Heme Induction with Delta-Aminolevulinic Acid Stimulates an Increase in Water and Electrolyte Excretion

Purpose. Studies were performed to examine hemodynamic and renal function before and after acute induction of the endogenous CO system with delta-aminolevulinic acid (DALA), which drives HO activity. Methods. In vivo studies were conducted on Inactin-anesthetized male Sprague Dawley rats (250–300 g) either with or without chronic pretreatment with L-NAME (50 mg/Kg, q12 hours x4d). Results. DALA (80 μmol/Kg, IV bolus) administration acutely increased endogenous CO production and HO-1 protein. In untreated and L-NAME-pretreated rats, DALA did not alter BP, GFR, or RBF but increased UF, UNaV, and UKV (untreated: Δ108.8 ± 0.28%, 172.1 ± 18.4%, and 165.2 ± 45.9%; pretreated: Δ109.4 ± 0.29%, 187.3 ± 26.9%, and 197.2 ± 45.7%). Acute administration of biliverdin (20 mg/kg, IV) and bilirubin (30 mg/kg, IV) to similarly treated animals did not alter UF, UNaV, and UKV. Conclusion. These results demonstrate that heme oxygenase induction increases urine and electrolyte excretion and suggest a direct tubular action of endogenous carbon monoxide

Using local communities to establish geographical boundaries for case studies

Aim: To discuss using local communities to establish geographical boundaries in a case study approach. Background: Case study is widely used in the social sciences to explore complex phenomena within a real-life setting. Applying case boundaries is vital to ensure cases are easily identifiable and similar enough to be treated as instances of the same phenomenon. Discussion: Post codes can be used to define geographical boundaries. A broad range of statistical data is collected from these populations including demographic information, which can assist in identifying communities that have issues or characteristics which may benefit from further research. Data collection from communities allows researchers to access appropriate populations. Conclusion: Using local communities to identify case boundaries helps to provide a clear periphery to the case, and generate local solutions to local problems. Implications for research/practice: Researchers using this approach benefit from being able to immerse themselves in the local community. This close engagement helps to ensure local community engagement with research projects and findings

Recruiting for Epigenetic Research: Facilitating the Informed Consent Process

Because the effects of epigenetic (gene-environment interaction) changes have been associated with numerous adverse health states, the study of epigenetic measures provides exciting research opportunities for biobehavioral scientists. However, recruitment for studies focusing on any aspect of genetics poses challenges. Multiple factors, including lack of knowledge regarding a research study, have been identified as barriers to recruitment. Strengthening the informed consent process through extended discussion has been found to be effective in recruiting for research studies in general, yet there is a paucity of information that focused on such a recruitment strategy for epigenetic studies. In this paper, we share our experiences with strategies to strengthen the informed consent process as well as provide samples of materials developed to heighten potential participants’ understanding of epigenetics, in 4 epigenetic research studies with women from diverse backgrounds experiencing a range of health issues. The combined enrollment success rate for epigenetic studies using the process was 89% with participants representing a diverse population. We posit that carefully developed recruitment scripts provided a foundation for improving potential participants’ understanding of the research project. Easy to understand illustrations of the epigenetic process provided a basis for active engagement and encouraged individual questions

Mothers' perceptions of overweight and obesity in their children

Background: Childhood obesity is a growing health concern and the literature implicates parents, particularly mothers. Aim: To develop understandings into the views of a group of mothers with an overweight or obese child, about their child's overweight or obesity. Method: A qualitative design informed by feminist insights. Eleven English speaking mothers of at least one overweight or obese child were drawn from a large urban community in metropolitan Australia to participate in this study. Results: Participants attributed their child's obesity to factors such as slow metabolism, sedentary lifestyle, familial or cultural factors, genetics, eating habits such as not drinking enough water, or not chewing food adequately. Participants were very concerned about their child's weight problems and their immediate concerns focussed on social problems associated with obesity/overweight. Conclusion: Understanding parental views about their children's overweight and obesity is a key step in forming effective liaisons between health professionals and parents

Perceived Stress Levels, Chemotherapy, Radiation Treatment and Tumor Characteristics Are Associated with a Persistent Increased Frequency of Somatic Chromosomal Instability in Women Diagnosed with Breast Cancer: A One Year Longitudinal Study

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage breast cancer and quantified their somatic chromosomal instability levels using a cytokinesis-blocked micronuclear/cytome assay at 4 timepoints: before chemotherapy (baseline); four weeks after chemotherapy initiation; six months after chemotherapy (at which time some women received radiotherapy); and one year following chemotherapy initiation. Overall, a significant change in instability frequencies was observed over time, with this change differing based on whether the women received radiotherapy (p=0.0052). Also, significantly higher instability values were observed one year after treatment initiation compared to baseline for the women who received: sequential taxotere/doxorubicin/cyclophosphamide (pp=0.014). Significant predictive associations for acquired micronuclear/cytome abnormality frequencies were also observed for race (p=0.0052), tumor type [luminal B tumors] (p=0.0053), and perceived stress levels (p=0.0129). The impact of perceived stress on micronuclear/cytome frequencies was detected across all visits, with the highest levels of stress being reported at baseline (p =0.0024). These findings suggest that the cancer-related exposome has an impact on both healthy somatic cells and tumor cells, and may lead to persistent chromosomal instability. In addition, stress was a significant predictor of chromosomal instability; thus, interventions that aim to reduce stress may reduce acquired soma-wide chromosomal instability for cancer survivors

Penalized Ordinal Regression Methods for Predicting Stage of Cancer in High-Dimensional Covariate Spaces

The pathological description of the stage of a tumor is an important clinical designation and is considered, like many other forms of biomedical data, an ordinal outcome. Currently, statistical methods for predicting an ordinal outcome using clinical, demographic, and high-dimensional correlated features are lacking. In this paper, we propose a method that fits an ordinal response model to predict an ordinal outcome for high-dimensional covariate spaces. Our method penalizes some covariates (high-throughput genomic features) without penalizing others (such as demographic and/or clinical covariates). We demonstrate the application of our method to predict the stage of breast cancer. In our model, breast cancer subtype is a nonpenalized predictor, and CpG site methylation values from the Illumina Human Methylation 450K assay are penalized predictors. The method has been made available in the ordinalgmifs package in the R programming environment

Is there an association between the use of complementary medicine and vaccine uptake: results of a pilot study

Objective. Despite the incredible success of paediatric immunisation, support is not universal. It has been suggested that complementary medicine practitioners enable vaccine rejection and his study aims to explore the relationship between complementary medicine use and paediatric vaccination. A total of 149 Australian parents were recruited via a parenting website and Facebook groups to complete an online questionnaire. Results. The majority of parents (66.4%) stated that their children’s vaccination status was up-to-date. Vaccination status was associated with parental education, area of residence, income, private health insurance, and having a Health Care Card (p < 0.05). Children’s vaccinations were more likely to be up-to-date if they had consulted a general practitioner in the previous 12 months (OR 21.75; p < 0.001), and less likely to be up-to-date if they had consulted a complementary medicine practitioner (OR 0.10; p < 0.001) in the same period. Concerns about vaccine safety and efficacy were the most common reasons for a child’s immunisation status not being up-to-date. These findings highlight an interface between lower vaccine uptake and visits to complementary medicine practitioners. These results emphasise the need to examine the routine paediatric care practices of complementary medicine practitioners as a crucial piece of the puzzle in understanding vaccine rejection

Prevalence and characteristics of Complementary and Alternative Medicine use by Australian children

This study was conducted to evaluate the prevalence and characteristics of complementary and alternative medicine (CAM) use, among Australian children and adolescents within the previous 12 months. Methods: Parents with children up to the age of 18 years were recruited from online parenting groups. Questions addressed demographic factors, socioeconomic status, conventional health service use, including vaccination status, and use of CAM. Results: A total of 149 parents responded to the study of which 73.8% (n=110) children had visited a CAM practitioner or used a CAM product in the previous 12 months. The two most frequently visited CAM practitioners were naturopath/herbalist (30.4%) and chiropractor (18.4%). The most commonly used products were vitamins/minerals (61.7%), and herbal medicine (38.8%). Children had also consulted with a general practitioner (89.8%), community health nurse (31.29%) and paediatrician (30.3%) over the same period. A total of 52% of parents did not disclose their child’s use of CAM to their medical provider. Children’s vaccination status was less likely to be up-to-date if they visited a CAM practitioner (OR 0.16; CI 0.07, 0.36; p<0.001) or used a CAM product (OR 0.25; CI 0.09, 0.64; p=0.004). Conclusion: Despite a lack of high quality research for efficacy and safety, many children are using CAM products and practices in parallel with conventional health services, often without disclosure. This highlights the need to initiate conversations with parents about their child’s use of CAM in order to ensure safe, coordinated patient care. The association between vaccine uptake and CAM use requires further investigation

Impact of antenatal antiretroviral drug exposure on the growth of children who are HIV-exposed uninfected: the national South African Prevention of Mother to Child Evaluation cohort study.

BACKGROUND: The relationship between in-utero antiretroviral (ARV) drug exposure and child growth needs further study as current data provide mixed messages. We compared postnatal growth in the first 18-months of life between children who are HIV-exposed uninfected (CHEU) with fetal exposure to ARV drugs (prophylaxis or triple-drug therapy (ART)) and CHEU not exposed to ARVs. We also examined other independent predictors of postnatal growth. METHODS: We analysed data from a national prospective cohort study of 2526 CHEU enrolled at 6-weeks and followed up 3-monthly till 18-months postpartum, between October 2012 and September 2014. Infant anthropometry was measured, and weight-for-age (WAZ) and length-for-age (LAZ) Z-scores calculated. Generalized estimation equation models were used to compare Z-scores between groups. RESULTS: Among 2526 CHEU, 617 (24.4%) were exposed to ART since -pregnancy (pre-conception ART), 782 (31.0%) to ART commencing post-conception, 879 (34.8%) to maternal ARV prophylaxis (Azidothymidine (AZT)), and 248 (9.8%) had no ARV exposure. In unadjusted analyses, preterm birth rates were higher among CHEU with no ARV exposure than in other groups. Adjusting for infant age, the mean WAZ profile was lower among CHEU exposed to pre-conception ART [-0.13 (95% confidence interval - 0.26; - 0.01)] than the referent AZT prophylaxis group; no differences in mean WAZ profiles were observed for the post-conception ART (- 0.05 (- 0.16; 0.07)), None (- 0.05 (- 0.26; 0.16)) and newly-infected (- 0.18 (- 0.48; 0.13)) groups. Mean LAZ profiles were similar across all groups. In multivariable analyses, mean WAZ and LAZ profiles  for the ARV exposure groups were completely aligned. Several non-ARV factors including child, maternal, and socio-demographic factors independently predicted mean WAZ. These include child male (0.45 (0.35; 0.56)) versus female, higher maternal education grade 7-12 (0.28 (0.14; 0.42) and 12 + (0.36 (0.06; 0.66)) versus ≤ grade7, employment (0.16 (0.04; 0.28) versus unemployment, and household food security (0.17 (0.03; 0.31). Similar predictors were observed for mean LAZ. CONCLUSION: Findings provide evidence for initiating all pregnant women living with HIV on ART as fetal exposure had no demonstrable adverse effects on postnatal growth. Several non-HIV-related maternal, child and socio-demographic factors were independently associated with growth, highlighting the need for multi-sectoral interventions. Longer-term monitoring of CHEU children is recommended