DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with Ulcerative Colitis (UC)

Introduction: Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and none assessing its relationship with lifestyle exposures. Aims & Methods: To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor - 1) and N-33 (tumour suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) whilst gene specific methylation was quantified using the COBRA method. Results: The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs 5.9%; p = 0.015 and 66% vs 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. Conclusions: For the first time, we have shown increased methylation in the promoter regions of the putative tumour suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggests that, inactivation through methylation of the putative tumour suppressor genes N-33 and ESR-1, may not be associated with colorectal carcinogenesis in UC

Is the biology of breast cancer changing? A study of hormone receptor status 1984-1986 and 1996-1997

Using archived tumours, those from 1984-1986 and 1996-1997 underwent immunohistochemistry for hormone receptors and grade analysis. A significant shift towards more ER-positive and low-grade disease was found; this appears to reflect screening practices, but could still influence survival

Analysis of prosthetic joint infections following invasive dental procedures in England

Importance Dentists in the United States are under pressure from orthopaedic surgeons and their patients with prosthetic joints to provide antibiotic prophylaxis (AP) before invasive dental procedures (IDP) to reduce the risk of late prosthetic joint infection (LPJI). This has been a common practice for decades despite a lack of evidence for an association between IDP and LPJI, a lack of evidence of AP efficacy, cost of providing AP, and risk of both adverse drug reactions and the potential for promoting antibiotic resistance. Objective Our objective was to quantify if there is any temporal association between IDP and subsequent LPJI. Design A case-crossover and time trend study of any potential association between IDP and LPJI. Setting The population of England (55 million) was chosen because AP has never been recommended to prevent LPJI in England and any association between IDP and LPJI would therefore be fully exposed. Participants All patients admitted to hospital in England for LPJI from December 25th, 2011, through March 31st, 2017, for whom dental records were available. Analyses were performed between May 2018 and June 2021. Exposures Exposure to IDP Main Outcomes and Measures A case-crossover analysis comparing the incidence IDP in the 3-months before LPJI hospital admission (case-period) with the incidence in the 12-months before that (control-period). Results We identified 9,427 LPJI hospital admissions with dental records (mean age 67), including 4,897 (52%) men. Of these, 2,385 (25.3%) had hip, 3,168 (33.6%) knee, 259 (2.8%) other and 3,615 (38.4%) unknown prosthetic joint types. Despite having sufficient statistical power to detect a clinically significant association, our analysis identified no significant temporal association between IDP and subsequent LPJI. Indeed, there was a lower incidence of IDP in the three months prior to LPJI (incidence rate ratio = 0.89, 95% confidence interval 0.82 to 0.96, p=0.002). Conclusions and Relevance In the absence of a significant positive association between IDP and LPJI, there is no rationale to administer AP before IDP in patients with prosthetic joints. Maintenance of good oral hygiene, however, may be important in preventing the small number of LPJI cases where oral bacterial species are implicated

Mental Health of Parents and Life Satisfaction of Children: A Within-Family Analysis of Intergenerational Transmission of Well-Being

This paper addresses the extent to which there is an intergenerational transmission of mental health and subjective well-being within families. Specifically it asks whether parents’ own mental distress influences their child’s life satisfaction, and vice versa. Whilst the evidence on daily contagion of stress and strain between members of the same family is substantial, the evidence on the transmission between parental distress and children’s well-being over a longer period of time is sparse. We tested this idea by examining the within-family transmission of mental distress from parent to child’s life satisfaction, and vice versa, using rich longitudinal data on 1,175 British youths. Results show that parental distress at year t-1 is an important determinant of child’s life satisfaction in the current year. This is true for boys and girls, although boys do not appear to be affected by maternal distress levels. The results also indicated that the child’s own life satisfaction is related with their father’s distress levels in the following year, regardless of the gender of the child. Finally, we examined whether the underlying transmission correlation is due to shared social environment, empathic reactions, or transmission via parent-child interaction

Infective endocarditis following invasive dental procedures: IDEA case-crossover study

Background Infective endocarditis is a heart infection with a first-year mortality rate of ≈ 30%. It has long been thought that infective endocarditis is causally associated with bloodstream seeding with oral bacteria in ≈ 40–45% of cases. This theorem led guideline committees to recommend that individuals at increased risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. However, to the best of our knowledge, there has never been a clinical trial to prove the efficacy of antibiotic prophylaxis and there is no good-quality evidence to link invasive dental procedures with infective endocarditis. Many contend that oral bacteria-related infective endocarditis is more likely to result from daily activities (e.g. tooth brushing, flossing and chewing), particularly in those with poor oral hygiene. Objective The aim of this study was to determine if there is a temporal association between invasive dental procedures and subsequent infective endocarditis, particularly in those at high risk of infective endocarditis. Design This was a self-controlled, case-crossover design study comparing the number of invasive dental procedures in the 3 months immediately before an infective endocarditis-related hospital admission with that in the preceding 12-month control period. Setting The study took place in the English NHS. Participants All individuals admitted to hospital with infective endocarditis between 1 April 2010 and 31 March 2016 were eligible to participate. Interventions This was an observational study; therefore, there was no intervention. Main outcome measure The outcome measure was the number of invasive and non-invasive dental procedures in the months before infective endocarditis-related hospital admission. Data sources NHS Digital provided infective endocarditis-related hospital admissions data and dental procedure data were obtained from the NHS Business Services Authority. Results The incidence rate of invasive dental procedures decreased in the 3 months before infective endocarditis-related hospital admission (incidence rate ratio 1.34, 95% confidence interval 1.13 to 1.58). Further analysis showed that this was due to loss of dental procedure data in the 2–3 weeks before any infective endocarditis-related hospital admission. Limitations We found that urgent hospital admissions were a common cause of incomplete courses of dental treatment and, because there is no requirement to record dental procedure data for incomplete courses, this resulted in a significant loss of dental procedure data in the 2–3 weeks before infective endocarditis-related hospital admissions. The data set was also reduced because of the NHS Business Services Authority’s 10-year data destruction policy, reducing the power of the study. The main consequence was a loss of dental procedure data in the critical 3-month case period of the case-crossover analysis (immediately before infective endocarditis-related hospital admission), which did not occur in earlier control periods. Part of the decline in the rate of invasive dental procedures may also be the result of the onset of illness prior to infective endocarditis-related hospital admission, and part may be due to other undefined causes. Conclusions The loss of dental procedure data in the critical case period immediately before infective endocarditis-related hospital admission makes interpretation of the data difficult and raises uncertainty over any conclusions that can be drawn from this study. Future work We suggest repeating this study elsewhere using data that are unafflicted by loss of dental procedure data in the critical case period. Trial registration This trial is registered as ISRCTN11684416. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 28. See the NIHR Journals Library website for further project information

Survival Analysis Part I: Basic concepts and first analyses

Survival analysis is a collection of statistical procedures for data analysis where the outcome variable of interest is time until an event occurs. Because of censoring - the nonobservation of the event of interest after a period of follow-up - a proportion of the survival times of interest will often be unknown. It is assumed that those patients who are censored have the same survival prospects as those who continue to be followed, that is, the censoring is uninformative. Survival data are generally described and modelled in terms of two related functions, the survivor function and the hazard function. The survivor function represents the probability that an individual survives from the time of origin to some time beyond time t. It directly describes the survival experience of a study cohort, and is usually estimated by the KM method. The logrank test may be used to test for differences between survival curves for groups, such as treatment arms. The hazard function gives the instantaneous potential of having an event at a time, given survival up to that time. It is used primarily as a diagnostic tool or for specifying a mathematical model for survival analysis. In comparing treatments or prognostic groups in terms of survival, it is often necessary to adjust for patient-related factors that could potentially affect the survival time of a patient. Failure to adjust for confounders may result in spurious effects. Multivariate survival analysis, a form of multiple regression, provides a way of doing this adjustment, and is the subject the next paper in this series

Less Work, Less Respect: Authors' Perceived Importance of Research Contributions and Their Declared Contributions to Research Articles

BACKGROUND: Attitudes towards authorship are connected with authors' research experience and with knowledge of authorship criteria of International Committee of Medical Journal Editors (ICMJE). The objective of this study was to assess association between authors' perceived importance of contributions for authorship qualification and their participation in manuscripts submitted to a journal. METHODS: Authors (n = 1181) of 265 manuscripts submitted to the Croatian Medical Journal were asked to identify and rate their contribution in the preparation of the submitted manuscript (0-none to 4-full for 11 listed contributions) and the importance of these contributions as authorship qualifications (0-none to 4-full). They were randomly allocated into 3 groups: the first (n = 90 manuscripts, n = 404 authors) first received the contribution disclosure form and then contribution importance-rating questionnaire; the second (n = 88 manuscripts, n = 382 authors) first received the rating questionnaire and then the contribution disclosure form, and the third group (n = 87 manuscripts, n = 395 authors) received both questionnaires at the same time. We compared authors' perception of importance of contribution categories. RESULTS: 1014 (85.9%) authors of 235 manuscripts responded. Authors who declared contribution to a specific category rated it as more important for authorship than those authors who did not contribute to the same category (P>0.005 for all contribution categories, Mann-Withney test). Authors qualifying for ICMJE authorship rated all contribution categories higher than non-qualifying authors. For all contributions, associations between perceived importance of contribution and actual author's contribution were statistically significant. CONCLUSIONS: Authorship seems to be not a normative issue subjective to categorization into criteria, but also a very personal view of the importance and value of one's contributions