The Effect of Fructose vs. Glucose Beverages on Low-Grade Systemic Inflammation

Thesis (Ph.D.)--University of Washington, 2016-04

Dietary carbohydrate source affects glucose concentrations, insulin secretion, and food intake in overweight cats

This study was undertaken to assess the impact of dietary carbohydrate source on food intake, body composition, glucose tolerance, insulin sensitivity, and glucose and insulin concentrations in overweight and obese cats with reduced insulin sensitivity. Sixteen overweight and obese cats were divided into two groups and randomly allocated one of two extruded diets formulated to contain similar starch content (33%) from different cereal sources (sorghum and corn versus rice). Meal response, glucose tolerance and insulin sensitivity tests were performed before and after a 6-week weight-maintenance phase and after an additional 8-week free-access feeding phase. Dual energy x-ray absorptiometry (DEXA)-derived body composition was determined in each cat before the study and after each test phase. Food intake was measured daily and body weight measured twice weekly for the duration of the study. When compared with the sorghum/corn-based diet, cats fed the rice-based diet consumed more energy and gained more weight in response to free-access feeding. Cats fed the rice-based diet also tended to have higher glucose concentrations and insulin secretion in response to a glucose load or a test meal. We conclude that a sorghum and corn blend is a superior carbohydrate source than rice for overweight cats with glucose intolerance and reduced insulin sensitivity. Such a diet may help to minimize overeating and additional weight gain, and may also reduce the risk of developing type 2 diabetes mellitus. (C) 2004 Elsevier Inc. All rights reserved.

Obesity in pre-school children: Issues and challenges for community based child health nurses

Childhood obesity is becoming a topical issue in both the health literature and the popular media and increasingly child health nurses are observing preschool children who appear to be disproportionately heavy for their height when plotted on standardised growth charts. In this paper literature related to childhood obesity in New Zealand and internationally is explored to identify current issues, and the implications of these issues for nurses in community based child health practice are discussed. Themes that emerged from the literature relate to the measurement of obesity, links between childhood and adult obesity and issues for families. A theme in the literature around maternal perception was of particular interest. Studies that investigated maternal perceptions of childhood obesity found that mothers identified their child as being overweight or obese only when it imposed limitations on physical activity or when the children were teased rather than by referring to individual growth graphs. The implications for nursing in the area of child health practice is discussed as nurses working in this area need an understanding of the complex and often emotive issues surrounding childhood obesity and an awareness of the reality of people's lives when devising health promotion strategies.

Breastfeeding and obesity at 14 years: A cohort study

Aim: To determine the influence of breastfeeding on overweight and obesity in early adolescence. Methods: Data about breastfeeding duration, BMI of children at 14 years, and confounding variables, were collected from an ongoing longitudinal study of a birth cohort of 7776 children in Brisbane. Prevalence of overweight and obesity at 14 years was assessed according to duration of breastfeeding, with logistic regression being used to adjust for the influence of confounders. Results: Data were available for 3698 children, and those not included were significantly different in age, educational level, income, race, birthweight, and small-for-gestational-age status. Breastfeeding for longer than six months was protective of obesity (OR 0.6, 95% CI 0.4, 0.96) though not of overweight. When confounding variables were considered the effect size diminished and lost statistical significance OR 0.8 (95% CI 0.5, 1.3). Breastfeeding for less than 6 months had no effect on either obesity or overweight though a trend was found for increased prevalence of overweight at 14 years with shorter periods of breastfeeding. Conclusion: This investigation contributes to the gathering body of evidence that breastfeeding for longer than 6 months has a modest protective effect against obesity in adolescence.

Milk feeding, solid feeding, and obesity risk:a review of the relationships between early life feeding practices and later adiposity

Childhood obesity is a major health issue with associated ill-health consequences during childhood and into later adolescence and adulthood. Given that eating behaviors are formed during early childhood, it is important to evaluate the relationships between early life feeding practices and later child adiposity. This review describes and evaluates recent literature exploring associations between child weight and the mode of milk feeding, the age of introducing solid foods and caregivers’ solid feeding practices. There are many inconsistencies in the literature linking early life feeding to later obesity risk and discrepancies may be related to inconsistent definitions, or a lack of control for confounding variables. This review summarizes the literature in this area and identifies the need for large scale longitudinal studies to effectively explore how early life feeding experiences may interact with each other and with nutritional provision during later childhood to predict obesity risk.

A computer based approach to improve the dietary and physical activity patterns of a diverse group of adolescents

Diet and physical activity patterns have been implicated as major factors in the increasing prevalence of childhood and adolescent obesity. It is estimated that between 16 and 33 percent of children and adolescents in the United States are overweight (CDC, 2000). Moreover, the CDC estimates that less than 50% of adolescents are physically active on a regular basis (CDC, 2003). Interventions must be focused to modify these behaviors. Facilitating the understanding of proper nutrition and need for physical activity among adolescents is the first step in preventing overweight and obesity and delaying the development of chronic diseases later in life (Dwyer, 2000). The purpose of this study was to compare the outcomes of students receiving one of two forms of education (both emphasizing diet and physical activity), to determine whether a computer based intervention (CBI) program using an interactive, animated CD-ROM would elicit a greater behavior change in comparison to a traditional didactic intervention (TDI) program. A convenience sample of 254 high school students aged 14-19 participated in the 6-month program. A pre-test post-test design was used, with follow-up measures taken at three months post-intervention. ^ No change was noted in total fat, saturated fat, fruit/vegetables, or fiber intake for any of the groups. There was also no change in perceived self-efficacy or perceived social support. Results did, however, indicate an increase in nutrition knowledge for both intervention groups (p<0.001). In addition, the CBI group demonstrated more positive and sustained behavior changes throughout the course of the study. These changes included a decrease in BMI (ppre/post<0.001, ppost/follow-up<0.001), number of meals skipped (ppre/post<0.001), and soda consumption (ppre/post=0.003, ppost/follow-up=0.03) and an increase in nutrition knowledge (ppre/post<0.001, ppre/follow-up <0.001), physical activity (ppre/post<0.05, p pre/follow-up<0.01), frequency of label reading (ppre/follow-up <0.0l) and in dairy consumption (ppre/post=0.03). The TDI group did show positive gains in some areas post intervention, however a return to baseline behavior was shown at follow-up. Findings of this study suggest that compared to traditional didactic teaching, computer-based nutrition and health education has greater potential to elicit change in knowledge and behavior as well as promote maintenance of the behavior change over time. ^

The relationship of fear of intimacy, body image avoidance and body mass index

Issues of body image and ability to achieve intimacy are connected to body weight, yet remain largely unexplored and have not been evaluated by gender. The underlying purpose of this research was to determine if avoidant attitudes and perceptions of one's body may hold implications toward its use in intimate interactions, and if an above average body weight would tend to increase this avoidance. The National Health and Nutrition Examination Survey (NHANES, 1999-2002) finds that 64.5% of US adults are overweight, with 61.9% of women and 67.2% of men. The increasing prevalence of overweight and obesity in men and women shows no reverse trend, nor have prevention and treatment proven effective in the long term. The researcher gathered self-reported age, gender, height and weight data from 55 male and 58 female subjects (determined by a prospective power analysis with a desired medium effect size (r=.30) to determine body mass index (BMI), determining a mean age of 21.6 years and mean BMI of 25.6. Survey instruments consisted of two scales that are germane to the variables being examined. They were (1) Descutner and Thelen of the University of Missouri‘s (1991) Fear-of-Intimacy scale; and (2) Rosen, Srebnik, Saltzberg, and Wendt's (1991) Body Image Avoidance Questionnaire. Results indicated that as body mass index increases, fear of intimacy increases (p<0.05) and that as body mass index increases, body image avoidance increases (p<0.05). The relationship that as body image avoidance increases, fear of intimacy increases was not supported, but approached significance at (p<0.07). No differences in these relationships were determined between gender groups. For age, the only observed relationship was that of a difference between scores for age groups [18 to 22 (group 1) and ages 23 to 34 (group 2)] for the relationship of body image avoidance and fear of intimacy (p<0.02). The results suggest that the relationship of body image avoidance and fear of intimacy, as well as age, bear consideration toward the escalating prevalence of overweight and obesity. An integrative approach to body weight that addresses issues of body image and intimacy may prove effective in prevention and treatment.

Low-income first time mothers: Effects on advanced practice nurse (APN) follow up telephone calls on maternal and infant health and health care charges

The United States has over 4 million births annually. Currently healthy women with non-complicated deliveries receive little to no routine postpartum support when discharged from the hospital. This is especially problematic if mothers are first time mothers, poor, have language barriers and little to no social support after giving birth. The purpose of this randomized clinical trial was to compare maternal and infant health outcomes, and health care charges between 2 groups of mothers and newborns. A control ( n = 69) group received routine posthospital discharge care. An intervention group (n = 70) received routine posthospital discharge care plus follow up telephone calls by advanced practice nurses (APNs) on days 3,7,14,21,28 and week 8. Both groups were followed for the first 8 weeks posthospital discharge following delivery to examine maternal health outcomes (perceived maternal stress, social support and perceived maternal physical health), infant health outcomes (routine medical follow up visits immunizations, weight gain), morbidity (urgent care visits, emergency room visits, rehospitalizations), health care charges (urgent care visits, emergency room visits, rehospitalizations) in both groups and charges for APN follow up in the intervention group only. Data were analyzed using descriptive statistics and two-sample t-tests. Study findings indicated that intervention group had significantly lower perceived maternal stress, significantly higher rating of perceived maternal health and higher levels of social support and by the end of the 2nd month posthospital discharge compared to control group mothers. Infants in the intervention group had: increased number of immunizations; fewer emergency room visits; and 1 infant rehospitalization compared to 3 infant rehospitalizations in the control group. The intervention groups' health care charges were significantly lower compared to the control group $14,333/$497 vs. $70,834/$1,068. These study results indicate that an intervention of APN follow up telephone calls in this sample of first time low-income culturally diverse mothers was an effective, safe, low cost, easy to apply intervention which improved mothers' and infants' health outcomes and reduced healthcare charges.

Overweight/Obesity and HIV Disease Progression in HIV+ Adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.

A influência da perda de peso no perfil inflamatório de mulheres com síndrome dos ovários policísticos

The polycystic ovary syndrome (PCOS) is considered the most common endocrine disorder in reproductive age women, with a prevalence ranging from 15 to 20%. In addition to hormonal and reproductive changes, it is common in PCOS the presence of risk factors for developing cardiovascular disease (CVD) and diabetes mellitus, insulin resistance (IR), visceral obesity, chronic low-grade inflammation and dyslipidemia. Due to the high frequency of obesity associated with PCOS, weight loss is considered as the first-line treatment for the syndrome by improving metabolic and normalizes serum androgens, restoring reproductive function of these patients. Objectives: To evaluate the inflammatory markers and IR in women with PCOS and healthy ovulatory with different nutritional status and how these parameters are displayed after weight loss through caloric restriction in with Down syndrome. Methods: Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed in serum samples from 40 women of childbearing age. The volunteers were divided into four groups: Group I (not eutrophic with PCOS, n = 12); Group II (not eutrophic without PCOS, n = 10), Group III (eutrophic with PCOS, n = 08) and Group IV (eutrophic without PCOS, n = 10). The categorization of groups was performed by body mass index (BMI), according to the World Health Organization (WHO) does not eutrophic, overweight and obesity (BMI> 25 kg / m²) and normal weight (BMI <24.9 kg / m²). IR was determined by HOMA-IR index. In the second phase of the study a controlled dietary intervention was performed and inflammatory parameters were evaluated in 21 overweight and obese women with PCOS, before and after weight loss. All patients received a low-calorie diet with reduction of 500 kcal / day of regular consumption with standard concentrations of macronutrients. Results: Phase 1: PCOS patients showed increased levels of CRP (p <0.01) and HOMAIR (p <0.01). When divided by BMI, both not eutrophic group with PCOS (I) as eutrophic with PCOS (III) showed increased levels of CRP (I = 2.35 ± 0,55mg / L and 2.63 ± III = 0,65mg / L; p <0.01) and HOMA-IR (I = 2.16 ± 2.54 and III = 1.07 ± 0.55; p <0.01). There were no differences in TNF-α and IL-6 between groups. Step 2: After the weight loss of 5% of the initial weight was reduced in all of the components of serum assessed inflammatory profile, PCR (154.75 ± 19:33) vs (78.06 ± 8.9) TNF α (10.89 ± 5.09) vs (6:39 ± 1:41) and IL6 (154.75 ± 19:33) vs (78.06 ± 08.09) (p <0:00) in association with improvement some hormonal parameters evaluated. Conclusion: PCOS contributed to the development of chronic inflammation and changes in glucose metabolism by increasing CRP, insulin and HOMA-IR, independent of nutritional status. The weight loss, caloric restriction has improved the inflammatory condition and hormonal status of the evaluated patients.

Avaliação da genotoxicidade em mulheres com síndrome dos ovários policísticos: impacto da dieta

Introduction: Polycystic Ovary Syndrome (PCOS), present in 6-12% of women of reproductive age, the criterion of Rotterdam, is characterized by hyperandrogenism, insulin resistance (IR) and its inflammatory state, exacerbated by obesity and factors associated with the increase in damage DNA. Weight loss, combined with healthy eating, acts restoring the reproductive and metabolic functions in the SOP, though its influence in reducing DNA damage in PCOS are unknown. Aim: To investigate whether there are differences between DNA damage markers and factors of cardiometabolic risk in women with PCOS and control, and evaluate the effectiveness of nutritional intervention in DNA damage markers and cardiometabolic risk markers in overweight and obese women with PCOS. Methods: the study was conducted in two studies and the participants were aged between 18 and 35 years. In the first study, a prospective case-control, were included 27 women diagnosed with PCOS and 20 controls. In the second study, clinical trial of nutritional intervention with 12-week calorie-restricted diet 500Kcal / day. The genotoxicity, DNA damage (intensity tail, tail moment and tail length) was evaluated by the comet assay. Anthropometric data, dietary intake, hormonal, biochemical and inflammatory were evaluated in different studies. Results: there was no significant difference between the DNA damage marker tail intensity (p = 0.18), tail moment (p = 0.76) and tail length (p = 0.109) in PCOS when compared to the control group. Data after nutritional intervention in PCOS women with overweight and obesity showed a decrease in DNA damage markers: tail intensity (24.35 ± 5.86 - pre-diet vs. 17.15 ± 5.04 -Post-diet) and tail moment (20.47 ± 7.85 - pre-diet vs. 14.13 ± 6.29 -post-diet) (p <0.001). Reduction of weight (3.5%) and decreased cardiometabolic markers IR and hyperandrogenism. Conclusion: women with PCOS have a worse cardiometabolic risk profile compared to control however similar genotoxicity identified by DNA damage. Nutritional intervention reduced the genotoxicity of overweight and obese women with PCOS, and reduce the factors of cardiometabolic risk.

Serious Game no tratamento de obesidade infantil: uma proposta de interação natural com monitoramento remoto

The number of overweight people has increased in the last few years. Factors such as attention to diet and changes in lifestyle are crucial in the prevention and control of obesity and diseases related to it. Experts believe that such actions are most effective when initiated during childhood, and that children raised in an environment that encourages physical activity ultimately become healthier adults. However, to arouse and maintain interest in such activities represent a major challenge, which are initially perceived as repetitive and boring, and, thus, soon abandoned. Computer games, traditionally seen as stimulants to a sedentary lifestyle are changing this perception using non-conventional controls that require constant movement of the player. Applications that combine the playfulness of such games to physical activity through devices, like Microsoft Kinect, might become interesting tools in this scenario, by using the familiarity of Natural User Interfaces along with the challenge and the fun of video games, in order to make attractive exercise routines for schoolchildren. The project carried out consists of an exergame composed of several activities designed and implemented with the participation of a Physical Educator, aimed at children between eight and ten years old, whose performance and progress can be remotely monitored by a professional via web interface. The application arising from this work was accompanied by tests with a group of graduating Physical Education students from the University of Rio Verde GO, and subsequently validated through questionnaires whose results are shown on this work.

Food Swamps, Obesity & Health Zoning Restrictions on Fast Food Restaurants

Protecting public health is the most legitimate use of zoning, and yet there is minimal progress in applying it to the obesity problem. Zoning could potentially be used to address both unhealthy and healthy food retailers, but lack of evidence regarding the impact of zoning and public opinion on zoning changes are barriers to implementing zoning restrictions on fast food on a larger scale. My dissertation addresses these gaps in our understanding of health zoning as a policy option for altering built, food environments.

Chapter 1 examines the relationship between food swamps and obesity and whether spatial mapping might be useful in identifying priority geographic areas for zoning interventions. I employ an instrumental variables (IV) strategy to correct for the endogeneity problems associated with food environments, namely that individuals may self-select into certain neighborhoods and may consider food availability in their decision process. I utilize highway exits as a source of exogenous variation .Using secondary data from the USDA Food Environment Atlas, ordinary least squares (OLS) and IV regression models were employed to analyze cross-sectional associations between local food environments and the prevalence of obesity. I find even after controlling for food desert effects, food swamps have a positive, statistically significant effect on adult obesity rates.

Chapter 2 applies theories of message framing and prospect theory to the emerging discussion around health zoning policies targeting food environments and to explore public opinion toward a list of potential zoning restrictions on fast-food restaurants (beyond moratoriums on new establishments). In order to explore causality, I employ an online survey experiment manipulating exposure to vignettes with different message frames about health zoning restrictions with two national samples of adult Americans age 18 and over (N1=2,768 and N2=3,236). The second sample oversamples Black Americans (N=1,000) and individuals with high school as their highest level of education. Respondents were randomly assigned to one of six conditions where they were primed with different message frames about the benefits of zoning restrictions on fast food retailers. Participants were then asked to indicate their support for six zoning policies on a Likert scale. Subjects also answered questions about their food store access, eating behaviors, health status and perceptions of food stores by type.

I find that a message frame about Nutrition and increasing Equity in the food system was particularly effective at increasing support for health zoning policies targeting fast food outlets across policy categories (Conditional, Youth-related, Performance and Incentive) and across racial groups. This finding is consistent with an influential environmental justice scholar’s description of “injustice frames” as effective in mobilizing supporters around environmental issues (Taylor 2000). I extend this rationale to food environment obesity prevention efforts and identify Nutrition combined with Equity frames as an arguably universal campaign strategy for bolstering public support of zoning restrictions on fast food retailers.

Bridging my findings from both Chapters 1 and 2, using food swamps as a spatial metaphor may work to identify priority areas for policy intervention, but only if there is an equitable distribution of resources and mobilization efforts to improve consumer food environments. If the structural forces which ration access to land-use planning persist (arguably including the media as gatekeepers to information and producers of message frames) disparities in obesity are likely to widen.

The Relationship of Fear of Intimacy, Body Image Avoidance and Body Mass Index

Issues of body image and ability to achieve intimacy are connected to body weight, yet remain largely unexplored and have not been evaluated by gender. The underlying purpose of this research was to determine if avoidant attitudes and perceptions of one’s body may hold implications toward its use in intimate interactions, and if an above average body weight would tend to increase this avoidance. The National Health and Nutrition Examination Survey (NHANES, 1999-2002) finds that 64.5% of US adults are overweight, with 61.9% of women and 67.2% of men. The increasing prevalence of overweight and obesity in men and women shows no reverse trend, nor have prevention and treatment proven effective in the long term. The researcher gathered self-reported age, gender, height and weight data from 55 male and 58 female subjects (determined by a prospective power analysis with a desired medium effect size (r =.30) to determine body mass index (BMI), determining a mean age of 21.6 years and mean BMI of 25.6. Survey instruments consisted of two scales that are germane to the variables being examined. They were (1) Descutner and Thelen of the University of Missouri’s (1991) Fear-of-Intimacy scale and (2) Rosen, Srebnik, Saltzberg, and Wendt’s (1991) Body Image Avoidance Questionnaire. Results indicated that as body mass index increases, fear of intimacy increases (p<0.05) and that as body mass index increases, body image avoidance increases (p<0.05). The relationship that as body image avoidance increases, fear of intimacy increases was not supported, but approached significance at (p<0.07). No differences in these relationships were determined between gender groups. For age, the only observed relationship was that of a difference between scores for age groups [18 to 22 (group 1) and ages 23 to 34 (group 2)] for the relationship of body image avoidance and fear of intimacy (p<0.02). The results suggest that the relationship of body image avoidance and fear of intimacy, as well as age, bear consideration toward the escalating prevalence of overweight and obesity. An integrative approach to body weight that addresses issues of body image and intimacy may prove effective in prevention and treatment.

Faktorer som påverkar vårdmötet mellan sjuksköterskan och föräldrar till överviktiga barn : Litteraturstudie

Bakgrund: Övervikt och fetma bland barn och ungdomar har ökat kraftigt under de senaste 20 åren. I Sverige har förekomsten av fetma ökat från 1 % till 4 %. Det finns flertalet orsaker till övervikt och fetma hos barn och ungdomar. Några av dem är genetiska faktorer, livsmedelskonsumtion, miljöfaktorer samt livsstilsfaktorer. Syfte: Att beskriva de faktorer som påverkar vårdmötet mellan sjuksköterskan och föräldrar till barn och ungdomar med övervikt eller fetma. Metod: Studien har genomförts som en litteraturöversikt och bestod av 13 artiklar. 10 med kvalitativ ansats och tre med kvantitativ ansats. Dessa hämtades i databaserna Cinahl och PubMed. Resultat: Det identifierades både hinder och möjligheter som kan uppstå i vårdmötet mellan sjuksköterskan och föräldrar. Dessa hinder och möjligheter presenteras i två kategorier med totalt fem subkategorier; Skuld och skamkänslor hos föräldrarna, förnekelse hos föräldrarna angående barnets vikt, öka medvetenheten om fördelarna med viktminskning, långsiktigt förtroende underlättar vårdmötet och anpassad kommunikation i vårdmötet mellan sjuksköterska och förälder. Slutsats: Flera faktorer identifierades som har betydelse för vårdmötet mellan sjuksköterska och föräldrar. De faktorer som utgjorde hinder i vårdmötet kan båda parter påverka så att förbättringar kan ske.