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Metabolic pathways are now considered as intrinsic virulence attributes of pathogenic bacteria and thus represent potential targets for antibacterial strategies. Here we focused on the role of the pentose phosphate pathway (PPP) and its connections with other metabolic pathways in the pathophysiology of Francisella novicida. The involvement of the PPP in the intracellular life cycle of Francisella was first demonstrated by studying PPP inactivating mutants. Indeed, we observed that inactivation of the tktA, rpiA or rpe genes severely impaired intramacrophage multiplication during the first 24 hours. However, time-lapse video microscopy demonstrated that rpiA and rpe mutants were able to resume late intracellular multiplication. To better understand the links between PPP and other metabolic networks in the bacterium, we also performed an extensive proteo-metabolomic analysis of these mutants. We show that the PPP constitutes a major bacterial metabolic hub with multiple connections to glycolysis, the tricarboxylic acid cycle and other pathways, such as fatty acid degradation and sulfur metabolism. Altogether our study highlights how PPP plays a key role in the pathogenesis and growth of Francisella in its intracellular niche.
To evaluate whether the risk of subsequent psoriasis and psoriatic arthritis development is increased in patients with uveitis.
In Taiwan's national health insurance research database, we identified 195,125 patients with new-onset uveitis between 2001 and 2013. We randomly selected 390,250 individuals without uveitis who were matched 21 to uveitis cases based on age, sex and year of enrolment. Selleck YUM70 The characteristics of the two groups were compared. Using multivariate Cox regression, hazard ratios (HRs) for psoriasis or psoriatic arthritis corresponding to uveitis were computed after adjustment for age, sex, insurance cost and comorbidities. In subgroup analyses, separate HRs for mild psoriasis, severe psoriasis and psoriatic arthritis were calculated.
The mean age of the study cohort was 50.2 ± 17.2 years. Hypertension, diabetes, hyperlipidaemia and obesity were more prevalent in the uveitis group (all p < 0.0001). The hazard of psoriasis or psoriatic arthritis development was significantly greater in the uveitis group than in the non-uveitis group (p < 0.0001); this increased risk persisted after adjustment for confounders [adjusted HR = 1.41; 95% confidence interval (CI), 1.33-1.48]. Adjusted HRs showed an increasing trend from mild psoriasis (1.35; 95% CI, 1.28-1.44) to severe psoriasis (1.59; 95% CI, 1.30-1.94) and psoriatic arthritis (1.97; 95% CI, 1.60-2.42).
This nationwide population-based cohort study revealed that patients with uveitis have an increased risk of subsequent psoriasis or psoriatic arthritis development.
This nationwide population-based cohort study revealed that patients with uveitis have an increased risk of subsequent psoriasis or psoriatic arthritis development.
Cardiorespiratory fitness is often impaired following stroke, and peak oxygen consumption (VO2peak) is an important prognostic value of all-cause mortality. The primary objective was to investigate whether functional walk tests assessed in the subacute phase after stroke added value in predicting VO2peak in chronic stroke, in addition to age, sex and functional dependency. Secondary objectives were to investigate associations between daily physical activity and functional walk tests, and with VO2peak in chronic stroke.
This prospective cohort study included eligible participants originally included in the randomized controlled trial Life After Stroke. Functional walk tests, i.e., six-minute walk test (6MWT) and maximal gait speed, were assessed at inclusion and 18 months later. VO2peak [ml/kg/min] was assessed by a cardiopulmonary exercise test on a treadmill 20 months after inclusion. Daily physical activity was measured by a uniaxial accelerometer (activPAL) at 18-month follow-up.
Ninety-two community and severely affected.
6MWT add significant value to the prediction of mean VO2peak in the chronic phase in mild strokes, in combination with age, sex and functional dependency. This prediction model may facilitate clinical decisions and rehabilitation strategies for mildly affected stroke survivors in risk of low levels of VO2peak. Future studies should validate the model in various stages after stroke and in patients moderately and severely affected.The SARS-CoV-2 pandemic is a major global threat that sparked global research efforts. Pre-clinical and biochemical SARS-CoV-2 studies firstly rely on cell culture experiments where the importance of choosing an appropriate cell culture model is often underestimated. We here present a bottom-up approach to identify suitable permissive cancer cell lines for drug screening and virus research. Human cancer cell lines were screened for the SARS-CoV-2 cellular entry factors ACE2 and TMPRSS2 based on RNA-seq data of the Cancer Cell Line Encyclopedia (CCLE). However, experimentally testing permissiveness towards SARS-CoV-2 infection, we found limited correlation between receptor expression and permissiveness. This underlines that permissiveness of cells towards viral infection is determined not only by the presence of entry receptors but is defined by the availability of cellular resources, intrinsic immunity, and apoptosis. Aside from established cell culture infection models CACO-2 and CALU-3, three highly permissive human cell lines, colon cancer cell lines CL-14 and CL-40 and the breast cancer cell line CAL-51 and several low permissive cell lines were identified. Cell lines were characterised in more detail offering a broader choice of non-overexpression in vitro infection models to the scientific community. For some cell lines a truncated ACE2 mRNA and missense variants in TMPRSS2 might hint at disturbed host susceptibility towards viral entry.Recent reclassification of the Klebsiella genus to include Klebsiella variicola, and its association with bacteremia and mortality, has raised concerns. We examined Klebsiella spp. infections among battlefield trauma patients, including occurrence of invasive K. variicola disease. Klebsiella isolates collected from 51 wounded military personnel (2009-2014) through the Trauma Infectious Disease Outcomes Study were examined using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis. K. variicola isolates were evaluated for hypermucoviscosity phenotype by the string test. Patients were severely injured, largely from blast injuries, and all received antibiotics prior to Klebsiella isolation. Multidrug-resistant Klebsiella isolates were identified in 23 (45%) patients; however, there were no significant differences when patients with and without multidrug-resistant Klebsiella were compared. link2 A total of 237 isolates initially identified as K. pneumoniae were analyzed, with 141 clinical isolates associated with infections (remaining were colonizing isolates collected through surveillance groin swabs). Using PCR sequencing, 221 (93%) isolates were confirmed as K. pneumoniae, 10 (4%) were K. variicola, and 6 (3%) were K. quasipneumoniae. Five K. variicola isolates were associated with infections. Compared to K. pneumoniae, infecting K. variicola isolates were more likely to be from blood (4/5 versus 24/134, p = 0.04), and less likely to be multidrug-resistant (0/5 versus 99/134, p less then 0.01). No K. variicola isolates demonstrated the hypermucoviscosity phenotype. Although K. variicola isolates were frequently isolated from bloodstream infections, they were less likely to be multidrug-resistant. Further work is needed to facilitate diagnosis of K. variicola and clarify its clinical significance in larger prospective studies.
To evaluate the accuracy of fully automated liver volume quantification vs. manual quantification using unenhanced as well as enhanced CT-image data as well as two different radiation dose levels and also two image reconstruction kernels.
The local ethics board gave its approval for retrospective data analysis. Automated liver volume quantification in 300 consecutive livers in 164 male and 103 female oncologic patients (64±12y) performed at our institution (between January 2020 and May 2020) using two different dual-energy helicals portal-venous phase enhanced, ref. tube current 300mAs (CARE Dose4D) for tube A (100 kV) and ref. 232mAs tube current for tube B (Sn140kV), slice collimation 0.6mm, reconstruction kernel I30f/1, recon. thickness of 0.6mm and 5mm, 80-100 mL iodine contrast agent 350 mg/mL, (flow 2mL/s) and unenhanced ref. tube current 100mAs (CARE Dose4D) for tube A (100 kV) and ref. 77mAs tube current for tube B (Sn140kV), slice collimation 0.6mm (kernel Q40f) were analyzed. The post-processingconstructions was exactly the same, both for the enhanced as well for the unenhanced image data sets (p> 0.05).
Results of fully automated liver volume quantification are accurate and comparable with those of manual liver volume quantification and the technique seems to be confident even if unenhanced lower-dose CT image data is used.
Results of fully automated liver volume quantification are accurate and comparable with those of manual liver volume quantification and the technique seems to be confident even if unenhanced lower-dose CT image data is used.
Untreated Familial Hypercholesterolemia (FH) leads to premature morbidity and mortality. link3 In France, its epidemiology and management are understudied in ambulatory care. We described the clinical profile, pharmacological management, and clinical outcomes in a French sample of FH patients.
This was a retrospective longitudinal study on patients from The Health Improvement Network (THIN®) database in France, between October 2016-June 2019. Patients ≥18 years, with probable/definite FH based on the Dutch Lipid Clinic Network (DLCN) criteria were included. Baseline characteristics, lipid profile, lipid-lowering therapy (LLT), low-density lipoprotein-cholesterol (LDL-C) goal achievement; and disease management at 6-month of follow-up were analyzed.
116 patients with probable (n = 70)/definite (n = 46) FH were included (mean age57.8±14.0 years; 56.0% women; 9.5% with personal history of cardiovascular events); 90 patients had data available at follow-up. At baseline, 77.6% of patients had LDL-C>190 mg/dL, 2iods and assessment of factors affecting LDL-C management, including lifestyle and diet, are needed.China is the key player in the globalization era and is eliminating its intra-national trade barrier. This process will affect interprovincial CO2 flows. This study recalculates interprovincial CO2 flows in China by using the latest MRIO table and applies a gravity model to assess how market segmentation affects interprovincial CO2 flows. Results show that the total volume of interprovincial embodied CO2 flow did not increase excessively from 2007 to 2012, but the pattern of embodied CO2 flow had changed a lot. Market segmentation significantly decreased the interprovincial embodied CO2 flows in China and within its sub-regions. At interregional level, market segmentation's negative effect was significant between Central and Western China. Other variables such as geographical distance showed a significant negative impact on interprovincial embodied CO2 flow in China. On the basis of our results, we raise some relevant policies to deal with the environmental inequality caused by the decrease in market segmentation.
Homepage: https://www.selleckchem.com/products/yum70.html
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