Assessment of the biocompatibility, stability, and suitability of novel thermoresponsive films for the rapid generation of cellular constructs

Stimuli responsive polymers (SRP) are of great interest in the bioengineering community due to their use in applications such as drug delivery and tissue engineering. One example of an SRP is poly(N-isopropyl acrylamide) or pNIPAM. This SRP has the capability of changing its conformation with a slight temperature change: adherent mammalian cells spontaneously release as a confluent cell sheet, which can be harvested for cell sheet engineering purposes. Since its initial use in 1968, many researchers have used pNIPAM to obtain a cell sheet composed of their cell type of interest. The differing protocols used for these diverse cell types, such as the conditions used for cell detachment, and the varying methods used for derivatizing substrates with pNIPAM have all led to conflicting reports on the utility of pNIPAM for cell sheet engineering purposes, as well as the relative cytotoxicity of the polymer. In this work, some of the key inconsistencies in the literature and previously unaddressed challenges when utilizing pNIPAM films are overcome for the purpose of rapid generation of cellular constructs, specifically spheroids. Pertinent characteristics of low temperature detachment are investigated for their effect on the kinetics of cell detachment. In addition, a novel, inexpensive method for obtaining pNIPAM films for mammalian cell detachment, combining pNIPAM with a sol-gel, was optimized and compared to plasma polymerization deposition. Furthermore, proper storage conditions (e.g. temperature and relative humidity) for these films were investigated to increase stability of the films for using tissue culture conditions. To increase the speed of generation of cell sheets, electrospun mats and hydrogels with a high surface area-to-volume ratio were developed. The result is a platform appropriate for the rapid formation of cellular constructs, such as engineered tissues and spheroids for cancer cell research

Hollow fibers for artificial lung applications

Artificial lungs are in use, but difficult issues remain in the field of membrane development related to fouling issues. Currently there are external artificial lungs circulating blood outside the body, taking out the carbon dioxide, and inserting oxygenated blood back into the body. An example of this type of machine is the ExtraCorporeal Membrane Oxygenation (ECMO) machine currently used in hospitals. The ECMO takes over the functions for both the lungs and the heart but is only available for short term use by patients with respiratory failure due to infections (1). The fibers in the machine develop fouling due to the fibers’ small surface areas coupled with their long term exposure to proteins in the blood. These factors continuously decrease the gas transfer abilities of the fibers until the machine is no longer effective at exchanging gases with the blood. The goal of this research is to create a lung that can function within the body until an actual lung becomes available using hollow fiber membranes with proteins attached to prevent fouling. A fouling study was performed on 17.8% polysulfone hollow fiber membranes with polydopamine and peptoid attached. Unmodified, polydopamine modified, and polydopamine and peptoid modified fibers were placed in a diffusion chamber with Bovine Serum Albumin (BSA) flowing on the outside of the fibers and oxygen flowing on the inside. Evapoporometry was run on the fibers to determine the pore size distribution of the fibers before and after the run. The evapoporometry of the fibers shows that the pores for the fibers after 48 hours in the chamber are smaller overall with a few larger pores from oxygen flowrate being too high, tearing the pores. There were also fewer pores overall in the fibers after the run; therefore, the fibers are fouling in the diffusion chamber. The oxygen concentration of the BSA was also measured while the BSA was run outside of the fibers in the chamber. The fibers were considered to be completely fouled when no more oxygen was able to diffuse into the BSA. The fouling was shown to take longer to occur in the protein coated fibers than in the unmodified fibers. Reference: (1) Downs, M. (2014, October 18). Artificial Lung Closer to Clinical Trial. Retrieved from WebMD: http://www.webmd.com/lung/features/ar tificial-lung-closer-to-clinical-trial

Relating Groundwater to Seasonal Wetlands in Southeastern Wisconsin, USA

Historically, drier types of wetlands have been difficult to characterize and are not well researched. Nonetheless, they are considered to reflect the precipitation history with little, if any, regard for possible relation to groundwater. Two seasonal coastal wetland types (wet prairie, sedge meadow) were investigated during three growing seasons at three sites in the Lake Michigan Basin, Wisconsin, USA. The six seasonal wetlands were characterized using standard soil and vegetation techniques and groundwater measurements from the shallow and deep systems. They all met wetland hydrology criteria (e.g., water within 30 cm of land surface for 5% of the growing season) during the early portion of the growing season despite the lack of appreciable regional groundwater discharge into the wetland root zones. Although root-zone duration analyses did not fit a lognormal distribution previously noted in groundwater-dominated wetlands, they were able to discriminate between the plant communities and showed that wet prairie communities had shorter durations of continuous soil saturation than sedge meadow communities. These results demonstrate that the relative rates of groundwater outflows can be important for wetland hydrology and resulting wetland type. Thus, regional stresses to the shallow groundwater system such as pumping or low Great Lake levels can be expected to affect even drier wetland types

Toward Indigenous visions of nature-based solutions: an exploration into Canadian federal climate policy

Political traction for nature-based solutions is rapidly growing as governments recognize their role in addressing the simultaneous climate and biodiversity crises. While there has been recognition of the role of Indigenous Peoples in nature-based solutions, there has also been limited academic review on their relationship. This paper explores how the Government of Canada’s conceptualization of nature-based solutions either support or prevent Indigenous sustainable self-determination. Drawing on past policy frameworks, we construct a novel four-dimensional sustainable self-determination policy lens focused on: Indigenous knowledge systems; Indigenous jurisdiction over land; the full and effective participation of Indigenous Peoples; and Indigenous Peoples as rights-holders to review a total of nine federal climate policy, planning, and science documents. Our analysis shows that while there is growing recognition of Indigenous rights, inclusion of Indigenous knowledge, and commitments to include the participation of Indigenous Peoples in the implementation of certain climate activities, there is a clear unwillingness to recognize Indigenous jurisdiction and Indigenous understandings of land as systems of reciprocal relations. Reframing nature-based solutions in the context of Canadian and international climate policy is essential not only to advance the self-determination of Indigenous Peoples, but also to create the ceremonial ground for Indigenous visions of nature-based solutions in order to address these joint crises

Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1

Overexpression of cyclin E, an activator of cyclin-dependent kinase 2, has been linked to human cancer. In cell culture models, the forced expression of cyclin E leads to aneuploidy and polyploidy, which is consistent with a direct role of cyclin E overexpression in tumorigenesis. In this study, we show that the overexpression of cyclin E has a direct effect on progression through the latter stages of mitotic prometaphase before the complete alignment of chromosomes at the metaphase plate. In some cases, such cells fail to divide chromosomes, resulting in polyploidy. In others, cells proceed to anaphase without the complete alignment of chromosomes. These phenotypes can be explained by an ability of overexpressed cyclin E to inhibit residual anaphase-promoting complex (APCCdh1) activity that persists as cells progress up to and through the early stages of mitosis, resulting in the abnormal accumulation of APCCdh1 substrates as cells enter mitosis. We further show that the accumulation of securin and cyclin B1 can account for the cyclin E–mediated mitotic phenotype

HUB City Steps: Methods and Early Findings From a Community-Based Participatory Research Trial to Reduce Blood Pressure Among African Americans

Background: Community-based participatory research (CBPR) has been recognized as an important approach to develop and execute health interventions among marginalized populations, and a key strategy to translate research into practice to help reduce health disparities. Despite growing interest in the CBPR approach, CBPR initiatives rarely use experimental or other rigorous research designs to evaluate health outcomes. This behavioral study describes the conceptual frameworks, methods, and early findings related to the reach, adoption, implementation, and effectiveness on primary blood pressure outcomes. Methods: The CBPR, social support, and motivational interviewing frameworks are applied to test treatment effects of a two-phased CBPR walking intervention, including a 6-month active intervention quasi experimental phase and 12-month maintenance randomized controlled trial phase to test dose effects of motivational interviewing. A community advisory board helped develop and execute the culturally-appropriate intervention components which included social support walking groups led by peer coaches, pedometer diary selfmonitoring, monthly diet and physical activity education sessions, and individualized motivational interviewing sessions. Although the study is on-going, three month data is available and reported. Analyses include descriptive statistics and paired t tests. Results: Of 269 enrolled participants, most were African American (94%) females (85%) with a mean age of 43.8 (SD = 12.1) years. Across the 3 months, 90% of all possible pedometer diaries were submitted. Attendance at the monthly education sessions was approximately 33%. At the 3-month follow-up 227 (84%) participants were retained. From baseline to 3-months, systolic BP [126.0 (SD = 19.1) to 120.3 (SD = 17.9) mmHg; p \u3c 0.001] and diastolic BP [83. 2 (SD = 12.3) to 80.2 (SD = 11.6) mmHg; p \u3c 0.001] were significantly reduced. Conclusions: This CBPR study highlights implementation factors and signifies the community’s active participation in the development and execution of this study. Reach and representativeness of enrolled participants are discussed. Adherence to pedometer diary self-monitoring was better than education session participation. Significant decreases in the primary blood pressure outcomes demonstrate early effectiveness. Importantly, future analyses will evaluate long-term effectiveness of this CBPR behavioral intervention on health outcomes, and help inform the translational capabilities of CBPR efforts

HUB City Steps: A 6-Month Lifestyle Intervention Improves Blood Pressure among a Primarily African-American Community

The effectiveness of community-based participatory research (CBPR) efforts to address the disproportionate burden of hypertension among African Americans remains largely untested. The objective of this 6-month, noncontrolled, pre-/post-experimental intervention was to examine the effectiveness of a CBPR intervention in achieving improvements in blood pressure, anthropometric measures, biological measures, and diet. Conducted in 2010, this multicomponent lifestyle intervention included motivational enhancement, social support provided by peer coaches, pedometer diary self-monitoring, and monthly nutrition and physical activity education sessions. Of 269 enrolled participants, 94% were African American and 85% were female. Statistical analysis included generalized linear mixed models using maximum likelihood estimation. From baseline to 6 months, blood pressure decreased significantly: mean (±standard deviation) systolic blood pressure decreased from 126.0±19.1 to 119.6±15.8 mm Hg, P=0.0002; mean diastolic blood pressure decreased from 83.2±12.3 to 78.6±11.1 mm Hg, P

HUB City Steps: A 6-Month Lifestyle Intervention Improves Blood Pressure among a Primarily African-American Community

The effectiveness of community-based participatory research (CBPR) efforts to address the disproportionate burden of hypertension among African Americans remains largely untested. The objective of this 6-month, noncontrolled, pre-/post-experimental intervention was to examine the effectiveness of a CBPR intervention in achieving improvements in blood pressure, anthropometric measures, biological measures, and diet. Conducted in 2010, this multicomponent lifestyle intervention included motivational enhancement, social support provided by peer coaches, pedometer diary self-monitoring, and monthly nutrition and physical activity education sessions. Of 269 enrolled participants, 94% were African American and 85% were female. Statistical analysis included generalized linear mixed models using maximum likelihood estimation. From baseline to 6 months, blood pressure decreased significantly: mean (±standard deviation) systolic blood pressure decreased from 126.0±19.1 to 119.6±15.8 mm Hg, P=0.0002; mean diastolic blood pressure decreased from 83.2±12.3 to 78.6±11.1 mm Hg, P

Management of Hypertriglyceridemia-Induced Acute Pancreatitis in a Nondiabetic Patient

Hypertriglyceridemia-induced acute pancreatitis treatment strategies are not well defined in current literature or guidelines. One therapy option is an insulin infusion accompanied by a dextrose infusion to avoid hypoglycemia. The purpose of this case report is to highlight dosing considerations for dextrose infusions in nondiabetic patients. We describe a case of hypertriglyceridemia-induced acute pancreatitis in a 34-year-old nondiabetic female patient treated with a reduced-dose insulin infusion, complicated by hypoglycemic episodes requiring dextrose infusion titrations. Empirical initiation of a higher dextrose concentration infusion with glucose level titrations should be considered to avoid hypoglycemia for nondiabetic patients treated with an insulin infusion to lower triglyceride levels. In this case, clinical pharmacy assistance was imperative for successful treatment with a reduced-dose insulin infusion and titrated dextrose infusion in the management of hypertriglyceridemia-induced acute pancreatitis

The signature of fine scale local adaptation in Atlantic salmon revealed from common garden experiments in nature

Understanding the extent, scale and genetic basis of local adaptation (LA) is important for conservation and management. Its relevance in salmonids at microgeographic scales, where dispersal (and hence potential gene flow) can be substantial, has however been questioned. Here, we compare the fitness of communally reared offspring of local and foreign Atlantic salmon Salmo salar from adjacent Irish rivers and reciprocal F-1 hybrid crosses between them, in the wild home\u27 environment of the local population. Experimental groups did not differ in wild smolt output but a catastrophic flood event may have limited our ability to detect freshwater performance differences, which were evident in a previous study. Foreign parr exhibited higher, and hybrids intermediate, emigration rates from the natal stream relative to local parr, consistent with genetically based behavioural differences. Adult return rates were lower for the foreign compared to the local group. Overall lifetime success of foreigners and hybrids relative to locals was estimated at 31% and 40% (mean of both hybrid groups), respectively. The results imply a genetic basis to fitness differences among populations separated by only 50km, driven largely by variation in smolt to adult return rates. Hence even if supplementary stocking programs obtain broodstock from neighbouring rivers, the risk of extrinsic outbreeding depression may be high