ALS patients and PAD: description and comparison of patients from a neuromuscular clinic in Canada.

Objectives: In Canada, patients with ALS (PALS) who meet specific criteria can request Medical Assistance in Dying (MAiD), also known as Physician-Assisted Death (PAD). However, little is known about the characteristics of those patients. This study describes PALS who died of MAiD and compares them with patients who died from natural disease complications.

ARSACS: Clinical Features, Pathophysiology and iPS-Derived Models.

Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease caused by mutations in the SACS gene. The first two mutations were identified in French Canadian populations 20 years ago. The disease is now known as one of the most frequent recessive ataxias worldwide.

Reduction of sacsin levels in peripheral blood mononuclear cells as a diagnostic tool for spastic ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a rare neurodegenerative disease caused by biallelic variants in the gene encoding for sacsin. More than 200 pathogenic variants have been identified to date, most of which are missense. It is likely that the prevalence of autosomal recessive spastic ataxia of Charlevoix-Saguenay is underestimated due to the lack of an efficient diagnostic tool able to validate variants of uncertain significance.

In Vitro Characterization of Motor Neurons and Purkinje Cells Differentiated from Induced Pluripotent Stem Cells Generated from Patients with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease mainly characterized by spasticity in the lower limbs and poor muscle control. The disease is caused by mutations in the gene leading in most cases to a loss of function of the sacsin protein, which is highly expressed in motor neurons and Purkinje cells. To investigate the impact of the mutated sacsin protein in these cells , induced pluripotent stem cell- (iPSC-) derived motor neurons and iPSC-derived Purkinje cells were generated from three ARSACS patients.

Persisting chemosensory impairments in 366 healthcare workers following COVID-19: an 11-month follow-up.

Olfactory and gustatory dysfunctions (OD, GD) are prevalent symptoms following COVID-19 and persist in 6%-44% of individuals post-infection. As only few reports have described their prognosis after 6 months, our main objective was to assess the prevalence of OD and GD 11-month post-COVID-19. We also aimed to determine intraclass correlation coefficients (ICC) of chemosensory self-ratings for the follow-up of chemosensory sensitivity.

CAPTURE ALS: the comprehensive analysis platform to understand, remedy and eliminate ALS.

The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development.

Chemosensory Dysfunctions Induced by COVID-19 Can Persist up to 7 Months: A Study of Over 700 Healthcare Workers.

Several studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Our objective is to describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution after infection.

Human Organ-Specific 3D Cancer Models Produced by the Stromal Self-Assembly Method of Tissue Engineering for the Study of Solid Tumors.

Cancer research has considerably progressed with the improvement of study models, helping to understand the key role of the tumor microenvironment in cancer development and progression. Over the last few years, complex 3D human cell culture systems have gained much popularity over models, as they accurately mimic the tumor microenvironment and allow high-throughput drug screening. Of particular interest, human 3D tissue constructs, produced by the self-assembly method of tissue engineering, have been successfully used to model the tumor microenvironment and now represent a very promising approach to further develop diverse cancer models.

High yield extraction of pure spinal motor neurons, astrocytes and microglia from single embryo and adult mouse spinal cord.

Extraction of mouse spinal motor neurons from transgenic mouse embryos recapitulating some aspects of neurodegenerative diseases like amyotrophic lateral sclerosis has met with limited success. Furthermore, extraction and long-term culture of adult mouse spinal motor neurons and glia remain also challenging. We present here a protocol designed to extract and purify high yields of motor neurons and glia from individual spinal cords collected on embryos and adult (5-month-old) normal or transgenic mice.

Sensory neurons accelerate skin reepithelialization via substance P in an innervated tissue-engineered wound healing model.

Keratinocytes are responsible for reepithelialization and restoration of the epidermal barrier during wound healing. The influence of sensory neurons on this mechanism is not fully understood. We tested whether sensory neurons influence wound closure via the secretion of the neuropeptide substance P (SP) with a new tissue-engineered wound healing model made of an upper-perforated epidermal compartment reconstructed with human keratinocytes expressing green fluorescent protein, stacked over a dermal compartment, innervated or not with sensory neurons.

Concise review: tissue-engineered skin and nerve regeneration in burn treatment.

Burns not only destroy the barrier function of the skin but also alter the perceptions of pain, temperature, and touch. Different strategies have been developed over the years to cover deep and extensive burns with the ultimate goal of regenerating the barrier function of the epidermis while recovering an acceptable aesthetic aspect. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain.

Nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and glial-derived neurotrophic factor enhance angiogenesis in a tissue-engineered in vitro model.

Skin is a major source of secretion of the neurotrophic factors nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) controlling cutaneous sensory innervation. Beside their neuronal contribution, we hypothesized that neurotrophic factors also modulate the cutaneous microvascular network. First, we showed that NGF, BDNF, NT-3, and GDNF were all expressed in the epidermis, while only NGF and NT-3 were expressed by cultured fibroblasts, and BDNF by human endothelial cells.

Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells.

The incorporation of Schwann cells in reconstructed skin (RS) could have a major role in achieving functional recovery of cutaneous sensory perception. We showed with a unique in vitro model of a tissue-engineered innervated reconstructed dermis that Schwann cells promoted a twofold increase in the number of sensory neurites migrating in the three-dimensional tissue as compared with the control. In addition, Schwann cells spontaneously colocalized along neurites and achieved the formation of myelin sheaths in vitro as assessed by transmission electron microscopy.

Vasculature guides migrating neuronal precursors in the adult mammalian forebrain via brain-derived neurotrophic factor signaling.

Adult neuronal precursors retain the remarkable capacity to migrate long distances from the posterior (subventricular zone) to the most anterior [olfactory bulb (OB)] parts of the brain. The knowledge about the mechanisms that keep neuronal precursors in the migratory stream and organize this long-distance migration is incomplete. Here we show that blood vessels precisely outline the migratory stream for new neurons in the adult mammalian forebrain.