Age-related difference in susceptibility of ApcMin/+ mice towards the chemopreventive efficacy of dietary aspirin and curcumin

The nonsteroidal anti-inflammatory drug aspirin and the spice curcumin retard adenoma formation when administered long-term to ApcMin/+ mice, a model of human familial adenomatous polyposis coli. Both agents interfere with cyclooxygenase activity. When aspirin is administered to ApcMin/+ mice only postweaning, but not before, it is inefficacious, while curcumin given postweaning is active. Here the hypothesis was tested that dietary aspirin (0.05%) or curcumin (0.2%) prevent or delay adenoma formation in offsprings when administered to ApcMin/+ mothers and up to the end of weaning, but not afterwards. Whereas curcumin was without effect when administered in this way, aspirin reduced numbers of intestinal adenomas by 21%. When aspirin given up to the end of weaning was combined with curcumin administered from the end of weaning for the rest of the animals' lifetime, intestinal adenoma numbers were reduced by 38%. The combination was not superior to intervention postweaning with curcumin alone. These results show that aspirin exerts chemopreventive activity in the ApcMin/+ mouse during tumour initiation/early promotion, while curcumin is efficacious when given at a later stage of carcinogenic progression. Thus, the results suggest that in this mouse model aspirin and curcumin act during different ‘windows’ of neoplastic development

The Distances of the Magellanic Clouds

The present status of our knowledge of the distances to the Magellanic Clouds is evaluated from a post-Hipparcos perspective. After a brief summary of the effects of structure, reddening, age and metallicity, the primary distance indicators for the Large Magellanic Cloud are reviewed: The SN 1987A ring, Cepheids, RR Lyraes, Mira variables, and Eclipsing Binaries. Distances derived via these methods are weighted and combined to produce final "best" estimates for the Magellanic Clouds distance moduli.Comment: Invited review article to appear in ``Post Hipparcos Cosmic Candles'', F. Caputo & A. Heck (Eds.), Kluwer Academic Publ., Dordrecht, in pres

Comparison of minimally invasive surgical approaches for hysterectomy at a community hospital: robotic-assisted laparoscopic hysterectomy, laparoscopic-assisted vaginal hysterectomy and laparoscopic supracervical hysterectomy

The study reported here compares outcomes of three approaches to minimally invasive hysterectomy for benign indications, namely, robotic-assisted laparoscopic (RALH), laparoscopic-assisted vaginal (LAVH) and laparoscopic supracervical (LSH) hysterectomy. The total patient cohort comprised the first 237 patients undergoing robotic surgeries at our hospital between August 2007 and June 2009; the last 100 patients undergoing LAVH by the same surgeons between July 2006 and February 2008 and 165 patients undergoing LAVHs performed by nine surgeons between January 2008 and June 2009; 87 patients undergoing LSH by the same nine surgeons between January 2008 and June 2009. Among the RALH patients were cases of greater complexity: (1) higher prevalence of prior abdominopelvic surgery than that found among LAVH patients; (2) an increased number of procedures for endometriosis and pelvic reconstruction. Uterine weights also were greater in RALH patients [207.4 vs. 149.6 (LAVH; P < 0.001) and 141.1 g (LSH; P = 0.005)]. Despite case complexity, operative time was significantly lower in RALH than in LAVH (89.9 vs. 124.8 min, P < 0.001) and similar to that in LSH (89.6 min). Estimated blood loss was greater in LAVH (167.9 ml) than in RALH (59.0 ml, P < 0.001) or LSH (65.7 ml, P < 0.001). Length of hospital stay was shorter for RALH than for LAVH or LSH. Conversion and complication rates were low and similar across procedures. Multivariable regression indicated that LAVH, obesity, uterine weight ≥250 g and older age predicted significantly longer operative time. The learning curve for RALH demonstrated improved operative time over the case series. Our findings show the benefits of RALH over LAVH. Outcomes in RALH can be as good as or better than those in LSH, suggesting the latter should be the choice primarily for women desiring cervix-sparing surgery

Spared unconscious influences of spatial memory in diencephalic amnesia

Spatial memory is crucial to our daily lives and in part strongly depends on automatic, implicit memory processes. This study investigates the neurocognitive basis of conscious and unconscious influences of object–location memory in amnesic patients with Korsakoff’s syndrome (N = 23) and healthy controls (N = 18) using a process-dissociation procedure in a computerized spatial memory task. As expected, the patients performed substantially worse on the conscious memory measures but showed even slightly stronger effects of unconscious influences than the controls. Moreover, a delayed test administered after 1 week revealed a strong decline in conscious influences in the patients, while unconscious influences were not affected. The presented results suggest that conscious and unconscious influences of spatial memory can be clearly dissociated in Korsakoff’s syndrome

Therapeutic utility of aspirin in the Apc(Min/+) murine model of colon carcinogenesis

BACKGROUND: In recent years it has become evident that nonsteroidal anti-inflammatory drugs, in particular aspirin represent a potential class of cancer chemotherapeutic agents. Despite the wealth of knowledge gained from epidemiological, clinical and animal studies, the effectiveness of aspirin to treat established gastrointestinal cancer has not been determined. The present study examines the ability of aspirin to treat established polyposis in Min/+ mice. METHODS: Min/+ mice with established polyposis were treated orally once daily from 12–16 weeks of age with either drug vehicle or aspirin (25 mg/kg). Upon completion of treatment, the number, location and size of intestinal tumours was determined. Additional variables examined were the number of apoptotic cells within tumours and COX activity. RESULTS: Administration of aspirin for 4 weeks to Min/+ mice produce no effect on tumour number compared to vehicle-treated Min/+ mice (65 ± 8 vs. 63 ± 9, respectively). In addition, aspirin had no effect on tumour size or location. However, aspirin treatment produced a greater than 2-fold (p < 0.05) increase in the number of apoptotic positive cells within tumours and significantly decreased hepatic PGE(2) content. CONCLUSIONS: Aspirin was found to have no effect on tumour number and size when administered to Min/+ mice with established polyposis. The findings in the present study call in to question the utility of aspirin as a stand-alone treatment for established GI cancer. However, aspirin's ability to significantly promote apoptosis may render it suitable for use in combinatorial chemotherapy

Consumer perceptions of co-branding alliances: Organizational dissimilarity signals and brand fit

This study explores how consumers evaluate co-branding alliances between dissimilar partner firms. Customers are well aware that different firms are behind a co-branded product and observe the partner firms’ characteristics. Drawing on signaling theory, we assert that consumers use organizational characteristics as signals in their assessment of brand fit and for their purchasing decisions. Some organizational signals are beyond the control of the co-branding partners or at least they cannot alter them on short notice. We use a quasi-experimental design and test how co-branding partner dissimilarity affects brand fit perception. The results show that co-branding partner dissimilarity in terms of firm size, industry scope, and country-of-origin image negatively affects brand fit perception. Firm age dissimilarity does not exert significant influence. Because brand fit generally fosters a benevolent consumer attitude towards a co-branding alliance, the findings suggest that high partner dissimilarity may reduce overall co-branding alliance performance

A standard numbering scheme for class C β-lactamases

Unlike classes A and B, a standardized amino acid numbering scheme has not been proposed for the class C (AmpC) β-lactamases, which complicates communication in the field. Here, we propose a scheme developed through a collaborative approach that considers both sequence and structure, preserves traditional numbering of catalytically important residues (Ser64, Lys67, Tyr150, and Lys315), is adaptable to new variants or enzymes yet to be discovered, and includes a variation for genetic and epidemiological applications

Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic

A new method for determining physician decision thresholds using empiric, uncertain recommendations

<p>Abstract</p> <p>Background</p> <p>The concept of risk thresholds has been studied in medical decision making for over 30 years. During that time, physicians have been shown to be poor at estimating the probabilities required to use this method. To better assess physician risk thresholds and to more closely model medical decision making, we set out to design and test a method that derives thresholds from actual physician treatment recommendations. Such an approach would avoid the need to ask physicians for estimates of patient risk when trying to determine individual thresholds for treatment. Assessments of physician decision making are increasingly relevant as new data are generated from clinical research. For example, recommendations made in the setting of ocular hypertension are of interest as a large clinical trial has identified new risk factors that should be considered by physicians. Precisely how physicians use this new information when making treatment recommendations has not yet been determined.</p> <p>Results</p> <p>We derived a new method for estimating treatment thresholds using ordinal logistic regression and tested it by asking ophthalmologists to review cases of ocular hypertension before expressing how likely they would be to recommend treatment. Fifty-eight physicians were recruited from the American Glaucoma Society. Demographic information was collected from the participating physicians and the treatment threshold for each physician was estimated. The method was validated by showing that while treatment thresholds varied over a wide range, the most common values were consistent with the 10-15% 5-year risk of glaucoma suggested by expert opinion and decision analysis.</p> <p>Conclusions</p> <p>This method has advantages over prior means of assessing treatment thresholds. It does not require physicians to explicitly estimate patient risk and it allows for uncertainty in the recommendations. These advantages will make it possible to use this method when assessing interventions intended to alter clinical decision making.</p

Nitrogen doping into titanium dioxide by the sol–gel method using nitric acid

N-doped TiO(2) has been prepared by use of sol-gel systems containing titanium alkoxide, with nitric acid as the nitrogen source. The time needed for gelation of the systems was drastically reduced by ultrasonic irradiation. The peaks assigned to the nitrate and nitrous ions were observed by FT-IR measurement during the sol-gel reaction. The N-doping was confirmed by the observation of N-O peaks in the XPS spectrum of the sample heated at 400 A degrees C. The nitrate ion acted as an oxidizer of the ethanol solvent and titanium species. The TiO(2) became doped with nitrogen oxide species as a result of reduction of nitrate ion incorporated into the dried gel samples. These results indicated that the added nitric acid was reduced during the sol-gel transition and heating process, and the resulting NO species were situated in the titania networks. The UV and visible photocatalytic activity of the samples was confirmed by the degradation of trichloroethylene.ArticleRESEARCH ON CHEMICAL INTERMEDIATES. 37(8):869-881 (2011)journal articl