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.

Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells

The POU domain transcription factor OCT4 is a key regulator of pluripotency in the early mammalian embryo and is highly expressed in the inner cell mass of the blastocyst. Consistent with its essential role in maintaining pluripotency, Oct4 expression is rapidly downregulated during formation of the trophoblast lineage. To enhance our understanding of the molecular basis of this differentiation event in humans, we used a functional genomics approach involving RNA interference-mediated suppression of OCT4 function in a human ESC line and analysis of the resulting transcriptional profiles to identify OCT4-dependent genes in human cells. We detected altered expression of >1,000 genes, including targets regulated directly by OCT4 either positively (NANOG, SOX2, REX1, LEFTB, LEFTA/EBAF DPPA4, THY1, and TDGF1) or negatively (CDX2, EOMES, BMP4, TBX18, Brachyury [T], DKK1, HLX1, GATA6, ID2, and DLX5), as well as targets for the OCT4-associated stem cell regulators SOX2 and NANOG. Our data set includes regulators of ACTIVIN, BMP, fibroblast growth factor, and WNT signaling. These pathways are implicated in regulating human ESC differentiation and therefore further validate the results of our analysis. In addition, we identified a number of differentially expressed genes that are involved in epigenetics, chromatin remodeling, apoptosis, and metabolism that may point to underlying molecular mechanisms that regulate pluripotency and trophoblast differentiation in humans. Significant concordance between this data set and previous comparisons between inner cell mass and trophectoderm in human embryos indicates that the study of human ESC differentiation in vitro represents a useful model of early embryonic differentiation in humans

Particulate number emissions during cold-start with diesel and biofuels: A special focus on particle size distribution

The share of biofuels in the transportation sector is increasing. Previous studies revealed that the use of biofuels decreases the size of particles (which is linked to an increase in particulate toxicity). Current emission regulations do not consider small particles (sub-23 nm); however, there is a focus in future emissions regulations on small particles. These and the fact that within cold-start emissions are higher than during the warmed-up operation highlight the importance of a research that studies particulate matter emissions during cold-start. This research investigates the influence of biofuel on PN and PM concentration, size distribution, median diameter and cumulative share at different size ranges (including sub-23 nm and nucleation mode) during cold-start and warm-up operations using diesel and 10, 15 and 20% mixture (coconut biofuel blended with diesel). During cold-start, between 19 and 29% of total PN and less than 0.8% of total PM were related to the nucleation mode (sub-50 nm). Out of that, the share of sub-23 nm was up to 9% for PN while less than 0.02% for PM. By using biofuel, PN increased between 27 and 57% at cold-start; while, the increase was between 4 and 19% during hot-operation. The median diameter also decreased at cold-start and the nucleation mode particles (including sub-23 nm particles) significantly increased. This is an important observation because using biofuel can have a more adverse impact within cold-start period which is inevitable in most vehicles’ daily driving schedules.<br/

Validation of the severity index by cardiac catheterization and Doppler echocardiography in patients with aortic sclerosis and stenosis

The severity index is a new echocardiographic measure that is thought to be an accurate indicator of aortic leaflet pathology in patients with AS. However, it has not been validated against cardiac catheterization or Doppler echocardiographic measures of AS severity nor has it been applied to patients with aortic sclerosis. The purposes of this study were to compare the severity index to invasive hemodynamics and Doppler echocardiography across the spectrum of calcific aortic valve disease, including aortic sclerosis and AS. 48 patients with aortic sclerosis and AS undergoing echocardiography and cardiac catheterization comprised the study population. The aortic valve leaflets were assessed for mobility (scale 1 to 6) and calcification (scale 1 to 4) and the severity index was calculated as the sum of the mobility and calcification scores according to the methods of Bahler et al. The severity index increased with increasing severity of aortic valve disease; the severity indices for patients with aortic sclerosis, mild to moderate AS and severe AS were 3.38 ± 1.06, 6.45 ± 2.16 and 8.38 ± 1.41, respectively. The aortic jet velocity by echocardiography and the square root of the maximum aortic valve gradient by cardiac catheterization correlated well with the severity index (r = 0.84, p < 0.0001; r = 0.84, p < 0.0001, respectively). These results confirm that the severity index correlates with hemodynamic severity of aortic valve disease and may prove to be a useful measure in patients with aortic sclerosis and AS

Evaluation of lymphocyte transformation test results in patients with delayed hypersensitivity reactions following the use of anticonvulsant drugs

Background/Aim: Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Methods: Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Results: Of 24 patients in the test group, 14 (58.3) had positive LTT results and 10 (41.7) had negative results. Among patients in the control group, 1 (4.2) had a positive LTT result and 23 (95.8) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT were 58.4, 95.8, 93.3 and 69.9, respectively. Conclusions: Considering the significant difference in LTT results between the case and control groups in patients receiving carbamazepine and phenytoin, and not observing such a difference in patients receiving phenobarbital and lamotrigine, LTT results are more valuable for the diagnosis of hypersensitivity reactions following the administration of carbamazepine and phenytoin. The LTT has good specificity but low sensitivity for the diagnosis of drug hypersensitivity reactions. © 2016 S. Karger AG, Basel

Susceptibility to mycobacterial disease due to mutations in IL-12R beta 1 in three Iranian patients

Immunogenetics and cellular immunology of bacterial infectious disease

Susceptibility to mycobacterial disease due to mutations in IL-12Rβ1 in three Iranian patients

In the last decade, autosomal recessive interleukin-12 receptor β1 (IL-12Rβ1) deficiency, the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD), has been diagnosed in a few children and adults with severe tuberculosis in Iran. Here, we report three cases referred to the Immunology, Asthma and Allergy ward at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD) at Masih Daneshvari Hospital from 2012 to 2017 with Mycobacterium tuberculosis and non-tuberculous mycobacteria infections due to defects in IL-12Rβ1 but with different clinical manifestations. All three were homozygous for either an IL-12Rβ1 missense or nonsense mutation that caused the IL-12Rβ1 protein not to be expressed on the cell membrane and completely abolished the cellular response to recombinant IL-12. Our findings suggest that the presence of IL-12Rβ1 deficiency should be determined in children with mycobacterial infections at least in countries with a high prevalence of parental consanguinity and in areas endemic for TB like Iran

Human Embryonic Stem Cells and Embryonal Carcinoma Cells Have Overlapping and Distinct Metabolic Signatures

While human embryonic stem cells (hESCs) and human embryonal carcinoma cells (hECCs) have been studied extensively at the levels of the genome, transcriptome, proteome and epigenome our knowledge of their corresponding metabolomes is limited. Here, we present the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry (GC-MS). Whilst some metabolites are common to both cell types, representing the self-renewal and house-keeping signatures, others were either higher (e.g., octadecenoic acid, glycerol-3-phosphate, 4-hydroxyproline) or lower (e.g., glutamic acid, mannitol, malic acid, GABA) in hESCs (H9) compared to hECCs (NTERA2), these represent cell type specific signatures. Further, our combined results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O2 while oxidative phosphorylation (OXPHOS) is impaired or even shut down. RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such as NDUFC1, UQCRB and COX, increase in TCA cycle activity and decreased lactate metabolism. These results shed light on the metabolite layer of pluripotent stem cells and could potentially establish novel metabolic markers of self renewal and pluripotency

Striking a Balance: Socioeconomic Development and Conservation in Grassland through Community-Based Zoning

The goal of preserving nature is often in conflict with economic development and the aspirations of the rural poor. Nowhere is this more striking than in native grasslands, which have been extensively converted until a mere fraction of their original extent remains. This is not surprising; grasslands flourish in places coveted by humans, primed for agriculture, plantations, and settlements that nearly always trump conservation efforts. The Umgano grassland conservation and poverty reduction project in KwaZulu-Natal Province, South Africa uses community-based spatial planning to balance the conversion of its lower-conservation value grasslands to a timber plantation, while conserving higher-value grasslands for heritage purposes and managed livestock grazing. Ten years after project launch, we measured the ecological and socioeconomic impacts of the project using Normalized Differential Vegetation Index remote sensing data and over 500 household interviews, as compared with similar non-conserved areas. Zoned management of the Umgano area had resulted in between 9% and 17% greater average peak production in the grassland areas compared to control sites. There was also a 21% gain in incomes for the roughly one hundred people employed by the forestry efforts, when compared to others in their village. Community-based spatial zoning is an overlooked tool for balancing conservation and development but may require, as we found in Umgano, certain critical factors including strong local leadership, an accountable financial management mechanism to distribute income, outside technical expertise for the zoning design, and community support