Atherosclerosis of Coronary Arteries as Predisposing Factor in Myocardial Infarction: An Autopsy Study.

The incidence of coronary heart disease has markedly increased in India over the past few years. Ischemic heart disease, the largest cause of morbidity and mortality in the developed and developing countries today is overwhelmingly contributed by atherosclerosis. The study highlights the impact of atherosclerotic lesions in the population of Rajkot district. We studied atherosclerotic lesions in coronary arteries in cases subjected to autopsy in last 4 years, to grade and to evaluate the atheromatous plaques; and to assess the cases of myocardial infarction amongst them. The study comprises dissected specimens of heart in total 360 cases subjected for autopsy. The vessels were examined for the presence of atherosclerotic lesions which were graded according to American Heart Association and examined for evidence of myocardial infarction. The study comprises the cases in age group between 20 to 80 years. Commonest type of atherosclerosis seen was grade-4. Left Anterior Descending Coronary was most commonly involved artery. Myocardial infarction was the cause of death in 35 cases (9.72%) The data obtained may form a baseline for the forthcoming studies

Role of Fine Needle Aspiration Cytology in Salivary Gland Pathology and its Histopathological Correlation: A Two Year Prospective Study in Western India.

Background and objectives: Salivary gland lesions account for 2-6.5% of all the neoplasms of the head and neck. Fine needle aspiration cytology (FNAC) is being increasingly used in the diagnosis of salivary gland lesions. The objective of this study was to evaluate the diagnostic accuracy and the sensitivity and specificity of FNAC in various salivary gland lesions in correlation with their histopathology, which helps in the appropriate therapeutic management. Methods: A total of 120 FNACs were done on salivary gland tumours from July 2010 to June 2012 in the Department of Pathology, P.D.U. Government Medical College, Rajkot (Gujarat, India). Formalin fixed (10%), surgically resected specimens were received, they were processed and slides were prepared for histopathological diagnosis. The stained cytological and histopathological slides were studied, analyzed and correlated. Results: The cytomorphological features were studied and analyzed and the following lesions were observed: Pleomorphic adenoma (88), Warthin’s tumour (2), Cystic lesion (4), Mucoepidermoid carcinoma (6), Acinic cell carcinoma (2), Primary lymphoma (2), Carcinoma EX pleomorphic adenoma(4), metastatic malignancy deposits (2), benign parotid tumour (8) and malignant tumour (unspecified)(2). A histopathological correlation was available in 78 cases. Out of these, 71 cases were true positive, 1 was false positive, 2 were false negative and 4 were true negative. Interpretation and conclusion: The overall sensitivity, specificity and the diagnostic accuracy were 97%, 80% and 92% respectively. Hence, the appropriate therapeutic management could be planned earlier. This study documents that FNAC of the salivary gland tumours is accurate, simple, rapid, inexpensive, well tolerated and harmless for the patient

Sponge Logics | Rethinking Thresholds Through a Porous Mass

This thesis contends that the separation and distinction between the envelope and the mass in contemporary architecture is to be resisted. Architect and theorist, Greg Lynn, argues that mass “is not only the outward shape of a building; it’s also the projection of shape, plan organization, spatial and sectional type, and façade”1.This critical reevaluation of the mass, and its relationship to the interior spaces and the building’s face, is particularly pertinent to the modern construction in Jaipur, Rajasthan, India. The character of the historicist and postmodern buildings that make up Jaipur is made solely based on the applied façade. This capstone argues that this strategy does not work at the building scale because it simply becomes an act of surface creation that does not impact the space beyond. Additionally, at the urban scale, the applied façade is an even weaker strategy with rigid boundaries that does not capitalize on the inherent richness of the urban grain. Rajput architecture, typical of Jaipur, used extravagance to project power and elevated the façade, an element of exclusion and inclusion, to reflect the social distinctions of the Kachwaha dynasty of Jaipur. Hawa Mahal, or the Palace of the Wind, is a prime example in that it serves as a screen for the court women to visually engage in the urban activities through its 953 jharokhas or windows but restricts physical interaction. This proposal learns from and updates Hawa Mahal’s conceptual, literal and socio-political thickness by challenging the role of the observer and the observed. Using the ideas of massing put forth by Lynn, this capstone reimagines the potential of a new type of architecture based on ‘sponge logics’ that transcends the established Rajput thresholds, enabling a more inclusive experience, indicative of the current society of Jaipur. The Hawa Mahal, acting as a screen, privileged the observer but sponge logics challenges the relationship between the observer and observed, mirroring the changing social dynamics of contemporary Jaipur. While a sponge can be identified autonomously, the lack of distinction between the mass, the structure and the façade make it part of an endless field condition that absorbs and transforms what is around it. The overall mass of a sponge is “an elaboration of conditions established locally” that can filtrate through the dense urban fabric of Jaipur.2 Doing so allows the street life of the city to filter in and the building life to filter out by sponge logics that identify the potential of a porous building to contribute to the enrichment of an already packed urban environment

In Silico Analysis Shows That Single Aminoacid Variations In Rhesus Macacque Fcγreceptor Affect Protein Stability And Binding Affinity To IgG1

Rhesus macaques are a widely used animal model of human diseases and related immune responses. Fc receptors (FcRs) mediate the interaction between antibody molecules and innate killing mechanisms, consequently eliminating the pathogen. In rhesus macaques, FcRs are highly polymorphic. To evaluate the potential influence of FcgR polymorphisms on the interaction with antibody molecules, we performed in silico analysis using SIFT, Provean, nsSNPAnalyzer, I-Mutant, MuSTAB and iPTREE-STAB web servers. V20G in FcγRI, I137K in FcγRII and I233V in FcγRIII were further analyzed structurally using FOLD-X, AMMP and Chimera to calculate changes in folding and interaction energy and for structure visualization. Results from our analysis suggest that the selected variations destabilize protein structure. Additionally, Q32R increases the binding affinity of FcγRI, whereas A131T decreases the binding affinity of FcγRII towards IgG1. Together, our results indicate that these substitutions might influence effector and regulatory mechanisms resulting from antibody/FcR interactions

DIVERSITY AND STRATEGIC HUMAN RESOURCE MANAGEMENT: LITERATURE REVIEW

This age of globalisation has made the world seem smaller. Which has made companies claim their foothold in other cultural diversities. Making the workforce more diverse than ever, and it is still becoming diverse day by day. The interest in the term diversity began in the United States of America in the 1980s.Workforce diversity has been and is one of the main problem for a manager of human resource management in modern companies. And despite noticing this grave problem, various models in this field of human resource management consider workforce as homogenous and generic. Leaders need to understand the need for managing diverse organization to their own strengths than neglecting or looking at it from just one viewpoint. This will increase efficiency and productivity of the organization as diverse teams will produce better results and the organization will gain a market advantage. The main aim of this paper is to view the literature of diversity among employees in strategic human resource management. Nevertheless, the efforts to develop and understand cross-culturality and diversity-oriented models still remain underdeveloped. The objective being, identifying limitations in previous research to drive positive future research in this field with newer models to determine a solution to this problem. There is a need to create strategies that create cultural environments incorporating values of humanity. And what this paper suggests is that we need is a completely new set of strategies of the human resource management to manage a heterogeneous workforce.     &nbsp

Identifying and eliminating inconsistencies in mappings across hierarchical ontologies

Recent years have seen a rapid proliferation of information sources e.g., on the World-wide Web, in virtually every area of human endeavor. Such autonomous information sources are based on different ontologies, i.e., conceptualizations of the entities, properties, and relationships in the respective domains of discourse. However, practical applications (e.g., building predictive models from disparate data sources, assembling composite web services using components from multiple repositories) call for mechanisms that bridge the semantic gaps between disparate ontologies using mappings that express terms (concepts, properties, and relationships) in a target ontology in terms of those in one or more source ontologies. Such mappings may be established by domain experts or automatically using tools designed to discover such mappings from data. In either case, it is necessary to check whether the resulting mappings are consistent, and if necessary, make them consistent by eliminating a subset of the mappings. We consider the problem of identifying the largest (maximum) subset of mappings in the restricted, yet practically important setting of hierarchical ontologies. Specifically, we consider mappings that assert that a concept in one ontology is a subconcept, superconcept, or equivalent concept of a concept in another ontology. We model the problem of identifying the largest consistent subset of such mappings between hierarchical ontologies as the problem of identifying the minimum feedback arc set in a directed acyclic graph (DAG). Because identifying minimum feedback arc set is known to be NP-hard, it follows that identifying the maximum subset of consistent mappings between hierarchical ontologies is NP-hard. We then explore several polynomial time algorithms for finding suboptimal solutions including a heuristic algorithm for (weighted) minimum feedback arc set problem in DAGs. We compare the performance of the various algorithms on several synthetic as well as real-world ontologies and mappings

Approaches to address the immunogenicity and immunosuppressive features of Isocitrate Dehydrogenase 1 mutated gliomas

The discovery of exploitable tumor-specific targets is central to the development of clinically relevant immunotherapeutic strategies for cancer. Mutations in isocitrate dehydrogenase 1 (IDH1), frequent in diffuse gliomas is one such target. The mutation IDH1R132H (mIDH1) is immunogenic, presented on human MHC-II molecules and induces CD4 T-cell responses in MHC-humanized A2DR1 tumor models as well as IDH1-mutated glioma patients when vaccinated with mIDH1-specific peptide vaccine. mIDH1, however plays the role of a double-edged knife. Its immunogenicity is compensated by the strong immunosuppressive environment orchestrated by the production of oncometabolite 2-HG that is imported by T-cells and leads to a suppression of their activation and proliferation. Inhibition of mIDH1 using small molecule inhibitors (IDH1i) has shown benefit in pre-clinical studies as therapy and has been associated with disease control in early clinical trials. Preclinical studies have also shown the ability of IDH1i to alleviate immunosuppression in the tumor microenvironment (TME). The impact of this inhibition on tumor infiltrating T-cells, however, has not been sufficiently evaluated. The first part of this work, therefore, aimed at deciphering the effect of IDH1i on tumor-infiltrating T-cell activity and fate in the tumor microenvironment using single-cell RNA and VDJ sequencing of tumor infiltrating immune cells. The lack of suitable murine glioma models where mIDH1 is presented in its native immunogenic capacity on human MHC-II molecules prompted the development of a novel syngeneic mIDH1 glioma model in MHC-humanized A2DR1 mice. Single-cell transcriptomic and T-cell receptor analysis of tumor infiltrating immune cells in IDH1i treated mice revealed an accumulation of infiltrating T-cells potentiated by IDH1i with an increased abundance of CD4 T-cells with a tumor reactive phenotype and a reduction in frequency regulatory T-cells as well as restoration of functional intercellular T-cell communication. Combination treatment of IDH1i and ICB provided a synergistic therapeutic benefit for mIDH1 A2DR1 gliomas. These findings suggest that reduction of 2-HG levels is necessary for enabling a functional anti-tumor immune response which is then exploitable by immune checkpoint blockade and warrants for clinical trials testing the efficacy of IDH1 inhibitors in combination with adjuvant immunotherapies such as vaccines or immune checkpoint inhibitors in patients with mIDH1 gliomas. The second part of this work focused on developing a setup for the identification and validation of mIDH1-reactive T-cell receptors (TCR) from IDH1RH-specific vaccinated A2DR1 mice and from the resected lesion of a glioma patient part of the NOA16 mIDH1 peptide vaccine trial. The latter revealed a unique transcriptional signature of mIDH1 reactive CD4 T-cells in the tumor microenvironment characterized by CXCL13 expression. The proof of principle identification of mIDH1 reactive TCRs demonstrates the feasibility of exploiting immune responses against CD4-restricted neo-epitopes as a first step in developing an adoptive TCR-transgenic T-cell therapy for glioma patient