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1.
Clin Infect Dis ; 73(7): e2109-e2116, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32766891

RESUMO

BACKGROUND: The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). METHODS: Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. RESULTS: In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]: .08-.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5-24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01-1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01-1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11-.85). CONCLUSIONS: Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.


Assuntos
Carcinoma Hepatocelular , Infecções por HIV , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Estudos Prospectivos , Resposta Viral Sustentada
2.
Clin Infect Dis ; 72(5): e96-e102, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33211801

RESUMO

BACKGROUND: In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. METHODS: This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. RESULTS: Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. CONCLUSIONS: After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.


Assuntos
Coinfecção , Varizes Esofágicas e Gástricas , Infecções por HIV , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Varizes Esofágicas e Gástricas/tratamento farmacológico , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/tratamento farmacológico , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Estudos Prospectivos , Resultado do Tratamento
3.
J Viral Hepat ; 28(6): 878-886, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33721377

RESUMO

Elbasvir/grazoprevir (EBR/GZR) use in drug users on opiate agonist therapy (OAT) is supported by the C-EDGE Co-STAR trial. SVR rates in this study were within those found in the rest of patients included by the EBR/GZR development programme. In clinical practice, however, efficacy could theoretically be lower. Thus, we aimed at evaluating the SVR rates of EBR/GZR among people who injected drugs (PWID) with and without OAT in clinical practice. Patients starting EBR/GZR included in the HEPAVIR-DAA (NCT02057003), recruiting HIV/HCV-coinfected patients or the GEHEP-MONO (NCT02333292), including HCV-monoinfected individuals, prospective cohorts were analysed. Overall SVR12 (ITT), discontinuations due to adverse effects and drop-outs were evaluated. The same analysis was carried out for PWID with and without OAT. 336 patients had started EBR/GZR and reached the SVR12 evaluation date. 318 [95%, 95% confidence interval (95% CI): 92%-98%] patients achieved SVR12. SVR12 was 97% (95% CI: 93%-99%, n/N = 141/145) among people who never used injecting drugs, 94% (95% CI: 88%-97%, n/N = 117/125) among PWIDs without OAT and 91% (95% CI: 81%-97%, n/N = 60/66) among PWIDs with OAT (p = 0.134). Five (1.5%) patients showed relapses, and two (0.6%) individuals showed viral breakthrough. The SVR12 rate for recent drug users was 69% (n/N = 18/26) compared with 97% (n/N = 276/284) for individuals without recent drug use (in the prior year) (p < 0.001). Among recent drug users, three (12%) showed relapses, and five (19%) were lost-to-follow-up. The SVR rates achieved with EBR/GZR were high in real-world conditions of use. However, PWID with recent drug use reach suboptimal response rates with EBR/GZR.


Assuntos
Hepatite C , Preparações Farmacêuticas , Amidas , Analgésicos Opioides , Antivirais/efeitos adversos , Benzofuranos , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Humanos , Imidazóis , Estudos Prospectivos , Quinoxalinas/efeitos adversos , Sulfonamidas
4.
J Org Chem ; 86(1): 223-234, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33232142

RESUMO

Deep eutectic solvents (DESs) have been considered "the organic reaction medium of the century" because they can be used as solvents and active catalysts in chemical reactions. However, experimental and theoretical studies are still needed to provide information on the structures of DESs, the kinetics and thermodynamics properties, the interactions between the DESs and the substrates, the effect of water on the DES supramolecular network and its physicochemical properties, and so forth. This information is very useful to understand the essence of the processes that take place in the catalysis of chemical reactions and, therefore, to help in the design of a DES for a specific reaction and sample. This article shows a systematic study of the impact of DES choline chloride/p-toluenesulfonic acid and DES choline chloride/p-toluenesulfonic acid-water in the aza-Michael addition of arylamines to maleimide to obtain aminopyrrolidine-2,5-dione derivatives. The derivatives are obtained under very mild reaction conditions with good yield. The global reaction is exothermic, spontaneous, permitted by enthalpy, and prohibited for entropy. The calculated potential energy surface shows a reaction mechanism of six steps controlled by enthalpy (except the last step that is controlled by entropy). The water incorporated in the supramolecular DES complex stabilizes the transition states and favors the enthalpy-driven binding. A set of H/D exchange NMR experiments validates the transition state existing in the fourth stage of the mechanism.

5.
J Phys Chem A ; 125(12): 2394-2401, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33754722

RESUMO

Three Cu(II) coordination compounds with 4-methyl imidazole were obtained, such as [Cu(C4H6N2)4(NO3)2], [Cu(C4H6N2)4Br2], and [Cu(C4H6N2)4Cl2]. Crystallographic studies confirmed their structural similarity with Cu(II) in the active site of endogenous copper-zinc superoxide dismutase (CuZn-SOD). The superoxide anion radical (O2•-) scavenging activity was evaluated by the non-enzymatic experimental assay and followed the trend [Cu(C4H6N2)4(NO3)2] > [Cu(C4H6N2)4Br2] > [Cu(C4H6N2)4Cl2]. The density functional theory and the hard and soft acids and bases principle showed the importance of the electron-deficient character of Cu(II) in the chemical reactivity of the coordination compounds; Cu(II) is the softest site in the molecule and it is preferred for the nucleophilic and radical attacks of the soft O2•-. A simple rule was obtained: "the electron-deficient character of Cu(II) is the key index for the O2•- scavenging activity and is modulated by the electron-releasing counteranion effect on the coordination compound".

6.
Molecules ; 26(16)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34443666

RESUMO

The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p < 0.05); when aromaticity increased, the antifungal activity decreased for series I and increased for series II. To verify the validity of the obtained equations, a new set of 44 benzofuran-4-ones was designed by replacing the nitrogen atom of the five-membered ring with oxygen in indol-4-ones. The NICS(0) and NICS(1) of benzofuran-4-ones were calculated and used to predict their biological activities using the previous equations. A set of 10 benzofuran-4-ones was synthesized and tested in eight human pathogenic fungi, showing the validity of the equations. The minimum inhibitory concentration (MIC) in yeasts was 31.25 µg·mL-1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 µg·mL-1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.


Assuntos
Antifúngicos/farmacologia , Benzofuranos/farmacologia , Fungos/efeitos dos fármacos , Antifúngicos/química , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/patogenicidade , Benzofuranos/química , Candida/efeitos dos fármacos , Candida/patogenicidade , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pichia/efeitos dos fármacos , Pichia/patogenicidade , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/farmacologia
7.
Gynecol Endocrinol ; 36(9): 829-834, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32063091

RESUMO

Oocyte maturation defect is a challenging situation in the management of infertility, the etiology may be related to endocrine causes, protocols used in ovarian stimulation, oocyte intrinsic defects or procedures in embryology laboratory. We report three Mexican females in treatment for primary infertility with non-mature oocytes after ovary stimulation and oocyte capture in whom a genetic diagnosis of TUBB8-oocyte maturation defect was revealed by exome sequencing. Two couples achieved pregnancies though oocyte donation after establishing the genetic etiology. Our results expand the role of TUBB8-disorders in patients of non-Asian ethnicity. Oocyte maturation defects of monogenic origin are a growing group of disorders that endocrinologists and reproductive medicine specialists should be aware in order to provide referral to genetics for establish a correct and opportune diagnosis.


Assuntos
Doenças Genéticas Inatas/terapia , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/terapia , Oogênese/genética , Tubulina (Proteína)/genética , Adulto , Análise Mutacional de DNA , Feminino , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/epidemiologia , Humanos , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/genética , México , Mutação , Linhagem , Gravidez , Prognóstico , Técnicas de Reprodução Assistida/estatística & dados numéricos , Resultado do Tratamento
8.
Molecules ; 25(7)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252296

RESUMO

A theoretical study of the effect of the substituent Z on the gas phase acidity of substituted benzoic acids ZC6H4COOH in terms of density functional theory descriptors (chemical potential, softness and Fukui function) is presented. The calculated gas phase ΔacidG° values obtained were close to the experimental ones reported in the literature. The good relationship between the ΔacidG° values and the electronegativity of ZC6H4COOH and its fragments, suggested a better importance of the inductive than polarizability contributions. The balance of inductive and resonance contributions of the substituent in the acidity of substituted benzoic acids showed that the highest inductive and resonance effects were for the -SO2CF3 and -NH2 substituents in the para- and ortho-position, respectively. The Fukui function confirmed that the electron-releasing substituent attached to the phenyl ring of benzoic acid decreased the acidity in the trend ortho > meta > para, and the electron-withdrawing substituent increased the acidity in the trend ortho < meta < para.


Assuntos
Benzoatos/química , Teoria da Densidade Funcional , Estrutura Molecular
9.
Rev Invest Clin ; 72(2): 103-109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32284626

RESUMO

BACKGROUND: The left atrial appendage (LAAp) resection is an effective treatment approach to reduce the risk of thromboembolism in patients with atrial fibrillation. OBJECTIVE: To study was to study the impact of removing atrial appendages in the production of natriuretic peptides (NPs) in conditions of volume overload and to develop an experimental model of LAAp resection. MATERIALS AND METHODS: In a swine model of ischemic heart failure (HF), serum NP levels were measured before (Basal-1A) and after (Basal-1B) a fluid overload. Animals were grouped as follows: (0) preserved appendages, (1) resected LAAp, and (2) both atrial appendages resected. Levels of NP were measured before (2A) and after a fluid overload (2B). RESULTS: Furin levels were higher in Group 0-2A than in Group 2-2A, and a significant increase was found in Group 0-2B compared to Groups 1-2B and 2-2B. Corin levels increased in Basal-1B versus Basal-1A. Atrial NP (ANP) decreased in Basal-1B compared to Basal-1A. After HF induction, ANP increased in Groups 2-2A and 2-2B. CONCLUSIONS: Resection of atrial appendages drastically modifies the natriuretic mechanisms of cardiac homeostasis, especially after a fluid overload challenge. Herein, we describe the face and predictive validation of an animal model of atrial appendage resection useful to investigations in translational medicine.


Assuntos
Apêndice Atrial/metabolismo , Apêndice Atrial/cirurgia , Modelos Animais de Doenças , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/cirurgia , Homeostase , Peptídeos Natriuréticos/biossíntese , Peptídeos Natriuréticos/fisiologia , Centros Médicos Acadêmicos , Animais , Masculino , Suínos
10.
Gac Med Mex ; 156(4): 279-285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831335

RESUMO

INTRODUCTION: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. OBJECTIVE: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs' antiproliferative activity and histological results. METHOD: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. RESULTS: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. CONCLUSIONS: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.


INTRODUCCIÓN: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. OBJETIVO: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. MÉTODO: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. RESULTADOS: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. CONCLUSIONES: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.


Assuntos
Stents Farmacológicos , Paclitaxel/administração & dosagem , Sirolimo/administração & dosagem , Animais , Modelos Animais de Doenças , Feminino , Seguimentos , Masculino , Microscopia , Desenho de Prótese , Coelhos , Espectrofotometria Infravermelho , Suínos
11.
J Hepatol ; 71(5): 876-888, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31279901

RESUMO

BACKGROUND & AIMS: Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available. METHODS: GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded. RESULTS: A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin. CONCLUSIONS: In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited. LAY SUMMARY: Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.


Assuntos
Anilidas/uso terapêutico , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Ciclopropanos/uso terapêutico , Farmacorresistência Viral/genética , Fluorenos/uso terapêutico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , Lactamas Macrocíclicas/uso terapêutico , Prolina/análogos & derivados , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/farmacologia , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , Estudos Prospectivos , Pirrolidinas , Retratamento , Espanha/epidemiologia , Resposta Viral Sustentada , Valina/análogos & derivados , Proteínas não Estruturais Virais/genética
12.
Molecules ; 22(3)2017 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-28282898

RESUMO

Chemical reactivity descriptors of indol-4-ones obtained via density functional theory (DFT) and hard-soft acid-base (HSAB) principle were calculated to prove their contribution in antifungal activity [...].


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Indóis/química , Indóis/farmacologia , Modelos Químicos , Modelos Moleculares , Algoritmos , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Eletricidade Estática , Relação Estrutura-Atividade
13.
Molecules ; 21(2): 200, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26907230

RESUMO

The Diels-Alder (DA) reaction provides an attractive route to increase the number of six member rings in substituted Polycyclic Aromatic Hydrocarbons (PAHs). The density functional theory (DFT) B3LYP method has been used in this work to inquire if the substitution of H over the edge of triindenetriphenylene (pristine hemifullerene 1) and pentacyclopentacorannulene (pristine hemifullerene 2), could improve the DA cycloaddition reaction with 1,3-butadiene. The substituents tested include electron-donating (NH2, OMe, OH, Me, i-Pr) and electron-withdrawing groups (F, COOH, CF3, CHO, CN, NO2). The electronic, kinetic and thermodynamic parameters of the DA reactions of the substituted hemifullerenes with 1,3-butadiene have been analyzed. The most promising results were obtained for the NO2 substituent; the activation energy barriers for reactions using this substituent were lower than the barriers for the pristine hemifullerenes. This leads us to expect that the cycloadditions to a starting fullerene fragment will be possible.


Assuntos
Butadienos/química , Fulerenos/química , Modelos Moleculares , Alcenos/química , Reação de Cicloadição , Elétrons , Cinética , Termodinâmica
14.
Sci Data ; 11(1): 737, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971820

RESUMO

We present a novel basin dataset for large-sample hydrological studies in Spain. BULL comprises data for 484 basins, combining hydrometeorological time series with several attributes related to geology, soil, topography, land cover, anthropogenic influence and hydroclimatology. Thus, we followed recommendations in the CARAVAN initiative for generating a truly open global hydrological dataset to collect these attributes. Several climatological data sources were used, and their data were validated by hydrological modelling. One of the main novelties of BULL compared to other national-scale datasets is the analysis of the hydrological alteration of the basins included in this dataset. This aspect is critical in countries such as Spain, which are characterised by rivers suffering from the highest levels of anthropisation. The BULL dataset is freely available at https://zenodo.org/records/10605646 .

15.
Enferm Infecc Microbiol Clin ; 31(7): 448-50, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-23523030

RESUMO

INTRODUCTION: A gradual increase in severe cases due to Streptococcus pyogenes or Streptococcus beta-hemolytic group A (SGA), has been detected in the last few decades. METHODS: Retrospective study of bacteremia due to S.pyogenes detected between January 2009 and January 2013 in Cartagena. The annual incidence for severe bacteremia has been estimated. RESULTS: Thirteen cases of SGA bacteremia were recorded. The incidence increased from 0.37 in 2009 to 2.5 cases/100,000 inhabitants in 2012. The predominant focus was skin and soft tissue infections (53%). Early mortality was 20%. CONCLUSION: Severe streptococcal disease is rare, but affects individuals with good functional status, and is associated with a high mortality.


Assuntos
Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia
16.
Molecules ; 18(9): 10254-65, 2013 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-23973997

RESUMO

The nucleophilic character and stability of the carbanions vs. alkoxides derived from 2,2,2-trifluoro-1-(9-anthryl)ethanol and 1-(9-anthryl)ethanol containing X electron-releasing and X electron-acceptor substituents attached to C-10, have been studied at the B3LYP/6-31+G(d,p) level of theory. Results analyzed in terms of the absolute gas-phase acidity, Fukui function, the local hard and soft acids and bases principle, and the molecular electrostatic potential, show that the central ring of the 9-anthryl group confers an ambident nucleophilic character and stabilizes the conjugated carbanion by electron-acceptor delocalization.


Assuntos
Antracenos/química , Trifluoretanol/análogos & derivados , Ânions/química , Estabilidade de Medicamentos , Eletroquímica , Modelos Químicos , Teoria Quântica , Termodinâmica , Trifluoretanol/química
17.
Molecules ; 18(2): 2243-54, 2013 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-23434874

RESUMO

Density Functional Theory has been used to model the Diels-Alder reactions of the fullerene fragments triindenetriphenilene and pentacyclopentacorannulene with ethylene and 1,3-butadiene. The purpose is to prove the feasibility of using Diels-Alder cycloaddition reactions to grow fullerene fragments step by step, and to dimerize fullerene fragments, as a way to obtain C60. The dienophile character of the fullerene fragments is dominant, and the reaction of butadiene with pentacyclopentacorannulene is favored.


Assuntos
Reação de Cicloadição/métodos , Dimerização , Fulerenos/química , Entropia , Hidrogenação , Cinética , Modelos Moleculares
18.
Cells ; 12(21)2023 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-37947651

RESUMO

Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids' pharmacological use remain subjects of discussion, since CAP also promotes epithelial-mesenchymal transition, in an ambivalence that has been referred to as "the double-edge sword". Here, we update the comparative discussion of relevant reports about capsaicinoids' bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids' immunomodulatory properties against cancer.


Assuntos
Capsicum , Neoplasias , Humanos , Capsaicina/farmacologia , Frutas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Biologia
19.
Arch Cardiol Mex ; 93(4): 391-397, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37972366

RESUMO

OBJECTIVE: The objectives of this study were to evaluate an automated device for ventilatory support based on AMBU manufactured in March 2020. METHODS: The ESSI-1 INC was evaluated through pulmonary mechanics and physiology parameters through compensatory spirometer tests (TISSOTs), and an artificial lung Model5600i Dual Adult PNEU VIEW SYSTEM; it was also compared to the anesthetic ventilatory support equipment (AEONMED 7500) in porcine models, measuring ventilatory, hemodynamic and gasometric parameters. RESULTS: This equipment (ESSI-1 INC) was successfully tested by mechanical and biological models, such as pigs in which its performance was evaluated in terms of variability of tidal volume, ventilation frequency, and I/E relationship versus the manual performance of two medical interns. All the results turned out as expected and were satisfactory. CONCLUSIONS: It is safe and effective equipment and should be tested and used in diverse clinical conditions to standardize the ventilatory safety and care of patients who require it.


OBJETIVO: Evaluar un dispositivo automatizado para la asistencia ventilatoria basado en un AMBU manufacturado en Marzo del 2020. MÉTODOS: El ESSI-1 INC fue evaluado por medio de parámetros fisiológicos y mecánica pulmonar a través de pruebas de espirómetro compensatorios (TISSOT); pulmón artificial (Modelo 5600i Dual Adult PNEU VIEW SYSTEM); así como su desempeño comparado a la máquina de anestesia (AEONMED 7500) en modelos porcinos, midiendo criterios ventilatorios, hemodinámicos y gasométricos. RESULTADOS: Este equipo (ESSI-1 INC) fue exitosamente probado por modelos mecánicos y biológicos, tales como cerdos donde su desempeño fue evaluado en términos de la variabilidad del volumen tidal, frecuencia ventilatoria, y relación I/E versus el desempeño manual de dos médicos. Todos los resultados finalizaron como se esperaba de forma satisfactoria. CONCLUSIONES: Es un equipo seguro y efectivo, el cual debería ser probado y usado en distintas condiciones clínicas para estandarizar la seguridad ventilatoria y cuidado de pacientes que lo requieran.


Assuntos
Cardiologia , Respiração Artificial , Animais , Humanos , Suínos , Espirometria , Respiração Artificial/instrumentação
20.
Psychol Trauma ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549385

RESUMO

OBJECTIVE: Since its first definition, the number of dimensions of the posttraumatic stress disorder (PTSD) has increased (e.g., 1 to 7). This could be caused by 2 methodological reasons. First, the studies do not select representative samples of the population and do not consider the magnitude of exposure to the same event. Second, they use nonrobust data analysis, which increases the number of dimensions artificially. The aim is to determine how many dimensions PTSD has, when both sources of error are controlled. METHOD: From 25,400 representative participants of the same population exposed to an earthquake and evaluated with the Davidson Trauma Scale, 127 smaller samples of 200 participants were obtained and classified according to the Mercalli magnitude. Parallel factor analyses (PFA), exploratory structural equations models (ESEM), and classic exploratory factor analysis (EFA) were applied to each sample. RESULTS: There were significant differences in fit and number of dimensions between the high and low Mercalli magnitude. In high exposure conditions: There were 1 dimension according to PFA and 3 according to EFA; ESEM and CFA indicated good fit. The main finding was that PTSD has a unique dimension that includes all of its symptoms. CONCLUSIONS: The need to use robust methods of analysis to evaluate data from samples homogeneously exposed to the same potentially traumatic event is argued. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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