Kids N Fitness: A Group-based Pediatric Weight Management Curriculum Adapted for a Clinical Care Model.

BACKGROUND: The current AAP clinical practice guidelines for the management of pediatric obesity recommend a structured, comprehensive, multi-disciplinary clinical intervention. However, there is a gap in the current literature on standardized curriculums for implementation of such programs. The objective of the present study is to adapt an evidenced-based, family- centered, weekly, weight management curriculum that addresses nutritional, physical activity and behavioral topics for a clinical care model at a tertiary care children's hospital. METHODS: The curriculum was adapted for use in six individual sessions offered monthly by a multidisciplinary team, including a health educator, physician, dietitian, physical therapist and psychologist. Each provider offered specific feedback and curriculum adaptation based on their specialty. All team members completed training with scheduled treatment fidelity monitoring during implementation. To evaluate the effectiveness of the adapted curriculum, 60 adolescents, ages 14-18 years, with overweight or obesity, and at least one family member, will complete the six month intervention. The primary outcome is mean change in zBMI and %BMIp95 at six month and 18 months. Secondary outcomes include retention, satisfaction, effect on metabolic factors and activity level. CONCLUSION: There is a paucity of literature on utilizing a standard curriculum in clinical weight management programs. Drawing from evidenced-based curriculum to strengthen clinical care creates an opportunity to improve existing clinical programs and potentially increase access and implementation of the current treatment recommendations for this high risk population.

Post-stimulus fMRI and EEG responses: Evidence for a neuronal origin hypothesised to be inhibitory.

Post-stimulus undershoots, negative responses following cessation of stimulation, are widely observed in functional magnetic resonance (fMRI) blood oxygenation level dependent (BOLD) data. However, the debate surrounding whether the origin of this response phase is neuronal or vascular, and whether it provides functionally relevant information, that is additional to what is contained in the primary response, means that undershoots are widely overlooked. We simultaneously recorded electroencephalography (EEG), BOLD and cerebral blood-flow (CBF) [obtained from arterial spin labelled (ASL) fMRI] fMRI responses to hemifield checkerboard stimulation to test the potential neural origin of the fMRI post-stimulus undershoot. The post-stimulus BOLD and CBF signal amplitudes in both contralateral and ipsilateral visual cortex depended on the post-stimulus power of the occipital 8-13Hz (alpha) EEG neuronal activity, such that trials with highest EEG power showed largest fMRI undershoots in contralateral visual cortex. This correlation in post-stimulus EEG-fMRI responses was not predicted by the primary response amplitude. In the contralateral visual cortex we observed a decrease in both cerebral rate of oxygen metabolism (CMRO2) and CBF during the post-stimulus phase. In addition, the coupling ratio (n) between CMRO2 and CBF was significantly lower during the positive contralateral primary response phase compared with the post-stimulus phase and we propose that this reflects an altered balance of excitatory and inhibitory neuronal activity. Together our data provide strong evidence that the post-stimulus phase of the BOLD response has a neural origin which reflects, at least partially, an uncoupling of the neuronal responses driving the primary and post-stimulus responses, explaining the uncoupling of the signals measured in the two response phases. We suggest our results are consistent with inhibitory processes driving the post-stimulus EEG and fMRI responses. We therefore propose that new methods are required to model the post-stimulus and primary responses independently, enabling separate investigation of response phases in cognitive function and neurological disease.

Elevated mercury concentrations in the feathers of grey-faced petrels (Pterodroma gouldi) in New Zealand.

Our objective was to measure the concentrations of Hg, As, Cd, Co, Cr, Cu, Pb, Sb, V and Zn in the body feathers of grey-faced petrel (Pterodroma gouldi), fluttering shearwater (Puffinus gavia), little shearwater (Puffinus assimilis) and common diving petrel (Pelecanoides urinatrix) from breeding colonies in New Zealand between 2006 and 2013. The mean Hg concentration (36.48ppm; SD=9.59) in grey-faced petrel feathers was approximately 8.5 to 14 times that detected in the other three species sampled. We detected no trend or differences in Hg concentrations in grey-faced petrels over the 8years of this study, but Hg concentrations varied between breeding colonies although there was no strong relationship with latitude. The elevated Hg concentrations detected in grey-faced petrels could pose a risk to the breeding performance of grey-faced petrels and the customary harvest of chicks by Maori (New Zealand's indigenous peoples).

Assessing potential errors of MRI-based measurements of pulmonary blood flow using a detailed network flow model.

MRI images of pulmonary blood flow using arterial spin labeling (ASL) measure the delivery of magnetically tagged blood to an image plane during one systolic ejection period. However, the method potentially suffers from two problems, each of which may depend on the imaging plane location: 1) the inversion plane is thicker than the imaging plane, resulting in a gap that blood must cross to be detected in the image; and 2) ASL includes signal contributions from tagged blood in conduit vessels (arterial and venous). By using an in silico model of the pulmonary circulation we found the gap reduced the ASL signal to 64-74% of that in the absence of a gap in the sagittal plane and 53-84% in the coronal. The contribution of the conduit vessels varied markedly as a function of image plane ranging from ∼90% of the overall signal in image planes that encompass the central hilar vessels to <20% in peripheral image planes. A threshold cutoff removing voxels with intensities >35% of maximum reduced the conduit vessel contribution to the total ASL signal to ∼20% on average; however, planes with large contributions from conduit vessels underestimate acinar flow due to a high proportion of in-plane flow, making ASL measurements of perfusion impractical. In other image planes, perfusion dominated the resulting ASL images with good agreement between ASL and acinar flow. Similarly, heterogeneity of the ASL signal as measured by relative dispersion is a reliable measure of heterogeneity of the acinar flow distribution in the same image planes.

Breed, age and gender distribution of dogs with chronic hepatitis in the United Kingdom.

Standardised histological criteria are now available for the diagnosis of canine chronic hepatitis (CH). CH is common in dogs, but no studies have reported breed, age and gender distributions in the United Kingdom (UK). The objective of this study was to determine which breeds had an increased risk for developing CH in the UK and to report the age and gender distribution for those breeds. The databases of six veterinary histopathology laboratories were searched for cases with a histological diagnosis of CH according to standardised criteria. The breed, age and gender of dogs was recorded and compared to a control population to calculate the odds ratio and 95% confidence intervals for developing CH. A total of 551 cases of CH were identified, consisting of 61 breeds. Nineteen breeds were represented by five or more cases. Breeds with an increased risk for developing CH included the American cocker spaniel, Cairn terrier, Dalmatian, Dobermann pinscher, English cocker spaniel, English springer spaniel, Great Dane, Labrador retriever and Samoyed. The median age at diagnosis for all breeds with CH was 8 years (range 7 months to 16 years). Dalmatians, Dobermann pinschers and English springer spaniels with CH were significantly younger than Cairn terriers, English cocker spaniels and Labrador retrievers with CH. Females were over-represented when all cases were examined together. In conclusion, several breeds in the UK have an increased risk of CH, some of which have not been previously reported.

Rapid intravenous infusion of 20 mL/kg saline alters the distribution of perfusion in healthy supine humans.

Rapid intravenous saline infusion, a model meant to replicate the initial changes leading to pulmonary interstitial edema, increases pulmonary arterial pressure in humans. We hypothesized that this would alter lung perfusion distribution. Six healthy subjects (29 ± 6 years) underwent magnetic resonance imaging to quantify perfusion using arterial spin labeling. Regional proton density was measured using a fast-gradient echo sequence, allowing blood delivered to the slice to be normalized for density and quantified in mL/min/g. Contributions from flow in large conduit vessels were minimized using a flow cutoff value (blood delivered > 35% maximum in mL/min/cm(3)) in order to obtain an estimate of blood delivered to the capillary bed (perfusion). Images were acquired supine at baseline, after infusion of 20 mL/kg saline, and after a short upright recovery period for a single sagittal slice in the right lung during breath-holds at functional residual capacity. Thoracic fluid content measured by impedance cardiography was elevated post-infusion by up to 13% (p<0.0001). Forced expiratory volume in 1s was reduced by 5.1% post-20 mL/kg (p=0.007). Infusion increased perfusion in nondependent lung by up to 16% (6.4 ± 1.6 mL/min/g baseline, 7.3 ± 1.8 post, 7.4 ± 1.7 recovery, p=0.03). Including conduit vessels, blood delivered in dependent lung was unchanged post-infusion; however, was increased at recovery (9.4 ± 2.7 mL/min/g baseline, 9.7 ± 2.0 post, 11.3 ± 2.2 recovery, p=0.01). After accounting for changes in conduit vessels, there were no significant changes in perfusion in dependent lung following infusion (7.8 ± 1.9 mL/min/g baseline, 7.9 ± 2.0 post, 8.5 ± 2.1 recovery, p=0.36). There were no significant changes in lung density. These data suggest that saline infusion increased perfusion to nondependent lung, consistent with an increase in intravascular pressures. Dependent lung may have been "protected" from increases in perfusion following infusion due to gravitational compression of the pulmonary vasculature.

Pulmonary perfusion heterogeneity is increased by sustained, heavy exercise in humans.

Exercise presents a considerable stress to the pulmonary system and ventilation-perfusion (Va/Q) heterogeneity increases with exercise, affecting the efficiency of gas exchange. In particular, prolonged heavy exercise and maximal exercise are known to increase Va/Q heterogeneity and these changes persist into recovery. We hypothesized that the spatial heterogeneity of pulmonary perfusion would be similarly elevated after prolonged exercise. To test this, athletic subjects (n = 6, Vo(2max) = 61 ml. kg(-1).min(-1)) with exercising Va/Q heterogeneity previously characterized by the multiple inert gas elimination technique (MIGET), performed 45 min of cycle exercise at approximately 70% Vo(2max). MRI arterial spin labeling measures of pulmonary perfusion were acquired pre- and postexercise (at 20, 40, 60 min post) to quantify the spatial distribution in isogravitational (coronal) and gravitationally dependent (sagittal) planes. Regional proton density measurements allowed perfusion to be normalized for density and quantified in milliliters per minute per gram. Mean lung density did not change significantly in either plane after exercise (P = 0.19). Density-normalized perfusion increased in the sagittal plane postexercise (P =or <0.01) but heterogeneity did not (all P >or= 0.18), likely because of perfusion redistribution and vascular recruitment. Density-normalized perfusion was unchanged in the coronal plane postexercise (P = 0.66), however, perfusion heterogeneity was significantly increased as measured by the relative dispersion [RD, pre 0.62(0.07), post 0.82(0.21), P < 0.0001] and geometric standard deviation [GSD, pre 1.74(0.14), post 2.30(0.56), P < 0.005]. These changes in heterogeneity were related to the exercise-induced changes of the log standard deviation of the ventilation distribution, an MIGET index of Va/Q heterogeneity (RD R(2) = 0.68, P < 0.05, GSD, R(2) = 0.55, P = 0.09). These data are consistent with but not proof of interstitial pulmonary edema as the mechanism underlying exercise-induced increases in both spatial perfusion heterogeneity and Va/Q heterogeneity.

Resting cerebral blood flow: a potential biomarker of the effects of HIV in the brain.

OBJECTIVE: HIV enters the brain soon after infection causing neuronal damage and microglial/astrocyte dysfunction leading to neuropsychological impairment. We examined the impact of HIV on resting cerebral blood flow (rCBF) within the lenticular nuclei (LN) and visual cortex (VC). METHODS: This cross-sectional study used arterial spin labeling MRI (ASL-MRI) to measure rCBF within 33 HIV+ and 26 HIV- subjects. Nonparametric Wilcoxon rank sum test assessed rCBF differences due to HIV serostatus. Classification and regression tree (CART) analysis determined optimal rCBF cutoffs for differentiating HIV serostatus. The effects of neuropsychological impairment and infection duration on rCBF were evaluated. RESULTS: rCBF within the LN and VC were significantly reduced for HIV+ compared to HIV- subjects. A 2-tiered CART approach using either LN rCBF < or =50.09 mL/100 mL/min or LN rCBF >50.09 mL/100 mL/min but VC rCBF < or =37.05 mL/100 mL/min yielded an 88% (29/33) sensitivity and an 88% (23/26) specificity for differentiating by HIV serostatus. HIV+ subjects, including neuropsychologically unimpaired, had reduced rCBF within the LN (p = 0.02) and VC (p = 0.001) compared to HIV- controls. A temporal progression of brain involvement occurred with LN rCBF significantly reduced for both acute/early (<1 year of seroconversion) and chronic HIV-infected subjects, whereas rCBF in the VC was diminished for only chronic HIV-infected subjects. CONCLUSION: Resting cerebral blood flow (rCBF) using arterial spin labeling MRI has the potential to be a noninvasive neuroimaging biomarker for assessing HIV in the brain. rCBF reductions that occur soon after seroconversion possibly reflect neuronal or vascular injury among HIV+ individuals not yet expressing neuropsychological impairment.

Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans.

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

Quantification of regional pulmonary blood flow using ASL-FAIRER.

Pulsed arterial spin labeling (ASL) techniques have been theoretically and experimentally validated for cerebral blood flow (CBF) quantification. In this study ASL-FAIRER was used to measure regional pulmonary blood flow (rPBF) in seven healthy subjects. Two general ASL strategies were investigated: 1) a single-subtraction approach using one tag-control pair acquisition at an inversion time (TI) matched to the RR-interval, and 2) a multiple-subtraction approach using tag-control pairs acquired at various TIs. The mean rPBF averaged 1.70 +/- 0.38 ml/min/ml when measured with the multiple-subtraction approach, and was approximately 2% less when measured with the single-subtraction method (1.66 +/- 0.24 ml/min/ml). Assuming an average lung density of 0.33 g/ml, this translates into a regional perfusion of approximately 5.5 ml/g/min, which is comparable to other measures of pulmonary perfusion. As with other ASL applications, a key problem with quantitative interpretation of the results is the physical gap between the tagging region and imaged slice. Because of the high pulsatility of PBF, ASL acquisition and data analysis differ significantly between the lung and the brain. The advantages and drawbacks of the single- vs. multiple-subtraction approaches are considered within a theoretical framework tailored to PBF.

Striate palmoplantar keratoderma arising from desmoplakin and desmoglein 1 mutations is associated with contrasting perturbations of desmosomes and the keratin filament network.

BACKGROUND: Several hereditary human diseases are now known to be caused by distinct mutations in genes encoding various desmosome components. Although the effects of some of these mutant genes have been analysed by targeted disruption experiments in mouse models, little is known about the cell and tissue changes in affected human patients. OBJECTIVES: To investigate the effects of heterozygous nonsense mutations in desmoplakin (Dp) and desmoglein (Dsg) 1 which cause the autosomal dominant disorder striate palmoplantar keratoderma (SPPK), focusing on changes in desmosome structure and composition and the associated keratin intermediate filament (KIF) network in palm skin, and in cultured keratinocytes generated from the same site. METHODS: We analysed palm and nonpalm skin sections from four SPPK patients with Dp mutations and one patient with a Dsg1 mutation with respect to tissue and subcellular morphologies, and correlated the in vivo and in vitro findings. RESULTS: Using electron microscopy, we found abnormalities of desmosomes and cell-cell adhesion in the suprabasal layers in the epidermis from patients with both Dsg1- and Dp-associated SPPK. These changes were more advanced in skin from patients with Dp mutations. Both Dp and Dsg1 mutations were accompanied by significantly reduced numbers of desmosomes in the suprabasal layers, while decreased desmosome size was evident only in Dsg1-associated SPPK. Confocal microscopy analysis showed marked differences in the expression of keratins and of desmosome components, both between the two types of SPPK, and between SPPK and normal skin. The expression of keratins K5, K14 and K10 was reduced in Dsg1-associated SPPK skin, whereas perinuclear aggregation of keratin filaments was more evident in Dp-associated SPPK. In both types of SPPK upregulation of K16 was pronounced and involucrin labelling was abnormal. CONCLUSIONS: Mutations in Dp and Dsg1 genes causing SPPK may be associated with perturbations in epidermal differentiation accompanied by a marked disruption of several components of the epidermal scaffold including desmosomes and the KIF network.

Parasite plastids: maintenance and functions.

Malaria and related parasites retain a vestigial, but biosynthetically active, plastid organelle acquired far back in evolution from a red algal cell. The organelle appears to be essential for parasite transmission from cell to cell and carries the smallest known plastid genome. Why has this genome been retained? The genes it carries seem to be dedicated to the expression of just two "housekeeping" genes. We speculate that one of these, called ycf24 in plants and sufB in bacteria, is tied to an essential "dark" reaction of the organelle--fatty acid biosynthesis. "Ball-park" clues to the function of bacterial suf genes have emerged only recently and point to the areas of iron homeostasis, [Fe-S] cluster formation and oxidative stress. We present experimental evidence for a physical interaction between SufB and its putative partner SufC (ycf16). In both malaria and plants, SufC is encoded in the nucleus and specifies an ATPase that is imported into the plastid.

The Poggendorff illusion: effect of distance between the parallel lines.

43 subjects observed Poggendorff figures with transverse line segments at a constant distance while the parallels were positioned closer or farther apart. At closer distances, no illusion occurred; at farther distances, the illusion diminished. The illusion no longer occurred when the parallels were located beyond the outside end of the transverse lines. Since illusions occurred only when the parallels physically touched the transverse line, this research emphasizes the importance of the intersection of figural elements in the production of the Poggendorff illusion.

Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, causing the skin disease striate palmoplantar keratoderma.

The adhesive proteins of the desmosome type of cell junction consist of two types of cadherin found exclusively in that structure, the desmogleins and desmocollins, coded by two closely linked loci on human chromosome 18q12.1. Recently we have identified a mutation in the DSG1 gene coding for desmoglein 1 as the cause of the autosomal dominant skin disease striate palmoplantar keratoderma (SPPK) in which affected individuals have marked hyperkeratotic bands on the palms and soles. In the present study we present the complete exon-intron structure of the DSG1 gene, which occupies approximately 43 kb, and intron primers sufficient to amplify all the exons. Using these we have analysed the mutational changes in this gene in five further cases of SPPK. All were heterozygotic mutations in the extracellular domain leading to a truncated protein, due either to an addition or deletion of a single base, or a base change resulting in a stop codon. Three mutations were in exon 9 and one in exon 11, both of which code for part of the third and fourth extracellular domains, and one was in exon 2 coding for part of the prosequence of this processed protein. This latter mutation thus results in the mutant allele synthesising only 25 amino acid residues of the prosequence of the protein so that this is effectively a null mutation implying that dominance in the case of this mutation was caused by haploinsufficiency. The most severe consequences of SPPK mutations are in regions of the body where pressure and abrasion are greatest and where desmosome function is most necessary. SPPK therefore provides a very sensitive measure of desmosomal function.

Estimation of respiration-induced noise fluctuations from undersampled multislice fMRI data.

Functional MRI time series data are known to be contaminated by highly structured noise due to physiological fluctuations. Significant components of this noise are at frequencies greater than those critically sampled in standard multislice imaging protocols and are therefore aliased into the activation spectrum, compromising the estimation of functional activations and the determination of their significance. However, in this work it is demonstrated that unaliased noise information is available in multislice data, and can be used to estimate and reduce noise due to high-frequency respiratory-related fluctuations. Magn Reson Med 45:635-644, 2001. Published 2001 Wiley-Liss, Inc.

Nonlinear temporal dynamics of the cerebral blood flow response.

The linearity of the cerebral perfusion response relative to stimulus duration is an important consideration in the characterization of the relationship between regional cerebral blood flow (CBF), cerebral metabolism, and the blood oxygenation level dependent (BOLD) signal. It is also a critical component in the design and analysis of functional neuroimaging studies. To study the linearity of the CBF response to different duration stimuli, the perfusion response in primary motor and visual cortices was measured during stimulation using an arterial spin labeling technique with magnetic resonance imaging (MRI) that allows simultaneous measurement of CBF and BOLD changes. In each study, the perfusion response was measured for stimuli lasting 2, 6, and 18 sec. The CBF response was found in general to be nonlinearly related to stimulus duration, although the strength of nonlinearity varied between the motor and visual cortices. In contrast, the BOLD response was found to be strongly nonlinear in both regions studied, in agreement with previous findings. The observed nonlinearities are consistent with a model with a nonlinear step from stimulus to neural activity, a linear step from neural activity to CBF change, and a nonlinear step from CBF change to BOLD signal change.

Putting spatial attention on the map: timing and localization of stimulus selection processes in striate and extrastriate visual areas.

This study investigated the cortical mechanisms of visual-spatial attention in a task where subjects discriminated patterned targets in one visual field at a time. Functional magnetic imaging (fMRI) was used to localize attention-related changes in neural activity within specific retinotopic visual areas, while recordings of event-related brain potentials (ERPs) traced the time course of these changes. The earliest ERP components enhanced by attention occurred in the time range 70-130 ms post-stimulus onset, and their neural generators were estimated to lie in the dorsal and ventral extrastriate visual cortex. The anatomical areas activated by attention corresponded closely to those showing increased neural activity during passive visual stimulation. Enhanced neural activity was also observed in the primary visual cortex (area V1) with fMRI, but ERP recordings indicated that the initial sensory response at 50-90 ms that was localized to V1 was not modulated by attention. Modeling of ERP sources over an extended time range showed that attended stimuli elicited a long-latency (160-260 ms) negativity that was attributed to the dipolar source in area V1. This finding is in line with hypotheses that V1 activity may be modulated by delayed, reentrant feedback from higher visual areas.

Detection power, estimation efficiency, and predictability in event-related fMRI.

Experimental designs for event-related functional magnetic resonance imaging can be characterized by both their detection power, a measure of the ability to detect an activation, and their estimation efficiency, a measure of the ability to estimate the shape of the hemodynamic response. Randomized designs offer maximum estimation efficiency but poor detection power, while block designs offer good detection power at the cost of minimum estimation efficiency. Periodic single-trial designs are poor by both criteria. We present here a theoretical model of the relation between estimation efficiency and detection power and show that the observed trade-off between efficiency and power is fundamental. Using the model, we explore the properties of semirandom designs that offer intermediate trade-offs between efficiency and power. These designs can simultaneously achieve the estimation efficiency of randomized designs and the detection power of block designs at the cost of increasing the length of an experiment by less than a factor of 2. Experimental designs can also be characterized by their predictability, a measure of the ability to circumvent confounds such as habituation and anticipation. We examine the relation between detection power, estimation efficiency, and predictability and show that small increases in predictability can offer significant gains in detection power with only a minor decrease in estimation efficiency.