Standardized workflow for multiplexed charge detection mass spectrometry on orbitrap analyzers.

Individual ion mass spectrometry (IMS) is the Orbitrap-based extension of the niche mass spectrometry technique known as charge detection mass spectrometry (CDMS). While traditional CDMS analysis is performed on in-house-built instruments such as the electrostatic linear ion trap, IMS extends CDMS analysis to Orbitrap analyzers, allowing charge detection analysis to be available to the scientific community at large. IMS simultaneously measures the mass-to-charge ratios (m/z) and charges (z) of hundreds to thousands of individual ions within one acquisition event, creating a spectral output directly into the mass domain without the need for further spectral deconvolution.

Docosahexaenoic Acid-Infused Core-Shell Fibrous Membranes for Prevention of Epidural Adhesions.

Avoiding epidural adhesion following spinal surgery can reduce clinical discomfort and complications. As the severity of epidural adhesion is positively correlated with the inflammatory response, implanting a fibrous membrane after spinal surgery, which can act as a physical barrier to prevent adhesion formation while simultaneously modulates postoperative inflammation, is a promising approach to meet clinical needs. Toward this end, we fabricated an electrospun core-shell fibrous membrane (CSFM) based on polylactic acid (PLA) and infused the fiber core region with the potent natural anti-inflammatory compound docosahexaenoic acid (DHA).

Corrigendum: Raised plasma neurofilament light protein levels are associated with abnormal MRI outcomes in newborns undergoing therapeutic hypothermia.

[This corrects the article DOI: 10.3389/fneur.2018.

Correction: The Omega-3 Fatty Acid Eicosapentaenoic Acid Accelerates Disease Progression in a Model of Amyotrophic Lateral Sclerosis.

[This corrects the article DOI: 10.1371/journal.pone.

Improved Signal Processing for Mass Shifting Ions in Charge Detection Mass Spectrometry.

The quality of data in charge detection mass spectrometry depends on accurate determination of ion charge. While the method of selective temporal overview of resonant ions (STORI) has proven to be highly enabling for determining the charge of ions that survive for variable amounts of time, it assumes that the ion frequency exactly matches the frequency being used in the calculation. Any mismatches result in low charge estimates.

Trimethylamine N-Oxide as a Mediator Linking Peripheral to Central Inflammation: An In Vitro Study.

In this study, the plausible role of trimethylamine N-oxide (TMAO), a microbiota metabolite, was investigated as a link between peripheral inflammation and the inflammation of the central nervous system using different cell lines. TMAO treatment favored the differentiation of adipocytes from preadipocytes (3T3-L1 cell line). In macrophages (RAW 264.

Serum amyloid P component accumulates and persists in neurones following traumatic brain injury.

The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to A amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of A fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content.

Newborns with Favourable Outcomes after Perinatal Asphyxia Have Upregulated Glucose Metabolism-Related Proteins in Plasma.

Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality globally. Although mild therapeutic hypothermia (TH) may improve outcomes in selected babies, the mechanism of action is not fully understood. A proteomics discovery study was carried out to analyse proteins in the plasma of newborns with HIE.

Long-chain omega-3 polyunsaturated fatty acids are reduced in neonates with substantial brain injury undergoing therapeutic hypothermia after hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Although therapeutic hypothermia is an effective treatment, substantial chronic neurological impairment often persists. The long-chain omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, offer therapeutic potential in the post-acute phase.

Dynamic Data-Independent Acquisition Mass Spectrometry with Real-Time Retrospective Alignment.

Data-independent acquisition (DIA) mass spectrometry has grown in popularity in recent years, because of the reproducibility and quantitative rigor of a systematic tandem mass spectrometry (MS/MS) sampling method. However, traditional DIA methods may spend valuable instrument time acquiring MS/MS spectra with no usable information in them, affecting sensitivity and quantitative performance. We developed a DIA strategy that dynamically adjusts the MS/MS windows during the chromatographic separation.

Correlation between initial tumor enlargement and magnetic resonance imaging characteristics following linear accelerator-based stereotactic radiosurgery for acoustic neuromas.

Background: Initial tumor enlargement (or pseudoprogression) instead of true tumor progression is a common phenomenon in patients with acoustic neuromas who are treated with stereotactic radiosurgery (SRS). This phenomenon can affect clinical decision-making and patient management. This study assessed the correlation between initial tumor enlargement and magnetic resonance imaging characteristics in patients with acoustic neuromas who were treated with linear accelerator (LINAC)-based SRS.

Advances in Visualizing Microglial Cells in Human Central Nervous System Tissue.

Neuroinflammation has recently been identified as a fundamentally important pathological process in most, if not all, CNS diseases. The main contributor to neuroinflammation is the microglia, which constitute the innate immune response system. Accurate identification of microglia and their reactivity state is therefore essential to further our understanding of CNS pathophysiology.

The Expression of Active CD11b Monocytes in Blood and Disease Progression in Amyotrophic Lateral Sclerosis.

Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis.

Characterisation of Severe Traumatic Brain Injury Severity from Fresh Cerebral Biopsy of Living Patients: An Immunohistochemical Study.

Traumatic brain injury (TBI) is an extremely complex disease and current systems classifying TBI as mild, moderate, and severe often fail to capture this complexity. Neuroimaging cannot resolve the cellular and molecular changes due to lack of resolution, and post-mortem tissue examination may not adequately represent acute disease. Therefore, we examined the cellular and molecular sequelae of TBI in fresh brain samples and related these to clinical outcomes.

Co-Delivery of Docosahexaenoic Acid and Brain-Derived Neurotropic Factor from Electrospun Aligned Core-Shell Fibrous Membranes in Treatment of Spinal Cord Injury.

To restore lost functions while repairing the neuronal structure after spinal cord injury (SCI), pharmacological interventions with multiple therapeutic agents will be a more effective modality given the complex pathophysiology of acute SCI. Toward this end, we prepared electrospun membranes containing aligned core-shell fibers with a polylactic acid (PLA) shell, and docosahexaenoic acid (DHA) or a brain-derived neurotropic factor (BDNF) in the core. The controlled release of both pro-regenerative agents is expected to provide combinatory treatment efficacy for effective neurogenesis, while aligned fiber topography is expected to guide directional neurite extension.

Alterations in the Stool Microbiome in Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy.

Background: Hypoxic-ischemic encephalopathy (HIE) is associated with brain injury in newborns and may lead to disability or death. Mild therapeutic hypothermia (TH) is an effective neuroprotective intervention and an established standard of care in western countries. The gut microbiome, the genomic and physicochemical contribution of the gut microbiota, serves important functions and is increasingly recognized as a major influencer on development.

Lipid Profiles from Dried Blood Spots Reveal Lipidomic Signatures of Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is associated with perinatal brain injury, which may lead to disability or death. As the brain is a lipid-rich organ, various lipid species can be significantly impacted by HIE and these correlate with specific changes to the lipidomic profile in the circulation. Objective: To investigate the peripheral blood lipidomic signature in dried blood spots (DBS) from newborns with HIE.

Neuronal let-7b-5p acts through the Hippo-YAP pathway in neonatal encephalopathy.

Despite increasing knowledge on microRNAs, their role in the pathogenesis of neonatal encephalopathy remains to be elucidated. Herein, we identify let-7b-5p as a significant microRNA in neonates with moderate to severe encephalopathy from dried blood spots using next generation sequencing. Validation studies using Reverse Transcription and quantitative Polymerase Chain Reaction on 45 neonates showed that let-7b-5p expression was increased on day 1 in neonates with moderate to severe encephalopathy with unfavourable outcome when compared to those with mild encephalopathy.

Impact of Diabetic Hyperglycemia on Clinical Outcomes in Patients with Diabetes Mellitus Following Traumatic Brain Injury.

Aim: To identify the effect of patients with diabetes mellitus (DM) with traumatic brain injury (TBI) in Taiwan.

Material And Methods: Data from the trauma registry in Chang Gung Memorial Hospital, Linkou, Taiwan were collected and reviewed. Several clinical characteristics and outcomes were extracted and analyzed.

Alleviation of neuropathic pain by over-expressing a soluble colony-stimulating factor 1 receptor to suppress microgliosis and macrophage accumulation.

Microglial proliferation and activation and macrophage accumulation are implicated in neuropathic pain development. In this study, we aim to suppress microgliosis and macrophage accumulation by over-expressing a non-functional soluble colony stimulating factor-1 receptor (sCSF1R) using an adeno-associated virus 9 vector (AAV9). AAV9/sCSF1R and the control vector AAV9/GFP were intrathecally administered into the lumbar spine of adult C57BL/6 mice.

Isotopic Resolution of Protein Complexes up to 466 kDa Using Individual Ion Mass Spectrometry.

Native mass spectrometry involves transferring large biomolecular complexes into the gas phase, enabling the characterization of their composition and stoichiometry. However, the overlap in distributions created by residual solvation, ionic adducts, and post-translational modifications creates a high degree of complexity that typically goes unresolved at masses above ∼150 kDa. Therefore, native mass spectrometry would greatly benefit from higher resolution approaches for intact proteins and their complexes.

Raised Plasma Neurofilament Light Protein Levels After Rewarming Are Associated With Adverse Neurodevelopmental Outcomes in Newborns After Therapeutic Hypothermia.

To determine the predictive value of plasma neurofilament light protein (NfL) as a prognostic marker for outcomes in babies who have undergone therapeutic hypothermia (TH) for hypoxic ischemic encephalopathy (HIE). NfL levels from three groups of term newborns were compared: (1) those with mild HIE who did not receive TH, (2) newborns treated with TH who had minimal or no brain injury on MRI, and (3) newborns treated with TH who had substantial brain injury on MRI. Follow-up outcomes were collected from 18 months onward.