Upper instrumented vertebra pedicle screw loosening following adult spinal deformity surgery: incidence and outcome analysis.

Objective: Surgical correction of adult spinal deformity (ASD) is associated with a high rate of hardware complication that can be challenging to predict. Hardware integrity and alignment after surgery are typically followed with standing radiography, where pedicle screw loosening may be incidentally identified but the clinical significance of which is often unclear. This study aimed to identify the incidence and implications of pedicle screw loosening at the upper instrumented vertebra (UIV) after surgical correction of ASD.

Clearance and transport of amyloid β by peripheral monocytes correlate with Alzheimer's disease progression.

Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer's disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry.

Multi-institutional review of characteristics and management of gunshot wounds to the spine.

Background Context: Gunshot wounds (GSWs) to the vertebral column represent an important cause of morbidity and mortality in the United States, constituting approximately 20% of all spinal injuries. The management of these injuries is an understudied and controversial topic, given its heterogeneity and lack of follow-up data.

Purpose: To characterize the management and follow-up of GSWs to the spine.

Allograft nerve repair to prevent sensorimotor loss after nerve sheath tumor resection.

Acellularized nerve allografts (ANAs) have been developed as substitutes for nerve autograft to promote nerve regeneration after surgical repair. In this video, the authors demonstrate operative techniques for using ANAs to repair potentially functional nerve fascicles during tumor resection. A 67-year-old female with schwannomatosis requested resection of a painful enlarging mass of the left ulnar nerve proximal to the elbow.

Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease.

Introduction: Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions.

Methods: In three stages, a total of 34 leukocyte antigens were examined by flow cytometry immunophenotyping. Data were analyzed by logistic regression and receiver operating characteristic (ROC) analyses.

Topographical Distribution and Phenotype of Resident Meibomian Gland Orifice Immune Cells (MOICs) in Mice and the Effects of Topical Benzalkonium Chloride (BAK).

Meibomian gland orifices (MGOs) are located along the eyelid margin and secrete meibum into the tear film. The profile of resident innate immune cells (ICs) at this site is not well understood. The distribution and phenotype of resident ICs around MGOs in mice was investigated and herein defined as MGO-associated immune cells (MOICs).

P2X7-mediated alteration of membrane fluidity is associated with the late stages of age-related macular degeneration.

We have shown deficits in monocyte phagocytosis from patients with age-related macular degeneration (AMD). Cell membrane fluidity is known to affect phagocytic capacity and leucocyte functionality more generally. Therefore, we examined membrane fluidity of peripheral blood leucocytes in human patients with AMD and in the P2X7 null mouse model of AMD using flow cytometry with a fluorescent probe for fluidity, TMA-DPH.

Identification of Leukocyte Surface P2X7 as a Biomarker Associated with Alzheimer's Disease.

Alzheimer's disease (AD) has shown altered immune responses in the periphery. We studied P2X7 (a proinflammatory receptor and a scavenger receptor) and two integrins, CD11b and CD11c, on the surface of circulating leukocytes and analysed their associations with Aβ-PET, brain atrophy, neuropsychological assessments, and cerebrospinal fluid (CSF) biomarkers. Total 287 age-matched, sex-balanced participants were recruited in a discovery cohort and two validation cohorts through the AIBL study and studied using tri-colour flow cytometry.

Associations of plasma soluble CD22 levels with brain amyloid burden and cognitive decline in Alzheimer's disease.

CD22 has been suggested to contribute to Alzheimer's disease (AD) pathogenesis by inhibiting microglial amyloid β (Aβ) phagocytosis. Soluble CD22 (sCD22) generated by cleavage from cell membranes may be a marker of inflammation and microglial dysfunction; but alterations of sCD22 levels in AD and their correlation with AD biomarkers remain unclear. Plasma sCD22 levels were measured in cognitively normal non-AD participants and patients with preclinical AD and AD dementia from a Chinese cohort and the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing.

Flow cytometry identifies an early stage of platelet apoptosis produced by agonists of the P2X1 and P2X7 receptors.

Platelets express P2X1 receptors and our data also show the expression of P2X7 receptors. We studied the role of both receptors in platelet apoptosis by incubation of PRP with P2X agonists, then centrifuged to remove viable platelets, and analyzed the supernatant by flow cytometry to identify a sparse platelet-derived population that stained with MitoTracker dyes and CD41. BzATP, a potent agonist of P2X receptors, and ABT737, an activator of intrinsic apoptosis, produced altered platelets that stained moderately for annexin V and corresponded to an early stage apoptotic platelet (ESAP).

Posterior Lumbar Facet Replacement and Arthroplasty.

There is an ongoing desire for the development of motion-preserving facet replacement devices as an alternative to rigid fixation in hopes of better preserving the natural kinematics of the lumbar spine. Theoretically, such a construct would simultaneously address pain associated with spinal instability and prevent abnormal load distribution and adjacent segment degeneration. Several such devices have been developed including the Anatomic Facet Replacement System, the Total Facet Arthroplasty System, and the Total Posterior Arthroplasty System.

Neurology trial registrations on ClinicalTrials.gov between 2007 and 2018: A cross-sectional analysis of characteristics, early discontinuation, and results reporting.

Background: Increasing neurological disease burden and advancing treatment options require clinical trials to expand the evidence base of clinical care. We aimed to characterize neurology clinical trials registered between October 2007 and April 2018 and identify features associated with early discontinuation and results reporting.

Methods: We compared 16,994 neurology (9.

Regulation of the Acute Sickness Response by the P2RX7 Receptor.

Background: The acute sickness response to infection is a stereotyped set of illness manifestations initiated by proinflammatory signals in the periphery but mediated centrally. P2RX7 is a highly polymorphic gene encoding an ATP-gated cationic pore, widely expressed on immune cells and the brain, and regulating the NLRP3 inflammasome, as well as diverse neural functions.

Methods: Associations between P2RX7 genotype, pore activity, and illness manifestations were examined in a cohort with acute viral and bacterial infections (n = 484).

Cell Therapy for Stroke: A Mechanistic Analysis.

Cell therapy has been widely recognized as a promising strategy to enhance recovery in stroke survivors. However, despite an abundance of encouraging preclinical data, successful clinical translation remains elusive. As the field continues to advance, it is important to reexamine prior clinical trials in the context of their intended mechanisms, as this can inform future preclinical and translational efforts.

Erratum: Fructose Promotes Uptake and Activity of Oligonucleotides with Different Chemistries in a Context-Dependent Manner in Mice.

[This corrects the article DOI: 10.1038/mtna.2016.

A Primer on Human Brain Organoids for the Neurosurgeon.

Human brain organoids emerged in 2013 as a technology that, unlike prior in Vitro neural models, recapitulates brain development with a high degree of spatial and temporal fidelity. As the platform matured with more accurate reproduction of cerebral architecture, brain organoids became increasingly valuable for studying both normal cortical neurogenesis and a variety of congenital human brain disorders. While the majority of research utilizing human brain organoids has been in the realm of basic science, clinical applications are forthcoming.

A P2RX7 single nucleotide polymorphism haplotype promotes exon 7 and 8 skipping and disrupts receptor function.

P2X7 is an ATP-gated membrane ion channel that is expressed by multiple cell types. Brief exposure to ATP induces the opening of a nonselective cation channel; while repeated or prolonged exposure induces formation of a transmembrane pore. This process may be partially regulated by alternative splicing of full-length P2RX7A pre-mRNA, producing isoforms that delete or retain functional domains.

Assays to Measure Purinoceptor Pore Dilation.

The P2X7 receptor is a classic purinoceptor/ion channel. After activated by ATP, it opens a cation selective channel, which dilates to a large pore over tens of seconds, allowing the entry of big molecules. This unique feature is often used to evaluate this receptor's function with DNA-binding dyes (MW 300-400 Da), such as ethidium bromide and Yo-Pro-1.

Hexose Potentiates Peptide-Conjugated Morpholino Oligomer Efficacy in Cardiac Muscles of Dystrophic Mice in an Age-Dependent Manner.

Insufficient delivery of oligonucleotides to muscle and heart remains a barrier for clinical implementation of antisense oligonucleotide (AO)-mediated exon-skipping therapeutics in Duchenne muscular dystrophy (DMD), a lethal monogenic disorder caused by frame-disrupting mutations in the DMD gene. We previously demonstrated that hexose, particularly an equal mix of glucose:fructose (GF), significantly enhanced oligonucleotide delivery and exon-skipping activity in peripheral muscles of mdx mice; however, its efficacy in the heart remains limited. Here we show that co-administration of GF with peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO, namely, BMSP-PMO) induced an approximately 2-fold higher level of dystrophin expression in cardiac muscles of adult mdx mice compared to BMSP-PMO in saline at a single injection of 20 mg/kg, resulting in evident phenotypic improvement in dystrophic mdx hearts without any detectable toxicity.

P2X7 receptor signaling during adult hippocampal neurogenesis.

Neurogenesis is a persistent and essential feature of the adult mammalian hippocampus. Granular neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation of new memories. Regulation of hippocampal neurogenesis is complex and multifaceted, and numerous signaling pathways converge to modulate cell proliferation, apoptosis, and clearance of cellular debris, as well as synaptic integration of newborn immature neurons.

Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells.

Live-cell flow cytometry is increasingly used among cell biologists to quantify biological processes in a living cell culture. This protocol describes a method whereby live-cell flow cytometry is extended upon to analyze the multiple functions of P2X7 receptor activation in real-time. Using a time module installed on a flow cytometer, live-cell functionality can be assessed and plotted over a given time period to explore the kinetics of calcium influx, transmembrane pore formation, and phagocytosis.

Targeting P2X7 receptors as a means for treating retinal disease.

Age-related macular degeneration and glaucoma are the commonest causes of irreversible vision loss in industrialized countries. The purine ATP is known to regulate a range of cellular functions in the retina via its action on P2 receptors, especially the P2X7 receptor. Although agents that attenuate P2X7 receptor function have been in development for many years, no compound is currently approved for the treatment of eye disease.