Introduction of protein vaccine candidate based on AP65, AP33, and α-actinin proteins against Trichomonas vaginalis parasite: an immunoinformatics design.

BACKGROUND: Trichomonas vaginalis is the most common nonviral sexually transmitted disease (STI) worldwide. Vaccination is generally considered to be one of the most effective methods of preventing infectious diseases. Using AP65, AP33 and α-actinin proteins, this research aims to develop a protein vaccine against Trichomonas vaginalis. METHODS: Based on the B-cell and T-cell epitope prediction servers, the most antigenic epitopes were selected, and with the necessary evaluations, epitope-rich domains of three proteins, AP65, AP33, and α-actinin, were selected and linked. Subsequently, the ability of the vaccine to interact with toll-like receptors 2 and 4 (TLR2 and TLR4) was assessed. The stability of the interactions was also studied by molecular dynamics for a duration of 100 nanoseconds. RESULTS: The designed protein consists of 780 amino acids with a molecular weight of 85247.31 daltons. The results of the interaction of the vaccine candidate with TLR2 and TLR4 of the immune system also showed that there are strong interactions between the vaccine candidate protein with TLR2 (-890.7 kcal mol-1) and TLR4 (-967.3 kcal mol-1). All parameters studied to evaluate the stability of the protein structure and the protein-TLR2 and protein-TLR4 complexes showed that the structure of the vaccine candidate protein is stable alone and in complex with the immune system receptors. Investigation of the ability of the designed protein to induce an immune response using the C-ImmSim web server also showed that the designed protein is capable of stimulating B- and T-cell lymphocytes to produce the necessary cytokines and antibodies against Trichomonas vaginalis. CONCLUSIONS: Overall, our vaccine may have potential protection against Trichomonas vaginalis. However, for experimental in vivo and in vitro studies, it may be a good vaccine candidate.

Prevalence of medication errors and its related factors in Iranian nurses: an updated systematic review and meta-analysis.

BACKGROUND: Nurses may make medication errors during the implementation of therapeutic interventions, which initially threaten the patient's health and safety and prolong their hospital stay. These errors have always been a challenge for healthcare systems. Given that factors such as the timing, type, and causes of medication errors can serve as suitable predictors for their occurrence, we have decided to conduct a review study aiming to investigate the prevalence of medication errors and the associated factors among Iranian nurses. METHODS: In this systematic review and meta-analysis, studies were searched on PubMed, Web of Science, Scopus, Google Scholar, IranMedex, Magiran, and SID databases using a combination of keywords and Boolean functions. The study that reported the prevalence of medication errors among nurses in Iran without time limitation up to May 2023 was included in this study. RESULTS: A total of 36 studies were included in the analysis. The analysis indicates that 54% (95% CI: 43, 65; I2 = 99.3%) of Iranian nurses experienced medication errors. The most common types of medication errors by nurses were wrong timing 27.3% (95% CI: 19, 36; I2 = 95.8%), and wrong dosage 26.4% (95% CI: 20, 33; I2 = 91%). Additionally, the main causes of medication errors among nurses were workload 43%, fatigue 42.7%, and nursing shortage 38.8%. In this study, just 39% (95% CI: 27, 50; I2 = 97.1%) of nurses with medication errors did report their errors. Moreover, the prevalence of medication errors was more in the night shift at 41.1%. The results of the meta-regression showed that publication year and the female-to-male ratio are good predictors of medical errors, but they are not statistically significant(p > 0.05). CONCLUSIONS: To reduce medication errors, nurses need to work in a calm environment that allows for proper nursing interventions and prevents overcrowding in departments. Additionally, considering the low reporting of medication errors to managers, support should be provided to nurses who report medication errors, in order to promote a culture of reporting these errors among Iranian nurses and ensure patient safety is not compromised.

Prevalence of needle stick and its related factors in Iranian health worker: an updated systematic review and meta-analysis.

Background: Healthcare workers (HCWs) are at risk of acquiring blood-borne infections such as hepatitis B, hepatitis C, and human immunodeficiency virus through needlestick injuries (NSIs). We aimed to investigate the prevalence of needlestick injuries and other related indicators among HCWs in Iran through a systematic review and meta-analysis. Methods: We searched various databases until the end of May 2023 for studies reporting the prevalence of NSIs among healthcare workers in Iran. We used a random model with 95% confidence intervals (CIs) to analyse the data and the Joanna Briggs Institute (JBI) tool to evaluate the quality of included studies. We conducted and reported the study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: We included 87 studies in the analysis and found that 47% (95% CI = 42-52, I2 = 98.9%) of Iranian HCWs experienced NSI. NSIs were most frequently related to syringe needles (58%; 95% CI = 52-65, I2 = 96.8%) and most often caused by recapping (30%; 95% CI = 22-38, I2 = 98.5%). In this study, 56% (95% CI = 45-67, I2 = 98.6%) of HCWs with NSIs did not report their injury. Moreover, the prevalence of NSIs the highest in the morning shift (0.44; 95% CI = 0.36-0.53, I2 = 97.2%), emergency unit (0.20; 95% CI = 0.16-0.24, I2 = 93.7%), and intensive care unit (0.20; 95% CI = 0.16-0.24, I2 = 94.3%). Conclusions: To reduce the high prevalence of NSIs, HCWs, especially those in emergency departments, should use safety equipment. Healthcare managers should provide a calm and stress-free environment for HCWs, educate them on safety principles and standards, and support experienced HCWs with NSIs.

Trematode Cercariae from Lymnaea gedrosiana in the Caspian Sea Littoral in Iran: a one health concern.

Introduction: Lymnaea gedrosiana snails are hosts to a variety of trematode cercaria of public and veterinary health importance. In Guilan Province, Iran, a region with a high level of fish and bird farming and wetlands important for migratory birds, little is known about the trematode cercaria from L. gedrosiana. Methods: From April 2020 to October 2021, six freshwater sites in Guilan Province were sampled for Lymnaeidae snails three times per season (spring, summer, autumn and winter). Snails were exposed to light and heat to induce cercaria shedding and shredded cercaria were identified morphologically and molecularly. Results: In total, 5,712 Lymnaeidae snails were collected of which 3,288 (57.6%) were identified to be L. gedrosiana with 54.3% containing trematode cercaria. Snail and cercaria recovery were highest in the spring and summer. Trematode cercaria identified included Telorchis assula, Hypoderaeum conoideum, Apharyngostrigea pipientis, Sanguinicola cf. inermis, Opisthioglyphe ranae, Diplostomum pseudospathaceum, and Australapatemon burti. Discussion: The four trematodes D. pseudospathaceum, S. inermis, A. burti, and A. pipientis have not been previously reported in Iran; all four of these can infect migratory birds. The most common cercaria found, H. conoideum (18.3% of the snails) is of zoonotic importance. The third most common cercaria found, S. inermis (10.0% of the snails) is detrimental to fish production. Given the importance of the wetlands in the region for wildlife and migratory birds as well as the number of fish and bird farms in the area, efforts to control L. gedrosiana snails are needed to protect wildlife and human health. In addition, monitoring programs should be implemented to identify and prevent introductions of new trematode species.

Design peptide and multi-epitope protein vaccine candidates against monkeypox virus using reverse vaccinology approach: an in-silico study.

Monkeypox is a zoonotic virus that has recently affected different countries worldwide. On July 23, 2022, the WHO declared the outbreak of monkeypox as a public health emergency of international concern. Surveillance studies conducted in Central Africa in the 1980s and later during outbreaks in the same region showed smallpox vaccines to be clinically somewhat effective against Monkeypox virus. However, there is no specific vaccine against this virus. This research used bioinformatics techniques to establish a novel multi-epitope vaccine candidate against Monkeypox that can induce a strong immune response. Five well-known antigenic proteins (E8L, A30L, A35R, A29L, and B21R) of the virus were picked and assessed as possible immunogenic peptides. Two suitable peptide candidates were selected according to bio-informatics analysis. Based upon in silico evaluation, two multi-epitope vaccine candidates (ALALAR and ALAL) were built with rich-epitope domains consisting of high-ranking T and B-cell epitopes. After predicting and evaluating the 3D structure of the protein candidates, the most efficient 3D models were considered for docking studies with Toll-like receptor 4 (TLR4) and the HLA-A * 11:01, HLA-A*01:01, HLA-A*02:01, HLA-A*03:01, HLA-A*07:02, HLA-A*15:01, HLA-A*30:01 receptors. Subsequently, molecular dynamics (MD) simulation of up to 150 nanoseconds was employed to assess the durability of the interaction of the vaccine candidates with immune receptors. MD studies showed that M5-HLA-A*11:01, ALAL-TLR4, and ALALAR-TLR4 complexes were stable during simulation. Analysis of the in silico outcomes indicates that the M5 peptide and ALAL and ALALAR proteins may be suitable vaccine candidates against the Monkeypox virus.Communicated by Ramaswamy H. Sarma.

Computational screening of FDA-approved drugs to identify potential TgDHFR, TgPRS, and TgCDPK1 proteins inhibitors against Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is one of the most successful parasites in the world, because about a third of the world's population is seropositive for toxoplasmosis. Treatment regimens for toxoplasmosis have remained unchanged for the past 20 years, and no new drugs have been introduced to the market recently. This study, performed molecular docking to identify interactions of FDA-approved drugs with essential residues in the active site of proteins of T. gondii Dihydrofolate Reductase (TgDHFR), Prolyl-tRNA Synthetase (TgPRS), and Calcium-Dependent Protein Kinase 1 (TgCDPK1). Each protein was docked with 2100 FDA-approved drugs using AutoDock Vina. Also, the Pharmit software was used to generate pharmacophore models based on the TgDHFR complexed with TRC-2533, TgPRS in complex with halofuginone, and TgCDPK1 in complex with a bumped kinase inhibitor, RM-1-132. Molecular dynamics (MD) simulation was also performed for 100 ns to verify the stability of interaction in drug-protein complexes. Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis evaluated the binding energy of selected complexes. Ezetimibe, Raloxifene, Sulfasalazine, Triamterene, and Zafirlukast drugs against the TgDHFR protein, Cromolyn, Cefexim, and Lactulose drugs against the TgPRS protein, and Pentaprazole, Betamethasone, and Bromocriptine drugs against TgCDPK1 protein showed the best results. These drugs had the lowest energy-based docking scores and also stable interactions based on MD analyses with TgDHFR, TgPRS, and TgCDPK1 drug targets that can be introduced as possible drugs for laboratory investigations to treat T. gondii parasite infection.

The Immunization of Protoscolices P29 DNA Vaccine on Experimental Cystic Echinococosis in Balb/c Mice.

PURPOSE: Cystic Echinococosis is one of the important parasitic diseases that is considered as a problem economics and health in many parts of the world. Many efforts have been performed for controlling the disease in the world. To reach a reliable vaccine against Cystic Echinococosis is one of the important duty of governments. Several antigen of hydatid cyst for vaccine candidate have been evaluated. In this study, P-29 antigen has been used for this purpose. METHODS: E.g P29 antigen was cloned in Escherichia coli and transfected into the Chinese hamster ovary cell for antigen proliferation and used for vaccination in Balb/c mice. The recombinant antigen E.g-29 was shown using Western blot test. Two dilution of DNA vaccine (pCEgP-29) including 50 µg/100 µl and 100 µg/100 µl were prepared. Twenty four Balb/C male 6-8 week mouse were divided in 4 groups. The groups were included in 2 vaccination groups (pcEg.P29 50 µg/100 µl and 100 µg/100 µl dilution) as immunized groups and 2 groups of plasmid and PBS as control. The mice were injected intramuscularly 3 times with 2 weeks interval. After 3 weeks from last injection, all groups were challenged intraperitonealy with 2000 protoscolices. After 5 months, the mice were euthanized by ketamine/xylasine injection and number, size, and weight of cysts were recorded. RESULTS: Immunization rate was up to 93% in vaccinated group when compared with the control group. CONCLUSION: The results of this study showed that rEg.P29 could be considered as an effective vaccine for controlling of E. granulosus prevalence in intermediated host.

A Simulation-Based Optimization Model to Study the Impact of Multiple-Region Listing and Information Sharing on Kidney Transplant Outcomes.

More than 8000 patients on the waiting list for kidney transplantation die or become ineligible to receive transplants due to health deterioration. At the same time, more than 4000 recovered kidneys from deceased donors are discarded each year in the United States. This paper develops a simulation-based optimization model that considers several crucial factors for a kidney transplantation to improve kidney utilization. Unlike most proposed models, the presented optimization model incorporates details of the offering process, the deterioration of patient health and kidney quality over time, the correlation between patients' health and acceptance decisions, and the probability of kidney acceptance. We estimate model parameters using data obtained from the United Network of Organ Sharing (UNOS) and the Scientific Registry of Transplant Recipients (SRTR). Using these parameters, we illustrate the power of the simulation-based optimization model using two related applications. The former explores the effects of encouraging patients to pursue multiple-region waitlisting on post-transplant outcomes. Here, a simulation-based optimization model lets the patient select the best regions to be waitlisted in, given their demand-to-supply ratios. The second application focuses on a system-level aspect of transplantation, namely the contribution of information sharing on improving kidney discard rates and social welfare. We investigate the effects of using modern information technology to accelerate finding a matching patient to an available donor organ on waitlist mortality, kidney discard, and transplant rates. We show that modern information technology support currently developed by the United Network for Organ Sharing (UNOS) is essential and can significantly improve kidney utilization.

Cost-Effectiveness of Antibody-Based Induction Therapy in Deceased Donor Kidney Transplantation in the United States.

BACKGROUND: Induction therapy in deceased donor kidney transplantation is costly, with wide discrepancy in utilization and a limited evidence base, particularly regarding cost-effectiveness. METHODS: We linked the United States Renal Data System data set to Medicare claims to estimate cumulative costs, graft survival, and incremental cost-effectiveness ratio (ICER - cost per additional year of graft survival) within 3 years of transplantation in 19 450 deceased donor kidney transplantation recipients with Medicare as primary payer from 2000 to 2008. We divided the study cohort into high-risk (age > 60 years, panel-reactive antibody > 20%, African American race, Kidney Donor Profile Index > 50%, cold ischemia time > 24 hours) and low-risk (not having any risk factors, comprising approximately 15% of the cohort). After the elimination of dominated options, we estimated expected ICER among induction categories: no-induction, alemtuzumab, rabbit antithymocyte globulin (r-ATG), and interleukin-2 receptor-antagonist. RESULTS: No-induction was the least effective and most costly option in both risk groups. Depletional antibodies (r-ATG and alemtuzumab) were more cost-effective across all willingness-to-pay thresholds in the low-risk group. For the high-risk group and its subcategories, the ICER was very sensitive to the graft survival; overall both depletional antibodies were more cost-effective, mainly for higher willingness to pay threshold (US $100 000 and US $150 000). Rabbit ATG appears to achieve excellent cost-effectiveness acceptability curves (80% of the recipients) in both risk groups at US $50 000 threshold (except age > 60 years). In addition, only r-ATG was associated with graft survival benefit over no-induction category (hazard ratio, 0.91; 95% confidence interval, 0.84-0.99) in a multivariable Cox regression analysis. CONCLUSIONS: Antibody-based induction appears to offer substantial advantages in both cost and outcome compared with no-induction. Overall, depletional induction (preferably r-ATG) appears to offer the greatest benefits.

Selenium Ameliorate Peripheral Nerve Ischemic-Reperfusion Injury via Decreased TNF-α.

Selenium is considered as a trace element that plays antioxidant role in the body. So, the aim of this study was to evaluate the effect of selenium on ameliorating of sciatic nerve ischemia-reperfusion injury. Eighty (80) adult male Wistar rats weighing 250-300 g were used. They were divided into 10 groups (n = 8). Then, femoral vessels were obstructed by using 4/0 silk and splitknot techniques. After 3-h ischemia for all the groups, reperfusion was applied for different periods: 3, 7, 14, and 28 days. In half of each experimental group, 0.2 mg/kg selenium was injected intraperitoneally, coinciding with ischemia. After reperfusion, according to the grouping, rats were killed by using high dose of anesthetic drug and then sciatic nerve was removed and fixed. Then, tissue samples were processed and subsequently stained with hematoxylin-eosin, apoptosis, and immunohistochemistry stains. On the third day of reperfusion, the amount of TNF-α as an inflammatory marker of ischemia-reperfusion acute phase increased. On the seventh day of reperfusion, the amount of NF-кB as an apoptotic index and infiltration of mast cells increased in the tissue as a result of development of inflammation. But, on the 14th day of reperfusion, the amount of NF-кB as an apoptotic index decreased to the lowest amount. On the 28th day of reperfusion, the amount of TNF-α as an inflammatory marker decreased to its lowest level. Prescription of selenium concurrent with development of ischemia can reduce the damage caused by sciatic nerve ischemia-reperfusion.