Old Testament Word-Studies: 10. Time and Eternity

n/

Is health-related quality of life associated with the risk of low-energy wrist fracture: a case-control study

<p>Abstract</p> <p>Background</p> <p>Some risk factors for low-energy wrist fracture have been identified. However, self-reported measures such as health-related quality of life (HRQOL) have not been examined as potential risk factors for wrist fracture. The aims of this study were to compare HRQOL prior to a low-energy wrist fracture in elderly patients (≥ 50 years) with HRQOL in age- and sex-matched controls, and to explore the association between HRQOL and wrist fracture after adjusting for known risk factors for fracture such as age, weight, osteoporosis and falls.</p> <p>Methods</p> <p>Patients with a low-energy wrist fracture (n = 181) and age- and sex-matched controls (n = 181) were studied. Shortly after fracture (median 10 days), patients assessed their HRQOL before fracture using the Short Form 36 (SF-36). Statistical tests included <it>t </it>tests and multivariate logistic regression analysis.</p> <p>Results</p> <p>Several dimensions of HRQOL were significantly associated with wrist fracture. The direction of the associations with wrist fracture varied between the different sub-dimensions of the SF-36. After controlling for demographic and clinical variables, higher scores on <it>general health </it>(odds ratio (OR) = 1.31, 95% confidence interval (CI) = 1.10–1.56), <it>bodily pain </it>(OR = 1.18, 95% CI = 1.03–1.34) and <it>mental health </it>(OR = 1.39, 95% CI = 1.09–1.79) were related to an increased chance of being a wrist fracture patient rather than a control. In contrast, higher scores on <it>physical role limitation </it>(OR = 0.87, 95% CI = 0.79–0.95) and <it>social function </it>(OR = 0.65, 95% CI 0.53–0.80) decreased this chance. Significant associations with wrist fracture were also found for living alone (OR = 1.91, 95% CI 1.07–3.4), low body mass index (BMI) (OR = 0.92, 95% CI 0.86–0.98), osteoporosis (OR = 3.30, 95% CI 1.67–6.50) and previous falls (OR = 2.01, 95% CI 1.16–3.49).</p> <p>Conclusion</p> <p>Wrist fracture patients perceive themselves to be as healthy as the controls before fracture. Our data indicate that patients with favourable and unfavourable HRQOL measures may be at increased risk of wrist fracture.</p

Effects of chirality on the intracellular localization of binuclear ruthenium(II) polypyridyl complexes

Interest in binuclear ruthenium(II) polypyridyl complexes as luminescent cellular imaging agents and for biomedical applications is increasing rapidly. We have investigated the cellular localization, uptake, and biomolecular interactions of the pure enantiomers of two structural isomers of [μ-bipb(phen)4Ru2]4+ (bipb is bis(imidazo[4,5-f]-1,10-phenanthrolin-2-yl)benzene and phen is 1,10-phenanthroline) using confocal laser scanning microscopy, emission spectroscopy, and linear dichroism. Both complexes display distinct enantiomeric differences in the staining pattern of fixed cells, which are concluded to arise from chiral discrimination in the binding to intracellular components. Uptake of complexes in live cells is efficient and nontoxic at 5 μM, and occurs through an energy-dependent mechanism. No differences in uptake are observed between the structural isomers or the enantiomers, suggesting that the interactions triggering uptake are rather insensitive to structural variations. Altogether, these findings show that the complexes investigated are promising for future applications as cellular imaging probes. In addition, linear dichroism shows that the complexes exhibit DNA-condensing properties, making them interesting as potential gene delivery vectors

Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation

Background-In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. Methods and Results-Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD. Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling of IL-6, D-dimer, hsCRP, and a 1-unit increase in an IL-6 and D-dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD, 23 died during follow-up. Hazard ratios (95% CI) for all-cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL-6, D-dimer, hsCRP, and the IL-6 and D-dimer score. Conclusions-Higher IL-6 and D-dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD even

A Dominant Negative ERβ Splice Variant Determines the Effectiveness of Early or Late Estrogen Therapy after Ovariectomy in Rats

The molecular mechanisms for the discrepancy in outcome of initiating estrogen therapy (ET) around peri-menopause or several years after menopause in women are unknown. We hypothesize that the level of expression of a dominant negative estrogen receptor (ER) β variant, ERβ2, may be a key factor determining the effectiveness of ET in post-menopausal women. We tested this hypothesis in ovariectomized nine month-old (an age when irregular estrous cycles occur) female Sprague Dawley rats. Estradiol treatment was initiated either 6 days (Early ET, analogous to 4 months post-menopause in humans), or 180 days (Late ET, analogous to 11 years post-menopause in humans) after ovariectomy. Although ERβ2 expression increased in all OVX rats, neurogenic and neuroprotective responses to estradiol differed in Early and Late ET. Early ET reduced ERβ2 expression in both hippocampus and white blood cells, increased the hippocampal cell proliferation as assessed by Ki-67 expression, and improved mobility in the forced swim test. Late ET resulted in either no or modest effects on these parameters. There was a close correlation between the degree of ERβ2 expression and the preservation of neural effects by ET after OVX in rats, supporting the hypothesis that persistent elevated levels of ERβ2 are a molecular basis for the diminished effectiveness of ET in late post-menopausal women. The correlation between the expression of ERβ2 in circulating white blood cells and brain cells suggests that ERβ2 expression in peripheral blood cells may be an easily accessible marker to predict the effective window for ET in the brain

Falls in the general elderly population: a 3- and 6- year prospective study of risk factors using data from the longitudinal population study 'Good ageing in Skane'.

Accidental falls in the elderly are a major health problem, despite extensive research on risk factors and prevention. Only a limited number of multifactorial, long-term prospective studies have been performed on risk factors for falls in the general elderly population. The aim of this study was to identify risk factors predicting falls in a general elderly population after three and six years, using a prospective design

Kinetic Recognition of Nucleic Acids - Studies on the DNA Binding Selectivity of Threading Ruthenium Complexes

Despite the great progress in our understanding of DNA during the past half-century, there are many important aspects of its chemical and biological role yet to be explored. The principles by which it selectively interacts with other molecules have attracted much interest due to the relevance for fundamental cellular processes, as well as for the development of diagnostic probes and effective pharmaceutical agents. This Thesis describes the study of the process in which a planar aromatic moiety, hindered by bulky substituents on both ends, is threaded through the DNA double helix. Dumb-bell shaped binuclear ruthenium complexes of the type [\ub5-(bidppz)(L)4Ru2]4+, L = phenanthroline (P) or bipyridine (B) bind upon mixing with DNA rapidly on the outside of the double-helix, after which they rearrange to an intercalated binding mode. Passing one large metal centre between the strands requires large transient distortions of the duplex, leading to extremely slow binding kinetics that is sensitive to DNA sequence as well as ruthenium complex structure. This work has (1) addressed the mechanisms behind this “kinetic recognition” and (2) identified potential DNA structural targets. Both enantiomers of chiral analogues P and B require several hours at 50\ub0C to rearrange to the threaded binding mode in mixed sequence DNA. Alternating AT polymers, on the other hand, are intercalated within a few minutes at room temperature. The ratio between the forward rates is estimated to vary between 65 (ΛΛ-P) and 2500 (ΛΛ-B). Studies with AT-tract oligonucleotides show that more than one complete helix turn of AT-DNA is required for efficient threading, a stretch considerably larger than the complexes themselves. Long AT-stretches are however not the only kinetically favored targets; subjecting mixed sequence DNA to negative supercoiling can increase the threading rate by as much as two orders of magnitude. Accelerated intercalation is also observed with partially unpaired DNA. Dissociation from mixed sequence DNA displays half-lives of up to 38 h at physiological temperature, the slowest release reported for a reversibly bound agent. The selectivity demonstrated by the binuclear ruthenium complexes in vitro make them interesting in the development of new agents against parasitic protozoa with AT-rich DNA

Kinetic Recognition of Nucleic Acids - Studies on the DNA Binding Selectivity of Threading Ruthenium Complexes

Despite the great progress in our understanding of DNA during the past half-century, there are many important aspects of its chemical and biological role yet to be explored. The principles by which it selectively interacts with other molecules have attracted much interest due to the relevance for fundamental cellular processes, as well as for the development of diagnostic probes and effective pharmaceutical agents. This Thesis describes the study of the process in which a planar aromatic moiety, hindered by bulky substituents on both ends, is threaded through the DNA double helix. Dumb-bell shaped binuclear ruthenium complexes of the type [\ub5-(bidppz)(L)4Ru2]4+, L = phenanthroline (P) or bipyridine (B) bind upon mixing with DNA rapidly on the outside of the double-helix, after which they rearrange to an intercalated binding mode. Passing one large metal centre between the strands requires large transient distortions of the duplex, leading to extremely slow binding kinetics that is sensitive to DNA sequence as well as ruthenium complex structure. This work has (1) addressed the mechanisms behind this “kinetic recognition” and (2) identified potential DNA structural targets. Both enantiomers of chiral analogues P and B require several hours at 50\ub0C to rearrange to the threaded binding mode in mixed sequence DNA. Alternating AT polymers, on the other hand, are intercalated within a few minutes at room temperature. The ratio between the forward rates is estimated to vary between 65 (ΛΛ-P) and 2500 (ΛΛ-B). Studies with AT-tract oligonucleotides show that more than one complete helix turn of AT-DNA is required for efficient threading, a stretch considerably larger than the complexes themselves. Long AT-stretches are however not the only kinetically favored targets; subjecting mixed sequence DNA to negative supercoiling can increase the threading rate by as much as two orders of magnitude. Accelerated intercalation is also observed with partially unpaired DNA. Dissociation from mixed sequence DNA displays half-lives of up to 38 h at physiological temperature, the slowest release reported for a reversibly bound agent. The selectivity demonstrated by the binuclear ruthenium complexes in vitro make them interesting in the development of new agents against parasitic protozoa with AT-rich DNA