Clinician Perspectives Highlight the Need for Early Dyadic Coping Skills for People Living with Amyotrophic Lateral Sclerosis.

Context: A diagnosis of ALS can be challenging, and many people find ways to adapt. At the same time, emotional distress can arise early after an ALS diagnosis even when high quality multidisciplinary care is provided. When emotional distress occurs, it can become chronic over time, and can affect both the person living with ALS and their care-partner (together called a dyad).

Intermuscular coherence as an early biomarker for amyotrophic lateral sclerosis: The protocol for a prospective, multicenter study.

Objective: To describe the protocol of a prospective study to test the validity of intermuscular coherence (IMC) as a diagnostic tool and biomarker of upper motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

Methods: This is a multicenter, prospective study. IMC of muscle pairs in the upper and lower limbs is gathered in ∼650 subjects across three groups using surface electrodes and conventional electromyography (EMG) machines.

A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD.

Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients. Here we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs in ALS-FTD, including in presymptomatic C9orf72 mutation carriers.

Extracellular matrix particle-glycosaminoglycan composite hydrogels for regenerative medicine applications.

Tissue extracellular matrix (ECM) is a complex material made up of fibrous proteins and ground substance (glycosaminoglycans, GAGs) that are secreted by cells. ECM contains important biological cues that modulate cell behaviors, and it also serves as a structural scaffold to which cells can adhere. For clinical applications, where immune rejection is a constraint, ECM can be processed using decellularization methods intended to remove cells and donor antigens from tissue or organs, while preserving native biological cues essential for cell growth and differentiation.

Chondroitin Sulfate-Based Biocompatible Crosslinker Restores Corneal Mechanics and Collagen Alignment.

Purpose: To evaluate the crosslinking effect of functionalized chondroitin sulfate (CS) in an ex vivo rabbit cornea model.

Methods: Chondroitin sulfate molecules were chemically modified with the N-hydroxysuccinimide (NHS) group. Enucleated rabbit eyes were crosslinked with 2, 5, or 10 mg/mL CS-NHS solution for 30 or 60 minutes.

Metabolically Active Three-Dimensional Brown Adipose Tissue Engineered from White Adipose-Derived Stem Cells.

Brown adipose tissue (BAT) has a unique capacity to expend calories by decoupling energy expenditure from ATP production, therefore BAT could realize therapeutic potential to treat metabolic diseases such as obesity and type 2 diabetes. Recent studies have investigated markers and function of native BAT, however, successful therapies will rely on methods that supplement the small existing pool of brown adipocytes in adult humans. In this study, we engineered BAT from both human and rat adipose precursors and determined whether these ex vivo constructs could mimic in vivo tissue form and metabolic function.

Metabolic variations in normal and fibrotic human laryngotracheal-derived fibroblasts: A Warburg-like effect.

Objectives/hypothesis: Laryngotracheal stenosis (LTS) is a chronic fibrotic disease characterized by fibroblast proliferation, collagen deposition, and matrix remodeling in the lamina propria of the larynx and/or trachea. Current medical therapies are limited by a poor understanding of the effector cell's (fibroblasts) cellular biology and metabolism. The purpose of this study was to compare cellular proliferation, function, and metabolism between normal and LTS-derived fibroblasts in vitro.

Dysregulated Macrophages Are Present in Bleomycin-Induced Murine Laryngotracheal Stenosis.

Objective: To define the inflammatory cell infiltrate preceding fibrosis in a laryngotracheal stenosis (LTS) murine model.

Study Design: Prospective controlled murine study.

Setting: Laboratory.

Rapamycin inhibits human laryngotracheal stenosis-derived fibroblast proliferation, metabolism, and function in vitro.

Objective: To determine if rapamycin inhibits the growth, function, and metabolism of human laryngotracheal stenosis (LTS)-derived fibroblasts.

Study Design: Controlled in vitro study.

Setting: Tertiary care hospital in a research university.

Excitotoxic lesions of the bed nucleus of the stria terminalis (BNST) attenuate the effects of repeated stress on weight gain: evidence for the recruitment of BNST activity by repeated, but not acute, stress.

Exposure to repeated stress can lead to diverse and widespread behavioral consequences, including reduction in food and water intake and subsequent diminution in weight gain. Many reports have suggested that repeated stress substantially alters the neurochemistry, morphology and physiology of neurons within the bed nucleus of the stria terminalis (BNST). Here we investigate the role of the BNST in mediating the reduced weight gain observed during repeated stress.

Controlled release of vascular endothelial growth factor enhances intestinal adaptation in rats with extensive small intestinal resection.

Background: Vascular endothelial growth factor (VEGF) has been shown to be an essential factor in the intestinal adaption after extensive bowel resection. The present study investigates the controlled release of VEGF as a way to improve intestinal adaptation.

Materials And Methods: Biodegradable microspheres with or without VEGF were made using a double emulsion technique.