Bulletin of Computer Science and Electrical Engineering (BCSEE)
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Understanding Large Physiological Variation: Genomics, Genes, and Gene Expression
No full textStudies investigating genotype to phenotype relationships have demonstrated that genetic variation is biologically important; however, the evolutionary significance of these relationships and variation maintenance remains poorly understood. Here, three wild populations of the small teleost fish Fundulus heteroclitus: one locally heated by thermal effluent from a nuclear power plant (TE) and two reference populations that do not experience local heating (10 km north and 3.5 km south) were used. This experimental design was intended to test the central hypothesis that the TE population is locally adapted when compared to the north and south reference sites. Temperature specific metabolic and thermal tolerance traits, tissue specific (heart and brain) mRNA expression, and genetic variation (single nucleotide polymorphisms, SNPs) are compared among populations. Few differences exist among populations in physiological traits, mRNA expression, or SNPs. Instead, large inter-individual variation in metabolic and thermal tolerance traits is irrespective of population. This large variation is explained by tissue and acclimation temperature specific mRNA expression patterns, with different mRNAs in heart and brain tissue from similar pathways explaining trait variation. Whole genome sequencing for the same individuals that physiological traits and mRNA expression were measured in allowed direct (genome wide association, GWAS) and indirect (expression quantitative trait loci, eQTL) associations with physiological traits to be examined. Many significant eQTL explain single and multivariate mRNA expression patterns. These tissue specific eQTL are dominated by trans-acting factors (found on different chromosomes than the mRNAs they impact). This thesis contributes new knowledge on the evolutionary importance of biological variation. </p
The Ecology, Conservation, and Management of the Everglades' Herpetofaunal Community
No full textThe Everglades ecosystem is a globally unique ecosystem that is recognized as a natural world heritage site, North-America’s only sub-tropical preserve, the largest sawgrass prairie in the world, and is home to nearly 6 dozen threatened or endangered species. Unfortunately, like many other ecosystems, the Everglades has been subjected to a wide variety of anthropogenic impacts that include wholesale habitat destruction, dramatic changes in sheet water flow, large numbers of invasive species, and consumptive exploitation both through overharvesting of fauna and resource acquisition. While the impact of these changes has been documented extensively for taxa such as wading birds, small mammals, and fishes, almost nothing has been documented about long-term changes in herpetofaunal abundance, distribution, or community composition. To address this lacuna, I utilized long-term data analysis, landscape level experiments, natural history studies, and population and community ecology analysis. I analyzed analyzed three long-term datasets that monitored amphibian abundances in the Everglades ecosystem across multiple decades, utilized a multi-year, landscape scale experiment to determine the impacts of changing hydrological regimes on the Everglades herpetofaunal community, used a combination of morphological analysis and DNA barcoding to analyze the dietary components of the two giant salamanders (the Greater Siren (Siren lacertina) and the Two-Toed Amphiuma (Amphiuma means)), undertook the largest multi-year capture-mark-recapture study on both species to estimate population demographics and a multi-year radio tracking study to determine seasonal movement patterns and estimate home-range sizes, and finally conducted an Everglades wide amphibian sampling project that was designed to understand the environmental drivers of amphibian abundance and community composition across the Greater Everglades Ecosystem. </p
Inhibition of Inflammatory RAGE Signaling in Breast Cancer and Metabolic Diseases
No full textThe Receptor for Advanced Glycation End-products (RAGE) is normally expressed at low levels, but is highly expressed in a variety of inflammatory states. RAGE has been implicated in pathogenic progression of cancer and various metabolic diseases, and therefore provides a potential therapeutic target in these disease states. RAGE knockout (RKO) mice are viable and display no developmental defects, suggesting therapeutic targeting of RAGE to be a viable approach. Our lab has identified two RAGE inhibitors that can be used in both in vitro and in vivo models: FPS-ZM1 (FPS) and TTP-488 (TTP). Previously, our lab has established one of these inhibitors, FPS, as a therapeutic that markedly reduced morbidity in breast cancer (BrC) and diabetes mouse models. We additionally noticed that in diabetic models, RAGE inhibition helped rescue a normal hepatic phenotype. Because of the implication of RAGE in the characteristic inflammation of BrC and metabolic diseases, as well as a growing cohort of the American population susceptible to both of these pathologies, I looked to see if RAGE presented a viable target in these disease states. First, I further optimized our drugs and characterized the effect of RAGE in syngeneic and spontaneous BrC models. Through these drug optimization experiments, I generated significant downregulation of metastasis using FPS. Secondly, I tested whether or not RAGE inhibition could affect the pathophysiological progression of diabetes, obesity, and fatty liver disease in mice. These data demonstrated a visible downregulation of hepatic lipid accumulation in drug treated mice. This work should pave the way for future studies to elucidate the role that RAGE plays in driving the inflammation of BrC and metabolic disorders, identify how each drug mechanistically inhibits RAGE signaling, and develop preclinical studies to therapeutically target RAGE in these individual and comorbid states.</p
Impact of Neighborhood Disadvantage on High-Risk Oncotype DX Recurrence Scores and Breast Cancer Survival
No full textObjective: Evaluate the association between neighborhood disadvantage and Oncotype DX score, a surrogate for tumor biology, among a national cohort. Summary Background Data: Women living in disadvantaged neighborhoods have shorter breast cancer (BC) survival, even after accounting for individual-level, tumor, and treatment characteristics. This suggests unaccounted social and biological mechanisms by which neighborhood disadvantage may impact BC survival. Methods: This cross-sectional study included Stage I and II, ER+ /HER2- BC patients with Oncotype DX score data from the National Cancer Database from 2004-2019. Multivariate regression models tested the association of neighborhood-level income on Oncotype DX score controlling for age, race/ethnicity, insurance, clinical stage, and education. Cox regression assessed overall survival. Results: Of the 294,283 total BC patients selected, the majority were non-Hispanic White (n=237,197, 80.6%) with 7.6% non-Hispanic Black (n=22,495) and 4.5% Other (n=13,383). 27.1% (n=79,7254) of the population lived in the most disadvantaged neighborhoods with an annual neighborhood-level income of $48,000. On multivariate analysis controlling for age, race/ethnicity, insurance status, neighborhood-level education, and pathologic stage, patients in disadvantaged neighborhoods had a greater risk of high- versus low-risk Oncotype DX scores compared to those in advantaged neighborhoods [OR=1.04 (1.01-1.07), P =0.0067]. Conclusion and Relevance: This study takes a translational epidemiologic approach to identify that women living in the most disadvantaged neighborhoods have more aggressive tumor biology, as determined by the Oncotype DX score
Perspectives from Demography and Geography
No full textReports of impending Jewish demographic implosion are mistaken, Sheskin contends in this chapter. While American Jews are somewhat older and less fertile than the population as a whole, surveys indicate significant numerical growth over the past several decades, thanks in part to immigration from the former Soviet Union and, it appears, from the readiness of offspring of intermarried couples to identify as Jewish. To be sure, there has been a noticeable decline in religious practice—a development related to a proportional shift in the Jewish population from the Northeast and Midwest to the South and West. Nevertheless, the strength of Jewish cultural and educational institutions gives the lie to the belief that Judaism in America is in a continuous downward spiral. All in all, Sheskin is cautiously optimistic that the future of the American Jewish community is secure
Correlative Analysis of Wastewater Trends with Clinical Cases and Hospitalizations through Five Dominant Variant Waves of COVID-19
No full textFood Faiths Diet, Religion, and the Science of Spiritual Eating.
No full textFood Faiths explores how individuals use scientific concepts about food and diet as the basis for a spiritual practice. The book examines how science filters through popular culture to affect the spiritual inclinations of individuals and investigates the influence of science, biomedicine, and nutrition on contemporary spirituality
Fibromyxoid Nephrogenic Adenoma A Series of 43 Cases Reassessing Predisposing Conditions, Clinical Presentation, and Morphology
No full textNephrogenic adenoma is a benign epithelial lesion of the genitourinary tract that arises from the reimplantation and proliferation of shed renal tubular cells in areas of urothelial injury and denudation. Fibromyxoid nephrogenic adenoma is a rare variant that consists of compressed spindle-shaped renal epithelial cells in a fibromyxoid background. Only 14 observations of this variant are reported in the literature. We performed a retrospective analysis of fibromyxoid nephrogenic adenomas from 3 large reference centers. We identified 43 lesions in 6 women and 36 men (2 in 1 man) with a median age of 72 years (range, 31 to 94 y). Median lesion size was 0.7 cm (range, 0.2 to 5 cm). Nephrogenic adenomas were in the bladder (n=15), prostate/prostatic urethra (n=14), kidney (n=7), ureter (n=3), penile urethra (n=3), and urethral diverticulum (n=1). One of the kidney lesions developed in an end-stage kidney and radiologically mimicked cancer. Of 37 patients with information, 36 had predisposing conditions including prior biopsy, transurethral resection of bladder tumor, resection, Foley catheter, BCG treatment, urinary stones, (chemo)radiation, or diverticulum. Only 4/37 (10.8%) had a history of prior irradiation. Fifteen lesions had pure fibromyxoid morphology and 28 were admixed classic and fibromyxoid patterns. Three nephrogenic adenomas involved prostatic stroma, 3 renal sinus fat, 2 muscularis propria (1 bladder, 1 renal pelvis), 1 perinephric fat, and 1 corpus spongiosum. Ten fibromyxoid nephrogenic adenomas were intermixed with urothelial carcinoma, 1 with prostate adenocarcinoma, and 1 with malignant melanoma. By immunohistochemistry, PAX8 was positive in all the examined lesions (n=31). Napsin A was negative in all examined fibromyxoid nephrogenic adenomas (n=30). Twenty of them had classic nephrogenic adenoma component which was positive for napsin A. Similar to classic nephrogenic adenoma, fibromyxoid nephrogenic adenoma can occur anywhere along the urinary tract and is associated with a prior history that causes urothelial injury. In nearly a quarter of the cases, fibromyxoid nephrogenic adenoma extended beyond the lamina propria. Unlike previously suggested, fibromyxoid nephrogenic adenoma is not specifically related to prior radiation therapy. Awareness of this variant is important to avoid misdiagnosis and overtreatment
Efficacy of transcutaneous posterior tibial nerve stimulation in functional constipation
No full textMost children with functional constipation (FC) improve with conventional treatments. However, a proportion of children have poor treatment outcomes. Management of intractable FC may include botulinum toxin injections, transanal irrigation, antegrade enemas, colonic resections, and in some cases sacral nerve stimulation (SNS). SNS is surgically placed, not readily available and expensive. Posterior tibial nerve stimulation (PTNS) allows transmission of electronic impulses and retrograde stimulation to the sacral nerve plexus in a portable, simple and non-invasive fashion. To assess the efficacy and safety of transcutaneous PTNS for the treatment of FC in children. Single-center, prospective interventional study. Children 4-14 years with Rome IV diagnosis of FC received ten daily PTNS (30 min/day) sessions. Electrodes placed over skin of ankle. Strength of stimulus was below pain threshold. Outcomes were assessed during treatment and 7 days after. Twenty-three subjects enrolled. Two children excluded (acute gastroenteritis, COVID-19 contact). Twenty completed the study (4-14 years), (8.4 ± 3.2 years, 71.4% female). We found significant improvement in the consistency of bowel movements (BM) (p = 0.005), fecal incontinence (FI) (p = 0.005), abdominal pain presence (p = < 0.001) and intensity (p = 0.005), and a significant for improvement in blood in stools (p = 0.037). There was 86.3% improvement in abdominal pain. 96.7% reported treatment satisfaction. Only one child required rescue therapy.
We found significant improvement in stool consistency, FI, abdominal pain, and hematochezia. This suggests that transcutaneous PTNS could be a promising noninvasive treatment for FC in children. Large studies are needed.
• Functional constipation is one of the most common disorders in children. • Current management of functional constipation consists of an integrative approach that includes medications, diet and behavioral strategies.
• Posterior tibial nerve stimulation is a novel noninvasive and easy to use therapy that can improve stool consistency, fecal incontinence and blood in stools