Characterization and optimization of actuating poly(ethylene glycol) diacrylate/acrylic acid hydrogels as artificial muscles
Large volume deficiencies in skeletal muscle tissue fail to heal with conservative treatments, and improved treatment methods are needed. Tissue engineered scaffolds for skeletal muscle need to mimic the optimal environment for muscle development by providing the proper electric, mechanical, and chemical cues. Electroactive polymers, polymers that change in size or shape in response to an electric field, may be able to provide the optimal environment for muscle growth. In this study, an electroactive polymer made from poly(ethylene glycol) diacrylate (PEGDA) and acrylic acid (AA) is characterized and optimized for movement and biocompatibility. Hydrogel sample thickness, overall polymer concentration, and the ratio of PEGDA to AA were found to significantly impact the actuation response. C2C12 mouse myoblast cells attached and proliferated on hydrogel samples with various ratios of PEGDA to AA. Future experiments will produce hydrogel samples combined with aligned guidance cues in the form of electrospun fibers to provide a favorable environment for muscle development.
Carotid endarterectomy in octogenarian veterans: does age affect outcome? A single-center experience
The efficacy of carotid endarterectomy (CEA) in octogenarians is controversial. Recent reports have examined this question in the general population, but little data exist on veterans. With the emergence of carotid artery stenting, we need to evaluate the role of CEA in treating elderly veterans with carotid stenosis.
Retrospective chart review of all CEAs performed between January 1995 and December 2004.
A total of 286 procedures were performed in 239 patients; 39 procedures were performed in 33 octogenarians, and 247 procedures were performed in 206 younger veterans. Both groups had similar preoperative comorbidities. There were no statistically significant differences between octogenarians and younger veterans for postoperative stroke (2% vs. 1%), death (0% vs. 1%), myocardial infarction (5% vs. 2%), length of stay (7 ± 19 vs. 3 ± 8 days), or 4-year survival (53% vs. 57%).
CEA can be safely performed in octogenarian veterans with outcomes similar to younger veterans.
Hydrogel Microsphere Encapsulation of a Cell-Based Gene Therapy System Increases Cell Survival of Injected Cells, Transgene Expression, and Bone Volume in a Model of Heterotopic Ossification
Bone morphogenetic proteins (BMPs) are well known for their osteoinductive activity, yet harnessing this capacity remains a high-priority research focus. We present a novel technology that delivers high BMP-2 levels at targeted locations for rapid endochondral bone formation, enhancing our preexisting cell-based gene therapy system by microencapsulating adenovirus-transduced cells in nondegradable poly(ethylene glycol) diacrylate (PEGDA) hydrogels before intramuscular delivery. This study evaluates the in vitro and in vivo viability, gene expression, and bone formation from transgenic fibroblasts encapsulated in PEGDA microspheres. Fluorescent viability and cytotoxicity assays demonstrated >95% viability in microencapsulated cells. ELISA and alkaline phosphatase assays established that BMP-2 secretion and specific activity from microencapsulated AdBMP2-transduced fibroblasts were not statistically different from monolayer. Longitudinal transgene expression studies of AdDsRed-transduced fibroblasts, followed through live animal optical fluorescent imaging, showed that microencapsulated cells expressed longer than unencapsulated cells. When comparable numbers of microencapsulated AdBMP2-transduced cells were intramuscularly injected into mice, microcomputed tomography evaluation demonstrated that the resultant heterotopic bone formation was approximately twice the volume of unencapsulated cells. The data suggest that microencapsulation protects cells and prolongs and spatially distributes transgene expression. Thus, incorporation of PEGDA hydrogels significantly advances current gene therapy bone repair approaches.
Cell microencapsulation with synthetic polymers
The encapsulation of cells into polymeric microspheres or microcapsules has permitted the transplantation of cells into human and animal subjects without the need for immunosuppressants. Cell‐based therapies use donor cells to provide sustained release of a therapeutic product, such as insulin, and have shown promise in treating a variety of diseases. Immunoisolation of these cells via microencapsulation is a hotly investigated field, and the preferred material of choice has been alginate, a natural polymer derived from seaweed due to its gelling conditions. Although many natural polymers tend to gel in conditions favorable to mammalian cell encapsulation, there remain challenges such as batch to batch variability and residual components from the original source that can lead to an immune response when implanted into a recipient. Synthetic materials have the potential to avoid these issues; however, historically they have required harsh polymerization conditions that are not favorable to mammalian cells. As research into microencapsulation grows, more investigators are exploring methods to microencapsulate cells into synthetic polymers. This review describes a variety of synthetic polymers used to microencapsulate cells. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 846–859, 2015.
Architecture of Columnar Nacre, and Implications for Its Formation Mechanism
We analyze the structure of Haliotis rufescens nacre, or mother-of-pearl, using synchrotron spectromicroscopy and x-ray absorption near-edge structure spectroscopy. We observe imaging contrast between adjacent individual nacre tablets, arising because different tablets have different crystal orientations with respect to the radiation’s polarization vector. Comparing previous data and our new data with models for columnar nacre growth, we find the data are most consistent with a model in which nacre tablets are nucleated by randomly distributed sites in the organic matrix layers.
M1/70 attenuates blood-borne neutrophil oxidants, activation, and myofiber damage following stretch injury
The purpose of this study was to determine the role of the CD11b-dependent respiratory burst in neutrophil oxidant generation and activation, interleukin-8 (IL-8) production, and myofiber damage after muscle stretch injury by using the monoclonal antibody M1/70 to block this pathway. Twelve male New Zealand White rabbits were randomly assigned to a treatment group: M1/70 (n = 6), IgG isotype control (n = 3), or saline control (n = 3). After intravenous injection of the assigned agent under gas anesthesia, a standardized single-stretch injury was created in the right tibialis anterior, whereas the left tibialis anterior underwent a sham surgery. Blood-borne neutrophil oxidant generation and CD11b receptor density and plasma IL-8 levels were measured pre- and 24 h postinjury. Damage was assessed histologically at the hematoma site by counting torn myofibers. M1/70 group demonstrated decreased blood-borne neutrophil oxidant generation (P < 0.05) and CD11b receptor density (P < 0.05), an increase in plasma IL-8 concentration (P < 0.01), and less torn myofibers (P < 0.01) compared with IgG isotype or saline control groups. These data indicate that 1) CD11b-dependent respiratory burst is a major source of oxidants produced by the neutrophil, and that treatment with M1/70 2) attenuates neutrophil activation status, 3) increases plasma IL-8 concentration, and 4) minimizes myofiber damage 24 h postmuscle stretch injury.
Situational Predictors of Sexual Risk Episodes Among Men with HIV who Have Sex with Men
Background: Men with HIV who have sex with men (MSM) represent the largest group of people living with HIV/AIDS in the United States. It is important to understand the sexual risk-taking behaviours that may be linked to the transmission of HIV and other sexually transmitted infections in this population. Models of HIV risk that focus solely on personal factors have been demonstrated to be ineffective at explaining risk behaviour. Rather, in order to fully understand sexual risk-taking, it is important to examine the factors linked to high-risk sexual situations and not solely the factors linked to potentially high-risk people.
Methods: A diverse sample of 100 MSM with HIV completed a 6-week internet-based sex diary that collected detailed information on recent sexual encounters. In total, information on over 250 sexual episodes was collected and analysed. Generalised linear mixed models were used to examine situational predictors of risk episodes.
Results: Analyses revealed that drug use by self and sex partners (examined individually and together) were positively related to risk episodes. Likewise, having a sex partner met online and having a sexual encounter in a sex party or bathhouse setting was linked to risk episodes. Sexual episodes that involved a sex-partner who was perceived as sexually desirable and those involving communication about HIV and/or condom use with partners each were negatively related to risk.
Conclusions: Situational factors play an important role in explaining sexual risk-taking among MSM with HIV. Researchers should place a greater focus on drug use and characteristics of sex partners and settings in which sexual behaviours occur as situational predictors of risk in order to comprehensively understand sexual risk-taking in this population.
Online Network Influences on Emerging Adults’ Alcohol and Drug Use
Researchers have reported that network characteristics are associated with substance use behavior. Considering that social interactions within online networks are increasingly common, we examined the relationship between online network characteristics and substance use in a sample of emerging adults (ages 18–24) from across the United States (N = 2,153; M = 21 years old; 47 % female; 70 % White). We used regression analyses to examine the relationship between online ego network characteristics (i.e., characteristics of individuals directly related to the focal participant plus the relationships shared among individuals within the online network) and alcohol use and substance use, respectively. Alcohol use was associated with network density (i.e., interconnectedness between individuals in a network), total number of peer ties, and a greater proportion of emotionally close ties. In sex-stratified models, density was related to alcohol use for males but not females. Drug use was associated with an increased number of peer ties, and the increased proportion of network members’ discussion and acceptance of drug use, respectively. We also found that online network density and total numbers of ties were associated with more personal drug use for males but not females. Conversely, we noted that social norms were related to increased drug use and this relationship was stronger for females than males. We discuss the implications of our findings for substance use and online network research.
Substance Use and Sexual Risk Behavior in HIV-Positive Men who Have Sex with Men: An Episode-Level Analysis
Men who have sex with men (MSM) make up nearly half of all people living with HIV in the United States. The prevalence of the epidemic in this population makes it vitally important to understand the transmission of the infection and to develop methods to prevent its spread. The current study uses longitudinal diary methods to examine relationships between substance use and unprotected anal intercourse in a sample of 158 HIV-positive, mostly ethnic minority MSM. Results indicate that both general substance use and use of specific drugs (i.e., inhalants, cocaine, crack, and club drugs) have a substantial impact on the sexual risk behavior of this population.
Understanding the Role of mHealth and Other Media Interventions for Behavior Change to Enhance Child Survival and Development in Low-and Middle-Income Countries: An Evidence Review
Given the high morbidity and mortality among children in low- and middle-income countries as a result of preventable causes, the U.S. government and the United Nations Children’s Fund convened an Evidence Summit on Enhancing Child Survival and Development in Lower- and Middle-Income Countries by Achieving Population-Level Behavior Change on June 3–4, 2013, in Washington, D.C. This article summarizes evidence for technological advances associated with population-level behavior changes necessary to advance child survival and healthy development in children under 5 years of age in low- and middle-income countries. After a rigorous evidence selection process, the authors assessed science, technology, and innovation papers that used mHealth, social/transmedia, multiplatform media, health literacy, and devices for behavior changes supporting child survival and development. Because of an insufficient number of studies on health literacy and devices that supported causal attribution of interventions to outcomes, the review focused on mHealth, social/transmedia, and multiplatform media. Overall, this review found that some mHealth interventions have sufficient evidence to make topic-specific recommendations for broader implementation, scaling, and next research steps (e.g., adherence to HIV/AIDS antiretroviral therapy, uptake and demand of maternal health service, and compliance with malaria treatment guidelines). While some media evidence demonstrates effectiveness in changing cognitive abilities, knowledge, and attitudes, evidence is minimal on behavioral endpoints linked to child survival. Population level behavior change is necessary to end preventable child deaths. Donors and low- and middle-income countries are encouraged to implement recommendations for informing practice, policy, and research decisions to fully maximize the impact potential of mHealth and multimedia for child survival and development.
Despite the overall decline in under-5 mortality rates from 12.6 million in 1990 to 6.6 million in 2012, 21,000 under-5 child deaths occur daily (You, Bastian, Wu, & Wardlaw, 2013). Many of these under-5 child deaths could be averted with wider deployment of existing prevention and treatment interventions. Healthy behaviors on the part of families, communities, and health systems (e.g., completing vaccinations, using oral rehydration, breast feeding, spacing pregnancies, handwashing, and home compliance with treatment guidelines) could dramatically accelerate reductions in under-5 mortality (Black, Morris, & Bryce, 2003; Lozano et al., 2011; Rajaratnam et al., 2010). Health professionals, governments, and researchers have implemented a number of interventions to address the health of children in low- and middle-income countries (LMICs), often focusing on improving the coverage and quality of interventions of known efficacy. To date, there has been no systematic review of the science, technology, and innovation-based support related to the effectiveness of evidence-based interventions that could aid in the elimination of under-5 child morbidity and mortality in LMICs.
Communication and media platforms have been used to promote change in health behaviors for decades. Printed pamphlets, billboards, radio, television, the Internet, and now mobile devices have all been used to communicate information to a range of populations (Free et al., 2013; Naugle & Hornik, 2014). Rapid changes have occurred in technologies and their availability, as well as in the ways individuals and groups use and interface with these technologies. As with technological developments of the past, the modern emergence of mobile health (mHealth) and new social/transmedia platforms affords another opportunity for reaching, teaching, connecting, motivating, and empowering individuals and groups to address specific health concerns.
Despite the relatively nascent state of these fields, at present, globally thousands of activities are underway across the reproductive, maternal, newborn and child health continuum that leverage mHealth and social/transmedia strategies (Labrique, Vasudevan, Chang, & Mehl, 2012). These activities have the potential to impact maternal, neonatal, and child health survival by changing caregiver behavior and catalyzing and improving the delivery of interventions. These strategies also have the ability to improve access to information and enhance community-driven demand for quality services (Labrique et al., 2012).
The Evidence Summit on Enhancing Child Survival and Development in Lower- and Middle-Income Countries by Achieving Population-Level Behavior Change was intended to review critical evidence to inform LMIC governments, donors, and development practitioners on the interventions effective in changing behavior to reduce under-5 mortality and enhance healthy child development (Pablos-Méndez & Fox, 2012). Six evidence review teams (ERTs) were recruited to consider various research areas related to behavior change and child survival (Balster, Levy, & Stammer, 2014). The broad goal for the science, technology, and innovation (STI) ERT was to (a) review the evidence and determine which STI behavioral interventions result in population-level behavior change that could contribute to child survival and healthy development; and (b) make informed recommendations to LMICs, donors and development practitioners on practice, programs, policy, and research. A related review was prepared for this Summit which focused on mass media interventions (Naugle & Hornik, 2014). Our article reports results from the STI ERT, which focused on four areas: mHealth, social/transmedia, health literacy, and devices. For health literacy and devices, there were an insufficient number of studies to support causal attribution of interventions to outcomes or perform a substantial evidence review; thus, we focused our efforts on mHealth, social/transmedia, and other media. The evidence review included areas such as use of mHealth for compliance with antiretroviral treatment in adults with HIV, which has both direct implications (e.g., perinatal transmission of HIV and transmission via breast feeding) and indirect implications (e.g., therapeutic compliance) for child survival. We present these results in detail to ensure (a) visibility on the adequacy of study design for intended area of evidence generation and (b) reporting of critical context (e.g., rural vs. urban) and implementation elements that may be helpful when considering adaptation or adoption. We also provide insight into the challenges to conducting high-quality research on the effectiveness of technology platforms and gaps that these types of interventions can fill to improve child survival.