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1.
Front Plant Sci ; 15: 1416538, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011310

RESUMO

Optimization of a breeding program requires assessing and quantifying empirical genetic trends made through past efforts relative to the current breeding strategies, germplasm, technologies, and policy. To establish the genetic trends in the Kenyan Highland Maize Breeding Program (KHMP), a two-decade (1999-2020) historical dataset from the Preliminary Variety Trials (PVT) and Advanced Variety Trials (AVT) was analyzed. A mixed model analysis was used to compute the genetic gains for traits based on the best linear unbiased estimates in the PVT and AVT evaluation stages. A positive significant genetic gain estimate for grain yield of 88 kg ha-1 year-1 (1.94% year-1) and 26 kg ha-1 year-1 (0.42% year-1) was recorded for PVT and AVT, respectively. Root lodging, an important agronomic trait in the Kenya highlands, had a desired genetic gain of -2.65% year-1 for AVT. Results showed improvement in resistance to Turcicum Leaf Blight (TLB) with -1.19% and -0.27% year-1 for the PVT and AVT, respectively. Similarly, a significant genetic trend of -0.81% was noted for resistance to Gray Leaf Spot (GLS) in AVT. These findings highlight the good progress made by KHMP in developing adapted maize hybrids for Kenya's highland agroecology. Nevertheless, the study identified significant opportunities for the KHMP to make even greater genetic gains for key traits with introgression of favorable alleles for various traits, implementing a continuous improvement plan including marker-assisted forward breeding, sparse testing, and genomic selection, and doubled haploid technology for line development.

2.
Front Plant Sci ; 14: 1196134, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37476178

RESUMO

China's and Europe's dependence on imported protein is a threat to the food self-sufficiency of these regions. It could be solved by growing more legumes, including alfalfa that is the highest protein producer under temperate climate. To create productive and high-value varieties, the use of large genetic diversity combined with genomic evaluation could improve current breeding programs. To study alfalfa diversity, we have used a set of 395 alfalfa accessions (i.e. populations), mainly from Europe, North and South America and China, with fall dormancy ranging from 3 to 7 on a scale of 11. Five breeders provided materials (617 accessions) that were compared to the 400 accessions. All accessions were genotyped using Genotyping-by-Sequencing (GBS) to obtain SNP allele frequency. These genomic data were used to describe genetic diversity and identify genetic groups. The accessions were phenotyped for phenology traits (fall dormancy and flowering date) at two locations (Lusignan in France, Novi Sad in Serbia) from 2018 to 2021. The QTL were detected by a Multi-Locus Mixed Model (mlmm). Subsequently, the quality of the genomic prediction for each trait was assessed. Cross-validation was used to assess the quality of prediction by testing GBLUP, Bayesian Ridge Regression (BRR), and Bayesian Lasso methods. A genetic structure with seven groups was found. Most of these groups were related to the geographical origin of the accessions and showed that European and American material is genetically distinct from Chinese material. Several QTL associated with fall dormancy were found and most of these were linked to genes. In our study, the infinitesimal methods showed a higher prediction quality than the Bayesian Lasso, and the genomic prediction achieved high (>0.75) predicting abilities in some cases. Our results are encouraging for alfalfa breeding by showing that it is possible to achieve high genomic prediction quality.

3.
Medicina (Kaunas) ; 59(7)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37512014

RESUMO

Background and Objectives: Coagulation disorders during COVID-19 infection are associated with a poorer prognosis and higher disease severity because thrombosis and inflammation are two processes that interfere with each other. A very important issue for clinicians is timely and adequate hemostasis and inflammation monitoring to prevent and treat potentially lethal consequences. The aim of this study was to identify specific hemostatic parameters that are associated with a higher risk of intrahospital mortality. Materials and Methods: This study was approved by the Ethics Committee of the Clinical Center Nis in Serbia. One hundred and forty-two patients presented with COVID-19 ARDS and were admitted to the ICU in the Clinic for Anesthesiology at the Clinical Center Nis from 14 April 2020 to 25 May 2020. Upon admission, blood was collected for biochemical and coagulation testing. The data obtained were analyzed using the Statistical Package for Social Sciences (SPSS v. 25, Chicago, IL, USA). Results: Among all the parameters assessed, older age; increased levels of fibrinogen, INR, D-dimer, and presepsin; and higher results in the platelet aggregation tests (aggregation induced by adenosine diphosphate based on the ADP test (AU/min), aggregation induced by arachidonic acid based on the ASPI test (AU/min), and aggregation induced by thrombin based on the TRAP test (AU/min)) and some assays of the viscoelastic test (clot amplitude after 5 min in the extrinsic coagulation pathway based on the A5 EX-test (mm), clot amplitude after 10 min in the extrinsic coagulation pathway based on the A10 EX-test (mm), clot amplitude after 5 min regarding functional fibrinogen based on the A5 FIB-test (mm), clot amplitude after 10 min regarding functional fibrinogen based on the A10 FIB-test (mm), and maximum clot firmness based on the MCF FIB-test (mm)); and lower values of viscoelastic clotting time in the extrinsic coagulation pathway based on the CT EX-test (s) were significantly correlated with mortality. In the multivariate analysis, D-dimer levels above 860 ng/mL, higher TRAP test value bins, and values above the normal reference range of the A10 FIB test were found to be independent predictors of mortality. Conclusions: Sophisticated hemostasis parameters can contribute to early risk assessment, which has initially been performed only on the basis of patients' clinical status. Hypercoagulability is the main coagulation disorder in COVID-19 infection.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Trombose , Humanos , Tromboelastografia/efeitos adversos , Tromboelastografia/métodos , COVID-19/complicações , Hemostasia , Transtornos da Coagulação Sanguínea/etiologia , Trombose/diagnóstico , Trombose/etiologia , Fibrinogênio , Inflamação/complicações , Fragmentos de Peptídeos , Receptores de Lipopolissacarídeos
4.
Phlebology ; 38(7): 458-465, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37343246

RESUMO

OBJECTIVE: The aim of this study was to establish the efficacy of three different strengths of compression systems in the prevention of venous leg ulcer (VLU) recurrences during a 10-year follow up period. METHODS: An open, prospective, randomized, single-center study included 477 patients (240 men, 237 women; mean age 59 years). Patients were randomized into three groups: Group A) 149 patients (allocated to wear elastic stocking 18-25 mmHg). Group B) 167 patients (wearing compression device exerting 25-35 mmHg), and Group C) 161 patients (treated with multilayer compression system exerting 35-50 mmHg). RESULTS: Overall, 65% (234/360) of patients had recurrent VLU within 10 years. Recurrence occurred in 120 (96%) of 125 in group A, in 89 (66.9%) of 133 patients in group B and in 25 (24.5%) of 102 patients in group C (p < 0.05). CONCLUSION: Compression systems with the higher compression class provide lower recurrence rate.


Assuntos
Úlcera Varicosa , Cicatrização , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Seguimentos , Úlcera Varicosa/prevenção & controle , Meias de Compressão , Recidiva
5.
Medicina (Kaunas) ; 59(2)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36837419

RESUMO

Background and Objectives: The saphenous vein is one of the most common used grafts (SVG) for surgical revascularization. The mechanism of the SVGs occlusion is still unknown. Surgical preparation techniques have an important role in the early and late graft occlusion. Our study analyzed the influence of the three different surgical techniques on the histological and immunohistochemical characteristics of the vein grafts. Methods: Between June 2019 and December 2020, 83 patients who underwent surgical revascularization were prospectively randomly assigned to one of the three groups, according to saphenous vein graft harvesting (conventional (CVH), no-touch (NT) and endoscopic (EVH)) technique. The vein graft samples were sent on the histological (hematoxylin-eosin staining) and immunohistochemical (CD31, Factor VIII, Caveolin and eNOS) examinations. Results: The CVH, NT, and EVH groups included 27 patients (mean age 67.66 ± 5.6), 31 patients (mean age 66.5 ± 7.4) and 25 patients (mean age 66 ± 5.5), respectively. Hematoxylin-eosin staining revealed a lower grade of microstructural vein damage in the NT group (2, IQR 1-2) in comparison with CVH and EVH (3, IQR 2-4), (4, IQR 2-4) respectively (p < 0.001). Immunohistochemical examination revealed a high grade of staining in the NT group compared to the CVH and EVH group (CD 31 antibody p = 0.02, FVIII, p < 0.001, Caveolin, p = 0.001, and eNOS, p = 0.003). Conclusion: The best preservation of the structural vein integrity was in the NT group, while the lowest rate of leg wound complication was in the EVH group. These facts increase the interest in developing and implementing the endoscopic no-touch technique.


Assuntos
Ponte de Artéria Coronária , Veia Safena , Idoso , Humanos , Pessoa de Meia-Idade , Caveolinas/análise , Ponte de Artéria Coronária/métodos , Endoscopia , Veia Safena/química , Veia Safena/patologia , Veia Safena/transplante , Grau de Desobstrução Vascular
6.
Iran J Public Health ; 51(10): 2244-2252, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36415799

RESUMO

Background: Falls have been one of the leading causes of injury-related deaths among the elderly, having an increasing trend in many countries. We investigated trends of fall-related mortality among people aged ≥65 yr in Serbia. Methods: Based on official data, we calculated unintentional fall-related mortality rate (MR) from 1998 to 2017, using join point regression analysis to determine annual percentage changes (APC). Starting from 2005, doctors from Serbian Public Health Institute have been controlling the quality of death certificates. Results: In the 1998-2004 period, MR decreased in men and women aged 65-74 and men aged ≥85 (by -12.4; -13.0; and -15.1% yearly) followed by an upward trend in men and women aged 65-74 (by 76.3 vs.40.2%yearly) from 2004 to 2007 and men aged ≥85 (by 13.7% yearly) from 2004 to 2017. MR decreased among women aged ≥85 (by -9.8% yearly) from 1998 to 2008 and then increased (by 9.0% yearly) from 2008 to 2017. In men and women aged 75-84, an increase of MR (by 7.4 vs.3.1%) was observed during the entire study period. In all age groups, except women aged ≥85, significant negative correlation was found between fall-related deaths and ill-defined and unknown causes of deaths. Conclusion: Control of death certificates by physicians from the Institute of Public Health led to the better reporting of the increasing trend of fall-related mortality among the elderly. Policy makers must investigate risk factors for fall and then adopt national guidelines for prevention and treatment of fall-related injury.

7.
Tissue Cell ; 79: 101904, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36058048

RESUMO

Sepsis is a life-threatening organ dysfunction. An animal model mimicking sepsis utilizes lipopolysaccharide (LPS), an endotoxin recognized as the most potent bacterial mediator of sepsis. Melatonin (MLT), an effective anti-inflammatory and antioxidant agent, is a promising adjunctive drug for sepsis. This study aimed to estimate the potential of MLT in preventing LPS-induced liver damage in Wistar rats by determining the levels of serum and tissue biochemical markers that reflect liver state and function, i.e., serum levels of transaminases and albumin, as well as a panel of oxidative stress-related biomarkers. Additionally, a pathohistological analysis of liver tissue was conducted. Pre-treatment with MLT prevented an LPS-induced increase in serum and tissue liver damage markers and a decrease in the tissue antioxidant capacity, in both enzymatic and non-enzymatic systems. Micromorphological liver tissue changes mirrored the alterations observed in the biochemical status. In rats with LPS-induced sepsis, melatonin was shown to be a crucial antioxidant and anti-inflammatory agent, with vital roles in the alleviation of oxidative stress, causing an increase of the antioxidant capacities and the improvement of the liver's microscopic appearance.


Assuntos
Melatonina , Sepse , Ratos , Animais , Melatonina/farmacologia , Lipopolissacarídeos/toxicidade , Antioxidantes , Ratos Wistar , Apoptose , Sepse/induzido quimicamente , Sepse/tratamento farmacológico , Fígado , Modelos Animais de Doenças
8.
Clin Appl Thromb Hemost ; 28: 1076029620939181, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35187959

RESUMO

Venous thromboembolism (VTE) is a multifactorial disease that can possibly affect any part of venous circulation. The risk of VTE increases by about 2 fold in pregnant women and VTE is one of the major causes of maternal morbidity and mortality. For decades superficial vein thrombosis (SVT) has been considered as benign, self-limiting condition, primarily local event consequently being out of scope of well conducted epidemiological and clinical studies. Recently, the approach on SVT has significantly changed considering that prevalence of lower limb SVT is twice higher than both deep vein thrombosis (DVT) and pulmonary embolism (PE). The clinical severity of SVT largely depends on the localization of thrombosis, when it concerns the major superficial vein vessels of the lower limb and particularly the great saphenous vein. If untreated or inadequately treated, SVT can potentially cause DVT or PE. The purpose of this review is to discuss the complex interconnection between SVT and risk factors in pregnancy and to provide evidence-based considerations, suggestions, and recommendations for the diagnosis and treatment of this precarious and delicate clinical entity.


Assuntos
Anticoagulantes/uso terapêutico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/prevenção & controle , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Península Balcânica , Feminino , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
9.
Toxins (Basel) ; 13(10)2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34678980

RESUMO

Maize is one of the leading export products in the Republic of Serbia. As a country where economic development depends on agriculture, maize production plays a critical role as a crop of strategic importance. Potential aflatoxin contamination of maize poses a risk to food and feed safety and tremendous economic losses. No aflatoxin contamination of maize samples harvested in 2019 and 2020 in different localities in the Republic of Serbia was detected by the Enzyme-Linked Immunosorbent Assay (ELISA) test and High-Performance Liquid Chromatography (HPLC) method. On the other hand, the Cluster Amplification Patterns (CAP) analyses of the isolated Aspergillus flavus strains from 2019 maize samples confirmed the presence of key biosynthesis genes responsible for aflatoxin production. Artificial inoculation and subsequent HPLC analysis of the inoculated maize samples confirmed the high capacity of the A. flavus strains for aflatoxin production, pointing to a high risk of contamination under favorable conditions. Prevention of aflatoxin contamination is primarily based on A. flavus control, where biocontrol agents play a significant role as sustainable disease management tools. In this study, antagonistic activity screening of the novel strains belonging to the Bacillus genus indicated superior suppression of A. flavus strains by two Bacillus strains isolated from the rhizosphere of Phaseolus vulgaris.


Assuntos
Aspergillus flavus/genética , Doenças das Plantas/microbiologia , Zea mays/microbiologia , Aflatoxinas/genética , Aflatoxinas/metabolismo , Bacillus/fisiologia , Agentes de Controle Biológico , Variação Genética , Doenças das Plantas/prevenção & controle , Sérvia
10.
Rev Cardiovasc Med ; 22(3): 1053-1062, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565107

RESUMO

Elderly patients scheduled for major elective vascular surgery are at high risk for a major adverse cardiac events (MACE). The objectives of the study were: (1) To determine the individual discriminatory ability of four risk prediction models and four biomarkers in predicting MACEs in elderly patients undergoing major elective vascular surgery; (2) to find a prognostic model with the best characteristics; (3) to examine the significance of all preoperative parameters; and (4) to determine optimal cut-off values for biomarkers with best predictor capabilities. We enrolled 144 geriatric patients, aged 69.97 ± 3.73 years, with a 2:1 male to female ratio. Essential inclusion criteria were open major vascular surgery and age >65 years. The primary outcome was the appearance of MACEs within 6 months. These were noted in 33 (22.9%) patients. The most frequent cardiac event was decompensated heart failure, which occurred in 22 patients (15.3%). New onset atrial fibrillation was registered in 13 patients (9%), and both myocardial infarction and ventricular arrhythmias occurred in eight patients each (5.5%). Excellent discriminatory ability (AUC >0.8) was observed for all biomarker combinations that included the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). The most predictive two-variable combination was the Geriatric-Sensitive Cardiac Risk Index (GSCRI) + NT-proBNP (AUC of 0.830 with a 95% confidence interval). Female gender, previous coronary artery disease, and NT-proBNP were three independent predictors in a multivariate model of binary logistic regression. The Cox regression multivariate model identified high-sensitivity C-reactive protein and NT-proBNP as the only two independent predictors.


Assuntos
Doença da Artéria Coronariana , Insuficiência Cardíaca , Idoso , Biomarcadores , Feminino , Humanos , Masculino , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
11.
Cent Eur J Public Health ; 29(2): 83-89, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34245546

RESUMO

OBJECTIVES: Globally, child mortality from external causes is in decline, but it is still among the leading causes of child deaths. The aim of this first national study was to determine trends of mortality rates from external causes among children aged 1-14 years in Serbia. METHODS: Mortality data were collected from the database of the Statistical Office of Serbia. Joinpoint analysis was used to assess the average annual percentage change (APC) and the corresponding 95% confidence interval (CI) in mortality from 1997 to 2016. RESULTS: In the 1997-2016 period, there were 1,388 child deaths from external causes. They contributed to 29.4% of child mortality in total, from 34.8% in 1997 to 21.8% in 2016. Mortality rate was two times higher among boys (8.1 per 100,000) than girls (4.1 per 100,000). Transport accidents (37.6%), followed by drowning and submersion (18.2%), represented more than half of all deaths due to external causes. Since 1997, mortality rate showed a significant downward trend in boys by -5.4% (95% CI -6.8 to -3.9) yearly for unintentional injuries and significantly by -10% (95% CI -19.0 to 0.1) yearly for intentional injuries. Among girls, death rate for unintentional injuries decreased significantly by -7.1% (95% CI -9.0 to -5.1) yearly and decreased insignificantly for intentional injuries by -2.1% (95% CI -15.3 to 13.1) yearly. CONCLUSIONS: The external causes of death, despite the substantial decline in mortality, are still present among children aged 1-14 years in Serbia. Therefore, implementation of nationwide programmes for prevention of external causes of death is urgent.


Assuntos
Ferimentos e Lesões , Adolescente , Causalidade , Causas de Morte , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Masculino , Anamnese , Mortalidade , Sérvia/epidemiologia
12.
Comput Biol Med ; 132: 104346, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33774271

RESUMO

The voltage-gated sodium channel Nav1.7 can be considered as a promising target for the treatment of pain. This research presents conformational-independent and 3D field-based QSAR modeling for a series of aryl sulfonamide acting as Nav1.7 inhibitors. As descriptors used for building conformation-independent QSAR models, SMILES notation and local invariants of the molecular graph were used with the Monte Carlo optimization method as a model developer. Different statistical methods, including the index of ideality of correlation, were used to test the quality of the developed models, robustness and predictability and obtained results were good. Obtained results indicate that there is a very good correlation between 3D QSAR and conformation-independent models. Molecular fragments that account for the increase/decrease of a studied activity were defined and used for the computer-aided design of new compounds as potential analgesics. The final evaluation of the developed QSAR models and designed inhibitors were carried out using molecular docking studies, bringing to light an excellent correlation with the QSAR modeling results.


Assuntos
Relação Quantitativa Estrutura-Atividade , Canais de Sódio Disparados por Voltagem , Simulação por Computador , Humanos , Simulação de Acoplamento Molecular , Canal de Sódio Disparado por Voltagem NAV1.7 , Dor
13.
Vasc Endovascular Surg ; 55(5): 461-466, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33622185

RESUMO

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) in uPAR soluble form is produced when the uPAR is cleaved from the cell membrane during the inflammatory process. Postoperative atrial fibrillation (AF) is the most common perioperative cardiac arrhythmia. It is speculated that elevated suPAR has a role in the development of AF. The aim of our study was to investigate the predictive role of preoperative suPAR in the occurrence of AF during the first 6 months after major vascular surgery. METHODS: We included 119 male and 63 female patients with an average age of 67.19 ± 6.02 years, without permanent/persistent AF. Basic predictive model (BASIC) included traditional risk factors for AF: age, gender, body mass index-BMI, smoking status, presence of arterial hypertension, diabetes mellitus and dyslipidemia. RESULTS: Over the 6-month period, 19 (10.4%) patients had one new episode of atrial fibrillation and 2 patients (1.1%) had 2 episodes of paroxysmal atrial fibrillation. Paroxysms of AF were significantly more frequent in patients who had a resection of an abdominal aneurysm than in patients with other types of major vascular surgery. BASIC had good discriminatory ability in the prediction of AF paroxysms during the first 6 months after surgery (AUC = 0.715, 95%CI 0.590-0.840). Adding suPAR to the basic model significantly improved the discriminative ability of the predictive model for AF episodes (ΔAUC = 0.238, p < 0.001). The predictive performance of the model BASIC+CRP+suPAR, measured using AUC, NRI and IDI statistics, was very similar to the model BASIC+suPAR. CONCLUSION: AF is a common complication in surgical patients with high mortality and morbidity. suPAR could improve the ability of traditional risk factors to predict its occurrence up to 6 months after major vascular surgery.


Assuntos
Fibrilação Atrial/etiologia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/sangue , Doenças Vasculares/diagnóstico
14.
Phlebology ; 36(5): 407-413, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33251939

RESUMO

AIM: Beside the intention of early detection and optimal treatment of deep venous thrombosis (DVT), the aim of this study was to investigate the influence of chronobiological rhythms on the etiopathogenesis of unprovoked deep vein thrombosis of the lower limbs with monitoring of seasonal variations in biochemical parameters. PATIENTS AND METHODOLOGY: The prospective clinical trial included all consecutive hospitalized patients and outpatients diagnosed with DVT at the Vascular Surgery Clinic of the Clinical Center in Nis, starting from January 2013 to December 2014. RESULTS: There was no statistically significant difference in correlation between the distribution of the incidence of DVT of the lower limbs (p = 0.582), sex (p = 0.350), age (p = 0.385) and localization (p = 0.886) and the seasons. Creatinine levels were significantly higher in patients who developed DVT in spring than in those who developed DVT in winter (p < 0.05), while LDL cholesterol levels were significantly higher in patients diagnosed with DVT in winter than in those diagnosed with DVT in autumn (p < 0.05). CONCLUSION: According to the results of the study, it can be concluded that in the territory of South Serbia, the seasons are not significantly related to the incidence, sex, age and localization of unprovoked DVT of the lower limbs. Creatinine levels were significantly higher in patients who developed DVT in spring than in those who developed DVT in winter, while LDL cholesterol levels were significantly higher in patients during winter than during autumn.


Assuntos
Trombose Venosa , Humanos , Incidência , Extremidade Inferior , Estudos Prospectivos , Fatores de Risco , Trombose Venosa/epidemiologia
15.
J Biomol Struct Dyn ; 38(8): 2304-2313, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31215331

RESUMO

Cholesteryl ester transfer protein (CETP) belongs to the group of enzymes which inhibition have the application in the treatment of cardiovascular diseases. This study presents QSAR modeling for a set of compounds acting as CETP inhibitors based on the Monte Carlo optimization with SMILES notation and molecular graph-based descriptors, and field-based 3D modeling. A 3D QSAR model was developed for one random split into the training and test sets, whereas conformation independent QSAR models were developed for three random splits, with the results suggesting there is an excellent correlation between them. Various statistical approaches were used to assess the statistical quality of the developed models, including robustness and predictability, and the obtained results were very good. This study used a novel statistical metric known as the index of ideality of correlation for the final assessment of the model, and the results that were obtained suggested that the model was good. Also, molecular fragments which account for the increases and/or decreases of a studied activity were defined and then used for the computer-aided design of new compounds as potential CETP inhibitors. The final assessment of the developed QSAR model and designed inhibitors was done using molecular docking, which revealed an excellent correlation with the results from QSAR modeling.Communicated by Ramaswamy H. Sarma.


Assuntos
Proteínas de Transferência de Ésteres de Colesterol , Doença das Coronárias , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Simulação por Computador , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade
16.
Med Princ Pract ; 28(1): 63-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30391950

RESUMO

OBJECTIVE: The aim of our study was to find the best model with sufficient power to improve the risk stratification in major vascular surgery patients during the first 30 days after this procedure. The discriminatory power of 4 biomarkers (troponin I [TnI], N-terminal prohormone of brain natriuretic peptide [NT-proBNP], creatine kinase-MB isoenzyme [CK-MB], high-sensitivity C-reactive protein [hs-CRP]) was tested as well as 2 risk assessment models and 13 different combinations of them. SUBJECTS AND METHODS: The study included 122 patients (77% men, 23% women) with an average age of 67.03 ± 4.5 years. An aortobifemoral bypass was performed in 6.56% of the patients, a femoropopliteal bypass in 18.85%, and 49.18% received open surgical reconstruction of the carotid arteries. A total of 25.41% of the patients were given an aortobi-iliac bypass. RESULTS: During the first 30 days, 13 patients (10.7%) had 17 cardiac complications. The most common complication was the new onset of atrial fibrillation (35.3%). During the first 10 days, 10 patients had 1 complication and 2 patients had 2 cardiac events, while 1 patient had 3 complications. By comparing combinations of scores and markers, it was shown that revised cardiac risk index (RCRI) + Vascular Portsmouth Physiological and Operative Severity Score (V-POSSUM) + hsTnI and RCRI + V-POSSUM + hsTnI + NT-proBNP with 100% sensitivity, > 80% specificity had the best discriminatory ability (AUC 0.924 and 0.933, respectively; p < 0.001 for both models) for cardiac complications during the 30 days after surgery. CONCLUSION: Combinations of traditional preoperative risk factors and scores can enhance the assessment of major adverse cardiac events (MACE) in patients preparing for large vascular surgery. Using only one risk score in these patients seems to be underperforming in preoperative risk assessment.


Assuntos
Biomarcadores/sangue , Cardiopatias/epidemiologia , Medição de Risco/métodos , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Creatina Quinase Forma MB/sangue , Feminino , Cardiopatias/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Curva ROC , Fatores de Risco , Sérvia/epidemiologia , Tempo , Troponina I/sangue
17.
Biomed Res Int ; 2018: 4381527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271785

RESUMO

INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is an extensively used simple risk stratification tool advocated by the European Society of Cardiology and European Society of Anesthesiology (ESC/ESA). PURPOSE: The aim of this study was to find the best model for predicting 3-month cardiovascular complications in elective major vascular surgical patients using preoperative clinical assessment, calculation of the RCRI and Vascular Physiological and Operative Severity Score for the enumeration of mortality and morbidity (V-POSSUM) scores, and the preoperative levels of N-terminal brain natriuretic peptide (NT pro-BNP), high-sensitivity troponin I (hs TnI), and high-sensitivity C-reactive protein (hs CRP). MATERIALS AND METHODS: We included 122 participants in a prospective, single-center, observational study. The levels of NT pro-BNP, hs CRP, and hs TnI were measured 48 hours prior to surgery. During the perioperative period and 90 days after surgery the following adverse cardiac events were recorded: myocardial infarction, arrhythmias, pulmonary edema, acute decompensated heart failure, and cardiac arrest. RESULTS: During the first 3 months after surgery 29 participants (23.8%) had 50 cardiac complications. There was a statistically significant difference in the RCRI score between participants with and without cardiac complications. ROC analysis showed that a combination of RCRI with hs TnI has good discriminatory power (AUC 0.909, p<0,001). By adding NT pro-BNP concentrations to the RCRI+hs TnI+V-POSSSUM combination we obtained the model with the best predictive power for 3-month cardiac complications (AUC 0.963, p<0,001). CONCLUSION: We need to improve preoperative risk assessment in participants scheduled for major vascular surgery by combining their clinical scores with biomarkers. Therefore, it is possible to identify patients at risk of cardiovascular complications who need adequate preoperative diagnosis and treatment.


Assuntos
Medição de Risco , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Biomarcadores , Proteína C-Reativa/análise , Procedimentos Cirúrgicos Eletivos , Feminino , Cardiopatias , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco
18.
J Vasc Surg Venous Lymphat Disord ; 6(6): 717-723, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30131303

RESUMO

BACKGROUND: Venous leg ulcers (VLUs) are a major health problem because of their high prevalence and associated high cost of care. Despite the widespread use of compression, treatment recurrence rates remain high. Numerous studies have suggested that regular use of compression stockings reduces VLU recurrences. However, there are limited data concerning how long compression hosiery should be worn after ulcer healing and which class of compression hosiery achieves better results in the prevention of VLU recurrences. METHODS: An open, prospective, randomized, single-center study with a 5-year follow-up was performed to establish the efficacy of two different strengths of knee-high compression hosiery (class 2 and class 3) in the prevention of VLU recurrences. The study included patients with recently healed venous ulcers and no significant arterial disease, rheumatoid disease, diabetes mellitus, and restriction in range of ankle movement. Overall, 361 patients were randomized, and 308 patients (170 men, 138 women; mean age, 59 years) completed the study. Patients were randomized into two groups: group A, 186 patients who wore a heel-less open-toed elastic class 3 compression device knitted in tubular form (Tubulcus; Laboratoires Innothera, Arcueil, France); and group B, 175 patients who wore a class 2 elastic stocking (Rudo, Nis, Serbia). All patients were instructed to wear compression stockings continuously for the first 2 years of follow-up (both during the day and at night). In the third, fourth, and fifth years of follow-up, patients were instructed to wear elastic stockings during the day only. The main outcome measures were recurrence of leg ulceration and compliance with the treatment. RESULTS: Rates of ulcer recurrence after the 5 years of follow-up were 28.98% for the compression class 3 group and 60% for the compression class 2 group (P < .001, log-rank test). Patients in the compression class 3 group experienced significantly longer absolute (46 vs 40 months; P < .001, Mann-Whitney U test) and proportional (77% vs 67%; P < .001, Mann-Whitney U test) ulcer-free time after 5 years than those in the compression class 2 group. Rates of noncompliance after 5 years were 10.23% for the compression class 3 group and 6.25% for the compression class 2 group (P = .188, χ2 test). CONCLUSIONS: The results obtained in this study suggest that class 3 compression stockings provide a statistically significant lower recurrence rate compared with the class 2 compression stockings.


Assuntos
Meias de Compressão , Úlcera Varicosa/terapia , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Elasticidade , Desenho de Equipamento , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Fatores de Risco , Sérvia , Fatores de Tempo , Resultado do Tratamento , Úlcera Varicosa/diagnóstico
19.
Comput Biol Chem ; 75: 32-38, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29734080

RESUMO

Up to this date, there has been an ongoing debate about the mode of action of general anesthetics, which have postulated many biological sites as targets for their action. However, postoperative nausea and vomiting are common problems in which inhalational agents may have a role in their development. When a mode of action is unknown, QSAR modelling is essential in drug development. To investigate the aspects of their anesthetic, QSAR models based on the Monte Carlo method were developed for a set of polyhalogenated ethers. Until now, their anesthetic action has not been completely defined, although some hypotheses have been suggested. Therefore, a QSAR model should be developed on molecular fragments that contribute to anesthetic action. QSAR models were built on the basis of optimal molecular descriptors based on the SMILES notation and local graph invariants, whereas the Monte Carlo optimization method with three random splits into the training and test set was applied for model development. Different methods, including novel Index of ideality correlation, were applied for the determination of the robustness of the model and its predictive potential. The Monte Carlo optimization process was capable of being an efficient in silico tool for building up a robust model of good statistical quality. Molecular fragments which have both positive and negative influence on anesthetic action were determined. The presented study can be useful in the search for novel anesthetics.


Assuntos
Anestésicos Gerais/química , Éteres/química , Hidrocarbonetos Halogenados/química , Polímeros/química , Relação Quantitativa Estrutura-Atividade , Modelos Moleculares , Método de Monte Carlo , Software
20.
Int Wound J ; 10(5): 516-26, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22716023

RESUMO

The International Compression Club (ICC) is a partnership between academics, clinicians and industry focused upon understanding the role of compression in the management of different clinical conditions. The ICC meet regularly and from these meetings have produced a series of eight consensus publications upon topics ranging from evidence-based compression to compression trials for arm lymphoedema. All of the current consensus documents can be accessed on the ICC website (http://www.icc-compressionclub.com/index.php). In May 2011, the ICC met in Brussels during the European Wound Management Association (EWMA) annual conference. With almost 50 members in attendance, the day-long ICC meeting challenged a series of dogmas and myths that exist when considering compression therapies. In preparation for a discussion on beliefs surrounding compression, a forum was established on the ICC website where presenters were able to display a summary of their thoughts upon each dogma to be discussed during the meeting. Members of the ICC could then provide comments on each topic thereby widening the discussion to the entire membership of the ICC rather than simply those who were attending the EWMA conference. This article presents an extended report of the issues that were discussed, with each dogma covered in a separate section. The ICC discussed 12 'dogmas' with areas 1 through 7 dedicated to materials and application techniques used to apply compression with the remaining topics (8 through 12) related to the indications for using compression.


Assuntos
Consenso , Úlcera da Perna/terapia , Meias de Compressão , Bélgica , Congressos como Assunto , Humanos , Cooperação Internacional
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