Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis.

Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical.

Impaired signaling for neuromuscular synaptic maintenance is a feature of Motor Neuron Disease.

A central event in the pathogenesis of motor neuron disease (MND) is the loss of neuromuscular junctions (NMJs), yet the mechanisms that lead to this event in MND remain to be fully elucidated. Maintenance of the NMJ relies upon neural agrin (n-agrin) which, when released from the nerve terminal, activates the postsynaptic Muscle Specific Kinase (MuSK) signaling complex to stabilize clusters of acetylcholine receptors. Here, we report that muscle from MND patients has an increased proportion of slow fibers and muscle fibers with smaller diameter.

Phase 1b dose-escalation, safety, and pharmacokinetic study of IC14, a monoclonal antibody against CD14, for the treatment of amyotrophic lateral sclerosis.

Background: The primary objective was to demonstrate the safety and tolerability of monoclonal antibody against CD14 (IC14) (atibuclimab) in amyotrophic lateral sclerosis patients. The secondary objectives were pharmacokinetics, pharmacodynamics, and preliminary effects on disease status and biomarkers.

Methods: In this open-label, dose-escalation trial, IC14 was administered at 2 mg/kg intravenous (IV) followed by 1 mg/kg/d IV × 3 (n = 3) and in subsequent patients at 4 mg/kg IV followed by 2 mg/kg/d IV × 3 (n = 7) (NCT03487263).

Monocyte CD14 and HLA-DR expression increases with disease duration and severity in amyotrophic lateral sclerosis.

To investigate changes in immune markers and frequencies throughout disease progression in patients with amyotrophic lateral sclerosis (ALS). : In this longitudinal study, serial blood samples were collected from 21 patients with ALS over a time period of up to 16 months. Flow cytometry was used to quantitate CD14, HLA-DR, and CD16 marker expression on monocyte subpopulations and neutrophils, as well as their cell population frequencies.

Clinical and electrophysiological examination of pinch strength in patients with amyotrophic lateral sclerosis.

Background: The split-hand concept has highlighted the preferential wasting of the thenar side of the hand in amyotrophic lateral sclerosis (ALS). Our objective is to re-explore pinch grip strength to assess whether it has the potential to be a practical biomarker of ALS.

Methods: We measured different pinch grip strengths (thumb, index, and fifth) using a pinch gauge from both hands of 54 ALS patients and correlated this with the Medical Research Council (MRC) score, the upper-limb component of the revised ALS Functional Rating Scale - Revised (ALSFRS-R) score, and compound muscle action potentials (CMAPs) that comprise the split-hand index.

Monocytes and neutrophils are associated with clinical features in amyotrophic lateral sclerosis.

Immunity has emerged as a key player in neurodegenerative diseases such as amyotrophic lateral sclerosis, with recent studies documenting aberrant immune changes in patients and animal models. A challenging aspect of amyotrophic lateral sclerosis research is the heterogeneous nature of the disease. In this study, we investigate the associations between peripheral blood myeloid cell populations and clinical features characteristic of amyotrophic lateral sclerosis.

Hypermetabolism in ALS is associated with greater functional decline and shorter survival.

Objective: To determine the prevalence of hypermetabolism, relative to body composition, in amyotrophic lateral sclerosis (ALS) and its relationship with clinical features of disease and survival.

Methods: Fifty-eight patients with clinically definite or probable ALS as defined by El Escorial criteria, and 58 age and sex-matched control participants underwent assessment of energy expenditure. Our primary outcome was the prevalence of hypermetabolism in cases and controls.

Whole exome sequencing and DNA methylation analysis in a clinical amyotrophic lateral sclerosis cohort.

Background: Gene discovery has provided remarkable biological insights into amyotrophic lateral sclerosis (ALS). One challenge for clinical application of genetic testing is critical evaluation of the significance of reported variants.

Methods: We use whole exome sequencing (WES) to develop a clinically relevant approach to identify a subset of ALS patients harboring likely pathogenic mutations.

Study of motor asymmetry in ALS indicates an effect of limb dominance on onset and spread of weakness, and an important role for upper motor neurons.

In amyotrophic lateral sclerosis (ALS), onset and spread of upper motor neuron (UMN) and lower motor neuron (LMN) dysfunction is typically asymmetric. Our aim was to investigate the relationship between limb dominance and the onset and spread of clinical UMN and LMN dysfunction in ALS. We studied 138 ALS subjects with unilateral and concordant limb dominance, from two tertiary centres.

Defining the state of knowledge with respect to food, nutrition, physical activity, and the prevention of cancer.

The 1997 World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) report, Food, Nutrition and the Prevention of Cancer: a global perspective, has become the most authoritative statement on the topic. WCRF International has begun the process of producing its second global report on food, nutrition, physical activity, and the prevention of cancer. The process is in three stages.

A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue.

The aim of the study was to see if topical aloe vera gel would be beneficial in reducing the identified skin side-effects of radiation therapy, including erythema, pain, itching, dry desquamation, and moist desquamation, when compared with aqueous cream. The secondary aim was to assess the effect of other factors known to predict severity of radiation skin reaction, ie, breast size, smoking habit, and one or more drainages of lymphocele after surgery, on other skin side effects. A Phase III study was conducted involving 225 patients with breast cancer after lumpectomy or partial mastectomy, who required a course of radiation therapy using tangential fields.

The technological edge.

The development of a real-time 2D-3D duplex ultrasonic scanner offers faster diagnostic imaging.