A new method for non-labeling attomolar detection of diseases based on an individual gold nanorod immunosensor

Herein, we present the use of a single gold nanorod sensor for detection of diseases on an antibody-functionalized surface, based on antibody–antigen interaction and the localized surface plasmon resonance (LSPR) ?max shifts of the resonant Rayleigh light scattering spectra. By replacing the cetyltrimethylammonium bromide (CTAB), a tightly packed self-assembled monolayer of HS(CH2)11(OCH2CH2)6OCH2COOH(OEG6) has been successfully formed on the gold nanorod surface prior to the LSPR sensing, leading to the successful fabrication of individual gold nanorod immunosensors. Using prostate specific antigen (PSA) as a protein biomarker, the lowest concentration experimentally detected was as low as 111 aM, corresponding to a 2.79 nm LSPR ?max shift. These results indicate that the detection platform is very sensitive and outperforms detection limits of commercial tests for PSA so far. Correlatively, its detection limit can be equally compared to the assays based on DNA biobarcodes. This study shows that a gold nanorod has been used as a single nanobiosensor to detect antigens for the first time; and the detection method based on the resonant Rayleigh scattering spectrum of individual gold nanorods enables a simple, label-free detection with ultrahigh sensitivity.

An Excess of Risk-Increasing Low-Frequency Variants Can Be a Signal of Polygenic Inheritance in Complex Diseases

In most complex diseases, much of the heritability remains unaccounted for by common variants. It has been postulated that lower-frequency variants contribute to the remaining heritability. Here, we describe a method to test for polygenic inheritance from lower-frequency variants by using GWAS summary association statistics. We explored scenarios with many causal low-frequency variants and showed that there is more power to detect risk variants than to detect protective variants, resulting in an increase in the ratio of detected risk to protective variants (R/P ratio). Such an excess can also occur if risk variants are present and kept at lower frequencies because of negative selection. The R/P ratio can be falsely elevated because of reasons unrelated to polygenic inheritance, such as uneven sample sizes or asymmetric population stratification, so precautions to correct for these confounders are essential. We tested our method on published GWAS results and observed a strong signal in some diseases (schizophrenia and type 2 diabetes) but not others. We also explored the shared genetic component in overlapping phenotypes related to inflammatory bowel disease (Crohn disease [CD] and ulcerative colitis [UC]) and diabetic nephropathy (macroalbuminuria and end-stage renal disease [ESRD]). Although the signal was still present when both CD and UC were jointly analyzed, the signal was lost when macroalbuminuria and ESRD were jointly analyzed, suggesting that these phenotypes should best be studied separately. Thus, our method may also help guide the design of future genetic studies of various traits and diseases.

Periodontitis and systemic diseases:A record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases

Background There has been an explosion in research into possible associations between periodontitis and various systemic diseases and conditions. Aim To review the evidence for associations between periodontitis and various systemic diseases and conditions, including chronic obstructive pulmonary disease (COPD), pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer, and to document headline discussions of the state of each field. Periodontal associations with diabetes, cardiovascular disease and adverse pregnancy outcomes were not discussed by working group 4. Results Working group 4 recognized that the studies performed to date were largely cross-sectional or case-control with few prospective cohort studies and no randomized clinical trials. The best current evidence suggests that periodontitis is characterized by both infection and pro-inflammatory events, which variously manifest within the systemic diseases and disorders discussed. Diseases with at least minimal evidence of an association with periodontitis include COPD, pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. The working group agreed that there is insufficient evidence to date to infer causal relationships with the exception that organisms originating in the oral microbiome can cause lung infections. Conclusions The group was unanimous in their opinion that the reported associations do not imply causality, and establishment of causality will require new studies that fulfil the Bradford Hill or equivalent criteria. Precise and community-agreed case definitions of periodontal disease states must be implemented systematically to enable consistent and clearer interpretations of studies of the relationship to systemic diseases. The members of the working group were unanimous in their opinion that to develop data that best inform clinicians, investigators and the public, studies should focus on robust disease outcomes and avoid surrogate endpoints. It was concluded that because of the relative immaturity of the body of evidence for each of the purported relationships, the field is wide open and the gaps in knowledge are large. © 2013 European Federation of Periodontology and American Academy of Periodontology.

Integrated care pathways for airway diseases (AIRWAYS-ICPs)

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

Family-based associations in measures of psychological distress and quality of life in a cardiac screening clinic for inheritable cardiac diseases: a cross-sectional study

BACKGROUND: Family-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic.

METHODS: Prospective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data.

RESULTS: There was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance.

CONCLUSIONS: High levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has implications for family screening and intervention programmes.

Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs () across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of  from imputed SNPs (5.1× enrichment; p = 3.7 × 10⁻¹⁷) and 38% (SE = 4%) of  from genotyped SNPs (1.6× enrichment, p = 1.0 × 10⁻⁴). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of  despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease.

Challenges in secondary prevention of cardiovascular diseases: A review of the current practice

With the changing demography of populations and increasing prevalence of co-morbidity, frail patients and more complex cardiac conditions, the modern medicine is facing novel challenges leading to rapid innovation where evidence and experiences are lacking. This scenario is also evident in cardiovascular disease prevention, which continuously needs to accommodate its ever changing strategies, settings, and goals. The present paper summarises actual challenges of secondary prevention, and discusses how this intervention should not only be effective but also efficient. By this way the paper tries to bridge the gaps between research and real-world findings and thereby may find ways to improve standard care.