Although it is well established that mammary tumorigenesis converts transforming growth factor-beta (TGF-beta) from a tumor suppressor to a tumor promoter, the molecular, cellular and microenvironmental mechanisms underlying the dichotomous nature of TGF-beta in mammary epithelial cells (MECs) remains to be determined definitively. Aberrant upregulation of the inducible cyclooxygenase, Cox-2, occurs frequently in breast cancers and is associated with increasing disease severity and the acquisition of metastasis; however, the impact of Cox-2 expression on normal and malignant MEC response to TGF-beta remains unknown. We show here that TGF-beta induced Cox-2 expression in normal MECs during their acquisition of an epithelial-mesenchymal transition (EMT) phenotype. Moreover, stable Cox-2 expression in normal MECs stimulated their invasion, EMT and anchorage-independent growth and inhibited their activation of Smad2/3 by TGF-beta. Conversely, antagonizing TGF-beta signaling in malignant, metastatic MECs significantly reduced their expression of Cox-2 as well as enhanced their activation of Smad2/3 by TGF-beta. Along these lines, elevated Cox-2 expression elicited prostaglandin E(2) (PGE(2)) production and the autocrine activation of EP receptors, which antagonized Smad2/3 signaling in normal and malignant MECs. Importantly, rendering normal and malignant MECs Cox-2 deficient inhibited their production of PGE(2) and acquisition of an EMT morphology as well as potentiated their nuclear accumulation of Smad2/3 and transcription of plasminogen activator inhibitor-1 and p15 messenger RNA. Collectively, our findings establish Cox-2 as a novel antagonist of Smad2/3 signaling in normal and malignant MECs; they also suggest that chemotherapeutic targeting of Cox-2 may offer new inroads in restoring the tumor-suppressing activities of TGF-beta in malignant, metastatic breast cancers.

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Ketamine is a unique anesthetic drug that provides analgesia, hypnosis, and amnesia with minimal respiratory and cardiovascular depression. Because of its sympathomimetic properties it would seem to be an excellent choice for patients with depressed ventricular function in cardiac surgery. However, its use has not gained widespread acceptance in adult cardiac surgery patients, perhaps due to its perceived negative psychotropic effects. Despite this limitation, it is receiving renewed interest in the United States as a sedative and analgesic drug for critically ill-patients. In this manuscript, the authors provide an evidence-based clinical review of ketamine use in cardiac surgery patients for intensive care physicians, cardio-thoracic anesthesiologists, and cardio-thoracic surgeons. All MEDLINE indexed clinical trials performed during the last 20 years in adult cardiac surgery patients were included in the review.

Healthcare waste (HCW) management and segregation are essential to ensure safety, environmental protection and cost control. Poor HCW management increase risks and costs for healthcare institutions. On-going surveillance and training are important to maintain good HCW practices. Our objectives were to evaluate and improve HCW practices at Hospital Bloom, San Salvador, El Salvador. We studied HCW disposal practices by observing waste containers, re-segregating waste placed in biohazardous waste bags, and administering a seven-itemsknowledge survey before and after training in waste management at Hospital Bloom. The training was based on national and international standards. We followed total biohazardous waste production before and after the training. The hospital staff was knowledgeable about waste segregation practices, but had poor compliance with national policies. Re-segregating waste in biohazardous waste bags showed that 61% of this waste was common waste, suggesting that the staff was possibly unaware of the cost of mis-segregating healthcare waste. After staff training in HCW management, the correct responses increased by 44% and biohazardous waste disposal at the hospital reduced by 48%. Better segregation of biohazardous waste and important savings can be obtained by HCW management education of hospital staff. Hospitals can benefit from maximising the use of available resources by sustaining best practices of HCW, especially those in hospitals in lower-middle-income countries.

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RSV caused high hospitalization rates and admission to intensive care units, especially among those with underlying illnesses and young infants. The data presented here will be useful for strategies to improve outcomes in children at risk of complications.

AWT is complex and multifactorial; it may be reduced by educating parents and care providers about infection and infection control and improving the availability of antibiotics and associated supplies. These interventions will most likely reduce ICU admissions and possibly LOS and increase the survival of pediatric oncology patients at SPMC.