Risk of breast cancer and other cancers in heterozygotes for ataxia-telangiectasia

Mortality from cancer among 178 parents and 236 grandparents of 95 British patients with ataxia-telangiectasia was examined. For neither parents nor grandparents was mortality from all causes or from cancer appreciably elevated over that of the national population. Among mothers, three deaths from breast cancer gave rise to a standardized mortality ratio of 3.37 (95% confidence interval (CI): 0.69–9.84). In contrast, there was no excess of breast cancer in grandmothers, the standardized mortality ratio being 0.89 (95% CI: 0.18–2.59), based on three deaths. This is the largest study of families of ataxia-telangiectasia patients conducted in Britain but, nonetheless, the study is small and CIs are wide. However, taken together with data from other countries, an increased risk of breast cancer among female heterozygotes is still apparent, though lower than previously thought. © 1999 Cancer Research Campaig

Perspectives of ammunition users on the use of lead ammunition and its potential impacts on wildlife and humans

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: All data supporting the results in this paper are available from Zenodo (digital repository): https://zenodo.org/record/2653514#.XMbMXKbsZD8 (Newth et al., 2019).1. Recent national and international policy initiatives have aimed to reduce the exposure of humans and wildlife to lead from ammunition. Despite restrictions, in the UK, lead ammunition remains the most widespread source of environmental lead contamination to which wildlife may be exposed. 2. The risks arising from the use of lead ammunition and the measures taken to mitigate these have prompted intense and sometimes acrimonious discussion between stakeholder groups, including those advancing the interests of shooting, wildlife conservation, public health and animal welfare. 3. However, relatively little is known of the perspectives of individual ammunition users, despite their role in adding lead to the environment and their pivotal place in any potential changes to practice. Using Q‐methodology, we identified the perspectives of ammunition users in the UK on lead ammunition in an effort to bring forward evidence from these key stakeholders. 4. Views were characterised by two statistically and qualitatively distinct perspectives: (a) Open to change—comprised ammunition users that refuted the view that lead ammunition is not a major source of poisoning in wild birds, believed that solutions to reduce the risks of poisoning are needed, were happy to use non‐lead alternatives and did not feel that the phasing out of lead shot would lead to the demise of shooting; and (b) Status quo—comprised ammunition users who did not regard lead poisoning as a major welfare problem for wild birds, were ambivalent about the need for solutions and felt that lead shot is better than steel at killing and not wounding an animal. They believed opposition to lead ammunition was driven more by a dislike of shooting than evidence of any harm. 5. Adherents to both perspectives agreed that lead is a toxic substance. There was consensus that involvement of stakeholders from all sides of the debate was desirable and that to be taken seriously by shooters, information about lead poisoning should come from the shooting community

The specificity of phage testing for MAP — where might it fit into the diagnostic armoury?

The current individual tools available for the diagnosis of Johne's disease are far from suitable to tackle this endemic disease. Culture, polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) tests, when used together can be useful in managing the disease in the later stages of infection at a herd level. They are, however, ill-suited to detecting the causative agent Mycobacterium avium subsp. paratuberculosis (MAP) at the early stages of infection and at an individual level. Phage technology offers another tool in the attempt to better manage and control this disease. Phage-technology has been demonstrated to rapidly and sensitively detect and specifically identify viable MAP in the milk and blood of cattle. Although in relatively-early stages of development phage technology offers a strong addition to the armoury of tests used to detect MAP in blood and milk, and may go on to be part of ongoing control measures to reduce the burden of disease to farmers and veterinarians

Factors affecting phage D29 infection: a tool to investigate different growth states of mycobacteria

Bacteriophages D29 and TM4 are able to infect a wide range of mycobacteria, including pathogenic and non pathogenic species. Successful phage infection of both fast- and slow-growing mycobacteria can be rapidly detected using the phage amplification assay. Using this method, the effect of oxygen limitation during culture of mycobacteria on the success of phage infection was studied. Both D29 and TM4 were able to infect cultures of M. smegmatis and Mycobacterium avium subspecies paratuberculosis (MAP) grown in liquid with aeration. However when cultures were grown under oxygen limiting conditions, only TM4 could productively infect the cells. Cell attachment assays showed that D29 could bind to the cells surface but did not complete the lytic cycle. The ability of D29 to productively infect the cells was rapidly recovered (within 1 day) when the cultures were returned to an aerobic environment and this recovery required de novo RNA synthesis. These results indicated that under oxygen limiting conditions the cells are entering a growth state which inhibits phage D29 replication, and this change in host cell biology which can be detected by using both phage D29 and TM4 in the phage amplification assay

Evaluation of the limitations and methods to improve rapid phage-based detection of viable Mycobacterium avium subsp. paratuberculosis in the blood of experimentally infected cattle

Background Disseminated infection and bacteraemia is an underreported and under-researched aspect of Johne’s disease. This is mainly due to the time it takes for Mycobacterium avium subsp. paratuberculosis (MAP) to grow and lack of sensitivity of culture. Viable MAP cells can be detected in the blood of cattle suffering from Johne’s disease within 48 h using peptide-mediated magnetic separation (PMMS) followed by bacteriophage amplification. The aim of this study was to demonstrate the first detection of MAP in the blood of experimentally exposed cattle using the PMMS-bacteriophage assay and to compare these results with the immune response of the animal based on serum ELISA and shedding of MAP by faecal culture. Results Using the PMMS-phage assay, seven out of the 19 (37 %) MAP-exposed animals that were tested were positive for viable MAP cells although very low numbers of MAP were detected. Two of these animals were positive by faecal culture and one was positive by serum ELISA. There was no correlation between PMMS-phage assay results and the faecal and serum ELISA results. None of the control animals (10) were positive for MAP using any of the four detection methods. Investigations carried out into the efficiency of the assay; found that the PMMS step was the limiting factor reducing the sensitivity of the phage assay. A modified method using the phage assay directly on isolated peripheral blood mononuclear cells (without PMMS) was found to be superior to the PMMS isolation step. Conclusions This proof of concept study has shown that viable MAP cells are present in the blood of MAP-exposed cattle prior to the onset of clinical signs. Although only one time point was tested, the ability to detect viable MAP in the blood of subclinically infected animals by the rapid phage-based method has the potential to increase the understanding of the pathogenesis of Johne’s disease progression by warranting further research on the presence of MAP in blood

Reproductive morbidity among Iranian women; issues often inappropriately addressed in health seeking behaviors

<p>Abstract</p> <p>Background</p> <p>Reproductive morbidity has a huge impact on the health and quality of life of women. We aimed to determine the prevalence of reproductive morbidities and the health seeking behavior of a nationally representative sample of Iranian urban women.</p> <p>Methods</p> <p>A sample of 1252 women, aged 18-45 years, was selected using the multi stage, stratified probability sampling procedure. Data were collected through interviews and physical, gynecological and ultrasonographic examinations.</p> <p>Results</p> <p>Reproductive tract infection (RTIs), pelvic organ prolapse (POP) and menstrual dysfunction were the three main groups of morbidities with a prevalence of 37.6%, 41.4% and 30.1%., respectively. Our study demonstrated that 35.1, 34.5 and 9.6 percent of women experienced one, two or these reproductive organ disorders mentioned, respectively, while 20.6 percent of participants had none of these disorders. Findings also showed that the majority of women who suffered from reproductive morbidities (on average two out of three) had not sought appropriate care for these except for infertility.</p> <p>Conclusions</p> <p>Reproductive health morbidities impose a large burden among Iranian women and have negative impact on their reproductive health and wellbeing.</p

Prediction model and prognostic index to estimate clinically relevant pelvic organ prolapse in a general female population

Introduction and hypothesis: Estimation on prevalence and distribution of pelvic organ prolapse (POP) signs in a general female population is difficult. We therefore developed and validated

ATM haplotypes and breast cancer risk in Jewish high-risk women

While genetic factors clearly play a role in conferring breast cancer risk, the contribution of ATM gene mutations to breast cancer is still unsettled. To shed light on this issue, ATM haplotypes were constructed using eight SNPs spanning the ATM gene region (142 kb) in ethnically diverse non-Ashkenazi Jewish controls (n=118) and high-risk (n=142) women. Of the 28 haplotypes noted, four were encountered in frequencies of 5% or more and accounted for 85% of all haplotypes. Subsequently, ATM haplotyping of high-risk, non-Ashkenazi Jews was performed on 66 women with breast cancer and 76 asymptomatic. One SNP (rs228589) was significantly more prevalent among breast cancer cases compared with controls (P=4 × 10−9), and one discriminative ATM haplotype was significantly more prevalent among breast cancer cases (33.3%) compared with controls (3.8%), (P⩽10−10). There was no significant difference in the SNP and haplotype distribution between asymptomatic high-risk and symptomatic women as a function of disease status. We conclude that a specific ATM SNP and a specific haplotype are associated with increased breast cancer risk in high-risk non-Ashkenazi Jews