BTB domain mutations perturbing KCTD15 oligomerisation cause a distinctive frontonasal dysplasia syndrome.

INTRODUCTION: KCTD15 encodes an oligomeric BTB domain protein reported to inhibit neural crest formation through repression of Wnt/beta-catenin signalling, as well as transactivation by TFAP2. Heterozygous missense variants in the closely related paralogue KCTD1 cause scalp-ear-nipple syndrome. METHODS: Exome sequencing was performed on a two-generation family affected by a distinctive phenotype comprising a lipomatous frontonasal malformation, anosmia, cutis aplasia of the scalp and/or sparse hair, and congenital heart disease. Identification of a de novo missense substitution within KCTD15 led to targeted sequencing of DNA from a similarly affected sporadic patient, revealing a different missense mutation. Structural and biophysical analyses were performed to assess the effects of both amino acid substitutions on the KCTD15 protein. RESULTS: A heterozygous c.310G>C variant encoding p.(Asp104His) within the BTB domain of KCTD15 was identified in an affected father and daughter and segregated with the phenotype. In the sporadically affected patient, a de novo heterozygous c.263G>A variant encoding p.(Gly88Asp) was present in KCTD15. Both substitutions were found to perturb the pentameric assembly of the BTB domain. A crystal structure of the BTB domain variant p.(Gly88Asp) revealed a closed hexameric assembly, whereas biophysical analyses showed that the p.(Asp104His) substitution resulted in a monomeric BTB domain likely to be partially unfolded at physiological temperatures. CONCLUSION: BTB domain substitutions in KCTD1 and KCTD15 cause clinically overlapping phenotypes involving craniofacial abnormalities and cutis aplasia. The structural analyses demonstrate that missense substitutions act through a dominant negative mechanism by disrupting the higher order structure of the KCTD15 protein complex.

Why some children with externalising problems develop internalising symptoms: testing two pathways in a genetically sensitive cohort study.

BACKGROUND: Children with externalising problems are at risk of developing internalising problems as they grow older. The pathways underlying this developmental association remain to be elucidated. We tested two processes that could explain why some children with externalising problems develop internalising symptoms in preadolescence: a mediation model whereby the association between early externalising and later new internalising symptoms is explained by negative experiences; and a genetic model, whereby genes influence both problems. METHODS: We used data from the Environmental Risk (E-Risk) Study, a 1994-1995 birth cohort of 2,232 twins born in England and Wales. We assessed externalising and internalising problems using combined mothers' and teachers' ratings at age 5 and 12. We measured bullying victimisation, maternal dissatisfaction and academic difficulties between age 7 and 10 and used linear regression analyses to test the effects of these negative experiences on the association between early externalising and later internalising problems. We employed a Cholesky decomposition to examine the genetic influences on the association. RESULTS: Children with externalising problems at age 5 showed increased rates of new internalising problems at age 12 (r = .24, p < .001). Negative experiences accounted for some of the association between early externalising and later internalising problems. Behavioural-genetic analyses indicated that genes influencing early externalising problems also affected later internalising problems. CONCLUSIONS: Our findings highlight the role of genetic influences in explaining why some children with externalising problems develop internalising symptoms in preadolescence. Negative experiences also contribute to the association, possibly through gene-environment interplay. Mental health professionals should monitor the development of internalising symptoms in young children with externalising problems.

Multiple point-of-testing nutrition counseling sessions reduce risk factors for chronic disease among older adults.

The objectives of this study were to explore the relationships of baseline dietary intakes and frequency of attendance at point-of-testing nutrition counseling sessions to selected risk factors for chronic diseases during a 3-year intervention. This study was part of a large multidisciplinary, community-based health outreach project conducted in a rural community of northern Louisiana. Screenings, point-of-testing counseling, weekly group exercise sessions, and group nutrition education sessions were provided over a period of 3 years. Outcome variables assessed at 6-month intervals over 3 years were body mass index (BMI), systolic and diastolic blood pressure, fasting blood glucose, and total and LDL cholesterol and dietary intake. Repeated measure analysis of variance was used to investigate the impact of the frequency of counseling sessions on outcome variables. Paired t-tests were used to identify points at which significant changes occurred. A total of 159 subjects ages 65 years and older participated in this study. The majority of the participants were female (62%) and White (82%). Attending the point of testing counseling for more than two sessions was important for a significant improvement in BMI (p ≤ 0.001), LDL cholesterol (p ≤ 0.03), blood glucose (p ≤ 0.03), and diastolic blood pressure (p ≤ 0.045). Participants who attended at least three sessions had significant reductions in risk factors for obesity and related chronic diseases, underscoring the importance of follow-up sessions after health screening.

Nutritional status and food insecurity in hemodialysis patients.

OBJECTIVE: The purpose of this study was to determine whether a relationship exists between nutrition status and food security of patients on hemodialysis (HD). DESIGN: A descriptive correlation study. SETTING: This study consisted of HD patients undergoing treatment at three northeast Louisiana dialysis centers. PATIENTS: Ninety-eight HD patients participated in the study. The mean age of subjects was 59.1 +/- 14.2 years. The sample was 44% white and 56% black; 49% male and 51% female. RESULTS: Multiple linear regression and chi2 analysis were used to assess relationships between demographics and food insecurity scores and Subjective Global Assessment scores. Race significantly predicted food insecurity (beta = 0.248; P = .019), with black patients being more food insecure than white subjects. A significant positive relationship was found between the level of education and Subjective Global Assessment scores (beta = 0.222; P = .037). In this sample, 16.3% of the subjects were found to be food insecure, and 64.3% of the patients were mildly to moderately malnourished, whereas another 13.3% were severely malnourished. CONCLUSIONS: Future research in this area should include food security questions related to the ability to obtain foods for health. Renal health care professionals should assess patients for possible food insecurity so that appropriate interventions can be implemented.

Implementation of dietitian recommendations for enteral nutrition results in improved outcomes.

A primary role of the registered dietitian (RD) is to assess nutritional needs of patients in states of physiological stress and illness and to recommend changes to diet and tube feedings when warranted. However, implementation of changes is dependent upon the physician accepting the recommendations of the RD. This study evaluated outcomes of two groups of enterally fed patients in a long-term acute-care facility in northwest Louisiana: (a) those for whom the physician accepted RD recommendations; and (b) those for whom the physician did not accept RD recommendations. Data showed that physician-prescribed enteral formulas provided 10.0% less kilocalories and 7.8% less protein than the RD-assessed needs. t tests showed that when RD recommendations were implemented, patients had a significantly shorter length of stay (28.5+/-1.8 vs 30.5+/-4.8 days, P<0.05), as well as significantly improved albumin (0.13+/-0.17 vs -0.44+/-0.21 g/dL [1.3+/-1.7 vs -4.4+/-2.1 g/L], P<0.05) and weight gains (0.51+/-0.1 vs -0.42+/-0.2%, P<0.05) when compared to those who continued with physician's orders. These data suggest that if RDs had the authority to write nutrition orders and provide early nutrition intervention, patient care would improve.

Are patients with diabetes receiving the same message from dietitians and nurses?

PURPOSE: The purpose of this study was to determine if registered dietitian (RD) and registered nurse (RN) certified diabetes educators (CDEs) provide similar recommendations regarding carbohydrates and dietary supplements to individuals with diabetes. METHODS: A survey was mailed to CDEs in the southern United States. Participants were asked to indicate their recommendations for use of carbohydrates, fiber, artificial sweeteners, and 12 selected dietary and herbal supplements when counseling individuals with diabetes. RESULTS: The survey sample consisted of 366 CDEs: 207 were RNs and 159 were RDs. No statistically significant differences were found between RNs and RDs in typical carbohydrate recommendations for treatment of diabetes. However, RDs were more likely than RNs to make recommendations for fiber intake or use of the glycemic index. A significant difference also was found in the treatment of hypoglycemia: RNs were more likely than RDs to recommend consuming a carbohydrate source with protein to treat hypoglycemia. CONCLUSIONS: Although some differences existed, RD and RN CDEs are making similar overall recommendations in the treatment of individuals with diabetes.

The effect of diet education on the laboratory values and knowledge of hemodialysis patients with hyperphosphatemia.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of 20 to 30 minutes per month of additional diet education on monthly laboratory values (phosphorus, calcium, parathyroid hormone, and calcium/phosphorus product) and knowledge of dietary phosphorus management in hemodialysis patients with hyperphosphatemia. DESIGN: A quasi-experimental design. SETTING: Three outpatient dialysis centers owned by the same corporation in 1 southern state. PATIENTS: Based on a 3-month average serum phosphorus >6.0 mg/dL, 70 patients were selected for participation; 63 dialysis patients completed the study, 32 in the experimental group and 31 in the control group. INTERVENTION: All patients completed a before-and-after knowledge test and had monthly blood samples drawn. Each month, the same registered dietitian provided the routine laboratory results review with control group. The experimental group received the routine laboratory review plus 20 to 30 minutes of additional diet education specifically targeting phosphorus. Main outcome measures Before-and-after knowledge test results and baseline and final serum calcium, phosphorus, parathyroid hormone, and calcium/phosphorus product levels. RESULTS: At baseline, there were no significant differences in any of the laboratory values, but the knowledge level of the experimental group was greater (P <.05) After 6 months, gains in knowledge were significantly higher in the intervention group, and the serum phosphorus and calcium/phosphorus product levels were significantly lower (P <.01) than in the control group. CONCLUSION: Based on this research, those patients who received extra education monthly showed positive changes, which may be beneficial in reducing hyperphosphatemia.

Comparison of digital photography to weighed and visual estimation of portion sizes.

OBJECTIVE: The primary goal was to test the validity of digital photography for measuring food portion sizes compared with weighed foods and with direct visual estimation. SAMPLES: A total of 60 test meals consisting of 10 different portion sizes from six different university cafeteria menus were prepared and weighed. DESIGN: Food selections and plate waste, as estimated by digital photography and direct visual estimation, were compared with weighed foods. For each method, three observers independently estimated portion sizes of each food. Observers expressed the portion sizes as a percentage of a standard serving. These percentages were multiplied by the weight of the standard portion to yield estimated weights. Statistical analyses To test validity, the estimates of food weights derived from both methods were compared with weighed foods using correlations and were compared with each other using Bland-Altman regression analysis. RESULTS: For the digital photography and direct visual estimation methods, estimates of the portion sizes for food selections, plate waste, and food intake were highly correlated with weighed foods. Both methods tended to yield small overestimates or underestimates. Bland-Altman regression found the two estimation methods to yield comparable results (bias less than 1.5 g). APPLICATIONS/CONCLUSIONS: These findings support the validity of the digital photography method for measuring portion sizes. Digital photography may be most useful for measuring food intake in settings that allow for the direct observation of food selections and plate waste but require minimum disruption of the eating environment, and allow unhurried estimates of portion sizes.

Nutrition support at the end of life: opinions of Louisiana dietitians.

The purpose of this study was to determine the opinions of registered dietitians in Louisiana concerning nutrition support at the end of life. A questionnaire was mailed to the 777 active members of the Louisiana Dietetic Association. Questions addressed 3 issues: removal of nutrition support, the role of patients and family in decision making, and the role of the dietitian in decisions to use nutrition support for the terminally ill. A mean composite score was determined for each category. Kruskal-Wallis 1-way ANOVA was conducted on the composite scores to determine differences in responses by age, years of practice, and area of current practice. At least 60% of the respondents agreed with foregoing, withholding, or withdrawing nutrition support at the end of life. Most of the dietitians agreed that the patient or family is more qualified than the health care professional to make decisions about nutrition support at the end of life. More than 95% of the dietitians agreed that the dietitian should be involved in the decision-making process. However, only 50% of the dietitians felt fully qualified to provide the information needed to help a patient or family make the decision about nutrition support at the end of life. Differences of opinions about the removal of nutrition support were found by age, number of years of practice, and current area of practice. Results from this study may encourage dietitians to explore their own attitudes and seek continuing education on ethical dilemmas to enable them to make better decisions, provide better care, and become better patient advocates.