Mapping 123 million neonatal, infant and child deaths between 2000 and 2017.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

Knockdown of SIX4 inhibits pancreatic cancer cells via apoptosis induction.

Sine oculis homeobox 4 (SIX4), a critical transcription factor modulating organ development, potentially participates in tumorigenesis through numerous pathways. Here, we investigated siRNA-mediated knockdown effects of SIX4 on pancreatic cancer cells and underlying molecular mechanisms. The expression of SIX4 in pancreatic cancer and adjacent tissues were investigated in clinical tissue samples and bioinformatically approved by gene expression omnibus (GEO) database. Appropriate siRNA transfected into PANC1 pancreatic cancer cells in order to SIX4 knockdown. The survival, migration, invasion, colony formation, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle in the cancer cells were investigated after knockdown of SIX4. In addition, expression of genes involved in apoptosis and metastasis were assessed in the transfected cancer cells in mRNA and protein levels. High-throughput analysis using GEO database confirmed the overexpression of SIX4 in pancreatic cancer tissues by six independent pancreatic cancer microarrays. Knockdown of SIX4 by specific siRNA significantly decreased survival, colony formation, and mitochondrial membrane potential of the cancer cells. Further assessments demonstrated that knockdown of SIX4 increases the apoptosis and autophagy rates in the cancer cells through modifying the expression of related genes. Moreover, a significant decrease in migration and invasion rates were observed in SIX4 suppressed group. Furthermore, frequency of the cells transfected with SIX4 siRNA increased slightly in G1 and Sub-G1 phases of cell cycle. Our study suggested that siRNA-mediated knockdown of SIX4 increases the pancreatic cancer cells death and reduces the invasion and migration of the cancer cells through different molecular pathways.

Chimeric antigen receptor T (CAR-T) cells: Novel cell therapy for hematological malignancies.

Over the last decade, the emergence of several novel therapeutic approaches has changed the therapeutic perspective of human malignancies. Adoptive immunotherapy through chimeric antigen receptor T cell (CAR-T), which includes the engineering of T cells to recognize tumor-specific membrane antigens and, as a result, death of cancer cells, has created various clinical benefits for the treatment of several human malignancies. In particular, CAR-T-cell-based immunotherapy is known as a critical approach for the treatment of patients with hematological malignancies such as acute lymphoblastic leukemia (ALL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and non-Hodgkin's lymphoma (NHL). However, CAR-T-cell therapy of hematological malignancies is associated with various side effects. There are still extensive challenges in association with further progress of this therapeutic approach, from manufacturing and engineering issues to limitations of applications and serious toxicities. Therefore, further studies are required to enhance efficacy and minimize adverse events. In the current review, we summarize the development of CAR-T-cell-based immunotherapy and current clinical antitumor applications to treat hematological malignancies. Furthermore, we will mention the current advantages, disadvantages, challenges, and therapeutic limitations of CAR-T-cell therapy.

Iranian Hydatid Disease Registry: Establishment and Implementation of a Neglected Tropical Disease Registry.

BACKGROUND: Cystic echinococcosis (CE) or hydatid disease is a global public health concern which imposes considerable economic costs on the communities in endemic regions. CE surveillance data are not adequately reliable. The present study reports the development and outcomes of a CE registry in Iran. METHODS: Hydatid Registry (HydatidReg) was initially established as a single-center registry in 2014 after the ethical approval of KMU. Following a call from MoHME to promote registry of different diseases and health outcomes, a call for participation was announced and all the Iranian Universities of Medical Sciences were requested to contribute to the registry. Subsequently, a nation-wide registry of hydatid disease was established in 2016. With a global perspective, HydatidReg joined the European Register of Cystic Echinococcosis (ERCE). A data collection form based on minimum dataset was designed and standard operating procedures (SOPs) were prepared to ensure standardized patient enrolment in the registry. A biobank system with two-dimensional barcoding was established along with HydatidReg for management and organization of biological specimens. RESULTS: As of March 2021, a total of 690 patients were enrolled in the registry. HydatidReg registered 362 (17.3%) out of the total 2097 patients enrolled in ERCE. Quality control (QC) of the data demonstrated 91.2% completeness and 80% timeliness. In the biobank, 322 biological specimens from 184 CE patients have been deposited including 70 blood, 96 sera and 156 parasite materials. CONCLUSION: High-quality data in the HydatidReg registry provided opportunities for health professionals to improve quality of care and organize meaningful research.

Preparation and evaluation of the exotoxin A nano-gold conjugate as a vaccine candidate for Pseudomonas aeruginosa infections.

OBJECTIVES: Pseudomonas aeruginosa is an opportunistic pathogen that is an important cause of nosocomial infections. This bacterium produces various virulence factors, among which exotoxin A is significantly involved in mortality and morbidity. In this study, we evaluated the immunogenicity of native exotoxin A extracted from the P. aeruginosa and its conjugation with gold nanoparticles in the animal model. MATERIALS AND METHODS: Exotoxin A was first extracted and purified from the culture medium of P. aeruginosa PAO1 by selective precipitation and dialysis. The gold nanoparticles were prepared using the Turkevich method and conjugated to the prepared exotoxin A by electrostatic force. The size and conjugation were confirmed using electron microscopy and Fourier transform infrared spectrometry (FTIR), respectively. The immunogenicity of prepared ExoA-gold nanoparticles was investigated in the mice model. RESULTS: The results indicated that nano-gold particles can be conjugated to the native exotoxin A with high efficiency. Immunogenicity investigation demonstrated that antibody titers produced against native exotoxin A and its conjugate to nano-gold particles are significant in a mouse model (P<0.005). Moreover, significant protection against 2×LD50 P. aeruginosa infection was observed in animals immunized with nano-gold-exotoxin A as compared with control groups (P=0.00). CONCLUSION: Our study indicated that exotoxin A can be produced with acceptable purity in the laboratory, and conjugated to gold nanoparticles. Based on these results nano-gold-exotoxin A conjugate is highly immunogenic and can be considered a potential vaccine candidate for P. aeruginosa infections.

The Development of a Minimum Data Set for an Infertility Registry.

Effective decision making in the healthcare setting is highly dependent on access to reliable and robust data and information. A minimum data set is a standard assessment instrument that is used during the data collection process to ensure that decision makers have access to a consistent set of information. The objective of the current study was to develop a minimum data set for infertility patients that can be employed as the basis for an infertility registry in Iran. A systematic review resulted in the identification of 2,501 articles and 17 patient forms from infertility centers that were relevant to the study objectives. Of these, 10 articles met all the inclusion and exclusion criteria, and 232 data elements were subsequently extracted from these papers. The data elements were classified by three experts and validated via two rounds of a Delphi technique. The accessibility of the data elements was then evaluated during a focus group discussion. Finally, 146 data elements were selected as the minimum data set. The proposed minimum data set could provide the basis for standardization of infertility treatments. Synchronizing the various data sets that are currently in use will be necessary to allow sharing of data across infertility registries.

Determination of the most important risk factors of gestational diabetes in Iran by group analytical hierarchy process.

BACKGROUND: The outbreak of gestational diabetes has a significant increase during recent years. This disease has complications for mother and her baby. Screening is an opportunity for preventing of gestational diabetes complications. OBJECTIVE: The aim of this research was to determine the most important risk factors for Gestational Diabetes Mellitus (GDM) in Iran according to the expert's views by Group Analytical Hierarchy Process. MATERIALS AND METHODS: In this cross-sectional study, papers related to the prevalence and risk factors of GDM in Iran from 1992-2015 were reviewed. By studying texts and Up to Date databases, 10 risk factors for gestational diabetes were collected. Among these 10 items, the risk factors that have become significant based on studying literature in Iran were selected for analysis. Group Analytical Hierarchy Process (GAHP) questionnaire distributed among all experts. RESULTS: 8 risk factors of gestational diabetes were significant in Iran. The analysis of experts' views showed that "History of GDM or disorder in glucose tolerance in pregnancy" is the most important risk factor for developing GDM (40.7%). The second and third most important risk factors were "History of macrosomia (infant birth weight > 4.1 Kg)" (20.2%) and" History of diabetes in first degree relatives" (10.7%). CONCLUSION: Suggesting screening based on the determined order of these risk factors can reduce the cost and stress in pregnant women. Also, it makes patient identifying faster. The healthcare sector can consider these priorities determined in experts' views to prevent gestational diabetes.

The pedagogical effect of a health education application for deaf and hard of hearing students in elementary schools.

BACKGROUND: Deaf or hard-of-hearing children experience difficulties in learning health principles. But technology has significantly improved their ability to learn. The challenge in e-learning is to design attractive applications while having an educational aspect. OBJECTIVE: The aims of this study were to determine the pedagogical effectiveness of a health education application for deaf and hard of hearing students in elementary schools, and to investigate the student's perceptions in different educational grades about the educational effectiveness of the text, graphics, video clips, and animation in the application. METHODS: The study design was quasi experimental and was conducted in Mashhad in 2016. Study population were deaf or hard-of-hearing students in elementary schools. The intervention included health application training to deaf and hard-of-hearing students in Mashhad. A questionnaire was used for data gathering. The pedagogical effectiveness was determined by measuring the modified Adapted Pedagogical Index. This index was created based on the characteristics of the application and study population. Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney tests with Bonferroni adjustment by SPSS 22. RESULTS: Eighty-two students participated in the intervention. The value of modified Adapted Pedagogical Index was 0.669, indicating that the application was effective. The results of Kruskal-Wallis H and Mann-Whitney U test showed significant differences in different educational grades. (p<0.008). CONCLUSION: Using information technology can improve the education of deaf and hard-of-hearing students. Modified Adapted Pedagogical Index can be used for evaluation of non-interactive applications for elementary school children who are deaf or hard of hearing.

The effects of crocin on the symptoms of depression in subjects with metabolic syndrome.

BACKGROUND: Studies have suggested that metabolic syndrome (MetS) is associated with increased depressive symptoms, and reducing depression in subjects with MetS is important. Crocin, an active component of saffron, has useful properties for subjects with MetS, including antidepressant properties. OBJECTIVES: The aim of the study was to assess the effect of a preparation of crocin on the symptoms of depression in subjects with MetS, and the relationship between changes in those symptoms and the serum pro-oxidant/anti-oxidant balance (PAB). MATERIAL AND METHODS: This sub-study was carried out on 34 subjects with MetS from the authors' previous randomized double-blind controlled clinical trial (RCT), all of whom met the inclusion criteria for this study. The subjects were randomly assigned to treatment and placebo groups (n = 17 in each group) and received each 30 mg of crocin (2 tablets of 15 mg) or placebo for 8 weeks. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). The BDI questionnaire was completed for each subject at the baseline and at the end of the 8th week of treatment. Blood samples were taken from the subjects before and after the intervention period. Statistical analyses were performed using the SPSS for Windows, v. 16 (SPSS Inc., Chicago, USA). RESULTS: Out of the 34 participants enrolled, 33 completed the trial. The degree of depression decreased significantly in the crocin group (p = 0.005), but not in the placebo group (p > 0.05), and the difference between the 2 groups was statistically significant (p = 0.013). No significant relationship was observed between changes in depression symptoms and changes in the serum PAB (p > 0.05). CONCLUSIONS: This study demonstrates that at a dose of 30 mg per day for 8 weeks, crocin reduced the symptoms of depression in subjects with MetS compared to the control group, and this effect was independent of its effect on the serum PAB.