Objective: Subclinical chronic inflammation could be a unifying factor linking type 2 diabetes (T2D) and atherosclerosis. The beneficial effects of physical activity on a reduced risk of coronary ...heart disease could at least in part be mediated by improved markers of inflammation. Research design and methods: The aim of this study was to determine the effect of 4 weeks of physical training on plasma concentrations of interleukin (IL)-6, C-reactive protein (CRP), adiponectin and IL-10 in 60 individuals with normal glucose tolerance, impaired glucose tolerance (IGT) or T2D. Results: In patients with IGT and T2D, significant improvement in body fat, fitness level, glucose metabolism and insulin sensitivity after 4 weeks of physical training was associated with significantly improved plasma concentrations of adiponectin and CRP, but not IL-6. Regression analysis demonstrated only for the anti-inflammatory parameters adiponectin and IL-10 a significant relationship with the decrease in fasting plasma glucose, whereas changes in IL-6 and CRP were not significantly related to changes in fasting plasma glucose, body fat, maximal oxygen uptake, or insulin sensitivity. In a multivariate linear regression analysis, only changes in circulating adiponectin, fasting plasma glucose and percentage body fat were determinants of changes in insulin sensitivity. Conclusions: Physical training was associated with a near normalization of adiponectin and CRP plasma concentrations in subjects with IGT and T2D. Increased insulin sensitivity after training was most strongly related to changes in adiponectin plasma concentrations, in fasting plasma glucose and percentage body fat, whereas changes in IL-6, IL-10 and CRP plasma concentrations did not significantly contribute to improved insulin sensitivity.
Airway inflammation is common in severe asthma despite antiinflammatory therapy with corticosteroids. Lipoxin A(4) (LXA(4)) is an arachidonic acid-derived mediator that serves as an agonist for ...resolution of inflammation.
Airway levels of LXA(4), as well as the expression of lipoxin biosynthetic genes and receptors, in severe asthma.
Samples of bronchoalveolar lavage fluid were obtained from subjects with asthma and levels of LXA(4) and related eicosanoids were measured. Expression of lipoxin biosynthetic genes was determined in whole blood, bronchoalveolar lavage cells, and endobronchial biopsies by quantitative polymerase chain reaction, and leukocyte LXA(4) receptors were monitored by flow cytometry.
Individuals with severe asthma had significantly less LXA(4) in bronchoalveolar lavage fluids (11.2 +/- 2.1 pg/ml) than did subjects with nonsevere asthma (150.1 +/- 38.5 pg/ml; P < 0.05). In contrast, levels of cysteinyl leukotrienes were increased in both asthma cohorts compared with healthy individuals. In severe asthma, 15-lipoxygenase-1 mean expression was decreased fivefold in bronchoalveolar lavage cells. In contrast, 15-lipoxgenase-1 was increased threefold in endobronchial biopsies, but expression of both 5-lipoxygenase and 15-lipoxygenase-2 in these samples was decreased. Cyclooxygenase-2 expression was decreased in all anatomic compartments sampled in severe asthma. Moreover, LXA(4) receptor gene and protein expression were significantly decreased in severe asthma peripheral blood granulocytes.
Mechanisms underlying pathological airway responses in severe asthma include lipoxin underproduction with decreased expression of lipoxin biosynthetic enzymes and receptors. Together, these results indicate that severe asthma is characterized, in part, by defective lipoxin counterregulatory signaling circuits.
There is a close relationship between muscle loss (sarcopenia) and bone loss (osteoporosis), integrated in the term ‘osteosarcopenia’; however, detailed muscle phenotyping is under-represented in ...musculoskeletal studies.Muscle phenotyping in both humans and animal models, such as mice and zebrafish, requires validation and agreement.Parameters of muscle strength and function should be measured in health and disease while considering age and sex differences.Animal models, such as mice and zebrafish, add valuable information and detail on muscle development and function, but need careful assessment to provide translatable insights.
Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term ‘osteosarcopenia’, is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action ‘Genomics of MusculoSkeletal traits Translational Network’ (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.
Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term ‘osteosarcopenia’, is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action ‘Genomics of MusculoSkeletal traits Translational Network’ (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.
A facultative anaerobic, Gram-positive staining, endospore-forming bacterium, isolated from the rhizosphere of cucumber (
), was taxonomically investigated. Based on 16S rRNA gene sequence similarity ...comparisons, strain AP-6
clustered together with other species of the genus
and showed highest similarities with
LMG 21831
(99.1 %),
LMG 21834
(98.7 %) and
LMG 21838
(98.5 %). The 16S rRNA gene sequence similarity to the sequences of the type strains of other species of the genus
was 98.5 % or less. Chemotaxonomic features supported the grouping of the strain in the genus
; for example, the major fatty acids were anteiso-C
, iso-C
and C
, the polar lipid profile contained the major components diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified glycolipid, the major quinone was menaquinone MK-7 and the major compound in the polyamine pattern was spermidine. Additionally, DNA-DNA hybridization with
LMG 21831
,
LMG 21834
and
LMG 21838
resulted in relatedness values that were clearly below 70 %. Physiological and biochemical test results were also different from those of the most closely related species. As a consequence, AP-6
represents a novel species of the genus
, for which the name
sp. nov. is proposed, with AP-6
( = CIP 110974
= CCM 8651
) as the type strain.
For fully characterizing renal cell carcinoma (RCC), information about the 3D tissue microstructure is essential. Histopathology, which represents the current diagnostic gold standard, is destructive ...and only provides 2D information. 3D X-ray histology endeavors to overcome these limitations by generating 3D data. In a laboratory environment, most techniques struggle with limited resolution and the weak X-ray attenuation contrast of soft tissue. We recently developed a laboratory-based method combining nanoscopic X-ray CT with a cytoplasm-specific X-ray stain. Here, we present the application of this method to human RCC biopsies. The NanoCT slices enable pathological characterization of crucial structures by reproducing tissue morphology with a similar detail level as corresponding histological light microscopy images. Beyond that, our data offer deeper insights into the 3D configuration of the tumor. By demonstrating the compatibility of the X-ray stain with standard pathological stains, we highlight the feasibility of integrating staining based NanoCT into the pathological routine.
Background and purpose Strategies to manage tibial fractures include nonoperative and operative approaches. Strategies to enhance healing include a variety of bone stimulators. It is not known what ...forms of management for tibial fractures predominate among Canadian orthopedic surgeons. We therefore asked a representative sample of orthopedic trauma surgeons about their management of tibial fracture patients.
Methods This was a cross-sectional survey of 450 Canadian orthopedic trauma surgeons. We inquired about demographic variables and current tibial shaft fracture management strategies.
Results 268 surgeons completed the survey, a response rate of 60%. Most respondents (80%) managed closed tibial shaft fracture operatively; 47% preferred reamed intramedullary nailing and 40% preferred unreamed. For open tibial shaft fractures, 59% of surgeons preferred reamed intramedullary nailing. Some surgeons (16%) reported use of bone stimulators for management of uncomplicated open and closed tibial shaft fractures, and almost half (45%) made use of this adjunctive modality for complicated tibial shaft fractures. Low-intensity pulsed ultrasound and electrical stimulation proved equally popular (21% each) and 80% of respondents felt that a reduction in healing time of 6 weeks or more, attributed to a bone stimulator, would be clinically important.
Interpretation Current practice regarding orthopedic management of tibial shaft fractures in Canada strongly favors operative treatment with intramedullary nailing, although respondents were divided in their preference for reamed and unreamed nailing. Use of bone stimulators is common as an adjunctive modality in this injury population. Large randomized trials are needed to provide better evidence to guide clinical decision making regarding the choice of reamed or unreamed nailing for tibial shaft fractures, and to inform surgeons about the actual effect of bone stimulators.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Recent meta-analyses of genome-wide association studies in general populations of European descent have identified 28 loci for lung function.
We sought to identify novel lung function loci ...specifically for asthma and to confirm lung function loci identified in general populations.
Genome-wide association studies of lung function (percent predicted FEV1 ppFEV1, percent predicted forced vital capacity, and FEV1/forced vital capacity ratio) were performed in 4 white populations of European descent (n = 1544), followed by meta-analyses.
Seven of 28 previously identified lung function loci (HHIP, FAM13A, THSD4, GSTCD, NOTCH4-AGER, RARB, and ZNF323) identified in general populations were confirmed at single nucleotide polymorphism (SNP) levels (P < .05). Four of 32 loci (IL12A, IL12RB1, STAT4, and IRF2) associated with ppFEV1 (P < 10−4) belong to the TH1 or IL-12 cytokine family pathway. By using a linear additive model, these 4 TH1 pathway SNPs cumulatively explained 2.9% to 7.8% of the variance in ppFEV1 values in 4 populations (P = 3 × 10−11). Genetic scores of these 4 SNPs were associated with ppFEV1 values (P = 2 × 10−7) and the American Thoracic Society severe asthma classification (P = .005) in the Severe Asthma Research Program population. TH2 pathway genes (IL13, TSLP, IL33, and IL1RL1) conferring asthma susceptibility were not associated with lung function.
Genes involved in airway structure/remodeling are associated with lung function in both general populations and asthmatic subjects. TH1 pathway genes involved in anti-virus/bacterial infection and inflammation modify lung function in asthmatic subjects. Genes associated with lung function that might affect asthma severity are distinct from those genes associated with asthma susceptibility.
1 Institut für Angewandte Mikrobiologie, Justus-Liebig-Universität Giessen, Heinrich-Buff-Ring 2632, D-35390 Giessen, Germany
2 Fachgebiet Hygiene und Umweltmikrobiologie, Technische Universität ...Berlin, D-13353 Berlin, Germany
3 Institut für Hygiene und Umweltmedizin, Rheinisch-Westfälische Technische Hochschule, D-52057 Aachen, Germany
4 Institut für Bakteriologie, Mykologie und Hygiene, Veterinärmedizinische Universität, A-1210 Vienna, Austria
5 Institut für Mikrobiologie und Genetik, Universität Wien, A-1030 Vienna, Austria
Correspondence Peter Kämpfer peter.kaempfer{at}agrar.uni-giessen.de
A Gram-negative, rod-shaped, non-spore-forming, yellow-pigmented bacterium (strain B2 T ) isolated from wastewater of a sequence batch reactor showing enhanced phosphorus removal was investigated to determine its taxonomic status. Complete 16S rRNA gene sequence analysis indicated that the organism should be placed in the genus Chryseobacterium . The strain contained a polyamine pattern with sym -homospermidine as the major compound, menaquinone MK-6 as the predominant menaquinone and ai-C 15 : 0 , i-C 15 : 0 and C 16 : 1 as the major fatty acids. Phosphatidylethanolamine and several unidentified lipids were detected in the polar lipid profile. Phylogenetically, strain B2 T was most closely related to Chryseobacterium indoltheticum and Chryseobacterium gleum (96·2 and 95·9 % 16S rRNA gene sequence similarity, respectively). The phylogenetic distance from any validly described species within the genus Chryseobacterium , as indicated from 16S rRNA gene sequence similarities, and its phenotypic properties demonstrate that strain B2 T represents a novel species, for which the name Chryseobacterium defluvii sp. nov. is proposed; the type strain is B2 T (=DSM 14219 T =CIP 107207 T ).
The EMBL accession number for the 16S rRNA gene sequence of strain B2 T is AJ309324.
This study is a systematic review of interventions to improve adherence to guideline recommendations for prescribing opioids for chronic noncancer pain.
Investigators searched CINAHL, Embase, ...MEDLINE, PsycINFO, the Cochrane Library, and Joanna Briggs Institute Evid Based Pract database from inception until June 3, 2019. Interventional studies to improve adherence to recommendations made by opioid guidelines for chronic noncancer pain in North America were eligible if outcomes included adherence to guideline recommendations or change in quantity of opioids prescribed. Data were extracted independently and in duplicate. Quantitative synthesis was performed using random effects meta-analysis. Confidence in evidence was determined using the Grades of Recommendation, Assessment, Development, and Evaluation.
A total of 20 studies (8 controlled and 12 prospective cohort) involving 1,491 providers and 72 clinics met inclusion. Interventions included education, audit and feedback, interprofessional support, shared decision making, and multifaceted strategies. Multifaceted interventions improved the use of urine drug testing (n=2, or =2.31, 95% CI=1.53, 3.49, z=3.98, p<0.01; high-certainty evidence), treatment agreements (n=2, or =1.96, 95% CI=1.47, 2.61, z=4.56, p<0.01; moderate-certainty evidence), and mental health screening (n=2, 2.57-fold, 95% CI=1.56, 4.24, z=2.32, p=0.02; low-certainty evidence) when prescribing opioids for chronic noncancer pain. Very low–certainty evidence suggests that several interventions improved the use of treatment agreements, urine drug testing, and prescription drug monitoring programs.
Mostly very low–certainty evidence supports a number of interventions for improving adherence to risk management strategies when prescribing opioids for chronic noncancer pain; however, the effect on patient important outcomes (e.g., overdose, addiction, death) is uncertain.
Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor alpha ...(IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown.
Allelic substitutions in IL4Ralpha are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE.
Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Ralpha. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE.
In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately.
SNPs in IL4Ralpha, which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.
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