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Introduction: Transfusion-transmitted malaria (TTM), from a malaria infected donor, is an accidental Plasmodium infection, which is one of the concerns of blood transfusion issue in the world. Countries have adopted different strategies for donor selection and improving criteria to overcome these concerns, In the Iranian Blood Transfusion Organization (IBTO), donors who refer to blood transfusion centers after registration are screened by the physicians based on interview and examination. This prevention due to the possibility of malaria infection is called malaria donor deferral strategy. Methods: In this study 248 malaria blood donation deferral samples were selected and evaluated by microscopic, serological and molecular methods, after completing the questionnaire. Results: The results of the survey of the questionnaires showed that 30 cases were deferred from donating blood due to having a history of malaria infection. In microscopic examination, Plasmodium ring was observed in 2 samples and 2 samples were also reported as suspicious. In serological examination, 23 cases (9.27%) were reported positive. All cases were reported negative for the presence of malaria parasite DNA. Conclusions: The adoption of TTM prevention strategies depends on the malaria endemicity of the geographical area. According to the IBTO instructions, donors are examined and interviewed by a blood transfusion physician’s and owning to traveling or residency in endemic area or malaria infection, deferred temporary or permanently. Recent study reveal that the strategy of donor selection and deferral in the IBTO, with little residual risk of malaria transmitting, is sufficient to prevent the occurrence of TTM in Iran.

Objectives The use of leukoreduction filters has been highly increased in Iranian Blood Transfusion Centers within the last decade to provide sufficient leukoreduced blood products from healthy repeated donors for alloimmunized or sensitive recipients. Leucoflex LCR5, the dominant brand which procured by the Iranian Blood Transfusion Organization, is the most updated generation of the filters used around the world. Material and methods In this study, we recovered trapped leukocytes from these filters using different buffer solutions and optimized elution method. The count of recovered cells assessed by cell counter, and cell viability was detected using trypan blue staining. The percent of leukocyte subpopulations was evaluated using a panel of monoclonal antibodies and flow cytometric analysis. Results It illustrated that a buffer solution consistent with PBS in pH 7.2 containing 2 mM EDTA and 4% (w/w) Dextran 40 was the best buffer for LCR5 filter backflushing. The white cell counted as 4.56 × 108 Granulocytes, 3.34 × 108 Lymphocytes, and 0.64 × 108 Monocytes according to analysis with auto hemoanalysis and flow cytometric methods. Conclusion The study guides and assists blood management systems in arranging a national blood profile database for future cell therapy strategies. Also, the recovered cells could be of significance in stem cell research, cellular interaction studies as well as novel molecular developments in drug discovery.

Background/objective Hemophilia A is a genetic disorder through which patients suffer from recurrent bleeding. This can be caused by a defect in human plasma coagulation factor VIII. High incidence of FVIII inhibitors in some severe hemophilia A patients after FVIII therapy is a considerable complication. Determination of good predictive factors can improve the safety of this treatment. HLA-II have been shown as a predictive element for inhibitor development. The goal of this study is to determine the association between HLA-DRB1*15:03, HLA-DRB1*11 and HLA-DRB1*01:01 alleles and FVIII inhibitors in severe hemophilia A patients in Iran. Materials/methods HLA-DRB1 genotyping was performed using Multiplex sequences Specific Primers (PCR-SSP) in two groups of severe hemophilia A patients comprising 51 and 50 individuals with and without FVIII inhibitors respectively. The levels of inhibitor were determined through Nijmegen-modified Bethesda assay. HLA-DRB1 allele frequencies were compared between groups by using multiple logistic regression models. Results HLA-DRB1*01:01 allele frequency was significantly higher in patients without inhibitor ORadj: 2.7 (95%CI: 1.08, 6.97; P = 0.034). There wasn’t any statistically significant difference in HLA-DRB1*11 allele frequency between groups ORadj: 0.7 (95%CI: 0.27, 1.82; P = 0.47). There was no connection between HLA-DRB1*15:03 and inhibitor development ORadj: 0.94 (95%CI: 0.38, 2.35; P = 0.94). Conclusion An association between HLA-DRB1*01:01 and paucity of FVIII inhibitor showed that this allele has probably a protective effect in severe hemophilia A patients in Iran. Determination of the predictive and protective alleles are beneficial in pre-treatment activities and decrease the risk of unsuccessful therapy with FVIII in each population.

This study aims to determine the most frequent titers of anti-A and anti-B (both presumed immunoglobulin [Ig]M and IgG) in Iranian group O blood donors and to compare these titer values with those found in other studies. In addition, alloantibody production and plasma levels of four IgG subclasses were compared between the high-titer and non-high-titer study groups. This study investigated anti-A and anti-B titers in 358 plasma samples. Based on these results, two study groups (high-titer and non-high-titer) were formed. Antibody detection tests were performed to detect unexpected antibodies to D, C, c, E, e, K, k, Fya, Fyb, Jka, Jkb, M, N, S, s, P1, Lea, and Leb. Four IgG subclasses were also evaluated through nephelometry assay. The most frequent titer obtained by room temperature and indirect antiglobulin tube tests was 256. The frequency of titers ≥512 was 31.5 percent. None of the cases showed unexpected RBC alloantibodies. IgG2 levels were significantly higher in the high-titer group. Evaluation of isoagglutinin titers in group O Iranian blood donors can provide insight into the frequency of isoagglutinin titers both within the Iranian population and as compared with other populations. A significant difference in IgG2 levels between the high-titer and non-high-titer groups was identified. More investigation needs to be conducted on the root cause of this finding. Immunohematology 2021;37:5-12 . This study aims to determine the most frequent titers of anti-A and anti-B (both presumed immunoglobulin [Ig]M and IgG) in Iranian group O blood donors and to compare these titer values with those found in other studies. In addition, alloantibody production and plasma levels of four IgG subclasses were compared between the high-titer and non–high-titer study groups. This study investigated anti-A and anti-B titers in 358 plasma samples. Based on these results, two study groups (high-titer and non–high-titer) were formed. Antibody detection tests were performed to detect unexpected antibodies to D, C, c, E, e, K, k, Fya, Fyb, Jka, Jkb, M, N, S, s, P1, Lea, and Leb. Four IgG subclasses were also evaluated through nephelometry assay. The most frequent titer obtained by room temperature and indirect antiglobulin tube tests was 256. The frequency of titers ≥512 was 31.5 percent. None of the cases showed unexpected RBC alloantibodies. IgG2 levels were significantly higher in the high-titer group. Evaluation of isoagglutinin titers in group O Iranian blood donors can provide insight into the frequency of isoagglutinin titers both within the Iranian population and as compared with other populations. A significant difference in IgG2 levels between the high-titer and non–high-titer groups was identified. More investigation needs to be conducted on the root cause of this finding. Immunohematology 2021;37:5–12 .

It is well understood that patients with different diseases may have a variety of specific proteins (e.g., type, amount, and configuration) in their plasmas. When nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may incorporate some of the disease-specific proteins. Using gold (Au) NPs with different surface properties and corona composition, we have developed a technology for the discrimination and detection of two neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a variety of techniques, including UV-visible spectra, colorimetric response analyses and liquid chromatography-tandem mass spectrometry, we found the corona-NP complexes, obtained from different human serums, had distinct protein composition, including some specific proteins that are known as AD and MS biomarkers. The colorimetric responses, analyzed by chemometrics and statistical methods, demonstrate promising capabilities of the technology to unambiguously identify and discriminate AD and MS. The developed colorimetric technology might enable a simple, inexpensive and rapid detection/discrimination of neurodegenerative diseases.

Background Epidemiological studies have probed the correlation between telomere length and the risk of lung cancer, but their findings are inconsistent in this regard. The present meta-analysis study has been carried out to demonstrate the association between relative telomere length in peripheral blood leukocytes and the risk of lung cancer using an established Q-PCR technique. Methods A systematic search was carried out using PubMed, EMBASE, and ISI before 2015. A total of 2925 cases of lung cancer and 2931 controls from 9 studies were employed to probe the relationship between lung cancer and telomere length .ORs were used at 95% CI. Random-effects models were used to investigate this relationship based on the heterogeneity test. Heterogeneity among studies was analyzed employing subgroup analysis based on type studies and the year of publication. Results Random-effects meta-analysis revealed that patients with lung cancer were expected to have shorter telomere length than the control (1.13, 95% CI: 0.82-1.81, P=0.46). The summary of the pooled ORs of telomere length in adenocarcinoma lung cancer patients was 1 (95%CI=0.68-1.47, I2=93%) compared to patients with squamous cell lung cancer, which was 1.78 (95% CI=1.25-2.53, I2=3.9%). The meta-regression revealed that the effect of telomere length shortening, decreased and increased with the year of publication and the age of risks to lung cancer, was clearly related to short telomeres lengths. Conclusion Lung cancer risks clearly related with short telomeres lengths. In patients with breathing problems, lung cancer risk can be predicted by telomere length adjustment with age, sex, and smoking.

Background: Tax-1 protein of Human T-cell Leukemia Virus type 1(HTLV-1) serves as a key transcriptional regulatory gene product and has a crucial role in transactivating genes of infected cells by employing their transcriptional factors. This modulation includes induction of genes which encode CC-chemokines and their receptors. In this study, a recombinant vector containing Tax-1 gene was made and tested for its ability to induce CCR5 (CC chemokine receptor 5) expression in K562 cell line. Methods: In order to perform this research, two blood samples of HTLV-1 positive were obtained from Urmia blood transfusion center. After DNA extraction, a complete sequence of Tax-1 gene was amplified by specific primers. Recombinant vectors carrying Tax-1 gene were synthesized and transformed into Escherichia coli (E. coli). After bacteria transformation, bacteria containing recombinant plasmid were selected and purified. Then, the recombinant shuttle vectors, pCDNA3.1-TAX, were transfected into the cell culture (K562 cell line). Expression of CCR5 was measured after 72 hr by Syber Green Real-Time PCR method compared to control cell culture. Normalization was done with GAPDH as a standard gene. Results: Cloning of Tax-1 gene in the vector, pCDNA3.1 was confirmed by colony PCR, restriction digestion, and sequencing methods. Expression of Tax-1 and CCR5 genes were confirmed by real time PCR and also, expression of CCR5 gene showed an 8-fold increase in comparison to mock-treated controls (p

Background: Mutations in the coding region of the Chemokine Receptor 5 (CCR5) genes reduce or eliminate CCR5 expression in immune cells and progression of HCV infection. This study aimed to investigate the role of this mutation in HCV infection in Iranian patients in comparison with healthy individuals. Methods: 100 HCV infected patients and 100 healthy individuals were randomly selected. The CCR5Δ32 genotypes were determined using specific primers and PCR method. Results: The agarose gel electrophoresis showed a189-bp fragment from wild type for both alleles of CCR5 gene. The CCR5-Δ32 allele was not found in any HCV infected and healthy subjects. Conclusion: The mutation in CCR5 gene was not detected in any of the two groups; therefore, the role of CCR5 gene expression in immune cells and progression of HCV infection needs to be studied in larger samples in our country.

Blood transfusion services are vital components of healthcare systems all over the world. In this paper, a generalized network optimization model is developed for a complex blood supply chain in accordance with Iranian blood transfusion organization (IBTO) structure. This structure consist of four types facilities. Blood collection centers, blood collection and processing centers, mobile teams and blood transfusion center have various duties in IBTO structure. The major contribution is to develop a novel hybrid approach based on stochastic programming, e-constraint and robust optimization (HSERO) to simultaneously model two types of uncertainties by including stochastic scenarios for total blood donations and polyhedral uncertainty sets for demands. An accelerated stochastic Benders decomposition algorithm is proposed to solve the problem modeled in this paper. To speed up the convergence of the solution algorithm, valid inequalities are introduced to get better quality lower bounds. In addition, a Pareto-optimal cut generation scheme is used to strengthen the Benders optimality cuts. Numerical illustrations are given to verify the mathematical formulation and also to show the benefits of using the HSERO approach. At the end, the performance improvements achieved by the valid inequalities and the Pareto-optimal cuts are demonstrated in a real world application.

Telomeres contain TTAGGG repetitive sequences and are located at the end of human chromosomes. Telomere dysfunction is associated with some age-related and chronic diseases, but its relationship with foods, dietary patterns, and occupational class in the young male population is not yet known. In this cross-sectional study, 300 healthy men, residents of Tehran, aged 25–40 years were enrolled from January to December 2016. We employed a cross-sectional study of 300 healthy people, residents of Tehran, aged 25-40 years. A food frequency questionnaire was used to obtain food intakes of all participants and converted into actual food intake (g/day). The principal components analysis was used to determine dietary patterns and other demographic characteristics. Leukocyte telomere length (TL) was measured by quantitative real-time polymerase chain reaction (PCR) to measure number of telomere repeat copy number (T) to the relative number of 36B4 copies (S) (T/S ratio). T/S in office-workers, waste recyclers, and other workers were 1.22 ± 0.4, 1.08 ± 0.3, and 1.094 ± 0.34, respectively. The results of multivariate linear regression adjusted for age, body mass index (BMI), and smoking were showed that whole grains (β = 0.02; p = .05), refined grains, fruits and vegetables, fish and dairy products were associated with an increase in log-T/S, but consumption of nuts and seeds (β = −0.00072; p = .06), meats (β = −0.00043; p = .9), produced meats (β = −0.00238; p = .03), oils and solid fats (β = −0.00146; p = .03) had a negative relationship with log-T/S in all studied occupational classes. A positive relationship was reported between the healthy (β = 0.017; p = .2) and traditional dietary pattern (β = 0.012; p = .4) with log-T/S, but western pattern identified negative relationship (β = −0.004; p = .7). Adherence to a healthy (with consumption whole grains, refined grains, dairy, and cereals) and then traditional pattern with increased consumption of fruits, vegetables and whole grains, fish and dairy products are necessary to prevent TL destruction in all studied occupational classes.

West Nile virus (WNV) can be transmitted by blood transfusions and organ transplants. This study was a retrospective study which was performed in Blood Transfusion Center to evaluate the WNV infection in blood donors in Iran. A total of 540 blood samples were taken from volunteer healthy donors who referred for blood donation to Chabahar Blood Center. The presence of WNV was studied by detecting immunoglobulin G (IgG) WNV by enzyme linked immune sorbent assay (ELISA). Demonstration of elevated WNV IgG confirmed by immunoflouorescence assay (IFA) Euroimmun kit. Out of the 540 samples 17.96 % (97 cases) were seropositive by ELISA and 1.48 % (8 cases) was seropositive by IFA. This means that 8.24 % of ELISA seropositive samples were confirmed by IFA. Special attention should be paid to criteria of donor selection, albeit positive results may be due to a previous infection in these donors.

Blood and plasma are unique resources and access to these products save life. In this study, albumin demand and surplus plasma makes it possible to use local experiences in plasma industry for preparation of albumin so plasma was heated after stabilization; afterward denatured proteins were precipitated and separated by continuous centrifuge system. The supernatant contained albumin was filtrated, diafiltrated, ultrafiltrated, formulated and pasteurized. Albumin preparation in pilot scale with heat denaturation was performed for the first time in Iran. This method using surplus plasma is recommended for all countries that have no access to plasma fractionation industry. Therefore with more attention it has potential for use in the production of safe plasma derived products and thereby it can be used as a safe product in clinic.

Risk of dengue virus in the blood supply has been demonstrated in recent studies. In this paper, Chabahar in Sistan and Baluchestan province, south east of Iran, was selected for studying dengue infection because of its climatic and geographical situation in the middle of the transit way between East Asia and other countries. The blood samples were taken from volunteer healthy donors who were referred to the Chabahar Blood Center for blood donation. The presence of dengue virus (DENV) was studied by detecting IgG to DENV by enzyme linked immune sorbent assay (ELISA). Reactive ELISA results were confirmed by an immune flouorescence assay (IFA). According to the results, some of the healthy donors were infected by DENV, which could not been recognized in donor selection. Therefore, special attention should be paid to the criteria of donor selection and additional screening tests are recommended.

SUMMARY Aim In many countries, there is surplus plasma which is thrown out. Due to the high cost of albumin as a pharmaceutical product, it is not widely available for all patients. Therefore, we considered direct preparation of albumin in the plasma bag. Background Human plasma has many unique features compared with prepared pharmaceutical products because of its human origin. In countries which do not have a plasma fractionation industry, shortages for plasma products are commonplace. Methods Albumin stabiliser was added to the plasma in the bag to stabilised albumin molecule and make it resistant to heat. When the plasma bag was heated, other plasma proteins are irreversibly precipitated and can be separated by centrifugation. Finally, albumin is filtered and pasteurized in plasma bag. Results The purity of prepared albumin is >99% and the yield is 21 g per liter of plasma. Polymer content of pasteurized albumin measuring with High Performance Liquid Chromatography (HPLC) was less than 1%. Conclusions Since albumin preparation in plasma bag is a simple and cheap technology, it has the potential for use in the production of a safe plasma derived product, although suitability for human use would require appropriate clinical assessment for safety. Using this method, albumin could be prepared from all types of plasma. This method is suggested as a possible method of albumin production for all countries which do not have a plasma fractionation industry and even for the countries with low plasma supplies.

Timely delivering of the required blood and blood products to beneficiaries is one of the most critical issues during disaster strikes. Risks are the events that can interrupt the process and hinder the blood supply chains from attaining their predetermined goals. In this paper, we designed a process map that shows the workflow of the blood supply chain visually from donation to the distribution of blood products to the hospital. Then, the risks associated with each activity of the main processes identified. By aggregation of expert judgments using the fuzzy Delphi method, the final list of risks extracted. Then the identified risks were classified and consequently, by using fault tree analysis (FTA), the probability of failure in the blood supply chain in each main level calculated. Findings can help related organisations to manage the risks better and design effective mitigation plans.

IVIG can be prepared from fractionation of normal human plasma and it is used as a therapeutic drug for treatment of various diseases. IVIG has been for some time the high-growth product within the plasma derived products, at both a global and a national country level. Fractionation was performed according to Cohn method with some modifications. Fraction II was first produced and then it was used for purification and virus inactivation steps. Two methods of virus inactivation (pasteurization at 60 degrees C for 10 hours and solvent/detergent treatment with TnBP and Tween 80) were used and validated. A chromatography method (cation exchange chromatography on CM Sepharose FF) was also added to obtain high purity. The final product (in liquid and freeze dried formulation) meets European Pharmacopeias requirements. The amount of PKA and aggregates was beyond the acceptance limit. The intactness of the IVIG was also examined by circular dichroism (secondary and tertiary structure). It was stable after 6 months of storage. Since Iran market is completely dependant on importation of plasma derived products, it is important to develop such methods for production of IVIG to obtain regional demands.

The safety of plasma derived medicinal products, such as immunoglobulin, depends on viral inactivation steps that are incorporated into the production process. Several attempts have been made to validate the effectiveness of these inactivation methods against a range of physio-chemically diverse viruses. Treatment with solvent/detergent (S/D) and pasteurization (P) has been continuously used in our IgG production and these methods were analysed in this study as models of viral inactivation. Bovine Viral Diarrhoea Virus (BVDV), Herpes Simplex Virus (HSV) and Vesicular Stomatitis Virus (VSV) were employed as models of HCV, HBV and HIV respectively. Polio and Reo viruses also were used as stable viruses to chemical substances. The infectivity of a range of viruses before and after treatment with two methods of viral inactivation was measured by end point titration and their effectiveness expressed as Logarithmic Reduction Factors (LRF). Solvent/detergent treatment reduced the amount of enveloped viruses by 5-6 logs. The reduction factor was between 5-6 logs for all viruses used in the pasteurization process. A final log reduction factor was obtained as the sum of the two individual methods. Both inactivation methods have advantages and disadvantages with respect to their ability to inactivate viruses. Thus,combination of two robust virus inactivation steps, solvent/detergent and pasteurization, increases the safety margin of immunoglobulin preparations.

Pasteurization was investigated as a method of inactivating virus during the preparation of immunoglobulin for intravenous use. The effect of pH, protein concentration and the presence of protein stabilizers on the structure of immunoglobulin G (IgG) molecules during pasteurization was investigated using an immunoglobulin solution derived from a Cohn's fraction II preparation. Changes in the secondary and tertiary structure of IgG molecules as well as the degree of polymerization of protein were investigated using spectrophotometry, circular dichroism and size exclusion chromatography. Only slight changes in secondary and tertiary structure were observed after pasteurization in a 10 g L(-1) immunoglobulin solution at pH 4.5 and 5.5 in the absence of stabilizer and in a 50 g L(-1) immunoglobulin solution at pH 5.5 in the presence of glycine and sucrose or sorbitol. Concentrations of immunoglobulin solution below 20 g L(-1) were not denatured when pasteurized at pH 4.5 in the absence of stabilizers. High concentrations of immunoglobulin solution required stabilizers such as glycine and sorbitol or sucrose to prevent or reduce denaturation during pasteurization.

It is now well known that the primary interactions of biological entities (e. g., tissues and cells) with nano-particles (NPs) are strongly influenced by the protein composition of the "corona" (i. e., the NP surface attached proteins). The composition of the corona strongly depends on the protein source (e. g., human plasma). Because the protein source determines the NP corona, it is reasonable to hypothesize that humans with specific disease(s) may have specific NP coronas. To test this hypothesis, we incubated two different hydrophobic/hydrophilic types of NPs (polystyrene and silica) with plasma from human subjects with different diseases and medical conditions (e. g., breast cancer, diabetes, hypercholesterolemia, rheumatism, fauvism, smoking, hemodialysis, thalassemia, hemophilia A and B, pregnancy, common cold and hypofibrinogenemia). Our results demonstrate that the type of disease has a crucial role in the protein composition of the NP corona. Based on these results, we introduce the concept of the "personalized protein corona" (PPC) as a determinant factor in nano-biomedical science. This study will help researchers rationally design experiments based on the "personalized protein corona" for clinical and biological applications.