Mastication efficiency among stroke survivors with dysphagia / 中华物理医学与康复杂志

Objective:To compare the effect of age and gender on mastication efficiency between healthy volunteers and dysphagic stroke survivors and to document any correlation of mastication efficiency with mandible movements.Methods:Thirty-two stroke survivors with dysphagia and 84 healthy volunteers were asked to chew two-color gum. Their chewing efficiency was indicated by the degree of color mixing after chewing (SDHue). The SDHue value was evaluated using ViewGum software. The healthy volunteers were further divided into an age 20-40 years group, a 41-60 years group and an over-60 group. The SDHue values were compared among the 3 groups. The SDHue values were correlated with clinical mandibule movement scores.Results:Among the healthy volunteers, those older than 60 years had significantly higher SDHue values on average than those between 20 and 40 years. However, no significant gender difference was observed. The dysphagic stroke survivors had, on average, significantly higher SDHue results than the healthy volunteers, and those results were positively correlated with their mandible movement scores.Conclusions:Mastication efficiency tends to be age-related but not gender-related. Among those with post-stroke dysphagia mandible movement is positively correlated with mastication efficiency.

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection

Antibodies from SARS-CoV-2 vaccines may target epitopes which reduce durability or increase the potential for escape from vaccine-induced immunity. Using a novel synthetic vaccinology pipeline, we developed rationally immune focused SARS-CoV-2 Spike-based vaccines. N-linked glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and comprehensive in vitro screening, we incorporated glycans into the Spike Receptor-Binding Domain (RBD) and assessed antigenic profiles. We developed glycan coated RBD immunogens and engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicited potent neutralizing antibodies in guinea pigs, hamsters and multiple mouse models, including human ACE2 and human B cell repertoire transgenics. RBD nanoparticles encoding wild-type and the P.1 SARS-CoV-2 variant induced high levels of cross-neutralizing antibodies. Single, low dose immunization protected against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of novel, potent coronavirus vaccines.

Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.

Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health, social, and economic infrastructures. Here, we assess immunogenicity and anamnestic protective efficacy in rhesus macaques of the intradermal (ID)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800. INO-4800 is an ID-delivered DNA vaccine currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and neutralizing antibody responses against both the D614 and G614 SARS-CoV-2 spike proteins. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T and B cell responses. These responses were associated with lower viral loads in the lung and with faster nasal clearance of virus. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system which are likely important for providing durable protection against COVID-19 disease.

SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a global pandemic of COVID-19 resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >8 million people worldwide with >2 million cases in the US (June 17th, 2020). There is an urgent need for vaccines and therapeutics to combat the spread of this coronavirus. Similarly, the development of diagnostic and research tools to determine infection and vaccine efficacy are critically needed. Molecular assays have been developed to determine viral genetic material present in patients. Serological assays have been developed to determine humoral responses to the spike protein or receptor binding domain (RBD). Detection of functional antibodies can be accomplished through neutralization of live SARS-CoV2 virus, but requires significant expertise, an infectible stable cell line, a specialized BioSafety Level 3 (BSL-3) facility. As large numbers of people return from quarantine, it is critical to have rapid diagnostics that can be widely adopted and employed to assess functional antibody levels in the returning workforce. This type of surrogate neutralization diagnostic can also be used to assess humoral immune responses induced in patients from the large number of vaccine and immunotherapy trials currently on-going. Here we describe a rapid serological diagnostic assay for determining antibody receptor blocking and demonstrate the broad utility of the assay by measuring the antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine and using sera from infected patients.

Decannulation of dysphagic patients after a tracheotomy / 中华物理医学与康复杂志

Objective:To explore the value of flexible endoscopic evaluation of swallowing (FEES) in guiding the decannulation of neurological disease patients with dysphagia after a tracheotomy.Methods:The FEES results of 188 neurological disease patients with dysphagia who had undergone a tracheotomy were analyzed retrospectively. The utility of FEES evaluation indexes (including glottis activity, the classification of pharyngeal secretions and residues as well as penetration-aspiration grade) for predicting the success of decannulation was explored.Results:One hundred and nine of the patients (the success group) were decannulated successfully and 79 (the failure group) were not, a success rate of 57%. The abnormal glottis activity rate among the failure group was 55%, significantly higher than among the success group (21%). The pharyngeal secretion classifications and penetration-aspiration grades among the success group were also significantly lower than among the failure group, on average. The average course of recovery from the tracheotomy was 184 days in the success group, significantly shorter than that of the failure group (292 days). No significant differences in residues were observed.Conclusion:The glottis activity, secretions and intake aspiration evaluated using FEES are of great value for guiding the decannulation of neurological disease patients with dysphagia after a tracheotomy.

Effects of high-flow airway humidification in patients with dysphagia after tracheotomy / 中华物理医学与康复杂志

Objective:To explore the effect of high-flow airway humidification on aspiration and residues in cases of dysphagia after a tracheotomy.Methods:Seventeen persons with dysphagia after a tracheotomy were asked to swallow 5ml of a thick liquid when their tracheal cannula was either connected to a high-flow airway humidification system or blocked, or the cuff was empty or full. Endoscopic evaluation was then used to grade the residue and aspiration in the different conditions.Results:There were significant differences in the residuals grading and aspiration among the four conditions. The average penetration-aspiration scale grade was significantly lower when the subject was connected to high-flow airway humidification than in the other three conditions. The grade of residuals was also significantly lower.Conclusion:High-flow airway humidification can effectively improve the swallowing of persons with dysphagia after a tracheotomy.