A systematic review of recall errors associated with portion size estimation aids in children.

To reduce errors in portion size estimation, a number of aids have been developed and tested. This systematic review synthesizes what is known about error associated with use of different portion size estimation aids (PSEAs) within self-reported dietary recall studies in children (aged ≤18 years). Eight electronic databases were searched using relevant keywords. From 8184 records identified and screened, 327 full texts were retrieved, with 10 records representing 9 studies meeting inclusion criteria. Studies using proxy reporting were excluded. Thirteen PSEAs were identified. To facilitate comparisons between different types of aids they were categorized into 'physical 2-dimensional (2D)', 'digital 2D' and '3-dimensional' PSEAs. Seven were physical 2D (e.g. food atlas), two were digital 2D (i.e. computer-based), and four were 3D (e.g. modelling clay, household items). Comparisons of PSEAs within studies found the smallest estimation errors for digital 2D and largest for 3D aids. Errors in relation to food type were varied, with portions of amorphous foods overestimated in multiple studies. No effects for recall interval time or sex were identified. One study reported a significant improvement in estimation error with increasing age. Across studies, large variations in study design and reporting of estimation error hindered the synthesis of evidence regarding the influence of different types of PSEAs on accuracy. While a definitive conclusion about the most accurate PSEA could not be drawn, a check-list to guide future PSEA development and testing has been proposed in the current review. This will assist comparability with future studies of PSEAs for children facilitate development of more accurate PSEAs in the future.

Dietary glycemic index and glycemic load in relation to changes in body composition measures during adolescence: Northern Ireland Young Hearts Study.

BACKGROUND: Epidemiologic evidence on the influence of dietary glycemic index (GI) and glycemic load (GL) on the development of obesity is limited. OBJECTIVE: This prospective study examined the associations between dietary GI and GL and changes in body composition measures during adolescence. DESIGN: In a representative sample of Northern Irish adolescents aged 12 years at baseline and 15 years at follow-up (n=426), dietary intake was assessed by a diet history interview. Body composition measures included body mass index (BMI; kg m(-2)), BMI z-score, sum of four skinfold thicknesses, percentage body fat, fat mass index (FMI; kg m(-2)) and fat-free mass index (kg m(-2)). RESULTS: After adjustment for potential confounding factors, baseline GI was associated with increased change in FMI. Mean (95% confidence interval) values of changes in FMI according to tertiles of baseline GI were 0.41 (0.25, 0.57), 0.42 (0.26, 0.58) and 0.67 (0.51, 0.83) kg m(-2), respectively (P for trend=0.03). There was no significant association of baseline GI with changes in other body composition measures (P for trend≥0.054). Conversely, baseline GL showed no association with changes in any of the measures (P for trend≥0.41). Furthermore, changes in GI or GL were not associated with changes in any of the measures (P for trend≥0.16). CONCLUSION: Dietary GI at age 12 years was independently associated with increased change in FMI between ages 12 and 15 years in a representative sample from Northern Ireland, whereas dietary GL showed no association with changes in any of the body composition measures examined.

Perceived 'healthiness' of foods can influence consumers' estimations of energy density and appropriate portion size.

OBJECTIVE: To compare portion size (PS) estimates, perceived energy density (ED) and anticipated consumption guilt (ACG) for healthier vs standard foods. METHODS: Three pairs of isoenergy dense (kJ per 100 g) foods-healthier vs standard cereals, drinks and coleslaws-were selected. For each food, subjects served an appropriate PS for themselves and estimated its ED. Subjects also rated their ACG about eating the food on a scale of 1 (not at all guilty) to 5 (very guilty). RESULTS: Subjects (n=186) estimated larger portions of the healthier coleslaw than that of the standard version, and perceived all healthier foods to be lower in ED than their standard alternatives, despite being isoenergy dense. Higher ACG was associated with the standard foods. Portion estimates were generally larger than recommendations and the ED of the foods was underestimated. CONCLUSIONS: The larger portions selected for the 'reduced fat' food in association with lower perceived ED and ACG suggests that such nutrition claims could be promoting inappropriate PS selection and consumption behaviour. Consumer education on appropriate portions is warranted to correct such misconceptions.

Supermarket own brand foods: lower in energy cost but similar in nutritional quality to their market brand alternatives.

BACKGROUND: The present study aimed to compare the nutritional quality (NQ) and energy costs (EC) (£ MJ(-1) ) of own brand (OB) versus market brand (MB) foods in 2010 and 2012. METHODS: A list of processed foods (n = 32) was identified based on the most frequently consumed foods in the UK. Total fat, saturated fat, sugars, salt and energy density (ED) (kJ g(-1) ) in 2010 and 2012 were compared for six OB and one MB version of each food using a NQ scoring method based on the Food Standards Agency's Traffic Light System (TLS). Additional information (fruit, vegetable and nut content; protein; fibre and sodium) was recorded in 2012, and NQ was assessed using the Food Standards Agency's nutrient profiling model (NPM). The EC of the food baskets (FB) was compared in 2010 and 2012. RESULTS: There were no differences in overall NQ between OB and MB FB in 2010 (TLS, P = 0.978) or 2012 (TLS, P = 0.840; NPM, P = 0.696). However, the MB FB was highest in EC in 2010 and 2012 (both P < 0.001). There was an inverse relationship between the ED and EC of the MB foods in 2010 (r = -0.484; P = 0.005) and 2012 (r = -0.452; P = 0.009). CONCLUSIONS: The MB FB was higher in EC than the OB FB in 2010 and 2012 but not superior in overall NQ based on both the TLS and NPM.

Identification of cardiovascular genes in omentum from morbidly obese patients with type 2 diabetes.

BACKGROUND: The metabolic syndrome describes the association between obesity and co-morbidities including insulin resistance, hypertension, dyslipidemia, and cardiovascular (CV) disease. Adipokines produced from omentum contribute to the risk of CV disease and increase the inflammatory state. This study examines the gene expression differences in the omental tissue of morbidly obese diabetic and non-diabetic patients. METHODS: Twenty morbidly obese patients undergoing bariatric surgery were included. Ten patients were diabetic and 10 were non-diabetic. Omental samples were collected intraoperatively and snap frozen. Total RNA was extracted using the Trizol reagent and purified with the RNeasy kit (Qiagen). Microarray experiments were performed using the Affymetrix Gene 1.0 ST array and data was analyzed with the Partek 6.3 program using an unpaired t-test (P<0.05). The gene expression profiles of the diabetic group were compared with the non-diabetic group. Using the Ingenuity program, the gene list generated from the microarray analysis was evaluated and real-time quantitative PCR (qPCR) was used to validate the array data. RESULTS: Compared with the non-diabetic group, the diabetic obese patients showed 79 upregulated genes and 4 downregulated genes with >1.4-fold difference in expression. Ingenuity analysis showed numerous dysregulated genes associated with CV disease including leptin, Von Willebrand factor, P-selectin, angiopoietin-1 (ANGPT1), phospholipase A2 (group VII), and periostin osteoblast specific factor. Microarray results for the earlier mentioned genes were confirmed with qPCR. The results were analyzed with respect to the presence or absence of hyperlipidemia, hypertension, and coronary artery disease. In patients with hyperlipidemia, ANGPT1 and P-selectin were upregulated 1.9- and 2.9-fold, respectively. CONCLUSIONS: This microarray analysis of omental tissue from morbidly obese diabetic patients documents a host of upregulated genes related to CV disease. This study provides further evidence that diabetic status predisposes obese patients to a higher risk of developing CV disease.

Novel splice variants of sFlt1 are upregulated in preeclampsia.

Soluble fms-like tyrosine kinase-1 (sFlt1) is a truncated splice variant of Flt1, which is upregulated in preeclampsia. In this study we sought to characterize the unique C-terminus of sFlt. Through bioinformatic analyses, we identified two novel sFlt1 splice variants and two previously described sFlt1 splice variants. The novel variants are identical to the previously described sFlt1_v1 through exon 13, but then diverge to unique 3' termini consisting of a novel exon 15 (sFlt1_v2 and sFlt1_v3) or an extension of exon 14 (sFlt1_v4). Quantitative PCR showed that three out of four sFlt variants were upregulated in placenta of women with preeclampsia. Mass spectrometry analysis of sFlt1 purified from placental serum confirmed the presence of sFlt1_v1 protein, and an additional variant which includes sequence derived from exon 14. siRNA experiments targeting each variant confirmed that three of the four variants contribute significantly to total sFlt1 expression by cytotrophoblasts in vitro. These findings provide evidence that human placenta expresses a family of sFlt1 splice variants, at least three of which are expressed as proteins, and which appear to be globally upregulated in preeclampsia.

Investigation of the medium-term effects of Olibratrade mark fat emulsion on food intake in non-obese subjects.

OBJECTIVE: To investigate the effect of Olibra fat emulsion on medium-term food intake and appetite in non-obese subjects. DESIGN: Double-blind, placebo-controlled, within-subject crossover. SETTING: University of Ulster, Coleraine. SUBJECTS: A total of 28 subjects (14 male, 14 female). INTERVENTIONS: Subjects were randomly assigned to receive either a 200 g portion of test (5 g of Olibra fat) or control (5 g milk fat) yoghurt for breakfast for 2 x 3 week 'study' phases, separated by a 3-week 'wash-out' phase. On days 1, 8 and 22 of the study phases, food intake 4 h post-consumption of the yoghurt was assessed by pre- and post-covert weighing at an ad libitum buffet-style test lunch. Throughout each of these study days, appetite was assessed using visual analogue scales (VAS) at regular intervals. For the remainder of the study days, and the following 24 h ('post-study days'), subjects reported their food intake using weighed dietary records. RESULTS: Consumption of the Olibra emulsion had no significant effect on mean energy, macronutrient or amounts of food consumed at the lunch 4 h post-consumption. Self-reported food intakes indicated that there was no significant effect of the emulsion on energy intakes for the remainder of each study day and post-study days. There was considerable individual variation in food intakes following consumption of the Olibra emulsion, with 46, 59 and 57% of subjects reducing their energy intakes at lunch on days 1, 8 and 22. There was no consistent effect of the emulsion on appetite ratings. CONCLUSIONS: In contrast to earlier studies, there was no evidence of a short- or medium-term effect of the Olibra emulsion on food intake or appetite. This could be owing to numerous confounding factors influencing eating behaviour and/or the different study design used in the present study.

Childhood obesity prevention studies: lessons learned and to be learned.

OBJECTIVE: To provide an overview of methodological issues in the design, delivery and evaluation of childhood obesity prevention programmes. DESIGN: Review of existing literature. SETTING: International. RESULTS: Interventions have varied considerably with regard to their design, subject selection criteria, sample size, attrition rates, intervention components and duration of both the intervention and the follow-up phases. However, overall, there is only a limited body of consistent, high-quality evidence on which valid and generalisable conclusions can be drawn about best practices for the prevention of childhood obesity. CONCLUSIONS: Although the rationale for targeting children and adolescents through primary prevention is now compelling, effective obesity prevention remains elusive. There is increasing consensus that prevention of childhood obesity necessitates multifaceted health promotion interventions based on population health principles. By definition, such interventions should have a range of outcome indicators of effectiveness, generalisability and sustainability, not just the traditional ones focused on individual lifestyle behaviour change. Given the complexity and intricacy of population-based intervention programmes, multiple methods of data collection which combine both qualitative and quantitative approaches will need to be fully exploited in order to move towards evidence-based practice in the future.

Endoscopic transnasal pituitary surgery: report on 180 cases.

The endoscopic transnasal approach is an evolving technique for treating lesions in the sella turcica. Since this method was introduced at our institution 4 years ago, the majority of transsphenoidal procedures are performed with it. The records of all patients having endoscopic transnasal hypophysectomy at the Mayo Clinic during the last 4 years were reviewed retrospectively. The criteria analyzed were safety, functional and cosmetic outcome, and complications. During the 4-year period, the operative procedure was modified to improve operative exposure and safety. The results of our review showed a significant decrease in length of hospital stay, reduced operative time, reduced need for nasal packing, and elimination of a sublabial incision. The complication rate was equivalent to that reported for the traditional transseptal transsphenoidal approach. As the neurosurgeons at our institution gained experience with this approach, an increasing number of pituitary microadenomas were resected safely and successfully. In addition, because of the limited septal dissection, this approach is particularly helpful for revision operations. This approach also can be used for the full range of pituitary lesions and in conjunction with adjunctive techniques, including frontal craniotomy and gamma-knife irradiation. Currently, the endoscopic transsphenoidal approach is the method preferred for surgically treating pituitary lesions in adults at our institution.

Head and neck paragangliomas: physiology and biochemistry.

Paragangliomas of the head and neck are derivatives of neural crest cells, comprising part of the diffuse neuroendocrine system. Indeed, paragangliomas encompass a unique subset of tumors of the head and neck. Their biochemistry and physiology are similar to other neuroendocrine tumors unlike tumors based on location. This article discusses their distinct biologic attributes.

A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation.

Both the risk and the rate of development of atherosclerosis are increased in diabetics, but the mechanisms involved are unknown. Here we report a glucose-mediated increase in CD36 mRNA translation efficiency that results in increased expression of the macrophage scavenger receptor CD36. Expression of CD36 was increased in endarterectomy lesions from patients with a history of hyperglycemia. Macrophages that were differentiated from human peripheral blood monocytes in the presence of high glucose concentrations showed increased expression of cell-surface CD36 secondary to an increase in translational efficiency of CD36 mRNA. We obtained similar data from primary cells isolated from human vascular lesions, and we found that glucose sensitivity is a function of ribosomal reinitiation following translation of an upstream open reading frame (uORF). Increased translation of macrophage CD36 transcript under high glucose conditions provides a mechanism for accelerated atherosclerosis in diabetics.

Clinical and pathophysiologic correlates of 1064-nm Nd:Yag laser treatment of reticular veins and venulectasias.

BACKGROUND: The goal of sclerotherapy, laser therapy, and intense pulsed-light therapy is to produce long-term, cosmetically significant elimination of disfiguring leg veins. This study examines the histologic and clinical effects of using a 1064-nm Nd:YAG laser system on lower extremity vessels. DESIGN: A single treatment using the following parameters: wavelength, 1064 nm (multiple synchronized pulsing); spot size, 6 mm; pulse duration, 14 milliseconds (single pulse); and fluence, 130 J/cm(2). SETTING: Private dermatology practice. PATIENTS: Thirteen women (mean age, 38.5 years) with blue venulectasia, 0.5 to 1.5 mm in diameter (class 2), and reticular veins, 1.5 to 3.0 mm in diameter (class 3), on the thighs. MAIN OUTCOME MEASURES: Examination of treated and untreated areas by 2 masked observers using macrophotography (1, 2, 3, and 6 months after treatment), Doppler, and optical chromatographic changes. Findings from three 2-mm punch biopsies from treated (immediately and 4 weeks after treatment) and untreated sites. Routine histologic examination; special stains (for elastic and connective tissue and for mucopolysaccharides); and immunohistochemical analysis for expression of the heat shock protein hsp70, tie2 (an endothelial cell-specific receptor tyrosine kinase), and transforming growth factors beta1 and beta2. RESULTS: Eight patients (62%) manifested 75% to 100% clearing of treated vessel surface area. Treated areas revealed perivascular hemorrhage, thrombi, fragmentation and homogenization of elastic fibers, and eosinophilia of vessel walls. Expression of hsp70 and transforming growth factor beta was increased in treated vessels. CONCLUSIONS: Our data confirm the effectiveness of 1064-nm Nd:YAG laser treatment in clearing dilated lower extremity veins, probably by heat-induced vessel damage and subsequent fibrosis. Maintenance of clearing was achieved for up to 6 months. However, the presence of recanalized thrombi in some of the specimens suggests the potential for long-term vessel reappearance.

p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells.

The development of atherosclerotic lesions results from aberrant cell migration, proliferation, and extracellular matrix production. In advanced lesions, however, cellular apoptosis, leading to lesion remodeling, predominates. During lesion formation, the neurotrophins and the neurotrophin receptor tyrosine kinases, trks B and C, are induced and mediate smooth muscle cell migration. Here we demonstrate that a second neurotrophin receptor, p75(NTR), is expressed by established human atherosclerotic lesions and late lesions that develop after balloon injury of the rat thoracic aorta. The p75(NTR), a member of the tumor necrosis factor/FAS receptor family, can modulate trk receptor function as well as initiate cell death when expressed in cells of the nervous system that lack kinase-active trk receptors. p75(NTR) expression colocalizes to neointimal cells, which express smooth muscle cell alpha-actin and are expressed by cultured human endarterectomy-derived cells (HEDC). Areas of the plaque expressing p75(NTR) demonstrate increased TUNEL positivity, and HEDC undergo apoptosis in response to the neurotrophins. Finally, neurotrophins also induced apoptosis of a smooth muscle cell line genetically manipulated to express p75(NTR), but lacking trk receptor expression. These studies identify the regulated expression of neurotrophins and p75(NTR) as an inducer of smooth muscle cell apoptosis in atherosclerotic lesions.

Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-beta type II receptor.

Atherosclerotic lesions may progress due to a "failure to die" by vascular repair cells. Egr-1, a zinc finger transcription factor, is elevated more than 5-fold in human carotid lesions relative to the adjacent tunica media. Lesion cells in vitro also express 2-3-fold higher Egr-1 mRNA and protein levels but express much lower levels of the transforming growth factor-beta (TGF-beta) Type II receptor (TbetaR-2) and are functionally resistant to the antiproliferative effects of TGF-beta. Lesion cells fail to express a TbetaR-2 promoter/chloramphenicol acetyltransferase (CAT) construct but overexpress an Egr-1-inducible platelet-derived growth factor-A promoter/CAT construct. Transfection of Egr-1 cDNA represses TbetaR-2/CAT constructs but induces PDGF-A/CAT. Egr-1 transfection reduces the levels of TbetaR-2 and confers resistance to the antiproliferative effect of TGF-beta1. Egr-1 can interact directly with both the -143 Sp1 site and the positive regulatory element 2 (PRE2) (ERT/ets) region of the TbetaR-2 promoter. Thus, although activating a family of stress-responsive genes, Egr-1 also transcriptionally represses one of the major inhibitory pathways that restrains vascular repair.

Evaluation of the thyroid nodule.

BACKGROUND: Clinically detectable thyroid nodules occur in up to 4% of the population in the United States. With ultrasound, nodules may be found in up to 50% of those over 50 years of age. METHODS: The author reviews his own experience as well as that of others to define a sound clinical approach to the differential diagnosis and detection of thyroid cancer. RESULTS: Prior neck irradiation is a risk factor for thyroid malignancy. The association of a thyroid nodule with enlarged lymph nodes or fixation of the nodule to strap muscles or the trachea suggests malignancy. A diffusely multinodular gland is usually benign. CONCLUSIONS: Thyroid function tests rarely help a differential diagnosis. Fine-needle aspiration is the "gold standard" for diagnosis. Tiny "incidentalomas" are often followed with repeat monitoring for change of size or character.

TGF-betas and TGF-beta receptors in atherosclerosis.

Based on diverse evidence in animals and humans, it has been hypothesized that atherosclerosis, and other injury-induced hyperplasias such as restenosis, may result from a failure in endogenous inhibitory systems that normally limit wound repair and induce regression of wound repair cells. A key defect in one of these inhibitory pathways, the TGF-beta system, has been identified and characterized in both animal models and in human lesions and lesion-derived cells. Cells derived from human lesions are resistant to the antiproliferative and apoptotic effects of TGF-beta, while their normal counterparts from the vascular media are potently inhibited and killed. Both cell types increase PAI-1 production, switch actin phenotypes in response to TGF-beta1, and produce similar levels of TGF-beta activity. Membrane cross-linking of (125)I-TGF-beta1 indicates that normal human SMC express Type I, II and III receptors. The Type II receptor is strikingly decreased in lesion cells, with little change in the Type I or III receptors. RT-PCR confirmed that the Type II TGF-beta1 receptor mRNA is reduced in lesion cells. Subsequent analysis of human lesion vs normal tissues confirmed that the Type I receptor was consistently present in the lesion, while the Type II receptor was much more variable, and commonly absent in both coronary artery and carotid artery lesions. Transfection of the Type II receptor into lesion cells partially restores the growth inhibitory response to TGF-beta1, implying that signaling remains intact. A subset of patients, and cells derived from their lesions, exhibit acquired mutations in the Type II receptor that would explain their resistance, though the majority of cells are resistant without obvious mutational defects. Thus, it is currently being tested whether transcriptional defects or abnormalities in receptor processing may explain the low levels of the Type II receptor. Because TGF-beta1 is overexpressed in fibroproliferative vascular lesions, receptor-negative cells would be allowed to grow in a slow, but uncontrolled fashion, while overproducing extracellular matrix components.

The effect of growth factors, cytokines, and extracellular matrix proteins on fibronectin production in human vascular smooth muscle cells.

PURPOSE: Although 60% to 80% of the mature intimal hyperplastic plaque is composed of extracellular matrix (ECM) proteins, little is known about the factors that stimulate smooth muscle cells (SMCs) to produce these proteins. A major component of the ECM protein is fibronectin. Thus we studied fibronectin production and its response to various growth factors, cytokines, and other ECM proteins that are released at the time of vascular injury. METHODS: Quiescent cultured human SMCs were stimulated for varying intervals with increasing concentrations of agonist. Fibronectin in the cell medium was assayed by immunoblotting with a fibronectin-specific antibody. RESULTS: After 72 hours of stimulation, transforming growth factor-beta (10 ng/mL) had the most profound effect on fibronectin production (9.6- +/- 2.1-fold; P <.05), followed by epidermal growth factor (100 ng/mL; 5.0- +/- 0.1-fold; P <.05, for both). Surprisingly, the platelet-derived growth factors (AA, AB, and BB) and fibroblast growth factor did not stimulate fibronectin production. Among the matrix proteins studied, only collagen type I (20 microg/mL) stimulated fibronectin production (1.9- +/- 0.1-fold; P <.05), whereas collagen type IV and laminin had no effect. The contractile protein angiotensin II (100 ng/mL) was a weak stimulant of fibronectin (1.6- +/- 0.2-fold; P <.05). Time course studies of fibronectin production up to 72 hours revealed kinetics that varied with each agonist. Transforming growth factor-beta stimulated significant early production of fibronectin, whereas fibronectin production in response to epidermal growth factor and collagen type I was initially modest but increased with time. The effect of angiotensin II did not become evident until 72 hours. CONCLUSION: Cytokines, growth factors, and matrix proteins have varying quantitative effects on ECM protein production by human vascular SMCs. Knowledge of the factors that influence ECM protein production may allow for the design of specific inhibitors that can prevent intimal hyperplasia.

High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis.

To understand the mRNA transcript profile in the human atherosclerotic lesion, RNA was prepared from the fibrous cap versus adjacent media of 13 patients undergoing carotid endarterectomy. cDNA expression arrays bearing 588 known genes indicated that lesions express unexpectedly high levels of the early growth response gene, Egr-1 (NGFI-A), a zinc-finger transcription factor that modulates a cluster of stress-responsive genes including PDGF and TGF-beta. Expression of Egr-1 was an average of 5-fold higher in the lesion than in the adjacent media, a result confirmed by RT-PCR, and many Egr-1-inducible genes were also strongly elevated in the lesion. Time-course analyses revealed that Egr-1 was not induced ex vivo. Immunocytochemistry indicated that Egr-1 was expressed prominently in the smooth muscle-actin positive cells, particularly in areas of macrophage infiltration, and in other cell types, including endothelial cells. Induction of atherosclerosis in LDL receptor-null mice by feeding them a high-fat diet resulted in a progressive increase in Egr-1 expression in the aorta. Thus, induction of Egr-1 by atherogenic factors may be a key step in coordinating the cellular events that result in vascular lesions.