Activation of T cells specific for insulin B chain amino acids 9 to 23 (B9-23) is essential for the initiation of type 1 diabetes (T1D) in non-obese diabetic mice. We previously reported that peptide/MHC complexes containing optimized B9-23 mimotopes can activate most insulin-reactive pathogenic T cells. Varespladib (mAb287) targeting these complexes prevented disease in 30-50% of treated animals (compared to 10% of animals given an isotype control). The incomplete protection is likely due to the relatively low affinity of the antibody for its ligand and limited specificity. Here, we report an enhanced reagent, mAb757, with improved specificity, affinity, and efficacy in modulating T1D. Importantly, mAb757 bound with nanomolar affinity to agonists of both “type A” and “type B” cells and suppressed “type B” cells more efficiently than mAb287. When given weekly starting at 4 weeks of age, mAb757 protected ~70% of treated mice from developing T1D for at least 35 weeks, while mAb287 only delayed disease in 25% of animals under the same conditions. #link# Consistent with its higher affinity, mAb757 was also able to stain antigen-presenting cells loaded with B9-23 mimotopes in vivo. We conclude that monoclonal antibodies that can block the presentation of pathogenic T cell receptor epitopes are viable candidates for antigen-specific immunotherapy for T1D.As a novel long-acting recombinant human insulin analogue, it is necessary to carry out the preclinical research for insulin LysArg. The purpose of this study was to characterise the pharmacokinetic, tissue distribution and excretion of insulin LysArg and provide a reference for its development. Three methods were used to measure the content of insulin LysArg in biological samples after a single subcutaneous administration in rats, including radioassay, radioassay after precipitation with TCA and separation by HPLC. After Subcutaneous administration of recombinant insulin LysArg 1, 2, 4 U/kg in rats, it showed both Cmax and AUC0-t were positively correlated with the dose. In the meanwhile, after a single subcutaneous administration of recombinant insulin LysArg at 2 U/kg in rats, the amount of radioactivity in most organs was highest at 1.5 h and then decreased gradually, no accumulation was found. The highest level of insulin LysArg was observed in the kidney. Like other macromolecules, insulin LysArg was mainly excreted from urine. The study fully illustrated the pharmacokinetic pattern of insulin LysArg, provided valuable informations to support its further development about safety and toxicology.NeuroEvolution (NE) refers to a family of methods for optimizing Artificial Neural Networks (ANNs) using Evolutionary Computation (EC) algorithms. NeuroEvolution of Augmenting Topologies (NEAT) is considered one of the most influential algorithms in the field. Eighteen years after its invention, a plethora of methods have been proposed that extend NEAT in different aspects. In this article, we present a systematic literature review (SLR) to list and categorize the methods succeeding NEAT. Our review protocol identified 232 papers by merging the findings of two major electronic databases. Applying criteria that determine the paper’s relevance and assess its quality, resulted in 61 methods that are presented in this article. Our review article proposes a new categorization scheme of NEAT’s successors into three clusters. NEAT-based methods are categorized based on 1) whether they consider issues specific to the search space or the fitness landscape, 2) whether they combine principles from NE and another domain, or 3) the particular properties of the evolved ANNs. The clustering supports researchers 1) understanding the current state of the art that will enable them, 2) exploring new research directions or 3) benchmarking their proposed method to the state of the art, if they are interested in comparing, and 4) positioning themselves in the domain or 5) selecting a method that is most appropriate for their problem.

The vHIT device, which has a mechanism based on measuring the VOR gain, helps us to quickly evaluate six semicircular canals.

The aim of this study was to establish normative values for semicircular canal function with the video head impulse test (vHIT) battery in normal adolescents.

100 (50 females, 50 males) individuals aged 11-18 years, with a mean age of 14.99 years, were included in the study.

As a result of the vHIT evaluations performed with vHIT Otometrics ICS Impulse A/S Taastrup, Denmark, the mean lateral canal vestibulo-ocular reflex (VOR) gain value was 0.96, the mean anterior canal VOR gain value was 0.89, and the mean posterior canal VOR gain value was 0.87, all of which were within the normal value range.

While the VOR gain values and asymmetry values are within the normal value range and are similar to the literature, no statistically significant correlation was observed between these values and age. As a result, the vHIT battery is an easy, fast, and practical test method that can be used in adolescents.

While the VOR gain values and asymmetry values are within the normal value range and are similar to the literature, no statistically significant correlation was observed between these values and age. As a result, the vHIT battery is an easy, fast, and practical test method that can be used in adolescents.

Considering the key role of health care providers in integrating assistive technologies into clinical settings (e.g., in/outpatient rehabilitation) and home, this study explored the care providers’ perspectives on

to the implementation of the Cognitive Orthosis for coOking (COOK) for adults with traumatic brain injury (TBI) within clinical contexts and homes.

Using a qualitative descriptive approach, semi-structured individual interviews and focus groups were carried out with experienced care providers of adults with TBI (

 = 30) in Ontario-Canada. Qualitative analysis based on the Miles

approach was used.

According to the participants, COOK could potentially be used with individuals with cognitive impairments (TBI and non-TBI) to increase safety and independence in meal preparation and support healthcare providers. However, limited access to funding, clients’ lack of motivation/knowledge, and the severity of their cognitive and motor impairments were perceived as potential barriers. Facilitators to the use of COOK include training sessions, availability of private/provincial financing, and comprehensive assessments by a clinical team prior to use.