Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary, Canada? A mediation analysis.

PURPOSE: According to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada. METHODS: Data collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement. RESULTS: Income inequality was not significantly associated with higher depressive symptoms (ß = 0.32, 95%CI = -0.067, 0.70), anxiety symptoms (ß = 0.11, 95%CI = -0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (ß = -0.13, 95%CI = -0.15, -0.097), while community engagement was not significantly associated with depressive symptoms (ß = 0.059, 95%CI = -0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (ß = -0.17, 95%CI = -0.20, -0.13) but not with higher levels of community engagement (ß = 0.14, 95%CI = -0.14, 0.41). CONCLUSION: The current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.

Parents' stage of change for diet and physical activity: influence on childhood obesity.

Highly visible public health education efforts have resulted in increased awareness of the childhood obesity epidemic but not a related decline in the number of overweight children. The Transtheoretical Model was used to examine the associations among child risk factors, parent's knowledge of factors associated with childhood obesity and their access to healthy foods in their community and parent's stage of change (SOC) in making behavior changes to improve their child's diet and level of physical activity. Parents (n = 124) of children between 6-12 years of age were surveyed. Perceived weight of the child and the child's body mass index (BMI) were found to be associated with parent's SOC for food portions and dietary fats, yet this was not observed for the fruits and vegetables or physical activity domains. Food availability and parent's childhood obesity knowledge was not found to be associated with parent's SOC. This study provides evidence that intervention efforts that stress knowledge of the causes and harmful effects of being overweight may have limited effectiveness.

A positive test of East Antarctica-Laurentia juxtaposition within the Rodinia supercontinent.

The positions of Laurentia and other landmasses in the Precambrian supercontinent of Rodinia are controversial. Although geological and isotopic data support an East Antarctic fit with western Laurentia, alternative reconstructions favor the juxtaposition of Australia, Siberia, or South China. New geologic, age, and isotopic data provide a positive test of the juxtaposition with East Antarctica: Neodymium isotopes of Neoproterozoic rift-margin strata are similar; hafnium isotopes of approximately 1.4-billion-year-old Antarctic-margin detrital zircons match those in Laurentian granites of similar age; and a glacial clast of A-type granite has a uraniun-lead zircon age of approximately 1440 million years, an epsilon-hafnium initial value of +7, and an epsilon-neodymium initial value of +4. These tracers indicate the presence of granites in East Antarctica having the same age, geochemical properties, and isotopic signatures as the distinctive granites in Laurentia.

Attitudes of women with chronic pelvic pain to the gynaecological consultation: a qualitative study.

OBJECTIVE: To describe the attitudes that women with chronic pelvic pain (CPP) attending gynaecology clinics have to their consultations and to determine the ways in which their health care can be improved. DESIGN: Qualitative study using semistructured individual interviews. SETTING: UK gynaecology outpatient clinics in district general and teaching hospitals. SAMPLE: Twenty-six women with CPP. METHODS: Semistructured individual interviews were conducted. Data gathering and analysis followed a grounded theory approach. MAIN OUTCOME MEASURES: Women's wishes regarding their care and their actual experiences of care. RESULTS: Four main themes emerged. The women wanted (a) personal care, which they often did not receive; (b) to feel understood and to be taken seriously, although they often felt dismissed, which applied both to women with and without an explanation for their pain; (c) explanation as much as cure, but an adequate explanation was often not provided; and (d) to be reassured, which often they were not. Effective reassurance was complex as it included general reassurance and specific reassurance about cause and treatment. CONCLUSIONS: Improvements are needed in the outpatient care of women presenting with CPP. Changes should focus on providing more personal care, so that presenting problems are seen to be taken seriously, findings and management are appropriately explained, and women are more effectively reassured. Interventions need to be developed that meet these needs and tested to determine if they are feasible, acceptable, and improve outcomes.

Ancient maize from Chacoan great houses: where was it grown?

In this article, we compare chemical (87Sr/86Sr and elemental) analyses of archaeological maize from dated contexts within Pueblo Bonito, Chaco Canyon, New Mexico, to potential agricultural sites on the periphery of the San Juan Basin. The oldest maize analyzed from Pueblo Bonito probably was grown in an area located 80 km to the west at the base of the Chuska Mountains. The youngest maize came from the San Juan or Animas river floodplains 90 km to the north. This article demonstrates that maize, a dietary staple of southwestern Native Americans, was transported over considerable distances in pre-Columbian times, a finding fundamental to understanding the organization of pre-Columbian southwestern societies. In addition, this article provides support for the hypothesis that major construction events in Chaco Canyon were made possible because maize was brought in to support extra-local labor forces.

Molecular analysis of the prostate-specific antigen upstream gene enhancer.

BACKGROUND: Our objective was to identify factors other than androgen receptor that bind to and regulate the prostate-specific antigen (PSA) upstream gene enhancer (PSE). METHODS: DNAse I footprinting and electromobility shift assays (EMSA) were performed over the PSE using lysates from PSA-producing cell lines, LNCaP and LAPC4, and nonproducing PSA cell lines, PC-3 cells, U937 monocytes, and Namalwa B cells. Mutational analysis and transient transfection assays were used to determine the contributions made by different elements towards the regulation of the enhancer. RESULTS: Three distinct regions surrounding androgen response elements of the PSE were found to bind unknown ubiquitous and cell type-specific proteins. These regions, when mutated in a PSE reporter construct, were shown to be required for maximal activation in LNCaP cells. CONCLUSIONS: These results correlate unknown sequence-specific DNA binding proteins with androgen-mediated regulation of a prostate-specific gene, thus providing further insight into the mechanism of PSA gene expression.

The cost of medical care for patients with cystic fibrosis in a health maintenance organization.

BACKGROUND: Cystic fibrosis (CF) is the most common life-shortening genetic disorder among white individuals worldwide. Previous estimates of the costs of medical care have been based on expert opinion rather than observed costs. Accurate cost estimates are needed to enable evaluation of the cost-effectiveness of new interventions and prenatal genetic screening recommendations. OBJECTIVE: To evaluate the cost of medical care for patients (N = 136) served by a health maintenance organization with a CF center. METHODS: Retrospective analysis of data from computerized cost databases and the Cystic Fibrosis Foundation annual survey. Severity of disease was classified based on the percent predicted forced expiratory volume at 1 second. RESULTS: The annual cost of medical care in 1996 averaged $13 300 and ranged from $6200 among patients with mild disease to $43 300 among patients with severe disease. Of total costs, 47% were from hospitalization, 18% were from DNase (Pulmozyme), 12% were from clinic visits, and 10% were from outpatient antibiotics. When the observed costs were used to estimate the costs of medical care for the entire population of CF patients in the United States, these costs were estimated to be $314 million per year in 1996 dollars. CONCLUSIONS: We conclude that the cost of medical care for CF varies greatly with severity but is substantial even among patients with mild disease. These findings underscore the need for strategies to ensure good health insurance coverage and high quality care for all individuals with this condition.

Audit of waste collected over one week from ten dental practices. A pilot study.

An audit of the waste practices of ten general dental surgeries identified problems that have occurred due to the lack of specific dental guidelines or codes of practice in this area. Occupational health and safety requirements for types and locations of sharps containers, and lack of consensus on what constitutes a sharp, were identified as areas needing attention. Cross-infection control items, such as gloves, masks, single-use cups, and protective coverings, were found to constitute up to 91 per cent of total waste. When infectious waste was reclassified by the audit team as 'that waste which was visibly blood stained,' a reduction in waste in this category was made, during the audit, at each practice. The practice of disposing of radiographic fixer and developer into the sewerage system occurred in three out of the ten practices, even though the Australian Dental Association Inc. has discouraged this practice.

Transcriptional repression by p53 involves molecular interactions distinct from those with the TATA box binding protein.

In addition to serving a role as a DNA binding-dependent transcriptional activator, p53 has been reported to repress a variety of promoters that lack p53 binding sites. Data from recent studies have suggested that this activity is mediated via an interaction between p53 and the TATA box binding protein (TBP). To investigate the functional relevance of this interaction in vivo, we have performed transient transfection assays in Drosophila Schneider cells. Wild-type p53 was found to repress expression from TATA box- but not initiator (Inr)-containing promoters activated by GAL4-VP16, GAL4-ftzQ or Sp1. A mutant p53(His175), defective in DNA binding and transcriptional activation, also inhibited TATA-dependent transcription activated by Sp1. However, p53 was unable to repress a basal TATA promoter stimulated by overexpression of TBP. Furthermore, overexpression of TBP failed to rescue the p53-mediated repression of activated transcription and a p53 mutant with its N-terminal TBP interaction domain intact, but defective in transcriptional activation and binding to TBP-associated factors (TAFs), was similarly defective in transcriptional repression. These data suggest that a p53-TBP interaction is not sufficient for transcriptional repression by p53 and that repression involves an interaction between p53 and other factors, such as TAFs, that are required for activated but not basal transcription. We suggest that p53-mediated repression results from squelching of a factor limiting for activated transcription from TATA- but not Inr-containing promoters.

Functional interaction between p53, the TATA-binding protein (TBP), andTBP-associated factors in vivo.

The transcriptional activator p53 is known to interact with components of the general transcription factor TFIID in vitro. To examine the relevance of these associations to transcriptional activation in vivo, plasmids expressing a p53-GAL4 chimera and Drosophila TATA-binding protein (dTBP) were transfected into Drosophila Schneider cells. p53-GAL4 and dTBP displayed a markedly synergistic effect on activated transcription from a GAL4 site-containing reporter that was at least 10-fold greater than observed with other activators tested. A mutant p53 previously shown to be defective in both transcriptional activation in vivo and in binding to TBP-associated factors (TAFs) in vitro, although still capable of binding dTBP, did not cooperate with dTBP, suggesting that TAFs may contribute to this synergy. Providing further support for this possibility, transfected dTBP assembled into rapidly sedimenting complexes and could be immunoprecipitated with anti-TAF antibodies. While overexpression of any of several TAFs did not affect basal transcription, in either the presence or the absence of cotransfected dTBP, overexpression of TAFII230 inhibited transcriptional activation mediated by p53-GAL4 as well as by GAL4-VP16 and Sp1. Overexpression of TAFII40 and TAFII60 also inhibited activation by p53-GAL4 but had negligible effects on activation by GAL4-VP16 and Sp1, while TAFII110 did not affect any of the activators. TAF-mediated inhibition of activated transcription could be rescued by high levels of exogenous dTBP, which also restored full synergy. These data demonstrate for the first time that functional interactions can occur in vivo between TBP, TAFs, and p53.

p53 inhibits DNA replication in vitro in a DNA-binding-dependent manner.

The p53 tumor suppressor gene product is a sequence-specific DNA-binding protein that is necessary for the G1 arrest of many cell types. Consistent with its role as a cell cycle checkpoint factor, p53 has been shown to be capable of both transcriptional activation and repression. Here we show a new potential role for p53 as a DNA-binding-dependent regulator of DNA replication. Constructs containing multiple copies of the ribosomal gene cluster (RGC) p53 binding site cloned on the late side of the polyomavirus origin were used in in vitro replication assays. In the presence of p53, the replication of these constructs was strongly inhibited, while the replication of constructs containing a mutant version of the RGC site was not affected by p53. Several tumor-derived mutant p53 proteins were unable to inhibit replication of the construct with wild-type RGC sites. Additionally, the transactivator GAL4-VP16 was unable to inhibit replication of a construct containing GAL4 binding sites adjacent to the polyomavirus origin. We also show that the inhibition by p53 can occur from sites cloned as far as 600 bp from the origin. Preincubation experiments suggest that p53 inhibits replication at a step mediated by ATP, possibly by inhibiting the binding of polyomavirus T antigen to the core origin. The presence of an endogenous p53 binding site in the polyomavirus origin suggests potential mechanisms for the observed inhibition.

Xenopus laevis p53 protein: sequence-specific DNA binding, transcriptional regulation and oligomerization are evolutionarily conserved.

The well conserved human and murine p53 proteins are tetramers that can activate transcription from templates bearing p53 binding sites. Since the normal function of mammalian p53 is necessary for preserving the stability of genome, we examined the properties of purified Xenopus p53 (Xp53) to determine whether it shares similar biochemical activities. Xp53 was shown to bind specifically to sites containing the p53 consensus sequence derived for human p53. Moreover, Xp53 transactivates reporter genes containing a human p53 response element in vivo. Finally, Xp53 can be cross-linked into tetramers in a manner similar to human p53. However, Xp53 forms hetero-oligomers with human or murine p53 only very ineffectively, in contrast to the efficient hetero-oligomer formation that occurs between human and murine p53 polypeptides. Taken together, our data indicate that sequence specific DNA binding, transcriptional regulation and oligomerization of p53 are common properties of vertebrate p53 proteins, and thus they are likely to be required for the biological activity of the protein.

Cooperative DNA binding of p53 with TFIID (TBP): a possible mechanism for transcriptional activation.

The p53 tumor-suppressor gene product, a sequence-specific DNA-binding protein, has been shown to act both as a transcriptional activator and repressor in vivo and in vitro. Consistent with its roles in regulating transcription are recent observations that p53 binds directly to the TATA box-binding protein (TBP) subunit of the basal transcription factor TFIID. Here, we show that p53 cooperates with either recombinant TBP or partially purified TFIID in binding to a DNA fragment containing both a specific p53-binding site (RGC) and a TATA box (RGC-TATA). Surprisingly, both TBP and TFIID also stimulate p53 binding to DNA containing a specific p53-binding site but lacking a TATA box. These data are supported by the observation that p53 and Drosophila TBP combinatorily activate transcription in vivo. Our results suggest that p53 activates transcription through the formation of a more stable p53-TFIID-promoter complex. We also examined whether p53 might affect the ability of TBP or TFIID to interact with DNA containing a TATA box but lacking a p53-binding site. Although p53 strongly inhibited the interaction of TBP with such DNA, it had virtually no effect on TFIID binding. Thus, transcriptional repression by p53 may require additional functions other than inhibiting TBP binding.

Phenytoin increases gene expression for platelet-derived growth factor B chain in macrophages and monocytes.

The mechanism by which phenytoin (PHT) induces gingival overgrowth remains unclear. We hypothesized that PHT increases macrophage production of platelet-derived growth factor (PDGF), an important cytokine in connective tissue growth and repair, and that excessive production PDGF in gingiva could lead to redundant growth. To test the hypothesis, rat peritoneal macrophages and human blood monocytes were cultured in the presence of PHT (5 to 20 micrograms/ml medium) or an equal volume of its solvent for 3 days and tested for expression of PDGF-B mRNA by in situ hybridization. Approximately 300 cells/culture well were examined (3 wells/drug level) for positive indication of PDGF-B mRNA. Data were compared by chi square test. All levels of PHT in both cell types induced a 2- to 8-fold increase in PDGF-B mRNA positive cells, significant in all cases at P < 0.001. Northern blot analysis of RNA from similarly cultured rat macrophages confirmed these findings. Cells treated with 10 micrograms PHT/ml medium or solvent revealed 2.2 +/- 0.3 and 1.0 +/- 0.2 (mean +/- SEM) arbitrary units PDGF mRNA respectively (t tests, P < 0.05). Additionally, rat macrophages were cultured in presence of 5 micrograms PHT/medium or its solvent and medium was analyzed for PDGF secretion by radioimmunoassay. Mean values (+/- SEM) were 1.28 +/- 0.49 and 0.78 +/- 0.07 ng/mg protein respectively (t test, P < 0.05). These data showed that PHT augmented the expression of c-sis, the gene for PDGF-B, and offered a possible explanation for PHT-induced gingival overgrowth.