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This study examines the role of Black churches in AIDS/HIV prevention. This is a pilot survey study design administered to 11 churches represented by 11 ministers and one church member. The analysis is both qualitative and quantitative. The results showed that most of the ministers had spoken with their congregation on HIV/AIDS. A few ministers had previously sponsored or taken part in HIV/AIDS workshops and disseminated HIV/AIDS educational material in the African American community. None of the churches had an established HIV/AIDS prevention program. Most of the ministers were receptive to implementing an HIV/AIDS prevention program, provided that it did not violate the church doctrines. The findings in this study suggest that Black churches represent an important potential resource for HIV/AIDS prevention. For success, the initial strategy should involve the minister in the early planning stage. Future research should focus on expanding the scope of this study and improving communication between the church, community-based organizations, and health professionals. [ABSTRACT FROM AUTHOR]

Mechanical circulatory support (MCS) devices can bridge the gap to transplant whilst awaiting a viable donor heart. The Realheart Total Artificial Heart is a novel positive-displacement MCS that generates pulsatile flow via bileaflet mechanical valves. This study developed a combined computational fluid dynamics and fluid-structure interaction (FSI) methodology for simulating positive displacement bileaflet valves. Overset meshing discretised the fluid domain, and a blended weak-strong coupling FSI algorithm was combined with variable time-stepping. Four operating conditions of relevant stroke lengths and rates were assessed. The results demonstrated this modelling strategy is stable and efficient for modelling positive-displacement artificial hearts.

Background: Individuals with type 1 diabetes (T1D) are more likely to achieve optimal glycemic management when they have frequent visits with their health care team. There is a potential benefit of frequent, telemedicine interventions as an effective strategy to lower hemoglobin A1c (HbA1c)., Objective: The objective is this study was to understand the provider- and system-level factors affecting the successful implementation of a virtual care intervention in type 1 diabetes (T1D) clinics., Methods: Semistructured interviews were conducted with managers and certified diabetes educators (CDEs) at diabetes clinics across Southern Ontario before the COVID-19 pandemic. Deductive analysis was carried out using the Theoretical Domains Framework, followed by mapping to behavior change techniques to inform potential implementation strategies for high-frequency virtual care for T1D., Results: There was considerable intention to deliver high-frequency virtual care to patients with T1D. Participants believed that this model of care could lead to improved patient outcomes and engagement but would likely increase the workload of CDEs. Some felt there were insufficient resources at their site to enable them to participate in the program. Member checking conducted during the pandemic revealed that clinics and staff had already developed strategies to overcome resource barriers to the adoption of virtual care during the pandemic., Conclusions: Existing enablers for high-frequency virtual care for T1D can be leveraged, and barriers can be overcome with targeted clinical incentives and support., (©Stephanie de Sequeira, Justin Presseau, Gillian L Booth, Lorraine L Lipscombe, Isabelle Perkins, Bruce A Perkins, Rayzel Shulman, Gurpreet Lakhanpal, Noah Ivers. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 08.12.2022.)

Promoting human flourishing among the sick and the dying as the spiritual goal of life-union with Christ-presents one of the most challenging experiences for patients, families, clinicians, and the Christian community in today's healthcare environment. This article will present a framework and the important Catholic moral principles that can help guide and facilitate ethical decisions in end-of-life care that promotes and protects human dignity, freedom, and human flourishing in Christ as the telos of the journey of hope in the Christian community., Summary: As members of the Christian Community we have been called to bring the healing message of salvation and hope to one another. This ministry calls each of us to reach beyond ourselves and to touch our loved ones, our neighbors, those made vulnerable by the circumstances of their illness and to protect and defend human dignity, freedom and promote human flourishing. As Jesus did in his own time, each of us is called to help bring healing and wholeness to the sick and the dying in our world. How we can respond to our obligation to care for the sick and dying at the end-of-life, grounded in the principles of the Catholic moral tradition that govern our care and treatment decisions, is the focus of this paper., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© Catholic Medical Association 2020.)

Microphysiological systems and organs-on-chips promise to accelerate biomedical and pharmaceutical research by providing accurate in vitro replicas of human tissue. Aside from addressing the physiological accuracy of the model tissues, there is a pressing need for improving the throughput of these platforms. To do so, scalable data acquisition strategies must be introduced. To this end, we here present an instrumented 24-well plate platform for higher-throughput studies of engineered human stem cell-derived cardiac muscle tissues that recapitulate the laminar structure of the native ventricle. In each well of the platform, an embedded flexible strain gauge provides continuous and non-invasive readout of the contractile stress and beat rate of an engineered cardiac tissue. The sensors are based on micro-cracked titanium-gold thin films, which ensure that the sensors are highly compliant and robust. We demonstrate the value of the platform for toxicology and drug-testing purposes by performing 12 complete dose-response studies of cardiac and cardiotoxic drugs. Additionally, we showcase the ability to couple the cardiac tissues with endothelial barriers. In these studies, which mimic the passage of drugs through the blood vessels to the musculature of the heart, we regulate the temporal onset of cardiac drug responses by modulating endothelial barrier permeability in vitro.

Six broad-host-range plasmid vectors were developed to study gene expression in Bartonella henselae. The vectors were used to express a beta-galactosidase reporter gene in B. henselae and to generate antisense RNA for gene knockdown. When applied to ompR, a putative transcription response regulator of B. henselae, this antisense RNA gene knockdown strategy reduced bacterial invasion of human endothelial cells by over 60%.

Legionella pneumophila infection of mice induces proinflammatory cytokines and Th1 immunity as well as rapid increases in serum levels of IL-12 and IFNgamma and splenic IL-12Rbeta2 expression. Delta-9-tetrahydrocannabinol (THC) treatment prior to infection causes a shift from Th1 to Th2 immunity and here we demonstrate that CB(1) and CB(2) cannabinoid receptors mediate different aspects of the shift. Using cannabinoid receptor antagonists and cannabinoid receptor gene deficient mice (CB(1) (-/-) and CB(2) (-/-)), we showed that both CB(1) and CB(2) receptors were involved in the THC-induced attenuation of serum IL-12 and IFNgamma. IFNgamma production is dependent upon signaling through IL-12Rbeta2 (beta2) and THC treatment suppressed splenic beta2 message; moreover, this effect was CB(1) but not CB(2)-dependent from studies with receptor antagonists and CB1(-/-) and CB2(-/-) mice. Furthermore, observed increases in IL-4 induced by THC, were not involved in the drug effect on beta2 from studies with IL-4 deficient mice. The GATA-3 transcription factor is necessary for IL-4 production and is selectively expressed in Th2 cells. GATA-3 message levels were elevated in spleens of THC-treated and L. pneumophila-infected mice and the effect was shown to be CB(2) but not CB(1)-dependent. Furthermore, GATA-3 regulatory factors were modulated in that Notch ligand Delta4 mRNA was decreased and Jagged1 increased by THC also in a CB2-dependent manner and splenic NFkappaB p65 was increased. Together, these results indicate that CB(1) and CB(2) mediate the THC-induced shift in T helper activity in L. pneumophila-infected mice, with CB(1) involved in suppressing IL-12Rbeta2 and CB(2) involved in enhancing GATA-3.

Bacillus anthracis produces lethal toxin (LT) and edema toxin (ET), and they suppress the function of LPS-stimulated dendritic cells (DCs). Because DCs respond differently to various microbial stimuli, we compared toxin effects in bone marrow DCs stimulated with either LPS or Legionella pneumophila (Lp). LT, not ET, was more toxic for cells from BALB/c than from C57BL/6 (B6) as measured by 7-AAD uptake; however, ET suppressed CD11c expression. LT suppressed IL-12, IL-6, and TNF-alpha in cells from BALB/c and B6 mice but increased IL-1beta in LPS-stimulated cultures. ET also suppressed IL-12 and TNF-alpha, but increased IL-6 and IL-1beta in Lp-stimulated cells from B6. Regarding maturation marker expression, LT increased MHCII and CD86 while suppressing CD40 and CD80; ET generally decreased marker expression across all groups. We conclude that the suppression of cytokine production by anthrax toxins is dependent on variables, including the source of the DCs, the type of stimulus and cytokine measured, and the individual toxin tested. However, LT and ET enhancement or suppression of maturation marker expression is more related to the marker studied than the stimuli or cell source. Anthrax toxins are not uniformly suppressive of DC function but instead can increase function under defined conditions.

Dendritic cells (DCs) have a critical role in linking innate to adaptive immunity, and this transition is regulated by the up-regulation of costimulatory and major histocompatibility complex (MHC) molecules as well as Toll-like receptors. These changes in DCs have been observed to occur following microbial infection, and in the present study, we examined the effect of Legionella pneumophila infection on the expression of these DC markers. We showed that bone marrow-derived DC cultures from BALB/c mice infected with live L. pneumophila resulted in the up-regulation of Toll-like receptors 2 and 4 and the activation of CD40, CD86, and MHC class I/II molecules.

The progression of Legionella pneumophila infection in macrophages is controlled by the Lgn1 gene locus, which expresses the nonpermissive phenotype in cells from BALB/c mice but the permissive phenotype in cells from A/J mice. Activation of dendritic cells and macrophages by L. pneumophila is mediated by the pathogen recognition receptor Toll-like receptor 2 (TLR2); furthermore, Legionella induces innate and adaptive immune cytokines by the MyD88-dependent pathway. TLR9 is coupled to MyD88 and mediates the production of interleukin-12 (IL-12) in dendritic cells infected with other facultatively intracellular pathogens. In the current study, L. pneumophila growth in dendritic cells from BALB/c and A/J mice was examined along with the role of TLR9 in the induction of IL-12 in these cells. Dendritic cells from both strains were nonpermissive for L. pneumophila intracellular growth, suggesting that the products of the Lgn1 gene locus that control intracellular growth in macrophages do not control the growth of Legionella in dendritic cells. In addition, chloroquine treatment suppressed IL-12 p40 production in response to Legionella treatment in dendritic cells and macrophages from BALB/c and A/J mice. Furthermore, the TLR9 inhibitor ODN2088 suppressed the Legionella-induced IL-12 production in dendritic cells from both mouse strains. These results suggest that L. pneumophila is similar to other intracellular bacteria in that it stimulates the production of immune-transitioning cytokines, such as IL-12, through activation of TLR9 and that this receptor provides a common mechanism for sensing these types of microbes and inducing innate and adaptive immunity.

Marijuana cannabinoids, such as delta-9-tetrahydrocannabinoid (THC), suppress type 1 T-helper 1 (Th1) immunity in a variety of models, including infection with the intracellular pathogen Legionella pneumophila (Lp). To examine the cellular mechanism of this effect, bone marrow-derived dendritic cells (DCs) were purified from BALB/c mice and studied following infection and drug treatment. DCs infected in vitro with Lp were able to protect mice when injected prior to a lethal Lp infection; however, the immunization potential of the Lp-loaded cells along with Th1 cytokine production was attenuated by THC treatment at the time of in vitro infection. In addition, THC-treated and Lp-loaded DCs were poorly stimulated in culture-primed splenic CD4(+) T cells to produce interferon-gamma; however, this stimulating deficiency was reversed by adding recombinant interleukin (IL)-12p40 protein to the cultures. Moreover, THC treatment inhibited the expression of DC maturation markers, such as major histocompatibility complex class II and costimulatory molecules CD86 and CD40 as determined by flow cytometry and suppressed the Notch ligand, Del-ta4, as determined by reverse transcription-polymerase chain reaction. However, THC treatment did not affect other DC functions, such as intracellular killing of Lp, determined by colony-forming unit counts of bacteria, and Lp-induced apoptosis, determined by annexin V staining. In conclusion, the data suggest that THC inhibits Th1 activation by targeting essential DC functions, such as IL-12p40 secretion, maturation, and expression of costimulatory and polarizing molecules.

Delta-9-tetrahydrocannabinol (THC) injection suppresses serum interleukin-12 (IL-12) levels in Legionella pneumophila-infected mice. Dendritic cells are a major producer of IL-12 and mouse, bone marrow-derived dendritic cell cultures produced high levels of the IL-12p40 following L. pneumophila infection. Treatment with THC suppressed this cytokine response in a concentration-dependent manner and the endocannabinoid, 2-arachidonoyolglycerol, less potently suppressed cytokine production. Dendritic cells expressed mRNA for cannabinoid receptor 1 (CB(1)), cannabinoid CB(2) receptor, and vanilloid receptor 1 (TRPV1) and the addition of the G(i) inhibitor, pertussis toxin, completely attenuated suppression induced by 3 and 6 muM THC but not by 10 muM THC. Furthermore, THC suppression was partially attenuated in dendritic cells from cannabinoid CB(1) receptor and CB(2) receptor knockout mice and in dendritic cells co-treated with THC and cannabinoid receptor antagonists. Cytokine suppression was not attenuated by pretreatment with the TRPV1 antagonist, capsazepine. These results suggest that THC-induced suppression of serum IL-12 is partly due to a suppression of IL-12 production by dendritic cells and that G(i) signaling and cannabinoid receptors, but not TRPV1, are involved in this suppressive effect.

The primary polyphenol in green tea extract is the catechin epigallocatechin gallate (EGCG). Various studies have shown significant suppressive effects of catechin on mammalian cells, either tumor or normal cells, including lymphoid cells. Previous studies from this laboratory reported that EGCG has marked suppressive activity on murine macrophages infected with the intracellular bacterium Legionella pneumophila (Lp), an effect mediated by enhanced production of both tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (IFN-gamma). In the present study, primary murine bone marrow (BM)-derived dendritic cells (DCs), a phagocytic monocytic cell essential for innate immunity to intracellular microorganisms, such as Lp, were stimulated in vitro with the microbial stimulant lipopolysaccharide (LPS) from gram-negative bacteria, the cell wall component from gram-positive bacteria muramyldipeptide (MDP) or infected with Lp. Production of the T helper cell (Th1)-activating cytokine, interleukin-12 (IL-12) and the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha),produced mainly by phagocytic cells and important for antimicrobial immunity, was determined in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Treatment of the cells with EGCG inhibited, in a dose-dependent manner, production of IL-12. In contrast, enhanced production of TNF-alpha occurred in a dose-dependent manner in the DC cultures stimulated with either soluble bacterial product or infected with Lp. Thus, the results of this study show that the EGCG catechin has a marked effect in modulating production of these immunoregulatory cytokines in stimulated DCs, which are important for antimicrobial immunity, especially innate immunity. Further studies are necessary to characterize the physiologic function of the effect of EGCG on TNF-alpha and IL-12 during Lp infection, and the mechanisms involved.