ASU Scholarship Showcase

Background: In the USA, stillbirth (in utero fetal death ≥20 weeks gestation) is a major public health issue. Women who experience stillbirth, compared to women with live birth, have a nearly sevenfold increased risk of a positive screen for post-traumatic stress disorder (PTSD) and a fourfold increased risk of depressive symptoms. Because the majority of women who have experienced the death of their baby become pregnant within 12–18 months and the lack of intervention studies conducted within this population, novel approaches targeting physical and mental health, specific to the needs of this population, are critical. Evidence suggests that yoga is efficacious, safe, acceptable, and cost-effective for improving mental health in a variety of populations, including pregnant and postpartum women. To date, there are no known studies examining online-streaming yoga as a strategy to help mothers cope with PTSD symptoms after stillbirth.

Methods: The present study is a two-phase randomized controlled trial. Phase 1 will involve (1) an iterative design process to develop the online yoga prescription for phase 2 and (2) qualitative interviews to identify cultural barriers to recruitment in non-Caucasian women (i.e., predominately Hispanic and/or African American) who have experienced stillbirth (N = 5). Phase 2 is a three-group randomized feasibility trial with assessments at baseline, and at 12 and 20 weeks post-intervention. Ninety women who have experienced a stillbirth within 6 weeks to 24 months will be randomized into one of the following three arms for 12 weeks: (1) intervention low dose (LD) = 60 min/week online-streaming yoga (n = 30), (2) intervention moderate dose (MD) = 150 min/week online-streaming yoga (n = 30), or (3) stretch and tone control (STC) group = 60 min/week of stretching/toning exercises (n = 30).

Discussion: This study will explore the feasibility and acceptability of a 12-week, home-based, online-streamed yoga intervention, with varying doses among mothers after a stillbirth. If feasible, the findings from this study will inform a full-scale trial to determine the effectiveness of home-based online-streamed yoga to improve PTSD. Long-term, health care providers could use online yoga as a non-pharmaceutical, inexpensive resource for stillbirth aftercare.

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight.

Salmonella enterica serovar Typhimurium strains belonging to sequence type ST313 are a major cause of fatal bacteremia among HIV-infected adults and children in sub-Saharan Africa. Unlike “classical” non-typhoidal Salmonella (NTS), gastroenteritis is often absent during ST313 infections and isolates are most commonly recovered from blood, rather than from stool. This is consistent with observations in animals, in which ST313 strains displayed lower levels of intestinal colonization and higher recovery from deeper tissues relative to classic NTS isolates. A better understanding of the key environmental factors regulating these systemic infections is urgently needed. Our previous studies using dynamic Rotating Wall Vessel (RWV) bioreactor technology demonstrated that physiological levels of fluid shear regulate virulence, gene expression, and stress response profiles of classic S. Typhimurium. Here we provide the first demonstration that fluid shear alters the virulence potential and pathogenesis-related stress responses of ST313 strain D23580 in a manner that differs from classic NTS.

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection.

A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD⁵⁰ of D23580 in female BALB/c mice was 4.7 x 10⁵ CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580.

This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans–induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance.

Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.

Strategies are needed to improve repopulation of decellularized lung scaffolds with stromal and functional epithelial cells. We demonstrate that decellularized mouse lungs recellularized in a dynamic low fluid shear suspension bioreactor, termed the rotating wall vessel (RWV), contained more cells with decreased apoptosis, increased proliferation and enhanced levels of total RNA compared to static recellularization conditions. These results were observed with two relevant mouse cell types: bone marrow-derived mesenchymal stromal (stem) cells (MSCs) and alveolar type II cells (C10). In addition, MSCs cultured in decellularized lungs under static but not bioreactor conditions formed multilayered aggregates. Gene expression and immunohistochemical analyses suggested differentiation of MSCs into collagen I-producing fibroblast-like cells in the bioreactor, indicating enhanced potential for remodeling of the decellularized scaffold matrix. In conclusion, dynamic suspension culture is promising for enhancing repopulation of decellularized lungs, and could contribute to remodeling the extracellular matrix of the scaffolds with subsequent effects on differentiation and functionality of inoculated cells.

Background: GoGirlGo! (GGG) is designed to increase girls’ physical activity (PA) using a health behavior and PA-based curriculum and is widely available for free to afterschool programs across the nation. However, GGG has not been formally evaluated. The purpose of this pilot study was to evaluate the effectiveness of the GGG curricula to improve PA, and self-efficacy for and enjoyment of PA in elementary aged girls (i.e., 5-13 years).

Methods: Nine afterschool programs were recruited to participate in the pilot (within subjects repeated measures design). GGG is a 12-week program, with a once a week, one-hour lesson with 30 minutes of education and 30 minutes of PA). Data collection occurred at baseline, mid (twice), post, and at follow-up (3-months after the intervention ended). PA was assessed via accelerometry at each time point. Self-efficacy for and enjoyment of PA was measured using the Self-Efficacy Scale and the Short-PA enjoyment scale and was assessed at baseline, post, and follow-up. Fidelity was assessed at midpoint.

Results: Across all age groups there was a statistically significant increase in PA. Overall, on days GGG was offered girls accumulated an average of 11 minutes of moderate-to-vigorous PA compared to 8 minutes during non-GGG days. There was a statistically significant difference in girls’ self-efficacy for PA reported between baseline and post, which was maintained at follow-up. An improvement in enjoyment of PA for girls was found between baseline and follow-up. According to fidelity assessment, 89% of the activities within the curriculum were completed each lesson. Girls appeared to respond well to the curriculum but girls 5-7 years had difficulties paying attention and understanding discussion questions.

Conclusions: Even though there were statistically significant differences in self-efficacy for PA and enjoyment of PA, minimal increases in girls’ PA were observed. GGG curricula improvements are warranted. Future GGG programming should explore offering GGG every day, modifying activities so that they are moderate-to-vigorous in intensity, and providing additional trainings that allow staff to better implement PA and improve behavior management techniques. With modifications, GGG could provide a promising no-cost curriculum that afterschool programs may implement to help girls achieve recommendations for PA.

Background: Research provides strong evidence for improvements in depressive symptoms as a result of physical activity participation in many populations including pregnant and post-partum women. Little is known about how women who have experienced stillbirth (defined as fetal death at 20 or more weeks of gestation) feel about physical activity or use physical activity following this experience. The purpose of this study was to qualitatively explore women’s beliefs about physical activity following a stillbirth.

Methods: This was an exploratory qualitative research study. Participants were English-speaking women between the ages of 19 and 44 years who experienced a stillbirth in the past year from their recruitment date. Interviews were conducted over the phone or in-person based on participants’ preferences and location of residence and approximately 30–45 minutes in length.

Results: Twenty-four women participated in the study (M age = 33 ± 3.68 years; M time since stillbirth = 6.33 ± 3.06 months). Women’s beliefs about physical activity after stillbirth were coded into the following major themes: barriers to physical activity (emotional symptoms and lack of motivation, tired, lack of time, guilt, letting go of a pregnant body, and seeing other babies), benefits to physical activity (feeling better emotionally/mentally, helping women to cope or be therapeutic), importance of physical activity (working through grief, time for self), motivators for physical activity (body shape/weight, health, more children, be a role model, already an exerciser). Health care providers and their role in physical activity participation was also a major theme.

Conclusions: This is the first study to qualitatively explore beliefs about physical activity in women after a stillbirth. Women who have experienced stillbirth have unique beliefs about physical activity related to their experience with stillbirth. Findings from this study may help to improve the health and quality of life for women who have experienced stillbirth by utilizing physical activity as a strategy for improving depressive symptoms associated with experiencing a stillbirth. Future research in this area is highly warranted.