Reducing Disparities by way of a Cancer Disparities Research Training Program

Background: For minority populations, there is a continuing disparity in the burden of death and illness from cancer. Research to address this disparity should be conducted by investigators who can best understand and address the needs of culturally diverse communities. However, minorities are under-represented in health-related research. The goal of this project was to develop and evaluate an approach to motivating and preparing master’s degree students for careers dedicated to cancer disparities research. Method: A Cancer Disparities Research Training Program (CDRTP) was initiated in 2010. The program consists of coursework, practicum experiences, and research opportunities. Assessment of the curriculum is based on monitoring achievement of evaluation indicators and includes a quantitative assessment and qualitative approach. Results: In its first three years, the program graduated 20 trainees, all of whom were minorities (18 African Americans and two Asians). When asked about career goals, two-thirds of the trainees indicated interest in pursuing careers in research on cancer prevention and control. The trainees expressed high satisfaction with the courses, instructor, materials, and curriculum. Although trainees had suggestions about course details, evaluations overall were positive. Across focus groups, three recurrent themes emerged regarding activities to enhance the student experience: having a wider variety of topics, more guest speakers, and field trips. Conclusion: The CDRTP was intended to recruit students – primarily African Americans – into research on prevention and control of cancer disparities. Although final evaluation of the program’s overall outcome will not be available for several years, a preliminary evaluation indicates the program is being successful

Protocol development to overcome bioprocess bottlenecks in the large-scale expansion of high quality hIPSC aggregates in vertical-wheel bioreactors

Human-induced pluripotent stem cells (hiPSCs) have generated a great deal of attention owing to their capacity for self-renewal and trilineage differentiation. hiPSCs are cultured as adherent colonies at small scale, which is sufficient to generate cells for experimental purposes but impractical to achieve large quantities for clinical applications. Bioreactor-based processes are the method of choice for efficient expansion and differentiation of cells. Current protocols for the expansion of hiPSCs, however, utilize horizontal impeller, paddle, or rocking wave mixing method bioreactors which require large static cell-culture starting populations and achieve only moderate cell fold increases within the bioreactor. We have recently demonstrated that the vertical-wheel bioreactor produces a unique fluid flow pattern that results in a homogeneous distribution of hydrodynamic forces, making it the opportune environment for systematic bioprocess optimization of hiPSC expansion. Please click Additional Files below to see the full abstract

Computational fluid dynamic characterization of vertical-wheel bioreactors used for effective scale-up of human induced pluripotent stem cell aggregate culture

Innovations in engineering and bioprocess development have accelerated the transition of induced pluripotent stem cell (iPSC) cultivation and use from the bench-top to large-scale clinical manufacturing. Owing to their potency, proliferation capabilities, and ability to overcome the challenges associated with traditional sources of pluripotent stem cells (PSCs), iPSCs have generated significant interest in the field of regenerative medicine for more than a decade. However, traditional bench scale methods to expand iPSCs, including petri dishes and T-flasks, are insufficient to achieve clinically relevant numbers. For iPSC treatments, cell dosages will range from 109 – 1012 cells per patient depending on the therapeutic target. To achieve the required number of cells in an effective and scalable manner, bioreactors will need to be used. Induced pluripotent stem cells (iPSCs) have proven to be extremely sensitive to the bioreactor hydrodynamic environment, making the use of suspension bioreactors to produce quality-assured cells at clinical and commercial scales very challenging. The PBS vertical-wheel (VW) bioreactor combines radial and axial flow components to produce uniform hydrodynamic force distributions, making it a promising platform to overcome the scale-up challenges associated with iPSCs. Please click Additional Files below to see the full abstract

Osteoprotegerin reduces osteoclast resorption activity without affecting osteogenesis on nanoparticulate mineralized collagen scaffolds.

The instructive capabilities of extracellular matrix-inspired materials for osteoprogenitor differentiation have sparked interest in understanding modulation of other cell types within the bone regenerative microenvironment. We previously demonstrated that nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffolds efficiently induced osteoprogenitor differentiation and bone healing. In this work, we combined adenovirus-mediated delivery of osteoprotegerin (AdOPG), an endogenous anti-osteoclastogenic decoy receptor, in primary human mesenchymal stem cells (hMSCs) with MC-GAG to understand the role of osteoclast inactivation in augmentation of bone regeneration. Simultaneous differentiation of osteoprogenitors on MC-GAG and osteoclast progenitors resulted in bidirectional positive regulation. AdOPG expression did not affect osteogenic differentiation alone. In the presence of both cell types, AdOPG-transduced hMSCs on MC-GAG diminished osteoclast-mediated resorption in direct contact; however, osteoclast-mediated augmentation of osteogenic differentiation was unaffected. Thus, the combination of OPG with MC-GAG may represent a method for uncoupling osteogenic and osteoclastogenic differentiation to augment bone regeneration

Cardiac beriberi and malnutrition: rare complication of paracoccidioidomycosis

Paracoccidioidomycosis is an endemic systemic mycosis that predominates in southern Mexico, parts of Central America, and South America. It is caused by a dimorphic fungus and is generally acquired through the lungs, from where it disseminates. Paracoccidioidomycosis has different clinical manifestations that require differentiation with tuberculosis, Hodgkin disease, several systemic and subcutaneous mycoses, and squamous cell carcinoma. Radiologic abnormalities in the lung fields may be seen. Mucous membrane lesions occasionally occur. The diagnosis is confirmed by finding yeast-like elements of P. brasiliensis in microscopic examinations of wet preparations of specimens submitted for mycologic studies. The occurrence of malnutrition and particularly beri beri conditions concomitant with paracoccidioidomycosis is uncommon. We report a case of a patient of low socio-economic status, without  permanent employment , possibly carrying out work as a bricklayer or working on small farms during the harvest season, with a five-year history of oral cavity lesions, which resulted  in difficulty eating  and  thus weight loss. A diagnosis of paracoccidioidomycosis was made through direct microscopy examination, culture and multisystem involvement was confirmed through imaging tests, including dilatation and dysfunction of the right ventricle. The hypothesis of Cardiac Beri-Beri related to thiamine deficiency was raised. The treatment was carried out with thiamine supplementation and liposomal amphotericin B, with excellent clinical evolution of the patient. This case highlights the importance of early recognition of paracoccidioidomycosis in its early stages and the adoption of proactive measures in the search for possible organic complications caused by nutritional deficiencies in prolonged cases

Engineered Polymer Composites Through Electrospun Nanofiber Coating of Fiber Tows

Composite materials offer significant weight savings in many aerospace applications. The toughness of the interface of fibers crossing at different angles often determines failure of composite components. A method for toughening the interface in fabric and filament wound components using directly electrospun thermoplastic nanofiber on carbon fiber tow is presented. The method was first demonstrated with limited trials, and then was scaled up to a continuous lab scale process. Filament wound tubes were fabricated and tested using unmodified baseline towpreg material and nanofiber coated towpreg

Sex and stressor modality influence acute stress-induced dynamic changes in corticolimbic endocannabinoid levels in adult Sprague Dawley rats

Research over the past few decades has established a role for the endocannabinoid system in contributing to the neural and endocrine responses to stress exposure. The two endocannabinoid ligands, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), both play roles in regulating the stress response and both exhibit dynamic changes in response to stress exposure. Most of this previous research, however, was conducted in male rodents. Given that, especially in rodents, the stress response is influenced by sex, an understanding of how these dynamic responses of endocannabinoids in response to stress is influenced by sex could provide insight into sex differences of the acute stress response. We exposed adult, Sprague Dawley rats to different commonly utilized acute stress modalities, specifically restraint, swim and foot shock stress. Thirty minutes following stress onset, we excised the amygdala, hippocampus and medial prefrontal cortex, corticolimbic brain regions involved in the stress response, to measure endocannabinoid levels. When AEA levels were altered in response to restraint and swim stress, they were reduced, whereas exposure to foot shock stress led to an increase in the amygdala. 2-AG levels, when they were altered by stress exposure were only increased, specifically in males in the amygdala following swim stress, and in the hippocampus and medial prefrontal cortex overall following foot shock stress. This increase in 2-AG levels following stress only in males was the only sex difference found in stress-induced changes in endocannabinoid levels. There were no consistent sex differences observed. Collectively, these data contribute to our further understanding of the interactions between stress and endocannabinoid function

NASA's Functional Task Test: High Intensity Exercise Improves the Heart Rate Response to a Stand Test Following 70 Days of Bedrest

Cardiovascular adaptations due to spaceflight are modeled with 6deg head-down tilt bed rest (BR) and result in decreased orthostatic tolerance. We investigated if high-intensity resistive and aerobic exercise with and without testosterone supplementation would improve the heart rate (HR) response to a 3.5-min stand test and how quickly these changes recovered following BR. During 70 days of BR male subjects performed no exercise (Control, n=10), high intensity supine resistive and aerobic exercise (Exercise, n=9), or supine exercise plus supplemental testosterone (Exercise+T, n=8; 100 mg i.m., weekly in 2-week on/off cycles). We measured HR for 2 min while subjects were prone and for 3 min after standing twice before and 0, 1, 6, and 11 days after BR. Mixed-effects linear regression models were used to evaluate group, time, and interaction effects. Compared to pre-bed rest, prone HR was elevated on BR+0 and BR+1 in Control, but not Exercise or Exercise+T groups, and standing HR was greater in all 3 groups. The increase in prone and standing HR in Control subjects was greater than either Exercise or Exercise+T groups and all groups recovered by BR+6. The change in HR from prone to standing more than doubled on BR+0 in all groups, but was significantly less in the Exericse+T group compared to the Control, but not Exercise group. Exercise reduces, but does not prevent the increase in HR observed in response to standing. The significantly lower HR response in the Exercise+T group requires further investigation to determine physiologic significance

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases

Joint Strength Optimization and Damping Assessment of NiTi-Polymer Matrix Hybrid Composites

Approaches to optimize the adhesive joint strength between shape memory alloy ribbons and carbon fiber-reinforced epoxy composites were investigated for potential use as either an actuating structure or a dampening composite for structural applications. The interfacial bond strength between nickel-titanium (NiTi) and a polymer matrix composite (PMC) was measured by double lap shear testing as a function of NiTi surface treatment and adhesive material. The effect of NiTi surface treatment on damping was investigated using dynamic mechanical analysis. Lap shear data show that treating the surfaces of NiTi ribbons by light sandblasting and primer application increased the interfacial bond strength by 20 percent over the baseline composite structure. Lap shear data also reveal that out of three different film adhesives investigated, samples bonded with AF 191U and Hysol 9696U display the highest adhesive joint strengths. Optical microscopy reveals that most samples failed by either cohesive failure within the adhesive or by adhesive failure at either the adhesive/PMC or NiTi/adhesive interface. Adhering NiTi to the PMC did not appear to negatively impact damping performance; however, a more thorough examination into NiTi's role on vibration damping should be investigated