Covert airflow obstruction dominates the overt ones in interstitial lung disease: An appraisal.

Background & objectives The co-presence of non-emphysematous airflow obstruction in interstitial Lung disease (ILD) is not elaborated. The present study aims the job with spirometry. Methods ILD affected individuals with or without airflow obstruction (FEV1/FVC<0.7 or >0.7) on spirometry were compared in terms of FEV1 and FEF25-75 derived variables [FEF25-75 (%-predicted), FEV1-FEF25-75 distance, reversibility of FEV1 and FEF25-75 to salbutamol and change in FEV1 and FEF25-75 in %-predicted values]. Those showing significant difference (P=0.0001) suggesting obstruction were selected to draw respective receiver operating curve (ROC) curves to identify the best cut-off value for individual parameters. The efficacy of each surrogate was tested to identify airflow obstruction in both the initial 'overlap' as well as the 'unmixed' ILD affected individual for the presence of airflow obstruction. Results FEV1/FVC identified 30 overlap from 235 ILDs. The FEF25-75 (%-predicted), FEV1-FEF25-75 distance, FEF25-75 reversibility (in ml) and FEV1 (%-predicted) were significantly (P<0.0001) different between the two groups. Of these, the FEF25-75 (%-predicted) had high specificity and sensitivity (93.33 and 79.47%) to identify airflow limitation in the initial unmixed ILD-group. The surrogates with their cut off values identified 92 extra individuals making it 122/235 (51.91%) of ILD having airflow obstruction. The 'unmixed' group showed higher frequency and degree of FEV1 reversibility. Interpretation & conclusions The findings of this study suggest that the airflow obstruction in ILD involves both the intrathoracic large and small airways. Although seemingly parallel, their relative status (qualitative and quantitative) needs research especially in light of the a etio pathology and the extent of involvement of ILD.

Supramolecular Assembly of Amino Acid Based Cationic Polymer for Efficient Gene Transfection Efficiency in Triple Negative Breast Cancer.

The success of gene therapy is enormously dependent on an efficient gene carrier, and in this context, cationic polymers still continue to play a major role particularly with respect to the safety issue compared to viral vectors. Developing an efficient gene carrier system having promising gene transfection efficiency with low toxicity is the foremost impediment associated with a nonviral carrier. Here, we explored amino acid based biocompatible polymers synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization where glycine (Gly), leucine (Leu), and phenyl alanine (Phe) amino acids were used as the pendent groups of the polymeric brushes. The presence of both a hydrophobic group (long chain aliphatic group associated with the RAFT agent) and hydrophilic amino groups was associated with the supramolecular assembly of the polymeric chain having hydrodynamic sizes within the range of 150-300 nm with a positive zeta potential of 30 ± 5 mV. All polymers showed very low toxicity and possessed >80% cell viability even at a very high concentration of 1000 µg/mL against both normal and cancerous cells. In addition to this, the polymers also showed excellent blood compatibility, and negligible hemolysis was observed at the concentration of 500 µg/mL. All polymers showed efficient DNA complexation capability as well as excellent protection of DNA against highly negatively charged surfactant and enzymatic digestion, although the efficiency was dependent on the N/P ratio of polymer/DNA complexes. Interestingly, the phenyl alanine moiety containing polymer brush P(HEMA-Phe-NH2) showed a hexagonal shaped nanoparticle after complexation with pDNA and consequently showed higher cellular uptake, resulting in a higher transfection efficiency in a triple negative breast cancer cell, the MDA-MB-231 cell. Therefore, the synthesized polymer containing an amino acid pendent group, especially the phenyl alanine moiety, may be a promising nonviral gene carrier system in gene therapy application in the future.