Comprehensive microarray analysis of severe preeclampsia placenta to identify differentially expressed genes, biological pathways, hub genes, and their related non-coding RNAs.

INTRODUCTION: Preeclampsia (PE) is a serious pregnancy-related complication caused by high blood pressure in pregnant women. The severe form has more devastating effects. According to the growing evidence, the placenta is a crucial component in the pathogenesis of PE, and eliminating it will alleviate symptoms. METHODS: GEO's severe preeclampsia placenta microarray datasets; GSE147776, GSE66273, GSE102897, and GSE10588, were chosen to identify differentially expressed genes (DEGs) in different biological pathways. The analysis of hub genes and related non-coding RNAs was done as well. RESULTS: A total of 347 DEGs with adj p-value <0.05 and ǀlog2FoldChangeǀ> 0.5 were discovered between severe PEs and healthy pregnancies, including 204 over-expressed genes and 143 under-expressed genes. The MCC method identified ISG15, IFI44L, MX2, OAS2, MX1, FN1, LDHA, ITGB3, TKT, HK2 genes as the top ten hub genes. Interactions between hub genes and noncoding RNAs were also conducted. The most enriched pathways were as follows; HIF-1 signaling pathway; Pathways in cancer; Alanine, aspartate and glutamate metabolism; Arginine biosynthesis; Human papillomavirus infection; Glycolysis/Gluconeogenesis; Central carbon metabolism in cancer; Valine, leucine and isoleucine degradation; Cysteine and methionine metabolism; and Galactose metabolism. DISCUSSION: This is a secondary data analysis conducted on severe preeclampsia placenta to identify differentially expressed genes, biological pathways, hub-genes, and related noncoding RNAs. Functional studies are crucial to understanding the precise role of these genes in the pathogenesis of PE. Also, accepting a gene as a diagnostic or prognostic marker for early diagnosis and management of PE requires multiple lines of evidence.

An Overview on Prevalence and Detection Approaches of BRAF V600E Mutation in Anaplastic Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Background: BRAF V600E mutation is proved critical in the progression and invasion of thyroid cancer, and as a prognostic biomarker. As anaplastic thyroid cancer (ATC) is a rare and aggressive form of thyroid cancer, this study was conducted to provide a view on prevalence of BRAF V600E as well as the best molecular diagnostic method in ATC patients. Methods: A comprehensive literature search was performed from their inception to Oct 2022 in PubMed, Scopus, Google Scholar, and Web of Science (WoS). The data of the prevalence of ATC were extracted. Moreover, the diagnostic feature of the available diagnostic tools was extracted to measure the sensitivity and specificity. To pool the prevalence data, we used meta-proportion analysis and diagnostic meta-analysis was conducted to determine the specificity and sensitivity of the immunohistochemistry method in detecting BRAF V600E mutation among patients with ATC. Results: Overall, 34 studies were included in this meta-analysis. The incidence of BRAF V600E was shown 33% in the 978 patients. The sensitivity and specificity of IHC in detecting BRAF V600E were detected 78.9% (95%CI: 60.1-97.2), and 69.7% (95%CI: 41.2-98.1), respectively. Conclusion: IHC had an acceptable prognostic profile for detecting BRAF V600E in ATC patients. The diagnosis of BRAF mutation is critical in clinical trials and may be helpful for choosing proper-targeted therapy strategies in ATC patients.

Pre- and Post-surgical Prevalence of Thiamine Deficiency in Patients Undergoing Bariatric Surgery: a Systematic Review and Meta-analysis.

Thiamine deficiency is a life-threatening nutritional abnormality observed in the patients with obesity and following bariatric surgery. The aim of the present study is to determine the prevalence of thiamine deficiency prior to and after bariatric procedures. PubMed, Web of Science, Google scholar, CENTRAL, ProQuest, and Scopus were searched to retrieve relevant studies containing data on thiamine deficiency in patients with obesity who underwent bariatric surgery. A proportional meta-analysis approach was used to pool the prevalence of thiamine deficiency prior and after surgery. Our comprehensive literature search retrieved 41 studies with relevant data. The pooled prevalence of thiamine deficiency was 7% (95% CI: 4-12%) at baseline. We observed that 19% (95% CI: 0-68%), 9% (95% CI: 3-17%), and 6% (95% CI: 3-9%) of patients had developed thiamine deficiency at 3 months, 6 months, and 1 year after surgery, respectively. We also report that the prevalence of thiamine deficiency in pregnant women who had history of bariatric surgery. The rate was highest in the first trimester (12%) compared to that in the second (8%) and third (10%) trimesters. The baseline prevalence is 7% for thiamine deficiency in bariatric surgery candidates. The prevalence rate of thiamin deficiency increased to 19% and 9% 3 and 6 months after surgery; however, the rate decreased to 6% 1 year after surgery. Due to the higher prevalence of thiamine deficiency in the early post-operative phase, close monitoring during this period is recommended. A similar strategy should be implemented for pregnant women with history of bariatric surgery in their first trimester.

A Novel ARMC5 Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing.

Background: Primary macronodular adrenocortical hyperplasia (PMAH) is a rare form of adrenal Cushing's syndrome with incomplete penetrance which may be sporadic or autosomal dominant. The inactivation of the ARMC5 gene, a potential tumor suppressor gene, is one of the associated causes of PMAH. This study aimed to identify the variant responsible for Iranian familial PMAH. Methods: The proband, a 44-year-old woman, was directed to whole-exome sequencing (WES) of the blood sample to discover a germline variant. In addition, the identified causative variant was confirmed and segregated in other and available unaffected family members. Results: The novel germline heterozygous missense variant, c.2105C>A in the ARMC5 gene, was found, and the same germline variant as the proband was confirmed in two affected sisters. This variant was detected in the brother of the proband with an asymptomatic condition and this considered because of incomplete penetrance and age-dependent appearance. The function of the ARMC5 protein would be damaged by the identified variant, according to in silico and computer analyses that followed. Conclusion: The new germline ARMC5 variation (c.2105C>A, (p. Ala702Glu)) was interpreted as a likely pathogenic variant based on ACMG and Sherloc standards. PMAH may be diagnosed early using genetic testing that shows inherited autosomal dominant mutations in the ARMC5 gene.

NGLY1 deficiency: Novel variants and literature review.

NGLY1 deficiency is a recently described autosomal recessive disorder, involved in deglycosylation of proteins, and for that reason grouped as the congenital disorders of deglycosylation together with the lysosomal storage disorders. The typical phenotype is characterized by intellectual disability, liver malfunctioning, muscular hypotonia, involuntary movements, and decreased or absent tear production. Liver biopsy demonstrates vacuolar amorphous cytoplasmic storage material. NGLY1 deficiency is caused by bi-allelic variants in NGLY1 which catalyzes protein deglycosylation. We describe five patients from two families with NGLY1 deficiency due to homozygosity for two novel NGLY1 variants, and compare their findings to those of earlier reported patients. The typical features of the disorder are present in a limited way, and there is intra-familial variability. In addition in one of the families the muscle atrophy and posture abnormalities are marked. These can be explained either as variability of the phenotype or as sign of slowly progression of features as the present affected individuals are older than earlier reported patients.

Urinary exosomal expression of long non-coding RNAs as diagnostic marker in bladder cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) and exosomes have been regarded as components of cell signal transmission that modulate indigenous cellular microenvironments. Exosomes also participate in relocation of functional lncRNAs between cells. METHODS: In the present study, we evaluated expression of LINC00355, LINC00958, UCA1-201, UCA1-203, and MALAT1 lncRNAs in urinary exosomes isolated from transitional cell carcinoma (TCC) of bladder, non-malignant urinary disorders, and normal subjects. RESULTS: LINC00355, UCA1-203, and MALAT1 expression was significantly higher in TCC patients compared to controls (non-malignant or normal samples). However, UCA1-201 expression was significantly decreased in TCC patients compared with controls. LINC00355 and MALAT1 expression was significantly lower in cigarette smokers and opium-addicted TCC patients, respectively. On the other hand, LINC00355 expression tended to be higher in opium-addicted TCC patients. The proposed panel of lncRNAs (composed of UCA1-201, UCA1-203, MALAT1, and LINC00355) had 92% sensitivity and 91.7% specificity for diagnosis of bladder cancer from normal samples. CONCLUSION: Transcript levels of lncRNAs in urinary exosomes are potential diagnostic bio-markers in bladder cancer.

Molecular analysis of testis biopsy and semen pellet as complementary methods with histopathological analysis of testis in non-obstructive azoospermia.

PURPOSE: Non-obstructive azoospermia (NOA) is one the many causes of male infertility (10 %) resulting from testicular failure. Multiple testicular biopsies fail to find mature sperm in at least 50 % of cases Therefore; hunting for sensitive and specific biomarkers of spermatogenesis that could better determine the fertility status in NOA can lead to improved management of male infertility. Therefore, we evaluated sperm production through analyses of germ cell-specific transcripts (DAZ, TSPY1, SPTRX3 and SPTRX1) in semen and testicular biopsies of men with azoospermia. METHODS: We collected semen (N=83) and testis biopsies (N=31) from men with non-obstructive azoospermia. We later extracted RNA and synthesized cDNA using washed semen precipitate and testicular tissues. We also performed semi-nested PCR with designed specific primers. Using H&E method, an expert pathologist performed the histopathological evaluation. Having categorized the patients into three groups based on histopathological results, we calculated the agreement between molecular results of semen and tissues with histopathological findings for each patient using Kappa statistical test. RESULTS: Molecular findings of precipitated semen and testicular tissues were in disagreement with histopathological results in most cases. Molecular analysis of testis biopsies showed significant difference (Kappa coefficient=0.009, P value=0.894) with histopathological results; TSPY1, DAZ, SPTRX3 and SPTRX1 were respectively detected in 94 %, 94 %, 17.6 % and 52.9 % of men diagnosed with germ cell aplasia. CONCLUSIONS: Molecular analysis of semen does not provide sufficient sensitivity and specificity to be used as a screening test at the present time, but it is a useful adjunct to histopathological methods in men with NOA. Spermatid/sperm specific transcripts indicated the possibility to find mature sperm following repeated multiple testicular sperm extraction (TESE) or microdisection TESE (mTESE).

Genotyping of Echinococcus granulosus Isolates from Human Clinical Samples Based on Sequencing of Mitochondrial Genes in Iran, Tehran.

BACKGROUND: The present study was aimed to investigate molecular diversity of Echinococcus granulosus isolates collected from human clinical samples using two mitochondrial genes cox1 and nad1 in Iran. METHODS: Forty seven human hydatid cysts were collected through surgery from two hospitals in Tehran during 2010-2012. To determine the fertility of protoscoleces, the cyst fluids were subjected to morphological microscopic examinations. Protoscoleces were removed from each cyst and their total genomic DNAs were extracted. PCR was performed to amplify fragments of 450 and 400 base pair (bp) for cox1 and nad1 genes, respectively. Genotype diversity and sequence variation of the strains were studied by bioinformatics software and in comparison with those mtDNA sequences already deposited in GenBank. RESULTS: Sixteen, (53.3%), 13 (43.3%), and 1 (3.3%) samples were related to lung, liver, and spleen, respectively. The remained 17 unfertile samples were excluded from the study. From the 29 isolates, 86.7% (n=26) and 10% (n=3) were related to G1, and G3 genotypes, respectively. The sole isolate with G6 genotype was obtained from lung sample. Analysis of concatenated sequences of cox1+nad1 indicated the presence of 11 haplotypes among our strains that were related to genotypes G1 (n=9), G3 (n=1) and G6 (n=1). CONCLUSION: In consistent to other reports from Iran, genotypes G1, G3, and G6 were observed in our human isolates. The rate of G3 genotype was however higher than other studies implying that human can be considered as a new appropriate host for G3 genotype. Further studies with more sample size from different geographic areas of Iran are needed for E. granulosus mapping.

Contributory role of viral infection in congenital tumour development.

Congenital tumours are a group of distinct infrequent disorders whose exact aetiologies have not clearly been understood so far. Viral infection seems to be one of the key factors involved in the carcinogenesis of certain tumours. This study was performed to assess whether viral DNAs are present in the congenital tumours or not. Nucleic acid from 31 congenital tumours was extracted. Detection of Epstein-Barr virus, Cytomegalovirus (CMV), adenovirus, Herpes simplex virus 1 (HSV1) and 2, Human herpes virus 6 (HHV6), and BK virus was performed using polymerase chain reaction. Viral nucleic acid was detected in eight subjects (25.8%), mostly adenovirus, CMV, and HHV6. Despite their low frequencies, a possible role could be identified for viral infections in tumour development or progression.

Alpha 1 antitrypsin deficiency in infants with neonatal cholestasis.

OBJECTIVE: Alpha1-antitrypsin deficiency (A1ATD) is the most important indication for liver transplantation in children. The gene frequencies vary in different ethnic groups. In the present study, we attempt to determine the frequencies of the most common defective alleles, Z and S, in Iranian children suffering from idiopathic neonatal cholestasis. Eighty-seven infants were typed for Z and S alleles. METHODS: In a single center study, 87 consecutive liver biopsies from infants with cholestasis were reviewed and patients with neonatal cholestasis enrolled in the study and cases with confirmed biliary tract atresia excluded. Formalin fixed paraffin embedded blocks were used for DNA extraction. AAT genotype was determined by polymerase chain reaction (PCR) assay and amplification of the two most common deficiency variants, S and Z alleles, and then sequencing of PCR products. FINDINGS: There were 48 (55.2%) males and 39 (44.8%) females, with a median age of 60 days. Out of 87 of the study subject, 2 (2.2%) were heterozygous for the S allele, and no ZZ, SS or MZ individual was found in the patients. No other polymorphism was found in the sequencing results. CONCLUSION: In comparison to other populations, AAT deficiency seems not to be an important etiologic factor for neonatal cholestatic liver disease in Iran; however, further studies are recommended to estimate the true mutant gene frequencies.

The effect of a care program on pain intensity of cancer patients who underwent surgery and hospitalized in Sayyed-Al-Shohada Hospital of Isfahan University of Medical Sciences in 2011.

INTRODUCTION: One of the most frequent issues nurses encounter with after or during cancer-related surgeries is pain. For postoperative pain relief, different nonpharmacologic interventions, such as nurse-patient communication, mental support, preoperative education, and consultation can be used. Doing such interventions may decrease postoperative pain. However, the research results regarding the effect of such measurements on pain intensity is contradictory. So in this research study the effect of a pain management plan on pain intensity after cancer surgery was assessed. MATERIALS AND METHODS: The present study is a pre- and posttest case and control clinical trial, which was conducted in Sayyed-Al-Shohada Hospital of Isfahan University of Medical Sciences in 2011. Care program consisted of pain education, communication with the patient, and pain measurement. Seventy patients were sampled based on the inclusion criteria and randomly assigned in 2 groups. Data were collected using American Pain Society-patient outcome questionnaire, which measured pain intensity. RESULTS: In the experimental group, the mean score of pain intensity before surgery and in the first 12-24 h after surgery was less than the control group. Also comparing pain intensity mean differences before and in the first 12 h, before and in the first 24 h indicated that the experimental group had lower scores than the control group, but these differences were not statistically significant. In both the groups, in the first 24 h following surgery the mean score of pain intensity decreased significantly. DISCUSSION: Results of the present research study suggested that a nursing pain management program consisting consultation, education, and pain assessment may have a clinical effect on cancer patient pain intensity following surgery. However, these results were not statistically significant. This might be due to the limited sample size as well as conducting the program in a short period of time. It is recommended that effects of such a program on the pain intensity will be examined further with a larger sample and in a longer period of time.

Study on effect of massage therapy on pain severity in orthopedic patients.

BACKGROUND: Pain as a main social problem has involved millions of people. Usually pharmaceutical methods use for treating pain but they have side effects which make them less effective. Massage is one of the effective ways for reducing pain after surgery. The aim of this study was to evaluate the effect of massage therapy on pain severity in orthopedic patients. METHODS: This is a clinical trial study on 60 arthroscopic knee surgery patients who were hospitalized in men's orthopedic ward of Al-Zahra and Kashani hospitals. A two part questionnaire was used for collecting data. Samples were selected using easy continuity method and then they were randomly divided into two groups. In intervention group, besides routine treatments, patients were massaged by the researcher for 20 minutes each day and pain severity was evaluated before and after the massage. Data was analyzed using descriptive and inferential statistics and SPSS software. RESULTS: Results showed that there was a meaningful different between mean score of pain severity before and after the massage in intervention group (p < 0.001) but this difference wasn't meaningful in control group (p = 0.32). Also comparing the mean score of pain severity in both groups before any interventions showed that there were no meaningful differences (p = 0.34) but this difference was meaningful after interventions (p = 0.001). CONCLUSIONS: Considering massage as a safe and effective intervention, it could be used as an easy, cheap and executable method for treating pain in all medical health care centers and even at patient's home.

Assessing the effect of two praying methods on the life quality of patients suffering from cancer hospitalized at Seyedo Shohada medical center of Isfahan University of Medical Sciences.

BACKGROUND: Life quality and its promotional strategies among patients with acute and debilitating diseases, especially cancer, have been considered from a long time ago by medical and nursing societies. One of the methods to promote the patient's life quality is spiritual care which can be in form of prayer. The results of the studies done about the choice of the best praying method for the patients involves a lot of challenges. Thus, the researchers decided to examine the effect of two individual and choral praying methods on the life quality of the cancer-stricken patients. METHODS: The present study was conducted in two-staged clinical trial using pre-post test administration in which the researcher examined the effect of two individual and choral praying methods on the life quality of 70 cancer-stricken patients. Data collection to assess the life quality was performed by World Health Organization Brief Life Quality Questionnaire. RESULTS: The current research showed that the life quality score was increased in the individual-choral group after the intervention. Also, comparing the average life quality score in the two groups of individual and choral praying revealed a significant difference in which the quality of life had improved more in the choral praying group than in the individual praying group. CONCLUSIONS: The findings of the present study indicated the positive effect of praying and supplication on the life quality of cancer-stricken patients. Generally, choral praying has a better effect on the life quality of cancer-stricken patients compared with praying individually. More studies with a larger sample size are suggested in order to verify the effect of praying on the life quality of cancer-stricken patients.