Prevalence and Course of Endocrinopathy in POEMS Syndrome.

Context: POEMS syndrome is a rare multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, and skin changes, among other features.

Objective: To describe the prevalence and course of endocrine dysfunction in POEMS.

Design: Cohort study with systematic review of the endocrinopathy in POEMS.

POEMS syndrome.

Purpose Of Review: To provide an overview of polyneuropathy organomegaly endocrinopathy M-protein and skin changes (POEMS) syndrome, detailing new insights into pathogenesis, prognostic factors, treatments, and outcome scores.

Recent Findings: With the development of large multicentre national cohorts of patients, POEMS syndrome is evolving into a well characterized multisystem hematoneurological syndrome. Without early diagnosis significant disability results from the neuropathy.

Muscle Stem Cell Immunostaining.

Muscle stem cells (MuSCs) are essential for maintaining muscle homeostasis by providing progenitor cells for muscle regeneration after injury and in muscular diseases. MuSC properties dynamically change, reflecting physiology or pathological status. For instance, MuSCs are activated after muscle injury, but become exhausted in late stages of Duchenne Muscular Dystrophy (DMD) disease and senescent during aging.

Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. Rational developments in neuroimmunological treatment.

Background And Purpose: The aim was to assess the therapeutic potential of bortezomib in the treatment of refractory N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis and its potential in other immune-mediated, B-cell-driven neurological diseases.

Methods: Two cases of severe NMDAR antibody encephalitis, resistant to first and second line therapy with steroids, intravenous immunoglobulins, plasma exchange, cyclophosphamide and rituximab, were treated with four and five cycles of 1.3 mg/m bortezomib at 350 and 330 days following initial presentation.

Active neurocysticercosis at the Hospital for Tropical Diseases, London: a clinical case series.

Background: Neurocysticercosis is the commonest infectious cause of epilepsy in endemic countries, and accounts for a greater number of cases worldwide than any other single pathology. Infection is associated with long-term exposure in low-income countries, although acquisition after travel has been recognized. The standard of care in the UK is inpatient treatment with anti-helminthic drugs and steroids.

Dystonin-A3 upregulation is responsible for maintenance of tubulin acetylation in a less severe dystonia musculorum mouse model for hereditary sensory and autonomic neuropathy type VI.

Hereditary sensory and autonomic neuropathy type VI (HSAN-VI) is a recessive human disease that arises from mutations in the dystonin gene (DST; also known as Bullous pemphigoid antigen 1 gene). A milder form of HSAN-VI was recently described, resulting from loss of a single dystonin isoform (DST-A2). Similarly, mutations in the mouse dystonin gene (Dst) result in severe sensory neuropathy, dystonia musculorum (Dstdt).

Human adenoviral DNA association with nucleosomes containing histone variant H3.3 during the early phase of infection is not dependent on viral transcription or replication.

Adenovirus (Ad) DNA undergoes dynamic changes in protein association as the virus progresses through its replicative cycle. Within the virion, the Ad DNA associates primarily with the virus-encoded, protamine-like protein VII. During the early phase of infection (∼6 h), the viral DNA showed declining association with VII, suggesting that VII was removed from at least some regions of the viral DNA.

Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis.

TDP-43 (encoded by the gene ) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous to dissect TDP-43 function at physiological levels both and Interestingly, we find that mutations within the C-terminal domain of TDP-43 lead to a gain of splicing function.

Expression of Pannexin 1 and Pannexin 3 during skeletal muscle development, regeneration, and Duchenne muscular dystrophy.

Pannexin 1 (Panx1) and Pannexin 3 (Panx3) are single membrane channels recently implicated in myogenic commitment, as well as myoblast proliferation and differentiation in vitro. However, their expression patterns during skeletal muscle development and regeneration had yet to be investigated. Here, we show that Panx1 levels increase during skeletal muscle development becoming highly expressed together with Panx3 in adult skeletal muscle.

Celecoxib treatment improves muscle function in mdx mice and increases utrophin A expression.

Duchenne muscular dystrophy (DMD) is a genetic and progressive neuromuscular disorder caused by mutations and deletions in the dystrophin gene. Although there is currently no cure, one promising treatment for DMD is aimed at increasing endogenous levels of utrophin A to compensate functionally for the lack of dystrophin. Recent studies from our laboratory revealed that heparin treatment of mdx mice activates p38 MAPK, leading to an upregulation of utrophin A expression and improvements in the dystrophic phenotype.

The snowball effect of RNA binding protein dysfunction in amyotrophic lateral sclerosis.

This scientific commentary refers to ‘TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis’, by Deshaies . (doi:10.1093/brain/awy062).

The role of mitochondria in stem cell fate and aging.

The importance of mitochondria in energy metabolism, signal transduction and aging in post-mitotic tissues has been well established. Recently, the crucial role of mitochondrial-linked signaling in stem cell function has come to light and the importance of mitochondria in mediating stem cell activity is becoming increasingly recognized. Despite the fact that many stem cells exhibit low mitochondrial content and a reliance on mitochondrial-independent glycolytic metabolism for energy, accumulating evidence has implicated the importance of mitochondrial function in stem cell activation, fate decisions and defense against senescence.

No laughing matter: subacute degeneration of the spinal cord due to nitrous oxide inhalation.

Background: Whilst the dangers of 'legal highs' have been widely publicised in the media, very few cases of the neurological syndrome associated with the inhalation of nitrous oxide (NO) have been reported. Here we set out to raise awareness of subacute degeneration of the spinal cord arising from recreational NO use so that formal surveillance programs and public health interventions can be designed.

Methods: Case series documenting the clinical and investigational features of ten consecutive cases of subacute degeneration of the spinal cord presenting to a hospital with a tertiary neurosciences service in East London.

GYG1 causing progressive limb girdle myopathy with onset during teenage years (polyglucosan body myopathy 2).

An 84-year-old lady with slowly progressive limb and axial muscle weakness with onset in her teens was referred for genetic investigations. Targeted next generation sequencing (NGS) revealed a homozygous mutation GYG1 in exon5:c.487delG:p.

Cytokine Profiling of Serum Allows Monitoring of Disease Progression in Inclusion Body Myositis.

Background: Inclusion body myositis is a late onset inflammatory myopathy lacking reliable serum biomarkers for diagnosis and for disease progression.

Objective: To identify diagnostic and predictive biomarkers, cytokine profiling is used to assess the potential of cytokines to discriminate between cases and controls and to assess whether treatment with methotrexate can influence biomarkers associated with disease progression.

Methods: The diagnostic and follow-up potential of 48 cytokines was tested using Bioplex-assay and ELISA in sera of healthy individuals, IBM patients and patients with other neuromuscular disorders.

G-quadruplex-binding small molecules ameliorate FTD/ALS pathology and .

Intronic GGGGCC repeat expansions in are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively. Repeat expansions have been proposed to cause disease by both the repeat RNA forming foci that sequester RNA-binding proteins and through toxic dipeptide repeat proteins generated by repeat-associated non-ATG translation. GGGGCC repeat RNA folds into a G-quadruplex secondary structure, and we investigated whether targeting this structure is a potential therapeutic strategy.

Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential Biomarker for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is caused by homozygous mutation of the survival motor neuron 1 (SMN1) gene. Disease severity inversely correlates to the amount of SMN protein produced from the homologous SMN2 gene. We show that SMN protein is naturally released in exosomes from all cell types examined.

Repairing Mitochondrial Dysfunction in Disease.

Mitochondria are essential organelles for many aspects of cellular homeostasis, including energy harvesting through oxidative phosphorylation. Alterations of mitochondrial function not only impact on cellular metabolism but also critically influence whole-body metabolism, health, and life span. Diseases defined by mitochondrial dysfunction have expanded from rare monogenic disorders in a strict sense to now also include many common polygenic diseases, including metabolic, cardiovascular, neurodegenerative, and neuromuscular diseases.

Circulating Progenitor Cell Response to Exercise in Wheelchair Racing Athletes.

Introduction: Circulating progenitor cells (CPC) are a heterogeneous population of stem/progenitor cells in peripheral blood that participate in tissue repair. CPC mobilization has been well characterized in able-bodied persons but has not been previously investigated in wheelchair racing athletes. The purpose of this study was to characterize CPC and CPC subpopulation mobilization in elite wheelchair racing athletes in response to acute, upper-extremity aerobic exercise to determine whether CPC responses are similar to ambulatory populations.