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 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.

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 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.

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.

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.

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.

Assessment and partial purification of serine protease inhibitors from Rhipicephalus (Boophilus) annulatus larvae / Avaliação e purificação parcial dos inibidores da serina protease de larvas do Rhipicephalus (Boophilus) annulatus

Ticks are rich sources of serine protease inhibitors, particularly those that prevent blood clotting and inflammatory responses during blood feeding. The tick Rhipicephalus (Boophlus) annulatus is an important ectoparasite of cattle. The aims of this study were to characterize and purify the serine protease inhibitors present in R. (B.) annulatus larval extract. The inhibitors were characterized by means of one and two-dimensional reverse zymography, and purified using affinity chromatography on a trypsin-Sepharose column. The analysis on one and two-dimensional reverse zymography of the larval extract showed trypsin inhibitory activity at between 13 and 40 kDa. Through non-reducing SDS-PAGE and reverse zymography for proteins purified by trypsin-Sepharose affinity chromatography, some protein bands with molecular weights between 13 and 34 kDa were detected. Western blotting showed that five protein bands at 48, 70, 110, 130 and 250 kDa reacted positively with immune serum, whereas there was no positive reaction in the range of 13-40 kDa. Serine protease inhibitors from R. (B.) annulatus have anti-trypsin activity similar to inhibitors belonging to several other hard tick species, thus suggesting that these proteins may be useful as targets in anti-tick vaccines.

Carrapatos são uma rica fonte de inibidores da serina protease, particularmente aqueles que previnem coagulação e respostas inflamatórias durante a alimentação com sangue. O carrapato Rhipicephalus (B.) annulatus é um ectoparasita importante de bovinos. O objetivo deste estudo foi caracterizar e purificar os inibidores da serina protease presentes no extrato de larva do R. (B.) annulatus. Os inibidores foram caracterizados através de zimografia reversa uni e bidimensional e purificados com cromatografia de afinidade em uma coluna de sepharose-tripsina. A análise do extrato de larva pela zimografia reversa uni e bidimensional mostrou atividade inibitória de tripsina entre 13 e 40 kDa. Através de SDS-PAGE e zimografia reversa para proteínas purificadas pela cromatografia por sepharose-tripsina, algumas bandas de proteínas com pesos moleculares entre 13 e 34 kDa foram detectadas. Western blotting mostrou que cinco bandas de proteínas a 48, 70, 110, 130 e 250 kDa reagiram positivamente com o soro imune, enquanto não houve reação positiva nas bandas 13-40 kDa. Inibidores da serina protease do R. (B.) annulatus têm atividade antitripsina semelhante àquelas dos inibidores de outras espécies de carrapatos duros, sugerindo, assim, que essas proteínas podem ser úteis como alvo de vacinas contra carrapatos.