Human saliva as a tool to investigate intimate partner violence

Human saliva mirrors body’s health and well-being and many of the biomolecules present in blood or urine can also be found in salivary secretions. However, biomolecular concentrations in saliva are usually one tenth to one thousandth of the levels in blood (Pfaffe et al., 2011). Sensitive detection technology platforms are therefore required to detect biomolecules in saliva. Another road block to the advancement of salivary diagnostics is the lack of information related to healthy state saliva vs. a diseased saliva, baseline levels and reference ranges and diurnal variations. Saliva has numerous advantages over blood or urine as a diagnostic fluid: (a) the non-invasive nature of sample collection and the simple, safe, painless and cost-effective methods to collect it; (b) unskilled personnel can collect saliva samples at multiple time points; and (c) the total protein concentration is approximately a quarter of that is present in plasma, which makes it easier to investigate low abundance proteins (Pfaffe et al., 2011). Currently, saliva assays are routinely used to determine, diseases such as HIV, drugs and substances of abuse to provide information on exposure and give qualitative information on the type of illicit drug used (Kintz et al., 2009), cortisol levels for diagnosing Cushing’s syndrome (Doi et al., 2008), and use for biomonitoring of exposure to chemicals (Caporossi et al., 2010) to measure hormones (Gröschl, 2009)....

Stress, the hippocampus and the HPA axis: Implications for the development of psychotic disorders

The experience of stress is commonly implicated in models of the onset of psychotic disorders. However, prospective studies investigating associations between biological markers of stress and the emergence of psychotic disorders are limited and inconclusive. One biological system proposed as the link between the psychological experience of stress and the development of psychosis is the Hypothalamic-Pituitary-Adrenal (HPA) axis. This paper summarizes and discusses evidence supporting a role for HPA-axis dysfunction in the early phase of schizophrenia and related disorders. METHOD A selective review of psychiatric and psychological research on stress, coping, HPA-axis, the hippocampus and psychotic disorders was performed, with a particular focus on the relationship between HPA-axis dysfunction and the onset of psychotic disorders. RESULTS Individual strands of past research have suggested that the HPA-axis is dysfunctional in at least some individuals with established psychotic disorders; that the hippocampus is an area of the brain that appears to be implicated in the onset and maintenance of psychotic disorders; and that an increase in the experience of stress precedes the onset of a psychotic episode in some individuals. Models of the onset and maintenance of psychotic disorders that link these individual strands of research and strategies for examining these models are proposed in this paper. CONCLUSIONS The current literature provides some evidence that the onset of psychotic disorders may be associated with a higher rate of stress and changes to the hippocampus. It is suggested that future research should investigate whether a relationship exists between psychological stress, HPA-axis functioning and the hippocampus in the onset of these disorders. Longitudinal assessment of these factors in young people at 'ultra' high risk of psychosis and first-episode psychosis cohorts may enhance understanding of the possible interaction between them in the early phases of illness.

Endurance exercise and DNA stability: Is there a link to duration and intensity?

It is commonly accepted that regular moderate intensity physical activity reduces the risk of developing many diseases. Counter intuitively, however, evidence also exists for oxidative stress resulting from acute and strenuous exercise. Enhanced formation of reactive oxygen and nitrogen species may lead to oxidatively modified lipids, proteins and nucleic acids and possibly disease. Currently, only a few studies have investigated the influence of exercise on DNA stability and damage with conflicting results, small study groups and the use of different sample matrices or methods and result units. This is the first review to address the effect of exercise of various intensities and durations on DNA stability, focusing on human population studies. Furthermore, this article describes the principles and limitations of commonly used methods for the assessment of oxidatively modified DNA and DNA stability. This review is structured according to the type of exercise conducted (field or laboratory based) and the intensity performed (i.e. competitive ultra/endurance exercise or maximal tests until exhaustion). The findings presented here suggest that competitive ultra-endurance exercise (>4h) does not induce persistent DNA damage. However, when considering the effects of endurance exercise (<4h), no clear conclusions could be drawn. Laboratory studies have shown equivocal results (increased or no oxidative stress) after endurance or exhaustive exercise. To clarify which components of exercise participation (i.e. duration, intensity and training status of subjects) have an impact on DNA stability and damage, additional carefully designed studies combining the measurement of DNA damage, gene expression and DNA repair mechanisms before, during and after exercise of differing intensities and durations are required.

Letter: Brain natriuretic peptide is a potentially useful screening tool for the detection of cardiovascular disease in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have a significantly higher risk of coronary heart disease, despite being less likely to report symptoms of angina, and are more likely to experience unrecognised myocardial infarction and sudden cardiac death than non-RA controls.1 Furthermore, left ventricular diastolic dysfunction has been described in up to 40% of patients with RA.2...

Clinical factors associated with the humoral immune response to influenza vaccination in chronic obstructive pulmonary disease

Background and objective Individuals with chronic obstructive pulmonary disease (COPD) are at a high risk of developing significant complications from infection with the influenza virus. It is therefore vital to ensure that prophylaxis with the influenza vaccine is effective in COPD. The aim of this study was to assess the immunogenicity of the 2010 trivalent influenza vaccine in persons with COPD compared to healthy subjects without lung disease, and to examine clinical factors associated with the serological response to the vaccine. Methods In this observational study, 34 subjects (20 COPD, 14 healthy) received the 2010 influenza vaccine. Antibody titers at baseline and 28 days post-vaccination were measured using the hemagglutination inhibition assay (HAI) assay. Primary endpoints included seroconversion (≥4-fold increase in antibody titers from baseline) and the fold increase in antibody titer after vaccination. Results Persons with COPD mounted a significantly lower humoral immune response to the influenza vaccine compared to healthy participants. Seroconversion occurred in 90% of healthy participants, but only in 43% of COPD patients (P=0.036). Increasing age and previous influenza vaccination were associated with lower antibody responses. Antibody titers did not vary significantly with cigarette smoking, presence of other comorbid diseases, or COPD severity. Conclusion The humoral immune response to the 2010 influenza vaccine was lower in persons with COPD compared to non-COPD controls. The antibody response also declined with increasing age and in those with a history of prior vaccination.

Risedronate in adults with osteogenesis imperfecta type I: Increased bone mineral density and decreased bone turnover, but high fracture rate persists

Summary Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. Introduction Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. Methods Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. Results Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm 2, p=0.007; mean Z-score, -1.93 vs. -1.58, p=0.002), with no significant change at TH. P1NP fell by 37% (p=0.00041), with no significant change in bone ALP (p=0.15). Bone pain did not change significantly (p=0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. Conclusions Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

Genetic and genomic studies of PADI4 in rheumatoid arthritis

Objectives. Strong genetic association of rheumatoid arthritis (RA) with PADI4 (peptidyl arginine deiminase) has previously been described in Japanese, although this was not confirmed in a subsequent study in the UK. We therefore undertook a further study of genetic association between PADI4 and RA in UK Caucasians and also studied expression of PADI4 in the peripheral blood of patients with RA. Methods. Seven single-nucleotide polymorphisms (SNP) were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism in 111 RA cases and controls. A marker significantly associated with RA (PADI4_100, rs#2240339) in this first data set (P = 0.03) was then tested for association in a larger group of 439 RA patients and 428 controls. PADI4 transcription was also assessed by real-time quantitative PCR using RNA extracted from peripheral blood mononuclear cells from 13 RA patients and 11 healthy controls. Results. A single SNP was weakly associated with RA (P = 0.03) in the initial case-control study, a single SNP (PADI4_100) and a two marker haplotype of that SNP and the neighbouring SNP (PADI4_04) were significantly associated with RA (P = 0.02 and P = 0.03 respectively). PADI4_100 was not associated with RA in a second sample set. PADI4 expression was four times greater in cases than controls (P = 0.004), but expression levels did not correlate with the levels of markers of inflammation. Conclusion. PADI4 is significantly overexpressed in the blood of RA patients but genetic variation within PADI4 is not a major risk factor for RA in Caucasians.

Osteoclast formation from circulating precursors in osteoporosis

Objective: An imbalance between bone formation and bone resorption is thought to underlie the pathogenesis of reduced bone mass in osteoporosis. Bone resorption is carried out by osteoclasts, which are formed from marrow-derived cells that circulate in the monocyte fraction. Ihe aim of this study was to determine the role of osteoclast formation in the pathogenesis of bone loss in osteoporosis. Methods: The proportion of circulating osteoclast precursors and their relative sensitivity to the osteoclastogenic effects of M-CSF, 1,25(OH)2D3 and RANKL were assessed in primary osteoporosis patients and normal controls. Results: Although there was no difference in the number of circulating osteoclast precursors in osteoporosis patients and normal controls, osteoclasts formed from osteoporosis patients exhibited substantially increased resorptive activity relative to normal controls. Although no increased sensitivity to the osteoclastogenic effects of 1,25(OH)2D3 or M-CSF was noted, increased bone resorption was found in osteoporosis peripheral blood mononuclear cell (PBMC) cultures to which these factors were added. Conclusion: Our findings suggest that osteoclast functional activity rather than formation is increased in primary involutional osteoporosis and that dexamethasone acts to increase osteoclast formation.

A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure

The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 x 10(-8)) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 x 10(-6)). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure.

Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients

Introduction Recent reports have highlighted the prevalence of vitamin D deficiency and suggested an association with excess mortality in critically ill patients. Serum vitamin D concentrations in these studies were measured following resuscitation. It is unclear whether aggressive fluid resuscitation independently influences serum vitamin D. Methods Nineteen patients undergoing cardiopulmonary bypass were studied. Serum 25(OH)D3, 1α,25(OH)2D3, parathyroid hormone, C-reactive protein (CRP), and ionised calcium were measured at five defined timepoints: T1 - baseline, T2 - 5 minutes after onset of cardiopulmonary bypass (CPB) (time of maximal fluid effect), T3 - on return to the intensive care unit, T4 - 24 hrs after surgery and T5 - 5 days after surgery. Linear mixed models were used to compare measures at T2-T5 with baseline measures. Results Acute fluid loading resulted in a 35% reduction in 25(OH)D3 (59 ± 16 to 38 ± 14 nmol/L, P < 0.0001) and a 45% reduction in 1α,25(OH)2D3 (99 ± 40 to 54 ± 22 pmol/L P < 0.0001) and i(Ca) (P < 0.01), with elevation in parathyroid hormone (P < 0.0001). Serum 25(OH)D3 returned to baseline only at T5 while 1α,25(OH)2D3 demonstrated an overshoot above baseline at T5 (P < 0.0001). There was a delayed rise in CRP at T4 and T5; this was not associated with a reduction in vitamin D levels at these time points. Conclusions Hemodilution significantly lowers serum 25(OH)D3 and 1α,25(OH)2D3, which may take up to 24 hours to resolve. Moreover, delayed overshoot of 1α,25(OH)2D3 needs consideration. We urge caution in interpreting serum vitamin D in critically ill patients in the context of major resuscitation, and would advocate repeating the measurement once the effects of the resuscitation have abated.

Seeing pedestrians at night : visual clutter does not mask biological motion

Although placing reflective markers on pedestrians’ major joints can make pedestrians more conspicuous to drivers at night, it has been suggested that this “biological motion” effect may be reduced when visual clutter is present. We tested whether extraneous points of light affected the ability of 12 younger and 12 older drivers to see pedestrians as they drove on a closed road at night. Pedestrians wore black clothing alone or with retroreflective markings in four different configurations. One pedestrian walked in place and was surrounded by clutter on half of the trials. Another was always surrounded by visual clutter but either walked in place or stood still. Clothing configuration, pedestrian motion, and driver age influenced conspicuity but clutter did not. The results confirm that even in the presence of visual clutter pedestrians wearing biological motion configurations are recognized more often and at greater distances than when they wear a reflective vest.

Characterising the homeostatic and hedonic markers of the susceptible phenotype

Over the years, approaches to obesity prevention and treatment have gone from focusing on genetic and other biological factors to exploring a diversity of diets and individual behavior modification interventions anchored primarily in the power of the mind, to the recent shift focusing on societal interventions to design ";temptation-proof"; physical, social, and economic environments. In spite of repeated calls to action, including those of the World Health Organization (WHO), the pandemic continues to progress. WHO recently projected that if the current lifestyle trend in young and adult populations around the world persist, by 2012 in countries like the USA, health care costs may amount to as much as 17.7% of the GDP. Most importantly, in large part due to the problems of obesity, those children may be the first generation ever to have a shorter life expectancy than that of their parents. This work presents the most current research and proposals for addressing the pandemic. Past studies have focused primarly on either genetic or behavioral causes for obesity, however today's research indicates that a strongly integrated program is the best prospect for success in overcoming obesity. Furthermore, focus on the role of society in establishing an affordable, accessible and sustainable program for implementing these lifestyle changes is vital, particularly for those in economically challenged situations, who are ultimately at the highest risk for obesity. Using studies from both neuroscience and behavioral science to present a comprehensive overview of the challenges and possible solutions, The brain-to-society approach to obesity prevention focuses on what is needed in order to sustain a healthy, pleasurable and affordable lifestyle.

Isolation and characterisation of novel microsatellite and mitochondrial DNA markers for the Eastern Water Dragon (Physignathus lesueurii)

Habitat fragmentation as a result of urbanisation is a growing problem for native lizard species. The Eastern Water Dragon (Physignathus lesueurii) is a social arboreal agamid lizard, native to Australia. This species represents an ideal model species to investigate the effect of urbanisation because of their prominent abundance in the urban landscape. Here we describe the isolation and characterisation of a novel set of 74 di-, tri-, and tetramicrosatellites from which 18 were selected and optimised into two multiplexes. The 18 microsatellites generated a total 148 alleles across the two populations. The number of alleles per locus varied from 2 to 18 alleles and measures of Ho and He varied from 0.395 to 0.877 and from 0.441 to 0.880, respectively. We also present primers for four novel mitochondrial DNA (mtDNA) markers. The combined length of the four mtDNA marker pairs was 2,528 bp which included 15 nucleotides changes. In comparison to threatened species, which are generally characterised by small population sizes, the Eastern Water Dragon represents an ideal model species to investigate the effect of urbanisation on their behavioural ecology and connectivity patterns among populations.

Development and characterisation of tri- and tetra-nucleotide polymorphic microsatellite markers for skipjack tuna (Katsuwonus pelamis)

Skipjack tuna (katsuwonus pelamis) (SJT) is the largest tuna fishery in all the major oceans around the world, and the largest marine fishery in Sri Lanka. Knowledge of genetic population structure and effective population size of SJT in the Indian Ocean and other major oceans, however, is still lacking for better management practices and conservation strategies. We developed microsatellite genetic markers using SJT around Sri Lanka in the Indian Ocean, and characterise one tri- and seven tetra-nucleotide microsatellite loci isolated from enriched genomic libraries from SJT, to provide tools for addressing both conservation and fisheries management questions. An analysis of these eight microsatellite markers in two populations of SJT from eastern Sri Lanka (n = 44) and the Maldives Islands (n = 53) showed that all eight microsatellites were polymorphic with an average number of alleles per locus of 11.80 (range 5-27). Expected heterozygosities at marker loci ranged from 0.450 to 0.961. These markers are being used currently to characterise population structure and extent of natural gene flow in SJT populations from the eastern and western Indian Ocean. No significant linkage disequilibrium was detected among any loci pairs.

Transcriptomics approaches to identify genes and markers for production traits in giant freshwater prawn Macrobrachium rosenbergii

This study used next generation sequencing technologies to investigate growth in a cultured crustacean. The objective was to identify and characterise specific gene loci that contribute important phenotypic variation to growth as well as to develop a large set of SNP markers in candidate genes for assessing correlations between specific mutations and individual growth performance. The genomic dataset generated provides a fundamental resource for application in future crustacean stock improvement programs. Ultimately, the data can be applied to development of culture lines with improved growth performance.