Understanding motivational drivers and barriers to patient participation in diabetes research are important to ensure research is relevant and valuable. Young adults with type 1 diabetes (T1D) completed a 31-question qualitative survey evaluating participant experience, understanding, and motivators and barriers to research involvement. A total of 35 participants, 19-28 years of age, 60% female, completed the survey. Motivating factors included personal benefit, relationship with the study team, curiosity, financial compensation, altruism, and nostalgia. Older participants (>22 years) reported higher levels of trust in the study team (p = 0.02) and their relationship with the study team positively influenced their decision to participate (p = 0.03). Financial compensation was a strong motivator for participants with higher education (p = 0.02). Age, sex, education level, and trust in the study team influenced participants' understanding. Barriers included logistics and lack of familial support. Important motivational drivers and barriers to participation in research by young adults with T1D must be considered to increase research engagement and facilitate the discovery of new knowledge.

Despite the long-held belief that growth hormone supplementation provides psychosocial benefits to patients with Turner syndrome (TS), this assumption has never been rigorously tested in a randomized control trial. As a sub-study of the Canadian growth-hormone trial, parent-, and patient-completed standardized questionnaires were used to compare 70 girls with TS who received injections (GH group) and 61 similarly followed untreated TS controls (C) on multiple facets of psychosocial functioning. Questionnaires were given (i) at baseline (session 1, mean age = 10.4 y), (ii) before estrogen therapy for puberty induction (session 2, mean age = 13.0 y), (iii) after 1 year of estrogen therapy (session 3, mean age = 14.4 y), and (iv) when growth stopped (session 4, mean age = 16.3 y). Groups were compared for multiple facets of psychosocial function within social, behavioral, self-esteem, and academic domains. Results were also correlated with indices of adult height. We found no global (i.e., across-session) group differences on any scales or subscales of the four domains. In both GH and C groups, age-related improvements were seen for social problems, externalizing behavior problems, and school functioning and age-related declines for social competence and social relations. Both parents and patients claimed GH received less teasing than C but C had more friends than GH. Results from analyses conducted within individual sessions showed that while GH at early sessions claimed to be more popular, more socially engaged, better adapted, and to have higher self-esteem than C, C was reported to be less anxious, depressed, and withdrawn than GH at adult height. The correlation analyses revealed different effects of adult height and height gain on outcome for the two groups. In GH, both height parameters were correlated with multiple parent- and/or self-reported indices from the four psychosocial domains, whereas in C, only adult height and two indices (viz., total self-concept and school functioning), were correlated. The observed modest gains in psychosocial functioning for patients with TS treated with GH highlight the need for alternative approaches to assist them in coping with the challenges of their condition.

To determine the presence of vascular markers of premature atherosclerosis and metabolic correlates in a prospectively followed cohort of antiretroviral treated HIV-infected children. Vascular assessment included: carotid intima-media thickness and brachial artery reactivity using vascular ultrasound; peripheral pulse wave velocity (PWV) using photoplethysmography; central PWV, arterial stiffness and impedance indices using an Echo-Doppler method; and only at follow-up, augmentation index and PWV by applanation tonometry. Disease markers, oral glucose tolerance, fasting lipid profiles and abdominal fat (single slice CT scan) were also determined. Twenty children were assessed at baseline (median age 12.6 [range 8.5–18.5] years; 50

Osteoporosis-pseudoglioma sydrome (OPPG) is an autosomal recessive disorder with early-onset severe osteoporosis and blindness, caused by biallelic loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Heterozygous carriers exhibit a milder bone phenotype. Only a few splice mutations in LRP5 have been published. We present clinical and genetic data for four patients with novel LRP5 mutations, three of which affect splicing. Patients were evaluated clinically and by radiography and bone densitometry. Genetic screening of LRP5 was performed on the basis of the clinical diagnosis of OPPG. Splice aberrances were confirmed by cDNA sequencing or exon trapping. The effect of one splice mutation on LRP5 protein function was studied. A novel splice-site mutation c.1584+4A>T abolished the donor splice site of exon 7 and activated a cryptic splice site, which led to an in-frame insertion of 21 amino acids (p.E528_V529ins21). Functional studies revealed severely impaired signal transduction presumably caused by defective intracellular transport of the mutated receptor. Exon trapping was used on two samples to confirm that splice-site mutations c.4112-2A>G and c.1015+1G>T caused splicing-out of exons 20 and 5, respectively. One patient carried a homozygous deletion of exon 4 causing the loss of exons 4 and 5, as demonstrated by cDNA analysis. Our results broaden the spectrum of mutations in LRP5 and provide the first functional data on splice aberrations.

OBJECTIVES: Vitamin D plays a critically important role in the development, growth, and mineralization of the skeleton during its formative years, and performs an equally essential role in maintaining a healthy mineralized skeleton for adults of all ages. We evaluated the vitamin D status and risk factors for vitamin D deficiency in healthy breast-fed newborns and their nursing mothers.METHODS: Serum 25-hydroxyvitamin D (250HD), calcium, phosphorus, and alkaline phosphatase levels were measured in 54 newborns and their nursing mothers whose ages ranged from 18 to 38 y. The relation between serum 25OHD level and demographic factors was analyzed. Bone mineral density was measured in the mothers with a serum 25OHD level below 25 nmol/L to determine the extent of bone mineralization.RESULTS: The mean serum 25OHD level in the 54 mothers was 29.11 ± 10.47 nmol/L. Forty-six percent of the mothers had serum 25OHD levels below 25 nmol/L. The risk factors for low maternal serum 25OHD level were found in decreasing order of importance as follows: low socioeconomic class (odds ratio [OR] = 8.1, P = 0.000), being covered (OR = 4.3, P = 0.023), and low educational level (OR = 3.5, P = 0.033). The mean serum 25OHD level in the newborns was 18.62 ± 8.00 nmol/L. Eighty percent of the newborns had serum 25OHD levels below 25 nmol/L. There was a significant correlation between the serum 25OHD levels of the newborns and their mothers (r = 0.63, P = 0.01). The most important risk factor for low serum 25OHD level in the newborn was a maternal 25OHD level below 25 nmol/L (OR = 15.2, P = 0.002), followed a covered mother (OR = 6.8, P = 0.011). Bone mineral densitometry showed osteopenia in 40% of the women with serum 25OHD levels below 25 nmol/L. All women were from a lower socioeconomic class and 80% were covered.CONCLUSIONS: Vitamin D deficiency is still a common and serious health problem of women of reproductive age and their babies in developing countries at the outset of a new millennium.

Objective: To determine the extent and degree of abnormalities of serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor (PI)-treated and PI-naive HIV-infected children.Design: A cross-sectional study involving HIV-infected children, 3-18 years of age, in a paediatric tertiary care centre.Main outcome measures: Total, HDL and LDL-cholesterol, triglycerides, glucose, insulin, proinsulin and C-peptide were determined in the fasting state. Insulin resistance was assessed using the homeostatic model assessment-insulin resistance (HOMA-IR). Abdominal adipose tissue distribution was determined by single-slice computed tomography at the umbilical level.Results: Thirty PI-treated and 20 PI-naive children were evaluated (76% prepubertal). PI-treated children had significantly higher total cholesterol (P = 0.0021), LDL-cholesterol (P = 0.019) and triglycerides (P = 0.0018). Serum glucose, insulin, proinsulin and C-peptide, the insulin : glucose ratio, HOMA-IR and abdominal adipose tissue distribution were similar in the two groups. Clinical and immunological HIV categories, viral load, CD4 cell count and stavudine therapy were not significantly associated with serum lipids, insulin resistance or abdominal adipose tissue distribution. The predictor variable most strongly associated with fasting serum insulin and HOMA-IR was the Tanner stage. Age was the most significant predictor variable of the visceral : subcutaneous adipose tissue ratio.Conclusion: In this cohort of predominantly prepubertal HIV-infected children, PI therapy was associated with an atherogenic dyslipidemia but not with insulin resistance or abnormal abdominal adipose tissue distribution. The results suggest that children, particularly prepubertal children, are less susceptible than adults to Pl-induced changes in glucose homeostasis and abdominal adipose tissue distribution. (C) 2003 Lippincott Williams Wilkins.

X-Linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia, rickets, and impaired growth. Despite oral phosphate and 1,25-dihydroxyvitamin D(3) treatment, many patients have suboptimal growth and bone healing. The aim of this study was to assess whether age at treatment onset impacts the outcome. Growth data, biochemistry, and radiographs of 19 well-controlled patients with XLH were analyzed retrospectively. Patients were divided into two groups based on the age at treatment onset (group 1, <1.0 yr; group 2, >or=1.0 yr). The median height z-score was higher in group 1 (n = 8) than in group 2 (n = 11) at treatment onset [-0.4 SD score (SDS) vs. -1.7 SDS; P = 0.001], at the end of the first treatment year (-0.7 SDS vs. -1.8 SDS; P = 0.009), throughout childhood (P > 0.05) and until predicted adult height (-0.2 SDS vs. -1.2 SDS; P = 0.06). The degree of hypophosphatemia was similar in both groups, but serum alkaline phosphatase remained higher in group 2 throughout childhood. Radiographic signs of rickets were more marked in group 2, but even patients with early treatment developed significant skeletal changes of rickets. These data suggest that treatment commenced in early infancy results in improved outcome in patients with XLH, but does not completely normalize skeletal development.