Bentonmichelsen0241
Endothelial cells are among the fundamental building blocks for vascular tissue engineering. However, a clinically viable source of endothelium has continued to elude the field. find more Here, we demonstrate the feasibility of sourcing autologous endothelium from human fat - an abundant and uniquely dispensable tissue that can be readily harvested with minimally invasive procedures. We investigate the challenges underlying the overgrowth of human adipose tissue-derived microvascular endothelial cells by stromal cells to facilitate the development of a reliable method for their acquisition. Magnet-assisted cell sorting strategies are established to mitigate the non-specific uptake of immunomagnetic microparticles, enabling the enrichment of endothelial cells to purities that prevent their overgrowth by stromal cells. This work delineates a reliable method for acquiring human adipose tissue-derived microvascular endothelial cells in large quantities with high purities that can be readily applied in future vascular tissue engineering applications.Neuroscientific studies on the function of the basal ganglia often examine the behavioral performance of patients with movement disorders, such as Parkinson's disease (PD) and dystonia (DT), while simultaneously examining the underlying electrophysiological activity during deep brain stimulation surgery. Nevertheless, to date, there have been no studies comparing the cognitive performance of PD and DT patients during surgery. In this study, we assessed the memory function of PD and DT patients with the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). We also tested their cognitive performance during the surgery using a continuous recognition memory test. The results of the MoCA and MMSE failed to reveal significant differences between the PD and DT patients. Additionally, no significant difference was detected by the intraoperative memory test between the PD and DT patients. The intraoperative memory test scores were highly correlated with the MMSE scores and MoCA scores. Our data suggest that DT patients perform similarly to PD patients in cognitive tests during surgery, and intraoperative memory tests can be used as a quick memory assessment tool during surgery.Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.Terpios hoshinota is a thin encrusting sponge that overgrows live scleractinian corals and it is linked to coral loss in many reefs. However, our knowledge of the species associated with this sponge species is poor. During a periodical survey of T. hoshinota in 2020, we found tiny snails crawling on the sponge in the subtropical waters around Okinawa Island, Japan. We observed egg capsules inside the sponge tissue and veliger larvae released from the egg capsules. Molecular analyses of both the snails and veliger larvae (cytochrome oxidase I, COI) showed that they were identical and belonged to Joculator sp. link2 (family Cerithiopsidae). There was no direct observation of predation on the sponge by this snail; however, to the best of our knowledge, this is the first report on a close association between a snail and the sponge T. hoshinota.Reconfigurable reflective surfaces can alter the propagation environment to improve wireless communication and power transfer. Paramount to this operation-which has attracted much attention recently-is the assumption that the reflective surface has prior knowledge of the propagation environment, for example, the direction/location of the transmitter and the intended receiver(s). To address this need, we propose a reconfigurable reflective metasurface with integrated sensing capabilities. By modifying the tunable meta-atoms constituting the metasurface, we couple small portions of the incident wave to an array of sensing waveguides. As an illustrative example, we demonstrate the ability to use the sampled incident wave to detect its angle of arrival. In addition, we propose and numerically demonstrate the possibility to reduce the required sensors, i.e., the number of radio frequency (RF) chains needed to acquire the sensed signals, by leveraging the inherent metasurface's tunable multiplexing capability. A reconfigurable reflective metasurface with integrated sensing capabilities can benefit wireless communications, wireless power transfer, RF sensing, and smart sensors.It is unknown how sequential drug patterns convey information on a patient's health status and treatment guidelines rarely account for this. Drug-agnostic longitudinal analyses of prescription trajectories in a population-wide setting are needed. In this cohort study, we used 24 years of data (1.1 billion prescriptions) from the Danish prescription registry to model the risk of sequentially redeeming a drug after another. Drug pairs were used to build multistep longitudinal prescription trajectories. These were subsequently used to stratify patients and calculate survival hazard ratios between the stratified groups. The similarity between prescription histories was used to determine individuals' best treatment option. Over the course of 122 million person-years of observation, we identified 9 million common prescription trajectories and demonstrated their predictive power using hypertension as a case. Among patients treated with agents acting on the renin-angiotensin system we identified four groups patients prescribed angiotensin converting enzyme (ACE) inhibitor without change, angiotensin receptor blockers (ARBs) without change, ACE with posterior change to ARB, and ARB posteriorly changed to ACE. In an adjusted time-to-event analysis, individuals treated with ACE compared to those treated with ARB had lower survival probability (hazard ratio, 0.73 [95% CI, 0.64-0.82]; P less then 1 × 10-16). Replication in UK Biobank data showed the same trends. Prescription trajectories can provide novel insights into how individuals' drug use change over time, identify suboptimal or futile prescriptions and suggest initial treatments different from first line therapies. Observations of this kind may also be important when updating treatment guidelines.We assessed whether high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, expressed by an increased TG/HDL-C ratio, predict coronary atherosclerotic disease (CAD) outcomes in patients with stable angina. We studied 355 patients (60 ± 9 years, 211 males) with stable angina who underwent coronary computed tomography angiography (CTA), were managed clinically and followed for 4.5 ± 0.9 years. The primary composite outcome was all-cause mortality and non-fatal myocardial infarction. At baseline, the proportion of males, patients with metabolic syndrome, diabetes and obstructive CAD increased across TG/HDL-C ratio quartiles, together with markers of insulin resistance, hepatic and adipose tissue dysfunction and myocardial damage, with no difference in total cholesterol or LDL-C. At follow-up, the global CTA risk score (HR 1.06, 95% confidence interval (CI) 1.03-1.09, P = 0.001) and the IV quartile of the TG/HDL-C ratio (HR 2.85, 95% CI 1.30-6.26, P less then 0.01) were the only independent predictors of the primary outcome. The TG/HDL-C ratio and the CTA risk score progressed over time despite increased use of lipid-lowering drugs and reduction in LDL-C. In patients with stable angina, high TG and low HDL-C levels are associated with CAD related outcomes independently of LDL-C and treatments.Trial registration. EVINCI study ClinicalTrials.gov NCT00979199, registered September 17, 2009; SMARTool study ClinicalTrials.gov NCT04448691, registered June 26, 2020.Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressively enlarging cysts. Here we elucidate the interplay between oxidative stress, mitochondrial dysfunction, and metabolic derangement using two mouse models of PKD1 mutation, PKD1RC/null and PKD1RC/RC. Mouse kidneys with PKD1 mutation have decreased mitochondrial complexes activity. Targeted proteomics analysis shows a significant decrease in proteins involved in the TCA cycle, fatty acid oxidation (FAO), respiratory complexes, and endogenous antioxidants. Overexpressing mitochondrial-targeted catalase (mCAT) using adeno-associated virus reduces mitochondrial ROS, oxidative damage, ameliorates the progression of PKD and partially restores expression of proteins involved in FAO and the TCA cycle. In human ADPKD cells, inducing mitochondrial ROS increased ERK1/2 phosphorylation and decreased AMPK phosphorylation, whereas the converse was observed with increased scavenging of ROS in the mitochondria. Treatment with the mitochondrial protective peptide, SS31, recapitulates the beneficial effects of mCAT, supporting its potential application as a novel therapeutic for ADPKD.Fluorescence Lifetime Imaging (FLIM) is an intrinsically quantitative method to screen for protein-protein interactions and is frequently used to record the outcome of signal transduction events. link3 With new highly sensitive and photon efficient FLIM instrumentation, the technique also becomes attractive to screen, with high temporal resolution, for fast changes in Förster Resonance Energy Transfer (FRET), such as those occurring upon activation of cell signaling. The second messenger cyclic adenosine monophosphate (cAMP) is rapidly formed following activation of certain cell surface receptors. cAMP is subsequently degraded by a set of phosphodiesterases (PDEs) which display cell-type specific expression and may also affect baseline levels of the messenger. To study which specific PDEs contribute most to cAMP regulation, we knocked down individual PDEs and recorded breakdown rates of cAMP levels following transient stimulation in HeLa cells stably expressing the FRET/FLIM sensor, Epac-SH189. Many hundreds of cells were recorded at 5 s intervals for each condition.