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Formin homology 2 domain-containing 3 (FHOD3) gene has emerged as one of the main non-sarcomeric genes associated with hypertrophic cardiomyopathy (HCM), but no cases of biallelic variants associated with disease have been described to date. From 2014 until 2021, FHOD3 was evaluated in our center by next-generation sequencing in 22 806 consecutive unrelated probands. The p.Arg637Gln variant in FHOD3 was enriched in our HCM cohort (284 of 9668 probands; 2.94%) compared with internal controls (64 of 11 480; 0.59%) and gnomAD controls (373 of 64 409; 0.58%), with ORs of 5.40 (95% CI: 4.11 to 7.09) and 5.19 (95% CI: 4.44 to 6.07). The variant affects a highly conserved residue localised in a supercoiled alpha helix considered a clustering site for HCM variants, and in heterozygosis can act as a predisposing factor (intermediate-effect variant) for HCM, with an estimated penetrance of around 1%. Additionally, seven homozygous carriers of p.Arg637Gln in FHOD3 were identified. All but one (unaffected) showed an early presentation and a severe HCM phenotype. All this information suggest that p.Arg637Gln variant in FHOD3 is a low-penetrant variant, with an intermediate effect, that contributes to the development of HCM in simple heterozygosis, being associated with a more severe phenotype in homozygous carriers.
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Cardiomiopatia Hipertrófica , Humanos , Cardiomiopatia Hipertrófica/genética , Fenótipo , Homozigoto , Penetrância , Heterozigoto , Forminas/genéticaRESUMO
The standard molar enthalpy of formation for trimellitic acid (TMAc) in the crystalline phase at 298.15 K, ΔfHm°(cr), was calculated experimentally from the enthalpy of combustion through combustion calorimetry experiments. Likewise, the standard molar enthalpy of sublimation was determined from the standard molar enthalpy of fusion and from the standard molar enthalpy of vaporization from differential scanning calorimetry and thermogravimetry, respectively. Subsequently, the standard molar enthalpies of formation in the gas-phase at 298.15 K, ΔfHm°(g), were calculated. The enthalpies of formation for TMAc, hemimellitic, and trimesic acids were predicted using multiple linear regression (MLR) with a nonreplacement evaluation technique. MLR was applied to the data set that allowed estimating these thermochemical properties with an R2 greater than 0.99. This model was used to compare the predicted and experimental results for benzene carboxylic acids.
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INTRODUCTION: Electrical cardioversion (ECV) is a frequently used procedure for restoring sinus rhythm in atrial fibrillation (AF); however, the rate of recurrence is high. The identification of patients at high risk of recurrence could influence the decision-making process. The present study evaluates the predictive value of risk scores in atrial fibrillation recurrence after elective electrical cardioversion. METHODS: Unicentric, observational, and prospective study of adult patients who have undergone an elective ECV as rhythm control strategy between July 2017 and September 2022. RESULTS: From the 283 analyzed patients (mean age 63.95 ± 10.76212, 74.9% male); 99 had paroxysmal AF (35%) and 159 (59%) presented AF recurrence during a follow-up of 6 months. In patients with post-ECV AF recurrence, the period of time from diagnosis until the performance of the procedure was longer (393 ± 891 vs. 195 ± 527, p = .02). No paroxysmal AF (71.3% vs. 57.8%, p = .02) and LA dilatation with >40 mL/m2 (35.9% vs. 23.3%, p = .02) volumes were more frequent within these patients. AF recurrence was more frequent in patients who had previous ECV (HR = 1.32; 95% CI: 1.12-2.35; p = .01) and more than 1 shock to recover sinus rhythm (HR = 1.62; 95% CI: 1.07-1.63; p = .01). The SLAC, ALARMEc, ATLAS, and CAAP-AF scores were statistically significant, although with a moderate predictive capacity for post-ECV recurrence. CONCLUSIONS: Risk scores analyzed showed a modest value predicting AF recurrence after ECV. Previous ECV, and greater difficulty in restoring SR were independent predictors of recurrence.
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Fibrilação Atrial , Adulto , Humanos , Masculino , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Estudos Prospectivos , Cardioversão Elétrica/métodos , Eletrocardiografia , Fatores de Risco , Recidiva , Resultado do TratamentoRESUMO
The Jatropha curcas cake, a protein-rich by-product of biofuel production, was the subject of our study. We identified and quantified the ACE inhibitory, antioxidant, and antidiabetic activities of bioactive peptides from a Jatropha curcas L. var Sevangel protein isolate. The protein isolate (20.44% recovered dry matter, 38.75% protein content, and 34.98% protein yield) was subjected to two enzyme systems for hydrolysis: alcalase (PEJA) and flavourzyme (PEJF), recording every 2 h until 8 h had passed. The highest proteolytic capacity in PEJA was reached at 2 h (4041.38 ± 50.89), while in PEJF, it was reached at 6 h (3435.16 ± 59.31). Gel electrophoresis of the PEJA and PEJF samples showed bands corresponding to peptides smaller than 10 kDa in both systems studied. The highest values for the antioxidant capacity (DPPH) were obtained at 4 h for PEJA (56.17 ± 1.14), while they were obtained at 6 h for PEJF (26.64 ± 0.52). The highest values for the antihypertensive capacity were recorded at 6 h (86.46 ± 1.85) in PEJF. The highest antidiabetic capacity obtained for PEJA and PEJF was observed at 6 h, 68.86 ± 8.27 and 52.75 ± 2.23, respectively. This is the first report of their antidiabetic activity. Notably, alcalase hydrolysate outperformed flavourzyme hydrolysate and the cereals reported in other studies, confirming its better multi-bioactivity.
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Inibidores da Enzima Conversora de Angiotensina , Antioxidantes , Hipoglicemiantes , Jatropha , Proteínas de Plantas , Jatropha/química , Hidrólise , Antioxidantes/química , Antioxidantes/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Subtilisinas/metabolismo , Subtilisinas/química , EndopeptidasesRESUMO
BACKGROUND: Despite the improvements in supportive care for allogeneic-hematopoietic cell transplantation (allo-HCT) recipients, infectious complications and infection-related mortality (IRM) continue to be a major issue for transplantation centers. METHODS: We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo-HCT) or HLA-identical HCT at a tertiary referral center during 2013-2020. Patients in the haplo-HCT group received post-transplant cyclophosphamide (PT-Cy), and all received reduced-intensity conditioning regimens. RESULTS: More haplo-HCT recipients presented severe infections in the pre-engraftment period (22.4% vs. 6.7%, p = 0.003). Viral (14.9% vs. 4.5%, p = 0.016) and fungal (12.1% vs. 1.1%, p = 0.003) etiologies were more common in this period in this group. The 100-day and 2-year cumulative incidence of IRM was 15% and 21% for the haplo-HCT and 5.6% and 17% for the HLA-identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002). CONCLUSIONS: No differences in IRM were observed based on allo-HCT type, with more haplo-HCT patients suffering from severe infections in the pre-engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Pacientes Ambulatoriais , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ciclofosfamida , Doadores de Tecidos , Condicionamento Pré-Transplante , Estudos RetrospectivosRESUMO
BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP), stiff-person syndrome (SPS), neuromyelitis optica spectrum disorders (NMOSD) and severe refractory myasthenia gravis (MG) are immune-mediated neurological diseases that severely affect patients' functionality and quality of life, with a considerable percentage undergoing relapse or not responding to conventional treatment options. Autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a potential second-line treatment alternative. METHODS: We performed a literature review in PubMed/Medline, EMBASE, Web of Science and Cochrane Library from inception to September 2021 of reported cases and studies of CIDP, SPS, NMOSD and MG that underwent HSCT as a treatment option. RESULTS: A total of 173 patients who underwent HSCT were found, including 32 patients described in case reports and 60 in a phase 2 clinical trial with CIDP, 29 patients with SPS, 42 patients with NMOSD and 10 patients with refractory MG. Complete remission was documented in 68/92 patients with CIDP, 13/29 with SPS and 10/10 with MG. From the NMOSD cases, 24/42 were relapse-free at last follow-up, with 13/33 having negative anti-AQ4 antibodies after HSCT. From all the included studies, only 8/173 patients received an allogeneic HSCT, 4/8 after a failed auto-HSCT. All showed clinical improvement and disease remission. CONCLUSION: HSCT has the potential to induce long-term remission in patients with CIDP, NMOSD, SPS or MG with adequate safety and tolerability. Collaboration between centers is needed to implement larger, homogeneous prospective studies, focusing on immunological correlates of favorable long-term response.
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Transplante de Células-Tronco Hematopoéticas , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Estudos Prospectivos , Qualidade de Vida , Transplante AutólogoRESUMO
AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.
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Cardiomiopatia Hipertrófica , Proteínas Musculares/genética , Proteínas Quinases/genética , Cardiomiopatia Hipertrófica/genética , Heterozigoto , Humanos , Mutação , SarcômerosRESUMO
Urbanization can negatively impact natural protected areas near or surrounded by cities, and such impacts include untreated wastewater discharge, leachates from dumpsters, e-waste, and road dust. In this research, we show that not only large cities with industry are prone to be polluted, but also young touristic cities with high population increase rate can suffer from urban contamination. We evaluated metal pollution in a natural protected area within a 50-year-old city without conventional industry that was likely contaminated by the urban sprawl around the protected area. We tested water, zooplankton, sediment and plant samples for metallic elements to evaluate their bioaccumulation in zooplankton, enrichment factors and geoaccumulation index values in sediments, and translocation factors in plants. Finally, we evaluated the ecological risk due to metal contamination. Metals at levels above our detection limit (20 µg/L) were not found in the water and zooplankton samples. The sediments and plants in the storm drain section of the protected area had a greater concentration of metals and wastewater indicators (coliforms) than those in the rest of the lagoon. Moreover, signs of Al, Cu, Ni, Zn, Cr, Pb, and Ti contamination were found in the plant tissues. We estimated that the ecological risk of this natural protected area surrounded by the city of Cancun (Mexico) ranged from mild to strong, with Zn being the metal of most concern. The results highlight that young touristic cities around the world will endure contamination from urban sources; signs or early warnings of contamination must be identified to prevent and resolve such issues.
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Metais Pesados , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Metais Pesados/análise , México , Águas Residuárias , ÁguaRESUMO
In this work we have studied the Shannon information entropy for two hyperbolic single-well potentials in the fractional Schrödinger equation (the fractional derivative number (0
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We present a study of the structural evolution of tantalum cluster anions Tan-, 6 ≤ n ≤ 13 using a combination of trapped ion electron diffraction (TIED) experiments with a variety of electronic structure methods. A genetic algorithm has been employed to establish a set of likely structures for each cluster, their geometries and energetics have been studied by density functional theory (DFT), random phase approximation, and two-component (2C) DFT methods, which include spin-orbit coupling. We find octahedral structures for Ta6- and Ta8- as well as structures based on the pentagonal bipyramid (Ta7- and Ta9-). Ta10--Ta12- are defective icosahedral structures and Ta13- is a distorted icosahedron. For most clusters, we find a good agreement between the theoretically predicted ground-state structures, especially those determined by the 2C method and the TIED results.
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Chronic kidney disease (CKD) has been typically implicated in cardiovascular risk, considering the function the kidney has related to blood pressure, vitamin D, red blood cell metabolism, and electrolyte and acid-base regulation. However, neurological consequences are also attributed to this disease. Among these, recent large epidemiological studies have demonstrated an increased risk for Parkinson's disease (PD) in patients with CKD. Multiple studies have evaluated individually the association of blood pressure, vitamin D, and red blood cell dysmetabolism with PD, however, no study has reviewed the potential mechanisms related to these components in context of CKD and PD. In this review, we explored the association of CKD and PD and linked the components of the former to propose potential pathways explaining a future increased risk for PD, where renin-angiotensin system, oxidative stress, and inflammation have a main role. Potential preventive and therapeutic interventions based on these associations are also explored. More preclinical studies are needed to confirm the potential link of CKD conditions and future PD risk, whereas more interventional studies targeting this association are warranted to confirm their potential benefit in PD.
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Doença de Parkinson/complicações , Insuficiência Renal Crônica/complicações , Humanos , Inflamação/complicações , Inflamação/metabolismo , Estresse Oxidativo/fisiologia , Doença de Parkinson/metabolismo , Insuficiência Renal Crônica/metabolismo , Sistema Renina-Angiotensina/fisiologiaRESUMO
INTRODUCTION AND AIM: Occult hepatitis B virus infection (OBI) is characterized by the presence of replication-competent hepatitis B virus (HBV) DNA in the liver and/or serum of patients with undetectable levels of the HBV surface antigen (HBsAg). Due to the shared infection routes HIV positive patients are at higher risk of developing OBI, thus, the aim of this study was to determine the frequency of OBI in Mexican HIV-infected patients and to identify mutations in the HBV S gene that could be associated to the development of OBI. MATERIALS AND METHODS: Plasma samples from 50 HIV-infected patients with undetectable levels of the HBsAg were obtained and analyzed. The Core, PreS and S genes were amplified by nested PCR and sequenced by the Sanger method. To analyze HBV diversity in the OBI-positive patients, ten sequences of 762bp from the HBV S gene were selected, cloned, and subsequently sequenced for mutational analyses. RESULTS: OBI infection was found with a frequency of 36% (18/50). All the HBV sequences corresponded to the H genotype. The most common mutations were: C19Y, Q129H, E164D, and I195M, with a frequency of 44%, 36%, 39% and 48% respectively. CONCLUSIONS: In this study, we report the presence of OBI in a cohort of Mexican HIV-infected patients with an overall prevalence of 36%. Mutational analyses revealed that four non-silent mutations were frequent in different regions of the HBsAg gene, suggesting that they might be associated to the development of OBI in this population, nevertheless, further studies are required to determine their role in the pathogenesis of OBI.
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Coinfecção , Infecções por HIV/virologia , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B/virologia , Mutação , Adulto , Idoso , Análise Mutacional de DNA , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/etnologia , Hepatite B/sangue , Hepatite B/diagnóstico , Hepatite B/etnologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Epidemiologia Molecular , Taxa de Mutação , Fatores de Risco , Carga ViralRESUMO
Lately, focus on the relation between Parkinson's disease (PD) and Diabetes has risen greatly, as neuroprotective properties have been attributed to insulin use. Several studies have assessed the effect of glitazones, an insulin-sensitizing agent, in diabetic population on PD future risk. However, reports on the effect of their use have been heterogeneous. We aimed to synthesize the available scientific evidence which assesses the effect of glitazone use in type 2 diabetes patients on PD incidence. A systematic review was performed on multiple electronic databases. Considered for inclusion were studies that assessed the incidence of PD in type 2 diabetes glitazone users. Two reviewers worked independently and in duplicate to assess all studies, extract information and assess the methodological quality in each included study. Four high quality retrospective cohorts fulfilled inclusion criteria. Comparison groups varied across studies. In each study, incidence of PD was lower in glitazone-exposed patients compared to their respective comparison group. Pooled analysis showed lesser risk of PD in ever versus never glitazone users (RR 0.75 [95% C.I. 0.67-0.85; p < .0001; I2 = 0]). Our pooled analysis showed lesser risk of PD in glitazone versus non glitazone users, however, we advise to take results with caution since results are non-adjusted to possible confounding variables, furthermore, different glitazone-exposure time, follow up and comparison groups are aspects that also need to be pointed out. More clinical research focused on glitazone use and its relation with PD is needed, as this could result in new potential treatment modalities.
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Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Doença de Parkinson/prevenção & controle , Tiazolidinedionas/uso terapêutico , Humanos , Incidência , Doença de Parkinson/epidemiologiaRESUMO
BACKGROUND: During pregnancy, the Zika virus (ZIKV) replicates in the placenta and central nervous system (CNS) of infected fetuses; nevertheless, the ability of ZIKV to replicate in other fetal tissues has not been extensively characterized. METHODS: We researched whether dissemination of congenitally-acquired ZIKV outside the CNS exists by searching for the accumulation of the viral envelope protein, ZIKV ribonucleic acid (RNA), and infectious viral particles in different organs of a deceased newborn with Congenital Zika Syndrome. A real-time qualitative polymerase chain reaction (qPCR) was used to detect ZIKV RNA in the brain, thymus, lungs, kidneys, adrenal glands, spleen, liver, and small intestine. The same tissues were analyzed by indirect immunofluorescence and immunoperoxidase assays using the monoclonal antibody 4G2 to detect ZIKV envelope antigens. Isolation of infectious ZIKV in a cell culture was carried out using brain and kidney samples. RESULTS: A postmortem, virological analysis of multiple organs, such as the kidneys (epithelial cells in the renal tubules), lungs (bronchial epithelia), thymus (epithelial cells inside the Hassall's corpuscles), and brain (neurons, ependymal cells, and macrophages) revealed the presence of ZIKV RNA and envelope antigens. Other tissues of the deceased newborn tested positive by qPCR for Epstein-Barr virus and human herpesvirus 6, including the brain cortex (Epstein-Barr) and the thymus, kidneys, and adrenal glands (human herpesvirus 6). The kidneys were identified as a significant niche for viral replication, given that infectious particles were successfully isolated from renal tissues. CONCLUSIONS: Our findings demonstrate the ability of congenitally-acquired ZIKV to produce disseminated infections and the viral tropism towards epithelial cells.
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Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia , Zika virus/genética , Antígenos Virais , Autopsia , Biópsia , Coinfecção , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Transmissão Vertical de Doenças Infecciosas , Nefropatias/patologia , Nefropatias/virologia , México/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Vigilância em Saúde Pública , RNA Viral , Adulto Jovem , Zika virus/imunologia , Zika virus/ultraestrutura , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissãoRESUMO
We characterized natural vertical transmission of Zika virus in pools of Aedes aegypti larvae hatched from eggs collected in Jojutla, Morelos, Mexico. Of the 151 pools analyzed, 17 tested positive for Zika virus RNA; infectious Zika virus was successfully isolated from 1 of the larvae pools (31N) in C6/36 cells. Real-time quantitative PCR and indirect immunofluorescence assays confirmed the identity of the isolate, named Zika virus isolate 31N; plaque assays in Vero cells demonstrated the isolate's infectivity in a mammalian cell line. We obtained the complete genome of Zika virus isolate 31N by next-generation sequencing and identified 3 single-nucleotide variants specific to Zika virus isolate 31N using the meta-CATS tool. These results demonstrate the occurrence of natural vertical transmission of Zika virus in wild Ae. aegypti mosquitoes and suggest that this transmission mode could aid in the spread and maintenance of Zika virus in nature.
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Aedes/virologia , Mosquitos Vetores/virologia , Zika virus/fisiologia , Animais , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Microbiologia Ambiental , Genoma Viral , Humanos , Transmissão Vertical de Doenças Infecciosas , Larva , México/epidemiologia , Filogenia , Vigilância em Saúde Pública , Células Vero , Carga Viral , Ensaio de Placa Viral , Sequenciamento Completo do Genoma , Zika virus/classificação , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologiaRESUMO
INTRODUCTION: The most widespread venous sites of access for implantation intravenous implantable cardiac electronic device (CIED) are the cephalic and subclavian vein. Fluoroscopy-guided axillary venous access is an alternative, but efficacy and safety have not been studied under equal conditions. The aim of the present study is to compare the efficacy and safety of fluoroscopy-guided axillary vs cephalic vein access in CIED implant. METHODS AND RESULTS: Two hundred and forty patients were randomized to receive CIED implantation by the fluoroscopy-guided axillary vein access vs cephalic vein access. The implantation success, the procedure times and the complications were recorded. A comparison of the results of operators was made. The success rate of the randomized venous access was superior in the axillary group than in cephalic (98.3% vs 76.7%, P < .001). Time to access (6.8 ± 3.1 minute vs 13.1 ± 5.8 minutes, P < .001) and implantation duration was significantly shorter in the axillary group than in the cephalic group (42.3 ± 11.6 minutes vs 50.5 ± 13.3 minutes, P < .001). There was no difference in the incidence of complication and inter-operator success rate, complications rate and time to access. CONCLUSION: The fluoroscopy-guided axillary venous access is safe and has a better success rate and faster execution time compared with the cephalic vein access. When the results were compared among the study operators, neither in the axillary nor in the cephalic group there were differences in the success rate, the complication rate, and the time to access. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT03860090.
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Veia Axilar/diagnóstico por imagem , Cateterismo Periférico , Desfibriladores Implantáveis , Marca-Passo Artificial , Flebografia , Implantação de Prótese/instrumentação , Radiografia Intervencionista , Idoso , Idoso de 80 Anos ou mais , Cateterismo Periférico/efeitos adversos , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Flebografia/efeitos adversos , Implantação de Prótese/efeitos adversos , Punções , Radiografia Intervencionista/efeitos adversos , Espanha , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: European Guidelines on Myocardial Revascularization recommend clopidogrel loading dose added to acetylsalicylic acid in elective percutaneous coronary interventions (PCIs). However, there is few evidence supporting this recommendation and other P2Y12 inhibitors have not been tested in these patients. PURPOSE: To evaluate the effectiveness and safety of different loading doses of clopidogrel and ticagrelor in patients without double antiplatelet therapy and stable coronary artery disease (SCAD) undergoing elective PCI. METHODS: Retrospective study of 147 consecutive patients with SCAD undergoing elective PCI. Loading P2Y12 inhibitor doses evaluated were: clopidogrel 600 mg, clopidogrel 300 mg, clopidogrel 150 mg, and ticagrelor 180 mg. We analyzed the occurrence of major adverse cardiovascular events and periprocedural myocardial infarction. RESULTS: One hundred twenty-five patients were treated with clopidogrel (16 with clopidogrel 150 mg, 7 with clopidogrel 300 mg, and 93 with clopidogrel 600 mg) and 21 with ticagrelor 180 mg at the catheterization laboratory. The ticagrelor group had a significantly lower postprocedural peak of troponin-I (0.7 ± 3.4 vs. 0.3 ± 0.7 ng/mL; P = 0.02). There were no differences between groups in terms of major bleeding and hemoglobin drop after PCI (0.6 ± 0.8 vs. 4 ± 0.6; P = 0.8). The median of follow-up was 17 months (interquartile range 9-32.7). At the end of follow-up, major adverse cardiovascular event rate was not different between groups. CONCLUSIONS: In patients without dual antiplatelet therapy undergoing elective PCI, the use of ticagrelor showed lower postprocedural myocardial injury without more bleeding complications.
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Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticagrelor/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Human astrovirus (HAstV) constitutes a major cause of acute gastroenteritis in children. The viral 5' and 3' untranslated regions (UTR) have been involved in the regulation of several molecular mechanisms. However, in astrovirues have been less characterized. Here, we analyzed the secondary structures of the 5' and 3' UTR of HAstV, as well as their putative target sites that might be recognized by cellular factors. To our knowledge, this is the first bioinformatic analysis that predicts the HAstV 5' UTR secondary structure. The analysis showed that both the UTR sequence and secondary structure are highly conserved in all HAstVs analyzed, suggesting their regulatory role of viral activities. Notably, the UTRs of HAstVs contain putative binding sites for the serine/arginine-rich factors SRSF2, SRSF5, SRSF6, SRSF3, and the multifunctional hnRNPE2 protein. More importantly, putative binding sites for PTB were localized in single-stranded RNA sequences, while hnRNPE2 sites were localized in double-stranded sequence of the HAstV 5' and 3' UTR structures. These analyses suggest that the combination of SRSF proteins, hnRNPE2 and PTB described here could be involved in the maintenance of the secondary structure of the HAstVs, possibly allowing the recruitment of the replication complex that selects and recruits viral RNA replication templates.
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Simulação por Computador , Mamastrovirus/genética , Proteínas/metabolismo , Regiões não Traduzidas/genética , Sequência de Bases , Sítios de Ligação , Conformação de Ácido NucleicoRESUMO
Dengue fever is one of the most common viral infections in the world. Although a vaccine against dengue virus (DENV) has been approved in several countries, this disease is still considered a public health priority worldwide. The ability of three small interfering RNAs (FG-siRNAs) targeting conserved sequences in the NS4B and NS5 regions of the DENV genome to inhibit DENV replication was tested in vitro in both Vero and C6/36 cells. The FG-siRNAs were effective against DENV-1, -3, and -4, but not DENV-2. A fourth siRNA specifically targeting the NS5 region of the DENV-2 genome (SG-siRNA) was designed and tested against two different DENV-2 strains, showing high levels of inhibition in both mammalian and insect cells.