Higher expression of SALL4-A isoform is correlated with worse outcomes and progression of the disease in subtype of testicular germ cell tumours.

BACKGROUND: The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumours. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation. METHODS: The expression and clinical significance of isoform 'A' of SALL4 was evaluated in 124 testicular germ cell tumours (TGCTs) subtypes, adjacent 67 normal tissues and 22 benign tumours, using immunohistochemistry on tissue microarrays (TMA). RESULTS: A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumours compared to the normal tissues. Seminoma and yolk sac tumours had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumour recurrence (P = 0.04) and invasion of the epididymis (P = 0.011). CONCLUSIONS: SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.

What may encourage or deter health services utilization by people living with or at the risk of HIV/AIDS in special health centers? Qualitative evidence from a stigmatized community.

BACKGROUND: Behavioral Diseases Counseling Centers (BDCCs) and Vulnerable Women's Counseling Centers (VWCCs) in Iran are the main peripheral centers that offer educational, counseling, diagnostic, preventive, curative and protective services to individuals living with or at high risk of contracting HIV/AIDS and female sex workers respectively. Due to the social stigma surrounding HIV in Iran, this study aims to identify the factors that may hinder or encourage HIV/AIDS patients and women with risky sexual behaviors from visiting these centers. METHODS: Conducted in 2023, this qualitative study involved individuals visiting BDCCs and VWCCs in two western provinces of Iran, Ilam and Kermanshah. The study participants included 21 health staff members working in BDCCs and VWCCs and 20 HIV/AIDS patients and vulnerable women with unsafe sexual behaviors referring to these centers. Purposive, snowball and maximum variation sampling techniques were applied to interview the participants. Interviews were conducted between January 5th and May 21st, 2023, using a semi-structure guideline. Interviews were transcribed and content analysis approach was applied to analyze data using MAXQDA20 software. RESULTS: According to the findings, the barriers and facilitators of visiting specialized centers for HIV/AIDS patients and vulnerable women were categorized into three main categories, 10 subcategories and 35 sub-subcategories including: Medical and operational processes (4 subcategories and 12 sub-subcategories), mutual interactions between the personnel and visitors (people living with and at the risk of getting HIV/AIDS) (3 subcategory and 13 sub-subcategories), and physical characteristics of the centers (3 subcategories and 10 sub-subcategories). CONCLUSIONS: To improve the performance of BDCCs and VWCCs and encourage people living with and at the risk of contracting HIV/AIDS to visit these centers regularly, health policy makers should consider modifying clinical processes, physical features, personnel behaviors and visitors' concerns raised by the interviewees and the issues identified in this study.

Effect of the COVID-19 pandemic on utilization of essential health services in Iran evidence from an interrupted time series analysis.

BACKGROUND: The COVID-19 disrupted the provision of essential health services in numerous countries, potentially leading to outbreaks of deadly diseases. This study aims to investigate the effect of the COVID-19 pandemic on the utilization of essential health services in Iran. METHODS: An analytical cross-sectional study was conducted using interrupted time series (ITS) analysis. Data about five indicators, including 'childhood vaccination, infant care, hypertension screening, diabetes screening, and breast cancer screening,' were obtained from the electronic health record System in two-time intervals: 15 months before (November 2018 to January 2020) and 15 months after (January 2020 to May 2021) the onset of the COVID-19 pandemic. The data were analyzed by utilizing ITS. In addition, a Poisson model was employed due to the usage of count data. The Durbin-Watson (DW) test was used to identify the presence of lag-1 autocorrelation in the time series data. All statistical analysis was performed using R 4.3.1 software, considering a 5% significance level. RESULTS: The ITS analysis showed that the COVID-19 pandemic significantly affected the utilization of all essential health services (P < 0.0001). The utilization of hypertension screening (RR = 0.51, p < 0.001), diabetes screening (RR = 0.884, p < 0.001), breast cancer screening (RR = 0.435, p < 0.001), childhood vaccination (IRR = 0.947, p < 0.001), and infant care (RR = 1.666, p < 0.001), exhibited a significant decrease in the short term following the pandemic (P < 0.0001). However, the long-term trend for all service utilization, except breast cancer screening (IRR = 0.952, p < 0.001), demonstrated a significant increase. CONCLUSIONS: The COVID-19 pandemic affected utilization of essential health care in Iran. It is imperative to utilize this evidence to develop policies that will be translated into targeted planning and implementation to sustain provision and utilization of essential health services during public health emergencies. It is also vital to raise awareness and public knowledge regarding the consequences of interruptions in essential health services. In addition, it is important to identify the supply- and demand-side factors contributing to these disruptions.

What factors influence couples' decisions to have children? Evidence from a systematic scoping review.

BACKGROUND: One of the most significant demographic challenges over the past three decades has been the substantial reduction in fertility rates, worldwidely. As a developing country, Iran has also experienced a rapid decline in fertility over the past decades. Understanding factors influencing fertility is essential for development programs. Moreover, it's crucial to study the parameters that affect the intention for childbearing in any society. Therefore, through a systematic scoping review, the present study investigates the factors influencing couples' decisions toward childbearing. METHODS: This study was a systematic scoping review conducted in 2023. To design and conduct this scoping review, Joanna Briggs Institute's Protocol (Institute TJB, The Joanna Briggs Institute Reviewers ' manual 2015; methodology for JBI scoping reviews, 2015) was used and the framework presented by Levac et al. (2010) was also used as a guide for conducting this review. Studies were searched in three main databases including ISI Web of Sciences, PubMed, and Scopus, using a predefined search strategy. Google Scholar was also used for complementary search. The search period was from 2002 to 2022. RESULTS: A total of 18,454 studies were identified across three primary databases. After evaluating articles in three distinct phases based on title, abstract, and full-text, 46 articles were deemed eligible for inclusion in the scoping review. The qualitative analysis of the collected data from the selected studies through the scoping review led to classifying factors influencing households' desire for childbearing into eight main themes and 101 sub-themes. The main themes associated with factors impacting households' intention for childbearing encompass individual determinants, demographic and familial influencing factors, cultural elements, social factors, health-related aspects, economic considerations, insurance-related variables, and government support/incentive policies. CONCLUSIONS: Comprehensive and holistic attention from governments and officials toward the various factors affecting households' intention and behavior regarding childbearing appears beneficial and effective. Furthermore, given the relative ineffectiveness of some of the current government's supportive/incentive policies to increase couples' desire for childbearing, it seems necessary to review and amend these policies. This review should address the most significant challenges and factors contributing to couples' reluctance to childbearing or strengthen factors that can play a substantial role in fostering fertility and childbearing desires.

Development of a potent recombinant scFv antibody against the SARS-CoV-2 by in-depth bioinformatics study: Paving the way for vaccine/diagnostics development.

BACKGROUND: The SARS-CoV-2 has led to a worldwide disaster. Thus, developing prophylactics/therapeutics is required to overcome this public health issue. Among these, producing the anti-SARS-CoV-2 single-chain variable fragment (scFv) antibodies has attracted a significant attention. Accordingly, this study aims to address this question: Is it possible to bioinformatics-based design of a potent anti-SARS-CoV-2 scFv as an alternative to current production approaches? METHOD: Using the complexed SARS-CoV-2 spike-antibodies, two sets analyses were performed: (1) B-cell epitopes (BCEs) prediction in the spike receptor-binding domain (RBD) region as a parameter for antibody screening; (2) the computational analysis of antibodies variable domains (VH/VL). Based on these primary screenings, and docking/binding affinity rating, one antibody was selected. The protein-protein interactions (PPIs) among the selected antibody-epitope complex were predicted and its epitope conservancy was also evaluated. Thereafter, some elements were added to the final scFv: (1) the PelB signal peptide; (2) a GSGGGGS linker to connect the VH-VL. Finally, this scFv was analyzed/optimized using various web servers. RESULTS: Among the antibody library, only one met the various criteria for being an efficient scFv candidate. Moreover, no interaction was predicted between its paratope and RBD hot-spot residues of SARS-CoV-2 variants-of-Concern (VOCs). CONCLUSIONS: Herein, a step-by-step bioinformatics platform has been introduced to bypass some barriers of traditional antibody production approaches. Based on existing literature, the current study is one of the pioneer works in the field of bioinformatics-based scFv production. This scFv may be a good candidate for diagnostics/therapeutics design against the SARS-CoV-2 as an emerging aggressive pathogen.

Comparison of Essential and Toxic Metals Levels in some Herbal Teas: a Systematic Review.

In the present study, we reviewed the literature as a systematic review to investigate the concentration of some metals (essential, none essential, and toxic metals) in herbal teas and their health risks. The search extended the literature from the database, including Google Scholar, PubMed, and Scopus, using the terms "herbal teas" combined with "heavy metals, essential metals, thyme, rosemary, chamomile, and tea" also with "iron, zinc, aluminum, chromium, cobalt, nickel, manganese, arsenic, cadmium, and lead" in titles and abstracts. The search was limited to articles published from 2012 to 2023 years. Initially, 212 articles were found; by detailed consideration, only 49 papers fit the inclusion criteria and were selected for further study. The mean of metal concentration, standard deviation, data distribution, and sample size were applied to generate data from the articles. The results indicated that all commonly consumed herbal teas included metals. None of them meet the requirements of the WHO requirements. However, more than 70% of their health risks are acceptable. The risks of arsenic and lead in tea and cadmium in black tea were considerably higher than in others. According to the review results, it is important to prevent heavy metal contamination of herbal teas by modifying cultivation patterns and also to prevent to consumption of low-quality herbal teas.

The effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia Patients-Clinical cohort study.

BACKGROUND: Cervical cancer is one of the most common malignancies in women, and its treatment has many side effects. Therefore, in this research, the effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia (CIN) patients were investigated. METHODS: 15 patients who met the inclusion criteria and diagnosed as CIN II and CIN III were included in the study. The vaccine was injected inside the cervix (neoplasia site) at increasing doses during 21 days, and they were evaluated for adverse events. NDV antibody titer was measured in 90 days and the levels of ki-67 and p16 proteins were studied by immunohistochemistry. Also, the levels of some important inflammatory cytokines in the serum of CIN patients were measured and finally the patients were evaluated according to the final outcomes and the reduction of tumor lesions. RESULTS: Only in the first dose of vaccine some patients showed flu-like symptoms. The accumulation of NDV antibodies started on the 7th day of the study and increased until the 90th day. Administration of LaSota vaccine had no significant effect on the expressions of Ki-67 and p16 proteins. Nevertheless, a decrease in the serum levels of Il-1ß was observed in patients after the administration of the vaccine, but the serum levels of both Il-2 and INF-γ upregulated significantly. Also, vaccine administration had no significant effect in reducing CIN grades and lesions. CONCLUSIONS: In general, we concluded that LaSota strain of NDV vaccine has no therapeutic effectiveness in CIN patients.

Design, development, and assessment of a novel multi-peptide vaccine targeting PspC, PsaA, and PhtD proteins of Streptococcus pneumoniae.

Pneumococcus is the top cause of diseases such as pneumonia/meningitis, and of secondary infections after viral respiratory diseases like COVID-19/flu. Pneumococcal protein-based vaccines consisting of proteins with various functions in virulence might provide a qualified alternative for present vaccines. In this project, PspC, PsaA, and PhtD proteins were considered to anticipate B/T-cell epitopes using immunoinformatics to develop 4 multi-peptide constructs (C, A, and D individual constructs, and a fusion construct CAD). We tested whether vaccination with CAD is able to elicit more efficient protective responses against infection than vaccination with the individual constructs or combination of C + A + D. Based on the in silico results, the constructs were predicted to be antigenic, soluble, non-toxic, and stable, and also be able to provoke humoral/cellular immune reactions. When mice were immunized with the fusion protein, significantly higher levels of IgG and cytokines were induced in serum. The IgG in the fusion group had an effective bioactivity for pneumococcus clearance utilizing the complement pathway. The mice immunized with fusion protein were the most protected from challenge. This report for the first time presents a novel multi-peptide vaccine composed of immunodominant peptides of PspC, PsaA, and PhtD. In general, the experimental results supported the immunoinformatics predictions.

Factors affecting the choice of treatment center by infertile couples: A cross-sectional study in Yazd Reproductive Sciences Institute.

Background: Infertility is one of the critical health issues in Iran. There are more than 70 specialized infertility treatment centers in Iran, of which the Yazd Reproductive Sciences Institute, is one of the most important ones. Objective: This study aimed to determine the factors influencing infertile couples' choice of Yazd Reproductive Sciences Institute. Materials and Methods: This cross-sectional study was conducted on 275 infertile couples aged 18 and older, referring to Yazd Reproductive Sciences Institute, Yazd, Iran from September 2021 to March 2022. Data were gathered using a 2-part questionnaire. Data analysis was done through SPSS software. We used descriptive statistics, Kruskal-Wallis, Mann-Whitney, and t test for data analysis. Results: Most participants were individuals who came from other provinces of Iran (74.9%) and were referred to the Yazd Reproductive Sciences Institute. Among the 4 categories that influenced couples' decision to choose this center, factors related to the personnel and treatment staff received the highest score (75.83), while personal factors received the lowest score (65.76). The average score for factors related to doctors was 72.90, and for factors related to the center, it was 73.65. The satisfaction with personnel and treatment staff varied based on participants' education levels, with those who had lower levels of education reporting higher levels of satisfaction (p < 0.001). Conclusion: The primary factors contributing to the success of the Yazd Reproductive Sciences Institute in attracting clients were the dedication and expertise of the staff, as well as the esteemed reputation of the doctors at the center.

Molecular and Antigen Detection, Phylogenetics, and Immunoinformatics Study of the Zoonotic Coronavirus in Iranian Diarrheic Calves.

Background: Bovine coronaviruses (BCoVs) are zoonotic diseases that result in substantial economic losses due to mortality, impaired growth, and increased medication expenses in large animals. These viruses pose a risk to children who live beside infected animal, as they can cause diarrhea. This study was dedicated to molecular and antigen detections and phylogenetic and immunoinformatics analysis of zoonotic coronavirus (CoV) in Iran. Materials and Methods: A total of 77 diarrheic samples were collected from Holstein dairy herds in selected provinces of Iran. Samples were tested by capture antibody enzyme-linked immunosorbent assay (ELISA) to detect CoV and reverse transcriptase-polymerase chain reaction (RT-PCR) for verification of detection and also genotyping of spike glycoprotein in CoV-positive samples. After statistical analysis, nucleotide sequence alignment, and nucleotide and protein phylogenetic tree construction, the centralized sequence for vaccine strains was obtained using computationally optimized broadly reactive antigen (COBRA)'s center-of-the-tree (COT) method. Results: Twenty-two (28.5%) and eight (10.3%) of 77 samples were positive according to RT-PCR and ELISA, respectively. (Basic Local Alignment Search Tool) BLAST and phylogenetic analysis revealed that most similar sequences to the Iranian CoV sequence were for European countries. Furthermore, there were strong correlations to other CoVs in humans and wild and domesticated animals. As CoV has variable COT, the most recent strains and COBRA vaccine strains were obtained. Conclusion: Based on the high prevalence of this viral disease in calves and its economic impact on the breeding industry, as well as the potential transmission to humans and correlation with World Health Organization (WHO) One Health approach guidelines, the study emphasizes the importance of implementing preventive strategies such as animal vaccination.

An experimental study of the effects of bacteria on asphaltene adsorption and wettability alteration of dolomite and quartz.

The adsorption of asphaltene on the rock surface and the changes in its wettability are very relevant issues in flow assurance and oil recovery studies, and for carbonate reservoirs, they are even more important. During microbial enhanced oil recovery (MEOR) processes, wettability alteration is considered a crucial mechanism leading to improved oil recovery. Therefore, it is essential to understand the mechanisms of surface wettability changes by bacteria and biosurfactants and find new and reliable methods to prevent asphaltene adsorption. Hence, the main aim of this research was to investigate the effect of a mixture of thiobacillus thiooxidans and thiobacillus ferooxidans microorganisms with an optimum effective temperature of around 30 °C (referred to as mesophilic bacteria), as well as a mixture of two moderate thermophiles Sulfobacillus thermosulfidooxidans for operating temperatures around 50 °C (referred to as moderately thermophilic bacteria) on the adsorption of asphaltene samples isolated from two different crude oils onto main reservoir minerals (i.e., quartz and dolomite). The results indicated that after two weeks of mineral aging in moderate thermophilic bacteria, the adsorption of asphaltene on both minerals increased between 180 and 290%. Fourier-transform infrared spectroscopy (FTIR) analysis for quartz and dolomite samples demonstrated that after aging in bacterial solution, bonds related to the adsorption of bacterial cells and biosurfactant production appear, which are the main factors of change in wettability. Alteration in wettability towards hydrophilicity expands hydrogen bonds on the surface, thus improving asphaltene adsorption due to polar interaction. Asphaltene 1 changed the contact angle of dolomite from 53.85° to 90.51° and asphaltene 2 from 53.85° to 100.41°. However, both strains of bacteria caused a strong water-wetting effect on the dolomite rock samples. The influence of moderate thermophilic bacteria on surface wettability is more significant than that of mesophilic bacteria, which may be caused by the high protein content of these bacteria, which expands hydrogen bonding with the surface. Adsorption of asphaltenes on dolomite rocks previously aged with bacteria showed that the wetted rock samples retained their water-wet state. This study highlights the dual impact of the used microorganisms. On one hand, they significantly reduce contact angles and shift wettability towards a strongly water-wet condition, a crucial positive factor for MEOR. On the other hand, these microorganisms can elevate the adsorption of asphaltenes on reservoir rock minerals, posing a potential challenge in the form of formation damage, particularly in low-permeability reservoirs.

Preparation, Purification and Performance Evaluation of Polyclonal Antibody Against SARS-CoV-2 Produced in Rat.

Purpose: Among all known human coronaviruses, some viruses (e.g., SARS-CoV-2) cause severe pneumonia or even death. With the regard to its spread and the importance of its rapid identification/treatment, and because pAbs are relatively cheap, able to bind to more sites on antigens and even neutralize them, this study was done for the production and purification of anti-SARS-CoV-2 polyclonal antibodies (pAb) in rats. Methods: Viral antigen purification was performed by PEG/NaCl precipitation. The efficiency of the sucrose cushion method was also investigated to produce a purer antigen. Immunization was done and antibody purification was performed by ammonium sulfate precipitation (33%), dialysis, and ion-exchange chromatography. Western blotting and enzyme-linked immunosorbent assay (ELISA) were performed to verify the antibody specificity. All data were analyzed by SPSS software. Results: The results showed that the amount of concentrated virus increased with the increase of PEG concentration. Moreover, the sucrose cushion method increased its purity. Besides, induction of immune response in rats for pAb production with high titers was reached via these antigens and ELISA/western blot results indicated a suitable antibody-antigen interaction. Additionally, it was shown that ion-exchange chromatography could be a suitable technique for IgG purification. Conclusion: Herein, we presented a simple and cheap method for the purification of whole viral particles with relatively high quality. The results verified that these antigens could elicit a good immune response in the rat. The obtained pAbs showed a good specificity toward SARS-CoV-2 antigens. Accordingly, this study proposes a promising method for viral vaccine development.

Comparative Analysis and Identification of Spike Mutations in Iranian COVID-19 Samples from the First Three Waves of Disease.

Background: The spike surface glycoprotein of SARS-CoV-2 is the essential protein in virus attachment to the target cell and cell entrance. As this protein contains immunodominant epitopes and is the main target for immune recognition, it is the critical target for vaccine and therapeutics development. In the current research, we analyzed the variability and mutations of the spike glycoprotein isolated from 72 COVID-19-positive patients from Iran's first three waves of disease. Materials and Methods: The RNA was extracted from nasopharyngeal samples of confirmed COVID-19 cases and served as a template for cDNA synthesis and reverse transcriptase polymerase chain reaction. The reverse transcriptase polymerase chain reaction products of each sample were assembled and sequenced. Results: After analysis of 72 sequences, we obtained 46 single nucleotide polymorphisms, including 23 that produce amino acid changes. Our analysis showed that the most frequent mutation was the D614G (in the samples of the second and third waves). Conclusions: Our findings suggest that developing effective vaccines requires identifying the predominant variants of SARS-CoV-2 in each community.

Iranian Health System Response to the COVID-19 Pandemic.

Introduction: The COVID-19 pandemic has created several challenges for countries all over the world. Different countries have taken different measures to fight this pandemic and reduce its challenges depending on their cultural, economic, and social structures. This study aims to understand and explain the Iranian health system's response to fighting the COVID-19 pandemic from the managers' and authorities' perspective. Method: This study is a basic applied research performed under a qualitative approach. In the survey, 30 experts including the managers of health centers and deputies and heads of the Ministry of Health and Medical Education and Medical Universities were selected by purposive snowball sampling and participated in semi-structured interviews from March to May 2020. The researchers explained the actions of the Iranian health system in fighting the COVID-19 pandemic in 2020 by content analysis. Results: As a result, 14 subthemes were found and classified into four major themes, including the informative and regulative actions (two subthemes), administrative and supportive actions (six subthemes), preventive and curative actions (three subthemes), and resource-related actions (three subthemes). Conclusions: Due to its strong health structures, such as urban and rural health networks, various general and specialized hospitals, experienced doctors, and committed health staff, Iran has taken practical actions in fighting the COVID-19 pandemic. However, the findings of this study and its relevant measures can help combat this pandemic in countries with similar social and cultural structures or counter future similar crises.

Translation and validation of the Persian version of diabetic foot ulcer scaleshort form (DFS-SF).

Foot ulcer in diabetic patients could often result in significantly impaired quality of life. This study aimed to translate and validate the DFS-SF in Iran. The DFS-SF was translated into Persian, and then its validity and reliability were tested in 262 patients with DFUs. Content validity was evaluated using content validity ratio (CVR) and content validity index (CVI), and criterion validity was assessed through Spearman's correlation between dimensions of the DFS-SF and the EQ-5D-5L. Construct validity was measured using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and convergent-discriminant validity was examined by calculating the average variance extracted (AVE) and composite reliability (CR). Cronbach's alpha and intraclass correlation coefficient (ICC) were calculated to evaluate the reliability of the measure. CVR ≥0.66 and CVI = 0.81 were calculated. Spearman's correlation ranged from 0.23 to 0.78 across all dimensions. The results of EFA showed that all six dimensions of the DFS-SF had an eigenvalue more than 1; accounting for 68.88% of the total variance. CFA confirmed the DFS-SF as a six-dimension structure with good fit indices of χ2/df = 2.15 < 5, RMSEA = 0.06 < 0.08, CFI = 0.91 ≥ 0.90, TLI = 0.90 ≥ 0.90, and RMR = 0.04, as well as with adequate fit indices of GFI = 0.84 ≤ 0.90, NFI = 0.86 ≤ 0.90. Estimates of ≥0.50 for AVE were not observed in two of the six dimensions and CR ≥0.70 was obtained for all dimensions. The reliability was calculated with a Cronbach's alpha of 0.89 and ICC >0.69 for all dimensions. Our findings confirmed the validity and reliability of the Persian DFS-SF; therefore, it can be used to assess QoL in patients with DFSs in clinical and research settings in Iran.

Immunoinformatics-aided design of a new multi-epitope vaccine adjuvanted with domain 4 of pneumolysin against Streptococcus pneumoniae strains.

BACKGROUND: Streptococcus pneumoniae (Pneumococcus) has remained a leading cause of fatal infections such as pneumonia, meningitis, and sepsis. Moreover, this pathogen plays a major role in bacterial co-infection in patients with life-threatening respiratory virus diseases such as influenza and COVID-19. High morbidity and mortality in over one million cases, especially in very young children and the elderly, are the main motivations for pneumococcal vaccine development. Due to the limitations of the currently marketed polysaccharide-based vaccines, non-serotype-specific protein-based vaccines have received wide research interest in recent years. One step further is to identify high antigenic regions within multiple highly-conserved proteins in order to develop peptide vaccines that can affect various stages of pneumococcal infection, providing broader serotype coverage and more effective protection. In this study, immunoinformatics tools were used to design an effective multi-epitope vaccine in order to elicit neutralizing antibodies against multiple strains of pneumococcus. RESULTS: The B- and T-cell epitopes from highly protective antigens PspA (clades 1-5) and PhtD were predicted and immunodominant peptides were linked to each other with proper linkers. The domain 4 of Ply, as a potential TLR4 agonist adjuvant candidate, was attached to the end of the construct to enhance the immunogenicity of the epitope vaccine. The evaluation of the physicochemical and immunological properties showed that the final construct was stable, soluble, antigenic, and non-allergenic. Furthermore, the protein was found to be acidic and hydrophilic in nature. The protein 3D-structure was built and refined, and the Ramachandran plot, ProSA-web, ERRAT, and Verify3D validated the quality of the final model. Molecular docking analysis showed that the designed construct via Ply domain 4 had a strong interaction with TLR4. The structural stability of the docked complex was confirmed by molecular dynamics. Finally, codon optimization was performed for gene expression in E. coli, followed by in silico cloning in the pET28a(+) vector. CONCLUSION: The computational analysis of the construct showed acceptable results, however, the suggested vaccine needs to be experimentally verified in laboratory to ensure its safety and immunogenicity.

Experimental measurement and modeling of asphaltene adsorption onto iron oxide and lime nanoparticles in the presence and absence of water.

Asphaltene precipitation and its adsorption on different surfaces are challenging topics in the upstream and downstream of the oil industries and the environment. In this research, the phenomenon of asphaltenes adsorption in the presence and absence of water on the surface of magnetite, hematite, calcite, and dolomite nanoparticles (NPs) was investigated. Five asphaltenes of different origins, four NPs as adsorbents and Persian Gulf water were used for three-phase (asphaltene/toluene solution + NPs + water) experiments. Characterization of asphaltenes and NPs was performed using Fourier transform infrared spectroscopic (FTIR), dynamic light scattering (DLS), elemental analysis, and field emission scanning electron microscopy (FESEM). Adsorption experiments were performed in two- (asphaltene/toluene solution + NPs) and three-phase systems. The results showed that the most effective parameters for asphaltene adsorption onto these NPs are the asphaltene composition, namely nitrogen content, and the aromaticity of asphaltenes. The significant effects of these parameters were also confirmed by the relevancy factor function as a sensitivity analysis. In the competition of asphaltene adsorption capacity by NPs, iron oxide NPs had the highest adsorption (Magnetite NPs > Hematite NPs > Calcite NPs > Dolomite NPs). From the results of the experiments in the presence of water phase, it could be pointed out that the asphaltenes adsorption onto the NPs was accompanied by a decrease compared to the experiments in the absence of water. The modeling also showed that physical adsorption has a significant contribution to the asphaltenes adsorption on the surface of iron oxides and lime NPs. The results of this research can assist in a better understanding of the asphaltene adsorption phenomenon and the role of iron oxide and lime NPs in solving this problem.

Expression, purification, and study on the efficiency of a new potent recombinant scFv antibody against the SARS-CoV-2 spike RBD in E. coli BL21.

Many efforts have been made around the world to combat SARS-CoV-2. Among these are recombinant antibodies considered to be suitable as an alternative for some diagnostics/therapeutics. Based on their importance, this study aimed to investigate the expression, purification, and efficiency of a new potent recombinant scFv in the E. coli BL21 (DE3) system. The expression studies were performed after confirming the scFv cloning into the pET28a vector using specific PCRs. After comprehensive expression studies, a suitable strategy was adopted to extract and purify periplasmic proteins using Ni2+-NTA resin. Besides the purified scFv, the crude bacterial lysate was also used to develop a sandwich ELISA (S-ELISA) for the detection of SARS-CoV-2. The use of PCR, E. coli expression system, western blotting (WB), and S-ELISA confirmed the functionality of this potent scFv. Moreover, the crude bacterial lysate also showed good potential for detecting SARS-CoV-2. This could be decreasing the costs and ease its utilization for large-scale applications. The production of high-quality recombinant proteins is essential for humankind. Moreover, with attention to the more aggressive nature of SARS-CoV-2 than other coronaviruses, the development of an effective detection method is urgent. Based on our knowledge, this study is one of the limited investigations in two fields: (1) The production of anti-SARS-CoV-2 scFv using E. coli [as a cheap heterologous host] in relatively high amounts and with good stability, and (2) Designing a sensitive S-ELISA for its detection. It may also be utilized as potent therapeutics after further investigations.

Safety and Effectiveness of Cinnomer® on Disease Characteristics, Depression, and Quality of Life of Patients with Multiple Sclerosis: A Phase IV, Post-marketing, Prospective, Multicenter Study.

BACKGROUND: Every patient diagnosed with definite multiple sclerosis (MS) should begin disease modifying therapies. Cinnomer® contains 40 mg glatiramer acetate (GA) and is available in prefilled syringes and autoinjector devices. METHODS: A phase IV multicenter study was conducted to explore the safety and effectiveness of Cinnomer® in the treatment of MS. Study-related data were collected for 14 months. RESULTS: Totally, 368 Iranian relapsing-remitting MS patients in nine cities were enrolled. The patients were either treatment naïve (n=191) or switchers (n=177). Cinnomer® treatment was associated with a significant reduction in annual relapse rate (ARR) (RR: 0.65, 95% CI: 0.43, 0.98). Final mean Expanded Disability Status Scale (EDSS) scores showed improvement from baseline (difference: -0.21, 95% confidence interval (CI): -0.34, -0.08). There was a significant decrease in gad-enhancing lesions during treatment (difference: -0.38, 95% CI: -0.64, -0.12). The mean score for the depression measure (21-item BDI-II questionnaire) significantly improved (difference: -2.39, 95% CI: -3.74, -1.03). There was a significant change in the "psychological well-being" dimension (P=0.02) (in line with BDI-II scores) and "rejection" MusiQoL dimensions (P=0.04). The adverse events documented throughout the study were not unexpected for GA and were principally not serious. CONCLUSION: Safety measures were in line with the known profiles of GA. The results suggest that Cinnomer® is effective with respect to clinical outcomes and from the patient's perspective and in reducing MRI-measured MS activity.

Criteria for the selection of complementary private health insurance: the experience of a large organisation in Iran.

BACKGROUND: Expenses related to employee's health benefit packages are rising. Hence, organisations are looking for complementary health financing arrangements to provide more financial protection for employees. This study aims to develop criteria to choose the most appropriate complementary health insurance company based on the experience of a large organisation in Iran. METHODS: This study was conducted in 2021 in Iran, in the Foundation of Martyrs and Veterans Affairs to find as many applicable criteria as possible. To develop a comprehensive list of criteria, we used triangulation in data sources, including review of relevant national and international documents, in-depth interviews of key informants, focus group discussion, and examining similar but unpublished checklists used by other organisations in Iran. The list of criteria was prioritised during focus group discussions. We used the best-worst method as a multi-criteria decision making method and a qualitative consensus among the key informants to value the importance of each of the finalised criteria. FINDINGS: Out of 85 criteria, we selected 28 criteria to choose an insurer for implementing complementary private health insurance. The finalised criteria were fell into six domains: (i) Previous experience of the applicants; (ii) Communication with clients; (iii) Financial status; (iv) Health care providers' network; (v) Technical infrastructure and workforce; (vi) and Process of reviewing claims and reimbursement. CONCLUSION: We propose a quantitative decision-making checklist to choose the best complimentary private health insurance provider. We invite colleagues to utilise, adapt, modify, or develop these criteria to suit their organisational needs. This checklist can be applied in any low- and middle-income country where the industry of complementary health insurance is blooming.