Dyslipidemia is Associated with Unfit and Overweight-Obese Children and Adolescents

Background

Both poor aerobic fitness and obesity, separately, are associated with abnormal lipid profiles.

Objective

To identify possible relationships of dyslipidemia with cardiorespiratory fitness and obesity, evaluated together, in children and adolescents.

Methods

This cross-sectional study included 1,243 children and adolescents (563 males and 680 females) between 7 and 17 years of age from 19 schools. Obesity was assessed using body mass index (BMI) measurements, and cardiorespiratory fitness was determined via a 9-minute run/walk test. To analyze the lipid profile of each subject, the following markers were used: total cholesterol, cholesterol fractions (high-density lipoprotein and low-density lipoprotein) and triglycerides. Data were analyzed using SPSS v. 20.0, via prevalence ratio (PR), using the Poisson regression.

Results

Dyslipidemia is more prevalent among unfit/overweight-obese children and adolescents compared with fit/underweight-normal weight boys (PR: 1.25; p = 0.007) and girls (PR: 1.30, p = 0.001).

Conclusions

The prevalence of dyslipidemia is directly related to both obesity and lower levels of cardiorespiratory fitness.     

Prevalence of Cardiovascular Risk Factors in Hemodialysis Patients - The CORDIAL Study

Background

There are scarce epidemiological data on cardiovascular risk profile of chronic hemodialysis patients in Brazil.

Objective

The CORDIAL study was designed to evaluate cardiovascular risk factors and follow up a hemodialysis population in a Brazilian metropolitan city.

Methods

All patients undergoing regular hemodialysis for chronic renal failure in all fifteen nephrology centers of Porto Alegre were considered for inclusion in the baseline phase of the CORDIAL study. Clinical, laboratory and demographic data were obtained in medical records and in structured individual interviews performed in all patients by trained researchers.

Results

A total of 1215 patients were included (97.3% of all hemodialysis patients in the city of Porto Alegre). Their average age was 58.3 years old, 59.5% were male and 62.8% were white. The prevalence of cardiovascular risk factors observed was 87.5% for hypertension, 84.7% for dyslipidemia, 73.1% for sedentary lifestyle, 53.7% for tobacco use, and 35.8% for diabetes. In a multivariate adjusted analysis, we found that sedentary lifestyle (p = 0.032, PR 1.08 - 95%CI: 1.01-1.15), dyslipidemia (p = 0.019, PR 1.08 - 95%CI: 1.01-1.14), and obesity (p < 0.001, PR 1.96 - 95%CI: 1.45-2.63) were more frequent in women; and hypertension (p = 0.018, PR 1.06 - 95%CI: 1.01-1.11) and tobacco use (p = 0.006, PR 2.7 - 95%CI: 1.79-4.17) were more often found among patients under 65 years old. Sedentary lifestyle was independently associated with time in dialysis less than 12 months (p < 0.001, PR 1.23 - 95% CI: 1.14-1.33).

Conclusion

Hemodialysis patients in this southern metropolitan Brazilian city have a high prevalence of cardiovascular risk factors resembling many northern countries.     

Cardiometabolic risk factors in the Agarwal business community in India: Jaipur Heart Watch-6

Background

Agarwal is one of the largest business communities in India. To determine prevalence of cardiovascular risk factors and their distribution according to educational status (ES) in this community we performed a study.

Methods

1781 (men 1039, women 742) of 2500 selected subjects (71.2%) were evaluated and fasting blood sample obtained in 1130.

Results

Age-adjusted prevalence of risk factors was tobacco use 12.2%, sedentary habits 54.2%, overweight/obesity 54.4%, obesity 19.5%, abdominal obesity 61.2%, hypertension 36.0%, diabetes 19.2%, hypercholesterolemia ≥200 mg/dl 25.8%, low HDL cholesterol 29.2%, hypertriglyceridemia 32.8% and metabolic syndrome 22.3%. Low ES subjects had significantly greater prevalence of sedentary habits, low fruit/vegetable intake, hypertension, low HDL cholesterol and diabetes.

Conclusions

Cardiometabolic risk factors are highly prevalent in the Agarwal business community. Prevalence is greater in subjects with low educational status.     

Male Gender and Arterial Hypertension are Plaque Predictors at Coronary Computed Tomography Angiography

Background

Systemic Arterial Hypertension (SAH) is one of the main risk factors for Coronary Artery Disease (CAD), in addition to male gender. Differences in coronary artery lesions between hypertensive and normotensive individuals of both genders at the Coronary Computed Tomography Angiography (CCTA) have not been clearly determined.

Objective

To Investigate the calcium score (CS), CAD extent and characteristics of coronary plaques at CCTA in men and women with and without SAH.

Methods

Prospective cross-sectional study of 509 patients undergoing CCTA for CAD diagnosis and risk stratification, from November 2011 to December 2012, at Instituto de Cardiologia Dante Pazzanese. Individuals were stratified according to gender and subdivided according to the presence (HT +) or absence (HT-) of SAH.

Results

HT+ women were older (62.3 ± 10.2 vs 57.8 ± 12.8, p = 0.01). As for the assessment of CAD extent, the HT+ individuals of both genders had significant CAD, although multivessel disease is more frequent in HT + men. The regression analysis for significant CAD showed that age and male gender were the determinant factors of multivessel disease and CS ≥ 100. Plaque type analysis showed that SAH was a predictive risk factor for partially calcified plaques (OR = 3.9).

Conclusion

Hypertensive men had multivessel disease more often than women. Male gender was a determinant factor of significant CAD, multivessel disease, CS ≥ 100 and calcified and partially calcified plaques, whereas SAH was predictive of partially calcified plaques.     

Efficacy of Patient Selection for Diagnostic Coronary Angiography in Suspected Coronary Artery Disease

Background

Guidelines recommend that in suspected stable coronary artery disease (CAD), a clinical (non-invasive) evaluation should be performed before coronary angiography.

Objective

We assessed the efficacy of patient selection for coronary angiography in suspected stable CAD.

Methods

We prospectively selected consecutive patients without known CAD, referred to a high-volume tertiary center. Demographic characteristics, risk factors, symptoms and non-invasive test results were correlated to the presence of obstructive CAD. We estimated the CAD probability based on available clinical data and the incremental diagnostic value of previous non-invasive tests.

Results

A total of 830 patients were included; median age was 61 years, 49.3% were males, 81% had hypertension and 35.5% were diabetics. Non-invasive tests were performed in 64.8% of the patients. At coronary angiography, 23.8% of the patients had obstructive CAD. The independent predictors for obstructive CAD were: male gender (odds ratio [OR], 3.95; confidence interval [CI] 95%, 2.70 - 5.77), age (OR for 5 years increment, 1.15; CI 95%, 1.06 - 1.26), diabetes (OR, 2.01; CI 95%, 1.40 - 2.90), dyslipidemia (OR, 2.02; CI 95%, 1.32 - 3.07), typical angina (OR, 2.92; CI 95%, 1.77 - 4.83) and previous non-invasive test (OR 1.54; CI 95% 1.05 - 2.27).

Conclusions

In this study, less than a quarter of the patients referred for coronary angiography with suspected CAD had the diagnosis confirmed. A better clinical and non-invasive assessment is necessary, to improve the efficacy of patient selection for coronary angiography.     

Prevalence of Ischemia on Myocardial Perfusion Scintigraphy of Pre- and Postmenopausal Women

Background

In postmenopausal women, the presence of risk factors for coronary artery disease (CAD) increases. However, the difference in prevalence of ischemia between pre- and postmenopausal women with multiple risk factors for CAD has not been well established.

Objectives

To compare the prevalence of ischemia on Tc^99m-sestamibi myocardial perfusion scintigraphy (MPS) in pre-and postmenopausal women, and to evaluate whether menopause can be considered an independent risk predictor of ischemia in women with multiple risk factors for CAD.

Methods

This study retrospectively assessed 500 MPS of pre- and postmenopausal women with multiple risk factors for CAD. Statistical analysis was performed by using Fisher exact test and univariate and multivariate analysis, a p value ≤ 0.05 being considered significant.

Results

Postmenopausal women represented 55.9% of the sample; 83.3% were hypertensive; 28.9%, diabetic; 32.1%, smokers; 25%, obese; 61.2% had high cholesterol levels; and 34.3% had known CAD. Postmenopausal women were more often hypertensive, diabetic and dyslipidemic, and had lower functional capacity on exercise testing (p = < 0.005). The presence of ischemia on MPS did not significantly differ between the pre- and postmenopausal groups (p = 0.395). The only variable associated with ischemia on MPS was known CAD (p = 0.004).

Conclusion

The results suggest that, in women with multiple risk factors for CAD, menopause was not an independent predictor of ischemia on MPS. Those data support the idea that the investigation of ischemia via MPS in women with multiple risk factors for CAD should begin prior to menopause.     

Angiographic prevalence and pattern of coronary artery disease in women

Background

There are not many studies describing the prevalence and pattern of “coronary artery disease” (CAD) in women undergoing “coronary angiography” (CAG). Hence, uncertainty thrives with regard to the angiographic prevalence and pattern of CAD in women.

Objective

Our objective was to study the prevalence and pattern of CAD among women undergoing CAG.

Methods

Data of 500 women who underwent CAG for suspected CAD over 3 years were retrospectively analyzed. They were classified into young group (age < 55 years) and elderly group (age ≥ 55 years). Angiographic profile of “left main disease” (LMD) was also studied.

Results

There was greater prevalence of obstructive CAD especially double vessel disease and triple vessel disease in elderly group while normal coronaries were more prevalent in young group. There was equal distribution of non-significant lesions and intermediate lesions between the two groups. The prevalence of LMD is 3.4%, obstructive CAD is 45.4%, and multivessel disease is 28%. The prevalence of LMD and multivessel disease is 31.4%. The pattern of involvement of coronary arteries was same between the two groups; left anterior descending artery is the most commonly affected vessel. Chronic total occlusion mostly involved right coronary artery. Bifurcation lesion involving distal left main coronary artery is the most prevalent pattern of LMD.

Conclusion

There has been a change with regard to clinical presentation and onset of risk factors for CAD at young age, but the load of atherosclerotic burden and pattern of involvement of coronary arteries have not changed in women.     

Blood Pressure Control in Hypertensive Patients in the "Hiperdia Program": A Territory-Based Study

Background

Systemic hypertension is highly prevalent and an important risk factor for cardiovascular events. Blood pressure control in hypertensive patients enrolled in the Hiperdia Program, a program of the Single Health System for the follow-up and monitoring of hypertensive patients, is still far below the desired level.

Objective

To describe the epidemiological profile and to assess blood pressure control of patients enrolled in Hiperdia, in the city of Novo Hamburgo (State of Rio Grande do Sul, Brazil).

Methods

Cross-sectional study with a stratified cluster random sample, including 383 adults enrolled in the Hiperdia Program of the 15 Basic Health Units of the city of Porto Alegre, conducted between 2010 and 2011. Controlled blood pressure was defined as ≤140 mmHg × 90 mmHg. The hypertensive patients were interviewed and their blood pressure was measured using a calibrated aneroid device. Prevalence ratios (PR) with 95% confidence interval, Wald''s χ² test, and simple and multiple Poisson regression were used in the statistical analysis.

Results

The mean age was 63 ± 10 years, and most of the patients were females belonging to social class C, with a low level of education, a sedentary lifestyle, and family history positive for systemic hypertension. Diabetes mellitus (DM) was observed in 31%; adherence to the antihypertensive treatment in 54.3%; and 33.7% had their blood pressure controlled. DM was strongly associated with inadequate BP control, with only 15.7% of the diabetics showing BP considered as controlled.

Conclusion

Even for hypertensive patients enrolled in the Hiperdia Program, BP control is not satisfactorily reached or sustained. Diabetic hypertensive patients show the most inappropriate BP control.     

Risk Factors Associated with High Blood Pressure in Two-to Five-Year-Old Children

Background

Over recent decades, the prevalence of high blood pressure (BP) has increased among children. Several risk factors are involved in the genesis of high BP during childhood, and their early identification can prevent the development of that disease.

Objectives

To assess the prevalence of high BP and associated factors in children.

Methods

Cross-sectional, population-based study, carried out at the household. This study included 276 two- to five-year-old children in the city of Goiânia, state of Goiás, and assessed their BP, sociodemographic characteristics, birth weight, high BP family history, passive smoking, maternal breastfeeding, dietary habits, sedentary lifestyle and nutritional status. Poisson regression was used to assess the association between risk factors and high BP.

Results

Their mean age was 3.1 ± 0.79 years, and high BP and overweight were observed in 19.9% and 11.2% of the children, respectively. Direct association of high BP was identified with age [prevalence ratio (PR) = 2.3; 95%CI: 1.2 - 4.8; p = 0.017] and overweight (PR = 2.0; 95%CI: 1.2 - 3.6; p = 0.014). No other variable associated with high BP.

Conclusions

The prevalence of high BP in children was high. Overweight and younger children had greater prevalence of high BP.     

Risk of Ionizing Radiation in Women of Childbearing Age undergoing Radiofrequency Ablation

Background

The International Commission of Radiology recommends a pregnancy screening test to all female patients of childbearing age who will undergo a radiological study. Radiation is known to be teratogenic and its effect is cumulative. The teratogenic potential starts at doses close to those used during these procedures. The prevalence of positive pregnancy tests in patients undergoing electrophysiological studies and/or catheter ablation in our midst is unknown.

Objective

To evaluate the prevalence of positive pregnancy tests in female patients referred for electrophysiological study and/or radiofrequency ablation.

Methods

Cross-sectional study analyzing 2,966 patients undergoing electrophysiological study and/or catheter ablation, from June 1997 to February 2013, in the Institute of Cardiology of Rio Grande do Sul. A total of 1490 procedures were performed in women, of whom 769 were of childbearing age. All patients were screened with a pregnancy test on the day before the procedure.

Results

Three patients tested positive, and were therefore unable to undergo the procedure. The prevalence observed was 3.9 cases per 1,000 women of childbearing age.

Conclusion

Because of their safety and low cost, pregnancy screening tests are indicated for all women of childbearing age undergoing radiological studies, since the degree of ionizing radiation needed for these procedures is very close to the threshold for teratogenicity, especially in the first trimester, when the signs of pregnancy are not evident.     

Electrophysiological Studies and Radiofrequency Ablations in Children and Adolescents with Arrhythmia

Background

Radiofrequency ablation is the standard non-pharmacological treatment for arrhythmias in pediatric patients. However, arrhythmias and their associated causes have particular features in this population.

Objective

To analyze the epidemiological characteristics and findings of electrophysiological diagnostic studies and radiofrequency ablations in pediatric patients referred to the Electrophysiology Unit at Instituto de Cardiologia do Rio Grande do Sul, in order to characterize the particularities of this population.

Methods

Cross-sectional study with 330 electrophysiological procedures performed in patients aged less than 20 years between June 1997 and August 2013.

Results

In total, 330 procedures (9.6% of the overall procedures) were performed in patients aged less than 20 years (14.33 ± 3.25 years, age range 3 months to 19 years), 201 of which were males (60.9%). A total of 108 (32.7%) electrophysiological diagnostic studies were performed and of these, 48.1% showed abnormal findings. Overall, 219 radiofrequency ablations were performed (66.3%) with a success rate of 84.8%. The presence of an accessory pathway was the most prevalent finding, occurring in 158 cases (72.1%), followed by atrioventricular nodal reentrant tachycardia (16.8%), typical atrial flutter (3.1%) and extrasystoles originating from the right ventricular outflow tract (2.7%). Three patients developed complications during ablation (1.4%). Among congenital heart diseases, which occurred in 51 (15.4%) patients, atrial sept defect was the most frequent (27.4%), followed by ventricular sept defect (25.4%) and Ebstein''s anomaly (17.6%).

Conclusion

Electrophysiological study and radiofrequency ablation are effective tools for diagnosis and treatment of arrhythmias in the pediatric population.     

Metabolic Syndrome and Importance of Associated Variables in Children and Adolescents in Guabiruba - SC,Brazil

Background

The risk factors that characterize metabolic syndrome (MetS) may be present in childhood and adolescence, increasing the risk of cardiovascular disease in adulthood.

Objective

Evaluate the prevalence of MetS and the importance of its associated variables, including insulin resistance (IR), in children and adolescents in the city of Guabiruba-SC, Brazil.

Methods

Cross-sectional study with 1011 students (6-14 years, 52.4% girls, 58.5% children). Blood samples were collected for measurement of biochemical parameters by routine laboratory methods. IR was estimated by the HOMA-IR index, and weight, height, waist circumference and blood pressure were determined. Multivariate logistic regression models were used to examine the associations between risk variables and MetS.

Results

The prevalence of MetS, IR, overweight and obesity in the cohort were 14%, 8.5%, 21% and 13%, respectively. Among students with MetS, 27% had IR, 33% were overweight, 45.5% were obese and 22% were eutrophic. IR was more common in overweight (48%) and obese (41%) students when compared with eutrophic individuals (11%; p = 0.034). The variables with greatest influence on the development of MetS were obesity (OR = 32.7), overweight (OR = 6.1), IR (OR = 4.4; p ≤ 0.0001 for all) and age (OR = 1.15; p = 0.014).

Conclusion

There was a high prevalence of MetS in children and adolescents evaluated in this study. Students who were obese, overweight or insulin resistant had higher chances of developing the syndrome.     

Elevated Blood Pressure and Obesity in Childhood: A Cross-Sectional Evaluation of 4,609 Schoolchildren

Background:

The incidence of obesity in children is increasing worldwide, primarily in urbanized, high-income countries, and hypertension development is a detrimental effect of this phenomenon.

Objective:

In this cross-sectional study, we evaluated the prevalence of excess weight and its association with high blood pressure (BP) in schoolchildren.

Methods:

Here 4,609 male and female children, aged 6 to 11 years, from 24 public and private schools in Maringa, Brazil, were evaluated. Nutritional status was assessed by body mass index (BMI) according to cutoff points adjusted for sex and age. Blood pressure (BP) levels above 90th percentile for gender, age and height percentile were considered elevated.

Results:

The prevalence of excess weight among the schoolchildren was 24.5%; 16.9% were overweight, and 7.6% were obese. Sex and socioeconomic characteristics were not associated with elevated BP. In all age groups, systolic and diastolic BP correlated with BMI and waist and hip measurements, but not with waist-hip ratio. The prevalence of elevated BP was 11.2% in eutrophic children, 20.6% in overweight children [odds ratio (OR), 1.99; 95% confidence interval (CI), 1.61-2.45], and 39.7% in obese children (OR, 5.4; 95% CI, 4.23-6.89).

Conclusion:

Obese and overweight children had a higher prevalence of elevated BP than normal-weight children. Our data confirm that the growing worldwide epidemic of excess weight and elevated BP in schoolchildren may also be ongoing in Brazil.     

Prevalence of Burnout Syndrome in Patients Admitted with Acute Coronary Syndrome

Background

Burnout Syndrome is the extreme emotional response to chronic occupational stress, manifesting as physical and mental exhaustion. Although associated with higher prevalence of cardiovascular risk factors, no study so far has evaluated whether the Burnout Syndrome could be a prevalent factor in non-elderly individuals active in the labor market, admitted for acute coronary syndrome (ACS).

Objective

To evaluate the prevalence of the Burnout Syndrome in non-elderly, economically active patients, hospitalized with ACS.

Methods

Cross-sectional study conducted in a tertiary and private cardiology center, with economically active patients aged <65 years, hospitalized with diagnosis of ACS. The Burnout Syndrome was evaluated with the Burnout Syndrome Inventory (BSI), which assesses workplace conditions and four dimensions that characterize the syndrome: emotional exhaustion (EE), emotional distancing (EmD), dehumanization (De) and professional fulfillment (PF). The Lipp’s Stress Symptoms Inventory for Adults (LSSI) was applied to evaluate global stress.

Results

Of 830 patients evaluated with suspected ACS, 170 met the study criteria, 90% of which were men, overall average age was 52 years, and 40.5% had an average income above 11 minimum wages. The prevalence of the Burnout Syndrome was 4.1%. When we evaluated each dimension individually, we found high EE in 34.7%, high De in 52.4%, high EDi in 30.6%, and low PF in 5.9%. The overall prevalence of stress was 87.5%.

Conclusion

We found a low prevalence of Burnout Syndrome in an economically active, non-elderly population among patients admitted for ACS in a tertiary and private hospital.     

Modifiable Risk Factors in Young Adults With First Myocardial Infarction

Background

Modifiable risk factors (RFs) play an important role in the development and prognosis of acute myocardial infarction (AMI).

Aging attenuates the association of central obesity with the accumulation of metabolic risk factors when assessed using the waist circumference measured at the umbilical level (the Japanese standard method)

Objective:

The objective of this study was to clarify the generation and gender differences in the association between central obesity and the accumulation of metabolic risk factors (RFs) in the Japanese population.

Material and methods:

A total of 12 389 subjects (age: 18–80 years) without receiving medication for diabetes, dyslipidemia or hypertension were enrolled in this study and divided according to age and gender. In each group, we performed analyses as follows: (1) a receiver operating characteristic (ROC) analysis to evaluate the utility of the waist circumference (WC) for detecting subjects with multiple RFs of metabolic syndrome (MS); (2) a cross-sectional study to examine the relationship between the WC and the odds ratio (OR) for detecting those subjects and (3) a longitudinal study to examine how longitudinal changes (Δ) in WC over a 1-year period affected the values of each metabolic RF.

Results:

With age, the WC cutoff values yielding the maximum Youden index for detecting subjects with multiple RFs increased only in women, and the areas under the curves of the ROC analysis of WC for detecting those subjects decreased in both genders. The positive correlation between the WC and the OR for detecting subjects with multiple RFs became weaker with age, especially in women. In the longitudinal study, the significant correlation between ΔWC and Δ each metabolic RF, except for hypertension, and between ΔWC and Δ the number of RFs became weaker with age in women, whereas the significant correlation between ΔWC and Δ the number of RFs was not affected with age in men. In women aged ⩾60 years, none of the changes in each metabolic RF were significantly associated with ΔWC.

Conclusions:

Aging attenuates the association of central obesity with the accumulation of metabolic RFs, especially in women.     

High blood Pressure in children and its correlation with three definitions of obesity in childhood

Background

Several authors have correlated the increase of cardiovascular risk with the nutritional status, however there are different criteria for the classification of overweight and obesity in children.

Objectives

To evaluate the performance of three nutritional classification criteria in children, as definers of the presence of obesity and predictors of high blood pressure in schoolchildren.

Methods

Eight hundred and seventeen children ranging 6 to 13 years old, enrolled in public schools in the municipality of Vila Velha (ES) were submitted to anthropometric evaluation and blood pressure measurement. The classification of the nutritional status was established by two international criteria (CDC/NCHS 2000 and IOTF 2000) and one Brazilian criterion (Conde e Monteiro 2006).

Results

The prevalence of overweight was higher when the criterion of Conde e Monteiro (27%) was used, and inferior by the IOTF (15%) criteria. High blood pressure was observed in 7.3% of children. It was identified a strong association between the presence of overweight and the occurrence of high blood pressure, regardless of the test used (p < 0.001). The test showing the highest sensitivity in predicting elevated BP was the Conde e Monteiro (44%), while the highest specificity (94%) and greater overall accuracy (63%), was the CDC criterion.

Conclusions

The prevalence of overweight in Brazilian children is higher when using the classification criterion of Conde e Monteiro, and lower when the criterion used is IOTF. The Brazilian classification criterion proved to be the most sensitive predictor of high BP risk in this sample.     

Impact of atherosclerosis risk factors on the clinical presentation of arterial occlusive disease in Arabic patients

BACKGROUND:

Although the risk factors for atherosclerosis have been identified, their impact on the presentation of arterial occlusive disease has not been studied among Arabs.

OBJECTIVE:

To determine the correlation between atherosclerotic risk factors and the extent and presentation of atherosclerotic disease in different arterial systems.

METHODS:

The present case-control study was performed on a consecutive series of Arabic patients over one year. There were two groups – an atherosclerotic group, which included patients with peripheral arterial disease, extracranial cerebrovascular disease or coronary artery disease (CAD), and the control group, which included patients admitted to one of the general surgical units who were free from atherosclerotic disease. All patients underwent evaluation of risk factors (diabetes mellitus [DM], smoking, dyslipidemia and hypertension) for atherosclerosis and systemic assessment of the vascular tree.

RESULTS:

Two hundred fifteen patients in the atherosclerotic group and 191 patients in the control group were included in the study. There were positive correlations between the prevalence of DM, smoking, dyslipidemia and the severity of presentation of peripheral arterial disease, and the extent of CAD. The correlation between the incidence of DM and the severity of presentation of CAD was also significant. The correlation was also positive between the incidence of ex-smoking and hypertension, and the severity of presentation of extracranial cerebrovascular disease.

CONCLUSION:

Different risk factors may interact in different ways in the clinical presentation of atherosclerotic disease in different arterial systems.