Environmentally Relevant Iron Oxide Nanoparticles Produce Limited Acute Pulmonary Effects in Rats at Realistic Exposure Levels.

Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter. Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeOxNPs) but their results have been contradictory, with some indicating no or minor effects and others finding effects including oxidative stress and inflammation. Most studies, however, did not use materials reflecting the characteristics of FeOxNPs present in the environment. We, therefore, analysed the potential toxicity of FeOxNPs of different forms (Fe3O4, α-Fe2O3 and γ-Fe2O3) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually and in a mixture (FeOx-mix). A preliminary in vitro study indicated Fe3O4 and FeOx-mix were more cytotoxic than either form of Fe2O3 in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro (0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague-Dawley rats, nose-only exposure, 50 µg/m3 and 500 µg/m3, 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored responses at the molecular level via multi-omics analyses at concentrations below those at which significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation experiments used aerosol concentrations chosen to produce similar levels of particle deposition on the airway surface as were delivered in vitro. These were markedly higher than environmental concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or BEAS-2B cells to suggest adverse effects.

Fat emulsion intragastric stability and droplet size modulate gastrointestinal responses and subsequent food intake in young adults.

BACKGROUND: Intragastric creaming and droplet size of fat emulsions may affect intragastric behavior and gastrointestinal and satiety responses. OBJECTIVES: We tested the hypotheses that gastrointestinal physiologic responses and satiety will be increased by an increase in intragastric stability and by a decrease in fat droplet size of a fat emulsion. METHODS: This was a double-blind, randomized crossover study in 11 healthy persons [8 men and 3 women, aged 24 ± 1 y; body mass index (in kg/m(2)): 24.4 ± 0.9] who consumed meals containing 300-g 20% oil and water emulsion (2220 kJ) with 1) larger, 6-µm mean droplet size (Coarse treatment) expected to cream in the stomach; 2) larger, 6-µm mean droplet size with 0.5% locust bean gum (LBG; Coarse+LBG treatment) to prevent creaming; or 3) smaller, 0.4-µm mean droplet size with LBG (Fine+LBG treatment). The participants were imaged hourly by using MRI and food intake was assessed by using a meal that participants consumed ad libitum. RESULTS: The Coarse+LBG treatment (preventing creaming in the stomach) slowed gastric emptying, resulting in 12% higher gastric volume over time (P < 0.001), increased small bowel water content (SBWC) by 11% (P < 0.01), slowed appearance of the (13)C label in the breath by 17% (P < 0.01), and reduced food intake by 9% (P < 0.05) compared with the Coarse treatment. The Fine+LBG treatment (smaller droplet size) slowed gastric emptying, resulting in 18% higher gastric volume (P < 0.001), increased SBWC content by 15% (P < 0.01), and significantly reduced food intake by 11% (P < 0.05, equivalent to an average of 411 kJ less energy consumed) compared with the Coarse+LBG treatment. These high-fat meals stimulated substantial increases in SBWC, which increased to a peak at 4 h at 568 mL (range: 150-854 mL; P < 0.01) for the Fine+LBG treatment. CONCLUSION: Manipulating intragastric stability and fat emulsion droplet size can influence human gastrointestinal physiology and food intake.

Technologies That Assess the Location of Physical Activity and Sedentary Behavior: A Systematic Review.

BACKGROUND: The location in which physical activity and sedentary behavior are performed can provide valuable behavioral information, both in isolation and synergistically with other areas of physical activity and sedentary behavior research. Global positioning systems (GPS) have been used in physical activity research to identify outdoor location; however, while GPS can receive signals in certain indoor environments, it is not able to provide room- or subroom-level location. On average, adults spend a high proportion of their time indoors. A measure of indoor location would, therefore, provide valuable behavioral information. OBJECTIVE: This systematic review sought to identify and critique technology which has been or could be used to assess the location of physical activity and sedentary behavior. METHODS: To identify published research papers, four electronic databases were searched using key terms built around behavior, technology, and location. To be eligible for inclusion, papers were required to be published in English and describe a wearable or portable technology or device capable of measuring location. Searches were performed up to February 4, 2015. This was supplemented by backward and forward reference searching. In an attempt to include novel devices which may not yet have made their way into the published research, searches were also performed using three Internet search engines. Specialized software was used to download search results and thus mitigate the potential pitfalls of changing search algorithms. RESULTS: A total of 188 research papers met the inclusion criteria. Global positioning systems were the most widely used location technology in the published research, followed by wearable cameras, and radio-frequency identification. Internet search engines identified 81 global positioning systems, 35 real-time locating systems, and 21 wearable cameras. Real-time locating systems determine the indoor location of a wearable tag via the known location of reference nodes. Although the type of reference node and location determination method varies between manufacturers, Wi-Fi appears to be the most popular method. CONCLUSIONS: The addition of location information to existing measures of physical activity and sedentary behavior will provide important behavioral information.

Prevalence and socio-demographic correlates of obesity in the British Army.

BACKGROUND: The trend of escalating obesity has prompted some armed forces to employ comprehensive health surveys to report obesity trends and prevalence, the findings of which suggest that obesity is a growing concern in these specific populations. AIM: To provide an appraisal of obesity prevalence and risk to obesity-related diseases in the British Army in relation to age, gender, military rank and employment. SUBJECTS AND METHOD: An observational cohort study (n = 50 635) consisting of 47 173 men and 3462 women was drawn from a study sample hosted on the Fitness Information Software System (FISS) (n = 54 854). Multiple logistic regression techniques were employed separately for men and women. RESULTS: According to BMI, 56.7% of the study population were overweight and of those individuals 12% were obese. Whilst a higher percentage of males were obese (12.2% and 8.6%, respectively), when waist circumference data were added to the BMI data, the results indicate that females displayed a higher percentage of risk to obesity-related diseases than males (30.4% and 24%, respectively). CONCLUSIONS: Armed service personnel should be made aware of the implications of obesity in regards to health and occupation. Specific focus should be given to those older individuals employed in managerial positions undertaking low levels of occupational physical activity.

Combination of electrochemistry and nuclear magnetic resonance spectroscopy for metabolism studies.

During the development of new materials demonstrating biological activity, prediction and identification of reactive intermediates generated in the course of drug metabolism in the human liver is of great importance. We present a rapid and purely instrumental method for the structure elucidation of possible phase I metabolites. With electrochemical (EC) conversion adopting the oxidative function of liver-inherent enzymes and nuclear magnetic resonance (NMR) spectroscopy enabling structure elucidation, comprehensive knowledge on potential metabolites can be gained. Paracetamol (APAP) has been known to induce hepatotoxicity when exceeding therapeutic doses and was therefore selected as the test compound. The reactive metabolite N-acetyl-p-benzoquinone imine has long been proven to be responsible for the toxic side effects of APAP and can easily be generated by EC. EC coupled online to NMR is a straightforward technique for structure elucidation of reactive drug intermediates at an early stage in drug discovery.

Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes.

A transcriptome analysis compared gene expression in human bone biopsy samples taken from lumbar spine and iliac crest, sites that experience high and low levels of mechanical stress, respectively. The analysis revealed that the zinc finger protein of cerebellum (Zic) family member transcription factor Zic1 was the most up-regulated gene in the lumbar spine (202-fold; P<10(-7)) in comparison with the iliac crest. Software analysis of differential gene expression in the biopsy samples identified the ciliary-related proteins PATCH1 and GLI-Kruppel family members Gli1 and Gli3 as part of a potential molecular network associated with Zic1. RT-PCR confirmed the expression of Zic1, Gli1, and Gli3 and other related key signaling mediators in osteoblastic cells and osteocytes in vitro. Zic1 was immunolocalized in the cytosol and nucleus of the murine osteocyte cell line MLO-Y4 and osteoblast-like cells MC3T3-E1 and in primary rat osteoblasts. MLO-Y4 cells subjected to prolonged oscillatory fluid flow showed increased localization of Zic1 in the nucleus with diminished levels in the cytosol, but no such changes were seen in MC3T3-E1 cells. A shear stress-induced increase in T-cell factor/lymphoid enhancer factor transcriptional activity was abolished by Zic1 gene silencing. These results suggest that Zic1, perhaps together with Gli1 and Gli3, may act as a link between mechanosensing and Wnt signaling. We conclude that Zic1, a neural developmental transcription factor, plays an important role in shear flow mechanotransduction in osteocytes.

The association between obesity related health risk and fitness test results in the British Army personnel.

OBJECTIVE: In the British Army, fitness is assessed by a load carriage test (Annual Fitness Test, AFT) and by a three event Personal Fitness Assessment (PFA). Body composition based on body mass index (BMI) and abdominal circumference (AC) is also part of a mandatory annual assessment. This study examined the influence of BMI and AC on fitness test results within a comprehensive sample of British Army personnel. DESIGN: Secondary analyse were carried out on data obtained from the 2011 Defence Analytical Services and Advice (DASA) database for 50,635 soldiers (47,173 men and 3,462 women). METHODS: Comparisons using loglinear analysis were made between groups of individuals classified by body mass index as obese (≥30kg/m2) and not obese (<30kg/m2), and further classified using combined BMI and AC for obesity-related health risks to compare "no risk" with "increased risk." RESULTS: Not obese or "no risk" soldiers had a significant relationship with success in the AFT (p<0.01) and PFA (p<0.01). Of those soldiers who attempted the AFT, 99% of men and 92% of women passed; for the PFA, 92% of men and 91% of women passed. Obese or "at risk" soldiers were more likely to fail and far less likely to take both tests (p<0.05). Compared to older obese soldiers, young obese soldiers were more likely to attempt the tests. CONCLUSIONS: We conclude that BMI and AC are useful indicators of fitness test outcome in the British Army.

Ten years of lesbian health survey research in the UK West Midlands.

BACKGROUND: Very little is known about the physical health needs of lesbian and bisexual women in the UK; most research has looked at mental or sexual health only. This article reports the results of four surveys carried out in the West Midlands between 1995 and 2005. METHODS: The first two surveys were conducted in 1995-6 by a volunteer group, with participants from a lesbian health conference (n = 69) and in a convenience sample from a wide range of relevant groups and venues (n = 354). The second two surveys were commissioned by the West Midlands South Strategic Health Authority in partnership with the Gay Men's Health Network and were conducted in 2002 (n = 449) and 2005 (n = 166) and again used convenience sampling methods including the internet. RESULTS: The mean age of respondents varied between 29-33 years and 5-7% were from a non-white ethnic background. The smoking rates varied from 42% o 55%, being twice the West Midlands regional average of 21% for women aged 16 or more. Similarly, problems with alcohol were reported in 25-37% of respondents, higher than the West Midlands regional average of 7% for women aged 16+. The prevalence of any mental health problem varied between 31-35% and any suicide attempt between 20-31%. Only 29-45% had revealed their sexual orientation to their GP and of these, approximately 50% had experienced a positive reaction. CONCLUSION: The results suggest health needs that current UK health services may not be meeting. There is a need to identify and target specific health measures for lesbians and bisexual women in order to ensure improved physical and mental health in the longer term.

Novel technology to help understand the context of physical activity and sedentary behaviour.

When used in large, national surveillance programmes, objective measurement tools provide prevalence estimates of low physical activity guideline compliance and high amounts of sedentary time. There are undoubtedly a plethora of reasons for this but one possible contributing factor is the current lack of behavioural context offered by accelerometers and posture sensors. Context includes information such as where the behaviour occurs, the type of activity being performed and is vital in allowing greater refinement of intervention strategies. Novel technologies are emerging with the potential to provide this information. Example data from three ongoing studies is used to illustrate the utility of these technologies. Study one assesses the concurrent validity of electrical energy monitoring and wearable cameras as measures of television viewing. This study found that on average the television is switched on for 202 min d-1 but is visible in just 90 min of wearable camera images with a further 52 min where the participant is in their living room but the television is not visible in the image. Study two utilises indoor location monitoring to assess where older adult care home residents accumulate their sedentary time. This study found that residents were highly sedentary (sitting for an average of 720 min d-1) and spent the majority of their time in their own rooms with more time spent in communal areas in the morning than in the afternoon. Lastly, study three discusses the use of proximity sensors to quantify exposure to a height adjustable desk. These studies are example applications of this technology, with many other technologies available and applications possible. The adoption of these technologies will provide researchers with a more complete understanding of the behaviour than has previously been available.

Mechanistic understanding of molecular initiating events (MIEs) using NMR spectroscopy.

Toxicological risk assessments in the 21st century are increasingly being driven by the Adverse Outcome Pathways (AOP) conceptual framework in which the Molecular Initiating Event (MIE) is of fundamental importance to pathway progression. For those MIEs that involve covalent chemical reactions, such as protein haptenation, determination of relative rates and mechanisms of reactions is a prerequisite for their understanding. The utility of NMR spectroscopy as an experimental technique for effectively providing reaction rate and mechanistic information for early assessment of likely MIE(s) has been demonstrated. To demonstrate the concept, model systems exemplifying common chemical reactions involved in the covalent modification of proteins were utilized; these involved chemical reactions of electrophilic species (representing different mechanistic classes) with simple amine and thiol nucleophiles acting as surrogates for the reactive groups of lysine and cysteine protein side chains respectively. Such molecular interactions are recognized as critical mechanisms in a variety of chemical and drug toxicities, including respiratory and skin sensitization and liver toxicity as well as being the key mechanism of action for a number of therapeutic agents.

Identification of transcriptional macromolecular associations in human bone using browser based in silico analysis in a giant correlation matrix.

Intracellular signaling is critically dependent on gene regulatory networks comprising physical molecular interactions. Presently, there is a lack of comprehensive databases for most human tissue types to verify such macromolecular interactions. We present a user friendly browser which helps to identify functional macromolecular interactions in human bone as significant correlations at the transcriptional level. The molecular skeletal phenotype has been characterized by transcriptome analysis of iliac crest bone biopsies from 84 postmenopausal women through quantifications of ~23,000 mRNA species. When the signal levels were inter-correlated, an array containing >260 million correlations was generated, thus recognizing the human bone interactome at the RNA level. The matrix correlation and p values were made easily accessible by a freely available online browser. We show that significant correlations within the giant matrix are reproduced in a replica set of 13 male vertebral biopsies. The identified correlations differ somewhat from transcriptional interactions identified in cell culture experiments and transgenic mice, thus demonstrating that care should be taken in extrapolating such results to the in vivo situation in human bone. The current giant matrix and web browser are a valuable tool for easy access to the human bone transcriptome and molecular interactions represented as significant correlations at the RNA-level. The browser and matrix should be a valuable hypothesis generating tool for identification of regulatory mechanisms and serve as a library of transcript relationships in human bone, a relatively inaccessible tissue.

The correlates and treatment of obesity in military populations: a systematic review.

OBJECTIVE: The emergence of obesity as a distinct disease could have far reaching consequences for an organisation where optimum health and physical fitness are required for personnel to perform their occupational roles effectively. The objectives of this paper are to systematically review the literature concerning correlates and treatment of obesity in military populations. METHODS: Through computerised searches of English language studies, 17 papers were identified (treatment (13), correlates (4)). RESULTS: Successful treatment interventions incorporated exercise, healthy eating information, behavioural modification, self-monitoring, relapse prevention, and structured follow-up and were supported by trained personnel. Efficacy due to physical activity was underreported. Reduction in body fat rather than body weight was the most significant outcome. The major significant correlates of obesity were being enlisted personnel, male, ≥35 years of age, African-American/Hispanic ethnicity, and married (with spouse present). CONCLUSION: This systematic review highlights the deficit in knowledge concerning treatment and the lack of engagement in relation to the specific correlates of obesity in military populations.

Lumbar fractures involving five vertebrae: a case report.

We report a 20-year-old man who sustained lumbar fractures involving 5 vertebrae following a road traffic accident. He was initially treated non-operatively to allow multiple pedicles to heal. He developed post-traumatic kyphosis for which corrective osteotomy and posterior spinal instrumented fusion was performed. He achieved a good functional outcome. We emphasise the need for careful radiological evaluation in patients with high-energy trauma, and the option of treating such complex injuries by non-operative means. If post-traumatic kyphosis develops, it can be dealt with later and the most mobile segments of the lumbar spine can be preserved.

Skeletal site-related variation in human trabecular bone transcriptome and signaling.

BACKGROUND: The skeletal site-specific influence of multiple genes on bone morphology is recognised, but the question as to how these influences may be exerted at the molecular and cellular level has not been explored. METHODOLOGY: To address this question, we have compared global gene expression profiles of human trabecular bone from two different skeletal sites that experience vastly different degrees of mechanical loading, namely biopsies from iliac crest and lumbar spinal lamina. PRINCIPAL FINDINGS: In the lumbar spine, compared to the iliac crest, the majority of the differentially expressed genes showed significantly increased levels of expression; 3406 transcripts were up- whilst 838 were down-regulated. Interestingly, all gene transcripts that have been recently demonstrated to be markers of osteocyte, as well as osteoblast and osteoclast-related genes, were markedly up-regulated in the spine. The transcriptome data is consistent with osteocyte numbers being almost identical at the two anatomical sites, but suggesting a relatively low osteocyte functional activity in the iliac crest. Similarly, osteoblast and osteoclast expression data suggested similar numbers of the cells, but presented with higher activity in the spine than iliac crest. This analysis has also led to the identification of expression of a number of transcripts, previously known and novel, which to our knowledge have never earlier been associated with bone growth and remodelling. CONCLUSIONS AND SIGNIFICANCE: This study provides molecular evidence explaining anatomical and micro-architectural site-related changes in bone cell function, which is predominantly attributable to alteration in cell transcriptional activity. A number of novel signaling molecules in critical pathways, which have been hitherto not known to be expressed in bone cells of mature vertebrates, were identified.