SUMMARY Variability in induced pluripotent stem cell (iPSC) lines remains a concern for disease modeling and regenerative medicine. We have used RNA sequencing analysis and linear mixed models to examine the sources of gene expression variability in 317 human iPSC lines from 101 individuals. We found that ~50% of genome-wide expression variability is explained by variation across individuals and identified a set of expression quantitative trait loci that contribute to this variation. These analyses coupled with allele specific expression show that iPSCs retain a donor specific gene expression pattern. Network, pathway and key driver analyses showed that Polycomb targets contribute significantly to the non-genetic variability seen within and across individuals, highlighting this chromatin regulator as a likely source of reprogramming-based variability. Our findings therefore shed light on variation between iPSC lines and illustrate the potential for our dataset and other similar large-scale analyses to identify underlying drivers relevant to iPSC applications.

In order to teach suitable feeding and hygiene practices to a group of randomly selected Qashqa'i tribe families with 406 children aged 0 -59 months, a culturally appropriate community-based education intervention approach was used. To assess the impact of the intervention on the study group, another group of families with 405 children were randomly selected to serve as the controls. At the beginning of the intervention programme both groups of children had access to a similar diet, consisting of cereals, beans, oil, sugar, milk and yoghurt. Baseline data, age, gender, weight, height and mean arm circumference (MAC), were obtained before the intervention. Using Hubley's behavioural change model, the components of which deal with beliefs, attitudes, subjective norms and enabling factors, the research team studied the behaviour of the family members and tried to change their nutritional behaviour. This was achieved by designing a suitable education programme to be carried out for 12 months. During the programme, families were instructed to follow different methods of food preparation and cooking practices. The final data were collected 3 months after the end of the intervention programme. The results indicated that the children in the study group gained: 1·16 (SD 1·2) kg body weight, 0·033 (SD 0·05) m in height, 0·0067 (SD 0·015) m in MAC, 0·8 (SD 1) in weight-for-age Z-score, 0·97 (SD 1·7) in height-for-age Z-score and 0·28 (SD 1·8) in weight-for-height Z-score by the end of the study. The corresponding values for the control group were 0·42 (SD 1·0), 0·0167 (SD 0·047), 0·0017 (SD 0·012), 0·35 (SD 1·1), 0·56 (SD 1·5) and 0·014 (SD 1·6) respectively and the differences were statistically significant (P, 0·05). These findings suggest that educational interventions involving parents and/or other family members who might play a role in the care behaviour and care resources are important in feeding the children energy-and protein-enriched, hygienic, simple and cheap foods. Such practices could improve child growth even under conditions of poverty.

Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we used a conventional lentiviral transduction method to derive humaninduced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole-body imaging technology, we demonstrated that after tail vein injection, these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor-bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumorbearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help to overcome problems associated with allogeneic transplantation of other types of human NSCs. STEM CELLS

Insertion of a transgene into a defined genomic locus in human embryonic stem cells (hESCs) is crucial in preventing random integration-induced insertional mutagenesis, and can possibly enable persistent transgene expression during hESC expansion and in their differentiated progenies. Here, we employed homologous recombination in hESCs to introduce heterospecific loxP sites into the AAVS1 locus, a site with an open chromatin structure that allows averting transgene silencing phenomena. We then performed Cre recombinase mediated cassette exchange using baculoviral vectors to insert a transgene into the modified AAVS1 locus. Targeting efficiency in the master hESC line with the loxP-docking sites was up to 100%. Expression of the inserted transgene lasted for at least 20 passages during hESC expansion and was retained in differentiated cells derived from the genetically modified hESCs. Thus, this study demonstrates the feasibility of genetic manipulation at the AAVS1 locus with homologous recombination and using viral transduction in hESCs to facilitate recombinase-mediated cassette exchange. The method developed will be useful for repeated gene targeting at a defined locus of the hESC genome.

BackgroundThe purpose of this study is to assess attitudes toward premarital dating and sexual encounters in individuals aged 15–49 years in Tehran.MethodsUtilizing the attitudes section of an original cross-sectional study (n = 755) aimed at assessing sexual health needs of adults, this paper examined personal attitudes towards premarital dating, non-sexual relationships and sexual encounters in both male and female adults aged between 15–49 years. Multi-stage cluster random sampling and a validated/reliable questionnaire were used. Descriptive, bivariate and multivariate analyses were conducted using statistical software.ResultsThe results indicated that the majority of the participants were supportive of dating. Almost three-fourths of the males were more positively inclined towards non-sexual, yet tactile, affectionate interactions between unmarried males and females as opposed to only half of the females (70 % vs. 50.5 %). Also, males held significantly more liberal attitudes than females in their acceptance of premarital sex. On preserving virginity prior to marriage, 43 % of the males felt that it was important for a female to be a virgin, whereas only 26 % felt it was important for males to remain a virgin. Interestingly, more females (61 %) supported the importance of a female’s virginity compared with the importance of males’ virginity (48 %). This study showed that, being a male, of a younger age, single, and being less religious or being secular were important determinants of a liberal sexual attitude.ConclusionThese results might reflect a socio-cultural transition in the sexual attitudes of different age groups of participants - a phenomenon that will need empirical studies to unpack in the Iranian socio-cultural context.

Background: The United States Department of Health and Human Services (USDHHS)recommends that adults achieve 150 minutes per week of moderate-intensity aerobic activity.Most African American women do not meet these guidelines. The purpose of this study was to determine the efficacy of an intervention based on the fourth generation, multi-theory model (MTM) of health behavior change for initiating and sustaining physical activity among African American women when compared to a first generation, knowledge-based intervention. Methods: The randomized controlled trial (RCT) utilized a pre-test, post-test and 6-week followup evaluation with an experimental (n=25) group and a comparison group (n=23). Process evaluation for satisfaction and program fidelity was conducted along with impact evaluation for changes in MTM constructs, intent to initiate and sustain physical activity, minutes of physical activity, body mass index (BMI), waist circumference and blood pressure in hypertensives. Results:The MTM-based intervention proved significantly efficacious in increasing the minutes of physical activity from pre-test mean of 37 minutes to 172 minutes at follow-up (mean difference135.08 minutes, 95% CI: 106.04 to 164.13, P<0.0001), reducing waist circumference from pretest mean of 39 inches to 38 inches at follow-up (mean difference -1.12 inches, 95% CI: -1.70 to-0.545, P<0.001) and modifying the MTM construct of changes in physical environment from a mean of 7 units at pre-test to 9 units at follow-up (mean difference 2.08 units, 95% CI: 0.73 to 3.43, P<0.004) when compared to the knowledge-based intervention over time. Conclusion: There were directional improvements in the mean scores for most of the study variables over time for the MTM intervention group and statistically significant improvement in minutes of physical activity and waist circumference.

Sexual and reproductive health (SRH) knowledge is an important predictor of an individual's sexual behavior; however, little is known regarding this issue among Iranians. This study assessed sexual and reproductive health knowledge among men and women aged 15 to 49 years in Tehran. A total of 755 men and women aged 15 to 49 years were recruited using multistage, random cluster sampling in June 2014. An illustrative anonymous questionnaire endorsed by the World Health Organization (WHO) was used to collect the data. Bivariate and multivariate analyses were performed. The results showed that men and women were moderately knowledgeable about sexual and reproductive health (mean score of SRH knowledge = 39, range: 26 to 52); however, myths and misperceptions prevailed in different aspects of SRH. For example, only 45% of women and 38.7% of men accurately knew that a person infected with human immunodeficiency virus (HIV) can look healthy. Friends were identified as the primary or secondary source of knowledge about puberty and sex-related issues. A multivariate analysis showed that being female (coefficient = 0.139, p < 0.001) and being married (coefficient = 0.180, p < 0.001) were significant predictors of better SRH knowledge, while being young (age group 15 to 24) was a significant determinant of poor SRH knowledge (coefficient = -0.161, p < 0.001) when other influencing factors were controlled. Culturally appropriate and age-specific comprehensive education is recommended, particularly for men, the unmarried, and the younger generation in Iran.

Objective: This study among 400 undergraduate students enrolled at Jackson State University (JSU) study aimed to assess knowledge about HIV and AIDS among African-American undergraduate students attending a historically black college and university. A cross-sectional survey was conducted. Data were collected using a validated, self-administered, and standardized questionnaire on knowledge regarding risks for HIV and AIDS. Three hundred and eighty-six students (96.5%) had good knowledge about HIV and AIDS, although some participants had misconceptions about the modes of HIV infection transmission. There were no significant gender differences for HIV and AIDS knowledge among the participants (χ2 = 3.05; P = 0.08). In general we concluded that JSU undergraduate students had adequate knowledge about HIV transmission modes and AIDS, although some participants had misconceptions about the routes of HIV infection transmission. Hence, this study calls for strengthening HIV and AIDS awareness education among undergraduate students.