bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI116 Inhibition Of Mitochondrial Fission And Restoration Of Mitochondrial Function Attenuates Vascular Calcification
Authors: Hee Kwon So , Kim Min-Ji , Zerwa Siddique , Kim Seahan , Jueun Byun , Jeon Jae-Han , Lee In-Kyu 
Published: October 2023

Abstract
Disclosure: S. Kwon: None. M. Kim: None. S. Zerwa: None. S. Kim: None. B. Jueun: None. J. Jeon: None. I. Lee: None.
Objectives: Vascular calcification is associated with cardiovascular disease mortality, especially in patients with diabetes mellitus and chronic kidney disease. One of proposed mechanisms for development of vascular calcification suggested mitochondrial dysfunction of vascular smooth muscle cells (VMSCs), especially excessive mitochondrial fission that led to apoptosis and tissue calcium deposit formation. In existing literature, Vitamin B1 inhibited mitochondrial fission and improved mitochondrial function. This study investigated whether inhibiting mitochondrial fission prevents vascular calcification in vitro and in vivo by using inorganic phosphate and cholecalciferol-induced vascular calcification models, respectively. Methods: VMSCs from thoracic aorta of 4-week-old rats were treated by 2.6mM inorganic phosphate and 2mM calcium chloride to induce calcification. 6-week-old male C57BL/6J mice were given vitamin B1 analogue solution or water with daily oral gavage for 13 days, then aortic calcification was induced by subcutaneous injection of 5.5×10-5 IU/kg cholecalciferol for 3 days before sacrifice. Cells and tissues were stained for calcium deposition, (van Kossa stain), apoptosis (TUNEL) and mitochondrial morphology (Mitotracker). Western blotting and quantitative real-time PCR were used to assess calcification pathways and mitochondrial function. Tissue calcium content, normalized with total protein contents, was measured to quantify the extent of calcification. Mitochondrial oxygen consumption ratio (OCR) and mitochondrial membrane potential (JC-1 dye staining) were assessed to analyze quantified mitochondrial function. Results: Calcium deposition in both in vivo and in vitro models were alleviated by vitamin B1 analogue through inhibition of mitochondrial fission and restoration of mitochondrial function. In addition, vitamin B1 analogue downregulated expression of genes related to calcification and osteogenesis, such as bone morphogenic protein 2, osteocalcin, osteopontin, and runt-related transcription factor 2. Conclusion: Prevention of mitochondrial dysfunction in VSMCs may be a viable therapeutic strategy for treatment of vascular calcification.
Presentation: Friday, June 16, 2023
FRI118 3D Reconstruction Of Mitochondria From Human Heart Failure Structures Is Associated With Alterations In CHCHD6 And CHCHD3 Expression
Authors: Gail Marshall Andrea , Vue Zer , Garza-Lopez Edgar , Beasley Heather , Exil Vernat , Actkins Ky'Era , Miller-Fleming Tyne , Othrell Hinton Antentor 
Published: October 2023

Abstract
Disclosure: A.G. Marshall: None. Z. Vue, PhD: None. E. Garza-Lopez: None. H. Beasley, PhD: None. V. Exil: None. K. Actkins: None. T. Miller-Fleming: None. A.O. Hinton: None.
Heart failure (HF) is accompanied by symptoms and signs caused by cardiac dysfunction, resulting in reduced longevity. Critically, HF has been associated with mitochondria dysfunction, causing pathophysiology that might contribute to age-dependent decrease in cardiac function. Thus, we hypothesize that reduced cardiac function in response to HF, affects mitochondrial function and morphology. To test this, we investigated mitochondrial morphological changes using 3D reconstruction from 4 control human hearts and 4 human heart failure patients. Mitochondrial samples were 3D rendered and quantified using serial block facing-scanning electron microscopy and the Amira software. From our HF reconstructions, there are many phenotypes, including fragmentation, nanotunnels, and mitochondrial clustering, compared to controls, which may be associated to mitochondrial dysfunction. Surprisingly, we saw altered expression of CHCHD6 and CHCHD3 in human heart failure samples, based on immunofluorescence. Thus, we knocked out CHCHD6 and CHCHD3 in mouse fibroblasts, myotubes and human-induced pluripotent stem cell-derived cardiomyocytes and saw fragmentation in all three models. Presently, HF represents an unmet need with no approved clinical therapies for damaged myocardium replacement. Here, we suggest that CHCHD3 and CHCHD6 may be a molecular target that functions in the development of HF and possibly develop novel therapeutics for the treatment of HF.
Presentation: Friday, June 16, 2023
FRI122 Determinants Of Primary Aldosteronism Screening In The US: A Nationwide Physician Survey Study
Authors: Turcu Adina F , Salman Zara , Marie Konzen Sonja , Zhang Lei , Liu Haiping , Zhao Lili , Suzer Gurtekin Tuba , Papaleontiou Maria 
Published: October 2023

Abstract
Disclosure: A.F. Turcu: None. Z. Salman: None. S.M. Konzen: None. L. Zhang: None. H. Liu: None. L. Zhao: None. T. Suzer Gurtekin: None. M. Papaleontiou: None.
Background: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, affecting up to 25% of patients with treatment-resistant hypertension. PA contributes to cardiovascular and renal morbidity and mortality, via mechanisms additive to hypertension. Early detection and targeted therapy of PA mitigate the risk of such complications. Despite this, only a minute fraction of patients at risk are ever screened for PA. Objective: To ascertain triggers and barriers for PA screening across US practices. Methods: Physicians treating hypertension, including internists, family practitioners, cardiologists, nephrologists, and endocrinologists, were randomly selected from active members of the American Medical Association. Physicians were surveyed on their practice of PA screening. Multivariable logistic regression was performed to determine factors associated with PA screening. Results: Of 633 response-eligible physicians, 425 (67%) completed the survey, including 32.4% family practitioners, 26.9% internists, 13.2% cardiologists, 12.2% endocrinologists, and 11.8% Nephrologists. Of the respondents, 230 (55.2%) were men; 63% identified as White, 24% Asian, and 6% Black. Most participants reported that resistant hypertension (84.5%), and hypertension and spontaneous hypokalemia (81.4%) prompt them to screen for PA. Conversely, a minority reported diuretic-induced hypokalemia (26%), obstructive sleep apnea (10%), or atrial fibrillation (6.2%) as triggers for PA screening. Compared with internists, endocrinologists and nephrologists were more likely, and family practitioners were less likely to screen for PA in patients with hypertension and hypokalemia, early-onset hypertension, or adrenal nodules. Barriers to PA screening included clinic visit time constraints (37.4%), poor ancillary support (28.1%), testing logistic concerns (26.2%), ability to control hypertension with medications (20.5%), and belief that PA is rare (20.2%). Female physicians and family practitioners were more likely to report not being familiar with results’ interpretation and next steps, and not having time to keep abreast with expert guidelines; private practitioners were most likely to report reimbursement concerns. Conclusions: Heterogeneity in screening for PA exists among physicians at the frontline of hypertension care. Increasing awareness and developing tools to facilitate PA screening are crucial for the recognition and adequate care of millions of patients with hypertension.
Presentation: Friday, June 16, 2023
FRI125 Recurrence Of Primary Aldosteronism Long-Term After Adrenalectomy For Aldosterone-Producing Adenoma With KCNJ5 Gene Mutation: A Two-Cases Report
Authors: Aiga Ko , Kometani Mitsuhiro , Aono Daisuke , Karashima Shigehiro , Yoneda Takashi 
Published: October 2023

Abstract
Disclosure: K. Aiga: None. M. Kometani: None. D. Aono: None. S. Karashima: None. T. Yoneda: None.
Primary aldosteronism (PA) is a major cause of secondary hypertension. PA is known to have higher prevalence of cerebral or cardiovascular complications, indicating the importance of early detection and treatment for PA. PA is caused by autonomous secretion of aldosterone in the adrenal glands. PA is characterized by high plasma aldosterone concentration, low plasma renin activity and hypokalemia. PA is classified into unilateral PA (aldosterone-producing adenoma [APA] or unilateral hyperplasia) and bilateral PA (bilateral adrenal hyperplasia). PA with aldosterone excess in bilateral adrenal glands is defined as bilateral PA. On the other hand, PA with aldosterone excess in unilateral adrenal gland is defined as unilateral PA. Strategies for PA treatment depends on the subtype of PA. Medication by mineralocorticoid receptor antagonists is a common treatment for bilateral PA. Adrenalectomy is the most efficient treatment for unilateral PA. In general, patients tend to maintain normal serum potassium level and blood pressure after adrenalectomy, and recurrence of PA is extremely rare. Recently, mutation in the gene named KCNJ5 was found to derive APA. Herein, we report two cases of PA recurrence more than 10 years after surgical treatment for APA. Somatic mutation in KCNJ5 was detected in the first occurrence of PA in both cases. First case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. Second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Tissues of the adrenal gland were obtained from adrenalectomy in both cases. Histopathological analysis revealed presence of one adenoma in the first case, while two adenomas were confirmed in the second case. Somatic mutation in KCNJ5 gene was detected in both cases. To date, there are no specific guidelines established for the management of recurrent PA. Early detection is crucial for the prevention of severe cardiovascular diseases. Long-term follow-up is recommended after the treatment of PA.
Presentation: Friday, June 16, 2023
THU253 The Hemoglobin Wayne Variant And Association With Falsely Elevated HbA1c
Authors: Mulpuri Neha , Bryant Ananda , Shahin Daryoush , Soe Kyaw 
Published: October 2023

Abstract
Disclosure: N. Mulpuri: None. A. Bryant: None. D. Shahin: None. K. Soe: None.
Background: Hemoglobin Wayne (Hb Wayne) is a rare, silent alpha chain variant caused by a frameshift mutation in the HbA2 gene. Although clinically silent, this mutation falsely elevates HbA1c values. Clinical cases: We are presenting three cases of Hb Wayne patients referred to our diabetes clinic within the last 5 years. All three cases were Caucasian-American males diagnosed with uncontrolled diabetes based on high HbA1c values of ranging from 10.1-10.6 %. One of the patients was initially started on metformin while the other patients’ treatment plan included dietary and lifestyle modifications. Review of the labs showed that renal function, complete blood count and fasting plasma glucose were within the normal range. High HbA1c value was noted by routine screening lab without having any symptoms related to DM or features of insulin resistance. The discrepancy between high HbA1c values and other glycemic index parameters (serum glucose and FSBG values) was noted. Subsequently, further work up was done (repeat HbA1c with different assay and fructosamine) to verify the diagnosis of uncontrolled DM. Fructosamine levels and repeat HbA1c with a different assay (enzymatic assay at Quest lab) were normal. Hemoglobin electrophoresis confirmed presence of an abnormal alpha variant consistent with Hb Wayne. The patients were reassured and educated about this Hb variant, and no further treatment for DM was pursued. Conclusion: Rare hemolgobinopathies may be more common than previously expected as they can be clinically silent and easily overlooked. While HbA1c has been an important clinical tool for diagnosis and management of diabetes, clinicians should look for underlying reasons which can affect HbA1c assay if there is any discrepancy between HbA1c, FSBG and plasma glucose values. The laboratory at our institution uses cation- exchange High Performance Liquid Chromatography method (Bio-Rad D-100 instrument) resulting in falsely high HbA1c values. Some hemoglobinopathies can affect the widely used HbA1c testing method such as CE-HPLC. The impact on HbA1c values will differ depending on hemoglobin variant and specific method and assay used. Given the limitations of HbA1c testing, clinicians should avoid relying heavily on HbA1c values in management and diagnosis of diabetes. It is vital that clinicians use their clinical judgment to correlate HbA1c with other clinical parameters such as continuous glucose monitoring data, glycated albumin,1,5 anhydroglucitrol (1,5 –AG), fingerstick blood glucose, plasma glucose and fructosamine values.
Presentation: Thursday, June 15, 2023
THU262 Improvement Of Pharmacokinetic Properties Of Vasoactive Intestinal Peptide Through Backbone Modifications
Authors: Al Najar Mathew S , Lipchik Andrew M 
Published: October 2023

Abstract
Disclosure: M.S. Al Najar: None. A.M. Lipchik: None.
Vasoactive Intestinal Peptide (VIP) is a 28 amino acid neuropeptide hormone that is a part of the glucagon/secretin family. VIP has myriad physiological functions, including incretin effects, immune modulation, corneal wound repairing, and lacrimal secretion. VIP executes these functions through activation of two B1 family of G-protein-coupled receptors, VPAC1 and VPAC2, leading to cAMP production. Previous research has demonstrated that VIP has immense therapeutic potential in treating many diseases including type 2 diabetes, cardiovascular disease, and autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, and Crohn's disease. Although VIP has proven to be pharmacologically active in these diseases, its utility as a therapeutic is limited due to its short half-life in circulation (less than one minute) caused by proteolytic degradation. Previous efforts have been made to improve serum stability through peptide stapling using lactamization and olefin-metathesis. However, both strategies failed to increase the stability of VIP. Additional strategies are needed to improve serum stability of VIP. A potential alterative approach is the utilization of peptide backbone modifications to prevent proteolytic recognition and degradation. The introduction of unnatural amino acids and analogs such as N-methyl amino acids and peptoids into the VIP sequence alters the peptide bond by placement of a methyl group or a side chain on the amine. Here, we present a library of VIP analogs containing N-methyl amino acids and peptoid substitutions. The serum stability, structural conformation, and pharmacological activity of the VIP analog library was compared and tested against wild-type VIP. The incorporation of N-methyl amino acids or peptoid residues demonstrated significant improvement in stability in human serum. In addition, the VIP analogs maintained alpha-helical confirmation similar to wild-type VIP. Finally, the VIP analogs were shown to maintain pharmacological activity as VPAC1 agonist as measured by cAMP production and glucose-dependent insulin secretion. Together, these results display the incorporation of unnatural amino acids with modified backbones can improve pharmacokinetics while maintaining pharmacodynamics of VIP, allowing for the potential use of VIP as a therapeutic.
Presentation: Thursday, June 15, 2023
THU270 Efficacy Of Patient Support Program On Management Of Cardiovascular Risk Factors For Adults With Type 2 Diabetes Mellitus
Authors: Shah Abhishek , Damse Sneha , Thiyagarajah Premalatha , Soulat karine , Ahadome Theo 
Published: October 2023

Abstract
Disclosure: A. Shah: None. S. Damse: None. P. Thiyagarajah: None. K. Soulat: None. T. Ahadome: None.
Efficacy Of Patient Support Program On Management Of Cardiovascular Risk Factors For Adults With Type 2 Diabetes Mellitus.
Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease. Patients with T2DM have 2 to 3 times the risk of cardiovascular mortality and morbidity.1 This study aimed to assess the efficacy of an intensive intervention strategy in improving cardiovascular risk factors, HbA1C level in high-risk patients with T2DM. Methods: An interventional program with a multi component strategy was delivered by Wellthy therapeutics over a period of 40 weeks. The program had interventions including customized dietary plans, behavioral interventions, including stress management and coping skills training, lifestyle counseling, disease awareness and self-management training of symptoms at home. Interventions were initiated by certified health coaches via chats and calls. A high-risk diabetic cohort whose HbA1C greater than 10% were recruited by convenience sampling method. Intervention Statistical analysis was done using SPSS version 21. Results: The mean age of patients was 48.49±14.46. The mean of HbA1C, Total Cholesterol, LDL, Triglycerides, BMI at baseline was 11.4, 195.42, 125.9, 247.26, 26.77 respectively. The mean of HbA1C, Total Cholesterol, LDL, Triglycerides, BMI at the endline was 9.70, 181.98, 119.82, 195.34, 25.95 respectively. The effect of the Paired Ttest witnessed that intensive intervention strategy had a statistically significant improvement in effect on the cardiovascular risk factors from baseline to follow up p&lt;0.05.(HbA1C p=.001, Total cholesterol p=.019, Triglycerides p=.002, BMI p=.007). Conclusion: This program played a highly significant role in managing cardiovascular risk factors by training patients in self-monitoring, medication adherence, and knowledge on disease awareness. There is increasing evidence that these interventions can support modification of lifestyle risk factors among people with coronary T2DM; however, existing interventions are disparate. These types of interventions play a potential role in meeting the individual needs and preferences to optimize self-management of their disease.
Presentation: Thursday, June 15, 2023
THU279 Long duration Of CFTR Modulators Consistently Improve Glucose Metabolism Parameters In Patients With Cystic Fibrosis
Authors: Cohen Amitay , Mass Alon , Zangen David , Cohen-Cymberknoh Malena 
Published: October 2023

Abstract
Disclosure: A. Cohen: None. A. Mass: None. D. Zangen: None. M. Cohen-Cymberknoh: None.
Background: Impaired glycemic control and consequently Cystic fibrosis Related Diabetes (CFRD) due to gradual pancreatic β-cell dysfunction is a common complication (upto 50% in adults) in patients with cystic fibrosis (CF.) The novel use of CFTR modulators (CFTRm), improve pulmonary function and reduce disease exacerbations. Data regarding the long-term effect of CFTRm on glycemic control is limited. In this observational-retrospective study, we evaluate the effect of CFTRm on the classical pathophysiological deterioration in glucose tolerance in patients with CF. Methods and Results: 15 patients with CF (ages 13-37) treated with CFTRm were followed by routine Oral Glucose Tolerance Test (OGTT). OGTT Results of Pre and 3-81 months (mean 28) post initiation of CFTRm therapy were compared and also classified to 4 classic categories: normal glucose tolerance (NGT), indeterminate (INDET), impaired glucose tolerance (IGT) and diabetes (CFRD). The end point of OGTT at 120 minutes significantly improved post CFTRm therapy being 159.7 (80-419.4) compared to 130.4 (54-286) pre-CFTRm (p = 0.047). Regarding the categories sub-classification of patients: Two patients with CFRD improved after CFTRm therapy to NGT or INDET. 2 with INDET pre-therapy improved to NGT post therapy.Of 3 patients with IGT, 2 improved to NGT or INDET and 1 worsened to CFRD. Out of the 6 patients who had NGT pre CFTRm therapy, 4 remained NGT, one worsened to INDET, and one became CFRD. Conclusions: This is the first and largest study so far demonstrating consistent significant improvement in glycemic control in CFRD after CFTRm treatment of at least 3 months duration. Treatment seems to delay and possibly reverse the deterioration in glycemic control that is typical to the natural history of patients with cystic fibrosis. Larger studies are indicated but awareness to the current findings may prevent hypoglycemic events while staying on a fixed insulin dose while on CFTRm therapy.
Presentation: Thursday, June 15, 2023
THU281 Real-World Survey Of Adherence To Guidelines Regarding Type 1 Diabetes And Aerobic Exercise
Authors: Anthony Henske Joseph , Beach Gavin , Albashaireh Arwa 
Published: October 2023

Abstract
Disclosure: J.A. Henske: None. G. Beach: None. A. Albashaireh: None.
Background: Managing hyperglycemia and hypoglycemia before, during, and after aerobic exercise remains one of the greatest challenges for those living with type 1 diabetes. Several publications offer guidelines and recommendations but it is not well established to what extent these are followed by those living with diabetes. In order to assess the implementation and awareness of these guidelines and in particular guidelines around risk of hypoglycemia and safety recommendations, we created an online survey which was posted to focused social media groups limited to adults with type 1 diabetes who run, jog, or walk for exercise. Results: The entire 96-question survey was completed by 102 adults with a mean age of 42 and a mean duration of diabetes of 20 years. The self-reported average HbA1c of respondents was 7.1%. 68% of respondents reported exercise 4 or more days per week. Average mileage was 23 miles per week. The respondents were predominantly female (69%), Caucasian (94%), and from the United States (78%). There was a high rate of technology use as 97% of respondents report using CGM and 75% are using insulin pumps. 80% reported learning about diabetes and exercise mostly from trial and error, 46% from social media, 32% from their medical team, 28% from online searches, some using multiple methods. 27% of respondents reported fear of hypoglycemia as a significant barrier to exercise and 36% reported increased glucose variability as a result of exercise. 19% of respondents reported having hypoglycemia unawareness. 3% reported never having symptoms of hypoglycemia at any glucose level, 21% feel first symptoms with BG &lt;50mg/dL, 26% at 50-60 mg/dL, and 40% at 60-70mg/dL. Despite published guidelines, 73% reported that they exercise even if severe hypoglycemia &lt;50mg/dL in the last 24 hours, 74% do not check for ketones even if unexplained hyperglycemia &gt;250mg/dL prior to exercise. 11% reported exercising with ketones present in blood or urine. 10% reported developing DKA after exercise. 86% experienced the need to stop exercise due to hypoglycemia and 18% reported a severe hypoglycemic event during exercise. 49% report not wearing diabetes identification during exercise. 41% reported difficulty with overnight hypoglycemia after exercise. Conclusion: In a real-world survey of 102 individuals with relatively well-controlled type 1 diabetes (mean A1c 7.1%) who walk, run, or jog extensively for exercise (23 miles per week), hypoglycemia awareness and management is a significant concern and barrier for them. Implementation science efforts and increased awareness of current guidelines and development of an educational curriculum surrounding type 1 diabetes and exercise may prove helpful to improve outcomes.
Presentation: Thursday, June 15, 2023