bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Visceral Adipose Tissue (VAT) Inflammation Is Not Associated With Perforin Deficiency in Type 2 Diabetes Mellitus (DM) Subjects as Compared to Health Controls
Authors: Shukla Ravindra Kumar , Choudhary Ramkaran , Lodha Mahendra , Rodha Mahaveer singh , Bajpai Nitin , Purohit Purvi , Sharma Praveen , Garg M K 
Published: May 2021

Abstract
Introduction: Role of T cells in VAT inflammation is poorly characterised. Perforin deficiency is associated with autoimmune inflammatory diseases like Hemophagocytosis Lymphohistiocytosis,as also in context of type 1 DM pathogenesis. Data from animal models suggest that perforin deficiency leads to VAT inflammation1Objective: We hypothesized CD8+/perf+ and CD56+/perf+ cells to be decreased in type 2 DM as compared to healthy controls. The present study also explored the difference in activation of T/NK cells between two groups Methods: 2×2 cm omental tissue was obtained from subjects undergoing elective abdominal surgery. The sample was transported in RPMI solution and stored in -80 ℃. Processing involved thawing, incubation at 37.6 ℃ for 24 hours with type IV Collagenase (1 mg/ml, Sigma Aldrich) 1ml/g of tissue,centrifuge (32g for 10 min at 10℃). The resultant Stromal Vascular fraction (SVF) was suspended in phosphate buffer saline (PBS), passed through cell strainer to make single cell suspension. It was again centrifuged and tagged with CD markers of interest. Fc block was added and single cell solution with FACS fluid prepared. It was run in BD CANTO-2 flow cytometer as described2Results: Of seventeen samples analysed, twelve samples of type 2 diabetes subjects were compared with five healthy controls. All results are presented in median. The diabetics had higher HbA1c (8.1 % vs 6%), higher BMI (28 kg/m2 vs 24 kg/m2), hsCRP(2.1 mg/dl Vs 0.9 mg/dl) but there was no difference in HOMA-Ir (5 vs 5.2 mU/L/mg/dl). The percentage of CD4+ + CD8+ cells/g of VAT was similar in both cases and control (20 × 103 Vs 23× 103). CD8+/CD45+/perf+ and CD56+/CD45+/perf+ could not be identified in any of the samples. Although CD8+/CD45+/perf-- and CD56+/CD45+/perf-- cells were identified. Next, we analysed the same cells for cytotoxic activation by 107a. The percentage of 107a positivity was low in CD 8+ (7% and 4 % respectively in cases and control) and CD 56+ cells (10% and 9 % respectively in cases and control),Although clinically type 2 DM subjects were obese and had inflammation (i.e higher hsCRP), there was no difference in VAT activation of immune cells studied. Also, we could not delineate perforin in any of the samples. Conclusion: Taken together this work suggests VAT T cell immune milieu in human Type 2 DM is different from mouse model. It is neither characterised by perforin deficiency nor activation of T cell/NK cell. This study points towards the probability that, the role of T cell/NK cells in human VAT infiltration could be fundamentally different from mice models. Further studies should be focussed on functional characteristics of these cells and interaction with VAT macrophages. References 1. Xavier S. Revelo et al Diabetes 2015;64:90–103 2. Wetzels S et al J Vis Exp. 2018 Mar 6;(133):57319.
Is Insulin Resistance at Baseline a Predictor of Weight Loss After Bariatric Surgery?
Authors: Borges-Canha Marta , Neves João Sérgio , Mendonça Fernando , Silva Maria Manuel , Costa Cláudia , Cabral Pedro , Guerreiro Vanessa , Lourenço Rita , Meira Patrícia , Salazar Cristina Daniela , Ferreira Maria João , Pedro Jorge , Sande Ana , Belo Sandra , Souto Selma S B , Lau Eva , Freitas Paula , Carvalho Davide 
Published: May 2021

Abstract
Background: Obesity is a multifactorial disease that is strongly associated to other metabolic disorders, such as insulin resistance and type 2 diabetes. Bariatric surgery is nowadays considered the most effective treatment of morbid obesity. The role of insulin resistance (IR) in weight loss after bariatric surgery is highly unknown.
Aim: To evaluate the association between Insulin Resistance (IR) and percentage of excess weight loss (EWL%) one, two, three and four years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our centre between January 2010 and July 2018 were included. Patients were excluded if they had diabetes. We evaluated baseline Homeostatic Model Assessment of IR (HOMA-IR), Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index (QUICKI) and Matsuda and DeFronzo index, and performed a linear regression concerning each year’s EWL%.
Results: After applying the exclusion criteria, 1723 patients were included in this analysis. The logarithm of HOMA-beta was negatively associated with EWL% at second-, third- and fourth-years post-surgery (β=-1.04 [-1.82 to -0.26], p&lt;0.01; β=-1.16 [-2.13 to -0.19], p=0.02; β=-1.29 [-2.64 to 0.06], p=0.061, respectively), adjusting for age, sex, body mass index and type of surgery. This was not observed in the first-year post-surgery nor for the other indexes. Glycaemia at baseline was also positively associated to EWL% at second- and third-years post-surgery.
Conclusion: IR at baseline seems to be associated to long term weight loss, explicitly after the first year post bariatric surgery.
Low Health Literate State Does Not Negatively Affect Final Weight Loss After a Laparoscopic Gastric Bypass Procedure
Authors: Twickler Theodorus Bartholomeus , Marije Dubbelman , Feskens Pierre , van den Broek Jos 
Published: May 2021

Abstract
Weight loss surgery is an effective treatment in patients with morbid obesity, but its benefit depends on self-care management afterwards Self-care management is partly influenced by individual’s health literacy. The level of individual’s health literate state (HLS) could determine the person’s health behavior with a subsequent effect on final weight loss We therefore hypothesized that a low HLS may result in a worse post-bariatric surgery outcome (final weight loss) compared to them with a high HLS. A retrospective study was performed including 78 patients (male vs female: 23% vs 77%, respectively; mean age 43 years (SD 12)) who underwent a laparoscopic gastric bypass (LGB) procedure. All patients were invited to perform in a review in which HLS was estimated using Rapid Estimate of Adult Literacy in Medicine- Dutch (REALM-D) and Newest Vital Sign- Dutch (NVS-D) questionnaires. Anthropometric information, such as weight at 0, 3, 6 9 and 12 months after surgery, was collected. Mean preoperative weight was 128.0 kg (SD 21.1) and patients had an average weight loss of 42.2 kg (SD 12.0) after 12 months. Almost half of the population (49%) was low educated, 38% had medium education and 13% was high educated. Of all patients, 22% had an inadequate HLS, according to the REALM-D. Following the NVS-D, 14% was characterized with an inadequate HLS. Patients with an inadequate HLS had an average weight loss of 40.2 kg (SD 13.8) or 31.5% (SD 8.1), while patients with an adequate HLS had an average weight loss of 42.8 kg (SD 11.4 or 33.3 % (SD 6.6). Following the NVS-D, preoperative weight was 123.6 (SD 20.5) for patients with an inadequate HLS and 128.7 (SD 21.1) for patients with an adequate HLS. Patients with an inadequate HLS had an average weight loss of 39.8 kg (SD 14.2) or 31.5% (SD 8.5), patients with an adequate HLS had an average weight loss of 42.6 kg (SD 11.6) or 33.1 % (SD 6.7). This reduce after 12 months did not significantly differ between patients with an inadequate and adequate HLS according to the REALM-D (B = - 1.806, P = 0.350) and NVS-D (B= -0.357, P = 0.885) after correction for age, gender and preoperative weightWeight reduction did not significantly differ between patients with inadequate or adequate health literacy levels, one year after LGB.
Prevalence of Childhood Obesity in the United States 1999 - 2018: A 20-Year Analysis
Authors: Li Hang Long , Tsoi Man Fung , Feng Qi , Cheung Ching-Lung , Cheung Tommy , Cheung Bernard M Y 
Published: May 2021

Abstract
Introduction: Obesity is a public health crisis in the US. Childhood obesity is associated with multiple comorbidities in the adulthood, including metabolic syndrome, cardiovascular diseases, and premature death. A recent study found that the prevalence of childhood obesity varied according to age and ethnicity. This study aims to evaluate the long-term trends and the underexplored socioeconomic factors associated with childhood obesity.
Method: From the US National Health and Nutrition Examination Survey from 1999 to 2018, 35 907 children aged 2–19 with body mass index (BMI) data were included. Prevalence of obesity and severe obesity, defined as BMI ≥95th percentile and ≥120% of 95th percentile of US Centers for Disease Control and Prevention growth charts, respectively. Trends in prevalence of obesity and subgroup analyses according to age group, sex, ethnicity, language used in interview, household education level, and household income level, were analyzed. Data analysis was performed using the R statistical package “survey” (version 3.6.3).
Results: The prevalence of obesity and severe obesity increased from 14.7 [95% CI: 12.9–17.0] % to 19.2 [17.2–21.0] % and 3.9 [2.9–5.0] % to 6.1 [4.8–8.0] % in 1999–2018, respectively (p=0.001 and p=0.014 for obesity and severe obesity, respectively). In 2017–8, the prevalence of obesity among children from Spanish-speaking households was 24.4 [22.4–27.0] %, higher than children from English-speaking households (p=0.027). Children from households with high education level and high income level had a lower prevalence of obesity compared to those with low education level and low income level (p=0.003 and p=0.002 for education level and income level, respectively). Compared to girls, boys had higher prevalence of obesity (p=0.002) and severe obesity (p=0.004).
Conclusion: The prevalence of childhood obesity in America kept increasing during the period 1999–2018 despite various public health initiatives. The problem is worse in children with lower socioeconomic status, and in children from Spanish-speaking households. Public health interventions are urgently needed to halt the rising trend of childhood obesity, and measures specifically catering to children from Spanish-speaking families should be put in place.
The Absence of Cortisol Awakening Response Is Associated With Personality Traits in Bariatric Women
Authors: Ostinelli Giada , Pelletier Melissa , Iceta Sylvain , Michaud Andreanne , Begin Catherine , Tchernof Andre 
Published: May 2021

Abstract
Background: There is a large body of evidence linking obesity to the HPA axis and cortisol secretion or metabolism. Early work hypothesized that obesity onset may be associated with over-activation of the HPA axis, causing an extenuation of the system. The cortisol awakening response (CAR) has been suggested to be a reliable marker of HPA axis activity and has already been examined in samples of individuals with obesity. Our objective was to compare individuals showing a morning cortisol peak (CAR responders) from those who did not (non-responders) and identify possible metabolic or psychological differences among these two groups. Our hypothesis was that the two groups differed in the level of anxiety and aspects of their personality rather than in their metabolic profile. Methods: CAR response was determined using a baseline to peak cut-off of 2.5 nM. Nine CAR non-responder women awaiting bariatric surgery (BMI: 50.8 ± 4.6 kg/m2) were compared to 9 sex- and age-matched CAR responders (BMI: 48.1 ± 5.9 kg/m2). Participants collected salivary cortisol upon awakening as well as 15, 30 minutes after and responded to psychological questionnaires that measured anxiety (State and trait anxiety inventory questionnaire) and personality traits (Temperament and character inventory). Results: Non-responders were all non-diabetic women aged 37 ± 8 years. There was no significant difference between CAR responders and non-responders in terms of BMI or waist circumference. No difference was found in metabolic variables such as glycaemia or the lipid profile. As expected, non-responders had a significantly lower CAR AUCi when compared to responders (p&lt;0.001). However there was no difference in awakening cortisol concentration. Despite our hypothesis, no significant difference was found in general level of anxiety between the two groups. Finally, we analyzed aspects of human personality. We found that CAR responders scored significantly higher in character traits such as self-directedness (p=0.02), cooperativeness (p=0.03) and self-transcendence (p&lt;0.01). Conclusion: The CAR differences in women with severe obesity are not associated with adiposity. Our data show that non-responders exhibit traits related to reduced self-determination and responsibility but also lower level of self-consciousness and helpfulness, which could be associated with a reduction in patient compliance and possibly less weight loss after surgery.
Trends in the Racial and Ethnic Disparity and Predictors of Hepatic Steatosis: Data From NHANES III and NHANES 2017–2018
Authors: Shaheen Magda , Pan Deyu , Schrode Katrina , Kermah Dulcie , Najjar Sonia Michael , Friedman Theodore C 
Published: May 2021

Abstract
Hepatic steatosis is a serious problem worldwide and it affects Hispanics at a higher rate than Blacks. This disparity is an important public health problem. The purpose of this study was to examine the trend in the racial/ethnic disparity of hepatic steatosis among a representative sample of the U.S. adult ≥20 years old in two time-periods. Data from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 2017–2018 were analyzed. The sample size in the two respective cycles was 13,910 and 5,492 respectively. Hepatic steatosis in NHANES III was diagnosed using ultrasound while in NHANES 2017–2018, fibroscan was used. We analyzed the data using bivariate Chi square, and multiple logistic regression to adjusting for confounding variables and considering the design and sample weights. In both time-periods, Mexican American had the highest prevalence of hepatic steatosis (28% in NHANES III and 43% in NHANES 2017–2018) compared to the other racial/ethnic groups (p&lt;0.05). In the adjusted logistic regression model, relative to the white population, Mexican-Americans had 40% higher odds of hepatic steatosis in NHANES III (adjusted odds ratio [AOR]=1.4, 95% confidence level [CL]=1.1–1.9, p&lt;0.05) and 200% higher odds of hepatic steatosis in NHANES 2017–2018 (AOR=2.0, 95% CL=1.3–3.1, p&lt;0.05). The common predictors of hepatic steatosis in the two time periods were gender, high waist-to-hip ratio, borderline and high levels of triglyceride, and prediabetes and diabetes as diagnosed by HbA1c (p&lt;0.05). For CRP, independent of the method used, mild and significant inflammation were predictors of hepatic steatosis (p&lt;0.05). In NHANES 2017–2018, participants ≥ 65 years (compared to 20–34 years of age) and Blacks (relative to Whites) had a lower chance of hepatic steatosis in the adjusted regression model (p&lt;0.05), and those inactive (relative to those who met the physical activity guideline) had a higher chance of hepatic steatosis (p&lt;0.05). The increased prevalence of hepatic steatosis in 2017–2018 compared to 1988–1994, may be related to the obesity epidemic, although differences in methodological factors may also play a role. Our study indicated that the racial/ethnic disparity in hepatic steatosis especially among Mexican American persisted over time. Future work is needed to explore the persistence of the racial/ethnic disparity of hepatic steatosis and its underlying mechanisms.
Acquired Brain Injury-Induced Hyperphagia and Obesity, Successfully Treated With a GLP-1 Agonist
Authors: Ngu Michael , Blocher Nissa , Segal Miriam 
Published: May 2021

Abstract
Background: Several Glucagon-like peptides 1 (GLP-1s) were approved since 2005 for the treatment of DM & obesity. Their usefulness in other conditions is not well studied. We present two cases of hyperphagia after TBI successfully treated with GLP-1 agonists. Clinical cases: Case 1: A 54-year-old female with a history of multiple traumatic brain injuries (multiple falls and a ski accident) complained of years of insatiable hunger leading to hyperphagia and over 20 pounds weight gain. With tremendous will-power, she avoided additional weight gain by adopting a strict meal-plan and increasing her water intake (10–12 liters a day) to relieve her hunger. She sipped so much water, that her sodium remained 123 - 133 mmol/L (ref: 135–146) with dilute urine. Initial tests revealed: IGF-1 315 ng/ml (52–328), FSH 77.5 mIU/ml (23–116.3), LH 24.3 mIU/ml (14.2–52.3), prolactin 17.1 ng.ml (10–54.7), estradiol 17 (&lt;31), TSH 1.09mIU/ml (0.45–4.5), FT4 1.0 ng/dl(0.8–1.8), all within the normal limit for her age. Semaglutide 0.25mg/week was started and increased to 0.5mg/week. Within the first six months of treatment, she experienced 22 pounds of weight loss, hunger relief, less water sipping behavior, and more enjoyment of food. Her sodium rose to 137 mmol/L. Case 2: A 40-year-old female, s/p craniectomy and aneurysm clipping due to intracranial hemorrhage complicated by an ischemic stroke developed sudden, documented, 45-pound weight gain over thirteen months despite aggressive lifestyle modification attempts. Initial labs revealed: TSH 1.33 mIU/ml (0.45–4.5), FT4 1.22 ng/dl (0.8–1.8), midnight salivary cortisol 0.03 mcg/dl (&lt;0.09), ruling out hypothyroidism and Cushing syndrome. Liraglutide 1.8mg/day was started and has resulted to date in 26 pounds (11.8% of maximum weight) by 9 months with an associated decrease in subjective hunger. Conclusion: Hyperphagia can be seen in brain injury, in response to some medications, and some genetic conditions, like Prader-Willi. The exact mechanisms are not clear am may be multifactorial. In the case of brain injury, proposed mechanisms include insatiable hunger due to ventromedial hypothalamic or brain stem dysfunction, or disinhibition and poor impulse control due to frontal lobe injury. GLP-1’s may act on the causal mechanism for increased hunger, or it may result in clinical improvement through a parallel pathway. More studies are warranted to investigate the application of GLP-1’s to hyperphagia.
Association of NOS3 and TNF Genetic Polymorphisms With the Predisposition to Elevated Cholesterol, Retrospective Study
Authors: Ayesh Hazem , Ayesh Sajida S , Beran Azizullah , Ayesh Suhail 
Published: May 2021

Abstract
Background: Endothelial nitric oxide synthetase (eNOS) encoded by NOS3 gene has an important role in modulating vascular endothelial function. TNFα gene is responsible for coding TNFα protein that plays a significant role in regulating body inflammation and lipid metabolism. Many studies reported an association between NOS3 and TNFα genetic polymorphisms and elevated total cholesterol (TC) level, low-density lipoprotein (LDL), triglyceride (TG). In this study, we investigated the association of NOS3 (G&gt;T) rs1799983 and TNFα -308G&gt;A rs1800629 genetic polymorphisms with TC level.
Methods: A random sample of 250 subjects with an elevated TC level (defined by TC level ≥ 200mg/dL) compared with 500 healthy subjects. Sample obtained from Palestinian adults who consented to genetic and biochemical testing. Subjects genotyped for NOS3 SNP (G &gt; T) rs1799983 and TNFα -308G&gt;A rs1800629 using ARMS PCR. TC level was obtained for all subjects. Logistic regression analysis adjusted for age and body mass index (BMI) was performed to test for association between NOS3 and TNFα genetic polymorphisms and TC level.
Results: NOS3 T allele was significantly more frequent in the elevated TC group, (odds ratio = 1.8, 95% CI =1.02–3.18) with likelihood ratio statistically significant (P = 0.004). Homozygous TNFα variant was more frequent in the elevated cholesterol group without a statistically significant association (P = 0.54).
Discussion: Many studies reported an association between NOS3 and TNFα genetic polymorphisms and elevated TC levels. Homozygous NOS3 variant was associated with a 1.8-fold increase in the risk of high TC after adjustment for age and BMI. TNFα polymorphism didn’t show a statistically
significant association with having elevated TC levels. With the increasing popularity and availability of genetic testing, NOS3 can serve as a screening tool to identify people with high risk for elevated TC. Further studies are required to understand the exact role of NOS3 genetic polymorphism in cholesterol metabolism.
Conclusion: NOS3 genetic polymorphism had a statistically significant relationship with TC levels. These results support the association between NOS3 polymorphism and elevated TC.
Breast Cancer Endocrine Therapy Exhausts Adipocyte Progenitors Promoting Weight Gain and Glucose Intolerance
Authors: Wellberg Elizabeth A , Johnson-Murguia Stevi , MacLean Paul S , Johnson James D , Reusch Jane E B , Scalzo Rebecca L 
Published: May 2021

Abstract
Breast cancer survivors treated with anti-estrogen therapies report weight gain and have an elevated risk of type 2 diabetes. Here, we show that current tamoxifen use did not influence body mass index but associated with larger breast adipocyte diameter only in women with obesity, suggesting adipose tissue may be targeted by breast cancer therapies. To understand the mechanisms behind these clinical findings, we investigated the impact of estrogen deprivation and tamoxifen in a relevant pre-clinical murine model of obesity. Specifically, mature female mice were housed at thermoneutrality and fed either a low-fat/low-sucrose (LFLS) or a high-fat/high-sucrose (HFHS) diet. Consistent with the high expression of Esr1 observed in single-cell RNA sequencing of mesenchymal stem cells from mouse adipose tissue, endocrine therapies associated with adipose accumulation and preadipocyte expansion, but resulted in adipocyte progenitor depletion only in the context of HFHS. Consequently, 7-week endocrine therapy supported adipocyte hypertrophy and was associated with hepatic steatosis, hyperinsulinemia, insulin resistance, and glucose intolerance, particularly in HFHS fed females. We administered HFHS fed females either metformin or pioglitazone, glucose lowering drugs used to treat diabetes, or treadmill interval exercise during endocrine therapy with the goal of improving whole body metabolism. All interventions prevented the effects of tamoxifen but not estrogen deprivation on adipocyte size and insulin resistance in HFHS-fed mice. This translational study suggests that endocrine therapies may act via ER-alpha to directly disrupt adipocyte progenitors and support adipocyte hypertrophy, leading to ectopic lipid deposition that may promote hyperinsulinemia, insulin resistance and type 2 diabetes. Interventions that target insulin action should be considered for some women receiving life-saving endocrine therapies for breast cancer.