bluuebunny/crossref_metadata_2025 huggingface dataset:
The spectrum of sepsis-associated encephalopathy: a clinical perspective
Authors: Sonneville Romain , Benghanem Sarah , Jeantin Lina , de Montmollin Etienne , Doman Marc , Gaudemer Augustin , Thy Michael , Timsit Jean-François
Published: October 2023

Sepsis-associated encephalopathy is a severe neurologic syndrome characterized by a diffuse dysfunction of the brain caused by sepsis. This review provides a concise overview of diagnostic tools and management strategies for SAE at the acute phase and in the long term. Early recognition and diagnosis of SAE are crucial for effective management. Because neurologic evaluation can be confounded by several factors in the intensive care unit setting, a multimodal approach is warranted for diagnosis and management. Diagnostic tools commonly employed include clinical evaluation, metabolic tests, electroencephalography, and neuroimaging in selected cases. The usefulness of blood biomarkers of brain injury for diagnosis remains limited. Clinical evaluation involves assessing the patient's mental status, motor responses, brainstem reflexes, and presence of abnormal movements. Electroencephalography can rule out non-convulsive seizures and help detect several patterns of various severity such as generalized slowing, epileptiform discharges, and triphasic waves. In patients with acute encephalopathy, the diagnostic value of non-contrast computed tomography is limited. In septic patients with persistent encephalopathy, seizures, and/or focal signs, magnetic resonance imaging detects brain injury in more than 50% of cases, mainly cerebrovascular complications, and white matter changes. Timely identification and treatment of the underlying infection are paramount, along with effective control of systemic factors that may contribute to secondary brain injury. Upon admission to the ICU, maintaining appropriate levels of oxygenation, blood pressure, and metabolic balance is crucial. Throughout the ICU stay, it is important to be mindful of the potential neurotoxic effects associated with specific medications like midazolam and cefepime, and to closely monitor patients for non-convulsive seizures. The potential efficacy of targeted neurocritical care during the acute phase in optimizing patient outcomes deserves to be further investigated. Sepsis-associated encephalopathy may lead to permanent neurologic sequelae. Seizures occurring in the acute phase increase the susceptibility to long-term epilepsy. Extended ICU stays and the presence of sepsis-associated encephalopathy are linked to functional disability and neuropsychological sequelae, underscoring the necessity for long-term surveillance in the comprehensive care of septic patients.
Efficient ilamycins production utilizing Enteromorpha prolifera by metabolically engineered Streptomyces atratus
Authors: Jiang Yu-Xi , Zheng Gao-Fan , Chen Long-Chao , Yang Na , Xin Xiu-Juan , Ma Jun-Ying , Ju Jian-Hua , Wu Hui , Zhao Ming , Wang Ruida , An Fa-Liang
Published: October 2023

With the invasion of green tides and the increase of urban green areas worldwide, multimillion tons of Enteromorpha need to be reutilized. In this study, Enteromorpha prolifera powder is considered a promising biomass resource for the production of commercial chemical products production. Ilamycins, novel cyclic heptapeptides with significant anti-TB activities, are isolated from Streptomyces atratus SCSIO ZH16, a deep-sea-derived strain. Using EP powder as a nitrogen source, the production of ilamycins reached 709.97 mg/L through optimization of the nitrogen source using the engineered strain S. atratus SCSIO ZH16 ΔR. After mutant strain constructions and tests, strain S. atratus SCSIO ZH16 ΔR::bldD EP powder achieved a higher production titer of ilamycins. Furthermore, the production titer of ilamycins and ilamycin E reached 1561.77 mg/L and 745.44 mg/L, respectively, in a 5 L bioreactor. This study suggests that E. prolifera is a promising and eco-friendly nitrogen source for the production of ilamycins.
Aryl sulfoxide scaffold useful as herbicide
Authors: Kim Heeeun , Hwang Inseoung , Ryu Sungbock , Han Keedon , Kwon Yonghoon
Published: October 2023

The escalating demand for effective and sustainable weed management strategies, driven by urbanization expansion, is a critical challenge. Herbicides are pivotal tools in modern agriculture, addressing this challenge. Developing novel herbicides with enhanced efficacy and minimal environmental impact is crucial for food security and ecological balance. While numerous herbicides have been developed with varying availability over time and regions, there's a continuous need for innovation. In this study, we explored relatively understudied sulfoxide-containing herbicides and synthesized a smaller yet substantial sulfoxide scaffold for herbicide development. Through screening Digitaria ciliaris (Retz.) Koeler, Amaranthus lividus L., and Solanum nigrum L., we observed promising herbicidal efficacy, especially against Wild Amaranth. Encouraged by preliminary findings, we recognize the potential for refining the core structure. In summary, we fashioned a structurally simple sulfoxide scaffold showcasing discernible herbicidal impact on broadleaf weeds.
The validity of the Czech version of Body Appreciation Scale-2 for adolescents
Authors: Kvardova Nikol , Lacko David , Machackova Hana
Published: October 2023

Background

Understanding the formation of body image is critical for the prevention and treatment of eating disorders, especially in adolescence, when body image develops significantly. One of the important facets of body image is body appreciation, which consists of positive feelings and attitudes towards the body regardless of its perceived “flaws”. To measure body appreciation, Body Appreciation Scale-2 (Tylka and Wood-Barcalow in Body Image 12:53–67, 2015a), a unidimensional 10-item measure, has been developed and routinely used in body image research. The current study examined the validity (i.e., factor structure, gender and age invariance, associations with other constructs) of the Czech version of Body Appreciation Scale-2 for adolescents.

Methods

The study used two large samples of Czech adolescents, aged 13–18 (N1 = 613, M = 15.5, 52% girls; N2 = 1,530, M = 15.4, 50% girls). The data were collected in August 2021 (N1) and November 2020 (N2) through an online survey. For the data analysis, we used confirmatory factor analysis (CFA), multi-group confirmatory factor analysis (MG-CFA), and Structural Equation Modeling (SEM).

Results

Our findings supported the proposed unidimensional factor structure and the gender (i.e., girls, boys) and age (i.e., 13–15, 16–18) scalar invariance of the Czech version of Body Appreciation Scale-2. The data also showed the expected positive correlations with body satisfaction and self-esteem, and negative correlations with media-ideal internalization, appearance schematicity, and depression. Furthermore, we discovered that body appreciation was more strongly connected to media-ideal internalization and depression for girls than boys.

Conclusions

The present study provided robust evidence that supports the validity of the Czech version of Body Appreciation Scale-2 and its usability for the assessment of body appreciation in Czech adolescents. We also proposed future directions for the research on body appreciation based on the explored gender differences.
PsyCARE study: assessing impact, cost-effectiveness, and transdiagnostic factors of the Italian ministry of health’s “psychological bonus” policy
Authors: Benzi Ilaria M.A. , Compare Angelo , Tona Antonino La , Di Nuovo Santo , Lazzari David , Lingiardi Vittorio , Coco Gianluca Lo , Parolin Laura
Published: October 2023

Background

The prevalence of anxiety and depression disorders is surging worldwide, prompting a pressing demand for psychological interventions, especially in less severe cases. Responding to this need, the Italian government implemented the “Psychological Bonus” (PB) policy, allotting 25 million euros for mental health support. This policy entitles individuals to a minimum of four to twelve psychological sessions. In collaboration with the National Board of Italian Psychologists, our study assesses this policy’s effectiveness. Indeed, the PsyCARE study aims to examine the utilization of the Psychological Bonus, evaluate its impact on adult and adolescent participants’ psychological well-being through pre- and post-intervention assessments and six-month follow-up, and conduct a longitudinal cost-effectiveness analysis of this policy. A secondary aim is to investigate the influence of these interventions on transdiagnostic factors, including emotion regulation and epistemic trust.

Methods

The study involves licensed psychotherapists and their patients, both adults and adolescents, benefiting from the Psychological Bonus. Data collection is underway and set to conclude in December 2023. Psychotherapists will provide diagnostic information and assess patient functioning. In addition, patients will be evaluated on mental health aspects such as clinical symptoms, emotion regulation, epistemic trust, and quality of life. We will employ linear mixed-effects models to analyze the outcomes, accounting for both fixed and random effects to capture the hierarchical structure of the data.

Discussion

We anticipate the study’s findings will highlight reduced psychological distress and improved quality of life for participants and demonstrate the Psychological Bonus policy’s cost-effectiveness. The study will gather data on the role of specific versus nonspecific therapeutic factors in psychotherapy while adopting a patient-tailored approach to identify effective therapeutic elements and examine transdiagnostic factors. Overall, this study’s findings will guide future measures within the Italian healthcare system, fostering a psychological health culture and providing valuable insights to the broader public.

Study registration

https://osf.io/6zk2j
Evaluating the anti-urolithiasis potential of Ficus religiosa seed GC MS evaluated phytoconstituents based on their in-vitro antioxidant properties and in-silico ADMET and molecular docking studies
Authors: Pinipay Felicity , Rokkam Rajesh , Botcha Satyanarayana , Tamanam Raghava Rao
Published: October 2023

Background

Urolithiasis, the deposit of stones in the urinary tract is a pertinent clinical issue in daily practice that imposes a burden on the human health system. Ficus religiosa plant has historically been useful in preventing urolithiasis. There is currently no information on phytochemical profiling that specifies the precise phytochemicals in the seed that are active against urolithiasis.

Methods

F. religiosa seeds were extracted with different solvents in increasing order of their polarity by Soxhlet extraction. All the extracts were evaluated for their antioxidant potential. GC–MS profiling of the most potent antioxidant F. religiosa seed extract was done to evaluate the phytoconstituents. To evaluate the pharmacokinetics and drug-likeness properties of these compounds in silico ADMET analysis was done. To comprehend the binding potential of the best ADMET evaluated phytochemicals contained in the F. religiosa seed extract against the several protein targets (matrix metalloproteinases (MMP-2, MMP-9), and Human calcium-sensing receptor (CaSR)) and antioxidant enzymes (Glutathione S-transferase (GST), glutathione-disulfide reductase (GR), glutathione peroxidase (GPX), and superoxide dismutase (SOD)) involved in urolithiasis, multi targets based virtual screening tests were done using Autodock Vina tool.

Results

GC–MS profiling revealed the presence of 53 different compounds. Of all these compounds, based on ADMET analysis 2-Methoxy-4-vinylphenol; 3,5-Di-tert-butylphenol; diethyl benzene-1,2-dicarboxylate; 4-hydroxy-3,5-dimethoxybenzaldehyde; 2-methoxy-4-prop-2-enylphenol; and bis (2-methyl propyl) benzene-1,2-dicarboxylate were found to have best pharmacokinetics and drug-likeness properties. In the autodocking studies, 3,5-Di-tert-butyl phenol is proved to be the best of all in terms of binding energies with the selected targets.

Conclusion

The findings of this study suggest a framework for employing F. religiosa seed ethyl acetate extract as a potent herbal treatment for urolithiasis.
Endoscopic clip-induced acute appendicitis in a patient on chronic hemodialysis: a case report with literature review
Authors: Yomogida Daichi , Fujisawa Yuhei , Takeji Akari , Takeda Yasuhito , Tomita Yoshiharu , Shirota Yukihiro
Published: October 2023

Background

Foreign body-induced acute appendicitis is rare but could most often be caused by fish bones; those caused by endoscopic clips are highly rare. Herein, we report a case of acute appendicitis caused by endoscopic clips that developed 2 years after the endoscopic procedure.

Case presentation

A 68-year-old man with a 2-year history of hemodialysis (HD) for diabetic nephropathy visited our hospital with pain in the right lower quadrant. He had undergone endoscopic submucosal dissection (ESD) for gastric adenoma 2 years earlier. Abdominal computed tomography revealed acute gangrenous appendicitis and a high-density structure lodged in the appendix. This structure was determined to be an endoscopic clip that was lodged in the patient’s appendix for 2 years. The patient underwent an emergency laparoscopic appendectomy, and an endoscopic clip covered by a fecalith was found in the appendix.

Conclusion

Endoscopic clips usually fall off spontaneously in approximately a week and pass through stool. However, in this case, appendicitis developed 2 years after the ESD. An emergency surgical appendectomy may be recommended for appendicitis caused by foreign bodies. Prophylactic appendectomy or removal of foreign bodies should be considered for HD patients, even in the absence of symptoms owing to the potential severity of appendicitis in such patients.
Spectrum and prevalence of renal dysfunction among heart failure patients attending tertiary care hospital: first report from Somalia
Authors: Jeele Mohamed Osman Omar , Hussein Ahmed Abdirahman , Mohamud Mohamed Abdullahi , Adani Abdulkamil Abdullahi , Mohamud Mohamed Farah Yusuf
Published: October 2023

Introduction

Heart failure is one of the major global health problems that we face today, worldwide. The main objective of our study is to evaluate the spectrum and prevalence of renal dysfunction among heart failure patients in Mogadishu, Somalia. The design of the study is a retrospective descriptive study aimed at heart failure patients who presented to the largest tertiary care center in southern somalia between January 2021 to september 2021. Demographic data, co-morbidities, types of heart failure, causes of heart failure and the presence or absence of renal dysfunction were analysed.

Results

Overall 180 heart failure patients were enrolled in the study. The mean age of the participants was 62.26 ± 14 years. Regarding the age group, patients aged between 61–80 years was the most abundant participants with (n = 87, 48.3%). Regarding the type of heart failure in our study, HFpEF was the most common type in our respondents with frequency of (n = 85, 47.2%). When analysed the cause of heart failure among patients; hypertension was the most common cause of heart failure (n = 90, 50%). Also, hypertension was the most common co-morbidity among our patients (n = 106, 59%), followed by coronary artery diseases (n = 50, 28%). The prevalence of renal dysfunction in heart failure patients was (n = 37, 20.6%). Our analysis showed that among the 37 renal dysfunction patients, 12.3% of them (n = 22) were CKD (chronic kidney disease) while the remaining 8.3% (n = 15) had AKI (acute kidney injury). We found a significant correlation between gender and renal dysfunction in heart failure patients with (95% CI: 0.098–0.574, OR: 0.237, p value: < 0.001). Males were 2 and half times more likely to develop renal failure than females.

Conclusions

we found that the prevalence of renal dysfunction in heart failure patients is 20.6%. It was more prevalent in males and elderly population.
OR10-06 Changes In Resting Energy Expenditure And Metabolic Adaptation In Adolescents Two Years After Sleeve Gastrectomy Compared With Non-surgical Controls And Determinants Of These Changes
Authors: Singhal Vibha , Pedreira Clarissa C , Tuli Shubhangi , Haidar Lea Abou , Lee Hang , Bredella Miriam A , Misra Madhusmita
Published: October 2023

Disclosure: V. Singhal: None. C.C. Pedreira: None. S. Tuli: None. L.A. Haidar: None. H. Lee: None. M.A. Bredella: None. M. Misra: None.

Background: Weight loss is typically associated with reductions in resting energy expenditure (REE), which may limit the extent of weight loss after sleeve gastrectomy (SG), the most common metabolic and bariatric surgery (MBS) in youth. REE may be impacted by changes in body composition and gut peptides following SG. Current data regarding changes in measured REE (mREE) and metabolic adaptations in adolescents after MBS are limited. Objectives: To evaluate changes in mREE, estimated REE (eREE), metabolic adaptation (difference in mREE – eREE), body composition, and gut peptides in youth after SG compared to non-surgical controls (NS) over two years. Methods: Youth 14-22 years old undergoing SG (n=24) and NS controls with severe obesity (n=28) were enrolled in this study. mREE was determined by indirect calorimetry. The Mifflin equation was used to calculate eREE. To account for effects of changes in FFM and total body weight (TBW), we evaluated mREE/FFM, mREE/TBW, eREE/FFM, and eREE/TBW. Dual energy X-ray absorptiometry (DXA) was used to measure body composition. Fasting plasma levels of ghrelin, peptide YY (PYY), glucagon-like peptide 1 (GLP-1), and insulin were measured. All measurements were performed at baseline and two years later. Results: Mean age and sex did not differ across groups. Body mass index (BMI) at baseline trended higher in SG vs. NS [43.60 (39.81, 49.39) vs. 41.60 (37.83, 48.21) kg/m2, (p=0.051)]. Mean change in BMI was higher in SG than NS (–11.5 ± 1.21 vs. 1.47 ± 0.58 kg/m2, p<0.0001). SG had a within group decrease in mREE of 400.96 ± 69.49 kcal/d (p<0.0001) and in eREE of 325.68 ± 34.73 kcal/d (p<0.0001) over 2 years. While mREE and eREE decreased in SG, both measures increased in NS over 2 years (p<0.0001 for both). Changes in mREE/FFM, mREE/TBW, and eREE/FFM over 2 years did not differ between groups (p=0.14, 0.24 and 0.61 respectively) while eREE/TBW increased in SG and decreased in NS (p< 0.0001). Metabolic adaptation over 2 years did not differ between groups (p=0.335). Ghrelin and insulin levels decreased over 2 years following SG but PYY and GLP-1 did not change significantly. Within SG, metabolic adaptation was positively associated with 2-year change in FFM (Spearman ρ= 0.57 p=0.009), but not with changes in gut peptides over 2 years. Conclusion: Despite significant decreases in BMI after SG in youth, surgical and non-surgical groups did not differ for changes in mREE/FFM and metabolic adaptation over 2 years.

Presentation: Friday, June 16, 2023
FRI046 Clinical Phenotyping Of Adults With Genetic Obesity
Authors: Welling Mila Sofie , Mohseni Mostafa , Meeusen Renate E H , Boon Mariëtte R , de Groot Cornelis J , van Haelst Mieke M , Visser Jenny A , van den Akker Erica L T , van Rossum Elisabeth F C
Published: October 2023

Disclosure: M.S. Welling: None. M. Mohseni: None. R.E. Meeusen: None. M.R. Boon: None. C.J. de Groot: None. M.M. van Haelst: None. J.A. Visser: None. E.L. van den Akker: None. E.F. van Rossum: None.

Introduction: In rare cases of obesity, genetic defects lead to hyperphagia and severe early-onset obesity. Genetic testing in patients with a suspected genetic obesity phenotype is important, as it can lead to patient-tailored treatment advice. For children, the Endocrine Society (ES) recommends genetic testing in children with early-onset of obesity (<5 years) and hyperphagia. It is unclear whether these recommendations can also be used in adult obesity care. Therefore, we aimed to phenotype adult patients with genetic obesity disorders. In addition, we assessed the suitability of the pediatric ES recommendations in these patients. Methods: We analyzed clinical data of patients with non-syndromic genetic obesity (NSO) and syndromic genetic obesity (SO), who visited our academic obesity center (Erasmus Medical Center, Rotterdam, the Netherlands). A standardized medical questionnaire, including topics concerning e.g. age of onset of obesity, hunger and satiation, was assessed. Anthropometrics, body composition (bio-impedance analysis), and resting energy expenditure (REE, indirect calorimetry) were measured. Differences between the NSO and SO groups were studied. Results: Sixty-six patients, of which n=26 with NSO and n=40 with SO, were included: median BMI and age at intake were 41.2 vs 39.2 kg/m2 and 25.7 vs 24.8 yrs, respectively (ns). The median age of onset of obesity was 2.5 [1-5] yrs in NSO and 9.5 [4-14] yrs in SO (p<0.001). Impaired appetite regulation was present in both groups: increased feelings of hunger in 64.0 vs 51.3% and impaired satiation in 47.1 vs 32.0% in NSO vs SO (ns). Binge eating was reported in 63.2% of SO, compared to 40.0% in NSO (p=0.071). The pediatric ES recommendations were fulfilled in 57.5% of NSO and 27.5% of SO (p=0.014). Compared to NSO, SO had a higher prevalence of intellectual deficit (3.8 vs 55.0%, p<0.001), autism (7.7 vs 26.3%, p=0.061) and retinal problems (0 vs 20.0%, p=0.015). There were no differences in body composition or REE. Conclusion: We report distinct phenotypic features concerning the age of onset of obesity, appetite regulation, and the presence of intellectual deficit, autism and retinal problems in adults with non-syndromic genetic obesity or syndromic genetic obesity. Additionally, this study demonstrates that the Endocrine Society’s recommendations for genetic testing in children with obesity, do not suit well for adults with obesity. Recommendations for genetic testing in adults with obesity are needed.

Presentation: Friday, June 16, 2023
FRI047 Clinical Characteristics Of Patients With Morbid Obesity With Semaphorines (SEMA3D,E,G) And PLXNA3&4 Gene Variants
Authors: Berra Maddie , Khattab Ahmed , Ten Svetlana B , Bhangoo Amrit Pal S
Published: October 2023

Disclosure: M. Berra: None. A. Khattab: None. S.B. Ten: None. A.S. Bhangoo: None.

Aim of the study: To describe the clinical characteristics of patients with morbid obesity with SEMA3D,E,G and PLXNA3&4 gene variants. Introduction: Heterozygous variants of SEMA3s and their receptors PLXNA3 and 4 were described in cases of morbid obesity (Ref1). SEMA3 genes encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. SEMA3s signaling pathway is important for POMC neurons projections from the arcuate to the paraventricular nucleus. Methods: Patients with morbid obesity underwent genetic testing at the Prevention Genetics after obtaining consent. Results: Heterozygous gene variants were found in 8 cases, 3 males, 5 females, from 2 to 22 yrs., average BMI 33.3±8.6 kg/m2, 5 Hispanics, 2 Caucasians, 1 Asian. All cases presented with early morbid obesity from 2-4 yrs. of age, hyperphagia. Leptin was measured in 4 cases and was low for the degree of obesity (5.8-7.8 ng/ml). They had fatty liver, elevated triglycerides 168±33; had HDL 41.7±6.9 (data presented as avg±SDS).16 yrs. old female, BMI 31.2, PLXN3, c.1556G>A, p.Arg519His variant. Father had morbid obesity, treated with bariatric surgery lap band procedure.8 yrs. old girl, BMI 28.7, PLXN3, c.1733C>T, p.Ala578Val variant. Maternal aunt had bariatric surgery.22 yrs. old female, BMI 53, PLXNA4, c.1982C>T, p.Ser661Leu variant. She had impaired glucose tolerance, PCOS, a nodular goiter, impaired glucose tolerance, 2 sisters and a brother had bariatric surgery.16 yrs. old boy, BMI 35.5, SEMA3D, c.1048T>C, p.Ser350Pro variant. He had anxiety, panic attacks, depression. His PGF and paternal uncle has morbid obesity. 16 yrs. old girl, BMI 30.9, SEMA3G, c.2305>G variant. She had impaired fasting glucose, elevated prolactin and amenorrhea. Mother and MGM had morbid obesity. 2 year old male with BMI of 30.1, SEMA3E, c.1443A>T, p.Glu481Asp variant. Mother had morbid obesity.4 year old female with BMI of 23.7, SEMA3G, c.2086GA, p.Gly696Arg variant. She has autism, epilepsy and motor delay. Mother and maternal aunt had morbid obesity.11 year old male, BMI 33.6, PLXNA4, c.4896CA, p.Asp1632Glu variant. MGF had morbid obesity. Conclusion: Clinical phenotype of patients with heterozygous variants of Semaphorins and its receptors shows presence of severe obesity from a young age of 2-4 yrs. All had a very strong family history of morbid obesity. These children developed insulin resistance with elevated TG and fatty liver from a young age. Leptin levels in few were low for the degree of obesity.

Ref1. van der Klaauw AA, Farooqi IS et.al. Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance. Cell. 2019 Feb 7;176(4):729-742.e18. doi: 10.1016/j.cell.2018.12.009. PMID: 30661757.

Presentation: Friday, June 16, 2023
FRI049 Correlation Between Tri-Ponderal Mass Index And Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-3 In Children And Adolescent
Authors: Choi Iee Ho , Kim Min Sun
Published: October 2023

Disclosure: I.H. Choi: None. M. Kim: None.

Purpose: We aimed to investigate relation between Tri-ponderal mass index (TMI) and Insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) which has been known to be associated with growth and development of fat. Methods: 1630 children and adolescent has been selected among patient who has visited Jeonbuk National University children’s hospital and been diagnosed as normal. Patient’s medical chart were reviewed retrospectively about age, sex, height, weight, Body mass index (BMI), TMI, IGF-I, IGFBP-3. Male group and female group were categorized into 4 age groups and weight group such as underweight, normal, overweight, obesity according to BMI and TMI. Correlation between each of BMI, TMI and IGF-I, IGF-I standard deviation score (SDS), IGFBP-3, IGFBP-3 SDS, IGF-I/IGFBP-3 ratio were analyzed. Results: In male group, significant correlation between BMI and IGF-I, IGF-I SDS, IGFBP-3, IGFBP-3 SDS, IGF-I/IGFBP-3 ratio was observed only in normal weight group. But Significant correlation was observed in normal weight group between TMI and IGF-I, IGF-I SDS, IGFBP-3, IGFBP-3 SDS, IGF-I/IGFBP-3 ratio, also in overweight group between TMI and IGF-I, IGFBP-3, IGFBP-3 SDS. In female group, significant correlation for BMI was observed in normal weight group with all variable and in overweight group with IGFBP-3, IGFBP-3 SDS. Significant correlation for TMI was observed in normal weight group with all variable except IGFBP-3 SDS, and in overweight group with all variable, also in obesity group with IGFBP-3 SDS (rho=0.571, p=0.041). Conclusions: TMI may have significant correlation with IGF-I and IGFBP-3 in overweight and obesity group more than BMI. Especially IGFBP-3 SDS with TMI may be more helpful to evaluate overweight and obesity in female adolescent

Presentation: Friday, June 16, 2023
FRI054 Partial Lipodystrophy As A Manifestation Of Autoimmune Polyglandular Syndrome 1
Authors: Agarwal Shubham , Xing Chao , Anderson Mark Stuart , Garg Abhimanyu
Published: October 2023

Disclosure: S. Agarwal: None. C. Xing: None. M.S. Anderson: Stock Owner; Self; Medtronic Diabetes, Merck. A. Garg: None.

Background: Autoimmune polyglandular syndrome 1 (APS1) is a rare autosomal recessive disorder due to mutations in AIRE gene that manifests mainly with chronic mucocutaneous candidiasis, primary hypoparathyroidism and adrenal insufficiency. We report an extremely rare APS1 patient who developed partial lipodystrophy during adulthood. Clinical Case: This 39-year-old white female developed frequent diaper rashes, oral thrush and tetany at the age of one year due to candidiasis and hypoparathyroidism. At 6 years, she developed hypothyroidism. At 11 years, she developed fatigue, excessive thirst, and anorexia due to primary adrenal insufficiency. At 13 years of age, she had thelarche and adrenarche but never attained menarche. At 14 years, she underwent a sibling matched allogenic bone marrow transplant due to multiple antibiotic-refractory fungal infections. At 35 years, her serum triglycerides level was 904 mg/dL and loss of subcutaneous fat from the upper and lower extremities and hips was noted but she had increased subcutaneous fat on the chest and abdomen as well as buffalo hump. Thigh skinfold thickness was 8 mm (<10th percentile of normal). A whole-body dual-energy X-ray absorptiometry revealed a total body fat of 38% with lower extremity fat of 25%-27% (<1st percentile of normal). Whole exome sequencing on DNA extracted from saliva revealed two pathogenic variants in AIRE gene; c.83T>C; p.Leu28Pro and c.769C>T; p.Arg257* confirming the diagnosis of APS1. No other pathogenic variants were noted in the known lipodystrophy genes. Serum was negative for anti-perilipin 1 autoantibody. Discussion: Biallelic mutations in the AIRE hinder the process of selective apoptosis of T-cells in the thymic medulla that have a strong affinity to self-antigens leading to autoimmunity manifesting as APS1. Previously, a 5-year-old boy with APS1 was reported to develop generalized lipodystrophy and his serum was positive for anti-perilipin 1 autoantibody. Recently, serum anti-perilipin-1 autoantibodies have also been reported in the Aire gene knock out mice. In contrast, our patient has partial lipodystrophy and was negative for anti-perilipin 1 autoantibody. This suggests that patients with APS1 may harbor many different autoantibodies against adipocyte expressed proteins and develop different patterns of autoimmune lipodystrophies.

Presentation: Friday, June 16, 2023
SAT140 A Rare Case Of Asymptomatic Severe Refractory Hypoglycemia Due To Hyper-Warburgism In A Young Patient With T-cell Acute Lymphoblastic Leukemia (ALL)
Authors: Choe Suhrim
Published: October 2023

Disclosure: S. Choe: None.

Background: Hyper-Warburgism, exaggerated Warburg effect, is a rare but serious paraneoplastic syndrome caused by excess glucose consumption by cancer cells through glycolytic pathway leading to lactic acidosis and treatment refractory hypoglycemia. Neuroglycopenic symptoms are absent in these patients hence patients do not meet Whipple triad. Clinical Case: A 33yo African American male with past medical history of recently diagnosed cardiomyopathy and atrial fibrillation was initially admitted to outside institution for cardiac ablation then subsequently transferred to our institution for escalation of care in the setting of post-procedural persistent hypoglycemia. He reported symptoms of fatigue and poor appetite. He noted an unintentional weight loss of 30lb over the past 2 weeks. However, he denied fever, night sweats, classic signs and symptoms of hypoglycemia. Vital signs and physical examination were unremarkable. Clinical manifestation of neuroglycopenia was absent despite serum glucose as low as 46 while serum lactate of 23.8 mmol/L (0.5-2 mmol/L). Initial laboratory test notable for lactic acid of 24.2 mmol/L, glucose of 57 mg/dL, bicarbonate of 12 mEq/L, anionic gap of 39 mEq/L, beta hydroxybutyrate of 5.3 mmol/L, IGF-1 of 192 ng/mL (75–212 ng/ml), IGF-II of 570 ng/mL (288–736 ng/ml), AM cortisol of 14.3 μg/dl, ACTH of 41.6 pg/ml, hemoglobin A1c of 4.8 %, fasting insulin of 1 IU/liter, C-peptide of 0.4 ng/ml, and pro-insulin of 2.9 pg/ml. Given suppression of insulin and proinsulin levels and IGF-II level >275 ng/ml, noninsulin-mediated hypoglycemia was suspected. A CT of chest/abdomen/pelvis revealed a subpleural soft tissue mass involving the posterior mediastinum measuring 4.4 x 3.6 x 3.7 cm, diffuse bilateral renal involvement suspicious for renal lymphoma, adenopathy in the bilateral inguinal, axillary, and external iliac chains. Bone marrow biopsy was performed and result was consistent with T-cell ALL. 20% dextrose infusion was titrated up to keep his BG above 70 mg/dl and high dose steroids was initiated to bridge to chemotherapy. Chemotherapy was initiated soon after confirmation of diagnosis by bone marrow biopsy. The lactic acidosis and hypoglycemia dramatically improved shortly after. PET/CT done 4 weeks after first cycle of chemotherapy failed to identify active disease proving the patient’s good response to chemotherapy. Conclusion: The patient presented with noninsulin-mediated hypoglycemia due to rapid glucose use by cancer cell leading to hyper-Warburgism, evident by severe lactic acidosis, spontaneous hypoglycemia, and large tumor burden on CT scan. Absence of neuroglycopenia presumable due to brain using lactate as fuel and, for this reason, Whipple triad cannot be applied to diagnose hypoglycemia in this case. Chemotherapy must be initiated timely manner as it would resolve metabolic abnormalities dramatically as it was seen in our patient.

Presentation: Saturday, June 17, 2023
SAT167 Risk Of Life Threatening Hypoglycemia When Using U-100 Insulin Syringes To Administer R U-500 Insulin
Authors: Rizwan Tehlil , Alchalabi Marwah , Arora Gunjan , Qureshi Ursula N , Qureshi Faisal
Published: October 2023

Disclosure: T. Rizwan: None. M. Alchalabi: None. G. Arora: None. U.N. Qureshi: None. F. Qureshi: None.

Background: Humulin R U-500 is a concentrated human insulin indicated to improve glycemic control in adults and children with diabetes mellitus requiring more than 200 units of insulin per day. R U-500 insulin is five times more concentrated than U-100 insulin. Clinical Case: A 42-Year-old woman with medical history of depression, hidradenitis, morbid obesity, hypertension, hyperlipidemia, chronic headache, and type 2 diabetes mellitus was on R U-500 insulin, Jardiance, and Victoza. Patient presented with low blood glucose levels. Patient reported that her home insulin regimen is 20 units of R U-500 insulin with meals. Her home glucose diary showed blood glucose levels as low as 30-50 mg/dL. Recent hemoglobin A1c was 6.5%. Of note, the patient was unaware of hypoglycemic symptoms. Upon taking detailed history, and discussing insulin injection technique, it was apparent that the patient was administering insulin correctly. Upon further inquiry, the patient reported not being aware of the specialized R U-500 syringe. Patient expressed unfamiliarity after being shown images of the correct R U-500 syringe. It became apparent that the patient was using a U-100 insulin syringe to draw from R U-500 insulin vial which means she was receiving an incorrect dosage. Filling the U-100 syringe to the 20-unit mark with R U-500 insulin will deliver 100 units of R U-500 insulin which puts the patient at risk of severe hypoglycemia. During hospital stay, U-500 R insulin, Victoza, and Jardiance were stopped, the patient was started on basal and bolus insulin regimen, and blood glucose levels were monitored with meals and at bedtime. Blood glucose levels improved to 140-180 mg/dL. Upon hospital discharge, the patient was encouraged to switch to R U-500 KwikPen as this will be more accurate and safe.

Conclusion: The U.S. Food and Drug Administration approved a dedicated syringe for the administration of Humulin R U-500 insulin, which is now the only device approved for use with U-500 insulin vial. Do not switch between types of syringes because it may increase the risk of dosing errors.

Presentation: Saturday, June 17, 2023
SAT435 The Quest Of Elevated Dhea-s: Is It A Tumor Or Is It Ashwagandha?
Authors: Patel Shivani , Aluko Oluwatomisin A , Gallagher Thomas
Published: October 2023

Disclosure: S. Patel: None. O.A. Aluko: None. T. Gallagher: None.

Introduction: Ashwagandha (Withania somnifera) is a popular Indian ayurvedic herb that is readily available over the counter in the United States. Ashwagandha is known to increase in testosterone and DHEA-s levels in men. We hereby report a case of a female who had elevated DHEA-s due to intake of Ashwagandha. Case Report: A 27 year old female with past medical history of vitamin D deficiency, anxiety, X linked heterozygous adrenoleukodystrophy presents to establish care with endocrinology with complaints of unintentional weight gain of about 25lbs, inability to lose weight with lifestyle modifications, dizziness, light headedness and occasional salt cravings. Medication history is significant for using ashwagandha 600mg twice daily, probiotic-10. Vitals were BP 102/70 mmHg, HR 108 beats/min, RR 18 breaths/min, SpO2 98%, BMI 31.28kg/m2. Laboratory evaluation showed AM cortisol of 21.6 ug/dL H (6.2-19.4 ug/dL), ACTH 6.2 pg/mL (7.2-63.3 pg/mL), DHEA-s >1000 ug/dL H (84.8-378 ug/dL), TSH 1.39 IU/mL (0.45-4.5 IU/mL), free t4 2.39 ng/dL H (0.82-1.77 ng/dL), IGF-1 252 ng/mL (91-308 ng/mL), 1mg dexamethasone suppression test resulted AM cortisol of 1.5 ug/dL (6.2-19.4 ug/dL). Subsequently, further work up revealed 17 hydroxyprogesterone of 158 ng/dL (luteal phase 35-290 ng/dL), total testosterone 176 ng/dL H (13-71 ng/dL), free testosterone 1.8 pg/mL (0-4.2 pg/mL), androstenedione 113 ng/dL (41-262 ng/dL), LH 2.5 mIU/mL (follicular phase 2.0-12.6 mIU/mL), FSH, 3.6 mIU/mL (follicular phase3.5-12.5 mIU/mL). Patient underwent CT abdomen and pelvis with and without contrast which showed normal adrenal glands, prominent right ovary and US Pelvis was recommended. Pelvic ultrasound showed normal ovaries. MRI pelvis with and without contrast revealed 1cm right ovarian hemorrhagic cyst. Patient was subsequently asked to stop all over the counter supplement medications and a DHEA-s level was checked about 6 weeks and was markedly reduced to 435 ug/dL. TSH and free t4 improved to 0.789 IU/mL and free t4 1.43 ng/dL respectively. Conclusion: This case highlights that over the counter, readily available supplements that are marketed for reducing stress may cause remarkable alteration of natural physiology. Ashwagandha’s use in men have been known to cause elevations in DHEA-s in men and this case highlights that Ashwagandha’s use in women can also cause elevation in DHEA-s and how a simple intervention of eliminating Ashwagandha can improve DHEA-s levels

Presentation: Saturday, June 17, 2023
SAT445 Exposure To Perfluoroalkyl Substances At Preconception In Association With Metabolic Phenotype In Women From Singapore
Authors: Cohen Nathan J , Yao Meizhen , Midya Vishal , India-Aldana Sandra , Andra Syam S , Narasimhan Srinivasan , Meher Anil K , Arora Manish , Yen Chan Jerry Kok , Chan Shiao Yng , Kway Yeshe , Michael Navin , Sadanathan Suresh A , Eriksson Johan G , Sendhil Velan S , Hian Tan Kok , Oulhote Youssef , Huang Jonathan , Valvi Damaskini
Published: October 2023

Disclosure: N.J. Cohen: None. M. Yao: None. V. Midya: None. S. India-Aldana: None. S.S. Andra: None. S. Narasimhan: None. A.K. Meher: None. M. Arora: None. J.K. Chan: None. S.Y. Chan: None. Y. Kway: None. N. Michael: None. S.A. Sadanathan: None. J.G. Eriksson: None. S.S. Velan: None. T.K. Hian: None. Y. Oulhote: None. J. Huang: None. D. Valvi: None.

Background and Aim: Exposure to perfluoroalkyl substances (PFAS) may result in adverse metabolic health outcomes, but few studies have focused on preconception PFAS exposures and metabolic dysregulation which could impact pregnancy. We assessed cross-sectional and prospective associations between preconception PFAS concentrations and glucose regulation, insulin sensitivity, and magnetic resonance imaging (MRI) based adiposity measures in a Singaporean cohort of women who were actively attempting to conceive. Methods: Our analyses included 384 participants from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), from which 126 underwent abdominal MRI at preconception. 15 different PFAS in preconception plasma samples were measured, and metabolic measures were cross-sectionally assessed at preconception (waist-to-height ratio [WHtR], 2-hour oral glucose tolerance test [OGTT] indices, and MRI-based measures of abdominal adiposity and liver fat), and prospectively at 24-28 weeks of gestation (2-hour OGTT indices). We used linear regression models to assess associations between individual PFAS and metabolic phenotype at preconception and pregnancy. In addition, we used Bayesian weighted quantile sum (BWQS) regression to assess the joint associations of the PFAS mixture with study outcomes. Results: We observed negative associations between perfluorononanoic acid (PFNA) concentrations and visceral adipose tissue (VAT; log2-transformed) volume (β per doubling of PFNA=-0.12 cm3, 95% CI -0.24, 0.00) and log2-transformed liver fat percentage (β=-0.28%, 95% CI -0.52, -0.04). Inverse associations were observed between the individual PFAS and most mid-pregnancy OGTT indices and insulin resistance, but were not statistically significant. Associations were not statistically significant for all preconception OGTT indices. Conclusions: We did not find strong evidence for an association between preconception PFAS concentrations and prenatal metabolic outcomes in young women in Singapore. Cross-sectional analyses indicated reduced adiposity in VAT volume and liver fat percentage with increasing PFAS concentration, which requires further investigation in prospective, more diverse, and larger studies.

Presentation: Saturday, June 17, 2023
SAT638 Understanding Heritable Metabolic Alterations Upon Paternal Preconception Nicotine Exposure
Authors: Aguiar Stephanie Rose , Chamorro-Garcia Raquel
Published: October 2023

Disclosure: S.R. Aguiar: None. R. Chamorro-Garcia: None.

Exposure to endocrine-disrupting chemicals (EDCs) found in our environment can increase the risk of susceptibility to metabolic diseases, such as obesity and type 2 diabetes. Tobacco products harbor a cluster of harmful EDCs that are inhaled by smokers and dispersed through the air. Previous research showed that tobacco exposure during pregnancy can lead to developmental alterations that increase the risk of metabolic disease in the offspring later into adulthood. Although global tobacco use is higher among men than women, little is known about how paternal exposure to tobacco products contribute to metabolic disease in future unexposed generations. Paternal preconception exposure to environmental factors have been shown to lead to increased risk of disease in future offspring, though mechanisms of these heritable alterations remain unclear. Our research focuses on determining the mechanisms through which paternal preconception exposure to tobacco-related chemicals, such as nicotine, lead to metabolic disease, and the underlying mechanism of epigenetic inheritance of these metabolic traits. We hypothesize that paternal nicotine exposure elicits alterations in the paternal germline (i.e., sperm) that are transferred to the zygote upon fertilization leading to metabolic alterations in unexposed offspring. We found that paternal preconception exposure to nicotine leads to insulin resistance and increased plasma ghrelin levels in F1 females. In F1 males, we found different metabolic alterations in the form of altered fasting glucose levels and decreased plasma glucagon levels. Taken together, our current data suggest that paternal preconception nicotine exposure may alter ghrelin signaling pathways that lead to metabolic disruption in F1 females, as well as alter glycogen mobilization in F1 males. To determine the mechanism behind these heritable metabolic alterations observed in paternal nicotine-exposed offspring, we will investigate small non-coding RNA populations in the sperm of nicotine-treated sires. We will characterize heritable alterations during early embryogenesis by whole genome transcriptomics. These approaches will identify the mechanisms behind heritable metabolic alterations observed in offspring paternally-exposed to nicotine, as well as indicate what specific transcripts are impacted during early embryogenesis that give rise to these phenotypes. This project will provide insights into the intergenerational metabolically disruptive effects of paternal tobacco use and the mechanism of inheritance that drives these phenotypes, ultimately providing more evidence to change tobacco policies and legislation.

Presentation: Saturday, June 17, 2023
SAT639 Electronic Cigarettes-exposed Mice Have Impairments In Skeletal Muscle Mediated By Impaired Ampk Activation
Authors: Rivera Juan Carlos , Espinoza-Derout Jorge , Hasan Kamrul M , Lao Candice , Wilson Julian Bryant , Shao Xuesi M , Tintut Yin , Jordan Maria , Roos Kenneth P , Sinha-Hikim Amiya P , Friedman Theodore C
Published: October 2023

Disclosure: J. Rivera: None. J. Espinoza-Derout: None. K.M. Hasan: None. C. Lao: None. J.B. Wilson: None. X.M. Shao: None. Y. Tintut: None. M. Jordan: None. K.P. Roos: None. A.P. Sinha-Hikim: None. T.C. Friedman: None.

Electronic cigarettes (E-Cig) are a relatively new way to deliver nicotine (Nic). E-Cigs are gaining popularity, especially among youth and young adults, who do not realize their harmful health effects. Our laboratory has been a pioneer in demonstrating the adverse effects of E-Cigs on the liver and the heart. Skeletal muscle is a bigger tissue with physical and metabolic importance fundamental for human health. We previously reported that IP injection of Nic with a “second-hit” such as a high-fat diet (HFD) caused skeletal muscle damage. This study evaluated the detrimental effects of E-Cigs administration on skeletal muscle. We used an E-Cig inhalation model to deliver Nic in a similar way to humans. C57BL6 mice were fed with an HFD, divided into three groups, and exposed to a saline solution (control group), commercially available E-Cig (bluCig) in absence of Nic (E-Cig 0%), or E-Cig with the presence of Nic (E-Cig 2.4%) for 12 weeks. Results showed that the skeletal muscle exposed to E-Cig 2.4% had a reduction of the phosphorylation of the metabolic regulator, AMPK, and the pro-lipolytic enzyme ATGL as measured by western blot analyses in relation to control saline and E-Cig 0% groups. This metabolic impairment was accompanied by a reduction of the homeostatic mechanism, autophagy by a decrease of the ratio LC3II/LC3I, in the group exposed to E-Cig 2.4% in relation to the saline group. Electron microscopy showed intramyofibrillar mitochondrial with cristolysis, vacuolization, and intramyocellular lipid deposits in the E-Cig 2.4% group. Additionally, we observed an increase in oxidative stress suggested by the increase of the antioxidant enzyme HO-1 in the E-Cig 2.4%, and the reduction of the protein levels of SOD1 and SOD2. Finally, the previous changes trigger the activation of cellular stress pathways such as the phosphorylation of p38 and the increase in inflammasome protein, Nrlp3 in the E-Cig 2.4% compared to the saline group. This study suggests skeletal muscle abnormalities in mice vaping E-Cig 2.4% can alter muscle health. We believe these abnormalities will have important consequences in the skeletal muscle considering the early life stage of the consumers.

Presentation: Saturday, June 17, 2023