Mass Spectrometry Advances in Analysis of Glioblastoma.

Some cancers such as glioblastoma (GBM), show minimal response to medical interventions, often only capable of mitigating tumor growth or alleviating symptoms. High metabolic activity in the tumor microenvironment marked by immune responses and hypoxia, is a crucial factor driving tumor progression. The many developments in mass spectrometry (MS) over the last decades have provided a pivotal tool for studying proteins, along with their posttranslational modifications.

Clustering of biphenyl oxamide ions by chiral recognition.

Gels created by self-assembly of small organic molecules are dynamic soft materials that have unique properties and demanding characterization. Four chiral gelators, with two valinol- or leucinoloxamido arms attached to the 2,2'-positions of the proatropisomeric biphenyl group were chosen to show that the electrospray ionization mass spectrometry (ESI-MS) could be used to differentiate the gelation feature of the chiral compounds and also to shed light on the gelation processes. By inspecting the gelation of several solvents, we showed that () proved to be the most efficient gelator, forming the largest observable assemblies in the gas phase.

Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides.

Three new phenanthridine peptide derivatives (, , and ) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions in all three compounds. Computational analysis revealed that compounds alternate between bent and open conformations, highlighting the latter's crucial influence on successful polynucleotide recognition.

Development and deployment of cyclical focal muscle vibration system to improve walking performance in multiple sclerosis.

Vibration, a potent mechanical stimulus for activating muscle spindle primary afferents, may improve gait performance in persons with multiple sclerosis (MS), but has yet to be developed and deployed for multiple leg muscles with application during walking training. This study explored the development of a cyclic focal muscle vibration (FMV) system, and the deployment feasibility to correct MS walking swing phase deficits in order to determine whether this intervention warrants comprehensive study. The system was deployed during twelve, two-hour sessions of walking with cyclic FMV over six weeks.

A Muscle-First, Electromechanical Hybrid Gait Restoration System in People With Spinal Cord Injury.

The development of a hybrid system for people with spinal cord injuries is described. The system includes implanted neural stimulation to activate the user's otherwise paralyzed muscles, an exoskeleton with electromechanical actuators at the hips and knees, and a sensory and control system that integrates both components. We are using a muscle-first approach: The person's muscles are the primary motivator for his/her joints and the motors provide power assistance.

Effect of Joint Friction Compensation on a "Muscle-First" Motor-Assisted Hybrid Neuroprosthesis.

This study assessed the metabolic energy consumption of walking with the external components of a "Muscle-First" Motor Assisted Hybrid Neuroprosthesis (MAHNP), which combines implanted neuromuscular stimulation with a motorized exoskeleton. The "Muscle-First" approach prioritizes generating motion with the wearer's own muscles via electrical stimulation with the actuators assisting on an as-needed basis. The motorized exoskeleton contributes passive resistance torques at both the hip and knee joints of 6Nm and constrains motions to the sagittal plane.

Walking after incomplete spinal cord injury with an implanted neuromuscular electrical stimulation system and a hinged knee replacement: a single-subject study.

Study Design: Single-subject repeated measures study.

Objectives: Neuromuscular electrical stimulation (NMES) can enhance walking for people with partial paralysis from incomplete spinal cord injury (iSCI). This single-subject study documents an individual's experience who both received an experimental implanted NMES system and underwent clinical bilateral hinged total knee arthroplasty (TKA).

Oxygen Consumption While Walking With Multijoint Neuromuscular Electrical Stimulation After Stroke.

This case study evaluated the effect of implanted multijoint neuromuscular electrical stimulation gait assistance on oxygen consumption relative to walking without neuromuscular electrical stimulation after stroke. The participant walked slowly with an asymmetric gait pattern after stroke. He completed repeated 6-min walk tests at a self-selected walking speed with and without hip, knee, and ankle stimulation assistance.

The transformation from 2°-amine to 3°-amine of cyclam ring alters the fragmentation patterns of 1-tosylcytosine-cyclam conjugates.

The novel N-1-sulfonylcytosine-cyclam conjugates 1 and 2 conjugates are ionized by electrospray ionization mass spectrometry (ESI MS) in positive and negative modes (ES and ES ) as singly protonated/deprotonated species or as singly or doubly charged metal complexes. Their structure and fragmentation behavior is examined by collision induced experiments. It was observed that the structure of the conjugate dictated the mode of the ionization: 1 was analyzed in ES mode while 2 in positive mode.

C5-Morpholinomethylation of N1-sulfonylcytosines by a one-pot microwave assisted Mannich reaction.

A fast and efficient route for the introduction of a methylene bridged-amine (morpholinomethyl) functionality in the C5 position of the sulfonylated cytosine nucleobase has been developed. First, novel N1-sulfonylcytosine derivatives 3-6 were prepared by the condensation of silylated cytosine with selected sulfonyl chlorides. They were subsequently transformed to 5-morpholinomethyl-N1-sulfonylcytosine derivatives (8, 12-15) using microwave irradiation.

The Metal Effect on Self-Assembling of Oxalamide Gelators Explored by Mass Spectrometry and DFT Calculations.

Gels formed by self-assembly of small organic molecules are of wide interest as dynamic soft materials with numerous possible applications, especially in terms of nanotechnology for functional and responsive biomaterials, biosensors, and nanowires. Four bis-oxalamides were chosen to show if electrospray ionization mass spectrometry (ESI-MS) could be used as a prediction of a good gelator and also to shed light on the gelation processes. By inspecting the gelation of several solvent, we showed that bis(amino acid)oxalamide 1 proved to be the most efficient, also being able of forming the largest observable assemblies in the gas phase.

Long-Term Performance and User Satisfaction With Implanted Neuroprostheses for Upright Mobility After Paraplegia: 2- to 14-Year Follow-Up.

Objective: To quantify the long-term (>2y) effects of lower extremity (LE) neuroprostheses (NPs) for standing, transfers, stepping, and seated stability after spinal cord injury.

Design: Single-subject design case series with participants acting as their own concurrent controls, including retrospective data review.

Setting: Hospital-based clinical biomechanics laboratory with experienced (>20y in the field) research biomedical engineers, a physical therapist, and medical monitoring review.

Effect of exoskeletal joint constraint and passive resistance on metabolic energy expenditure: Implications for walking in paraplegia.

An important consideration in the design of a practical system to restore walking in individuals with spinal cord injury is to minimize metabolic energy demand on the user. In this study, the effects of exoskeletal constraints on metabolic energy expenditure were evaluated in able-bodied volunteers to gain insight into the demands of walking with a hybrid neuroprosthesis after paralysis. The exoskeleton had a hydraulic mechanism to reciprocally couple hip flexion and extension, unlocked hydraulic stance controlled knee mechanisms, and ankles fixed at neutral by ankle-foot orthoses.

Quantification of free fatty acids in human stratum corneum using tandem mass spectrometry and surrogate analyte approach.

The free fatty acids (FFAs) are one of the major components of the lipids in the stratum corneum (SC), the uppermost layer of the skin. Relative composition of FFAs has been proposed as a biomarker of the skin barrier status in patients with atopic dermatitis (AD). Here, we developed an LC-ESI-MS/MS method for simultaneous quantification of a range of FFAs with long and very long chain length in the SC collected by adhesive tape (D-Squame).

A muscle-driven approach to restore stepping with an exoskeleton for individuals with paraplegia.

Background: Functional neuromuscular stimulation, lower limb orthosis, powered lower limb exoskeleton, and hybrid neuroprosthesis (HNP) technologies can restore stepping in individuals with paraplegia due to spinal cord injury (SCI). However, a self-contained muscle-driven controllable exoskeleton approach based on an implanted neural stimulator to restore walking has not been previously demonstrated, which could potentially result in system use outside the laboratory and viable for long term use or clinical testing. In this work, we designed and evaluated an untethered muscle-driven controllable exoskeleton to restore stepping in three individuals with paralysis from SCI.

Accelerometer-based step initiation control for gait-assist neuroprostheses.

Electrical activation of paralyzed musculature can generate or augment joint movements required for walking after central nervous system trauma. Proper timing of stimulation relative to residual volitional control is critical to usefully affecting ambulation. This study evaluates three-dimensional accelerometers and customized algorithms to detect the intent to step from voluntary movements to trigger stimulation during walking in individuals with significantly different etiologies, mobility limitations, manual dexterities, and walking aids.

A stimulation-driven exoskeleton for walking after paraplegia.

An untethered version of a stimulation-driven exoskeleton was evaluated for its ability to restore walking after paralysis from spinal cord injury. The hybrid neuroprosthesis (HNP) combined a passive variable-constraint exoskeleton for stability and support with functional neuromuscular stimulation (FNS) to contract the paralyzed muscles to drive limb movement. This self-contained HNP was operated by an onboard controller that sampled sensor signals, generated appropriate commands to both the exoskeletal constraints and integrated stimulator, and transmitted data wirelessly via Bluetooth to an off-board computer for real-time monitoring and recording for offline analysis.

Impact of an implanted neuroprosthesis on community ambulation in incomplete SCI.

Objective: Test the effect of a multi-joint control with implanted electrical stimulation on walking after spinal cord injury (SCI).

Design: Single subject research design with repeated measures.

Setting: Hospital-based biomechanics laboratory and user assessment of community use.

Feasibility of Restoring Walking in Multiple Sclerosis with Multichannel Implanted Electrical Stimulation.

A patient with multiple sclerosis-related gait dysfunction was followed over the course of his disease. Despite aggressive treatment, he developed significant weakness in ankle dorsiflexors and hip and knee flexors and was no longer capable of consistently taking a step on his own. With electrical stimulation of hip and knee flexors and ankle dorsiflexors using implanted electrodes, he was able to consistently walk short distances as far as 30 m, thus significantly improving his Expanded Disability Status Scale score.

ESI-MS studies of the non-covalent interactions between biologically important metal ions and N-sulfonylcytosine derivatives.

The aim of this report is to present the electrospray ionization mass spectrometry results of the non-covalent interaction of two biologically active ligands, N-1-(p-toluenesulfonyl)cytosine, 1-TsC, 1 and N-1-methanesulfonylcytosine, 1-MsC, 2 and their Cu(II) complexes Cu(1-TsC-N3) Cl , 3 and Cu(1-MsC-N3) Cl and 4 with biologically important cations: Na , K , Ca , Mg and Zn . The formation of various complex metal ions was observed. The alkali metals Na and K formed clusters because of electrostatic interactions.

Improving Walking with an Implanted Neuroprosthesis for Hip, Knee, and Ankle Control After Stroke.

Objective: The objective of this work was to quantify the effects of a fully implanted pulse generator to activate or augment actions of hip, knee, and ankle muscles after stroke.

Design: The subject was a 64-year-old man with left hemiparesis resulting from hemorrhagic stroke 21 months before participation. He received an 8-channel implanted pulse generator and intramuscular stimulating electrodes targeting unilateral hip, knee, and ankle muscles on the paretic side.

Improving stand-to-sit maneuver for individuals with spinal cord injury.

Background: Users of neuroprostheses employing electrical stimulation (ES) generally complete the stand-to-sit (STS) maneuver with high knee angular velocities, increased upper limb support forces, and high peak impact forces at initial contact with the chair. Controlling the knee during STS descent is challenging in individuals with spinal cord injury (SCI) due to the decreasing joint moment available with increased knee angle in response to ES.

Methods: The goal of this study was to investigate the effects of incorporating either (1) a coupling mechanism that coordinates hip and knee flexion or (2) a mechanism that damps knee motion to keep the knee angular velocity constant during the STS transition.

Mass spectrometry and theoretical studies on N-C bond cleavages in the N-sulfonylamidino thymine derivatives.

The reactivity of new biologically active thymine derivatives substituted with 2-(arylsulfonamidino)ethyl group at N1 and N3 position was investigated in the gas phase using CID experiments (ESI-MS/MS) and by density functional theory (DFT) calculations. Both derivatives show similar chemistry in the negative mode with a retro-Michael addition (Path A(-)) being the most abundant reaction channel, which correlate well with the fluoride induced retro-Michael addition observed in solution. The difference in the fragmentation of N-3 substituted thymine 5 and N-1 substituted thymine 1 in the positive mode relates to the preferred cleavage of the sulfonyl group (m/z 155, Path B) in N-3 isomer and the formation of the acryl sulfonamidine 3 (m/z 309) via Path A in N-1 isomer.