A Pulsatile Flow System to Engineer Aneurysm and Atherosclerosis Mimetic Extracellular Matrix.

Alterations of blood flow patterns strongly correlate with arterial wall diseases such as atherosclerosis and aneurysm. Here, a simple, pumpless, close-loop, easy-to-replicate, and miniaturized flow device is introduced to concurrently expose 3D engineered vascular smooth muscle tissues to high-velocity pulsatile flow versus low-velocity disturbed flow conditions. Two flow regimes are distinguished, one that promotes elastin and impairs collagen I assembly, while the other impairs elastin and promotes collagen assembly. This latter extracellular matrix (ECM) composition shares characteristics with aneurysmal or atherosclerotic tissue phenotypes, thus recapitulating crucial hallmarks of flow-induced tissue morphogenesis in vessel walls. It is shown that the mRNA levels of ECM of collagens and elastin are not affected by the differential flow conditions. Instead, the differential gene expression of matrix metalloproteinase (MMP) and their inhibitors (TIMPs) is flow-dependent, and thus drives the alterations in ECM composition. In further support, treatment with doxycycline, an MMP inhibitor and a clinically used drug to treat vascular diseases, halts the effect of low-velocity flow on the ECM remodeling. This illustrates how the platform can be exploited for drug efficacy studies by providing crucial mechanistic insights into how different therapeutic interventions may affect tissue growth and ECM assembly.

Effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in children with metabolic syndrome: a triple-masked controlled trial / Efeitos da suplementação de vitamina D sobre a resistência à insulina e fatores de risco cardiometabólico em crianças com síndrome metabólica: ensaio clínico triplo-cego controlado

OBJECTIVE: this triple-masked controlled trial aimed to assess the effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in obese children and adolescents. METHODS: the study comprised 50 participants, aged 10 to16 years, who were randomly assigned into two groups of equal number. In this 12-week trial, one group received oral vitamin D (300,000 IU) and the other group received placebo. Cardiometabolic risk factors, insulin resistance, and a continuous value of metabolic syndrome (cMetS) were determined. Statistical analysis was conducted after adjustment for covariate interactions. RESULTS: overall, 21 patients in the vitamin D group and 22 in the placebo group completed the trial. No significant difference was observed in the baseline characteristics of the two groups. After the trial, in the vitamin D group, serum insulin and triglyceride concentrations, as well as HOM -IR and C-MetS decreased significantly, both when compared with the baseline and with the placebo group. No significant difference was observed when comparing total cholesterol, LDL-C, HDL-C, fasting blood glucose, and blood pressure. CONCLUSION: the present findings support the favorable effects of vitamin D supplementation on reducing insulin resistance and cardiometabolic risk factors in obese children. .

Este ensaio clínico triplo-cego controlado visa investigar os efeitos da suplementação de vitamina D sobre a resistência à insulina e os fatores de risco cardiometabólico em crianças e adolescentes obesos. O estudo contou com 50 participantes com idade entre 10 e 16 anos, aleatoriamente divididos em dois grupos de igual número de participantes. Neste ensaio clínico de 12 semanas, um grupo recebeu vitamina D via oral (300000 IU) e o outro grupo recebeu placebo. Foram determinados fatores de risco cardiometabólico, resistência à insulina e valor contínuo da síndrome metabólica (cMetS). A análise estatística foi conduzida após o ajuste das interações covariáveis. No todo, 21 pacientes no grupo vitamina D e 22 no grupo placebo concluíram o ensaio clínico. Nenhuma diferença significativa foi encontrada nas características de base dos dois grupos estudados. Após o ensaio clinico, no grupo vitamina D, as concentrações séricas de insulina e triglicerídeos, bem como HOMA-RI e cMetS caíram significativamente em comparação ao início do estudo; e também em comparação ao grupo placebo. Nenhuma diferença significativa foi vista ao comparar o colesterol total, LDL-C, HDL-C, glicemia de jejum e pressão sanguínea. Nossas conclusões indicam efeitos favoráveis da suplementação de vitamina D sobre a redução da resistência à insulina e de fatores de risco cardiometabólico em crianças obesas.

Effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in children with metabolic syndrome: a triple-masked controlled trial.

OBJECTIVE: This triple-masked controlled trial aimed to assess the effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in obese children and adolescents. METHODS: The study comprised 50 participants, aged 10 to 16 years, who were randomly assigned into two groups of equal number. In this 12-week trial, one group received oral vitamin D (300,000 IU) and the other group received placebo. Cardiometabolic risk factors, insulin resistance, and a continuous value of metabolic syndrome (cMetS) were determined. Statistical analysis was conducted after adjustment for covariate interactions. RESULTS: Overall, 21 patients in the vitamin D group and 22 in the placebo group completed the trial. No significant difference was observed in the baseline characteristics of the two groups. After the trial, in the vitamin D group, serum insulin and triglyceride concentrations, as well as HOM -IR and C-MetS decreased significantly, both when compared with the baseline and with the placebo group. No significant difference was observed when comparing total cholesterol, LDL-C, HDL-C, fasting blood glucose, and blood pressure. CONCLUSION: The present findings support the favorable effects of vitamin D supplementation on reducing insulin resistance and cardiometabolic risk factors in obese children.

Vitamin D status of 6- to 7-year-old children living in Isfahan, Iran.

INTRODUCTION: Vitamin D is essential for the maintenance of good health, and vitamin D deficiency has been reported from many countries, including those with a lot of sunshine. This study was conducted to evaluate the vitamin D status in healthy 6- to 7-year-old children in Isfahan, Iran. MATERIAL AND METHODS: Five hundred and thirteen healthy children were enrolled. Serum PTH and 25-hydroxyvitamin D (25-OHD) were measured. Dietary vitamin D intake, duration of daily sunlight exposure, and percentage of exposed body surface area were determined. 25-OHD levels < 20 ng/mL and < 10 ng/mL were defined as mild and severe vitamin D deficiency, respectively. The ROC curve was utilized to obtain a local cut-off point of vitamin D deficiency. RESULTS: 25-OHD was < 20 ng/mL in 3% and < 33 ng/mL (local cut-off point of vitamin D deficiency) in 26% of subjects. Duration of sunlight exposure and daily intake of vitamin D had significant effects on serum level of vitamin D. CONCLUSIONS: A high prevalence of vitamin D deficiency in Isfahan children was observed in this study. Improvements in duration of sunlight exposure and daily intake of vitamin D can prevent vitamin D deficiency in these children.

Granulosa cell tumor in a six-year-old girl presented as precocious puberty.

Ovarian sex cord-stromal tumors, including granulose cell tumors (GCTs), are a group of neoplasms that occur rarely, especially in children. Only 0.1 percent of all ovarian tumors and 4-5 percent of GCTs occur in children. The most common presentation of these tumors in children is precocious puberty. We report a 6 years old girl with isosexual precocity, presented as premature thelarche and vaginal bleeding. Ultrasonography of pelvis showed a hypoechoic solid mass of left ovary.Microscopic features of the resected mass were characteristic of juvenile GCT. Although in most of girls with precocious puberty, the etiology is idiopathic, important causes, such as ovarian tumors must be considered.