Twelve-month results from a randomized controlled trial comparing differential target multiplexed spinal cord stimulation and conventional spinal cord stimulation in subjects with chronic refractory axial low back pain not eligible for spine surgery.

Background: Successful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1).

Methods: This is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States.

Improvements in Therapy Experience With Evoked Compound Action Potential Controlled, Closed-Loop Spinal Cord Stimulation-Primary Outcome of the ECHO-MAC Randomized Clinical Trial.

Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain. However, over- or underdelivery of the SCS may occur because the spacing between the stimulating electrodes and the spinal cord is not fixed; spacing changes with motion and postural shifts may result in variable delivery of the SCS dose and, in turn, a suboptimal therapy experience for the patient. The evoked compound action potential (ECAP)-a measure of neural activation-may be used as a control signal to adapt SCS parameters in real time to compensate for this variability.

Differential Target Multiplexed Spinal Cord Stimulation for the Treatment of Chronic Intractable Upper Limb Pain: 12-Month Results From a Prospective, Multicenter Study.

Objectives: This prospective, open-label, single-arm, multicenter study evaluated the use of differential target multiplexed (DTM) spinal cord stimulation (SCS) therapy for chronic upper limb pain (ULP).

Materials And Methods: A total of 58 candidates for SCS who had chronic ULP were enrolled at 11 sites in the USA. The safety and effectiveness of DTM SCS for treating chronic intractable ULP were evaluated over 12 months.

µPhos: a scalable and sensitive platform for high-dimensional phosphoproteomics.

Mass spectrometry has revolutionized cell signaling research by vastly simplifying the analysis of many thousands of phosphorylation sites in the human proteome. Defining the cellular response to perturbations is crucial for further illuminating the functionality of the phosphoproteome. Here we describe µPhos ('microPhos'), an accessible phosphoproteomics platform that permits phosphopeptide enrichment from 96-well cell culture and small tissue amounts in <8 h total processing time.

Interplay between Mg and Ca at multiple sites of the ryanodine receptor.

RyR1 is an intracellular Ca channel important in excitable cells such as neurons and muscle fibers. Ca activates it at low concentrations and inhibits it at high concentrations. Mg is the main physiological RyR1 inhibitor, an effect that is overridden upon activation.

Spatial distribution of selenium-mercury in Arctic seabirds.

Mercury (Hg) is a metallic trace element toxic for humans and wildlife that can originate from natural and anthropic sources. Hg spatial gradients have been found in seabirds from the Arctic and other oceans, suggesting contrasting toxicity risks across regions. Selenium (Se) plays a protective role against Hg toxicity, but its spatial distribution has been much less investigated than that of Hg.

Effects of cooling on thyroid hormone secretion and growth of eastern bluebird (Sialia sialis) nestlings.

Achieving endothermic homeothermy is a critical aspect of avian development. In pre-homeothermic altricial nestlings, variation in parental brooding behavior results in variable exposure of nestlings to cooling, with consequences for the developing endocrine system. Nestlings facing repeated cooling challenges may benefit from upregulation of thyroid hormone secretion, allowing for earlier onset of thermoregulatory capability to mitigate the potentially negative effects of exposure to non-optimal temperatures during development.

Peptide collision cross sections of 22 post-translational modifications.

Recent advances have rekindled the interest in ion mobility as an additional dimension of separation in mass spectrometry (MS)-based proteomics. Ion mobility separates ions according to their size and shape in the gas phase. Here, we set out to investigate the effect of 22 different post-translational modifications (PTMs) on the collision cross section (CCS) of peptides.

Challenges in using transcriptome data to study the c-di-GMP signaling network in clinical isolates.

In the type strain PA14, 40 genes are known to encode for diguanylate cyclases (DGCs) and/or phosphodiesterases (PDEs), which modulate the intracellular pool of the nucleotide second messenger c-di-GMP. While in general, high levels of c-di-GMP drive the switch from highly motile phenotypes towards a sessile lifestyle, the different c-di-GMP modulating enzymes are responsible for smaller and in parts nonoverlapping phenotypes. In this study, we sought to utilize previously recorded gene expression datasets on 414 clinical isolates to uncover transcriptional changes as a result of a high expression of genes encoding DGCs.

Evoked compound action potentials during spinal cord stimulation: effects of posture and pulse width on signal features and neural activation within the spinal cord.

Evoked compound action potential (ECAP) recordings have emerged as a quantitative measure of the neural response during spinal cord stimulation (SCS) to treat pain. However, utilization of ECAP recordings to optimize stimulation efficacy requires an understanding of the factors influencing these recordings and their relationship to the underlying neural activation.We acquired a library of ECAP recordings from 56 patients over a wide assortment of postures and stimulation parameters, and then processed these signals to quantify several aspects of these recordings (e.

Selenium-binding protein 1 (SELENBP1) is a copper-dependent thiol oxidase.

Selenium-binding protein 1 (SELENBP1) was reported to act as a methanethiol oxidase (MTO) in humans, catalyzing the conversion of methanethiol to hydrogen peroxide, hydrogen sulfide and formaldehyde. Here, we identify copper ions as essential to this novel MTO activity. Site-directed mutagenesis of putative copper-binding sites in human SELENBP1 produced as recombinant protein in E.

A network of DZF proteins controls alternative splicing regulation and fidelity.

Proteins containing DZF (domain associated with zinc fingers) modules play important roles throughout gene expression, from transcription to translation. Derived from nucleotidyltransferases but lacking catalytic residues, DZF domains serve as heterodimerization surfaces between DZF protein pairs. Three DZF proteins are widely expressed in mammalian tissues, ILF2, ILF3 and ZFR, which form mutually exclusive ILF2-ILF3 and ILF2-ZFR heterodimers.

Prognostic Value of Machine Learning-based Time-to-Event Analysis Using Coronary CT Angiography in Patients with Suspected Coronary Artery Disease.

Purpose: To assess the long-term prognostic value of a machine learning (ML) approach in time-to-event analyses incorporating coronary CT angiography (CCTA)-derived and clinical parameters in patients with suspected coronary artery disease.

Materials And Methods: The retrospective analysis included patients with suspected coronary artery disease who underwent CCTA between October 2004 and December 2017. Major adverse cardiovascular events were defined as the composite of all-cause death, myocardial infarction, unstable angina, or late revascularization (>90 days after index scan).

Convolutional neural networks on risk stratification of patients with suspected coronary artery disease undergoing coronary computed tomography angiography.

To assess the prognostic value of convolutional neural networks (CNN) on coronary computed tomography angiography (CCTA) in comparison to conventional computed tomography (CT) reporting and clinical risk scores. 5468 patients who underwent CCTA with suspected coronary artery disease (CAD) were included. Primary endpoint was defined as a composite of all-cause death, myocardial infarction, unstable angina or late revascularization (> 90 days after CCTA).

Telomere length correlates with physiological and behavioural responses of a long-lived seabird to an ecologically relevant challenge.

Determinants of individual variation in reallocation of limited resources towards self-maintenance versus reproduction are not well known. We tested the hypothesis that individual heterogeneity in long-term 'somatic state' (i) explains variation in endocrine and behavioural responses to environmental challenges, and (ii) is associated with variation in strategies for allocating to self-maintenance versus reproduction. We used relative telomere length as an indicator of somatic state and experimentally generated an abrupt short-term reduction of food availability (withdrawal of food supplementation) for free-living seabirds (black-legged kittiwakes, ).

Mercury contamination and potential health risks to Arctic seabirds and shorebirds.

Since the last Arctic Monitoring and Assessment Programme (AMAP) effort to review biological effects of mercury (Hg) on Arctic biota in 2011 and 2018, there has been a considerable number of new Arctic bird studies. This review article provides contemporary Hg exposure and potential health risk for 36 Arctic seabird and shorebird species, representing a larger portion of the Arctic than during previous AMAP assessments now also including parts of the Russian Arctic. To assess risk to birds, we used Hg toxicity benchmarks established for blood and converted to egg, liver, and feather tissues.

Transcatheter implantation of covered stents serving as extravascular conduits-Proof of a CT-based approach in three cases.

Background: Covered stents perform similar to surgically implanted conduits, although the stents work inside of vessels. We present a computed tomography (CT)-based workflow for the implantation of covered stents as extravascular conduits.

Methods: We selected three different use cases: 1.

Cooling increases corticosterone deposition in feathers of eastern bluebird chicks.

Exposure to noxious stimuli early in life can both activate and shape the development of the hypothalamic-pituitary-adrenal (HPA) axis in birds and other vertebrates, with the potential for lifelong consequences. Studies assessing early HPA axis activation often rely on collection of blood samples to evaluate circulating glucocorticoid levels. However, blood sampling in small altricial young is invasive, limited by animal size, and not sufficient to provide detailed information about hormone exposure over protracted periods of time.

Quantitative meta-analysis reveals no association between mercury contamination and body condition in birds.

Mercury contamination is a major threat to the global environment, and is still increasing in some regions despite international regulations. The methylated form of mercury is hazardous to biota, yet its sublethal effects are difficult to detect in wildlife. Body condition can vary in response to stressors, but previous studies have shown mixed effects of mercury on body condition in wildlife.

A Clinical Feasibility Study of Spinal Evoked Compound Action Potential Estimation Methods.

Objectives: Spinal cord stimulation (SCS) is a treatment for chronic neuropathic pain. Recently, SCS has been enhanced further with evoked compound action potential (ECAP) sensing. Characteristics of the ECAP, if appropriately isolated from concurrent stimulation artifact (SA), may be used to control, and aid in the programming of, SCS systems.

A New Direction for Closed-Loop Spinal Cord Stimulation: Combining Contemporary Therapy Paradigms with Evoked Compound Action Potential Sensing.

Spinal cord stimulation (SCS) utilizes the delivery of mild electrical pulses via epidural electrodes placed on the dorsal side of the spinal cord, typically to treat chronic pain. The first clinical use of SCS involved the delivery of paresthesia inducing, low-frequency waveforms to the neural targets corresponding to the painful areas. Contemporary SCS therapies now leverage novel therapeutic pathways to limit paresthesia and deliver superior clinical outcomes.

Radiation Dose and Image Quality of a High-Pitch Prospective Spiral First Approach in Coronary Computed Tomography Angiography (CCTA).

To investigate a high-pitch spiral first (HPSF) approach for coronary computed tomography angiography (CCTA) in an unselected patient cohort and compare diagnostic yield and radiation exposure to CCTAs acquired via conventional, non-high-pitch spiral first (NHPSF) scan regimes. All consecutive patients from 1 January 2015 to 31 December 2017 were included. Two investigation protocols (HPSF/NHPSF) were used with the aim to achieve diagnostic image quality of all coronary segments.