Evaluation of the toxic activity of anorectic diethylpropion in Chinese hamster ovary cells.

Diethylpropion has been available in the market for treating obesity for over 50 years. Refined studies are lacking to fully elucidate its action spectrum. The aim of our study was to evaluate possible toxic effects of anorectic diethylpropion in Chinese hamster ovary (CHO) cells. Comet assay (detects breaks in the DNA strand), micronucleus test (detects clastogenic/aneugenic damage), and cell survival test (detects cytotoxic damage) were used to evaluate the toxic effects. In comet assay, we found that the damage scores with diethylpropion treatments at the concentrations of 20 and 40 µg/mL were more significant ( p < 0.05) than that of the negative control. When assessing the possible aneugenic and/or clastogenic damage caused by the drug in CHO cells, we found no difference ( p > 0.05) in the values of micronucleated cells when comparing different diethylpropion treatments and the negative control. Regarding the cell viability, for all the diethylpropion concentrations tested, higher values ( p < 0.05) of apoptosis were found compared with those of the negative control. In relation to the number of necrotic cells, no difference ( p > 0.05) was noted between the means of the three concentrations of diethylpropion evaluated and the negative control. In the experimental conditions, we conclude that diethylpropion has weak genotoxic and cytotoxic activities.

Ovarian structure and oogenesis of catfish Pimelodella vittata (Lütken, 1874) (Siluriformes, Heptapteridae).

The morphology of the ovaries and oogenesis of Pimelodella vittata were studied using anatomical and histological techniques to provide information of its reproductive biology. Eighty adult females were captured trimonthly during the period November 2005 to October 2006. The ovaries are paired, saculiform organs, which are coated with tunica albuginea and contain ovigerous lamellae, where the oocytes develop before being released into the ovarian lumen and following the ovarian duct until reaching the genital papilla. Oogenesis was divided into stages based on the alterations to the nucleus, ooplasm and surrounding follicular layers. Oogonia form groups from the germinal epithelium have asynchronous development and differentiate into initial perinucleolar oocytes. The formation of the zona pellucida is initiated in the advanced perinucleolar oocytes reaching a thickness of 1.46±0.58 µm in the vitellogenic oocytes. The follicular cells are squamous in perinucleolar oocytes, become cubical in the pre-vitellogenic oocytes and prismatic in the vitellogenic oocytes with a height of 11.20±4.74 µm. The histochemical reactions indicate that zona pellucida, cortical alveoli and yolk globules contain neutral glycoproteins and the follicular cells contain neutral glycoproteins in association with carboxylated and sulphated glycoconjugates. Statistical analyses showed significant differences in the diameter of the oocytes and follicular cells height as oocytes matured. This study represents the first data about the ovarian structure and oogenesis of this species.

Food consumption by young adults living in Ribeirão Preto, SP, 2002/2004

There is evidence showing a close relationship between diet and the occurrence of non-communicable chronic diseases. The present study assessed food consumption in a 2002/2004 cohort of young adults born in 1978/79 in Ribeirão Preto, SP, Brazil. The composition of the habitual diet consumed by a sample of 2063 individuals aged 23-25 years was analyzed using a validated semi-quantitative food frequency questionnaire based on studies of prevention of non-communicable chronic diseases. The Dietsys software was used for dietary calculations. In terms of WHO/2003 recommendations, there was a high mean daily consumption of energy from fat (consumption: 35.4 percent; recommendation: 15-30 percent), a low mean intake of energy from carbohydrates (47.5 percent; 55-75 percent) and a low mean consumption of total fibers (15.2 g; >25 g). Mean intake of energy from fatty acids (10 percent; <10 percent) and protein (15.6 percent; 10-15 percent) was within recommended limits. When compared to the recommendations of the food pyramid adapted to the Brazilian population, adequate intake was observed only regarding the meat group (consumption: 1.9 portions; recommended: 1-2). There was a low consumption of vegetables (2.9; 4-5), fruits (1.2; 3-5), breads (3.6; 6-9), and dairy products (1.7; 3), with excessive fat and sugar intake (5.7; 1-2). We conclude that the inadequate food consumption observed in this young population may be associated with the development of excess weight and may contribute to the triggering of non-communicable chronic diseases.

Food consumption by young adults living in Ribeirão Preto, SP, 2002/2004.

There is evidence showing a close relationship between diet and the occurrence of non-communicable chronic diseases. The present study assessed food consumption in a 2002/2004 cohort of young adults born in 1978/79 in Ribeirão Preto, SP, Brazil. The composition of the habitual diet consumed by a sample of 2063 individuals aged 23-25 years was analyzed using a validated semi-quantitative food frequency questionnaire based on studies of prevention of non-communicable chronic diseases. The Dietsys software was used for dietary calculations. In terms of WHO/2003 recommendations, there was a high mean daily consumption of energy from fat (consumption: 35.4%; recommendation: 15-30%), a low mean intake of energy from carbohydrates (47.5%; 55-75%) and a low mean consumption of total fibers (15.2 g; >25 g). Mean intake of energy from fatty acids (10%; <10%) and protein (15.6%; 10-15%) was within recommended limits. When compared to the recommendations of the food pyramid adapted to the Brazilian population, adequate intake was observed only regarding the meat group (consumption: 1.9 portions; recommended: 1-2). There was a low consumption of vegetables (2.9; 4-5), fruits (1.2; 3-5), breads (3.6; 6-9), and dairy products (1.7; 3), with excessive fat and sugar intake (5.7; 1-2). We conclude that the inadequate food consumption observed in this young population may be associated with the development of excess weight and may contribute to the triggering of non-communicable chronic diseases.

Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling.

Data about the impact of bariatric surgery (BS) and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD), bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16). The data were compared to those obtained for women of normal weight (CG, N = 11) and for obese women (OG, N = 12). Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I) and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 +/- 62 vs OG = 230 +/- 37 vs OGg = 128 +/- 19 ng/mL) were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.

Depressive symptoms and C-reactive protein in a Brazilian urban community.

Psychological depression is an independent risk factor for coronary artery disease. C-reactive protein has been implicated as a mediator of the effect of psychological depression. Several studies have found that individuals, especially men, who report higher levels of psychological depression also have higher levels of C-reactive protein. The current study was undertaken to replicate these results in a Brazilian population, in which there is a much wider range of variation in both background characteristics (such as socioeconomic status) and coronary artery disease risk factors. A sample of 271 individuals was interviewed using the Center for Epidemiological Studies Depression Scale. Fasting blood samples were obtained and evaluated for C-reactive protein (assessed by a turbidimetric immunoassay using a Dade Behring kit) analysis in a subsample (N = 258) of individuals. The mean +/- SD C-reactive protein for the entire sample was 0.43 +/- 0.44, with 0.42 +/- 0.48 for men and 0.43 +/- 0.42 mg/L for women. Data were analyzed using multiple regression analysis, controlling for age, sex, body mass index, socioeconomic status, tobacco use, and both total cholesterol and low-density lipoprotein cholesterol. Higher reported depressive symptoms were correlated with higher C-reactive protein for men (partial r = 0.298, P = 0.004) and with lower C-reactive protein for women (partial r = -0.154, P = 0.059). The differences in the associations for men and women could be a result of differential effects of sex hormones on stress reactivity and immune response. On the other hand, this difference in the associations may be related to gender differences in the disclosure of emotion and the effect that self-disclosure has on physical health and immune response.

Health in early adulthood: the contribution of the 1978/79 Ribeirão Preto birth cohort.

The increase in non-communicable chronic diseases of adults is due to demographic changes and changes in the risk factors related to physical activity, smoking habits and nutrition. We describe the methodology for the evaluation of persons at 23/25 years of age of a cohort of individuals born in Ribeirão Preto in 1978/79. We present their socioeconomic characteristics and the profile of some risk factors for chronic diseases. A total of 2063 participants were evaluated by means of blood collection, standardized questionnaires, anthropometric and blood pressure measurements, and methacholine bronchoprovocation tests. The sexes were compared by the chi-square test, with alpha = 0.05. Obesity was similar among men and women (12.8 and 11.1%); overweight was almost double in men (30.3 vs 17.7%). Weight deficit was higher among women than among men (8.6 and 2.6%). Women were more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was similar between sexes, with 63% consuming large amounts (30 to 39.9 g/day). Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8%), hypertension was six times more frequent (40.9 vs 6.4%); altered triglyceride (16.1 vs 9.8%) and LDL proportions (5.4 vs 2.7%) were also higher in men, while women had a higher percentage of low HDL (44.7 vs 39.5%). Asthma and bronchial hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among women. The high prevalence of some risk factors for chronic diseases among young adults supports the need for investments in their prevention.

Depressive symptoms and C-reactive protein in a Brazilian urban community

Psychological depression is an independent risk factor for coronary artery disease. C-reactive protein has been implicated as a mediator of the effect of psychological depression. Several studies have found that individuals, especially men, who report higher levels of psychological depression also have higher levels of C-reactive protein. The current study was undertaken to replicate these results in a Brazilian population, in which there is a much wider range of variation in both background characteristics (such as socioeconomic status) and coronary artery disease risk factors. A sample of 271 individuals was interviewed using the Center for Epidemiological Studies Depression Scale. Fasting blood samples were obtained and evaluated for C-reactive protein (assessed by a turbidimetric immunoassay using a Dade Behring kit) analysis in a subsample (N = 258) of individuals. The mean ± SD C-reactive protein for the entire sample was 0.43 ± 0.44, with 0.42 ± 0.48 for men and 0.43 ± 0.42 mg/L for women. Data were analyzed using multiple regression analysis, controlling for age, sex, body mass index, socioeconomic status, tobacco use, and both total cholesterol and low-density lipoprotein cholesterol. Higher reported depressive symptoms were correlated with higher C-reactive protein for men (partial r = 0.298, P = 0.004) and with lower C-reactive protein for women (partial r = -0.154, P = 0.059). The differences in the associations for men and women could be a result of differential effects of sex hormones on stress reactivity and immune response. On the other hand, this difference in the associations may be related to gender differences in the disclosure of emotion and the effect that self-disclosure has on physical health and immune response.

Health in early adulthood: the contribution of the 1978/79 Ribeirão Preto birth cohort

The increase in non-communicable chronic diseases of adults is due to demographic changes and changes in the risk factors related to physical activity, smoking habits and nutrition. We describe the methodology for the evaluation of persons at 23/25 years of age of a cohort of individuals born in Ribeirão Preto in 1978/79. We present their socioeconomic characteristics and the profile of some risk factors for chronic diseases. A total of 2063 participants were evaluated by means of blood collection, standardized questionnaires, anthropometric and blood pressure measurements, and methacholine bronchoprovocation tests. The sexes were compared by the chi-square test, with alpha = 0.05. Obesity was similar among men and women (12.8 and 11.1 percent); overweight was almost double in men (30.3 vs 17.7 percent). Weight deficit was higher among women than among men (8.6 and 2.6 percent). Women were more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was similar between sexes, with 63 percent consuming large amounts (30 to 39.9 g/day). Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8 percent), hypertension was six times more frequent (40.9 vs 6.4 percent); altered triglyceride (16.1 vs 9.8 percent) and LDL proportions (5.4 vs 2.7 percent) were also higher in men, while women had a higher percentage of low HDL (44.7 vs 39.5 percent). Asthma and bronchial hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among women. The high prevalence of some risk factors for chronic diseases among young adults supports the need for investments in their prevention.

Familial hypercholesterolemia in Brazil.

The Brazilian population has heterogeneous ethnic origins and is unevenly distributed in a country of continental dimensions. In addition to the Portuguese colonists until the end of the World War II Brazil received almost 5 million immigrants who settled mainly in the south and southeast. This features of the Brazilian population have two important consequences for the inherited diseases that are associated with an ethnic background: their frequencies are different in various regions of the country reflecting a variety of ethnic origins and variable degrees of admixtures. There was no report about the molecular basis of hypercholesterolemia in Brazil until our report in 1996 that the Lebanese allele is the most common cause of the disease in our country: 10 out of the 30 families were of Arab origin, and the Lebanese allele was detected in 9 of the 10 unrelated families of Arab origin. In addition, the abnormal gene is associated with the same haplotype at the LDL-R locus in all but one family, suggesting single origin for this mutation. Recently we described seven mutations in exons 4, 7, 12 and 14 and a new mutation in exon 15. In another region of our state, eight mutation already described and seven new mutations were described and interesting no common mutations were find. We can conclude that the complex history and structure of the Brazilian population, which was formed by the contribution of a large number of ethnic components that are in a state of increasing miscegenation, is reflected in the frequency and regional distribution of the more common hereditary diseases.

Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians.

The genetic basis for dementias is complex. A common polymorphism in the apolipoprotein E (APOE) gene is considered to be the major risk factor in families with sporadic and late-onset Alzheimer's disease as well as in the general population. The distribution of alleles and genotypes of the APOE gene in late-onset Alzheimer's disease (N = 68), other late-life dementias (N = 39), and in cognitively normal controls (N = 58) was determined, as also was the risk for Alzheimer's disease associated with the epsilon4 allele. Peripheral blood samples were obtained from a total of 165 individuals living in Brazil aged 65-82 years. Genomic DNA was amplified by the polymerase chain reaction and the products were digested with HhaI restriction enzyme. APOE epsilon2 frequency was considerably lower in the Alzheimer's disease group (1%), and the epsilon3 allele and epsilon3/epsilon3 genotype frequencies were higher in the controls (84 and 72%, respectively) as were the epsilon4 allele and epsilon3/epsilon4 genotype frequencies in Alzheimer's disease (25 and 41%, respectively). The higher frequency of the epsilon4 allele in Alzheimer's disease confirmed its role as a risk factor, while epsilon2 provided a weak protection against development of the disease. However, in view of the unexpectedly low frequency of the epsilon4 allele, additional analyses in a more varied Brazilian sample are needed to clarify the real contribution of apolipoprotein E to the development of Alzheimer's disease in this population.

Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians

The genetic basis for dementias is complex. A common polymorphism in the apolipoprotein E (APOE) gene is considered to be the major risk factor in families with sporadic and late-onset Alzheimer's disease as well as in the general population. The distribution of alleles and genotypes of the APOE gene in late-onset Alzheimer's disease (N = 68), other late-life dementias (N = 39), and in cognitively normal controls (N = 58) was determined, as also was the risk for Alzheimer's disease associated with the epsilon4 allele. Peripheral blood samples were obtained from a total of 165 individuals living in Brazil aged 65-82 years. Genomic DNA was amplified by the polymerase chain reaction and the products were digested with HhaI restriction enzyme. APOE epsilon2 frequency was considerably lower in the Alzheimer's disease group (1 percent), and the epsilon3 allele and epsilon3/epsilon3 genotype frequencies were higher in the controls (84 and 72 percent, respectively) as were the epsilon4 allele and epsilon3/epsilon4 genotype frequencies in Alzheimer's disease (25 and 41 percent, respectively). The higher frequency of the epsilon4 allele in Alzheimer's disease confirmed its role as a risk factor, while epsilon2 provided a weak protection against development of the disease. However, in view of the unexpectedly low frequency of the epsilon4 allele, additional analyses in a more varied Brazilian sample are needed to clarify the real contribution of apolipoprotein E to the development of Alzheimer's disease in this population

The X-X-/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample.

Studies that consider polymorphisms within the apolipoprotein B (apo B) gene as risk factors for coronary artery disease (CAD) have reported conflicting results. The aim of the present study was to search for associations between two DNA RFLPs (XbaI and EcoRI) of the apo B gene and CAD diagnosed by angiography. In the present study we compared 116 Brazilian patients (92 men) with CAD (CAD+) to 78 control patients (26 men) without ischemia or arterial damage (CAD-). The allele frequencies at the XbaI (X) and EcoRI (E) sites did not differ between groups. The genotype distributions of CAD+ and CAD- patients were different (chi (1) = 6.27, P = 0.012) when assigned to two classes (X-X-/E+E+ and the remaining XbaI/EcoRI genotypes). Multivariate logistic regression analysis showed that individuals with the X-X-/E+E+ genotype presented a 6.1 higher chance of developing CAD than individuals with the other XbaI/EcoRI genotypes, independently of the other risk factors considered (sex, tobacco consumption, total cholesterol, hypertension, and triglycerides). We conclude that the X-X-/E+E genotype may be in linkage disequilibrium with an unknown variation in the apo B gene or with a variation in another gene that affects the risk of CAD.

The X-X-/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample

Studies that consider polymorphisms within the apolipoprotein B (apo B) gene as risk factors for coronary artery disease (CAD) have reported conflicting results. The aim of the present study was to search for associations between two DNA RFLPs (XbaI and EcoRI) of the apo B gene and CAD diagnosed by angiography. In the present study we compared 116 Brazilian patients (92 men) with CAD (CAD+) to 78 control patients (26 men) without ischemia or arterial damage (CAD-). The allele frequencies at the XbaI (X) and EcoRI (E) sites did not differ between groups. The genotype distributions of CAD+ and CAD- patients were different (chi²(1) = 6.27, P = 0.012) when assigned to two classes (X-X-/E+E+ and the remaining XbaI/EcoRI genotypes). Multivariate logistic regression analysis showed that individuals with the X-X-/E+E+ genotype presented a 6.1 higher chance of developing CAD than individuals with the other XbaI/EcoRI genotypes, independently of the other risk factors considered (sex, tobacco consumption, total cholesterol, hypertension, and triglycerides). We conclude that the X-X-/E+E genotype may be in linkage disequilibrium with an unknown variation in the apo B gene or with a variation in another gene that affects the risk of CAD

Six years of treatment with the HELP system of a patient with familial hypercholesterolemia.

The purpose of the present report is to demonstrate the long-term efficacy and safety of heparin-induced extracorporeal lipoprotein precipitation (HELP) of LDL-c and fibrinogen in the management of familial hypercholesterolemia. From June 1992 to June 1998 a 22-year-old young male patient with familial hypercholesterolemia (double heterozygote for C660X and S305C) resistant to medication and diet and with symptomatic coronary artery disease (angina) was treated weekly with 90-min sessions of the HELP system. The patient had also been previously submitted to right coronary artery angioplasty. The efficacy of the method was evaluated by comparing the reduction of total cholesterol, LDL-c and fibrinogen before and after the sessions and before and after initiation of the study (data are reported as averages for each year). During the study, angina episodes disappeared and there were no detectable adverse effects of the treatment. Total cholesterol (TC), fibrinogen, and LDL-c decreased significantly after each session by 59.6, 66.1 and 64%, respectively. HDL-c showed a nonsignificant reduction of 20.4%. Comparative mean values pre- and post-treatment values in the study showed significant differences: TC (488 vs 188 mg/dl), LDL-c (416.4 vs 145 mg/dl), and fibrinogen (144.2 vs 57.4 mg/dl). There was no significant change in HDL-c level: 29.4 vs 23 mg/dl. These data show that the HELP system, even for a long period of time, is a safe and efficient mode of treatment of familial hypercholesterolemia and is associated with disappearance of angina symptoms.

Six years of treatment with the HELP system of a patient with familial hypercholesterolemia

The purpose of the present report is to demonstrate the long-term efficacy and safety of heparin-induced extracorporeal lipoprotein precipitation (HELP) of LDL-c and fibrinogen in the management of familial hypercholesterolemia. From June 1992 to June 1998 a 22-year-old young male patient with familial hypercholesterolemia (double heterozygote for C660X and S305C) resistant to medication and diet and with symptomatic coronary artery disease (angina) was treated weekly with 90-min sessions of the HELP system. The patient had also been previously submitted to right coronary artery angioplasty. The efficacy of the method was evaluated by comparing the reduction of total cholesterol, LDL-c and fibrinogen before and after the sessions and before and after initiation of the study (data are reported as averages for each year). During the study, angina episodes disappeared and there were no detectable adverse effects of the treatment. Total cholesterol (TC), fibrinogen, and LDL-c decreased significantly after each session by 59.6, 66.1 and 64 percent, respectively. HDL-c showed a nonsignificant reduction of 20.4 percent. Comparative mean values pre- and post-treatment values in the study showed significant differences: TC (488 vs 188 mg/dl), LDL-c (416.4 vs 145 mg/dl), and fibrinogen (144.2 vs 57.4 mg/dl). There was no significant change in HDL-c level: 29.4 vs 23 mg/dl. These data show that the HELP system, even for a long period of time, is a safe and efficient mode of treatment of familial hypercholesterolemia and is associated with disappearance of angina symptoms

Socioeconomic factors and adult body composition in a developing society

Objective: To examine socioeconomic variables in relation to three indices of adult body composition: the body mass index: and, percent body fat and lean-to-fat body mass ratio, both derived from bioelectric impedance analysis. Purpose: To investigate the relationship between obesity and socioeconomic variables in a developing country. Research methods and procedures: A cross-sectional survey of four neighborhoods differing in socioeconomic status. A random sample of 304 healthy adults, 181 females and 123 males, age range 18-78. Body composition was measured with the body mass index derived from height and weight, and the assessments of percent body fat and the ratio of lean-to-fat body mass derived from bioelectric impedance analysis. Results: Using a linear model with age as a covariate and sex as an additional factor, there were significant interaction effects between sex and socioeconomic group for all three of the body composition variables (p < 0,005). Analysis of trends within sex revealed primarily a linear association between socioeconomic group and body composition for males (p < 0,001), and a curvilinear association between socioeconomic group and body composition for females (p < 0.03). Discussion: The association of socioeconomic status and body composition is significant for males and females, but the pattern of the association varies by gender. It is argued that these results can be explained by three processes: socioeconomic differences in caloric demands of labor: socioeconomic differences in the social value attached to food: and, gender differences in standards of physical attractiveness

[Morbid obesity in women - eating style and quality of life]. / Obesidade mórbida em mulheres--estilos alimentares e qualidade de vida.

Morbid obesity has been widely studied due to its high incidence and its bad consequences to health. Studies about obesity have been emphasized some important aspects such as eating styles and quality of life. This study aim to investigate the eating styles and the quality of life of women with morbid obesity, patients in treatment at the Ambulatory of Eating Disorders, University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo. Sixty women were assessed, 30 obese (Body Mass Index--BMI > or = 40 kg/m2) and 30 nonobese (BMI 20 to 25 kg/m2). A semi-structured interview, the Dutch Eating Behaviour Questionnaire and the Short-form Health Survey: Medical Outcomes Study were used for the assessment, after translate to portuguese and adapted. The data were rated and quantified and the groups were statistically analyzed through the Tests of Mann-Whitney. The groups differed significantly as for restrained (p < or = 0.001) and emotional eating (p < or = 0.01), and did not differ as for external eating. The groups also differed in quality of life, concerning physical and social limitations (p < or = 0.001), the presence of emotional indicators (p < or = 0.001) and general health condition (p < or = 0.001). Findings suggest that eating styles contribute to explain the difficult of eating control--but are not only factor in the obesity characterization. Moreover, morbidly obese women presented a quality of life more compromised and have an adequate perception of their physical, social and emotional limitations. That might favor a therapeutic approach to them.