A simulation model for colorectal cancer screening: potential of stool tests with various performance characteristics compared with screening colonoscopy.

OBJECTIVE: Many new stool tests intended to detect neoplastic cells or cell products are developed at present for colorectal cancer (CRC) screening. The aim of this study was to simulate a population-based screening setting to assess and compare the potential for early detection and prevention of CRC of screening based on stool tests with different sensitivity and specificity and of screening with colonoscopy as a primary screening tool. METHOD: A Markov model was developed aimed to estimate the proportion of CRC cases which are early detected or prevented due to screening as well as the number of equired stool tests and colonoscopies per early detected or prevented CRC case. Model outcomes were calculated for the offer of annual stool testing from age 55 to 74 in combination with colonoscopic follow-up of positive test results and for the offer of screening colonoscopy as a primary screening tool at ages 55 and 65. The long-lasting risk reduction of colonoscopy allowing the removal of precancerous lesions was taken into account quantitatively. RESULTS: For a variety of stool tests with different performance characteristics, the proportion of CRC cases early detected or prevented was estimated to be higher for stool testing in combination with colonoscopic follow-up of positive test results compared with screening colonoscopy assuming levels of compliance to be expected for the respective screening scheme. Optimizing performance characteristics of stool tests in terms of detecting precancerous lesions, in addition to those in terms of detecting CRC, seemed to be crucial for maximizing effectiveness of CRC screening with stool tests. CONCLUSION: Screening based on new stool tests with colonoscopic follow-up of positive test results might offer a high potential for early detection or prevention of CRC.     

Membrane depolarization is the initial action of crotoxin on isolated murine skeletal muscle.

Although much is known about the pathogenesis of crotoxin-induced muscle damage, the initial site and action of the toxin is still not clear. In this study we used an electrochromic fluorescent dye, Di-4-ANEPPS, to measure the changes in membrane potential of isolated murine omohyoid muscle to determine if depolarization could be one of the initial effects of crotoxin. Omohyoid isolates were pre-loaded with 1 microM Di-4-ANEPPS, exposed to various crotoxin treatments, and the change in fluorescence was recorded using either a dual-wavelength spectrofluorometer or digital imaging. Spectrofluorometry indicated that crotoxin depolarized isolated omohyoid muscles within 4 min as indicated by an increase in fluorescence to 122% of control values. Crotoxin also induced depolarization of extensor digitorum longus and soleus muscles as indicated by an increase in fluorescence of 140 and 110% of the control, respectively. Fluorescent images obtained from omohyoid muscle preparations exposed to crotoxin and Di-4-ANEPPS revealed localized areas of increased fluorescence, muscle contractions, derangement of myofibrils, and differing sensitivity to crotoxin of different muscle cells. Light microscopy results confirmed this variable disruption of muscle cell integrity and differing sensitivity to crotoxin. An increase in creatine kinase release rates confirmed damage to the plasma membrane. We conclude that plasma membrane depolarization is most likely the earliest indicator of cell damage from crotoxin and is quickly followed by hypercontraction of myofilaments, disruption of the plasma membrane, release of creatine kinase and necrosis.     

Early lens aging is accelerated in subjects with a high risk of ischemic heart disease: an epidemiologic study

Background  

Ischemic heart disease (IHD) is one of the most important causes of mortality and morbidity in the Western world. There is a relationship between aging of the lens of the human eye and cardiovascular disease. The present study was conducted to examine if the risk of ischemic heart disease could be estimated by fluorophotometric assessment of lens aging.     

Variation of Mean Absolute Relative Differences of Continuous Glucose Monitoring Systems Throughout the Day

Background:There is an increasing use of continuous glucose monitoring (CGM) by people with diabetes. Measurement performance is often characterized by the mean absolute relative difference (MARD). However, MARD is influenced by a number of factors and little is known about whether MARD is stable throughout the day.Material and Methods:A total of 24 participants with type 1 diabetes were enrolled in the study. The study was performed for seven in-patient days. Participants wore two CGM systems in parallel and performed additional frequent blood glucose (BG) measurements. On two days, glucose excursions were induced.MARD was calculated between pairs of CGM and BG values, with BG values serving as reference values. ARD values calculated from CGM-BG pairs were grouped by hour of the day. Results were analyzed separately for glucose excursion days and for regular days.Results:Total MARDs for the complete study duration were 12.5% ± 3.6% and 13.2% ± 2.4% (n = 24). Throughout the day marked variability of MARD was observed (8.0% ± 1.3%-16.3% ± 2.9% (G5); 9.1% ± 1.4%-16.3% ± 5.3% (FL), up to n = 157 each). Low(est) MARD values were observed before breakfast and dinner, when subjects were in or near a fasting state. Especially after breakfast and lunch, MARD values were higher than average.Conclusions:Analytical performance of the two CGM systems, assessed by MARD, was found to vary markedly throughout the day. Activities of daily life likely triggered these variations. An increasing number of CGM users base therapeutic decisions on CGM values, and they should be aware of these variations of performance throughout the day.     

Female adolescents' perceptions of male partners' pregnancy desire

Our objective was to examine the relationship between pregnancy desire among female adolescents and their perception of desire for pregnancy in their male partners. This is an observational cross-sectional study which examined 92 surveys administered to adolescent women between the ages of 14 to 19 years at two obstetrical care services serving a population from limited socioeconomic backgrounds. Participants were all pregnant or awaiting pregnancy test results. Participants were asked about their levels of pregnancy happiness and desire and their partners' levels of pregnancy happiness and desire. Spearman's correlation coefficient was calculated and discordant pairs were examined with McNemar's test. Logistic regression was utilized to examine the relationship between male and female pregnancy happiness and desire. We found that there was a significant correlation between the adolescents' feelings about pregnancy and their perceptions of their male partners' feelings about pregnancy (0.326; P = .004). McNemar's test indicated that male partners were significantly more likely to be reported to feel positively about the pregnancy than female partners (P = .017). Female adolescents who reported male partners who felt positively about the pregnancy were four times as likely to report having desired their pregnancy now or sooner (odds ratio [OR] = 4.35). We conclude that male partners may impact adolescent pregnancy desire. Further prospective studies are needed and male-focused adolescent pregnancy interventions should be developed.     

Structural characterization and cytotoxic properties of a 4-O-methylglucuronoxylan from castanea sativa. 2. Evidence of a structure-activity relationship

Xylans were purified from delignified holocellulose alkaline extracts of Castanea sativa (Spanish chestnut) and Argania spinosa (Argan tree) and their structures analyzed by means of GC of their per-trimethylsilylated methylglycoside derivatives and (1)H NMR spectroscopy. The structures deduced were characteristic of a 4-O-methylglucuronoxylan (MGX) and a homoxylan (HX), respectively, with degrees of polymerization ranging from 182 to 360. In the case of MGX, the regular or random distribution of 4-O-methylglucuronic acid along the xylosyl backbone--determined by MALDI mass spectrometry after autohydrolysis of the polysaccharide--varied and depended both on the botanical source from which they were extracted and on the xylan extraction procedure. The MGX also inhibited in different ways the proliferation as well as the migration and invasion capability of A431 human epidermoid carcinoma cells. These biological properties could be correlated with structural features including values of the degree of polymerization, 4-O-MeGlcA to xylose ratios, and distribution of 4-O-MeGlcA along the xylosyl backbone, giving evidence of a defined structure-activity relationship.