Perfusion Cell Seeding and Expansion in Dual Mechanical Stimulation Bioreactor for In Vitro Tissue Development

BACKGROUND: Engineered tissues are an exciting potential source of small diameter vascular grafts due to limited supply and patency of available alternatives. Engineered tissue vascular grafts (ETVGs) will provide physiological function that resembles native arteries and maintain the required mechanical properties as they integrate with host tissue. Mechanical stimulation during incubation encourages proper cell alignment and increases extracellular matrix deposition. The enhanced organization of the engineered tissue leads to improved compliance over synthetic alternatives without sacrificing strength and may lead to better integration in vivo. METHODS: We have developed a bioreactor that mechanically trains grafts during incubation. To test the seeding efficiency of the bioreactor, rat vascular smooth muscle cells (VSMC) were seeded onto electrospun PCL scaffolds by perfusion at various cell concentrations then incubated Page | 15 for 1 week under static conditions. We assessed gross morphology with H&E; collagen with picrosirius red; and VSMC density with DAPI. ETVGs were further evaluated with mechanical testing and scanning electron microscopy to evaluate mechanical and microstructural properties. RESULTS: Cells were successfully seeded evenly onto the luminal surface of electrospun PCL scaffolds. Cells remained viable and continued to proliferate and deposit ECM throughout incubation. CONCLUSIONS: Progress in the ETVG paradigm requires a systematic approach toward better understanding of the cause-effect interplay between implant properties, host reactions, and their modulation with controllable parameters. Future directions involve the assessment of the effects of mechanical training on growth and remodeling of engineered tissues in vitro and subsequent effects on the foreign body response post-implantation in a murine model.https://scholarscompass.vcu.edu/gradposters/1115/thumbnail.jp

Elastic Foundations as Heterogeneous Adventitial Boundary Condition for the Assessment of Aortic Wall and Peri-Aortic Stiffness from Dense-MRI Data Using Inverse FEM Approach

Background: The establishment of in vivo, patient-specific, and regionally resolved techniques to quantify aortic properties is key for improving risk assessment in clinical practice and scientific understanding of cardiovascular growth and remodeling. Many in vivo studies quantify vascular stiffness using Pulse Wave Velocity. This method provides an averaged measure of stiffness for the entire aorta, ignoring variations in wall stiffness and boundary conditions. Previous studies using Displacement Encoding with Stimulated Echoes Magnetic Resonance Imaging (DENSE-MRI) suggested that the infrarenal abdominal aorta (IAA) deforms heterogeneously throughout the cardiac cycle. Method: Herein, we hypothesize that the aortic wall strain heterogeneity is driven in healthy aortas by adventitial tethering to perivascular tissues that can be modeled with elastic foundation boundary conditions (EFBC) using a collection of linear-springs with a circumferential distribution of stiffness. Nine healthy-human IAAs were modeled using patient-specific imaging and displacement fields from SSFP and DENSE MRI, followed by assessment of aortic wall properties and heterogeneous EFBC parameters using inverse Finite Element Method (FEM). Results: In contrast to traction-free boundary condition, prescription of EFBC reduced the nodal displacement error by 60% and reproduced the DENSE-derived strain distribution. Estimated aortic stiffness was in agreement with previously reported experimental test data. The distribution of normalized EFBC stiffness was consistent among all patients and spatially correlated to standard peri-aortic anatomical features. Conclusion: Results suggest that EFBCs can be generalized for human adults with normal anatomy. This approach is computationally inexpensive, making it ideal for large-population clinical research and incorporation into computational cardiovascular fluid-structure analyses.https://scholarscompass.vcu.edu/gradposters/1113/thumbnail.jp

Biomechanical behavior of bioprosthetic heart valve heterograft tissues: characterization, simulation, and performance

The use of replacement heart valves continues to grow due to the increased prevalence of valvular heart disease resulting from an ageing population. Since bioprosthetic heart valves (BHVs) continue to be the preferred replacement valve, there continues to be a strong need to develop better and more reliable BHVs through and improved the general understanding of BHV failure mechanisms. The major technological hurdle for the lifespan of the BHV implant continues to be the durability of the constituent leaflet biomaterials, which if improved can lead to substantial clinical impact. In order to develop improved solutions for BHV biomaterials, it is critical to have a better understanding of the inherent biomechanical behaviors of the leaflet biomaterials, including chemical treatment technologies, the impact of repetitive mechanical loading, and the inherent failure modes. This review seeks to provide a comprehensive overview of these issues, with a focus on developing insight on the mechanisms of BHV function and failure. Additionally, this review provides a detailed summary of the computational biomechanical simulations that have been used to inform and develop a higher level of understanding of BHV tissues and their failure modes. Collectively, this information should serve as a tool not only to infer reliable and dependable prosthesis function, but also to instigate and facilitate the design of future bioprosthetic valves and clinically impact cardiology

"I go I die, I stay I die, better to stay and die in my house": understanding the barriers to accessing health care in Timor-Leste.

BACKGROUND: Despite public health care being free at the point of delivery in Timor-Leste, wealthier patients access hospital care at nearly twice the rate of poorer patients. This study seeks to understand the barriers driving inequitable utilisation of hospital services in Timor-Leste from the perspective of community members and health care managers. METHODS: This multisite qualitative study in Timor-Leste conducted gender segregated focus groups (n = 8) in eight districts, with 59 adults in urban and rural settings, and in-depth interviews (n = 8) with the Director of community health centres. Communication was in the local language, Tetum, using a pre-tested interview schedule. Approval was obtained from community and national stakeholders, with written consent from participants. RESULTS: Lack of patient transport is the critical cross-cutting issue preventing access to hospital care. Without it, many communities resort to carrying patients by porters or on horseback, walking or paying for (unaffordable) private arrangements to reach hospital, or opt for home-based care. Other significant out-of-pocket expenses for hospital visits were blood supplies from private suppliers; accommodation and food for the patient and family members; and repatriation of the deceased. Entrenched nepotism and hospital staff denigrating patients' hygiene and personal circumstances were also widely reported. Consequently, some respondents asserted they would never return to hospital, others delayed seeking treatment or interrupted their treatment to return home. Most considered traditional medicine provided an affordable, accessible and acceptable substitute to hospital care. Obtaining a referral for higher level care was not a significant barrier to gaining access to hospital care. CONCLUSIONS: Onerous physical, financial and socio-cultural barriers are preventing or discouraging people from accessing hospital care in Timor-Leste. Improving access to quality primary health care at the frontline is a key strategy for ensuring universal access to health care, pursued alongside initiatives to overcome the multi-faceted barriers to hospital care experienced by the vulnerable. Improving the availability and functioning of patient transport services, provision of travel subsidies to patients and their families and training hospital staff in standards of professional care are some options available to government and donors seeking faster progress towards universal health coverage in Timor-Leste

Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial

Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N = 35) when compared to placebo (N = 34). Furthermore, at D2 just patients treated with ayahuasca (N = 14), and not with placebo (N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769)

Geo-environmental mapping using physiographic analysis: constraints on the evaluation of land instability and groundwater pollution hazards in the Metropolitan District of Campinas, Brazil

Geo-environmental terrain assessments and territorial zoning are useful tools for the formulation and implementation of environmental management instruments (including policy-making, planning, and enforcement of statutory regulations). They usually involve a set of procedures and techniques for delimitation, characterisation and classification of terrain units. However, terrain assessments and zoning exercises are often costly and time-consuming, particularly when encompassing large areas, which in many cases prevent local agencies in developing countries from properly benefiting from such assessments. In the present paper, a low-cost technique based on the analysis of texture of satellite imagery was used for delimitation of terrain units. The delimited units were further analysed in two test areas situated in Southeast Brazil to provide estimates of land instability and the vulnerability of groundwater to pollution hazards. The implementation incorporated procedures for inferring the influences and potential implications of tectonic fractures and other discontinuities on ground behaviour and local groundwater flow. Terrain attributes such as degree of fracturing, bedrock lithology and weathered materials were explored as indicators of ground properties. The paper also discusses constraints on- and limitations of- the approaches taken

An extensive reef system at the Amazon River mouth

Large rivers create major gaps in reef distribution along tropical shelves. The Amazon River represents 20% of the global riverine discharge to the ocean, generating up to a 1.3 x 10(6)-km(2) plume, and extensive muddy bottoms in the equatorial margin of South America. As a result, a wide area of the tropical North Atlantic is heavily affected in terms of salinity, pH, light penetration, and sedimentation. Such unfavorable conditions were thought to imprint a major gap in Western Atlantic reefs. We present an extensive carbonate system off the Amazon mouth, underneath the river plume. Significant carbonate sedimentation occurred during lowstand sea level, and still occurs in the outer shelf, resulting in complex hard-bottom topography. A permanent near-bottom wedge of ocean water, together with the seasonal nature of the plume's eastward retroflection, conditions the existence of this extensive (similar to 9500 km(2)) hard-bottom mosaic. The Amazon reefs transition from accretive to erosional structures and encompass extensive rhodolith beds. Carbonate structures function as a connectivity corridor for wide depth-ranging reef-associated species, being heavily colonized by large sponges and other structure-forming filter feeders that dwell under low light and high levels of particulates. The oxycline between the plume and subplume is associated with chemoautotrophic and anaerobic microbial metabolisms. The system described here provides several insights about the responses of tropical reefs to suboptimal and marginal reef-building conditions, which are accelerating worldwide due to global changes.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERS)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)BrasoilMCTIBrazilian NavyU.S. NSFGordon and Betty Moore Foundation (GBMF)Univ Fed Rio de Janeiro UFRJ, Inst Biol, BR-21941599 Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, COPPE, Inst Alberto Luiz Coimbra Posgrad & Pesquisa Engn, Lab Sistemas Avancados Gestao Prod, BR-21941972 Rio de Janeiro, RJ, BrazilInst Pesquisas Jardim Bot Rio de Janeiro, BR-22460030 Rio De Janeiro, RJ, BrazilUniv Sao Paulo, Inst Oceanog, BR-05508120 Sao Paulo, SP, BrazilUniv Fed Espirito Santo, Dept Oceanog, BR-29199970 Vitoria, ES, BrazilUniv Estadual Norte Fluminense, Lab Ciencias Ambientais, Ctr Biociencias & Biotecnol, BR-28013602 Campos Dos Goytacazes, RJ, BrazilUniv Fed Fluminense, Inst Geociencias, BR-24210346 Niteroi, RJ, BrazilUniv Fed Fluminense, Inst Biol, BR-24210130 Niteroi, RJ, BrazilUniv Fed Rio de Janeiro, Museo Nacl, BR-20940040 Rio De Janeiro, RJ, BrazilFed Univ Para, Inst Estudos Costeiros, BR-68600000 Braganca, PA, BrazilUniv Fed Sao Paulo, Dept Ciencias Mar, BR-11070100 Santos, SP, BrazilUniv Fed Pernambuco, Dept Oceanog, BR-50670901 Recife, PE, BrazilUniv Georgia, Dept Marine Sci, Athens, GA 30602 USAUniv Fed Paraiba, BR-58297000 Rio Tinto, PB, BrazilUniv Estadual Santa Cruz, Dept Ciencias Biol, BR-45650000 Ilheus, BA, BrazilUniv Fed Sao Paulo, Dept Ciencias Mar, BR-11070100 Santos, SP, BrazilU.S. NSF: OCE-0934095GBMF: 2293GBMF: 2928Web of Scienc