Silica nanowires templated by amyloid-like fibrils

Many peptides self-assemble to form amyloid fibrils. We previously explored the sequence propensity to form amyloid using variants of a designed peptide with sequence KFFEAAAKKFFE. These variant peptides form highly stable amyloid fibrils with varied lateral assembly and are ideal to template further assembly of non-proteinaceous material. Herein, we show that the fibrils formed by peptide variants can be coated with a layer of silica to produce silica nanowires using tetraethyl-orthosilicate. The resulting nanowires were characterized using electron microscopy (TEM), X-ray fiber diffraction, FTIR and cross-section EM to reveal a nanostructure with peptidic core. Lysine residues play a role in templating the formation of silica on the fibril surface and, using this library of peptides, we have explored the contributions of lysine as well as arginine to silica templating, and find that sequence plays an important role in determining the physical nature and structure of the resulting nanowires

Hand Osteoarthritis Severity is Associated with Total Knee Joint Replacements Independently of BMI. The Ages-Reykjavik Study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To identify factors associated with having total knee replacement due to osteoarthritis in the AGES-Reykjavik Study, a large population based study of elderly Icelanders. METHODS: Information about total knee and hip joint replacements (TKR,THR) and hand OA (HOA) severity was available in 2195 males and 2975 females, mean age 76±6 years. The prevalence of TKR was 223 (4.3%) and THR 316 (6.1%). We performed a backwards binary logistic regression analysis of possible OA associated variables including age, gender, abdominal circumference, BMI, hs-CRP, cholesterol, statin use, bone mineral density of the spine, education and smoking history as well as HOA severity and the presence of THR. RESULTS: Only three factors showed significant associations with TKR; BMI (p=3.5x10(-17)), HOA severity (p=2.9x10(-8)) and THR (p=0.0002). The highest quintile of BMI was associated with a fivefold risk of TKR compared with the lowest (8% vs 1.6%), and severe HOA had a 2.4 fold risk compared with those with no HOA (8% vs 3.3%). There was no statistical interaction between BMI and HOA. Thus, individuals with BMI30.3 and severe HOA had a prevalence of 13.4%. CONCLUSIONS: Hand and hip osteoarthritis in conjunction with BMI are strongly associated with the prevalence of TKR due to osteoarthritis. Together, BMI and HOA severity seem to contribute to the majority of the total TKR prevalence. While BMI has long been recognized as the major risk factor for TKR, the influence of osteoarthritis at other sites may have been underestimated

The Off Shell ρ\rho-ω\omega Mixing in the QCD Sum Rules

The $q^2$ dependence of the $\rho-\omega$ mixing amplitude is analyzed with the use of the QCD sum rules and the dispersion relation. Going off shell the mixing decreases, changes sign at $q^2 \simeq 0.4 m_{\rho}^2 > 0$ and is negative in the space like region. Implications of this result to the isospin breaking part of the nuclear force are discussed.Comment: 26 pages + 11 figures (PostScript

Calculation of gluon and four-quark condensates from the operator expansion

The magnitudes of gluon and four-quark condensates are found from the analysis of vector mesons consisting of light quarks (the families of $\rho$ and $\omega$ mesons) in the 3 loops approximation. The QCD model with infinite number of vector mesons is used to describe the function $R(s)$. This model describes well the experimental function $R(s)$. Polarization operators calculated with this model coincide with the Wilson operator expansion at large $Q^2$. The improved perturbative theory, such that the polarization operators have correct analytical properties, is used. The result is $<0 | (\alpha_s/\pi) G^2 | 0 > = 0.062 \pm 0.019 GeV^4$. The electronic widths of $\rho(1450)$ and $\omega(1420)$ are calculated.Comment: 18 pages, latex, changed content slightl

Longitudinal Association Between Education and Disability in Older Adults Living in Iceland

BACKGROUND: Disabilities among older adults are associated with cumulative adversities such as low socioeconomic status (SES), poor nutrition, and lack of access to medical care and education. However, there is little evidence on the long-term association between education and disability status among older adults in Iceland. The aim of the study was to examine the association between mid-life education and prevalence of disability in activities of daily living (ADL) and mobility disability in late-life using 25 years of longitudinal data. METHODS: A large community-based population residing in Reykjavik, Iceland participated in a longitudinal study with an average of 25 years of follow-up (N=5764, mean age 77±6 yrs, 57.7% of women) Mid-life education was categorized into 2 groups (primary and secondary versus college and university). Disability status in late life was defined with ADL and mobility disability with a binary outcome (no difficulty versus any difficulty). Logistic regression analysis was used to examine the association. RESULTS: After controlling for age and gender, and midlife health risk factors, those who had high education at mid-life were less likely to have ADL disability (Odds Ratio (OR) = 0.75, 95% Confidence Interval (CI): 0.64 ~ 0.88, P ≤ 0.001) and mobility disability (OR = 0.72, 95% CI: 0.61 ~ 0.86, P < 0.001) compared with those who had low education in mid-life. CONCLUSION: People with high mid-life education were less likely to have ADL and mobility disability after 25 years later.Peer reviewe

Pseudoscalar Glueball Mass: QCD vs. Lattice Gauge Theory Prediction

We study whether the pseudoscalar glueball mass in full QCD can differ from the prediction of quenched lattice calculations. Using properties of the correlator of the vacuum topological susceptibility we derive an expression for the upper bound on the QCD glueball mass. We show that the QCD pseudoscalar glueball is lighter than the pure Yang-Mills theory glueball studied in quenched lattice calculations. The mass difference between those two states is of order of $1/N_c$. The value calculated for the $0^{-+}$ QCD glueball mass can not be reconciled with any physical state observed so far in the corresponding channel. The glueball decay constant and its production rate in $J/\psi$ radiative decays are calculated. The production rate is large enough to be studied experimentally.Comment: 18 pages, LaTex fil

Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: a pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction &gt; 5.0×10−8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD

Increasing response to a postal survey of sedentary patients – a randomised controlled trial [ISRCTN45665423]

BACKGROUND: A systematic review identified a range of methods, which can influence response rates. However, analysis specific to a healthcare setting, and in particular, involving people expected to be poor responders, was missing, We examined the effect of pre-warning letters on response rates to a postal survey of sedentary patients whom we expected a low rate of response. METHODS: Participants were randomised to receive a pre-warning letter or no pre-warning letter, seven days before sending the main questionnaire. The main questionnaire included a covering letter and pre-paid return envelope. After seven days, non-responders were sent a reminder letter and seven days later, another reminder letter with a further copy of the questionnaire and return envelope. RESULTS: 627 adults, with a mean age of 48 years (SD 13, range 18 to 78) of whom 69.2% (434/627) were women, were randomised. 49.0% (307/627) of patients were allocated to receive a pre-warning letter and 51.0% (320/627) no pre-warning letter, seven days in advance of posting the main questionnaire. The final response rate to the main questionnaire was 30.0% (92/307) amongst those sent a pre-warning letter and 20.9% (67/320) not sent a pre-warning letter, with an adjusted odds ratio of 1.60 (95% CI 1.1, 2.30). CONCLUSIONS: The relatively low cost method of sending a pre-warning letter had a modest impact on increasing response rates to a postal questionnaire sent to a group of patients for whom a low response rate was anticipated. Investigators should consider incorporating this simple intervention when conducting postal surveys, to reduce the potential for nonresponse bias and to increase the study power. Methods other than postal surveys may be needed however when a low response rate to postal surveys is likely

Communicating with people living with dementia who are nonverbal: the creation of Adaptive Interaction

Loss of verbal language production makes people with dementia appear unreachable. We previously presented a case study applying nonverbal communication techniques with a lady with dementia who could no longer speak, which we termed Adaptive Interaction. The current small-n study examines the applicability of Adaptive Interaction as a general tool for uncovering the communication repertoires of non-verbal individuals living with dementia. Communicative responses of 30 interaction sessions were coded and analysed in two conditions: Standard (Baseline) and Adaptive Interaction (Intervention). All participants retained the ability to interact plus a unique communication repertoire comprising a variety of nonverbal components, spanning eye gaze, emotion expression, and movement. In comparison to Baseline sessions, Intervention sessions were characterised by more smiling, looking at ME and imitation behaviour from the people with dementia. These findings allude to the potential of Adaptive Interaction as the basis for interacting with people living with dementia who can no longer speak