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EXPRESS: Plasma from Type 1 Diabetes Patients Promotes Pro-atherogenic Cholesterol Transport in Human Macrophages

Accacha, Siham Acacha; Kasselman, Lora J; Mejia-Corletto, Jorge; Srivastava, Ankita; Voloshyna, Iryna; Renna, Heather A; De Leon, Joshua; Levine, Robert L; Reiss, Allison Bethanne
Hyperglycemia, one of the major risk factors for atherosclerosis, leads to the accumulation of Advanced glycation end products (AGEs), contributing to cardiovascular complications. Such accumulation may accelerate the progression of vascular disease in patients with diabetes. Reverse cholesterol transport (RCT) protein, ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) and cholesterol 27-hydroxylase facilitate cholesterol removal from macrophages. AGE inhibits reverse cholesterol transport by reducing the expression of ABCA1 and ABCG1. This study aimed to evaluate whether plasma from poorly controlled adolescents with type 1 diabetes (T1D) disrupts cholesterol homeostasis in human monocytes/macrophages. Twenty healthy controls (HC) and 20 patients with T1DM, 10 to 19 years old, were enrolled. Naïve THP-1 macrophages were exposed to plasma from each HC and patient with T1D. Following incubation, mRNA for cholesterol efflux (ABCA1, ABCG1, 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low-density lipoprotein (LOX)-1, CXCL16) were isolated. Foam cell formation was quantified to confirm the pro-atherogenic effects of T1D plasma on macrophages. Results showed that T1D plasma had an elevated level of CML-modified proteins and upregulated CXCL16 and, to a lesser degree, ScR-A1. This change in gene expression in the presence of T1D plasma is associated with increased lipid accumulation and foam cell formation by THP-1 macrophages. In our study, these cells' uptake of an AGE product occurred mainly through the SR-A1 and CXCL16 receptors, leading to increased intracellular oxidized LDL. We conclude that AGEs may contribute to accelerated atherosclerosis in diabetes through effects on both forward and reverse cholesterol movement.
PMID: 39417428
ISSN: 1708-8267
CID: 5718702

Dried blood spot sampling for growth hormone stimulation testing as an alternative to conventional serum sampling-a pilot proof of concept study [Meeting Abstract]

Ilaka-Chibuluzo, S; Saenger, P; Levine, R L
Objectives We are investigating for the first time the reliability of using a highly sensitive GH-ELISA assay for quantification of growth hormone levels from dried blood spots (
EMBASE:637233345
ISSN: 1663-2826
CID: 5158002

Non-autoimmune hyperthyroidism caused by a somatic mosaic GNAS gene mutation involving part of the thyroid gland

Franca, Monica M; Levine, Robert L; Pappa, Theodora; Ilaka-Chibuluzo, Sandra; Rothberger, Gary D; Dumitrescu, Alexandra M; Refetoff, Samuel
Non-autoimmune hyperthyroidism caused by activating mutations in the GNAS gene is a rare condition. Here we report a 5-year-old girl diagnosed with non-autoimmune hyperthyroidism and tall stature harboring a somatic mosaic gain-of-function mutation in the GNAS gene (NM_080425.3: c.2530C>T;p.Arg844Cys previously reported as NM_000516.5:c.601C>T;p.Arg201Cys) and referred thereafter as R201C, in three of four quadrants of the thyroid gland. Provision of a molecular diagnosis may avoid unnecessary complete ablation of the thyroid gland.
PMID: 31910104
ISSN: 1557-9077
CID: 4294852

An evaluation of a 'BE NICE Champion' program: A bullying intervention program for registered nurses

Keller, Ronald; Allie, Tammy; Levine, Robert
AIM/OBJECTIVE:To explore the experiences, perceptions, and attitudes of registered nurses (RNs) who completed the BE NICE Champion training program; a home-grown program that provides RNs tools to intervene when bullying is observed; using the -4S's-: Stand-by, Support, Speak up, and Sequester. BACKGROUND:The growing body of literature surrounding the negative impact bullying has on individuals and organizations suggests the need to develop more effective prevention and intervention programs. METHOD/METHODS:A qualitative focus group approach utilizing a purposive sample of 25 RNs who participated in the training program. RESULTS:Three consistent themes emerged from a content analysis of the transcripts: (a) awareness and understanding, (b) applying the 4S's, and (c) feeling prepared and empowered. Additional themes included: impact on the work environment and additional program recommendations tailored to nursing leadership. IMPLICATIONS FOR NURSING MANAGEMENT/CONCLUSIONS:Leaders need to demonstrate a commitment to address bullying. Implementing this program can positively impact their environment. CONCLUSION/CONCLUSIONS:The program and use of the 4S's adequately provided RNs with confidence to intervene when bullying was observed. RNs felt better equipped to respond due to the techniques learned and appreciated our organizational commitment to address bullying. Furthermore, the program may be strengthened by incorporating recommendations discussed.
PMID: 30615232
ISSN: 1365-2834
CID: 3579802