bluuebunny/crossref_metadata_2025_split huggingface dataset:
2453-PUB: Changes in Metabolic Syndrome and Diabetes Risk: A Nationwide Longitudinal Cohort Study
Authors: LEE MIN-KYUNG , KWON HYUK-SANG , SONG KI-HO , LEE JAE HYUK 
Published: June 2019

Background: Metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes. We aimed to examine whether changes in metabolic syndrome over a two-year span were associated with the development of type 2 diabetes.
Methods: This prospective cohort study included 10,806,716 adults aged &gt;20 years without a history of type 2 diabetes, using the South Korean National Health Insurance Service database. Metabolic syndrome components were measured at baseline and two years later. Diabetes risk over a four-year period was estimated using Cox proportional hazards models.
Results: During a mean follow-up of 4.08 years, 848,859 individuals were diagnosed with type 2 diabetes. Multivariable-adjusted hazard ratios (HRs) for developing diabetes were 1.501 in individuals with metabolic syndrome at baseline and without it two years later, 1.768 in those without metabolic syndrome at baseline and with it two years later, and 2.327 with metabolic syndrome both at baseline and two years later compared with those without metabolic syndrome at either time point. The HRs for diabetes were increased with the number of metabolic syndrome components at baseline and two years later, and decreased significantly with a decrease in the number of components (p for trend &lt; 0.0001). The risk of diabetes was more strongly associated with changes in metabolic syndrome in individuals aged between 20 and 39 years.
Conclusions: Changes in metabolic syndrome could predict the development of type 2 diabetes. In addition, the risk of type 2 diabetes showed a stronger association with metabolic syndrome in young adults. These observations suggest that improving metabolic syndrome is important to prevent type 2 diabetes, particularly for young adults.

Disclosure
M. Lee: None. H. Kwon: None. K. Song: None. J. Lee: None.

Funding
Korean National Research Foundation (2018R1D1A1B07049079)
2458-PUB: Prevalence and Correlates of Sleep Disorders in Greek Patients with Type 2 Diabetes: Comparison of an Urban and a Semiurban Population
Authors: PAPAZAFIROPOULOU ATHANASIA , STAMATELATOU MARIA , XOURGIA ELENI , MPOUMI LOUISA , GEORGOPOULOS ELIAS , TZIOMALOS GEORGE , SOLIDAKI SOFIA , DASENAKI MARIA , MELIDONIS ANDREAS 
Published: June 2019

Background and Aims: Sleep disturbances are common among individuals with type 2 diabetes (T2D). The aim of this study was to estimate the prevalence and correlates of sleep disorders in Greek diabetics and differences between an urban and semi-urban population.
Materials and Methods: The study population was comprised of 308 T2D patients [139 patients from Piraeus (urban population, group A) and 169 patients from Sitia (semi-urban population, group B)]. In all patients, quality of sleep was evaluated by administering the Pittsburgh Sleep Quality Index (PSQI) through an interview. The PSQI is a self-report questionnaire that assesses sleep quality and quantity over a month-long period.
Results: Mean PSQI score of group A was 11.22 ± 6.44 and 88.5% (n=123) of the participants had a PSQI score ≥5, indicating poor quality of sleep. Mean PSQI score of group B was 12.48 ± 5.85, and 88.8% (n=140) had a PSQI score ≥5. Incidence of a PSQI score ≥5 did not differ between the two groups (P=0.13). Logistic regression analysis, after adjustment for sex, BMI, presence of hypertension and dyslipidemia, smoking, diabetes complications, and oral antidiabetic treatment, showed that PSQI ≥5 in total sample population was associated with insulin treatment [odds ratio (OR): 0.03, 95% confidence interval (95% CI): 0.31-0.99], and HbA1c (OR: 6.56, 95% CI: 1.93-16.14). In group A, poor sleep quality was associated with insulin treatment (OR: 0.02, 95% CI: 0.10-0.84), and HbA1c (OR: 7.55, 95% CI: 1.97-18.81). In group B, poor sleep quality was associated only with age (OR: 1.36, 95% CI: 1.06-1.74).
Conclusion: Our study suggested that Greek patients with T2D have a high prevalence of sleep disorders with similar incidence for urban and semi-urban population. Insulin treatment and HbA1c were the greatest predictors of sleep disorders. Identifying sleep disorders in T2D and treating them early might improve patient's quality of life.

Disclosure
A. Papazafiropoulou: None. M. Stamatelatou: None. E. Xourgia: None. L. Mpoumi: None. E. Georgopoulos: None. G. Tziomalos: None. S. Solidaki: None. M. Dasenaki: None. A. Melidonis: None.
247-OR: Real-World Effectiveness of SGLT2 Inhibitors vs. GLP-1 Receptor Agonists in Patients With and Without Cardiovascular Disease
Authors: PATORNO ELISABETTA , PAWAR AJINKYA , SCHNEEWEISS SEBASTIAN , GLYNN ROBERT J. , KIM DAE H. , EVERETT BRENDAN M. , BESSETTE LILY G. , KIM SEOYOUNG C. 
Published: June 2019

Both SGLT2i inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) have shown cardiovascular (CV) benefits in CV outcome trials among patients with type 2 diabetes (T2D) and established CV disease (CVD). Whether these agents are associated with differential CV effects and mortality in real-world T2D patients with and without CVD is unclear. Using Medicare and 2 U.S. commercial claims datasets (4/2013-12/2016), we identified 1:1 propensity score-matched patients aged ≥18 years with T2D initiating a SGLT2i or a GLP-1 RA with and without CVD (32,064 and 101,210 matched pairs, respectively). We assessed a composite CV outcome [myocardial infarction (MI) or stroke], mortality, and hospitalization for heart failure (HHF), and estimated hazard ratios (HRs) and 95% CIs adjusting for &gt;140 baseline covariates. Compared to GLP-1 RA, the HR for the composite CV outcome was 1.10 (95% CI 0.95-1.26) for SGLT2i initiators with CVD, and 1.23 (1.08-1.41) for initiators without CVD, over a mean 8.4-month follow-up (Table). Initiators of the two drugs with and without CVD had similar mortality risk, but SGLT2i users had 31-33% reductions in HHF risk [0.67 (0.55-0.81) and 0.69 (0.51-0.92)]. This study suggests robust reductions in rates of HHF associated with SGLT2i vs. GLP-1, but in primary prevention, where HHF was less common, benefits were offset by somewhat increased risk of MI and stroke.

Disclosure
E. Patorno: Research Support; Self; National Institute on Aging. Other Relationship; Self; Boehringer Ingelheim International GmbH. A. Pawar: None. S. Schneeweiss: Consultant; Self; Aetion, WHISCON, LLC. R.J. Glynn: Research Support; Self; AstraZeneca, Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Pfizer Inc. D.H. Kim: None. B.M. Everett: Advisory Panel; Self; American College of Cardiology. Consultant; Self; Abbott Laboratories, Amgen Inc., National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Roche Diagnostic USA. Research Support; Self; Novartis Pharmaceuticals Corporation. Other Relationship; Spouse/Partner; Merck & Co., Inc. Other Relationship; Self; UpToDate. Other Relationship; Spouse/Partner; UpToDate. L.G. Bessette: None. S.C. Kim: Research Support; Self; Bristol-Myers Squibb Company, Genentech, Inc., Pfizer Inc.
2472-PUB: JNK1 Plays a Causal Role in Palmitate-induced ß-Cell Dysfunction In Vivo
Authors: MING YUNG JUSTIN HOU , NGA YEUNG LUCY SHU , NAHLE ASHRAF , KOULAJIAN KHAJAG , GIACCA ADRIA 
Published: June 2019

In obesity, chronically elevated circulating free fatty acids (FFA) potentially cause ß-cell dysfunction which leads to type 2 diabetes (T2D). In vitro data have identified various cellular mechanisms leading to FFA-induced ß-cell dysfunction including activation of inflammatory kinase c-Jun N-terminal kinase (JNK). In the ß-cell, JNK1 responds to oxidative stress or ER stress, which can both be caused by FFA. Previous in vitro studies from our group have demonstrated that islets of JNK1-null mice are protected from the effect of palmitate but not oleate on inducing ß-cell dysfunction, suggesting that activation of JNK1 is specific to saturated FFA. Thus, we hypothesized that saturated FFA-induced ß-cell dysfunction is mediated in part by JNK.
Due to its detergent effects, palmitate cannot be infused directly into circulation. Thus, ethylpalmitate was used, as the ethyl group reduces the toxic effect. Mice can hydrolyze the ethyl group in circulation, producing palmitate and ethanol. JNK1-null (KO) mice and their littermate controls (WT) were infused with ethylpalmitate or ethanol vehicle for 48 hours, after which their pancreatic islets were isolated for ex vivo determination of insulin secretion.
We confirmed that ethylpalmitate infusion does significantly increase plasma FFA as compared to vehicle infusion. We found that WT mice infused with ethylpalmitate demonstrated significantly decreased insulin secretion as compared with WT mice infused with vehicle, whereas JNK1-null mice infused with ethylpalmitate had similar insulin secretion as controls. These data suggest that JNK1 plays a causal role in saturated FFA-induced ß-cell dysfunction in vivo.

Disclosure
J. Yung: None. L. Yeung: None. A. Nahle: None. K. Koulajian: None. A. Giacca: Research Support; Self; Jazz Pharmaceuticals.

Funding
Canadian Institutes of Health Research
2477-PUB: Blood Beta Hydroxybutyrate Levels in Adult Patients Presenting to Emergency Department
Authors: DEPCZYNSKI BARBARA , LEE ALEXANDRA T. , VARNDELL WAYNE F. , CHIEW ANGELA L. 
Published: June 2019

Ketone bodies are an important alternate fuel source with fasting. Our aim was to describe point of care blood beta hydroxybutyrate (BHB) in patients presenting to emergency (ED). We performed a retrospective study. The population consisted of adult patients attending emergency department of a tertiary referral hospital who had a BHB measurement and venous blood gas measurement (VBG) performed at presentation to ED. Between March-September 2018 inclusive, 4356 patients had at least one VBG performed, and of these 842 patients had at least one BHB level performed whilst in ED. Of the whole cohort, 604 patients were admitted and 238 discharged from ED or short stay ward. Results are shown as mean±SD (range). Age was 62.5±21.6 years (16.1-102.5). 55% of cohort were male. Length of stay was 6.23±9.99 days (0.35-77.77), and Charlson score 1.91±2.03 (0-15). Blood glucose (BG) was 10.5 ±7.3mmol/L (2-54mmol/L), lactate 2.2±1.7mmol/L (0.3-21), and BHB 0.6±1.2mmol/L (0-8.4). Of the whole cohort, 404 patients had diabetes. Excluded from subsequent analysis were 18 cases of diabetic ketoacidosis and 6 cases of hyperosmotic hyperglycaemic syndrome. Of this cohort, BHB level did not differ according to diabetes status (0.52±0.9mmol/L those with diabetes versus 0.41±0.75mmol/L in those without) yet BG (13.7±7.4mmol/L versus 6.8±2.8mmol/L, p&lt;0.01) was higher as was lactate (2.3±1.6mmol/L versus 2.1±1.8mmol/L, p&lt;0.05). Where acute vomiting was documented to be present versus not recorded, BHB was higher (0.64±1.0 mmol/L versus 0.43±0.81mmol/L). Where acute ethanol intake was documented, BHB was not significantly higher (0.66±1.34mmol/L versus 0.44±0.79mmol/L). BHB ≥3mmol/L was seen in 2.9% of those with diabetes and 2.1% of those without diabetes. Although serum albumin was no different, BMI was lower in those with BHB ≥ 3mmol/L (23.5±7.7kg/m2 versus 27.6±6.9kg/m2). Ketosis is commonly seen in ED, is associated with reduced oral intake and is not confined to those with diabetes.

Disclosure
B. Depczynski: None. A.T. Lee: None. W.F. Varndell: None. A.L. Chiew: None.
2495-PUB: Negative Relationship between Obesity and Cardio Ankle Vascular Index in Diabetic Patients
Authors: SUYUAN WANG , CHENGHUI ZHANG , YUNHONG WU , MINGXIA LI 
Published: June 2019

Introduction: The aim of this study is to explore the relationship between obesity and cardio-ankle vascular index (CAVI) in Tibet diabetic patients.
Method: Related data of hospitalized diabetic patients during May 2017 to November 2018 were collected and analyzed. Eligible patients were diagnosed diabetic patients aged from 18 to 80. The exclusion criteria were malignant tumor, patients who has been undertaken surgery in the past 6 months. Logistic regression was used to analyze the relationship between CAVI and Obesity.
Result: A total of 1025 patients were enrolled, 758(73.95%) were female. Patients were divided into 3 groups according their BMI, 335 patients were normal in weight(BMI≤24kg/m2), 463 were overweight(24kg/m2≤BMI≤28kg/m2) and 227 were obesity(BMI≥28kg/m2). The age of these patients were 54.81±9.6. CAVI among three groups were 8.58±1.12, 8.34±1.16, 8.12±1.2, respectively (P&lt;0.001). After adjustment for age, gender, SBP, DBP, and duration of diabetes, BMI was negatively associated with CAVI (β=-0.067, 95% CI -0.090∼-0.059, P&lt;0.001), CAVI was lower in overweight (β=-0.265, 95% CI -0.382∼-0.147, P&lt;0.001)and obesity (β=-0.558, 95% CI -0.702∼-0.413, P&lt;0.001) groups. We also found a negative relationship between waist circumference(β=-0.020, 95% CI -0.025∼-0.014, P&lt;0.001), abdominal obesity (β=-0.369, 95% CI -0.494∼-0.245, P&lt;0.001), and CAVI.
Conclusion: We found a negative relationship between BMI and CAVI in diabetic patients, further study is required to find out possible mechanism and its influence on the onset of CVD.

Disclosure
W. Suyuan: None. Z. Chenghui: None. W. Yunhong: None. L. Mingxia: None.
2497-PUB: Relationship between Visceral Obesity and Periodontal Disease in Women
Authors: JACOMOSSI ANGELO CÉSAR FERNANDES 
Published: June 2019

Obesity consists in a risk condition to several chronic diseases. The relationship of excessive adiposity and oral health has been the target of extensive investigations. To assess the association of visceral obesity (VO) and periodontal disease (PD) we evaluated 24 visceral obese women, assessing the periodontal heathy and the body fat distribution. Visceral obesity was defined by the waist to hip measurement (W/H) greater than 0.85. Periodontal disease was assessed by the Community Periodontal Index (CPI). Bioimpedanciometry was performed in all women, in addition to blood sample collection to glucose and plasma insulin dosage to calculate the Homeostatic Model Assessment - Insulin Resistance (HOMA-IR). The data were correlated by the following statistical analysis: the Shapiro-Wilk test to analyze the normality of the data. Pearson's parametric correlation test to investigate the correlation between HOMA-IR, Body Mass Index (BMI), the ratio percentage of visceral fat and total fat (%VF/%TF) and W/H. Spearman's non-parametric correlation test to investigate the correlation among the HOMA-IR, CPI, percentual total fat (%TF) and visceral fat (%VF) variables. Spearman's nonparametric correlation test to investigate the correlation among the CPI, %TF, %VF, %VF/% TF, BMI and W/H variables. We found a positive correlation between CPI e CA/CQ [r:0,4442; 95% CI -0.01199 to 0.7473; P (two-tailed) 0,0498]; and between CPI e %VF [0,4522; 95% CI -0.001949 to 0.7517; P (two-tailed) 0,0453]. It was not possible to find a positive correlation between CPI and %TF [r:0.2681; 95% CI - 0.2114 to 0.6436; P (two-tailed) 0.2531], as well as for the relationship between CPI and HOMA-IR [r:-0,344; P (two-tailed) 0.35; ns]. The other analyzes performed did not also show positive correlation. The firsts results suggest a positive correlation between PD and VO. But, the lack of correlation between CPI and HOMA-IR, contradicts this. Further studies should be performed to better clarify this issue.

Disclosure
A.C.F. Jacomossi: None.
2499-PUB: Sagittal Abdominal Diameter (SAD): A Marker of Metabolic Syndrome, Insulin Resistance (HOMA-IR) among Saudi Type 2 Diabetes Mellitus (T2DM) Patients
Authors: TOURKMANI AYLA , RSHEED ABDULAZIZ BIN , ANSARA HEBA , ALHARBI TURKI , FOUAD MOSTAFA 
Published: June 2019

Abdominal obesity has been identified as an important risk factor for T2DM. Anthropometric measures (BMI, waist circumference (WC) and hip circumference (HC) are commonly used in evaluating obesity. One major shortcoming of these measure are their inability to distinguish between abdominal and visceral adipose tissue. SAD (i.e., the height of the abdomen when lying supine) predict the amount of visceral fat and several studies showed its strong correlation with insulin resistance, hyperinsulinemia as well as its prediction of metabolic syndrome.
The study is ongoing and aimed to evaluate SAD as predictor of metabolic syndrome components and (HOMA-IR) among Saudi T2DM patients.
A cross-sectional sample of 433 T2DM subjects (256 female and 177 male) with mean age of 57.2±11.7 (18-86) years was suitable for analysis. Mean SAD, BMI, WC and HC were 15.6±3.7 cm, 32.9±6, 105.5±12 cm and 113.3±12.7 cm respectively; mean HbA1c and C-peptide were 8.5%±1.5 and 754.6±471pmol/L respectively. SAD (Sensitivity, specificity) with correspondence to metabolic syndrome were (77%, 77%) in males and (72%, 53%) in females. The area below the ROC curve was 14.1 cm for males and 14.75 cm for females.
In Females, Each 1 cm increase in SAD increased 29% of HOMA-IR (aOR 1.293), 95% CI: 1.084-1.542; P = 0.004) and HbA1c increased 70%of moderate to severe HOMA-IR(aOR 1.703, 95% CI: 1.285-2.256; P = 0.001). In males, HbA1c and total cholesterol increased moderate to severe HOMA-IR by 50% and 90% respectively (aOR 1.999, 95% CI: 1.123-3.56; P = 0.019). Insulin level among female (aOR1.051, 95% CI: 1.005-1.098; P = 0.028) and HbA1c among male (aOR1.427, 95% CI: 1.06-1.921; P =0.019) increased 5% and 42% of metabolic syndrome risk respectively.
SAD was a strong predicator of insulin resistance in Female Saudi T2DM patients. The lower cut-off points of SAD in both genders compared with International threshold as well as SAD prediction of metabolic syndrome should be further examined.

Disclosure
A. Tourkmani: None. A. Bin Rsheed: None. H. Ansara: None. T. AlHarbi: None. M. fouad: None.
2500-PUB: Mir-302 Protects against Glucolipotoxicity-Induced ß-Cell Dysfunction and Apoptosis through the Regulation of MST1 and PDX1
Authors: HUANG CHIEN-NING , LI HSIN-HUA , KORNELIUS EDY , YANG YI SUN , HO HSIAO-LI , BAI YI-CHIAO , KUO CHIEN-YIN , PENG CHIUNG-HUEI , LIN CHIH-LI 
Published: June 2019

Evidence is now revealed that the cytotoxic effect caused by elevated levels of plasma glucose and free fatty acids, also called as glucolipotoxicity, is particularly harmful for pancreatic β-cell. In fact, the mammalian Ste20-like kinase 1 (MST1) can mediate glucolipotoxicity-induced β-cell damages by degradation of pancreatic and duodenal homeobox 1 (PDX-1), which is known to play an essential role in maintaining β-cell function and survival. Interestingly, the activation of the pluripotency-related microRNA cluster miR-302 can protect β-cells from glucolipotoxicity-induced apoptosis. However, few studies have examined the related mechanism in detail. In the present study, we investigated the protective roles of miR-302 on rat pancreatic RINm5F β-cells, and demonstrated that MST1 was confirmed as a target of miR-302. As a result, the activation of miR-302restored the expression of PDX1 by inactivating MST1 thus ameliorating glucolipotoxicity-induced β-cell impairments. In addition, miR-302 also upregulated endogenous antioxidant signaling and autophagic activities during glucolipotoxicity, suggesting the anti-aging process may be also involved in miR-302-mediated protection.
In conclusion, our study suggests that miR-302 may serve as a potential target for developing new diagnoses and therapies to reduce glucolipotoxicity in β-cells.

Disclosure
C. Huang: None. H. Li: None. E. Kornelius: None. Y. Yang: None. H. Ho: None. Y. Bai: None. C. Kuo: None. C. Peng: None. C. Lin: None.

Funding
Ministry of Science and Technology of Taiwan (105-2314-B-040-013-MY3)
255-LB: The Role of Th1, Th2, Th17, and Treg Cells in Various Clinical Phases of Type 1 Diabetes
Authors: OZGUR BURCIN AYDIN , CINAR SUZAN , OZTURK DERYA , COSKUNPINAR ENDER , GUROL ALI OSMAN , YILMAZ M. TEMEL 
Published: June 2019

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycaemia due to insulin production/secretion disorder or insulin resistance caused by various pathogenetic mechanisms. T helper cells (Th) play an important role in the pathogenesis of the disease. In our study, peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood samples from newly diagnosed, 1 year and 5 year type 1 diabetes (T1D) patients (8 patients) and 8 healthy controls, and cultured for 24 hours under unstimulated and stimulated conditions. After culture, the cell ratios of Th1, Th2, Th17, and regulator T (Treg) and the intracellular levels of IFN-γ, TNF-α, IL-10, TGF-β, IL-5, IL-13, IL-17 and IL-21 cytokines were evaluated using Flow Cytometry; whereas mRNA expressions of the transcription factors T-bet, GATA3, ROR-γt and FOXP3 of these cells were determined by Real-Time PCR. Reduced CD4+CD25high cell ratios were detected in newly diagnosed T1D patients under unstimulated conditions. CD4+CD25high cells were found to be reduced in the newly diagnosed and 1 year group of patients compared to healthy controls under IL-2 stimulated conditions. Intracellular IFN-γ and TNF-α levels were low in all patients under unstimulated and IL-12 stimulated conditions. IL-17A and IL-21 were found to be high in patients with unstimulated and IL-6 stimulated conditions. Expressions of IL-10 and TGF-β have been observed to be reduced in patients. Th1/Th2, Th17/Treg and Th1/Treg ratios were higher in the patient groups. FOXP3 and GATA3 mRNA expressions were found to be low in patients, while RORγt and T-bet mRNA levels were higher than healthy controls under stimulated and unstimulated conditions. Our results suggest that Th cell subgroups play an important role in the pathogenesis of T1D.

Disclosure
B. Aydin Ozgur: None. S. Cinar: None. D. Ozturk: None. E. Coskunpinar: None. A.O. Gurol: None. M. Yilmaz: None.
261-OR: Core-Shell Spherification: A New Microencapsulation Platform for Hyaluronic Acid and PEGDA
Authors: KARANU FRANCIS , HARRINGTON STEPHEN , OTT LINDSEY 
Published: June 2019

Cell microencapsulation associated with islet transplantation is a rapidly expanding field. Traditional alginate microspheres still suffer from poor biocompatibility, and microencapsulation of more advanced hydrogels is challenging due to their slower gelation rates. We have developed a novel, non-cytotoxic, non-emulsion based method to produce hydrogel microspheres compatible with a wide variety of materials, called Core-Shell Spherification (CSS). Here, we demonstrate fabrication of microspheres via CSS derived from two slow-hardening hydrogels: hyaluronic acid (HA) and polyethylene glycol diacrylate (PEGDA). HA microspheres were manufactured with two different crosslinking methods: thiolation and methacrylation. Microspheres of methacrylated HA (MeHA) had the greatest swelling ratio, the largest average diameter and the lowest diffusion barrier. In contrast PEGDA microspheres had the smallest diameters, the lowest swelling ratio and the highest diffusion barrier, while microspheres of thiolated HA (ThHA) had characteristics that were in between the other two groups. To test the ability of the hydrogels to protect cells while promoting function, diabetic NOD mice received xenotransplants via intraperitoneal injections of PEGDA or MeHA microencapsulated canine islets. PEGDA microspheres reversed diabetes for the length of the study (up to 16 weeks). In contrast, islets encapsulated in MeHA microspheres at the same dose restored normoglycemia, but only transiently (3-4 weeks). Non-encapsulated canine islet transplanted at the same dose did not restore normoglycemia for any length of time.
In conclusion, CSS appears to offer several advantages to current cell encapsulation technologies, including a non-toxic microencapsulation procedure compatible with various hydrogel types.

Disclosure
F. Karanu: Employee; Self; LIkarda LLC. S. Harrington: Employee; Self; Likarda, LLC. L. Ott: Employee; Self; Likarda, LLC.