Cytochrome P450 Gene Expression Modulates Anoxia Sensitivity in Caenorhabditis Elegans

With an increasing population suffering from obesity or Diabetes Mellitus (DM), it is more pertinent than ever to understand how physiological changes impact cellular processes. Patients with DM often suffer from obesity, hyperglycemia, altered fatty acids that contribute to vascular dysfunction, and increased risk to ischemia. Caenorhabditis elegans is a model system used to study the conserved insulin signaling pathway, cellular responses in whole organisms and the impact a glucose diet has on oxygen deprivation (anoxia) responses. RNA-sequencing (RNA-Seq) was used to analyze the expression of genes in the anoxia sensitive populations of N2 (wild-type) fed glucose and hyl-2(tm2031), a mutant with altered ceramide metabolism. Comparison of the altered transcripts in the anoxia sensitive populations revealed 199 common transcripts- 192 upregulated and 7 downregulated. One of the gene families that have altered expression in the anoxia sensitive populations encode for Cytochrome P450 (CYP). CYPs are located both in the mitochondria and endoplasmic reticulum (ER), but the CYPs of interest are all predicted to be mainly subcellularly localized to the ER. Here, I determined that knock-down of specific cyp genes, using RNA interference (RNAi), increased anoxia survival in N2 animals fed a standard diet. Anoxia sensitivity of the hyl-2(tm2031) animals was supressed by RNAi of cyp-25A1 or cyp-33C8 genes. These studies provide evidence that the CYP detoxification system impacts oxygen deprivation responses. using hsp-4::GFP animals, a transcriptional reporter for ER unfolded protein response (UPR), I further investigated the impact of cyp knock-down, glucose, and anoxia on ER UPR due to the prediction of CYP-33C8 localization to the ER. Glucose significantly increased ER UPR and cyp knock-down non-significantly increased ER UPR. Measurements of ER UPR due to anoxia were made difficult, but representative images show an increase in ER stress post 9-hour anoxia exposure. This study provides evidence that glucose affects ER stress and that ER stress is involved in oxygen deprivation responses

Hyperparathyroidism subsequent to radioactive iodine therapy for Graves\u27 disease

BACKGROUND: The development of primary hyperparathyroidism (PHPT) after radioactive iodine (RAI) treatment for thyroid disease is poorly characterized. The current study is the largest reported cohort and assesses the disease characteristics of patients treated for PHPT with a history of RAI exposure. METHODS: A retrospective analysis comparing patients, with and without a history of RAI treatment, who underwent surgery for PHPT. RESULTS: Twenty-eight of the 469 patients had a history of RAI treatment, all for Graves\u27 disease. Patients with a history of RAI exposure had similar disease characteristics compared to control; however, patients with a history of RAI treatment had a higher rate of recurrence (7.4% vs 1.2%, p = 0.012). CONCLUSION: PHPT in patients with a history of RAI treatment can be approached in the same manner as RAI naive PHPT patients; however, the risk of recurrence of PHPT in RAI exposed patients may be higher

The Dynamics of Credit Spreads in Hotel Mortgages and Signaling Implications

This paper investigates the loan pricing of risk in a market with short term leases (hotels) relative to longer term leases (office properties) with respect to how news on the economy, capital and real estate markets is incorporated in loan pricing using a vector autoregression (VAR) framework. The hotel loan pricing data provides a unique laboratory to study loan pricing adjustments given the short-term nature of the hotel leases. We examine the information content of hotel credit spreads in two stages. After establishing the impact of economic variables on loan pricing and the informational content of the incremental risk spread, we next examine how loan pricing adjusts in response to expected delinquencies. We find that improvement in general economic conditions, an increase in forward looking corporate profitability, an increase in capital availability and/or an increase in the demand for hotel services forecast a decline in the hotel risk premium differential. Thus, the relative loan prices—the spread—reflect systematic risk. We also find that hotel spreads themselves contain important economic information. Unexpected increases in hotel spreads predict hotel delinquencies. In other words, lenders appear to set interest rates on hotel mortgages in anticipation of hotel delinquencies and foreclosures in future periods. Lenders do not appear to consider past delinquencies in their setting their rate

Developing the DELTA: Capturing cultural changes in undergraduate departments

Departments are now recognized as an important locus for sustainable change on university campuses. Making sustainable changes typically requires a shift in culture, but culture is complex and difficult to measure. For this reason, cultural changes are often studied using qualitative methods that provide rich, detailed data. However, this imposes barriers to measuring culture and studying change at scale (i.e., across many departments). To address this issue, we introduce the Departmental Education and Leadership Transformation Assessment (DELTA), a new survey aimed at capturing cultural changes in undergraduate departments. We describe the survey’s development and validation and provide sugges-tions for its utility for researchers and practitioners

Microwave Components with MEMS Switches

RF MEMS switches with metal-metal contacts are being developed for microwave applications where broadband, high linearity performance is required. These switches provide less than 0.2 dB insertion loss through 40 GHz. This paper describes the integration of these switches into selected microwave components such as reconfigurable antenna elements, tunable filters, switched delay lines, and SPDT switches. Microwave and millimeter wave measured results from these circuits are presented

Intraoperative PTH Monitoring in Normohormonal Primary Hyperparathyroidism

Background: A subset of patients with primary hyperparathyroidism present with inappropriately normal PTH levels despite elevated serum calcium, called normohormonal primary hyperparathyroidism (NHPHP). This disease variant presents a clinical dilemma regarding intraoperative parathyroid hormone (IOPTH) monitoring during parathyroidectomy when using the standard criteria of a ≥ 50% reduction in IOPTH from baseline to determine surgical success. This study aimed to determine what percent reduction in post-excision IOPTH from baseline in NHPHP patients would yield a high cure rate similar to that of classic primary hyperparathyroidism. Methods: This was a single surgeon, single institution retrospective cohort study of patients that underwent parathyroidectomy between July 2013 and February 2020. Demographic, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHPHP were compared to those with classic primary hyperparathyroidism. Results: 496 patients were included in the study. 66 (13.3%) were of the normohormonal variant based on preoperative intact PTH levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the normohormonal groups were not significantly different from their classic counterparts: 98.4% and 100.0% vs 97.1% and 97.1%, p = 1.000. The median percent decline in post-excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.8% and 80.4% compared to their respective controls of 87.3% and 87.1%, p = 0.017 and p=0.001. Conclusion: A ≥ 75% decline in 15-minute post-excision IOPTH level from baseline can be used as a more stringent criterion for achieving high rates of cure in patients with NHPHP that undergo parathyroidectomy

Diet Significantly Influences the Immunopathology and Severity of Kidney Injury in Male C57Bl/6J Mice in a Model Dependent Manner

Diet is a leading causative risk factor for morbidity and mortality worldwide, yet it is rarely considered in the design of preclinical animal studies. Several of the nutritional inadequacies reported in Americans have been shown to be detrimental to kidney health; however, the mechanisms responsible are unclear and have been largely attributed to the development of diabetes or hypertension. Here, we set out to determine whether diet influences the susceptibility to kidney injury in male C57Bl/6 mice. Mice were fed a standard chow diet, a commercially available “Western” diet (WD), or a novel Americanized diet (AD) for 12 weeks prior to the induction of kidney injury using the folic acid nephropathy (FAN) or unilateral renal ischemia reperfusion injury (uIRI) models. In FAN, the mice that were fed the WD and AD had worse histological evidence of tissue injury and greater renal expression of genes associated with nephrotoxicity and monocyte infiltration as compared to mice fed chow. Mice fed the AD developed more severe renal hypertrophy following FAN, and gene expression data suggest the mechanism for FAN differed among the diets. Meanwhile, mice fed the WD had the greatest circulating interleukin-6 concentrations. In uIRI, no difference was observed in renal tissue injury between the diets; however, mice fed the WD and AD displayed evidence of suppressed inflammatory response. Taken together, our data support the hypothesis that diet directly impacts the severity and pathophysiology of kidney disease and is a critical experimental variable that needs to be considered in mechanistic preclinical animal studies