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PURPOSE: Oral contraception is one of the most popular contraceptive methods both in adults and adolescents. However, the effects of oral contraception on lipids in adolescents are not well studied. METHODS: Lipid profiles were measured and contraceptive use was assessed in 14- to 19-year-old female participants of the prospective population-based Early Vascular Ageing-Tyrol Study between 2015 and 2018, twice on average 22 months apart. RESULTS: For this analysis, data from 828 young women with a median age of 17.0 years were available. Of them, 317 (38%) used oral contraceptives (OCs). OC users had a slightly higher systolic and diastolic blood pressure and larger changes over time and were more likely to use cigarettes than nonusers. Total cholesterol (179.6 vs. 162.4 mg/dL), low-density lipoprotein-cholesterol (106.4 vs. 94.6 mg/dL), and triglycerides (104.0 vs. 67.0 mg/dL) were significantly higher in OC users after multivariable adjustment in linear regression models. No difference in high-density lipoprotein-cholesterol between the two groups was found. In 558 females, follow-up data were available. Those who initiated OC use had on average 15.4 mg/dL higher low-density lipoprotein-cholesterol and 36.2 mg/dL higher triglyceride level changes between baseline and follow-up than never users. Duration of OC use did not show a significant association with lipid levels and changes. DISCUSSION: We showed an independent association between OC use and blood lipids as well as lipid trajectories over time in a large cohort of healthy adolescents. These changes are especially relevant to consider in adolescents with other risk factors for dyslipidemia or other cardiovascular risk factors.
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Anticonceptivos Orales , Humanos , Adolescente , Femenino , Anticonceptivos Orales/administración & dosificación , Estudios Prospectivos , Adulto Joven , Lípidos/sangre , Triglicéridos/sangre , Presión Sanguínea/efectos de los fármacos , LDL-Colesterol/sangre , Colesterol/sangreRESUMEN
(1) Background: Unhealthy dietary behaviors are estimated to be one of the leading causes of death globally and are often shaped at a young age. Here, we investigated adolescent diet quality and its predictors, including nutrition knowledge, in two large Central European cohorts. (2) Methods: In 3056 participants of the EVA-Tyrol and EVA4YOU prospective population-based cohort studies aged 14 to 19 years, diet quality was assessed using the AHEI-2010 and DASH scores, and nutrition knowledge was assessed using the questionnaire from Turconi et al. Associations were examined utilizing multivariable linear regression. (3) Results: The mean overall AHEI-2010 score was 42%, and the DASH score was 45%. Female participants (60.6%) had a significantly higher diet quality according to the AHEI-2010 and DASH score. AHEI-2010 and DASH scores were significantly associated (p < 0.001) with sex, school type, smoking, and total daily energy intake. The DASH score was additionally significantly associated (p < 0.001) with age, socioeconomic status, and physical activity. Participants with better nutrition knowledge were more likely to be older, to attend a general high school, to live in a high-income household, to be non-smokers, and to have a higher diet quality according to the AHEI-2010 and DASH score. (4) Conclusions: Predictors of better diet quality included female sex, physical activity, educational level, and nutrition knowledge. These results may aid focused interventions to improve diet quality in adolescents.
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Dieta , Humanos , Adolescente , Femenino , Estudios Prospectivos , Dieta/métodos , Encuestas y Cuestionarios , EscolaridadRESUMEN
BACKGROUND AND AIMS: Preterm birth has been linked with an increased risk of cardiovascular (CV) disease from childhood into adolescence and early adulthood. In this study, we aimed to investigate differences in CV health profiles between former term- and preterm-born infants in a cohort of Tyrolean adolescents. METHODS: The Early Vascular Aging (EVA)-Tyrol study is a population-based non-randomized controlled trial, which prospectively enrolled 14- to 19-year-old adolescents in North Tyrol, Austria and South Tyrol, Italy between 2015 and 2018. Metrics of CV health (body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), smoking, physical activity, dietary patterns, total cholesterol and fasting blood glucose) were assessed and compared between former term- and preterm-born girls and boys. RESULTS: In total, 1,491 study participants (59.5% female, mean age 16.5 years) were included in the present analysis. SBP and DBP were significantly higher in former preterm-born adolescents (mean gestational age 34.6 ± 2.4 weeks) compared to term-born controls (p < 0.01). In the multivariate regression analysis these findings remained significant after adjustment for potential confounders in all models. No differences were found in all other CV health metrics. The number of participants meeting criteria for all seven health metrics to be in an ideal range was generally very low with 1.5% in former term born vs. 0.9% in former preterm born adolescents (p = 0.583). CONCLUSIONS: Preterm birth is associated with elevated SBP and DBP in adolescence, which was even confirmed for former late preterm-born adolescents in our cohort. Our findings underscore the importance of promoting healthy lifestyles in former term- as well as preterm-born adolescents. In addition, we advise early screening for hypertension and long-term follow-up in the group of preterm-born individuals.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Hipertensión , Nacimiento Prematuro , Recién Nacido , Masculino , Lactante , Adolescente , Femenino , Humanos , Adulto , Niño , Adulto Joven , AustriaRESUMEN
Background: Homocysteine (Hcy) has been associated with an adverse cardiovascular risk profile in adolescents. Assessment of the association between plasma Hcy levels and clinical/laboratory factors might improve our understanding of the pathogenesis of cardiovascular disease. Methods: Hcy was measured in 1,900 14- to 19-year-old participants of prospective population-based EVA-TYROL Study (44.3% males, mean age 16.4 years) between 2015 and 2018. Factors associated with Hcy were assessed by physical examination, standardized interviews, and fasting blood analysis. Results: Mean plasma Hcy was 11.3 ± 4.5â µmol/L. Distribution of Hcy was characterized by extreme right skew. Males exhibited higher Hcy and sex differences increased with increasing age. Univariate associations with Hcy emerged for age, sex, body mass index, high-density lipoprotein cholesterol, and for factors pertaining to blood pressure, glucose metabolism, renal function, and diet quality, whereas the most important multivariate predictors of Hcy were sex and creatinine. Discussion: Clinical and laboratory factors associated with Hcy in adolescents were manifold, with sex and high creatinine identified as strongest independent determinants. These results may aid when interpreting future studies investigating the vascular risk of homocysteine.
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Materials synthesis via liquid-like mineral precursors has been studied since their discovery almost 25 years ago, because their properties offer several advantages, for example, the ability to infiltrate small pores, the production of non-equilibrium crystal morphologies or mimicking textures from biominerals, resulting in a vast range of possible applications. However, the potential of liquid-like precursors has never been fully tapped, and they have received limited attention in the materials chemistry community, largely due to the lack of efficient and scalable synthesis protocols. Herein, the "scalable controlled synthesis and utilization of liquid-like precursors for technological applications" (SCULPT) method is presented, allowing the isolation of the precursor phase on a gram scale, and its advantage in the synthesis of crystalline calcium carbonate materials and respective applications is demonstrated. The effects of different organic and inorganic additives, such as magnesium ions and concrete superplasticizers, on the stability of the precursor are investigated and allow optimizing the process for specific demands. The presented method is easily scalable and therefore allows synthesizing and utilizing the precursor on large scales. Thus, it can be employed for mineral formation during restoration and conservation applications but can also open up pathways toward calcium carbonate-based, CO2 -neutral cements.
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BACKGROUND AND AIMS: Assessment of comprehensive lipoprotein subclass profiles in adolescents and their relation to vascular disease may enhance our understanding of the development of dyslipidemia in early life and inform early vascular prevention. METHODS: Nuclear magnetic resonance was used to measure lipoprotein profiles, including lipids (cholesterol, free cholesterol, triglycerides, phospholipids) and apolipoproteins (apoB-100, apoA1, apoA2) of 17 lipoprotein subclasses (from least dense to densest: VLDL-1 to -6, IDL, LDL-1 to -6, HDL-1 to -4) in n = 1776 14- to 19-year olds (56.6% female) and n = 3027 25- to 85-year olds (51.5% female), all community-dwelling. Lipoprotein profiles were related to carotid intima-media thickness (cIMT) as ascertained by sonography. RESULTS: Adolescents compared to adults had lower triglycerides, total, LDL, and non-HDL cholesterol, and apoB, and higher HDL cholesterol. They showed 26.6-59.8% lower triglyceride content of all lipoprotein subclasses and 21.9-51.4% lower VLDL lipid content. Concentrations of dense LDL-4 to LDL-6 were 36.7-40.2% lower, with also markedly lower levels of LDL-1 to LDL-3, but 24.2% higher HDL-1 ApoA1. In adolescents, only LDL-3 to LDL-5 subclasses were associated with cIMT (range of differences in cIMT for a 1-SD higher concentration, 4.8-5.9 µm). The same associations emerged in adults, with on average 97 ± 42% (mean ± SD) larger effect sizes, in addition to LDL-1 and LDL-6 (range, 6.9-11.3 µm) and HDL-2 to HDL-4, ApoA1, and ApoA2 (range, -7.0 to -17.7 µm). CONCLUSIONS: Adolescents showed a markedly different and more favorable lipoprotein profile compared to adults. Dense LDL subclasses were the only subclasses associated with cIMT in adolescents, implicating them as the potential preferred therapeutic target for primary prevention of cardiovascular disease at this age. In adults, associations with cIMT were approximately twice as large as in adolescents, and HDL-related measures were additionally associated with cIMT.
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Grosor Intima-Media Carotídeo , Lipoproteínas , Adolescente , Adulto , HDL-Colesterol , Estudios de Cohortes , Femenino , Humanos , Masculino , Estudios Prospectivos , TriglicéridosRESUMEN
BACKGROUND: In recent years, there has been increasing evidence that asthma is associated with atherosclerosis and cardiovascular disease. However, data in children and adolescents are scarce and conflicting. We aimed to assess the impact of asthma with and without an allergic component on the carotid intima-media thickness in a large pediatric population. METHODS: The community-based early vascular ageing-Tyrol cohort study was performed between May 2015 and July 2018 in North, East (Austria) and South Tyrol (Italy) and recruited youngster aged 14 years and above. Medical examinations included anthropometric measurements, fasting blood analysis, measurement of the carotid intima-media thickness by high-resolution ultrasound, and a physician guided interview. RESULTS: The mean age of the 1506 participants was 17.8 years (standard deviation 0.90). 851 (56.5%) participants were female. 22 subjects had a physician diagnosis of non-allergic asthma, 268 had inhalative allergies confirmed by a positive radio-allergo-sorbent-test and/or prick test, and 58 had allergic asthma. Compared to healthy controls, participants with non-allergic asthma (411.7 vs. 411.7 µm; p = 0.932) or inhalative allergy (420.0 vs. 411.7 µm; p = 0.118) did not have significantly higher carotid intima-media thickness (cIMT). However, participants with allergic asthma had significantly higher cIMT (430.8 vs. 411.7; p = 0.004) compared to those without and this association remained significant after multivariable adjustment for established cardiovascular risk factors. CONCLUSION: Allergic asthma in the youth is associated with an increased carotid intima-media thickness. Physicians should therefore be aware of allergic asthma as a potential cardiovascular risk factor in children and adolescents. Trial Registration Number The EVA-Tyrol Study has been retrospectively registered at clinicaltrials.gov under NCT03929692 since April 29, 2019.
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Envejecimiento/fisiología , Asma/complicaciones , Enfermedades Cardiovasculares/etiología , Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Adolescente , Asma/diagnóstico , Asma/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Niño , Femenino , Humanos , Incidencia , Masculino , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia/tendenciasRESUMEN
PURPOSE: A significant proportion of noncommunicable diseases in adults has its roots in adolescence, and this is particularly true for cardiovascular disease and stroke. Detection of vascular and metabolic risk factors at young ages may aid disease prevention. METHODS: In 2,088 adolescents sampled from the general population of Tyrol, Austria, and South Tyrol, Italy, we systematically assessed the frequency of yet unknown vascular and metabolic risk conditions that require further diagnostic workup or intervention (lifestyle counselling or pharmacotherapy). The health screening included medical history taking, fasting blood analysis, and blood pressure and body measurements and was performed at schools. To recruit a representative sample of adolescents, equal proportions (about 67%) of schools were invited per school type and region. RESULTS: Adolescents were on average 16.4 (standard deviation 1.1) years old, and 56.4% were female. A proportion of 22.8% (95% confidence interval [CI], 19.6-26.3) had previous or current physician-confirmed diseases. The health screening newly detected relevant medical conditions in 45.4% [95% CI, 41.5-49.4] (55.8% [95% CI, 52.7-58.7] in boys and 37.4% [95% CI, 35.0-39.8] in girls, p < .001). The most prevalent were elevated blood pressure and hypertension, metabolic syndrome, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and subclinical hypothyroidism. Detection of risk conditions did not depend on socioeconomic status but increased with age and body mass index. CONCLUSIONS: Vascular health screening in adolescents at schools has a high diagnostic yield and may aid guideline-recommended prevention in the youth. Implementation should carefully consider national differences in healthcare systems, resources, and existing programs.
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Enfermedades Cardiovasculares , Instituciones Académicas , Adolescente , Adulto , Índice de Masa Corporal , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Femenino , Humanos , Lactante , Estilo de Vida , Masculino , Prevalencia , Factores de RiesgoRESUMEN
Background Cardiovascular disease depends on the duration and time course of risk factor exposure. Previous reports on risk factors of progression of carotid intima-media thickness (cIMT) in the young were mostly restricted to high-risk populations or susceptible to certain types of bias. We aimed to unravel a risk factor signature for early vessel pathology based on repeated ultrasound assessments of the carotid arteries in the general population. Methods and Results Risk factors were assessed in 956 adolescents sampled from the general population with a mean age of 15.8±0.9 years, 56.2% of whom were female. cIMT was measured at baseline and on average 22.5±3.4 months later by high-resolution ultrasound. Effects of baseline risk factors on cIMT progression were investigated using linear mixed models with multivariable adjustment for potential confounders, which yielded significant associations (given as increase in cIMT for a 1-SD higher baseline level) for alanine transaminase (5.5 µm; 95% CI: 1.5-9.5), systolic blood pressure (4.7 µm; 0.3-9.2), arterial hypertension (9.5 µm, 0.2-18.7), and non-high-density (4.5 µm; 0.7-8.4) and low-density lipoprotein cholesterol (4.3 µm; 0.5-8.1). Conclusions Systolic blood pressure, arterial hypertension, low-density and non-high-density lipoprotein cholesterol, and alanine transaminase predicted cIMT progression in adolescents, even though risk factor levels were predominantly within established reference ranges. These findings reemphasize the necessity to initiate prevention early in life and challenge the current focus of guideline recommendations on high-risk youngsters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03929692.
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Grosor Intima-Media Carotídeo , Hipertensión , Adolescente , Femenino , Humanos , Alanina Transaminasa , Arterias Carótidas/diagnóstico por imagenRESUMEN
BACKGROUND AND AIMS: Ideal cardiovascular health (CVH) behaviors in adolescents are defined by body mass index (BMI), diet, physical activity and smoking, and are directly associated with better health in later life. To further improve health prevention programs we investigated the prevalence of these behaviors in a cohort of healthy adolescents and focused on the associations with sex, age, and education. METHODS AND RESULTS: The Early Vascular Aging Tyrol study is a cross-sectional study assessing 14- to 19-year-old pupils and apprentices in Western Austria and South Tyrol. Between May 2015 and July 2018 2047 adolescents (43.6% males, mean age 16.4 years) with complete data for all 4 health behaviors were included. The prevalence of ideal body mass index (BMI) was 78.3%, of ideal physical activity 42.5%, of non-smoking 70.4% and of ideal diet 8.1%. Females showed a higher smoking prevalence and a lower physical activity, but better dietary habits than males. Older adolescents of both sexes had lower prevalence of ideal smoking and diet. Apprentices and pupils of vocational schools had a higher BMI and a less favorable diet compared to secondary academic school students. Smoking prevalence was highest in apprentices. Non-ideal BMI was independently associated with smoking. CONCLUSION: In our cohort, only a minority showed ideal CVH behaviors which were best in adolescents younger than 16 years. We observed significant differences between males and females and a clear impact of school education with apprentices being at risk for non-ideal CVH behaviors. CLINICAL TRIAL REGISTRATION NUMBER: NCT03929692, clinicaltrials.gov.
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Conducta del Adolescente , Enfermedades Cardiovasculares/prevención & control , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Estilo de Vida Saludable , Conducta de Reducción del Riesgo , Adolescente , Factores de Edad , Austria/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Dieta Saludable , Escolaridad , Ejercicio Físico , Conducta Alimentaria , Femenino , Estado de Salud , Humanos , Masculino , No Fumadores , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Conducta Sedentaria , Factores Sexuales , Fumar/efectos adversos , Fumar/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare inborn errors of metabolism with autosomal recessive inheritance that may cause life-threatening events. Treatment with triheptanoin, a synthetic seven-carbon fatty acid triglyceride compound with an anaplerotic effect, seems beneficial, but clinical experience is limited. We report our long-term experience in an Austrian cohort of LC-FAOD patients. METHODS: We retrospectively assessed clinical outcome and total hospitalization days per year before and after start with triheptanoin by reviewing medical records of 12 Austrian LC-FAOD patients RESULTS: For 12 Austrian LC-FAOD patients at three metabolic centers, triheptanoin was started shortly after birth in 3/12, and between 7.34 and 353.3 (median 44.5; mean 81.1) months of age in 9/12 patients. For 11 pediatric patients, mean duration of triheptanoin intake was 5.3 (median 3.9, range 1.2-15.7) years, 10/11 pediatric patients have an ongoing intake of triheptanoin. One patient quit therapy due to reported side effects. Total hospitalization days per year compared to before triheptanoin treatment decreased by 82.3% from 27.1 (range 11-65) days per year to 4.8 (range 0-13) days per year, and hospitalization days in the one year pre- compared to the one year post-triheptanoin decreased by 69.8% from 27.1 (range 4-75) days to 8.2 (range 0-25) days. All patients are in good clinical condition, show normal psychomotor development and no impairment in daily life activities. CONCLUSION: In this retrospective observational study in an Austrian LC-FAOD cohort, triheptanoin data show improvement in disease course. Triheptanoin appears to be a safe and beneficial treatment option in LC-FAOD. For further clarification, additional prospective randomized controlled trials are needed.
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Errores Innatos del Metabolismo Lipídico , Austria , Niño , Ácidos Grasos , Humanos , Estudios Prospectivos , Estudios Retrospectivos , TriglicéridosRESUMEN
BACKGROUND AND AIMS: Atherosclerosis starts early in life. We aimed to assess the dimension and progression of the intima-media thickness, a surrogate marker for early vascular aging, and its association with a broad palette of cardiovascular risk and lifestyle factors in a large cohort of healthy adolescents. METHODS: The EVA-Tyrol cohort study enrolled 1573 adolescents with a mean age of 16.0 years (SD 0.9). 1000 participants had a prospective follow-up after 22.1 months on average (SD 3.4). Cardiovascular risk and lifestyle factors were evaluated by standardized interviews, physical examination, and fasting blood analyses. Carotid intima-media thickness (cIMT) was measured at baseline and follow-up by high-resolution ultrasound. Aortic intima-media thickness (aIMT) was assessed during follow-up only. RESULTS: Several vascular risk factors like elevated blood pressure (4.7%â¯>â¯95th percentile), overweight (9.2%â¯>â¯95th percentile) and smoking (29.7%) were already prevalent at this age. Maximum cIMT progressed by 2.78⯵m (95% CI, 0.39-5.17) per year. In multivariable linear regression analysis, sex, body weight, systolic blood pressure, LDL-cholesterol and physical activity were independent predictors of cIMT both at baseline and follow-up. In addition, alanine-aminotransferase, a laboratory surrogate of non-alcoholic fatty liver disease, was independently associated with cIMT at follow-up and pack-years of smoking with aIMT. CONCLUSIONS: Unfavourable lifestyle and vascular risk factors were prevalent in adolescents and several of them were associated with vessel wall thickness, even though effect sizes were modest and cIMT variability was limited. These data suggest adolescence as a prime age range for early vascular prevention.
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Aterosclerosis , Factores de Riesgo de Enfermedad Cardiaca , Estilo de Vida , Adolescente , Envejecimiento , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiología , Grosor Intima-Media Carotídeo , Humanos , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To assess the time point during infancy and early childhood at which greater than expected weight gain is associated with overweight in adolescence. STUDY DESIGN: Current height, weight, and body mass index (BMI) were assessed in 1520 adolescents (mean age of boys, 15.52 ± 0.84 years; mean age of girls, 15.37 ± 0.77 years). Information on weight and height trajectories during infancy and early childhood (birth and 6 other time points) was extracted from mother-child booklets. Conditional relative weights were computed to estimate greater or lower than expected weight gain (ie, soft tissue gain at a specific age independent of linear growth), and their association with BMI in adolescence was investigated using linear regression analysis. RESULTS: The mean BMI in adolescence was 21.77 ± 3.69 in boys and 21.70 ± 3.50 in girls. The proportion of overweight was 14.8% in each group. Overweight adolescents had significantly higher weight z-scores at birth, 1.2 month, 3.3 months, 7.6 months, 1 year, 2 years, and 4 years of age as compared with normal-weight adolescents. There were significant positive associations of weight z-scores and conditional relative weights with adolescent BMI at all ages except birth, which were strongest after the first year of life. In a majority of overweight adolescents, overweight had manifested within the first 4 years of life. CONCLUSIONS: Greater than expected weigh gain at any time in the first years of life is associated with an increased BMI in adolescence. The effect is strongest after the first year.
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Peso al Nacer , Índice de Masa Corporal , Obesidad Infantil/epidemiología , Aumento de Peso , Adolescente , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
BACKGROUND: According to the World Health Organization, cardiovascular diseases (CVDs) are the leading non-communicable cause of death. Awareness of the individual risk profile is crucial to implement a healthy lifestyle and prevent CVDs. Multiple studies demonstrated that atherosclerosis, the main cause of CVDs, begins early in life. Therefore, it may be necessary to start prevention programs already in childhood. METHODS: The EVA-Tyrol study is a population-based non-randomized controlled trial that will prospectively enroll 2000 participants from high schools and training companies in North- and East-Tyrol (Austria) and South-Tyrol (Italy). Participants will be assigned to either an intervention (n = 1500) or a control (n = 500) group. Intervention group participants will be enrolled at the 10th school grade (mean age 15-16 years), undergo two examinations within a two-year interval, with follow-up at the 12th grade (mean ages 17-18 years). Control group participants will be enrolled at the 12th grade (mean age 17-18 years). Medical examination will include anthropometric measurements, comprehensive lifestyle and dietary questionnaires, a fasting blood sample, high-resolution ultrasound of the carotid arteries, and measurement of carotid-femoral pulse wave velocity. Active intervention will consist of (1) enhancing knowledge about CVDs, (2) individual medical counseling based on the results of the baseline examination, (3) an online health promotion tool and (4) involvement of participants in planning and implementation of health promotion projects. Effectiveness of the intervention will be assessed by comparing the proportion subjects with ideal health metrics as defined by the American Heart Association between study groups. DISCUSSION: This study aims to improve cardiovascular health in Tyrolean adolescents by demonstrating the efficacy of a multi-layer health promotion program and may yield novel insights into the prevalence of vascular risk conditions and mechanisms of early vascular pathologies in adolescents. TRIAL REGISTRATION: EVA-Tyrol has been retrospectively registered at clinicaltrials.gov under NCT03929692 since April 29, 2019.
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Enfermedades Cardiovasculares/prevención & control , Promoción de la Salud , Estilo de Vida Saludable , Conducta de Reducción del Riesgo , Servicios de Salud Escolar , Adolescente , Conducta del Adolescente , Factores de Edad , Austria/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Consejo , Femenino , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados no Aleatorios como Asunto , Estudios Prospectivos , Factores Protectores , Factores de RiesgoRESUMEN
Prenatal closure of foramen ovale without CHD is a rarely reported entity. Therefore, clinical and echocardiographic findings are poorly defined in these patients. We report a patient with prenatal closure of foramen ovale that presented with severe pulmonary hypertension of the newborn and left ventricular failure. Judicious management strategies were utilised to successfully treat both life-threatening conditions.
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Foramen Oval/fisiopatología , Insuficiencia Cardíaca/etiología , Hipertensión Pulmonar/etiología , Bosentán/administración & dosificación , Ecocardiografía , Femenino , Foramen Oval/diagnóstico por imagen , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/tratamiento farmacológico , Recién Nacido , Masculino , Embarazo , Citrato de Sildenafil/administración & dosificación , Resultado del Tratamiento , Ultrasonografía PrenatalRESUMEN
BACKGROUND: The nucleation-promoting factor cortactin is expressed and promotes tumor progression and metastasis in various cancers. However, little is known about the biological role of cortactin in the progression of pancreatic ductal adenocarcinoma (PDAC). METHODS: Cortactin and phosphorylated cortactin (Y421) were investigated immunohistochemically in 66 PDAC tumor specimens. To examine the functional role of cortactin in PDAC, we modulated cortactin expression by establishing two cortactin knockout cell lines (Panc-1 and BxPC-3) with CRISPR/Cas9 technique. Cortactin knockout was verified by immunoblotting and immunofluorescence microscopy and functional effects were determined by cell migration and invasion assays. A proteomic screening approach was performed to elucidate potential binding partners of cortactin. RESULTS: Immunohistochemically, we observed higher cortactin expression and Tyr421-phosphorylation in PDAC metastases compared to primary tumor tissues. In PDAC cell lines Panc-1 and BxPC-3, knockdown of cortactin impaired migration and invasion, while cell proliferation was not affected. Three-dimensional spheroid culturing as a model for collective cell migration enhanced cortactin expression and Tyr421-phosphorylation. The activation of cortactin as well as the migratory capacity of PDAC cells could significantly be reduced by dasatinib, a Src family kinase inhibitor. Finally, we identified gelsolin as a novel protein interaction partner of cortactin in PDAC. CONCLUSION: Our data provides evidence that cohesive cell migration induces cortactin expression and phosphorylation as a prerequisite for the gain of an invasive, pro-migratory phenotype in PDAC that can effectively be targeted with dasatinib.
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Ionizing radiation (IR) is frequently applied in the treatment of rectal adenocarcinoma, however, there is marked variance in the response to radiochemotherapy between individual tumors. In our previous investigations, it was shown that the overexpression of heterogeneous nuclear ribonucleoprotein K (hnRNP K) confers radioresistance to malignant melanoma and colorectal carcinoma (CRC) in vitro, however, the underlying mechanism remains to be elucidated. As hnRNP K, a p53 binding partner and cofactor for the transcriptional activation of p53 target genes, is overexpressed in CRC, the present study investigated the possible radioprotective effect of the hnRNP K/p53induced upregulation of p21 (also known as WAF1/CIP1) in rectal adenocarcinoma. Immunohistochemistry was performed for hnRNP K, p53 and p21 in a series of 68 consecutive cases of rectal adenocarcinoma with full molecular characterization following radiochemotherapy and 14 corresponding pretherapeutic biopsies, and the results were correlated with clinicopathological characteristics and the percentage of vital tumor cells following therapy. In addition, pathway analyses, protein immunoprecipitation, western immunoblotting and immunofluorescence microscopy were performed to identify dysregulated kinase signaling and hnRNP K targets upon exposure of CRC cells to IR. Although the fraction of vital tumor cells upon neoadjuvant therapy was significantly higher in hnRNP K/p21positive tumors (P=0.0047 and P=0.0223, Students' ttest), no significant association was found between the protein expression levels of hnRNP K, p53 and p21 (P>0.05, χ2 test). Irradiation enhanced apoptotic pathway activation via p53/CHK2 phosphorylation and poly (ADPribose) polymerase cleavage, and induced the overexpression and interaction of hnRNP K and p53. However, p53 Ser15phosphorylation was independent of the presence of hnRNP K, and there was no measurable effect of hnRNP K on the expression of p21 in vitro. Taken together, the results of the present study support a radioprotective role for hnRNP K, which may be mediated through an interaction with p53, however, this effect appears to be independent of the hnRNP K/p53induced upregulation of p21 in rectal adenocarcinoma.
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Quimioradioterapia , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/radioterapia , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Línea Celular Tumoral , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Ribonucleoproteína Heterogénea-Nuclear Grupo K/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunoprecipitación , Masculino , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genéticaRESUMEN
OBJECTIVE: To assess the impact of being born preterm or small for gestational age (SGA) on early vascular aging (EVA) in a cohort of healthy Tyrolean adolescents. STUDY DESIGN: This study is part of an ongoing clinical trial, EVA Tyrol, a regional cohort study being conducted in western Austria. EVA was assessed in adolescents (mean age, 16 years) by means of carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (cIMT), and blood pressure measurements. Adolescents were grouped as either term or preterm. Subsequently, being born SGA was taken into consideration in subgroup analysis. Complete data on gestational age and birth weight were available for 930 adolescents. RESULTS: Systolic blood pressure and diastolic blood pressure were significantly higher in the preterm (mean gestational age, 34.8 ± 2.3 weeks) and appropriate for gestational age (AGA) group than in the term and AGA group (P < .05). This finding remained significant in linear regression analysis after adjustment for covariables in all models. PWV was significantly higher in the term-SGA group than in the term-AGA group (6.67 ± 1.73 m/s vs 6.07 ± 1.09 m/s; P < .05). In the linear regression analysis, this finding remained significant in all models. There were no differences in cIMT between study groups. CONCLUSION: Being born preterm or SGA might render persons susceptible to EVA. Long-term follow-up of preterm and SGA individuals is warranted to confirm these results.
Asunto(s)
Presión Sanguínea/fisiología , Grosor Intima-Media Carotídeo , Recien Nacido Prematuro/fisiología , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Análisis de la Onda del Pulso , Adolescente , Austria , Arteria Carótida Común/fisiología , Estudios de Cohortes , Femenino , Arteria Femoral/fisiología , Humanos , Recién Nacido , Modelos Lineales , MasculinoRESUMEN
AIMS: Expression of PSMA (prostate-specific membrane antigen) has been demonstrated in various cancers, including pancreatic ductal adenocarcinoma (PDAC). However, PSMA expression in PDAC-associated neovasculature has so far not been systematically analyzed. METHODS AND RESULTS: We analyzed PSMA expression in 81 PDAC tissue samples from 61 patients. Microvessel density (MVD) was assessed by software-based image analysis and showed a mean MVD of 63.7 microvessels/0.785 mm2. PSMA was practically absent in tumor tissue (5.3%) and PDAC cell lines (0/7) but could be detected in tumor-associated neovasculature in 53.2% of cases. There was no association between neovascular PSMA expression and clinicopathological tumor characteristics. Samples with PSMA+ neovasculature showed increased MVD; however, this result was not statistically significant (p > 0.05). Presence of PSMA+ neovessels correlated with overall survival under palliative chemotherapy (894 versus 400 days; HR 0.42; 95% CI: 0.12 to 0.87; p < 0.05). CONCLUSION: PSMA expression in tumor-associated neovasculature is a common feature and associated with improved overall survival under palliative chemotherapy in PDAC. Our results point towards a possible association between PSMA expression and response to therapy which might be based on enhanced intratumoral bioavailability of systemic chemotherapy.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antígenos de Superficie/genética , Carcinoma Ductal Pancreático/tratamiento farmacológico , Glutamato Carboxipeptidasa II/genética , Neovascularización Patológica/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Microvasos/metabolismo , Microvasos/patología , Persona de Mediana Edad , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Cuidados PaliativosRESUMEN
AIM: This study assessed whether feeding preterm infants unpasteurized breastmilk (1) decreases the rate of late-onset sepsis and necrotizing enterocolitis and (2) increases the rate of postnatally acquired cytomegalovirus infections. SUBJECTS AND METHODS: Between January 2008 and July 2013, preterm infants below 32 completed weeks of gestational age admitted to the neonatal intensive care unit of Innsbruck Medical University (Innsbruck, Austria) (n=344) were eligible for the study. Of those, 323 fed breastmilk were retrospectively enrolled in the study. Two groups were formed, with 164 infants being fed unpasteurized and 159 infants being fed pasteurized breastmilk. RESULTS: There was no significant difference in the rate of late-onset sepsis or necrotizing enterocolitis between the unpasteurized and pasteurized breastmilk groups (late-onset sepsis, 15.9% versus 15.1% [p=0.486]; necrotizing enterocolitis, 2.4% versus 4.4% [p=0.254]). The number of infants diagnosed with postnatally acquired cytomegalovirus infection was significantly higher in the unpasteurized group (39.3%) compared with the pasteurized group (4.2%) (p=0.008). CONCLUSIONS: Feeding preterm infants unpasteurized breastmilk increases the rate of postnatally acquired cytomegalovirus infections. However, we also demonstrate a nonsignificant trend to a decreased rate of necrotizing enterocolitis in the unpasteurized group, which needs to be confirmed in larger studies.