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  • Beyond Purity Culture: Exploring History, Implications, and Alternatives

    Howard, Shelby Duncan; McAfee School of Theology
    This thesis offers a careful examination of the history and ethical implications of the purity culture movement upon the American evangelical teenage population and offers an alternative approach coined True Love Honors. The harm experienced by many participants in True Love Waits and other evangelical purity culture programs creates a moral dilemma for the American evangelical church today to reflect and develop a new ethical framework for sexual ethics for adolescents. The purpose of this research is to explore primary and secondary accounts of purity culture to understand specific ethical problems within the movement unto research of applicable ethical frameworks and approaches that may offer the substance lacking in the current sexual ethical norm. The concluding results identify three particular areas of lack which may be redressed by an ethic informed by feminist care ethics and privileging the values of autonomy, consent, and honor. For further study, I recommend the intersection of LGBTQIA+ youth with purity culture, contemporary thought on purity culture by Joshua Harris and other public figures of the early movement, and trauma-informed study on purity culture unto victims of sexual and domestic violence.
  • NOVEL MICROPARTICLE-BASED MICRONEEDLE VACCINE FOR ZIKA VIRUS

    Kale, Akanksha; College of Pharmacy
    NOVEL MICROPARTICLE-BASED MICRONEEDLE VACCINE FOR ZIKA VIRUS (Under the guidance of Dr. Martin D’Souza) Zika is an infectious viral disease caused due to the Zika virus. The primary mode of transmission for this virus is through mosquito bites. The common symptoms of the disease include fever, headache, conjunctivitis, muscle pain, and joint pain. Vertical transmission during pregnancy can result in microcephaly, congenital Zika syndrome, and other congenital abnormalities. Zika can also lead to Guillain-Barr Syndrome – an autoimmune disorder affecting the peripheral nervous system. After the global outbreak of Zika in 2015-2016, the World Health Organization declared a public health emergency of international concern. Research related to Zika has been included in the R and D priority list by the WHO. However, there are no approved treatments or vaccines available for Zika. Current vaccine candidates in research include whole-inactivated vaccines, nucleic acid vaccines, vectored vaccines, and subunit vaccines that are administered via conventional intramuscular or subcutaneous routes. These routes are invasive and painful, thereby reducing patient compliance. To explore a less painful alternative, we investigated the feasibility of the transdermal route as a vaccine delivery strategy for the Zika virus using polymeric microparticle-loaded microneedle patches. Integration of the particulate vaccine strategy and the transdermal route of administration together presented the potential to be efficacious in preventing Zika in a patient-compliant manner. The first part of the project included the formulation of poly(lactic-co-glycolic) acid (PLGA) polymeric vaccine microparticles (MP) encapsulating the inactivated Zika virus, along with adjuvant MP encapsulating Alhydrogel® and MPL-A®. We characterized the vaccine MP for size, surface charge, morphology, encapsulation efficiency, and antigen integrity. Further, we evaluated the immunogenicity and cytotoxicity of vaccine MP in vitro in murine dendritic cells. Vaccine MP with adjuvants induced significantly higher production of nitric oxide, a marker of innate immunity, when compared to the untreated cells. In addition, vaccine MP with or without adjuvants induced increased autophagy in murine dendritic cells when compared to inactivated Zika virus, which is critical in antigen presentation. Vaccine MP along with adjuvant MP also enhanced the expression of antigen-presenting molecules – MHC I and MHC II as well as co-stimulatory molecules – CD80 and CD40 in murine dendritic cells. Next, we evaluated in vivo efficacy of vaccine MP with and without adjuvants in a preclinical murine model by measuring the immune response after intramuscular administration. Vaccine MP with adjuvants induced significant IgG, Ig2a, IgG1, and IgG3 titers as compared to the control group of untreated mice. After the challenge with live Zika virus, vaccinated mice showed higher antibody titers and enhanced expression of helper CD4 and CD8 cell surface markers in splenocytes and lymphocytes. Splenocytes of vaccinated mice also showed enhanced expression of IFN-γ required for cytotoxic cell-mediated immune response. Thus, the immunogenic efficiency of the particulate Zika vaccine was established. In the next part of the study, we embedded Zika vaccine MPs with adjuvant MPs in dissolving microneedles (MNs) administered via the transdermal route as a pain-free vaccine strategy. We characterized the MNs for needle length, pore formation, and dissolvability when applied to murine skin. Further, we evaluated the in vivo efficacy of vaccine MPs-loaded MNs with or without adjuvants by measuring immune response after transdermal immunization. Vaccine MPs-loaded dissolving MNs with adjuvants induced significant IgG, IgG1, IgG2a, and IgG3 titers in immunized mice compared to the untreated control group. After the dosing regimen, animals were challenged with the Zika virus, monitored for seven days, and sacrificed to collect spleen and lymph nodes. Lymphocytes and splenocytes from immunized mice showed significant expression of helper (CD4) and cytotoxic (CD8a) cell surface markers than the control group. Thus, the promising results of this study put forth a ‘proof-of-concept’ for a pain-free transdermal vaccine strategy against Zika.
  • TRINITARIAN THEOLOGY AND CHRISTIAN SELF-UNDERSTANDING: EXAMINING THE THEOLOGICAL AND PHILOSOPHICAL IMPLICATIONS OF A RELATIONAL TRINITY IN RESPONSE TO FUNCTIONAL SUBORDINATIONISM

    Blanton, Rachel Grace; McAfee School of Theology
    In the conservative evangelical Church, a growing argument has been made for a hierarchical Trinity in which the Son is eternally subordinated to the Father in role and function, which pits itself against the trinitarian doctrine established by the early Church through the Nicene Creed. This conception of a hierarchical Trinity is often known as subordinationism or functional subordinationism, which brings into question the nature and role of Christ within the Godhead and in relation to humanity. The Council of Nicaea in 325 CE solidified and legitimated the beginnings of Trinitarian doctrine, established the nature of Christ, and yielded the Nicene Creed, which made the Church’s stance on the Trinity permanent: the Godhead is of one substance. Subordinationism believes in tandem with Christ’s subordinate role that women are to be subordinate to men, which has deep reverberations in the personal lives of Christians, the greater Church, and society. Two case studies will be analyzed: the 2022 Dobbs v. Jackson ruling, which overturned Roe v. Wade, and evangelical “role relationship” theology. This thesis has both theological and philosophical goals. The theological goals are to firmly establish an understanding that the Triune God exists through the relationship of the three divine Persons by using the works of modern Protestant, Catholic, and eastern Orthodox theologians and to explore the nature and soteriological work of Christ. Philosophically, this work looks to Georg Wilhelm Friedrich Hegel to understand the nature of Christ expressed through the Infinite’s desire for reconciliation of the finite via the incarnation. This work finds overwhelming support for a relational Trinity established through theological and philosophical thought and connects the two through Christ to explain how our understanding of Christ’s role in the Trinity reverberates into our own lives and that the Trinity acts as a model for human relations. Lastly, this work will look toward the eschaton and the missional role of the Triune God in reconciliation, which has profound implications for understanding our God in relation.
  • Q and the Passion - Challenging the Consensus View

    Collier, Steven D.; McAfee School of Theology
    This thesis challenges the consensus viewpoint of biblical scholarship that Q, the sayings source common to Matthew and Luke, contains no Passion account. Based on the absence of a Passion in Q (the Argument from Silence), the consensus view concludes Q’s theology is divergent from the cross-centered theology of Matthew and Luke. The purpose of the present study is to refute the Argument from Silence, and show that Q did in fact contain Passion material. With a Passion, Q must have had a theology more congruent with Matthew and Luke. The research methodology is source utilization, the study of how ancient writers used sources based on the then available technology of document production. Based on deviations from Mark in content, but more importantly order, source utilization points to a second non-Markan written source in Luke’s Passion, which source provided the alternative content and order. Q could be the second source because (a) the non-Markan portion of Luke’s Passion contains numerous sayings of Jesus consistent with Q’s genre as a sayings source, and (b) these non-Markan sayings also have thematic resonance with Q. The Minor Agreements of Matthew and Luke against Mark in their respective Passion accounts further support these findings. The Minor Agreements demonstrate Matthew’ s awareness of: (1) non-Markan sayings thematically related to Q, and (2) non-Markan material precisely at the point where Luke deviates from Markan order, and is therefore following the order of the second written source. Based on all of these results, I conclude Q is in fact the second written source for much of the non-Markan Passion material in Luke, and the material is echoed to a lesser extent in Matthew. I will pull the analysis together and propose an addition to Q of about 300 words of Passion material drawn from Luke and Matthew. I will end with a brief discussion of the implications of a Q Passion. These include rebuttal of the Argument from Silence, consequences for the Synoptic Problem and ramifications for the theology of Q and the history of early Christianity.
  • DIRECT VASODILATORY EFFECTS OF SODIUM GLUCOSE CO-TRANSPORTER 2 INHIBITORS (SGLT2is) AND THE UNDERLYING MOLECULAR MECHANISMS IN RESISTANCE MESENTERIC ARTERIES

    Hasan, Ahasanul; College of Pharmacy
    Sodium glucose co-transporter 2 inhibitors (SGLT2is) are a novel class of oral glucose-lowering drugs. In the USA, the FDA has authorized canagliflozin (Cana), dapagliflozin (Dapa), empagliflozin (Empa), ertugliflozin (Ertu), and bexagliflozin (Bexa) for use to treat type 2 diabetic mellitus (T2DM). Recent cardiovascular outcome trials (CVOTs) indicated cardio-reno protection due to SGLT2is' blood pressure (BP)-lowering effects. Even though numerous long-term processes have been implicated to lower BP, issues still remain to explain the immediate BP-lowering effects of SGLT2is as revealed in recent CVOTs trials. One plausible mechanism may be direct modulation of contractility of resistance arteries which regulate peripheral resistance (R) and thus, blood pressure. Hence, we investigated SGLT2is Empa, Dapa, and Cana's ability to relax resistance mesenteric arteries and the underlying molecular mechanism (s). Pressurized arterial myography and pharmacological inhibitors were utilized to study the direct effect of SGLT2is on the contractility of freshly isolated, resistant mesenteric arteries from rats. We discovered that acute administration of SGLT2is (Empa, Dapa, and Cana) causes concentration-dependent vasodilation in myogenic and phenylephrine (PE)-preconstricted resistant mesenteric arteries, irrespective of SGLT2 inhibition. SGLT2is-evoked vasodilation was blocked by non-selective inhibition of smooth muscle cell voltage-gated K+ (KV) channels. However, the SGLT2is' KV channel specificity varies as Empa targeted KV1.5 and KV7, Dapa targeted KV7, and Cana targeted KV1.5, KV2.1, and KV7. In contrast, KV1.3, ATP-sensitive K+ (KATP) channels, SERCA pump, and small-, intermediate-, and large-conductance Ca2+-activated K+ channels (SKCa, IKCa, and BKCa) did not reduce SGLT2is-induced vasodilation. Furthermore, vasodilation was unaffected by NO-sGC-PKG and prostacyclin (PGI2) inhibition. Besides, SGLT2is-evoked vasodilation was unchanged by endothelium denudation. Overall, our results suggest that the vasodilatory action of SGLT2is like Empa, Dapa, and Cana may be independent of SGLT2 inhibition and mediated by its action on other molecular targets such as smooth muscle cell KV channels with varying specificity. Our findings reveal for the first time SGLT2is' direct vasodilatory activity in resistance arteries, which may explain their blood pressure lowering effects as demonstrated in CVOTs studies and their cardio-reno protective effects. The reported vasodilatory effects may lower blood pressure in vivo, but more research is needed.

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