UAB Digital Commons (Univ. of Alabama at Birmingham)
Not a member yet
32303 research outputs found
Sort by
Analysing Post-Mortem Interval By Blood Metabolomics
Get PDFAccurate estimation of the postmortem interval (PMI) is a critical aspect of forensic investigations, aiding in time-of-death determination. This study employs High-Performance Liquid Chromatography Mass Spectroscopy (HPLCMS) and Gas Chromatography-Mass Spectrometry (GC-MS) to analyze postmortem metabolic changes and identify potential biomarkers for PMI estimation analyses through metabolomics. Blood serum samples from ante mortem samples (AMS) and postmortem samples (PMS) were categorized into Control (0 hrs), Early PMI (25–58 hrs), and Late PMI (92–163 hrs) groups. Multivariate statistical analyses, including Partial Least Squares-Discriminant Analysis (PLS-DA), Variable Importance in Projection (VIP) scoring, and metabolic pathway evaluations, were conducted to assess biochemical alterations over time. HPLC analysis revealed that adenosine diphosphate (ADP), lactate and citrate were observed in control samples but declined postmortem due to ATP depletion and metabolic degradation. Lactate showed an irregular trend. Amino acids such as isoleucine, methionine, and phenylalanine increased in early PMI, indicating proteolysis, while glycocholate and creatine levels were elevated in late PMI, signifying lipid and muscle degradation. GC-MS further identified ten key metabolites, including L-Proline, L-Leucine, L-Methionine, L-Alanine, and Lactic Acid, as critical indicators of metabolic progression. Lactic Acid and Threonine were predominant in early PMI, while L-Proline, L-Leucine, L-Alanine and L-Methionine exhibited significant increases in late PMI. Palmitelaidic acid, Palmitic acid, Linoleic acid, and Stearic acid were only found in GCMS. These findings confirm systematic postmortem metabolic shifts, identifying key metabolites as potential PMI biomarkers. Lactate and Lactic acid follow same metabolic path yet have different trend in HPLC and GCMS which require further analysis. Despite promising results, limitations like small sample size and lack of validated standards highlight the need for further research. Future studies should integrate a larger sample size and improve statical analysis to enhance PMI estimation accuracy, strengthening the forensic applicability of metabolomics
Targeting the Thyroid-Stimulating Hormone Receptor (TSHR) in Thyroid Cancer
Get PDFRadioactive iodine (RAI) has been effective in the treatment of thyroid cancer, the most common endocrine neoplasia, since its introduction into clinical use over eighty years ago. However, not all patients benefit from RAI. Up to 20% of patients with well-differentiated thyroid cancer (WDTC) become radioactive iodine refractory (RAI-R). These RAI-R patients have 5-year survival rates of 50% and 10-year survival rates of 10%. In addition, more aggressive subtypes including oncocytic thyroid carcinoma (OC), poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC) are less responsive to RAI therapy. Despite accounting for less than 5% of annual thyroid cancer cases, PDTC and ATC represent more than half of annual thyroid cancer mortality. To address the need for new diagnostic and therapeutic strategies in these patients, this study explores the thyroid-stimulating hormone receptor (TSHR) as an alternative target in thyroid cancer. We described the frequency of TSHR expression in OC (62%), PDTC (58%), and ATC (0%) relative to established expression patterns in WDTC (90%), with particular emphasis placed on expression patterns in RAI-R disease. As thyroid cancer loses endogenous TSHR expression in monolayer cell culture, we established cell lines with stable TSHR expression. We used these cell lines to evaluate TSHR-targeted radiopharmaceuticals. We designed PET radiopharmaceuticals based on two recombinant human thyroid-stimulating hormone analogues, TR1402 and thyrotropin-alfa, radiolabeled with 89Zr (t1/2 = 78.4 h, β+=23%). We performed in vitro assessments of these TSHR-targeted tracers including cell uptake, receptor blocking, internalization, and binding affinity. We evaluated tumor uptake and biodistribution with in vivo PET imaging and ex vivo biodistribution using a subcutaneous xenograft model established in male and female athymic nude mice. The results of these studies show targeting the TSHR is a promising approach for RAI-R and aggressive thyroid cancers. The PET tracers in this study can be used as the basis for future work to design a theranostic TSHR-targeted approach
Young Adult Chronic Disease And Midlife Subjective Well-Being And Mental Health: Does Social Milestone Achievement Mediate The Link?
Get PDFNearly one-in-four young adults ages 18-34 have a chronic disease, which has been linked to worse midlife mental health. Prior studies have little-examined the mechanism behind this association. The life course perspective suggests that because chronic disease in young adulthood is an unexpected and “off-time” event it may disrupt the achievement and timing of key social milestones. Inability to achieve or perceived delays in achieving the social markers of adulthood (e.g., completing school, homeownership, marriage) may therefore lead to worse midlife mental health. To address this proposition, I used panel data from the Youth Development Study (YDS and multivariate regression techniques to examine the association between young adult chronic disease and midlife mental health, formally testing whether social milestone achievement and timing mediate this association. Overall, I find that chronic disease in early adulthood is associated with poorer self-rated health, lower mastery, more depressive affect, and having a mood disorder in midlife. These associations persist net of controls for individual sociodemographic characteristics, adolescent self-esteem, and parent socioeconomic status. Although associated with lower odds of achieving specific milestones (i.e., owning a home, starting a career, being financially independent, cohabiting, and getting married), achieving fewer milestones overall, and late perceived timing or not expecting to achieve a milestone, I find limited evidence that individual social milestones mediate the association between young adult chronic disease and midlife mental health. Achieving fewer total social milestones and perceptions of being off-time (or not expecting to achieve a milestone at all) partially mediate the association. Taken together, these findings suggest that although young adults with chronic disease achieve fewer social milestones (especially financial) and perceive themselves as off-time this does not explain their worse mental health in midlife. Future research should examine differences in the timing of diagnosis and disease severity, as well as consider whether young adult chronic disease spurs a cognitive transformation that decouples social milestone achievement from perceptions of self, discarding the normative expectations of social milestone achievement, and leading to lower subjective-well-being simply because one has a chronic disease