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Find video protocols related to scientific articles indexed in Pubmed.
Aging reduces glial uptake and promotes extracellular accumulation of A? from a lentiviral vector.
Front Aging Neurosci
PUBLISHED: 08-15-2014
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We used a lentiviral system for expressing secreted human A? in the brains of young and old APOE knock-in mice. This system allowed us to examine A? metabolism in vivo, and test the effects of both aging and APOE genotype, two of the strongest risk factors for Alzheimer's disease. We injected the A?1-42 lentivirus into the motor cortex of young (2 month old) and old (20-22 month old) APOE3 and APOE4 mice. After 2 weeks of lentiviral expression, we analyzed the pattern of A? accumulation, glial activation, and phosphor-tau. In young mice, A? accumulated mainly within neurons with no evidence of extracellular A?. Significantly higher levels of intraneuronal A? were observed in APOE4 mice compared to APOE3 mice. In old mice, APOE4 predisposed again to higher levels of A? accumulation, but the A? was mainly in extracellular spaces. In younger mice, we also observed A? in microglia but not astrocytes. The numbers of microglia containing A? were significantly higher in APOE3 mice compared to APOE4 mice, and were significantly lower in both genetic backgrounds with aging. The astrocytes in old mice were activated to a greater extent in the brain regions where A? was introduced, an effect that was again increased by the presence of APOE4. Finally, phospho-tau accumulated in the region of A? expression, with evidence of extracellular phospho-tau increasing with aging. These data suggest that APOE4 predisposes to less microglial clearance of A?, leading to more intraneuronal accumulation. In older brains, decreased clearance leads to more extracellular A?, and more downstream consequences relating to astrocyte activation and phospho-tau accumulation. We conclude that both aging and APOE genotype affect pathways related to A? metabolism by microglia.
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Early Atherosclerosis Relates to Urinary Albumin Excretion and Cardiovascular Risk Factors in Adolescents With Type 1 Diabetes: Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT).
Diabetes Care
PUBLISHED: 07-28-2014
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The origins of cardiovascular and renal disease in type 1 diabetes begin during childhood. We aimed to evaluate carotid (cIMT) and aortic intima-media thickness (aIMT) and their relationship with cardiovascular risk factors and urinary albumin excretion in adolescents with type 1 diabetes in the Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT).
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Public health campaign to promote hand hygiene before meals in a college of veterinary medicine.
J Vet Med Educ
PUBLISHED: 07-02-2014
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Veterinary students can be exposed to environmental infectious agents in school that may include zoonotic pathogens. Encouraging effective hand hygiene can minimize the spread of zoonoses and promote public health and the One Health concept among veterinary students. The purpose of this study was to determine if a campaign could improve hand hygiene among veterinary students at extracurricular meetings serving meals. Nine Kansas State University College of Veterinary Medicine (KSU-CVM) extracurricular organizations participated in the study, sanitizer was provided at each meeting, and baseline hand-hygiene data were observed. A hand-hygiene opportunity was defined as any student observed to approach the buffet food line. Sanitizer use (yes/no) and gender (male/female) were recorded. Campaign interventions included a 3.5-minute educational video and a novel motivational poster. The video was presented to all first-year, second-year, and third-year veterinary students. Posters encouraging hand sanitization were displayed on doors and tables alongside sanitizers at each meeting. Observational hand-hygiene data were collected immediately after introduction of interventions and again 3 months later. Environmental sampling for presence of bacteria in and around meeting locations was also performed. Observed hand hygiene was lowest during baseline (11.0% ± 1.7), improved significantly post-intervention (48.8% ± 3.2), and remained improved at 3-month follow-up (33.5% ± 4.0). Females had higher probability of hand sanitizing (35.9% ± 2.2) than males (21.4% ± 2.4) (p<.01). Clostridium perfringens was isolated from 2/42 samples, and Salmonella spp. were isolated from 4/42 samples. A short-term public health campaign targeting veterinary students successfully improved hand hygiene before meals.
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Trends in incidence of type 1 diabetes among non-Hispanic white youth in the u.s., 2002-2009.
Diabetes
PUBLISHED: 06-04-2014
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The SEARCH for Diabetes in Youth Study prospectively identified youth aged <20 years with physician-diagnosed diabetes. Annual type 1 diabetes (T1D) incidence per 100,000 person-years (95% CI) overall, by age-group, and by sex were calculated for at-risk non-Hispanic white (NHW) youth from 2002 through 2009. Joinpoint and Poisson regression models were used to test for temporal trends. The age- and sex-adjusted incidence of T1D increased from 24.4/100,000 (95% CI 23.9-24.8) in 2002 to 27.4/100,000 (26.9-27.9) in 2009 (P for trend = 0.0008). The relative annual increase in T1D incidence was 2.72% (1.18-4.28) per year; 2.84% (1.12-4.58) per year for males and 2.57% (0.68-4.51) per year for females. After adjustment for sex, significant increases were found for youth aged 5-9 years (P = 0.0023), 10-14 years (P = 0.0008), and 15-19 years (P = 0.004) but not among 0-4-year-olds (P = 0.1862). Mean age at diagnosis did not change. The SEARCH study demonstrated a significant increase in the incidence of T1D among NHW youth from 2002 through 2009 overall and in all but the youngest age-group. Continued surveillance of T1D in U.S. youth to identify future trends in T1D incidence and to plan for health care delivery is warranted.
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Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009.
JAMA
PUBLISHED: 05-06-2014
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Despite concern about an "epidemic," there are limited data on trends in prevalence of either type 1 or type 2 diabetes across US race and ethnic groups.
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Eighteen year weight trajectories and metabolic markers of diabetes in modernising China.
Diabetologia
PUBLISHED: 04-30-2014
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Although obesity is a major risk factor for diabetes, little is known about weight gain trajectories across adulthood, and whether they are differentially associated with metabolic markers of diabetes.
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Relative validity and reliability of an FFQ in youth with type 1 diabetes.
Public Health Nutr
PUBLISHED: 04-01-2014
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To evaluate the relative validity and reliability of the SEARCH FFQ that was modified from the Block Kids Questionnaire.
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Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study.
Pediatrics
PUBLISHED: 03-31-2014
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To estimate temporal changes in the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 or type 2 diabetes in youth and to explore factors associated with its occurrence.
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Patient Perception of Midlevel Providers in Pediatric Diabetes Care.
Diabetes Educ
PUBLISHED: 03-20-2014
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The purpose of this study was to evaluate perceptions of the role of midlevel providers among pediatric type 1 diabetes patients.
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Change in adiposity minimally affects the lipid profile in youth with recent onset type 1 diabetes.
Pediatr Diabetes
PUBLISHED: 03-18-2014
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Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D.
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Survivorship: sexual dysfunction (male), version 1.2013.
J Natl Compr Canc Netw
PUBLISHED: 03-12-2014
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Various anticancer treatments, especially those directed toward the pelvis, can damage blood vessels and reduce circulation of blood to the penis and/or damage the autonomic nervous system, resulting in higher rates of erectile dysfunction in survivors than in the general population. In addition, hormonal therapy can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for male sexual problems, namely erectile dysfunction.
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Survivorship: sexual dysfunction (female), version 1.2013.
J Natl Compr Canc Netw
PUBLISHED: 03-04-2014
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Cancer treatment, especially hormonal therapy and therapy directed toward the pelvis, can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. Thus, sexual dysfunction is common in survivors and can cause increased distress and have a significant negative impact on quality of life. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for female sexual problems, including those related to sexual desire, arousal, orgasm, and pain.
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Longitudinal association between television watching and computer use and risk markers in diabetes in the SEARCH for Diabetes in Youth Study.
Pediatr Diabetes
PUBLISHED: 02-26-2014
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The study provides evidence of the longitudinal association between screen time with hemoglobin A1c (HbA1c) and cardiovascular risk markers among youth with type 1 diabetes (T1D) and type 2 diabetes (T2D).
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Antecedent hypoglycaemia does not diminish the glycaemia-increasing effect and glucoregulatory responses of a 10 s sprint in people with type 1 diabetes.
Diabetologia
PUBLISHED: 02-26-2014
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A 10 s sprint has been reported to provide a means to prevent acute post-exercise hypoglycaemia in young adults with type 1 diabetes because of its glycaemia-raising effect, but it is unclear whether this effect is impaired by antecedent hypoglycaemia. The purpose of this study was to investigate whether antecedent hypoglycaemia impairs the glycaemia-raising effect of a 10 s sprint in individuals with type 1 diabetes.
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Spatial and temporal variation in type 1 diabetes incidence in Western Australia from 1991 to 2010: increased risk at higher latitudes and over time.
Health Place
PUBLISHED: 02-14-2014
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This study analysed spatial and temporal variation in childhood incidence of type 1 diabetes mellitus (T1DM) among Western Australia?s 36 Health Districts from 1991 to 2010. There was a strong latitudinal gradient of 3.5% (95% CI, 0.2-7.2) increased risk of T1DM per degree south of the Equator, as averaged across the range 15-35° south. This pattern is consistent with the hypothesis of vitamin D deficiency at higher latitudes. In addition there was a 2.4% (95% CI, 1.3-3.6) average increase in T1DM incidence per year. These effects could not be explained by population density, socioeconomic status, remoteness or ethnicity.
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Transient Fanconi syndrome in Quarter horses.
Can. Vet. J.
PUBLISHED: 02-04-2014
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Two Quarter horses with weight loss had glucosuria, euglycemia, and a mild metabolic acidosis suggesting a proximal renal tubular defect. Further testing revealed transient generalized aminoaciduria, lactic aciduria, and glucosuria, indicating Fanconi syndrome. Both horses recovered with supportive therapy. This is the first report of acquired Fanconi syndrome in horses.
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Outcomes of photorefractive keratectomy enhancement after LASIK.
J Refract Surg
PUBLISHED: 01-29-2014
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To report the outcomes of photorefractive keratectomy (PRK) enhancement after LASIK for patients diagnosed as having hyperopic and myopic refractive errors.
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The influence of rare genetic variation in SLC30A8 on diabetes incidence and ?-cell function.
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-28-2014
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The variant rs13266634 in SLC30A8, encoding a ?-cell-specific zinc transporter, is associated with type 2 diabetes. We aimed to identify other variants in SLC30A8 that increase diabetes risk and impair ?-cell function, and test whether zinc intake modifies this risk. DESIGN/OUTCOME: We sequenced exons in SLC30A8 in 380 Diabetes Prevention Program (DPP) participants and identified 44 novel variants, which were genotyped in 3445 DPP participants and tested for association with diabetes incidence and measures of insulin secretion and processing. We examined individual common variants and used gene burden tests to test 39 rare variants in aggregate.
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Survivorship: introduction and definition. Clinical practice guidelines in oncology.
J Natl Compr Canc Netw
PUBLISHED: 01-24-2014
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Many cancer survivors experience physical and/or psychosocial side effects, which can be severe, debilitating, and sometimes permanent. These NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment for health care professionals who work with survivors of adult-onset cancer in the posttreatment period. These introductory sections of the guidelines include the panel's definition of cancer survivors, a discussion of the effects of cancer and its treatment, general principles and standards for survivorship care, and guidance regarding screening for problems that require further assessment.
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Cardiovascular health in adolescents with type 1 diabetes: the SEARCH CVD study.
Pediatr Diabetes
PUBLISHED: 01-22-2014
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In their Strategic Impact Goal Statement, the American Heart Association focused on primordial prevention of cardiovascular risk factors by defining metrics for ideal cardiovascular health (ICH). The prevalence of ICH among youth with type 1 diabetes is unknown. Youth with type 1 diabetes face an increased risk of cardiovascular disease (CVD) as they age. The purpose of this report was to examine the prevalence of ICH in a population of youth with type 1 diabetes and to examine the association of ICH with measures of cardiovascular structure and function.
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Differential activation of chemically identified neurons in the caudal nucleus of the solitary tract in non-entrained rats after intake of satiating vs. non-satiating meals.
Physiol. Behav.
PUBLISHED: 01-20-2014
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Satiety signals arising from the gastrointestinal (GI) tract and related digestive organs during food ingestion and digestion are conveyed by vagal sensory afferents to the hindbrain nucleus of the solitary tract (NST). Two intermingled but chemically distinct NST neuronal populations have been implicated in meal size control: noradrenergic (NA) neurons that comprise the A2 cell group, and glucagon-like peptide-1 (GLP-1)-positive neurons. Previous results indicate that A2 neurons are activated in a meal size-dependent manner in rats that have been acclimated/entrained to a feeding schedule in order to increase meal size, whereas feeding under the same conditions does not activate GLP-1 neurons. The present study was designed to test the hypothesis that both A2 and GLP-1 neuronal populations are recruited in non-entrained rats after voluntary first-time intake of an unrestricted, satiating volume of liquid Ensure. DBH-positive A2 neurons within the caudal visceral NST were progressively recruited to express cFos in rats that consumed progressively larger volumes of Ensure. Among these DBH-positive neurons, the prolactin-releasing peptide (PrRP)-positive subset was more sensitive to feeding-induced activation than the PrRP-negative subset. Notably, significant activation of GLP-1-positive neurons occurred only in rats that consumed the largest volumes of Ensure, corresponding to nearly 5% of their BW. We interpret these results as evidence that progressive recruitment of NA neurons within the caudal NST, especially the most caudally-situated PrRP-positive subset, effectively "tracks" the magnitude of GI satiety signals and other meal-related sensory feedback. Conversely, GLP-1 neurons may only be recruited in response to the homeostatic challenge of consuming a very large, unanticipated meal.
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Prevalence of and disparities in barriers to care experienced by youth with type 1 diabetes.
J. Pediatr.
PUBLISHED: 01-16-2014
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To describe the prevalence of access and process barriers to health care and to examine their relationship to sociodemographic and disease factors in a large and diverse cohort of US youth with type 1 diabetes.
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Serum C-reactive protein and immunoglobulin G antibodies to periodontal pathogens may be effect modifiers of periodontitis and hyperglycemia.
J. Periodontol.
PUBLISHED: 01-13-2014
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Serum C-reactive protein (CRP) is elevated in both periodontitis and type 2 diabetes mellitus through inflammation. Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis have been found in periodontal pockets in patients with diabetes. This study examines effect modification by examining the extent to which the associations between periodontitis and hyperglycemia were different by levels of serum CRP and periodontal pathogens.
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Angioedema of the upper aerodigestive tract: risk factors associated with airway intervention and management algorithm.
Int Forum Allergy Rhinol
PUBLISHED: 01-10-2014
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Angioedema of the upper aerodigestive tract can lead to significant airway obstruction. To date no articles have delineated risk factors for progression after initial evaluation.
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No association of dietary fiber intake with inflammation or arterial stiffness in youth with type 1 diabetes.
J. Diabetes Complicat.
PUBLISHED: 01-08-2014
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To examine the association of dietary fiber intake with inflammation and arterial stiffness among youth with type 1 diabetes (T1D) in the US.
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Risk of second primary tumors in men diagnosed with prostate cancer: a population-based cohort study.
Cancer
PUBLISHED: 01-06-2014
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The survival of men diagnosed with prostate cancer has improved over time, and the current 10-year relative survival rate is 99.7%. The long survival of patients with this common cancer raises questions about the risk of a second primary cancer and the need for continued surveillance.
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Early detection of factual knowledge deficiency and remediation in otolaryngology residency education.
Laryngoscope
PUBLISHED: 01-03-2014
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Within otolaryngology residency training, the annual Otolaryngology Training Examination (OTE) is the primary method used to assess, quantify, and compare the factual knowledge acquired by each resident. The objective of this study was to develop a more frequent method for tracking of factual knowledge to prevent educational delay.
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Haploinsufficiency of del(5q) genes, Egr1 and Apc, cooperate with Tp53 loss to induce acute myeloid leukemia in mice.
Blood
PUBLISHED: 01-02-2014
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An interstitial deletion of chromosome 5, del(5q), is the most common structural abnormality in primary myelodysplastic syndromes (MDS) and therapy-related myeloid neoplasms (t-MNs) after cytotoxic therapy. Loss of TP53 activity, through mutation or deletion, is highly associated with t-MNs with a del(5q). We previously demonstrated that haploinsufficiency of Egr1 and Apc, 2 genes lost in the 5q deletion, are key players in the progression of MDS with a del(5q). Using genetically engineered mice, we now show that reduction or loss of Tp53 expression, in combination with Egr1 haploinsufficiency, increased the rate of development of hematologic neoplasms and influenced the disease spectrum, but did not lead to overt myeloid leukemia, suggesting that altered function of additional gene(s) on 5q are likely required for myeloid leukemia development. Next, we demonstrated that cell intrinsic loss of Tp53 in hematopoietic stem and progenitor cells haploinsufficient for both Egr1 and Apc led to the development of acute myeloid leukemia (AML) in 17% of mice. The long latency (234-299 days) and clonal chromosomal abnormalities in the AMLs suggest that additional genetic changes may be required for full transformation. Thus, loss of Tp53 activity in cooperation with Egr1 and Apc haploinsufficiency creates an environment that is permissive for malignant transformation and the development of AML.
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Maternal and family factors and child eating pathology: risk and protective relationships.
J Eat Disord
PUBLISHED: 01-01-2014
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Previous studies have found associations between maternal and family factors and child eating disorder symptoms. However, it is not clear whether family factors predict eating disorder symptoms specifically, or relate to more general child psychopathology, of which eating disorder symptoms may be one component. This study aimed to identify maternal and family factors that may predict increases or decreases in child eating disorder symptoms over time, accounting for children's body mass index z-scores and levels of general psychological distress.
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?-Catenin induces T-cell transformation by promoting genomic instability.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-26-2013
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Deregulated activation of ?-catenin in cancer has been correlated with genomic instability. During thymocyte development, ?-catenin activates transcription in partnership with T-cell-specific transcription factor 1 (Tcf-1). We previously reported that targeted activation of ?-catenin in thymocytes (CAT mice) induces lymphomas that depend on recombination activating gene (RAG) and myelocytomatosis oncogene (Myc) activities. Here we show that these lymphomas have recurring Tcra/Myc translocations that resulted from illegitimate RAG recombination events and resembled oncogenic translocations previously described in human T-ALL. We therefore used the CAT animal model to obtain mechanistic insights into the transformation process. ChIP-seq analysis uncovered a link between Tcf-1 and RAG2 showing that the two proteins shared binding sites marked by trimethylated histone-3 lysine-4 (H3K4me3) throughout the genome, including near the translocation sites. Pretransformed CAT thymocytes had increased DNA damage at the translocating loci and showed altered repair of RAG-induced DNA double strand breaks. These cells were able to survive despite DNA damage because activated ?-catenin promoted an antiapoptosis gene expression profile. Thus, activated ?-catenin promotes genomic instability that leads to T-cell lymphomas as a consequence of altered double strand break repair and increased survival of thymocytes with damaged DNA.
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Diabetes Self-Management Education Patterns in a US Population-Based Cohort of Youth With Type 1 Diabetes.
Diabetes Educ
PUBLISHED: 11-18-2013
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PurposeThe purpose of this study is to describe (1) the receipt of diabetes self-management education (DSME) in a large, diverse cohort of US youth with type 1 diabetes (T1DM), (2) the segregation of self-reported DSME variables into domains, and (3) the demographic and clinical characteristics of youth who receive DSME.MethodsData are from the US population-based cohort SEARCH for Diabetes in Youth. A cross-sectional analysis was employed using data from 1273 youth <20 years of age at the time of diagnosis of T1DM. Clusters of 19 self-reported DSME variables were derived using factor analysis, and their associations with demographic and clinical characteristics were evaluated using polytomous logistic regression.ResultsNearly all participants reported receiving DSME content consistent with "survival skills" (eg, target blood glucose and what to do for low or high blood glucose), yet gaps in continuing education were identified (eg, fewer than half of the participants reported receiving specific medical nutrition therapy recommendations). Five DSME clusters were explored: receipt of specific MNT recommendations, receipt of diabetes information resources, receipt of clinic visit information, receipt of specific diabetes information, and met with educator or nutritionist. Factor scores were significantly associated with demographic and clinical characteristics, including race/ethnicity, socioeconomic status, and diabetes self-management practices.ConclusionsHealth care providers should work together to address reported gaps in DSME to improve patient care.
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Phage T7 Gp2 inhibition of Escherichia coli RNA polymerase involves misappropriation of ?70 domain 1.1.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-11-2013
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Bacteriophage T7 encodes an essential inhibitor of the Escherichia coli host RNA polymerase (RNAP), the product of gene 2 (Gp2). We determined a series of X-ray crystal structures of E. coli RNAP holoenzyme with or without Gp2. The results define the structure and location of the RNAP ?(70) subunit domain 1.1 inside the RNAP active site channel, where it must be displaced by the DNA upon formation of the open promoter complex. The structures and associated data, combined with previous results, allow for a complete delineation of the mechanism for Gp2 inhibition of E. coli RNAP. In the primary inhibition mechanism, Gp2 forms a protein-protein interaction with , preventing the normal egress of from the RNAP active site channel. Gp2 thus misappropriates a domain of the RNAP holoenzyme, , to inhibit the function of the enzyme.
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Both dietary protein and fat increase postprandial glucose excursions in children with type 1 diabetes, and the effect is additive.
Diabetes Care
PUBLISHED: 10-29-2013
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OBJECTIVE To determine the separate and combined effects of high-protein (HP) and high-fat (HF) meals, with the same carbohydrate content, on postprandial glycemia in children using intensive insulin therapy (IIT). RESEARCH DESIGN AND METHODS Thirty-three subjects aged 8-17 years were given 4 test breakfasts with the same carbohydrate amount but varying protein and fat quantities: low fat (LF)/low protein (LP), LF/HP, HF/LP, and HF/HP. LF and HF meals contained 4 g and 35 g fat. LP and HP meals contained 5 g and 40 g protein. An individually standardized insulin dose was given for each meal. Postprandial glycemia was assessed by 5-h continuous glucose monitoring. RESULTS Compared with the LF/LP meal, mean glucose excursions were greater from 180 min after the LF/HP meal (2.4 mmol/L [95% CI 1.1-3.7] vs. 0.5 mmol/L [-0.8 to 1.8]; P = 0.02) and from 210 min after the HF/LP meal (1.8 mmol/L [0.3-3.2] vs. -0.5 mmol/L [-1.9 to 0.8]; P = 0.01). The HF/HP meal resulted in higher glucose excursions from 180 min to 300 min (P < 0.04) compared with all other meals. There was a reduction in the risk of hypoglycemia after the HP meals (odds ratio 0.16 [95% CI 0.06-0.41]; P < 0.001). CONCLUSIONS Meals high in protein or fat increase glucose excursions in youth using IIT from 3 h to 5 h postmeal. Protein and fat have an additive impact on the delayed postprandial glycemic rise. Protein had a protective effect on the development of hypoglycemia.
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A 10-s Sprint Performed After Moderate-Intensity Exercise Neither Increases nor Decreases the Glucose Requirement to Prevent Late-Onset Hypoglycemia in Individuals With Type 1 Diabetes.
Diabetes Care
PUBLISHED: 10-15-2013
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OBJECTIVE To determine whether performing a 10-s sprint after moderate-intensity exercise increases the amount of carbohydrate required to maintain euglycemia and prevent late-onset postexercise hypoglycemia relative to moderate-intensity exercise alone. RESEARCH DESIGN AND METHODS Seven individuals with type 1 diabetes underwent a hyperinsulinemic-euglycemic clamp and performed 30 min of moderate-intensity exercise on two separate occasions followed by either a 10-s maximal sprint effort or no sprint. During the following 8 h, glucose infusion rate to maintain euglycemia and rates of glucose appearance and disappearance were measured continuously. RESULTS In response to exercise and throughout the 8-h recovery period, there were no differences in glucose infusion rate, blood glucose levels, plasma insulin concentrations, and rates of glucose appearance and disappearance between the two experimental conditions (P > 0.05). CONCLUSIONS A 10-s sprint performed after 30 min of moderate-intensity exercise does not affect the amount of carbohydrate required to maintain euglycemia postexercise in individuals with type 1 diabetes.
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Far-red fluorescence gene reporter tomography for determination of placement and viability of cell-based gene therapies.
Opt Express
PUBLISHED: 10-10-2013
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Non-invasive injectable cellular therapeutic strategies based on sustained delivery of physiological levels of BMP-2 for spinal fusion are emerging as promising alternatives, which could provide sufficient fusion without the associated surgical risks. However, these injectable therapies are dependent on bone formation occurring only at the specific target region. In this study, we developed and deployed fluorescence gene reporter tomography (FGRT) to provide information on in vivo cell localization and viability. This information is sought to confirm the ideal placement of the materials with respect to the area where early bone reaction is required, ultimately providing three dimensional data about the future fusion. However, because almost all conventional fluorescence gene reporters require visible excitation wavelengths, current in vivo imaging of fluorescent proteins is limited by high tissue absorption and confounding autofluorescence. We previously administered fibroblasts engineered to produce BMP-2, but is difficult to determine 3-D information of placement prior to bone formation. Herein we used the far-red fluorescence gene reporter, IFP1.4 to report the position and viability of fibroblasts and developed 3-D tomography to provide placement information. A custom small animal, far-red fluorescence tomography system integrated into a commercial CT scanner was used to assess IFP1.4 fluorescence and to demark 3-D placement of encapsulated fibroblasts with respect to the vertebrae and early bone formation as assessed from CT. The results from three experiments showed that the placement of the materials within the spine could be detected. This work shows that in vivo fluorescence gene reporter tomography of cell-based gene therapy is feasible and could help guide cell-based therapies in preclinical models.
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Nutrition therapy recommendations for the management of adults with diabetes.
Diabetes Care
PUBLISHED: 10-09-2013
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There is no standard meal plan or eating pattern that works universally for all people with diabetes. In order to be effective, nutrition therapy should be individualized for each patient/client based on his or her individual health goals; personal and cultural preferences; health literacy and numeracy; access to healthful choices; and readiness, willingness, and ability to change. Nutrition interventions should emphasize a variety of minimally processed nutrient dense foods in appropriate portion sizes as part of a healthful eating pattern and provide the individual with diabetes with practical tools for day-to-day food plan and behavior change that can be maintained over the long term.
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Validation of pediatric diabetes case identification approaches for diagnosed cases by using information in the electronic health records of a large integrated managed health care organization.
Am. J. Epidemiol.
PUBLISHED: 10-07-2013
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We explored the utility of different algorithms for diabetes case identification by using electronic health records. Inpatient and outpatient diagnosis codes, as well as data on laboratory results and dispensing of antidiabetic medications were extracted from electronic health records of Kaiser Permanente Southern California members who were less than 20 years of age in 2009. Diabetes cases were ascertained by using the SEARCH for Diabetes in Youth Study protocol and comprised the "gold standard." Sensitivity, specificity, positive and negative predictive values, accuracy, and the area under the receiver operating characteristic curve (AUC) were compared in 1,000 bootstrapped samples. Based on data from 792,992 youth, of whom 1,568 had diabetes (77.2%, type 1 diabetes; 22.2%, type 2 diabetes; 0.6%, other), case identification accuracy was highest in 75% of bootstrapped samples for those who had 1 or more outpatient diabetes diagnoses or 1 or more insulin prescriptions (sensitivity, 95.9%; positive predictive value, 95.5%; AUC, 97.9%) and in 25% of samples for those who had 2 or more outpatient diabetes diagnoses and 1 or more antidiabetic medications (sensitivity, 92.4%; positive predictive value, 98.4%; AUC, 96.2%). Having 1 or more outpatient type 1 diabetes diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification, code 250.x1 or 250.x3) had the highest accuracy (94.4%) and AUC (94.1%) for type 1 diabetes; the absence of type 1 diabetes diagnosis had the highest accuracy (93.8%) and AUC (93.6%) for identifying type 2 diabetes. Information in the electronic health records from managed health care organizations provides an efficient and cost-effective source of data for childhood diabetes surveillance.
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Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial.
JAMA
PUBLISHED: 09-26-2013
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Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events.
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Maternal smoking during pregnancy and the risk of childhood type 1 diabetes in Western Australia.
Diabetologia
PUBLISHED: 09-17-2013
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The aim of this study was to investigate the association between maternal smoking during pregnancy and type 1 diabetes in the offspring, using complete population data sources available in Western Australia.
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Prevalence of Diabetes Mellitus in U.S. Youth in 2009: The SEARCH for Diabetes in Youth Study.
Diabetes Care
PUBLISHED: 09-16-2013
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ObjectiveTo estimate the prevalence of diabetes in U.S. youth aged < 20 years in 2009 and to estimate the total number of youth with diabetes in U.S. by age, race/ethnicity, and diabetes type.Research Design and MethodsTo address one of its primary aims, the SEARCH for Diabetes in Youth Study identified youth aged < 20 years on 12/31/2009 with physician diagnosed diabetes in selected areas of Colorado, Ohio, South Carolina and Washington, among health plan members of Kaiser Permanente Southern California and among American Indians living on reservations in Arizona and New Mexico. Diabetes was classified as type 1, type 2 or other. Race/ethnicity was by self- report.ResultsFrom a population of 3,458,974 youth aged < 20 years, 7,695 with diabetes were identified (2.22/1000) - 6,668 with type 1 (1.93/1000), 837 with type 2 (0.24/1000) and 190 (0.05/1000) with other diabetes types. Prevalence increased with age, was slightly higher in females than males, and was most prevalent in non-Hispanic White (NHW) and least prevalent in Asian/Pacific Islanders, with Native American and Black youth having the highest prevalence of type 2 diabetes. An estimated 191,986 U.S. youth aged < 20 years have diabetes; 166,984 type 1, 20,262 type 2 diabetes, and 4,740 other types.ConclusionDiabetes mellitus, one of the leading chronic diseases in childhood, affects over 190,000 (1 out of 433) youth less than age 20 years in the US, with racial and ethnic disparities seen in diabetes prevalence, overall and by diabetes type.
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Correlates of treatment patterns among youth with type 2 diabetes.
Diabetes Care
PUBLISHED: 09-11-2013
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OBJECTIVE To describe treatment regimens in youth with type 2 diabetes and examine associations between regimens, demographic and clinical characteristics, and glycemic control. RESEARCH DESIGN AND METHODS This report includes 474 youth with a clinical diagnosis of type 2 diabetes who completed a SEARCH for Diabetes in Youth study visit. Diabetes treatment regimen was categorized as lifestyle alone, metformin monotherapy, any oral hypoglycemic agent (OHA) other than metformin or two or more OHAs, insulin monotherapy, and insulin plus any OHA(s). Association of treatment with demographic and clinical characteristics (fasting C-peptide [FCP], diabetes duration, and self-monitoring of blood glucose [SMBG]), and A1C was assessed by ?(2) and ANOVA. Multiple linear regression models were used to evaluate independent associations of treatment regimens and A1C, adjusting for demographics, diabetes duration, FCP, and SMBG. RESULTS Over 50% of participants reported treatment with metformin alone or lifestyle. Of the autoantibody-negative youth, 40% were on metformin alone, while 33% were on insulin-containing regimens. Participants on metformin alone had a lower A1C (7.0 ± 2.0%, 53 ± 22 mmol/mol) than those on insulin alone (9.2 ± 2.7%, 77 ± 30 mmol/mol) or insulin plus OHA (8.6 ± 2.6%, 70 ± 28 mmol/mol) (P < 0.001). These differences remained significant after adjustment (7.5 ± 0.3%, 58 ± 3 mmol/mol; 9.1 ± 0.4%, 76 ± 4 mmol/mol; and 8.6 ± 0.4%, 70 ± 4 mmol/mol) (P < 0.001) and were more striking in those with diabetes for ?2 years (7.9 ± 2.8, 9.9 ± 2.8, and 9.8 ± 2.6%). Over one-half of those on insulin-containing therapies still experience treatment failure (A1C ?8%, 64 mmol/mol). CONCLUSIONS Approximately half of youth with type 2 diabetes were managed with lifestyle or metformin alone and had better glycemic control than individuals using other therapies. Those with longer diabetes duration in particular commonly experienced treatment failures, and more effective management strategies are needed.
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The significance of serum total immunoglobulin E for in vitro diagnosis of allergic rhinitis.
Int Forum Allergy Rhinol
PUBLISHED: 08-11-2013
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Allergic rhinitis is diagnosed by clinical parameters with no widely accepted screening test. Measurement of total serum immunoglobulin E (IgE) has limited use in the general population due to a low negative predictive value. The value of total IgE level in select populations undergoing in vitro allergy testing remains unknown. The aim of this study is to determine the utility of total serum IgE in the in vitro diagnosis of allergic rhinitis.
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Acute hyperglycaemia does not alter nitric oxide-mediated microvascular function in the skin of adolescents with type 1 diabetes.
Eur. J. Appl. Physiol.
PUBLISHED: 08-05-2013
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We assessed the impact of an acute bout of hyperglycaemia on nitric oxide (NO)-mediated microvascular function in the skin of adolescents with type 1 diabetes (T1DM).
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Albuminuria according to status of autoimmunity and insulin sensitivity among youth with type 1 and type 2 diabetes.
Diabetes Care
PUBLISHED: 07-11-2013
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To evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes. RESEARCH DESIGN AND METHODS SEARCH: is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score <25th percentile for the United States general youth population. DAA status was based on positivity for the 65-kD isoform of glutamate decarboxylase and insulinoma-associated protein 2 antigens. The four etiologic diabetes type groups were as follows: DAA(+)/insulin-sensitive (IS) (n = 1,351); DAA(+)/insulin-resistant (IR) (n = 438); DAA(-)/IR (n = 379); and DAA(-)/IS (n = 233). Urinary albumin:creatinine ratio (UACR) was measured from a random urine specimen. Multivariable regression analyses assessed the independent relationship between the four diabetes type groups and magnitude of UACR.
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Nutritional factors and preservation of C-peptide in youth with recently diagnosed type 1 diabetes: SEARCH Nutrition Ancillary Study.
Diabetes Care
PUBLISHED: 06-27-2013
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To test the novel hypothesis that nutritional factors previously associated with type 1 diabetes etiology or with insulin secretion are prospectively associated with fasting C-peptide (FCP) concentration among youth recently diagnosed with type 1 diabetes.
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Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth.
J. Clin. Endocrinol. Metab.
PUBLISHED: 06-14-2013
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Our study aims were to determine the frequency of MODY mutations (HNF1A, HNF4A, glucokinase) in a diverse population of youth with diabetes and to assess how well clinical features identify youth with maturity-onset diabetes of the young (MODY).
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Age, period and cohort effects on adult body mass index and overweight from 1991 to 2009 in China: the China Health and Nutrition Survey.
Int J Epidemiol
PUBLISHED: 06-14-2013
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Contributions of age-period-cohort effects to increases in BMI and overweight among Chinese adults must be resolved in order to design appropriate interventions. The objectives were to (i) describe the period effect on BMI and overweight among Chinese adults from 1991 to 2009 and assess modification of this effect by age (e.g. cohort effect) and gender, and (ii) quantify the influence of household income and community urbanicity on these effects.
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Assessment of printed patient-educational materials for chronic kidney disease.
Am. J. Nephrol.
PUBLISHED: 06-07-2013
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Awareness of chronic kidney disease (CKD) is suboptimal among patients with CKD, perhaps due to poor readability of patient education materials (PEMs). We reviewed the suitability and readability of common PEMs that focused on 5 content areas: basics of CKD, risk factors for CKD development, risk factors for CKD progression, complications of CKD and self-management strategies to improve kidney health.
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Correlates of medical nutrition therapy and cardiovascular outcomes in youth with type 1 diabetes.
J Nutr Educ Behav
PUBLISHED: 06-04-2013
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To examine whether the types of medical nutrition therapies (MNTs) taught to and used by youth with type 1 diabetes (T1D) vary by sociodemographic characteristics and cardiovascular (CVD) risk factors.
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Dominant role of oncogene dosage and absence of tumor suppressor activity in Nras-driven hematopoietic transformation.
Cancer Discov
PUBLISHED: 06-03-2013
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Biochemical properties of Ras oncoproteins and their transforming ability strongly support a dominant mechanism of action in tumorigenesis. However, genetic studies unexpectedly suggested that wild-type (WT) Ras exerts tumor suppressor activity. Expressing oncogenic Nras(G12D) in the hematopoietic compartment of mice induces an aggressive myeloproliferative neoplasm that is exacerbated in homozygous mutant animals. Here, we show that increased Nras(G12D) gene dosage, but not inactivation of WT Nras, underlies the aggressive in vivo behavior of Nras(G12D/G12D) hematopoietic cells. Modulating Nras(G12D) dosage had discrete effects on myeloid progenitor growth, signal transduction, and sensitivity to MAP-ERK kinase (MEK) inhibition. Furthermore, enforced WT N-Ras expression neither suppressed the growth of Nras-mutant cells nor inhibited myeloid transformation by exogenous Nras(G12D). Importantly, NRAS expression increased in human cancer cell lines with NRAS mutations. These data have therapeutic implications and support reconsidering the proposed tumor suppressor activity of WT Ras in other cancers.
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A logically derived diet to stop MS relapses.
Med. Hypotheses
PUBLISHED: 05-28-2013
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This brief document outlines reasons for expecting that diets which cause gout should help prevent multiple sclerosis relapses.
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Long-term outcome of insulin pump therapy in children with type 1 diabetes assessed in a large population-based case-control study.
Diabetologia
PUBLISHED: 05-23-2013
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We determined the impact of insulin pump therapy on long-term glycaemic control, BMI, rate of severe hypoglycaemia and diabetic ketoacidosis (DKA) in children.
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Spatial patterning of supermarkets and fast food outlets with respect to neighborhood characteristics.
Health Place
PUBLISHED: 05-21-2013
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A large body of literature has reported differences in exposure to environments supporting either healthy (e.g. supermarkets) or unhealthy (e.g. fast food outlets) dietary choices by neighborhood characteristics. We explored the associations of both supermarkets and fast food outlets availability with neighborhood characteristics, and clustering of these two outlet types in a largely rural state. Compared to block groups without a supermarket, those with a supermarket had a significantly higher income, higher housing value, larger population with high school education and above, lower minority population and lower population living below poverty even after controlling for urbanicity and population density of census block groups. Surprisingly, a similar relationship was found for block groups with and without fast food outlets. This was due to spatial co-occurrence and clustering of fast food outlets around supermarket locations. Hence, future studies exploring the associations of food environment with diet or diet-related health outcome should concurrently examine all aspects of food environment (healthy and unhealthy).
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Body mass index and waist circumference: Relationship to cardiometabolic risk factors in children - Busselton Health Study 2005-2007.
J Paediatr Child Health
PUBLISHED: 04-28-2013
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This study aims to analyse the continuous relationship of each cardiometabolic risk factor with body mass index (BMI) and waist circumference percentiles in a population-based sample of children.
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A population-based study of risk factors for severe hypoglycaemia in a contemporary cohort of childhood-onset type 1 diabetes.
Diabetologia
PUBLISHED: 04-16-2013
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Severe hypoglycaemia is a major barrier to optimising glycaemic control. Recent changes in therapy, however, may have altered the epidemiology of severe hypoglycaemia and its associated risk factors. The aim of this study was to examine the incidence rates and risk factors associated with severe hypoglycaemia in a contemporary cohort of children and adolescents with type 1 diabetes.
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Transition from pediatric to adult care for youth diagnosed with type 1 diabetes in adolescence.
Pediatrics
PUBLISHED: 03-25-2013
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Youth with type 1 diabetes mellitus are at risk for poor glycemic control as they age into adulthood. The aim of this study was to describe sociodemographic and clinical correlates of poor glycemic control associated with the transfer of care from pediatric to adult diabetes providers among a cohort of youth with type 1 diabetes diagnosed in adolescence.
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The influence of exposure to maternal diabetes in utero on the rate of decline in ?-cell function among youth with diabetes.
J. Pediatr. Endocrinol. Metab.
PUBLISHED: 03-24-2013
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Abstract We explored the influence of exposure to maternal diabetes in utero on ? cell decline measured by fasting C-peptide (FCP) among 1079 youth <20 years with diabetes, including 941 with type 1 and 138 with type 2 diabetes. Youths exposed to maternal diabetes had FCP levels that were 17% lower among youth with type 2 diabetes [95% confidence interval (CI): -34%, +6%] and 15% higher among youth with type 1 diabetes (95%CI: -14%, +55%) than their unexposed counterparts, although differences were not statistically significant (p=0.13 and p=0.35, respectively). Exposure to maternal diabetes was not associated with FCP decline in youth with type 2 (p=0.16) or type 1 diabetes (p=0.90); nor was the effect of in utero exposure on FCP modified by diabetes type. Findings suggest that exposure to maternal diabetes in utero may not be an important determinant of short-term ?-cell function decline in youth with type 1 or type 2 diabetes.
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Discordant risk: overweight and cardiometabolic risk in Chinese adults.
Obesity (Silver Spring)
PUBLISHED: 03-19-2013
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Recent US work identified "metabolically healthy overweight" and "metabolically at risk normal weight" individuals. Less is known for modernizing countries with recent increased obesity.
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UK vaccination schedule: persistence of immunity to hepatitis B in children vaccinated after perinatal exposure.
Arch. Dis. Child.
PUBLISHED: 03-09-2013
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To assess persistence of immunity to hepatitis B (HBV) in primary school children vaccinated following perinatal exposure.
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An evaluation of pharmacology curricula in Australian science and health-related degree programs.
BMC Med Educ
PUBLISHED: 03-04-2013
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Pharmacology is a biomedical discipline taught in basic science and professional degree programs. In order to provide information that would facilitate pharmacology curricula to be refined and developed, and approaches to teaching to be updated, a national survey was undertaken in Australia that investigated pharmacology course content, teaching and summative assessment methods.
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Dysregulated fear predicts social wariness and social anxiety symptoms during kindergarten.
J Clin Child Adolesc Psychol
PUBLISHED: 03-04-2013
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Fearful temperament is associated with risk for the development of social anxiety disorder in childhood; however, not all fearful children become anxious. Identifying maladaptive trajectories is thus important for clarifying which fearful children are at risk. In an unselected sample of 111 two-year-olds (55% male, 95% Caucasian), Buss ( 2011 ) identified a pattern of fearful behavior, dysregulated fear, characterized by high fear in low threat situations. This pattern of behavior predicted parent- and teacher-reported withdrawn/anxious behaviors in preschool and at kindergarten entry. The current study extended original findings and examined whether dysregulated fear predicted observed social wariness with adults and peers, and social anxiety symptoms at age 6. We also examined prosocial adjustment during kindergarten as a moderator of the link between dysregulated fear and social wariness. Consistent with predictions, children with greater dysregulated fear at age 2 were more socially wary of adults and unfamiliar peers in the laboratory, were reported as having more social anxiety symptoms, and were nearly 4 times more likely to manifest social anxiety symptoms than other children with elevated wariness in kindergarten. Results demonstrated stability in the dysregulated fear profile and increased risk for social anxiety symptom development. Dysregulated fear predicted more social wariness with unfamiliar peers only when children became less prosocial during kindergarten. Findings are discussed in relation to the utility of the dysregulated fear construct for specifying maladaptive trajectories of risk for anxiety disorder development.
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Self-reported dietary intake of youth with recent onset of type 2 diabetes: results from the TODAY study.
J Acad Nutr Diet
PUBLISHED: 02-27-2013
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Despite the widely recognized importance of diet in managing diabetes, few studies have documented usual dietary intake in young people with type 2 diabetes. The objectives of our study were to assess dietary intake among a large, ethnically diverse cohort of young people with type 2 diabetes and compare intake to current recommendations. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study is a multicenter randomized clinical trial of 699 youth aged 10 to 17 years. At baseline, following a run-in period that included standard diabetes education, diet was assessed using a food frequency questionnaire between 2004 and 2009. Analysis of variance and nonparametric tests were used to compare mean and median nutrient intakes; logistic regression was used to compare the odds of meeting predefined dietary intake recommendation cutpoints between subgroups of age, sex, and race-ethnicity. Percent of energy from saturated fat was consistently 13% to 14% across all subgroups-substantially exceeding national recommendations. Overall, only 12% of youth met Healthy People 2010 guidelines for intake of <10% of energy from saturated fat and only 1% of youth met American Diabetes Association recommendations for intake of <7% of energy from saturated fat. Dietary intake fell substantially below other Healthy People 2010 targets; only 3% met calcium intake goals, 11% met fruit consumption goals, 5% met vegetable consumption goals, and 67% met grain intake goals. Overall, dietary intake in this large cohort of young people with type 2 diabetes fell substantially short of recommendations, in ways that were consistent by sex, age, and race-ethnicity. The data suggest a critical need for better approaches to improve dietary intake of these young people.
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Sedentary behavior and physical activity in youth with recent onset of type 2 diabetes.
Pediatrics
PUBLISHED: 02-11-2013
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With the rise of type 2 diabetes in youth, it is critical to investigate factors such as physical activity (PA) and time spent sedentary that may be contributing to this public health problem. This article describes PA and sedentary time in a large cohort of youth with type 2 diabetes and compares these levels with other large-scale investigations.
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Fructose intake and cardiovascular risk factors in youth with type 1 diabetes: SEARCH for diabetes in youth study.
Diabetes Res. Clin. Pract.
PUBLISHED: 02-01-2013
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High consumption of dietary fructose has been shown to contribute to dyslipidemia and elevated blood pressure in adults, but there are few data in youth, particularly those at greater risk of cardiovascular disease (CVD). The aim of this study was to examine the association between fructose intake and CVD risk factors in a diverse population of youth with type 1 diabetes (T1D).
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Dnmt3b is a haploinsufficient tumor suppressor gene in Myc-induced lymphomagenesis.
Blood
PUBLISHED: 01-11-2013
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The drivers of abnormal DNA methylation in human cancers include widespread aberrant splicing of the DNMT3B gene, producing abnormal transcripts that encode truncated proteins that may act as dominant negative isoforms. To test whether reduced Dnmt3b dosage can alter tumorigenesis, we bred Dnmt3b(+/-) mice to Eµ-Myc mice, a mouse model susceptible to B-cell lymphomas. Eµ-Myc/Dnmt3b(+/-) mice showed a dramatic acceleration of lymphomagenesis, greater even than that observed in Eµ-Myc mice that express a truncated DNMT3B isoform found in human tumors, DNMT3B7. This finding indicates that Dnmt3b can act as a haploinsufficient tumor suppressor gene. Although reduction in both Dnmt3b dosage and expression of DNMT3B7 within the Eµ-Myc system had similar effects on tumorigenesis and DNA hypermethylation, different molecular mechanisms appear to underlie these changes. This study offers insight into how de novo DNA methyltransferases function as tumor suppressors and the sensitivity of Myc-induced lymphomas to DNA methylation.
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Rapid healing of femoral defects in rats with low dose sustained BMP2 expression from PEGDA hydrogel microspheres.
J. Orthop. Res.
PUBLISHED: 01-07-2013
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Current strategies for bone regeneration after traumatic injury often fail to provide adequate healing and integration. Here, we combined the poly (ethylene glycol) diacrylate (PEGDA) hydrogel with allogeneic "carrier" cells transduced with an adenovirus expressing BMP2. The system is unique in that the biomaterial encapsulates the cells, shielding them and thus suppressing destructive inflammatory processes. Using this system, complete healing of a 5?mm-long femur defect in a rat model occurs in under 3 weeks, through secretion of 100-fold lower levels of protein as compared to doses of recombinant BMP2 protein used in studies which lead to healing in 2-3 months. New bone formation was evaluated radiographically, histologically, and biomechanically at 2, 3, 6, 9, and 12 weeks after surgery. Rapid bone formation bridged the defect area and reliably integrated into the adjacent skeletal bone as early as 2 weeks. At 3 weeks, biomechanical analysis showed the new bone to possess 79% of torsional strength of the intact contralateral femur. Histological evaluation showed normal bone healing, with no infiltration of inflammatory cells with the bone being stable approximately 1 year later. We propose that these osteoinductive microspheres offer a more efficacious and safer clinical option over the use of rhBMP2.
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