Influence of TAT-peptide polymerization on properties and transfection activity of TAT/DNA polyplexes.

Use of bioactive cationic peptides as gene carriers is limited by instability of their DNA complexes in vivo and by the loss of their biological activity due to undesired interactions of their bioactive parts with the DNA. To overcome the two major limitations, biodegradable high-molecular-weight form of TAT peptide (POLYTAT) sensitive to cellular redox-potential gradients was synthesized in this study by oxidative polycondensation. Physicochemical and transfection properties of DNA polyplexes based on POLYTAT were investigated and compared with polyplexes based on TAT polymer prepared by in situ template-assisted polymerization. Physicochemical properties of TAT-based polyplexes were affected by the molecular weight and method of polymerization of the TAT peptide. All TAT-based DNA polyplexes exhibited reduced cytotoxicity when compared with control polyethylenimine (PEI) polyplexes. Polyplexes based on both high-molecular-weight TAT polypeptides exhibited increased transfection efficiency compared to control TAT peptide but lower than that of PEI polyplexes. The evidence shows that transfection activity of TAT-based polyplexes is strongly dependent on the presence of chloroquine and therefore suggests that TAT polyplexes are internalized by an endocytosis. Overall, high-molecular-weight reducible polycations based on bioactive peptides has the potential as versatile carriers of nucleic acids that display low cytotoxicity and can prove to be especially beneficial in cases that require surface presentation of membrane-active or cell-specific targeting peptides.     

A concept-based retrieval system for thoracic radiology

Current digital information systems in radiology are insufficient to accommodate the retrieval needs of academicians. Significant efforts are required in retrieving clinical cases for teaching and research. We describe a prototype system that supports intelligent case retrieval based on a combined specification of patient demographics, radiologic findings, and pathologic diagnoses. The documents for these cases can be distributed among multiple heterogeneous data bases. The system features automatic indexing of radiology and pathology reports, a comprehensive lexicon for thoracic radiology, an interface to a hospital information system, radiology information system, and picture archiving and communication systems, and a graphical user interface for query formulation and results visualization. The prototype system was developed within the domain of thoracic radiology involving patients with lung cancer.     

Covid-19 Pandemic: Resumption of Orthopedic Care and Medical Education

Covid-19 is a respiratory disease caused by coronavirus 2 (SARS-CoV-2) first identified in Wuhan, China (December 2019). The disease rapidly crossed the barrier of countries, continents and spread globally. Non-pharmaceutical measures such as social distancing, face mask, frequent hand washing and use of sanitizer remained the best available option to prevent the spread of disease. OPD, IPD admissions, elective O. Ts were curtailed. Orthopedic care was only limited to emergency and semi-urgent procedures like necrotizing fasciitis, open fracture, and compartment syndrome. These measures were taken to preserve infrastructure and manpower to manage covid-19 pandemic. The children were thought to have a low susceptibility to covid-19 as compared to an adult. Deferring the patient during pandemic has led to high orthopedic disease burden, morbidity and disease-related sequelae, hence elective care must be resumed with modified hospital infrastructure. Resumption of elective/emergent orthopedic care should be slow, phasic and strategic, much similar to unlocking. Cases must be stratified depending on covid status and severity. Dedicated O.Ts with neutral/negative pressure and HEPA filter for covid positive and suspected patients are to be used. All symptomatic and suspected patients should be investigated for covid-19 by RT-PCR, blood counts and CT scan. Regional anaesthesia should be preferred to General anaesthesia. Power drill/saw/burr/pulse lavage should be minimized to avoid aerosol generation. Postoperatively continuous surveillance and monitoring to be done for covid related symptoms. Medical institutes rapidly shifted to the online mode of education. Blended learning (virtual & physical) and imparting skills have to be continued in post covid phase with equitable distribution of teaching hours to students of different years.     

A Theoretical Model for the Margination of Particles within Blood Vessels

The margination of a particle circulating in the blood stream has been analyzed. The contribution of buoyancy, hemodynamic forces, van der Waals, electrostatic and steric interactions between the circulating particle and the endothelium lining the vasculature has been considered. For practical applications, the contribution of buoyancy, hemodynamic forces and van der Waals interactions should be only taken into account, whilst the effect of electrostatic and steric repulsion becomes important only at very short distances from the endothelium (1–10 nm). The margination speed and the time for margination t_s have been estimated as a function of the density of the particle relative to blood , the Hamaker constant A and radius R of the particle. A critical radius R_c exists for which the margination time t_s has a maximum, which is influenced by both and A: the critical radius decreases as the relative density increases and the Hamaker constant decreases. Therefore, particles used for drug delivery should have a radius smaller than the critical value (in the range of 100 nm) to facilitate margination and interaction with the endothelium. While particles used as nanoharvesting agents in proteomics or genomics analysis should have a radius close to the critical value to minimize margination and increase their circulation time.     

Novel antidiabetic and hypolipidemic agents. 5. Hydroxyl versus benzyloxy containing chroman derivatives.

Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues having an aminoalkyl group as a linker between the chroman ring and 4-[5-(2,4-dioxo-1, 3-thiazolidinyl)methyl]phenoxy moiety seem to be better than troglitazone. In vitro transactivation assays of PPARgamma have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.     

Autologous Therapies in Dermatology

Autologous therapy is a therapeutic intervention that uses an individual’s cells or tissues, which are processed outside the body, and reintroduced into the donor. This emerging field presently represents a mere tip of the iceberg with much knowledge and applications yet to be discovered. It, being free from risks of hypersensitivity reactions and transmission of infectious agents, has been explored in various fields, such as plastic surgery, orthopedics, and dermatology. This review article focuses on various forms of autologous therapies used in dermatology along with their applications and mechanisms of action.Autologous therapy is a novel therapeutic intervention that uses an individual’s cells or tissues, which are processed outside the body and reintroduced into the donor. Currently, this form of therapy has broad applications in modern medicine, orthopedics, and therapeutic and cosmetic dermatology.