Don’t Diss the Reninjaza: A Case for Integrating Traditional Birthing Attendants into the Allopathic System to Improve Prenatal Health in Rural Madagascar

This project seeks to prove the practicality of using Reninjazas (traditional birthing attendants) in rural Madagascar to better prenatal care and diminish the maternal and infant mortality rates in this country. Prenatal care is of vital importance to expecting mothers. Without it, birth defects, complicated labor and delivery, miscommunications concerning fetal development, and even death can occur (Mayo Clinic, 2014). There is no doubt that the lack of adequate prenatal care in Madagascar contributes to its unfortunately high maternal and infant death statistics. While listed as “moderate” in terms of severity, the maternal and infant mortality rates in Madagascar are significantly higher than in other systems, such as in the US (CIA, 2014). Because of this, there has been a push in recent years to implement an allopathic system in this country to improve maternal care. However, these “pushers,” albeit with good intentions, want to put into effect a system that will not work in Madagascar. With the geographic, financial, and cultural barriers in this country, a completely allopathic prenatal care arrangement is not feasible. Therefore, those who wish to improve prenatal health in Madagascar should work to create an integrated healthcare system that utilizes the Reninjazas, and recognizes their practice as legitimate

Doctor of Philosophy

dissertationFibrinolysis, the proteolytic degradation of the fibrin fibers th a t stabilize blood clots, is initiated when tissue-type plasminogen activator (tPA) activates plasminogen to plasmin, the main fibrinolytic enzyme. Many experiments have shown that coarse clots made of thick fibers lyse more quickly than fine clots made of thin fibers, despite the fact that individual thick fibers lyse more slowly than individual thin fibers. Other experiments show the opposite result. Reaction-diffusion models have been the standard tool for investigating fibrinolysis, and have been successful in capturing the wave-like behavior of lysis seen in experiments. These previous models treat the distribution of fibrin within a clot as homogeneous, and therefore cannot be used directly to study lysis of fine and coarse clots. We create a model that includes a spatially heterogeneous fibrin concentration, as well as a more accurate description of the role of fibrin as a cofactor in the activation of plasmin. Our model predicts spatiotemporal protein distributions in reasonable quantitative agreement with experimental data. The model also predicts observed behavior such as a front of lysis moving through the clot with an accumulation of lytic proteins at the front. In spite of the model improvements, however, we find that one-dimensional (1-D) continuum models are unable to accurately describe the observed differences in lysis behavior between fine and coarse clots. Hence, we develop a three-dimensional (3-D) stochastic multiscale model of fibrinolysis. A microscale model representing a fiber cross section and containing detailed biochemical reactions provides information about single fiber lysis times and the length of time tPA stays bound to a given fiber cross section. Data from the microscale model is used in a macroscale model of the full fibrin clot, from which we obtain lysis front velocities and tPA distributions. We find that the number of fibers in a clot impacts lysis rate, but so does the number of tPA molecules relative to the surface area of the clot exposed to those molecules. Depending on the values of these two quantities (tPA number and surface area), for given kinetic parameters, the model predicts coarse clots lyse faster or slower than fine clots, thus providing a possible explanation for the divergent experimental observations. We also use the model to predict values of unmeasured reaction rates and to suggest desirable characteristics of fibinolytic drugs. We find that a tPA variant that binds less strongly to fibrin causes faster degradation rates than normal tPA. We conclude by studying the effect of the inhibitors a 2-antiplasmin ( a 2-AP), plasminogen activator inhibitor-1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) on lysis. We find that a 2-AP is the stongest inhibitor, but lysis is most delayed when a 2-AP and TAFI work together

Mental Well-Being, Academic Experience, and Dropout Intention among Counseling Students Affected by the Shift to Online Instruction during the COVID-19 Pandemic

The COVID-19 pandemic has exacerbated challenges for many counseling students due to the threat of COVID-19 and the rapid shift to online learning, possibly resulting in increased mental health problems and dropout rates. This convergent mixed-methods study aimed to investigate the impact of COVID-19-related experiences and shift to online learning on (a) counseling students’ mental well-being, (b) academic experience, and (c) dropout intentions among a sample of 405 counseling students across 45 states. Path analysis results showed an excellent model fit (χ2 = 5.612, p = .47, CFI = 1.000, SRMR = .025, RMSEA = .000, 90% CI [.000, .063]) and revealed that non-classroom student-faculty interactions positively predicted program commitment (β = .32, p \u3c .001) and that mental well-being positively predicted program commitment (β = .22, p \u3c .001). Program commitment in turn negatively predicted dropout intentions (β = –.22, p \u3c .001). Findings suggest that counselor educators/programs must heed and address students’ pressing mental health and learning needs by improving student-faculty communication and developing pedagogies that fit with online/hybrid instruction during this pandemic and beyond

A hybrid icebreaking resistance model to accommodate damage to the ice sheet

An analytical framework was constructed to interchange ice resistance components from existing ice resistance calculation methods. Within this framework, the Lindqvist analytical method bending ice resistance component was substituted with a value obtained from a finite element static model of the ice sheet. A parametric study of this substitution was performed with error correction to within 12% over the entire range of parameter variation. The finite element ice sheet model was then damaged; and then the average ice bending resistance was obtained, substituted into the Lindqvist analytical method, and quantified as a change in the total ice resistance. Therefore, a hybrid ice resistance model was developed that accounts for the effect of damage to the bending resistance component, and enables further study of unconventional icebreaking methods.http://archive.org/details/ahybridicebreaki1094534623Lieutenant Junior Grade, United States Coast GuardApproved for public release; distribution is unlimited

Microscale structural changes of individual fibrin fibers during fibrinolysis

Fibrinolysis is the enzymatic digestion of fibrin, the primary structural component in blood clots. Mechanisms of fibrin fiber digestion during lysis have long been debated and obtaining detailed structural knowledge of these processes is important for developing effective clinical approaches to treat ischemic stroke and pulmonary embolism. Using dynamic fluorescence microscopy, we studied the time-resolved digestion of individual fibrin fibers by the fibrinolytic enzyme plasmin. We found that plasmin molecules digest fibers along their entire lengths, but that the rates of digestion are non-uniform, resulting in cleavage at a single location along the fiber. Using mathematical modeling we estimated the rate of plasmin arrival at the fiber surface and the number of digestion sites on a fiber. We also investigated correlations between local fiber digestion rates, cleavage sites, and fiber properties such as initial thickness. Finally, we uncovered a previously unknown tension-dependent mechanism that pulls fibers apart during digestion. Taken together these results promote a paradigm shift in understanding mechanisms of fibrinolysis and underscore the need to consider fibrin tension when assessing fibrinolytic approaches.ECU Open Access Publishing Support Fun

Serum short chain fatty acids mediate hippocampal BDNF and correlate with decreasing neuroinflammation following high pectin fiber diet in mice

IntroductionDietary components, such as prebiotic fiber, are known to impact brain chemistry via the gut-brain axis. In particular, short chain fatty acids (SCFAs) generated from excessive soluble fiber consumption are thought to impact neuroimmune signaling and brain function through increased production of neurotropic factors. Given reports that high dietary fiber intake is associated with increased mental health and improved quality of life scores, we set out to identify whether changes in SCFA levels as a result of a high soluble fiber diet mediate hippocampal neuroinflammation and brain derived neurotrophic factor (BDNF) in mice.MethodsAdult male and female C57BL/6 mice were fed a 1-month high pectin fiber or cellulose-based control diet. Following 1 month of excessive pectin consumption, serum SCFAs were measured using gas chromatography–mass spectrometry (GC-MS) and hippocampal cytokines and BDNF were assessed via multiplex magnetic bead immunoassay.ResultsPectin-based fiber diet increased circulating acetic acid in both sexes, with no effect on propionic or butyric acid. In the hippocampus, a high fiber diet decreased TNFa, IL-1ß, IL-6, and IFNγ and increased BDNF levels. Furthermore, increased SCFA levels were inversely correlated with neuroinflammation in the hippocampus, with acetic acid revealed as a strong mediator of increased BDNF production.ConclusionCollectively, these findings highlight the beneficial effects of fiber-induced molecular changes in a brain region known to influence mood- and cognition-related behaviors. Dietary composition should be considered when developing mental health management plans for men and women with an emphasis on increasing soluble fiber intake

Ambivalent roles of carboxypeptidase B in the lytic susceptibility of fibrin

Background Removal of C-terminal lysine residues that are continuously exposed in lysing fibrin is an established anti-fibrinolytic mechanism dependent on the plasma carboxypeptidase TAFIa, which also removes arginines that are exposed at the time of fibrinogen clotting by thrombin. Objective To evaluate the impact of alterations in fibrin structure mediated by constitutive carboxypeptidase activity on the function of fibrin as a template for tissue plasminogen activator-(tPA) induced plasminogen activation and its susceptibility to digestion by plasmin. Methods and results We used the stable carboxypeptidase B (CPB), which shows the same substrate specificity as TAFIa. If 1.5 – 6 μM fibrinogen was clotted in the presence of 8 U/mL CPB, a denser fibrin network was formed with thinner fibers (the median fiber diameter decreased from 138 – 144 nm to 89 – 109 nm as established with scanning electron microscopy). If clotting was initiated in the presence of 5 – 10 μM arginine, a similar decrease in fiber diameter (82 -95 nm) was measured. The fine structure of arginine-treated fibrin enhanced plasminogen activation by tPA, but slowed down lysis monitored using fluorescent tPA and confocal laser microscopy. However, if lysis was initiated with plasmin in CPB-treated fibrin, the rate of dissolution increased to a degree corresponding to doubling of the plasmin concentration. Conclusion The present data evidence that CPB activity generates fine-mesh fibrin which is more difficult to lyse by tPA, but conversely, CPB and plasmin together can stimulate fibrinolysis, possibly by enhancing plasmin diffusion

A role for the IgH intronic enhancer Eμ in enforcing allelic exclusion

The intronic enhancer (Eμ) of the immunoglobulin heavy chain (IgH) locus is critical for V region gene assembly. To determine Eμ's subsequent functions, we created an Igh allele with assembled VH gene but with Eμ removed. In mice homozygous for this Eμ-deficient allele, B cell development was normal and indistinguishable from that of mice with the same VH knockin and Eμ intact. In mice heterozygous for the Eμ-deficient allele, however, allelic exclusion was severely compromised. Surprisingly, this was not a result of reduced suppression of V-DJ assembly on the second allele. Rather, the striking breakdown in allelic exclusion took place at the pre-B to immature B cell transition. These findings reveal both an important role for Eμ in influencing the fate of newly arising B cells and a second checkpoint for allelic exclusion

A Student-Centered Self-Identity Approach to Harm Reduction in Adolescents

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