COMPARISON OF CARTILAGE TYPE IIIA AND IIIB TYMPANOPLASTY IN INDIAN PATIENTS WITH CHRONIC SUPPURATIVE OTITIS MEDIA

Objective: This prospective comparative study determined the efficacy of type III tympanoplasty using homologous septal spur cartilage in patients with chronic otitis medis (COM).Methods: We selected patients by random sampling. Complete otolaryngologica examination including otological examination, tuning fork tests, pure tone audiometry (PTA), and relevant investigations was done. Post-tympanoplasty residual air-bone gap (ABG) was graded. Type III tympanoplasty was done for all and followed up until month 6.Results: Of 50 patients, 70.0% were men. Mean age was 27.72±10.81 years, 24 and 26 patients underwent type IIIA and IIIB tympanoplasty, respectively. Pre-operative mean PTA and ABG was 50.08 dB and 38.27 dB, respectively. Pre-operative ABG of 31–60 dB was seen in 41 patients while nine had an ABG of 0–30 dB. Overall, pre- and post-operative PTA was 50.24 dB and 28.54 dB, respectively. Overall, pre- and post-operative ABG was 38.32 dB and 16.40 dB (III A 36.92 dB and 14.79 dB; III B 39.62 dB and 17.88 dB). Mean overall hearing gain postoperatively in PTA was 21.70 dB (type III A 22.33 dB, III B −21.115 dB). Overall, ABG closure was 23.53 dB (type III A 22.333 dB, III B −21.115 dB). None had failure (>30 dB). Good ABG of 10–20 dB was seen in 72% and 78% of patients at month 3 and 6, respectively.Conclusion: Significant post-operative hearing improvement was seen in both types of tympanoplasty using homologous cartilage graft for ossicular reconstruction. Type III A is better than type IIIB as the stapes superstructure is vital for hearing

In silico strategies on prion pathogenic conversion and inhibition from PrPC -PrPSc

Published ArticleTo date, various therapeutic strategies identified numerous anti-prion compounds and antibodies that stabilize PrPC, block the conversion of PrPC-PrPSc and increased effect on PrPSc clearance. However, no suitable drug has been identified clinically so far due to the poor oral absorption, low blood-brain-barrier [BBB] penetration, and high toxicity. Although some of the drugs were proven to be effective in prion-infected cell culture and whole animal models, none of them increased the rate of survival compared to placebo. Areas covered: In this review, the authors highlight the importance of in silico approaches like molecular docking, virtual screening, pharmacophore analysis, molecular dynamics, QSAR, CoMFA and CoMSIA applied to detect molecular mechanisms of prion inhibition and conversion from PrPC-PrPSc. Expert opinion: Several in silico approaches combined with experimental studies have provided many structural and functional clues on the stability and physiological activity of prion mutants. Further, various studies of in silico and in vivo approaches were also shown to identify several new small organic anti-scrapie compounds to decrease the accumulation of PrPres in cell culture, inhibit the aggregation of a PrPC peptide, and possess pharmacokinetic characteristics that confirm the drug-likeness of these compounds

Computer Applications in Metallurgical Research

This paper outlines the current efforts in computer applications in metallurgical research at the Defence Metallurgical Research Laboratory, Hyderabad. Work being done on armour penetration studies, optimization of armour profiles for fighting vehicles, computer control of multifunction 2000 tonne forge press, drawing of processing mechanism maps, process modelling of titanium sponge production and methods of curve fitting to experimental data, is described and briefly discussed

Age- and Disease-Dependent HERV-W Envelope Allelic Variation in Brain: Association with Neuroimmune Gene Expression

Background: The glycoprotein, Syncytin-1, is encoded by a human endogenous retrovirus (HERV)-W env gene and is capable of inducing neuroinflammation. The specific allele(s) responsible for Syncytin-1 expression in the brain is uncertain. Herein, HERV-W env diversity together with Syncytin-1 abundance and host immune gene profiles were examined in the nervous system using a multiplatform approach. Results: HERV-W env sequences were encoded by multiple chromosomal encoding loci in primary human neurons compared with less chromosomal diversity in astrocytes and microglia (p,0.05). HERV-W env RNA sequences cloned from brains of patients with systemic or neurologic diseases were principally derived from chromosomal locus 7q21.2. Within the same specimens, HERV-W env transcript levels were correlated with the expression of multiple proinflammatory genes (p,0.05). Deep sequencing of brain transcriptomes disclosed the env transcripts to be the most abundant HERV-W transcripts, showing greater expression in fetal compared with healthy adult brain specimens. Syncytin-1’s expression in healthy brain specimens was derived from multiple encoding loci and linked to distinct immune and developmental gene profiles. Conclusions: Syncytin-1 expression in the brain during disease was associated with neuroinflammation and was principally encoded by a full length provirus. The present studies also highlighted the diversity in HERV gene expression within th

Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis

Newly emerging multi-drug resistant strains of Mycobacterium tuberculosis (M.tb) severely limit the treatment options for tuberculosis (TB); hence, new antitubercular drugs are urgently needed. The mymA operon is essential for the virulence and intracellular survival of M.tb and thus represents an attractive target for the development of new antitubercular drugs. This study is focused on the structure-function relationship of Fatty Acyl-CoA Synthetase (FadD13, Rv3089) belonging to the mymA operon. Eight site-directed mutants of FadD13 were designed, constructed and analyzed for the structural-functional integrity of the enzyme. The study revealed that mutation of Lys487 resulted in ∼95% loss of the activity thus demonstrating its crucial requirement for the enzymatic activity. Comparison of the kinetic parameters showed the residues Lys172 and Ala302 to be involved in the binding of ATP and Ser404 in the binding of CoenzymeA. The influence of mutations of the residues Val209 and Trp377 emphasized their importance in maintaining the structural integrity of FadD13. Besides, we show a synergistic influence of fatty acid and ATP binding on the conformation and rigidity of FadD13. FadD13 represents the first Fatty Acyl-CoA Synthetase to display biphasic kinetics for fatty acids. FadD13 exhibits a distinct preference for C26/C24 fatty acids, which in the light of earlier reported observations further substantiates the role of the mymA operon in remodeling the cell envelope of intracellular M.tb under acidic conditions. A three-dimensional model of FadD13 was generated; the docking of ATP to the active site verified its interaction with Lys172, Ala302 and Lys487 and corresponded well with the results of the mutational studies. Our study provides a significant understanding of the FadD13 protein including the identification of residues important for its activity as well as in the maintenance of structural integrity. We believe that the findings of this study will provide valuable inputs in the development of inhibitors against the mymA operon, an important target for the development of antitubercular drugs

Associations Between Telomere Attrition, Genetic Variants in Telomere Maintenance Genes, and Non-Small Cell Lung Cancer Risk in the Jammu and Kashmir Population of North India

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk. METHODS: We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR. RESULTS: Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values = 0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values = 0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p = 0.0004). CONCLUSION: This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings

Efficacy of organic and inorganic mulching materials on weed count, growth, and yield of aonla (Emblica officinalis) cv. NA 7

Studies were carried out in NA 7 cultivar of aonla (Emblica officinalis Gaertn) to assess the efficacy of organic and inorganic mulching materials on growth, flowering and yield during 2013 and 2014. Treatments consisted of mulching materials, viz. black polythene, white polythene, paddy straw, saw dust, sarkanda, dry grass with control (unmulched). The results indicated that maximum increase in tree height (0.55 m), tree spread in north-south (0.23 m) and east-west (0.17 m) and tree volume (11.11 cm3) was recorded in black polythene mulch, while it was minimum in control. The black polythene mulch reduced the weed growth in terms of count and weight by cent per cent. As far as floral characteristics, plant with black polythene mulch were the first to flower (11 April 2013), with maximum duration of flowering (23 days) and male : female flower ratio (22:1). Black polythene mulch was superior to all other mulching treatments in terms of yield attributes as it registered maximum fruit set (56.15%), minimum fruit drop (55.87%) and higher yield/tree (72.77 kg/tree). Thus, it can be concluded that black polythene improved the tree growth, flowering, fruit production and lowered weed population of aonla cv. NA 7 as compared to control in rainfed areas

Immunomodulatory Function of Interleukin 28B During Primary Infection With Cytomegalovirus

Background. Feedback mechanisms between interferons α and λ (IFNs) may be affected by single nucleotide polymorphisms (SNP) in interleukin 28B (IL-28B; IFN-λ3) promoter region and may influence cytomegalovirus (CMV) replication. Methods. We associated IL-28B SNPs with the risk of CMV replication after transplantation. Next, we examined the effect of IL-28B genotypes on IL-28B, and IFN-stimulated gene (ISG) expression, and CMV replication in human foreskin fibroblast (HFF) and peripheral blood mononuclear cells (PBMCs). Results. Transplant recipients with an IL-28B SNP (rs8099917) had significantly less CMV replication (P = .036). Both HFF-cells and PBMCs with a SNP showed lower IL-28B expression during infection with CMV, but higher "antiviral” ISG expression (eg, OAS1). Fibroblasts with a SNP had a 3-log reduction of CMV replication at day 4 (P = .004). IL-28B pretreatment induced ISG expression in noninfected fibroblasts, but a relative decrease of ISG expression could be observed in CMV-infected fibroblasts. The inhibitory effects of IL-28B could be abolished by siRNA or antagonistic peptides against the IL-28 receptor. In fibroblasts, inhibition of IL-28 signaling resulted in an increase of ISG expression and 3-log reduction of CMV-replication (P = .01). Conclusions. We postulate that IL-28B may act as a key regulator of ISG expression during primary CMV infection. IL-28B SNPs may be associated with higher antiviral ISG expression, which results in better replication contro

Chemokine-cytokine networks in the head and neck tumor microenvironment

Head and neck squamous cell carcinomas (HNSCCs) are aggressive diseases with a dismal patient prognosis. Despite significant advances in treatment modalities, the five-year survival rate in patients with HNSCC has improved marginally and therefore warrants a comprehensive understanding of the HNSCC biology. Alterations in the cellular and non-cellular components of the HNSCC tumor micro-environment (TME) play a critical role in regulating many hallmarks of cancer development including evasion of apoptosis, activation of invasion, metastasis, angiogenesis, response to therapy, immune escape mechanisms, deregulation of energetics, and therefore the development of an overall aggressive HNSCC phenotype. Cytokines and chemokines are small secretory proteins produced by neoplastic or stromal cells, controlling complex and dynamic cell–cell interactions in the TME to regulate many cancer hallmarks. This review summarizes the current understanding of the complex cytokine/chemokine networks in the HNSCC TME, their role in activating diverse signaling pathways and promoting tumor progression, metastasis, and therapeutic resistance development.This study was supported by Ramalingaswami Fellowship (Grant number: D.O.NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi to Muzafar A. Macha. Sidra Medicine Precision Program funded this research to Mohammad Haris (5081012001, 5081012001) and Ajaz A. Bhat (5081012003)