Effects of 12-O-tetradecanoylphorbol-13-acetate on the incorporation of labelled precursors into RNA, DNA and protein in epidermis, dermis and subcutis from precancerous mouse skin with reference to enhanced tumorigenesis

The effects of a single application of 1.8 nmol 12-O-tetra-decanoylphorbol-13-acetate (TPA) on precursor incorporation into RNA, DNA and protein in the epidermis, dermis and subcutis from 3-methylcholanthrene (MCA) injected precancerous mouse skin were studied at various time points between 3 and 96 h. In the precancerous tissues, the rates of incorporation of [3H]uridine into RNA did not alter appreciably from those in the control tissues; while the rates of [3H]methylthymidine incorporation into DNA were elevated with peaks appearing between 6 and 12 h, at 24 h and at 72 h in epidermis, dermis and subcutis. The rate of incorporation of [14C] leucine into protein was markedly elevated in all the three tissues which showed 3-4 sharp peaks. The maximum stimulation ranged between 14 and 20 times that of the control. A single application of TPA to the precancerous mouse skin induced early stimulation of precursor incorporation into all the three macromolecules in epidermis, dermis and subcutis. The increased stimulation was maintained for 36- 72 h. The patterns of incorporation of [3H]methylthymidine into DNA gave rise to 2-3 peaks of elevated uptake in each tissue up to 36-48 h. A lowered rate of DNA synthesis between 48 and 60 h was followed by a peak at 72 h. In each group, epidermal mitotic activity correlated well with spurts of precursor incorporation into cellular DNA. The observations indicate that TPA recruits more cells into the DNA synthetic phase and accelerates selective growth of preneoplastic cells during tumor progression

Evaluation of carcinogenic/co-carcinogenic activity of a common chewing product, pan masala, in mouse skin, stomach and esophagus

Pan masala, a dry powdered mixture of areca nut, catechu, lime, unspecified spices and flavoring agents, has gained widespread popularity as a chewing substitute in India. In this study, the carcinogenic and tumor-promoting potential of an ethanolic pan masala extract (EPME) was determined using skin of S/RVCri-ba mice and forestomach and esophagus of ICRC mice as the target tissues. Carcinogenic activity of pan masala was tested by painting the mouse skin for 40 weeks with EPME or by gavage feeding for 6 months. Following initiation with 9,10-dimethylbenz(a)anthracene (DMBA), carcinogenesis of mouse skin was promoted with different doses of EPME, while gastric- and esophageal-tumor-promoting activity was determined by administering EPME by gavage to animals initiated with diethylnitrosamine (DEN). The ability of EPME to effect progression of skin papilloma to carcinoma and cutaneous alterations after a single or multiple EPME treatment were also evaluated. EPME at 25 mg per dose promoted skin-papilloma formation between 30 and 40 weeks of treatment and enhanced the rate of conversion of papilloma to carcinoma. Induction of mild epidermal hyperplasia, dermal edema, increase in epidermal mitotic activity and the rate of epidermal and dermal DNA synthesis by EPME correlated well with its skin-tumor-promoting potential. In ICRC mice, EPME was inactive as a complete carcinogen, but effectively promoted the development of forestomach and esophageal papilloma and carcinoma in a concentration-dependent manner. The tumor incidence at 25 mg EPME per dose was comparable with that obtained in the 12-0-tetradecanoylphorbol-13 acetate(TPA)-treated group. The findings indicate that habitual pan-masala use may exert carcinogenic and co-carcinogenic influence

Are female children more vulnerable to the long-term effects of maternal depression during pregnancy?

BACKGROUND: Female fetuses are more vulnerable to high levels of maternal glucocorticoids. We examined whether exposure to prenatal maternal depression, a condition associated with high glucocorticoids, carries greater risk for depression at 12 and 18 years in girls. METHODS: Our sample comprised 7959 mothers and children from the Avon Longitudinal Study of Parents and Children following imputation for missing data. Maternal depression was assessed pre-and post-natally, and offspring depression at ages 12 and 18. We used logistic regression models to examine the relationship between exposure to prenatal and postnatal depression and offspring depression at 18 and 12 and interactions with gender. RESULTS: There was an interaction between prenatal depression and gender (P=0.027) and between postnatal depression and gender (P=0.027) for offspring depression at 18. Following adjustment in pre-natally depressed mothers, the odds ratio for offspring depression at 18 was 1.55 (95% c.i. 1.03-2.34) for girls and 0.54 (0.23-1.26) for boys. In post-natally depressed mothers, the odds ratio for offspring depression at 18 was 1.15 (0.70-1.89) in girls and 3.13 (1.52-6.45) in boys. However there was no evidence for interaction between prenatal or postnatal depression and gender (P=0.559 and 0.780 respectively) for offspring depression at 12. LIMITATIONS: As expected with this large cohort spanning over 18 years, there was loss-to-follow-up. CONCLUSIONS: This is the first evidence in humans that increased vulnerability of female fetuses to maternal stress responses during pregnancy persists into adolescence. One explanation for gender differences emerging later is more depressive symptomatology is attributed to heritable risk at 12, whereas biological processes involved in brain development at 18 may be influenced by foetal programming. If replicated, this study has potential to help understand intergenerational transmission of depression, a leading cause of morbidity worldwide

Long-term carcinogenicity of pan masala in Swiss mice

Carcinogenicity of pan masala, a dry powdered chewing mixture of areca nut, catechu, lime, spices and flavoring agents was evaluated by means of the long-term animal bio-assay 6- to 7-week old male and female S/RVCri mice were divided randomly into intermediate and lifetime exposure groups and fed normal diet without pan masala - (zero dose) or diet containing 2.5% and 5% pan masala. Animals in the intermediate-exposure group (n = 10/gender/dose group) were killed after 6, 12 or 18 months of treatment, while those in the lifetime-exposure group (n = 54/gender/dose group) were killed when moribund or at the termination of the experiment at 24 months. Several tissues were processed for histopathological examination. The body weight and survival rate of mice fed pan masala were lower than that of the controls. Histopathological observations of tissues from control animals did not reveal any neoplastic alterations. However, lifetime feeding of pan masala induced adenoma of the liver, stomach, prostate and sebaceous glands, also forestomach papilloma, liver hamartoma, hepatoma and hemangioma, carcinoma of the forestomach, adenocarcinoma of the lung and liver, and testicular lymphoma. Neoplastic lesions appeared mainly in the liver (n = 13), stomach (n = 3) and lung (n = 8). Lung adenocarcinoma, the most frequent malignant tumor type, was observed in 2/120 mice in the intermediate-exposure group and in 8/216 animals in the lifetime-exposure group. Statistical analysis of tumor-induction data revealed a significant dose-related increase in lung adenocarcinomas but not in liver and stomach neoplasms indicating that lung is the major target tissue for the carcinogenic action of pan masala

The home advantage over the first 20 seasons of the English Premier League: Effects of shirt colour, team ability and time trends

This study explored the relationship between teams' home shirt colour and the magnitude of the home advantage in English professional soccer. Secondary aims were to explore the consistency of the home advantage over time and the relationship between the home advantage and team ability. Archival data from 7720 matches contested over the first 20 seasons of the English Premier League were analysed. The data show that teams wearing red are more successful than teams wearing other colours, and that teams are more successful in home games than in away games (home advantage index = 0.608). The home advantage has also remained consistent over time (1992/1993-2011/2012) and is greater in low-ability teams (teams with lower league positions) than in high-ability teams. After controlling for team ability, it was found that teams opting for red shirts in their home games did not show a greater home advantage than teams opting for other colour shirts. Two possibilities for this finding are offered: (1) shirt colour is not a contributing factor to team success, or (2) changes in psychological functioning associated with viewing or wearing red stay with team members after the shirt colour has been changed. It is recommended that researchers continue to explore the effect of shirt colour on athlete and team behaviour and further explore how team ability can affect the magnitude of the home-field advantage. © 2012 International Society of Sport Psychology

Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years.

OBJECTIVE: Maternal antenatal depression and anxiety are associated with increased risk of childhood behavioural and emotional problems in offspring; it remains unclear to what extent this is due to a maternal biological impact on foetal development. Here, we compare associations between maternal and paternal antenatal depression and anxiety with offspring anxiety disorders, thus controlling for some genetic and shared environmental factors. METHODS: We used data from the ALSPAC population cohort including measures of antenatal parental depression and anxiety. At 18 years, offspring completed the CIS-R interview, yielding diagnoses for anxiety disorders. Results were adjusted for confounding variables including parental postnatal depression and anxiety. RESULTS: Children of women with antenatal depression (18 weeks gestation), had an increased risk of anxiety disorders at 18 years of age (11.1% vs. 6.2%; adj. OR 1.75 (1.19, 2.58); p=0.01). Children of women with antenatal anxiety had increased risk of co-morbid anxiety and depression (adj. OR 1.39 (1.06, 1.82); p=0.02). No such associations were found with paternal antenatal depression or anxiety. LIMITATIONS: There was a high attrition rate from the original cohort to the CIS-R completion at 18 years postpartum. Parental mood was only assessed together at one time point during the antenatal period. CONCLUSIONS: The differences in the association between maternal and paternal mood during pregnancy and child outcomes supports the hypothesis that foetal programming may account, at least in part, for this association. We highlight the potential opportunity for preventative intervention by optimising antenatal mental health

Educational interventions involving physical manipulatives for improving children's learning and development: A scoping review

Physical manipulatives (PMs) are concrete objects used during hands-on learning activities (e.g., building blocks, fraction tiles, counters), and are widely used in primary-school teaching, especially during maths instruction. This scoping review collated studies that have examined the effectiveness of educational PM interventions with pre-primary and primary-age children. A total of 102 studies met the inclusion criteria and were synthesised in the review. Most studies included a sample of children aged 4–6 years and were conducted in a school setting. They spanned 26 different countries, but almost all took place in high- or middle-income contexts, mainly in the USA. Interventions were grouped into three main learning domains: maths, literacy and science. Considerable heterogeneity was identified across the review studies in terms of the PMs and hands-on activities used (e.g., block building, shape sorting, paper folding, enactment with figurines). Evidence relating to effectiveness of the intervention programmes was synthesised, with the most promising findings identified in the maths domain. Benefits to children's spatial, literacy and science skills were also reported. Overall, however, the evidence was mixed: other studies found that PMs were not associated with learning benefits, and many were hindered by methodological shortcomings. This calls for caution when drawing conclusions about the overall effectiveness of PM interventions. Nevertheless, the findings illustrate the many ways hands-on PM activities can be incorporated into children's early learning experiences. Recommendations for further research and for using PMs in practice are made

Can guidance during play enhance children’s learning and development in educational contexts? A systematic review and meta-analysis

This systematic review and meta-analysis considered evidence of guided play compared to direct instruction or free play to support children's learning and development. Interventions from 39 studies were reviewed (published 1977–2020); 17 were included in meta-analysis (Ntotal = 3893; Mchildage = 1–8 years; Mgirls 49.8%; Methnicity White 41%, African American/Black 28%, Hispanic 19%). Guided play had a greater positive effect than direct instruction on early maths skills (g = 0.24), shape knowledge (g = 0.63), and task switching (g = 0.40); and than free play on spatial vocabulary (g = 0.93). Differences were not identified for other key outcomes. Narrative synthesis highlighted heterogeneity in the conceptualization and implementation of guided play across studies

Preventing enduring behavioural problems in young children through early psychological intervention (Healthy Start, Happy Start): study protocol for a randomized controlled trial.

BACKGROUND: Behavioural problems are common in early childhood, and can result in enduring costs to the individual and society, including an increased risk of mental and physical illness, criminality, educational failure and drug and alcohol misuse. Most previous research has examined the impact of interventions targeting older children when difficulties are more established and harder to change, and have rarely included fathers. We are conducting a trial of a psychological intervention delivered to families with very young children, engaging both parents where possible. METHODS: This study is a two-arm, parallel group, researcher-blind, randomized controlled trial, to test the clinical effectiveness and cost-effectiveness of a parenting intervention, Video Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) for parents of young children (12-36 months) at risk of behavioural difficulties. VIPP-SD is an evidence-based parenting intervention developed at Leiden University in the Netherlands which uses a video-feedback approach to support parents, particularly by enhancing parental sensitivity and sensitive discipline in caring for children. The trial will involve 300 families, who will be randomly allocated into either an intervention group, who will receive the video-feedback intervention (n = 150), or a control group, who will receive treatment as usual (n = 150). The trial will evaluate whether VIPP-SD, compared to treatment as usual, leads to lower levels of behavioural problems in young children who are at high risk of developing these difficulties. Assessments will be conducted at baseline, and 5 and 24 months post-randomization. The primary outcome measure is a modified version of the Preschool Parental Account of Child Symptoms (Pre-PACS), a structured clinical interview of behavioural symptoms. Secondary outcomes include caregiver-reported behavioural difficulties, parenting behaviours, parental sensitivity, parental mood and anxiety and parental relationship adjustment. An economic evaluation will also be carried out to assess the cost-effectiveness of the intervention compared to treatment as usual. DISCUSSION: If shown to be effective, the intervention could be delivered widely to parents and caregivers of young children at risk of behavioural problems as part of community based services. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN58327365 . Registered 19 March 2015