núcleo Celular , Sequência de Aminoácidos , Sequência Conservada/genética , Evolução Molecular , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/metabolismo , Genes Reporter , Células HEK293 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Secundária de Proteína , Proteínas Recombinantes de Fusão/metabolismo , Relação Estrutura-Atividade
14.
J Infect Dis ; 206(2): 220-8, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22551809

RESUMO

Benznidazole is the frontline drug used against Trypanosoma cruzi, the causative agent of Chagas disease. However, treatment failures are often reported. Here, we demonstrate that independently acquired mutations in the gene encoding a mitochondrial nitroreductase (TcNTR) can give rise to distinct drug-resistant clones within a single population. Following selection of benznidazole-resistant parasites, all clones examined had lost one of the chromosomes containing the TcNTR gene. Sequence analysis of the remaining TcNTR allele revealed 3 distinct mutant genes in different resistant clones. Expression studies showed that these mutant proteins were unable to activate benznidazole. This correlated with loss of flavin mononucleotide binding. The drug-resistant phenotype could be reversed by transfection with wild-type TcNTR. These results identify TcNTR as a central player in acquired resistance to benznidazole. They also demonstrate that T. cruzi has a propensity to undergo genetic changes that can lead to drug resistance, a finding that has implications for future therapeutic strategies.


Assuntos
Resistência a Medicamentos/genética , Nitroimidazóis/farmacologia , Nitrorredutases/genética , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Alelos , Sequência de Aminoácidos , Animais , Chlorocebus aethiops , Clonagem Molecular , Regulação da Expressão Gênica , Variação Genética , Dados de Sequência Molecular , Mutação , Nitrorredutases/química , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Ratos , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/genética , Células Vero
15.
Clin Pharmacol Ther ; 113(2): 321-327, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36372942

RESUMO

Pharmacogenetic implementation programs are increasingly feasible due to the availability of clinical guidelines for implementation research. The utilization of these resources has been reported with selected drug-gene pairs; however, little is known about how prescribers respond to pharmacogenetic recommendations for statin therapy. We prospectively assessed prescriber interaction with point-of-care clinical decision support (CDS) to guide simvastatin therapy for a diverse cohort of primary care patients enrolled in a clinical pharmacogenetics program. Of the 1,639 preemptively genotyped patients, 298 (18.2%) had an intermediate function (IF) OATP1B1 phenotype and 25 (1.53%) had a poor function (PF) phenotype, predicted by a common single nucleotide variant in the SLCO1B1 gene (c.521T>C; rs4149056). Clinicians were presented with CDS when simvastatin was prescribed for patients with IF or PF through the electronic health record. Importantly, 64.2% of the CDS deployed at the point-of-care was accepted by the prescribers and resulted in prescription changes. Statin intensity was found to significantly influence prescriber adoption of the pharmacogenetic-guided CDS, whereas patient gender or race, prescriber type, or pharmacogenetic training status did not significantly influence adoption. This study demonstrates that primary care providers readily adopt pharmacogenetic information to guide statin therapy for the majority of patients with preemptive genotype data.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Inibidores de Hidroximetilglutaril-CoA Redutases , Sinvastatina , Genótipo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Farmacogenética/métodos , Sinvastatina/uso terapêutico , Humanos
16.
Am J Med Sci ; 363(1): 64-68, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32732076

RESUMO

Adrenal medullary hyperplasia is a cause of increased secretion of catecholamines by the adrenal gland that is rarely considered among the differential diagnoses of endocrine hypertension. We report the case of a 48-year-old Hispanic woman who presented for evaluation of resistant hypertension with several episodes of hypertensive crisis. The clinical presentation, biochemical results, and abdominal computed tomography scan suggested the possibility of a pheochromocytoma; however, an iodine-123-meta-iodobenzylguanidine (123I-MIBG) uptake study combined with single-photon emission computed tomography (SPECT) and computed tomography (CT) scan showed diffusely increased metabolic activity in both adrenal glands. The patient underwent left adrenalectomy, and the pathology study revealed the presence of adrenal medullary hyperplasia. After surgery, blood pressure control was achieved with one antihypertensive drug, and the patient did not have recurrent hypertensive crisis. Relevant findings obtained from a whole genomic sequence done on a whole blood DNA sample from the patient are discussed.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/patologia , Adrenalectomia , Feminino , Humanos , Hiperplasia , Hipertensão/etiologia , Pessoa de Meia-Idade , Feocromocitoma/patologia
17.
Biomedica ; 42(2): 278-289, 2022 06 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35867921

RESUMO

Introduction: About 80-95% of patients infected with the human immunodeficiency virus (HIV) develop skin manifestations, which are markers of the patients' immune status. Objective: To describe the dermatologic manifestations and the clinical and sociodemographic factors of hospitalized patients diagnosed with HIV and their correlation with CD4 T-lymphocyte count. Materials and methods: We conducted an observational, cross-sectional, and retrospective study of the medical records of 227 adult patients with HIV diagnosis evaluated by dermatology in a hospital in Medellín, Colombia. Results: We included 227 patient records with 433 dermatologic manifestations, 64.4% of them infectious. The most frequent manifestations were oral candidiasis, condylomata acuminata, and drug reactions. Moreover, a statistically significant relationship was found between disseminated herpes zoster virus and secondary syphilis with a CD4 count between 200-499 cells/mm3 (p=0.04 and 0.028, respectively). There was also a statistically significant relationship between oral candidiasis and a CD4 count of less than 100 cells/mm3 (p=0.008). Conclusions: The relationship between disseminated herpes zoster with CD4 between 200-499 cells/mm3 suggests that, despite having high CD4 counts, severe forms of the disease may occur due to possible T-cell dysfunction and depletion of the immune system. Additionally, the relationship between oral candidiasis and CD4 less than 100 cells/mm3 indicates the potential role of oral candidiasis as an essential marker of weakened immune status in HIV patients.


Introducción. Entre el 80 y el 95 % de los pacientes infectados por el virus de inmunodeficiencia humana (HIV) desarrollan manifestaciones en la piel que sirven como marcadores de su estado inmunológico. Objetivos. Describir las manifestaciones dermatológicas y los factores clínicos y sociodemográficos de los pacientes hospitalizados con diagnóstico de HIV y su correlación con el recuento de linfocitos T CD4. Materiales y métodos. Se hizo un estudio observacional de corte transversal y retrospectivo a partir del registro de las historias clínicas de 227 pacientes mayores de edad con diagnóstico de HIV, evaluados por dermatología en un hospital de Medellín, Colombia. Resultados. Los 227 registros daban cuenta de 433 manifestaciones dermatológicas, el 64,4 % de ellas infecciosas. Las tres manifestaciones más frecuentes fueron candidiasis oral, condilomas acuminados y reacciones a medicamentos. Se encontró una relación estadísticamente significativa entre el virus del herpes zóster (HZ) diseminado y la sífilis secundaria, con un recuento de CD4 entre 200 y 499 células/mm3 (p=0,04 y 0,028, respectivamente), y entre la candidiasis oral y un recuento de CD4 menor de 100 células/mm3 (p=0,008). Conclusiones. La relación entre el herpes zóster diseminado y un recuento de CD4 entre 200 y 499 células/mm3 sugiere que, a pesar de los recuentos altos, se pueden presentar formas graves de la enfermedad debido a una posible disfunción de las células T y el agotamiento del sistema inmunológico. La relación entre la candidiasis oral y un recuento de CD4 menor de 100 células/mm3 plantea la posibilidad de considerar esta infección micótica como un marcador importante de debilitamiento inmunológico de los pacientes con HIV.


Assuntos
Candidíase , Infecções por HIV , Herpes Zoster , Colômbia/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Estudos Retrospectivos
18.
Brain Res ; 1783: 147836, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35182572

RESUMO

OBJECTIVE: Evaluate changes in brain activity of trainees during laparoscopic surgical training from electroencephalographic (EEG) signals in an ecological scenario with few restrictions for the user. DESIGN: Longitudinal study with two follow-up measurements in the first and last session of a 4-week training with LapSim laparoscopic surgery simulator. Variables analyzed include EEG neuronal activations in theta and alpha bands, tasks performance measures, and subjective measures such as perception of mental workload. SETTING: Medical School, Universidad de Antioquia, Medellin, Colombia. PARTICIPANTS: First-year surgical residents (n = 16, age = 28.0 ± 2.6 years old, right-handed, 9 females) RESULTS: Significant improvements in tasks performance were found together with changes in neuronal activity over frontal and parietal cortex. These changes were also correlated with task performance through training sessions. CONCLUSIONS: The use of neurophysiological measures such as electroencephalography combined with source separation techniques allows evaluating neural changes associated with motor training. The experiment proposed in this work establishes less controlled recording conditions leading to a more realistic analysis scenario to cognitive assessment in residents training.


Assuntos
Competência Clínica , Laparoscopia , Adulto , Encéfalo/cirurgia , Simulação por Computador , Eletroencefalografia/métodos , Feminino , Humanos , Laparoscopia/educação , Laparoscopia/métodos , Estudos Longitudinais , Masculino
19.
Animals (Basel) ; 12(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36077930

RESUMO

The main marketed parts of squid are the mantle, the head with tentacles, and fins. However, when the whole squid does not meet quality standards for human consumption it can be used for broiler feed. The objective of the study was to include giant squid (Dosidicus gigas) meal (GSM) in broiler rations to increase the content of the n-3 fatty acids eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) in chicken meat. Two hundred Ross 380 chickens, half male, half female, and one day old, were randomly distributed in a 4x2x2 factorial arrangement. The factors were the treatment (0%, 1.67%, 3.34%, and 5.01% of GSM in the diet), sex, and content of n-3 in the legs with thighs and the breasts. Each treatment had five repetitions with 10 birds each. There were no differences (p > 0.05) in the production parameters for both sexes. The contents of EPA, DPA, and DHA increased in the females and in the legs with thighs (p < 0.05) with GSM. Acceptance for the flavor and texture of meat was higher in the treatment with 1.67% GSM than in the other treatments. It is concluded that GSM is an alternative for increasing the amount of n-3 in chicken meat.

20.
Am J Med Sci ; 364(5): 583-594, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35508283

RESUMO

BACKGROUND: In regards to breast cancer (BC), survival or disease-free periods are still compromised mainly in Triple Negative (TN) and HER2 tumors. The participation of estrogen receptor (ER) has been reported as crucial in the signaling pathways, including the NOTCH pathway. The study was aimed to evaluate the expression of NOTCH1 and NOTCH3 in BC and its relationship with the presence of ER, as well as with relapses. METHODS: NOTCH1 and NOTCH3 expression was evaluated in BC using Oncomine database, Breast Cancer Gene Expression Miner database and Kaplan Meier Plotter. Subsequently, detection of NOTCH1 and NOTCH3 in 100 paraffin-embedded BC samples from Mexican patients was achieved by immunohistochemistry (IHC) and RT-qPCR, a group of benign breast tumors were included as controls. Relapses were evaluated by BC subtypes and their relationship with NOTCH1 and NOTCH3 expression, as well as with ER expression. RESULTS: The analyses from public databases of TN and HER2 groups, which are estrogen receptor-negative (ERN), revealed NOTCH1 and NOTCH3 expression variability. The overexpression was associated with lower relapse-free survival (P = 0.00019). These data were concordant with results from tumor samples of patients included in this study, which showed overexpression of NOTCH1 and NOTCH3 in ERN tumors, as well as lower relapse-free survival (P < 0.0001). CONCLUSIONS: NOTCH1 and NOTCH3 were found to be overexpressed mainly in ERN tumors. HER2 and TN groups, are related to higher relapse rates. Therefore, anti-NOTCH therapy could be justified and implemented in conventional treatments of high-risk BC groups.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/metabolismo , Imuno-Histoquímica , Recidiva Local de Neoplasia/genética , Receptores de Estrogênio/genética , Transdução de Sinais , Receptores Notch
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