A Comparative Study on Morphochemical Properties and Osteogenic Cell Differentiation within Bone Graft and Coral Graft Culture Systems

The objective of this study was to compare the morphological and chemical composition of bone graft (BG) and coral graft (CG) as well as their osteogenic differentiation potential using rabbit mesenchymal stem cells (rMSCs) in vitro. SEM analysis of BG and CG revealed that the pores in these grafts were interconnected, and their micro-CT confirmed pore sizes in the range of 107-315 µm and 103-514 µm with a total porosity of 92% and 94%, respectively. EDS analysis indicated that the level of calcium in CG was relatively higher than that in BG. FTIR of BG and CG confirmed the presence of functional groups corresponding to carbonyl, aromatic, alkyl, and alkane groups. XRD results revealed that the phase content of the inorganic layer comprised highly crystalline form of calcium carbonate and carbon. Atomic force microscopy analysis showed CG had better surface roughness compared to BG. In addition, significantly higher levels of osteogenic differentiation markers, namely, alkaline phosphatase (ALP), Osteocalcin (OC) levels, and Osteonectin and Runx2, Integrin gene expression were detected in the CG cultures, when compared with those in the BG cultures. In conclusion, our results demonstrate that the osteogenic differentiation of rMSCs is relatively superior in coral graft than in bone graft culture system.     

The interaction index, a novel information-theoretic metric for prioritizing interacting genetic variations and environmental factors

We developed an information-theoretic metric called the Interaction Index for prioritizing genetic variations and environmental variables for follow-up in detailed sequencing studies. The Interaction Index was found to be effective for prioritizing the genetic and environmental variables involved in GEI for a diverse range of simulated data sets. The metric was also evaluated for a 103-SNP Crohn''s disease dataset and a simulated data set containing 9187 SNPs and multiple covariates that was modeled on a rheumatoid arthritis data set. Our results demonstrate that the Interaction Index algorithm is effective and efficient for prioritizing interacting variables for a diverse range of epidemiologic data sets containing complex combinations of direct effects, multiple GGI and GEI.     

Discovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy

Indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as a target for small-molecule immunotherapy for the treatment of a variety of cancers including renal cell carcinoma and metastatic melanoma. This work focuses on the identification of IDO1 inhibitors containing replacements or isosteres for the amide found in BMS-986205, an amide-containing, IDO1-selective inhibitor currently in phase III clinical trials. Detailed subsequently are efforts to identify a structurally differentiated IDO1 inhibitor via the pursuit of a variety of heterocyclic isosteres, leading to the discovery of highly potent, imidazopyridine-containing IDO1 inhibitors.     

Serum protein profile studies of cervical cancers in monitoring of tumor response to radiotherapy using HPLC-LIF: A pilot study

ObjectiveExploration of the feasibility of serum protein profiles for monitoring tumor radioresponse in cervical cancers using HPLC-LIF system.Materials and methodsTwenty-one subjects were recruited in the study. Out of them 7 were healthy, 14 were cervical cancer patients who undertook fractionated radiotherapy (RT) with 2 Gy per fraction over 25 fractions, for 5 weeks followed by 2 applications of intracavitary brachytherapy once a week.Blood collected from above subjects was processed to obtain serum. Serum chromatograms of ‘normal’ (n=7) and conspicuous probes before RT (n=14, ‘malignant’) and 24 h after second fraction of RT (n=13, ‘2-RT’), were recorded using an In-house-built HPLC-LIF set-up. Data were analyzed in two approaches: (1) classical method using relative intensities of selected peaks, (2) principal component analysis (PCA).Clinical assessment of tumor radioresponse was carried out 4 months after first fraction of RT and the degree of the tumor shrinkage was determined as an index of radioresponsiveness (complete response (CR): 100% shrinkage, partial response (PR): ≥50% shrinkage, and no response (NR): ≤50% shrinkage) which was further correlated with the analysis of 2-RT serum chromatograms.ResultsNormal vs. malignant chromatograms demonstrated pronounced differences in the 800–1800 s region. Malignant vs. 2-RT chromatograms showed minute variations in the 1300–1800 s region. Our analysis, in both of the approaches, produced clear differentiation between ‘normal’ and ‘malignant’, whereas differentiation between ‘malignant’ and ‘2-RT’ was minimal. Clinical evaluation of the tumor radioresponse yielded that out of 13 patients (one patient discontinued the radiotherapy) ten showed CR, two showed PR and one NR. In case of prediction of tumor radioresponse, analysis of the 2-RT chromatograms produced only minor differentiation among CR, PR and NR groups.ConclusionProtein profiling of serum samples differentiated ‘normal’ from ‘malignant’, but could not differentiate ‘malignant’ from ‘2-RT’. Also this technique has limited application in prediction of tumor radioresponse.     

Cochlear implantation in branchio-oto-renal syndrome — A surgical challenge

Branchio-oto-renal syndrome (Melnick-Fraser Syndrome) is a rare Autosomal Dominant disorder characterized by the syndromic association of branchial cysts or fistulae along with external, middle & inner malformations and renal anomalies. Incomplete penetrance and variable expressivity are common with the phenotypic variation ranging from mild to severe forms & consisting of various eye, ear, oral and craniofacial abnormalities. Mutations in the EYA1 gene on chromosomal site 8q13.3 are identified as the primary cause of BOR syndrome. We present a 3year old child with BOR syndrome, who came to us with bilateral low set, malformed ears & profound cochlear hearing loss along with bilateral branchial fistulae & unilateral renal agenesis. This child underwent successful cochlear implantation recently. The clinical presentation, pre-operative investigations, intra-operative findings & post-op habilitation status are presented with special highlights on the unique facial nerve course along with middle and inner ear anomalies which posed a surgical challenge during cochlear implantation.     

Alveolar soft part sarcoma of tongue base — A rare presentation of a rare tumor

Alveolar soft part sarcoma is a rare, aggressive malignancy of uncertain histologic origin and enigmatic clinical behaviour. It has a characteristic histopathological picture, with a propensity for vascular invasion and distant metastasis. We report a case of alveolar soft part sarcoma involving the tongue base in an adolescent female. She underwent laser assisted excision of the tongue base tumour followed by post-operative radiotherapy. The clinical presentation, histopathological picture, immunohistochemical & cytogenetic studies, radio-imaging, management protocols and prognosis of this tumor have been discussed.