Assessment of anastomotic leakage: A Novel System for the Training of Surgeons to Perform a Tubular Anastomosis and Objectively Evaluate Anastomotic Leak

Introduction: Dehiscence of the suture line of an anastomosis can lead to reoperation, temporary or permanent stoma, and even sepsis or death. Few techniques for the laboratory training of tubular anastomosis use ex-vivo animal tissues. We describe a novel model that can be used in the laboratory for the training of anastomosis in tubular tissues and objectively assess any anastomotic leak. [See PDF for complete abstract]

AN OCCUPATIONAL INJURY MANAGEMENT INFORMATION SYSTEM FOR THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON

The purpose of this research and development project was to develop a method, a design, and a prototype for gathering, managing, and presenting data about occupational injuries.^ State-of-the-art systems analysis and design methodologies were applied to the long standing problem in the field of occupational safety and health of processing workplace injuries data into information for safety and health program management as well as preliminary research about accident etiologies. The top-down planning and bottom-up implementation approach was utilized to design an occupational injury management information system. A description of a managerial control system and a comprehensive system to integrate safety and health program management was provided.^ The project showed that current management information systems (MIS) theory and methods could be applied successfully to the problems of employee injury surveillance and control program performance evaluation. The model developed in the first section was applied at The University of Texas Health Science Center at Houston (UTHSCH).^ The system in current use at the UTHSCH was described and evaluated, and a prototype was developed for the UTHSCH. The prototype incorporated procedures for collecting, storing, and retrieving records of injuries and the procedures necessary to prepare reports, analyses, and graphics for management in the Health Science Center. Examples of reports, analyses, and graphics presenting UTHSCH and computer generated data were included.^ It was concluded that a pilot test of this MIS should be implemented and evaluated at the UTHSCH and other settings. Further research and development efforts for the total safety and health management information systems, control systems, component systems, and variable selection should be pursued. Finally, integration of the safety and health program MIS into the comprehensive or executive MIS was recommended. ^

Cis-acting elements and developmental regulators govern toxin gene expression in Bacillus anthracis

Expression of the structural genes for the anthrax toxin proteins is coordinately controlled by host-related signals such as elevated CO2 , and the trans-acting positive regulator, AtxA. No specific binding of AtxA to the toxin gene promoters has been demonstrated and no sequence-based similarities are apparent in the promoter regions of toxin genes. We hypothesized that the toxin genes possess common structural features that are required for positive regulation. To test this hypothesis, I performed an extensive characterization of the toxin gene promoters. I determined the minimal sequences required for atxA-mediated toxin gene expression and compared these sequences for structural similarities. In silico modeling and in vitro experiments indicated significant curvature within these regions. Random mutagenesis revealed that point mutations associated with reduced transcriptional activity, mostly mapped to areas of high curvature. This work enabled the identification of two potential cis-acting elements implicated in AtxA-mediated regulation of the toxin genes. In addition to the growth condition requirements and AtxA, toxin gene expression is under growth phase regulation. The transition state regulator AbrB represses atxA expression to influence toxin synthesis. Here I report that toxin gene expression also requires sigH, a gene encoding the RNA polymerase sigma factor associated with development in B. subtilis. In the well-studied B. subtilis system, σH is part of a feedback control pathway that involves AbrB and the major response regulator of sporulation initiation, Spo0A. My data indicate that in B. anthracis, regulatory relationships exist between these developmental regulators and atxA . Interestingly, during growth in toxin-inducing conditions, sigH and abrB expression deviates from that described for B. subtilis, affecting expression of the atxA gene. These findings, combined with previous observations, suggest that the steady state level of atxA expression is critical for optimal toxin gene transcription. I propose a model whereby, under toxin-inducing conditions, control of toxin gene expression is fine-tuned by the independent effects of the developmental regulators on the expression of atxA . The growth condition-dependent changes in expression of these regulators may be crucial for the correct timing and uninterrupted expression of the toxin genes during infection. ^

The chronobiology of the menstrual life sequence of American women

Seasonal variation in menarche, menstrual cycle length and menopause was investigated using Tremin Trust data. Too, self-reported hot flash data for women with natural and surgically-induced menopause were analyzed for rhythms.^ Menarche data from approximately 600 U.S. women born between 1940 and 1970 revealed a 6-month rhythm (first acrophase in January, double amplitude of 58%M). A notable shift from a December-January peak in menarche for those born in the 1940s and 1950s to an August-September peak for those born in the 1960s was observed. Groups of girls 8-14 and 15-17 yr old at menarche exhibited a seasonal difference in the pattern of menarche occurrence of about 6 months in relation to each other. Girls experiencing menarche during August-October were statistically significantly younger than those experiencing it at other times. Season of birth was not associated with season of menarche.^ The lengths of approximately 150,000 menstrual intervals of U.S. women were analyzed for seasonality. Menstrual intervals possibly disturbed by natural (e.g., childbirth) or other events (e.g., surgery, medication) were excluded. No 6- or 12-month rhythmicities were found for specific interval lengths (14-24, 25-31 and 32-56 days) or ages in relation to menstrual interval (9-11, 12-13, 15-19, 20-24, 25-39, 40-44 and 44 yr old and older).^ Hot flash data of 14 women experiencing natural menopause (NM) and 11 experiencing surgically-induced menopause (SIM) did not differ in frequency of hot flashes. Hot flashes in NM women exhibited 12- and 8-hr, but not 24-hr rhythmicities. Hot flashes in SIM women exhibited 24- and 12-hr, but not 8-hr, rhythmicities. Regardless of type of menopause, women with a peak frequency in hot flashes during the morning (0400 through 0950) were distinguishable from those with such in the evening (1600 through 2159).^ Data from approximately 200 U.S. women revealed a 6-month rhythm in menopause with first peak in May. No significant 12-month variation in menopause was detected by Cosinor analysis. Season of birth and age at menopause were not associated with season of menopause. Age at menopause declined significantly over the years for women born between 1907 and 1926, inclusive. ^

Genetic variants within the Wnt/ B-catenin signaling pathway as indicators of bladder cancer clinical outcomes

The genetic factors that influence bladder cancer clinical outcomes are largely unknown. In this clinical outcomes study, I assessed genetic variations in the Wnt/β-catenin stem-cell pathway genes for association with recurrence and progression. A total of 230 SNPS in 40 genes from the Wnt/β-catenin pathway were genotyped in 419 histologically confirmed non-muscle invasive bladder cancer cases. Several significant associations were observed in the clinical outcomes analysis. Under the dominant model WNT8B: rs4919464 (HR: 1.55, 95% CI: 1.17-2.06, P=2.2x10-3) and WNT8B: rs3793771 (HR: 1.54, 95% CI: 1.09-1.62, P=4.6x10-3 ) were statistically significantly associated with an increase risk of recurrence while two other variants, APC2: rs11668593 (HR: 2.50, 95% CI: 1.43-4.35, P=1.2x10-3) and LRP5 : rs312778 (HR: 1.81, 95% CI: 1.23-2.65, P=2.7x10-3), were significantly associated with recurrence risk under the recessive model of inheritance. Four SNPs in the recessive model were associated with an increased risk of progression (AXIN2: rs1544427, LRP5: rs312778, AXIN1: rs370681, AXIN1: rs2301522). LRP5: rs312778 had the most significant increased risk of progression with a 2.68 (95% CI: 1.52-4.72, P=6.4x10-4)-fold increased risk. Stratification analysis based on treatment regimen (transurethral resection (TUR) and Bacillus Calmette-Guérin (BCG)) was also performed. Individuals with at least one variant in AXIN2: rs2007085 were found to have a 2.09 (95% CI: 1.24-3.52, P=5.4x10-3) -fold increased risk of recurrence in those that received TUR only, and no statistically significant effect was seen in those that received BCG. Individuals who received TUR with at least one variant in LEF1: rs10516550 were found to have a 2.26 (95% CI: 1.22-4.18, P=9.7x10-3)-fold increase risk of recurrence and no statistically significant effect was found in individuals who received BCG. Also, the recessive model of LRP6: rs2302684 in TUR only treatment was shown to have a 1.95 (95%CI: 1.18-3.21, P=8.8x10 -3)-fold increased risk of recurrence, and a suggested protective effect associated with a (HR: 0.83, 95% CI: 0.51-1.37, P=0.468) decreased risk of recurrence. Together, these findings implicate the Wnt/β-catenin stem-cell pathway as playing a role in bladder cancer clinical outcomes and have important implications for personalization of future treatment regimens. ^