BACKGROUND: Currently, there is an urgent need for scalable and reliable in vitro models to assess the effects oftherapeutic entities on the human liver. Hepatoma cell lines, including Huh-7, show weakly resemblance to humanhepatocytes, limiting their significance in toxicity studies. Co-culture of hepatic cells with non-parenchymal cells, and thepresence of extracellular matrix have been shown to influence the biological behavior of hepatocytes. The aim of this studywas to generate the scalable and functional hepatic micro-tissues (HMTs). METHODS: The size-controllable HMTs were generated through co-culturing of Huh-7 cells by mesenchymal stem cellsand human umbilical vein endothelial cells in a composite hydrogel of liver-derived extracellular matrix and alginate, usingan air-driven droplet generator. RESULTS: The generated HMTs were functional throughout a culture period of 28 days, as assessed by monitoringglycogen storage, uptake of low-density lipoprotein and indocyanine green. The HMTs also showed increased secretionlevels of albumin, alpha-1-antitrypsin, and fibrinogen, and production of urea. Evaluating the expression of genes involvedin hepatic-specific and drug metabolism functions indicated a significant improvement in HMTs compared to two-dimensional(2D) culture of Huh-7 cells. Moreover, in drug testing assessments, HMTs showed higher sensitivity tohepatotoxins compared to 2D cultured Huh-7 cells. Furthermore, induction and inhibition potency of cytochrome P450enzymes confirmed that the HMTs can be used for in vitro drug screening. CONCLUSION Overall, we developed a simple and scalable method for generation of liver micro-tissues, using Huh-7,with improved hepatic-specific functionality, which may represent a biologically relevant platform for drug studies.

BACKGROUND: Currently, there is an urgent need for scalable and reliable in vitro models to assess the effects oftherapeutic entities on the human liver. Hepatoma cell lines, including Huh-7, show weakly resemblance to humanhepatocytes, limiting their significance in toxicity studies. Co-culture of hepatic cells with non-parenchymal cells, and thepresence of extracellular matrix have been shown to influence the biological behavior of hepatocytes. The aim of this studywas to generate the scalable and functional hepatic micro-tissues (HMTs). METHODS: The size-controllable HMTs were generated through co-culturing of Huh-7 cells by mesenchymal stem cellsand human umbilical vein endothelial cells in a composite hydrogel of liver-derived extracellular matrix and alginate, usingan air-driven droplet generator. RESULTS: The generated HMTs were functional throughout a culture period of 28 days, as assessed by monitoringglycogen storage, uptake of low-density lipoprotein and indocyanine green. The HMTs also showed increased secretionlevels of albumin, alpha-1-antitrypsin, and fibrinogen, and production of urea. Evaluating the expression of genes involvedin hepatic-specific and drug metabolism functions indicated a significant improvement in HMTs compared to two-dimensional(2D) culture of Huh-7 cells. Moreover, in drug testing assessments, HMTs showed higher sensitivity tohepatotoxins compared to 2D cultured Huh-7 cells. Furthermore, induction and inhibition potency of cytochrome P450enzymes confirmed that the HMTs can be used for in vitro drug screening. CONCLUSION Overall, we developed a simple and scalable method for generation of liver micro-tissues, using Huh-7,with improved hepatic-specific functionality, which may represent a biologically relevant platform for drug studies.

Objective: The goal of the present study was to investigate the rate of chromosomal aneuploidies in surplus embryos after sex determination at the cleavage stage. Then, the same chromosomal aneuploidies were evaluated in blastocysts after extended culture. Methods: Sixty-eight surplus embryos were biopsied at the cleavage stage and incubated for an additional 3 days to allow them to reach the blastocyst stage. The embryos were reanalyzed via fluorescence in situ hybridization (FISH) to examine eight chromosomes (13, 15, 16, 18, 21, 22, X, and Y) in both cleavage-stage embryos and blastocysts. Results: Although the total abnormality rate was lower in blastocysts (32.35%) than in cleavage-stage embryos (45.58%), the difference was not significant (p=0.113). However, when we restricted the analysis to autosomal abnormalities, we observed a significant difference in the abnormality rate between the cleavage-stage embryos (44.11%) and the blastocysts (17.64%, p=0.008). A higher rate of sex chromosomal abnormalities was also observed in cleavage-stage embryos (29.4%) than in blastocysts (14.70%, p=0.038). Conclusion The data indicated that embryo biopsy should be conducted at the blastocyst stage rather than the cleavage stage. The results also emphasized that examination of common chromosomal aneuploidies apart from sex selection cycles can be conducted in the blastocyst stage with the FISH method.

Objective: Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL. Methods: Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n=20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment. Results: Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of PRM1, PRM2, and the PRM1/PRM2 ratio after treatment. Conclusion Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.

Artificial neural networks (ANNs) have been used in a wide variety of real-world applications and it emerges as a promising field across various branches of medicine. This review aims to identify the role of ANNs in spinal diseases. Literature were searched from electronic databases of Scopus and Medline from 1993 to 2020 with English publications reported on the application of ANNs in spinal diseases. The search strategy was set as the combinations of the following keywords: “artificial neural networks,” “spine,” “back pain,” “prognosis,” “grading,” “classification,” “prediction,” “segmentation,” “biomechanics,” “deep learning,” and “imaging.” The main findings of the included studies were summarized, with an emphasis on the recent advances in spinal diseases and its application in the diagnostic and prognostic procedures. According to the search strategy, a set of 3,653 articles were retrieved from Medline and Scopus databases. After careful evaluation of the abstracts, the full texts of 89 eligible papers were further examined, of which 79 articles satisfied the inclusion criteria of this review. Our review indicates several applications of ANNs in the management of spinal diseases including (1) diagnosis and assessment of spinal disease progression in the patients with low back pain, perioperative complications, and readmission rate following spine surgery; (2) enhancement of the clinically relevant information extracted from radiographic images to predict Pfirrmann grades, Modic changes, and spinal stenosis grades on magnetic resonance images automatically; (3) prediction of outcomes in lumbar spinal stenosis, lumbar disc herniation and patient-reported outcomes in lumbar fusion surgery, and preoperative planning and intraoperative assistance; and (4) its application in the biomechanical assessment of spinal diseases. The evidence suggests that ANNs can be successfully used for optimizing the diagnosis, prognosis and outcome prediction in spinal diseases. Therefore, incorporation of ANNs into spine clinical practice may improve clinical decision making.

STUDY DESIGN: Case-control. PURPOSE: To determine optimal cut-off value for body mass index (BMI) in predicting surgical success in patients with lumbar spinal canal stenosis (LSCS). OVERVIEW OF LITERATURE: BMI is an essential variable in the assessment of patients with LSCS. METHODS: We conducted a prospective study with obese and non-obese LSCS surgical patients and analyzed data on age, sex, duration of symptoms, walking distance, morphologic grade of stenosis, BMI, postoperative complications, and functional disability. Obesity was defined as BMI of ≥30 kg/m². Patients completed the Oswestry Disability Index (ODI) questionnaire before surgery and 2 years after surgery. Surgical success was defined as ≥30% improvement from the baseline ODI score. Receiver operating characteristic (ROC) analysis was used to estimate the optimal cut-off values of BMI to predict surgical success. In addition, correlation was assessed between BMI and stenosis grade based on morphology as defined by Schizas and colleague in total, 189 patients were eligible to enter the study. RESULTS: Mean age of patients was 61.5±9.6 years. Mean follow-up was 36±12 months. Most patients (88.4%) were classified with grades C (severe stenosis) and D (extreme stenosis). Post-surgical success was 85.7% at the 2-year follow-up. A weak correlation was observed between morphologic grade of stenosis and BMI. Rates of postoperative complications were similar between patients who were obese and those who were non-obese. Both cohorts had similar degree of improvement in the ODI at the 2-year follow-up. However, patients who were non-obese presented significantly higher surgical success than those who were obese. In ROC curve analysis, a cut-off value of ≤29.1 kg/m² for BMI in patients with LSCS was suggestive of surgical success, with 81.1% sensitivity and 82.2% specificity (area under the curve, 0.857; 95% confidence interval, 0.788–0.927). CONCLUSION: This study showed that the BMI can be considered a parameter for predicting surgical success in patients with LSCS and can be useful in clinical practice.
Body Mass Index ; Case-Control Studies ; Cohort Studies ; Constriction, Pathologic ; Follow-Up Studies ; Humans ; Obesity ; Postoperative Complications ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Spinal Canal ; Walking

STUDY DESIGN: Prospective clinical study. PURPOSE: To translate and validate the Quality of Life Questionnaire of the European Foundation for Osteoporosis (ECOS-16) in patients with osteoporotic vertebral fractures in Iran. OVERVIEW OF LITERATURE: It is important to assess the psychometric properties of instruments measuring patient-reported outcomes. METHODS: The translation was performed using the backward-forward translation method. The final version was generated by consensus among the translators. Every woman who had a T-score of <−2.5 completed ECOS-16. Patients were divided into two study groups according to the World Health Organization's criteria: those with at least one vertebral fracture (surgery group) and those with no fractures (control group). They were asked to respond to the questionnaire at three points in time: preoperative and twice within 1-week interval after surgery assessments (6-month follow-up). The 36-item short-form health survey (SF-36) also was completed. The psychometric properties of the questionnaire were assessed using internal consistency, test-retest reliability, convergent validity, discriminant validity, and responsiveness. RESULTS: Of 137 recruited women, 39 underwent surgery and 98 did not. Analysis of the ECOS-16 scales showed an appropriate reliability with Cronbach's alpha of >0.70 for all scales. Test-retest reliability as indicated by intraclass correlation coefficient was found to be 0.85 (0.68–0.91). Additionally, the correlation of each item with its hypothesized domain of the ECOS-16 showed acceptable results, suggesting that the items had a substantial relationship with their own domains. Further analysis also indicated that the questionnaire was responsive to change (effect size, 0.85; standardized response mean, 0.93) (p<0.001). Significant correlations existed between scores of similar subscales of ECOS-16 and SF-36 (p<0.001). CONCLUSIONS: ECOS-16 is an acceptable, reliable, valid, and responsive measure to assess the quality of life in patients with osteoporotic vertebral fractures.
Clinical Study ; Consensus ; Female ; Global Health ; Health Surveys ; Humans ; Iran ; Methods ; Osteoporosis ; Prospective Studies ; Psychometrics ; Quality of Life ; Reproducibility of Results ; Weights and Measures

STUDY DESIGN: Cross-sectional study. PURPOSE: To translate and validate the Fukushima lumbar spinal stenosis (LSS) scale 25 (FLS-25) for use in Iran. OVERVIEW OF LITERATURE: Tools measuring patient-reported outcomes should satisfy certain psychometric properties. METHODS: FLS-25 is a self-administered scale for evaluating symptoms of LSS. A forward-backward procedure was applied to translate the questionnaire from English into Persian. A sample of patients with LSS completed the questionnaire at two points in time: once before surgery and once 6 months after the surgery. The Neurogenic Claudication Outcome Score (NCOS) was also used for assessment. The psychometric properties of FLS-25 were evaluated for internal consistency, test-retest and interobserver reliabilities, responsiveness to change, known-group comparison, and convergent validity. RESULTS: In all, 131 patients were included in the study. The mean age of the patients was 61.4 (standard deviation, 11.1) years. The Cronbach's alpha coefficient for FLS-25 was 0.89. Test-retest reliability as carried out by the intraclass correlation coefficient was 0.94 (95% confidence interval, 0.95). Interobserver agreement as measured by the kappa statistics also was found to be acceptable (kappa value, 0.88), and validity was found to be satisfactory. The instrument was able to discriminate between the subgroups of patients who differed in symptom severity. The correlation between FLS-25 and NCOS scores was excellent, indicating good convergent validity (r=0.82, p<0.001). The results also indicated that the instrument was responsive to change (p<0.001). CONCLUSIONS: The Iranian version of FLS-25 performed well, and the findings suggest that it is a valid measure of symptom severity in LSS patients.
Cross-Sectional Studies ; Humans ; Iran ; Psychometrics ; Reproducibility of Results ; Spinal Stenosis*

OBJECTIVES: Infertility has a significant impact on a women's quality of life (QOL). Infertile women face with physical and mental challenges during their postmenopausal period. Therefore, the present study aimed to evaluate the QOL among Iranian infertile women in the postmenopausal period using a valid and reliable instrument. METHODS: In this cross-sectional study both snowball and social networking methods were used for sampling. Two demographic and QOL questionnaire were used for data collection. The QOL questionnaire includes 41 items which measure the QOL in five dimensions: socioeconomic, mental health, religiousness, physical health and future imagining. Data analyzed was carried out in IBM SPSS ver. 20.0 using descriptive statistic, χ2 test, and Fisher test. A P value of 0.01 or less was considered significant. RESULTS: Overall 211 eligible participants were studied. Some participants obtained full score on socioeconomic, religiousness, physical health and future imagining dimensions of QOL but none on the mental health dimension of the QOL. Only, 6.6% of study participants have a good QOL. There was a significant relationship between age and financial provider whit status of QOL. CONCLUSION: Most Iranian infertile women in the postmenopausal period have poor or moderate QOL. Therefore, improving the QOL among these women should be considered.
Cross-Sectional Studies* ; Data Collection ; Female ; Humans ; Infertility ; Menopause ; Mental Health ; Postmenopause* ; Quality of Life*

STUDY DESIGN: Cross-sectional. PURPOSE: To translate and culturally adapt an Iranian version of the Pain Sensitivity Questionnaire (PSQ) in Iran. OVERVIEW OF LITERATURE: Instruments measuring patient reported outcomes should satisfy certain psychometric properties. METHODS: The PSQ was translated following cross-cultural adaptation guidelines. A total of 101 patients with lumbar disc herniation (LDH), and 39 healthy cases were included in the study. All participants completed the PSQ and the Pain Catastrophizing Scale (PCS). The internal consistency, test-retest reliability, known group comparison, criterion validity and item-scale correlations were assessed. RESULTS: The mean age of participants was 51.7 years. Reliability, validity and correlation of PSQ and PCS showed satisfactory results. Cronbach's alpha coefficients were 0.81 for PSQ-total, 0.82 for PSQ-minor, and 0.82 for PSQ-moderate. The intraclass correlation coefficients value was 0.84 (0.616-0.932) indicating an excellent test-retest reliability. The instrument discriminated well between sub-groups of patients who differed in a standard predictive measure of LDH surgery (the Finneson-Cooper score). Total PSQ were also significantly correlated with the total scores of the PCS, lending support to its good convergent validity. Additionally, the correlation of each item with its hypothesized domain on the PSQ indicated acceptable results, suggesting that the items had a substantial relationship with their own domains. CONCLUSIONS: The adapted Iranian PSQ is a valid and reliable questionnaire for the assessment of pain in patients with LDH.
Catastrophization ; Humans ; Iran ; Outcome Assessment (Health Care)* ; Psychometrics ; Reproducibility of Results