A hierarchical dynamic model used for investigating feed efficiency and its relationship with hepatic gene expression in APOE*3-Leiden.CETP mice

Background: Feed efficiency (FE) is an important trait for livestock and humans. While the livestock industry focuses on increasing FE, in the current obesogenic society it is more of interest to decrease FE. Hence, understanding mechanisms involved in the regulation of FE and particularly how it can be decreased would help tremendously in counteracting the obesity pandemic. However, it is difficult to accurately measure or calculate FE in humans. In this study, we aimed to address this challenge by developing a hierarchical dynamic model based on humanized mouse data. Methods: We analyzed existing experimental data derived from 105 APOE*3-Leiden.CETP (E3L.CETP) mice fed a high-fat high-cholesterol (HFHC) diet for 1 (N = 20), 2 (N = 19), 3 (N = 20), and 6 (N = 46) month. We developed an ordinary differential equation (ODE) based model to estimate the FE based on the longitudinal data of body weight and food intake. Since the liver plays an important role in maintaining metabolic homeostasis, we evaluated associations between FE and hepatic gene expression levels. Depending on the feeding duration, we observed different relationships between FE and hepatic gene expression levels. Results: After 1-month feeding of HFHC diet, we observed that FE was associated with vitamin A metabolism, arachidonic acid metabolism, and the PPAR signaling pathway. After 3- and 6-month feeding of HFHC diet, we observed that FE was associated most strongly with expression levels of Spink1 and H19, genes involved in cell proliferation and glucose metabolism, respectively. Conclusions: In conclusion, our analysis suggests that various biological processes such as vitamin A metabolism, hepatic response to inflammation, and cell proliferation associate with FE at different stages of diet-induced obesity.</p

On the Coexistence of Diagonal and off-Diagonal Long-Range Order, a Monte Carlo Study

The zero temperature properties of interacting 2 dimensional lattice bosons are investigated. We present Monte Carlo data for soft-core bosons that demonstrate the existence of a phase in which crystalline long-range order and off-diagonal long-range order (superfluidity) coexist. We comment on the difference between hard and soft-core bosons and compare our data to mean-field results that predict a larger coexistence region. Furthermore, we determine the critical exponents for the various phase transitions.Comment: 7 pages and 8 figures appended in postscript, KA-TFP-93-0

Human intestinal microbiota composition is associated with local and systemic inflammation in obesity.

OBJECTIVE: Intestinal microbiota have been suggested to contribute to development of obesity, but the mechanism remains elusive. We relationship between microbiota composition, intestinal permeability, inflammation in non-obese and obese subjects. DESIGN AND METHODS: Fecal microbiota composition of 28 subjects (BMI 18.6-60.3kg/m2 ) was analyzed phylogenetic profiling microarray. Fecal calprotectin and plasma C- protein levels were determined to evaluate intestinal and systemic Furthermore, HbA1c , and plasma levels of transaminases and lipids were Gastroduodenal, small intestinal, and colonic permeability were assessed multi-saccharide test. RESULTS: Based on microbiota composition, the population segregated into two clusters with predominantly obese (15/19) exclusively non-obese (9/9) subjects. Whereas intestinal permeability differ between clusters, the obese cluster showed reduced bacterial decreased Bacteroidetes/Firmicutes ratio, and an increased abundance of pro-inflammatory Proteobacteria. Interestingly, fecal calprotectin was detectable in subjects within the obese microbiota cluster (n=8/19, Plasma C-reactive protein was also increased in these subjects correlated with the Bacteroidetes/Firmicutes ratio (rs =-0.41, p=0.03). CONCLUSIONS: Intestinal microbiota alterations in obese subjects are with local and systemic inflammation, suggesting that the obesity- microbiota composition has a pro-inflammatory effect

Distribution of Brown Adipose Tissue Radiodensity in Young Adults: Implications for Cold [18F]FDG-PET/CT Analyses

Procedures: We measured 125 individuals after a personalized cooling protocol with a static [18F]FDG-PET/CT scan. We quantified BAT using different combination of threshold in every single HU for all participants. Results: We observed that the SUV threshold influences BAT quantification by [18F]FDG-PET/ CT scans more than the HU range. We found that the range from − 50 to − 10 HU had the highest proportion of total BAT volume (43.2 %), which represents 41.4 % of the total BAT metabolic activity in our cohort. We also observed that BAT volume was not different between categories of body mass index, as well as BAT activity (SUVmean). In addition, BAT was less dense in women than in men, although the BAT activity (SUVmean) was higher in all ranges of HU. We also observed that the radiodensity of BAT located in the cervical area was mainly in the range from − 50 to − 10 HU. Conclusion: Therefore, all future human studies using static [18F]FDG-PET/CT scans should include BAT in the radiodensity range from − 50 to − 10 HU.This study was supported by the Spanish Ministry of Economy and Competitiveness, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393) and Retos de la Sociedad (DEP2016-79512-R), Fondos Estructurales de la Unión Europea (FEDER), by the Spanish Ministry of Education (FPU 13/04365), by the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016 - Excellence actions: Unit of Excellence on Exercise and Health (UCEES) - and Plan Propio de Investigación 2018 - Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (FEDER, ref. SOMM17/6107/UGR)

Hydrocortisone-associated death and hospital length of stay in patients with sepsis:A retrospective cohort of large-scale clinical care data

PURPOSE: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in the prevention of death in septic patients. Here we evaluated the association between hydrocortisone treatment and mortality in patients diagnosed with sepsis in a large-scale clinical dataset.METHODS: Data from patients between 2008 and 2019 were extracted from the retrospective Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients who received hydrocortisone after diagnosis were matched using propensity-score matching with patients who did not, to balance confounding (by indication and contraindication) factors between the groups. 90-day mortality and survivors' length of hospital stay was compared between patients who did or did not receive hydrocortisone.RESULTS: A total of 31,749 septic patients were included in the study (mean age: 67, men: 57.3%, in-hospital mortality: 15.6%). 90-day mortality was higher among the 1802 patients receiving hydrocortisone when compared with the 6348 matched non-users (hazard ratio: 1.35, 95% CI: 1.24-1.47). Hydrocortisone treatment was also associated with increased in-hospital mortality (40.9% vs. 27.6%, p &lt; 0.0001) and prolonged hospital stay in those who survived until discharge (median 12.6 days vs. 10.8 days, p &lt; 0.0001). Stratification for age, gender, ethnicity, occurrence of septic shock, and the need for vasopressor drug administration such as (nor)epinephrine did not reveal sub-population(s) benefiting of hydrocortisone use.CONCLUSION: Hydrocortisone treatment is associated with increased risk of death as well as prolonged hospital stay in septic patients. Although residual confounding (by indication) cannot be ruled out completely due to the observational nature of the study, the present study suggests clinical implication of hydrocortisone use in patients with sepsis.</p

Hydrocortisone-associated death and hospital length of stay in patients with sepsis:A retrospective cohort of large-scale clinical care data

PURPOSE: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in the prevention of death in septic patients. Here we evaluated the association between hydrocortisone treatment and mortality in patients diagnosed with sepsis in a large-scale clinical dataset.METHODS: Data from patients between 2008 and 2019 were extracted from the retrospective Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients who received hydrocortisone after diagnosis were matched using propensity-score matching with patients who did not, to balance confounding (by indication and contraindication) factors between the groups. 90-day mortality and survivors' length of hospital stay was compared between patients who did or did not receive hydrocortisone.RESULTS: A total of 31,749 septic patients were included in the study (mean age: 67, men: 57.3%, in-hospital mortality: 15.6%). 90-day mortality was higher among the 1802 patients receiving hydrocortisone when compared with the 6348 matched non-users (hazard ratio: 1.35, 95% CI: 1.24-1.47). Hydrocortisone treatment was also associated with increased in-hospital mortality (40.9% vs. 27.6%, p &lt; 0.0001) and prolonged hospital stay in those who survived until discharge (median 12.6 days vs. 10.8 days, p &lt; 0.0001). Stratification for age, gender, ethnicity, occurrence of septic shock, and the need for vasopressor drug administration such as (nor)epinephrine did not reveal sub-population(s) benefiting of hydrocortisone use.CONCLUSION: Hydrocortisone treatment is associated with increased risk of death as well as prolonged hospital stay in septic patients. Although residual confounding (by indication) cannot be ruled out completely due to the observational nature of the study, the present study suggests clinical implication of hydrocortisone use in patients with sepsis.</p

Hydrocortisone-associated death and hospital length of stay in patients with sepsis:A retrospective cohort of large-scale clinical care data

PURPOSE: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in the prevention of death in septic patients. Here we evaluated the association between hydrocortisone treatment and mortality in patients diagnosed with sepsis in a large-scale clinical dataset.METHODS: Data from patients between 2008 and 2019 were extracted from the retrospective Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients who received hydrocortisone after diagnosis were matched using propensity-score matching with patients who did not, to balance confounding (by indication and contraindication) factors between the groups. 90-day mortality and survivors' length of hospital stay was compared between patients who did or did not receive hydrocortisone.RESULTS: A total of 31,749 septic patients were included in the study (mean age: 67, men: 57.3%, in-hospital mortality: 15.6%). 90-day mortality was higher among the 1802 patients receiving hydrocortisone when compared with the 6348 matched non-users (hazard ratio: 1.35, 95% CI: 1.24-1.47). Hydrocortisone treatment was also associated with increased in-hospital mortality (40.9% vs. 27.6%, p &lt; 0.0001) and prolonged hospital stay in those who survived until discharge (median 12.6 days vs. 10.8 days, p &lt; 0.0001). Stratification for age, gender, ethnicity, occurrence of septic shock, and the need for vasopressor drug administration such as (nor)epinephrine did not reveal sub-population(s) benefiting of hydrocortisone use.CONCLUSION: Hydrocortisone treatment is associated with increased risk of death as well as prolonged hospital stay in septic patients. Although residual confounding (by indication) cannot be ruled out completely due to the observational nature of the study, the present study suggests clinical implication of hydrocortisone use in patients with sepsis.</p