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OBJECTIVES/SPECIFIC AIMS: Our objective is to understand the influence of the features comprising metabolic syndrome (central obesity, raised fasting plasma glucose, triglycerides, blood pressure, and decreased HDL cholesterol) on brain structure in men and women. With the understanding that MetS is a strong predictor of gray matter volume loss in specific brain regions, in this study we sought to quantify the influence of each of the metabolic syndrome biometric variables on the structures involved in the neural signature of metabolic syndrome. METHODS/STUDY POPULATION: We conducted multiple linear regression analyses on a cross-sectional sample of 800 individuals from the Genetics of Brian Structure (GOBS) image archive (352 men and 448 women). GOBS is an offshoot of the San Antonio Heart Study involving an extended pedigree of Mexican Americans from the greater San Antonio area. Its goal is to localize, identify, and characterize genes/quantitative trait loci associated with variations in brain structure and function (Winkler, 2010). The archive has continuously added participants from approximately 40 families since 2006. Neuroanatomic (T1-weighted MRI scans obtained on a Siemens 3T scanner and processed using FSL), neurocognitive, and biometric phenotypes have been obtained for each subject (including blood lipids). Linear regressions were run using SPSS and incorporated biometric and gray matter volume values obtained from 800 GOBS participants. RESULTS/ANTICIPATED RESULTS: Linear regressions incorporating metabolic syndrome variables as dependent variables and gray matter volume from regions involved in the neural signature of metabolic syndrome as predictors show significant predictive patterns that are largely similar between men and women, with some differences. Another linear regression conducted with gray matter volume from the neural signature of metabolic syndrome as the dependent variable and metabolic syndrome variables as predictors show that waist circumference and triglycerides are the greatest predictors of gray matter volume loss in men, and fasting plasma glucose and waist circumference are the greatest predictors of gray matter volume loss in women. DISCUSSION/SIGNIFICANCE OF IMPACT: Significant sex differences in the relationships between metabolic syndrome variables and gray matter volume changes between brain regions comprising the neural signature of metabolic syndrome were identified. waist circumference, fasting plasma glucose, and triglycerides are the most reliable predictors of gray matter volume loss. The variance in gray matter volume of the neural signature of metabolic syndrome in men is more significantly explained by waist circumference and triglycerides (when accounting for age) and in women is more significantly explained by waist circumference and fasting plasma glucose (when accounting for age). A model of metabolic syndrome that emphasizes a risk of neurodegeneration should focus on waist circumference for both men and women and weigh the remaining variables accordingly by sex (triglycerides in men and fasting plasma glucose in women).
In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.
During May 2015, an increase in Salmonella Agona cases was reported from western Sydney, Australia. We examine the public health actions used to investigate and control this increase. A descriptive case-series investigation was conducted. Six outbreak cases were identified; all had consumed cooked tuna sushi rolls purchased within a western Sydney shopping complex. Onset of illness for outbreak cases occurred between 7 April and 24 May 2015. Salmonella was isolated from food samples collected from the implicated premise and a prohibition order issued. No further cases were identified following this action. Whole genome sequence (WGS) analysis was performed on isolates recovered during this investigation, with additional S. Agona isolates from sporadic-clinical cases and routine food sampling in New South Wales, January to July 2015. Clinical isolates of outbreak cases were indistinguishable from food isolates collected from the implicated sushi outlet. Five additional clinical isolates not originally considered to be linked to the outbreak were genomically similar to outbreak isolates, indicating the point-source contamination may have started before routine surveillance identified an increase. This investigation demonstrated the value of genomics-guided public health action, where near real-time WGS enhanced the resolution of the epidemiological investigation.
We studied neuroinflammation in individuals with late-life, depression, as a
risk factor for dementia, using [11C]PK11195 positron emission
tomography (PET). Five older participants with major depression and 13
controls underwent PET and multimodal 3T magnetic resonance imaging (MRI),
with blood taken to measure C-reactive protein (CRP). We found significantly
higher CRP levels in those with late-life depression and raised
[11C]PK11195 binding compared with controls in brain regions
associated with depression, including subgenual anterior cingulate cortex,
and significant hippocampal subfield atrophy in cornu ammonis 1 and
subiculum. Our findings suggest neuroinflammation requires further
investigation in late-life depression, both as a possible aetiological
factor and a potential therapeutic target.
Carbon nanotubes (CNTs) have unique thermal/electrical/mechanical properties and high aspect ratios. Growth of CNTs directly onto reactive material substrates (such as metals and carbon based foam structures, etc.) to create a micro-carbon composite layer on the surface has many advantages: possible elimination of processing steps and resistive junctions, provision of a thermally conductive transition layer between materials of varying thermal expansion coefficients, etc. Compared to growing CNTs on conventional inert substrates such as SiO2, direct growth of CNTs onto reactive substrates is significantly more challenging. Namely, control of CNT growth, structure, and morphology has proven difficult due to the diffusion of metallic catalysts into the substrate during CNT synthesis conditions. In this study, using a chemical vapor deposition method, uniform CNT layers were successfully grown on copper foil and carbon foam substrates that were pre-coated with an appropriate buffer layer such as Al2O3 or Al. SEM images indicated that growth conditions and, most notably, substrate surface pre-treatment all influence CNT growth and layer structure/morphology. The SEM images and pull-off testing results revealed that relatively strong bonding existed between the CNT layer and substrate material, and that normal interfacial adhesion (0.2‒0.5 MPa) was affected by the buffer layer thickness. Additionally, the thermal properties of the CNT/substrate structure were evaluated using a laser flash technique, which showed that the CNT layer can reduce thermal resistance when used as a thermal interface material between bonded layers.
Milrinone may be an appropriate adjuvant therapy for infants with persistent pulmonary hypertension of the newborn. We aimed to describe the effect of milrinone administration on right and left ventricular function in infants with persistent pulmonary hypertension not responding to inhaled nitric oxide after 4 hours of administration.
Materials and methods
This is a retrospective review of infants born after or at 34 weeks of gestation with persistent pulmonary hypertension who received milrinone treatment. The primary endpoint was the effect of milrinone on myocardial performance and haemodynamics, including right and left ventricular outputs, tissue Doppler velocities, right ventricle and septal strain, and strain rate. Secondary endpoints examined included duration of inhaled nitric oxide and oxygen support.
A total of 17 infants with a mean (standard deviation) gestation and birth weight of 39.8 (2.0) weeks and 3.45 (0.39) kilograms, respectively, were included in the study. The first echocardiogram was performed 15 hours after the commencement of nitric oxide inhalation. Milrinone treatment was started at a median time of 1 hour after the echocardiogram and was associated with an increase in left ventricular output (p=0.04), right ventricular output (p=0.004), right ventricle strain (p=0.01) and strain rate (p=0.002), and left ventricle s` (p<0.001) and a` (p=0.02) waves. There was a reduction in nitric oxide dose and oxygen requirement over the subsequent 72 hours (all p<0.05).
The use of milrinone as an adjunct to nitric oxide is worth further exploration, with preliminary evidence suggesting an improvement in both oxygenation and myocardial performance in this group of infants.
As in much of the world, Australia’s birds have suffered greatly from habitat loss, feral predators and direct exploitation. Less universal have been the declines caused by post-colonial changes in fire regime after 40 000 years of Indigenous fire management. Climate change and a disengagement by Australians from nature loom as threats for the future. However, Australia is a country of climatic extremes and many birds are well-adapted to stressful conditions. Given adequate investment, all the major classes of threat have potential solutions, with particular success in recent decades in the removal of feral predators from islands and in reducing the by-catch from fishing. The biggest threat of all is possibly a failure to invest in conservation as modern lifestyles take people further and further away from the natural environment.
Australia’s birds are, like those in so much of the world, travelling poorly. Of the 1239 species and subspecies regularly occurring in Australia, 17% are Threatened or Near Threatened on the basis of the IUCN Red List Criteria (Garnett et al. 2011). This number has been increasing steadily (Szabo et al. 2012a) and, while originally it was taxa of Australia’s oceanic islands that were most likely to be threatened, taxa from the mainland are now starting to slip away (Szabo et al. 2012b). Sadly some of those most threatened are the most distinctive; birds at the end of long slender branches of the evolutionary tree whose closest relatives are long gone. Other species, however, are thriving under the conditions that have arisen over the past few centuries of intense development.
Early investigators regarded the soil as an inert framework of soil grains of various sizes covered with a continuous film of water, and the properties which in theory it should possess under such a hypothesis were found not to accord too well with the results of experiment. But when the existence of soil colloids was understood, the differences between theory and experiment tended to disappear one by one, as shown by the work of Bouyoncos in America in 1915 and of Keen in England in 1914, 1919, and 1920.
The temperature of the air depends on so many varying factors that its prediction is a matter of considerable difficulty, and can only be made with any degree of certainty when the minimum number of these factors is at work. Underground temperatures are dependent not only on the same factors as affect the air temperature, but, in addition, are much more affected by conductivity, rainfall, evaporation, latent heat, etc., and thus the changes in temperature beneath the surface of the soil constitute a much more complex problem.
In my previous paper to the Society on the same subject I came to the conclusion that the temperature of the surface of open cultivated soil fell rapidly at the beginning of a calm clear night until it was such a number of degrees below the temperature at the 4-in. depth as to make the upward conduction from that depth to the surface balance the radiation. After this stage was reached the surface and 4-in. temperatures fell at the same rate.
If, therefore, the temperatures of the surface and 4-in. depth and the conductivity of the layer of soil between the 4-in. depth and the surface were known from readings of electrical resistance thermometers, and the rate of radiation was calculated from the value of the relative humidity, I suggested that it might be possible to forecast the minimum soil temperature for a calm clear night as early as the previous afternoon.
We aimed to investigate the diagnostic accuracy of contact endoscopy in evaluating oral and oropharyngeal mucosal lesions.
Between January 2010 and December 2011, 34 patients with lesions of the oral and oropharyngeal mucosa were enrolled in the study. Comparison between initial contact endoscopy results and ‘gold standard’ tissue biopsy was undertaken.
Nine patients had histologically confirmed squamous cell carcinoma, 2 had carcinoma in situ, 3 had dysplastic lesions and 20 patients had various benign lesions. Contact endoscopy demonstrated sensitivity and specificity of 89 and 100 per cent respectively in the evaluation of malignant lesions. Benign lesions were correctly categorised in 50 per cent of cases (10/20). The video images from contact endoscopy could not be interpreted in six cases.
Contact endoscopy demonstrates high sensitivity and specificity in the imaging of malignant lesions with reduced reliability in the evaluation of benign lesions. Significant shortcomings also exist in the design of current technology that we believe represent a significant barrier to the reliable collection of useful video data.
SMYB1 is a Schistosoma mansoni protein highly similar to members of the Y-box binding protein family. Similar to other homologues, SMYB1 is able to bind double- and single-stranded DNA, as well as RNA molecules. The characterization of proteins involved in the regulation of gene expression in S. mansoni is of great importance for the understanding of molecular events that control morphological and physiological changes in this parasite. Here we demonstrate that SMYB1 is located in the cytoplasm of cells from different life-cycle stages of S. mansoni, suggesting that this protein is probably acting in mRNA metabolism in the cytoplasm and corroborating previous findings from our group that showed its ability to bind RNA. Protein–protein interactions are important events in all biological processes, since most proteins execute their functions through large supramolecular structures. Yeast two-hybrid screenings using SMYB1 as bait identified a partner in S. mansoni similar to the SmD3 protein of Drosophila melanogaster (SmRNP), which is important in the assembly of small nuclear ribonucleoprotein complexes. Also, pull-down assays were conducted using immobilized GST-SMYB1 proteins and confirmed the SMYB1-SmRNP interaction. The interaction of SMYB1 with a protein involved in mRNA processing suggests that it may act in processes such as turnover, transport and stabilization of RNA molecules.
Over the past decade, large outbreaks of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have occurred in correctional facilities across the country. Although many have been managed with aggressive interventions, response to standard infection control procedures has been variable, highlighting our incomplete understanding of staphylococcal transmission in this setting. Environmental contamination has recently emerged as a possible target for novel prevention and control strategies. This study sought to characterize the relationship between environmental contamination and clinical infection in this vulnerable population.
We conducted a case-control study of S. aureus environmental contamination at 2 New York State (NYS) maximum security prisons: Sing Sing (men) and Bedford Hills (women).
IN ITS BREADTH OF SUBJECT MATTER, this collection of essays written in honour of Professor Eric Fernie is representative of his own scholarly concerns, which extend well beyond the boundaries of medieval European architecture, a field to which he has contributed with particular brilliance. Even so, the spectrum of topics covered in the book does not aim to encompass the totality of Eric's interests, excluding as it does, perforce, comic-book illustration, or science fiction.
We are grateful, in the first instance, to Eric's family for raising the idea of this collection, whose theme of ‘architecture and interpretation’ was devised by Sandy Heslop, and to Pamela Tudor-Craig for encouraging the project in its very early stages. Our contributors have responded with remarkable patience and good grace to various requests. We would also like to thank Nicola Coldstream, Peter Draper, Karin Kyburz, Zoe Opačić, and Christopher Wilson for their assistance with the book in various ways, as well as Jocelyn Anderson, who prepared the index. Publication has been made possible by generous financial support from the Research Committee of the Courtauld Institute of Art; the School of World Art Studies, University of East Anglia; a Stroud Bursary from the Society of Architectural Historians of Great Britain; and the Norfolk and Norwich Archaeological Society.