Partial replacement of dietary (n-6) fatty acids with medium-chain triglycerides decreases the incidence of spontaneous colitis in interleukin-10-deficient mice.
J Nutr. 2009 Mar;139(3):603-10. Epub 2009 Jan 6. PMID: 19126671
Josep Mañé, Elisabet Pedrosa, Violeta Lorén, Isabel Ojanguren, Lourdes Fluvià, Eduard Cabré, Gerhard Rogler, Miquel A Gassull
Enteral nutrition has a primary therapeutic effect in active Crohn's disease. It is unknown which nutrient(s) account for this action, but a role for both the amount and type of dietary fat has been postulated. Some clinical and experimental data suggest that medium-chain triglycerides (MCT) may reduce intestinal inflammation. We aimed to assess the effect of replacing part of the dietary fat with MCT on the incidence and severity of colitis in interleukin (IL)-10(-/-) mice under specific pathogen-free conditions. Twenty-four IL-10(-/-) 4-wk-old mice were randomized to receive a control diet based on sunflower oil [(n-6) fatty acids (FA)] and an experimental isocaloric, isonitrogenous diet with 50% sunflower and 50% coconut oil (MCT diet). When the mice were 12 wk old, they were killed and the colon was examined for the presence of colitis, lymphocyte subpopulations and apoptosis, ex vivo cytokine production in supernatant of colon explants, toll-like receptor (TLR)-2 and TLR-9 mRNA, and FA profile in colonic tissue homogenates. Colitis incidence was lower in the IL-10(-/-) mice fed the MCT diet (1/12) than in the mice fed the control diet (8/12; P = 0.03). The histological damage score was also lower in the former (P < 0.0005). Feeding the MCT diet resulted in fewer total and apoptotic intraepithelial CD3+ and lamina propria CD3+CD4+ lymphocytes, as well as downregulated production of IL-6 and interferon-gamma, and reduced TLR-9 mRNA. We conclude that partial replacement of dietary (n-6) FA with MCT decreases the incidence of colitis in a model of spontaneous intestinal inflammation and provide experimental arguments for a possible primary therapeutic effect of MCT in human Crohn's disease.
Article Published Date : Mar 01, 2009
Prognostic factors of prostate cancer mortality in a Finnish randomized screening trial.
Int J Urol. 2017 Dec 10;:
Authors: Neupane S, Steyerberg E, Raitanen J, Talala K, Pylväläinen J, Taari K, Tammela TL, Auvinen A
OBJECTIVES: To identify the prognostic factors of prostate cancer death among patients enrolled in a Finnish prostate cancer screening trial.
METHODS: Data on TNM stage, Gleason score, serum prostate-specific antigen at diagnosis, comorbidity and primary treatment were collected from medical records, as well as date and cause of death from Statistics Finland. Four prognostic risk groups were defined based on TNM stage, Gleason score and prostate-specific antigen at diagnosis. Hazard ratios and their 95% confidence intervals for prostate cancer death were calculated using Cox regression and competing-risk analysis with follow up from randomization. The differences in the effects of prognostic factors were assessed using interaction terms.
RESULTS: The 15-year survival was significantly lower among cases in the control arm compared with the screening arm (0.90 vs 0.92). However, the survival advantage was limited to screen-detected cases (0.94 vs 0.91 in cases detected outside screening). The prognostic risk group was the strongest factor predicting survival in the control arm, but weaker in screen-detected cases. Advanced disease was associated with substantially poorer outcome in cases detected outside screening than in screen-detected disease. Primary treatment had a similar effect in all groups. Comorbidity had a small prognostic effect in the control arm only.
CONCLUSIONS: Prognostic factors had a different effect on the outcome of cases detected through screening as those diagnosed otherwise. A high diagnostic prostate-specific antigen and advanced disease carried a poor prognosis, especially among the cases detected outside screening, even when lead-time was eliminated. This shows that the screening resulted in earlier treatment among the cases in the screening arm.
PMID: 29224236 [PubMed - as supplied by publisher]
DNA Methylation Analysis from Blood Spots: Increasing Yield and Quality for Genome-Wide and Locus-Specific Methylation Analysis.
Methods Mol Biol. 2018;1708:605-619
Authors: Ghantous A, Hernandez-Vargas H, Herceg Z
Blood represents an easily accessible human tissue for numerous research and clinical applications, including surrogate roles for biomarkers of other tissues. Dried blood spots (DBS) are space- and cost-efficient storage forms of blood while stably retaining many of its chemical constituents. Consequently, neonatal DBS are routinely collected in many countries, and their biobanks represent gold mines for research. However, the utility of DBS is restricted by the limited amount and quality of extractable biomolecules (including DNA), especially for genome-wide profiling. In particular, DNA methylome analysis in DBS has proven to be technically challenging, mainly due to the requirement for stringent preprocessing, such as bisulfite conversion. Moreover, DNA amplification, required to increase its yield, often leads to a bias in the analysis, particularly in methylome profiles. Thus, it is important to develop methodologies that maximize both the yield and quality of DNA from DBS for downstream analyses. Using a combination of in-house-derived and modified commercial extraction methods, we developed two robust protocols that produced increased DNA yield and quality from DBS. Though both protocols are more efficient relative to other published methods, one protocol yields less DNA compared to the other, but shows improved 260/280 spectrophotometric ratios, which are useful for sample quality assessment. Both protocols consist of two sequential phases, each involving several critical steps. Phase I comprises blood extraction off the filter papers, cell lysis, and protein digestion. Phase II involves DNA precipitation, purification, and elution. Results from subsequent locus-specific and genome-wide DNA methylation analyses demonstrate the high quality, reproducibility, and consistency of the data. This work may prove useful to meet the increased demand for research on DBS, particularly with a focus on the epigenetic origins of human diseases and newborn screening programs.
PMID: 29224166 [PubMed - in process]
Electrochemical Applications in Metal Bioleaching.
Adv Biochem Eng Biotechnol. 2017 Dec 10;:
Authors: Tanne CK, Schippers A
Biohydrometallurgy comprises the recovery of metals by biologically catalyzed metal dissolution from solids in an aqueous solution. The application of this kind of bioprocessing is described as "biomining," referring to either bioleaching or biooxidation of sulfide metal ores. Acidophilic iron- and sulfur-oxidizing microorganisms are the key to successful biomining. However, minerals such as primary copper sulfides are recalcitrant to dissolution, which is probably due to their semiconductivity or passivation effects, resulting in low reaction rates. Thus, further improvements of the bioleaching process are recommendable. Mineral sulfide dissolution is based on redox reactions and can be accomplished by electrochemical technologies. The impact of electrochemistry on biohydrometallurgy affects processing as well as analytics. Electroanalysis is still the most widely used electrochemical application in mineralogical research. Electrochemical processing can contribute to bioleaching in two ways. The first approach is the coupling of a mineral sulfide to a galvanic partner or electrocatalyst (spontaneous electron transfer). This approach requires only low energy consumption and takes place without technical installations by the addition of higher redox potential minerals (mostly pyrite), carbonic material, or electrocatalytic ions (mostly silver ions). Consequently, the processed mineral (often chalcopyrite) is preferentially dissolved. The second approach is the application of electrolytic bioreactors (controlled electron transfer). The electrochemical regulation of electrolyte properties by such reactors has found most consideration. It implies the regulation of ferrous and ferric ion ratios, which further results in optimized solution redox potential, less passivation effects, and promotion of microbial activity. However, many questions remain open and it is recommended that reactor and electrode designs are improved, with the aim of finding options for simplified biohydrometallurgical processing. This chapter focuses on metal sulfide dissolution via bioleaching and does not include other biohydrometallurgical processes such as microbial metal recovery from solution.
PMID: 29224081 [PubMed - as supplied by publisher]
Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey.
Biol Trace Elem Res. 2017 Dec 09;:
Authors: Li J, Xiao C, Yang H, Zhou Y, Wang R, Cao Y
Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P < 0.001). Serum ferritin, transferrin, and soluble transferrin receptor (sTfR)/log ferritin index were significant in different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.
PMID: 29224080 [PubMed - as supplied by publisher]
Comparison between whole-body and head and neck neurovascular coils for 3-T magnetic resonance proton resonance frequency shift thermography guidance in the head and neck region.
Lasers Med Sci. 2017 Dec 09;:
Authors: Ginat DT, Anthony GJ, Christoforidis G, Oto A, Dalag L, Sammet S
The purpose of this study is to compare the image quality of magnetic resonance (MR) treatment planning images and proton resonance frequency (PRF) shift thermography images and inform coil selection for MR-guided laser ablation of tumors in the head and neck region. Laser ablation was performed on an agar phantom and monitored via MR PRF shift thermography on a 3-T scanner, following acquisition of T1-weighted (T1W) planning images. PRF shift thermography images and T2-weighted (T2W) planning images were also performed in the neck region of five normal human volunteers. Signal-to-noise ratios (SNR) and temperature uncertainty were calculated and compared between scans acquired with the quadrature mode body integrated coil and a head and neck neurovascular coil. T1W planning images of the agar phantom produced SNRs of 4.0 and 12.2 for the quadrature mode body integrated coil and head and neck neurovascular coil, respectively. The SNR of the phantom MR thermography magnitude images obtained using the quadrature mode body integrated coil was 14.4 versus 59.6 using the head and neck coil. The average temperature uncertainty for MR thermography performed on the phantom with the quadrature mode body integrated coil was 1.1 versus 0.3 °C with the head and neck coil. T2W planning images of the neck in five human volunteers produced SNRs of 28.3 and 91.0 for the quadrature mode body integrated coil and head and neck coil, respectively. MR thermography magnitude images of the neck in the volunteers obtained using the quadrature mode body integrated coil had a signal-to-noise ratio of 8.3, while the SNR using the head and neck coil was 16.1. The average temperature uncertainty for MR thermography performed on the volunteers with the body coil was 2.5 versus 1.6 °C with the head and neck neurovascular coil. The quadrature mode body integrated coil provides inferior image quality for both basic treatment planning sequences and MR PRF shift thermography compared with a neurovascular coil, but may nevertheless be adequate for clinical purposes.
PMID: 29224048 [PubMed - as supplied by publisher]
Association of the TG/HDL-C and Non-HDL-C/HDL-C Ratios with Chronic Kidney Disease in an Adult Chinese Population.
Kidney Blood Press Res. 2017 Dec 08;42(6):1141-1154
Authors: Wen J, Chen Y, Huang Y, Lu Y, Liu X, Zhou H, Yuan H
BACKGROUND/AIMS: Evidence indicates a role for dyslipidemia in the development of chronic kidney disease (CKD). However, the association of lipid abnormalities and their ratios with kidney disease using the new CKD Epidemiology Collaboration (CKD-EPI) equation is not well understood.
METHODS: This cross-sectional study included 48,054 adult subjects. CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2 or dipstick-positive proteinuria. Logistic regression models were used to examine the relationship between lipid variables and CKD.
RESULTS: The prevalence of CKD in this study was 3.7%. When the participants exhibited higher serum triglyceride (TG), a higher TG/high-density lipoprotein cholesterol (TG/HDL-c) ratio or a higher non-HDL-c/HDL-c ratio or HDL-c in a lower quartile, the prevalence of CKD tended to be higher. The multivariate adjusted odds ratios for CKD per 1 standard deviation increase in lipid level were 1.17 (1.10-1.23) for TG, 0.86 (0.79-0.93) for HDL-c, 1.21 (1.13-1.31) for the TG/HDL-c ratio, and 1.14 (1.06-1.22) for the non-HDL-c/HDL-c ratio. No significant association was detected between CKD and total cholesterol (TC), non-HDL-c or the low-density lipoprotein cholesterol/HDL-c (LDL-c/HDL-c) ratio.
CONCLUSION: In this relatively healthy adult Chinese population, the CKD-EPI equation determined that the TG/HDL-c and non-HDL-c/HDL-c ratios as well as TG and HDL-c correlate with the prevalence of CKD.
PMID: 29224024 [PubMed - as supplied by publisher]
Diagnostic Ureteroscopy Prior to Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma Increased the Risk of Intravesical Recurrence.
Urol Int. 2017 Dec 08;:
Authors: Tan P, Xie N, Yang L, Liu L, Tang Z, Wei Q
OBJECTIVE: To assess the impact of diagnostic ureteroscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC).
MATERIALS AND METHODS: A systematic literature search of the Medline, Embase, PubMed, and Cochrane library was performed in August 2017. Cumulative analyses of available hazard ratios (HRs) and their 95% CI were conducted using Stata version 12.0.
RESULTS: Eleven studies including 4,057 participants were included, with a total of 1,403 patients diagnosed with IVR during the follow-up period. The pooled HRs of eight studies suggested that diagnostic URS prior to RNU significantly increased the IVR risk after RNU (HR 1.53, 95% CI 1.31-1.77; p < 0.001). However, the preoperative diagnostic URS was not associated with cancer-specific survival (HR 0.72; p = 0.11), metastasis-free survival (HR 1.09; p = 0.60) or overall survival (HR 1.12; p = 0.73). No publication bias was observed (Begg, p = 0.90; Egger, p = 0.71).
CONCLUSIONS: Regardless, the diagnostic URS prior to RNU might increase the IVR risk in patients with UTUC. As ureteroscopy provides important prognostic and therapeutic value and guides decisions in UTUC, more future studies should be performed to find a novel way to mitigate the potential risk of IVR after RNU, such as chemoprophylaxis after endoscopy.
PMID: 29224014 [PubMed - as supplied by publisher]
Analysis of the interactions between environmental and food contaminants, cadmium and deoxynivalenol, in different target organs.
Sci Total Environ. 2017 Dec 07;622-623:841-848
Authors: Le TH, Alassane-Kpembi I, Oswald IP, Pinton P
Cadmium (Cd), a common and widespread toxic heavy metal, and mycotoxins such as deoxynivalenol (DON) are frequent contaminants of the food supply. Most of the data on their toxicity concern their effects when present alone. However, consumers can be exposed to a cocktail of DON and Cd. To improve the understanding of their combined toxicity, the effects of DON and Cd alone or in combination were investigated in different human cell lines from the kidney (HEK-293), intestine (Caco-2), blood (HL-60) and liver (HepG2). Cytotoxicity was assessed through ATP measurement and types of interactions determined by the Isobologram-Combination index method. HEK-293 cells were exposed to increasing doses of DON, Cd and their combination at different ratios (DON/Cd of 2/1; 1/1; 1/2 and 1/8). Regardless of the ratio, the type of interaction observed in HEK-293 cells ranged from moderate antagonism to nearly additive with increasing cytotoxicity. In Caco-2 cells, the interactions ranged from nearly additive to antagonism whatever the ratio. At ratio 1/1, in HL-60 and HepG2 cells, interactions ranged from synergy to antagonism depending on the cytotoxicity level. Using human cells lines, this study indicates that the consequences of combined exposure to environmental and food contaminants are specific to the target organ. Further studies are needed to confirm these data in vivo.
PMID: 29223910 [PubMed - as supplied by publisher]
The role of groundwater discharge fluxes on Si:P ratios in a major tributary to Lake Erie.
Sci Total Environ. 2017 Dec 07;622-623:814-824
Authors: Maavara T, Slowinski S, Rezanezhad F, Van Meter K, Van Cappellen P
Groundwater discharge can be a major source of nutrients to river systems. Although quantification of groundwater nitrate loading to streams is common, the dependence of surface water silicon (Si) and phosphorus (P) concentrations on groundwater sources has rarely been determined. Additionally, the ability of groundwater discharge to drive surface water Si:P ratios has not been contextualized relative to riverine inputs or in-stream transformations. In this study, we quantify the seasonal dynamics of Si and P cycles in the Grand River (GR) watershed, the largest Canadian watershed draining into Lake Erie, to test our hypothesis that regions of Si-rich groundwater discharge increase surface water Si:P ratios. Historically, both the GR and Lake Erie have been considered stoichiometrically P-limited, where the molar Si:P ratio is greater than the ~16:1 phytoplankton uptake ratio. However, recent trends suggest that eastern Lake Erie may be approaching Si-limitation. We sampled groundwater and surface water for dissolved and reactive particulate Si as well as total dissolved P for 12months within and downstream of a 50-km reach of high groundwater discharge. Our results indicate that groundwater Si:P ratios are lower than the corresponding surface water and that groundwater is a significant source of bioavailable P to surface water. Despite these observations, the watershed remains P-limited for the majority of the year, with localized periods of Si-limitation. We further find that groundwater Si:P ratios are a relatively minor driver of surface water Si:P, but that the magnitude of Si and P loads from groundwater represent a large proportion of the overall fluxes to Lake Erie.
PMID: 29223908 [PubMed - as supplied by publisher]
Analytical indicators to characterize Particulate Organic Matter (POM) and its evolution in French Vertical Flow Constructed Wetlands (VFCWs).
Sci Total Environ. 2017 Dec 07;622-623:801-813
Authors: Kania M, Gautier M, Ni Z, Bonjour E, Guégan R, Michel P, Jame P, Liu J, Gourdon R
The design of French VFCWs leads to the formation of a sludge layer at the surface of the first filters due to the retention of suspended solids from the percolation of unsettled wastewater. This layer plays a major role in the system but still little is known on its characteristics and evolutions. In this study, suspended solids and sludge deposits sampled from two French VFCW plants were analyzed by different methods in the objective to assess the evolution of particulate organic matter (POM) along the treatment chain and within the sludge layer, and identify relevant analytical indicators of these phenomena. The treatment chain included an aerobic trickling filter followed by FeCl3 injection and two successive stages of filters. Thermal analyses showed that OM contents of suspended solids decreased along the treatment chain. POM in inflow suspended solids was predominantly composed of reactive, biodegradable compounds which were partly hydrolyzed and mineralized notably at the trickling filter stage. 3D fluorescence spectra collected from aqueous POM extracts confirmed the evolution of organic matter from low-molecular reactive compounds to more complex and stable structures such as humic-like substances. FTIR confirmed the mineralization of POM's reactive constituents along the treatment chain by the decrease in the intensities of the characteristics bands of aliphatic compounds or proteins, and its humification in the sludge deposits through the relative increase of the bands at 1634cm-1 (vC=O) and 1238cm-1 (δC=O and/or δOH). Isotopic ratios δ2H/1H and δ15N/14N were found to be good indicators of POM evolutions. The higher values of δ2H/1H and δ15N/14N ratios measured in sludge deposits as compared to inflow suspended solids were related to POM humification and to microbial processes of POM hydrolysis and mineralization, respectively.
PMID: 29223907 [PubMed - as supplied by publisher]
Exposure to low concentrations of air pollutants and adverse birth outcomes in Brisbane, Australia, 2003-2013.
Sci Total Environ. 2017 Dec 07;622-623:721-726
Authors: Chen G, Guo Y, Abramson MJ, Williams G, Li S
BACKGROUND: It's unclear whether exposures to low-level air pollution have adverse effects on birth outcomes, and which trimester-specific pregnant exposure is sensitive.
OBJECTIVES: To investigate the effects of maternal exposure during each trimester and the whole pregnancy to particles with aerodynamic diameter<2.5μm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) on preterm birth (PTB) and low birth weight (LBW).
METHODS: Daily data on birth records, air quality, and weather conditions were collected in Brisbane, Australia during 2003-2013. Mean concentrations of air pollutants were calculated for each trimester of pregnancy. Cox proportional hazards models were used to examine the associations between air pollution and birth outcomes. Multi-pollutant models and stratified analyses by ambient temperature were performed.
RESULTS: Exposures to PM2.5, SO2, NO2, and O3 during the whole pregnancy were associated with increased risk of PTB [IQR HRs (hazard ratios with an interquartile range increase in air pollutants) and 95% confidence intervals (CIs): 1.05 (1.02, 1.08), 1.12 (1.09, 1.16), 1.07 (1.01, 1.13), and 1.13 (1.10, 1.16), respectively] and LBW [IQR HRs and 95% CIs: 1.06 (1.02, 1.10), 1.12 (1.08, 1.16), 1.11 (1.03, 1.18), and 1.13 (1.09, 1.17), respectively]. Highest HRs were observed during trimester 3, and lowest in trimester 1. For each air pollutant, stronger effects on PTB and LBW were present for exposure to low and moderate temperatures than exposure to high ambient temperature.
CONCLUSIONS: Exposures to low-level air pollutants are related to adverse birth outcomes. More effective policies for air quality control could contribute to improving neonatal health.
PMID: 29223898 [PubMed - as supplied by publisher]
Intensity ratio to improve black hole assessment in multiple sclerosis.
Mult Scler Relat Disord. 2017 Dec 02;19:140-147
Authors: Adusumilli G, Trinkaus K, Sun P, Lancia S, Viox JD, Wen J, Naismith RT, Cross AH
BACKGROUND: Improved imaging methods are critical to assess neurodegeneration and remyelination in multiple sclerosis. Chronic hypointensities observed on T1-weighted brain MRI, "persistent black holes," reflect severe focal tissue damage. Present measures consist of determining persistent black holes numbers and volumes, but do not quantitate severity of individual lesions.
OBJECTIVE: Develop a method to differentiate black and gray holes and estimate the severity of individual multiple sclerosis lesions using standard magnetic resonance imaging.
METHODS: 38 multiple sclerosis patients contributed images. Intensities of lesions on T1-weighted scans were assessed relative to cerebrospinal fluid intensity using commercial software. Magnetization transfer imaging, diffusion tensor imaging and clinical testing were performed to assess associations with T1w intensity-based measures.
RESULTS: Intensity-based assessments of T1w hypointensities were reproducible and achieved > 90% concordance with expert rater determinations of "black" and "gray" holes. Intensity ratio values correlated with magnetization transfer ratios (R = 0.473) and diffusion tensor imaging metrics (R values ranging from 0.283 to -0.531) that have been associated with demyelination and axon loss. Intensity ratio values incorporated into T1w hypointensity volumes correlated with clinical measures of cognition.
CONCLUSIONS: This method of determining the degree of hypointensity within multiple sclerosis lesions can add information to conventional imaging.
PMID: 29223871 [PubMed - as supplied by publisher]
Elevated inflammatory Lp-PLA2 and IL-6 link e-waste Pb toxicity to cardiovascular risk factors in preschool children.
Environ Pollut. 2017 Dec 07;234:601-609
Authors: Lu X, Xu X, Zhang Y, Zhang Y, Wang C, Huo X
Cardiovascular toxicity of lead (Pb) manifests primarily as an effect on blood pressure and eventual increased risk of atherosclerosis and cardiovascular events. Therefore, we investigated vascular inflammatory biomarkers and cardiovascular effects of Pb-exposed children. A total of 590 children (3-7 years old) were recruited from Guiyu (n = 337), an electronic waste (e-waste)-exposed group, and Haojiang (n = 253), a reference group, from November to December 2016. We measured child blood Pb levels (BPbs), and systolic and diastolic blood pressure. Pulse pressure was calculated for the latter two. Serum biomarkers including lipid profiles and inflammatory cytokines, and plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) were detected. Unadjusted regression analysis illustrated that higher ln-transformed BPb associated with lower systolic blood pressure and pulse pressure. After adjustment for various confounders, the relational degree of lnBPb and blood pressure measures became slightly attenuated or not significant. Elevated BPb was associated with higher Lp-PLA2, interleukin (IL)-6, triglycerides (TG) and lower high-density lipoprotein (HDL). Lp-PLA2 remained inversely associated with pulse pressure and HDL, but positively with ratios of total cholesterol to HDL (Tc/HDL) and low-density lipoprotein to HDL (LDL/HDL). IL-6 was associated negatively with systolic blood pressure, pulse pressure and HDL, and positively associated with TG, Tc/HDL and LDL/HDL. The mediation effect of biomarkers on the association of BPb with pulse pressure was insignificant except for Lp-PLA2. Available data supports the conclusion that e-waste-exposed children with higher BPbs and concomitant abnormal measures of cardiovascular physiology have an augmented prevalence of vascular inflammation, as well as lipid disorder.
PMID: 29223817 [PubMed - as supplied by publisher]
Total and differential white blood cell counts and hemodynamic parameters in first-episode psychosis.
Psychiatry Res. 2017 Dec 06;260:307-312
Authors: Moody G, Miller BJ
There is evidence for blood inflammatory abnormalities in patients with first-episode psychosis (FEP). The monocyte- and neutrophil-to-lymphocyte ratios (MLR; NLR) are markers of inflammation and endothelial dysfunction, and predictors of cardiovascular disease, the leading cause of death in schizophrenia. We investigated relationships between white blood cell (WBC) counts and hemodynamic parameters associated with cardiovascular disease risk in 25 subjects age 18-50 hospitalized for FEP and 44 controls. Subjects had a blood draw, vital signs, and medical history. Patients with FEP had significantly higher NLR, MLR, pulse pressure, and rate pressure product (RPP) than controls (p < 0.05 for each), after controlling for potential confounders. In linear regression analyses, higher monocytes were a significant predictor of higher pulse pressure (p = 0.033) and higher MLR predicted RPP at the trend level (p = 0.051) in FEP, after controlling for potential confounders. To our knowledge, ours is the first report of increased RPP, a measure of myocardial workload, in FEP. We also replicated findings of increased NLR, MLR and pulse pressure in FEP. Our findings underscore that measurement of routine vital signs and blood total and differential WBC counts are germane to the clinical care of patients with psychosis as markers of cardiovascular disease risk.
PMID: 29223800 [PubMed - as supplied by publisher]
New insights into the influence of Monofluorination on Dimyristoylphosphatidylcholine membrane properties: A solid-state NMR study.
Biochim Biophys Acta. 2017 Dec 06;:
Authors: Gagnon MC, Strandberg E, Ulrich AS, Paquin JF, Auger M
Solid-state 19F NMR spectroscopy is a method of choice to study the interactions between lipid membranes and other molecules such as peptides, proteins or drugs. Numerous fluorine-labeled NMR probes have been developed over the last few years, especially fluorine-labeled peptides. In order to develop a new kind of NMR reporter molecule and a complementary approach to fluorine-labeling of peptides, we synthesized six monofluorinated derivatives of the lipid dimyristoylphosphatidylcholine (F-DMPC), with the fluorine atom located along the acyl chain linked to the central glycerol position. To better understand the behavior of these fluorine-labeled lipids, we report here the investigation of F-DMPC membrane properties using solid-state 2H-, 15N-, 19F and 31P NMR spectroscopy. This study was carried out on pure F-DMPC bilayers as well as F-DMPC/DMPC mixtures at various ratios. Slight perturbations were observed for pure F-DMPC multilamellar vesicles (MLVs), most noticeable for lipids with the fluorine atom located at the extremities of the acyl chain. On the other hand, no significant perturbations were observed for F-DMPC/DMPC MLVs containing up to 25% F-DMPC, nor for any fluorine-labeled bilayers that were prepared as macroscopically oriented samples. To test the interaction with some representative peptides, 15N-labeled α-helical antimicrobial peptides (AMPs) were incorporated into F-DMPC/DMPC (1/3) bilayers. 15N SS-NMR analyses confirmed that the known orientation of each AMP in pure DMPC was preserved in the presence of 25% monofluorinated DMPC, irrespective of the position of the 19F-label. In summary, F-DMPC/DMPC (1/3) model membranes can be used as NMR reporter to study membrane interactions with other molecules.
PMID: 29223532 [PubMed - as supplied by publisher]
REVEAL risk scores applied to riociguat-treated patients in PATENT-2: Impact of changes in risk score on survival.
J Heart Lung Transplant. 2017 Nov 11;:
Authors: Benza RL, Farber HW, Frost A, Ghofrani HA, Gómez-Sánchez MA, Langleben D, Rosenkranz S, Busse D, Meier C, Nikkho S, Hoeper MM
BACKGROUND: The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score (RRS) calculator was developed using data derived from the REVEAL registry, and predicts survival in patients with pulmonary arterial hypertension (PAH) based on multiple patient characteristics. Herein we applied the RRS to a pivotal PAH trial database, the 12-week PATENT-1 and open-label PATENT-2 extension studies of riociguat. We examined the effect of riociguat vs placebo on RRS in PATENT-1, and investigated the prognostic implications of change in RRS during PATENT-1 on long-term outcomes in PATENT-2.
METHODS: RRS was calculated post hoc for baseline and Week 12 of PATENT-1, and Week 12 of PATENT-2. Patients were grouped into risk strata by RRS. Kaplan-Meier estimates were made for survival and clinical worsening-free survival in PATENT-2 to evaluate the relationship between RRS in PATENT-1 and long-term outcomes in PATENT-2.
RESULTS: A total of 396 patients completed PATENT-1 and participated in PATENT-2. In PATENT-1, riociguat significantly improved RRS (p = 0.031) and risk stratum (p = 0.018) between baseline and Week 12 compared with placebo. RRS at baseline, and at PATENT-1 Week 12, and change in RRS during PATENT-1 were significantly associated with survival (hazard ratios for a 1-point reduction in RRS: 0.675, 0.705 and 0.804, respectively) and clinical worsening-free survival (hazard ratios of 0.736, 0.716 and 0.753, respectively) over 2 years in PATENT-2.
CONCLUSIONS: RRS at baseline and Week 12, and change in RRS, were significant predictors of both survival and clinical worsening-free survival. These data support the long-term predictive value of the RRS in a controlled study population.
PMID: 29223470 [PubMed - as supplied by publisher]
Impact of positive surgical margins on overall survival after partial nephrectomy-A matched comparison based on the National Cancer Database.
Urol Oncol. 2017 Dec 06;:
Authors: Shum CF, Bahler CD, Sundaram CP
INTRODUCTION: The impact of positive surgical margins (PSM) in partial nephrectomy (PN) has been a controversy. Previous studies on the relationship between PSM and overall survival (OS) were either underpowered or had highly dissimilar groups. We used the National Cancer Database with propensity score matching to determine the association between PSM and OS after PN.
MATERIALS AND METHODS: We identified patients with T1/T2 N0M0 renal cancer treated with PN between 2004 and 2009, and divided them into 2 groups based on their margin status. We used propensity score matching to ensure similarities in age, comorbidity score (CCI), tumor size, histology, and grade between groups. Covariates were compared by χ2 test. Cox multiple regression was used to estimate the hazard ratios (HR) for all-cause mortality. OS between matched groups were compared by log-rank, Breslow and Tarone-Ware tests.
RESULTS: After excluding those with missing data on margin or survival status, 20,762 patients were eligible for matching. Each matched group had 1,265 patients, similar in age, sex, race, CCI, tumor size, histology, and grade. There were 386 recorded all-cause mortalities over a median follow-up duration of 72.6 months. Cox multiple regression showed a higher risk of all-cause mortality among cases with PSM (HR: 1.393, P = 0.001). Old age, high CCI, and large tumors had higher risks, while papillary and chromophore histologic subtypes had lower risks. PSM was associated with significantly worse OS by log-rank, Breslow, and Tarone-Ware tests.
CONCLUSION: PSM is associated with significantly worse OS after PN.
PMID: 29223360 [PubMed - as supplied by publisher]
Expression of phytoglobin affects nitric oxide metabolism and energy state of barley plants exposed to anoxia.
Plant Sci. 2017 Dec;265:124-130
Authors: Cochrane DW, Shah JK, Hebelstrup KH, Igamberdiev AU
Class 1 plant hemoglobins (phytoglobins) are upregulated during low-oxygen stress and participate in metabolism and cell signaling via modulation of the levels of nitric oxide (NO). We studied the effects of overexpression and knockdown of the class 1 phytoglobin gene in barley (Hordeum vulgare L.) under low-oxygen stress. The overexpression of phytoglobin reduced the amount of NO released, while knockdown significantly stimulated NO emission. It has previously been shown that NO inhibits aconitase activity, so decreased aconitase activity in knockdown plants acts as a biomarker for high internal NO levels. The overexpression of phytoglobin corresponded to higher ATP/ADP ratios, pyrophosphate levels and aconitase activity under anoxia, while knockdown of phytoglobin resulted in the increased level of protein nitrosylation, elevation of alcohol dehydrogenase and nitrosoglutathione reductase activities. The overexpressing plants showed various signs of stunted growth under normoxia, but were the only type to germinate and survive under hypoxia. The results show that overexpression of phytoglobin protects plant cells via NO scavenging and improves their low-oxygen stress survival. However, it may not be useful for cereal crop improvement since it comes with a significant interference with normoxic NO signalling pathways.
PMID: 29223334 [PubMed - in process]
Glucocorticoid hormone treatment enhances the cytokine production of regulatory T cells by upregulation of Foxp3 expression.
Immunobiology. 2017 Oct 06;:
Authors: Ugor E, Prenek L, Pap R, Berta G, Ernszt D, Najbauer J, Németh P, Boldizsár F, Berki T
OBJECTIVE: Despite the fact that glucocorticoids (GC) are important therapeutic tools, their effects on regulatory T cells (Treg) are not well defined. The aim of our work was to investigate how GCs influence in vivo the thymic (tTreg) and peripheral Treg (pTreg) differentiation, survival and cytokine production.
METHODS: Tregs were detected with flow cytometry in lymphatic organs of 4-6 weeks old BALB/c mice after repeated (2-4days), high-dose in vivo GC treatment using CD4/CD25 cell surface and Foxp3/IL-10/TGFβ/glucocorticoid receptor (GR) intracellular staining. Cytokine, Foxp3, and GR mRNA levels of sorted CD4+CD25high T cells were analyzed using RT-PCR. Foxp3 and GR localization in Treg cells was investigated with confocal microscopy.
RESULTS: GC treatment of mice resulted in increased relative tTreg frequency in the thymus, which was due to decreased total thymocyte numbers with unchanged absolute tTreg cell count. In contrast the relative pTreg cell ratio in secondary lymphatic organs decreased or showed no changes after GC treatment, while the absolute number of pTregs decreased. Elevated intracellular IL-10+ and TGFβ+ tTreg and pTreg ratios were measured in GC-treated animals, accompanied with elevated Foxp3 mRNA expression. In addition, GC treatment caused increased TGFβ and IL-35 mRNA expression in CD4+CD25high+ splenic and elevated IL-10 mRNA level in thymic tTregs. GR expression of thymic tTreg cells was lower than in pTregs. GC treatment caused an opposite change in GR levels, elevating GR in tTregs but decreasing it in pTregs. We observed a nuclear localization of GR in both tTregs and pTregs, which showed high colocalization (∼60%) with Foxp3 transcription factor. These data suggest an interaction of these two transcription factors with further increase due to GC treatment in splenic pTregs.
CONCLUSION: Our data show selective survival of tTregs and elevated production of immunosuppressive cytokines by Treg cells after GC treatment, which may contribute to the immunosuppressive effects of GCs.
PMID: 29223294 [PubMed - as supplied by publisher]