E. Whitney Evans

Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease

Parkinsons disease (PD; OMIM #168600) is the second most common neurodegenerative disorder in the Western world and presents as a progressive movement disorder. The hallmark pathological features of PD are loss of dopaminergic neurons from the substantia nigra and neuronal intracellular Lewy body inclusions. Parkinsonism is typically sporadic in nature; however, several rare familial forms are linked to genetic loci, and the identification of causal mutations has provided insight into the disease process. PARK8, identified in 2002 by Funayama and colleagues, appears to be a common cause of familial PD. We describe here the cloning of a novel gene that contains missense mutations segregating with PARK8-linked PD in five families from England and Spain. Because of the tremor observed in PD and because a number of the families are of Basque descent, we have named this protein dardarin, derived from the Basque word dardara, meaning tremor.

Food Selectivity in Children with Autism Spectrum Disorders and Typically Developing Children

OBJECTIVES To define food selectivity and compare indices of food selectivity among children with autism spectrum disorders (ASDs) and typically developing children, and to assess the impact of food selectivity on nutrient adequacy. STUDY DESIGN Food selectivity was operationalized to include food refusal, limited food repertoire, and high-frequency single food intake using a modified food frequency questionnaire and a 3-day food record. Food selectivity was compared between 53 children with ASDs and 58 typically developing children age 3-11 years. Nutrient adequacy was assessed relative to the dietary reference intakes. RESULTS The children with ASDs exhibited more food refusal than typically developing children (41.7% of foods offered vs 18.9% of foods offered; P <.0001). They also had a more limited food repertoire (19.0 foods vs 22.5 foods; P <.001). Only 4 children with ASDs and 1 typically developing child demonstrated high-frequency single food intake. Children with a more limited food repertoire had inadequate intake of a greater number of nutrients. CONCLUSIONS Our findings suggest that food selectivity is more common in children with ASDs than in typically developing children, and that a limited food repertoire may be associated with nutrient inadequacies.

Phosphodiesterase 4D and 5-lipoxygenase activating protein in ischemic stroke.

Risk for ischemic stroke is mediated by both environmental and genetic factors. Although several environmental exposures have been implicated, relatively little is known about the genetic basis of predisposition to this disease. Recent studies in Iceland identified risk polymorphisms in two putative candidate genes for ischemic stroke: phosphodiesterase 4D (PDE4D) and 5‐lipoxygenase activating protein (ALOX5AP). A collection of North American sibling pairs concordant for ischemic stroke and two cohorts of prospectively ascertained North American ischemic stroke cases and control subjects were used for evaluation of PDE4D and ALOX5AP. Although no evidence supported linkage of ischemic stroke with either of the two candidate genes, single‐nucleotide polymorphisms and haplotypic associations were observed between PDE4D and ischemic stroke. There was no evidence of association between variants of ALOX5AP and ischemic stroke. These data suggest that common variants in PDE4D may contribute to the genetic risk for ischemic stroke in multiple populations. Ann Neurol 2005;58:351–361

Clinical and positron emission tomography of Parkinson's disease caused by LRRK2

We have recently identified mutations in a gene leucine‐rich repeat kinase–2 (LRRK2), which cause autosomal dominant Parkinsons disease. Here, we describe two families with autosomal dominant Parkinsons disease caused by a LRRK2 G2019S mutation. We present here a clinical description of patients, including 6‐18F‐fluoro‐L‐dopa positron emission tomography and discuss the potential implications of this mutation, which alters a conserved residue in a domain required for kinase activation. Ann Neurol 2005;57:453–456

BMI report cards: will they pass or fail in the fight against pediatric obesity?

Purpose of review Pediatric obesity has reached epidemic proportions in the USA and Europe. The use of BMI report cards is one approach to addressing the epidemic that is gaining popularity across the USA and in the UK. Recent findings Recent findings suggest that parents of overweight children underestimate child weight status and the majority of pediatric overweight and obesity goes undiagnosed in primary care settings in the USA. Although there is no argument against the efficacy of tracking a childs BMI and informing parents of their childs weight status, there is considerable controversy surrounding whether schools should be involved in BMI screening. Research on the efficacy of BMI report cards suggests that parental awareness of weight status is not improved by BMI report cards. Findings are inconclusive on whether BMI report cards lead to changes in weight-related health behaviors, and there is no evidence to suggest that report cards ultimately impact weight status. Additionally, research indicates that BMI report cards may increase dieting, a risk factor for both increased weight and eating disorders in adolescents. Summary Research does not suggest that BMI report cards will be effective in reducing rates of pediatric overweight and obesity. Instead, recent findings show that the potential for harm may outweigh possible benefits. States and countries that mandate the use of BMI report cards should make evaluation of these policies a priority.

Dietary Intake and Severe Early Childhood Caries in Low-Income, Young Children

Evidence suggests that risk for early childhood caries (ECCs), the most common chronic infectious disease in childhood, is increased by specific eating behaviors. To identify whether consumption of added sugars, sugar-sweetened beverages (SSBs), and 100% fruit juice, as well as eating frequency, are associated with severe ECCs, cross-sectional data collected from a sample of low-income, racially diverse children aged 2 to 6 years were used. Four hundred fifty-four children with severe ECCs and 429 caries-free children were recruited in 2004-2008 from three pediatric dental clinics in Columbus, OH; Cincinnati, OH; and Washington, DC. Dietary data were obtained from one parent-completed 24-hour recall and an interviewer-administered food frequency questionnaire (FFQ). Multivariate logistic regression analyses were conducted to assess associations between severe ECCs and dietary variables. On average, children with severe ECCs consumed 3.2-4.8 fl oz more SSBs (24-hour recall=1.80 vs 1.17; P< 0.001; FFQ=0.82 vs 0.39; P<0.001) and reported significantly more daily eating occasions (5.26 vs 4.72; P<0.0001) than caries-free children. After controlling for age, sex, race/ethnicity, maternal education, recruitment site, and family size, children with the highest SSB intake were 2.0 to 4.6 times more likely to have severe ECCs compared with those with the lowest intake, depending on dietary assessment method (24-hour recall odds ratio 2.02, 95% CI 1.33 to 3.06; FFQ odds ratio 4.63, 95% CI 2.86 to 7.49). The relationship between eating frequency and severe ECC status was no longer significant in multivariate analyses. Specific dietary guidance for parents of young children, particularly regarding SSB consumption, could help reduce severe ECC prevalence.

The role of eating frequency on total energy intake and diet quality in a low-income, racially diverse sample of schoolchildren

OBJECTIVE The relationship of meal and snacking patterns with overall dietary intake and relative weight in children is unclear. The current study was done to examine how eating, snack and meal frequencies relate to total energy intake and diet quality. DESIGN The cross-sectional associations of eating, meal and snack frequencies with total energy intake and diet quality, measured by the Healthy Eating Index 2005 (HEI-2005), were examined in separate multivariable mixed models. Differences were examined between elementary school-age participants (9-11 years) and adolescents (12-15 years). SETTING Two non-consecutive 24 h diet recalls were collected from children attending four schools in the greater Boston area, MA, USA. SUBJECTS One hundred and seventy-six schoolchildren, aged 9-15 years. RESULTS Overall, 82% of participants consumed three daily meals. Eating, meal and snack frequencies were statistically significantly and positively associated with total energy intake. Each additional reported meal and snack was associated with an 18·5% and a 9·4% increase in total energy intake, respectively (P<0·001). The relationships of eating, meal and snack frequencies with diet quality differed by age category. In elementary school-age participants, total eating occasions and snacks increased HEI-2005 score. In adolescents, each additional meal increased HEI-2005 score by 5·40 points (P=0·01), whereas each additional snack decreased HEI-2005 score by 2·73 points (P=0·006). CONCLUSIONS Findings suggest that snacking increases energy intake in schoolchildren. Snacking is associated with better diet quality in elementary school-age children and lower diet quality in adolescents. Further research is needed to elucidate the role of snacking in excess weight gain in children and adolescents.

Healthy eating index and metabolically healthy obesity in U.S. adolescents and adults

OBJECTIVE To determine whether dietary quality differs between metabolically-healthy-obese (MHO) and metabolically-abnormal-obesity (MAO) in a nationally representative sample. METHODS National Health and Nutrition Examination Survey (NHANES) data (2007-2008; 2009-2010) were used to identify obese adolescents (≥95th body mass index (BMI) %tile) and adults (≥30kg/m(2)). MHO was defined as <2 abnormal cardiometabolic risk factors (elevated blood pressure, triglycerides, glucose, low high density lipoprotein cholesterol (HDL-C); or on medications). Healthy Eating Index 2005 (HEI-2005) scores were calculated from 24-hour recall data. General linear regression models determined whether HEI-2005 scores differed between MHO and MAO after controlling for age, race, gender, NHANES wave, BMI, physical activity and health status by age group (12-18; 19-44; 45-85years). RESULTS Compared with MAO, MHO adolescents (n=133) had higher total HEI-2005 score, higher milk scores, and higher scores from calories from solid fats, alcohol beverages and added sugars. MHO women 19-44years (n=240) had higher total HEI-2005, higher whole fruit, higher whole grain and higher meat and bean scores compared with MAO. No significant differences were observed between MHO and MAO for HEI-2005 total scores in men 19-44years, or adults 45-85years. CONCLUSION MHO adolescents and women 19-44years have better dietary compliance to the U.S. guidelines when compared with MAO, suggesting potential intervention targets to improve cardiometabolic risk within obesity.

Comprehensive Screening of a North American Parkinson’s Disease Cohort for LRRK2 Mutation

Background: Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective: To identify mutations causing Parkinson’s disease (PD) in a cohort of North Americans with familial PD. Methods: We sequenced exons 1–51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results: One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2.

Clinical Pain Catastrophizing in Women With Migraine and Obesity

Obesity is related to migraine. Maladaptive pain coping strategies (eg, pain catastrophizing) may provide insight into this relationship. In women with migraine and obesity, we cross‐sectionally assessed: (1) prevalence of clinical catastrophizing; (2) characteristics of those with and without clinical catastrophizing; and (3) associations of catastrophizing with headache features.