Serum uric acid levels on admission and prognosis of acute coronary syndrome: a bi-institutional report

Objective: This study aimed to determine the association between the baseline serum uric acid (SUA) level and the short-term outcomes of patients with acute coronary syndrome (ACS). Methods: In this retrospective, bi-institutional study, patients with a diagnosis of ACS were recruited and followed-up for 30 days regarding the development of major adverse cardiovascular and cerebrovascular events (MACCEs). The associations between the SUA level upon admission and cardiovascular morbidities and patient prognosis were examined using univariate and multivariate analyses. Results: A total of 145 patients with ACS, with a mean age of 67.5±12.2 years, were recruited in this study. The rates of cardiovascular risk factors were higher in patients with elevated SUA levels. A cumulative MACCE was reported in 42 (29%) patients (19.5% in normal individuals and 39.7% in patients with elevated SUA levels, respectively; P=0.007). Based on the receiver operating characteristic (ROC) curve analysis, an on-admission SUA level above 6.9 mg/dL could discriminate patients with MACCE from those without MACCE during 30 days of follow-up (AUC=0.637; 95% CI: 0.553–0.715), with 64.3% sensitivity and 66% specificity. Based on multivariate logistic regression analysis, an elevated SUA level was associated with an increased risk of MACCE (odds ratio, 15.353; 95% CI: 2.026–116.328). Conclusion: In patients with ACS, an elevated baseline SUA level was associated with a higher prevalence of cardiovascular risk factors and morbidities, as well as an increased risk of MACCE in a short-term follow-up.&nbsp

Three Novel Mutations in Iranian Patients with Tay-Sachs Disease

ABSTRACT Background: Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. Methods: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. Results: Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. Conclusion: In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations

Three Novel Mutations in Iranian Patients with Tay-Sachs Disease

ABSTRACT Background: Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. Methods: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. Results: Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. Conclusion: In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations

Ectopic high endothelial venules in pancreatic ductal adenocarcinoma: A unique site for targeted delivery.

BACKGROUND: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79. METHODS: Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC. FINDINGS: The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was more robust than non-conjugated NPs. Treatment with MECA79-Taxol-NPs augmented the delivery of Paclitaxel (Taxol) to the tumor site and significantly reduced the tumor size. This effect was associated with a higher apoptosis rate of PDAC cells and reduced vascularization within the tumor. INTERPRETATION: Targeting the HEVs of PDAC using MECA79-NPs could lay the ground for the localized delivery of a wide variety of drugs including chemotherapeutic agents. FUND: National Institutes of Health (NIH) grants: T32-EB016652 (B·B.), NIH Cancer Core Grant CA034196 (L.D.S.), National Institute of Allergy and Infectious Diseases grants R01-AI126596 and R01-HL141815 (R.A.)

Study of Sperm Chromatin in Infertile Men with Globozoospermia: A Systematic Review Article

Background and Aim: Globozoospermia is a severe sperm morphological abnormality in men that characterized by round-headed spermatozoa with low or absence acrosome structure in their sperm samples. In these men, high level of DNA damage and abnormal chromatin packaging also were reported. These deficiencies can consider as the main etiologies of infertility in these infertile men. The aim of this article is to study the sperm chromatin structure in infertile men with globozoospermia. Materials and Methods: In this systematic review article, 77 articles related to protamine deficiency, DNA damage, aneuploidy in globozoospermic men were collected via data bases such as PubMed, Google Scholar, Scopus since 1971-2017. Ethical Considerations: This study with research ethics code IR.ACECR.ROYAN.REC.1396.204 have been approved at research ethics committee of Royan Institute. Findings: Mean percentage of sperm DNA fragmentation and protamine deficiency were significantly higher in infertile men with globozoospermia compared to fertile men. While, the results of chromosome aneuploidy were controversial in infertile men with globozoospermia within studies. Conclusion: In addition to abnormal acrosome formation, as main etiology of failed fertilization, in infertile men with globozoospermia, high level of sperm abnormal chromatin packaging and DNA damage can be also involved in this phenomenon. Therefore, antioxidant therapy before intra-cytoplasmic sperm injection technique were suggested for these individuals to minimize sperm chromatin damage

Relationship between the Position of the Mandibular Third Molar with Different Vertical Skeletal Dimensions on the Panoramic Images in Patients Referred to Isfahan (Khorasgan) University Dental School

Due to the increased prevalence of third molar impaction and the complications and existence of disagreements regarding the predicting factors for the impaction of this tooth, the aim of this study was to evaluate the relationship between the position of the mandibular third molar with different vertical skeletal dimensions on the panoramic images.Materials & Methods:This cross sectional study was carried out on lateral cephalogram and orthopantomogram records of 130 orthodontic patients visiting to Isfahan (Khorasgan) University Dental School. Age range of the sample was 20-35 years. Various facial forms were determined with mandibular plane angle (SN-GoGn), jarabak index and Y-axis; S-GN–Frankfort plane. Beta angle; which is the angle between intersecting long axis of mandibular second molar and mandibular third molar was measured to determine the angle of eruption of mandibular third molar. Eruption pattern was classified as per Pell & Gregory and winter’s system. The data were analyzed by Chi-square test (p value < 0.05).Results:There was a significant difference in the frequency distribution of growth pattern on the left side of the jaw (p value = 0.048). There was no significant difference in the frequency distribution of the eruption pattern in the right side of the jaw (p value = 0.11).There was no significant difference in the frequency distribution of eruption surface in the right face between different facial forms (p value = 0.49) But on the left side of the jaw there was a significant difference between the three facial forms (p value = 0.049). Frequency distribution of mandibular third molar impaction was significantly different between the three facial forms (p value = 0.03). There was no significant difference between the three facial forms in terms of frequency of eruption angle in the right side of the jaw (p value = 0.25) and also in the left side of the jaw (p value = 0.15).Conclusion:The incidence of impaction was significantly more in patients with long face than in other two groups. The prevalence of surface and pattern of third molar eruption in only one side of jaw was significantly different between the three facial forms. There was no significant difference between the frequency of angle of eruption and facial skeletal types in both jaw

Expansion of umbilical cord blood hematopoietic stem cell on biocompatible nanofiber scaffolds: brief report

Background: Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach in treatment of hematologic malignancies and incompatibility of bone marrow. Umbilical cord blood (UCB) known as an alternative for hematopoietic stem/ progenitor cells (HPSC) for in allogenic transplantation. The main hindrance in application of HPSC derived from umbilical cord blood is the low volume of collected samples. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. Synthetic biomaterials such as nanofibers is used to produce synthetic niches. The aim of this study was the ex vivo expansion of hematopoietic stem cells on biocompatible nanofiber scaffolds. Methods: This study was done at Tarbiat Modares University from November 2012 to June 2013 and was a research study. Umbilical cord blood CD133+ hematopoietic stem cells were separated using MidiMacs (positive selection) system by means of monocolonal antibody (microbeads) CD133. Flow cytometry was used to assess the purity of cells. Cell culture was done on plate (2 Dimensional) and fibronectin conjougated polyether sulfone nanofiber scaffold (3 Dimensional). Colony assay test was used to asses the ability of colonization of cells. Results: Cell count analysis revealed the expansion of hematopoietic stem cells in cell culture plate (2D environment) and on nanofiber scaffold (3D environment) after 2 weeks. Expansion of cells in 2D environment was greater than 3D condition. Colony assay test revealed that the colonization ability of cells decreased after 2 weeks, but this decrease was lower in scaffold culture than plate culture. Conclusion: This study demonstrated that umbilical cord blood CD133+ hematopoietic stem cells can expand on fibronectin conjugated polyether sulfone scaffold and we can use this system for expanding of cells in vitro situation

Effect of The Receptor Activator of Nuclear Factor кB and RANK Ligand on In Vitro Differentiation of Cord Blood CD133+ Hematopoietic Stem Cells to Osteoclasts

Objective: Receptor activator of nuclear factor-kappa B ligand (RANKL) appears to be an osteoclast-activating factor, bearing an important role in the pathogenesis of multiple myeloma. Some studies demonstrated that U-266 myeloma cell line and primary myeloma cells expressed RANK and RANKL. It had been reported that the expression of myeloid and monocytoid markers was increased by co-culturing myeloma cells with hematopoietic stem cells (HSCs). This study also attempted to show the molecular mechanism of RANK and RANKL on differentiation capability of human cord blood HSC to osteoclast, as well as expression of calcitonin receptor (CTR) on cord blood HSC surface. Materials and Methods: In this experimental study, CD133+ hematopoietic stem cells were isolated from umbilical cord blood and cultured in the presence of macrophage colony-stimulating factor (M-CSF) and RANKL. Osteoclast differentiation was characterized by using tartrate-resistant acid phosphatase (TRAP) staining, giemsa staining, immunophenotyping, and reverse transcription-polymerase chain reaction (RT-PCR) assay for specific genes. Results: Hematopoietic stem cells expressed RANK before and after differentiation into osteoclast. Compared to control group, flow cytometric results showed an increased expression of RANK after differentiation. Expression of CTR mRNA showed TRAP reaction was positive in some differentiated cells, including osteoclast cells. Conclusion: Presence of RANKL and M-CSF in bone marrow could induce HSCs differentiation into osteoclast