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Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.
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Adaptação Fisiológica , Fatores de Risco de Doenças Cardíacas , Humanos , Feminino , Gravidez , Adulto , Função Ventricular Esquerda , Cardiomegalia/fisiopatologia , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/etiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/sangue , Volume Sistólico , Terceiro Trimestre da Gravidez , Diabetes Gestacional/fisiopatologia , Complacência (Medida de Distensibilidade) , Primeiro Trimestre da Gravidez , Obesidade/fisiopatologia , Obesidade/complicações , Fatores de RiscoRESUMO
This work investigated the mechanical transmission of Trypanosoma vivax by Stomoxys calcitrans to cattle in a region without a cyclic vector. The study involved two experiments, one with calves experimentally infected with T. vivax, in the acute phase of trypanosomosis (Experiment 1) and the other in the chronic phase (Experiment 2). In both experiments, two transmission methods were used with flies that had not fed for 24 h or had never fed: (i) Method 1: flies released freely in cattle pens (≈3,300 flies/pen for 10 days); and (ii) Method 2: flies placed in a feeding chamber (12 flies/animal). To develop Method 1 in the two experiments (acute and chronic phases), T. vivax-positive animals were kept with T. vivax-negative animals. Periodically, the Brener method, Woo method, blood smears, cPCR, ELISA, IFAT, and Imunoteste® were performed to detect T. vivax in the animals. We also recorded the animals' head tossing and hoof stomping and the number of flies near the pens' inner walls. Subsequently, biological testing was performed using lambs. For Method 2 in both experiments, flies inside the feeding chamber first fed on T. vivax-positive animals and later on negative animals. In both experiments and methods, we examined the flies for the presence of T. vivax through blood smears and cPCR of the proboscis and abdomen. In Experiment 2 (chronic phase), a test was conducted to determine how long trypomastigotes forms could survive on the blood of animals with different levels of parasitemia. None of the animals (calves and lambs) became infected with T. vivax or showed antibodies against it. During the evaluation period, the animals in the presence of the flies exhibited more hoof stomping and head tossing compared to those without flies (control). Additionally, there was an increase in the number of flies in the pens during the experiment. Only in Experiment 1 (acute phase) were T. vivax trypomastigotes and DNA found in the abdomen of the flies but not in the proboscis. In Experiment 2 (chronic phase), higher concentrations of trypomastigotes per milliliter of blood were associated with a shorter the lifespan of this stage of the parasite. In conclusion, under the variable conditions of the experiments (hosts, number of flies, and level of parasitemia), S. calcitrans was unable to mechanically transmit T. vivax to cattle.
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Muscidae , Animais , Ovinos , Bovinos , Trypanosoma vivax , Parasitemia , Carneiro Doméstico , AnticorposRESUMO
PURPOSE: The purpose of this study was to study the relationship between the presence of a deep lateral femoral notch sign (DLFNS) in anterior cruciate ligament (ACL)-injured patients and a higher posterior lateral tibial slope (LPTS), a reduced meniscal bone angle (MBA), a higher LPTS/MBA ratio and a higher incidence of concomitant injuries in primary ACL tears. METHODS: A retrospective case-control study was performed in patients submitted to primary ACL reconstruction with an available preoperative magnetic resonance imaging (MRI) scan. Patients with ACL tears and a femoral impactation with a depth ≥2 mm were assorted to the DLFNS group and patients with ACL tear and without a DLFNS to the control group. LPTS and MBA were measured in MRI. The presence of concomitant injuries (meniscal, posterior cruciate ligament, medial collateral ligament, lateral collateral ligament and bone injuries) was assessed in MRI. Quantitative data are presented in the median ± interquartile range (IQR). RESULTS: There were 206 patients included in the study, with 46 patients assorted to the DLFNS group and 160 patients to the control group. In the DLFNS group, the median LPTS was 6.7° (IQR: 4.0-8.2) versus 4.0° in the control group (IQR: 2.2-6.5) (p = 0.003). The LPTS/MBA ratio was significantly higher in the DLFNS group, with a median of 0.32 (IQR: 0.19-0.44), in comparison to the control group, with a median of 0.19 (IQR: 0.11-0.31) (p < 0.001). The multivariable logistic regression analysis showed that the LPTS is an independent risk factor to having a DLFNS (odds ratio [OR] = 1.161; 95% confidence interval [CI]: 1.042-1.293, p = 0.007). There was a higher incidence of concomitant lateral meniscal injuries in the DLFNS group (67% vs. 48%, p = 0.017). CONCLUSIONS: In patients with ACL tears, the presence of a DLFNS is associated with a steeper lateral posterior tibial slope, as well as a higher incidence of concomitant lateral meniscal injuries. LEVEL OF EVIDENCE: Level III.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Fêmur , Imageamento por Ressonância Magnética , Tíbia , Lesões do Menisco Tibial , Humanos , Estudos Retrospectivos , Masculino , Feminino , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/complicações , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Fêmur/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Lesões do Menisco Tibial/diagnóstico por imagem , Lesões do Menisco Tibial/cirurgia , Adulto Jovem , Adolescente , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/cirurgiaRESUMO
The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing.
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Insuficiência Cardíaca , Metabolômica , Humanos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/metabolismo , Metabolômica/métodos , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Metaboloma , Fatores de Risco de Doenças CardíacasRESUMO
Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.
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Doenças Cardiovasculares , Diabetes Gestacional , Hipertensão , Gravidez , Feminino , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Fatores de Risco , Período Pós-Parto , Obesidade/complicações , Obesidade/diagnóstico , Cardiomegalia , Biomarcadores , Fatores de Risco de Doenças CardíacasRESUMO
INTRODUCTION: Recurrence of atrial fibrillation (AF) within the blanking period after catheter ablation (CA) is traditionally classified as a transient and benign event. However, recent findings suggest that early recurrence (ER) is associated with late recurrence (LR), challenging the predefined "blanking period". We aimed to determine the clinical and procedural predictors of ER and LR after CA and establish the risk of LR in patients who experience ER. METHODS AND RESULTS: Retrospective single-centre study including all patients who underwent a first procedure of AF CA between 2017 and 2019. ER was defined as any recurrence of AF, atrial flutter or atrial tachycardia >30 s within 90 days after CA and LR as any recurrence after 90 days of CA. A total of 399 patients were included, 37% women, median age of 58 years [49-66] and 77% had paroxysmal AF. Median follow-up was 33 months (from 13 to 61). ER after CA was present in 14% of the patients, and LR was reported in 32%. Among patients who experienced ER, 84% also had LR (p < .001). Patients with ER had a higher prevalence of moderate/severe valvular heart disease, persistent AF, previous electrical cardioversion, a larger left atrium, higher coronary artery calcium score, and higher rates of intraprocedural electrical cardioversion and cardiac fibrosis on eletroanatomical mapping compared with patients without ER. After covariate adjustment, ER and female sex were defined as independent predictors of LR (hazard ratio [HR] 4.69; 95% confidence interval [CI], 2.99-7.35; p < .001 and HR 2.73; 95% CI, 1.47-5.10; p = .002, respectively). CONCLUSION: The risk of LR after an index procedure of CA was significantly higher in patients with ER (five-fold increased risk). These results support the imperative need to clarify the clinical role of the blanking period.
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Fibrilação Atrial , Ablação por Cateter , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/etiologia , Estudos Retrospectivos , Relevância Clínica , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , RecidivaRESUMO
PURPOSE: To evaluate the influence of different surface treatments on the clinical behavior of non-carious cervical sclerotic lesions (NCCLs) over an 18-month follow-up period. METHODS: 128 NCCLs from 32 volunteers were randomized into four groups (n=32): G1-control, without preoperative treatment of the dentin surface; G2, dentin conditioning with 17% ethylenediaminetetracetic acid (EDTA) for 2 minutes; G3, increase in dentin surface roughness with diamond bur and G4, increase in dentin surface roughness with diamond bur + dentin conditioning with 17% EDTA for 2 minutes. RESULTS: Differences between groups were tested using the Friedman test (α= 0.05). A questionnaire was administered to volunteers about risk factors related to NCCLs. The relationship between the questionnaire data and the clinical performance of the restorations was analyzed using the multiple logistic regression test (α= 0.05). The variables related to parafunctional habits, anxiety and/or depression were significantly related to the manifestation of postoperative sensitivity. Roughening the sclerotic dentin with a diamond bur increased postoperative sensitivity within 12 months. The presence of parafunctional habits and anxiety/depression may lead to postoperative sensitivity. CLINICAL SIGNIFICANCE: Roughening the sclerotic dentin with a diamond bur increased postoperative sensitivity within 12 months.
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Resinas Compostas , Dentina Secundária , Humanos , Dentina , Seguimentos , Ácido Edético , Restauração Dentária Permanente , Adesivos Dentinários , Dentina Secundária/patologia , DiamanteRESUMO
BACKGROUND: Abdominoplasties performed with Scarpa Fascia preservation, improve recovery and reduce complications, particularly seroma. Bariatric patients who experience massive weight loss frequently seek body contouring procedures and represent a high-risk group. This study aimed to evaluate the effects of abdominoplasty with Scarpa Fascia preservation versus the classical technique in a bariatric population. METHODS: A retrospective observational cohort study was performed between March 2015 and March 2021 in 65 postbariatric patients who underwent a classic full abdominoplasty (group A, N = 25) or a similar procedure except for the preservation of Scarpa fascia (group B, N = 40). Total and daily drain output, time until drain removal, long drainers (≥ 6 days), length of hospital stay, emergency department visit, readmission to the hospital, reoperation, local and systemic complications were the outcomes evaluated. RESULTS: Group B had a 3-day reduction in time until drain removal (p < 0.001), a 62.6% reduction of total drain output (p < 0.001) and a 3-day reduction in the length of the hospital stay (p < 0.001). Long drainers (≥ 6 days) were highly reduced (from 56.0% in group A to 7.5% in group B) (p < 0.001). There was a lower incidence of liquid collections in group B, with a 66.7% reduction in seroma incidence. CONCLUSIONS: Abdominoplasty with Scarpa Fascia preservation improves recovery by reducing drain output, allowing earlier drain removal and reducing long periods with suction drains. It also reduces hospital stay and seroma incidence. This technique modifies the high-risk postbariatric patient in such a major way that he behaves like a nonbariatric. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Abdominoplastia , Contorno Corporal , Masculino , Humanos , Estudos Retrospectivos , Seroma/etiologia , Seroma/prevenção & controle , Abdominoplastia/métodos , Fáscia , Contorno Corporal/métodosRESUMO
AIMS: Interleukin-6 (IL-6) is upregulated in response to infectious and inflammatory triggers and independently predicts all-cause mortality in acute heart failure (AHF). However, the association of IL-6 with cardiovascular outcomes and its interplay with C-reactive protein and infection, a major precipitating factor in AHF, remains poorly understood. METHODS AND RESULTS: The association between IL-6 and clinical outcomes (180 days) in AHF was evaluated using a cohort of 164 patients from the EDIFICA registry. Median IL-6 levels at admission were 17.4 pg/mL. Patients in the higher admission IL-6 tertile presented with lower blood pressure and more congestion, were diagnosed more frequently with infection, and had a longer hospital stay. Higher IL-6 levels were associated with increased risk of HF rehospitalization (hazard ratio per log2 3.69, 95% confidence interval (CI) 1.26-10.8, p =.017) and the composite of HF rehospitalization or cardiovascular death (hazard ratio per log2 3.50; 95% CI 1.28-9.57; p =.014), independently of major AHF prognosticators, including B-type natriuretic peptide and renal function. However, no independent associations were found for all-cause rehospitalization or mortality. Despite a moderate correlation of IL-6 with C-reactive protein (CRP) levels (R = .51), the latter were not associated with clinical outcomes in this population. CONCLUSIONS: IL-6 levels associate with higher rate of cardiovascular events in AHF, independently of classical prognosticators and evidence of infection, outperforming CRP as an inflammatory outcome biomarker.
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Insuficiência Cardíaca , Interleucina-6/sangue , Peptídeo Natriurético Encefálico , Doença Aguda , Biomarcadores , Proteína C-Reativa , Humanos , Prognóstico , Sistema de RegistrosRESUMO
Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AVS) are heart diseases accounting for most cardiac surgeries. These share many risk factors, such as age, diabetes, hypertension, or obesity, and similar pathogenesis, including endothelial disruption, lipid and immune cell infiltration, inflammation, fibrosis, and calcification. Unsuspected CAD and AVS are sometimes detected opportunistically through echocardiography, coronary angiography, and magnetic resonance. Routine biomarkers for early detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis. With a noninvasive collection, urine is appealing for biomarker assessment. We conducted a shotgun proteomics exploratory analysis of urine from 12 CAD and/or AVS patients and 11 controls to identify putative candidates to differentiate these diseases from healthy subjects. Among the top 20 most dysregulated proteins, TIMP1, MMP2 and vWF stood out, being at least 2.5× increased in patients with CAD/AVS and holding a central position in a network of protein-protein interactions. Moreover, their assessment in an independent cohort (19 CAD/AVS and 10 controls) evidenced strong correlations between urinary TIMP1 and vWF levels and a common cardiovascular risk factor - HDL (r = 0.59, p < 0.05, and r = 0.64, p < 0.01, respectively).
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Estenose da Valva Aórtica , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/diagnóstico , Proteômica , Fator de von Willebrand , Estenose da Valva Aórtica/diagnóstico , Angiografia Coronária , Biomarcadores , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologiaRESUMO
Prostate cancer (PCa) is one of the most lethal diseases in men, which justifies the search for new diagnostic tools. The aim of the present study was to gain new insights into the progression of prostate carcinogenesis by analyzing the urine proteome. To this end, urine from healthy animals and animals with prostate adenocarcinoma was analyzed at two time points: 27 and 54 weeks. After 54 weeks, the incidence of pre-neoplastic and neoplastic lesions in the PCa animals was 100%. GeLC-MS/MS and subsequent bioinformatics analyses revealed several proteins involved in prostate carcinogenesis. Increased levels of retinol-binding protein 4 and decreased levels of cadherin-2 appear to be characteristic of early stages of the disease, whereas increased levels of enolase-1 and T-kininogen 2 and decreased levels of isocitrate dehydrogenase 2 describe more advanced stages. With increasing age, urinary levels of clusterin and corticosteroid-binding globulin increased and neprilysin levels decreased, all of which appear to play a role in prostate hyperplasia or carcinogenesis. The present exploratory analysis can be considered as a starting point for studies targeting specific human urine proteins for early detection of age-related maladaptive changes in the prostate that may lead to cancer.
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Próstata , Neoplasias da Próstata , Animais , Carcinogênese/patologia , Modelos Animais de Doenças , Masculino , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/urina , Proteoma/química , Espectrometria de Massas em TandemRESUMO
We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.
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COVID-19/diagnóstico , Pessoal de Saúde , Reinfecção/diagnóstico , Reinfecção/virologia , SARS-CoV-2/isolamento & purificação , Eliminação de Partículas Virais , Adulto , Brasil/epidemiologia , COVID-19/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Reinfecção/terapiaRESUMO
NEW FINDINGS: What is the central question of this study? Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF), nearly doubling the risk of death: what are the RV functional and structural changes in HFpEF and how does aerobic exercise impact them? What is the main finding and its importance? The HFpEF ZSF1 rat model presents RV structural and functional changes mimicking the human condition. Aerobic exercise prevented the decline in VÌO2max , lowered surrogate markers of RV overload (e.g., higher mean and maximum systolic pressure) and improved diastolic dysfunction (e.g., end-diastolic pressure and relaxation time constant). This emphasizes the importance of using exercise to manage HFpEF. ABSTRACT: Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF) and is a marker of poor prognosis. We assessed the obese ZSF1 rat model of HFpEF to ascertain if these animals also develop RV dysfunction and evaluated whether aerobic exercise could prevent this. Obese ZSF1 rats were randomly allocated to an aerobic exercise training group (n = 7; treadmill running, 5 days/week, 60 min/day, 15 m/min for 5 weeks) or to a sedentary group (n = 7). We used lean ZSF1 rats (n = 7) as the control group. After 5 weeks, rats were submitted to an exercise tolerance test and invasive haemodynamic evaluation, killed and samples from the RV collected for histological analysis. Obese sedentary ZSF1 rats showed lower VÌO2max , RV pressure overload (e.g., higher mean and maximum systolic pressure) and diastolic dysfunction (e.g., higher minimum and end-diastolic pressure and relaxation time constant), paralleled by RV cardiomyocyte hypertrophy. Except for cardiomyocyte hypertrophy, aerobic exercise prevented these functional changes. Our data support that this model of HFpEF shows functional and structural changes in the RV that resemble the human HFpEF phenotype, reinforcing its utility to understand this pathophysiology and to adress novel therapeutic targets to manage HFpEF. In addition, we showed that aerobic exercise is cardioprotective for the RV. A deeper knowledge of the mechanisms underlying the benefits of aerobic exercise could also lead to the identification of therapeutic targets to be further explored.
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Insuficiência Cardíaca , Animais , Diástole/fisiologia , Ventrículos do Coração , Hemodinâmica , Ratos , Volume Sistólico/fisiologiaRESUMO
Heart-on-chip is an unprecedented technology for recapitulating key biochemical and biophysical cues in cardiac pathophysiology. Several designs have been proposed to improve its ability to mimic the native tissue and establish it as a reliable research platform. However, despite mimicking one of most vascularized organs, reliable strategies to deliver oxygen and substrates to densely packed constructs of metabolically demanding cells remain unsettled. Herein, we describe a new heart-on-chip platform with precise fluid control, integrating an on-chip peristaltic pump, allowing automated and fine control over flow on channels flanking a 3D cardiac culture. The application of distinct flow rates impacted on temporal dynamics of microtissue structural and transcriptional maturation, improving functional performance. Moreover, a widespread transcriptional response was observed, suggesting flow-mediated activation of critical pathways of cardiomyocyte structural and functional maturation and inhibition of cardiomyocyte hypoxic injury. In conclusion, the present design represents an important advance in bringing engineered cardiac microtissues closer to the native heart, overcoming traditional bulky off-chip fluid handling systems, improving microtissue performance, and matching oxygen and energy substrate requirements of metabolically active constructs, avoiding cellular hypoxia. Distinct flow patterns differently impact on microtissue performance and gene expression program.
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Bombas de Infusão , Dispositivos Lab-On-A-Chip , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Perfusão , Animais , Hipóxia Celular , Ratos , Ratos Sprague-Dawley , Técnicas de Cultura de TecidosRESUMO
BACKGROUND: Gastric dysbiosis has been hinted as a potential cause of gastric cancer. However, changes in microbiome throughout the major stages of gastric carcinogenesis remain mostly unknown. OBJECTIVE: To describe gastric microbiome at different stages, analysing for the first time dysbiosis specifically in patients with early gastric cancer (EGC). METHODS: Cross-sectional study including patients (n = 77) with endoscopically and histologically confirmed normal stomachs (controls; n = 25), advanced atrophic gastritis with intestinal metaplasia (IM; n = 18) and EGC (n = 34). Endoscopic biopsies from antrum and corpus (n = 154) were analyzed. Next-generation sequencing was performed characterizing microbial communities down to the species level based on full-length 16SrRNA gene profiling. RESULTS: Significant differences were found in the microbiome profile between the groups. Firmicutes were more frequent (p = .012) and Proteobacteria were less frequent (p = .04) both in the IM and EGC when comparing to controls. Relative frequency of Helicobacter pylori, when present, was much higher in the controls (83%) when comparing to the other groups (IM 1%, EGC 27%; p = .006), being the dominant bacteria only in the controls. Dysbiosis was present already and more significantly at the IM stage, with two bacteria progressively increasing from controls to IM then to cancer: Gemella from 1.48 to 3.9% (p = .014); and Streptococcus from 19.3 to 33.7% (p = .04), being the EGC dominant bacteria. CONCLUSIONS: Our results confirm Helicobacter pylori dominancy in non-atrophic stomachs and progressive dysbiosis throughout gastric carcinogenesis. Gemella but particularly Streptococcus is significantly increased in patients with EGC. Specific modulation of these bacteria may change gastric cancer risk.
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Gastrite Atrófica , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Helicobacter , Neoplasias Gástricas , Carcinogênese , Estudos Transversais , Mucosa Gástrica , Humanos , Metaplasia , EstômagoRESUMO
This paper investigated the effect of calcium addition on the formation and properties of aerobic granules under high (conventional SBR) and low (simultaneous fill/draw SBR) selection pressure. Additionally, the simultaneous removal of carbon, nitrogen, and phosphorus, and the operational stability were assessed. The conventional SBRs showed earlier granule development (20 days) than the simultaneous fill/draw SBRs. The effect of calcium on granulation was more accentuated in conventional SBRs, forming larger granules in a shorter interval of time due to the higher EPS production. Additionally, higher amounts of calcium were found in the EPS matrix, mainly during the formation of granules. The operation regime and the addition of calcium did not affect the removal of carbon, nitrogen, and phosphorus. However, they both influenced the granulation time, settleability characteristics, size, and granule composition.
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Cálcio , Esgotos , Aerobiose , Reatores Biológicos , Nitrogênio , Fósforo , Eliminação de Resíduos LíquidosRESUMO
OBJECTIVE: Evaluate interobserver and intraobserver reliability of hip arthroscopic classifications for labral tears. DESIGN: Retrospective diagnostic study of nonconsecutive patients. SETTING: Institutional study. PATIENTS: From a database of 278 hip arthroscopy videos for treatment of femoroacetabular impingement, 70 videos were chosen by simple random sampling. Exclusion criteria included presence of radiological arthrosis (Tonnis > 2), previous hip surgery, inadequate lesion palpation, poor image quality, and refusal to participate in the study. The final sample included 60 videos. INTERVENTIONS: Four hip surgeons evaluated the videos twice at 1-month intervals and classified the lesions according to Lage, Seldes, and Beck classifications for hip labral tears. MAIN OUTCOME MEASURES: Interobserver and intraobserver reliability with the percent of agreement and weighted Cohen kappa values. RESULTS: Patients had a mean age of 33 years (SD, 7; range, 18-47 years), and 32 (53%) were men. Femoroacetabular impingement types included combined (CAM and pincer) in 31 (52%), CAM in 27 (45%), and pincer in 2 (3%). For interobserver reliability, the average weighted kappa values were 0.68, 0.65, and 0.78 for the Lage, Seldes, and Beck classifications, respectively. For intraobserver reliability, the mean weighted kappa values were 0.87, 0.64, and 0.93 for the Lage, Seldes, and Beck classifications, respectively. CONCLUSIONS: Beck classification had the highest average values for interobserver and intraobserver agreements. Lage, Seldes, and Beck scores for acetabular labrum tears showed substantial interobserver agreement. In the intraobserver evaluation, the Seldes system presented substantial agreement, whereas Lage and Beck classifications were considered excellent agreement.
Assuntos
Artroscopia , Cartilagem Articular/lesões , Lesões do Quadril/classificação , Adolescente , Adulto , Cartilagem Articular/cirurgia , Feminino , Impacto Femoroacetabular/classificação , Impacto Femoroacetabular/diagnóstico , Impacto Femoroacetabular/cirurgia , Lesões do Quadril/diagnóstico , Lesões do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine.
Assuntos
Biomarcadores/urina , Peptídeos/análise , Urina/química , Humanos , ProteomaRESUMO
Aortic coarctation is a common congenital heart defect that often requires correction at a young age. Currently, success is defined by the achievement of a durable repair with low morbidity and mortality. We sought to systematically review the literature on risk factors for recoarctation and mortality in infants submitted to aortic arch coarctation repair under 1 year of age. PubMed and Scopus were searched for studies reporting risk factors for recoarctation and mortality from January 1989 to August 2019. Among the 1038 retrieved articles, 18 met the inclusion criteria, with a total of 2891 patients. The extracted risk factors for recoarctation were comprehensively summarized in the following categories: demographic variables, associated anomalies, clinical and repair variables, and morphometric variables. Younger age and lower weight were weak determinants of need for reintervention, while smaller aortic arch was a strong predictor of recoarctation. While balloon angioplasty is a clear risk factor for arch restenosis, the chosen surgical technique is not a strong risk factor. Associated minor cardiac anomalies and lower weight at surgery were important risk factors for death. Younger and smaller infants are at increased risk for adverse outcomes when submitted to aortic arch coarctation repair. This is particularly important when associated with smaller arch morphology. Strategies to improve the management of these patients may play a key role in improving their outcomes. Notably, surgical technique was not a strong predictor of recoarctation and mortality, suggesting that the choice of one over the other should be tailored.
Assuntos
Coartação Aórtica/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Fatores Etários , Angioplastia com Balão/efeitos adversos , Aorta Torácica/patologia , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Procedimentos Cirúrgicos Vasculares/efeitos adversosRESUMO
This work investigated the effect of Ca2+ (100â¯mgâ¯L-1) addition on the formation and maintenance of aerobic granular sludge in a simultaneous fill/draw mode sequencing batch reactor (SBR), operated with a low liquid upflow velocity (0.92â¯mâ¯h-1), in order to verify if Ca2+ presence compensates the low selection pressure imposed. Additionally, carbon and nutrients removals, granules characteristics and microbial community were evaluated. For this, two SBRs (R1, control, and R2, Ca2+-supplemented) were operated (6-h cycle). In general, Ca2+ supplementation affected positively the sludge settleability, although a larger fraction of inert solids was found in the granules. The total extracellular polymeric substances were the same for both reactors, and no remarkable differences were observed between their polysaccharides and proteins contents. Overall, Ca2+ addition in a simultaneous fill/draw mode SBR neither accelerated the granule formation nor improved the operational performance. The microbial community structure, especially in terms of bioactivity, was not affected as well. Therefore, the effect of divalent cations might be more pronounced in conventional SBRs, in which the selection pressure is higher.