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Long noncoding RNAs (lncRNAs) as regulatory molecules play important roles in early treatment and diagnosis of cancers. Considering the role of PPARγ in colorectal cancer (CRC) as a tumor suppressor, the GEO database was used to identify candidate genes that affect the activation of PPARγ protein in CRC cell lines. Then were selected 5 genes containing PPARγ response element (PPRE) in up to 4000 bp upstream and were affected by PPARγ protein activation in HT-29 colon cancer cell line using UCSC database. Expression meta-analysis was applied to map the expression network between candidate genes and all known lncRNAs through expression correlation and lncRNAs that correlated with a greater number of candidate genes (R 0.5, P.value0.001). Moreover, were selected 3 lncRNAs as lncRNAs affected by PPARγ protein activation. Next, the expression levels of candidate genes and lncRNAs were evaluated using RT-qPCR in HT-29 cell line. Results showed a significant increase (FDR0.05) in the expression level of 5 candidate genes and lncRNAs LINC01133, MBNL1-AS, LOC100288911 after treatment with pioglitazone as PPARγ ligand compared to the untreated group in HT-29 cells. Although additional tests are needed to confirm bioinformatics predictions, it can be concluded that increased expression of PPARγ may increase genes and lncRNAs expression. In summary, this study could be suggested identifying lncRNAs affected by PPARγ activation could be a new strategy in understanding the function and activity of PPARγ in colon cancer.

Long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs that do not encode proteins. These RNAs have various essential regulatory functions. Irregular expression of lncRNAs has been related to the pathological process of varied diseases, and are considered promising diagnostic biomarkers. LncRNAs can release into the circulation and be stable in body fluids as circulating lncRNAs. A subset of circulating lncRNAs that exist in exosomes are referred to as exosomal lncRNA molecules. These lncRNAs are highly stable and resist RNases. Exosomes have captured a great deal of attention due to their involvement in regulating communications between cells. In conditions of autoimmune disease, exosomes play critical roles in the pathological processes. In this context, circulating lncRNAs have been shown to modulate the immune response and indicated as prognosis and diagnostic biomarkers for autoimmune diseases. This review highlights the role of circulating lncRNAs (particularly exosomal) as diagnostic biomarkers for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, and Sjögren's syndrome.

Over the last 5 years, RNA sequencing (RNA-seq) has been established and is increasingly applied as an effective approach complementary to DNA sequencing in molecular diagnostics. Currently, three RNA phenotypes, aberrant expression, aberrant splicing, and allelic imbalance, are considered to provide information about pathogenic variants. By providing a high-throughput, transcriptome-wide functional readout on variants causing aberrant RNA phenotypes, RNA-seq has increased diagnostic rates by about 15% over whole-exome sequencing. This breakthrough encouraged the development of computational tools and pipelines aiming to streamline RNA-seq analysis for implementation in clinical diagnostics. Although a number of studies showed the added value of RNA-seq for the molecular diagnosis of individuals with Mendelian disorders, there is no formal consensus on assessing variant pathogenicity strength based on RNA phenotypes. Taking RNA-seq as a functional assay for genetic variants, we evaluated the value of statistical significance and effect size of RNA phenotypes as evidence for the strength of variant pathogenicity. This was determined by the analysis of 394 pathogenic variants, of which 198 were associated with aberrant RNA phenotypes and 723 benign variants. Overall, this study seeks to establish recommendations for integrating functional RNA-seq data into the the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines classification system.

Introduction The AURKA gene encodes a protein kinase involved in cell cycle regulation and plays an oncogenic role in many cancers. The main objective of this study is to analyze AURKA expression in 13 common cancers and its role in prognostic and drug resistance. Method Using the cancer genome atlas (TCGA) as well as CCLE and GDSC data, the level of AURKA gene expression and its role in prognosis and its association with drug resistance were evaluated, respectively. In addition, the expression level of AURKA was assessed in colorectal cancer (CRC) and gastric cancer (GC) samples. Besides, using Gene Expression Omnibus (GEO) data, drugs that could affect the expression level of this gene were also identified. Results The results indicated that the expression level of AURKA gene in 13 common cancers increased significantly compared to normal samples or it survived poorly (HR >1, p, The expression level of AURKA gene in 13 common cancers increased significantly compared to normal. The level of AURKA was significantly associated with resistance to SB 505124, NU‐7441, and irinotecan drugs (p

Foodborne and zoonotic viral pathogens are responsible for substantial morbidity and mortality worldwide. These viruses can be transmitted through foods such as dairy products to humans and cause several acute and chronic diseases. This study aimed to investigate the prevalence and profile of different foodborne and zoonotic viruses in raw cow milk samples. We collected 492 raw cow milk samples from local dairy markets in Qazvin, Iran. Then we evaluated the presence of hepatitis A virus, noroviruses, rotavirus, astrovirus, bovine leukaemia virus (BLV) and tick-borne encephalitis virus (TBEV) in samples using conventional and nested reverse transcription-polymerase chain reaction methods. We found that 34.95, 7.72, 25.81, 14.63, 66.86, 12.80 and 21.34% of raw milk samples were contaminated with norovirus GI, norovirus GII, hepatitis A virus, rotavirus, astrovirus, BLV and TBEV viruses, respectively. Interestingly, the samples collected from the city's south area revealed a higher prevalence of foodborne and zoonotic viruses. Astrovirus and its combination with norovirus GI were the most prevalent virus profiles. Also, the highest correlations were observed among the presence of rotavirus and hepatitis A viruses (0.36) and TBEV and norovirus GII (0.31). Considering the prevalence rate and virus profiles of different foodborne and zoonotic viruses in raw milk samples, hygiene practices and the pasteurization process are strongly suggested to be conducted throughout the cow milk production chain and in dairy industries to prevent infections with these pathogens.

Strong evidence indicated that high expression of HBXIP (also known as LAMTOR5) promotes cancer cells proliferation and helps cancer progression. Long non-coding RNAs (lncRNA) have also a crucial role in developing cancer. In this study, we aimed to determine the expression of LAMTOR5 and its nearby lncRNA, LAMTOR5-AS1 and investigate their potential as a biomarker in colorectal cancer (CRC) patients.75 tissues of colorectal tumors and non-tumor adjacent normal sampled in this study. After RNA procedure then RT-qPCR was applied for expression analysis. Moreover, in silico investigation also enrolled for predicting sponging effect of lncRNA with miRNAs.LAMTOR5 transcription level significantly overexpressed (p value 0.001) and has shown a diagnostic potential (AUC = 0.8) in CRC. LAMTOR5-AS1 did not indicate any remarkable expression change overall, but showed a significant overexpressed in elderly patients ( 60) with CRC (p value 0.0097). Moreover, the correlation analysis between LAMTOR5 and LAMTOR5-AS1 revealed a significant association in CRC (p value = 0.0074) which can be partly explained by its predicting act as a mediator with sponging effect on hsa-miR-let-7b-3p and hsa-miR-20a-5p.LAMTOR5 gene can be considered as prognostic biomarker for CRC. LAMTOR5-AS5 which is a nearby lncRNA of this gene could play a regulatory impact through its sponging effect on hsa-miR-let-7b-3p and hsa-miR-20a-5p which both have shown a significant impact on overall survival rate in CRC patients in high expression levels.

Among T helper (Th) lineages differentiated from naive CD4+ T cells, interleukin (IL)-17-producing Th17 cells are highly correlated with the pathogenesis of autoimmune disorders. This study aimed to clarify the involvement of miR-141-3p and miR-200a-3p in Th17 cell differentiation as well as explore their potential target genes involved. For this purpose, human naive CD4+ T cells were cultured under Th17 cell polarizing condition. The differentiation process was confirmed through measurement of IL-17 secretion using the ELISA method and assessment of Th17 cell-defining genes expression during the differentiation period. MiR-141-3p and miR-200a-3p downstream genes were identified via consensus and integration in silico approach and their expression pattern and alterations were evaluated by quantitative real-time PCR. Finally, direct interaction between both microRNAs (miRNAs) and their common predicted target sequences was approved by dual-luciferase reporter assay. Highly increased IL-17 secretion and Th17 lineage-specific genes expression confirmed Th17 cell differentiation. Our results have demonstrated that miR-141-3p and miR-200a-3p are Th17 cell-associated miRNAs and their expression level is upregulated significantly during Th17 cell induction. We have also found that retinoic acid receptor beta (RARB) gene, whose product has been reported as a negative regulator of Th17 cell generation, is a direct target of both miRNAs and its downregulation can affect the transcriptional level of JAK/STAT pathway genes. Overall, our results have identified two novel Th17 lineage-associated miRNAs and have provided evidence for the RARB-dependent mechanism of miR-141-3p and miR-200a-3p-induced Th17 cell differentiation and hence Th17-mediated autoimmunity.

Purpose Corrective osteotomy of a malunited distal radius conventionally relies on 2D imaging techniques for alignment planning and evaluation. However, this approach results in suboptimal bone repositioning, which is associated with poor patient outcomes. In this case series, we evaluate the use of novel patient-specific plates (PSPs), which feature navigation and fixation of bone segments as preoperatively planned in 3D. Methods Ten participants with distal radius malunion underwent CT scans for preoperative alignment planning. Patient-specific guides and plates were designed, 3D-printed, and sterilized for use in corrective surgery of the distal radius. Pre- and postoperative results were compared in regard to clinical, functional, and radiographic outcomes. Results The application of a PSP was successful in 7 of the 10 cases. After treatment, the residual alignment error was reduced by approximately 50% compared with conventional treatment. The use of PSPs reduced pain significantly. Pre- and postoperative results were pooled and demonstrated significant correlations between: (1) pain and malpositioning, (2) the range of pro- and supination motion, the MHOQ score, the EQ-5D-5L score and dorsovolar angulation, and (3) MHOQ score and proximodistal translation. Conclusion The correlation between malalignment and MHOQ score, EQ-5D-5L score, pain, and range of motion shows that alignment should be restored as well as possible. Compared to the conventional approach, which relies on 2D imaging techniques, corrective osteotomy based on 3D preoperative planning and intraoperative fixation with a PSP has been shown to improve bone alignment and reduce pain. Level of evidence IV.

Background length of stay (LOS) is the time between hospital admission and discharge. LOS has an impact on hospital management and hospital care functions. Methods A descriptive, retrospective study was designed on about 27,500 inpatients between March 2019 and 2020. Required data were collected from six wards (CCU, ICU, NICU, General, Maternity, and Women) in a teaching hospital. Clinical data such as demographic characteristics (age, sex), type of ward, and duration of hospital stay were analyzed by the R-studio program. Violin plots, bar charts, mosaic plots, and tree-based models were used to demonstrate the results. Results The mean age of the population was 40.8 ± 19.2 years. The LOS of the study population was 2.43 ± 4.13 days. About 60% of patients were discharged after staying one day in the hospital. After staying one day in the hospital, 67% of women were discharged. However, 23% of men were discharged within this time frame. The majority of LOS in the CCU, ICU, and NICU ranged from 5 to 9 days.; In contrast, LOS was one day in General, Maternity, and Woman wards. Due to the tree plot, there was a different LOS pattern between Maternity-Women and the CCU-General-ICU-NICU wards group. Conclusion We observed that patients with more severe diseases hospitalized in critical care wards had a longer LOS than those not admitted to critical care wards. The older patient had longer hospital LOS than the younger. By excluding Maternity and Woman wards, LOS in the hospital was comparable between males and females and demonstrated a similar pattern.

Early in the pandemic, New Jersey (NJ) long-term care facilities (LTCFs) witnessed severe COVID-19 illness. With limited surveillance to characterize the scope of infection, we estimated the prevalence of antibody to the SARS-CoV-2 nucleocapsid protein among residents and staff, to describe the epidemiology, and to measure antibody distribution by prior PCR/antigen status and symptomatology. 10 NJ LTCFs of 20 solicited with diverse geography and bed-capacities were visited between October 2020 and March 2021. A single serum was tested for total N-antibody (ELISA) by the state laboratory. Residents' demographics and clinical history were transcribed from the patient record. For staff, this information was solicited directly from employees, supplemented by prior PCR/antigen results from facilities. 62% of 332 residents and 46% of 661 staff tested N-antibody positive. In a multivariable logistic regression in residents, odds ratios for older age and admission prior before March 1, 2020 were significant. Among the staff, odds ratios for older age, ethnic-racial group, nursing-related job, and COVID-19 symptoms were significantly associated with N-antibody positivity. In a sub-analysis in five better record-keeping LTCFs, 90% of residents and 85% of staff with positive PCR/antigen results were seropositive for N-antibody, yet 25% of residents and 22% of staff were N-antibody positive but PCR/antigen and symptoms negative. The high rate of clinically unsuspected infections likely contributed to the spread. These findings argue for robust surveillance, regular screening of asymptomatic individuals, and vaccinating both residents and staff to abate the pandemic. The data also provide guidance to prevent future outbreaks.

Introduction: Escherichia coli is one of the most important agents involved in healthcare-associated infection, and resistance to quantum ammonium compounds (QACs) has become a major challenge for infection control practitioners. The aim of the current study was to determine the frequency of qacE and qacEΔ1 genes in E. coli isolated from hospitalized patients in Qazvin, Iran. Material and Methods: In the current cross-sectional study, 102 E. coli were collected from hospitals of Qazvin. All bacterial isolates were identified using standard laboratory methods and the antimicrobial susceptibility was evaluated by Kirby-Baer test. The presence of qacE and qacEΔ1 genes was investigated using polymerase chain reaction (PCR) technique. Results: In this study, 65 (63.7%) isolates showed a multidrug resistance (MDR) pattern which was resistant to at least three classes of antimicrobials including ß-lactams, aminoglycosides, and fluoroquinolones. The highest rates of resistance were observed against cefotaxime (75.5%) and nalidixic acid (66.7%). The PCR showed that 5 (4.9%) isolates harbored qacE gene, 62 (60.8%) isolates qacEΔ1, and 10 (9.8%) isolates carried both genes, simultaneously. There was a significant relationship between the QACs resistance and MDR pattern (P=0.03). Conclusion: This study indicated a significant resistance rate against disinfectant compounds in the studied hospitals. However, more attention should be paid to this critical issue in the infection control committees of the hospitals.

Introduction: Plasmid-induced quinolone resistance has raised a great concern in the treatment of serious infections worldwide. The aims of this study were to determine the antibiotic susceptibility, the frequency of qepA, aac(6')-Ib and qnr genes by PCR and sequencing, and typing of the resistant isolates using repetitive extragenic palindromic sequence-based PCR (REPPCR) in Pseudomonas aeruginosa isolated from burn wound infections. Methods: In the current cross-sectional study, 149 P. aeruginosa were isolated from the burn wound samples of patients admitted to Motahari hospital in Tehran, Iran, from February to December 2016. The bacterial isolates were identified using standard laboratory methods and their antibiotic susceptibility to quinolones was evaluated using the standard Kirby-Bauer method, according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The presence of aac(6')-Ib, qepA, qnrA, qnrB4, qnrB and qnrS genes was assessed using PCR and sequencing methods and clonal relationship of the resistant isolates was evaluated using REP-PCR method. Results: All (100%) isolates showed complete resistance to used quinolone compounds in this study. The qnr and qepA genes were not found, but all (100%) isolates were positive for the presence of aac(6')-Ib gene and the sequencing revealed that all (100%) belong to the aac(6')-Ib-cr variant. REP-PCR showed that the studied isolates belonged to three distinct clones of A (77.9%), B (18.1%), and C (4%). Conclusion: The findings of the present study indicated the presence of aac(6')-Ib-cr variant and lack of the contribution of qnr and qepA in the emergence of resistance to quinolones in P. aeruginosa isolated from burn patients. Considering the importance of clonal spread of these resistant isolates and their significant role in the development of clinical infections, especially in patients with burns, more attention should be paid to the prevention of the dissemination of these resistant isolates.

Breast cancer is one of the most malignant tumors in the world. It is, in fact, the second leading cause of cancer death in women. Recent research has identified the role of miR-182 in this disease as an oncogene agent. In this study, the association of rs4541843 in the flanking region of the miR-182 sequence with the susceptibility to breast cancer risk has been studied in the Iranian population. By using the PCR_RFLP, the genotype rs4541843 was determined in 161 patients and 164 control subjects. The genotypes of the individuals were analyzed statistically to find the association between rs4541843 and the breast cancer incidence and its pathological characteristics. The results revealed that due to the dominance of the G allele, the frequency of GG + AG genotypes, as compared with AA, had a significant correlation with the incidence of this disease in controls and cases (P = 0.022; OR = 0.523). Moreover, the genotypes AG and AA could significantly decrease the susceptibility to the breast cancer risk; also in the presence of the A allele (OR, 0.565; P = 0.015), the incidence of the disease could be decreased. Our results indicated that this SNP was associated with the breast cancer risk of the Iranian population. We suppose that rs4541843 may influence the processing of the mature miRNA by affecting the cleavage of Drosha. Therefore, this SNP can be considered as a candidate genetic marker for the susceptibility to breast cancer in the Iranian women.

Introduction: Aminoglycosides have been long used for antibacterial treatment and are still commonly used in clinical practice. Despite their extensive application and positive effects, drug-related toxicity is considered as the main obstacle for aminoglycosides. Aminoglycosides induce nephrotoxicity through the endocytosis and accumulation of the antibiotics in the epithelial cells of proximal tubule. Most importantly, however, a number of pharmacological agents were demonstrated to have protective activities against nephrotoxicity in experimental animals.Areas covered: In the present systematic review, the authors provide and discuss the mechanisms and epidemiological features of aminoglycoside-induced nephrotoxicity, and focus mainly on recent discoveries and key features of pharmacological interventions. In total, 39 articles were included in this review.Expert opinion: The majority of studies investigated gentamicin-induced nephrotoxicity in animal models. Antioxidants, chemicals, synthetic drugs, hormones, vitamins, and minerals showed potential values to prevent gentamicin-induced nephrotoxicity. Indicators used to evaluate the effectiveness of nephroprotection included antioxidative indexes, inflammatory responses, and apoptotic markers. Among the nephroprotective agents studied, herbs and natural antioxidant agents showed excellent potential to provide a protective strategy against gentamicin-induced nephrotoxicity.

Parkinson's disease (PD) is a frequent progressive neurodegenerative disorder. Impaired mitochondrial function is a major feature of sporadic PD. Some susceptibility or causative genes detected in PD are strongly associated with mitochondrial dysfunction including PGC1α, TFAM and GSK3β. microRNAs (miRNAs) are non‐coding RNAs whose altered levels are proven in disparate PD models and human brains. Therefore, the aim of this study was to detect modulations of miRs upstream of PGC1α, TFAM and GSK3β in association with PD onset and progress. In this study, a total of 33 PD subjects and 25 healthy volunteers were recruited. Candidate miRNA (miR‐376a) was selected through target prediction tools and literature survey. Chronic and acute in vitro PD models were created by MPP+‐intoxicated SHSY5Y cells. The levels of miR‐376a and aforementioned genes were assessed by RT‐qPCR. The expression of target genes was decreased in chronic model while there were dramatically up‐regulated levels of those genes in acute model of PD. miR‐376a was strongly altered in both acute and chronic PD models as well as PBMCs of PD patients. Our results also showed overexpression of PGC1α, and TFAM in PBMCs is inversely correlated with down‐regulation of miR‐376a, suggesting that miR‐376a possibly has an impact on PD pathogenesis through regulation of these genes which are involved in mitochondrial function. miR‐376a expression in PD‐derived PBMCs was also correlated with disease severity and may serve as a potential biomarker for PD diagnosis. This is the first study showing altered levels of miR‐376a in PD models and PBMCs, suggesting the probable role of this miRNA in PD pathogenesis. The present study also proposed TFAM and PGC1α as target genes of miR‐376a for the first time, through which it possibly can exert its impact on PD pathogenesis.

Although the relationship between TP53 mutation, TP53 metabolism pathways, and tumorigenesis has been investigated, pan-cancer analysis of TP53 mutations and related metabolism pathways is not completely available in common types of human cancers. Thus, this study was going to represent TP53 mutant-related metabolism genes and pathways in a pan-cancer study and investigate the relationship between selected genes and drug resistance.The DNA-seq data, RNA-seq data, and clinical information of 12 types of cancer were downloaded from the cancer genome atlas (TCGA) database. GSE70479 data were obtained from GEO database for validation of our TCGA data. To evaluate the survival rate of patients, GEPIA2 was applied. The CCLE and GDSC database were used to investigate drug resistance and sensitivity.Our findings indicated that TTN, MUC16, and TP53 were present in 12 types of cancer with high level of mutation frequency which abundance of TP53 mutations was higher. Mutant TP53-related (mTP53) pathways and genes including PKM, SLC16A3, HK2, PFKP, PHGDH, and CTSC were obtained from enrichment analysis and interestingly, top pathways were associated with metabolism including glycolysis and mTORC1 pathway. Our results showed the expression of some candidate genes correlated with immune markers, prognosis, and drug resistance.Top mutant genes for 12 cancers were highlighted while TP53 was selected as top mutant gene, and metabolic genes associated with the TP53 mutation were identified that some of which are important in poor prognosis. In doing so, mutations in TP53 could run some metabolic pathways and drug resistance and sensitivity.

Liver fibrosis is a multifactorial disease with microbial and non-microbial causes. In recent years

Long noncoding RNAs (lncRNAs) have been found to be correlated with different cell biological processes and progression of various types of cancers including colorectal cancer (CRC). CRC is one of the most widespread cancers, thus, introducing new methods or biomarkers for its early diagnosis are desirable. The Crucial role of

Investigating the specific pathways and their relation with survival, mutation, sensitivity, and resistance to various drugs in different stages of colorectal cancer (CRC) could be effective in cancer treatment. In this study, identifying the specific pathways in each stage of CRC compared to other stages was considered via meta-analytic methodology. The Cancer Genome Atlas (TCGA) data with gene set enrichment analysis (GSEA) software, and CRC RNA-Seq data were used to enrich and determine specific pathways as well as to evaluate the expression level of TOP RANK genes. In addition, The Cancer Cell Line Encyclopedia (CCLE) data were used to correlate candidate genes with drug resistance. Finally, using Gene Expression Omnibus (GEO) data, drugs that could affect the expression level of these genes were identified. Three specific molecular pathways, including oxidative phosphorylation (OXPHOS), regulation of transporter activity (RTA), and negative regulation of transmembrane receptor protein serine threonine kinase (NRSTK) have been identified as hub pathways for stages II, III, and IV, respectively (P 0.01). The expression level of TOP RANK genes in each stage increased on average twice compared to other stages (P 0.01), and CCNB1, DKK1, NOG genes were associated with survival in stages II and IV, respectively (P 0.01). The expression of some selected genes had a correlation with drug resistance and sensitivity (P 0.05). GEO data revealed that gamma-tocotrienol (g-T3), NSC319726, and Casiopeina Cas-II-gly may reduce the expression of, NDUFAF1, CCNB1, DKK1 genes, respectively (P 0.01). Specific pathways and TOP RANK genes could lead to cancer progression and malignancy, resistance to chemotherapy drugs, poor survival in patients, and metastasis. Therefore, identification and targeting these pathways at each stage could be crucial in inhibiting progression at different stages of CRC.

Background The COVID-19 pandemic has led the Canadian provincial governments to take unprecedented measures, including restrictions to healthcare services and pharmacists. Limited evidence exists on changes in prescription trends in Canada during the pandemic period. Objectives To examine the trend of prescription medications’ utilization before and during COVID-19, among incident and prevalent users in the general population. We examined 18 major classes of medications. Methods We used the administrative health databases from the province of Manitoba, Canada, to conduct a province-wide cross-sectional study. Incident and prevalent use was compared between two time periods; pre-COVID-19: July 2016-March 2020 and during COVID-19: April 2020-March 2021. Interrupted time series analysis using autoregressive models was used to quantify the change in level and slope in quarterly medication use among incident and prevalent users. Results The quarterly study population ranged from 1,353,485 to 1,411,630 Manitobans. The most common comorbidities were asthma (26.67%), hypertension (20.64%), and diabetes (8.31%). On average, the pandemic restrictions resulted in a 45.55% and 12.17% relative decline in the aggregated utilization of all drugs among both incident and prevalent users, respectively. Subclass analysis showed a 46.83%, 23.05%, and 30.98% relative drop among incident users of antibiotics, cardiovascular drugs and opioids use, respectively. We observed a significant slope increase during COVID-19 among the quarterly cardiovascular, antidiabetics, alpha-1 blockers, and statins incident users compared to the pre-COVID-19 period. We noted a significant decrease in level among NSAIDs, opioids, and antibiotic prevalent users, however, no significant changes in slope were observed. Conclusion Our findings show a significant impact of COVID-19 measures on prescription trends in the general population. The observed decline among several medication classes was temporary. Further research is needed to monitor prescription trends and better understand if those changes were associated with increased health services and worsened outcomes.

Obesity is one of the risk factors concerns of colorectal cancer (CRC), the most common type of gastrointestinal cancer, due to the changing lifestyle and especially diet. There are various molecular pathways associated with obesity and the risk of CRC incidence, such as insulin resistance or elevated plasma free fatty acids, which alter the signaling pathways of intestinal epithelial cells. The aim of this study was to better understand the significance of unsaturated fatty acid biosynthesis on pathogenesis of colon cancer in obese. Based on GSE20931 dataset, obese individuals affected by CRC had higher increased gene expression than non-obese individuals. The analysis showed that in obese individuals, the 16 signaling pathway genes were activated and increased (FDR0.05) significantly. The biosynthetic pathway of unsaturated fatty acids showed a cross-talk with the arachidonic acid metabolism pathway and the PPAR signaling pathway is influenced and regulated via these pathways. The biosynthetic pathway of unsaturated fatty acids consisting of 22 genes, were analyzed using GEO data and revealed that 4 genes (HSD17B12, TECR, FADS2, ELOVL5) from this pathway were significantly increased (FDR0.05). These data were validated based on TCGA data (Adj.p.value0.001). The expression level of candidate genes in HT-29 cells decreased significantly (P.value0.01), and PPARγ expression increased under linoleic acid treatment (200 μM) compared to control cells. Moreover, in presence of linoleic acid treatment, migration, colony formation, and proliferation decreased (P.value0.01) in presence of treatment. In summary, the Biosynthesis pathway of unsaturated fatty acids is an interesting and critical pathway in CRC.

Cell surface proteins (CSPs) are an important type of protein in different essential cell functions. This study aimed to distinguish overexpressed CSPs in colorectal cancer to investigate their biomarker, prognosis, and drug resistance potential. Raw data of three datasets including 1187 samples was downloaded then normalization and differential expression were performed. By the combination of the cancer genome atlas (TCGA) clinical data, survival analysis was carried out. Information of all CSPs was collected from cell surface protein atlas. The role of each candidate gene expression was investigated in drug resistance by CCEL and GDSC data from PharmacoGX. CRC samples including 30 tumor samples and adjacent normal were used to confirm data by RT-qPCR. Outcomes showed that 66 CSPs overexpressed in three datasets, and 146 CSPs expression associated with poor prognosis features in TCGA data that TIMP1 and QSOX2 can associate with poor patient survival independently. High-risk patients illustrated more fatality than low-risk patients based on the risk score calculated by the expression level of these genes. Receiver operating characteristic curve analysis showed that 39 CSPs as perfect biomarkers for diagnosis in CRC. Furthermore, QSOX2 and TIMP1 expression levels increased in tumor samples compared to adjacent normal samples. The Drug resistance analysis demonstrated ADAM12 and COL1A2 up-regulation among 66 overexpressed CSPs caused resistance to Venetoclax and Cyclophosphamide with a high estimate, respectively. Many CSPs are deregulated in CRC, and can be valuable candidates as biomarkers for diagnosis, prognosis, and drug resistance.

Parkinson disease (PD) is the second most common neurodegenerative disease; the evidence suggests that lncRNAs and miRNAs play an important role in regulating the PD-related genes. The purpose of this research was to introduce two novel lncRNAs as the biomarker of PD diagnosis and treatment. We evaluated the expression profiles of six nodes of two regulatory networks in the PBMCs which had been got from 38 PD patients and 20 healthy individuals by qRT-PCR. Then, we compared the expression of these RNAs in both early and late stages of PD with the controls to determine if their expression could be related to the severity of disease. Further, this study investigated the direct interaction between one of the lncRNAs and target miRNA by using the dual luciferase assay. The results of the expression profiles of six nodes of the two ceRNA networks shown that linc01128, hsa-miR-24-3p and hsa-miR-30c-5p expression were significantly downregulated. While, the Linc00938, LRRK2 and ATP13A2 expression were up-regulated in the PBMC of the PD patients, in comparison to the controls. In addition, this study demonstrated that linc00938 directly sponged hsa-miR-30c-5p. The present study, therefore, for the first time, revealed two candidate lncRNAs as the biomarkers in the PD patients.

Breast cancer is the most common cancer in women worldwide with remarkable proportion of the patients in advanced stage. Recently the importance of genetic mutations in cancers are well established and also the role of tumor suppressor genes such as

In the diagnostic work-up of Madelung deformity conventional radiographic imaging is often used, assessing the three-dimensional deformity in a two-dimensional manner. A three-dimensional approach could expand our understanding of Madelung deformity’s complex wrist anatomy, while removing inter- and intra-rater differences. We measured previous two-dimensional-based and newly developed three-dimensional-based parameters in 18 patients with Madelung deformity (28 wrists) and 35 healthy participants (56 wrists). Madelung deformity wrists have increased levels of ulnar tilt, lunate subsidence, lunate fossa angle, and palmar carpal displacement. The lunate fossa is more concave and irregular, and angles between scaphoid, lunate, and triquetral bones are decreased. These findings validate the underlying principles of current two-dimensional criteria and reveal previously unknown anatomical abnormalities by utilizing novel three-dimensional parameters to quantify the radiocarpal joint.

MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of the Parkinson’s disease (PD), an age related-neurodegenerative disorder. The aim of present study was to compare the expression profiles of a new set of candidate miRNAs related to aging and cellular senescence in peripheral blood mononuclear cells (PBMCs) obtained from the PD patients with healthy controls and then in the early and advanced stages of the PD patients with their controls to clarify whether their expression was correlated with the disease severity. We have also proposed a consensus-based strategy to interpret the miRNAs expression data to gain a better insight into the molecular regulatory alterations during the incidence of PD. We evaluated the miRNA expression levels in the PBMCs obtained from 36 patients with PD and 16 healthy controls by the reverse transcription-quantitative real-time PCR and their performance to discriminate the PD patients from the healthy subjects assessed using the receiver operating characteristic curve analysis. Also, we applied our consensus and integration approach to construct a deregulated miRNA-based network in PD with the respective targets and transcription factors, and the enriched gene ontology and pathways using the enrichment analysis approach were obtained. There was a significant overexpression of miR-885 and miR-17 and the downregulation of miR-361 in the PD patients compared to the controls. The blood expression of miR-885 and miR-17 tended to increase along with the disease severity. On the other hand, the lower levels of miR-361 in the early stages of the PD patients, as compared to controls, and its higher levels in the advanced stages of PD patients, as compared to the early stages of the PD patients, were observed. Combination of all three miRNAs showed an appropriate value of AUC (0.985) to discriminate the PD patients from the healthy subjects. Also, the deregulated miRNAs were linked to the known PD pathways and the candidate related target genes were presented. We revealed 3 candidate biomarkers related to aging and cellular senescence for the first time in the patients with PD. Our in-silico analysis identified candidate target genes and TFs, including those related to neurodegeneration and PD. Overall, our findings provided novel insights into the probable age-regulatory mechanisms underlying PD and a rationale to further clarify the role of the identified miRNAs in the PD pathogenesis.

The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to determine the effectiveness of probiotic supplementation on clinical symptoms, weight loss, glycemic control, lipid and hormonal profiles, and biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome (PCOS). Eligible studies were systematically searched from Cochrane Library, Embase, Medline, and Web of Science databases until January 2019. Cochran (Q) and I-square statistics were used to measure heterogeneity among included studies. Data were pooled by using random-effect model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Eleven articles were included in this meta-analysis. Probiotic supplementation significantly decreased weight (SMD − 0.30; 95% CI, − 0.53, − 0.07; P = 0.01), body mass index (BMI) (SMD − 0.29; 95% CI, − 0.54, − 0.03; P = 0.02), fasting plasma glucose (FPG) (SMD − 0.26; 95% CI, − 0.45, − 0.07; P

Background Given the rising popularity in body-contouring procedures (BCPs) in the United States, it is important to assess the currently unknown association between resident involvement and postoperative complications. As such, the aim of this study was to evaluate the impact of resident involvement on outcomes in BCPs using a large national database. Methods A retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database was performed (2006-2012) to identify patients undergoing BCPs, using relevant Current Procedural Terminology codes. Outcome measures included postoperative complications, hospital length of stay, and operation time. Multivariate regression models were used to assess the impact of resident involvement and resident experience on outcomes. Results A total of 9638 cases were identified, of which 3311 involved resident participation. Resident involvement was associated with significantly higher rates of complications (7.8% vs 4.4%; P = 0.003) and longer operation times (180.7 vs 171.9 minutes; P = 0.005). For each year increase of resident postgraduate year, there was a significant decrease in odds of complications (odds ratio, 0.906; P = 0.013) and operative time (-2.7 minutes; P = 0.001). Conclusions Resident involvement in BCPs was associated with an increased rate of overall complications in a large, national database. However, the clinical significance of these outcomes may be debated. Increased postgraduate year experience as a surgical resident was inversely associated with overall complications. Guided resident autonomy and earlier exposure to BCPs could lead to an optimization of clinical outcomes and resident education.

Helicobacter pylori growth requirements is a prerequisite to invade gastric epithelium and the process of injury to gastric cells will eventually lead to gastric cancer. The aim of this study is to investigate the effect of iron challenge on the expression of genes involved in iron homeostasis. The presence of Phosphoglucosamine mutase (glmM), cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) genes and mRNA expression of Iron Regulatory Protein 2 (IRP2), Transferrin Receptor (TFRC) and Ferritin Light Chain (FTL) genes in samples of 28 normal gastric mucosa, 33 chronic gastritis, 29 gastritis with intestinal metaplasia, 29 intestinal type adenocarcinoma patients were examined by real-time PCR. Immunohistochemistry was used to analyze cellular localization and protein levels. In the all H. pylori positive tissues, particularly in the basal regions of foveolar cells, TFRC was overexpressed (P

AIMS OF THE STUDY Our aim was to explore drug-induced liver injury (DILI) in Switzerland using the real-world data of the global pharmacovigilance database VigiBase™, with a special focus on the new drug class of checkpoint inhibitors. This is the first study investigating drug-related hepatic disorders in Switzerland in a global pharmacovigilance database. METHODS This was a retrospective study analysing the ICSRs (individual case safety reports) of the global pharmacovigilance database VigiBase™. We explored all ICSRs submitted in Switzerland within the last 10 years (1 July 2010 to 30 June 2020). For data extraction, the standardised MedDRA query (SMQ) “narrow drug-related hepatic disorders – severe events only” was applied. The ICSRs, drug-reaction pairs and adverse drug reactions were analysed descriptively, including a special focus on checkpoint inhibitors. For comparing the hepatic adverse drug reactions of pembrolizumab, nivolumab and ipilimumab, the reporting odds ratios (RORs) were calculated in a disproportionality analysis. RESULTS In total, 2042 ICSRs could be investigated, comprising 10,646 drugs and 6436 adverse drug reactions. Gender was equally distributed between male and female. Patients were on average 57 years old. The mortality rate was high, with fatal adverse reactions in over 10% of cases. On average, patients used five drugs including two suspected drugs. Paracetamol, amoxicillin/clavulanic acid, esomeprazole and atorvastatin ranked among the most frequently suspected drugs for severe drug-related hepatic disorders. However, Vigibase™ data are not appropriate for judging causality and these results should be interpreted with caution owing to the possible influences of comedication or comorbidity. An average of three adverse drug reactions per ICSR were reported, most frequently including hepatocellular injury, cholestatic liver injury, and liver injury. For checkpoint inhibitors, hepatitis was the most frequently reported hepatic adverse drug reaction. In comparison with nivolumab and ipilimumab, pembrolizumab had a significantly higher ROR for hepatitis (2.41, p = 0.016), but also a lower ROR for autoimmune hepatitis (0.11, p = 0.009). CONCLUSION Our findings highlight the importance for healthcare providers in Switzerland to pay special attention to possible drug-induced liver injuries because of their high mortality rate. The analysis of real-world data confirms the previous assumption that hepatitis is the most frequent hepatic adverse event for checkpoint inhibitors. Further clinical studies are warranted to directly compare hepatic adverse drug reactions to different checkpoint inhibitors.

Objective The aim of this study was to investigate the genetic relatedness and antimicrobial resistance among Shigella species isolated from food and stool samples. Using cross sectional study method, Shigella spp. were isolated from food and clinical samples using culture-based, biochemical and serological methods. Antimicrobial susceptibility and genetic relatedness among the isolates were evaluated using disk diffusion and RAPD-PCR methods respectively. Results The prevalence of Shigella spp. were 4.84 and 7.7% in food and stool samples respectively. All food isolates were Sh. sonnei. 91.42% of the Shigella stool isolates were Sh. sonnei. 62.5% of food isolates were resistant to tetracycline. 46.8, 50 and 65.8% of clinical isolates were resistant to imipenem, amikacin and azithromycin respectively. 50 and 85.7% of the food and clinical isolates respectively were MDR. Dendrogram generated by RAPD-PCR showed that the isolates from food and stool samples were categorized in a same group. Close genetic relatedness between MDR Shigella isolates from food and clinical samples indicate that foods can be considered as one of the main vehicles for transmission of MDR Shigella to human causing acute diseases. Survey of MDR Shigella among food and clinical samples is strongly suggested to be implemented.

BACKGROUND፡ Acinetobacter baumannii is a major contributor to nosocomial infections. Extended-spectrum ßlactamase (ESBL)-producing A. baumannii is spreading worldwide. We aimed to determine the frequency of ESBLencoding genes in clinical isolates of A. baumannii and to access their clonal relationship by repetitive extragenic palindromic-PCR (rep-PCR).METHODS: In this descriptive cross-sectional study, 203 isolates of A. baumannii were collected from Qazvin hospitals. The Identification of isolates was performed by standard laboratory methods. To verify ESBL production, all isolates were screened by disk agar diffusion and confirmed by the combined disk method. Subsequently, ESBL-encoding genes were detected by PCR and sequencing. Possible clonal association of ESBL-producing isolates was evaluated using rep-PCR.RESULTS: Two hundred (98.5%) isolates showed reduced susceptibility to one of the antibiotics used in the ESBL screening test, of which 127 isolates (62.6%) produced ESBL. PCR results showed blaOXA-1 (20.5%) was the most prevalent gene followed by blaTEM-1 (20%), blaGES-1 (15.7%), blaCTX-M-15 (7.9%), and blaPER-1(1.6%). Rep-PCR results revealed that ESBL-producing isolates belonged to clones A (85%), B (13.4%), and C (1.6%).CONCLUSION: Our study showed the significant presence of blaOXA-1, blaTEM-1, blaGES-1, blaCTX-M-15, and blaPER-1 genes in ESBLproducing A. baumannii isolates in the studied hospitals. This is the first report on the emergence of blaOXA-1 gene in these isolates in Iran. The use of comprehensive antimicrobial treatment guidelines based on laboratory data and appropriate infection control interventions are essential.

Flavonoids have been demonstrated to have the ability of sensitizing cancer cells to chemotherapy and inverse multidrug resistance via various mechanisms, such as modulating of pumps. The therapeutic effect of candidone, tephrosin, and bavachinin in treatment of cancer, particularly to overcome multidrug resistance (MDR) is largely unknown. The capacity of these agents in sensitization of MDR cells is investigated in the current work.We analyzed the impact of candidone, tephrosin, and bavachinin, as chemosensitizer on cell cytotoxicity, P-gp and ABCG2 mRNA expression level on two multidrug resistant cells, ABCG2 overexpressing human epithelial breast cancer cell line (MCF7/MX), and P-gp overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB). The inhibitory concentration of 50% (IC50) of daunorubicin in EPG85.257RDB cells in combination with IC10 of Bavachinin, Tephrosin, and Candidone were 6159 ± 948, 4186 ± 665, 730 ± 258 nM, and this data in MCF7/MX cell were 1773 ± 534, 7160 ± 405 and 3340 ± 622 nM respectively. These three flavonoids dose-dependently decreased the viability of MCF7/MX and EPG85.257RDB and significantly (p 0.05) decreased IC50 of daunorubicin and mitoxantrone except Tephrosin in MCF7/MX cells. Candidone and Bavachinin were the most potent chemosensitizer in EPG85.257RDB and MCF7/MX cells respectively. Flavonoids did not reduce mRNA expression of P-gp and ABCG2 after 72 h treatment, except Candidone in EPG85.257RDB and Bavachinin in MCF7/MX cells.This effect is not time-dependent, and flavonoids have their own patterns that are cell-dependent. In general, tephrosin, candidone, and bavachinin had the potential of sensitizing MDR cells to mitoxantrone and daunorubicin.

Background Th17 cells are a newly discovered subset of CD4+ T cells known as key participants in various immune responses and inflammatory conditions including autoimmune diseases. Mi(cro)RNAs are a family of non‐coding RNAs that regulate numerous critical immune functions. Immuno‐miRNAs modulate cell biological processes in T cells, such as differentiation and function of Th17 cells. The aim of the present study is to investigate the expression of miR‐9‐5p, miR‐193b‐3p, and autoimmunity‐related genes during human Th17 cells differentiation. Methods Human naïve CD4+ T cells were purified from peripheral blood mononuclear cells (PBMCs) by magnetic cell sorting system (MACS) and their purity was checked by flow‐cytometric analysis. Naïve CD4+ T cells were cultured under Th17‐polarizing condition for 6 days. IL‐ 17 secretion was determined by means of enzyme‐linked immunosorbent assay (ELISA). Next, the expression levels of miRNAs and putative targets genes were assessed by qRT‐PCR at different time points of differentiation. Results Our result showed dramatic downregulation of TCF7, MAP3K1, ENTPD1, and NT5E genes during human Th17 differentiation. Polarization also had a significant inducible effect on the expression of miR‐9 and miR‐193b over differentiation of human Th17 cells. According to our results, miR‐9‐5p and miR‐193b‐3p may contribute to Th17 differentiation probably by inhibiting the expression of negative regulators of Th17 differentiation. Conclusion This study confirmed deregulation of TCF7, MAP3K1, ENTPD1, and NT5E genes in Th17 differentiation process and introduced miR‐9 and miR‐193b as Th17 cell‐associated miRNAs, making them good candidates for further investigations., miR‐9‐5p and miR‐193b‐3p may contribute to human Th17 differentiation by inhibiting the expression of negative regulators of Th17 differentiation. This study confirmed deregulation of TCF7, MAP3K1, ENTPD1, and NT5E genes in Th17 differentiation process and introduced miR‐9 and miR193b as Th17 cell–associated miRNAs, making them good candidates for further investigations.

Recently, we have reported mutations in LARP7 gene, leading to neurodevelopmental disorders (NDDs), the most frequent cause of disability in children with a broad phenotype spectrum and diverse genetic landscape.Here, we present two Iranian patients from consanguineous families with syndromic intellectual disability, facial dysmorphism, and short stature.Whole-exome sequencing (WES) revealed a novel homozygous stop-gain (c.C925T, p.R309X) variant and a previously known homozygous acceptor splice-site (c.1669-1_1671del) variant in LARP7 gene, indicating the diagnosis of Alazami syndrome.These identified variants in patients with Alazami syndrome were consistent with previously reported loss of function variants in LARP7 and provide further evidence that loss of function of LARP7 is the disease mechanism.

The out-of-pocket payments for prescription medications can impose a financial burden on patients from low- and middle- incomes and who suffer from chronic diseases. The present study aims at evaluating the affordability of cardiovascular disease (CVD) medication in Iran. This includes measuring affordability through World Health Organization/Health Action International (WHO/HAI) methodology. In this method, affordability is characterized as the number of days' wages of the lowest-paid unskilled government worker. The different medication therapy scenarios are defined in mono-and combination therapy approaches. This method adds on to WHO/HAI methodology to discover new approaches to affordability assessments. The results show the differences in the medicines affordability when different approaches are used in mono-and combination therapy between 6 main sub-therapeutic groups of CVD. It indicates the medicine affordability is not a static concept and it changes dynamically between CVD therapeutic subgroups when it used alone or in combination with other medicines regarding patients&rsquo, characteristics and medical conditions. Hypertension and anti-arrhythmia therapeutic groups had the most non-affordability and hyperlipidemia had the most affordable medicines. Therefore, affordability can be considered as a dynamic concept, which not only affected by the medicine price but significantly affected by a patient&rsquo, s characteristics, the number of medical conditions, and insurance coverage.

Colorectal cancer (CRC) is one of the most common types of cancer which affects the colon and the rectum. Approximately one third of annual CRC mortality occurs due to the late detection of this type of cancer. Therefore, there is an urgent need for more powerful diagnostic and prognostic tools for identification and treatment of colorectal tumorigenesis. Non-coding RNAs (ncRNAs) have been implicated in the pathology of CRC and also linked to metastasis, proliferation, differentiation, migration, angiogenesis and apoptosis in numerous cancers. Recently, attention has turned towards ncRNAs as specific targets for diagnosis, prognosis and treatment of various types of cancers, including CRC. In this review, we have tried to outline the roles of ncRNAs, and their involvement in signaling pathways responsible for the progression of CRC.

INTRODUCTION: Health care-associated infections caused by metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa are a significant growing concern in patients with burns worldwide. The aims of this study were to determine the antibiotic susceptibility of and detect the presence of MBLs among P. aeruginosa isolates and assess their clonal relationship using enterobacterial repetitive intergenic consensus (ERIC)-PCR. METHODS: Non-duplicated clinical isolates (160) of P. aeruginosa were collected from patients with burns at the Motahari Hospital in Tehran, Iran. All isolates were identified using standard laboratory methods and further characterized for antimicrobial susceptibility. Any carbapenem-resistant isolates were then examined for MBL production by the E-test and MBL-encoding genes were detected by PCR. The clonal relatedness of MBL-producing isolates was assessed by ERIC-PCR. RESULTS: For multidrug-resistant isolates, the highest rates of susceptibility were observed for colistin 160 (100%), polymyxin B 160 (100%), and ceftazidime 32 (20%). In total, 69 (43.7%) isolates were identified as MBL producers. Twenty-eight (17.5%) isolates were positive for the bla VIM-1 gene followed by the bla IMP-1 (15.6%) and bla SPM-1 (5.6%) genes. ERIC-PCR revealed three separate genotypes, where type A (76.8%) was the most prevalent, followed by B (20.3%), and then C (2.9%). CONCLUSIONS: Our present study found that the bla IMP-1 and bla VIM-1 genes were present at a significant frequency and also detected the bla SPM-1 gene in P. aeruginosa isolates for the first time, highlighting the need for establishing suitable infection control measures to successfully treat patients and prevent further spread of these resistant organisms among patients with burns.

Purpose Various skeletal and soft tissue abnormalities have been identified in Madelung deformity and have been hypothesized to play a causal role in its progressive symptomatology; however, our pathological understanding of these changes remains limited. In this study, we biomechanically assessed the Madelung deformity wrist, using 4-dimensional computed tomography imaging. Methods Nine Madelung deformity wrists (5 patients; age, 24 ± 5 y) and 18 healthy wrists (9 volunteers; age, 28 ± 3 y) underwent 4-dimensional imaging during flexion-extension motion and radioulnar deviation. Carpal kinematics and radiocarpal joint parameters were quantified and compared. Results In Madelung deformity wrists, significantly decreased rotation was seen in the lunate (–4.6°) and the triquetrum (–4.8°) during flexion-extension motion. During radioulnar deviation, significant decreases were visible in lunate bone translation (–0.7 mm), triquetrum bone translation (–0.6 mm), and triquetrum bone rotation (–1.9°). Patients had significantly decreased articulating surface areas of the scaphoid (1.4 ± 0.2 cm2 versus 1.6 ± 0.2 cm2) and lunate (1.2 ± 0.4 cm2 versus 1.5 ± 0.3 cm2) fossa, and significantly increased radioscaphoid (1.3 ± 0.1 mm versus 1.2 ± 0.1 mm) and radiolunate (1.6 ± 0.2 mm versus 1.3 ± 0.3 mm) joint space thicknesses. Conclusions There is a decreased mobility of the lunate and triquetrum bones in Madelung deformity. Clinical relevance Four-dimensional imaging could be used in future studies that investigate the effect of surgical ligament release on carpal kinematics and subsequent wrist mobility.

There are several current trials investigating the effect of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with metabolic syndrome (MetS); however, their findings are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to summarize the existing evidence and collectively determine the effects of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. Two authors independently searched electronic databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science databases, until May 2018 in order to find relevant RCTs. The quality of the selected RCTs was evaluated using the Cochrane Collaboration risk of bias tool. Cochran's Q test and I-square (I2) statistic were used to determine whether heterogeneity exists across included trials. Standardized mean difference (SMD) and 95% CI between two intervention groups were used to determine pooled effect sizes. Out of 317 potential citations selected based on keywords, 24 RCTs met the inclusion criteria and were eligible for the current meta-analysis. The pooled results obtained by using the random-effects model showed that resveratrol supplementation significantly decreased C-reactive protein (CRP) (SMD = −0.55; 95% CI, −0.84, −0.26; P < 0.001; I2: 84.0) and tumor necrosis factor-α (TNF-α) (SMD = −0.68; 95% CI, −1.08, −0.28; P = 0.001; I2: 81.3) concentrations among patients with MetS and related disorders. Interleukin 6 (IL-6) (SMD = 0.05; 95% CI, −0.31, 0.41; P = 0.79; I2: 85.0) and superoxide dismutase (SOD) (SMD = 0.21; 95% CI, −3.16, 3.59; P = 0.90; I2: 97.7) concentrations did not significantly change following resveratrol supplementation. Resveratrol supplementation showed a promising lowering effect on some of the inflammatory markers among patients with MetS and related disorders. Additional prospective studies regarding the effect of resveratrol supplementation on biomarkers of inflammation and oxidative stress by using higher doses of resveratrol and longer duration of supplementation are necessary.

Background The steroid receptor RNA activator 1 (SRA1) gene is involved in the progression of various cancers via different molecular mechanisms mediated by long non-coding RNA SRA (lncRNA SRA). This study aimed to evaluate the lncRNA SRA effect on the tumor progression of colorectal cancer (CRC). Methods SRA1 expression was assessed in the cancer genome atlas datasets, CRC cell lines, and tumor specimens. Meta-analysis and gene co-expression network analysis were performed to identify pathways related to SRA1. RNA interference and cell treatment were utilized to examine the role of SRA1 expression in HT-29 and Caco-2 cell lines. Also, the effect of SRA1 expression was investigated on drug resistance, clinical parameters, and mutations in CRC samples. Results The SRA1 transcripts, especially lncRNA SRA, were dysregulated in CRC tissue samples compared with normal tissue samples. Furthermore, SRA1 depletion decreased colony formation and proliferation while induced apoptosis in HT-29 and Caco-2 cells. In silico analyses indicated that SRA1 level was correlated with expression levels of oxidative phosphorylation (OXPHOS) genes. LncRNA SRA expression increased in response to the increased oxidative capacity, and when lncRNA SRA was knocked down, the expression level of OXPHOS pathway genes, including NDUFB5 and ATP5F1B, was changed. Also, KRAS-mutant samples had the highest SRA1 expression level. Conclusions LncRNA SRA could function as an oncogene through the OXPHOS pathway in CRC, and serve as a potential biomarker for identifying CRC subtype with KRAS mutations. The findings suggest that lncRNA SRA might be a therapeutic target to inhibit cell proliferation in CRC.

Resveratrol (RSV), a natural polyphenol component, has diverse biological properties. It has been shown that RSV regulated the self-renewal and differentiation of several types of stem cells, but the precise role of this compound on regulation of human embryonic stem cells (hESCs) self- renewal remained to be elucidated. Here we have shown that RSV promoted hESCs proliferation through cell cycle modulation and up-regulation of anti-apoptotic markers, without affecting pluripotency. Furthermore, inhibition of SIRT1 by EX-527 resulted in suppression of RSV-induced enhancement of hESCs self-renewal. RSV exerted its beneficial effects by activation of MEK/ERK signaling pathway as verified by application of specific MEK inhibitor, PD0325901. In conclusion, RSV elevated self-renewal of hESCs at least partly via "SIRT1-MEK/ERK" axis. These findings provide a novel application of RSV for developing a defined medium for hESCs culture which could help to better understanding of the signaling events that govern self-renewal of hESCs.

Purpose: Unsafe behaviors are an important cause of accidents in adolescent age groups. This study was designed to examine the behaviors of adolescent pedestrians in southern Iran. Methods: This is a descriptive analytical cross-sectional study. The study population consisted of high school students in Shiraz, capital city of Fars Province, Iran. Five hundred and sixteen students were selected by multi-stage sampling. Data were collected by the use of three questionnaires, which included Persian copies of adolescent road user behavior questionnaire (ARBQ), Duke University Religious Index (DUREL), as well as the context and independent variables questionnaire. Results: The results showed that a decrease in dangerous behaviors on the road resulted in an increase in respondents' intrinsic religiosity. Also, engagement in unsafe crossing behavior in the road decreased with increasing respondents' intrinsic religiosity. Another finding showed that female students were less involved in dangerous play and planned protective behaviors on the road. Conclusion: Findings clearly indicate that intrinsic religiosity has a significant role in reducing the risky road behaviors of students. Hence, religion may improve road safety in school students' road behavior in Iran. Keywords: Religion, Traffic accidents, Road behaviors, Students

Purpose: Traffic injuries are among the leading causes of mortality and morbidity worldwide. Pedestrians have been considered as a high-risk group among road users, especially in middle- or low-income communities. This study attempted to determine the burden of pedestrians' fatalities in Fars, the southern province of Iran using years of life lost (YLL) approach. Methods: The data used in this study were retrieved from Fars Forensic Medicine Organization database on pedestrian traffic accidents. The YLL from 2009 to 2013 was estimated using the method presented by World Health organization. Some epidemiological characteristics of pedestrians' fatalities were analyzed by SPSS. Results: Although YLL among 1000 male pedestrians decreased from 2.5 in 2009 to 1.5 in 2013, it increased from 0.9 to 2.1 among 1000 females during the same period. Higher proportion of death was found in female, illiterate, and married pedestrians (p < 0.001). In addition, mortality was higher in pedestrians living the cities, during daytime, at home, and in hospitals (p < 0.001). Conclusion: Consistent with the global trends, burden of pedestrian accidents in Fars was also exceptionally high. Considering the national and cultural aspects of different countries, improving the safety of pedestrians demands a multi-dimensional approach with interventional factors concerning policies, rules, pedestrians, motor vehicles and environmental conditions taken into consideration. Key words: Accidents, traffic; Pedestrians; Burden of disease; Years of potential life lost

Summary Introduction. Pseudomonas aeruginosa is as an important opportunistic human pathogen, which is associated with several clinical infections that are usually difficult to treat because of resistance to multiple antimicrobials. The production of extendedspectrum ß-lactamases (ESBLs) is an important mechanism of ß-lactam resistance. The aims of this study were to determine the prevalence of ESBLs, antimicrobial susceptibility, and to detect the blaTEM, blaSHV, and blaCTX-M genes. Methods. In this study, carried out from March 2013 to December 2014, 266 P. aeruginosa isolates were collected from patients admitted to teaching hospitals of Qazvin and Tehran, Iran. All isolates were initially screened for ESBL production by disk diffusion method and were further confirmed using a combined disk method. Antimicrobial susceptibility of ESBL-producing isolates was determined by standard disk diffusion method. Polymerase Chain Reaction (PCR) and sequencing techniques were employed for detection of blaTEM, blaSHV, and blaCTX-M genes. Results. In total, 262 (98.5%) P. aeruginosa isolates were nonsusceptible to the used extended spectrum cephalosporins, and, among these, 75 (28.6%) isolates were ESBL producers. Fifty-nine (78.7%) of ESBL-producing isolates showed multidrug-resistance pattern. Of 75 ESBL-positive isolates, the blaTEM-1 (26.7%) was the most common gene, followed by blaCTX-M-15 (17.3%), blaSHV-1 (6.7%), and blaSHV-12 (4%), either alone or in combination. Conclusions. The results of this study showed the notable prevalence of ESBLs among the clinical isolates of P. aeruginosa in Iran, indicating the urgency for the implementation of appropriate follow-up measures for infection control and proper administration of antimicrobial agents in our medical settings.

Background: Diabetes imposes an enormous burden on patients, families, societies, and healthcare systems. Determining the affordability of medications is an important complicated and vague task, especially in low- and middle-income countries (LMICs). This study aimed to assess the affordability of diabetes medication therapy in Iran’s health system. Methods: This paper presents a scenario-based assessment of the affordability of all registered anti-diabetes medications in Iran in 2017. To this end, 4 medication therapy scenarios were defined as mono, dual, triple, and insulin therapy in accordance with the existing guidelines and clinicians’ opinions. Then the affordability ratio of each treatment scenario was determined for type 1 and type 2 diabetes drawing on the World Health Organization (WHO)/Health Action International (HAI) Methodology. If the affordability ratio for treatment schedules was more than 1, the patients’ out-of-pocket (OOP) expenses exceeded the lowest-paid unskilled government worker (LPGW)’ wage per day, and the treatment was labelled as non-affordable. Results: The results revealed that the mono, dual, and triple (non-insulin) medication therapies in type 2 diabetes were affordable, despite an increase in the dosage or a switch from the monotherapy to the combination therapy of oral medications. However, some treatment scenarios in the triple therapy, including oral plus insulin and some insulin only therapies, were proved to be non-affordable. In type 1 diabetes, only insulin glulisine, detemir, and lispro were non-affordable in monotherapy. Regarding the combination therapy, only isophane insulin with aspart or regular insulin were affordable treatments. Conclusion: Although oral medication therapies were documented to be affordable, insulin therapy, with current coverage conditions, for patients with lowest paid wages and those receiving even less is unaffordable and a major barrier to treatment; hence, policy-maker should consider targeting and more financial protection policies to improve the affordability of insulin therapies among this group of patients.

Background: Madelung deformity is a congenital wrist condition characterized by volar subluxation of the wrist caused by premature growth arrest of the distal radius. Progressive symptoms can necessitate surgical intervention, yet optimal treatment strategy remains unknown. The aim of this study is to determine treatment options, surgical indications, and operative outcomes for Madelung deformity. Methods: This study adhered to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. A comprehensive systematic review was performed to identify all studies describing surgical interventions for Madelung deformity. All studies were evaluated by level of evidence and a self-developed quality assessment tool. Results: Twenty-five studies met inclusion criteria; all case series with type IV level of evidence. Studies assessed pain, range of motion, aesthetic deformity, and grip strength. The primary indication for surgery was the presence of wrist pain. Various surgical procedures exist and could be categorized as radial lengthening, ulnar shortening, or a combination of both. All studies report postoperative pain reduction and most studies report an improved range of motion. Conclusions: A variety of surgical procedures reportedly have satisfactory outcomes. However, outcomes are reported in an inconsistent manner, prohibiting pooling of studies and comparisons of surgical procedures and their outcomes. We propose several methodological changes for implementation in future studies, increasing the quality of evidence to compensate for small patient numbers.

Background Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system affecting young adults. SNPs can be used as genetic biomarkers to identify disease-related genes such as MS. Moreover, SNPs can be considered as important determinants for an increased risk of autoimmune diseases such as MS. Studies have shown that miR-182 is of importance in Treg cell development and function as critical regulators in autoimmune disease. So far, no study has been conducted to investigate the association between rs4541843 polymorphism in pri-miR-182 and MS. In the present study, we assessed the frequency of rs4541843 different alleles and genotypes and their association with MS risk in Iranian population. Methods The rs4541843 was genotyped in 81 patients with MS and 89 healthy subjects, using the PCR-RFLP method. The frequency of alleles and genotypes and the association of this polymorphism with MS risk and the gender of the patients was then statistically analyzed. Results Statistical analysis showed the protective role of AA genotype against MS risk (P = .031, OR = 0.348) while there was no significance correlation between the frequency of rs4541843 different alleles and the other genotypes. Conclusion Our findings illustrated that the pri-miR-182 rs4541843 G>A polymorphism is associated with the risk of MS in Isfahan population. However, additional large-scale association studies in various ethnicities and more molecular studies are necessary to elaborate our findings.

BACKGROUND: Professional advancement in academic plastic surgery may depend on scholarly activity. The authors evaluate gender-based publishing characteristics in three international plastic surgery journals. METHODS: A retrospective review of all articles published in 2016 in the following journals was undertaken: Plastic and Reconstructive Surgery, Journal of Plastic, Reconstructive and Aesthetic Surgery, European Journal of Plastic Surgery, Annals of Surgery, and New England Journal of Medicine. Data were collected on lead author gender (first or senior author) and differences in author gender proportions, by journal, by article topic, and by geographic location were evaluated. RESULTS: Overall, 2610 articles were retrieved: 34.1 percent were from plastic surgery journals, 12.8 percent were from the Annals of Surgery, and 53.1 percent were from the New England Journal of Medicine. There was a lower proportion of female lead authors among plastic surgery journals compared with the Annals of Surgery and the New England Journal of Medicine (31 percent versus 39 percent versus 39 percent; p = 0.001). There were no differences in female lead author geographic location in the Annals of Surgery or the New England Journal of Medicine; within the plastic surgery journals, there were differences (p = 0.005), including a lower proportion arising from East Asia (15 percent) and a higher proportion arising from Canada (48 percent). Within plastic surgery, Plastic and Reconstructive Surgery had the lowest proportion of female lead author (p < 0.001). The proportion of female lead author varied by article topic (p < 0.001) and was notably higher in breast (45.6 percent) and lower in head and neck/craniofacial-orientated articles (25.0 percent). CONCLUSIONS: There are gender disparities in three mainstream plastic surgery journals-Plastic and Reconstructive Surgery, the Journal of Plastic, Reconstructive and Aesthetic Surgery, the European Journal of Plastic Surgery-and there are lower proportions of lead female authorship compared with the Annals of Surgery and the New England Journal of Medicine. Further research should focus on understanding any geographic disparities that may exist.

Sepsis is a serious and potentially life-threatening condition. Risk factors that are associated with the development of sepsis may differ as it relates to reconstructive flap surgery. The purpose of this study is to identify the incidence and predictors for sepsis in patients undergoing reconstructive flap surgery. The ACS-NSQIP database was queried from 2005 to 2016 for factors related to sepsis in patients undergoing reconstructive flap surgery. CPT codes were used to identify patient cohorts. A sepsis group was compared to a control group that underwent the same procedures without the postoperative manifestations of sepsis. Statistical analyses were performed to ascertain risk factors associated with the development of sepsis. 24,257 patients who underwent flap reconstruction were included in this study. Of these, 511 developed sepsis postoperatively (2.1%). Multivariate analysis showed that male gender (p