Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4×10−6 (serial isolates) to 4.5×10−6 (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5–17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude

Factors influencing elderly women's mammography screening decisions: implications for counseling

<p>Abstract</p> <p>Background</p> <p>Although guidelines recommend that clinicians consider life expectancy before screening older women for breast cancer, many older women with limited life expectancies are screened. We aimed to identify factors important to mammography screening decisions among women aged 80 and older compared to women aged 65–79.</p> <p>Methods</p> <p>Telephone surveys of 107 women aged 80+ and 93 women aged 65–79 randomly selected from one academic primary care practice who were able to communicate in English (60% response rate). The survey addressed the following factors in regards to older women's mammography screening decisions: perceived importance of a history of breast disease, family history of breast cancer, doctor's recommendations, habit, reassurance, previous experience, mailed reminder cards, family/friend's recommendations or experience with breast cancer, age, health, and media. The survey also assessed older women's preferred role in decision making around mammography screening.</p> <p>Results</p> <p>Of the 200 women, 65.5% were non-Hispanic white and 82.8% were in good to excellent health. Most (81.3%) had undergone mammography in the past 2 years. Regardless of age, older women ranked doctor's recommendations as the most important factor influencing their decision to get screened. Habit and reassurance were the next two highly ranked factors influencing older women to get screened. Among women who did not get screened, women aged 80 and older ranked age and doctor's counseling as the most influential factors and women aged 65–79 ranked a previous negative experience with mammography as the most important factor. There were no significant differences in preferred role in decision-making around mammography screening by age, however, most women in both age groups preferred to make the final decision on their own (46.6% of women aged 80+ and 50.5% of women aged 65–79).</p> <p>Conclusion</p> <p>While a doctor's recommendation is the most important factor influencing elderly women's mammography screening decisions, habit and reassurance also strongly influence decision-making. Interventions aimed at improving clinician counseling about mammography, which include discussions around habit and reassurance, may result in better decision-making.</p

Designing a patient-centered personal health record to promote preventive care

<p>Abstract</p> <p>Background</p> <p>Evidence-based preventive services offer profound health benefits, yet Americans receive only half of indicated care. A variety of government and specialty society policy initiatives are promoting the adoption of information technologies to engage patients in their care, such as personal health records, but current systems may not utilize the technology's full potential.</p> <p>Methods</p> <p>Using a previously described model to make information technology more patient-centered, we developed an interactive preventive health record (IPHR) designed to more deeply engage patients in preventive care and health promotion. We recruited 14 primary care practices to promote the IPHR to all adult patients and sought practice and patient input in designing the IPHR to ensure its usability, salience, and generalizability. The input involved patient usability tests, practice workflow observations, learning collaboratives, and patient feedback. Use of the IPHR was measured using practice appointment and IPHR databases.</p> <p>Results</p> <p>The IPHR that emerged from this process generates tailored patient recommendations based on guidelines from the U.S. Preventive Services Task Force and other organizations. It extracts clinical data from the practices' electronic medical record and obtains health risk assessment information from patients. Clinical content is translated and explained in lay language. Recommendations review the benefits and uncertainties of services and possible actions for patients and clinicians. Embedded in recommendations are self management tools, risk calculators, decision aids, and community resources - selected to match patient's clinical circumstances. Within six months, practices had encouraged 14.4% of patients to use the IPHR (ranging from 1.5% to 28.3% across the 14 practices). Practices successfully incorporated the IPHR into workflow, using it to prepare patients for visits, augment health behavior counseling, explain test results, automatically issue patient reminders for overdue services, prompt clinicians about needed services, and formulate personalized prevention plans.</p> <p>Conclusions</p> <p>The IPHR demonstrates that a patient-centered personal health record that interfaces with the electronic medical record can give patients a high level of individualized guidance and be successfully adopted by busy primary care practices. Further study and refinement are necessary to make information systems even more patient-centered and to demonstrate their impact on care.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00589173">NCT00589173</a></p

The Phenotypic Radiation Resistance of CD44+/CD24−or low Breast Cancer Cells Is Mediated through the Enhanced Activation of ATM Signaling

Cancer initiating cells (CIC) are stem-like cells. CIC may contribute not only to the initiation of cancer but also to cancer recurrence because of the resistance of CIC both to chemotherapy and radiation therapy. From the MCF-7 and MDA-MB231 breast cancer cell lines and primary culture of patient breast cancer cells, we isolated by flow cytometry a CIC subset of cells with the CD44+/CD24−or low phenotype. The CD44+/CD24−or low subset showed increased sphere formation and resistance to radiation compared to the non- CD44+/CD24−or low subset. The increased radiation resistance was not dependent on the result of altered non-homologous end joining (NHEJ) DNA repair activity as both NHEJ activity and expression of the various proteins involved in NHEJ were not significantly different between the CD44+/CD24−or low and non- CD44+/CD24−or low subsets. However, activation of ATM signaling was significantly increased in CD44+/CD24−or low cells compared to non- CD44+/CD24−or low cells in both from breast cancer cell lines and primary human breast cancer cells. Application of an ATM inhibitor effectively decreased the radiation resistance of CD44+/CD24−or low subset, suggesting that targeting ATM signaling may provide a new tool to eradicate stem-like CIC and abolish the radiation resistance of breast cancer

Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma

Survivin is unique for its expression in human malignancies but not in normal adult cells. It has been implicated in sensitisation to chemotherapy and as a prognostic marker in several common cancers. Immunohistochemistry for Survivin, P53 and BCL-2 expression as well as cell proliferative index (Ki-67) and apoptosis index (TUNEL) was conducted on 52 pancreatic and 12 ampullary adenocarcinomas. Survivin was detected in the cytoplasm of carcinoma cells in 46 (88%) of pancreatic tumours. P53 and BCL-2 were detected in 54% and 12% of pancreatic tumours, respectively. Proliferative index was 26.2±10.5% and apoptosis index was 1.38±0.69%. Prevalence of Survivin expression was significantly higher in P53-positive than in P53-negative cases (P=0.05) but was not associated with BCL-2 expression. Incrementally higher weighted scores of Survivin expression were associated with increased proliferative index (P=0.001). Furthermore, there was linear correlation between increased proliferative index and higher apoptosis index (P<0.001). Surprisingly, higher scores of Survivin expression were associated with increased apoptosis index (P=0.007). Survival characteristics were not influenced by Survivin, P53 or BCL-2 expression, apoptosis index or proliferative index. Ampullary carcinoma showed Survivin expression in 83% of cases. However, unlike pancreatic carcinoma, there was no correlation between Survivin and P53 expression or proliferative index. In conclusion, Survivin is expressed in the majority of pancreatic adenocarcinomas and correlates with both cellular proliferation and apoptosis. Molecular manipulation of Survivin expression may enhance chemotherapy and radiation therapy for pancreatic cancer