Evaluation of in vitro rat and human airway epithelial models for acute inhalation toxicity testing.

In vivo models (mostly rodents) are currently accepted by regulatory authorities for assessing acute inhalation toxicity. Considerable efforts have been made in recent years to evaluate in vitro human airway epithelial models (HAEM) as replacements for in vivo testing. In the current work, an organotypic in vitro rat airway epithelial model (RAEM), rat EpiAirway, was developed and characterized to allow a direct comparison with the available HAEM, human EpiAirway, in order to address potential interspecies variability in responses to harmful agents. The rat and human models were evaluated in 2 independent laboratories with 14 reference chemicals, selected to cover a broad range of chemical structures and reactive groups, as well as known acute animal and human toxicity responses, in 3 replicate rounds of experiments. Toxicity endpoints included changes in tissue viability (MTT assay), epithelial barrier integrity (TEER, transepithelial electrical resistance), and tissue morphology (histopathology). The newly developed rat EpiAirway model produced reproducible results across all replicate experiments in both testing laboratories. Furthermore, a high level of concordance was observed between the RAEM and HAEM toxicity responses (determined by IC25) in both laboratories, with R2=0.78 and 0.88 when analyzed by TEER; and R2=0.92 for both when analyzed by MTT. These results indicate that rat and human airway epithelial tissues respond similarly to acute exposures to chemicals. The new in vitro RAEM will help extrapolate to in vivo rat toxicity responses and support screening as part of a 3Rs program.

Evaluation of the toxicity of sodium dodecyl sulphate (SDS) in the MucilAir™ human airway model in vitro.

The aim of the study was to use multiple in vitro assays to assess the effects of a model irritant, sodium dodecyl sulphate (SDS) (≤10 mM (0.29 %, w/v)), on an in vitro model of the airway, MucilAir™. The use of MucilAir™ in recovery studies was also explored. A 24 h exposure increased IL-8 release at an SDS concentration ≥0.63 mM (0.018 %, w/v). Mucin secretion increased and transepithelial electrical resistance (TEER) decreased at SDS concentrations ≥1.25 mM (0.04 %, w/v). Cytotoxicity (lactate dehydrogenase (LDH) release into basolateral chamber) was observed at SDS concentrations of ≥2.5 mM (0.07 %, w/v). The sensitivity of the assays was IL-8 release > TEER = mucin secretion > LDH release. After 7 days, full or partial recovery was observed for intermediate concentrations of SDS using all assays but not at 5 and 10 mM SDS. Morphologically, erosion and cell loss were observed at these concentrations. Resazurin metabolism at 7 days tended to decrease in a dose-dependent manner at SDS concentrations above 2.5 mM (0.07 %, w/v). Together, these data support a No Observable Effect Level of 0.31 mM (0.009 % w/v) SDS and the use of MucilAir™ as a relevant model for airway toxicity studies.

Sleep duration and incidence of obesity in infants, children, and adolescents: a systematic review and meta-analysis of prospective studies.

Study Objectives: To assess the prospective relationship between sleep and obesity in a paediatric population. Methods: We performed a systematic search using PubMed, Embase, Web of Science, and Cochrane (up to September 25, 2017). Included studies were prospective, had follow-up of ≥1 year, had duration of sleep at baseline, and measures of incidence of overweight or obesity and/or changes in body mass index (BMI) z-score and BMI during follow-up. We extracted relative risks or changes in BMI z-score or BMI and 95% confidence intervals (CI) and pooled them using a random effect model. Results: Forty-two studies were included but, as there was significant heterogeneity, results are presented by age strata. Short sleep was associated with a greater risk of developing overweight or obesity in infancy (seven studies, 14738 participants, risk ratio [RR]: 1.40; 95% CI 1.19 to 1.65; p < .001), early childhood (eight studies, 31104 participants, RR: 1.57; 1.40 to 1.76; p < .001), middle childhood (three studies, 3005 participants, RR: 2.23; 2.18 to 2.27; p < .001), and adolescence (three studies, 26652 participants, RR: 1.30; 1.11 to 1.53; p < .002). Sleep duration was also associated with a significant change in BMI z-score (14 studies, 18 cohorts, 31665 participants; mean difference -0.03; -0.04 to -0.01 per hour sleep; p = .001) and in BMI (16 studies, 24 cohorts, 24894 participants; mean difference -0.03 kg/m2; -0.04 to -0.01 for every hour of increase in sleep; p = .001). Conclusions: Short sleep duration is a risk factor or marker of the development of obesity in infants, children, and adolescents.

A Dual X-Ray Absorptiometry Validated Geometric Model for the Calculation of Body Segment Inertial Parameters of Young Females.

The purpose of this study was to validate a new geometric solids model, developed to address the lack of female-specific models for body segment inertial parameter estimation. A second aim was to determine the effect of reducing the number of geometric solids used to model the limb segments on model accuracy. The full model comprised 56 geometric solids, the reduced model comprised 31, and the basic model comprised 16. Predicted whole-body inertial parameters were compared with direct measurements (reaction board, scales), and predicted segmental parameters with those estimated from whole-body dual x-ray absorptiometry scans for 28 females. The percentage root mean square error (%RMSE) for whole-body volume was <2.5% for all models and 1.9% for the full model. The %RMSE for whole-body center of mass location was <3.2% for all models. The %RMSE whole-body mass was <3.3% for the full model. The RMSE for segment masses was <0.5 kg (<0.5%) for all segments; Bland-Altman analysis showed the full and reduced models could adequately model thigh, forearm, foot, and hand segments, but the full model was required for the trunk segment. The proposed model was able to accurately predict body segment inertial parameters for females; more geometric solids are required to more accurately model the trunk.

Characterization of electrically evoked field potentials in the medial prefrontal cortex and orbitofrontal cortex of the rat: modulation by monoamines.

Medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) play critical roles in cognition and behavioural control. Glutamatergic, GABAergic, and monoaminergic dysfunction in the prefrontal cortex has been hypothesised to underlie symptoms in neuropsychiatric disorders. Here we characterised electrically-evoked field potentials in the mPFC and OFC. Electrical stimulation evoked field potentials in layer V/VI of the mPFC and layer V of the OFC. The earliest component (approximately 2 ms latency) was insensitive to glutamate receptor blockade and was presumed to be presynaptic. Later components were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX (20 µM)) and were assumed to reflect monosynaptic (latency 4-6 ms) and polysynaptic activity (latency 6-40 ms) mediated by glutamate via AMPA/kainate receptor. In the mPFC, but not the OFC, the monosynaptic component was also partly blocked by 2-amino-5-phosphonopentanoic acid (AP-5 (50-100µM)) indicating the involvement of NMDA receptors. Bicuculline (3-10 µM) enhanced the monosynaptic component suggesting electrically-evoked and/or glutamate induced GABA release inhibits the monosynaptic component via GABAA receptor activation. There were complex effects of bicuculline on polysynaptic components. In the mPFC both the mono- and polysynaptic components were attenuated by 5-HT (10-100 µM) and NA (30 and 60 µM) and the monosynaptic component was attenuated by DA (100 µM). In the OFC the mono- and polysynaptic components were also attenuated by 5-HT (100 µM), NA (10-100 µM) but DA (10-100 µM) had no effect. We propose that these pharmacologically characterised electrically-evoked field potentials in the mPFC and OFC are useful models for the study of prefrontal cortical physiology and pathophysiology.

The life and death of breast cancer cells: proposing a role for the effects of phytoestrogens on potassium channels.

Changes in the regulation of potassium channels are increasingly implicated in the altered activity of breast cancer cells. Increased or reduced expression of a number of K(+) channels have been identified in numerous breast cancer cell lines and cancerous tissue biopsy samples, compared to normal tissue, and are associated with tumor formation and spread, enhanced levels of proliferation, and resistance to apoptotic stimuli. Through knockout or silencing of K(+) channel genes, and use of specific or more broad pharmacologic K(+) channel blockers, the growth of numerous cell lines, including breast cancer cells, has been modified. In this manner it has been proposed that in MCF7 breast cancer cells proliferation appears to be regulated by the activity of a number of K(+) channels, including the Ca(2+) activated K(+) channels, and the voltage-gated K(+) channels hEAG and K(v)1.1. The effect of phytoestrogens on K(+) channels has not been extensively studied but yields some interesting results. In a number of cell lines the phytoestrogen genistein inhibits K(+) current through several channels including K(v)1.3 and hERG. Where it has been used, structurally similar daidzein has little or no effect on K(+) channel activity. Since many K(+) channels have roles in proliferation and apoptosis in breast cancer cells, the impact of K(+) channel regulation by phytoestrogens is of potentially great relevance.

Body composition of English Premier League soccer players: influence of playing position, international status, and ethnicity.

Body composition is a key consideration in the physical make-up of professional soccer players. The aims of the present study were to determine whether the body composition of professional soccer players varied according to playing position, international status or ethnicity, and to establish which variables best distinguished the soccer players from a reference group. Body composition was assessed using dual-energy X-ray absorptiometry in 64 male professional soccer players. Measured variables included bone mineral density and the relative amounts of lean and fat mass. Data were analysed using analysis of variance and stepwise discriminant function. The soccer players recorded better values than a reference group (n = 24) for all body composition compartments. Percent lean mass and bone mineral density were the variables best able to identify the soccer players (95.5% correctly classified). Differences in body composition were evident between goalkeepers and outfield players, but not between outfield playing positions. No differences were found on the basis of international status. The non-Caucasian players demonstrated significantly lower percent body fat (9.2 +/- 2.0%) than the Caucasian players (10.7 +/- 1.8%). It was concluded that body composition is important for elite soccer players, but that homogeneity between players at top professional clubs results in little variation between individuals.

Re/Affirming and re/conceptualizing disciplinary knowledge as the foundation for doctoral education.

Global shortages of nurses, limited resources, and increasing transnational crises mandate changes in healthcare planning and delivery. Disciplinary knowledge is integral to the development of nurse practitioners and researchers who can provide leadership role in addressing critical healthcare problems. This collaborative meditation examines how critical reflection about disciplinary knowledge in the context of nursing doctoral education facilitates this endeavor. Factors that constrain the development of disciplinary knowledge are discussed. Suggestions for further development of disciplinary knowledge are offered.

Expanding the obesity research paradigm to reach African American communities.

Obesity is more prevalent among African Americans and other racial and ethnic minority populations than among whites. The behaviors that determine weight status are embedded in the core social and cultural processes and environments of day-to-day life in these populations. Therefore, identifying effective, sustainable solutions to obesity requires an ecological model that is inclusive of relevant contextual variables. Race and ethnicity are potent stratification variables in U.S. society and strongly influence life contexts, including many aspects that relate to eating and physical activity behaviors. This article describes a synthesis initiated by the African American Collaborative Obesity Research Network (AACORN) to build and broaden the obesity research paradigm. The focus is on African Americans, but the expanded paradigm has broader implications and may apply to other populations of color. The synthesis involves both community and researcher perspectives, drawing on and integrating insights from an expanded set of knowledge domains to promote a deeper understanding of relevant contexts. To augment the traditional, biomedical focus on energy balance, the expanded paradigm includes insights from family sociology, literature, philosophy, transcultural psychology, marketing, economics, and studies of the built environment. We also emphasize the need for more attention to tensions that may affect African American or other researchers who identify or are identified as members of the communities they study. This expanded paradigm, for which development is ongoing, poses new challenges for researchers who focus on obesity and obesity-related health disparities but also promises discovery of new directions that can lead to new solutions.

Outcomes from Walk the Talk: a nursing intervention for Black women.

OBJECTIVE: Explore changes in walking behavior, blood pressure, and weight over the course of a pilot intervention designed to increase physical activity. DESIGN: A pre/post single group design was used to examine outcomes of a 12-month group intervention with 6-month follow-up. SAMPLE: Twenty-one sedentary hypertensive African American women residing in Mid-Missouri with a mean age of 50.3 years. INTERVENTION: A 3-hour monthly meeting was paired with an at-home walking component. RESULTS: Mean steps per day taken by participants were 3857 at baseline, 4060 at the end of the group intervention, and 5282 at the end of the follow-up period. Mean systolic blood pressure was 142 mmHg at baseline, 123 mmHg at intervention end, and 130 mmHg at 18 months. Mean diastolic blood pressure at baseline was 87 mmHg, 80 mmHg at 12 months, and 78 mmHg at the end of the follow-up period. Mean weight decreased from 206 lbs at baseline to 188 lbs at the end of the intervention. However, mean weight had increased to 213 lbs by the end of the 6-month follow-up. CONCLUSIONS: Outcomes from this pilot study are encouraging with respect to the potential of group level interventions as a strategy for promoting cardiovascular health among hypertensive African American women. It is particularly noteworthy that women maintained decreases in systolic blood pressure and further decreased diastolic blood pressure despite regaining weight during the follow-up period. Replication of this study with a larger sample size and control group will significantly enhance our ability to evaluate whether the unusual pattern of change in walking behavior noted in this pilot was a fluke or indicative of a slower pattern of change in this population.

Changes in steps per day over the course of a pilot walking intervention.

UNLABELLED: The objective of this study is to explicate changes in steps per day observed over the course of a pilot study concerned with promoting walking. A pre/post single group design was used to evaluate a 12-month group intervention with 6-month follow-up with a sample of twenty-one sedentary, hypertensive African American women 25-68 years of age. A 3-hour monthly meeting was paired with an at-home walking component. Results indicated that the total group experienced a slight increase (5%) in mean steps per day at the end of the 12-month intervention, while a subgroup experienced a 13% decrease. However, mean steps per day increased from baseline to 6-month follow-up for both groups. Mean steps per day increased from 3857 to 5582 (37%) for total group and from 4659 to 7038 (51%) for the subgroup. CONCLUSIONS: A group intervention can have a positive impact on promoting walking among African American women; however, multi-phased interventions may be necessary to assist this population meet current physical activity recommendations.

Achieving healthy weight in African-American communities: research perspectives and priorities.

The longstanding high burden of obesity in African-American women and the more recent, steeper than average rise in obesity prevalence among African-American children constitute a mandate for an increased focus on obesity prevention and treatment research in African-American communities. The African-American Collaborative Obesity Research Network (AACORN) was formed to stimulate and support greater participation in framing and implementing the obesity research agenda by investigators who have both social and cultural grounding in African-American life experiences and obesity-related scientific expertise. AACORN's examination of obesity research agenda issues began in 2003 in conjunction with the Think Tank on Enhancing Obesity Research at the National Heart, Lung, and Blood Institute (NHLBI). The assessment was subsequently expanded to take into account the overall NIH strategic plan for obesity research, literature reviews, and descriptions of ongoing studies. In identifying priorities, AACORN members considered the quality, quantity, focus, and contextual relevance of published research relevant to obesity prevention and treatment in African-American adults or children. Fifteen recommended research priorities are presented in five categories adapted from the NHLBI Think Tank proceedings: health effects, social and environmental context, prevention and treatment, research methods, and research training and funding. These recommendations from an African-American perspective build on and reinforce certain aspects of the NHLBI and overall NIH research agendas by providing more specific rationale and directions on areas for enhancement in the type of research being done or in the conceptualization and implementation of that research.

Recruitment and entrance of participants into a physical activity intervention for hypertensive African American women.

Decreasing health disparities between White Americans and racial/ethnic minority populations is a public health priority. An ongoing inability to attract sufficient numbers of African Americans and other people of color to participate in research studies is a major barrier to accomplishing this goal. Participation of racial/ethnic minorities in intervention studies is especially critical to the development of appropriate strategies to promote health among these populations. This article examines the effectiveness of preintervention meetings as well as interactions between African American research team members and potential participants as recruitment strategies. Intersections between recruitment and health promotion are also addressed.

It's all sacred: African American women's perspectives on spirituality.

In this study, we examined the meaning and function of spirituality for a group of African American women. Participants had been recruited for a focus group study exploring the significance of mother-daughter-sister relationships to the well being and health behavior choices of women. Women developed individually defined concepts of spirituality by combining Judeo-Christian traditions and African cosmology. Spirituality was a cornerstone of many participants' daily lives. It influenced women's decision-making and behavior across many realms. For example, many women came to the conclusion that domestic violence was not part of God's plan for their lives. Spiritual-based strategies may provide a rich foundation for innovative and efficacious health promotion interventions targeting African American women. Clinicians can assist in the co-creation of sacred spaces where women can connect with themselves and each other.

Interventions to promote physical activity among African American women.

The lack of routine physical activity among African American women places them at risk for negative health outcomes associated with inactivity. The number of studies focused on African American women has increased dramatically in the past decade. This review examined the intervention research literature testing strategies to increase activity among African American women. Eighteen studies with 1,623 subjects were retrieved. Diverse interventions, settings, and measures were reported. Common methodologic weaknesses included lack of randomization of subjects, single-group design, instruments without documented validity and reliability, significant attrition, and questionable timing of outcome variable measurement. Strategies to design and deliver culturally appropriate interventions are reviewed. Suggestions for future research, such as examining intragroup differences and communal resources, are provided.

Development of scholars interested in community-based health promotion research.

Culturally consistent community-based health promotion interventions have been identified as integral components of strategies to decrease health disparities. The limited number of culturally competent scholars impedes the development of appropriate interventions. This article examines issues relevant to the development of scholars interested in community-based health promotion research. It is the outcome of a series of discussions by the authors held over a 3-month period. Specific topics include classroom and communal educational opportunities to enhance cultural competence and creation of supportive environments for aspiring community-based scholars. Particular attention is given to the importance of ongoing opportunities for interaction between students and lay community scholars.

Talk that talk: storytelling and analysis rooted in African American oral tradition.

Stories are the foundation of qualitative research. However, the development of qualitative methods rooted in oral traditions remains largely unexplored by researchers. The contextual and historical influences on storytelling and storytaking are critical features of the African American oral tradition that are often ignored or minimized in qualitative research. Despite the complex and often contentious history of African Americans, their oral traditions have not been explored to reveal the depth of their lived experiences and the way those experiences inform their health concerns. The purpose of this article is twofold. First, dialogues about storytelling and storytaking are revisited and critiqued. Second, a comprehensive analytic process for gathering and interpreting stories rooted in African American oral tradition is outlined.

Molecular characterisation of bacteria in a wetland used to remove ammoniacal-N from landfill leachate.

Bacteria associated with leachate from a constructed, surface-flow wetland effective at removing ammonium-N, were characterised using molecular methods which bypass the need for cultivation. DNA was extracted from the sample and bacterial 16S rDNA sequences amplified and cloned. Ninety-six individual clones were re-amplified and analysed by restriction digestion and targeted sequencing. A collector's curve was used to estimate the total number of bacterial groups (operational taxonomic units, OTUs) in the sample at 47. Thirty-six clones representing 28 OTUs were sequenced and characterised by aligning them against published sequences. Of these, 10 were confidently identified, whilst for the remaining 18, the closest match was obtained. The sequences in 64% of the OTUs were similar to those of the Proteobacteria but no classical nitrifying bacteria were identified. However, alkaliphilic Methylomicrobium sp. that oxidise ammonium and bacteria from the genus Alcaligenes, at least one species of which is capable of heterotrophic nitrification, were detected.