Development of Lipidoid�CsiRNA Formulations for Systemic Delivery to the Liver

RNA interference therapeutics afford the potential to silence target gene expression specifically, thereby blocking production of disease-causing proteins. The development of safe and effective systemic small interfering RNA (siRNA) delivery systems is of central importance to the therapeutic application of siRNA. Lipid and lipid-like materials are currently the most well-studied siRNA delivery systems for liver delivery, having been utilized in several animal models, including nonhuman primates. Here, we describe the development of a multicomponent, systemic siRNA delivery system, based on the novel lipid-like material 98N₁₂-5(1). We show that in vivo delivery efficacy is affected by many parameters, including the formulation composition, nature of particle PEGylation, degree of drug loading, and biophysical parameters such as particle size. In particular, small changes in the anchor chain length of poly(ethylene glycol) (PEG) lipids can result in significant effects on in vivo efficacy. The lead formulation developed is liver targeted (>90% injected dose distributes to liver) and can induce fully reversible, long-duration gene silencing without loss of activity following repeat administration.     

Impact of Chemical Properties of Human Respiratory Droplets and Aerosol Particles on Airborne Viruses’ Viability and Indoor Transmission

The airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as a potential pandemic challenge, especially in poorly ventilated indoor environments, such as certain hospitals, schools, public buildings, and transports. The impacts of meteorological parameters (temperature and humidity) and physical property (droplet size) on the airborne transmission of coronavirus in indoor settings have been previously investigated. However, the impacts of chemical properties of viral droplets and aerosol particles (i.e., chemical composition and acidity (pH)) on viability and indoor transmission of coronavirus remain largely unknown. Recent studies suggest high organic content (proteins) in viral droplets and aerosol particles supports prolonged survival of the virus by forming a glassy gel-type structure that restricts the virus inactivation process under low relative humidity (RH). In addition, the virus survival was found at neutral pH, and inactivation was observed to be best at low (<5) and high pH (>10) values (enveloped bacteriophage Phi6). Due to limited available information, this article illustrates an urgent need to research the impact of chemical properties of exhaled viral particles on virus viability. This will improve our fundamental understanding of indoor viral airborne transmission mechanisms.     

Role of subjective visual vertical in patients with posterior canal benign paroxysmal positional vertigo as a prognostic marker after canalith repositioning maneuver

ObjectiveTo study the potential role of subjective visual vertical (SVV) as a prognostic marker for canalith repositioning maneuver (CRM) in patients with posterior canal benign paroxysmal positional vertigo (PC-BPPV) for the Indian population.MethodsSVV was examined in 30 patients with PC-BPPV before and after canalith repositioning maneuver and after complete resolution of PC-BPPV. Study parameters included the mean of 10 angular tilt readings and direction of deviation, which were compared before and after CRM and following complete resolution of PC-BPPV.ResultsThe angle of SVV tilt was greater and deviated towards the affected ear before CRM in all patients, which decreased significantly shortly after CRM and continued to decrease after complete resolution of PC-BPPV (p < 0.0001).ConclusionsSVV can be used to test utricular dysfunction in PC-BPPV. The angle of tilt improves in response to CRM, which may be used as a prognostic marker in patients with PC-BPPV receiving CRM.     

Spondylocostal dysplasia and brachydactyly associated with TBX6 and IHH variants: A case report

We report a preterm male neonate presenting with a short trunk, short neck, low hairline, deformed ears, preauricular skin tag, penoscrotal transposition (PT), palmar crease, short and broad fingers and toes (brachydactyly), hypoplastic and deep‐set nails, metatarsal abductus, and cross‐fused, small echogenic kidneys. Radiologic findings and genetic studies are consistent with spondylocostal dysostosis (SCD) and autosomal dominant brachydactyly. This is the first case report of spondylocostal dysostosis and brachydactyly associated with TBX6 and IHH variants. We reviewed the literature and compared our patient''s phenotype with previously reported cases of SCD.     

Fountains in the heart-biventricular coronary cameral fistulae and bilateral coronary artery to pulmonary artery fistulae

We describe about an elderly male presented to us with effort intolerance. He was diagnosed to have multiple coronary cameral fistulae and coronary pulmonary fistulae that gives an appearance of “Fountains In The Heart”. Such a combined existence of biventricular coronary cameral fistulae and bilateral coronary artery to pulmonary artery fistulae is an unforeseen entity that has never been described before in an individual.