Socioeconomic inequality in screen time frequency in children and adolescents: the weight disorders survey of the CASPIAN IV study

Background

This study aimed to assess the socioeconomic inequality and determinants of screen time (ST) frequency in Iranian children and adolescents.

Methods

This nationwide study was conducted as part of a national school-based surveillance program among 36,486 students consisting of 50.79% boys and 74.23% urban inhabitants, aged 6–18 years, living in urban and rural areas of 30 provinces of Iran. Socioeconomic inequality in ST, including the time spent for ST, watching TV and leisure-time working with computer, was assessed across quintiles of SES using concentration index (C) and slope index of inequality (SII).

Results

Overall, 36,486 students completed the study (response rate 91.25%). Their mean (SD) age was 12.14 (3.36) years. The national estimation of frequency of ST was 31.66% (95% CI 31.16–32.17) with ascending change from 20.80% (95% CI 19.81–21.82) to 36.66% (95% CI 35.47–37.87) from the first to the last quintal of SES. Estimated C value at national level was positive (0.08), which indicate inequality was in favor of low SES groups. Considering the SII values, at national level [? 0.16 (? 0.39, 0.06)], the absolute difference in ST frequency between the bottom and top of the socioeconomic groups had descending trends. In multivariate logistic regression model, family history of obesity, generalized obesity and age were the main significant determinants of prolonged ST, watching TV, and computer working (P < 0.001).

Conclusions

Socioeconomic inequality in ST frequency was in favor of low SES groups. These findings are useful for health policies, better programming and future complementary analyses.

     

Rotavirus VP6 as a potential vaccine candidate

By the age of 5 years, virtually all children have been infected by group A rotavirus (RVA), which is responsible for around half million mortality annually prior to vaccination. Relatively high rate of the morbidity and mortality highlights the necessity of applying preventive procedures particularly in developing countries. Two live attenuated RVA vaccines (Rotarix and RotaTeq) are licensed and now being used in many countries worldwide. Although these vaccines are shown to reduce the mortality up to 50%, several key questions yet remained to answer. Indeed, the licensed RV vaccines were found to be less effective in countries of sub‐Saharan Africa and Southeast Asia. Therefore, developing next generation RVA vaccines is warranted. VP6 is highly abundant and conserved protein that forms the middle layer of RV particles and was shown to be both antigenic and immunogenic. Although it does not induce neutralizing antibodies, different VP6 preparations were found to induce homologous and cross‐reactive immune responses with partial protection from RVA replication. Although the molecular mechanisms are not fully elucidated, VP6‐based RVA vaccine candidates are worthy of further consideration. This review aims to focus on different aspects of VP6 protein and its potentiality for an alternative RV vaccine against RV disease.     

Investigation of the Lipid-Modifying and Antiinflammatory Effects of Cornus mas L. Supplementation on Dyslipidemic Children and Adolescents

Cornus mas L. (CM) fruits are rich in anthocyanins and possess both antiinflammatory and antioxidant activities. The current study was conducted to investigate whether supplementation with CM could ameliorate lipid profile and vascular inflammation in dyslipidemic children and adolescents. In this randomized clinical trial, 40 dyslipidemic children and adolescents ages 9 to 16 years were assigned to receive 50 g of CM twice a day after lunch and dinner (n = 20, case group) or to continue their normal diet (n = 20, control group). The serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apo A-I, apo B, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), C-reactive protein (CRP), and anthropometric indices were determined at baseline and then after weeks 3 and 6 of the trial. After week 6 of the trial, the TC, TG, LDL-C, apo B, ICAM-1, and VCAM-1 levels in the CM group were significantly lower and the HDL-C and apo A-I levels higher than at baseline. After week 6 of the trial, none of these parameters in the control group, except for ICAM-1, was significantly altered from baseline. However, between-group comparison showed a significant difference only for apo A-I (p = 0.016) and a borderline significant difference for ICAM-1 (p = 0.076). No significant difference in body mass index, waist-to-hip ratio, or C-reactive protein was observed between the studied groups. The present findings revealed a trend toward amelioration of lipid profile and vascular inflammation following addition of CM to the daily diet of dyslipidemic children and adolescents but this needs to be verified by larger scale trials.     

Anxiety and success of in vitro fertilization

Objective

To assess the effects of anxiety on pregnancy rate after in vitro fertilization (IVF).

Study design

This was a prospective study of 180 infertile women who were referred for IVF treatment to two selected infertility treatment centers in Tehran. They were recruited at the last visit before the procedure by quota sampling and their anxiety was assessed using the State and Trait Anxiety Inventory, following which they were categorized, based on their anxiety scores, to high and low anxiety groups. A positive pregnancy test was considered as the criterion of success of treatment. Data were analyzed using SPSS 17. Pregnancy rates in the low and high anxiety groups were compared using the Chi square test.

Results

Pregnancy rates in the groups with high and low levels of state anxiety were not significantly different (11.1 vs. 10.1 percent; X², p > 0.05); neither were these rates significantly different in groups with high and low levels of trait anxiety (14.5 vs. 9 percent; X², P > 0.05).

Conclusion

High or low levels of state or trait anxiety have no effect on the pregnancy rate after IVF treatment. Counseling is necessary, however, to decrease anxiety in infertile women to improve their quality of life.     

Therapeutic effects of calcium & vitamin D supplementation in women with PCOS

ObjectiveTo evaluate the efficacy of calcium &; vitamin D supplementation in infertile women suffering from polycystic ovary syndrome (PCOS), and to assess levels of 25-hydroxy vitamin D in these patients.MethodsIn a case control study, 100 infertile PCOS women based on a randomly divided into two groups. Group I (n = 50) were treated with metformin 1500 mg/day, and group II (n = 50) treated with metformin 1500 mg/day plus Calcium 1000 mg/day and Vitamin D 100000 IU/month for 6 months. Patients were followed by transvaginal sonography at first, 3 and 6 months later for evaluating dominant follicle.BMI, menstrual regularity, follicle diameter, pregnancy, serum 25-OH-vitamin D level were matured and compared in two groups.ResultsBMI decreased almost significantly (25.49 ± 1.88 vs 26.28 ± 2.15, p: 0.054) in group II. A better improvement was gained in regulating menstrual abnormalities (70% vs 58%, p: 0.211), follicle maturation (28% vs 22%, p: 0.698), and infertility (18% vs 12%, p: 0.401) in group II compared with group I, but these results were not statistically significant. Eighty three percent of all the PCOS patients showed vitamin D deficiency while 35% were severely deficient. The serum 25-OH-vitamin D mean levels were 13.38 ± 6.48 ng/ml. Vitamin D deficiency was recompensed in 74% of the PCOS patients who had taken calcium &; vitamin D supplementation. There was no correlation between BMI and 25-OH-VD before and after the treatment (p ≥ 0.01).ConclusionThis study showed the positive effects of calcium &; vitamin D supplementation on weight loss, follicle maturation, menstrual regularity, and improvement of hyperandrogenism, in infertile women with PCOS.     

Effect of Ginger and Novafen on menstrual pain: A cross-over trial

Objective

Menstrual pain is a periodic pain which happens during the days of menses. The menstrual disturbances as a health problem among young girls affect not only reproductive, but also psychical health and quality of life. This study was done with the goal of comparing the effect of Ginger and Novafen on the menstrual pain.

The associations between noise annoyance and psychological distress with blood pressure in children and adolescents: The CASPIAN‐V Study

Although blood pressure (BP) tracks from childhood to adulthood, and the prevalence of pediatric primary hypertension is increasing, related determinants are not well understood. The role of noise pollution and psychological distress in increasing BP is well documented in adults, but it remains elusive in children. This study aims to investigate the association of noise annoyance and psychological distress with BP in a pediatric population. This national cross‐sectional study was conducted in 2015 on a sample of 14400 Iranian students, aged 7‐18 years. Information regarding noise annoyance and psychological distress were assessed using questionnaires, and BP values were measured. Levels of noise annoyance and psychological distress were classified based on tertiles to no/low, moderate, and high. Data of 14274 students were completed. The mean age of participants was 12.28 (0.05), with 51% boys and 71.4% urban inhabitant. Diastolic BP and mean arterial BP (MAP) had positive correlations with noise annoyance (regression coefficient: 0.028, 95 % CI: 0.005 ‐ 0.05 and 0.025, 95 % CI: 0.002 – 0.04, respectively). Participants with higher psychological distress were 15 % more likely to experience abnormally high BP compared to those with normal psychological status or mild distresses (OR: 1.15, 95 % CI: 1.003 – 1.34). Here, we found significant positive relationships between the level of noise annoyance and values of diastolic BP and MAP. Moreover, high psychological distress showed to increase the chance of abnormally high BP. The clinical impact of these findings should be assessed in further longitudinal studies.     

C-terminal region of activation-induced cytidine deaminase (AID) is required for efficient class switch recombination and gene conversion

Activation-induced cytidine deaminase (AID) introduces single-strand breaks (SSBs) to initiate class switch recombination (CSR), gene conversion (GC), and somatic hypermutation (SHM). CSR is mediated by double-strand breaks (DSBs) at donor and acceptor switch (S) regions, followed by pairing of DSB ends in two S regions and their joining. Because AID mutations at its C-terminal region drastically impair CSR but retain its DNA cleavage and SHM activity, the C-terminal region of AID likely is required for the recombination step after the DNA cleavage. To test this hypothesis, we analyzed the recombination junctions generated by AID C-terminal mutants and found that 0- to 3-bp microhomology junctions are relatively less abundant, possibly reflecting the defects of the classical nonhomologous end joining (C-NHEJ). Consistently, the accumulation of C-NHEJ factors such as Ku80 and XRCC4 was decreased at the cleaved S region. In contrast, an SSB-binding protein, poly (ADP)-ribose polymerase1, was recruited more abundantly, suggesting a defect in conversion from SSB to DSB. In addition, recruitment of critical DNA synapse factors such as 53BP1, DNA PKcs, and UNG at the S region was reduced during CSR. Furthermore, the chromosome conformation capture assay revealed that DNA synapse formation is impaired drastically in the AID C-terminal mutants. Interestingly, these mutants showed relative reduction in GC compared with SHM in chicken DT40 cells. Collectively, our data indicate that the C-terminal region of AID is required for efficient generation of DSB in CSR and GC and thus for the subsequent pairing of cleaved DNA ends during recombination in CSR.Activation-induced cytidine deaminase (AID) is essential for three different genetic events: class switch recombination (CSR), gene conversion (GC), and somatic hypermutation (SHM), which contribute to Ig gene diversification (1–5). Although AID generates single-strand breaks (SSBs) in the Ig genes, subsequent repair steps for CSR and GC are similar to each other but are distinct from SHM in their mechanistic properties, i.e, in (i) generation of the double-strand breaks (DSBs), (ii) recombination, and (iii) the requirement for uracil-DNA-glycosylase (UNG) for the pairing of the DSB ends (6–10). Despite the similarities between GC and CSR, their repair mechanisms have distinct features: CSR recombination requires nonhomologous end joining (NHEJ), and GC depends on homologous recombination (HR). During CSR, DSB ends normally are joined by classical NHEJ (C-NHEJ), which requires specific repair proteins such as Ku80, XRCC4, or DNA ligase IV (11, 12). In the absence of C-NHEJ, a back-up end-joining pathway called “alternative end joining” (A-EJ), which is reported to be slower and also more error prone than C-NHEJ, joins the broken DSBs ends (13). On the other hand, HR, the most common form of homology-directed repair, requires long sequence homology between donor and acceptor DNA to complete the recombination step by recruiting a distinct set of repair proteins such as RAD54, RAD52, and RAD51 to the break sites (14, 15).Various studies on AID mutations in the N-terminal or C-terminal regions (4, 8, 9, 16–19) have shown that N-terminal AID mutants are compromised for CSR and are defective in SHM, indicating that the N-terminal region of AID is required for DNA cleavage (9, 16, 19). On the other hand, the C-terminal region of AID, which contains a nuclear-export signal and is responsible for AID’s shuttling activity between the nucleus and cytoplasm, is required for CSR-specific activity but not for DNA cleavage activity and SHM (8, 16). Among the series of AID C-terminal mutants examined, two mutants show characteristic features: P20, which has an insertion of 34 amino acids at residue 182 and normal nuclear-cytoplasmic shuttling activity, and JP8Bdel, which has a 16-amino acid truncation at residue 183, accumulates in the nucleus, and shows higher DNA break activity at the donor switch (S) region (16, 17). Although several reports suggest that the C-terminal region of AID is involved in protein stability (20, 21), C-terminal mutants of AID stabilized by fusing the hormone-binding domain of estrogen receptor (ER) also show similar CSR-defective phenotypes (8). Taken together, these data suggest that the DNA cleavage activity and CSR-specific activity depend on different regions of AID (8, 19). In addition, the C-terminal region of AID is essential for the interaction of AID with poly (A)⁺ RNA via a specific cofactor (22). Because CSR requires de novo protein synthesis, we proposed that after DNA cleavage the C-terminal region of AID may be involved in the regulation of the recombination step through generation of a new protein (8, 16, 22).DSBs induced by AID during CSR ultimately are joined by the efficient DNA repair pathway that requires C-NHEJ factors such as Ku70/80 (12, 23). However, in the absence of C-NHEJ, the A-EJ pathway that relies on microhomology can join the broken DNA ends, although this pathway is associated with chromosomal translocations (11, 24). Previously, we reported that JP8Bdel enhances aberrant c-myc/IgH translocations and that it fails to carry out the efficient recombination between donor and acceptor S regions in the IgH locus (8). Therefore, it is important to examine whether the AID C-terminal mutants affect the S–S joining in CSR.In the current work we examined whether the C-terminal region of AID is involved in DNA synapse formation and recombination during CSR in CH12F3-2 and spleen B cells. We also examined the effect of AID C-terminal mutations on GC in chicken DT40 cells, which depends on HR between pseudo V genes and the downstream IgVλ region. Using these CSR- and GC-monitoring systems, we demonstrate that efficient CSR and GC require the C-terminal region of AID for the formation of DSB from SSB and subsequent end synapse. Considering these findings together, we conclude that, in addition to DNA cleavage, AID has a unique function in the generation of DSBs, which is required for S–S synapse formation and joining in CSR and recombination in GC.     

Design,synthesis, molecular docking study,and antibacterial evaluation of some new fluoroquinolone analogues bearing a quinazolinone moiety

BackgroundIncreasing bacterial resistance to quinolones is concerning. Hence, the development of novel quinolones by chemical modifications to overcome quinolone resistance is an attractive perspective in this context.ObjectiveIn this study, it is aimed to design and synthesize a novel series of functionalized fluoroquinolones using ciprofloxacin and sarafloxacin cores by hybridization of quinazolinone derivatives. This objective was tested by a comprehensive set of in vitro antibacterial assays in addition to SAR (structure–activity relationship) characterisation studies.MethodsA nucleophilic reaction of ciprofloxacin and sarafloxacin with 2-(chloromethyl)quinazolin-4(3H)-one in the presence of NaHCO₃ in dimethylformamide (DMF) was performed to obtain the desired compounds 5a-j. Novel compounds were characterised by ¹H, ¹³C- NMR and IR spectroscopy, MS and elemental analysis. In silico pharmacokinetics prediction assays and molecular docking studies were performed to explore the binding characteristics and interactions. Antibacterial activities of the novel compounds were evaluated by Broth microdilution, well diffusion and disc diffusion assays against three gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus and Enterococcus faecalis) and three gram-negative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli).ResultsThe compounds exhibited moderate to good activities against gram-positive bacteria and weak to moderate activities against gram-negative bacteria. Amongst all ciprofloxacin-derivatives, compound 5d was the most potent agent with high antibacterial activity against gram-positive bacteria, including MRSA and S. aureus ((minimum inhibitory concentration (MIC) = 16 nM for both), that is 60 times more potent than ciprofloxacin as parent drug. Compound 5i from sarafloxacin-derivatives was the most potent compound against MRSA and S. aureus (MIC = 0.125 μM). Well diffusion and disk diffusion assay results demonstrated confirmatory outcomes for the quantitative broth microdilution assay. Molecular docking study results were in accordance with the results of antibacterial activity assays.ConclusionThe results of the current study demonstrated that the novel ciprofloxacin and sarafloxacin derivatives synthesized here have promising antibacterial activities. Particularly, compounds 5d and 5i have potential for wider antibacterial applications following further analysis.Graphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00373-6) contains supplementary material, which is available to authorized users.