Citations

A number of inherited disorders result in renal cyst development. The most common form, autosomal dominant polycystic kidney disease (ADPKD), is a disorder most often diagnosed in adults and caused by mutation in PKD1 or PKD2. The PKD1 protein, polycystin-1, is a large receptor-like protein, whereas polycystin-2 is a transient receptor potential channel. The polycystin complex localizes to primary cilia and may act as a mechanosensor essential for maintaining the differentiated state of epithelia lining tubules in the kidney and biliary tract. Elucidation of defective cellular processes has highlighted potential therapies, some of which are now being tested in clinical trials. ARPKD is the neonatal form of PKD and is associated with enlarged kidneys and biliary dysgenesis. The disease phenotype is highly variable, ranging from neonatal death to later presentation with minimal kidney disease. ARPKD is caused by mutation in PKHD1, and two truncating mutations are associated with neonatal lethality. The ARPKD protein, fibrocystin, is localized to cilia/basal body and complexes with polycystin-2. Rare, syndromic forms of PKD also include defects of the eye, central nervous system, digits, and/or neural tube and highlight the role of cilia and pathways such as Wnt and Hh in their pathogenesis.

Background: Laparoscopic ventral hernia repair (LVHR) has gained wide acceptance by both surgeons and patients, but hernias that approach a bony prominence are more complex due to the difficulty of proper fixation. This study was conducted to evaluate the use of bone anchor mesh fixation for complex LVHR. Methods: A prospective study of patients having complex LVHR with bone anchors was conducted using patients from 2 academic institutions between July 2003 and December 2007. Patient demographic data, characteristics of the hernia, operative details, and postoperative outcomes were recorded. Results: A total of 30 patients who had LVHR using bone anchors were evaluated (20 women, 10 men; mean age 60.9 years, range 41-83 years). In all, 17 suprapubic and 13 lateral hernias were included, requiring a mean of 2.8 and 3.2 bone anchors, respectively. The average hernia defect was 263 cm 2 (range 35-690 cm 2 ), and the average mesh size was 663 cm 2 (range 255-1360 cm 2 ). Mean operative time was 218 minutes (range 98-420 minutes), with an estimated blood loss of 46 mL (range 10-100 mL). The average length of stay was 5.2 days (range 1-26 days). Seven patients (23.3%) developed postoperative complications, and 1 patient in this study died (mortality 3.3%). During follow-up of 13.2 months (range 1-26 months), 2 patients (6.7%) developed a recurrent hernia. Conclusions: Bone anchors can be used successfully in the laparoscopic repair of complex ventral hernias, particularly with suprapubic and lateral hernias that approach a bony prominence. The complication rate is acceptable, with a short hospital stay and low recurrence rate.

Abstract Motivation: Specific non-covalent binding of metal ions and ligands, such as nucleotides and cofactors, is essential for the function of many proteins. Computational methods are useful for predicting the location of such binding sites when experimental information is lacking. Methods that use structural information, when available, are particularly promising since they can potentially identify non-contiguous binding motifs that cannot be found using only the amino acid sequence. Furthermore, a prediction method that can utilize low-resolution models is advantageous because high-resolution structures are available for only a relatively small fraction of proteins. Results: SitePredict is a machine learning-based method for predicting binding sites in protein structures for specific metal ions or small molecules. The method uses Random Forest classifiers trained on diverse residue-based site properties including spatial clustering of residue types and evolutionary conservation. SitePredict was tested by cross-validation on a set of known binding sites for six different metal ions and five different small molecules in a non-redundant set of protein–ligand complex structures. The prediction performance was good for all ligands considered, as reflected by AUC values of at least 0.8. Furthermore, a more realistic test on unbound structures showed only a slight decrease in the accuracy. The properties that contribute the most to the prediction accuracy of each ligand were also examined. Finally, examples of predicted binding sites in homology models and uncharacterized proteins are discussed. Availability: Binding site prediction results for all PDB protein structures and human protein homology models are available at http://sitepredict.org/. Contact: bordner.andrew@mayo.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Pulmonary edema is a rare, potentially fatal complica tion associated with major resection of the lung, usually pneumonectomy. Although pulmonary edema in this setting can often be attributed to a variety of causes such as cardiac failure, bacterial pneumonia, and fluid overload, the specific syndrome of postpneumonec tomy pulmonary edema (PPE) occurs in the absence of these factors. PPE remains a diagnosis of exclusion, and its pathophysiology is poorly understood. Overzealous perioperative fluid administration has traditionally been implicated in clinical cases of postpneumonectomy pulmonary edema, but there is a body of evidence suggesting several other potential mechanisms. These include increases in cardiac output secondary to cat echolamine release, interruption of mediastinal lym phatic drainage, endothelial injury secondary to release of humoral factors or stretching of intercellular junc tions, hyperinflation, and other unknown factors.

Provision of anesthesia care to patients undergoing thoracoscopic procedures, especially video-assisted thoracoscopy, requires thorough knowledge of the sur gical procedure and the physiology of one-lung ventila tion, as well as meticulous attention to detail by the anesthesia personnel caring for these patients. Thoracos copy is used increasingly to perform almost the entire range of thoracic surgical procedures in a minimally invasive fashion. Excellent quality anesthetic care is necessary to assure the benefits of minimally invasive surgery to the maximum number of patients undergo ing thoracic surgery. This article will provide anesthesi ologists caring for patients undergoing thoracoscopy with the necessary working knowledge of the technical aspects of the procedure and understanding of the relevant anesthetic implications. Preoperative, intraop erative, and postoperative concerns will be addressed. The scope of this article will be limited to noncardiac uses of thoracoscopy.

Paraplegia is a major complication associated with repair of thoracoabdominal aortic aneurysms (TAAA). A number of therapies have been tried over the years, none of which has been successful. Recently, regional lumbar epidural cooling has been tried in an attempt to prolong the safe ischemic time during aortic cross- clamping. In approximately 90 patients in whom the authors have tried this technique, there was no de crease in the incidence of paraplegia in patients with type II TAAAs. This is perhaps not unanticipated be cause the paraplegia is related to a number of factors including the duration of the aortic cross-clamping, the adequacy of collateral circulation, embolization during the procedure, and perhaps thrombosis in situ. Given the multimodal cause of paraplegia, perhaps it is naive to think that a single therapy would be of benefit. Additional studies are necessary to explore the mecha nisms and to prove efficacy or lack of benefit of any techniques designed to decrease the incidence of paraplegia in patients undergoing TAAA repair.

The postoperative care of a patient who receives an intra-abdominal organ transplant is in some ways simi lar to that of any major intra-abdominal procedure. However, certain features unique to organ transplanta tion, such as the variable functional status of the newly transplanted graft, complications that are specific to the organ transplanted, and the side effects from immuno suppressive drugs, suggest that transplantation inten sive care is a distinct subspecialty in critical care medicine. Today, the majority of patients receiving an intra-abdominal transplant will have a relatively uncom plicated postoperative course. However, preoperative disposition, intraoperative misadventure, or immediate postoperative difficulty will require the availability of an intensivist experienced in transplantation. The future of intra-abdominal transplantation will be highly depen dent on progress in immunotherapy. Newer, more spe cific immunomodulators with fewer nonimmune toxici ties should result in improved organ receptance, less graft dysfunction, and improved patient survival.