22 research outputs found

    Pre-operative pulmonary assessment for patients with hip fracture

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    Hip fracture is a common injury among the elderly. Although patients who receive hip fracture surgery carry the best functional recovery compared to other treatment modalities, the presence of postoperative pulmonary complications, such as atelectasis, pneumonia, and pulmonary thromboembolism, may contribute to increased length of hospital stay, perioperative morbidity, and mortality. This review aims to provide evidence-based recommendations for preoperative assessment and perioperative strategies to reduce the risk of pulmonary complications after hip fracture surgery. Clinical assessment and basic laboratory results are sufficient to stratify the risk of postoperative pulmonary complications. Well-documented risk factors for pulmonary complications include advanced age, poor general health status, current infections, pre-existing cardiopulmonary diseases, hypoalbuminemia, and impaired renal function. Apart from optimizing the patient's medical conditions, interventions such as lung expansion maneuvers and thromboprophylaxis have been proven to be effective in reducing the risk of pulmonary complications after hip fracture surgery

    N-(phosphonacetyl)-L-aspartate induces TAp73-dependent apoptosis by modulating multiple Bcl-2 proteins: potential for cancer therapy

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    p53 is essential for the cellular responses to DNA damage that help to maintain genomic stability. However, the great majority of human cancers undergo disruption of the p53-network. Identification and characterization of molecular components important in both p53-dependent and -independent apoptosis might be useful in developing novel therapies for cancers. In the complete absence of p53, cells treated with N-(phosphonacetyl)-L-aspartate (PALA) continue to synthesize DNA slowly and eventually progress through S phase, suffering severe DNA damage that in turn triggers apoptosis, whereas cells with functional p53 undergo growth arrest. In the present study, we investigated apoptotic signaling in response to PALA and the role of p53 expression in this pathway. We found that treatment of cells lacking p53 with PALA induced TAp73, Noxa, and Bim and inactivation of these proteins with dominant negative plasmids or siRNAs significantly inhibited apoptosis, suggesting that PALA-induced apoptosis was mediated via TAp73-dependent expression of Noxa and Bim. However, PALA treatment inhibited the expression of ΔNp73 only in cells lacking p53 but not in cells expressing p53. In addition, PALA treatment inhibited Bcl-2, and overexpression of Bcl-2 significantly inhibited PALA-induced apoptosis. Moreover, expression of p53 in these cells protected them from PALA-induced apoptosis by activating p21, sustaining the expression of ΔNp73 and inhibiting the induction of Noxa and Bim. Taken together, our study identifies novel but opposing roles for the p53 and TAp73 in the induction of Noxa and Bim and regulation of apoptosis. Our data will help to develop strategies to eliminate cancer cells lacking p53 while protecting normal cells with wild-type p53
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