Differential developmental refinement of the intrinsic electrophysiological properties of CA1 pyramidal neurons from the rat dorsal and ventral hippocampus.

The dorsal and ventral regions of the rat longitudinal hippocampal axis are functionally distinct. That is, each region is associated with different behavioral tasks and disease susceptibilities due to underlying anatomical, and physiological differences. These differences are especially pronounced in area CA1, where significant differences in morphology, synaptic physiology, intrinsic excitability, and gene expression have been reported between CA1 pyramidal neurons from the dorsal (DHC) and ventral hippocampus (VHC). However, despite a significant amount of recent attention, a cogent picture of the intrinsic electrophysiological profile of DHC and VHC neurons has remained elusive, due, in part, to experiments performed on rats at different developmental time points. Moreover, the resulting intrinsic electrophysiological profiles are sufficiently different as to warrant a thorough investigation of the spatial and temporal changes in the intrinsic excitability of CA1 pyramidal neurons across developmental time. Accordingly, in this study, I have characterized the intrinsic electrophysiological properties of CA1 pyramidal neurons from acute hippocampal slices prepared from the DHC and VHC throughout an approximately 3-week developmental period (P14-P37). DHC and VHC neurons exhibited distinct intra-region changes (DHC or VHC) and inter-region differences (DHC versus VHC) in their intrinsic electrophysiological properties, which yielded two developmental timelines: (a) a common developmental timeline describing changes observed in both DHC and VHC neurons, and (b) a differential developmental timeline highlighting unique features observed in DHC neurons. Specifically, DHC neurons exhibited significant inter-region differences in RMP, input resistance, threshold, and spike frequency adaptation relative to VHC neurons, as well as an intra-region change in the rebound slope (a proxy for Ih ). These observations both integrate and reconcile previous work performed with rats at different developmental stages and suggest a distinct developmental trajectory for DHC neurons that might shed light on the normal physiological functions and disease susceptibility of the DHC.

Muscle Strength, Power, and Torque Deficits in Children With Type SS Sickle Cell Disease.

In African-American children aged 5 to 17 years with and without type SS sickle cell disease (SCD-SS), dominant hand maximal handgrip strength, peak power, and plantar flexion isometric maximal voluntary contraction (MVC) torque were compared with adjustments for body size and composition. Children with SCD-SS (n=21; age, 11±1 y) compared with healthy control children (n=23; 10±1 y) did not differ by age, sex, or maturation stage, but had significantly lower Z scores for height, weight, body mass index, arm circumference, upper arm muscle area, and lean mass-for-height. Children with SCD-SS had significantly lower unadjusted handgrip strength (16±2 vs. 23±2 kg, P<0.01), peak power (1054±107 vs. 1488±169 W, P<0.04) and MVC torques at 2 angles (10 degrees: 27±3 vs. 42±5 Nm; 20 degrees: 21±3 vs. 34±4 Nm; all P<0.05). Performance decrements persisted when handgrip strength was adjusted for lean body mass and fat mass explaining 66% of the variance; peak power adjusted for age, lean body mass, fat mass, and height explaining 91% of the variance; and the highest MVC torque (10-degree angle) adjusted for left leg length, lean mass-for-height, and fat mass-for-height Z scores explaining 65% of the variance. This suggests additional factors contribute to the attenuated anaerobic performance.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.

Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. METHODS: Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. RESULTS: A total of 110 subjects were enrolled (age 10.4 ±â€Š3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. CONCLUSIONS: LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.

Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease.

Suboptimal vitamin D (vit D) status (<32 ng/mL) is ubiquitous among African American children with type SS sickle cell disease (SCD-SS). The vit D supplemental dose to normalize vit D status is unknown. Five to 20-year-old African American children with (n=21) and without (n=23) SCD-SS were randomized to vit D3 supplementation (4000 or 7000 IU/d) and evaluated at 6 and 12 weeks for changes in vit D and SCD status. A dose was considered unsafe if serum calcium was elevated associated with elevated serum 25 hydroxyvitamin D (25(OH)D). At baseline 95% of subjects with SCD-SS and 87% of healthy controls had suboptimal vit D status (mean±SD, 19.2±7.2 and 22.3±9.3 ng/mL, respectively). After 12 weeks supplementation, both D3 doses were safe and well tolerated. Neither group achieved the a priori efficacy criterion of 25(OH)D≥32 ng/mL in >80% of subjects (45% in SCD-SS and 63% in controls). However, for both subjects with SCD-SS and healthy subjects by 12 weeks, deficient (<20 ng/mL) vit D status was eliminated only in those receiving 7000 IU/d. For subjects with SCD-SS, by 12 weeks there was a significant (all P<0.05) increase in fetal hemoglobin, decrease in high-sensitivity C-reactive protein, and reduction in the percentage of subjects with a high platelet count.

Vitamin B(12) status in children with cystic fibrosis and pancreatic insufficiency.

OBJECTIVES: Unexpectedly high serum B12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based, and enzyme-based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status in children with CF and PI. STUDY DESIGN: Serum B12 status was assessed in subjects (5-18 years) and categorized as elevated (serum B12 above reference range for age and sex [Hi-B12]) or within reference range (serum B12 within reference range for age and sex) for age and sex. Serum homocysteine, plasma B6, red blood cell folate, height, weight, and body mass index z scores, pulmonary function, energy, and dietary and supplement-based vitamin intake were assessed. RESULTS: A total of 106 subjects, mean age 10.4 ±â€Š3.0 years, participated in the study. Median serum B12 was 1083 pg/mL, with 56% in the Hi-B12 group. Dietary and supplement-based B12 intakes were both high representing 376% and 667% recommended dietary allowance (RDA), respectively. The Hi-B12 group had significantly greater supplement-based B12 intake than the serum B12 within reference range for age and sex group (1000% vs 583% RDA, P < 0.001). Multiple logistic regression analysis showed that high supplement-based B12 intake and age >12 years increased the risk of Hi-B12, whereas higher forced expiratory volume at 1 second (FEV1) decreased the risk (pseudo-R = 0.18, P < 0.001). CONCLUSIONS: Serum B12 was elevated in the majority of children with CF and PI. Supplement-based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B12 status. The health consequences of lifelong high supplement-based B12 intake and high serum B12 are unknown and require further study, as does the inversed correlation between serum B12 and forced expiratory volume at 1 second.

Fat-soluble vitamins in cystic fibrosis and pancreatic insufficiency: efficacy of a nutrition intervention.

OBJECTIVES: The aim of the study was to assess the impact of LYM-X-SORB (LXS), an organized lipid matrix that has been shown to be absorbable without pancreatic enzyme therapy on fat-soluble vitamin status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI). METHODS: Children with CF and PI were randomized to daily LXS or an isocaloric placebo comparison supplement for 12 months. Serum vitamins A (retinol), D (25-hydroxyvitamin D[25D]), E (α-tocopherol, α-tocopherol:cholesterol ratio), and K (percentage of undercarboxylated osteocalcin [%ucOC] and plasma proteins induced by vitamin K absence factor II [PIVKA II]) were assessed at baseline and 12 months. Dietary intake was determined using 3-day weighed food records and supplemental vitamin intake by a comprehensive questionnaire. RESULTS: A total of 58 subjects (32 boys, age 10.3 ± 2.9 years [mean ± standard deviation]) with complete serum vitamin, dietary and supplemental vitamin data were analyzed. After adjusting for dietary and supplemental vitamin intake, serum retinol increased 3.0 ± 1.4 µg/dL (coefficient ± standard error) (adjusted R2 = 0.02, P = 0.03) and vitamin K status improved as demonstrated by a decreased percentage of undercarboxylated osteocalcin of -6.0% ± 1.6% by 12 months (adjusted R2 = 0.15, P < 0.001). These changes occurred in both the LXS and placebo comparison groups. No changes in serum 25D or α-tocopherol were detected. Both nutrition interventions increased caloric intake a mean of 83 ± 666 kcal/day by 12 months. CONCLUSIONS: Vitamins A and K status improved, whereas vitamins D and E status was unchanged during 12 months of LXS and isocaloric placebo comparison supplement in children with CF and PI.

Differential expression of HCN subunits alters voltage-dependent gating of h-channels in CA1 pyramidal neurons from dorsal and ventral hippocampus.

The rodent hippocampus can be divided into dorsal (DHC) and ventral (VHC) domains on the basis of behavioral, anatomical, and biochemical differences. Recently, we reported that CA1 pyramidal neurons from the VHC were intrinsically more excitable than DHC neurons, but the specific ionic conductances contributing to this difference were not determined. Here we investigated the hyperpolarization-activated current (I(h)) and the expression of HCN1 and HCN2 channel subunits in CA1 pyramidal neurons from the DHC and VHC. Measurement of Ih with cell-attached patches revealed a significant depolarizing shift in the V(1/2) of activation for dendritic h-channels in VHC neurons (but not DHC neurons), and ultrastructural immunolocalization of HCN1 and HCN2 channels revealed a significantly larger HCN1-to-HCN2 ratio for VHC neurons (but not DHC neurons). These observations suggest that a shift in the expression of HCN1 and HCN2 channels drives functional changes in I(h) for VHC neurons (but not DHC neurons) and could thereby significantly alter the capacity for dendritic integration of these neurons.

Blood lead concentration is not altered by high-dose vitamin D supplementation in children and young adults with HIV.

OBJECTIVES: Optimal vitamin D status is known to have beneficial health effects and vitamin D supplements are commonly used. It has been suggested that vitamin D supplementation may increase blood lead in children and adults with previous lead exposure. The objective was to determine the safety regarding lead toxicity during 12 weeks of high-dose vitamin D3 supplementation in children and young adults with human immunodeficiency virus (HIV). METHODS: Subjects with HIV (8-24 years) were randomized to vitamin D3 supplementation of 4000 or 7000 IU/day and followed at 6 and 12 weeks for changes in serum 25-hydroxy vitamin D (25D) and whole-blood lead concentration. This was a secondary analysis of a larger study of vitamin D3 supplementation in children and adolescents with HIV. RESULTS: In 44 subjects (75% African American), the baseline mean ± standard deviation serum 25D was 48.3±18.6 nmol/L. Fifty percent of subjects had baseline serum 25D <50.0 nmol/L. Serum 25D increased significantly with D3 supplementation during the 12 weeks. No subject had a whole-blood lead >5.0 µg/dL at baseline or during subsequent visits. Whole-blood lead and 25D were not correlated at baseline, and were negatively correlated after 12 weeks of supplementation (P=0.014). Whole-blood lead did not differ between those receiving 4000 and 7000 IU of vitamin D3. CONCLUSIONS: High-dose vitamin D3 supplementation and the concomitant increased serum 25D did not result in increased whole-blood lead concentration in this sample of children and young adults living in a northeastern urban city.

Intrinsic excitability of CA1 pyramidal neurones from the rat dorsal and ventral hippocampus.

The hippocampus has a central role in learning and memory. Although once considered a relatively homogenous structure along the longitudinal axis, it has become clear that the rodent hippocampus can be anatomically and functionally divided into a dorsal component generally associated with spatial navigation, and a ventral component primarily associated with non-spatial functions that involve an emotional component. The ventral hippocampus (VHC) is also more sensitive to epileptogenic stimuli than the dorsal hippocampus (DHC), and seizures tend to originate in the VHC before spreading to other brain regions. Although synaptic and biochemical differences in DHC and VHC have been investigated, the intrinsic excitability of individual neurones from the DHC and VHC has received surprisingly little attention. In this study, we have characterized the intrinsic electrophysiological properties of CA1 pyramidal neurones from the DHC and the VHC using the whole-cell current-clamp method. Our results demonstrate that somatic current injections of equal magnitude elicit significantly more action potentials in VHC neurones than DHC neurones, and that this difference stems from the more depolarized resting membrane potential (RMP; 7 mV) and higher input resistance (R(in); 46 M measured from RMP) observed in VHC neurones. These differences in RMP and R(in) were also observed in dendritic whole-cell current-clamp recordings. Furthermore, morphological reconstructions of individual neurones revealed significant differences in the dendritic branching pattern between DHC and VHC neurones that could, in principle, contribute to the lower somatic R(in) of DHC neurones. Together, our results highlight significant differences in the intrinsic electrophysiological properties of CA1 pyramidal neurones across the longitudinal hippocampal axis, and suggest that VHC neurones are intrinsically more excitable than DHC neurones. This difference is likely to predispose the VHC to hyperexcitability.

Attenuated maximal muscle strength and peak power in children with sickle cell disease.

Dominant hand maximal handgrip strength evaluated with a handgrip dynamometer and peak power evaluated with a force plate, adjusted for body size and composition, were compared in African-American children aged 5 to 13 years, with and without type SS sickle cell disease (SCD-SS). Children with SCD-SS (n = 35; age, 9.0 ± 2.0 y) compared with healthy control children (n = 103; age, 8.6 ± 1.8 y) did not differ by age, sex, or pubertal status, yet had significantly lower Z scores for height, weight, body mass index, upper arm muscle area, upper arm fat area, fat mass-for-height and lean mass-for-height. Children with SCD-SS had significantly lower handgrip strength (12.7 ± 3.3 vs. 15.2 ± 5.1 kg, P < 0.008), peak power (882 ± 298 vs. 1167 ± 384 W, P < 0.001), and growth and body composition adjusted Z scores for handgrip strength (0.6 ± 1.3 standard deviations, P < 0.004) and peak power (male children = 1.0 ± 0.8 standard deviations, P < 0.0002; female children = 1.0 ± 1.7 standard deviations, P < 0.006). Maximal muscle strength and peak power are attenuated in children with SCD-SS compared with healthy control children beyond expectation for growth and body composition deficits suggesting that additional factors contribute to attenuation in anaerobic performance.

Vitamin D Supplementation Improves Health-Related Quality of Life and Physical Performance in Children with Sickle Cell Disease and in Healthy Children.

INTRODUCTION: No study determined if vitamin D supplementation improves health-related quality of life (HRQL) using pediatric Patient-Reported Outcomes Measurement Information System or physical functioning in type SS sickle cell disease (HbSS). METHOD: Subjects with HbSS (n = 21) and healthy subjects (n = 23) were randomized to daily oral doses (4,000 vs. 7,000 IU) of cholecalciferol (vitamin D3) and evaluated at 6 and 12 weeks for changes in serum 25 hydroxyvitamin D (25(OH)D), HRQL, and physical functioning. RESULTS: In subjects with HbSS, significant reductions in pain, fatigue, and depressive symptoms and improved upper-extremity function were observed. In healthy subjects, significant reductions in fatigue and improved upper-extremity function were observed. Significant improvements in peak power and dorsiflexion isometric maximal voluntary contraction torques were observed in both groups. In subjects with HbSS, improved plantar flexion isometric maximal voluntary contraction torques were observed. Both groups saw significant improvement in their total Bruininks-Oseretsky Test of Motor Proficiency score. DISCUSSION: Daily high-dose vitamin D supplementation for African American children with and without HbSS improved HRQL and physical performance.

Progressive dehydration causes a progressive decline in basketball skill performance.

PURPOSE: To determine the effect of 1, 2, 3, and 4% dehydration (DEH) versus euhydration (EUH) on basketball performance in adult male players. METHODS: Seventeen 17- to 28-yr-old male basketball players completed 3 h of interval treadmill walking (40 degrees C and 20% relative humidity) with or without fluid replacement. Subjects completed six trials in random order: 1) EUH with a carbohydrate-electrolyte solution (CES), 2) EUH control (flavored water with 0% carbohydrate and 18 mM sodium), 3) 1% DEH, 4) 2% DEH, 5) 3% DEH, and 6) 4% DEH. After a 70-min recovery period, subjects performed a sequence of continuous basketball drills designed to simulate a fast-paced game. Measures of overall skill performance during the 80-min game included 1) total time to complete basketball-specific movement drills (sprinting, defensive slides, sprinting-defensive slides combination, and repetitive jumping drills) and 2) total number of shots (foul-line and baseline jump shots, layups, three-point, 15-ft, free throws) made per game. RESULTS: Performance during all timed and shooting drills declined progressively as % DEH increased. Total time to complete basketball-specific movement drills was slower (1%: + 7 +/- 6; 2%: + 20 +/- 5 (P < 0.05); 3%: + 26 +/- 7 (P < 0.005); 4%: + 57 +/- 9 (P < 0.0001) s), and fewer shots were made during DEH versus EUH control (1%: -5 +/- 1; 2%: -6 +/- 2 (P < 0.05); 3%: -8 +/- 2 (P < 0.005); 4%: -10 +/- 1 (P < 0.0001) shots made). There were no significant differences in performance between CES and EUH control. CONCLUSION: Basketball players experienced a progressive deterioration in performance as DEH progressed from 1 to 4%. The threshold, or % DEH at which the performance decrement reached statistical significance, was 2% for combined timed and shooting drills.

Two percent dehydration impairs and six percent carbohydrate drink improves boys basketball skills.

PURPOSE: To determine the effects of exercise heat-induced two percent dehydration (DEH) and euhydration (EUH) with a six percent carbohydrate-electrolyte solution (CES) compared with placebo EUH (P EUH) on basketball skills in skilled young players. METHODS: Fifteen 12- to 15-yr-old boys underwent three separate 2-h exercise heat exposures (double blind, random order): 2% DEH by limiting fluid intake during exercise in the heat and basketball skill drills, EUH (no net weight change) with a 6% CES, and EUH with a flavored water placebo (P EUH). After recovery, subjects performed an orchestrated sequence of continuous basketball drills designed to simulate a game (12-min quarters + a 10-min halftime). Performance measures and component drills inherent to basketball included various individual and combined shooting percentages (3-point, 15-foot, free-throw shots), sprint (suicides, court widths), lateral movement (zigzags, lane slides), and defensive drill (combining lateral and front-to-back movement) times. RESULTS: Compared with P EUH (53 +/- 11%), combined shooting percentage was impaired by 2% DEH (45 +/- 9%; P = 0.002) and improved by CES intake (60 +/- 8%; P = 0.003). Total sprint times showed a similar effect (83 +/- 10 vs 78 +/- 9 vs 76 +/- 9 s; DEH vs P EUH vs CES; P < 0.001 and P = 0.04, respectively). Total lateral movement times were impaired by 2% DEH (73 +/- 8 vs 68 +/- 8 s; P = 0.001). CES improved total defensive drill times compared with 2% DEH (77 +/- 10 vs 82 +/- 10; P = 0.006). CONCLUSION: Deterioration in basketball skill performance accompanies two percent dehydration in skilled 12- to 15-yr-old basketball players. Additionally, EUH with a 6% CES significantly improves shooting performance and on-court sprinting over EUH with water.

High-dose vitamin D3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial.

BACKGROUND: Suboptimal vitamin D status is prevalent in HIV-infected patients and associated with increased risk of disease severity and morbidity. We aimed to determine 12-month safety and efficacy of daily 7000 IU vitamin D3 (vitD3) versus placebo to sustain increased serum 25-hydroxyvitamin D (25(OH)D) and improve immune status in HIV-infected subjects. METHODS: This was a double-blind trial of perinatally acquired HIV (PHIV)-infected subjects or behaviorally acquired HIV (BHIV)-infected subjects (5.0-24.9 years). Safety, 25(OH)D-related parameters and immune status were assessed at baseline, 3, 6 and 12 months. RESULTS: Fifty-eight subjects enrolled (67% male, 85% African American and 64% BHIV) and 50 completed with no safety concerns. In unadjusted analyses, there were no differences between randomization groups at baseline; at 3, 6 and 12 months, 25(OH)D was higher with supplementation than baseline and higher than with placebo (P < 0.05). In adjusted mixed models, in the supplementation group, the fixed effect of 25(OH)D was higher (P < 0.001). Percentage of naive T-helper cells (Th naive%) were significantly (P < 0.01) and T-helper cells (CD4%) marginally (P < 0.10) increased with supplementation in those taking highly active antiretroviral therapy (HAART), and RNA viral load was reduced (P ≤ 0.05). In exploratory linear models, change in 25(OH)D predicted RNA viral load at 3 and 12 months and CD4% at 3 months (P < 0.05). CONCLUSIONS: Daily 7000 IU vitD3 for 12 months was safe in HIV-infected subjects and effective in increasing 25(OH)D. Supplementation improved some clinically important HIV immune markers in subjects on HAART. Adjunct therapy with high-dose, daily vitD3 for HIV-infected subjects and for those on/off HAART requires further investigation.

Safety and Efficacy of High-Dose Daily Vitamin D3 Supplementation in Children and Young Adults Infected With Human Immunodeficiency Virus.

BACKGROUND: Suboptimal vitamin D (vitD) status is common in children and young adults infected with human immunodeficiency virus (HIV). The vitD supplemental dose needed to normalize vitD status in this population is unknown. METHODS: In this double-blind trial, subjects infected with HIV ages 8.3 to 24.9 years were randomized to vitD3 supplementation of 4000 IU/day or 7000 IU/day and evaluated at 6 and 12 week for changes in vitD status and HIV indicators. A dose was considered unsafe if serum calcium was elevated (above age and sex-specific range) associated with elevated serum 25 hydroxyvitamin D (25(OH)D); >160 ng/mL). RESULTS: At baseline, 95% of subjects (n = 44; 43% with perinatally acquired HIV, 57% with behaviorally acquired HIV) had a suboptimal serum 25(OH)D concentration of <32 ng/mL (mean ± standard deviation, 19.3 ± 7.4; range, 4.4-33.6 ng/mL). After 12 weeks (main outcome) of D3 supplementation, both D3 doses were safe and well tolerated, with no evidence of elevation of serum calcium concentrations or deterioration in HIV immunologic or virologic status. Sufficient vitD status, defined as serum 25(OH)D ≥32 ng/mL, was achieved in 81% of all subjects, and only the 7000 IU/day group (86%) achieved this a priori efficacy criterion in >80% of subjects. Change in serum 25(OH)D did not differ between HIV acquisition groups. CONCLUSIONS: A 7000 IU/day D3 supplementation was safe and effective in children and young adults infected with HIV.

Effect of a dietary intervention on growth and energy expenditure in children with cystic fibrosis.

BACKGROUND: The study aim was to determine the effect of a dietary intervention on growth, body composition and resting energy expenditure (REE) in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in a randomized, double blind, placebo-controlled trial. METHODS: Subjects (5 to 17 yrs) participated in a 12-month trial of the organized lipid matrix LYM-X-SORB™ (LXS) vs. placebo dietary supplements with similar calories, total fat and fatty acids. Dietary intake was assessed using 3-day weighed food records. Height (HAZ), weight (WAZ), BMI (BMIZ), mid-upper arm muscle (UAMAZ) and fat area (UAFAZ) Z-scores were calculated. Fat mass (FM) and fat-free mass (FFM) were obtained by whole body DXA. REE (kcal/d) was evaluated by indirect calorimetry at baseline, 3 and 12 months and %REE calculated using Schofield equations. No growth or REE differences were observed between LXS and placebo groups so data were pooled for analysis. RESULTS: 63 children (57% males, age 10.6 ± 2.9 yr, 43% receiving LXS) completed REE measurements. Caloric intake increased from a median of 2502 [1478, 4909] to 2616 [1660, 4125] kcal/d at 12 months. HAZ, WAZ and UAMAZ increased (p < 0.05) over 12 months. Mean REE was 109 ± 8% predicted at baseline and 107 ± 9% at 12 months (p < 0.05). REE (kcal/d) adjusted for FFM and FM decreased over 12 months ([mean ± SE] -31 ± 12 kcals, p < 0.01), significant only in males (-49 ± 16 kcals, p < 0.01). CONCLUSIONS: Over a 12 month nutrition intervention with either LXS or placebo, the growth status, muscle stores and REE improved. Sustained increased energy intake improved energy metabolism, growth and nutritional status in school age children with CF, PI and mild lung disease.

No improvement in suboptimal vitamin A status with a randomized, double-blind, placebo-controlled trial of vitamin A supplementation in children with sickle cell disease.

BACKGROUND: Suboptimal vitamin A status is prevalent in children with type SS sickle cell disease (SCD-SS) and is associated with hospitalizations and poor growth and hematologic status. The supplemental vitamin A dose that optimizes suboptimal vitamin A status in this population is unknown. OBJECTIVE: The efficacy of Recommended Dietary Allowance (RDA) doses (based on age and sex) of vitamin A (300, 400, or 600 µg retinyl palmitate/d) or vitamin A + zinc (10 or 20 mg zinc sulfate/d) compared with placebo to optimize vitamin A status was assessed in children aged 2.0-12.9 y with SCD-SS and a suboptimal baseline serum retinol concentration (<30 µg/dL). DESIGN: In this randomized, double-blind, placebo-controlled trial, vitamin A status (serum retinol, prealbumin, retinol-binding protein, and relative-dose-response test) and disease-related illness events were assessed. RESULTS: Twelve months of vitamin A supplementation at the doses recommended for healthy US children (based on age and sex) failed to improve serum retinol values in either group (vitamin A: n = 23; vitamin A + zinc: n = 18) compared with placebo (n = 21). By 12 mo, the increase (±SD) in serum retinol (3.6 ± 2.8 µg/dL) in those taking 600 µg vitamin A/d was significantly different from the decrease (±SD; -2.8 ± 2.4 µg/dL) in those taking 300 µg/d, which possibly suggests a dose-response relation (P < 0.05) with RDA doses. CONCLUSIONS: Compared with placebo, 12 mo of vitamin A supplementation at the RDA for healthy children did not improve serum retinol values in children with SCD-SS, which possibly suggests that higher doses are needed. However, the existence of alternative conclusions emphasizes the need for future research.

Suboptimal vitamin K status despite supplementation in children and young adults with cystic fibrosis.

BACKGROUND: For children and adolescents with cystic fibrosis (CF) and pancreatic insufficiency, the efficacy of routine vitamin K supplementation to normalize vitamin K status remains unclear. OBJECTIVE: This study examined and determined predictors of vitamin K status in subjects aged 8-25 y with CF and pancreatic insufficiency taking various vitamin K supplements. DESIGN: In 97 subjects, serum 25-hydroxyvitamin D [25(OH)D], dietary intake, vitamin K supplement intake, and vitamin K statusmdashdetermined on the basis of the percentage of serum undercarboxylated osteocalcin (%ucOC; sufficient: lt 20%) and plasma proteins induced by vitamin K absence-factor II (PIVKA-II; n = 60; sufficient: le 2 microg/L)mdashwere assessed. The vitamin K supplementation groups were as follows: lt 150 microg/d (low; multivitamins or no supplement), 150-999 microg/d (middle; CF-specific vitamins), and ge 1000 microg/d (high; mephyton). %ucOC values were compared with 140 healthy subjects aged 6-21 y. RESULTS: In subjects with CF, the median (range) %ucOC was 35% (3%, 76%) and the median (range) for PIVKA-II was 2 (0, 42) micro g/L. Subjects with CF had a higher %ucOC with low [45% (10%, 76%)] and medium [41% (3%, 66%)] supplement intakes but not with a high supplement intake [16% (4%, 72%)] compared with healthy subjects [23% (0%, 43%); both P lt 0.05]. Supplementation group for males and females and 25(OH)D and age for males were significant predictors of vitamin K status. CONCLUSIONS: Vitamin K status was often suboptimal despite routine supplementation. Only subjects taking high-dose vitamin K achieved a status similar to healthy subjects, and only the vitamin K supplementation dose predicted vitamin K status for males and females. These data suggest that higher doses of vitamin K are required.

Responses of lean and obese boys to repeated summer exercise in the heat bouts.

PURPOSE: To determine the degree of natural acclimatization and artificially induced acclimation-related changes during repeated exercise in the heat bouts in seven lean and seven obese 9- to 12-yr-old boys during summer months. METHODS: Beginning at random times during the summer, subjects underwent a 70-min exercise (30% VO(2max)) in the heat exposure (38 degrees C, 50% relative humidity) on six separate days. RESULTS: On day 1, obese children were less naturally acclimatized as indicated by significantly higher baseline core temperatures (T(c)) (obese = 37.62 +/- 0.06 vs lean = 37.41 +/- 0.06; P < 0.004). By day 6 versus day 1, significant reductions in baseline T(c) were evident in both groups (obese = 37.41 +/- 0.04 vs lean = 37.18 +/- 0.04; both P < 0.05). Baseline T(c) in obese subjects by day 6 was similar to that of lean subjects on day 1. Daily reductions in exercise T(c) were evident in both groups (final exercising T(c) day 1 vs day 6: obese = 38.15 +/- 0.05 vs 37.89 +/- 0.05; lean = 38.17 +/- 0.09 vs 37.72 +/- 0.06 degrees C; both P < 0.001), occurring at a significantly slower rate in obese subjects (final exercise T(c) day 6 - day 1: obese vs lean = -0.26 +/- 0.04 vs -0.45 +/- 0.08 degrees C; P < 0.05). Significant reductions in exercising heart rate (HR) occurred in the lean but not the obese subjects by day 6 (final exercising HR day 1 vs day 6: obese = 132 +/- 3 vs 131 +/- 3, P > 0.05; lean = 138 +/- 3 vs 127 +/- 3 bpm; P < 0.001). CONCLUSIONS: During summer months, obese children are less naturally heat-acclimatized and subsequently acclimate at a slower rate.