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INTRODUCTION/OBJECTIVE: Carotid stenosis (CS) is an important cause of ischemic stroke. Secondary prevention lies in performing a carotid endarterectomy (CEA) procedure, the recommended treatment in most cases. When 2 or more vascular regions are simultaneously affected by atherosclerosis, mainly the carotid arteries, coronary arteries, or limb arteries, a multivessel disease polyvascular disease (PVD) is present. This study aims to assess the potential role of PVD as a long-term predictor of major adverse cardiovascular events (MACE) and all-cause mortality in patients submitted to CEA. METHODS: From January 2012 to December 2021, patients submitted to CEA for carotid stenosis in a tertiary care and referral center were eligible from a prospective database. A posthoc survival analysis was performed using the Kaplan-Meier survival curve method. The primary outcome was the incidence of long-term MACE and all-cause mortality. Secondary outcomes included acute myocardial infarction (AMI), major adverse limb events (MALE), stroke, and acute heart failure (AHF). RESULTS: A total of 207 patients were enrolled, with a median follow-up of 63 months. The mean age was 70.4 ± 8.9, and 163 (78.7%) were male. There were 65 (31.4%) patients that had 2 arterial vascular territories affected, and 29 (14.0%) patients had PVD in 3 arterial beds. On multivariable analysis, both MACE and all-cause mortality had as independent risk factors age (aHR 1.039, P = 0.003; aHR 1.041, P = 0.019), chronic kidney disease (aHR 2.524, P = 0.003; aHR 3.377, P < 0.001) and PVD2 (aHR 3.381, P < 0.001; aHR 2.665, P = 0.013). PVD1 was only associated with MACE as a statistically significant risk factor (aHR 2.531, 1.439-4.450, P < 0.001). CONCLUSIONS: PVD in patients with cerebrovascular disease (CVD) was revealed to carry a 2-fold increased risk for all-cause mortality and MACE during long-term follow-up. PVD may be a simple yet valuable tool in predicting all-cause mortality, MACE, AMI, and MALE after CEA.
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Estenose das Carótidas , Endarterectomia das Carótidas , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Endarterectomia das Carótidas/efeitos adversos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Resultado do Tratamento , Fatores de Risco , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Medição de RiscoRESUMO
Myocardial injury following noncardiac surgery (MINS) is associated with higher mortality and major adverse cardiovascular event rates in the short- and long-term in patients undergoing carotid endarterectomy (CEA). However, its incidence is still unclear in this subset of patients. Therefore, this systematic review with meta-analysis aims to determine the incidence of MINS in patients undergoing CEA. Three electronic databases MEDLINE, Scopus, and Web of Science were used to search for studies assessing the occurrence of MINS in the postoperative setting of patients undergoing CEA. The incidence of MINS was pooled by random-effects meta-analysis, with sources of heterogeneity being explored by meta-regression and subgroup analysis (general anesthesia vs. regional anesthesia). Assessment of studies' quality was performed using National Heart, Lung, and Blood Institute Study Quality Assessment Tool, and Risk of Bias 2 tools. Twenty studies were included, with a total of 117,933 participants. Four of them were RCTs, while the remaining were cohort studies. All observational cohorts had an overall high risk of bias, except for Pereira Macedo et al. Three of them had repeated population, thus only data from the most recent one was considered. On the other hand, all RCT had an overall low risk of bias. In patients under regional anesthesia, the incidence of MINS in primary studies ranged between 2% and 15.3%, compared to 0-42.5% for general anesthesia. The meta-analytical incidence of MINS after CEA was of 6.3% [95% CI 2.0-10.6%], but severe heterogeneity was observed (I2=99.1%). MINS appears to be relatively common among patients undergoing CEA. The observed severe heterogeneity points to the need for further larger studies adopting consistent definitions of MINS and equivalent cut-off values.
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Estenose das Carótidas , Endarterectomia das Carótidas , Humanos , Endarterectomia das Carótidas/efeitos adversos , Resultado do Tratamento , Incidência , Fatores de Risco , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Estenose das Carótidas/cirurgia , Complicações Pós-OperatóriasRESUMO
INTRODUCTION: The intermittent intrapulmonary deflation (IID) technique is a recent airway clearance technique that intends to delay the onset of expiratory flow limitation (EFL) during exhalation. We showed in a previous study that IID increased the expiratory volume of COPD patients compared to quiet breathing and positive expiratory pressure (PEP) therapy. We hypothesized that it was due to the attenuation of the EFL. OBJECTIVES: To verify the physiologic effects of IID and PEP techniques on EFL with a mechanical lung model. METHODS: A mechanical lung model was created to assess the effects of IID and PEP techniques. The thorax was simulated by a plexiglas box in which an adult test lung was connected. A calibration syringe simulated the inspiratory phase. Later, with activation of the IID, the expiratory phase was driven by the deflation generated by the device. With PEP, the expiration occurred maintaining an expiratory pressure between 5 and 10 cmH2O. A pneumotachograph and a pressure transducer were placed in series for flow, volumes and pressure measurements. RESULTS: The model reproduced physiological characteristics of EFL. However, the deflation of the model was slowed by IID and PEP, and flow remained almost constant, so flow limitation was reduced. CONCLUSION: The IID and PEP attenuate EFL and increase exhaled volume in the in vitro model.
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Expiração , Pulmão , Adulto , Humanos , Expiração/fisiologia , Respiração Artificial/métodosRESUMO
The combination of a polyphenol, quercetin, with dasatinib initiated clinical trials to evaluate the safety and efficacy of senolytics in idiopathic pulmonary fibrosis, a lung disease associated with the presence of senescent cells. Another approach to senotherapeutics consists of controlling inflammation related to cellular senescence or "inflammaging", which participates, among other processes, in establishing pulmonary fibrosis. We evaluate whether polyphenols such as caffeic acid, chlorogenic acid, epicatechin, gallic acid, quercetin, or resveratrol combined with different senotherapeutics such as metformin or rapamycin, and antifibrotic drugs such as nintedanib or pirfenidone, could present beneficial actions in an in vitro model of senescent MRC-5 lung fibroblasts. A senescent-associated secretory phenotype (SASP) was evaluated by the measurement of interleukin (IL)-6, IL-8, and IL-1ß. The senescent-associated ß-galactosidase (SA-ß-gal) activity and cellular proliferation were assessed. Fibrosis was evaluated using a Picrosirius red assay and the gene expression of fibrosis-related genes. Epithelial-mesenchymal transition (EMT) was assayed in the A549 cell line exposed to Transforming Growth Factor (TGF)-ß in vitro. The combination that demonstrated the best results was metformin and caffeic acid, by inhibiting IL-6 and IL-8 in senescent MRC-5 cells. Metformin and caffeic acid also restore cellular proliferation and reduce SA-ß-gal activity during senescence induction. The collagen production by senescent MRC-5 cells was inhibited by epicatechin alone or combined with drugs. Epicatechin and nintedanib were able to control EMT in A549 cells. In conclusion, caffeic acid and epicatechin can potentially increase the effectiveness of senotherapeutic drugs in controlling lung diseases whose pathophysiological component is the presence of senescent cells and fibrosis.
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Senescência Celular , Fibroblastos , Pulmão , Polifenóis , Humanos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Senescência Celular/efeitos dos fármacos , Polifenóis/farmacologia , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Células A549 , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Metformina/farmacologia , Ácidos Cafeicos/farmacologia , Indóis/farmacologia , Senoterapia/farmacologia , Linhagem Celular , Fenótipo Secretor Associado à Senescência/efeitos dos fármacos , Sirolimo/farmacologia , Interleucina-8/metabolismo , Interleucina-8/genética , Fator de Crescimento Transformador beta/metabolismo , PiridonasRESUMO
BACKGROUND: Malignant hyperfunctioning thyroid nodules are rare and more likely to occur in follicular cancer types rather than papillary variants. The authors present a case of a papillary thyroid carcinoma associated with a hyperfunctioning nodule. METHODS: A single adult patient submitted to total thyroidectomy with the presence of thyroid carcinoma within hyperfunctioning nodules was selected. Additionally, brief literature was conducted. RESULTS: An asymptomatic 58-year-old male was subjected to routine blood analysis and a TSH level of <0.003 mIU/L was found. Ultrasonography revealed a 21 mm solid, hypoechoic, and heterogenous nodule with microcalcifications in the right lobe. A fine needle aspiration guided by ultrasound resulted in a follicular lesion of undetermined significance. A 99mTc thyroid scintigram was followed and identified a right-sided hyperfunctioning nodule. Another cytology was performed and a papillary thyroid carcinoma was derived as a result. The patient underwent a total thyroidectomy. Postoperative histology confirmed the diagnosis and a tumor-free margin with no vascular or capsular invasions. CONCLUSION: Hyperfunctioning malignant nodules are a rare association, although a careful approach should be led since major clinical implications arise. Selective fine needle aspiration in all suspicious ≥1 cm nodules should be considered.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Nódulo da Glândula Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , UltrassonografiaRESUMO
BACKGROUND: In noncardiac surgery, several biomarkers are known to play a role in predicting long-term complications, such as major adverse cardiovascular events (MACE), myocardial infarction, or death. Carotid endarterectomy (CEA) is considered a low to medium-risk surgery for carotid stenosis aimed at preventing stroke events. Brain natriuretic peptide (BNP) is a biomarker with potential prognostic value regarding MACE. Since its role in patients undergoing CEA is unknown, this study aims to assess the potential role of BNP as a short and long-term predictor of all-cause mortality and MACE in patients undergoing CEA. METHODS: From a prospective database, patients who underwent CEA under regional anesthesia (RA) at a tertiary hospital center were enrolled, and a post hoc analysis was conducted. Patients on which BNP levels were measured up to fifteen days before surgery, and two groups based on the BNP threshold (200 pg/mL) were defined and compared. Kaplan Meier survival curves and adjusted hazard ratios (aHR) were assessed by multivariable Cox regression. The primary outcome was the incidence of long-term MACE and all-cause mortality. Secondary outcomes included the incidence of AMI and AHF. RESULTS: A total of 89 patients were evaluated. The mean age of the cohort was 71.2 ± 8.7 years, with 71 (79.8%) males, and presented a median follow-up of 30 [13.5-46.4] months. BNP > 200 pg/mL has demonstrated positive predictive value for MACE (aHR: 5.569, confidence interval (CI): 2.441-12.7, p < 0.001) and all-cause mortality (aHR: 3.469, CI: 1.315-9.150, p = 0.018). CONCLUSION: BNP has been demonstrated to independently predict long-term all-cause mortality, MACE and AMI following CEA. It serves as a low-cost, ready-to-use biomarker, although further studies are necessary.
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BACKGROUND: R2CHA2DS2-VA score has been used to predict short and long-term outcomes in many cardiovascular diseases. This study aims to validate the R2CHA2DS2-VA score as a long-term major adverse cardiovascular events (MACE) predictor after carotid endarterectomy (CEA). Secondary outcomes were also assessed regarding the incidence of all-cause mortality, acute myocardial infarction (AMI), major adverse limb events (MALE), and acute heart failure (AHF). METHODS: From January 2012 to December 2021, patients (n = 205) from a Portuguese tertiary care and referral center that underwent CEA with regional anesthesia (RA) for carotid stenosis (CS) were selected from a previously collected prospective database, and a posthoc analysis was performed. Demographics and comorbidities were registered. Clinical adverse events were assessed 30 days after the procedure and in the subsequent long-term surveillance period. Statistical analysis was performed by the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: Of the patients enrolled, 78.5% were males with a mean age of 70.44 ± 8.9 years. Higher scores of R2CHA2DS2-VA were associated with long-term MACE (adjusted hazard ratio (aHR) 1.390; 95% confidence interval (CI) 1.173-1.647); and mortality (aHR 1.295; 95% CI 1.08-1.545). CONCLUSIONS: This study demonstrated the potential of the R2CHA2DS2-VA score to predict long-term outcomes, such as AMI, AHF, MACE, and all-cause mortality, in a population of patients submitted to carotid endarterectomy.
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Doenças Cardiovasculares , Estenose das Carótidas , Endarterectomia das Carótidas , Insuficiência Cardíaca , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Endarterectomia das Carótidas/efeitos adversos , Doenças Cardiovasculares/etiologia , Fatores de Risco , Resultado do Tratamento , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Infarto do Miocárdio/etiologia , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/etiologia , Acidente Vascular Cerebral/etiologia , Medição de Risco , Estudos RetrospectivosRESUMO
Contralateral carotid stenosis (clCS) has been described as a perioperative predictor of mortality after carotid endarterectomy (CEA). However, its predictive value on long-term cardiovascular events remains controversial. The study aims to assess the potential role of clCS as a long-term predictor of major adverse cardiovascular events (MACE) in patients who underwent CEA. From January 2012 to July 2020, patients undergoing CEA under regional anesthesia for carotid stenosis in a tertiary care and referral center were eligible from a prospective database, and a post hoc analysis was performed. The primary outcome consisted in the occurrence of long-term MACE. Secondary outcomes included all-cause mortality, stroke, myocardial infarction, acute heart failure, and major adverse limb events. A total of 192 patients were enrolled. With a median 50 months follow-up, chronic kidney disease (CKD) (mean survival time (MST) 51.7 vs. 103.3, P < 0.010) and peripheral artery disease (PAD) (MST 75.1 vs. 90.3, P = 0.001) were associated with decreased survival time. After propensity score matching (PSM), CKD (MST 49.1 vs. 106.0, P = 0.001) and PAD (MST 75.7 vs. 94.0, P = 0.001) maintained this association. On multivariate Cox regression analysis, contralateral stenosis was associated with higher MACE (hazard ratio (HR) = 2.035; 95% CI: 1.113-3.722, P = 0.021 and all-cause mortality (HR = 2.564; 95% CI: 1.276-5,152 P = 0.008). After PSM, only all-cause mortality (HR 2.323; 95% CI: 0.993-5.431, P = 0.052) maintained a significant association with clCS. On multivariable analysis, clCS (aHR 2.367; 95% CI: 1.174-4.771, P = 0.016), age (aHR 1.039, 95% CI: 1.008-1.070), CKD (aHR 2.803; 95% CI: 1.409-5.575, P = 0.003) and PAD (aHR 3.225, 95% CI: 1.695-6.137, P < 0.001) were independently associated with increased all-cause mortality. Contrary to MACE, clCS is a strong predictor of long-term all-cause mortality after CEA. However, MACE risk may compromise CEA benefits by other competitive events. Therefore, further studies are needed to establish the role of clCS on postoperative events and on patients' specific assessments in order to determine the best medical treatment and easy access to surgical intervention.
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Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Endarterectomia das Carótidas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
We are currently facing a pandemic that continuously causes high death rates and has negative economic and psychosocial impacts. Therefore, this period requires a quick search for viable procedures that can allow us to use safe and non-invasive clinical tools as prophylactic or even adjuvant methods in the treatment of COVID-19. Some evidence shows that photobiomodulation therapy (PBMT) can attenuate the inflammatory response and reduce respiratory disorders similar to acute lung injury (ALI), complications associated with infections, such as the one caused by the new Coronavirus (SARS-CoV-2). Hence, the aim of the present study was to evaluate the influence of PBMT (infrared low-level laser therapy) on the treatment of ALI, one of the main critical complications of COVID-19 infection, in an experimental model in rats. Twenty-four male Wistar rats were randomly allocated to three experimental groups (n = 8): control group (CG), controlled ALI (ALI), and acute lung injury and PBM (ALIP). For treatment, a laser equipment was used (808 nm; 30 mw; 1.68 J) applied at three sites (anterior region of the trachea and in the ventral regions of the thorax, bilaterally) in the period of 1 and 24 h after induction of ALI. For treatment evaluation, descriptive histopathological analysis, lung injury score, analysis of the number of inflammatory cells, and expression of interleukin 1 ß (IL-1ß) were performed. In the results, it was possible to observe that the treatment with PBMT reduced inflammatory infiltrates, thickening of the alveolar septum, and lung injury score when compared to the ALI group. In addition, PBMT showed lower immunoexpression of IL-1ß. Therefore, based on the results observed in the present study, it can be concluded that treatment with PBMT (infrared low-level laser therapy) was able to induce an adequate tissue response capable of modulating the signs of inflammatory process in ALI, one of the main complications of COVID-19.
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COVID-19 , Terapia com Luz de Baixa Intensidade , Animais , COVID-19/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Pulmão/patologia , Masculino , Ratos , Ratos Wistar , SARS-CoV-2RESUMO
OBJECTIVE: Patients undergoing carotid endarterectomy (CEA) may experiment neurologic deficits during the carotid cross-clamping due to secondary cerebral hypoperfusion. An associated risk of postoperative stroke incidence is also well established. This work aimed to assess the postoperative adverse events related to neurologic deficits in the awake test after clamping and to determine its predictive factors. Methods. From January 2012 to January 2018, 79 patients from a referral hospital that underwent CEA with regional anesthesia for carotid stenosis and manifested neurologic deficits were gathered. Consecutively selected controls (n = 85) were submitted to the same procedure without developing neurological changes. Postoperative complications such as stroke, myocardial infarction, all-cause death, and Clavien-Dindo classification were assessed 30 days after the procedure. Univariate and binary logistic regressions were performed for data assessment. Results. Patients with clamping associated neurologic deficits were significantly more obese than the control group (aOR = 9.30; 95% CI: 2.57-33.69; p = .01). Lower degree of ipsilateral stenosis and higher degree of contralateral stenosis were independently related to clamping intolerance (aOR = 0.70; 95% CI: 0.49-0.99; p = .047 and aOR = 1.30; 95% CI: 1.06-1.50; p = .009, respectively). Neurologic deficits were a main 30-day stroke predictor (aOR = 4.30; 95% CI: 1.10-16.71; p = .035). Conclusions. Neurologic deficits during carotid clamping are a predictor of perioperative stroke. Body mass index > 30 kg/m2, a lower degree of ipsilateral stenosis, and a higher degree of contralateral stenosis are independent predictors of neurologic deficits and, therefore, might play a role in the prevention of procedure-related stroke.
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Endarterectomia das Carótidas , Complicações Intraoperatórias , Doenças do Sistema Nervoso , Anestesia por Condução , Constrição Patológica/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Humanos , Complicações Intraoperatórias/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Acidente Vascular Cerebral/epidemiologiaRESUMO
The aim of this study was to compare testicle morpho-functional characteristics in bulls undergoing a single or two immunizations against GnRH. Nelore (Bos taurus indicus) bulls were randomly allocated into three experimental groups: G1 (n=12), a single 400 µg dose of anti-GnRH vaccine on day 0; G2 (n=11), a first 400 µg dose of anti-GnRH vaccine on day 0 followed by a second (boost) dose 30 days later; and control group (CG, n=12), 1 mL saline 0.9% at day 0. Every 30 days, from day 0 until slaughter at day 90, the bulls were weighed and underwent testicular biometry, semen collection and analysis, and blood sample collection for testosterone measurement. Immediately after slaughter, the testicles were removed and transport at 15°C to the laboratory for histopathological analysis. There was a decrease in testicular height (P=0.0476), width (P=0.0021), and in scrotal circumference (P=0.0001), after either a single (G1) or two (G2) immunizations against GnRH. Both G1 and G2 had lower testosterone concentrations than CG from day 60 on (P<0.01), but in G2, it was also lower than in G1 at day 90 (P=0.0006). All sperm parameters were affected by active immunization against GnRH (P<0.05), and in G2, averages were lesser (P<0.05) than in G1 from day 60 on. No signs of seminiferous tubule degeneration were found in any sample from the CG, contrasting with 75.0% and 100.0% of the samples from G1 and G2, respectively. In summary, immunocastration affected testicle morpho-functional characteristics in bulls in a time- and dose-dependent way.
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Testículo , Vacinas , Animais , Bovinos , Hormônio Liberador de Gonadotropina , Masculino , Escroto , Espermatozoides , TestosteronaRESUMO
The incidence of penile cancer (PeCa) is increasing worldwide, however, the highest rates are reported in underdeveloped countries. The molecular mechanisms that underly the onset and progression of these tumors are still unclear. Therefore, our goal was to determine the genome-wide copy number alterations and the involvement of human papiloma virus (HPV) (TP53 and RB1), inflammatory (COX2 and EGFR), and PI3K/AKT pathway (AKT1, AKT2, EGFR, ERBB3, ERBB4, PIK3CA, and PTEN) associated genes in patients with PeCa from a high incidence region in Brazil (Maranhão). HPV genotyping was performed by nest-PCR and genome sequencing, copy number alterations (CNAs) by array comparative genomic hybridization and gene copy number status, gene, and protein expression by quantitative polymerase chain reaction, reverse transcriptase-quantitative polymerase chain reaction, and immunohistochemistry, respectively. HPV genotyping revealed one of the highest frequencies of HPV reported in PeCa, affecting 96.4% of the cases. The most common CNAs observed were located at the HPV integration sites, such as 2p12-p11.2 and 14q32.33, where ADAM 6, KIAA0125, LINC00226, LINC00221, and miR7641-2, are mapped. Increased copy number of ERBB3 and EGFR genes were observed in association with COX2 and EGFR overexpression, reinforcing the role of the inflammatory pathway in PeCa, and suggesting anti-EGFR and anti-COX2 inhibitors as promising therapies for PeCa. Additionally, TP53 and RB1 messenger RNA downregulation was observed, suggesting the occurrence of other mechanisms for repression of these oncoproteins, in addition to the canonical HPV/TP53/RB1 signaling pathway. Our data reinforce the role of epigenetic events in abnormal gene expression in HPV-associated carcinomas and suggest the pivotal role of HPV driving CNAs and controlling gene expression in PeCa.
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Carcinoma de Células Escamosas/genética , Variações do Número de Cópias de DNA , Infecções por Papillomavirus/complicações , Neoplasias Penianas/genética , RNA Mensageiro/genética , Proteínas de Ligação a Retinoblastoma/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genômica , Humanos , Masculino , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Neoplasias Penianas/patologia , Neoplasias Penianas/virologia , Fatores de RiscoRESUMO
BACKGROUND: Rheumatoid Arthritis (RA) is an autoimmune systemic disease and in its pathogenesis participate several proinflammatory cytokines, including those produced by Th17 cells. We performed a systematic review aiming to assess the associations between polymorphisms in Th17 cytokines, namely IL-17A, IL-17F, IL-21 and IL-22, and susceptibility to RA. METHODS: We searched three electronic databases (MEDLINE, Scopus and Web of Science) for observational studies assessing the association between susceptibility to RA (or its clinical presentation) and polymorphisms of the cytokines IL-17A, IL-17F, IL-21 and IL-22. From the selected studies, we extracted information on the studied polymorphisms, assessed outcomes, and demographic characteristics of participants. We performed random effects meta-analyses assessing the associations between susceptibility to RA and different genotypes of the IL-17A rs2275913, IL-17Frs763780 andIL-17Frs2397084polymorphisms. Primary studies' quality was assessed using the Q-Genie tool. RESULTS: Fifteen studies were included in this systematic review. Five IL-17A polymorphisms were reported to be associated with susceptibility to RA. For the IL-17A rs2275913 polymorphism, our meta-analysis showed the AA genotype to be significantly associated with lower susceptibility to RA(ORâ¯=â¯0.76; 95%CIâ¯=â¯0.61-0.93;pâ¯=â¯0.01), while the opposite was observed for the GG genotype (ORâ¯=â¯1.20; 95%CIâ¯=â¯1.06-1.35;pâ¯=â¯0.01). Concerning IL-17Frs763780 polymorphism, theTT genotype was found to be significantly less frequent in RA patients(ORâ¯=â¯0.49; 95%CIâ¯=â¯0.31-0.77;pâ¯=â¯0.002), while the opposite was observed for the CT genotype (ORâ¯=â¯2.00; 95%CIâ¯=â¯1.03-3.87;pâ¯=â¯0.04). No significant associations were found regarding rs2397084polymorphisms. For IL-21, rs6822844 and rs4505848 were described to have significant associations with susceptibility to RA. No studies were found assessing IL-22 polymorphisms in RA. CONCLUSIONS: IL-17A rs2275913 and IL-17F rs763780 polymorphisms are significantly associated with susceptibility to RA and with different clinical characteristics of this disease.
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Artrite Reumatoide/genética , Interleucina-17/genética , Interleucinas/genética , Alelos , Artrite Reumatoide/metabolismo , Bases de Dados Genéticas , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Interleucina 22RESUMO
Isoflavones are phenolic secondary metabolites mainly occurring in soy and soybean products. Compared to glycoside forms, isoflavone aglycones present higher biological activities. This study evaluated the potential of microbial and enzymatic treatments in biotransformed isoflavones in their biologically active forms in soymilk. Seven different cultures of lactic acid bacteria and bifidobacteria associated with the action of immobilized tannase enzyme were screened for isoflavone glycoside biotransformation ability. The biotransformed soymilk samples were characterized regarding isoflavone profile, total phenolic content, and in vitro antioxidant activities. All bacterial strains showed a good growth capacity in soymilk matrix and produced ß-glucosidase enzyme, which hydrolyzed isoflavone glycosides into aglycones in soymilk after 24 h of fermentation. The microbial fermentation followed by tannase reaction (FT processes) resulted in the highest increase of bioactive aglycones (10.3- to 13.1-fold for daidzein, 10.4- to 12.3-fold for genistein, and 3.8- to 4.7-fold for glycitein), compared to control soymilk. Further, FT processes enhanced the total phenolic content (53-70%) and antioxidant activity by ORAC (69-102%) and FRAP (49-71%) assays of the soymilk matrix. Therefore, the combination of microbial fermentation and tannase treatment is a promising strategy to obtain a fermented soy product rich in bioactive isoflavones with greater health-promoting potential. KEY POINTS: ⢠Bacterial cultures and tannase enzyme displayed isoflavone deglycosylation activity. ⢠The addition of tannase following the fermentation maximized the isoflavone conversion. ⢠Increased isoflavone aglycones contributed to the improved antioxidant activity of soymilk.
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Isoflavonas , Leite de Soja , Antioxidantes , Biotransformação , Fermentação , Microbiologia de Alimentos , Isoflavonas/análiseRESUMO
OBJECTIVES: Carotid cross-clamping during endarterectomy exposes the patient to intraoperative neurological deficits due to embolism or cerebral hypoperfusion. To prevent further cerebrovascular incidents, resorting to shunt is frequently recommended. However, since this method is also considered a stroke risk factor, the use is still controversial. This study aims to shed some light on the best approach regarding the use of shunt in symptomatic cerebral malperfusion after carotid artery cross-clamping. METHODS: From January 2012 to January 2018, 79 patients from a tertiary referral hospital who underwent carotid endarterectomy with regional anesthesia for carotid artery stenosis and manifested post-clamping neurologic deficits were prospectively gathered. Shunt use was left to the decision of the surgeon and performed in 31.6% (25) of the patients. Demographics, comorbidities, imaging tests, and clinical/intraoperative features were evaluated. For data assessment, univariate analysis was performed. RESULTS: Regarding 30-day stroke, 30-day postoperative complications (stroke, surgical hematoma, hyperperfusion syndrome), and cranial nerve injury, no significant differences were found (P = 0.301, P = 0.460, and P = 0.301, respectively) between resource to shunt and non-shunt. Clamping and surgery times were significantly higher in the shunt group (P < 0.001 and P = 0.0001, respectively). CONCLUSIONS: Selective-shunting did not demonstrate superiority for patients who developed focal deficits regarding stroke or other postoperative complications. However, due to the limitations of this study, the benefit of shunting cannot be excluded. Further randomized trials are recommended for precise results on this matter with current sparse clinical evidence.
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Anestesia por Condução , Estenose das Carótidas/cirurgia , Circulação Cerebrovascular , Endarterectomia das Carótidas/instrumentação , Idoso , Idoso de 80 Anos ou mais , Anestesia por Condução/efeitos adversos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Estenose das Carótidas/fisiopatologia , Traumatismos dos Nervos Cranianos/etiologia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Buriti oil is rich in monounsaturated fatty acids, carotenoids and tocopherols and it is used for the treatment of various diseases. One strategy to restructure the triglycerides is enzymatic interesterification and nanocarriers have been employed to improve the solubility, bioavailability and stability of active compounds. This work aims to investigate the in vitro cytotoxicity of this structured oil in nanoemulsions and nanostructured lipid carriers to expand the applicability of the crude oil. None of the samples had a cytotoxic effect on Caco-2 and HepG2 cell lines at the concentrations tested. Structured lipids acted protecting against oxidative stress and lipid peroxidation. Additionally, no consumption of glutathione has been observed in both cells, and the compounds present in buriti oil are possibly acting as antioxidants. Thus, nanoparticles prepared with interesterified buriti oil had low cytotoxicity and high oxidative stability, with great potential for future applications.
Assuntos
Carotenoides , Portadores de Fármacos , Nanoestruturas , Óleos de Plantas , Células CACO-2 , Carotenoides/química , Carotenoides/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Avaliação de Medicamentos , Células Hep G2 , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Óleos de Plantas/química , Óleos de Plantas/farmacologiaRESUMO
Background: Patients undergoing carotid endarterectomy (CEA) may suffer from cerebral hypoperfusion during the carotid cross-clamping. Near-infrared spectroscopy cerebral oximetry (NIRS) is a non-invasive method of regional cerebral oxygen saturation measurement reflecting changes in cerebral blood flow during CEA. The main goal of the study was to evaluate the accuracy of the NIRS in detecting cerebral hypoperfusion during CEA under regional anesthesia (RA) and compare it with awake neurological testing. Patients and methods: A prospective observational study of 28 patients that underwent CEA in RA and manifested neurologic deficits, and 28 consecutive controls from a tertiary and referral center, was performed. All patients were monitored with NIRS cerebral oximetry and awake testing as the control technique. Subsequently, operating characteristic curve and Cohen's kappa coefficient were determined to evaluate the reliability of the monitoring test. Results: NIRS presented a sensitivity of 27.3% and a specificity of 89.3% in comparison to awake testing. Receiver operating characteristic (ROC) curve analysis demonstrated that a decrease of at least 20% in cerebral oxygen saturation is the best threshold to infer cerebral hypoperfusion. However, the respective area under the curve (AUROC) was 0.606 (95% CI: 0.456-0.756, P = 0.178) with a calculated Cohen's kappa of 0.179, P = 0.093. Regarding 30-days outcomes, only awake testing has shown significant associations with stroke and postoperative complications (P = 0.043 and P = 0.05), which were higher in patients with post-clamping neurologic deficits. Conclusions: NIRS demonstrated a reduced discriminative capacity for critical cerebral hypoperfusion, and does not seem to add substantial clinical benefits to the awake test.
Assuntos
Anestesia por Condução , Endarterectomia das Carótidas , Isquemia Encefálica , Circulação Cerebrovascular , Humanos , Monitorização Intraoperatória , Oximetria , Oxigênio , Estudos Prospectivos , Reprodutibilidade dos Testes , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
The advanced glycation end products (AGEs) constitute a wide variety of substances synthesized from interactions between amino groups of proteins and reducing sugars, which excess induces pathogenesis of chronic diseases. Brazil is the major producer of citrus, a low-cost source of hesperidin, which is a polyphenol recognized for its capacity to inhibit AGEs formation. This is the first work to evaluate the effects of a polyphenolic fraction derived from citrus wastes on the antiglycation and on the inhibition properties of digestive enzymes on the possibility to process these wastes in high value-added products. At concentrations of 10, 15 and 20 mg/mL inhibition of AGEs was higher than 60%. The extracts were able to inhibit by 76% the activity of pancreatic lipase and by 98% the activity of α-glucosidase. For the α-amylase the inhibition capacity was lower than 50%. Strong correlation was obtained among anti-glycation with polyphenolic content and antioxidant capacity.
Assuntos
Citrus/química , Inibidores Enzimáticos/química , Glicosídeo Hidrolases/antagonistas & inibidores , Lipase/antagonistas & inibidores , Polifenóis/química , alfa-Amilases/antagonistas & inibidores , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Bovinos , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Glicosilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Saccharomyces cerevisiae/enzimologia , SuínosRESUMO
RESEARCH BACKGROUND: Extracted from the pulp of an Amazonian fruit, buriti oil is rich in micronutrients with antioxidant properties and high biological value. The few studies available indicate that this oil could be used in a wide range of applications; however, there are no studies that work on the improvement in the characteristics of this oil for commercial application. The enzymatic interesterification is one of the tools available to improve the properties of oils and fats and our recent studies have demonstrated that the lipase could specifically act on buriti oil to produce structured lipids rich in oleic acid, while preserving most of the minor compounds present in this oil. Still looking for ways to expand the applicability of this raw oil, in this work, we are interested in studying the behaviour of this structured oil in nanostructured lipid carriers (NLCs). EXPERIMENTAL APPROACH: The NLCs were produced with interesterified buriti oil and the stability, droplet size, electrical charge, microstructure, polymorphism and antioxidant activity of the samples were evaluated by ORAC and FRAP methods. RESULTS AND CONCLUSIONS: The results showed that the interesterification formed more unsaturated triacylglycerols (TAGs), and NLCs prepared with interesterified buriti oil had smaller droplets than NLCs with crude buriti oil. Particles remained stable throughout the storage period and NLCs exhibited complex polymorphism with the presence of three crystalline forms. The oxygen radical absorbance capacity (ORAC) value was approx. 23% higher in nanolipid carries with structured lipids than in the nanolipid carriers with crude buriti oil, and the ferric reducing antioxidant power (FRAP) value 16% higher, demonstrating the influence of interesterification on the antioxidant activity of nanocarriers. Thus, NLCs prepared with interesterified buriti oil had small droplets, high stability and antioxidant capacity, and have a potential for nutritional and biological applications. NOVELTY AND SCIENTIFIC CONTRIBUTION: This research showed that interesterification positively influenced the physicochemical properties of NLCs, producing the oil rich in oleic acid, high stability and antioxidant capacity. Therefore, it may be interesting to use these nanocarriers to obtain efficient carrier systems for future applications.
RESUMO
Peripheral Arterial Disease (PAD) is a prevalent condition that predisposes the patients to major cardiovascular events. The majority of patients are asymptomatic, however PAD has a great impact in the patients' lifestyle due to its chronic nature. The Peripheral Arterial Questionnaire (PAQ) is a validated tool to quantify the patients' subjective experience of the disease. The aim of this work is to validate the Portuguese version of PAQ. A retrospective study of 59 patients with aortoiliac disease Trans-Atlantic Inter Society Consensus (TASC) type D from two centers in Portugal was conducted. Only 36 patients were able to answer the PAQ and two Portuguese validated questionnaires - a disease-specific (Walk Impairment Questionnaire - WIQ) and a generic one (EuroQol 5 dimensions - 5 level EQ5D-5L). Con- vergent validity of the PAQ was evaluated by correlating the extracted PAQ subscales and Summary score with the WIQ subscales and summary score, as with EQ5D-5L Summary score and EQ5D-5L index by calculating the covariance. The Portuguese version of the peripheral artery questionnaire presented a Cronbach's α for the Summary scale of 0.913. Mean inter-item correlation for the Physical Function domain was 0.471, 0.551 for the Perceived Disability, and 0.464 for Treat- ment Satisfaction. In summary, the Portuguese version of PAQ demonstrated a good level of discrimination between patients with or without symptomatic PAD and its severity and was sensitive to the presence of risk-factors relevant for PAD.