Diagnostic accuracy of prenatal ultrasound in coarctation of aorta: systematic review and individual participant data meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). METHODS: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. RESULTS: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z-score of < -2 in the sagittal (P = 0.003) and three-vessel-and-trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. CONCLUSIONS: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neuropsychiatric phenotypes of anti-NMDAR encephalitis: a prospective study.

BACKGROUND: Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. METHODS: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. RESULTS: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. CONCLUSIONS: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

Prediction of postnatal circulation in pulmonary atresia/critical stenosis with intact ventricular septum: systematic review and external validation of models.

OBJECTIVE: A favorable postnatal prognosis in cases of pulmonary atresia/critical stenosis with intact ventricular septum (PA/CS-IVS) is generally equated with the possibility of achieving biventricular (BV) repair. Identification of fetuses that will have postnatal univentricular (UV) circulation is key for prenatal counseling, optimization of perinatal care and decision-making regarding fetal therapy. We aimed to evaluate the accuracy of published models for predicting postnatal circulation in PA/CS-IVS using a large internationally derived validation cohort. METHODS: This was a systematic review of published uni- and multiparametric models for the prediction of postnatal circulation based on echocardiographic findings at between 20 and 28 weeks of gestation. Models were externally validated using data from the International Fetal Cardiac Intervention Registry. Sensitivity, specificity, predictive values, area under the receiver-operating-characteristics curves (AUCs) and proportion of cases with true vs predicted outcome were calculated. RESULTS: Eleven published studies that reported prognostic parameters of postnatal circulation were identified. Models varied widely in terms of the main outcome (UV (n = 3), non-BV (n = 3), BV (n = 3), right-ventricle-dependent coronary circulation (n = 1) or tricuspid valve size at birth (n = 1)) and in terms of the included predictors (single parameters only (n = 6), multiparametric score (n = 4) or both (n = 1)), and were developed on small sample sizes (range, 15-38). Nine models were validated externally given the availability of the required parameters in the validation cohort. Tricuspid valve diameter Z-score, tricuspid regurgitation, ratios between right and left cardiac structures and the presence of ventriculocoronary connections (VCC) were the most commonly evaluated parameters. Multiparametric models including up to four variables (ratios between right and left structures, right ventricular inflow duration, presence of VCC and tricuspid regurgitation) had the best performance (AUC, 0.80-0.89). Overall, the risk of UV outcome was underestimated and that of BV outcome was overestimated by most models. CONCLUSIONS: Current prenatal models for the prediction of postnatal outcome in PA/CS-IVS are heterogeneous. Multiparametric models for predicting UV and non-BV circulation perform well in identifying BV patients but have low sensitivity, underestimating the rate of fetuses that will ultimately have UV circulation. Until better discrimination can be achieved, fetal interventions may need to be limited to only those cases in which non-BV postnatal circulation is certain. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).

Longitudinal change of sFlt-1/PlGF ratio in singleton pregnancy with early-onset fetal growth restriction.

OBJECTIVE: To describe the evolution of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio in the last 5 weeks prior to delivery in singleton pregnancy complicated by early-onset fetal growth restriction (FGR), with or without pre-eclampsia (PE). METHODS: This was a prospective observational cohort study of early-onset FGR cases that underwent serial assessment of maternal serum sFlt-1/PlGF ratio from diagnosis to delivery. Measurements were made at weekly intervals and within the last 48 h before birth. Absolute values and percentage increase between time intervals were computed, and previously described cut-off values of 38 (suspicion of PE), 85 (aids diagnosis of PE) and 655 (high risk for imminent delivery) were used for analysis of the sFlt-1/PlGF ratio. We compared findings between cases with early-onset FGR only (n = 37) and those that additionally developed PE (n = 36). RESULTS: Overall perinatal survival was 63/73 (86.3%). A sFlt-1/PlGF ratio above 38 was observed 4 weeks before delivery in most FGR-only and FGR with PE cases (73% and 100%, respectively), but absolute values of sFlt-1/PlGF were significantly higher in FGR cases with PE. Extremely elevated values of the ratio (≥ 655) within the last 48 h before delivery were found in 65% of cases of FGR with PE, but in only 8% of isolated FGR cases (P < 0.001). CONCLUSION: Elevated sFlt-1/PlGF was observed in most early-onset FGR pregnancies from 4 weeks before delivery, and values were even higher if there was concurrent PE. However, serial measurements of the ratio were of limited value, being useful only to anticipate the need for imminent delivery in cases of FGR with PE when sFlt-1/PlGF values ≥ 655 were reached. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.

Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort.

PURPOSE: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. METHODS: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. RESULTS: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was <2 %. CONCLUSIONS: Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size.

Intake of total omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC cohort study.

BACKGROUND AND AIMS: The evidence about the benefits of omega-3 fatty acid intake on coronary heart disease (CHD) is not consistent. We thus aimed to assess the relation between dietary intake of total omega-3 fatty acids (from plant and marine foods) and marine polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the risk of CHD in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS AND RESULTS: The analysis included 41,091 men and women aged 20-69 years, recruited from 1992 to 1996 and followed-up until December 2004. Omega-3 fatty acid intake was estimated from a validated dietary questionnaire. Only participants with definite incident CHD event were considered as cases. Cox regression models were used to assess the association between the intake of total omega-3 fatty acids, EPA or DHA and CHD. A total of 609 participants (79% men) had a definite CHD event. Mean intakes of total omega-3 fatty acids, EPA and DHA were very similar in the cases and in the cohort, both in men and women. In the multivariate adjusted model, omega-3 fatty acids, EPA and DHA were not related to incident CHD in either men or women. The hazard ratios (HR) for omega-3 were 1.23 in men (95% CI 0.94-15.9, p = 0.20); and 0.77 in women (95% CI 0.46-1.30, p = 0.76). CONCLUSION: In the Spanish EPIC cohort, with a relatively high intake of fish, no association was found between EPA, DHA and total omega-3 fatty acid intake and risk of CHD.

Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct.

AIMS/HYPOTHESIS: Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. METHODS: We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. RESULTS: In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. CONCLUSIONS/INTERPRETATION: This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.

Dietary intake of acrylamide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: In 1994, acrylamide (AA) was classified as a probable human carcinogen by the International Agency for Research on Cancer. In 2002, AA was discovered at relatively high concentrations in some starchy, plant-based foods cooked at high temperatures. PATIENTS AND METHODS: A prospective analysis was conducted to evaluate the association between the dietary intake of AA and ductal adenocarcinoma of the exocrine pancreatic cancer (PC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort using Cox regression modeling. EPIC includes >500,000 men and women aged 35-75 at enrollment from 10 European countries. AA intake was estimated for each participant by combining questionnaire-based food consumption data with a harmonized AA database derived from the EU monitoring database of AA levels in foods, and evaluated in quintiles and continuously. RESULTS: After a mean follow-up of 11 years, 865 first incident adenocarcinomas of the exocrine pancreas were observed and included in the present analysis. At baseline, the mean dietary AA intake in EPIC was 26.22 µg/day. No overall association was found between continuous or quintiles of dietary AA intake and PC risk in EPIC (HR:0.95, 95%CI:0.89-1.01 per 10 µg/day). There was no effect measure modification by smoking status, sex, diabetes, alcohol intake or geographic region. However, there was an inverse association (HR: 0.73, 95% CI: 0.61-0.88 per 10 µg/day) between AA intake and PC risk in obese persons as defined using the body mass index (BMI, ≥ 30 kg/m(2)), but not when body fatness was defined using waist and hip circumference or their ratio. CONCLUSIONS: Dietary intake of AA was not associated with an increased risk of PC in the EPIC cohort.

Fabrication of hierarchical micro-nanotopographies for cell attachment studies.

We report on the development of micro/nanofabrication processes to create hierarchical surface topographies that expand from 50 nm to microns in size on different materials. Three different approaches (named FIB1, FIB2, and EBL) that combine a variety of techniques such as photolithography, reactive ion etching, focused ion beam lithography, electron beam lithography, and soft lithography were developed, each one providing different advantages and disadvantages. The EBL approach was employed to fabricate substrates comprising channels with features between 200 nm and 10 µm in size on polymethylmethacrylate (PMMA), which were then used to investigate the independent or competitive effects of micro- and nanotopographies on cell adhesion and morphology. Rat mesenchymal stem cells (rMSCs) were cultured on four different substrates including 10 µm wide and 500 nm deep channels separated by 10 µm distances (MICRO), 200 nm wide and 100 nm deep nanochannels separated by 200 nm distances (NANO), their combination in parallel (PARAL), and in a perpendicular direction (PERP). Rat MSCs behaved differently on all tested substrates with a high degree of alignment (as measured by both number of aligned cells and average angle) on both NANO and MICRO. Furthermore, cells exhibited the highest level of alignment on PARAL, suggesting a synergetic effect of the two scales of topographies. On the other hand, cells on PERP exhibited the lowest alignment and a consistent change in morphology over time that seemed to be the result of interactions with both micro- and nanochannels positioned in the perpendicular direction, also suggesting a competitive effect of the topographies.

Prediction of coarctation of the aorta in the second half of pregnancy.

OBJECTIVE: To determine which combination of cardiac parameters provides the best prediction of postnatal coarctation of the aorta (CoAo) in fetuses with cardiac asymmetry. METHODS: We selected all cases of disproportion of the ventricles and great vessels prenatally diagnosed between 2003 and 2010 at the Hospital Universitario '12 de Octubre', Madrid, Spain. Only appropriate-for-gestational age liveborn fetuses with isolated cardiac asymmetry and with complete postnatal follow-up were included in the study. Eighty-five cases were retrieved and analyzed. Logistic regression analysis was used to select the best predictors of CoAo. Optimal cut-offs for these parameters were identified and the corresponding likelihood ratios used to calculate the post-test probability of CoAo in each fetus. RESULTS: CoAo was confirmed in 41/85 neonates (48%). The parameters selected by logistic regression and their cut-off values were: gestational age at diagnosis ≤ 28 weeks, Z-score of diameter of the ascending aorta ≤ -1.5, pulmonary valve/aortic valve diameters ratio ≥ 1.6 and Z-score of the aortic isthmus diameter in the three vessels and trachea view ≤ -2. We divided the study group into two subgroups: Group A, in whom the diagnosis was made at ≤ 28 weeks' gestation (80% CoAo (32/40)); and Group B, in whom the diagnosis was made at > 28 weeks (20% CoAo (9/45)). The mean post-test probabilities of CoAo were higher in fetuses with CoAo than in normal fetuses in both subgroups (Group A, 82 vs 55%; P = 0.002 and Group B, 51 vs 20%; P < 0.001). In addition, a rate of growth of the aortic valve of ≤ 0.24 mm/week provided 80% sensitivity and 100% specificity for predicting CoAo in Group A. CONCLUSIONS: We have derived a multiparametric scoring system, combining size-based cardiac parameters and gestational age at diagnosis, which may improve the accuracy of fetal echocardiography for the stratification of the risk of CoAo. The objectivity and simplicity of its components may allow its implementation in fetal cardiology units.

Uterine artery Doppler and sFlt-1/PlGF ratio: usefulness in diagnosis of pre-eclampsia.

OBJECTIVE: To evaluate the usefulness of the mean pulsatility index of the uterine arteries (mPI-UtA) and automated measurement of the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio on suspicion or at diagnosis of pre-eclampsia (PE). METHODS: Patients with singleton pregnancies with PE (n = 60) diagnosed according to current recommendations, or with suspected PE (n = 32) defined by (1) blood pressure (BP) ≥ 160/100 mmHg, (2) BP ≥ 140/90 mmHg or proteinuria, together with suggestive clinical symptoms or (3) intrauterine growth restriction (IUGR) at < 34 + 0 weeks, were enrolled and mPI-UtA and the sFlt-1/PlGF ratio were measured. Values > 95(th) centile were considered abnormal. All cases were classified according to occurrence of PE and/or IUGR and subclassified, depending on gestational age at delivery, as early (< 34 + 0 weeks) or late (≥ 34 + 0 weeks). RESULTS: PE was confirmed in 72 cases, in which 32 early deliveries occurred. Isolated IUGR was diagnosed in nine early cases and one late case, while the remaining 10 cases were late deliveries without PE or IUGR. In pregnancies in which PE and IUGR were excluded, mPI-UtA was abnormal in 40% but the sFlt-1/PlGF ratio was normal in 100%. In early PE, mPI-UtA at diagnosis was abnormal in 100% of cases with IUGR and in 91% without IUGR, while sFlt-1/PlGF was abnormal in 100% and 96%, respectively. In late PE, mPI-UtA was abnormal in 50% and 37% of cases with and without IUGR while the sFlt-1/PlGF ratio was abnormal in 50% and 26%, respectively. CONCLUSION: Abnormal mPI-UtA and sFlt-1/PlGF ratio are common in early PE. In late PE, mPI-UtA is normal in most cases and thus not diagnostically useful. The sFlt-1/PlGF ratio shows high specificity but low sensitivity to confirm PE when suspected.

Wuschel overexpression promotes somatic embryogenesis and induces organogenesis in cotton (Gossypium hirsutum L.) tissues cultured in vitro.

KEY MESSAGE: This work shows that overexpression of the WUS gene from Arabidopsis enhanced the expression of embryogenic competence and triggered organogenesis from some cells of the regenerated embryo-like structures. Agrobacterium-mediated genetic transformation of cotton was described in the late 1980s, but is still time consuming and largely genotype dependant due to poor regeneration. To help solve this bottleneck, we over-expressed the WUSCHEL (WUS) gene, a homeobox transcription factor cloned in Arabidopsis thaliana, known to stimulate organogenesis and/or somatic embryogenesis in Arabidopsis tissues cultured in vitro. The AtWUS gene alone, and AtWUS gene fused to the GFP marker were compared to the GFP gene alone and to an empty construct used as a control. Somatic embryogenesis was improved in WUS expressed calli, as the percentage of explants giving rise to embryogenic tissues was significantly higher (×3) when WUS gene was over-expressed than in the control. An interesting result was that WUS embryogenic lines evolved in green embryo-like structures giving rise to ectopic organogenesis never observed in any of our previous transformation experiments. Using our standard in vitro culture protocol, the overexpression of AtWUS in tissues of a recalcitrant variety did not result in the production of regenerated plants. This achievement will still require the optimization of other non-genetic factors, such as the balance of exogenous phytohormones. However, our results suggest that targeted expression of the WUS gene is a promising strategy to improve gene transfer in recalcitrant cotton cultivars.

Dietary supplemented and meat-added antioxidants effect on the lipid oxidative stability of refrigerated and frozen cooked chicken meat.

The oxidation of fatty acids decreases the quality and shelf-life of meats. To reduce this process, dietary supplemented and meat-added antioxidants were evaluated on the lipid oxidative stability of cooked chicken meat. Broilers were fed 2 levels of vitamin E (10 or 100 mg•kg(-1) of feed; VE-10 and VE-100, respectively) or oregano essential oil (100 mg•kg(-1) of feed; OR-100). Additionally, honey (3%) or butylated hydroxytoluene (0.02%; BHT) were added to chicken meat from the control treatment (VE-10). Breast meat was ground, formed into patties, and cooked on electric grills until it reached an internal temperature of 74°C. Cooked meat was cooled at room temperature, packaged, and stored under refrigeration for 9 d (4°C) or frozen for 45 d (-20°C). The 2-thiobarbituric acid reactive substance test was used to quantify malondialdehyde (MDA) values in the meat. Data were analyzed using a repeated measures design, 5 treatments with 12 replications each, and the least squares means were compared with 4 orthogonal contrasts. The results showed that the meat of the VE-10 treatment had higher values of MDA (P ≤ 0.05) compared with the other antioxidant treatments in all the storage days. There were no differences (P ≥ 0.05) in MDA values between the dietary supplemented and meat-added antioxidant treatments. The meat added with honey had lower MDA values than the one with BHT (P ≤ 0.05). Meat of the VE-100 treatment showed lower MDA values than the one of OR-100 (P ≤ 0.05) in most storage days. In conclusion, supplementation of 10 mg•kg(-1) of vitamin E to the diet resulted in a higher development of lipid oxidation in the meat. Both dietary supplemented or meat-added antioxidants had similar effects on the lipid oxidative stability. The addition of honey maintained longer the lipid oxidative stability of the meat than BHT. Finally, dietary supplementation of vitamin E at the same level of oregano oil, 100 mg•kg(-1), resulted in a higher antioxidant effect on the meat.

Phase stabilization and optical response in the ultraviolet range, due to terbium concentration in hafnium oxide nanoparticles.

This work reports the influence of terbium trivalent ions on growing kinetics and the phase in hafnium oxide nanoparticles, as well as response to radiation in the range from 256 to 286. The nanoparticles were obtained by the hydrothermal route maintaining the temperature constant and varying the reaction time and the terbium concentration. The results show a gradual change in the phase with the concentration of terbium trivalent ions, going from the monoclinic phase, present at low concentrations, to the tetragonal phase, which appears from dopant concentrations greater than 5% at., increasing in amount with concentration of dopant. These phases appear as two perfectly defined morphologies. Furthermore, there is a significant change in radiative lifetimes when the tetragonal phase appears.

Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables. RESULTS: Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154). CONCLUSION: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.

Renin is an angiotensin-independent profibrotic mediator: role in pulmonary fibrosis.

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is probably the result of interplay between cytokines/chemokines and growth factors. The renin-angiotensin (Ang) system is involved, although its profibrotic effect is attributed to Ang II. However, recent studies suggest that renin, through a specific receptor, is implicated in fibrogenesis. In this study, the expression of renin and renin receptor was examined in normal and IPF lungs and fibroblasts. Normal human lung fibroblasts were stimulated with renin or transfected with renin small interfering RNA (siRNA), and the expression of transforming growth factor (TGF)-ß1 and α-1-type I collagen was analysed. Normal lungs and lung fibroblasts expressed renin, which was strongly upregulated in IPF lungs and fibroblasts (∼10-fold increase; p<0.05). Immunocytochemistry showed intense renin staining in IPF fibroblasts. Renin-stimulated lung fibroblasts displayed an increase in the expression of TGF-ß1 (mean ± sd 1.8 × 10(3) ± 0.2 × 10(3) versus 1.2 × 10(3)± 0.3 × 10(3) mRNA copies per 18S ribosomal RNA; p<0.01) and collagen (5.93 × 10(2)± 0.66 × 10(2) versus 3.28 × 10(2) ± 0.5 × 10(2); p<0.01), while knocking down renin expression using siRNA provoked a strong decrease of both molecules. These effects were independent of Ang II, since neither losartan nor captopril decreased these effects. Renin also decreased matrix metalloprotease-1 expression and induced TGF-ß1 activation (163 ± 34 versus 110 ± 15 pg active TGF-ß1 per mg total protein). These findings highlight the possible role of renin as an Ang II-independent profibrotic factor in lung fibrosis.