Multivariate Longitudinal Assessment of Kidney Function Outcomes on Graft Survival after Kidney Transplantation Using Multivariate Joint Modeling Approach: A Retrospective Cohort Study.

Background: The performance of a transplanted kidney is evaluated by monitoring variations in the value of the most important markers. These markers are measured longitudinally, and their variation is influenced by other factors. The simultaneous use of these markers increases the predictive power of the analytical model. This study aimed to determine the simultaneous longitudinal effect of serum creatinine and blood urea nitrogen (BUN) markers, and other risk factors on allograft survival after kidney transplantation. Methods: In a retrospective cohort study, the medical records of 731 renal transplant patients, dated July 2000 to December 2013, from various transplant centers in Mashhad (Iran) were examined. Univariate and multivariate joint models of longitudinal and survival data were used, and the results from both models were compared. The R package joineRML was used to implement joint models. P values <0.05 were considered statistically significant. Results: Results of the multivariate model showed that allograft rejection occurred more frequently in patients with elevated BUN levels (HR=1.68, 95% CI: 1.24-2.27). In contrast, despite a positive correlation between serum creatinine and allograft rejection (HR=1.49, 95% CI: 0.99-2.22), this relationship was not statistically significant. Conclusion: Results of the multivariate model showed that longitudinal measurements of BUN marker play a more important role in the investigation of the allograft rejection.

First seroepidemiological investigation of human enterovirus 71 in Iran.

BACKGROUND AND OBJECTIVES: Human Enterovirus 71 (EV-A71) is the causative agent for many dermal to neurological diseases especially polio-like paralysis outbreaks around the world. This study, the first of this kind in Iran, aimed to find neutralizing antibodies against EV-A71 in serum of healthy individuals in different age groups based on neutralization test (NT). MATERIALS AND METHODS: In this cross-sectional study, 547 serum samples were collected from healthy individuals who were referring for routine checkup tests (aged from under 6 months to over 31 years old) to Imam-Khomeini Hospital in Tehran during January-December 2015. Serum samples were examined by NT in cell culture to detect neutralizing antibodies against EV-A71. In the next step, some of the positive samples were subjected to complete titration to determine the exact titer of anti-EV-A71 antibodies. RESULTS: Of 547 samples, 310 (56.7%) were positive for EV-A71 neutralizing antibody. The presence of the antibody increased with age (p<0.001), and there was a significant statistical relationship between sex and the presence of antibody (p=0.009). CONCLUSION: Our results demonstrated an apparent but limited circulation of EV-A71 in our society. After the worldwide eradication of poliovirus, EV-A71 which can cause polio-likes syndrome, might be the new challenge for our health care system as regard more in depth research is however needed.

Evaluation of Growth Differentiation Factor-15 in Patients with or without Coronary Artery Disease.

BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor-beta cytokine superfamily expressed in human atherosclerotic plaque macrophages. In this study, we sought to compare GDF-15 between patients with coronary artery disease and control group. METHODS: In this cross-sectional study, 176 subjects were enrolled, consisted of 88 coronary artery disease patients (CAD group) and 88 non-CAD participants (control group. Clinical and demographic data, comprising of family history of CAD, history, and lifestyle factors, hypertension, diabetes, and some blood parameters (e.g. glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)), triglyceride, high-sensitivity C-reactive protein (hs-CRP)). RESULTS: Mean age of the patients was 55.5±11.1 years (age range: 28-80 years). Of all the participants, 91 (51.7%) were male and 85 (48.3%) female. Hs-CRP, LDL-C, and GDF-15 levels were significantly higher in the CAD patients (P=0.091, P=0.008, and P<0.001, respectively). Total cholesterol, hematocrit, and hemoglobin were significantly higher in the controls (P=0.002, P=0.011, and P=0.055, respectively). The area under the receiver operating characteristic curve yielded the satisfactory result of 0.9 (95% CI, 0.8-0.9; P<0.001). The optimum cut-off value of GDF-15 was 1233 ng/L with 71% specificity and 71% sensitivity for CAD diagnosis. CONCLUSION: These data suggest that serum GDF-15 might be useful in prediction of CAD.

Factors Affecting the Long-Term Survival of Kidney Transplantation in Northeastern of Iran between 2000 and 2015.

BACKGROUND: Graft and patient survival are of great importance after transplantation. This study aimed to determine the long-term survival rate of kidney transplantation and its effective factors among transplanted patients in Mashhad transplantation centers in northeastern Iran. METHODS: Overall, 618 kidney transplant recipients were examined in different transplantation centers during the years from 2000 to 2015 in a historical cohort study. The Kaplan-Meier method and the Log-rank test were used to calculate the survival rate of the kidney transplant, and to check the difference between survival curves respectively. Modeling of effective factors in survival rate was performed using Cox regression model. RESULTS: Overall, 1, 3, 5, 7, 10, and 15-year survival rate of kidney transplantation were 99%, 98%, 97%, 93%, 88 and 70% respectively. The adjusted hazard ratio indicated that variables such as recipient age >40 yr [HR=0.22, 95% CI=(0.071,0.691)], serum creatinine after transplantation >1.6 Mg/dl [HR=3.03, 95% CI=(1.284,7.125)], history of hypertension [HR=6.70, 95% CI=(2.746,16.348)], and BMI [HR (normal weight versus underweight)=0.26, 95% CI=(0.088,0.761), HR (over weight versus underweight)=0.13,95% CI=(0.038,0.442)] were significant factors on kidney transplant survival rate. CONCLUSION: The short-term transplant survival rate was good in transplant patients. What's more, through a consideration of variables such as age, creatinine serum after transplantation, history hypertension and body mass index, as well as proper planning to control their effect, it is possible to improve the long-term graft survival rate.

Correction to: Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts.

In the original publication, seventh author's name was incorrectly published as 'Maryam Golaram'.

Enteroviruses and Adenoviruses in stool specimens of paralytic children- can they be the cause of paralysis?

BACKGROUND AND OBJECTIVES: Acute flaccid paralysis (AFP) is a complicated clinical syndrome with a wide range of potential etiologies. Several infectious agents including different virus families have been isolated from AFP cases. In most surveys, Non-polio Enteroviruses (NPEVs) have been detected as main infectious agents in AFP cases; however, there are also some reports about Adenovirus isolation in these patients. In this study, NPEVs and Adenoviruses in stool specimens of AFP cases with or without Residual Paralysis (RP) with negative results for poliovirus are investigated. MATERIALS AND METHODS: Nucleic acid extractions from 55 AFP cases were examined by nested PCR or semi-nested PCR with specific primers to identify NPEVs or Adenoviruses, respectively. VP1 (for Enteroviruses) and hexon (for Adenoviruses) gene amplification products were sequenced and compared with available sequences in the GenBank. RESULTS: From 55 fecal (37 RP+ and 18 RP-) specimens, 7 NPEVs (12.7%) (2 cases in RP+) and 7 Adenoviruses (12.7%) (4 cases in RP+) were identified. Echovirus types 3, 17 and 30, Coxsackie virus A8, and Enterovirus 80 were among NPEVs and Adenoviruses type 2 and 41 were also identified. CONCLUSION: Our finding shows that NPEVs and Adenoviruses may be isolated from the acute flaccid paralyses but there is no association between the residual paralyses and virus detection.

Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant / Avaliação da potência terapêutica da vacina de DNA do papilomavírus humano-16 E7 isolada e com interleucina-18 como adjuvante genético

AIMS: Despite the existence of effective preventive vaccines for human papillomavirus (HPV), therapeutic vaccines that trigger cell-mediated immune responses are required to treat established infections and malignancies. The aim of this study was to evaluate the therapeutic potency of HPV-16 E7 deoxyribonucleic acid (DNA) vaccine alone and with interleukin (IL)-18. METHODS: In vitro expressions of IL-18 were performed on human embryonic kidney 293 cells and confirmed it by Western blotting methods. DNA vaccine was available from a previous study. A total of 45 female C57BL/6 mice divided into five groups (DNA vaccine, DNA vaccine adjuvanted with IL-18, pcDNA3.1, and phosphate buffer saline) were inoculated with murine tissue culture-1 cell line of HPV related carcinoma, expressing HPV-16 E6/E7 antigens. They were then immunized subcutaneously twice at a seven-day interval. The antitumor and antigen specific-cellular immunity were assessed by lymphocyte proliferation (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide: MTT) assay, lactate dehydrogenase release assay, IL-4 assay and interferon-gamma (IFN-γ) assay. Tumor size was followed for 62 days. RESULTS: MTT assay, which measures the lymphocyte proliferation in response to the specific antigen, increased in the co-administration and the DNA vaccine groups as compared to control and genetic adjuvant groups (p<0.001). The mice immunized with the co-administration generated significantly more IFN-γ and IL-4 than other immunized mice (p<0.001). Reduction of the tumor size in the co-administration and the DNA vaccine groups was significantly more pronounced than in the control and genetic adjuvant groups (p<0.001), but no statistically significant difference between DNA vaccine and co-administration groups (p=0.15) occurred. CONCLUSIONS: IL-18 as a genetic adjuvant and E7 DNA vaccine alone enhanced immune responses in mouse model systems against cervical cancer. However, using of IL-18 as a genetic adjuvant with E7 DNA vaccine had no significant synergistic effect on the immune responses in vivo.

OBJETIVOS: Apesar da existência de vacinas preventivas eficazes contra o papilomavírus humano (HPV), são necessárias vacinas terapêuticas que desencadeiem respostas imunes mediadas por células para tratar infecções e malignidades estabelecidas. O objetivo deste estudo foi avaliar a potência terapêutica da vacina de ácido desoxirribonucleico (DNA) HPV-16 E7 isolada e com interleucina (IL)-18. MÉTODOS: Expressões in vitro de IL-18 foram realizadas em células renais embrionárias humanas 293 e confirmadas por Western blotting. A vacina de DNA foi disponibilizada em um estudo anterior. Um total de 45 camundongos fêmeas C57BL/6 divididos em cinco grupos (vacina de DNA, vacina de DNA adjuvada com IL-18, pcDNA3.1 e solução salina tamponada com fosfato) e foram inoculados com linhagem murina-1 de carcinoma relacionado ao HPV, expressando antígenos E6 / E7 do HPV-16. Os animais foram então imunizados por via subcutânea duas vezes no intervalo de sete dias. A imunidade antitumoral e antígeno-celular específica foi avaliada pela proliferação de linfócitos (ensaio de brometo de 3- [4,5-dimetiltiazol-2-il] -2,5-difeniltetrazólio: MTT), ensaio de liberação de lactato desidrogenase, ensaio de IL-4 e ensaio de interferon-gama [IFN-γ]. O tamanho do tumor foi seguido por 62 dias. RESULTADOS: O ensaio MTT, que mede a proliferação de linfócitos em resposta ao antígeno específico, aumentou nos grupos de coadministração e de vacina de DNA em comparação aos grupos controle e adjuvante genético (p <0,001). Os camundongos imunizados com a coadministração geraram significativamente mais IFN-γ e IL-4 do que os outros camundongos imunizados (p<0,001). A redução do tamanho do tumor nos grupos de coadministração e de vacina de DNA foi significativamente mais acentuada do que nos grupos controle e adjuvante genético (p<0,001), mas não houve nenhuma diferença estatisticamente significativa entre os grupos vacina de DNA e coadministração (p=0,15). CONCLUSÕES: A IL-18 como adjuvante genético e a vacina de DNA E7 aumentaram as respostas imunes em sistemas modelo de camundongos contra o câncer cervical. No entanto, o uso de IL-18 como adjuvante genético com a vacina de DNA E7 não teve efeito sinérgico significativo nas respostas imunes in vivo.

The effects of water-pipe smoking on birth weight: a population-based prospective cohort study in southern Iran.

OBJECTIVES: Consecutive community health assessments revealed that water-pipe smoking in women and impaired growth in children were among the main health concerns in suburban communities in southern Iran. The aim of the present study was to identify the effects of water-pipe smoking during pregnancy on birth weight. METHODS: Data from a population-based prospective cohort study of 714 singleton live pregnancies in the suburbs of Bandar Abbas in southern Iran in 2016-2018 were used in this study. Data about water-pipe smoking patterns and birth weight were collected by questionnaires during and after the pregnancy. Low birth weight (LBW) was defined as a birth weight below 2,500 g. Statistical analyses were performed using generalized linear models, and the results were presented in terms of relative risk (RR) and 95% confidence intervals (CI). RESULTS: Fifty (8.2%) of the study subjects smoked water-pipe. The adjusted risk of LBW increased 2-fold in water-pipe smokers (adjusted RR [aRR], 2.09; 95% CI, 1.18 to 3.71), and by 2.0% for each 1-year increase in the duration of water-pipe smoking (aRR, 1.02; 95% CI, 0.99 to 1.05). CONCLUSIONS: Our results showed that water-pipe smoking during pregnancy was an important risk factor for LBW in this population sample from southern Iran. The introduction of regulations onto prevent water-pipe smoking and the implementation of community health action plans aiming at empowering women and increasing women's knowledge and awareness regarding the health consequences of water-pipe smoking are proposed.

Increased Urine Interleukin-17 and Interleukin-22 Levels in Patients With Candidal Urinary Tract Infection.

INTRODUCTION: Candiduria is common in the hospitalized patients. This study aimed to quantify interleukin (IL)-17 and IL-22 levels in urine of candiduric patients. MATERIALS AND METHODS: A case-control study was conducted on inpatients at Hashemi Nejad Kidney Center. Thirty-four patients were identified with Candida species in their urine samples (> 103 colony-forming units per milliliter and presence of Candida species only). Urine samples with concomitant infections were excluded. Thirty-four patients with negative direct examination and culture were included as the control patients. Interleulin-17 and IL-22 levels were measured in the lyophilized and nonlyophilized urine. The relevant cytokine titers of the two groups were compared, and the association of cytokine elevation and candiduria was investigated. RESULTS: The majority of the candiduric patients were from the intensive care and urology units of women. Only 4 patients (11.7%) manifested fever and dysuria. Massive leukocyturia was observed in 4 patients. Candida glabrata was the most commonly isolated species (44%). Levels of the urine IL-17 and IL-22 were significantly elevated in the candiduric patients, when compared to the noncandiduric controls. While an increased IL-17 level was significantly associated with candiduria (odds ratio, 1.09; 95% confidence interval, 1.003 to 1.17; P = .04), an increased IL-22 level was not. The results showed that lyophilized urine samples maximized the detection power of urinary cytokines. CONCLUSIONS: Our results indicated that direct examination, fungal urine culture, and investigation of urine IL-17 and IL-22 levels are useful tools for diagnosis of Candida urinary tract infection.

Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts.

Opioid system plays a significant role in pathophysiological processes, such as immune response and impacts on disease severity. Here, we investigated the effect of opioid system on the immunopathogenesis of respiratory syncytial virus (RSV) vaccine (FI-RSV)-mediated illness in a widely used mouse model. Female Balb/c mice were immunized at days 0 and 21 with FI-RSV (2 × 106 pfu, i.m.) and challenged with RSV-A2 (3 × 106 pfu, i.n.) at day 42. Nalmefene as a universal opioid receptors blocker administered at a dose of 1 mg/kg in combination with FI-RSV (FI-RSV + NL), and daily after live virus challenge (RSV + NL). Mice were sacrificed at day 5 after challenge and bronchoalveolar lavage (BAL) fluid and lungs were harvested to measure airway immune cells influx, T lymphocyte subtypes, cytokines/chemokines secretion, lung histopathology, and viral load. Administration of nalmefene in combination with FI-RSV (FI-RSV + NL-RSV) resulted in the reduction of the immune cells infiltration to the BAL fluid, the ratio of CD4/CD8 T lymphocyte, the level of IL-5, IL-10, MIP-1α, lung pathology, and restored weight loss after RSV infection. Blocking of opioid receptors during RSV infection in vaccinated mice (FI-RSV-RSV + NL) had no significant effects on RSV immunopathogenesis. Moreover, administration of nalmefene in combination with FI-RSV and blocking opioid receptors during RSV infection (FI-RSV + NL-RSV + NL) resulted in an increased influx of the immune cells to the BAL fluid, increases the level of IFN-γ, lung pathology, and weight loss in compared to control condition. Although nalmefene administration within FI-RSV vaccine decreases vaccine-enhanced infection during subsequent exposure to the virus, opioid receptor blocking during RSV infection aggravates the host inflammatory response to RSV infection. Thus, caution is required due to beneficial/harmful functions of opioid systems while targeting as potentially therapies.

Prevalence of sea, seb, sec, sed, and tsst-1 genes of Staphylococcus aureus in nasal carriage and their association with multiple sclerosis.

BACKGROUND: Microbial superantigens might initiate or exacerbate autoimmune responses against particular tissues, organs or systems. This study aimed to examine the prevalence of sea, seb, sec, sed, and tsst-1 genes of Staphylococcus aureus in nasal carriage and their association with multiple sclerosis (MS). METHODS: Nasal swabs were collected from 150 MS patients and 150 healthy individuals (control group) to isolate S. aureus and investigate their superantigen genes (sea, seb, sec, sed and tsst-1) using PCR. RESULTS: A total of 300 participants were enrolled in the study, matched for age and gender (150 patients in the MS group and 150 in the control group). The prevalence of S. aureus colonization in MS patients and control groups was 42% and 23.3%, respectively. There was a statistically significant association between S. aureus colonization and MS disease (p<0.001; odds ratio 2.4; 95% confidence interval 1.4-3.9). No significant association was observed between the presence of S. aureus harboring sea, seb, sec, sed and tsst-1 genes with MS disease. CONCLUSION: The rate of S. aureus nasal carriage is higher in patients with MS. Our study's results suggest that further investigation into whether there is a connection between MS and nasal exposure to staphylococcal superantigens is warranted.

The Relationship Between Professional Quality of Life and Caring Ability in Critical Care Nurses.

BACKGROUND: Critical care nursing has some features that may affect the ability of critical care nurses to provide care. Professionals as critical care nurses who deal with peoples' health and life often experience some levels of stress that affects their quality of life. OBJECTIVE: This study examined the relationship between professional quality of life and caring ability of critical care nurses. METHOD: In this descriptive correlational study, 253 critical care nurses working in the medical and surgical intensive care units of Tehran University of Medical Sciences were recruited by convenience sampling method. The data collection tools included demographic data form, Caring Ability Inventory, and questionnaire for professional quality of life version 5. RESULTS: There was a statistically significant positive relationship between the professional quality of life and the caring ability (P < .0001). A significant inverse relationship was found between burn-out subscale of compassion fatigue as one aspect of professional life quality with all 3 aspects of caring ability (knowledge, courage, and patience). Secondary traumatic stress, as another subscale of compassion fatigue (as one aspect of professional quality of life), had no statistically significant correlation with caring ability aspects of knowledge and patience. However, there was a significant inverse correlation between the secondary traumatic stress and courage aspect of caring ability (P < .0001). There was a statistically significant positive relationship between compassion satisfaction aspect of professional life quality with knowledge and patience aspects of caring ability, but there was not any relationship between the compassion satisfaction aspect of professional life quality and the courage aspect of caring ability. DISCUSSION: Improvement of critical care nurses' professional quality of life may increase their caring ability, thereby leading to better and more effective nursing care. Increased awareness by critical care nurse managers of the compassion fatigue phenomenon (secondary traumatic stress and burnout) and its effect on quality of critical care would be helpful in planning more specific strategies and preventing the onset and progression of these symptoms.

Genetic diversity and virulence genes of Salmonella enterica subspecies enterica serotype Enteritidis isolated from meats and eggs.

Salmonella enterica subspecies enterica serotype Enteritidis (S. Enteritidis) is one of the leading causes of food-borne gastroenteritis associated with the consumption of contaminated food products of animal origin. Little is known about the genetic diversity and virulence content of S. Enteritidis isolated from poultry meats and eggs in Iran. A total of 34 S. Enteritidis strains were collected from different food sources of animal origin in Tehran from May 2015 to July 2016. All of the S. Enteritidis strains were serotyped, antimicrobial susceptibility tested, and characterized for virulence genes. Pulsed-field gel electrophoresis (PFGE) was also applied for comparison of genetic relatedness. All of the strains harbored invA, hilA, ssrA, sefA, spvC, and sipA genes. A high prevalence of resistance against certain antibiotics such as cefuroxime (79.4%), nalidixic acid (47%), and ciprofloxacin (44.2%) was also observed. Regarding PFGE, S. Enteritidis strains from different sources showed considerable overlap, suggesting the lack of diversity among these isolates. Moreover, no correlation between virulence profiles or antibiotypes and PFGE clusters was observed. In conclusion, our study provided valuable information on virulence gene content, antibiotic resistance, and genetic diversity of S. Enteritidis isolated from food sources.

Evaluation of T Regulatory Lymphocytes Transcription Factors in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Patients.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4+CD25+ T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 (Foxp3), and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry. The demographic, history of disease, and severity of myelopathy were assessed by a checklist and the Osame motor disability score (OMDS). The mean OMDS for HAM/TSP was 4.82 ± 2.37 which had no significant correlation with Treg count or the expression of Foxp3, GITR, and PVL. The CD4+CD25+ cell counts had no significant differences between HAM/TSP and ACs. Findings revealed a higher PVL in HAM/TSPs (313.36 copies/104) compared to ACs (144.93 copies/104, p = 0.035). The Foxp3 and GITR mRNA levels were lower in HAM/TSP patients (11.78 and 13.80, respectively) than those in healthy carriers (18.44 and 21.00, p = 0.041 and 0.03, respectively). There was a significant correlation between Treg frequency and Foxp3 gene expression (R = 0.67, p = 0.006) and GITR and Foxp3 (R = 0.84, p = 0.042) in HAM/TSP patients. Furthermore, the transcription factors have strong correlations with CD4+CD25+ T cell frequencies. These findings suggest that HTLV-1 infection can modify the expression of main functional transcription factors, FOXP3 and GITR, which may lead to immune response deterioration of Tregs and consequently HAM/TSP manifestation.

Estimating the Transitional Probabilities of Smoking Stages with Cross-sectional Data and 10-Year Projection for Smoking Behavior in Iranian Adolescents.

BACKGROUND: Cigarette smoking is one of the most important health-related risk factors in terms of morbidity and mortality. In this study, we introduced a new method for deriving the transitional probabilities of smoking stages from a cross-sectional study and simulated a long-term smoking behavior for adolescents. METHODS: In this study in 2010, a total of 4853 high school students were randomly selected and were completed a self-administered questionnaire about cigarette smoking. We used smoothed age- and sex-specific prevalence of smoking stages in a probabilistic discrete event system for estimating of transitional probabilities. A nonhomogenous discrete time Markov chain analysis was used to model the progression of the smoking in 10 years ahead in the same population. The mean age of the students was 15.69 ± 0.73 years (range: 14-19). RESULTS: The smoothed prevalence proportion of current smoking varies between 3.58 and 26.14%. The age-adjusted odds of initiation in boys is 8.9 (95% confidence interval [CI]: 7.9-10.0) times of the odds of initiation of smoking in girls. Our study predicted that the prevalence proportion of current smokers increased from 7.55% in 2010 to 20.31% (95% CI: 19.44-21.37) for 2019. CONCLUSIONS: The present study showed a moderately but concerning prevalence of current smoking in Iranian adolescents and introduced a novel method for estimation of transitional probabilities from a cross-sectional study. The increasing trend of cigarette use among adolescents indicated the necessity of paying more attention to this group.

The Effect of Different microRNA Backbones on Artificial miRNA Expression and Knockdown Activity Against HIV-1 Replication.

BACKGROUND: Artificial microRNAs (miRNAs) are designed to develop an RNAi-based gene therapy. Recently, it has been suggested that the flanking sequences and terminal loop structure play a critical role in RNAi biogenesis and target recognition, but no extensive study regarding the different miRNA backbone for artificial miRNAs optimization has been conducted. OBJECTIVE: We tested three artificial miRNAs with human hsa-miR30a (common miRNA), hsa-miR150 (T cell specific miRNA), and hsa-miR122 (liver specific miRNA) backbones in HEK-293T and Jurkat cell lines. METHODS: Artificial miRNA processing and knockdown efficiency were analyzed by stem-loop RT-PCR, qRT-PCR, luciferase assay and target challenging. RESULTS: We identified strikingly different RNAi activities among these different artificial miRNAs. Our results demonstrated that expression and function of art-miR150 was more than art-miR30 and artmiR122 in both HEK-293T and Jurkat cell lines. Since the main difference in these artificial miRNAs was flanking sequences and terminal loop structure, the change between the expression and function of artificial miRNAs can be attributed to these structures. CONCLUSION: This study showed that expression of cell-specific artificial miRNA in target and nontarget cells is not different, but variation in flanking sequences and terminal loop can be involved in expression and function of artificial miRNAs. These results can be important for improving artificial miRNA design in RNAi-based gene therapy.

What Is the Best Parametric Survival Models for Analyzing Hemodialysis Data?

BACKGROUND: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are both common public health problems worldwide. Hemodialysis (HD) is one of the main ultimate modalities of renal replacement therapy in these patients. The aim of this study was to compare the different parametric (Weibull, Gamma, Gompertz, Log-logistic and Lognormal) survival models, in maintenance HD (MHD) patients. METHOD: This study was conducted from March 2004 to October 2013 and encompassed 544 ESRD patients under MHD in Hasheminejad Kidney Center, Tehran, Iran. Laboratory, clinical and demographic data were extracted from the Hemodialysis Data Processor Software, which had been designed for data collection in Hasheminejad Kidney Center. Exponential, Weibull, Gompertz, lognormal and log-logistic were used for analyzing survival of hemodialysis patient using STATA software. To compare these models Akaike Information criterion (AIC) and Cox-Snell residual were utilized. RESULTS: According to the both criteria (AIC and Cox-Snell residual), Weibull survival model manifested better results as compared with other models. According to this model, age at the time of admission (HR=1.015, p-value=0.018), walking ability (HR=0.656, p-value=0.010), diabetes mellitus as the underlying disease (HR=1.392, p-value=0.038), hemoglobin level (HR=0.790, p-value<0.001), serum creatinine (HR=0.803, p-value<0.001), serum protein (HR=0.747, p-value=0.010) and Single pool Kt/V(HR=0.092, p-value<0.001), had significant effect on survival of the hemodialysis patient. CONCLUSION: In our analysis Weibull distribution, which had the lowest AIC value, was selected as the most suitable model.

Causal Effect of Self-esteem on Cigarette Smoking Stages in Adolescents: Coarsened Exact Matching in a Longitudinal Study.

OBJECTIVES: Identification of the causal impact of self-esteem on smoking stages faces seemingly insurmountable problems in observational data, where self-esteem is not manipulable by the researcher and cannot be assigned randomly. The aim of this study was to find out if weaker self-esteem in adolescence is a risk factor of cigarette smoking in a longitudinal study in Iran. METHODS: In this longitudinal study, 4,853 students (14-18 years) completed a self-administered multiple-choice anonym questionnaire. The students were evaluated twice, 12 months apart. Students were matched based on coarsened exact matching on pretreatment variables, including age, gender, smoking stages at the first wave of study, socioeconomic status, general risk-taking behavior, having a smoker in the family, having a smoker friend, attitude toward smoking, and self-injury, to ensure statistically equivalent comparison groups. Self-esteem was measured using the Rosenberg 10-item questionnaire and were classified using a latent class analysis. After matching, the effect of self-esteem was evaluated using a multinomial logistic model. RESULTS: In the causal fitted model, for adolescents with weaker self-esteem relative to those with stronger self-esteem, the relative risk for experimenters and regular smokers relative to nonsmokers would be expected to increase by a factor of 2.2 (1.9-2.6) and 2.0 (1.5-2.6), respectively. CONCLUSION: Using a causal approach, our study indicates that low self-esteem is consistently associated with progression in cigarette smoking stages.

A Comparison between Accelerated Failure-time and Cox Proportional Hazard Models in Analyzing the Survival of Gastric Cancer Patients.

BACKGROUND: Gastric cancer is the one of the most prevalent reason of cancer-related death in the world. Survival of patients after surgery involves identifying risk factors. There are various models to detect the effect of risk factors on patients' survival. The present study aims at evaluating these models. METHODS: Data from 330 gastric cancer patients diagnosed at the Iran cancer institute during 1995-99 and followed up the end of 2011 were analyzed. The survival status of these patients in 2011 was determined by reopening the files as well as phone calls and the effect of various factors such as demographic, clinical, treatment, and post-surgical on patients' survival was studied. To compare various models of survival, Akaike Information Criterion and Cox-Snell Residuals were used. STATA 11 was used for data analyses. RESULTS: Based on Cox-Snell Residuals and Akaike Information Criterion, the exponential (AIC=969.14) and Gompertz (AIC=970.70) models were more efficient than other accelerated failure-time models. Results of Cox proportional hazard model as well as the analysis of accelerated failure-time models showed that variables such as age (at diagnosis), marital status, relapse, number of supplementary treatments, disease stage, and type of surgery were among factors affecting survival (P<0.05). CONCLUSION: Although most cancer researchers tend to use proportional hazard model, accelerated failure-time models in analogous conditions - as they do not require proportional hazards assumption and consider a parametric statistical distribution for survival time - will be credible alternatives to proportional hazard model.

The Effect of Time-to-Provider, Left-without-Treatment and Length-of-Stay on Patient Satisfaction in Training Hospitals' Emergency Department, Iran.

BACKGROUND: It is necessary to consider into hospital emergency services' quantity and quality in different aspects such as time-to-provider, left-without-treatment and length-of-stay. The aimof this research was to identify the effect of these factors on patient satisfaction in training hospitals. METHODS: In this descriptive-analytical and cross-sectional study, the sample size was calculated 768. The instrument included 54 questions and 8 sections. Three questions were in the field of following factors: 1) Time to provider was defined as the time from initial triage to initial provider evaluation. 2) Left-without-Treatment patients were defined as those who were initially triaged but were unable to be evaluated by a provider because they had left the ED. 3) Length-of-Stay was defined as time from initial triage to the time of final ED disposition, either discharge or admission. It was analyzed by descriptive statistics, simple logistic regression, multiple logistic regressions, simple linear regression and multiple linear regression. RESULTS: The time-to-provider lower than 15 minutes, LWOT and LOS lower than 6 hours were 92.8%, 3.9% and 90.3%, respectively. The mean of time-to-provider and the mean of LOS were 18.1 minutes and 202 minutes. Time-to-Provider affected satisfaction of admission, guardians, nursing care and managing proceedings (P<0.001). LOS affected satisfaction of admission, guardians and diagnosis proceedings (P<0.01). LWOT did not affect satisfaction and its domains (P>0.05). CONCLUSION: Decreasing time-to-provider and LOS has the effect on patient satisfaction in some domains. Furthermore, left-without-treatment rate is not a good proxy of patient satisfaction.