The value of age and medical history for predicting colorectal cancer and adenomas in people referred for colonoscopy

<p>Abstract</p> <p>Background</p> <p>Colonoscopy is an invasive and costly procedure with a risk of serious complications. It would therefore be useful to prioritise colonoscopies by identifying people at higher risk of either cancer or premalignant adenomas. The aim of this study is to assess a model that identifies people with colorectal cancer, advanced, large and small adenomas.</p> <p>Methods</p> <p>Patients seen by gastroenterologists and colorectal surgeons between April 2004 and December 2006 completed a validated, structured self-administered questionnaire prior to colonoscopy. Information was collected on symptoms, demographics and medical history. Multinomial logistic regression was used to simultaneously assess factors associated with findings on colonoscopy of cancer, advanced adenomas and adenomas sized 6 -9 mm, and ≤ 5 mm. The area under the curve of ROC curve was used to assess the incremental gain of adding demographic variables, medical history and symptoms (in that order) to a base model that included only age.</p> <p>Results</p> <p>Sociodemographic variables, medical history and symptoms (from 8,204 patients) jointly provide good discrimination between colorectal cancer and no abnormality (AUC 0.83), but discriminate less well between adenomas and no abnormality (AUC advanced adenoma 0.70; other adenomas 0.67). Age is the dominant risk factor for cancer and adenomas of all sizes. Having a colonoscopy within the last 10 years confers protection for cancers and advanced adenomas.</p> <p>Conclusions</p> <p>Our models provide guidance about which factors can assist in identifying people at higher risk of disease using easily elicited information. This would allow colonoscopy to be prioritised for those for whom it would be of most benefit.</p

European Society of Endodontology position statement: Management of deep caries and the exposed pulp

This position statement on the management of deep caries and the exposed pulp represents the consensus of an expert committee, convened by the European Society of Endodontology (ESE). Preserving the pulp in a healthy state with sustained vitality, preventing apical periodontitis and developing minimally invasive biologically based therapies are key themes within contemporary clinical endodontics. The aim of this statement was to summarize current best evidence on the diagnosis and classification of deep caries and caries‐induced pulpal disease, as well as indicating appropriate clinical management strategies for avoiding and treating pulp exposure in permanent teeth with deep or extremely deep caries. In presenting these findings, areas of controversy, low‐quality evidence and uncertainties are highlighted, prior to recommendations for each area of interest. A recently published review article provides more detailed information and was the basis for this position statement (Bjørndal et al. 2019, International Endodontic Journal, doi:10.1111/iej.13128). The intention of this position statement is to provide the practitioner with relevant clinical guidance in this rapidly developing area. An update will be provided within 5 years as further evidence emerges

The Protein Network Surrounding the Human Telomere Repeat Binding Factors TRF1, TRF2, and POT1

Telomere integrity (including telomere length and capping) is critical in overall genomic stability. Telomere repeat binding factors and their associated proteins play vital roles in telomere length regulation and end protection. In this study, we explore the protein network surrounding telomere repeat binding factors, TRF1, TRF2, and POT1 using dual-tag affinity purification in combination with multidimensional protein identification technology liquid chromatography - tandem mass spectrometry (MudPIT LC-MS/MS). After control subtraction and data filtering, we found that TRF2 and POT1 co-purified all six members of the telomere protein complex, while TRF1 identified five of six components at frequencies that lend evidence towards the currently accepted telomere architecture. Many of the known TRF1 or TRF2 interacting proteins were also identified. Moreover, putative associating partners identified for each of the three core components fell into functional categories such as DNA damage repair, ubiquitination, chromosome cohesion, chromatin modification/remodeling, DNA replication, cell cycle and transcription regulation, nucleotide metabolism, RNA processing, and nuclear transport. These putative protein-protein associations may participate in different biological processes at telomeres or, intriguingly, outside telomeres

In vitro evaluation of the microhardness of bovine enamel exposed to acid solutions after bleaching

Acid erosion is a superficial loss of enamel caused by chemical processes that do not involve bacteria. Intrinsic and extrinsic factors, such as the presence of acid substances in the oral cavity, may cause a pH reduction, thus potentially increasing acid erosion. The aim of this study was to evaluate the microhardness of bleached and unbleached bovine enamel after immersion in a soda beverage, artificial powder juice and hydrochloric acid. The results obtained for the variables of exposure time, acid solution and substrate condition (bleached or unbleached enamel) were statistically analyzed by the ANOVA and Tukey tests. It was concluded that a decrease in microhardness renders dental structures more susceptible to erosion and mineral loss, and that teeth left unbleached show higher values of microhardness compared to bleached teeth

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Biliary tract infections and their Microbiological Spectrum- A study from coastal region of Southern India

Objective: Biliary tract infections include cholangitis and cholecystitis. They are associated with high morbidity and mortality in elderly patients with co-morbid disease. The present study was undertaken to determine the microbial aetiology causing biliary tract infections and also to study their antimicrobial resistance profile.Materials &amp; methods: A retrospective study was conducted from January 2011 to December 2016 at the Enteric Diseases Division, Kasturba Medical College Hospital, Manipal. Patients with biliary tract infections admitted in tertiary referral health care hospital, Manipal were included for the study. Aerobic and anaerobic bacteriological and fungal aetiology of biliary tract infections were recorded along with their antimicrobial resistance profile.Results: Out of 307 bile samples sent for aerobic culture and susceptibly testing 187 (60.91%) were positive for culture, of which Escherichia coli (44.4%) was the predominant aetiology followed by Klebsiella pneumoniae (27.3%). Among the 14 samples sent for anaerobic culture, 5 (35.75%) specimens showed growth, of which Bacteroides fragilis group was found to be the predominant anaerobe. Among the 201 bacterial pathogens tested for their antimicrobial susceptibility, 108 (53.73%) isolates were resistant, out of which 9 were PDR Enterobacteriaceae with 12 ESBL strains. All the Candida species were susceptible to fluconazole with the exception of C. glabrata and C. krusei. All the anaerobic isolates were found to be susceptible to Metronidazole.Conclusions: The high rate of bacterial infection particularly gram-negative bacteria was recorded. It is necessary that antimicrobial therapy be initiated when culture or the clinical conditions reports caution. Routine aerobic and anaerobic culturing of bile samples with biliary tract infections are imperatively necessary. With the emergence of multidrug resistant pathogens and change in the microbiological spectrum of biliary tract infections, there is a need for the empirical antimicrobial therapy in every clinical setting.</jats:p