The association between TNP2 gene polymorphisms and Iranian infertile men with varicocele: A case-control study

Background: Numerous researches have provided great evidence that revealed the relationship between varicocele and sperm DNA damage. Objective: Because of the crucial role of nuclear transition proteins (TPs) in sperm DNA condensation and integrity, this case-control study was designed to study TNP2 gene nucleotide variations in Iranian patients with varicocele. Materials and Methods: PCR-SSCP and DNA sequencing were used to search for mutations in exons 1 & 2 of the TNP2 gene in 156 infertile patients with varicocele and 150 fertile men. Results: The results of sequencing showed three variants at positions c.301C > T (p.R101C), c.391C > T (p.R131 W), and g.IVS1-26G >C (rs8043625) of TNP2 gene. It was found that varicocele risk in men who have the CC genotype of g.IVS1-26G >C SNP is higher than those who don’t have these genotypes (according to Co-dominant model, Dominant model, Recessive model, and Over-dominant model). The haplotype-based analysis showed that (C/C/T) and (C/T/T) haplotypes were a risk factor of in patients with varicocele compared to controls (OR = 3.278, p = 0.000 and OR= 9.304, p = 0.038, respectively). Conclusion: Because of the significant difference in the genotype and allele frequencies of g.IVS1-26G >C SNP in the intronic region of TNP2 in patients with varicocele compared with controls and also because of the high conservation of this SNP position during evolution, this SNP may be involved in some important processes associated with the expression of this gene like mRNA splicing, but the exact mechanism is not clear

Lack of Pathogenic Mutation in the Human CAII Gene in an Individual Suffering Renal Tubular Acidosis

Renal tubular acidosis (RTA) is a rare genetic disorder. It has four clinical types, and type 3 demonstrates a mixed pattern of tubular dysfunction. The causative gene for type 3 RTA (CAII) is located on the 8q22 locus and encodes a protein called carbonic anhydrase II. In this study, we analyzed the entire exons and flanking regions of the CAII gene in a child suffering renal tubular acidosis with an autosomal recessive pattern that was diagnosed with type3 RTA. DNA was extracted from the blood sample of the patient and his parents by the salting out extraction method. The exons and flanking regions of the CAII gene were amplified using polymerase chain reaction (PCR). We performed exon direct sequencing by forward and reverse primers, which were designed by primer3 program. No mutation was found following the screening of the entire coding sequence of the CAII gene. It is likely that another gene might be involved in this case. In other words, other types of RTA have to be considered.Keywords: Renal Tubular Acidosis, distal, type 3; Gene; Polymerase Chain Reaction; Sequence Analysis, DNA

Validation of Urinary Glycosaminoglycans in Iranian patients with Mucopolysaccharidase type I: The effect of urine sedimentation characteristics

How to Cite This Article:Abdi M, Khatami Sh, Hakhamaneshi MS, Alaei MR, Azadi NA, Zamanfar D, Taghikhani M.Validation of Urinary Glycosaminiglycans in Iranian Patients with Mucopolysaccharidose Type I: The Effect of Urine Sedimentation Characteristics. Iran J Child Neurol. 2014; 8(4):39-45. AbstractObjectiveThe first line-screening test for mucopolysaccharidosis is based on measurement of urinary glycosaminoglycans. The most reliable test for measurement of urine glycosaminoglycans is the 1,9-dimethyleneblue colorimetric assay. Biological markers are affected by ethnical factors, for this reason, the World Health Organization recommends that the diagnostic test characteristics should be used to determine results for different populations. This study determines the diagnostic value of 1,9-dimethyleneblue tests for diagnosis of mucopolysaccharidosis type I patients in Iran.Materials & Methods In addition to routine urine analysis, the qualitative and quantitative measurements of urine glucosaminoglycans were performed with the Berry spot test and 1,9-dimethyleneblue assay. Diagnostic values of the tests were determined using the ROC curve.ResultsUrine total glycosaminoglycans were significantly higher in male subjects than in female subjects. Glycosaminoglycan concentration was markedly decreased in specimens with elevated white blood cell and epithelial cells count. Using a cut-off level of 10.37 mg/g creatinine, sensitivity, and specificity were 100% and 97.22%, respectively, for a 1,9-dimethyleneblue colorimetric assay.ConclusionUrine glycosaminoglycans concentration significantly differs in our studied population. In addition to determine diagnostic validity of the 1,9-dimethyleneblue test, our results demonstrate the usefulness of measuring glycosaminoglycans for early screening of mucopolysaccharidosis type I Iran. ReferencesJackson RL, Busch SJ, Cardin AD. Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiological reviews. 1991 Apr;71(2):481-539.Ghaderi S. The biochemistry base of mucopolysaccharidoses and approach to. Genetics in the 3rd millennium. [Educational]. 2006;4(1):711-22.Mizumoto S, Ikegawa S, Sugahara K. Human genetic disorders caused by mutations in genes encoding biosynthetic enzymes for sulfated glycosaminoglycans. The Journal of biological chemistry. 2013 Apr 19;288(16):10953-61.Salbach J, Rachner TD, Rauner M, Hempel U, Anderegg U, Franz S, et al. Regenerative potential of glycosaminoglycans for skin and bone. Journal of molecular medicine (Berlin, Germany). 2012 Jun;90(6):625-35.Coppa GV, Catassi C, Gabrielli O, Giorgi PL, Dall’Amico R, Naia S, et al. Clinical application of a new simple method for the identification of mucopolysaccharidoses. Helvetica paediatrica acta. 1987 Jun;42(5-6):419-23.Fuller M, Meikle PJ, Hopwood JJ. Glycosaminoglycan degradation fragments in mucopolysaccharidosis I. Glycobiology. 2004 May;14(5):443-50.Fuller M, Rozaklis T, Ramsay SL, Hopwood JJ, Meikle PJ. Disease-specific markers for the mucopolysaccharidoses. Pediatric research. 2004 Nov;56(5):733-8.Blau N, Duran M, Gibson K. Laboratory Guide to the Methods in Biochemical Genetics. First edition ed: Springer-Verlag Berlin Heidelberg; 2008. pp287-324.Dorfman A, Matalon R. The Hurler and Hunter syndromes. The American journal of medicine. 1969 Nov;47(5):691-707.Fratantoni JC, Hall CW, Neufeld EF. Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science (New York, NY. 1968 Nov 1;162(3853):570-2.Fratantoni JC, Hall CW, Neufeld EF. The defect in Hurler and Hunter syndromes. II. Deficiency of specific factors involved in mucopolysaccharide degradation. Proceedings of the National Academy of Sciences of the United States of America. 1969 Sep;64(1):360-6.Fratantoni JC, Neufeld EF, Uhlendorf BW, Jacobson CB. Intrauterine diagnosis of the hurler and hunter syndromes. The New England journal of medicine. 1969 Mar 27;280(13):686-8.Chamoles NA, Blanco MB, Gaggioli D, Casentini C. Hurler-like phenotype: enzymatic diagnosis in dried blood spots on filter paper. Clinical chemistry. 2001 Dec;47(12):2098-102.Nor A, Zabedah MY, Norsiah MD, Ngu LH, Suhaila AR. Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia. The Malaysian journal of pathology. 2010 Jun;32(1):35-42.De Muro P, Faedda R, Formato M, Re F, Satta A, Cherchi GM, et al. Urinary glycosaminoglycans in patients with systemic lupus erythematosus. Clinical and experimental rheumatology. 2001 Mar-Apr;19(2):125-30.Berry HK, Spinanger J. A paper spot test useful in study of Hurler’s syndrome. The Journal of laboratory and clinical medicine. 1960 Jan;55:136-8.Pennock CA, White F, Murphy D, Charles RG, Kerr H. Excess glycosaminoglycan excretion in infancy and childhood. Acta paediatrica Scandinavica. 1973 Sep;62(5):481-91.Berman ER, Vered J, Bach G. A reliable spot test for mucopolysaccharidoses. Clinical chemistry. 1971 Sep;17(9):886-90.Pennock CA. A review and selection of simple laboratory methods used for the study of glycosaminoglycan excretion and the diagnosis of the mucopolysaccharidoses. Journal of clinical pathology. 1976 Feb;29(2):111-23.Chan RW, Szeto CC. Advances in the clinical laboratory assessment of urinary sediment. Clinica chimica acta; international journal of clinical chemistry. 2004 Feb;340(1-2):67-78.Fogazzi GB, Garigali G. The clinical art and science of urine microscopy. Curr Opin Nephrol Hypertens. 2003 Nov;12(6):625-32.Berry HK. Screening for mucopolysaccharide disorders with the Berry spot test. Clinical biochemistry. 1987 Oct;20(5):365-71.de Jong JG, Hasselman JJ, van Landeghem AA, Vader HL, Wevers RA. The spot test is not a reliable screening procedure for mucopolysaccharidoses. Clinical chemistry. 1991 Apr;37(4):572-5.Mabe P, Valiente A, Soto V, Cornejo V, Raimann E. Evaluation of reliability for urine mucopolysaccharidosis screening by dimethylmethylene blue and Berry spot tests. Clinica chimica acta; international journal of clinical chemistry. 2004 Jul;345(1-2):135-40.Mahalingam K, Janani S, Priya S, Elango EM, Sundari RM. Diagnosis of mucopolysaccharidoses: how to avoid false positives and false negatives. Indian J Pediatr. 2004 Jan;71(1):29-32.de Jong JG, Wevers RA, Laarakkers C, Poorthuis BJ. Dimethyl methylene blue-based spectrophotometry of glycosaminoglycans in untreated urine: a rapid screening procedure for mucopolysaccharidoses. Clinical chemistry. 1989 Jul;35(7):1472-7.Panin G, Naia S, Dall’Amico R, Chiandetti L, Zachello F, Catassi C, et al. Simple spectrophotometric quantification of urinary excretion of glycosaminoglycan sulfates. Clinical chemistry. 1986 Nov;32(11):2073-6.Byers S, Rozaklis T, Brumfield LK, Ranieri E, Hopwood JJ. Glycosaminoglycan accumulation and excretion in the mucopolysaccharidoses: characterization and basis of a diagnostic test for MPS. Molecular genetics and metabolism. 1998 Dec;65(4):282-90.Carson NA, Neill DW. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Archives of disease in childhood. 1962 Oct;37:505-13.Huang KC, Sukegawa K, Orii T. Screening test for urinary glycosaminoglycans and differentiation of various mucopolysaccharidoses. Clinica chimica acta; international journal of clinical chemistry. 1985 Sep 30;151(2):147-56.Chih-Kuang C, Shuan-Pei L, Shyue-Jye L, Tuen-Jen W. MPS screening methods, the Berry spot and acid turbidity tests, cause a high incidence of false-negative results in sanfilippo and morquio syndromes. Journal of clinical laboratory analysis. 2002;16(5):253-8.Gallegos-Arreola MP, Machorro-Lazo MV, Flores-Martinez SE, Zuniga-Gonzalez GM, Figuera LE, Gonzalez-Noriega A, et al. Urinary glycosaminoglycan excretion in healthy subjects and in patients with mucopolysaccharidoses. Archives of medical research. 2000 Sep-Oct;31(5):505-10.Piraud M, Maire I, Mathieu M. Pitfalls of screening for mucopolysaccharidoses by the dimethylmethylene blue test. Clinical chemistry. 1993 Jan;39(1):163-4.Whitley CB, Spielmann RC, Herro G, Teragawa SS. Urinary glycosaminoglycan excretion quantified by an automated semimicro method in specimens conveniently transported from around the globe. Molecular genetics and metabolism. 2002 Jan;75(1):56-64

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Characteristic and follow-up of subglottic hemangiomas in Iranian children

Subglottic hemangiomas are very rare in compare with cutaneous form but can be life-threatening in the proliferating phase of tumor by airway obstruction. It should be considered in any child with recurrent, persistent and/or progressive, inspiratory or biphasic stridor, respiratory distress and feeding difficulties in the first months of life. It should be confirmed by endobronchoscopic evaluation. Affected infants are most likely to experience symptoms between the ages of 6 and 12 weeks. Infants who admitted and referred to our hospital with recurrent stridor, cough and respiratory distress were reviewed

Soil Contamination With Eggs of Toxocara Species in Public Parks of Karaj, Iran

Background: Human toxocariasis is one of the zoonotic helminth diseases that is usually occurred with exposure to contaminated soil. Both Toxocara canis and Toxocara cati are considered the causative agents of Toxocara infection. Objectives: This survey was intended to provide data on the Toxocara species eggs contamination in soil samples in the public parks of Karaj, Iran. Materials and Methods: This study was carried out among 200 soil samples collected from 12 public parks between August and September 2016 to examine the soil contamination with Toxocara species eggs. Soil samples were tested for the presence of Toxocara eggs using sucrose flotation method. Results: Prevalence of Toxocara species eggs in soil samples collected from public parks was 36.4%. The highest number of eggs recovered from 200 g of soil was 20. A total of 200 eggs were recovered and 7.6% were fully developed to embryonated egg stages. The contamination rate in the third region in 4 studied areas was higher than the other regions. A similar tendency was observed in park areas, so that parks higher than 5000 m2 were highly contaminated. Conclusion: According to the results of this study, soils of the public parks in Karaj are one of the main risk factors for human toxocariasis

Bi-objective single machine scheduling problem with stochastic processing times

In this study, a static single machine scheduling problem is investigated, where processing times are stochastic, due dates are deterministic and inserted idle time is allowed. Two objective functions are simultaneously taken into account, minimization of mean completion time and minimization of earliness and tardiness costs. A robust model is presented to tackle the problem, based on goal programming and a stochastic programming model named E-model. The proposed model not only obtains optimal operating systems, but also considers the variance of the objective functions and the correlation between them. Moreover, chance-constrained programming model is used to take into account the randomness in the constraints of the model. The model is presented with general distribution of processing times and the normal case is explored in experiments. Two sets of computational experiments are presented to test the efficiency of the proposed model. In the first set, the performance obtained by the bi-objective formulation is measured, where in the second set the performance obtained by incorporating robustness is measured. Results confirm the effectiveness of the proposed model, in both directions.</p

Evaluating the value of e-services (information technology) in Public institutions (Case Study of Tehran Municipality)

In this paper, a model for evaluating electronic services in nonprofit institutions is presented. The idea of this model was due to a vacuum of research in this field. Regarding this issue, independent variables have been extracted from the perspective of members of the research community for the evaluation of electronic services based on inductive method and fundamental conceptualization theory. These variables include governance issues, tools, and customers. Indicators for measuring two variables of government and a measurable tool refer to financial systems and based on cost accounting methodology. However, it was not possible to determine the amount (rials) of the customer variable in this way. Therefore, a process was developed using existing theoretical foundations, including the relative estimation method for accounting, the Delon and McLean evaluation model, and the value engineering and how these two variables influence the management and tools. Then, in order to test the model and development process, the municipality of Tehran decided to evaluate the electronic license of the traffic plan. The result of determining the value of electronic services allows the use of this model in real term