Mismanagement of Phenylketonuria: An Underlying Cause of Kwashiorkor

ObjectiveToo much restriction of dietary proteins can cause severe protein malnutrition,which can occur in adjusting the diet for some kinds of aminoacidopathies, urea cycle disorder and organic academia. This report presents the case of a 1.5-year-old boy with history of phenylketonuria with a three weeks history of erythematous scaly plaques and edema of his extremities; he had a history of similar skin manifestations three months earlier that resolved spontaneously. The patient had been on very restricted phenylalanine diet. Diagnosed with Kwashiorkor, a phenylalanine level of 0.4 mg/dl, the child was hospitalized and put on a special diet and given the appropriate antibiotic; after a few days of treatment his condition  improved. We underscore the importance of education for those considering prescription of diet restriction and emphasize the regulation of balanced diet in such patients.

Pfeiffer Type I Syndrome: A Genetically Proven Case Report

ObjectivePfeiffer Syndrome is as rare as Apert syndrome in the Western population. This condition is very rare in the Asian population. At the best of our knowledge this is the first genetically proven case report from Iran. The authors report with a review of literature, the case of a infant with Pfeiffer syndrome, manifested by Lacunar skull, ventriculomegaly, bicoronal craniosynostosis,frontal bossing, shallow orbits, parrot-like nose, umbilical hernia, broad and medially deviated great toes.

Freeman-Sheldon Syndrome: A Case Report

ObjectiveThe Freeman-Sheldon syndrome is a rare congenital myopathy and dysplasia, in which fibrotic contractures of the facial muscles result in the characteristic "whistling face". Difficulties with intubation may be attributed in part to microstomia and micrognathia. In addition to other deformities, limb myopathy results in ulnar flexion contractures of the hand and equinovarus/valgus deformities of the feet. Intravenous access may be difficult because of limb deformities and thickened subcutaneous tissues. Limbs may be encased in plaster casts or splints limiting the available sites for venepuncture. The authors report with a review of literature the case of an infant with Freeman-Sheldon syndrome, which his characteristics was mentioned above.

Molecular mechanisms of vitamin D plus Bisphenol A effects on adipogenesis in human adipose-derived mesenchymal stem cells

Background: Obesity is considered a major health concern and mounting evidence suggests that the exposure to environmental endocrine disruptors, including Bisphenol-A (BPA), may enhance the risk to develop the disease. Moreover, growing documents propose that the vitamin D may contribute to adipogenic signaling and lipid accumulation during adipocyte differentiation. We focused on the molecular mechanism of vitamin D and BPA in human adipose-derived mesenchymal stem cells (hADMSCs) which vitamin D and BPA may influence adipose tissue development and function. Methods: Human adipose-derived mesenchymal stem cells were cultured for 14 days in lipogenic differentiation media containing continuous concentrations of vitamin D plus BPA (0.1 nM or 10 nM). The expression of adipogenic markers including the peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBP α) CCAAT-enhancer-binding protein β (C/EBP β), fatty acid synthase (FASN), lipoprotein lipase (LPL), sterol regulatory element-binding protein-1c (SREBP1c), insulin-induced gene-2 (INSIG2), vitamin D receptor (VDR), estrogen receptor-beta (ER-β), fatty acid-binding protein-4 (FABP4), and glucose transporter-4 (GLUT4) was measured using Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Lipid accumulation was visualized with staining with Oil Red O. Results: In the morphological assessment of mesenchymal stem cells treated with a concentration of 10 nM vitamin D plus BPA, more lipid accumulations were observed in comparison with the group with 0.1 nM concentration. Treatment of hADMSCs with vitamin D plus BPA (0.1 nM) significantly inhibited the induction of PPARγ, C/EBP β, C/EBP α, and FASN related to adipocyte differentiation and development. However, the exposure of cells to the concentration of 10 nM vitamin D plus BPA induced the expression of these genes associated to the adipogenesis. The remarkable increase in the level of SREBP1c was associated to the suppression of INSIG2 in treated preadipocytes with 10 nM vitamin D plus BPA. Our findings showed that the expression of VDR, ERβ, GLUT4, and FABP4 were upregulated through differentiation with the highest concentrations in 0.1 nM vitamin D plus BPA group for VDR, ERβ, and GLUT4. Conclusions: Vitamin D plus BPA at concentration of 10 nM boosted the adipogenesis during the critical stages of adipocytes development, whereas it seems to inhibit this process at concentration of 0.1 nM. © 2021, The Author(s)

Correction to: 1,25-Dihydroxyvitamin D3 modulates adipogenesis of human adipose-derived mesenchymal stem cells dose-dependently (Nutrition & Metabolism, (2021), 18, 1, (29), 10.1186/s12986-021-00561-4)

Following publication of the original article 1, the authors identified an error in the affiliation of Dr. Mehdi Hedayati. © 2021, The Author(s)

Bisphenol A enhances adipogenic signaling pathways in human mesenchymal stem cells

Background: The endocrine disruptor Bisphenol-A (BPA), has been involved in dysregulating adipose tissue development and increasing the risk of obesity. The objective of this experiment was to investigate whether treatment of human mesenchymal stem cells with BPA could modulate adipogenesis and adipocyte differentiation. Methods: In this experimental study, the human adipose-derived mesenchymal stem cells (hASCs) were cultured for 2 weeks with continuous exposure to 10- 10 M or 10- 8 M concentrations of BPA. The extent of triglyceride accumulation was visualized by Oil Red O staining. To evaluate BPA effect on the expression levels of key adipogenic trascripotion factors and proteins, we used Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and ELISA. Results: The results presented a dose-dependent triglyceride accumulation in treated cells with BPA. Additionally, we observed that BPA induced transcription of the Peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT-enhancer-binding protein-alpha (C/EBPα), CCAAT-enhancer-binding protein-beta (C/EBPβ), sterol regulatory element-binding protein-1c (SREBP1c), Fatty acid synthase (FASN), and lipoprotein lipase (LPL); BPA suppressed the expression of Fatty acid binding protein-4 (FABP4) and Estrogen receptor-beta (ERβ). Conclusions: Our findings supported the hypothesis that BPA enhances adipogenic differentiation thereby may play a role in development of obesity and dysregulation of metabolic homoeostasis. © 2020 The Author(s)

1,25-Dihydroxyvitamin D3 modulates adipogenesis of human adipose-derived mesenchymal stem cells dose-dependently

Purpose: 1,25-dihydroxyvitamin D3 may regulate adipogenesis in adipocytes in-vitro, but little is known about possible molecular mechanisms related to the inhibitory effect of 1,25-dihydroxyvitamin D3 on adipogenesis in humans� adipose tissue. Methodology: In this study, human adipose-derived mesenchymal stem cells (hASCs) were cultured for 14 days in adipogenic differentiation media containing concentrations of 1,25-dihydroxyvitamin D3 (10�10�10�8 M). The extent of adipogenic differentiation in ASCs was assessed by Oil Red O staining and quantitative polymerase chain reaction (PCR) to determine expression levels of key adipogenic markers. Results: Our results showed that vitamin D receptor (VDR), as a mediator of most actions of 1,25-dihydroxyvitamin D3, glucose trasporter-4 (GLUT4),and fatty acid binding protein-4 (FABP4) was expressed in vitamin D-treated hASCs. However, the protein level of these markers was lower than the control group. Treatment of human preadipocytes with 1,25-dihydroxyvitamin D3 significantly altered expression of adipogenic markers and triglyceride accumulation in a dose-dependent manner. 1,25-dihydroxyvitamin D3 at concentration of 10�8 M enhanced expression of sterol regulatory element-binding protein-1c (SREBP1c), CCAAT-enhancer-binding protein-β (C/EBPβ), a mitotic clonal expansion, peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FASN), a marker of de novo lipogenesis,and lipoprotein lipase (LPL). Conclusion: Our findings revealed that 1,25-dihydroxyvitamin D3 may provoke adipocyte development in critical periods of adipogenesis at concentration of 10�8 M, thereby leading to a greater risk of obesity in adulthood and an augmented risk of obesity-related diseases including diabetes, cardiovascular diseases, and some cancers. © 2021, The Author(s)

Long-term outcome of posterior spinal fusion for the correction of adolescent idiopathic scoliosis

Background: Adolescent idiopathic scoliosis (AIS) is the most common form of idiopathic scoliosis, and surgery is considered as one of the therapeutic options. However, it is associated with a variety of irreversible complications, in spite of the benefits it provides. Here, we evaluated the long-term outcome of posterior spinal fusion (PSF) of AIS to shed more light on the consequences of this surgery. Methods: In a cross-sectional study, a total of 42 AIS patients who underwent PSF surgery were radiographically and clinically inspected for the potential post-operative complications. Radiographic assessments included the device failure, union status, and vertebral tilt below the site of fusion. Clinical outcomes were evaluated using the Oswestry disability index (ODI) and visual analogue scale (VAS). Results: The mean age of the surgery was 14.4 ± 5.1 years. The mean follow-up of the patients was 5.6 ± 3.2 years. Complete union was observed in all patients, and no device failure was noticed. Pre- and post-operative vertebral tilt below the site of fusion were 11.12° ± 7.92° and 6.21° ± 5.73°, respectively (p < 0.001). The mean post-operative ODI was 16.7 ± 9.8. The mean post-operative VAS was 2.1 ± 0.7. ODI value was positively correlated with follow-up periods (p = 0.04, r = 0.471). New degenerative disc disease (DDD) was observed in 6 out of 37 (16) patients. Conclusion: In spite of the efficacy and safety of PSF surgery of AIS, it might result in irreversible complications such as DDD. Moreover, the amount of post-operative disability might increase over the time and should be discussed with the patients. © 2018 The Author(s)

Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi�Bickel Syndrome

Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG�s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG�s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset. © Copyright © 2021 Eghbali, Fatemi, Salehpour, Abiri, Saei, Talebi, Olyaei, Yassaee and Modarressi

Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin

C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1–5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age