Childhood exposure to external ionising radiation and solid cancer risk

The increasing use of ionising radiation for diagnostic purposes has raised concern about potential iatrogenic damage, especially in children. In this review, we discuss some aspects of radiation-induced cancer in relation to age at exposure and measures that should be taken for limiting exposure in this sensitive population

Hybridization and hybrid speciation under global change

An unintended consequence of global change is an increase in opportunities for hybridization among previously isolated lineages. Here we illustrate how global change can facilitate the breakdown of reproductive barriers and the formation of hybrids, drawing on the flora of the British Isles for insight. Although global change may ameliorate some of the barriers preventing hybrid establishment, for example by providing new ecological niches for hybrids, it will have limited effects on environment-independent post-zygotic barriers. For example, genic incompatibilities and differences in chromosome numbers and structure within hybrid genomes are unlikely to be affected by global change. We thus speculate that global change will have a larger effect on eroding pre-zygotic barriers (eco-geographical isolation and phenology) than post-zygotic barriers, shifting the relative importance of these two classes of reproductive barriers from what is usually seen in naturally produced hybrids where pre-zygotic barriers are the largest contributors to reproductive isolation. Although the long-term fate of neo-hybrids is still to be determined, the massive impact of global change on the dynamics and distribution of biodiversity generates an unprecedented opportunity to study large numbers of unpredicted, and often replicated, hybridization ‘experiments’, allowing us to peer into the birth and death of evolutionary lineages

Radiation-induced malignancies following radiotherapy for breast cancer

With advances in diagnosis and treatment, breast cancer is becoming an increasingly survivable disease resulting in a large population of long-term survivors. Factors affecting the quality of life of such patients include the consequences of breast cancer treatment, which may have involved radiotherapy. In this study, we compare the incidence of second primary cancers in women who received breast radiotherapy with that in those who did not (non-radiotherapy). All women studied received surgery for their first breast cancer. Second cancers of the lung, colon, oesophagus and thyroid gland, malignant melanomas, myeloid leukaemias and second primary breast cancers were studied. Comparing radiotherapy and non-radiotherapy cohorts, elevated relative risks (RR) were observed for lung cancer at 10-14 years and 15 or more (15+) years after initial breast cancer diagnosis (RR 1.62, 95% confidence interval [CI] 1.05-2.54 and RR 1.49, 95% CI 1.05-2.14, respectively), and for myeloid leukaemia at 1-5 years (RR 2.99, 95% CI 1.13-9.33), for second breast cancer at 5-10 years (RR 1.34, 95% CI 1.10-1.63) and 15+ years (RR 1.26, 95% CI 1.00-1.59) and oesophageal cancer at 15+ years (RR 2.19, 95% CI 1.10-4.62)

CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection

Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapies fail to control the inflammation-driven tissue damage that occurs during Pseudomonas aeruginosa infection. Antibiotic treatment reduces bacterial burdens, but better interventions are needed to alleviate tissue damage resulting from local inflammation. We have previously documented that inhibition of macrophage migration inhibitory factor (MIF) reduces the bacterial levels and the inflammatory damage during keratitis. Here, we report that mice deficient for CD74, the putative MIF receptor, developed milder Pseudomonas aeruginosa-induced disease, characterized by decreased proinflammatory mediators and reduced bacterial presence in the cornea. However, topical inhibition of MIF using antibodies applied to the cornea further promoted recovery from disease, suggesting that in addition to MIF-dependent signaling events, MIF-triggered CD74-independent signaling pathways regulate sensitization to P. aeruginosa-induced infection

(Working title) Are We Meeting Oral Health Needs of Care Home Populations?

Aim: To evaluate care home (N) staff knowledge of oral care in comparison to NHS Quality Improvement Scotland (NHS QIS) guidelines. To identify barriers to delivering oral care and determine if Oral Health Educator (OHE) training had an effect upon staff knowledge of oral care delivery. Setting: The study was undertaken within Greater Glasgow, 2005 to 2007. Subjects and Methods: From 33 care homes (N), 28 participated in data gathering comprising 109 staff. A ‘knowledge check-list’ based upon daily oral care protocol from NHS QIS Best Practice Statement (BPS) served as template for knowledge assessment. An OHE undertook small group discussions related to the BPS in a sub-group of original participants and a second round of data collected. Results: The majority of staff (n=86, 79%) agreed that residents required assistance with oral care and placed oral care (n=85, 78%) as a moderate to high priority. Only 57% of managers and 49% of nurses had received training in oral care. Most staff (79% of managers, 85% of nurses) were unaware of the NHS QIS BPS. Deficiencies in knowledge of key areas within the BPS were identified. Between pre- and post-OHE training, significant differences were identified in prioritisation of oral care (p =0.009), perceived competence (p =0.005) and confidence giving advice (p =0.004). Following OHE intervention, knowledge of BPS protocol increased by 45%. Conclusion: Knowledge of oral care provision by carers for home residents requires substantial improvement. An OHE training programme structured around the NHS QIS BPS demonstrated a measurable increase in levels of staff knowledge of oral care

Assessing Susceptibility from Early-Life Exposure to Carcinogens

Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6–8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033–0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action

The characterisation of microsatellite markers reveals tetraploidy in the Greater Water Parsnip, Sium latifolium (Apiaceae).

BACKGROUND: The Greater Water Parsnip, Sium latifolium (Apiaceae), is a marginal aquatic perennial currently endangered in England and consequently the focus of a number of conservation translocation projects. Microsatellite markers were developed for S. latifolium to facilitate comparison of genetic diversity and composition between natural and introduced populations. RESULTS: We selected 65 S. latifolium microsatellite (MiSeq) sequences and designed primer pairs for these. Primer sets were tested in 32 individuals. We found 15 polymorphic loci that amplified consistently. For the selected 15 loci, the number of alleles per locus ranged from 8 to 17. For all loci, S. latifolium individuals displayed up to four alleles indicating polyploidy in this species. CONCLUSIONS: These are the first microsatellite loci developed for S. latifolium and each individual displayed 1-4 alleles per locus, suggesting polyploidy in this species. These markers provide a valuable resource in evaluating the population genetic composition of this endangered species and thus will be useful for guiding conservation and future translocations of the species

Why MSM in rural South African communities should be an HIV prevention research priority.

Research into HIV and men who have sex with men's (MSM) health in South Africa has been largely confined to the metropolitan centres. Only two studies were located making reference to MSM in rural contexts or same-sex behaviors among men in the same. There is growing recognition in South Africa that MSM are not only disproportionately affected by HIV and have been underserved by the country's national response, but that they contribute significantly to sustaining the high number of new infections recorded each year. We argue that to meet the objectives of the country's national strategic plan for HIV, STI and TB it is important we know how these behaviours may be contributing to the sustained rural HIV epidemic in the youngest age groups and determine what constitutes appropriate and feasible programmatic response that can be implemented in the country's public sector health services

Risk of hyperkalemia in patients with moderate chronic kidney disease initiating angiotensin converting enzyme inhibitors or angiotensin receptor blockers : a randomized study

Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are renoprotective but both may increase serum potassium concentrations in patients with chronic kidney disease (CKD). The proportion of affected patients, the optimum follow-up period and whether there are differences between drugs in the development of this complication remain to be scertained. Methods: In a randomized, double-blind, phase IV, controlled, crossover study we recruited 30 patients with stage 3 CKD under restrictive eligibility criteria and strict dietary control. With the exception of withdrawals, each patient was treated with olmesartan and enalapril separately for 3 months each, with a 1-week wash-out period between treatments. Patients were clinically assessed on 10 occasions via measurements of serum and urine samples. We used the Cochran-Mantel-Haenszel statistics for comparison of categorical data between groups. Comparisons were also made using independent two-sample t-tests and Welch's t-test. Analysis of variance (ANOVA) was performed when necessary. We used either a Mann-Whitney or Kruskal-Wallis test if the distribution was not normal or the variance not homogeneous. Results: Enalapril and olmesartan increased serum potassium levels similarly (0.3 mmol/L and 0.24 mmol/L respectively). The percentage of patients presenting hyperkalemia higher than 5 mmol/L did not differ between treatments: 37% for olmesartan and 40% for enalapril. The mean e-GFR ranged 46.3 to 48.59 ml/mint/1.73 m2 in those treated with olmesartan and 46.8 to 48.3 ml/mint/1.73 m2 in those with enalapril and remained unchanged at the end of the study. The decreases in microalbuminuria were also similar (23% in olmesartan and 29% in enalapril patients) in the 4 weeks time point. The percentage of patients presenting hyperkalemia, even after a two month period, did not differ between treatments. There were no appreciable changes in sodium and potassium urinary excretion. Conclusions: Disturbances in potassium balance upon treatment with either olmesartan or enalapril are frequent and without differences between groups. The follow-up of these patients should include control of potassium levels, at least after the first week and the first and second month after initiating treatment

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders