Antioxidant Status in the Soleus Muscle of Sprague-Dawley Rats in Relation to Duodenal-Jejunal Omega Switch and Different Dietary Patterns

Background. Obesity and chronic ingestion of lipid-rich meals are related to an enhanced oxidative stress (OS). Aims. To examine the influence of duodenal-jejunal omega switch surgery in combination with different diets on the antioxidative status in the soleus muscle of rats. Methods. After 8 weeks on a high-fat diet (HF) or control diet (CD), rats underwent duodenal-jejunal omega switch (DJOS) or SHAM (control) surgery. After surgery, for the next 8 weeks, half of DJOS/SHAM animals were kept on the same diet as before, and half had a changed diet. The total superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR) activity as well as malondialdehyde (MDA) concentration were measured in the soleus of rats. Results. CAT and GPx activity were significantly lower after DJOS surgery versus SHAM, regardless of the type of diet. The activity of CAT, SOD, GR, CuZnSOD, and GPx was altered in the CD/HF or HF/CD groups. After DJOS, the lowest muscle concentration of MDA was observed in the CD/CD group and the highest in CD/HF. Conclusions: DJOS surgery significantly decreases the antioxidative system in soleus muscles of rats. CD/HF and HF/CD dietary patterns lead to an increase in antioxidative activity, while remaining on unchanged diet (CD or HF) is associated with a reduced oxidative stress

Imaging Molecular Structure through Femtosecond Photoelectron Diffraction on Aligned and Oriented Gas-Phase Molecules

This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray Free-Electron Laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and dissociating, laseraligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.Comment: 24 pages, 10 figures, Faraday Discussions 17

Machine learning predicts cardiovascular events in patients with diabetes: The Silesia Diabetes-Heart Project.

We aimed to develop a machine learning (ML) model for predicting cardiovascular (CV) events in patients with diabetes (DM). This was a prospective, observational study where clinical data of patients with diabetes hospitalized in the diabetology center in Poland (years 2015 - 2020) were analyzed using ML. The occurrence of new CV events following discharge was collected in the follow-up time for up to 5 years and 9 months. An end-to-end ML technique which exploits the neighborhood component analysis for elaborating discriminative predictors, followed by a hybrid sampling/boosting classification algorithm, multiple logistic regression, or unsupervised hierarchical clustering was proposed. In 1735 patients with diabetes (53% female), there were 150 (8.65%) ones with a new CV event in the follow-up. Twelve most discriminative patients' parameters included coronary artery disease, heart failure, peripheral artery disease, stroke, diabetic foot disease, chronic kidney disease, eosinophil count, serum potassium level, and being treated with clopidogrel, heparin, proton pump inhibitor, and loop diuretic. Utilizing those variables resulted in the area under the receiver operating characteristic curve (AUC) ranging from 0.62 (95% Confidence Interval [CI] 0.56-0.68, p<0.01) to 0.72 (95%CI 0.66-0.77, p<0.01) across five non-overlapping test folds, whereas multiple logistic regression correctly determined 111/150 (74.00%) high-risk patients, and 989/1585 (62.40%) low-risk patients, resulting in 1100/1735 (63.40%) correctly classified patients (AUC: 0.72, 95%CI 0.66-0.77). ML algorithms can identify patients with diabetes at a high risk of new CV events based on a small number of interpretable and easy-to-obtain patients' parameters

Observation of a single protein by ultrafast X-ray diffraction

The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many. It was one of the arguments for building X-ray free-electron lasers. According to theory1, the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier, and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably explodes2. This was first demonstrated on biological samples a decade ago on the giant mimivirus3. Since then a large collaboration4 has been pushing the limit of the smallest sample that can be imaged5,6. The ability to capture snapshots on the timescale of atomic vibrations, while keeping the sample at room temperature, may allow probing the entire conformational phase space of macromolecules. Here we show the first observation of an X-ray diffraction pattern from a single protein, that of Escherichia coli GroEL which at 14 nm in diameter7 is the smallest biological sample ever imaged by X-rays, and demonstrate that the concept of diffraction before destruction extends to single proteins. From the pattern, it is possible to determine the approximate orientation of the protein. Our experiment demonstrates the feasibility of ultrafast imaging of single proteins, opening the way to single-molecule time-resolved studies on the femtosecond timescale

Robot-assisted image-guided transcranial magnetic stimulation for somatotopic mapping of the motor cortex: a clinical pilot study

Shape and exact location of motor cortical areas varies among individuals. The exact knowledge of these locations is crucial for planning of neurosurgical procedures. In this study, we have used robot-assisted image-guided transcranial magnetic stimulation (Ri-TMS) to elicit MEP response recorded for individual muscles and reconstruct functional motor maps of the primary motor cortex

Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser

Citation: Ekeberg, T., Svenda, M., Seibert, M. M., Abergel, C., Maia, F. R. N. C., Seltzer, V., . . . Hajdu, J. (2016). Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser. Scientific Data, 3. doi:10.1038/sdata.2016.60Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial

Background: Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. Methods: This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30–59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. Findings: Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of −1·0 percentage point (SE 0·1; −11 mmol/mol [SE 0·8]) vs −0·2 percentage points (SE 0·1; −2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: −0·8 percentage points, 95% CI −1·0 to −0·6;