Primary immunodeficiency disorders in Iran: Update and new insights from the third report of the national registry

Background: Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers. Methods: This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006. Results: A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %). Conclusions: Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases. © 2014 Springer Science+Business Media

A survey about existence currency of warm water fish in northern Alborz

Aquaculture is the most important part of Fisheries Organization duties in Iran. During several planning and developing programs, aquaculture productions had a considerable growth. Due to good potential, these productions were higher than the planed one. The North Alborz regions were investigated by four groups of experts. The regions which investigated were including 3 important provinces (e.g. Guilan, Mazandaran and Golestan). The area where investigated was 940 km along with coastal zone of Caspian Sea or 58678 km2 in total. Around 27% of aquaculture production came from this region. However, subdivision of fisheries can play important role in the economics in the region. The fisheries sub-sector has an important role in the economy of the region, and despite the great potential for agriculture and tourist industries in the North Alborz, there is a significant role in the prosperity of the fisheries activities. In the present study shows that Mazandaran and Guilan provinces has more potential in reservoirs and aquaculture production when compared with other provinces. Productions in Mazandaran either in reservoirs were less than Guilan province. Due to lee in reservoirs, Mazandaran had less investment when compared with Guilan province. The figures show that carrying capacity of aquaculture production for 3 provinces (Mazandaran, Guilan and Golestan) was higher than other provinces in the entire country. Due to, large land base, less investment, more interesting of farmers, no needs of complicated technology, farmer would be able to develop reservoirs as consequences to enhance productions. However, developing reservoirs and supporting of it's; can increase the contribution of warm water species in inland water

Investigation on probable viral agents associated with grass carp and silver carp mortality in Guilan province

Warm water aquaculture development along with import of eyed eggs, Broodstocks and ornamental fish also transferring of fingerlings and broodstocks from one province to another one has led to spreading of some unwanted diseases. According to the Gilan Fisheries Department report, mortality rate of silver carp(Hypophthalmichthys molitrix) in the summer of 2010 caused losing of silver carp production more than 1162 tons which was valued over than twenty-three milion rials that was increased to about 40 million rials in 1391. Also grass carp had a less mortality rate in some farms. Observed symptoms and severity of losses increased the probability of viral diseases such as spring viremia of carp, koi herpes virus and grass carp reovirus. In this research, totally 411 silver carp and grass carp with 5 to 2300 gram weight from 83 farms were sampled during 2011-2012. Clinical symptoms was different in various farms and subcutaneous hemorrhages on the flanks, red fin base or total fin and Red belly and operculum, mild exophthalmia, hemorrhaging in the abdominal cavity (yellow, transparent or red fluid) and petechial haemorrhages of skin and viscera and Ascites in abdominal cavity and some silver carps and grass carps were observed with palied liver and gill. In some cases swelling muscle was observed in Silver carp. Several fries with the severe emaciation were observed. Difference between clinical symptoms can indicate the presence of different causes of mortality in different farms. Various water colors from completely transparent to dark green, yellow or slightly brown observed in different pool, which shows the difference in overall culture management including water quality management. The minimum Water turbidity using secchi disk was 40 centimeters to one meter page in the fields. Source semi-deep wells or deep pools that were used as water source. Average water temperature, oxygen and pH in fileds 26/5-31 °C , 4/3-5/7 mg / L and 7/4-9/38. In order to virological surveys, sampling of internal organs, including kidneys, and spleen were done.and Homogeneous target tissues after spending 0/45 micron filter on EPC and BF2 cell line were inoculated to observe cell damage(CPE) in case of confirmation of antibody detection methods brilliant, RT-PCR and PCR done. In cell culture examination, a kind of cell damage (CPE-like changes) was observed after inoculating of 3 samples of Silver carp those were suspected to SVC, but in the second and third passages there were no sign of cell damage. It may be because of toxic effect of tissue filtrate on the cell monolayer. Concerning sample of Grass carp on two EPC and BF2 cells no evidence of cell damage was found. In indirect fluorescent antibody test, 72 hours after inoculation of tissues filtrates of of silver carp and grass carp samples on EPC, no positive reaction was observed. PCR and RT-PCR tests using specific primer pairs were done to test all of the silver carp and grass carp samples for SVC and KHV diseases Also for GCRV in grass carp samples. In addition, simultaneously commercial PCR kits applied for testing of SVC and KHV (IQ2000. Taiwan). The results of PCR and RT-PCR tests showed no evidence of robdovirus Carpio and grass carp reovirus RNA and no sign of koi herpesvirus DNA in tested samples. In conventional PCR and RT-PCR tests Using specific primer pairs none of positive bands related to SVCV(470 bp) and GCRV(292bp, 697bp and 320bp) were not confirmed in the tested samples. Also in electrophoresis of PCR products using IQ2000 kit revealed 471 bp and 640 bp negative bands in all samples and the positive bands were not observed. For confirmation of the results, three suspected samples were sent to Europe Union Reference Laboratory and none of mentioned diseases were confirmed. Simultaneously bacteriolocical examination applied for 26 using blood agar. In bacterial culture and related analyzes 6 isolates of Pseudomonas and 21isolates of Aeromonas hydrophila were detected from 26 farms while no virus was confirmed in the same samples. Based on the results of cell culture, PCR, RT-PCR and IFAT tests no one of SVCV, KHV and GCRV viruses were confirmed in tested samples. Therefore, the etiological reason of the mortalities in the tested farms was not viral diseases and should be prevent and control by biosecurity and health management in the farms

Pivotal Role of Inosine Triphosphate Pyrophosphatase in Maintaining Genome Stability and the Prevention of Apoptosis in Human Cells

Pure nucleotide precursor pools are a prerequisite for high-fidelity DNA replication and the suppression of mutagenesis and carcinogenesis. ITPases are nucleoside triphosphate pyrophosphatases that clean the precursor pools of the non-canonical triphosphates of inosine and xanthine. The precise role of the human ITPase, encoded by the ITPA gene, is not clearly defined. ITPA is clinically important because a widespread polymorphism, 94C>A, leads to null ITPase activity in erythrocytes and is associated with an adverse reaction to thiopurine drugs. We studied the cellular function of ITPA in HeLa cells using the purine analog 6-N hydroxylaminopurine (HAP), whose triphosphate is also a substrate for ITPA. In this study, we demonstrate that ITPA knockdown sensitizes HeLa cells to HAP-induced DNA breaks and apoptosis. The HAP-induced DNA damage and cytotoxicity observed in ITPA knockdown cells are rescued by an overexpression of the yeast ITPase encoded by the HAM1 gene. We further show that ITPA knockdown results in elevated mutagenesis in response to HAP treatment. Our studies reveal the significance of ITPA in preventing base analog-induced apoptosis, DNA damage and mutagenesis in human cells. This implies that individuals with defective ITPase are predisposed to genome damage by impurities in nucleotide pools, which is drastically augmented by therapy with purine analogs. They are also at an elevated risk for degenerative diseases and cancer

The urgent need for integrated science to fight COVID-19 pandemic and beyond

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc concern. We discuss in this treatise the importance of bringing the world’s scientists together to fnd efective solu‑ tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Probabilistic damage identification of a designed 9-story building using modal data in the presence of modeling errors

Validity and accuracy of model based identification techniques such as linear finite element (FE) model updating are sensitive to modeling errors. Models used for the design and performance assessment of civil structures often contain large modeling errors for certain frequency ranges of response. In other words, modeling errors have unequal effects on different vibration modes of structures. Therefore, the performance of FE model updating for damage identification is sensitive to the type and the subset of data used and to the residual weight factors. This study proposes a process to mitigate the effects of modeling errors by selecting the optimal subset of modes and the optimal modal residual weights. Multiple model updating classes are defined based on different subsets of modes and different weight factors. Structural damage is then identified using Bayesian model class selection and model averaging techniques over the results of all the considered model updating classes. In addition, a new likelihood function is defined to allow damage identification without the need for calibrating a reference FE model. Performance of the proposed damage identification process and the new likelihood function is evaluated numerically at multiple levels of modeling errors and structural damage on the SAC 9-story steel moment frame. It is shown that the structural damages can be identified with negligible bias when the proposed likelihood and updating process is implemented. © 2016 Elsevier Lt