Diverse Expression Patterns of EBV Oncogenes (LMP2A, EBV-Encoded microRNA, and EBV-encoded dUTPase) in EBV Associated Gastric Carcinoma and their Association with Viral Loads.

The chromogenic in situ hybridization (CISH) test is the gold standard for detecting Epstein-Barr virus (EBV)-associated gastric carcinoma (GC). Real-time (RT) PCR method is also a sensitive test that can detect the viral load in samples. As such, three EBV oncogenes were investigated in this study. RNA extraction and cDNA synthesis were performed on GC tissues of nine patients, who were previously confirmed to have EBVGC subtype. In addition, 44 patients that had positive RT-PCR but negative CISH results were also included as the control group. TaqMan RT-PCR analysis was performed to determine the expression of EBV-encoded microRNAs, and the expression of EBV-encoded dUTPase, as well as LMP2A, was analyzed by SYBR Green RT-PCR. EBV-encoded microRNAs and LMP2A were identified in 2 out of 9 (22%) EBVGC subtypes. In addition, EBV-encoded dUTPase was detected in 4 out of 9 (44.5%) EBVGC subtypes. EBV-encoded dUTPase was also expressed in a sample of the control group. The expression of LMP2A, EBV-encoded microRNAs, and EBV-encoded dUTPase viral oncogenes in patients with high EBV viral loads indicates that these expressions correlate with viral loads. Our findings indicate that the EBV-encoded dUTPase gene may have a role in EBVGC patients' non-response to treatment and might be considered a Biomarker-targeted therapy.

Effect of a newly developed ready-to-use supplementary food on growth indicators in children with mild to moderate malnutrition.

OBJECTIVES: Malnutrition is one of the leading causes of death among children younger than five years. In this study, we aimed to formulate a ready-to-use supplementary food (RUSF), based on local food products, and investigate its efficacy on growth indicators in children with mild to moderate malnutrition. STUDY DESIGN: This is a randomized controlled clinical trial. METHODS: This study was performed in six health centers in Shahr-e-Rey, Tehran, Iran, between April and October 2017. One hundred children, aged 24-59 months, with mild to moderate malnutrition (weight-for-height Z-score [WHZ] between -3 and -1) were randomly assigned to two groups to receive either 1-3 sachets of RUSF or normal diet for 8 weeks. All mothers and caregivers received nutrition education. Growth indicators including weight and height, WHZ, and body mass index (BMI), along with clinical outcomes, were assessed. RESULTS: Children who received RUSF had a significant increase in weight (1.44 ± 0.38 vs 0.7 ± 0.32 kg, respectively, P < 0.001), and BMI (1.2 ± 0.47 vs 0.35 ± 0.33 kg/m2, respectively, P < 0.001) compared with the control group. There was a greater daily weight gain during the first 4 weeks (P < 0.001) and throughout the study (P = 0.013) in the RUSF group. Daily height gain was considerably higher in the RUSF group during the first 4 weeks (P = 0.027). Children in the RUSF group had more improvement in WHZ (1.18 ± 0.41 vs 0.41 ± 0.31, P < 0.001) after supplementation. Besides, 92% of the RUSF and 12% of the control group reached to WHZ > -1 at the end of the study (P < 0.001). There was lower prevalence of diarrhea (12% vs 28.6%, respectively, P = 0.01) and marginally lower fever (16% vs 36.7%, respectively, P = 0.05) in the intervention than in the control group. CONCLUSIONS: A newly developed RUSF improved growth indicators and clinical outcomes in children with mild to moderate malnutrition. CLINICAL TRIAL REGISTRY NUMBER: IRCT2017021315536N6 (registered at www.irct.ir).

Slanted versus Augmented Recession for Horizontal Strabismus.

PURPOSE: To compare the surgical outcomes of slanted versus augmented recession in patients with horizontal strabismus. METHODS: In this randomized clinical trial, a total of 100 esotropic (ET) and exotropic (XT) patients with a high AC/A ratio which was defined as a difference of ≥ 10 prism diopters (pd) between the distance and near deviations were included if the patients had a distance deviation ≥ 15 pd. Patients were randomly assigned into the slanted (n = 26 in ET and n = 24 in XT group) and augmented recession groups (n = 25 in ET and n = 25 in XT group). In the slanted group, recession was performed on the superior and inferior poles of the muscle based on the distance and near deviations, respectively, while in the augmented recession group, the muscles were recessed 1.00 or 1.50 mm more than the standard amount according to the distance and near difference between 10 and 20 pd or > 20 pd, respectively. RESULTS: The mean age was 9.8 ± 9.6 years and 63% were female. There was a significant postoperative reduction of difference in convergence excess in ET cases compared to patients who underwent the augmented recession procedure (12.65 ± 6.16 vs 8.64 ± 6.1 pd, P = 0.014). Among our XT groups, there was no significant difference in postoperative reduction in the XT angle in the slanted group compared with the augmented group (P > 0.05). CONCLUSION: Slanted recession is recommended in convergence excess ET patients. In XT patients, either slanted or augmented recession may be chosen according to the priority and experience of the surgeon.

Prevalence of tuberculosis treatment non-adherence in Ethiopia: a systematic review and meta-analysis.

Non-adherence to treatment is one of the challenges facing global tuberculosis (TB) control. In Ethiopia, an extremely variable and high magnitude of TB treatment non-adherence have been reported from different parts of the country. However, there has been no attempt to estimate the pooled prevalence of non-adherence from this heterogeneous data. To review the available literature and estimate the overall prevalence of treatment non-adherence among patients with TB on first-line treatment in Ethiopia. A systematic review and meta-analysis of published articles on TB treatment non-adherence. We included 26 studies, which contained data on 37 381 patients with TB. The crude prevalence of non-adherence reported by the studies included was extremely variable (range 0.2-35%). The overall pooled estimate of non-adherence prevalence was 10.0% (95%CI 8.0-11.0). The pooled prevalence of patients lost to follow-up alone was 5.0% (95%CI 4.0-6.0), while the pooled prevalence of intermittent non-adherence was 20.0% (95%CI 15.0-25.0). The rate of TB treatment non-adherence in Ethiopia remains too high to achieve target treatment success rates and prevent drug resistance. Implementing an effective patient retention scheme, along with the DOTS strategy, is critical to improving treatment adherence and preventing drug resistance. .

Pathogenicity locus determinants and toxinotyping of Clostridioides difficile isolates recovered from Iranian patients.

Little is known about the toxin profiles, toxinotypes and variations of toxin Clostridioides difficile C (tcdC) in Iranian C. difficile isolates. A total of 818 stool specimens were obtained from outpatients (n = 45) and hospitalized patients (n = 773) in Tehran, Iran, from 2011 to 2017. The 44 C. difficile isolates were subjected to PCR of toxin C. difficile A (tcdA), toxin C. difficile B (tcdB), tcdA 3'-end deletion, toxinotyping and sequencing of the tcdC gene. Thirty-eight isolates (86.36%) were identified as tcdA and tcdB positive, and the remaining six isolates (13.63%) were nontoxigenic. All tcdA- and tcdB-positive isolates yielded an amplicon of 2535 bp by PCR for the tcdA 3' end. Fourteen (36.84%), seventeen (44.73%) and seven (18.43%) isolates belonged to wild-type, toxin C. difficile C subclone3 (tcdC-sc3) and tcdC-A genotype of tcdC, respectively. Thirty-one isolates (81.57%) belonged to toxinotype 0, and seven isolates (18.42%) were classified as toxinotype V. This study provides evidence for the circulation of historical and hypervirulent isolates in the healthcare and community settings. Furthermore, it was also demonstrated that the tcdC-A genotype and toxinotype V are not uncommon among Iranian C. difficile isolates.

Highly antibiotic-resistant Clostridium difficile isolates from Iranian patients.

AIMS: Little is known about the resistance rate and susceptibility profile of Clostridium difficile isolates in Iran. Therefore, the aim of present study is to assess the rate of drug-resistant C. difficile. METHODS AND RESULTS: During a 6-year period, four hospitals submitted 735 stool specimens from patients suspected for C. difficile infections to the anaerobic bacteriology laboratory. The 46 C. difficile isolates were subjected to disc diffusion and minimum inhibitory concentration (MIC) Test Strips. All isolates were susceptible to vancomycin (VAN) while the highly resistant phenotypes of metronidazole (MTZ) (67·4%), moxifloxacin (78·3%), ciprofloxacin (69·5%) and tetracycline (82·6%) were observed. Of more concern, 67·3% of C. difficile isolates displayed multidrug-resistant phenotypes. More than half of the isolates (n = 27, 58·6%) were coresistant to ciprofloxacin and moxifloxacin. The MIC90 of VAN was ≤2 mg l-1 , whereas this value for MTZ, ciprofloxacin, moxifloxacin and tetracycline was higher than the resistance breakpoints. According to the comparison of interpretive categories for two tests, the categorical agreement was less than 90% for VAN, ciprofloxacin and tetracycline. CONCLUSIONS: The disc diffusion method can be used to detect the isolates with reduced susceptibility to MTZ or moxifloxacin. The high rate of resistance to fluoroquinolones highlights the possibility of the emergence of hypervirulent strains in our settings. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides data regarding the high level of resistance against multiple antibiotics except VAN.

Early versus late traumatic cataract surgery and intraocular lens implantation.

PurposeTo determine the proper time for traumatic cataract surgery after open globe injuries.SettingFarabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.DesignRandomized clinical trial.Patients and methodsIn a randomized clinical trial, 30 eyes with traumatic cataract after open globe injury with IOL implantation underwent early (in the first week after the trauma) and 30 eyes underwent late cataract surgery (from the first to second month after the trauma). We excluded patients who were under 12-year-old. All patients were visited at 1 week, 4 weeks, 12 weeks, and 6 months after surgery. In each visit, patients were examined regarding visual acuity, intraocular pressure (IOP), anterior chamber inflammation, IOL position, and posterior synechiae. In addition, posterior segment evaluation and fundoscopy were performed. Intraoperative complication including posterior capsular rupture, anterior vitrectomy, and zonulysis as well as the site of IOL implantation were documented and post-operative complications including raised IOP, anterior chamber inflammation, visual axis opacity, posterior synechiae, subluxation of IOL, and IOL pigment deposition were listed.ResultsBest-corrected visual acuity 6 months after surgery was not different between the two groups. Also in early cataract surgery group, the rate of posterior capsular rupture was not significantly higher than the late surgery group (P=0.069). On the other hand, zonulysis was significantly higher in the late procedure group (P=0.039). Other complications including anterior vitrectomy, raised IOP, anterior chamber inflammation, visual axis opacity, posterior synechiae, subluxation of IOL, and IOL pigment deposition were not different in the two groups.ConclusionsEarly and late traumatic cataract surgery and IOL implantation after open globe injuries, have no significant difference regarding the post-surgical BCVA and prominent intraoperative and post-operative complications.

Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with malignancy type in a spectrum of common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and melanoma

Purpose. Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis. Methods. We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples. Results. We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer. Conclusions. These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results (AU)

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An interactive web-based intervention on nutritional status, physical activity and health-related quality of life in patient with metabolic syndrome: a randomized-controlled trial (The Red Ruby Study).

BACKGROUND/OBJECTIVES: Physical inactivity and unhealthy nutritional behaviors are recognized as the key factors in the cause and management of metabolic syndrome (MetS). The effectiveness of interactive web-based interventions on dietary intakes, physical activity and health-related quality of life (HRQOL) among people with MetS is currently unknown. METHODS: The two-arm randomized-controlled trial was conducted for patients with MetS from June through December 2012 in Tehran, Iran. Participants (n=160) were recruited through online registration on the study website. After free clinical assessments of eligible participants for MetS, they were randomly assigned to intervention and control groups (n=80). All participants received general information about cardiovascular diseases and MetS risk factors via the website. The intervention group logged in to interactive part including My Healthy Heart Profile, received tailored calorie-restricted diet and used all parts of the interactive prevention program. Anthropometric measures, glycemic status, lipid profile, physical activity and food intake were evaluated at the beginning and after 6-month follow-up. HRQOL was assessed at beginning, 3- and 6-month follow-up. RESULTS: There were no significant differences between the intervention and control groups on age, gender, education and MetS factors. In comparison with control group, the intervention group showed significant changes in moderate physical activity 260.3±473.6 vs 101.6±213.1 MET-min/week, walking 505.2±505.3 vs 321±884 MET-min per week, cholesterol intake -88.4±158.7 vs -8.3±6 mg per day, total calories -430.2±957.5 vs -392.9±34.7 kcal per day and sodium 1336.9±2467 vs 1342±3200.4 mmol per day. With regard to HRQOL, the intervention group showed greater improvement in general health and vitality (P<0.05 for all). CONCLUSION: These results indicate the positive impact of a lifestyle intervention by a web-based program on physical activity, dietary intake and several dimension of QoL. The use of web-based approaches is a great interest to manage patients at high cardiovascular risk, especially where the prevalence of obesity, MetS and diabetes is increasing.

The impact of primer sets on detection of the gene encoding biofilm-associated protein (Bap) in Acinetobacter baumannii: in silico and in vitro analysis.

The Acinetobacter baumannii virulence protein Bap is encoded by a large gene and contains both variable sequence and repetitive modules. To date, four primer sets targeting different regions of bap have been designed, but no study has evaluated all these primers simultaneously for detection of bap. Here, we assessed the effect of primer sets Bap I-IV, on detection of bap both in silico and in vitro. Using the primer set Bap II, all 143 tested strains yielded an amplicon corresponding to the bap gene. This primer set showed the highest sensitivity (100, 95% CI: 97·9-100%) compared to the other primer sets. This study demonstrates that primer set Bap II performs with optimal efficiency for detection of the bap gene among different strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study investigated the effect of nucleotide variation on PCR detection of the bap gene in various Acinetobacter baumannii strains. Since bap is the target gene for many detection assays, this variation can affect the detection efficiency. Here we present a primer set Bap II with optimal detection efficiency amongst 143 different strains, as shown by in silico and in vitro evidence.

Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with malignancy type in a spectrum of common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and melanoma.

PURPOSE: Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis. METHODS: We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples. RESULTS: We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer. CONCLUSIONS: These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results.

Evaluation of Serum and Urinary Neopterin Levels as a Biomarker for Occupational Exposure to Crystalline Silica.

BACKGROUND: Crystalline silica is a commonly used mineral in various industries and construction activities, and it is so important introducing potential biomarkers to identify early indicators of biological effects in its high-risk occupational exposures. AIM: The present study was aimed to assess the blood and urinary neopterin as an early biomarker of exposure in the workers of an insulator manufacturing plant who are exposed to crystalline silica. SUBJECTS AND METHODS: This analytical descriptive study was done among two groups of exposed workers (n = 55) and unexposed office workers (n = 38) of an insulator manufacturing plant. Statistical software R was used to determine sample size and select the participants by random sampling among nonsmoker workers. Sampling of airborne silica in breathing zone of participants was done based on the National Institute for Occupational Safety and Health method 7601. The urinary and blood samples were collected and prepared for analysis by high-performance liquid chromatography to determine the level of urinary and serum neopterin. All of the statistical analyses were carried out using SPSS 22. RESULTS: The airborne silica concentration was significantly different between two exposed and unexposed groups (P < 0.001, 0.27 [0.11] vs. 0.0028 [0.0006] mg/m3, respectively). The urinary neopterin in exposed group is significantly higher than the unexposed one (P < 0.001, 97.67 [30.24] vs. 55.52 [2.18] µmol/mol creatinine, respectively). Neopterin level of serum in exposed group is higher than the unexposed group, and there is a significant difference between them (P < 0.001, 6.90 [2.70] vs. 2.20 [1.20] nmol/l, respectively). The positive significant correlations were found between silica exposure concentration with urinary and serum neopterin (P < 0.001, r = 0.36 and 0.59, respectively). CONCLUSIONS: Considering the sensitively and easily measurement of neopterin in biological fluid and also the statistically significant positive relationships which were found between the airborne silica concentration and neopterin levels in the present study, the serum and urinary neopterin levels can be considered the potential biomarkers of silica exposure for doing further comprehensive studies in this area.

Re-evaluation of the first phenytoin paste healing effects on oral biopsy ulcers.

BACKGROUND: Until now, several formulations of topical phenytoin have been used to promote wound healing. AIM: This study was aimed at re-evaluating the effects of a newly formulated phenytoin mucoadhesive paste on wound healing after oral biopsy. SUBJECTS AND METHODS: In a double-blind clinical trial, 35 consecutive patients with oral lichenoid or lichen planus lesions were randomized into two groups. After incisional biopsy, patients applied simple, or 1% phenytoin paste at least three times a day (after each meal), for 4 days. They were evaluated every other day for size of wound closure, severity of pain, and diameter of the inflammatory halo. This study was approved by Medical Ethics committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran. Statistical analysis was performed using Mann-Whitney U test and Ordinal Logistic Regression. RESULTS: Of 35 patients, 17 (10 [10/17, 59%]) men, 7 (7/17, 41%) women, mean age: 40 (4.11) were in phenytoin group, and 18 (9 [9/9, 50%]) men, 9 (9/9, 50%) women, mean age: 43.1 (5.15) were in placebo group. There were no significant differences between both study groups in terms of age and sex (male/female ratio) (P = 0.76, P = 0.88). As all biopsies were done by means of punch number 8, the incisions were of 10 mm length. After second and third appointments, it was observed that patients in the treatment group showed quicker wound closure and less pain compared to control group significantly (P < 0.05). Although not significant, patients treated with phenytoin paste had smaller inflammatory halo than controls. CONCLUSION: Applying 1% phenytoin mucoadhesive paste on oral biopsy incisions resulted in accelerated wound healing and decrease in pain.

Relation between serum ferritin and liver and heart MRI T2* in beta thalassaemia major patients.

There is a need for higly accurate non-invasive methods for assessing organ iron content in thalassaemia patients. This study evaluated the relation between serum ferritin level, liver enzyme levels and hepatitis C antibody and liver and heart iron deposition assessed by MRI T2*. Data were obtained from the medical records of 156 thalassemia major patients in Tehran. There was a moderate negative correlation between serum ferritin and liver MRI T2* relaxation time (r = -0.535) and a weak negative correlation between serum ferritin and heart MRI T2* relaxation time (r = -0.361). Hepatitis C infection and liver enzyme levels did not confound or modify the relation between ferritin and liver or heart MRI T2*. Liver and heart MRI T2* readings were poorly correlated (r = 0.281). Routine evaluation of liver and heart iron content using MRI T2* is suggested to better evaluate the haemosiderosis status in thalassemia patients.

Relation between serum ferritin and liver and heart MRI T2 in beta thalassaemia major patients

There is a need for higly accurate non-invasive methods for assessing organ iron content in thalassaemia patients. This study evaluated the relation between serum ferritin level, liver enzyme levels and hepatitis C antibody and liver and heart iron deposition assessed by MRI T2 Data were obtained from the medical records of 156 thalassemia major patients in Tehran. There was a moderate negative correlation between serum ferritin and liver MRI T2 relaxation time [r= -0.535] and a weak negative correlation between serum ferritin and heart MRI T2 relaxation time [r= -0.361]. Hepatitis C infection and liver enzyme levels did not confound or modify the relation between ferritin and liver or heart MRI T2. Liver and heart MRI T2* readings were poorly correlated [r= 0. 281]. Routine evaluation of liver and heart iron content using MRI T2 is suggested to better evaluate the haemosiderosis status in thalassemia patients