Goodelarsson8391

BACKGROUND Gestational diabetes mellitus (GDM) is a common condition, often associated with high maternal and fetal morbidity. The use of new tools for early GDM screening can contribute to metabolic control to reduce maternal and fetal risk. This study aimed to ascertain whether maternal visceral adipose tissue (VAT) measurement by ultrasound during the first half of pregnancy can predict the occurrence of GDM during the third trimester. METHODS A prospective cohort study of 133 pregnant women with gestational age ≤20 weeks in an outpatient setting. VAT depth was measured by ultrasound at the maternal periumbilical region. GDM status was obtained through hospital charts during hospitalization to delivery. A Receiver Operator Characteristic (ROC) curve was used to determine the optimum threshold to predict GDM. RESULTS According to the ROC curve, a 45mm threshold was identified as the best cut-off value, with 66% of accuracy to predict GDM. Crude and adjusted odds ratios (OR) for GDM were 13.4 (95%CI 2.9-61.1) and 8.9 (95%CI 1.9-42.2), respectively. A similar result was obtained among pre-gravid non-obese women, with crude and adjusted OR of 16.6 (95%CI 1.9-142.6) and 14.4 (95%CI 1.7-125.7), respectively. Among pre-gravid obese patients, a 45mm threshold did not reach statistical significance to predict GDM. CONCLUSION The high and significant OR found before and after adjustments provides additional evidence of a strong association between VAT and GDM. It appears that VAT measurement during the first half of pregnancy has great potential in identifying non-obese women at high risk for GDM. This evidence can assist obstetricians in correctly allocating resources among populations of pregnant women at risk, determined not only by pre-gravid body mass index (BMI).Inactivation of the tumor suppressor p53 resulting from the binding with a negative regulator HDM2 is among the predominant defects in human cancers. p53-mimicking peptides whose conformational and proteolytic stability is enhanced by an all-hydrocarbon staple are being recognized as promising anticancer agents for disrupting the p53-HDM2 binding and reactivating p53. Herein, we conduct a computational modeling and thermodynamic characterization of stapled p53/HDM2 complex via molecular docking, simulations, and binding free energy analysis. The binding thermodynamics analysis is done based on the end-point calculation of the effective binding energy-a sum of the direct peptide-protein interaction energy and the dehydration penalty-and on its decomposition into contributions from specific groups constituting the complex. This allows us to investigate how individual amino acids in the stapled p53 and HDM2 contribute to the binding affinity. We find that not only the epitope residues (F19, W23 and L26), but also the hydrocarbon linker of the stapled p53 impart significant contributions. Our computational approach will be useful in designing new stapled peptides in which the staple location is also optimized to improve the binding affinity.One of the defining characteristics of the B cell receptor (BCR) is the extensive diversity in the repertoire of immunoglobulin genes that make up the BCR, resulting in broad range of specificity. Gammaherpesviruses are B lymphotropic viruses that establish life-long infection in B cells, and although the B cell receptor plays a central role in B cell biology, very little is known about the immunoglobulin repertoire of gammaherpesvirus infected cells. To begin to characterize the Ig genes expressed by murine gammaherpesvirus 68 (MHV68) infected cells, we utilized single cell sorting to sequence and clone the Ig variable regions of infected germinal center (GC) B cells and plasma cells. We show that MHV68 infection is biased towards cells that express the Igλ light chain along with a single heavy chain variable gene, IGHV10-1*01. This population arises through clonal expansion but is not viral antigen specific. Furthermore, we show that class-switching in MHV68 infected cells differs from that of uninfected cells. Fewer infected GC B cells are class-switched compared to uninfected GC B cells, while more infected plasma cells are class-switched compared to uninfected plasma cells. Additionally, although they are germinal center derived, the majority of class switched plasma cells display no somatic hypermutation regardless of infection status. Taken together, these data indicate that selection of infected B cells with a specific BCR, as well as virus mediated manipulation of class switching and somatic hypermutation, are critical aspects in establishing life-long gammaherpesvirus infection.This study was conducted to explore specific chill models and the mechanisms underlying rhizome bud dormancy break in Polygonatum kingianum. Rhizome buds were subjected to various chilling temperatures for different duration and then transferred to warm conditions for germination and subsequent evaluation of their response to temperature and chilling requirements. A CUkingianum model was constructed to describe the contribution of low temperature to the chill unit, and it was suggested that 2.97°C was the optimum temperature and that 11.54°C was the upper limit for bud release. The CASkingianum model showed the relationship between chilling accumulation and sprouting percentage; therefore, rhizome bud development could be predicted through the model. Weighted correlation network analysis (WGCNA) of transcriptomic data of endo-, eco- and nondormant rhizome buds generated 33 gene modules, 6 of which were significantly related to bud sprouting percentage. In addition, 7 significantly matched transcription factors (TFs) were identified from the promoters of 17 "real" hub genes, and DAG2 was the best matched TF that bound to AAAG element to regulate gene expression. The current study is valuable for developing a highly efficient strategy for seedling cultivation and provides strong candidates for key genes related to rhizome bud dormancy in P. kingianum.[This corrects the article DOI 10.1371/journal.pone.0225839.].The use of low doses of radium-224 (224Ra) chloride for the treatment of ankylosing spondylitis was stopped following the discovery that patients treated with it had a higher than control incidence of leukaemia and other cancers. This was so even though the treatment resulted in decreased pain and increased mobility-both of which are associated with decreased mortality. It was decided to re-analyze the epidemiological data looking at all causes of death. The risk of leukaemia, solid cancer, death from non-cancer causes and from all causes in a study populations of men that received either the typical dose of 5.6 to 11.1 MBq of 224Ra, any dose of 224Ra or no radium were compared using the Cox proportional hazard model. For patients that received the typical dose of 224Ra agreed with the excess cancer was similar to that reported in previous studies. In contrast, these patients were less likely to die from non-cancer diseases and from all causes of death than the control patients. No excess mortality was also found in the population of all males that received the radionuclide. It is concluded that 224Ra treatment administered at low doses to patients with ankylosing spondylitis did not impact mortality from all causes. The study demonstrates the need to consider all causes of death and longevity when assessing health impacts following irradiation.BACKGROUND While HIV infection is associated with increased cardiovascular risk, benefit from statin is not well established in HIV-infected adults. We assessed whether statins are associated with a decrease in carotid artery intima-media thickness (cIMT) progression and all-cause mortality in HIV-infected adults who are at elevated ASCVD risk and recommended for statins. METHODS Carotid IMT was measured at baseline and follow-up in 127 HIV-infected adults who meet ACC/AHA criteria to be on statins. Inverse probability of treatment weighting (IPTW) was used to address selection bias. Multivariable models were used to control for baseline characteristics. RESULTS 28 subjects (22%) were on statins and 99 subjects (78%) were not. Mean cIMT at baseline was 1.2 mm (SD = 0.34) in statin users and 1.1 mm (SD = 0.34) in non-users, and the multivariable adjusted difference was 0.05mm (95%CI -0.11, 0.21 p = 0.53). After 3.2 years of follow-up, average cIMT progression was similar in statin users and non-users (0.062mm/yr vs. 0.058 mm/yr) and the multivariable adjusted difference over the study period was 0.004 mm/yr (95% CI -0.018, 0.025, p = 0.74). All-cause mortality appeared higher in non-statin users compared with statin users, but the difference was not significant (adjusted HR = 0.74, 95%CI 0.17-3.29, p = 0.70). CONCLUSION In a HIV cohort who had elevated ASCVD risk and meet ACC/AHA criteria for statins, treatment with statins was not associated with a reduction in carotid atherosclerosis progression or total mortality. Future studies are needed to further explore the impact of statins on cardiovascular risk in the HIV-infected population.BACKGROUND Brachial-ankle pulse wave velocity (baPWV) is the simple, non-invasive, gold-standard method for assessing arterial stiffness. However, baPWV has been shown to be associated with renal dyfunction, with a few reports demonstrating an association between baPWV and postoperative acute kidney injury (AKI) among surgical patients. METHODS We retrospectively analyzed preoperative baPWV data that were prospectively collected from 164 patients who underwent off-pump coronary artery bypass grafting (CABG) between April 2013 and July 2019 (mean age 66.2 ± 10.3 years, 29.3% females). Primarily, baPWV was investigated as an independent predictor of postoperative AKI development; secondarily, the patients were divided into high and low PWV groups according to the optimal baPWV cut-off value. Postoperative complications, mortality, and mid-term survival were compared between the two groups. RESULTS AKI developed in 30 patients (18.3%). Univariate analysis showed that AKI was significantly associated with baPWV (20.2±7.3 vs. 16.2±2.8 m/s, p 75 years), hypertension, diabetes under insulin therapy, and EuroSCORE. Moreover, area under the curve (AUC) analysis indicated that PWV can predict AKI better than preoperative creatinine levels (AUC, 0.781 [95% confidence interval, 0.688-0.874] vs. find more 0.680 [0.568-0.792]). The group-dividing baPWV cut-off value for AKI was 19 m/s. There were no 30-day mortality. The in-hospital mortality rates in the high and the low PWV groups were 2.2% (n = 1) and 0.8% (n = 1), respectively (p = 0.484). Midterm survival rates were not different between the two groups, but the rate of composite neurologic complication composed of stroke and delirium, was higher, and rate of mechanical ventilatory support was longer, in the high PWV group. CONCLUSION Brachial-ankle pulse wave velocity was an independent predictor of postoperative AKI following off-pump CABG, and high baPWVs may affect the composite neurologic outcome and the duration of mechanical ventilatory support.BACKGROUND We aimed to determine the optimal approach with endoscopic biliary drainage (EBD) and corticosteroid (CS) for the treatment of IgG4-related sclerosing cholangitis (ISC). METHODS To evaluate the safety of EBD for treatment of biliary stricture caused by ISC, we assessed the risk of stent dislodgement and sought to determine the most appropriate time for stent removal. We also assessed the safety of treatment with CS alone for patients with obstructive jaundice, and the rate of and risk factors for biliary tract complications. RESULTS Sixty-nine patients with ISC treated with CS were enrolled. Twenty-eight patients (40.6%) were treated with EBD for biliary stricture before CS initiation. Intentional stent removal was performed in thirteen (46.4%) after confirming CS-induced improvement. Eleven of thirteen patients (84.6%) underwent stent removal within 1 month after CS initiation and all their stent removals were safely carried out without early (within two weeks) recurrence of obstructive jaundice. Ten of twenty-eight patients (35.