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Examining the Role of Family Cohesion and Simpatía in Patient-Physician Communication, Health Anxiety, and Health-Related Quality of Life Among Hispanic Prostate Cancer Survivors
No full textHispanic prostate cancer (PC) survivors experience elevated psychosocial distress and lower satisfaction with care compared to non-Hispanic White survivors, partly due to cultural barriers in patient-provider communication. Perceived efficacy in patient-physician interactions has been linked to lower health anxiety in cancer populations and may support better health-related quality of life (HRQoL). Family cohesion and simpatía, two culturally meaningful constructs, may shape how Hispanic PC survivors navigate medical interactions, with downstream effects on psychological and functional outcomes. This study examined whether family cohesion and simpatía were associated with survivors’ perceived efficacy in patient-physician interactions, and whether perceived efficacy was linked to lower health anxiety and, in turn, better general and disease-specific HRQoL, including urinary and sexual functioning. Baseline data were drawn from 206 Hispanic PC survivors enrolled in a randomized trial testing a culturally adapted stress management intervention. Structural equation modeling tested hypothesized pathways from family cohesion and simpatía to perceived efficacy in patient-physician interactions, from perceived efficacy to health anxiety, and from health anxiety to HRQoL outcomes, adjusting for sociodemographic, clinical, and acculturation covariates. Greater family cohesion was associated with higher perceived efficacy in patient-physician interactions, which in turn was associated with lower health anxiety. Higher health anxiety was associated with poorer urinary functioning and general HRQoL, but not sexual functioning. Family cohesion and perceived efficacy were also positively associated with general HRQoL. Findings highlight family cohesion and perceived efficacy in patient-physician interactions as protective factors, underscoring the importance of culturally informed survivorship care and communication-focused interventions for Hispanic PC survivors.</p
When Science Comes to Storytime: Exploring the Integration of Science and Literacy Through Preschool Teachers’ Shared Book Reading Practices in Support of Spanish-English Dual-Language Learners
No full textIn an English-dominant education system, Spanish–English dual-language learner (DLL) children remain underrepresented in research aimed at promoting equitable early learning environments, despite being a rapidly growing population in the United States (Basterra et al., 2010). Although strong oral language skills are known to support later academic outcomes for monolingual children (Snow et al., 1998), far less is known about how instructional practices support bilingual language development in early childhood. Science instruction has been shown to promote learning across academic domains (Bustamante et al., 2018; Halpin et al., 2023; Kermani & Aldemir, 2015; NRC, 2007, 2012), and shared storybook reading—particularly repeated readings—supports language, fluency, and comprehension (Anderson et al., 1985; Harris & Sipay, 1990; NICHD, 2000; Routman, 1991), suggesting that science-focused storybooks may be an effective context for integrated learning. This study examined preschool teachers’ instructional practices during shared reading of a Spanish-English bilingual science storybook in an intentionally Spanish-English bilingual preschool. Findings indicated that many teachers increased their use of three-dimensional science-related talk during a second reading. Teachers also reported valuing the translational-equivalent structure of the bilingual storybook for its flexibility in supporting instruction in both languages and for promoting bilingual development for students and teachers alike. By reframing science and literacy as bidirectional and mutually reinforcing, this study challenges siloed approaches to early instruction and highlights the instructional potential of their integration. In doing so, it addresses a critical gap in a literature that has largely focused on K–5 settings by extending research on using a bilingual science-focused storybook in bilingual preschool classrooms and offers qualitative insight into prereading, reading, and post-reading teacher practices that support bilingual learners.</p
Transitioning into Survivorship: Life Engagement and the Role of Positive Automatic Thoughts in Shaping Long-Term Recurrence Worries and Cancer-Related Distress in Breast Cancer Survivors
No full textReceiving a breast cancer diagnosis and undergoing treatment is profoundly stressful, with fear of recurrence posing a major long-term concern for survivors. Predictors of sustained recurrence worries and cancer-related distress remain underexplored. One potentially important factor is life engagement, defined as vitality, motivation, and meaningful engagement across emotional, physical, social, and cognitive domains. Life engagement aligns with interventions like behavioral activation, acceptance and commitment therapy, and meaning-centered psychotherapy, which support survivors’ psychological well-being. However, its role in shaping long-term distress during survivorship remains unclear.To address this gap, this study used structural equation modeling to develop a latent construct of life engagement in breast cancer survivors using items from established psychosocial measures. We tested whether life engagement one-year after surgery predicted recurrence worries and cancer-related distress four years later, and whether positive automatic thoughts at 18 months mediated these associations. Analyses included 210 breast cancer survivors who remained recurrence free during the first five years after diagnosis, controlling for age, race/ethnicity, cancer stage, and adjuvant or hormone therapies.Life engagement, conceptualized as social and recreational connection, experiential pleasure, and creative commitment, fit well as a second-order factor. Greater engagement at one-year predicted fewer recurrence worries, cancer intrusions, and avoidance behaviors at four years and was associated with more positive automatic thoughts at 18 months, though mediation was not observed. These findings extend the life engagement framework to breast cancer survivorship and suggest that life engagement may protect against long-term distress. The one-year follow-up period may represent a key window to identify survivors struggling to re-engage in life and incorporate engagement-focused interventions into survivorship care.</p
Photochemistry of Sulfur-Substituted Small Molecules Encapsulated Within a Water-Soluble Host
No full textSupramolecular chemistry is widely employed by nature to direct and control highly precise chemical transformations, most notably in enzyme–substrate systems, where noncovalent interactions provide both selectivity and rate enhancement. Inspired by these biological systems, we utilized the water-soluble supramolecular host octa-acid (OA) to investigate photochemical reactions under confined aqueous conditions.In this dissertation, we demonstrate that encapsulation within OA creates a unique microenvironment that alters reactivity, stabilizes reactive intermediates, and modulates reaction pathways. We first investigated the photochemistry of dispiro-substituted diketones and found that confinement within OA in borate buffer leads to the generation and remarkable stabilization of ketene intermediates, significantly extending their lifetimes relative to bulk water. We further examined strained thioxo derivatives and observed the formation of distinct photoproducts in the presence of OA, underscoring the profound influence of host–guest interactions and spatial confinement on photochemical outcomes. Additionally, we studied a 7-methoxythiocoumarin-based phototrigger, which is inherently hydrophobic. Encapsulation within OA enabled its solubilization in water and facilitated the photorelease of acidic products. Confinement promoted formation of a radical anion–type intermediate via a triplet-state pathway, providing new mechanistic insight into photochemical processes operating under confined conditions.Finally, a comparative mechanistic investigation of substitution effects in coumarin triggers at 2-position (oxygen versus sulfur) and the 7-position (methyl-substituted versus unsubstituted) revealed that subtle structural modifications critically govern excited-state behavior, intermediate formation, and overall reaction mechanisms within the supramolecular cavity. </p
Elucidating Disease Markers and Mechanisms of Primary Lateral Sclerosis
No full textPrimary lateral sclerosis (PLS) is a slowly progressive motor neuron disease (MND) characterized by the selective degeneration of upper motor neurons (UMNs). Patients typically present with spasticity, hyperreflexia, and progressive lower-limb muscle stiffness and weakness. A definitive diagnosis often requires several years, mainly due to the significant clinical overlap with the more common and severe MND, amyotrophic lateral sclerosis (ALS). Consequently, the causes and mechanisms of PLS have been understudied, resulting in limited basic knowledge needed to develop effective therapies. While the accumulation of DNA damage and diminished DNA repair capacities are well-established features of many neurodegenerative disorders, the role of genomic deterioration in PLS has not been previously evaluated. Moreover, previous technologies for evaluating DNA breakage are limited in their ability to map the precise locations of single- and double-strand breaks. To determine the degree to which genomic instability contributes to the pathophysiology of PLS, induced pluripotent stem cells (iPSCs) were generated from PLS patients and differentiated into cortical neurons, an approximation of the affected cell type, UMNs, in PLS. Using this model system, a single-nucleotide-resolution profiling technique, SSiNGLe, was applied to characterize genome-wide patterns of DNA single-strand breaks (SSBs). This work provides the first comprehensive map of DNA break patterns in human-derived neurons and demonstrates that SSBs are not randomly distributed across the genome; instead, they are enriched in promoters and enhancers, genomic elements involved in transcriptional regulation. The finding that DNA lesions in PLS disproportionately accumulate in transcribed regions of the genome implicates genomic deterioration as a major source of transcriptional dysregulation that leads to neuronal dysfunction and ultimately neuronal death.</p
Single Cell and Spatial Transcriptomics Approaches to Assess Fibroblast Heterogeneity After Spinal Cord Injury
No full textSpinal cord injury (SCI) triggers a highly heterogeneous and spatially dynamic wound response involving diverse myeloid and fibroblast populations. Here, we integrate high-resolution single-cell and spatial transcriptomics with novel genetic lineage tracing models to define the cellular composition of the spinal cord after injury, its temporal dynamics, and age-dependent molecular pathology of the SCI microenvironment.We identify previously unrecognized complexity within the myeloid cell subtypes, expanding on our initial analyses. Spatial mapping reveals that BAMs infiltrate the lesion epicenter and are positioned, even prior to injury, to act as early fibroblast activators—a role supported by colocalization analyses. Mature inflammatory macrophages dominate fibroblast interactions by 7 days post-injury (dpi), though immature monocytes do persist in the epicenter of the fibrotic scar, while microglia segregate into distinct proliferative and interferon-responsive populations which corral the fibroblasts. Notably, discrete “interferon islands” emerge throughout tissue distal to the lesion, indicating long-range perturbations in otherwise spared regions.The fibrotic scar was originally thought to be the result of the meninges being physically displaced into the parenchyma, though analyses by our lab demonstrated that the fibrotic scar develops even in the non-penetrating contusive injury, where perivascular fibroblasts are visualized delaminating from local vessels. Now, with the application of a larger scale single cell dataset and new genetic lineage tracing tools, we find that a combination of unique fibroblast niches contribute to the development and persistence of the scar...</p
Neighborhood Disadvantage and Anxiety in Women with Breast Cancer: The Buffering Role of Social Support
No full textBreast cancer is shaped by a complex interplay of biological, psychosocial, and environmental influences. One key environmental factor, neighborhood disadvantage, is a form of social adversity that has been linked to worse cancer outcomes. Anxiety, which is known to worsen breast cancer prognosis, is more prevalent among individuals living in disadvantaged neighborhoods. Emerging evidence suggests that low social support may intensify the relationship between neighborhood disadvantage and physiological stress. In this study, we examined the association between neighborhood disadvantage and multidimensional anxiety (i.e., generalized anxiety, breast cancer-specific anxiety, and anxious affect) and assessed whether social support from three sources (i.e., partner, adult female family members, friends) moderated this relationship. Women with breast cancer (N = 240) completed baseline measures and reported their residential addresses. Neighborhood disadvantage showed a negative significant association with the anxiety latent variable; however, the added direct path between neighborhood disadvantage and generalized anxiety symptoms revealed a positive significant relationship. When social support was included as a moderator, two significant interactions emerged. Simple slopes revealed that participants with low or average levels of friend instrumental support in disadvantaged neighborhoods displayed lower anxiety, as did those with average or high levels of partner negative support. The findings of this study suggest that generalized anxiety symptoms may be especially noticeable or prevalent among participants in disadvantaged neighborhoods. While two sources of social support emerged with moderating effects, these results should be interpreted with caution.</p
Reprogramming the Epigenome of (Pre)malignant Hematopoietic Cells with Retinoic Acid and Ascorbate
No full textEnhancing TET2 activity through genetic or pharmacologic approaches, such as ascorbate supplementation, can slow myeloid malignancy progression. However, ascorbate alone may be insufficient to fully activate TET2 in malignant cells due to pharmacokinetic constraints and the need for chromatin remodeling to enable effective epigenetic reprogramming. Here, we identify a novel mechanism to enhance TET2 activity via all-trans retinoic acid (ATRA), which induces RARA-mediated TET2 transcription in myeloid leukemia cells and synergizes with ascorbate to promote DNA hydroxymethylation and chromatin remodeling at key myeloid differentiation loci. Using Tet1/2/3-deficient mice and primary human AML models, we show that ATRA plus ascorbate more effectively induces differentiation, inhibits leukemia stem cell self-renewal in a TET2-dependent manner, and sensitizes AML cells to targeted therapies in vivo leading to improved survival. These findings support the combined use of ATRA and ascorbate as a strategy to enhance TET2 activity for the treatment of myeloid malignancies.</p
Phosphatidylserine Decarboxylase and Its Effects on Retinal Ganglion Cell Axonal Growth and Lipidomics
No full textOptic neuropathies lead to irreversible blindness that cannot be restored through current therapeutic interventions. Optic neuropathies result from damaged retinal ganglion cell (RGCs) axons that transmit the visual signal from the eye to the brain. Human glaucomatous optic nerves tissues present an aberrant accumulation of phosphatidylethanolamine (PE) by upregulated phosphatidylserine decarboxylase (PSD) expression and activity. PSD is a cristae-localized, mitochondrial enzyme that converts phosphatidylserine to PE. Concurrently, glaucomatous mouse models present short, spherical mitochondrial morphologies lacking cristae curvature. The relationship between PSD and RGC mitochondrial morphologies has not been studied. Optic nerve regeneration is a promising avenue for restoring lost vision. Regenerative optic nerve lipidomic profiles display reduced PE while regenerating RGC transcriptomics reveal downregulated PSD expression.This work evaluates PSD’s effects on RGC axonal growth, mitochondrial morphology, membrane fluidics by C-Laurdan, and lipidomics. We utilized AAV2-mediated gene modulation using C57BL/6 mouse RGCs in vitro and in vivo. PSD overexpression (PSDOE) and PSD knockdown (PSDKD) by three separate shRNAs (sh1, sh2, sh3) were assessed in stimulating RGC neurite outgrowth in vitro. Overall, PSDKD (PSDsh3) significantly increased RGC neurite outgrowth with minimal effects on mitochondrial morphology. PSDKD significantly increased somal membrane fluidity accompanied by lipid profiles presenting reduced cholesterol phosphatidylcholine, and saturated triacylglycerols. In contrast, PSDOE presented the shortest neurite outgrowth and short, spherical mitochondria. Using 2 month old C57BL/6 mice and in vivo optic nerve crush model, PSDKD by PSDsh3 significantly increased mCherry+CTB+ short-distance regenerating axons (<200µm). These results indicate that PSDKD stimulates RGC axon regenerative competency and is likely a good candidate for combinative therapies for long-distance regeneration.</p
Changes in Ambient [Ca2+] Impact Reproduction and Development in Lymnaea Stagnalis
No full textThe freshwater pond snail, Lymnaea stagnalis, is extremely well studied and a model organism in many scientific disciplines including physiology and ecotoxicology. This species produces egg masses that hatch within an average of 10-14 days of development with a fully developed CaCO3 shell. A lot is known regarding calcium (Ca2+) acquisition in adult mollusks but less is known about the development and Ca2+ acquisition of mollusk embryos. Ca2+ is a vital element for reproduction, development, and overall biological function. Previous studies have shown that the development of L. stagnalis is impaired by a reduction in ambient Ca2+ concentrations, and that adults prioritize Ca2+ uptake over other biological functions. In this study I delineate the impacts of Ca2+ on the reproduction and development of Lymnaea stagnalis. Impacts were determined through monitoring of the Ca2+ acquisition by laid egg masses as well as the provisioning and production of eggs by adults in varying Ca2+ environments. Adult L. stagnalis fully provision egg masses with [Ca2+] despite low [Ca2+] environments while significantly reducing reproductive output. Interestingly, there were no measured impacts on adult Ca2+ homeostasis, and adults did not consume more food to supplement their Ca2+ needs in low [Ca2+] conditions. Lymnaea stagnalis appears to be able to control the calcium content of their egg masses and control their reproductive output to adapt to changes in their environment. Results show that adult snails prioritize the quality of egg masses over quantity in low [Ca2+] environments. Limited reproduction in low [Ca2+] can have detrimental impacts on L. stagnalis populations as water acidification and freshwater [Ca2+] continues to impact aquatic systems.</p