Immune-related transcriptomic and epigenetic reconfiguration in BV2 cells after lipopolysaccharide exposure: an in vitro omics integrative study.

BACKGROUND: Molecular alterations affecting microglia have been consistently associated with the inflammatory response. These cells can have pro- or anti-inflammatory activity, phenotypes thought to be regulated by epigenetic mechanisms. Still, little is known about the details on how epigenetic marks regulate the expression of genes in the context of an inflammatory response. METHODS: Through CUT&RUN, we profiled four genome-wide histone marks (HM) (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in lipopolysaccharide-exposed cells and compared their distributions to control cells. Transcriptomic profiles were determined through RNA-seq and differentially expressed genes were identified and contrasted with the epigenetic landscapes. Other downstream analyses were also included in this study. RESULTS: Our results illustrate an effectively induced M1 phenotype in microglial cells derived from LPS exposure. We observed differential bound regions associated with the genes classically involved in the inflammatory response in the expected direction according to each histone modification. Consistently, our transcriptomic analysis yielded a conspicuous illustration of the LPS-induced immune activity showing the up-regulation of Nf-κB-induced mRNAs (TNF-α, nfκbiz, nfκbia) and other important genes (Marco, Il-6, etc.). Furthermore, we integrated both omics profiles and identified an important reconfiguration of the genome induced by LPS. The latter was depicted by 8 different chromatin states that changed between conditions and that associated with unique clusters of differentially expressed genes, which not only represented regulatory elements, but also underlined distinct biological functions (inhibition of morphogenesis; changes in metabolism, homeostasis, and cytokine regulation; activation of the inflammatory response). CONCLUSION: This study exhibits important differences in the distribution of histone modifications in treated and control BV2 cells, constituting an epigenetic reconfiguration that leads to the inflammatory response. Also, it highlights the importance of these marks' regulatory role in gene expression and provides possible targets for further studies in the context of inflammation.

Transcriptional dissection of symptomatic profiles across the brain of men and women with depression.

Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the associations between these structures and the expression of MDD remain highly sex specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes were also identified. Together, our findings suggest that the expression of distinct MDD symptom domains associates with sex-specific transcriptional structures across brain regions.

Transcriptional dissection of symptomatic profiles across the brain of men and women with depression.

Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains in males and females remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the association between these structures and the expression of MDD remains highly sex-specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes, and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes was also identified. Together, our findings suggest that the expression of distinct MDD symptom domains is associated with sex-specific transcriptional structures across brain regions.

Sex-Specific Retinal Anomalies Induced by Chronic Social Defeat Stress in Mice.

Major depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop the disease. Recently, the retina emerged as an effective way to investigate psychiatric disorders using the electroretinogram (ERG). In this study, cone and rod ERGs were performed in male and female C57BL/6 mice before and after chronic social defeat stress (CSDS). Mice were then divided as susceptible or resilient to stress. Our results suggest that CSDS reduces the amplitude of both oscillatory potentials and a-waves in the rods of resilient but not susceptible males. Similar effects were revealed following the analysis of the cone b-waves, which were faster after CSDS in resilient mice specifically. In females, rod ERGs revealed age-related changes with no change in cone ERGs. Finally, our analysis suggests that baseline ERG can predict with an efficacy up to 71% the expression of susceptibility and resilience before stress exposition in males and females. Overall, our findings suggest that retinal activity is a valid biomarker of stress response that could potentially serve as a tool to predict whether males and females will become susceptible or resilient when facing CSDS.

Application of community-based nutrition education needs assessment in reviewing the course plan of medical and nursing students.

Background: Training needs assessment is the process of recognizing educational needs. This study aimed to apply a community-based nutrition education needs assessment to revise the nutrition course plan in the curriculum of the doctorate of medicine and that of the baccalaureate of nursing. Methods: The study was designed in 2 phases: (1) nutritional needs assessment; (2) community-based revision of nutrition course plan. In the first phase, 13 nutrition professionals working in the region set out 5 priorities of nutrition-related health problems in the community by a training need assessment based on a survey and scoring system. Then, an expert panel determined the priorities of behavioral and nonbehavioral causes of the nutrition-related health problems by the nominal group technique (NGT). The results of the first phase were used to review the topics of nutrition course plans up to 20%. Results: The priorities identified in Abadan, Khorramshahr, and Shadegan were obesity and type 2 diabetes mellitus in adults as well as anemia in pregnant women, respectively. Also, wrong eating habits and insufficient nutrition knowledge were among the most important behavioral causes of nutrition-related health problems in the target community. These results were applied to a community-based review of nutrition course plans for medical and nursing students. Conclusion: The use of nutritional needs assessment approaches by a survey and nominal group technique with a group of professionals provided an opportunity for a community-based review of the nutrition course plan for medical and nursing students as a first phase in the development of a community-based nutrition course plane.

Evaluating the effect of Coriandrum sativum syrup on being migraine-free using mixture models.

Background: Coriandrum sativum (coriander) is prescribed as a treatment for headache in traditional Persian medicine. Several investigations have been carried out to find the medicinal properties of this plant. However, no study has evaluated the effectiveness of this plant on becoming migraine-free. Methods: Sixty-eight migraineurs were randomly allocated to two equal groups of intervention and control . Each received 500 mg of sodium valproate in addition to 15 mL of coriander or placebo syrup three times a day. We followed subjects and recorded their migraine duration in the 1st, 2nd, 3rd, and 4th weeks. We applied an appropriate statistical model so as to consider special features of the data, which led to more accurate results using SAS 9.4 Results: Our findings showed that the probability of being migraine-free was not only considerably higher in final weeks of the study (p<0.001) in all patients of the intervention group than placebo group, but it was also significantly higher in patients less than 30 years of age compared to patients older than 30 years old. Migraine duration in migraineurs using coriander syrup reduced considerably during the study (p<0.001). Conclusion: The finding of this study revealed that coriander has a significant effect both on the probability of being migraine free and the duration of migraine attacks. Its effects were more significant during the final weeks of study.

Determinants of nutritional knowledge, attitude, and practice among southwestern Iranian households: A community-based study.

BACKGROUND: Malnutrition is generally due to a lack of nutritional information rather than food deficiency. Therefore, the current knowledge, attitudes, and practice (KAP) of the target audience should be evaluated to eliminate malnutrition. However, KAP varies across demographic status and socioeconomic status (SES). AIM: The associations of nutritional KAP with demographic and socioeconomic variables were evaluated among households living in urban and rural areas of southwestern Iran. METHODS: A cross-sectional, population-based study was conducted on 842 household heads (492 urban and 350 rural) using a standardized NUTRIKAP Household Questionnaire. The data evaluating nutritional KAP as well as demographic and socioeconomic information were obtained using a multi-stage cluster sampling method. SES score was also computed. RESULTS: Urban households had a higher level of nutritional knowledge (p < 0.05) but a lower level of nutritional attitude (p < 0.001) and practice (p < 0.001) compared with the rural ones. Rural households with the poorest quintiles of SES were 0.4 times less likely to have good nutritional knowledge (adjusted odds ratio = 0.4, confidence interval: 0.2, 0.9; p < 0.05), compared with higher quintiles. Households with an over-60-years-old household head had significantly higher nutritional attitude (p < 0.05) and practice (p <0.01) scores than households with younger ones. Households with male household heads had a higher nutritional practice score compared with households with female ones. CONCLUSIONS: These results can indicate the role of demographic and socioeconomic determinants in KAP of Iranian households towards the principle of nutrition and can be effective in prioritizing the implementation of nutritional interventions including nutrition education for them.

Global and Regional Trends of Multiple Sclerosis Disability-Adjusted Life Years Rates: A 25-Year Assessment.

BACKGROUND: Multiple sclerosis (MS) burden of disease has been described by reporting the disability-adjusted life years (DALY) index. So far, no study has assessed the trend of MS DALY rates over time. METHOD: Age-standardized MS DALY rates for both sexes were reported every 5 years from 1990 to 2015 in 195 countries in the Global Burden of Disease Database (GBD) database. To assess the MS DALY rates' trends in each super region and throughout the world, we applied the Latent Growth Models. We also utilized the linear mixed model to evaluate the effect of development factor on MS DALY rates. RESULTS: Our results showed that 5 out of 7 GBD super regions had negative trends in MS DALY rates during these years and the remaining 2 - Latin America and the Caribbean (slope = 0.196, p < 0.05) and South Asia - slope = 0.057, p > 0.05 - had upward trends. Using a linear mixed model, we found that the mean difference of MS DALY rates was about 25 DALYs higher in developed countries compared to developing ones (p < 0.0001). CONCLUSION: In general, our findings revealed a global downward trend in the MS DALY rate. We also conclude that MS DALY rates are decreasing both in developed and developing countries, with a steeper slope in the developed world.

A placebo-controlled clinical trial to evaluate the effectiveness of massaging on infantile colic using a random-effects joint model.

BACKGROUND: Infantile colic viewed as a non-dangerous prevalent issue could lead to stress in parents and long-term negative consequences in ex-colicky children. Researchers have not been successful in finding a certain treatment for colic symptoms. Studies suggest completely different approaches as its treatment. Massage therapy as an alternative method in reducing colic symptoms has been recommended in several studies. METHODS: A total of 100 colicky infants in a single blind study were randomly specified to two equal groups of intervention and control. Infants in the intervention group received massage for 15-20 minutes once during the day and once at night before sleep, while infants in the control group were rocked for 15-25 minutes when the symptoms of colic appeared. Parents recorded the details of the colic symptoms in a diary every day. All these outcomes were modeled simultaneously via a random-effects joint model. RESULTS: Among 100 infants included in the analysis, 48% were female; 91% of all infants were breastfed and 54% of them were born via normal vaginal delivery. In general, the effect of massage therapy on colic symptoms was assessed using the joint model. Our findings illustrated that massaging colicky infants would substantially reduce colic symptoms and increase the sleep duration in babies compared with the rocking group (P<0.001). CONCLUSION: Massage therapy could be considered as an effective method in reducing colic symptoms. Mean of the symptoms dropped significantly in the intervention group compared with that in the rocking group. Our study also represents that a relevant and correct statistical model could result in more reliable findings.

High frequency of methicillin-resistant Staphylococcus aureus (MRSA) with SCCmec type III and spa type t030 in Karaj's teaching hospitals, Iran.

Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the most important antibiotic-resistant pathogen in many parts of the world over the past decades. This cross-sectional study was conducted to investigate MRSA isolated between July 2013 and July 2014 in Karaj, Iran. All tested isolates were collected in teaching hospitals from personnel, patients, and surfaces and each MRSA was analyzed by SCCmec and spa typing. Antibiotic susceptibility testing was accomplished by disk diffusion method. Out of 49 MRSA isolates from the Karaj's teaching hospitals, 82%, 10%, and 6% of the isolates were SCCmec types III, II, and I, respectively. The main spa type in this study was spa t030 with frequency as high as 75.5% from intensive care unit (ICU) of the hospitals and high rate of resistance to rifampicin (53%) was found in MRSA isolates. In conclusion, high frequency of spa t030 with SCCmec type III and MRSA phenotype illustrated circulating of one of the antibiotic-resistant strains in ICU of Karaj's teaching hospitals and emphasizes the need for ongoing molecular surveillance, antibiotic susceptibility monitoring, and infection control.

High prevalence of plasmid-mediated quinolone resistance determinants in Enterobacter cloacae isolated from hospitals of the Qazvin, Alborz, and Tehran provinces, Iran.

INTRODUCTION: Plasmid-mediated quinolone resistance (PMQR) is a growing clinical concern worldwide. The main aims of this study were to detect qnr-encoding genes and to evaluate the clonal relatedness of qnr-positive Enterobacter cloacae isolates. METHODS: A total of 116 E. cloacae isolates that were not susceptible to quinolone were obtained from seven hospitals in Tehran, five hospitals in Qazvin, and two hospitals in Karaj (Iran). Bacterial identification was performed using standard laboratory methods and API 20E strips. Quinolone resistance was determined using the Kirby-Bauer disk diffusion method according to the Clinical Laboratory Standards Institute (CLSI) guidelines. PCR and sequencing were employed to detect qnrA, qnrB, and qnrS genes, and clonal relatedness was assessed using the enterobacterial repetitive intergenic consensus (ERIC)-PCR method. RESULTS: In total, 45 (38.8%) and 71 (61.2%) of isolates showed high- and low-level quinolone resistance, respectively, and qnr-encoding genes were detected in 70 (60.3%) of them. qnrB1 [45 (38.8%) isolates] was the most commonly detected gene, followed by qnrS1 [28 (24.1%) isolates] and qnrB4 [18 (15.5%) isolates] either alone or in combination with other genes. The results of the ERIC-PCR revealed that 53 (75.7%) qnr-positive isolates were genetically unrelated. CONCLUSIONS: This study describes, for the first time, the high prevalence of the qnrB1, qnrS1, and qnrB4 genes among E. cloacae isolates in Iran. The detection of qnr genes emphasizes the need for establishing tactful policies associated with infection control measures in hospital settings in Iran.

High prevalence of plasmid-mediated quinolone resistance determinants in Enterobacter cloacae isolated from hospitals of the Qazvin, Alborz, and Tehran provinces, Iran

Abstract: INTRODUCTION: Plasmid-mediated quinolone resistance (PMQR) is a growing clinical concern worldwide. The main aims of this study were to detect qnr-encoding genes and to evaluate the clonal relatedness of qnr-positive Enterobacter cloacae isolates. METHODS: A total of 116 E. cloacae isolates that were not susceptible to quinolone were obtained from seven hospitals in Tehran, five hospitals in Qazvin, and two hospitals in Karaj (Iran). Bacterial identification was performed using standard laboratory methods and API 20E strips. Quinolone resistance was determined using the Kirby-Bauer disk diffusion method according to the Clinical Laboratory Standards Institute (CLSI) guidelines. PCR and sequencing were employed to detect qnrA, qnrB, and qnrS genes, and clonal relatedness was assessed using the enterobacterial repetitive intergenic consensus (ERIC)-PCR method. RESULTS: In total, 45 (38.8%) and 71 (61.2%) of isolates showed high- and low-level quinolone resistance, respectively, and qnr-encoding genes were detected in 70 (60.3%) of them. qnrB1 [45 (38.8%) isolates] was the most commonly detected gene, followed by qnrS1 [28 (24.1%) isolates] and qnrB4 [18 (15.5%) isolates] either alone or in combination with other genes. The results of the ERIC-PCR revealed that 53 (75.7%) qnr-positive isolates were genetically unrelated. CONCLUSIONS: This study describes, for the first time, the high prevalence of the qnrB1, qnrS1, and qnrB4 genes among E. cloacae isolates in Iran. The detection of qnr genes emphasizes the need for establishing tactful policies associated with infection control measures in hospital settings in Iran.

Factors influencing left ventricular hypertrophy in children and adolescents with or without family history of premature myocardial infarction.

BACKGROUND: Cardiovascular diseases are the highest ranking cause of mortality. The prevalence of cardiovascular diseases is increasing among people in developed and developing countries. Since left ventricular hypertrophy is one of the risk factors leading to extremely dangerous heart diseases and even sudden death at early ages, investigating its contributing factors can be beneficial. The purpose of this study was to determine factors contributing to left ventricular hypertrophy in students aged 7-18 years in Isfahan. Statistical population of this case-control study was the 7-18 year old students in Isfahan, who were studied in two groups of children with premature myocardial infarction in their parents and the control group. MATERIALS AND METHODS: After determining the sample size of 138 people, a two-part questionnaire was designed and demographic characteristics and anthropometric measures were recorded in students' profiles. The obtained information was analyzed using SPSS15 software and logistic regression model and the results were reported at P < 0.05. RESULT: The results showed that among the studied variables, gender, age, body mass index, and blood pressure were associated with the left ventricular hypertrophy. CONCLUSION: Considering the results and previous studies in this field, it was observed that left ventricular hypertrophy exists at early ages, which is very dangerous and can lead to heart diseases at early ages. Factors such as being overweight, having high blood pressure, and being male cause left ventricular hypertrophy and lead to undiagnosable heart diseases.

Barriers to Physical Activity in a Population-based Sample of Children and Adolescents in Isfahan, Iran.

OBJECTIVES: This study was conducted to explore the barriers to physical activity in a representative sample of Iranian children and adolescents. METHODS: The study was conducted in 2007 in urban and rural areas of Isfahan district in Iran. In the qualitative part, we used the grounded theory approach, including semi-structured focus group discussions and indepth interviews. The quantitative part comprised 600 randomly selected students. RESULTS: The qualitative study included 34 school students (16 girls), 20 parents (11 mothers) and 11 school staff. All students disclosed that studying was a priority. They pointed to lack of safe and easy-access place for physical activity and unsupportive family as the main barriers. Lack of self-confidence and low selfworth were the two other concepts developed in this context. Parents pointed to lack of safe and easy-access place for activity followed by the priority of studying. The concepts derived from interviews with school staff included unhealthy modeling of parents, priority of studying, and inadequate public knowledge about how to integrate physical activity in routine daily life. The quantitative survey comprised 600 students including 286 (47.8%) girls. Parents' education level had inverse association with children's physical activity level. Significant inverse associations of self-efficacy and physical activity levels were documented. CONCLUSIONS: Increasing the public knowledge about adopting physical activity habits in routine daily life, informing the families and students about the benefits of physical activity to improve learning, as well as providing safe places such as using the school facilities in non-school hours should be considered in planning effective preventive strategies and interventions.