bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-LB303 Behavioral Genotypes Associated With Adults With Obesity
Authors: James Kathy Shadle , Matsangas Panagiotis 
Published: May 2020

Abstract
The use of genetic testing to assist patients with weight loss is still relatively new. Genetic testing offers increased understanding of obesity risk, behaviors that can contribute to weight and much more. Research shows that patients are favorable to learning about how genetics influences their weight. As part of a larger project, this study aimed to identify the frequency of genotypes that influenced eating behavior traits of overweight and obese patients attending a medical weight loss clinic in southern California. All study procedures were approved by appropriate institutional review boards and administrators prior to initiation of the study. We used a quantitative retrospective design to identify participants with atypical eating behavior traits, i.e., (eating disinhibition, food desire, hunger, satiety, snacking, sweet taste, and the FTO obesity gene. The data were extracted from 75 genetic reports of patients who had completed a saliva sample with Pathway Genomics, San Diego, CA between 2017-2018. Analysis showed that 56 (75.7%) patients screened positive for eating disinhibition and 37 (50%) for food desire, whereas 29 (39.2%) were identified with the FTO gene. Also, 20 (27.0%) patients were positive for sweet taste, 13 (17.6%) satiety, 13 (17.6%) snacking, and 7 (9.46%) hunger. On average, patients screened positive for 2 (median value) eating behavior traits. Four (5.41%) patients screened positive for five eating behavior traits, the maximum observed in our sample. Biserial correlation analysis showed that satiety was correlated with the FTO gene (Pearson’s r=0.502, p&lt;0.001) and eating disinhibition was negatively correlated with hunger (Pearson’s r=-0.450, p=0.034). Overall, overweight and obese patients had a disproportionally high incidence of eating disinhibition, food desire, and the FTO obese gene. These atypical behaviors can contribute to their difficulty in losing weight. Specific strategies can be discussed with patients around their atypical behaviors with regular follow up appointments by the clinician. Genetic testing can provide important patient education to improve outcomes related to weight management and health outcomes.
SUN-LB17 The Association of Growth Hormone Treatment in Children With Short Stature With Idiopathic Scoliosis
Authors: Nam Hyo-Kyoung , Rhie Young-Jun , Lee Kee-Hyoung 
Published: May 2020

Abstract
Objectives: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, which occurs usually in the periods of growth spurts and puberty changes. The spinal curve progression in AIS is related to growth, skeletal maturity and sexual maturity. Growth hormone treatment has been used to improve final adult height by increasing growth velocity in children with short stature. Therefore, AIS is expected to occur more frequently in children treated with growth hormone. The aim of this study was to investigate the relationship between AIS and growth hormone treatment in short children. Methods: A total 115 subjects aged 2.1 to 16.9 years who had been treated with growth hormone because of growth hormone deficiency (n=83), idiopathic short stature (n=16) and small for gestational age (n=16) were included. Their medical records were reviewed retrospectively. The scoliosis angle of each subject was measured on the standing frontal radiograph according to the Cobb method. A curve with a Cobb angle of 10 degrees or more is defined scoliosis. Follow up Cobb angle were measured after 1-year of growth hormone treatment. Results: Cobb angle has been increased after 1-year growth hormone treatment (6.1±3.1 vs. 6.9±3.4, P=0.024). The change of Cobb angle was correlated with serum insulin like growth factor-1 level at baseline (r=0.274, P=0.003) and after 1-year of growth hormone treatment (r=0.220, P=0.020). There was no significant correlation between the change of Cobb angle and growth velocity. The prevalence of AIS has been increased after 1-yrear of growth hormone treatment (11.3% vs. 19.1%, P=0.009). Conclusion: Growth hormone treatment in children with short stature seems to be associated with occurring and worsening of AIS.
SUN-LB101 NRF2 Represses Obesity-Associated Adipose Tissue Inflammation in Mice
Authors: Yagishita Yoko , Uruno Akira , Kensler Thomas W , Yamamoto Masayuki 
Published: May 2020

Abstract
Obesity is associated with type 2 diabetes, cardiovascular disease and increased incidence of cancer. Chronic inflammation, mainly emanating from adipose tissue, has been proposed to be one of the links between obesity and these pathologies. Thus, identification of new targets against obesity and especially obesity-induced inflammation is needed urgently. Transcription factor Nrf2 (NF-E2-related-factor-2) plays a central role in cytoprotective responses to oxidative and electrophilic stresses and also exerts anti-inflammatory effects in rodent models of inflammation. However, whether activation of Nrf2 signaling pathway influences obesity-associated inflammation in adipose tissue is not well established. To this end, we generated mice with systemic activation of the Nrf2 pathway (Keap1flox/–), as well as mouse models with tissue-specific Nrf2 pathway activation: adipocyte-specific (Fabp4Cre::Keap1flox/ flox) and myeloid cell-specific (LymCre::Keap1flox/ flox). These mice were exposed to a high-fat diet (HFD) 60% kcal fat regimen for 6-weeks or crossed into the db/db background. Keap1flox/– mice showed a dramatic decrease of the numbers of F4/80-positive macrophages in white adipose tissue (WAT). Interestingly, both Fabp4Cre::Keap1flox/ flox and LymCre::Keap1flox/ flox mice showed suppression of F4/80-positive macrophages in WAT as well, suggesting enhanced Nrf2 signaling in either adipocytes or myeloid cells might contribute to anti-inflammatory effects in WAT under the stress of HFD. Transcript levels of inflammatory markers, especially macrophage F4/80 and Cd68 and the chemokine Ccl2 were decreased in the WAT from Keap1flox/– mice on the standard diet and also in the WAT of Keap1flox/– mice in the db/db background. Pharmacological activation of the Nrf2 pathway by treatment with CDDO-Im also suppressed Ccl2 expression in WAT of HFD fed mice and db/db mice. As CCL2 is a key mediator of macrophage accumulation in adipose tissue, we further studied the potential effect of Nrf2 on the transcriptional regulation of Ccl2 using 3T3-L1 preadipocyte and RAW264.7 macrophage cell lines. Treatment of both lines with the small molecule inducer of Nrf2, diethyl maleate significantly suppressed LPS-induced expression of Ccl2. Analysis using luciferase reporter assay revealed that a Nrf2 binding site in the Ccl2 5’ flanking region from -235 to +85 contributed to gene silencing of Ccl2 by activation of Nrf2. Our findings suggest that the druggable Nrf2 pathway may be an effective target to combat obesity-associated inflammation in adipose tissue and its’ concomitant metabolic disorders. Supported by AMED BINDS JP19am0101001 (MY), 19H05649 (MY), 16KK0195 (AU), NIH R35 CA197222 (TWK), JSPS OT 290125 (YY).
SUN-LB2 Undescended Testicle and Short Stature as Manifestation of Pituitary Stalk Interruption Syndrome a Report From Saudi Arabia
Authors: Ahmed Rania , robert Asirvatham Alwin 
Published: May 2020

Abstract
Background
Pituitary stalk interruption syndrome (PSIS) is a congenital disease with isolated growth hormone deficiency or multiple anterior pituitary hormone deficiencies. Here, the authors report a case of PSIS from Saudi Arabia.
Clinical Case
A 16 year old Saudi boy presented to the endocrine clinic with short stature and undescended testis, status post bilateral orchidopexy. He was delivered by caesarean section because of breech presentation and birth asphyxia. Investigation revealed underdeveloped secondary sexual characteristics with decreased facial and pubic hair growth. The patient height was 134 cm whereas the bone age was 9 - 11 years. Pelvis examination showed a scrotum with bilateral 1 mL testes and the stretch penile length was 3 cm.
The patient laboratory investigations showed hemoglobin level of 13 g/dL, serum sodium 140 mmol/L, serum potassium 4.1 mmol/L, serum chloride 102 mmol/L, calcium 9.1 mg/dL, random blood sugar 110 mg/dL and albumin 3.8 mg/dL. A pituitary hormone profile showed hypopituitarism with thyroid, and adrenal sparing. The patient free T4 was 17.3 pmol/L (9-25 pmol/L) and synacthen test revealed a morning baseline cortisol level of 6.5 µg/dL (normal = 4.3-22.4 ug/dL) with adrenocorticotrophic hormone of 9.8 pmol/L (1.1 - 13.2 pmol/L). Insulin-like growth factor 1 level 50 ng/dL (normal = 193.0 - 731.0 ug/L), follicle-stimulating hormone 0.35 µIU/mL (normal, 0.0-10.0), and leutinizing hormone 0.4 µIU/mL (normal = 1.2-7.8). The patient’s morning testosterone level showed 8 ng/dL (normal = 280-800 ng/dL) and prolactin 116 mIU/L (normal = 86 - 324 mIU/L). There were no symptom suggestive of posterior pituitary involvement like polyuria and polydipsia as urine and serum osmolality. The MRI examination showed no pituitary gland identified in the sella turcica and no clear pituitary stalk. A T1 hyperintense focus with post-contrast enhancement was identified posterior to the optic chiasma representing an ectopic posterior pituitary gland. The growth hormone and testosterone therapy were added to medical therapy of the patients and no thyroid or hydrocortisone replacement therapy was given.
Conclusion: Despite the fact that this is a rare disorder, it should always be kept in the differential diagnosis of a patient presenting with short stature. Patients with this disease have an excellent opportunity to reach normal height if they present before the joining of epiphyses.
SUN-LB125 Violet Sensitive Preoptic Area Neurons That Express Opsin 5 Regulate Thermogenesis and Energy Metabolism
Authors: Zhang Kevin X 
Published: May 2020

Abstract
The thermogenic potential of brown adipose tissue (BAT) is a promising therapeutic target in the treatment of obesity and metabolic disorders. The preoptic area (POA) is a region in the anterior hypothalamus responsible for autonomic thermoregulation by means of modulating BAT activity through sympathetic nerve activity (SNA). Neurons in the POA express opsin-5 (OPN5), an atypical opsin found in various extraretinal tissues and known to respond to violet wavelengths with a lambda-max of 380 nm. OPN5 has previously been shown to regulate seasonal breeding behavior in birds. Loss of OPN5 in mice have been demonstrated to impair circadian photoentrainment. We have also shown OPN5 to be required in retinal ganglion cells for in vivo entrainment of a retina circadian clock independent of the suprachiasmatic nucleus. To date, no other physiological role for mammalian OPN5 has been proposed. The same POA neurons that express OPN5 also engage the central thermoregulatory circuit that modulates BAT activity. We show that POA OPN5 neurons polysynaptically project to the BAT using a retrograde PRV-mRFP1 pseudorabies virus. Also via a genetically targeted glycoprotein-deleted rabies virus injected into the POA, we identified labeled neurons in the rostral raphe pallidus (rRPa), the lateral parabrachial nucleus (LPB), and the dorsomedial hypothalamus (DMH), all nuclei known to participate in central BAT thermoregulation. Opn5-/- mice better defend their core body temperature during acute 4°C challenge. Our results indicate this effect to be due to increased BAT thermogenesis and not heat retention or pyrexia. Furthermore, BAT thermogenesis target gene transcripts (Ucp-1, Prdm16, Pgc-1a) were elevated in these cold stressed Opn5-/- animals. To demonstrate the importance of OPN5’s violet light sensing function in cold defense, C57BL/6J mice reared from E16.5 without 380 nm light largely phenocopy Opn5-/- animals when acutely cold challenged. Furthermore, chemogenetic inhibition of POA OPN5 neurons further augments cold exposure defense and BAT activation. Indirect calorimetry studies reveal Opn5-/- mice to be hypermetabolic, consuming more food and having a higher energy expenditure than controls. Paradoxically, this increased turnover does not translate to weight-gain resistance under high fat challenge. Our results suggest a mechanism where near-UV sensitive hypothalamic OPN5 neurons regulate BAT thermogenesis directly, proposing that the mammalian autonomic thermoregulatory apparatus is light responsive.
SAT-LB47 Tension Pneumothorax Following Cabergoline Initiation for Macroprolactinoma
Authors: Go Muriel Tania , Ganesh Malini , Mascarell Susana 
Published: May 2020

Abstract
Background Pneumocephalus is a rare and life-threatening complication of dopamine agonists (DA) for the treatment of invasive giant prolactinomas. Here we present a catastrophic case of pneumocephalus following cabergoline therapy for invasive macroprolactinoma. Clinical Case A 49-year-old man presented with transient left-sided facial weakness for one day. MRI Brain showed no acute infarcts but revealed a 3.7cm pituitary macroadenoma extending into the sphenoid sinus and left cavernous sinus, encasing the left internal carotid artery with scattered hemorrhagic foci. He was discharged on cabergoline 0.25mg twice weekly for hyperprolactinemia of 7640 ng/mL (N 2.64-13.13 ng/mL). Four weeks later, he was readmitted for altered sensorium, clear rhinorrhea and positional headache. Work-up showed a prolactin of 204 ng/mL confirmed on dilution testing, and a random cortisol of 8.3 mcg/dL. MRI Brain revealed mass involution measuring 2.8cm with the central component replaced by air, and extensive pneumocephalus overlying bilateral cerebral hemispheres, within lateral ventricles and basal cisterns. Further DA therapy was held, and the patient was started on stress dose steroids. He underwent emergent surgical repair of the CSF leak, partial tumor resection and lumbar drain placement. Pathology confirmed pituitary adenoma staining positive for prolactin. Two weeks later, prolactin was 7157 ng/mL. Subsequent attempts to restart DA therapy was complicated by recurrent CSF leaks requiring two additional surgical repairs. After a complicated hospital course requiring prolonged intubation, tracheostomy and PEG tube placement, he was discharged to an acute rehabilitation center on low dose bromocriptine 2.5mg daily as well as maintenance hydrocortisone 10mg twice daily. Discussion CSF leak with pneumocephalus is a rare complication of DA therapy for invasive macroprolactinomas. It occurs due to disruption of the dura with an osseous defect of the skull base. Rapid volume reduction by DA leads to exposure of previously created pathologic opening in the skull base originally plugged by tumor itself until then. Out of 60 patients from 1980 to 2017 who developed DA therapy-induced CSF leak, more than half (57%) were on bromocriptine. Median initial prolactin was 5460 ng/ml and median time from therapy initiation to presence of rhinorrhea was 6 weeks, although it can occur as late as 2 years. The recommended definitive management of DA-induced rhinorrhea is surgical repair. Subsequently, there is no consensus on how to restart DA post-repair. Conclusion This case illustrates the importance of watchful monitoring of response after DA therapy initiation in invasive macroprolactinomas. Although data is sparse, there may be benefit in lower and less frequent dosing initially. Patient education regarding the risk of complications and signs/symptoms to watch out for with DA therapy is also crucial.
MON-LB113 Insulin Resistance in Type 1 Diabetes Managed With Metformin (INTIMET): Rationale and Study Design of a Randomised Placebo-Controlled Trial
Authors: Snaith Jennifer R , Samocha-Bonet Dorit , Holmes-Walker Deborah J , Greenfield Jerry R 
Published: May 2020

Abstract
Background: Insulin resistance is an under-recognised cardiovascular risk factor in type 1 diabetes (T1D). Individuals with T1D exhibit insulin resistance relative to those without diabetes. In T1D, tissue-specific insulin resistance (muscle, hepatic, adipose) is likely to partly drive increased cardiovascular risk. Adjunctive metformin improves muscle insulin sensitivity in T1D adolescents, but factors that predict responsiveness remain unknown.Objective: To report the rationale and design of the INTIMET study, a double-blind randomised, placebo-controlled trial of metformin in T1D.Methods: Forty adults aged 20-50 years with T1D, and 20 age- gender- and BMI- matched non-diabetic controls will be studied. T1D inclusion criteria are diagnosis &gt; 10 years, HbA1c 9.5% and fasting C-peptide &lt; 0.3nmol/L. Liver and muscle insulin sensitivity will be determined by the 2-stage hyperinsulinemic (20 and 60 mUm2)-euglycemic (5.5 mmol/L) clamp method with deuterated glucose. Subjects with T1D will be randomised to metformin extended-release 1500mg/d or matched placebo for 26 weeks. The primary endpoint is the change in hepatic insulin sensitivity, measured by suppression of endogenous glucose production (EGP) with the low-dose insulin clamp. Secondary endpoints include change in muscle and adipose tissue insulin sensitivity, arterial stiffness, HbA1c, glucose variability, frequency of hypoglycemia, insulin dose, anthropometry, body composition, lipid profile, liver fat and stiffness. Conclusion: The INTIMET study will quantify muscle, liver and adipose insulin-resistance in T1D, determine whether metformin is effective in improving insulin resistance in T1D and identify factors that predict metformin-responsiveness.
The trial is registered (Australian New Zealand Clinical Trial Registry, ACTRN12619001440112) and is actively recruiting in Sydney, Australia.
SUN-LB68 Advanced Glycation Endproducts Are Associated With Worse Bone Material Strength in Older Adults With and Without Type 2 Diabetes
Authors: Samakkarnthai Parinya , Sfeir Jad G , Atkinson Elizabeth J , Achenbach Sara J , Tweed Amanda J , Volkman Tammie L , Drake Matthew T , Farr Joshua N , Khosla Sundeep 
Published: May 2020

Abstract
Patients with Type 2 Diabetes (T2D) are at increased fracture risk despite having relatively normal or even increased BMD by DXA. The critical aspect of bone quality deterioration in T2D patients could explain this clinically important discrepancy. Material composition is a component of bone quality that has emerged as a potential factor contributing to fragility fractures in T2D patients. However, there is sparse evidence regarding whether T2D patients have decreased bone material properties compared with non-diabetic controls. We hypothesized that increased production of advanced glycation endproducts (AGEs) has an important role in reducing bone material strength in patients with and without diabetes. Thus, we used the OsteoProbe®, a bone microindentation device that provides an index of cortical bone material properties (Bone Material Strength index – BMSi) in men with T2D age ≥ 50 yrs or postmenopausal women with T2D and nondiabetic controls. We also utilized a non-invasive measure of skin AGEs (AGE Reader®) to evaluate AGEs accumulation through skin autofluorescence. Linear regression models were used to assess group differences with and without adjusting for age, Body Mass Index (BMI), and sex. Relationships between variables were assessed using adjusted Pearson correlations. A total of 152 T2D patients (mean age 68.5 ±7.6 yrs.; 59.2% men; HbA1C=7.7 ±1.0%; mean diabetes duration 15.5 yrs.) and 105 non-diabetic controls (mean age 67.2±8.8 yrs.; 41.0% men; HbA1C =5.4 ±0.3%) were recruited to the study. Overall, there was no difference in BMSi between T2DM and control subjects: unadjusted (p= 0.636); adjusted (p= 0.695). However, skin AGEs were negatively correlated with BMSi (r= -0.23, p &lt;0.001). In subgroup analyses, skin AGEs were also negatively associated with BMSi in both T2DM (r= -0.23, p=0.004) and control (r= -0.21, p=0.033) subjects. In conclusion, these findings demonstrate that a higher burden of AGEs is associated with worse bone quality. Our findings may explain the conflicting findings regarding reductions in BMSi in T2D because only T2D patients with a high level of AGEs accumulation have impaired BMSi. Moreover, the association of skin AGEs with BMSi in non-diabetic subjects emphasizes the important role of AGEs in decreasing bone quality and potentially contributing to fracture risk. Collectively, our data indicate that non-invasive skin AGEs measurement could be used as a tool to evaluate bone quality in patients with T2D as well as in the non-diabetic population.
MON-LB73 Incidence Rate of Post-Thyroidectomy Immediate Hypocalcemia and Its Relation to Pre-Operative Vitamin D and Parathyroid Hormone Levels
Authors: Sirajuddin Khadeeja , Asirvatham Alwin Robert , Alharbi Eman , Sirajuddin Fatima , Al Khahtani Nasir , Al-Gahmdi Abdullah , Al-KharashI Eyad , Alsaeed Abdulghani Habib 
Published: May 2020

Abstract
Aim: To find out the incidence rate of post-thyroidectomy immediate hypocalcemia within 48 hours and explore the association of pre-operative vitamin D and parathyroid hormone (PTH) levels.Methods: This retrospective study was conducted among 122 patients who underwent total thyroidectomy over one year (from January 2018 to December 2018) in Prince Sultan Military Medical City, Riyadh, Saudi Arabia. After thyroidectomy, all patients were admitted and observed for at least 24-48 hours. The postoperative hypocalcemia, alkaline phosphatase (ALP), phosphate (PO4), parathyroid hormone (PTH), and vitamin D level were collected.Results: During 2018 a total of 122 (mean age 41.6±1.2 years; females 90.2%) patients underwent total thyroidectomy. The mean calcium level in the first two days was 2.07 mmol/L and 2.01 mmol/L. Most of the cases of hypocalcemia occurred on day 1 postoperatively. Hypocalcemia mainly occurs in patients with benign pathology. The level of vitamin D in those patients with benign pathology was significantly lower as compared to those with malignant pathology (49±23 vs 62±25; P=0.009). The overall mean level of vitamin D was 54.6±25 (50-150 nmol/L). Interestingly, there were no correlation between pre-operative vitamin D, PTH level and postoperative hypocalcemia. There were no statistically significant differences between postoperative hypocalcemia with other parameters except for pre-operative alkaline phosphatase which was barely positive (P=0.052).Conclusion: The outcomes of this study manifestly illustrated that a significant decline in calcium level after the surgery. In contrast to previous studies, our findings did not show a significant correlation between vitamin D level and hypocalcemia. This could be due to small sample size. Furthermore, the mean level of vitamin D in our cohort was 54 which was within the normal range. Further, well-designed randomized controlled trials with greater sample sizes are necessary to validate our findings.