All-cause mortality and periodontitis in 60-70-year-old men: A prospective cohort study

Objective To investigate the association between periodontitis and mortality from all causes in a prospective study in a homogenous group of 60- to 70-year-old West European men. Methodology A representative sample of 1400 dentate men, (mean age 63.8, SD 3.0 years), drawn from the population of Northern Ireland, had a comprehensive periodontal examination between 2001 and 2003. Men were divided into thirds on the basis of their mean periodontal attachment loss (PAL). The primary endpoint, death from any cause, was analysed using Kaplan-Meier survival plots and Cox's proportional hazards model. Results In total, 152 (10.9%) of the men died during a mean follow-up of 8.9 (SD 0.7) years; 37 (7.9%) men in the third with the lowest PAL (<1.8 mm) died compared with 73 (15.7%) in the third with the highest PAL (>2.6 mm). The unadjusted hazard ratio (HR) for death in the men with the highest level of PAL compared with those with the lowest PAL was 2.11 (95% CI 1.42-3.14), p < 0.0001. After adjustment for confounding variables (age, smoking, hypertension, BMI, diabetes, cholesterol, education, marital status and previous history of a cardiovascular event) the HR was 1.57 (1.04-2.36), p = 0.03. Conclusion The European men in this prospective cohort study with the most severe loss of periodontal attachment were at an increased risk of death compared with those with the lowest loss of periodontal attachment.

Cigarette smoking and random serum cholesterol levels in a Northern Ireland general practice population of 18- to 20-year-old students and non-students

Coronary heart disease is the commonest cause of death in Northern Ireland, but few data exist on the incidence of risk factors in young adult students and non-students.

Coelum non animum muto? Milton's Neo-Latin Poetry and Catholic Italy

Milton’s Elegiarum Liber, the first half of his Poemata published in Poems of Mr John Milton Both English and Latin (1645), concludes with a series of eight Latin epigrams: five bitterly anti-Catholic pieces on the failed Gunpowder Plot of 1605, followed by three encomiastic poems hymning the praises of an Italian soprano, Leonora Baroni, singing in Catholic Rome. The disparity in terms of subject matter and tone is self-evident yet surprising in an epigrammatic series that runs sequentially. Whereas the gunpowder epigrams denigrate Rome, the Leonora epigrams present the city as a cultured hub of inclusivity, the welcome host of a Neapolitan soprano. In providing the setting for a human song that both enthrals its audience and attests to the presence of a divine power, Rome now epitomizes something other than brute idolatry, clerical habit or doctrine. And for the poet this facilitates an interrogation of theological (especially Catholic) doctrines. Coelum non animum muto, dum trans mare curro wrote the homeward-bound Milton in the autograph book of Camillo Cardoini at Geneva on 10 June 1639. But that this was an animus that could indeed acclimatize to religious and cultural difference is suggested by the Latin poems which Milton “patch [ed] up” in the course of his Italian journey. Central to that acclimatisation, as this chapter argues, is Milton’s quasi-Catholic self-fashioning. Thus Mansus offers a poetic autobiography of sorts, a self-inscribed vita coloured by intertextually kaleidoscopic links with two Catholic poets of Renaissance Italy and their patron; Ad Leonoram 1 both invokes and interrogates Catholic doctrine before a Catholic audience only to view the whole through the lens of a neo-Platonic hermeticism that may refreshingly transcend religious difference. Finally, Epitaphium Damonis, composed upon Milton’s return home, seems to highlight the potential interconnectedness of Protestant England and Catholic Italy, through the Anglo-Italian identity of its deceased subject, and through a pseudo-monasticism suggested by the poem’s possible engagement with the hagiography of a Catholic Saint. Perhaps continental travel and the physical encounter with the symbols, personages and institutions of the other have engendered in the Milton of the Italian journey a tolerance or, more accurately, the manipulation of a seeming tolerance to serve poetic and cultural ends.


First reviewer:
Haan: a fine piece by the senior neo-Latinist in Milton studies.

Second reviewer:
Chapter 7 is ... a high-spot of the collection. Its argument that in his Latin poetry Milton’s is a ‘quasi-Catholic self-fashioning’ stressing ‘the potential interconnectedness of Protestant England and Catholic Italy’ is striking and is advanced with learning, clarity and insight. Its sensitive exploration of the paradox of Milton’s coupling of humanistically complimentary and tolerant address to Roman Catholic friends with fiercely Protestant partisanship demonstrates that there is much greater complexity to his poetic persona than the self-construction and self-presentation of the later works would suggest. The essay is always adroit and sure-footed, often critically acute and illuminating (as, for example, in its discussion of the adjective and adverb mollis and molliter in Mansus, or in the identification in n. 99 of hitherto unnoticed Virgilian echoes). It has the added merits of being very well written, precise and apt in its citation of evidence, and absolutely central to the concerns of the volume.

The role of ECE1 variants in cognitive ability in old age and Alzheimer's disease risk

The ß-amyloid peptide may play a central role in Alzheimer's disease (AD) pathogenesis. We have evaluated variants in seven Aß-degrading genes (ACE, ECE1, ECE2, IDE, MME, PLAU, and TF) for association with AD risk in the Genetic and Environmental Risk in Alzheimer's Disease Consortium 1 (GERAD1) cohort, and with three cognitive phenotypes in the Lothian Birth Cohort 1936 (LBC1936), using 128 and 121 SNPs, respectively. In GERAD1, we identified a significant association between a four-SNP intragenic ECE1 haplotype and risk of AD in individuals that carried at least one APOE e4 allele (P = 0.00035, odds ratio = 1.61). In LBC1936, we identified a significant association between a different two-SNP ECE1 intragenic haplotype and non-verbal reasoning in individuals lacking the APOE e4 allele (P = 0.00036, ß = -0.19). Both results showed a trend towards significance after permutation (0.05 <P <0.10). A follow-up cognitive genetic study evaluated the association of ECE1 SNPs in three additional cohorts of non-demented older people. Meta-analysis of the four cohorts identified the significant association (Z <0.05) of SNPs in the ECE-1b promoter with non-verbal reasoning scores, particularly in individuals lacking the APOE e4 allele. Our genetic findings are not wholly consistent. Nonetheless, the AD associated intronic haplotype is linked to the 338A variant of known ECE1b promoter variant, 338C>A (rs213045). We observed significantly less expression from the 338A variant in two human neuroblastoma cell lines and speculate that this promoter may be subject to tissue-specific regulation.

‘Old wood’ effect in radiocarbon dating of prehistoric cremated bones?

Numerous reports of successful radiocarbon dating of cremated bones have emerged during the last decade. The success of radiocarbon dating cremated bones depends on the temperature during burning and the degree of recrystallisation of the inorganic bone matrix. During cremation bones undergo major morphological and mineralogical changes which have raised some interesting questions and discussion on the origin of the carbon source in archaeologically cremated bones. Recent laboratory experiments reveal that the properties of the combustion atmosphere play a significant role regarding the source carbon in cremated bones. Thus radiocarbon dating cremated bones is potentially dating the wood used for the cremation fire. Here we compare a high precision radiocarbon dated human bone with an associated dendrochronological age from an oak coffin. We find that the age discrepancy between the dendrochronological age and the cremated bone of 73 ± 26 14C yr is best accounted for by the so called ‘old wood’ effect.

Old drug, New target:Ellipticines selectively inhibit RNA Polymerase I transcription

Transcription byRNApolymerase I (Pol-I) is the main driving force behind ribosome biogenesis, a fundamental cellular process that requires the coordinated transcription of all three nuclear polymerases. Increased Pol-I transcription and the concurrent increase in ribosome biogenesis has been linked to the high rates of proliferation in cancers. The ellipticine family contains a number of potent anticancer therapeutic agents, some having progressed to stage I and II clinical trials; however, the mechanism by which many of the compounds work remains unclear. It has long been thought that inhibition of Top2 is the main reason behind the drugs antiproliferative effects. Here we report that a number of the ellipticines, including 9-hydroxyellipticine, are potent and specific inhibitors of Pol-I transcription, with IC50 in vitro and in cells in the nanomolar range. Essentially, the drugs did not affect Pol-II and Pol-III transcription, demonstrating a high selectivity.Wehave shown that Pol-I inhibition occurs by a p53-, ATM/ATR-, and Top2-independent mechanism. We discovered that the drug influences the assembly and stability of preinitiation complexes by targeting the interaction between promoter recognition factor SL1 and the rRNA promoter. Our findings will have an impact on the design and development of novel therapeutic agents specifically targeting ribosome biogenesis.

Community-living nonagenarians in northern ireland have lower plasma homocysteine but similar methylenetetrahydrofolate reductase thermolabile genotype prevalence compared to 70-89-year-old subjects

This cross-sectional study assessed relationships between plasma homocysteine, 'thermolabile' methylenetetrahydrofolatereductase (MTHFR) genotype, B vitamin status and measures of renal function in elderly (70-89 years) and nonagenarian (90+ years) subjects, with the hypothesis that octo/nonagenarian subjects who remain healthy into old age as defined by 'Senieur' status might show reduced genetic or environmental risk factors usually associated with hyperhomocysteinaemia. Plasma homocysteine was 9.1 micromol/l (geometric mean [GM]) for all elderly subjects. Intriguingly, homocysteine was significantly lower in 90+ (GM; 8.2 micromol/l) compared to 70-89-year-old subjects (GM; 9.8 micromol/l) despite significantly lower glomerular filtration rate (GFR) and serum B12 in nonagenarian subjects and comparable MTHFR thermolabile (TT) genotype frequency, folate and B6 status to 70-89-year-olds. For all elderly subjects, the odds ratio and 95% confidence intervals for plasma homocysteine being in the highest versus lowest quartile was 4.27 (2.04-8.92) for age 90 years, 3.4 (1.5-7.8) for serum folate 10.7nmol/l, 3.0 (0.9-10.2) for creatinine >140 compared

Changes in lymphocyte subsets, interleukin 2, and soluble interleukin 2 receptor in old and very old age

In this study, the changes in some of the cellular components of the immune system and the activity of the cytokine interleukin 2, important for immune activation and lymphocyte proliferation, were measured in a large cross-sectional study of all age groups including octogenarian and nonagenarian subjects. In 206 apparently well community-living subjects, the absolute lymphocyte count and T and B cell numbers fell a little in old and very old subjects. Within the T cell compartment, helper/inducer CD4+ T cells, together with their subsets identified as 'naive' (CD4+/CD45RA+) and 'memory' (CD4+/CD45RO+) cells, also showed a decline with increased age. The suppressor/cytotoxic CD8+ subset showed no age-related change. The levels of the cytokine interleukin 2 were very low in octogenarian and nonagenarian subjects, while the soluble interleukin 2 receptor levels increased with increasing age. The interleukin 2 levels were associated with number and percentage of the 'memory' (CD4+/CD45RO+) subset of T cells which mediates the host response to previously met antigens. Since the interleukin 2 values were very low in the oldest groups and were associated with a reduced 'memory' (CD4+/CD45RO+) compartment, this suggests a possible mechanism of why the very elderly subject is more susceptible to morbidity and mortality from infectious or other agents.