A 57-year-old male with a history of hypercholesterolemia and anxiety but otherwise in good health volunteered to donate the right lobe of his liver to his brother. The operation was performed uneventfully, without transfusion. Postoperatively he did well, until he developed tachycardia, profound hypotension, and coffee ground emesis on postoperative day 3. Despite resuscitative measures, he arrested and expired. Autopsy demonstrated gas gangrene of the stomach as the underlying cause of the hemorrhage and numerous colonies of Gram-positive bacilli were identified. Subsequent polymerase chain reaction (PCR) analysis identified these bacteria to be Clostridium perfringens (C. perfringens) type D. This patient's death was devastating, both to his family and his medical team. The impact of his death has transcended that of an individual occurrence. In conclusion, herein we present the facts and discuss this extraordinary example of florid clostridial infection and toxin-mediated shock. It was completely unexpected and probably unpreventable, and its cause was almost inconceivable. L iving donor liver transplants have been performed with increasing frequency. Formally and informally, 9 donor deaths have been reported. 1 -3 After performing more than 175 living donor liver transplants, we report the death of a donor in our program.The patient was a 57-year-old male with a history of hypercholesterolemia and anxiety but otherwise in good health, who volunteered to donate the right lobe of his liver to his brother. He had allergies to penicillin and bee venom. He took atorvastatin daily and clonazepam as needed. Preoperative evaluation followed our protocol. 4 Preoperative liver biopsy was normal. He was admitted the morning of surgery and received preoperative vancomycin and aztreonam.The operation was performed using previously described techniques. 5 The donor remained hemodynamically stable, required no transfusion, and was extubated in the operating room. Postoperative medications included epidural fentanyl, an H 2 -blocker, prophylactic antibiotics for 48 hours, and intravenous fluids. He stayed overnight in the recovery room and was transferred to the inpatient floor the following morning. Table 1 shows postoperative laboratory results. He was given liquids on postoperative day 1. Later, he felt so well that he asked his family for a lobster dinner from a local restaurant. The next morning, he felt well and sat in a chair. Temperature was 37.2°C, pulse was 79 beats per minute, and blood pressure was 126 / 69 mmHg. That evening, he complained of nausea and hiccups and was given metoclopramide and later thorazine. At midnight, his temperature was 36.8°C, his pulse was 115 beats per minute, and his blood pressure was 145 / 103 mmHg.Early on postoperative day 3, he was without complaints and sat in a chair. That afternoon, he again felt nauseated and had a small amount of guaiac-positive emesis. His tachycardia progressively worsened; 2 hours later he vomited again. Shortly thereafter, he became hypoxic and hypotens...

BackgroundAlzheimer's disease (AD) is the most common cause of dementia characterized by progressive cognitive impairment in the elderly people. The most dramatic abnormalities are those of the cholinergic system. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system, and hence, inhibition of AChE has emerged as one of the most promising strategies for the treatment of AD.MethodsIn this study, we suggest a workflow for the identification and prioritization of potential compounds targeted against AChE. In order to elucidate the essential structural features for AChE, three-dimensional pharmacophore models were constructed using Discovery Studio 2.5.5 (DS 2.5.5) program based on a set of known AChE inhibitors.ResultsThe best five-features pharmacophore model, which includes one hydrogen bond donor and four hydrophobic features, was generated from a training set of 62 compounds that yielded a correlation coefficient of R = 0.851 and a high prediction of fit values for a set of 26 test molecules with a correlation of R2 = 0.830. Our pharmacophore model also has a high Güner-Henry score and enrichment factor. Virtual screening performed on the NCI database obtained new inhibitors which have the potential to inhibit AChE and to protect neurons from Aβ toxicity. The hit compounds were subsequently subjected to molecular docking and evaluated by consensus scoring function, which resulted in 9 compounds with high pharmacophore fit values and predicted biological activity scores. These compounds showed interactions with important residues at the active site.ConclusionsThe information gained from this study may assist in the discovery of potential AChE inhibitors that are highly selective for its dual binding sites.

Cancer is a multifaceted disease that results from dysregulated normal cellular signaling networks caused by genetic, genomic and epigenetic alterations at cell or tissue levels. Uncovering the underlying protein signaling network changes, including cell cycle gene networks in cancer, aids in understanding the molecular mechanism of carcinogenesis and identifies the characteristic signaling network signatures unique for different cancers and specific cancer subtypes. The identified signatures can be used for cancer diagnosis, prognosis, and personalized treatment. During the past several decades, the available technology to study signaling networks has significantly evolved to include such platforms as genomic microarray (expression array, SNP array, CGH array, etc.) and proteomic analysis, which globally assesses genetic, epigenetic, and proteomic alterations in cancer. In this review, we compared Pathway Array analysis with other proteomic approaches in analyzing protein network involved in cancer and its utility serving as cancer biomarkers in diagnosis, prognosis and therapeutic target identification. With the advent of bioinformatics, constructing high complexity signaling networks is possible. As the use of signaling network-based cancer diagnosis, prognosis and treatment is anticipated in the near future, medical and scientific communities should be prepared to apply these techniques to further enhance personalized medicine.

Carnosine, a common dipeptide in mammals, has previously been shown to dissemble alpha-crystallin amyloid fibrils. To date, the dipeptide's anti-fibrillogensis effect has not been thoroughly characterized in other proteins. For a more complete understanding of carnosine's mechanism of action in amyloid fibril inhibition, we have investigated the effect of the dipeptide on lysozyme fibril formation and induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Our study demonstrates a positive correlation between the concentration and inhibitory effect of carnosine against lysozyme fibril formation. Molecular docking results show carnosine's mechanism of fibrillogenesis inhibition may be initiated by binding with the aggregation-prone region of the protein. The dipeptide attenuates the amyloid fibril-induced cytotoxicity of human neuronal cells by reducing both apoptotic and necrotic cell deaths. Our study provides solid support for carnosine's amyloid fibril inhibitory property and its effect against fibril-induced cytotoxicity in SH-SY5Y cells. The additional insights gained herein may pave way to the discovery of other small molecules that may exert similar effects against amyloid fibril formation and its associated neurodegenerative diseases.

Abstract-As integrated circuits become increasingly more complex and expensive, the ability to make post-fabrication changes will become much more attractive. This ability can be realized using programmable logic cores. Currently, such cores are available from vendors in the form of "hard" rectangular layouts. In this paper, we focus on an alternative approach for fine-grain programmability: vendors supply a synthesizable RTL version of their programmable logic core (a "soft" core) and the integrated circuit designer synthesizes the programmable logic fabric using standard cells. Although this technique suffers in terms of speed, density, and power overhead, the task of integrating such cores is far easier than the task of integrating "hard" cores into an ASIC or SoC. When the required amount of programmable logic is small, this ease of use may be more important than the increased overhead. This paper presents two synthesizable "soft" programmable logic core architectures and describes their associated place and route issues. We compare the two architectures to each other, and to a "hard" programmable logic core. We also show how these cores can be made more efficient by creating a nonrectangular architecture, an option not usually available to "hard" core vendors. Finally, a proof-of-concept integrated circuit containing one of these cores is described.Index Terms-Field-programmable gate arrays, programmable logic, SoC design.