International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21st Project.

BACKGROUND: Reference values for umbilical artery Doppler indices are used clinically to assess fetal well-being. However, many studies that have produced reference charts have important methodologic limitations, and these result in significant heterogeneity of reported reference ranges. OBJECTIVES: To produce international gestational age-specific centiles for umbilical artery Doppler indices based on longitudinal data and the same rigorous methodology used in the original Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. STUDY DESIGN: In Phase II of the INTERGROWTH-21st Project (the INTERBIO-21st Study), we prospectively continued enrolling pregnant women according to the same protocol from 3 of the original populations in Pelotas (Brazil), Nairobi (Kenya), and Oxford (United Kingdom) that had participated in the Fetal Growth Longitudinal Study. Women with a singleton pregnancy were recruited at <14 weeks' gestation, confirmed by ultrasound measurement of crown-rump length, and then underwent standardized ultrasound every 5±1 weeks until delivery. From 22 weeks of gestation umbilical artery indices (pulsatility index, resistance index, and systolic/diastolic ratio) were measured in a blinded fashion, using identical equipment and a rigorously standardized protocol. Newborn size at birth was assessed using the international INTERGROWTH-21st Standards, and infants had detailed assessment of growth, nutrition, morbidity, and motor development at 1 and 2 years of age. The appropriateness of pooling data from the 3 study sites was assessed using variance component analysis and standardized site differences. Umbilical artery indices were modeled as functions of the gestational age using an exponential, normal distribution with second-degree fractional polynomial smoothing; goodness of fit for the overall models was assessed. RESULTS: Of the women enrolled at the 3 sites, 1629 were eligible for this study; 431 (27%) met the entry criteria for the construction of normative centiles, similar to the proportion seen in the original fetal growth longitudinal study. They contributed a total of 1243 Doppler measures to the analysis; 74% had 3 measures or more. The healthy low-risk status of the population was confirmed by the low rates of preterm birth (4.9%) and preeclampsia (0.7%). There were no neonatal deaths and satisfactory growth, health, and motor development of the infants at 1 and 2 years of age were documented. Only a very small proportion (2.8%-6.5%) of the variance of Doppler indices was due to between-site differences; in addition, standardized site difference estimates were marginally outside this threshold in only 1 of 27 comparisons, and this supported the decision to pool data from the 3 study sites. All 3 Doppler indices decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age for each of the 3 indices are provided, as well as equations to allow calculation of any value as a centile and z scores. The mean pulsatility index according to gestational age = 1.02944 + 77.7456*(gestational age)-2 - 0.000004455*gestational age3. CONCLUSION: We present here international gestational age-specific normative centiles for umbilical artery Doppler indices produced by studying healthy, low-risk pregnant women living in environments with minimal constraints on fetal growth. The centiles complement the existing INTERGROWTH-21st Standards for assessment of fetal well-being

O Paradoxo dos Fumadores nas Síndromes Coronárias Agudas: Será Real?

INTRODUCTION: Smoking is associated with atherosclerotic disease, but there is controversy about its protective nature after acute coronary syndrome (ACS). OBJECTIVE: To determine the impact of smoking on the presentation, treatment and outcome of ACS. METHODS: We analyzed all consecutive patients with ACS in a single center between 2005 and 2014. Current smokers and never-smokers were compared. Independent predictors of in-hospital mortality and of a composite of all-cause mortality, rehospitalization for cardiovascular causes, angiography, percutaneous coronary intervention and coronary artery bypass grafting were assessed by multivariate logistic regression. RESULTS: A total of 2727 patients were included, 41.7% current smokers and 58.3% never-smokers. Current smokers were younger, more often male, had fewer comorbidities, a typical clinical presentation, lower heart rate, systolic blood pressure, Killip class, BNP/NT-pro-BNP and creatinine, better left ventricular systolic function and less severe coronary anatomy. ST-segment elevation myocardial infarction was more common in current smokers. Current smokers received more evidence-based treatments and had less in-hospital complications, in-hospital mortality and adverse outcomes at one year. More frequent percutaneous coronary intervention at one year was noted in current smokers. Smoking was not an independent predictor of outcome when the multivariate model was fully adjusted for baseline characteristics. CONCLUSION: The smoker's paradox was not observed in this population, since all differences in outcome were explained by smokers' more benign baseline characteristics.info:eu-repo/semantics/publishedVersio

Effect of the presence of surfactant and ionic liquids on the esterification of oleic acid catalyzed by immobilized lipase

Ionic liquids (ILs) and surfactants are widely used in order to increase the catalytic efficiency of lipases. In this sense, the present study aimed to evaluate the potential of different ionic liquids (C4MIM.Ac, C4MIM.HSO4, C4MIM.TF2N, C4MIM.BF4, C12MIM.I, and C12MIM.Cl), Aliquat 336 and di-2-ethylhexyl sodium sulfosuccinate (AOT) as adjuvants in the esterification of oleic acid with different alcohols catalyzed by Novozyme 435. First of all, it evaluates the effect of alkyl chain length of the alcohol and the positioning of the hydroxyl group. The selection of additives, made with isopropyl alcohol, pointed AOT and C4MIM.Ac as adjuvants effective on the potential of esterification of the enzyme (an increase of 35% in the potential of esterification). Using methanol, ethanol and 3-methyl-1-butanol, the C4MIM.Ac was proven not to be efficient, while the AOT shows adjuvant effect in the esterification of oleic acid with methanol (increasing in catalytic efficiency of enzyme in 21%).Key words: Esterification, di-2-ethylhexyl sodium sulfosuccinate (AOT), Ionic Liquids, Novozyme 435

Inducibility of Atrial Fibrillation During Electrophysiologic Evaluation is Associated with Increased Dispersion of Atrial Refractoriness

The impact of atrial dispersion of refractoriness (Disp_A) in the inducibility and maintenance of atrial fibrillation (AF) has not been fully resolved. AIM: To study the Disp_A and the vulnerability (A_Vuln) for the induction of self-limited (<60 s) and sustained episodes of AF. METHODS AND RESULTS: Forty-seven patients with paroxysmal AF (PAF): 29 patients without structural heart disease and 18 with hypertensive heart disease. Atrial effective refractory period (ERP) was assessed at five sites--right atrial appendage and low lateral right atrium, high interatrial septum, proximal and distal coronary sinus. We compared three groups: group A - AF not inducible (n=13); group B - AF inducible, self-limited (n=18); group C - AF inducible, sustained (n=16). Age, lone AF, hypertension, left atrial and left ventricular (LV) dimensions, LV systolic function, duration of AF history, atrial flutter/tachycardia, previous antiarrhythmics, and Disp_A were analysed with logistic regression to determine association with A_Vuln for AF inducibility. The ERP at different sites showed no differences among the groups. Group A had a lower Disp_A compared to group B (47+/-20 ms vs 82+/-65 ms; p=0.002), and when compared to group C (47+/-20 ms vs 80+/-55 ms; p=0.008). There was no significant difference in Disp_A between groups B and C. By means of multivariate regression analysis, the only predictor of A_Vuln was Disp_A (p=0.04). Conclusion: In patients with PAF, increased Disp_A represents an electrophysiological marker of A_Vuln. Inducibility of both self-limited and sustained episodes of AF is associated with similar values of Disp_A. These findings suggest that the maintenance of AF is influenced by additional factors

Epstein-Barr virus as a piece of the neurodegenerative disease mosaic

Neurodegenerative diseases (ND’s) affect approximately 6 million people in the US, and their incidence and severity is linked to genetic and environmental factors. Human herpesviruses such as Epstein-Barr virus (EBV), were recently implicated as potential infectious agents in the etiology of ND’s. Over 90% of the world’s population has EBV, which initially infects epithelial cells in the nasopharynx to then enter latency in B cells. EBV is a neurotropic virus and can infect astrocytes, neurons, and microglia. In addition, infected B and T cells travel through CNS access areas such as the Glymphatic System and the nasopharynx, where EBV could affect neuronal cell function. Processes such as autophagy, inflammation, and Reactive Oxygen Species (ROS) homeostasis are crucial to ND’s and have already been shown to be affected by EBV. While severe neuronal consequences are rare during EBV infection, little is known about its ability to promote neuronal dysfunction that could prime neuronal cells for ND development. We hypothesized that EBV had the potential to affect neuronal cellular processes that are relevant for the development and establishment of ND’s. To study these interactions in a practical, more easily accessible cell model than primary neuronal cells, we used retinoic-acid (RA) differentiated SH-SY5Y neuroblastoma cells, which have been widely accepted as a suitable cell line for ND studies. We exposed these cells to EBV virions and demonstrated the presence of intracellular viral genome via qPCR. Thus, we are the first ones to show that RA-differentiated SH-SY5Y neuroblastoma cells are permissive to EBV infection. Interestingly, while we did not detect lytic or latent viral transcripts in these cells, our data suggests that EBV-infected neuroblastoma cells have altered ROS homeostasis and decreased mitochondrial function, increased expression of inflammatory markers and autophagic flux block. Overall, we have established that EBV infection of neuronal cells has the potential to affect the neurodegenerative trifecta: ROS, autophagy, and inflammation. Future studies should focus on a more in-depth exploration of each of these processes under EBV infection to elucidate if the virus can act as a piece of the neurodegenerative mosaic

False Positive Responses to Head-Up Tilt Testing in Elderly Patients with Paroxysmal Atrial Fibrillation

The autonomic nervous system (ANS) plays a role as a modulator in the pathogenesis of paroxysmal atrial fibrillation (PAF). The clinical pattern of vagally mediated PAF has been observed mainly in young patients. Neurocardiogenic responses during orthostatic stress are related to autonomic reflexes in which the vagal influence predominates. AIM: To evaluate the susceptibility of elderly patients with PAF to activation of vasovagal syncope mechanisms. METHODS: We performed passive head-up tilt testing (HUT) in 34 patients (62% women, aged 72 +/- 7 years), with > or = 1 year of clinical history of PAF--19 without structural heart disease, 11 with hypertensive heart disease and 4 with coronary artery disease (who had no previous myocardial infarction, had undergone myocardial revascularization, and had no documented ischemia) (PAF group), and compared the results with those obtained in a group of 34 age-matched patients (53% women, aged 74 +/- 6 years), who underwent HUT due to recurrent syncope (Sc group). In this group, 21 had no documented heart disease and none had a clinical history of AF. There was no diabetes, congestive heart failure or syncope in the PAF group. After a supine resting period, the subjects were tilted at 70 degrees for 20 minutes while in sinus rhythm. No provocative agents were used to complement the HUT. ECG and blood pressure were continuously monitored (Task Force Monitor, CNSystems). The test was considered positive when syncope or presyncope occurred with bradycardia and/or arterial hypotension. Abnormal responses were classified as cardioinhibitory, vasodepressor or mixed. RESULTS: HUT was positive in seven patients of the PAF group--vasodepressor response in five and mixed in two (20.5% of the total; 26.3% of those without heart disease)--and in eight patients (vasodepressor in six and mixed in two) of the Sc group (p=NS). During HUT, three patients of the PAF group had short periods of self-limited PAF (in one, after vasodepressor syncope). There were no differences in gender distribution, age or heart disease. No cardioinhibitory responses or orthostatic hypotension were observed. CONCLUSION: In elderly patients with PAF, a significant number of false positive results during passive HUT may be expected, suggesting increased vasovagal reactions despite aging. This suggests that ANS imbalances may be observed in this population

International standards for fetal brain structures based on serial ultrasound measurements from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured by ultrasound, from healthy, well-nourished women, at low risk of impaired fetal growth and poor perinatal outcomes, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicentre, longitudinal study. We measured, in planes reconstructed from 3-dimensional (3D) ultrasound volumes of the fetal head at different time points in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle (AV), atrium of the posterior ventricle (PV) and cisterna magna (CM). The sample analysed was randomly selected from the overall FGLS population, ensuring an equal distribution amongst the eight diverse participating sites and of 3D ultrasound volumes across pregnancy (range: 15 - 36 weeks' gestation). Fractional polynomials were used to the construct standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were randomly selected. After exclusions, 3D ultrasound volumes from 442 fetuses born without congenital malformations were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures showed increasing size with gestation and increasing variability for the POF, SF, PV and CM. The 3rd , 5th , 50th , 95th and 97th smoothed centile are presented. The 5th centile of POF and SF were 2.8 and 4.3 at 22 weeks and 4.2 and 9.4mm at 32 weeks respectively. The 95th centile of PV and CM were 8.5 and 7.4 at 22 weeks and 8.5 and 9.4mm at 32 weeks respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcomes. We recommend these as international standards for the assessment of measurements obtained by ultrasound from fetal brain structures