Designing Acellular Injectable Biomaterial Therapeutics for Treating Myocardial Infarction and Peripheral Artery Disease.

As the number of global deaths attributed to cardiovascular disease continues to rise, viable treatments for cardiovascular events such as myocardial infarction (MI) or conditions like peripheral artery disease (PAD) are critical. Recent studies investigating injectable biomaterials have shown promise in promoting tissue regeneration and functional improvement, and in some cases, incorporating other therapeutics further augments the beneficial effects of these biomaterials. In this review, we aim to emphasize the advantages of acellular injectable biomaterial-based therapies, specifically material-alone approaches or delivery of acellular biologics, in regards to manufacturability and the capacity of these biomaterials to regenerate or repair diseased tissue. We will focus on design parameters and mechanisms that maximize therapeutic efficacy, particularly, improved functional perfusion and neovascularization regarding PAD and improved cardiac function and reduced negative left ventricular (LV) remodeling post-MI. We will then discuss the rationale and challenges of designing new injectable biomaterial-based therapies for the clinic

Striving Towards Efficient Curriculum Implementation

As an Early Learning Mentor Coach for a non-profit organization, my job is to ensure proper implementation of our curriculum within the classroom in order to be in compliance with our grant agreements. Through this process, I had to think of a way to support teaching staff and help them be successful without adding extra stress or hours to their workdays. Whether this was to be done through a binder, a reflection checklist, or a website, I needed to come up with something that was efficient, effective, and convenient for the teachers

Invisible Refugee: Examining the Board of Immigration Appeals\u27 Social Visibility Doctrine, The

This Law Summary first focuses on the development of the various approaches by the U.S. immigration court system in defining the term particular social group. Second, it discusses the cryptic evolution of the social visibility doctrine. Finally, it will explore how the conflicting applications of the social visibility doctrine among the U.S. courts of appeals have resulted in potentially unpredictable outcomes for those seeking protection in the United States, and it will suggest that a clarification of the social visibility doctrine by either the BIA or Supreme Court would alleviate the conflict

Extracellular Matrix Hydrogel Promotes Tissue Remodeling, Arteriogenesis, and Perfusion in a Rat Hindlimb Ischemia Model.

ObjectiveThis study aimed to examine acellular extracellular matrix based hydrogels as potential therapies for treating peripheral artery disease (PAD). We tested the efficacy of using a tissue specific injectable hydrogel, derived from decellularized porcine skeletal muscle (SKM), compared to a new human umbilical cord derived matrix (hUC) hydrogel, which could have greater potential for tissue regeneration because of its young tissue source age.BackgroundThe prevalence of PAD is increasing and can lead to critical limb ischemia (CLI) with potential limb amputation. Currently there are no therapies for PAD that effectively treat all of the underlying pathologies, including reduced tissue perfusion and muscle atrophy.MethodsIn a rodent hindlimb ischemia model both hydrogels were injected 1-week post-surgery and perfusion was regularly monitored with laser speckle contrast analysis (LASCA) to 35 days post-injection. Histology and immunohistochemistry were used to assess neovascularization and muscle health. Whole transcriptome analysis was further conducted on SKM injected animals on 3 and 10 days post-injection.ResultsSignificant improvements in hindlimb tissue perfusion and perfusion kinetics were observed with both biomaterials. End point histology indicated this was a result of arteriogenesis, rather than angiogenesis, and that the materials were biocompatible. Skeletal muscle fiber morphology analysis indicated that the muscle treated with the tissue specific, SKM hydrogel more closely matched healthy tissue morphology. Short term histology also indicated arteriogenesis rather than angiogenesis, as well as improved recruitment of skeletal muscle progenitors. Whole transcriptome analysis indicated that the SKM hydrogel caused a shift in the inflammatory response, decreased cell death, and increased blood vessel and muscle development.ConclusionThese results show the efficacy of an injectable ECM hydrogel alone as a potential therapy for treating patients with PAD. Our results indicate that the SKM hydrogel improved functional outcomes through stimulation of arteriogenesis and muscle progenitor cell recruitment

Changing Attitudes towards Hepatitis B among Asian Americans: From Saving Face to Getting Serious

Background: Asian Americans have the highest prevalence of hepatitis B virus (HBV) in the US. The San Francisco Hep B Free (SFHBF) campaign aimed to increase awareness and access to HBV education and services among Asian Americans in San Francisco. Purpose: We sought to examine attitudes and knowledge among Asian Americans regarding HBV at baseline (2009) and benefits of the SFHBF outreach campaign four years later (2013). Methods: Four focus groups were conducted (n=45) in 2009, followed by in-depth interviews (n=40) in 2013. Results: In 2009, many participants were misinformed about HBV symptoms and transmission. They also reported stigma associated with HBV, which hindered Asian Americans from discussing the disease and seeking services. The 2013 interviews revealed that SFHBF had contributed towards awareness of HBV screenings and vaccinations, and also instilled acute seriousness that HBV could affect them directly. Conclusion: The in-depth interviews conducted in 2013 illustrated that there was less concern about “saving face,” but a shift to a level of seriousness associated with HBV. Future efforts among Asian Americans should continue to focus on self-efficacy regarding HBV prevention, including screening and vaccination

Assessing the Need and Receptivity for an Integrated Healthy Sexual and Dating Relationships Intervention for Community College Students

Background: In emerging adulthood, youth often become involved in more serious romantic relationships. However, many lack the skills to avoid an unplanned pregnancy or sexually transmitted infection (STI), and to ensure a healthy dating relationship. Community college students serve nearly half of all undergraduate students in the United States; yet, community colleges typically lack resources for sexual health promotion. Purpose: To assess the need and receptivity for a web-based integrated healthy sexual and dating relationships intervention among community college students. Methods: In summer 2016, we partnered with three community colleges in South Central Texas to conduct an online survey of students’ sexual behaviors and dating relationships, and usability testing of activities from an integrated, web-based healthy sexual and dating relationship intervention. Results: Online survey participants (n=271) were 70% female, 38% Hispanic, 24% White, 17% Black, and 16% Asian; 20% self-identified as sexual minority; mean age was 20.8 years (SD = 2.05). Participants reported high rates of sexual risk behavior including sex without a condom or an effective birth control method, low use of long-acting reversible contraception, frequent use of emergency contraception, and low use of dual protection to prevent pregnancy and sexually transmitted infections. Two-thirds reported experiencing any type of dating violence perpetration or victimization in the past year. Usability testing participants (n=14) were 86% female, 42% Hispanic, 50% Asian/Pacific Islander, 14% Black, and 7% White; 71% were sexually experienced; mean age was 20.7 years (SD = 1.64). The web-based activities were highly rated in terms of usability parameters, and positively impacted short-term psychosocial outcomes related to condom use, accessing contraceptive health services, and constructive interpersonal conflict resolution. Conclusion: Findings underscore the high need and receptivity for an integrated healthy sexual and dating relationship web-based intervention among community college students, an understudied subgroup of youth in emerging adulthood

Number and type of guideline implementation tools varies by guideline, clinical condition, country of origin, and type of developer organization : Content analysis of guidelines

Guideline implementation tools (GI tools) can improve clinician behavior and patient outcomes. Analyses of guidelines published before 2010 found that many did not offer GI tools. Since 2010 standards, frameworks and instructions for GI tools have emerged. This study analyzed the number and types of GI tools offered by guidelines published in 2010 or later. Content analysis and a published GI tool framework were used to categorize GI tools by condition, country, and type of organization. English-language guidelines on arthritis, asthma, colorectal cancer, depression, diabetes, heart failure, and stroke management were identified in the National Guideline Clearinghouse. Screening and data extraction were in triplicate. Findings were reported with summary statistics. Eighty-five (67.5%) of 126 eligible guidelines published between 2010 and 2017 offered one or more of a total of 464 GI tools. The mean number of GI tools per guideline was 5.5 (median 4.0, range 1 to 28) and increased over time. The majority of GI tools were for clinicians (239, 51.5%), few were for patients (113, 24.4%), and fewer still were to support implementation (66, 14.3%) or evaluation (46, 9.9%). Most clinician GI tools were guideline summaries (116, 48.5%), and most patient GI tools were condition-specific information (92, 81.4%). Government agencies (patient 23.5%, clinician 28.9%, implementation 24.1%, evaluation 23.5%) and developers in the UK (patient 18.5%, clinician 25.2%, implementation 27.2%, evaluation 29.1%) were more likely to generate guidelines that offered all four types of GI tools. Professional societies were more likely to generate guidelines that included clinician GI tools. Many guidelines do not include any GI tools, or a variety of GI tools for different stakeholders that may be more likely to prompt guideline uptake (point-of-care forms or checklists for clinicians, decision-making or self-management tools for patients, implementation and evaluation tools for managers and policy-makers). While this may vary by country and type of organization, and suggests that developers could improve the range of GI tools they develop, further research is needed to identify determinants and potential solutions. Research is also needed to examine the cost-effectiveness of various types of GI tools so that developers know where to direct their efforts and scarce resources

Impact of Tumor Microenvironment and Epithelial Phenotypes on Metabolism in Breast Cancer

Cancer cells have altered metabolism, with increased glucose uptake, glycolysis, and biomass production. This study performed genomic and metabolomic analyses to elucidate how tumor and stromal genomic characteristics influence tumor metabolism

Breast cancer derived GM-CSF regulates arginase 1 in myeloid cells to promote an immunosuppressive microenvironment

Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (Arg-1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular L-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor derived GM-CSF as the primary regulator of myeloid cell Arg-1 expression and local immune suppression through a gene knockout screen of breast tumor cell-produced factors. The induction of myeloid cell Arg-1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3, p38 MAPK, and acid signaling through cAMP were required to activate myeloid cell Arg-1 expression in a STAT6 independent manner. Importantly, breast tumor cell-derived GM-CSF promoted tumor progression by inhibiting host anti-tumor immunity, driving a significant accumulation of Arg-1 expressing myeloid cells compared to lung and melanoma tumors with minimal GM-CSF expression. Blockade of tumoral GM-CSF enhanced the efficacy of tumor-specific adoptive T-cell therapy and immune checkpoint blockade. Taken together, breast tumor cell-derived GM-CSF contributes to the development of the immunosuppressive breast cancer microenvironment by regulating myeloid cell Arg-1 expression and can be targeted to enhance breast cancer immunotherapy