130 research outputs found

    Book Review: Bourgeois Hinduism, Or the Faith of the Modern Vedantists

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    A review of Bourgeois Hinduism, Or the Faith of the Modern Vedantists by Brian A. Hatcher

    Book Review: Hermeneutics and Hindu Thought: Toward a Fusion of Horizons

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    A review of Hermeneutics and Hindu Thought: Toward a Fusion of Horizons edited by Rita Sherma and Arvind Sharma

    Nine More- or Less-related Observations on Historical Approaches to Hindu-Christian Studies

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    For the purposes of this panel discussion, it seems more appropriate to make a series of suggestions and observations about the difficulties and promises of writing history within a Hindu-Christian framework than to offer a paper arguing a single point or perspective. Hindu-Christian history presents a particular set of challenges given the shifting political and material conditions that have attended the dramatic encounter between these disparate cultures and traditions. In what follows I attempt to articulate some of the larger issues with which I wrestle as I study and write Hindu-Christian history

    Reverend William Ward and His Legacy for Christian (Mis)perception of Hinduism

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    My assignment for this thematic issue of the Hindu-Christian Studies Bulletin is to address Christian misperceptions of Hinduism, which I shall do by evaluating the work and legacy of William Ward of Serampore, missionary to Bengal, and author on Hinduism in the early nineteenth century. First, however, I would like to make three preliminary observations about the idea of Christian misperception

    The Pitfalls of Trying to Be Different

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    For more than a decade Rajiv Malhotra has been known to the study of South Asian religion as a vigorous critic of the practices and frameworks that academics have employed to represent India to the West. Those who know him from his no-holds-barred online articles or by his unflinching confrontation with established scholars at academic meetings may be pleased by the rather different tone of Being Different: An Indian Challenge to Western Universalism, Malhotra’s latest attempt to intervene in the academic study of the religious traditions of the South Asian subcontinent. Whereas Malhotra has achieved much of his renown through intemperate language, he is and should be remembered also for his demands that practicing Hindus have a say in how they are represented and for provoking a needed self-examination by the scholarly community writing about the traditions of South Asia. These are not the primary concerns of Being Different, and if one reads it motivated by the lurid promise of a new assault by Malhotra on the motives, character, or methods of senior scholars in the study of Hinduism, one will discover the author pursuing a somewhat different agenda

    TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

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    Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

    The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

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    The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

    Minimizing Blood Loss in Spine Surgery.

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    Study Design: Broad narrative review. Objective: To review and summarize the current literature on guidelines, outcomes, techniques and indications surrounding multiple modalities of minimizing blood loss in spine surgery. Methods: A thorough review of peer-reviewed literature was performed on the guidelines, outcomes, techniques, and indications for multiple modalities of minimizing blood loss in spine surgery. Results: There is a large body of literature that provides a consensus on guidelines regarding the appropriate timing of discontinuation of anticoagulation, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and herbal supplements prior to surgery. Additionally, there is a more heterogenous discussion the utility of preoperative autologous blood donation facilitated by erythropoietin and iron supplementation for healthy patients slated for procedures with high anticipated blood loss and for whom allogeneic transfusion is likely. Intraoperative maneuvers available to minimize blood loss include positioning and maintaining normothermia. Tranexamic acid (TXA), bipolar sealer electrocautery, and topical hemostatic agents, and hypotensive anesthesia (mean arterial pressure (MAP)Hg) should be strongly considered in cases with larger exposures and higher anticipated blood loss. There is strong level 1 evidence for the use of TXA in spine surgery as it reduces the overall blood loss and transfusion requirements. Conclusion: As the volume and complexity of spinal procedures rise, intraoperative blood loss management has become a pivotal topic of research within the field. There are many tools for minimizing blood loss in patients undergoing spine surgery. The current literature supports combining techniques to use a cost- effective multimodal approach to minimize blood loss in the perioperative period

    Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

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    Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine
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