Epidemiologic Features and Risk Factors for Crimean-Congo Hemorrhagic Fever in Dhi Qar Province, Iraq.

BACKGROUND: Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Iraq, where recurrent epidemics have been constantly observed during the last five years. The present study aimed to determine the factors associated with Crimean-Congo hemorrhagic fever (CCHF) cases in Dhi Qar province during the year 2022. METHODS: A test-negative case-control design was used to analyze 621 CCHF patients, of which 162 were confirmed and 459 were suspected cases. To identify the confirmed and suspected cases, reverse transcriptase polymerase chain reaction (RT-PCR) was used. Suspected patients whose PCR test results were negative were selected as the control group. Data on potential risk factors for CCHF were collected as existing data for previous years for the same geographical locations in Dhi Qar province. Logistic regression analyses were used to determine the correlation between probable risk factors and confirmed CCHF cases. RESULTS: The incidence rate of CCHF was 6.8% per 100,000 people. The total number of deaths was 48 for patients with a case fatality rate of 7.7%. The patients' ages ranged from one year to 65 years, with an overall mean ± SD of 36.08 ± 18.29 years. A total of 98.2% of the patients were between 15 and 65 years of age; 58% of the reported patients were male, and the male-to-female ratio was 1.4:1. Additionally, contact with raw meat, animal contact, and tick bite had the highest percentages for CCHF positivity cases. CONCLUSIONS: Male gender, high-risk jobs like housewives, health staff, shepherds, butchers, animal dealers, slaughterhouse workers, veterinary staff, and farmers, tick bites, and contact with raw meat were statistically significant predictors for increasing CCHF incidence in Dhi Qar province during the year 2022.

Stability of Neutralizing Antibody of PastoCoAd Vaccine Candidates against a Variant of Concern of SARS-CoV-2 in Animal Models.

Background: Since the beginning of the SARS-CoV-2 pandemic, there have been mutations caused by new SARS-CoV-2 variants, such as Alpha, Beta, Gamma, Delta, and Omicron, recognized as the VOC worldwide. These variants can affect vaccine efficacy, disease control, and treatment effectiveness. The present study aimed to evaluate the levels of total and neutralizing antibodies produced by PastoCoAd vaccine candidates against the VOC strains at different time points. Methods: Two vaccine candidates were employed against SARS-CoV-2 using adenoviral vectors: prime only (a mixture of rAd5-S and rAd5 RBD-N) and heterologous prime-boost (rAd5-S/SOBERANA vaccine). The immunogenicity of these vaccine candidates was assessed in mouse, rabbit, and hamster models using ELISA assay and virus neutralization antibody test. Results: The immunogenicity results indicated a significant increase in both total and neutralizing antibodies titers in the groups receiving the vaccine candidates at various time points compared to the control group (p < 0.05). The results also showed that the PastoCoAd vaccine candidates Ad5 S & RBD-N and Ad5 S/SOBERANA could neutralize the VOC strains in the animal models. Conclusion: The ability of vaccine candidate to neutralize the VOC strains in animal models by generating neutralizing antibodies at different time points may be attributed to the use of the platform based on the Adenoviral vector, the N proteins in the Ad5 S & RBD-N vaccine candidate, and the SOBERANA Plus booster in the Ad5 S/SOBERANA vaccine candidate.

The prevalence of thyroid disorders in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to evaluate the prevalence of thyroid disorders in COVID-19 patients. DATA SOURCES: Scopus, PubMed, ISI Web of Science, and Google Scholar databases were used in this review. We also consider the results of grey literature. STUDY SELECTIONS: Cohort, cross-sectional, and case-control studies were included. DATA EXTRACTION AND SYNTHESIS: The required data were extracted by the first author of the article and reviewed by the second author. The Pooled prevalence of outcomes of interest was applied using the meta-prop method with a pooled estimate after Freeman-Tukey Double Arcsine Transformation to stabilize the variances. OUTCOMES AND MEASURED: The different thyroid disorders were the main outcomes of this study. The diseases include non-thyroidal illness syndrome, thyrotoxicosis, hypothyroidism, isolated elevated free T4, and isolated low free T4. RESULTS: Eight articles were included in our meta-analysis(Total participants: 1654). The pooled prevalence of events hypothyroidism, isolated elevated FT4, isolated low FT4, NTIS, and thyrotoxicosis were estimated (Pooled P = 3%, 95% CI:2-5%, I2: 78%), (Pooled P = 2%, 95% CI: 0-4%, I2: 66%), (Pooled P = 1%, 95% CI: 0-1%, I2: 0%), (Pooled P = 26%, 95% CI: 10-42%, I2: 98%), and (Pooled P = 10%, 95% CI: 4-16%, I2: 89%), respectively. CONCLUSION: Thyroid dysfunction is common in COVID-19 patients, with a high prevalence of non-thyroidal illness syndrome (NTIS) and thyrotoxicosis. Our meta-analysis found a 26% prevalence of NTIS and a 10% prevalence of thyrotoxicosis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022312601.

De novo KAT6B mutation causes Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome in an Iranian boy: a case report.

BACKGROUND: Say-Barber-Biesecker-Young-Simpson (SBBYS) (OMIM #603736, Ohdo syndrome variant) is a rare type of severe blepharophimosis intellectual disability syndrome, which is generally characterized by a global developmental delay, distinctive facial features, and intellectual disability with multiple congenital anomalies, including skeletal involvement, missing, or underdeveloped kneecaps, and genital anomalies, in affected males. It has been shown that mutations in the KAT6B gene, which is a lysine acetyltransferase-encoding gene, have been associated with SBBYS syndrome. All the known variants are dominant de novo mutations that result in protein truncation. CASE PRESENTATION: A 14-year-old Iranian Azeri boy with an intellectual disability, distinct dysmorphic facial features such as open-mouth expression, sparse medial eyebrows, widely spaced upward-slanted eyes, epicanthal folds, broad nasal bridge, low-set ears, anteverted ears, short philtrum, hypertelorism, microphthalmia is presented in this case study. Cryptorchidism was reported. Neurologically, the patient presented with poor eye contact, hypotonia, and speech difficulties. In the skeletal X-ray, underdeveloped kneecaps with some new features were observed. CONCLUSION: We present the first case of SBBYS syndrome in association with some new anomaly features in the Iranian population. Based on this diagnosis, we could provide the patient with a suitable plan of management as well as appropriate genetic counseling for his family.

Anti-tumor Effects of Cisplatin Synergist in Combined Treatment with Clostridium novyi-NT Spores Against Hypoxic Microenvironments in a Mouse Model of Cervical Cancer Caused by TC-1 Cell Line.

Purpose: Despite the development of anti-human papillomavirus (HPV) vaccines, cervical cancer is still a common disease in women, especially in developing countries. The presence of a hypoxic microenvironment causes traditional treatments to fail. In this study, we presented a combined treatment method based on the chemotherapeutic agent cisplatin and Clostridium novyi-NT spores to treat normoxic and hypoxic areas of the tumor. Methods: TC-1 Cell line capable of expressing HPV-16 E6/7 oncoproteins was subcutaneously transplanted into female 6-8 week old C57/BL6 mice. The tumor-bearing mice were randomly divided into four groups and treated with different methods after selecting a control group. Group 1: Control without treatment (0.1 mL sterile PBS intratumorally), Group: C. novyi-NT (107 C. novyi-NT). Group 3: Receives cisplatin intraperitoneally (10 mg/kg). Fourth group: Intratumoral administration of C. novyi-NT spores + intraperitoneal cisplatin. Western blot analysis was used to examine the effects of anti-hypoxia treatment and expression of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins. Results: The results clearly showed that combined treatment based on C. novyi-NT and cisplatin significantly reduced the expression of HIF-1 alpha and VEGF proteins compared to cisplatin alone. At the same time, the amount of necrosis of tumor cells in the combined treatment increased significantly compared to the single treatment and the control. At the same time, the mitotic count decreased significantly. Conclusion: Our research showed that developing a combined treatment method based on C. novyi-NT and cisplatin against HPV-positive cervical cancer could overcome the treatment limitations caused by the existence of hypoxic areas of the tumor.

Prevalence of preterm birth in Scandinavian countries: a systematic review and meta-analysis.

OBJECTIVES: As welfare societies, Scandinavian countries share characteristics of equality related to healthcare access, gender, and social services. However, cultural and lifestyle variations create country-specific health differences. This meta-analysis assessed the prevalence of preterm birth (PTB) and its categories in Scandinavian countries. METHODS: A systematic search in key databases of literature published between 1990 and 2021 identified studies of the prevalence of PTB and its categories. Following the use of the Freeman-Tukey double arcsine transformation, a meta-analysis of weighted data was performed using the random-effects model and meta-prop method. RESULTS: We identified 109 observational studies that involved 86,420,188 live births. The overall pooled prevalence (PP) of PTB was 5.3% (PP = 5.3%, 95% confidence interval [CI] 5.1%, 5.5%). The highest prevalence was in Norway (PP = 6.2%, 95% CI 5.3%, 7.0%), followed by Sweden (PP = 5.3%, 95% CI 5.1%, 5.4%), Denmark (PP = 5.2%, 95% CI 4.9%, 5.3%), and Iceland (PP = 5.0%, 95% CI 4.4%, 5.7%). Finland had the lowest PTB rate (PP = 4.9%, 95% CI 4.7%, 5.1%). CONCLUSIONS: The overall PP of PTB was 5.3%, with small variations among countries (4.9%-6.2%). The highest and lowest PPs of PTB were in Norway and Finland, respectively.

Molecular Investigation of the Association Among Common Interleukin-6 Polymorphism and Human Papillomavirus Genotypes with Cervical Cancer Among Iranian Women.

Cervical cancer is the fourth most commonly identified cancer and the third important reason for cancer-related death among women in less developed nations. Aside from the human papillomavirus (HPV), the host genetic factors, especially some polymorphisms in the interleukin 6 (IL-6) gene, might relate to the risk of cervical cancer. This study aims to investigate the molecular investigation of HPV infection and its association with the common polymorphism of IL-6 in cervical carcinoma in Iran. This case-control study collected 62 precancerous and cancerous lesions and 62 healthy samples from cancer-free women, subsequent negative colposcopy, and cervical cytology. The frequency of HPV genotypes and the genotyping of IL-6 rs1800795 and rs1800796 were done by different PCR techniques. Results were analyzed using the Epi Info version 7, 2012, with the χ2 test. Compared with cervical intraepithelial neoplasia grade 1 (CINI), the HPV positivity rate is saliently higher in CINII/III and squamous cell carcinoma (SCC) (56.25%, 66.66%, and 73.63%, respectively, p < 0.001). The HPV positivity rate is also higher in SCC in comparison with CINII/III (p < 0.01). Furthermore, the most detected HPV genotypes were HPV16 and 33 in CINI; HPV16, 31, and 35 in CINII/III; and HPV16 and 18 in SCC groups. HPV16 was the most commonly detected genotype in CINI, CINII/III, and SCC, accounting for 44.44%, 50%, and 71.42%, respectively. In addition, the frequency of GG, CG, and CC genotypes from rs1800795 polymorphism was 0.58, 0.32, and 0.10, respectively (p = 0.033), but in the control group, it was 0.70, 0.27, and 0.03, respectively. The findings suggest that HPV16 plays an important role in the emergence of cervical lesions in Iranian patients. As a result, rs1800795 CC genotype and HPV might increase cervical cancer risk in Iranian women.

Data-driven phenomapping for novel classification for cardiovascular outcomes compared with traditional obesity index: Tehran Lipid and Glucose Study.

OBJECTIVE: This study aimed to propose a data-driven framework for classification of at-risk people for cardiovascular outcomes regarding obesity and metabolic syndrome. DESIGN: A population-based prospective cohort study with a long-term follow-up. SETTING: Data from the Tehran Lipid and Glucose Study (TLGS) were interrogated. PARTICIPANTS: 12 808 participants of the TLGS cohort, aged ≥20 years who have followed for over 15 years were assessed. MAIN OUTCOME MEASURES: Data for 12 808 participants, aged ≥20 years who have followed for over 15 years, collected through TLGS as a prospective, population-based cohort study, were analysed. Feature engineering followed by hierarchical clustering was used to determine meaningful clusters and novel endophenotypes. Cox regression was used to demonstrate the clinical validity of phenomapping. The performance of endophenotype compared with traditional classifications was evaluated by the value of Akaike information criterion/Bayesian information criterion. R software V.4.2 was employed. RESULTS: The mean age was 42.1±14.9 years, 56.2% were female, 13.1%, 2.8% and 6.2% had experienced cardiovascular disease (CVD), CVD mortality and hard CVD, respectively. Low-risk cluster compared with the high risk had significant difference in age, body mass index, waist-to-hip ratio, 2 hours post load plasma glucose, triglyceride, triglycerides to high density lipoprotein ratio, education, marital status, smoking and the presence of metabolic syndrome. Eight distinct endophenotypes were detected with significantly different clinical characteristics and outcomes. CONCLUSION: Phenomapping resulted in a novel classification of population with cardiovascular outcomes, which can, better, stratify individuals into homogeneous subclasses for prevention and intervention as an alternative of traditional methods solely based on either obesity or metabolic status. These findings have important clinical implications for a particular part of the Middle Eastern population for which it is a common practice to use tools/evidence derived from western populations with substantially different backgrounds and risk profiles.

Sodium selenite preserves rBM-MSCs' stemness, differentiation potential, and immunophenotype and protects them against oxidative stress via activation of the Nrf2 signaling pathway.

BACKGROUND: The physiological level of reactive oxygen species (ROS) is necessary for many cellular functions. However, during the in-vitro manipulations, cells face a high level of ROS, leading to reduced cell quality. Preventing this abnormal ROS level is a challenging task. Hence, here we evaluated the effect of sodium selenite supplementation on the antioxidant potential, stemness capacity, and differentiation of rat-derived Bone Marrow MSCs (rBM-MSCs) and planned to check our hypothesis on the molecular pathways and networks linked to sodium selenite's antioxidant properties. METHODS: MTT assay was used to assess the rBM-MSCs cells' viability following sodium selenite supplementation (concentrations of: 0.001, 0.01, 0.1, 1, 10 µM). The expression level of OCT-4, NANOG, and SIRT1 was explored using qPCR. The adipocyte differentiation capacity of MSCs was checked after Sodium Selenite treatment. The DCFH-DA assay was used to determine intracellular ROS levels. Sodium selenite-related expression of HIF-1α, GPX, SOD, TrxR, p-AKT, Nrf2, and p38 markers was determined using western blot. Significant findings were investigated by the String tool to picture the probable molecular network. RESULTS: Media supplemented with 0.1 µM sodium selenite helped to preserve rBM-MSCs multipotency and keep their surface markers presentation; this also reduced the ROS level and improved the rBM-MSCs' antioxidant and stemness capacity. We observed enhanced viability and reduced senescence for rBM-MSCs. Moreover, sodium selenite helped in rBM-MSCs cytoprotection by regulating the expression of HIF-1 of AKT, Nrf2, SOD, GPX, and TrxR markers. CONCLUSIONS: We showed that sodium selenite could help protect MSCs during in-vitro manipulations, probably via the Nrf2 pathway.

Semiconducting eutectic materials for photocatalysis and photoelectrochemistry applications: a perspective.

The world of semiconductors has drastically improved human lifestyle due to its versatile applications. The demand for new efficient semiconductors is increasing day by day, giving birth to the idea of new synthesis methods. Here, the importance of semiconductor eutectic materials has been presented, as one of the potential candidates for solar-based devices such as photo-anodes for water splitting, along with the micro (µ) pulling method (as a synthesis method for semiconductor eutectic materials). A comparison of the efficiency of the present devices with the eutectic composites has been made, showing semiconductor eutectic materials as a better alternative. In addition, possible changes that can be achieved using the µ-pulling method to enhance the photo(electro)chemical (PEC) properties have focused on semiconducting eutectic materials in this article.

Molecular investigation of association between common IL-6 polymorphism with cytomegalovirus (CMV) infection and recurrent miscarriage in Iranian women.

BACKGROUND: Recurrent pregnancy loss (RPL) is described as two or more spontaneous abortions. To date, scientists in various fields of knowledge, such as genetics, endocrinology, anatomy, immunology, and microbiology, have identified some important factors that affect abortions; nonetheless, the precise basic etiology is not determined in up to 50% of RPL cases. Human cytomegalovirus (CMV) infection and host genetic background, like IL-6 SNP polymorphisms, play important roles in RPL etiology. OBJECTIVE: This study aimed to evaluate the relationships among single nucleotide polymorphisms (-634C/G and -174 G/C) in the IL-6 gene with CMV infection and the risk of RPL for early detection and treatment. MATERIALS AND METHODS: This case-control study was carried on 80 Iranian females with RPL and 80 healthy females as controls. DNA was extracted from samples and CMV and IL6 SNPs were detected using Tetra ARMS-PCR. Statistics were analyzed by Epi Info TM and SPSS software by X2 test for the roles of CMV detection and two polymorphisms in RPL. RESULTS: The results indicated an increased rate of CMV infection in the RPL group (44%) compared to the control group (25.45%). The prevalence of IL-6-634C/G genotype among RPL patients with CMV infection was 80%, while the frequency of this genotype among RPL patients without CMV infection was 50%. Furthermore, no substantial relation was found between IL-6-174 G/C genotypes and RPL (p = 0.005). CONCLUSION: This study not only indicated a significant role for CMV in RPL, but also showed an association between CMV and allele G in IL6-634 among Iranian women. In addition, the findings suggested the use of CMV and IL-6-634 GG genotypes as diagnostic and prognostic biomarkers for RPL in the Iranian population.

Adverse Pregnancy Outcomes and International Immigration Status: A Systematic Review and Meta-analysis.

Background: Disparities in health outcomes between immigrant and native-origin populations, particularly pregnant women, pose significant challenges to healthcare systems. The aim of this systematic-review and meta-analysis was to investigate the risk of adverse pregnancy outcomes among immigrant-women compared to native-origin women in the host country. Methods: PubMed (including MEDLINE), Scopus, and Web of Science were searched to retrieve studies published in English language up to September 2020. All observational studies examining the prevalence of at least one of the short-term single pregnancy outcomes for immigrants who crossed international borders compared to native-origin pregnant population were included. The meta-prop method was used for the pooled-estimation of adverse pregnancy-outcomes' prevalence. For pool-effect estimates, the association between the immigration-status and outcomes of interest, the random-effects model was applied using the model described by DerSimonian and Laird. I2 statistic was used to assess heterogeneity. The publication bias was assessed using the Harbord-test. Meta-regression was performed to explore the effect of geographical region as the heterogeneity source. Findings: This review involved 11 320 674 pregnant women with an immigration-background and 56 102 698 pregnant women as the native-origin population. The risk of emergency cesarean section (Pooled-OR = 1.1, 95%CI = 1.0-1.2), shoulder dystocia (Pooled-OR = 1.1, 95%CI = 1.0-1.3), gestational diabetes mellites (Pooled-OR = 1.4, 95%CI = 1.2-1.6), small for gestational age (Pooled-OR=1.3, 95%CI = 1.1-0.4), 5-min Apgar less than 7 (Pooled-OR = 1.2, 95%CI = 1.0-1.3) and oligohydramnios (Pooled-OR = 1.8, 95%CI = 1.0-3.3) in the immigrant women were significantly higher than those with the native origin background. The immigrant women had a lower risk of labor induction (Pooled-OR = 0.8, 95%CI = 0.7-0.8), pregnancy induced hypertension (Pooled-OR = 0.6, 95%CI = 0.5-0.7) preeclampsia (Pooled-OR = 0.7, 95%CI = 0.6-0.8), macrosomia (Pooled-OR = 0.8, 95%CI = 0.7-0.9) and large for gestational age (Pooled-OR = 0.8, 95%CI = 0.7-0.8). Also, the risk of total and primary cesarean section, instrumental-delivery, preterm-birth, and birth-trauma were similar in both groups. According to meta-regression analyses, the reported ORs were not influenced by the country of origin. Conclusion: The relationship between the immigration status and adverse perinatal outcomes indicated a heterogenous pattern, but the immigrant women were at an increased risk of some important adverse pregnancy outcomes. Population-based studies with a focus on the various aspects of this phenomena are required to explain the source of these heterogenicities.

A Systematic Review and Meta-Analysis of the Risk of Stillbirth, Perinatal and Neonatal Mortality in Immigrant Women.

Objectives: This study aimed to investigate the risk of stillbirth, perinatal and neonatal mortality in immigrant women compared to native-origin women in host countries. Methods: A systematic literature review and meta-analysis was conducted. Relevant studies were identified using a thorough literature search and their quality was appraised. The analysis of heterogeneous data was carried out using the random effects model and publication bias was assessed using the Harbord-test. Also, the pooled odds ratio of events was calculated through the DerSimonian and Laird, and inverse variance methods. Results: In the search process 45 studies were retrieved consisting of 8,419,435 immigrant women and 40,113,869 native-origin women. The risk of stillbirth (Pooled OR = 1.35, 95% CI = 1.22-1.50), perinatal mortality (Pooled OR = 1.50, 95% CI = 1.35-1.68), and neonatal mortality (Pooled OR = 1.09, 95% CI = 1.00-1.19) in the immigrant women were significantly higher than the native-origin women in host countries. According to the sensitivity analyses, all results were highly consistent with the main data analysis results. Conclusion: The immigrant women compared to the native-origin women had the higher risks of stillbirth, perinatal and neonatal mortality. Healthcare providers and policy makers should improve the provision of maternal and neonatal healthcare for the immigrant population.

Perinatal and Neonatal Outcomes in Immigrants From Conflict-Zone Countries: A Systematic Review and Meta-Analysis of Observational Studies.

Objectives: There are controversies regarding the risk of adverse pregnancy outcomes among immigrants from conflict-zone countries. This systematic review and meta-analysis aimed to investigate the risk of perinatal and neonatal outcomes among immigrants from conflict-zone countries compared to native-origin women in host countries. Methods: A systematic search on the databases of PubMed/MEDLINE, Scopus, and Web of Science was carried out to retrieve studies on perinatal and neonatal outcomes among immigrants from Somalia, Iraq, Afghanistan, Yemen, Syria, Nigeria, Sudan, Ethiopia, Eritrea, Kosovo, Ukraine, and Pakistan. Only peer-reviewed articles published in the English language were included in the data analysis and research synthesis. The odds ratio and forest plots were constructed for assessing the outcomes of interests using the DerSimonian and Laird, and the inverse variance methods. The random-effects model and the Harbord test were used to account for heterogeneity between studies and assess publication bias, respectively. Further sensitivity analysis helped with the verification of the reliability and stability of our review results. Results: The search process led to the identification of 40 eligible studies involving 215,718 pregnant women, with an immigration background from the conflict zone, and 12,806,469 women of native origin. The adverse neonatal outcomes of the risk of small for gestational age (Pooled OR = 1.8, 95% CI = 1.6, 2.1), a 5-min Apgar score <7 (Pooled OR = 1.4, 95% CI = 1.0, 2.1), stillbirth (Pooled OR = 1.9, 95% CI = 1.2, 3.0), and perinatal mortality (Pooled OR = 2, 95% CI = 1.6, 2.5) were significantly higher in the immigrant women compared to the women of native-origin. The risk of maternal outcomes, including the cesarean section (C-S) and emergency C-S, instrumental delivery, preeclampsia, and gestational diabetes was similar in both groups. Conclusion: Although the risk of some adverse maternal outcomes was comparable in the groups, the immigrant women from conflict-zone countries had a higher risk of neonatal mortality and morbidity, including SGA, a 5-min Apgar score <7, stillbirth, and perinatal mortality compared to the native-origin population. Our review results show the need for the optimization of health care and further investigation of long-term adverse pregnancy outcomes among immigrant women.

Trends in Leading Cancer Incidence among Iranian Women: Annual Cancer Registry Reports, 2003-2015.

BACKGROUND: Cancer is one of the most important causes of death in the world and has an increasing trend globally. We aimed at investigating the five leading cancers in Iranian women based on a 10-year history of cancer registry reports and illustrating the trends in all cancer sites and breast cancer as the top leading one from 2003 to 2015. METHODS: Data were obtained from national cancer registry study. Age-Specific Incidence Rate (ASR) data were obtained from Iran's annual national cancer registry reports between 2003 to 2010 and 2014 to 2015. Using Joinpoint regression, we analyzed incidence trends over time for all cancer sites and the top leading cancer from 2003 to 2015. RESULTS: Breast cancer was ranked first in Iranian women. Its ASR raised from 15.96 in 2003 to 32.63 in 2015. Results of trend analysis based on Annual Percent Change (APC) index showed 5.6 (95%CI: 2.9 to 8.3) and 4.6 (95%CI: 2.0 to 7.2) annual increase in the incidence of all cancer sites and breast cancer from 2003 to 2015, respectively. CONCLUSION: This study indicates significant increasing trends in all cancer sites and breast cancer incidence in Iran. Despite the national coverage of cancer registry over the past decade, more considerations should be taken into account, especially in Breast cancer.

A Systematic Review and Meta-Analysis of Male Infertility and the Subsequent Risk of Cancer.

OBJECTIVES: The primary objective of this systemic review and meta-analysis was to investigate the risk of developing composite outcome of all cancers, regardless of the type of cancer among men with infertility diagnosis compared to fertile counterparts. The secondary objective was to compare the pooled risk of developing individual specific cancers between two groups. METHODS: A systematic literature search was performed on the databases of PubMed (including Medline), Scopus, and Web of Science to retrieve observational studies published in English language from 01.01.1990 to 28. 02. 2021. They assessed cancer events in males with an infertility diagnosis compared to controls without infertility. The outcomes of interest were a composite outcome of cancers including all known cancer types, and also specific individual cancers. The fixed/random effects model was used to analyze heterogeneous and non-heterogeneous results. Publication bias was assessed using the Harbord test, Egger test, Begg test, and funnel plot. The pooled odds ratio of cancers was calculated using the DerSimonian and Laird, and inverse variance methods. Studies' quality and risk of bias were assessed using structured standard tools. RESULTS: We included eight cohort studies involving 168,327 men with the diagnosis of infertility and 2,252,806 men without it. The total number of composite outcome of cancers as well as individual cancers including prostate, testicular and melanoma were 1551, 324, 183 and 121 in the infertile men and 12164, 3875, 849, and 450 in the fertile men, respectively. The pooled OR of the composite outcome of cancers, regardless of the type of cancer, in men with infertility was 1.4 folds higher than those without infertility (pooled OR = 1.43, 95% confidence interval [CI]: 1.25-1.64). Meta-analysis of individual cancers including prostate, testicular and melanoma between two groups was carried out. The pooled ORs of testicular and prostate cancers in men with the diagnosis of infertility were significantly higher than controls without infertility (pooled OR = 1.91, 95% CI: 1.52-2.42 and pooled OR = 1.48, 95% CI: 1.05-2.08, respectively). Additionally, the pooled OR of melanoma in men with infertility was 1.3 folds higher than those without infertility (pooled OR = 1.31, 95% CI: 1.06-1.62). CONCLUSION: A greater risk of cancers in men with male infertility was found suggesting that the history of male infertility might be an important risk factor for developing cancers in later life. Further well-designed long-term population-based prospective studies, considering all known cancers and their accompanying risk factors should be conducted to support our findings.

Keratinocyte growth factor in focus: A comprehensive review from structural and functional aspects to therapeutic applications of palifermin.

Palifermin (Kepivance™) is the first therapeutic approved by the Food and Drug Administration for preventing and managing the oral mucositis provoked by myelotoxic and mucotoxic therapies. Palifermin is a recombinant protein generated from human keratinocyte growth factor (KGF) and imitates the function of endogenous KGF. KGF is an epithelial mitogen involved in various biological processes which belongs to the FGF family. KGF possesses a high level of receptor specificity and plays an important role in tissue repair and maintaining of the mucosal barrier integrity. Based on these unique features, palifermin was developed to enhance the growth of damaged epithelial tissues. Administration of palifermin has shown success in the reduction of toxicities of chemotherapy and radiotherapy, and improvement of the patient's quality of life. Notwithstanding all merits, the clinical application of palifermin is limited owing to its instability and production challenges. Hence, a growing number of ongoing researches are designed to deal with these problems and enhance the physicochemical and pharmaceutical properties of palifermin. In the current review, we discuss KGF structure and function, potential therapeutic applications of palifermin, as well as the latest progress in the production of recombinant human KGF and its challenges ahead.

GJB2 mutations in Iranian Azeri population with autosomal recessive nonsyndromic hearing loss (ARNSHL): First report of c.238 C>A mutation in Iran.

OBJECTIVE: Autosomal-recessive nonsyndromic hearing loss (ARNSHL) is a heterogeneous genetic disorder. Mutations in the gap junction protein beta 2 (GJB2) gene, encoding connexin 26, are a significant cause of ARNSHL in different ethnic groups. This study aimed to identify the frequency and type of GJB2 mutations in the Iranian Azeri population. METHODS: Fifty unrelated families presenting ARNSHL in Ardabil Province, the northwest of Iran, were studied to determine the frequency and type of GJB2 mutations leading to ARNSHL. ARMS-PCR screened all DNA samples to detect c.35delG; p. Gly12Val mutation. In addition, normal samples for c.35delG; p. Gly12Val were analyzed by direct sequencing for other GJB2 mutations. RESULT: Of the fifty families, 13 (26%) showed a GJB2 gene mutation, with c.35delG; p. Gly12Val mutation was the most prevalent one that occurred in eight (61.5%) out of the 13 families. Of the families, two were homozygous for c.358-360delGAC; p. Glu120del mutation, and one was homozygous for c.290dupA; p. Tyr97Ter and c.299-300delAT; p. His100Arg mutations. Also, we detected a novel mutation, c.238C>A; p. Gln80lys, in one of the families. CONCLUSION: Our findings are comparable to previous studies, indicating c.35d3lG; p. Gly12Val mutation in the GJB2 gene is the most common cause of GJB2-related hearing loss in the Iranian Azeri population. Furthermore, our study highlights the significance of ARNSHL screening programs of live births based on local population data in Iran.

Mild Gestational Diabetes and Adverse Pregnancy Outcome: A Systemic Review and Meta-Analysis.

Background and Objectives: Mild gestational diabetes (GDM) refers to the gestational hyperglycemia, which does not fulfill the diagnostic criteria for GDM. The results of studies on adverse pregnancy outcomes among women with mild GDM are controversial. Therefore, the aim of this systematic review and meta-analysis was to investigate the impact of mild GDM on the risk of adverse maternal and neonatal outcomes. Methods: A thorough literature search was performed to retrieve articles that investigated adverse maternal and neonatal outcomes in women with mild GDM in comparison with non-GDM counterparts. All populations were classified to three groups based on their diagnostic criteria for mild GDM. Heterogeneous and non-heterogeneous results were analyzed using the fixed/random effects models. Publication bias was assessed using the Harbord test. DerSimonian and Laird, and inverse variance methods were used to calculate the pooled relative risk of events. Subgroup analysis was performed based on mild GDM diagnostic criteria. Quality and risk of bias assessment were performed using standard questionnaires. Results: Seventeen studies involving 11,623 pregnant women with mild GDM and 53,057 non-GDM counterparts contributed to the meta-analysis. For adverse maternal outcomes, the results of meta-analysis showed that the women with mild GDM had a significantly higher risk of cesarean section (pooled RR: 1.3, 95% CI 1.2-1.5), pregnancy-induced hypertension (pooled RR: 1.4, 95% CI 1.1-1.7), preeclampsia (pooled RR: 1.3, 95% CI 1.1-1.5) and shoulder dystocia (pooled RR: 2.7, 95% CI 1.5-5.1) in comparison with the non-GDM population. For adverse neonatal outcomes, the pooled relative risk of macrosomia (pooled RR = 0.4, 95% CI: 1.1-1.7), large for gestational age (pooled RR = 1.7, 95% CI: 1.3-2.3), hypoglycemia (pooled RR = 1.6, 95% CI: 1.1-2.3), hyperbilirubinemia (pooled RR = 1.1, 95% CI: 1-1.3), 5 min Apgar <7 (pooled RR = 1.6, 95% CI: 1.1-2.4), admission to the neonatal intensive care unit (pooled RR = 1.5, 95% CI: 1.1-2.1), respiratory distress syndrome (pooled RR = 3.2, 95% CI: 1.8-5.5), and preterm birth (pooled RR = 1.4, 95% CI: 1.1-1.7) was significantly increased in the mild GDM women as compared with the non-GDM population. However, the adverse events of small for gestational age and neonatal death were not significantly different between the groups. Analysis of composite maternal and neonatal outcomes revealed that the risk of those adverse outcomes in the women with mild GDM in all classifications were significantly higher than the non-GDM population. Also, the meta-regression showed that the magnitude of those increased risks in both composite maternal and neonatal outcomes was similar. Conclusion: The risks of sever adverse neonatal outcomes including small for gestational age and neonatal mortality are not increased with mild GDM. However, the increased risks of most adverse maternal and neonatal outcomes are observed. The risks have similar magnitudes for all mild GDM diagnostic classifications.