Personality is a major predictor of physical health. While much information on this association exists, inconsistencies are present, and it is unknown whether findings from non-clinical samples generalize to patients with chronic and serious illnesses. Therefore, we aimed to contribute to this knowledge base through analysis of a cross-sectional study on the personality and health of adults with and without cancer diagnoses. A sample of 168 participants with no cancer histories, 212 men with prostate cancer, and 55 women with breast cancer completed the Mini-IPIP Big Five personality survey as well as brief measures of health behaviors and physical health. Results indicated that personality was associated with health behaviors and physical health across samples. Consistent with our hypotheses, conscientiousness and neuroticism had the most robust associations, with higher conscientiousness and lower neuroticism explaining better health behaviors and better physical health (health behavior rmax = -.23, physical health rmax = -.31). Higher extraversion was also associated with some indicators of better physical health (rmax = .20). Consistent with our hypotheses, correlations for openness were relatively small (health behavior rmax = .15, physical health rmax = .11). Associations for agreeableness were sporadic. Interactions showed a few differences between the non-clinical and oncology samples. Overall, personality is important for health behaviors and physical health in non-clinical and oncology samples. Findings suggest the need for more research on the implications of personality in samples of patients with chronic and serious illnesses. / acase@tulane.edu

Acute respiratory distress syndrome (ARDS) and infant respiratory distress syndrome (IRDS) are pulmonary diseases with a mortality rate of ∼40% and 75,000 deaths annually in the United States. Mechanical ventilation restores airway patency and gas transport but leads to ventilator-induced lung injury. Surfactant replacement therapy alleviates these effects in IRDS, but is ineffective due to surfactant delivery difficulties and deactivation by vascular proteins leaking into the airspace in ARDS. Here, we demonstrated that surfactant function can be substantially improved (up to 50%) in situ in an in vitro pulmonary airway model using unconventional flows that incorporate a short-term retraction of the air-liquid interface, leading to a net decrease in cellular damage. This research may provide a starting point for developing novel ventilation waveforms to improve surfactant function in edematous airways. / acase@tulane.edu

This study examines the relationship between parental personal mastery, parents' depressive symptoms and children's internalizing symptoms and externalizing behaviors. Respondents in this study included 282 four- year old children randomly sampled from classrooms in public sponsored pre-k programs and their parents who participated in the National Center for Early Development and Learning (NCEDL) study of pre-k quality. Personal mastery was measured using Pearlin and Schoole's (1978) Personal Mastery Scale and depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Internalizing symptoms and externalizing behaviors were measured using the Hightower Teacher-Child Rating Scale. It was expected that children of parents who displayed depressive symptoms and low personal mastery would exhibit a higher level of internalizing and externalizing problems than their peers. No support was found for a relation between parental depression and child outcomes. However, children of parents reporting high parental mastery exhibited fewer behavioral problems than their peers. This study underscores the importance of parental beliefs and suggests the value of including modules on personal mastery in programs to train parents to deal with child behavior problems. / acase@tulane.edu

Astrocytes display a complex, stellate morphology in the brain, commensurate with their role in regulating nearly every functional aspect of the central nervous system. Innate activation of astrocytes is a classic hallmark of neurologic injury and disorder, characterized by proliferation, process hypertrophy, and transition toward polygonal morphology. However, the extent and consistency of these morphological changes, especially in the context of distinct pathologies, remain largely unknown. Here, changes in the fine neuroanatomy of astrocytes in rhesus macaque monkeys were characterized under a variety of conditions with relevance to translational research, including autistic-like behavior, bacterial and viral infections. Brain slices from paraffin embedded tissue archives were stained for glial fibrillary acidic protein, a reactive astrocyte marker, and imaged for both grey and white matter astrocytes. These cells were 3D-reconstructed in Neurolucida software and morphometric data including soma size, process length, volume and branching were analyzed and aggregated by animal and condition. It was found that process complexity in white matter astrocytes atrophied during lentiviral infection and depressive behavior, with decreased arbor length and tip quantity observed in SIV-infected and self-injuring animals. However, the opposite was seen during a bacterial infection, with increased arbor complexity and process length seen in Brucella-infected animals. Additionally, astrocytes from animals receiving oral naltrexone treatment for self-injurious behavior displayed a reversion from atrophied cell phenotypes back to original, control morphology. Thus, astrocyte activation and subsequent remodeling is not consistent, but rather context-dependent on the specific pathology and cellular subtype, and may be a driving factor in neurocognitive disorder. / acase@tulane.edu

Stored red blood cell (sRBC) morphology is currently scored manually by technicians in a slow labor intensive process prone to error. This project proposes a way to simplify, automate, and expedite the morphology scoring process by using a novel microfluidic device that I designed to facilitate the flow of a single layer of red blood cells (RBCs). The appearance of this flow allows for the capture of a series of high clarity images captured via digital camera coupled to a microscope that are ideally suited for image analysis algorithm-based morphological scoring. During storage, RBCs heterogeneously shift from the form of discocyte to the reversibly altered form of discoechinocyte as storage lesion progresses. Beyond this level of degradation, the cell assumes the form of a spheroechinocyte or spherocyte and becomes irreparably damaged. The microfluidic device and image analysis algorithm developed in this research classified the individual morphology of 5000 RBCs taken from storage into the physiologically relevant category of either “discocyte,” “reversibly changed,” or “irreversibly changed.” This process took only 15 minutes. The accuracy in classification was verified as 92.6% in a separate trial when compared against classification of the same sample images via manual inspection. The morphological distribution of the RBC population remained consistent in both cases. The findings of this project suggest that microfluidic device assisted automated image analysis can provide a quick and effective way to quantitatively estimate the viability of a sRBC population and the extent of storage lesion endured. This technology could provide augmented RBC storage and transfusion research capabilities and have clinical applications, such as the ability to conveniently differentiate between the transfusion qualities of two sRBC units of the same age. / acase@tulane.edu

Oligonucleotides (ONs) are typically defined as short nucleic acid polymers that are 20 to 200 bases long. It has been well known that aptamers (single-stranded DNA or RNA ONs) can adopt distinct three-dimensional folded structures and bind to target proteins (or other target molecules) with high affinity and selectivity. While aptamers that target proteins represent a promising molecular recognition modality that exploits the self-folding nature of nucleic acids, alternative protein recognition elements, usually synthetic small molecules that are projected from an ON scaffold, can also be utilized for protein-binding purposes. In particular, ONs tethered to protein-binding small organic molecules have received recent attention due to the capability of synthetic molecules to serve as specific inhibitors of proteins associated with disease and so these synthetic moieties can complement or augment the molecular recognition capacity of ONs. Further, the ON domain can also (a) serve as a “barcode” to identify the synthetic fragments and (b) act as a scaffold to project them in a desired and programmable fashion. This dissertation starts with representative examples, wherein ONs serve as binding moieties and/or as projecting scaffolds for synthetic protein-recognition elements, discussed in chapter one, followed by the development of two novel ON-based protein inhibitors which further explore the approach of coupling synthetic protein-binding fragments with ON scaffolds. The first system, as described in chapter two, exhibits controllable protein inhibition against the target protein in selective response to a cancer-associated microRNA. The second system (explored in chapter three) features an aptamer core sequence flanked by small protein-binding elements. The resultant aptamer chimera is capable of forming a complex simultaneously with two target proteins, leading to dual inhibition. / acase@tulane.edu

Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. However, in humans, anecdotal reports abound regarding impaired cognition during pregnancy, colloquially termed baby brain. Epidemiological studies indicate that 50 to 80 percent of pregnant women report problems with thinking and/or with memory. When tested objectively, the most consistent finding indicates impaired verbal memory. However, no studies to date have focused specifically on the effects of pregnancy and motherhood on human spatial cognition. We used analogous tests of spatial memory and navigation at matched phases of reproduction to study changes in spatial memory across pregnancy and motherhood in both rats and humans. Parallel studies with closely matched paradigms allowed us to better understand evolutionary conservation of the effects of pregnancy and motherhood on spatial abilities, while contributing to our knowledge of each species individually. Results indicated a persistent advantage in object-in-place memory of primiparous female rats that emerged during lactation not during pregnancy, and was not related to non-mnemonic factors of anxiety or neophobia. On a modified water maze task to assess learning strategy, both primiparous and nulliparous females learned the task at similar rates and accuracies, but neither group demonstrated a preference for place strategy or stimulus-response strategy. In humans, pregnant and lactating women were not objectively impaired compared to women who had never been pregnant when tested on several measures of spatial performance to assess object-in-place memory and spatial navigation. Despite objectively equivalent performance, both pregnant and lactating women subjectively rated themselves as more impaired on spatial tasks than never-pregnant women. Disparate results on the effects of pregnancy and motherhood on cognitive function in rats and humans calls into question the fitness of the rat model as applied to human cognition. / acase@tulane.edu

The use of advanced functional polymer materials has gained an enormous impact during the past decades. Due to the fact that the physical properties of macromolecules are inherently dependent on their structure and connectivity on the nanoscale, precisely control over polymer architecture has been a longstanding goal for polymer chemists. The recent development of copper catalyzed azide-alkyne click chemistry provides a nearly quantitatively tool for macromolecular coupling. Through the combination of living polymerization and click chemistry, novel complex polymer architectures can be readily constructed, including star polymers, brush polymers, cyclic polymer and ladder polymers. While amphiphilic block copolymers have demonstrated their utility for a range of practical applications, the behavior of block copolymers that contain cyclic topologies remains largely unexplored due to limited synthetic access. In order to investigate their micelle formation, biocompatible cyclic amphiphilic poly(ethylene glycol)-block-polycaprolactone, c-(PEG-b-PCL), and tadpole shaped PEG-PCL, were synthesized by a combination of ring opening polymerization (ROP) and click chemistry. In addition, exactly analogous linear block copolymers have been prepared as control samples to elucidate the role of polymer architecture in their self-assembly and acid-catalyzed degradation. High purity homo-arm and mikto-arm poly(ethylene glycol) (PEG) stars were successfully prepared by the combination of epoxide ring openings and azide-alkyne click reactions. First, monohydroxy-PEG was modified via epoxide chemistry to bear one hydroxyl and one azide functionality at the same polymer chain end. An alkyne functionalized PEG chain was then coupled to the azide. Subsequently, the remaining hydroxyl could be reactivated by epoxide chemistry again to an azide and alcohol group. This enabled a step-wise coupling and reactivation of the end group to add a series of well-defined polymer arms onto a star polymer. The use of efficient reactions for this iterative route provided star polymers with an exact number of arms, and a tailorable degree of polymerization for each arm. Detailed characterization confirmed the high purity of multi-arm polyethylene glycol products. Novel cyclic brush-shaped polymers can be successfully prepared by using the CuAAC click coupling reaction. First, cyclic-shaped polymer bearing a single hydroxyl group can be synthesized by CuAAC click cyclization. After a one-step modification of the hydroxyl group by esterification with an azido-carboxylic acid, a “clickable†polymer ring was obtained. A linear polymer backbone with an alkyne functional group on every repeat unit was prepared by ATRP of acetoxystyrene followed by reduction to poly(4-hydroxystyrene) and esterification with pentynoic acid. Finally, by coupling multiple equivalents of the cyclic precursor onto the linear backbone, a cyclic brush-shaped polymer was prepared. This provides a highly efficient approach to prepare novel polymer architectures containing multiple cyclic components. / acase@tulane.edu

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Amphiphilic polymers are a subset of macromolecules that exhibit both hydrophobic and hydrophilic moieties within their covalently bonded structures. Because of the differing solubilities of the contrasting regions of the amphiphilic polymers, they exhibit an inherent ability to self-assemble in the solution phase where one block exhibits poor compatibility with the solvent. And by tuning the composition, size and shape of the polymers, a variety of morphologies of the assembly in solution were observed, like spherical micelle, vesicle, rod-like and lamellar. The propensity to self-assemble to complex structures makes them promising candidates in wide varieties of applications, for example, drug delivery, gene transfection, catalyst, and sensing. Nowadays, most of the researches of amphiphilic polymers have been focused on simple linear di-block copolymers. Amphiphilic non-linear architectures, like dendrimers, star polymers, hyperbranched polymers, brush polymers and cyclic polymers, have been proved to exhibit unique properties compare to their linear analogs, such as lower critical micelle concentrations and better-assembled strengths because the structures are covalently tethered together. These unique properties make them a particularly attractive vehicle in drug/gene delivery. However, investigations of the amphiphilic homopolymers are limited and the majority of work have been done is focused on charged polymers, anionic or cationic. The amphiphilic ionic homopolymers largely relied on the pH of the solution to assemble into complex morphologies, perturbation of pH could result in deformation of assemblies and pro-release of encapsulate. Also, extremely severe pH environment prohibit the usages of the amphiphilic polymers in biological systems. Well defined non-ionic amphiphilic linear homopolymers bearing hydrophobic decyl groups and hydrophilic tri(ethylene glycol) monomethyl ether groups was synthesized by atom transfer radical polymerization technique and the structures were confirmed by NMR and GPC. The low polyedispersity polymers, were found to readily self-assembled to form micelles in non-polar organic phase and reverse micelles in polar aqueous phase. The assemblies were studied with UV-vis spectroscopy, fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy to determine the critical micelle concentrations and assembly size in both conditions. The synthesis towards more complex architectures of the homopolymers was also investigated. / acase@tulane.edu