Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight.

Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station.

A RORγt cell instructs gut microbiota-specific T cell differentiation.

The mutualistic relationship of gut-resident microbiota and the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a largely non-aggressive immune cell compartment. The consequences of disturbing this balance include proximal inflammatory conditions, such as Crohn's disease, and systemic illnesses. This equilibrium is achieved in part through the induction of both effector and suppressor arms of the adaptive immune system.

Tuning immunity through tissue mechanotransduction.

Immune responses are governed by signals from the tissue microenvironment, and in addition to biochemical signals, mechanical cues and forces arising from the tissue, its extracellular matrix and its constituent cells shape immune cell function. Indeed, changes in biophysical properties of tissue alter the mechanical signals experienced by cells in many disease conditions, in inflammatory states and in the context of ageing. These mechanical cues are converted into biochemical signals through the process of mechanotransduction, and multiple pathways of mechanotransduction have been identified in immune cells.

Targeting IFN-λ Signaling Promotes Recovery from Central Nervous System Autoimmunity.

Type III IFNs (IFNLs) are newly discovered cytokines, acting at epithelial and other barriers, that exert immunomodulatory functions in addition to their primary roles in antiviral defense. In this study, we define a role for IFNLs in maintaining autoreactive T cell effector function and limiting recovery in a murine model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis. Genetic or Ab-based neutralization of the IFNL receptor (IFNLR) resulted in lack of disease maintenance during experimental autoimmune encephalomyelitis, with loss of CNS Th1 effector responses and limited axonal injury.

SARS-CoV-2, COVID-19 and the Ageing Immune System.

The coronavirus disease 2019 (COVID-19) pandemic is a global health threat with particular risk for severe disease and death in older adults and in adults with age-related metabolic and cardiovascular disease. Recent advances in the science of ageing have highlighted how ageing pathways control not only lifespan but also healthspan, the healthy years of life. Here, we discuss the ageing immune system and its ability to respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions.

T follicular helper (T) cells are critical in adaptive immune responses to pathogens and vaccines; however, what drives the initiation of their developmental program remains unclear. Studies suggest that a T cell antigen receptor (TCR)-dependent mechanism may be responsible for the earliest T cell-fate decision, but a critical aspect of the TCR has been overlooked: tonic TCR signaling. We hypothesized that tonic signaling influences early T cell development.

Tonic TCR Signaling Inversely Regulates the Basal Metabolism of CD4 T Cells.

The contribution of self-peptide-MHC signaling in CD4 T cells to metabolic programming has not been definitively established. In this study, we employed LLO118 and LLO56, two TCRtg CD4 T cells that recognize the same epitope. We previously have shown that LLO56 T cells are highly self-reactive and respond poorly in a primary infection, whereas LLO118 cells, which are less self-reactive, respond well during primary infection.

Cysteine Trisulfide Protects from Electrophile-Induced Death through the Generation of Cysteine Hydropersulfide.

Hydropersulfide and polysulfide species have recently been shown to elicit a wide variety of biological and physiological responses. In this study, we examine the effects of cysteine trisulfide (Cys-SSS-Cys; also known as thiocystine) treatment on . Previous studies in mammalian cells have shown that Cys-SSS-Cys treatment results in protection from the electrophiles.

Characteristics of Spontaneous Spinal Cord Infarction and Proposed Diagnostic Criteria.

Importance: Spinal cord infarction (SCI) is often disabling, and the diagnosis can be challenging without an inciting event (eg, aortic surgery). Patients with a spontaneous SCI are often misdiagnosed as having transverse myelitis. Diagnostic criteria for SCI are lacking, hindering clinical care and research.

Tuning T Cell Signaling Sensitivity Alters the Behavior of CD4 T Cells during an Immune Response.

Intricate processes in the thymus and periphery help curb the development and activation of autoreactive T cells. The subtle signals that govern these processes are an area of great interest, but tuning TCR sensitivity for the purpose of affecting T cell behavior remains technically challenging. Previously, our laboratory described the derivation of two TCR-transgenic CD4 T cell mouse lines, LLO56 and LLO118, which recognize the same cognate epitope with the same affinity.

Diagnostic and therapeutic spinal interventions: Epidural injections.

Epidural injections of local anesthetic or a corticosteroid are frequently given to diagnose and treat patients with radicular pain originating from any spinal level. The best-quality evidence supports a transforaminal approach in the lumbar spine. Many patients experience substantial benefit from a single therapeutic injection.

Diagnostic and therapeutic spinal interventions: Diskography.

Diskography (provocation diskography, disk stimulation) is an invasive diagnostic test performed to confirm or exclude internal disk disruption as the cause of axial spine pain. Diskography involves injecting fluid into the nucleus of the disk under manometric control; a positive response is reproduction of typical pain. Extensive but indirect literature validates diskography in the lumbar spine; it is less well-supported in the cervical or thoracic spine.

Diagnostic and therapeutic spinal interventions: Facet joint interventions.

Axial spine pain is a common condition that is due to facet joint disease in some patients. Local anesthetic blocks of the medial branches of the dorsal rami of the spinal nerves that innervate facet joints are used to identify painful facet joints. Subsequent radiofrequency neurotomy of the medial branches serving symptomatic facet joints may provide prolonged albeit impermanent pain relief.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is not always completely reversible: a case series.

We retrospectively reviewed clinical and imaging findings in 11 patients with stroke-like migraine attacks after radiation therapy (SMART) syndrome to better understand this disorder previously thought to be reversible. Six men and 5 women had complex bouts of neurologic impairment beginning, on average, 20 years after cerebral irradiation. All had characteristic, unilateral gyriform enhancement on MR imaging that developed within 2-7 days and typically resolved in 2-5 weeks.

Cervical spondylotic myelopathy.

The differential of cervical spondylotic myelopathy (CSM) is broad and includes multiple conditions that can cause and mimic myelopathy. In adults older than 55 years of age, CSM is the most common cause of myelopathy. This article summarizes the pathophysiology, clinical presentation, differential diagnosis, diagnostic evaluation, and natural history of CSM.

Adult-onset opsoclonus-myoclonus syndrome.

BACKGROUND Little is known about adult-onset opsoclonus-myoclonus syndrome (OMS) outside of individual case reports. OBJECTIVE To describe adult-onset OMS. DESIGN Review of medical records (January 1, 1990, through December 31, 2011), prospective telephone surveillance, and literature review (January 1, 1967, through December 31, 2011).

Cauda equina syndrome associated with longstanding instrumented spinal fusion.

Background: This study sought to describe a patient with a slowly progressive cauda equina syndrome (CES) who had imaging findings of the CES that occurs as a rare complication of ankylosing spondylitis (AS), but whose spinal fusion was due to thoracolumbosacral instrumentation, not spondyloarthropathy.

Methods: A 53-year-old woman presented with a 5-year history of slowly progressive CES affecting sensory and sphincter more than motor function many years after sequential instrumented fusions of her thoracic and then lumbosacral spine. Imaging studies showed enlargement of the caudal sac and dorsal arachnoid diverticula eroding into posterior elements of the lumbar spine similar to findings reported in patients with CES in longstanding AS.

Migraine update. Diagnosis and treatment.

Migraine is a common intermittently debilitating neurovascular disorder that affects younger adults, especially women. The diagnosis is generally made based on clinical criteria, with neuroimaging used in some cases to exclude secondary causes of headache. This article reviews current understanding of the mechanisms underlying migraine and approaches to treating it.

Cervical spondylotic myelopathy.

Background: Cervical spondylosis is part of the aging process and affects most people if they live long enough. Degenerative changes affecting the intervertebral disks, vertebrae, facet joints, and ligamentous structures encroach on the cervical spinal canal and damage the spinal cord, especially in patients with a congenitally small cervical canal. Cervical spondylotic myelopathy (CSM) is the most common cause of myelopathy in adults.

When and how to investigate the patient with headache.

The common complaint of headache usually has a benign cause, most often a primary headache syndrome. The history and neurologic and general physical examinations usually permit a definitive diagnosis. When in doubt, diagnostic testing is indicated.

Patient education in neurology.

Patient education is an important component of quality patient care and offers many potential benefits. Health care providers are responsible for giving patients the education they want and need to optimize their health and make health decisions. This review provides a definition of patient education; examines the potential benefits and effectiveness of patient education; builds a general framework for approaching patient education as it pertains to patient knowledge, behaviors, attitudes, and skills; and summarizes representative studies of patient education in selected neurologic conditions.