Molecular endocrinology of vitamin D on the epigenome level.
The molecular endocrinology of vitamin D is based on the facts that i) its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the nuclear receptor vitamin D receptor (VDR) and ii) the transcription factor VDR is the unique target of 1,25(OH)2D3 in the nucleus. Short-term alterations of the epigenome are primarily changes in the post-translational modification status of nucleosome-forming histone proteins, the consequences of which are i) a local increase or decrease in chromatin accessibility and ii) the activation or repression of gene transcription. Vitamin D has via VDR a direct effect on the expression of several hundred primary target genes implying numerous effects on the epigenome. Next-generation sequencing methods, such as ChIP-seq and FAIRE-seq, were applied to cellular model systems of vitamin D signaling, such as THP-1 human monocytes, and provided data for a chromatin model of vitamin D signaling. Key points of this model are that i) in the absence of ligand VDR binds to a limited number of loci within accessible chromatin, ii) a stimulation with ligand increases the number of DNA-bound VDR molecules, iii) VDR's access to genomic DNA is supported by pioneer factors, such as PU.1 in monocytes, iv) VDR binding leads to local opening of chromatin and v) the binding strength of topologically associating domain anchor forming CCCTC-binding factor sites upstream and downstream of prominent VDR binding sites is changing in response to ligand stimulation. This model provides the present basis of the molecular endocrinology of vitamin D and will be in future refined by the integration of vitamin D-sensitive chromatin markers and other genome-wide data, such as the 1,25(OH)2D3-sensitive binding of co-factors, chromatin modifying enzymes and chromatin remodeling proteins.


Ocular Symptoms of SARS-CoV-2: Indication of Possible Ocular Transmission or Viral Shedding.
The recently identified novel coronavirus (CoV), the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes the coronavirus disease 2019 (COVID-19). While published data about other highly infectious human COVs [that is, the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV)] provide helpful information about the infectivity of SARS-CoV-2, there is limited understanding surrounding knowledge of ocular manifestation of the virus. This paper reviews published data which reveal the presence of SARS-CoV-2 RNA in tears and conjunctival scrappings of some COVID-19 patients by real-time-polymerase chain reaction assay, although the detection rate is low compared to samples from respiratory sites. Nevertheless, the ocular complications from SARS-CoV-2 infection are uncommon. The evidence partly supports the eye as a portal of entry for SARS-CoV-2 to infect respiratory cells or viral shedding from respiratory cells via the nasolacrimal duct unto the ocular surface. The possibility of ocular secretions as source for SARS-CoV-2 to spread externally has substantial public health implications.


Probabilistic principal component analysis for metabolomic data.
Data from metabolomic studies are typically complex and high-dimensional. Principal component analysis (PCA) is currently the most widely used statistical technique for analyzing metabolomic data. However, PCA is limited by the fact that it is not based on a statistical model. Here, probabilistic principal component analysis (PPCA) which addresses some of the limitations of PCA, is reviewed and extended. A novel extension of PPCA, called probabilistic principal component and covariates analysis (PPCCA), is introduced which provides a flexible approach to jointly model metabolomic data and additional covariate information. The use of a mixture of PPCA models for discovering the number of inherent groups in metabolomic data is demonstrated. The jackknife technique is employed to construct confidence intervals for estimated model parameters throughout. The optimal number of principal components is determined through the use of the Bayesian Information Criterion model selection tool, which is modified to address the high dimensionality of the data. The methods presented are illustrated through an application to metabolomic data sets. Jointly modeling metabolomic data and covariates was successfully achieved and has the potential to provide deeper insight to the underlying data structure. Examination of confidence intervals for the model parameters, such as loadings, allows for principled and clear interpretation of the underlying data structure. A software package called MetabolAnalyze, freely available through the R statistical software, has been developed to facilitate implementation of the presented methods in the metabolomics field.


Measuring meaningful use.
To qualify for new federal funds intended to promote the widespread adoption and use of electronic health records, U.S. physician practices must meet the government's "meaningful use" benchmarks. Our analysis indicates that among physicians who have electronic health records, between 75-85 percent are already using functions that meet some of the proposed criteria for demonstrating meaningful use. But gaps remain. We provide a new analysis of baseline use of specific electronic health record functions among primary care physicians and medical and surgical specialists. The analysis can help researchers and policy makers measure more accurately the success of ongoing efforts to expand effective use of health information technology.


Humidity-regulated dormancy onset in the Fabaceae: a conceptual model and its ecological implications for the Australian wattle Acacia saligna.
Seed dormancy enhances fitness by preventing seeds from germinating when the probability of seedling survival and recruitment is low. The onset of physical dormancy is sensitive to humidity during ripening; however, the implications of this mechanism for seed bank dynamics have not been quantified. This study proposes a model that describes how humidity-regulated dormancy onset may control the accumulation of a dormant seed bank, and seed experiments are conducted to calibrate the model for an Australian Fabaceae, Acacia saligna. The model is used to investigate the impact of climate on seed dormancy and to forecast the ecological implications of human-induced climate change. The relationship between relative humidity and dormancy onset was quantified under laboratory conditions by exposing freshly matured non-dormant seeds to constant humidity levels for fixed durations. The model was field-calibrated by measuring the response of seeds exposed to naturally fluctuating humidity. The model was applied to 3-hourly records of humidity spanning the period 1972-2007 in order to estimate both temporal variability in dormancy and spatial variability attributable to climatic differences among populations. Climate change models were used to project future changes in dormancy onset. A sigmoidal relationship exists between dormancy and humidity under both laboratory and field conditions. Seeds ripened under field conditions became dormant following very short exposure to low humidity (<20 %). Prolonged exposure at higher humidity did not increase dormancy significantly. It is predicted that populations growing in a temperate climate produce 33-55 % fewer dormant seeds than those in a Mediterranean climate; however, dormancy in temperate populations is predicted to increase as a result of climate change. Humidity-regulated dormancy onset may explain observed variation in physical dormancy. The model offers a systematic approach to modelling this variation in population studies. Forecast changes in climate have the potential to alter the seed bank dynamics of species with physical dormancy regulated by this mechanism, with implications for their capacity to delay germination and exploit windows for recruitment.


Religiousness, spiritual seeking, and personality: findings from a longitudinal study.
The hypothesis that personality characteristics in adolescence can be used to predict religiousness and spiritual seeking in late adulthood was tested using a structural equation modeling framework to estimate cross-lagged and autoregressive effects in a two-wave panel design. The sample consisted of 209 men and women participants in the Berkeley Guidance and Oakland Growth studies. In late adulthood, religiousness was positively related to Conscientiousness and Agreeableness, and spiritual seeking was related to Openness to Experience. Longitudinal models indicated that Conscientiousness in adolescence significantly predicted religiousness in late adulthood above and beyond adolescent religiousness. Similarly, Openness in adolescence predicted spiritual seeking in late adulthood. The converse effect, adolescent religiousness to personality in late adulthood, was not significant in either model. Among women, adolescent Agreeableness predicted late-life religiousness and adolescent religiousness predicted late-life Agreeableness; both these effects were absent among men. Adolescent personality appears to shape late-life religiousness and spiritual seeking independent of early religious socialization.


Axonal loss in major sensorimotor tracts is associated with impaired motor performance in minimally disabled multiple sclerosis patients.
Multiple sclerosis is a neuroinflammatory disease of the CNS that is associated with significant irreversible neuro-axonal loss, leading to permanent disability. There is thus an urgent need for in vivo markers of axonal loss for use in patient monitoring or as end-points for trials of neuroprotective agents. Advanced diffusion MRI can provide markers of diffuse loss of axonal fibre density or atrophy within specific white matter pathways. These markers can be interrogated in specific white matter tracts that underpin important functional domains such as sensorimotor function. This study aimed to evaluate advanced diffusion MRI markers of axonal loss within the major sensorimotor tracts of the brain, and to correlate the degree of axonal loss in these tracts to precise kinematic measures of hand and foot motor control and gait in minimally disabled people with multiple sclerosis. Twenty-eight patients (Expanded Disability Status Scale < 4, and Kurtzke Functional System Scores for pyramidal and cerebellar function ≤ 2) and 18 healthy subjects underwent ultra-high field 7 Tesla diffusion MRI for calculation of fibre-specific measures of axonal loss (fibre density, reflecting diffuse axonal loss and fibre cross-section reflecting tract atrophy) within three tracts: cortico-spinal tract, interhemispheric sensorimotor tract and cerebello-thalamic tracts. A visually guided force-matching task involving either the hand or foot was used to assess visuomotor control, and three-dimensional marker-based video tracking was used to assess gait. Fibre-specific axonal markers for each tract were compared between groups and correlated with visuomotor task performance (force error and lag) and gait parameters (stance, stride length, step width, single and double support) in patients. Patients displayed significant regional loss of fibre cross-section with minimal loss of fibre density in all tracts of interest compared to healthy subjects (family-wise error corrected p-value < 0.05), despite relatively few focal lesions within these tracts. In patients, reduced axonal fibre density and cross-section within the corticospinal tracts and interhemispheric sensorimotor tracts were associated with larger force tracking error and gait impairments (shorter stance, smaller step width and longer double support) (family-wise error corrected p-value < 0.05). In conclusion, significant gait and motor control impairments can be detected in minimally disabled people with multiple sclerosis that correlated with axonal loss in major sensorimotor pathways of the brain. Given that axonal loss is irreversible, the combined use of advanced imaging and kinematic markers could be used to identify patients at risk of more severe motor impairments as they emerge for more aggressive therapeutic interventions.


Acid tolerance in Rhizobium meliloti strain WSM419 involves a two-component sensor-regulator system.
An acid-sensitive mutant, TG5-46, derived from Rhizobium meliloti WSM419 by Tn5 mutagenesis, fails to grow below pH 6.0 whereas the parent strain grows at pH 5.7. The DNA sequence of a 2.2 kb rhizobial DNA region flanking Tn5 in TG5-46 contains two open reading frames, ORF1 (designated actS) and ORF2 (designated actR), having high similarity to the sensor-regulator pairs of the two-component systems involved in signal transduction in prokaryotes. Insertion of an omega interposon into actS in R. meliloti WSM419 resulted in an acid-sensitive phenotype. A DNA fragment from the wild-type complemented the acid-sensitive phenotype of RT295 (ActS-) and TG5-46 (ActR-), while fragments containing only actR or actS complemented TG5-46 and RT295, respectively. The presence of multiple copies of actR complemented not only TG5-46 but also RT295. Cloning DNA upstream from actR and actS into a broad-host-range lacZ expression vector and measuring beta-galactosidase activities showed that both genes are constitutively expressed regardless of the external pH. Genomic DNA from all strains of R. meliloti, but no other bacteria tested, hybridized with an actRS probe at high stringency. These data implicate a two-component sensor-regulator protein pair in acid tolerance in R. meliloti and suggest their involvement in pH sensing and/or response by these bacteria.


Time trends in the incidence of parkinsonism in Olmsted County, Minnesota.
To investigate time trends in the incidence of parkinsonism and PD over a 15-year period (1976 to 1990). The authors used the medical records-linkage system of the Rochester Epidemiology Project to identify incidence cases of parkinsonism in Olmsted County, MN, over three 5-year periods, 1976 to 1980, 1981 to 1985, and 1986 to 1990. PD and other types of parkinsonism were classified using defined criteria. Population denominators were derived from census data and were corrected by removing prevalent cases of parkinsonism. Over the 15 years of the study, 364 cases of parkinsonism were identified; 154 (42%) of them had PD. The incidence of parkinsonism remained stable over the three 5-year periods for the age classes 0 to 39, 40 to 59, and 60 to 69 years. For the age class 70 to 99 years, there was some increase over time mainly owing to an increased incidence of drug-induced parkinsonism. The incidence of PD remained stable over the three 5-year periods for all age classes. Results were similar when considering men and women separately. No birth-cohort effect was present for parkinsonism. Comparison with three previous studies in the same population did not reveal any major long-term secular trends in the incidence of parkinsonism. The findings for PD over 15 years and comparison of the findings with historical data for parkinsonism over half a century suggest that no major environmental risk factors for PD (e.g., environmental toxins, drugs, diet constituents, or infectious agents) were introduced or removed from this population during these periods.


High density recording by superresolution in an optical disk memory system.
High density optical disk recording using an optical superresolution technique is proposed. By setting a shading band in the center of the collimating beam, the focused spot size on the recording medium is reduced to 80% compared with that of a conventional optical recording. The readout signal degradation affected by the focused spot sidelobe on the recording medium is suppressed by spatially extracting the main lobe region from the reflected back beam using a slit on a reimaged plane. The linear recording density has been improved to 1.2 times as high as that for a conventional optical recording using a normal resolution optical head.


Design of fluorescence resonance energy transfer (FRET)-based cGMP indicators: a systematic approach.
The intracellular signalling molecule cGMP regulates a variety of physiological processes, and so the ability to monitor cGMP dynamics in living cells is highly desirable. Here, we report a systematic approach to create FRET (fluorescence resonance energy transfer)-based cGMP indicators from two known types of cGMP-binding domains which are found in cGMP-dependent protein kinase and phosphodiesterase 5, cNMP-BD [cyclic nucleotide monophosphate-binding domain and GAF [cGMP-specific and -stimulated phosphodiesterases, Anabaena adenylate cyclases and Escherichia coli FhlA] respectively. Interestingly, only cGMP-binding domains arranged in tandem configuration as in their parent proteins were cGMP-responsive. However, the GAF-derived sensors were unable to be used to study cGMP dynamics because of slow response kinetics to cGMP. Out of 24 cGMP-responsive constructs derived from cNMP-BDs, three were selected to cover a range of cGMP affinities with an EC50 between 500 nM and 6 microM. These indicators possess excellent specifity for cGMP, fast binding kinetics and twice the dynamic range of existing cGMP sensors. The in vivo performance of these new indicators is demonstrated in living cells and validated by comparison with cGMP dynamics as measured by radioimmunoassays.


Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity.
Integrins are transmembrane heteromeric receptors that mediate interactions between cells and extracellular matrix (ECM). beta1, the most abundantly expressed integrin subunit, binds at least 12 alpha subunits. beta1 containing integrins are highly expressed in the glomerulus of the kidney; however their role in glomerular morphogenesis and maintenance of glomerular filtration barrier integrity is poorly understood. To study these questions we selectively deleted beta1 integrin in the podocyte by crossing beta1(flox/flox) mice with podocyte specific podocin-cre mice (pod-Cre), which express cre at the time of glomerular capillary formation. We demonstrate that podocyte abnormalities are visualized during glomerulogenesis of the pod-Cre;beta1(flox/flox) mice and proteinuria is present at birth, despite a grossly normal glomerular basement membrane. Following the advent of glomerular filtration there is progressive podocyte loss and the mice develop capillary loop and mesangium degeneration with little evidence of glomerulosclerosis. By 3 weeks of age the mice develop severe end stage renal failure characterized by both tubulointerstitial and glomerular pathology. Thus, expression of beta1 containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus.


Spot size and quality of scanning laser correction of higher order wavefront aberrations.
To investigate the effect of laser spot size on the outcome of aberration correction with scanning laser corneal ablation. Numerical simulation of ablation outcome. Correction of wavefront aberrations of Zernike modes from second to eighth order were simulated. Gaussian and top-hat beams of 0.6 to 2.0-mm full-width-half-maximum diameters were modeled. The fractional correction and secondary aberration (distortion) were evaluated. Using a distortion/correction ratio of less than 0.5 as a cutoff for adequate performance, we found that a 2 mm or smaller beam is adequate for spherocylindrical correction (Zernike second order), a 1 mm or smaller beam is adequate for correction of up to fourth order Zernike modes, and a 0.6 mm or smaller beam is adequate for correction of up to sixth order Zernike modes. Since ocular aberrations above Zernike fourth order are relatively insignificant, current scanning lasers with a beam diameter of 1 mm or less are theoretically capable of eliminating most of the higher order aberrations of the eye.


CCL2 shapes macrophage polarization by GM-CSF and M-CSF: identification of CCL2/CCR2-dependent gene expression profile.
The CCL2 chemokine mediates monocyte egress from bone marrow and recruitment into inflamed tissues through interaction with the CCR2 chemokine receptor, and its expression is upregulated by proinflammatory cytokines. Analysis of the gene expression profile in GM-CSF- and M-CSF-polarized macrophages revealed that a high CCL2 expression characterizes macrophages generated under the influence of M-CSF, whereas CCR2 is expressed only by GM-CSF-polarized macrophages. Analysis of the factors responsible for this differential expression identified activin A as a critical factor controlling the expression of the CCL2/CCR2 pair in macrophages, as activin A increased CCR2 expression but inhibited the acquisition of CCL2 expression by M-CSF-polarized macrophages. CCL2 and CCR2 were found to determine the extent of macrophage polarization because CCL2 enhances the LPS-induced production of IL-10, whereas CCL2 blockade leads to enhanced expression of M1 polarization-associated genes and cytokines, and diminished expression of M2-associated markers in human macrophages. Along the same line, Ccr2-deficient bone marrow-derived murine macrophages displayed an M1-skewed polarization profile at the transcriptomic level and exhibited a significantly higher expression of proinflammatory cytokines (TNF-α, IL-6) in response to LPS. Therefore, the CCL2-CCR2 axis regulates macrophage polarization by influencing the expression of functionally relevant and polarization-associated genes and downmodulating proinflammatory cytokine production.


Study of test of balance in tinnitus and vertigo patients.
The diagnosis of patient disorders in modern neurootological centers has to include not only history and examination but objective and quantitative tests. In this study, we stress the importance of a short but significant test used to study vestibular function--the vestibular test of balance. The most common and widespread technique used to evaluate a patient's equilibrium in static condition is the projection of the center of gravity with the patient in a standing position, which permits evaluation of visual, somatosensory, and vestibular contributions to stability or equilibrium. Modern physicians can improve their diagnoses by correlating patient history with clinical description and the results of exploration of vestibulospinal, retinoocular, and vestibuloocular systems of vertiginous patients.


Gastroprotective Value of Berries: Evidences from Methanolic Extracts of Morus nigra and Rubus niveus Fruits.
This study evaluated the gastroprotective value of the methanol extracts from fruits of Morus nigra L. (black mulberry (MEMN)) and Rubus niveus Thunb (raspberry (MERN)). The total phenolic compounds and flavonoids were measured, as well as the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenger activity. The gastroprotective effects of the extracts against 60% ethanol/0.3 M HCl were evaluated in mice. After that, the lipid hydroperoxides and reduced glutathione levels at ulcerated tissue were determined. The effects of extracts on H+/K+-ATPase activity were also verified. The extracts exhibited high contents of polyphenols; however, MERN presented 1.5-fold higher levels. The presence of flavonoids also was confirmed. In addition, MEMN (IC50 = 13.74 μg/mL) and MERN (IC50 = 14.97 μg/mL) scavenged DPPH radical. The MEMN reduced the ulcer area only at 300 mg/kg (p.o.) by 64.06%. Interestingly, MERN decreased the ulcer area in a superior potency (ED50 = 20.88 mg/kg), reducing the ulcer area by 81.86% at 300 mg/kg, and increased the gastric mucin levels. The antioxidant effects of extracts were evidenced by reduced lipoperoxides and increased reduction of glutathione amount in the gastric mucosa. However, MEMN or MERN did not change the H+/K+-ATPase activity. These results confirm that M. nigra and R. niveus are berries with a gastroprotective value by strengthening of gastric protective factors.


Targeting Iron in Colon Cancer via Glycoconjugation of Thiosemicarbazone Prochelators.
The implication of iron in the pathophysiology of colorectal cancer is documented at both the biochemical and epidemiological levels. Iron chelators are therefore useful molecular tools for the study and potential treatment of this type of cancer characterized by high incidence and mortality rates. We report a novel prochelation strategy that utilizes a disulfide redox switch to connect a thiosemicarbazone iron-binding unit with carbohydrate moieties targeting the increased expression of glucose transporters in colorectal cancer cells. We synthesized three glycoconjugates (GA2TC4, G6TC4, and M6TC4) with different connectivity and/or carbohydrate moieties, as well as an aglycone analog (ATC4). The sugar conjugates present increased solubility in neutral aqueous solutions, and the ester-linked conjugates M6TC4 and G6TC4 compete as effectively as d-glucose for transporter-mediated cellular uptake. The glycoconjugates show improved selectivity compared to the aglycone analog and are 6-11 times more toxic in Caco-2 colorectal adenocarcinoma cells than in normal CCD18-co colon fibroblasts.


High nonlinear figure-of-merit amorphous silicon waveguides.
The nonlinear response of amorphous silicon waveguides is reported and compared to silicon-on-insulator (SOI) samples. The real part of the nonlinear coefficient γ is measured by four-wave-mixing and the imaginary part of γ is characterized by measuring the nonlinear loss at different peak powers. The combination of both results yields a two-photon-absorption figure of merit of 4.9, which is more than 7 times higher than for the SOI samples. Time-resolved measurements and simulations confirm the measured nonlinear coefficient γ and show the absence of slow free-carrier effects versus ns free-carrier lifetimes in the SOI samples.


Field experimental evidence that stochastic processes predominate in the initial assembly of bacterial communities.
To assess the relative importance of environmental selection, dispersal and stochastic processes in structuring ecological communities, we conducted a bacterial community assembly experiment using microcosms filled with sterile liquid medium under field conditions in the Inner Mongolian grasslands. Multiple replicate microcosms containing different carbon substrates were placed at nine locations across three spatial scales (10, 300 and 10 000 m distance between locations) in such a way that the environment of microcosms varies independently of the geographical distance. The operational taxonomic units within the experimental communities were assessed via the terminal restriction fragment length polymorphism techniques on the 10th and 17th days after the onset of the experiment. We found no evidence of distance decay in community similarity, and communities within a given location were more similar to each other regardless of environment than communities at other locations within the same spatial scale. Variance partitioning indicated that location explained more compositional variation in microbial communities than environment, particularly on the 17th day, despite that environment and location in combination could only explain less than half of the total variation. These results suggest that bacterial dispersal is not limited by distance in this experiment, and community assembly in microcosms is not environmentally determined but governed by stochastic processes.


18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography fused imaging in malignant mesothelioma patients: looking from outside is not enough.
Malignant mesothelioma (MM) is an uncommon neoplasm with a poor prognosis usually associated with asbestos exposure. 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) has become an invaluable tool for the diagnosis, staging, and prognosis of this severe disease as it combines both anatomic and functional information in a single imaging procedure, allowing for improved management of this disease. For many authors, 18F-FDG-PET/CT is the cornerstone of the pre-therapeutic evaluation of mesothelioma patients, particularly when multimodal therapy (including extra-pleural pneumonectomy or omentectomy) is considered. However, while characteristic patterns have been reported as predictive of macroscopic pleural or peritoneal involvement, false negative findings are possible, both for pleural and peritoneal mesothelioma, during the initial diagnosis or during the patient's surveillance as illustrated by this report of three cases of suspected MM with negative PET/CT. This report highlights the limitations of PET/CT in the diagnostic evaluation of MM and the importance of histopathological confirmation by thoracoscopy and/or laparoscopy, which remain the most important diagnostic procedures in MM.


Terpenoid emissions from Quercus robur. A case study of Galicia (NW Spain).
Isoprene and monoterpenes emission fluxes emitted by Quercus robur seedlings were measured at a leaf scale in the field. Isoprene emissions were always predominant over the monoterpene ones, alpha-pinene, beta-pinene and camphene being the most abundant emitted monoterpenes. Emission fluxes were normalised at standard conditions of temperature and photosynthetically active radiation, PAR, (30 degrees C and 1000 micromol m(-2) s(-1) respectively) using temperature and light dependent algorithms. The standardised emission fluxes ranged from 43 to 73 microg g(DM)(-1) h(-1) for isoprene and from 0.04 to 2.95 microg g(DM)(-1) h(-1) for the monoterpenes. The values reported in the literature are within our experimental intervals. These standardised fluxes were used to estimate the Quercus robur emissions in Galicia (NW Spain). This region is characterised by its abundant forest extensions where Quercus robur occupies the second place in species abundance with a total of 195029 ha of Quercus robur pure stands. To estimate the region emission fluxes, both the extension and distribution of the forest areas and the regional climatic conditions over five years (2002-2006) were taken into account. The averaged annual fluxes regarding the forest extension were 0.04 t ha(-1) yr(-1) for isoprene and 0.52 kg ha(-1) yr(-1) for monoterpenes. This means averaged annual fluxes of 9730 t yr(-1) and 114 t yr(-1) for isoprene and monoterpenes, respectively. These values place Galicia as an important isoprene emitter power in Spain as a consequence of the extension of its forests more than of the climatic conditions.


DNA binding properties of the Arabidopsis floral development protein AINTEGUMENTA.
The Arabidopsis protein AINTEGUMENTA (ANT) is a member of a plant-specific family of transcription factors (AP2/EREBP) that share either one or two copies of an approximately 70 amino acid region called the AP2 repeat. DNA binding activity has been demonstrated previously for members of this family containing a single AP2 repeat. Using an in vitro selection procedure, the DNA binding specificity of the two AP2 repeat containing protein ANT was found to be 5'-gCAC(A/G)N(A/T)TcCC(a/g)ANG(c/t)-3'. This consensus site is much longer than sites recognized by proteins containing a single AP2 repeat and neither AP2 repeat of ANT was alone capable of binding to the selected sequences, suggesting that both AP2 repeats make DNA contacts. ANT binds to these DNA sequences as a monomer but a higher order complex is also observed at high protein concentrations. The ANT consensus site shows some similarity to the C-repeat/DRE elements bound by proteins that contain a single AP2 repeat, and we find that ANT binds weakly to such sites. We propose a model in which each AP2 repeat of ANT contacts adjacent sites within the consensus sequence. Our results suggest that the AP2 repeat can be utilized in different ways for DNA binding.


[Hyperbaric oxygenation in the treatment of patients with ischemic stroke].
Biochemical parameters (the gaseous composition and acid-base balance of the blood and cerebrospinal fluid (CSF) were investigated in patients with ischemic stroke in the process of hyperbaric oxygenation treatment. A characteristic peculiarity observed was the presence of compensated metabolic acidosis in the CSF which was most expressed in patients with an extensive focus of cerebral infarction. A characteristic change in the venous blood of the brain was the presence of compensated metabolic acidosis. Metabolic acidosis of the cerebral venous blood in patients treated with hyperbaric oxygenation significantly diminished as compared with the control group.


Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression.
The role of ATF4 (activating transcription factor 4) in osteoblast differentiation and bone formation was recently described using ATF4-deficient mice (Yang, X., Matsuda, K., Bialek, P., Jacquot, S., Masuoka, H. C., Schinke, T., Li, L., Brancorsini, S., Sassone-Corsi, P., Townes, T. M., Hanauer, A., and Karsenty, G. (2004) Cell 117, 387-398). However, the mechanisms of ATF4 in bone cells are still not clear. In this study, we determined the molecular mechanisms through which ATF4 activates the mouse osteocalcin (Ocn) gene 2 (mOG2) expression and mOG2 promoter activity. ATF4 increased the levels of Ocn mRNA and mOG2 promoter activity in Runx2-containing osteoblasts but not in non-osteoblastic cells that lack detectable Runx2 protein. However, ATF4 increased Ocn mRNA and mOG2 promoter activity in non-osteoblastic cells when Runx2 was co-expressed. Mutational analysis of the OSE1 (ATF4-binding site) and the two OSE2s (Runx2-binding sites) in the 657-bp mOG2 promoter demonstrated that ATF4 and Runx2 activate Ocn via cooperative interactions with these sites. Pull-down assays using nuclear extracts from osteoblasts or COS-7 cells overexpressing ATF4 and Runx2 showed that both factors are present in either anti-ATF4 and anti-Runx2 immunoprecipitates. In contrast, pull-down assays using purified glutathione S-transferase fusion proteins were unable to demonstrate a direct physical interaction between ATF4 and Runx2. Thus, accessory factors are likely involved in stabilizing interactions between these two molecules. Regions within Runx2 required for ATF4 complex formation and activation were identified. Deletion analysis showed that the leucine zipper domain of ATF4 is critical for Runx2 activation. This study is the first demonstration that cooperative interactions between ATF4 and Runx2/Cbfa1 stimulate osteoblast-specific Ocn expression and suggests that this regulation may represent a novel intramolecular mechanism regulating Runx2 activity and, thereby, osteoblast differentiation and bone formation.


Pseudomonas aeruginosa Quorum Sensing Systems as Drug Discovery Targets: Current Position and Future Perspectives.
Antimicrobial resistance (AMR) is a serious threat to public health globally, manifested by the frequent emergence of multidrug resistant pathogens that render current chemotherapy inadequate. Health organizations worldwide have recognized the severity of this crisis and implemented action plans to contain its adverse consequences and prolong the utility of conventional antibiotics. Hence, there is a pressing need for new classes of antibacterial agents with novel modes of action. Quorum sensing (QS), a communication system employed by bacterial populations to coordinate virulence gene expression, is a potential target that has been intensively investigated over the past decade. This Perspective will focus on recent advances in targeting the three main quorum sensing systems ( las, rhl, and pqs) of a major opportunistic human pathogen, Pseudomonas aeruginosa, and will specifically evaluate the medicinal chemistry strategies devised to develop QS inhibitors from a drug discovery perspective.


Effect of various surgical modalities in recurrent or persistent trigeminal neuralgia.
In recurrent or persistent idiopathic trigeminal neuralgia (TN) after initial operation, additional surgical procedures may be required. There are numerous articles reporting the outcomes of additional surgical treatment and it is unclear how best to treat patients with recurrent or persistent TN. We evaluated the subsequent therapeutic options for recurrent or persistent TN. The study was a retrospective study. The authors reviewed 29 patients (15 female/14 male) who underwent retreatments for recurrent or persistent symptoms after an initial operation. The mean follow-up duration was 56.4 months (range 12-78.7) from final treatment. Patients underwent a mean of 2.3 retreatments with a mean period of 26 months (range 1-72) between treatments. Final treatments were as follows: microvascular decompression (MVD) in 12 patients, percutaneous rhizotomy in 10, and radiosurgery in 7. Of the 29 patients, after final treatments, 9 patients (31%) achieved excellent results and 15 (52%) good results. Failure results were seen in 17% of patients with recurrent TN. In this study the authors demonstrate that percutaneous rhizotomy is recommended for most patients with recurrent pain after MVD, and MVD can be effective in patients with a history of failed percutaneous procedures. Radiosurgery can be utilized to treat those that have not responded to other surgical modalities.


Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells.
The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.


The three-year incidence of fracture in chronic kidney disease.
Knowing a person's fracture risk according to their kidney function, gender, and age may influence clinical management and decision-making. Using healthcare databases from Ontario, Canada, we conducted a cohort study of 679,114 adults of 40 years and over (mean age 62 years) stratified at cohort entry by estimated glomerular filtration rate ((eGFR) 60 and over, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m(2)), gender, and age (40-65 and over 65 years). The primary outcome was the 3-year cumulative incidence of fracture (proportion of adults who fractured (hip, forearm, pelvis, or proximal humerus) at least once within 3-years of follow-up). Additional analyses examined the fracture incidence per 1000 person-years, hip fracture alone, stratification by prior fracture, stratification by eGFR and proteinuria, and 3-year cumulative incidence of falls with hospitalization. The 3-year cumulative incidence of fracture significantly increased in a graded manner in adults with a lower eGFR for both genders and both age groups. The 3-year cumulative incidence of fracture in women over 65 years of age across the 5 eGFR groups were 4.3%, 5.8%, 6.5%, 7.8%, and 9.6%, respectively. Corresponding estimates for men over 65 years were 1.6%, 2.0%, 2.7%, 3.8%, and 5.0%, respectively. Similar graded relationships were found for falls with hospitalization and additional analyses. Thus, many adults with chronic kidney disease will fall and fracture. Results can be used for prognostication and guidance of sample size requirements for fracture prevention trials.


In-use activity, fuel use, and emissions of heavy-duty diesel roll-off refuse trucks.
The objectives of this study were to quantify real-world activity, fuel use, and emissions for heavy duty diesel roll-off refuse trucks; evaluate the contribution of duty cycles and emissions controls to variability in cycle average fuel use and emission rates; quantify the effect of vehicle weight on fuel use and emission rates; and compare empirical cycle average emission rates with the U.S. Environmental Protection Agency's MOVES emission factor model predictions. Measurements were made at 1 Hz on six trucks of model years 2005 to 2012, using onboard systems. The trucks traveled 870 miles, had an average speed of 16 mph, and collected 165 tons of trash. The average fuel economy was 4.4 mpg, which is approximately twice previously reported values for residential trash collection trucks. On average, 50% of time is spent idling and about 58% of emissions occur in urban areas. Newer trucks with selective catalytic reduction and diesel particulate filter had NOx and PM cycle average emission rates that were 80% lower and 95% lower, respectively, compared to older trucks without. On average, the combined can and trash weight was about 55% of chassis weight. The marginal effect of vehicle weight on fuel use and emissions is highest at low loads and decreases as load increases. Among 36 cycle average rates (6 trucks×6 cycles), MOVES-predicted values and estimates based on real-world data have similar relative trends. MOVES-predicted CO2 emissions are similar to those of the real world, while NOx and PM emissions are, on average, 43% lower and 300% higher, respectively. The real-world data presented here can be used to estimate benefits of replacing old trucks with new trucks. Further, the data can be used to improve emission inventories and model predictions. In-use measurements of the real-world activity, fuel use, and emissions of heavy-duty diesel roll-off refuse trucks can be used to improve the accuracy of predictive models, such as MOVES, and emissions inventories. Further, the activity data from this study can be used to generate more representative duty cycles for more accurate chassis dynamometer testing. Comparisons of old and new model year diesel trucks are useful in analyzing the effect of fleet turnover. The analysis of effect of haul weight on fuel use can be used by fleet managers to optimize operations to reduce fuel cost.


The nongravitational interactions of dark matter in colliding galaxy clusters.
Collisions between galaxy clusters provide a test of the nongravitational forces acting on dark matter. Dark matter's lack of deceleration in the "bullet cluster" collision constrained its self-interaction cross section σ(DM)/m < 1.25 square centimeters per gram (cm(2)/g) [68% confidence limit (CL)] (σ(DM), self-interaction cross section; m, unit mass of dark matter) for long-ranged forces. Using the Chandra and Hubble Space Telescopes, we have now observed 72 collisions, including both major and minor mergers. Combining these measurements statistically, we detect the existence of dark mass at 7.6σ significance. The position of the dark mass has remained closely aligned within 5.8 ± 8.2 kiloparsecs of associated stars, implying a self-interaction cross section σ(DM)/m < 0.47 cm(2)/g (95% CL) and disfavoring some proposed extensions to the standard model.


A Unified Approach to Targeting the Lysosome's Degradative and Growth Signaling Roles.
Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e., autophagy and macropinocytosis) while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQ) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy. Central nitrogen methylation of the DQ linker enhances lysosomal localization and potency. An in situ photoaffinity pulldown identified palmitoyl-protein thioesterase 1 (PPT1) as the molecular target of DQ661. PPT1 inhibition concurrently impairs mTOR and lysosomal catabolism through the rapid accumulation of palmitoylated proteins. DQ661 inhibits the in vivo tumor growth of melanoma, pancreatic cancer, and colorectal cancer mouse models and can be safely combined with chemotherapy. Thus, lysosome-directed PPT1 inhibitors represent a new approach to concurrently targeting mTORC1 and lysosomal catabolism in cancer.Significance: This study identifies chemical features of dimeric compounds that increase their lysosomal specificity, and a new molecular target for these compounds, reclassifying these compounds as targeted therapies. Targeting PPT1 blocks mTOR signaling in a manner distinct from catalytic inhibitors, while concurrently inhibiting autophagy, thereby providing a new strategy for cancer therapy. Cancer Discov; 7(11); 1266-83. ©2017 AACR.See related commentary by Towers and Thorburn, p. 1218This article is highlighted in the In This Issue feature, p. 1201.


Investigation of early cell-surface interactions of human mesenchymal stem cells on nanopatterned β-type titanium-niobium alloy surfaces.
Multi-potent adult mesenchymal stem cells (MSCs) derived from bone marrow have therapeutic potential for bone diseases and regenerative medicine. However, an intrinsic heterogeneity in their phenotype, which in turn results in various differentiation potentials, makes it difficult to predict the response of these cells. The aim of this study is to investigate initial cell-surface interactions of human MSCs on modified titanium alloys. Gold nanoparticles deposited on β-type Ti-40Nb alloys by block copolymer micelle nanolithography served as nanotopographical cues as well as specific binding sites for the immobilization of thiolated peptides present in several extracellular matrix proteins. MSC heterogeneity persists on polished and nanopatterned Ti-40Nb samples. However, cell heterogeneity and donor variability decreased upon functionalization of the gold nanoparticles with cyclic RGD peptides. In particular, the number of large cells significantly decreased after 24 h owing to the arrangement of cell anchorage sites, rather than peptide specificity. However, the size and number of integrin-mediated adhesion clusters increased in the presence of the integrin-binding peptide (cRGDfK) compared with the control peptide (cRADfK). These results suggest that the use of integrin ligands in defined patterns could improve MSC-material interactions, not only by regulating cell adhesion locally, but also by reducing population heterogeneity.


Exercise intolerance following heart transplantation: the role of pulmonary diffusing capacity impairment.
Although impairment of the diffusing capacity of the lung for carbon monoxide (DLCO) in heart transplant recipients is well-documented, there are limited data on its impact on exercise capacity in these patients. The aim of this study was to determine the effect of DLCO reduction on exercise capacity in heart transplant recipients. Descriptive cohort study. A regional cardiopulmonary transplant center. Twenty-six heart transplant recipients who were studied before and after transplantation compared with 26 healthy volunteers. Spirometry and static lung volumes were measured using body plethysmography, DLCO was measured using the single-breath technique, and progressive cardiopulmonary exercise was performed using a bicycle ergometer, continuous transcutaneous blood gas monitoring, and on-line analysis of minute ventilation, oxygen uptake (VO(2)), and carbon dioxide production. Before transplantation, the mean percent predicted for hemoglobin-corrected DLCO was reduced in patients (73.2%) compared to healthy control subjects (98.8%; p < 0.001) and declined significantly after transplantation (60.1%; p < 0.05). Although the mean maximal symptom-limited VO(2) (VO(2)max) increased after transplantation (increase, 41.3 to 48.6% of predicted; p < 0.05), it remained substantially lower than normal (92.9%; p < 0.001). There was a significant correlation between DLCO and VO(2)max after transplantation (r = 0.61; p = 0.001), but not before transplantation (r = 0.09; p = 0.66). DLCO was also inversely correlated with other respiratory responses to exercise, including the following: the ventilatory response to exercise (r = -0.44; p < 0.05); dead space to tidal volume ratio (r = -43; p < 0.05); and the alveolar-arterial oxygen gradient (r = -0. 45; p < 0.05), but there was no correlation between any of these variables and DLCO before transplantation. DLCO reduction after heart transplantation appears to represent persistent gas exchange impairment and contributes to exercise limitation in heart transplant recipients.


ICT Learning Technologies for Disabled People: Recommendations for Good Practice.
The use of ICT in education is becoming increasingly important and has potential advantages to disabled learners if the technologies are appropriately designed, including for accessibility and usability, and used. This paper presents the first sets of recommendations for learning technologies for disabled people aimed at disabled learners, teachers, developers and educational institutions respectively. They were developed as part of the work of the Enable Network for ICT Learning for Disabled People and involved input from both experts and end-users. The concise format facilitates production in a variety of formats and languages for accessibility and wide distribution. The paper discusses the recommendations and their relationship to existing guidelines.


Sexually Transmitted Infection Prevention With Long-Acting Reversible Contraception: Factors Associated With Dual Use.
Long-acting reversible contraception (LARC) is extremely effective in preventing pregnancy; however, it does not provide sexually transmitted infection (STI) prevention. Therefore, dual use is recommended for the prevention of STIs, in addition to pregnancy, by using LARC methods with condoms. This study assessed factors associated with LARC only use and dual-LARC and condom use among college women. The National College Health Assessment-II Fall 2012 to 2013 was used for this analysis. The analytic sample was restricted to women who used a LARC method (ie, intrauterine device or implant) (N = 1658). The main outcome was dual method use, LARC and condom, at last sex. An adjusted logistic regression model assessed sociodemographic factors (age, relationship, race), health care utilization (routine gynecological examination), and sexual behavior (number of partners) as factors associated with dual condom-LARC use at the last time of vaginal-sex. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated. Among women reporting LARC use, 24% used a condom. Dual users were less likely to have only 1 sexual partner (adjusted PR [aPR], 0.66; 95% CI, 0.54-0.81) and be in a relationship. Dual users were more likely than LARC-only users to be Hispanic (aPR, 1.34; 95% CI, 1.01-1.78), black (aPR, 1.40; 95% CI, 1.07-1.83), and biracial/multiracial (aPR, 1.38; 95% CI, 1.10-1.73). These findings illustrate differences between dual-condom LARC and LARC-only college users. It is likely that relationship status and number of partners influences perceived risk for STIs and decision making for dual use among this population.


The National Human Activity Pattern Survey (NHAPS): a resource for assessing exposure to environmental pollutants.
Because human activities impact the timing, location, and degree of pollutant exposure, they play a key role in explaining exposure variation. This fact has motivated the collection of activity pattern data for their specific use in exposure assessments. The largest of these recent efforts is the National Human Activity Pattern Survey (NHAPS), a 2-year probability-based telephone survey (n=9386) of exposure-related human activities in the United States (U.S.) sponsored by the U.S. Environmental Protection Agency (EPA). The primary purpose of NHAPS was to provide comprehensive and current exposure information over broad geographical and temporal scales, particularly for use in probabilistic population exposure models. NHAPS was conducted on a virtually daily basis from late September 1992 through September 1994 by the University of Maryland's Survey Research Center using a computer-assisted telephone interview instrument (CATI) to collect 24-h retrospective diaries and answers to a number of personal and exposure-related questions from each respondent. The resulting diary records contain beginning and ending times for each distinct combination of location and activity occurring on the diary day (i.e., each microenvironment). Between 340 and 1713 respondents of all ages were interviewed in each of the 10 EPA regions across the 48 contiguous states. Interviews were completed in 63% of the households contacted. NHAPS respondents reported spending an average of 87% of their time in enclosed buildings and about 6% of their time in enclosed vehicles. These proportions are fairly constant across the various regions of the U.S. and Canada and for the California population between the late 1980s, when the California Air Resources Board (CARB) sponsored a state-wide activity pattern study, and the mid-1990s, when NHAPS was conducted. However, the number of people exposed to environmental tobacco smoke (ETS) in California seems to have decreased over the same time period, where exposure is determined by the reported time spent with a smoker. In both California and the entire nation, the most time spent exposed to ETS was reported to take place in residential locations.


Whole-body vibration training elevates creatine kinase levels in sedentary subjects.
Whole body vibration (WBV) is an increasingly popular modality of muscle training, especially in sedentary subjects. We hypothesised that the vigorous muscle contractions elicited by WBV can cause muscle damage expressed as an elevation in muscle enzymes. Twenty inactive subjects, ten male and ten female, aged 22.7 ± 2.6, BMI 22.4 ± 2.1 were included based on the absence of regular physical activity as defined by international guidelines, and no history of recent trauma, musculoskeletal pathology, implanted prosthetics, cardiovascular disease or drug intake. The intervention consisted of one bout of high intensity WBV corresponding to a typical training session, involving all the major muscle groups. Plasma levels of muscle enzymes prior to and at 24, 48 and 96 hours post exercise (creatine kinase - CK, MB fraction, troponin I, aminotransferases and lactate dehydrogenase) were measured. In addition, blood lactate was assayed immediately after exercise. Delayed onset muscle soreness (DOMS) was evaluated using a visual analogical scale. Five participants (25%) showed a significant increase in post exercise CK levels (> double of baseline). Maximal value was 3520 U/l. No change was observed in CK-MB or troponin I. Lactate increased to 10.0 ± 2.4 in men and 6.9 ± 2.4 in women. All participants had some degrees of DOMS, without correlation to enzymatic changes. WBV can provoke high CK elevation in healthy, medication-free inactive subjects. Such an elevation is transient and harmless, but could be wrongly attributed to drug induced myopathy, as in patients treated with statins. Practitioners should bear this in mind before discontinuing a potential life saving drug.


Germline mutation in DOK7 associated with fetal akinesia deformation sequence.
Fetal akinesia deformation sequence syndrome (FADS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar) types. Previously, we and others reported that homozygous mutations in the fetal acetylcholine receptor gamma subunit (CHRNG) can cause both lethal and non-lethal MPS, demonstrating that pterygia resulted from fetal akinesia, and that mutations in the acetylcholine receptor subunits CHRNA1, CHRND, and Rapsyn (RAPSN) can also result in a MPS/FADS phenotype. We hypothesised that mutations in other acetylcholine receptor related genes may interfere with neurotransmission at the neuromuscular junction and so we analysed 14 cases of lethal MPS/FADS without CHRNG, CHRNA1, CHRNB1, CHRND, or RAPSN mutations for mutations in DOK7. A homozygous DOK7 splice site mutation, c.331+1G>T, was identified in a family with three children affected with lethal FADS. Previously DOK7 mutations have been reported to underlie a congenital myaesthenic syndrome with a characteristic "limb girdle" pattern of muscle weakness. This finding is consistent with the hypothesis that whereas incomplete loss of DOK7 function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype.


End-of-life prognostic indicators in patients with COPD: part 2.
In the UK, chronic respiratory diseases cause 13% of adult disability. The major chronic respiratory disease is chronic obstructive pulmonary disease (COPD), a condition involving chronic airway inflammation that causes airflow obstruction and destruction of lung tissue. This leads to a progressive loss of respiratory membrane, which accounts for the clinical manifestation of COPD, which is difficulty maintaining sufficient gas exchange to meet metabolic demands. The primary cause is smoking, with the vast majority of COPD patients having a past or present history of smoking. However, exposure to industrial pollutants is also a contributing factor, as is a rare genetic predisposition to developing COPD.


White matter integrity determined with diffusion tensor imaging in older adults without dementia: influence of amyloid load and neurodegeneration.
Pathophysiologic mechanisms leading to loss of white matter integrity and the temporal positioning of biomarkers of white matter integrity relative to the biomarkers of gray matter neurodegeneration and amyloid load in the course of Alzheimer disease (AD) are poorly understood. To investigate the effects of AD-related gray matter neurodegeneration and high β-amyloid on white matter microstructure in older adults without dementia. A population-based, longitudinal cohort study was conducted. Participants included in the Mayo Clinic Study of Aging (N = 701) who underwent magnetic resonance imaging, diffusion tensor imaging (DTI), and positron emission tomography studies with diagnoses of cognitively normal ([CN] n = 570) or mild cognitive impairment ([MCI] n = 131) were included. Both groups were divided into biomarker-negative, amyloid-positive-only, neurodegeneration-positive-only, and amyloid plus neurodegeneration-positive groups based on their amyloid load shown on carbon 11-labeled Pittsburgh Compound B positron emission tomography, AD hypometabolic pattern shown on fludeoxyglucose F 18 positron emission tomography, and/or hippocampal atrophy shown on magnetic resonance imaging. Fractional anisotropy (FA) determined using DTI. No FA alterations were observed in biomarker-negative MCI and amyloid-positive-only CN and MCI groups compared with biomarker-negative CN participants on voxel-based analysis (P < .05; familywise error corrected). Conversely, the neurodegeneration-positive-only and amyloid plus neurodegeneration-positive CN and MCI groups consistently had decreased FA in the fornix, which correlated with cognitive performance (ρ = 0.38; P < .001). Patients with MCI had more extensive white matter involvement than did those with CN, and the greatest FA decreases were observed in the amyloid plus neurodegeneration-positive MCI group (P < .05; familywise error corrected). A high amyloid load does not influence diffusion tensor imaging-based measures of white matter integrity in the absence of coexistent gray matter neurodegeneration in older adults without dementia.


Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA).
For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival (P=0.006) in patients on anticoagulation compared with patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant (P=0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95% confidence interval, 0.66-0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. http://www.clinicaltrials.gov. Unique identifier: NCT01347216.


Metagenomic Approach for Identification of the Pathogens Associated with Diarrhea in Stool Specimens.
The potential to rapidly capture the entire microbial community structure and/or gene content makes metagenomic sequencing an attractive tool for pathogen identification and the detection of resistance/virulence genes in clinical settings. Here, we assessed the consistency between PCR from a diagnostic laboratory, quantitative PCR (qPCR) from a research laboratory, 16S rRNA gene sequencing, and metagenomic shotgun sequencing (MSS) for Clostridium difficile identification in diarrhea stool samples. Twenty-two C. difficile-positive diarrhea samples identified by PCR and qPCR and five C. difficile-negative diarrhea controls were studied. C. difficile was detected in 90.9% of C. difficile-positive samples using 16S rRNA gene sequencing, and C. difficile was detected in 86.3% of C. difficile-positive samples using MSS. CFU inferred from qPCR analysis were positively correlated with the relative abundance of C. difficile from 16S rRNA gene sequencing (r(2) = -0.60) and MSS (r(2) = -0.55). C. difficile was codetected with Clostridium perfringens, norovirus, sapovirus, parechovirus, and anellovirus in 3.7% to 27.3% of the samples. A high load of Candida spp. was found in a symptomatic control sample in which no causative agents for diarrhea were identified in routine clinical testing. Beta-lactamase and tetracycline resistance genes were the most prevalent (25.9%) antibiotic resistance genes in these samples. In summary, the proof-of-concept study demonstrated that next-generation sequencing (NGS) in pathogen detection is moderately correlated with laboratory testing and is advantageous in detecting pathogens without a priori knowledge.


Identification of the Involvement of Potassium Channels in Fibromyalgia.
Fibromyalgia is a central sensitivity syndrome that presents with chronic pain, fatigue, cognitive dysfunction, and disordered sleep. The pathophysiology which due to multisensory hypersensitivity of the central nervous system involves neuronal excitability leading to central sensitization. Treatments of the challenges associated with the complexities of fibromyalgia involve combinations of pharmacological and non-pharmacological therapeutic approaches which often offer limited benefit. Potassium (K+) channels play a fundamental role in establishing and maintaining stability of neuronal activity. The large molecular diversity and distribution of K+ channels support involvement in a broad range of physiological functions. In nociceptive pathways, neuronal hyperexcitability leading to pain sensation has been associated with reduced function of K+ channels and loss of cellular control. This article reviews the evidence of involvement of K+ channels in fibromyalgia. A potential role both in the pathophysiological processes responsible for the symptoms of fibromyalgia and as therapeutic targets for the management of the condition is considered.


Proteome profiling of breast cancer biopsies reveals a wound healing signature of cancer-associated fibroblasts.
Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study, we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near, and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. All mass analysis data have been made fully accessible via ProteomeXchange, DOI PXD001311 and PXD001323-8. Comparison of tissue proteomics data with all of those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1, and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.


Fluorographene: a two-dimensional counterpart of Teflon.
A stoichiometric derivative of graphene with a fluorine atom attached to each carbon is reported. Raman, optical, structural, micromechanical, and transport studies show that the material is qualitatively different from the known graphene-based nonstoichiometric derivatives. Fluorographene is a high-quality insulator (resistivity >10(12) Ω) with an optical gap of 3 eV. It inherits the mechanical strength of graphene, exhibiting a Young's modulus of 100 N m(-1) and sustaining strains of 15%. Fluorographene is inert and stable up to 400 °C even in air, similar to Teflon.


Investigating the distribution of the Yangtze finless porpoise in the Yangtze River using environmental DNA.
Determining the distribution of the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, YFP) in the Yangtze River has to date relied on traditional visual and counting methods, but such field surveys are time-consuming and expensive. Analyses using environmental DNA (eDNA) to investigate the presence and range of endangered aquatic species have proven to be more economical and effective detection methods, and are a non-invasive approach to sampling. A challenge of relying on eDNA for YFP monitoring is that the Yangtze River is characterized by high turbidity and a strong current. Here, we used an eDNA-based approach to estimate the presence of YFP at 18 sites in the Yangtze River in August 2017 and at an additional 11 sites in January 2018. At each sampling site, we filtered six 1 L water samples with 5 µm pore size filter paper and quantified the amount of YFP eDNA in each water sample using quantitative real-time polymerase chain reaction (qPCR). In addition, YFP eDNA was successfully detected in locations where we visually observed YFP, as well as in locations where YFP were not observed directly. We found that our eDNA-based method had higher detection rates than traditional field survey methods. Although YFP was visually observed in the Yangtze River in winter, water samples collected during the summer contained significantly higher YFP eDNA than winter water samples. Our results demonstrate the potential effectiveness of eDNA detection methods in determining the distribution of YFP in the Yangtze River.


Muscle activation during resistance training with no external load - effects of training status, movement velocity, dominance, and visual feedback.
To explore the acute effects of training status, movement velocity, dominance, and visual feedback on muscle activation and rating of perceived exertion (RPE) during resistance training with no external load (no-load resistance training; NLRT). Thirty-three men (17 untrained and 16 trained), performed elbow flexions in four NLRT sessions: 1) slow velocity with EMG visual feedback, 2) slow velocity without EMG visual feedback, 3) fast velocity with EMG feedback, and 4) fast velocity without EMG feedback. RPE was measured using the Borg Discomfort scale. EMG for the biceps and triceps were recorded for both arms. EMG feedback had no influence on RPE. The peak and mean EMG values were not different for the biceps (93.8±11.5% and 50±13.1%) and triceps (93.7±23.9% and 49.6±16.2%). The results revealed a difference in the training status, with higher peak EMG for untrained than for trained participants (96.9±20% vs. 90.2±15.6%). However the values for mean EMG were not different between the untrained and trained (50.3±15.7% vs. 49.2±13.7%) participants. There was no difference in the peak (92.8±19% vs. 94.7±20.4%) and mean (49.8±15.0% vs. 49.7±14.5%) EMG values for the dominant and non-dominant sides. Peak EMG values were not different between faster and slower velocities (93.6±19.6% and 93.9±17.8%). However, mean EMG was higher for slower (50.5±14.4%) than for faster (48.5±15.4%) velocities. The peak and mean EMG during contractions with (93.3±17.5% and 49.5±14.1%) and without visual feedback (94.2±19.9% and 50±15.4%) were not significantly different. NLRT produces high levels of muscle activation independent of training, status, dominance, movement velocity, and visual feedback.


Outcomes of community health worker interventions.
To conduct a systematic review of the evidence on characteristics of community health workers (CHWs) and CHW interventions, outcomes of such interventions, costs and cost-effectiveness of CHW interventions, and characteristics of CHW training. We searched MEDLINE, Cochrane Collaboration resources, and the Cumulative Index to Nursing and Allied Health Literature for studies published in English from 1980 through November 2008. We used standard Evidence-based Practice Center methods of dual review of abstracts, full-text articles, abstractions, quality ratings, and strength of evidence grades. We resolved disagreements by consensus. We included 53 studies on characteristics and outcomes of CHW interventions, 6 on cost-effectiveness, and 9 on training. CHWs interacted with participants in a broad array of locations, using a spectrum of materials at varying levels of intensity. We classified 8 studies as low intensity, 18 as moderate intensity, and 27 as high intensity, based on the type and duration of interaction. Regarding outcomes, limited evidence (five studies) suggests that CHW interventions can improve participant knowledge when compared with alternative approaches such as no intervention, media, mail, or usual care plus pamphlets. We found mixed evidence for CHW effectiveness on participant behavior change (22 studies) and health outcomes (27 studies): some studies suggested that CHW interventions can result in greater improvements in participant behavior and health outcomes when compared with various alternatives, but other studies suggested that CHW interventions provide no statistically different benefits than alternatives. Low or moderate strength of evidence suggests that CHWs can increase appropriate health care utilization for some interventions (30 studies). The literature showed mixed results of effectiveness when analyzed by clinical context: CHW interventions had the greatest effectiveness relative to alternatives for some disease prevention, asthma management, cervical cancer screening, and mammography screening outcomes. CHW interventions were not significantly different from alternatives for clinical breast examination, breast self-examination, colorectal cancer screening, chronic disease management, or most maternal and child health interventions. Six studies with economic and cost information yielded insufficient data to evaluate the cost-effectiveness of CHW interventions relative to other community health interventions. Limited evidence described characteristics of CHW training; no studies examined the impact of CHW training on health outcomes. CHWs can serve as a means of improving outcomes for underserved populations for some health conditions. The effectiveness of CHWs in numerous areas requires further research that addresses the methodological limitations of prior studies and that contributes to translating research into practice.


Characterization of a catalase from red-lip mullet (Liza haematocheila): Demonstration of antioxidative activity and mRNA upregulation in response to immunostimulants.
Reactive oxygen species, generated in all the aerobic organisms, can cause oxidative stress. Excessive ROS may become a source of carcinogen due to DNA damage, lipid peroxidation, cell injury, and cell death. In order to prevent these adverse effects of ROS, antioxidant enzymes have evolved in aerobic organisms. Catalase is a major antioxidant enzyme that breaks down excessive H2O2 and inhibits apoptotic cell death. Here we molecularly characterized catalase from red-lip mullet. The cDNA sequence of LhCAT consists of an ORF of 1545 bp, which encodes a 527 amino acid peptide (~60 kDa). Based on bioinformatics analysis, LhCAT possesses a domain architecture characteristic of catalases, including a catalase proximal active site signature and a catalase proximal heme-ligand signature. It also has heme and NADPH binding sites homologous to previously described catalases. Pairwise alignment with its homologs revealed that LhCAT shares 95.1% identity with Oplegnathus fasciatus catalase and 97.4% similarity with Sparus aurata catalase. An uprooted phylogenetic tree demonstrated that LhCAT resides in a clade with catalases from other teleosts and exhibits a close relationship with Oplegnathus fasciatus catalase. Among twelve tissue types, we observed the highest LhCAT mRNA expression in the liver, followed by blood. Immune challenge by Lactococcus garvieae, or Poly I:C in the blood or spleen resulted in up-regulation at 24 h post injection. We also tested the antioxidant activity of recombinant LhCAT against hydrogen peroxide and found its optimal concentration to be 12.5 μg/mL. Collectively, these data suggested that LhCAT play an important role in antioxidant defense and immune response of red-lip mullet.


Valve durability after transcatheter aortic valve implantation.
Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure to treat severe symptomatic aortic stenosis. While the TAVI procedure can be performed safely and provide excellent 5-year results, little is known about long-term durability. TAVI valves are composed of bioprosthetic leaflets are prone to deterioration, which are categorized as structural valve deterioration (SVD) and non-SVD. SVD refers to an intrinsic pathology of the leaflets or stent structure with mechanisms that include leaflet calcification, leaflet tear, stent fracture, or stent creep. Non-SVD processes include valve thrombosis, infective endocarditis and patient prosthesis mismatch. TAVI valves degenerate by similar mechanisms as bioprosthetic surgical aortic valves. Unique mechanisms that contribute to TAVI degeneration include valve crimpling, balloon expansion, stent under-expansion and valve thrombosis. The absence of a universally accepted definition of SVD poses a challenge in estimating valve durability. Traditional surgical bioprosthetic aortic valves have demonstrated excellent durability with clinically relevant SVD of 6.6% at 10-year follow up. Long-term durability of TAVI valves, however, remain poorly defined. From meta-analysis TAVI trials, SVD was estimated at 7% at 5 years. With iterative improvements in TAVI valve construction and deployment techniques, long-term durability may improve. Until long-term outcomes are better understood, TAVI should be used with caution in younger patients.


Frequencies of IL-2- and IL-4-secreting T cells in naive and antigen-stimulated lymphocyte populations.
The relative frequencies of IL-2-and IL-4-secreting precursors in naive and Ag-primed populations were investigated by using limiting dilution analysis. Cells capable of IL-4 production in lymphoid populations freshly isolated from mice were rare in comparison with those producing IL-2 when the cells were stimulated by nominal Ag, by alloantigens, or by mitogens. One cycle of in vitro Ag restimulation and rest, however, enabled us to detect high proportions of IL-4-secreting cells among keyhole limpet hemocyanin-primed lymph node cells. With cultures set up at monoclonal cell doses, it was shown that IL-2 and IL-4 are secreted by separate precursor populations at this stage of their development. The IL-4-secreting cells were further shown to be dependent upon the presence of IL-2, either secreted by separate precursors or exogenously added, for the production of detectable amounts of IL-4. Analysis of the frequencies of helper cells producing both IL-2 and IL-4 at various stages of the in vivo immune response and the requirements for their growth and differentiation should give a better understanding of the relative contributions of each cell type.


SU-E-T-135: Investigation of Commercial-Grade Flatbed Scanners and a Medical- Grade Scanner for Radiochromic EBT Film Dosimetry.
To evaluate the characteristics of commercial-grade flatbed scanners and medical-grade scanners for radiochromic EBT film dosimetry. Performance aspects of a Vidar Dosimetry Pro Advantage (Red), Epson 750 Pro, Microtek ArtixScan 1800f, and Microtek ScanMaker 8700 scanner for EBT2 Gafchromic film were evaluated in the categories of repeatability, maximum distinguishable optical density (OD) differentiation, OD variance, and dose curve characteristics. OD step film by Stouffer Industries containing 31 steps ranging from 0.05 to 3.62 OD was used. EBT films were irradiated with dose ranging from 20 to 600 cGy in 6×6 cm2 field sizes and analyzed 24 hours later using RIT113 and Tomotherapy Film Analyzer software. Scans were performed in transmissive mode, landscape orientation, 16-bit image. The mean and standard deviation Analog to Digital (A/D) scanner value was measured by selecting a 3×3 mm2 uniform area in the central region of each OD step from a total of 20 scans performed over several weeks. Repeatability was determined from the variance of OD step 0.38. Maximum distinguishable OD was defined as the last OD step whose range of A/D values does not overlap with its neighboring step. Repeatability uncertainty ranged from 0.1% for Vidar to 4% for Epson. Average standard deviation of OD steps ranged from 0.21% for Vidar to 6.4% for ArtixScan 1800f. Maximum distinguishable optical density ranged from 3.38 for Vidar to 1.32 for ScanMaker 8700. A/D range of each OD step corresponds to a dose range. Dose ranges of OD steps varied from 1% for Vidar to 20% for ScanMaker 8700. The Vidar exhibited a dose curve that utilized a broader range of OD values than the other scanners. Vidar exhibited higher maximum distinguishable OD, smaller variance in repeatability, smaller A/D value deviation per OD step, and a shallower dose curve with respect to OD.


Examining differences in cigarette smoking prevalence among young adults across national surveillance surveys.
Accurate smoking prevalence data is critical for monitoring, surveillance, and evaluation. However, estimates of prevalence vary across surveys due to various factors. This study examines smoking prevalence estimates for 18-21 year olds across six U.S. national telephone, online and in-person surveys for the years 2013 and 2014. Estimates of ever smoking ranged from 35% to 55%. Current smoking ranged from 16% to 30%. Across the three modalities, household surveys were found to yield the highest estimates of smoking prevalence among 18 to 21 year olds while online surveys yielded the lowest estimates, and this was consistent when stratifying by gender and race/ethnicity. Assessments of the joint effect of gender, race/ethnicity, educational attainment and survey mode indicated that the relative differences in the likelihood of smoking were consistent across modes for gender and education groups. However, the relative likelihood of smoking among minority groups compared with non-Hispanic Whites varied across modes. Gender and racial/ethnic distributions for most surveys significantly differed from the U.S. Census. Over and underrepresentation of certain demographic subpopulations, variations in survey question wording, and social desirability effects may explain modality differences in smoking estimates observed in this study. Further research is needed to evaluate the effect of survey mode on variation in smoking prevalence estimates across national surveys, particularly for young adult populations.


A questionnaire measuring staff perceptions of Lean adoption in healthcare: development and psychometric testing.
During the past decade, the concept of Lean has spread rapidly within the healthcare sector, but there is a lack of instruments that can measure staff's perceptions of Lean adoption. Thus, the aim of the present study was to develop a questionnaire measuring Lean in healthcare, based on Liker's description of Lean, by adapting an existing instrument developed for the service sector. A mixed-method design was used. Initially, items from the service sector instrument were categorized according to Liker's 14 principles describing Lean within four domains: philosophy, processes, people and partners and problem-solving. Items were lacking for three of Liker's principles and were therefore developed de novo. Think-aloud interviews were conducted with 12 healthcare staff from different professions to contextualize and examine the face validity of the questionnaire prototype. Thereafter, the adjusted questionnaire's psychometric properties were assessed on the basis of a cross-sectional survey among 386 staff working in primary care. The think-aloud interviews led to adjustments in the questionnaire to better suit a healthcare context, and the number of items was reduced. Confirmatory factor analysis of the adjusted questionnaire showed a generally acceptable correspondence with Liker's description of Lean. Internal consistency, measured using Cronbach's alpha, for the factors in Liker's description of Lean was 0.60 for the factor people and partners, and over 0.70 for the three other factors. Test-retest reliability measured by the intra-class correlation coefficient ranged from 0.77 to 0.88 for the four factors. We designed a questionnaire capturing staff's perceptions of Lean adoption in healthcare on the basis of Liker's description. This Lean in Healthcare Questionnaire (LiHcQ) showed generally acceptable psychometric properties, which supports its usability for measuring Lean adoption in healthcare. We suggest that further research focus on verifying the usability of LiHcQ in other healthcare settings, and on adjusting the instrument if needed.


Pediatric hereditary autoinflammatory syndromes.
To describe the most prevalent pediatric hereditary autoinflammatory syndromes. A review of the literature including relevant references from the PubMed and SciELO was carried out using the keywords autoinflammatory syndromes and child. The hereditary autoinflammatory syndromes are caused by monogenic defects of innate immunity and are classified as primary immunodeficiencies. These syndromes are characterized by recurrent or persistent systemic inflammatory symptoms and must be distinguished from infectious diseases, autoimmune diseases, and other primary immunodeficiencies. This review describes the epidemiological, clinical and laboratory features, prognosis, and treatment of the main autoinflammatory syndromes, namely: familial Mediterranean fever; TNF receptor associated periodic syndrome; the cryopyrinopathies; mevalonate kinase deficiency; pediatric granulomatous arthritis; pyogenic arthritis, pyoderma gangrenosum and acne syndrome; Majeed syndrome; and deficiency of interleukin 1 receptor antagonist. The cryopyrinopathies discussed include neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic, cutaneous and articular syndrome), Muckle-Wells syndrome, and familial cold autoinflammatory syndrome. Pediatricians must recognize the clinical features of the most prevalent autoinflammatory syndromes. Early referral to a pediatric rheumatologist may allow early diagnosis and institution of treatment, with improvement in the quality of life of these patients.


How not to cut health care costs.
Health care providers in much of the world are trying to respond to the tremendous pressure to reduce costs--but evidence suggests that many of their attempts are counterproductive, raising costs and sometimes decreasing the quality of care. Kaplan and Haas reached this conclusion after conducting field research with more than 50 health care provider organizations. Administrators looking for cuts typically work from the line-item expense categories on their P&Ls, they found. This may appear to generate immediate results, but it usually does not reflect the optimal mix of resources needed to efficiently deliver excellent care. The authors describe five common mistakes: (1) Reducing support staff. This often lowers the productivity of clinicians, whose time is far more expensive. (2) Underinvesting in space and equipment. The costs of these are consistently an order of magnitude smaller than personnel costs, so cuts here are short-sighted if they lower people's productivity. (3) Focusing narrowly on procurement prices and neglecting to examine how individual clinicians actually consume supplies. (4) Maximizing patient throughput. Physicians achieve greater overall productivity by spending more time with fewer patients. (5) Failing to benchmark and standardize. Administrators, in collaboration with clinicians, should examine all the costs of treating patients' conditions. This will uncover multiple opportunities to improve processes in ways that lower total costs and deliver better care.


Needles in hay: chest pain as the presenting symptom in children with serious underlying cardiac pathology.
Chest pain in children is common, but rarely heralds serious underlying cardiac pathology. Despite this, the anxiety of missing a potentially life threatening condition creates a large burden of referrals and diagnostic testing. We evaluated patients diagnosed with 1 of 9 serious cardiac diseases and detailed the clinical signs and symptoms of the patients presenting with chest pain. Patients diagnosed between the ages of 7 and 21 years from January 2000 to December 2009 at Children's Hospital Boston (CHB) were identified from a database using diagnostic and billing codes for aortic dissection, coronary anomalies, dilated cardiomyopathy, hypertrophic cardiomyopathy, myocarditis, pericarditis, pulmonary embolus, pulmonary hypertension, and Takayasu arteritis. Patients with previously diagnosed congenital or acquired heart disease were excluded. Four hundred eighty-four patients were included and 35% presented with chest pain. Forty-one (24%) of these patients with chest pain were diagnosed in the outpatient cardiology clinic, while the remaining 130 patients (76%) were diagnosed in the emergency department (ED) or inpatient setting. Coronary artery anomalies were the most common diagnosis made in cardiology clinic, and 16 of the 23 (70%) patients with serious coronary anomalies had exercise-induced chest pain. Patients presenting to the ED or inpatient units tended to have other important nonspecific symptoms (35-44%), high-risk past medical histories (12%), physical examination findings (32%), and electrocardiogram (ECG) abnormalities (78%) that heighten clinical suspicion of cardiac disease. Identifying underlying cardiac pathology in the CHB outpatient cardiology department in patients presenting with chest pain is rare, with only 41 cases over a 10-year period. The presence of exertional chest pain was important in identifying patients with coronary artery anomalies. A detailed history and physical examination, along with a critical review of an ECG, seem to identify those patients with rare diseases who need further diagnostic testing.


A roadmap for the XCMS family of software solutions in metabolomics.
Global profiling of metabolites in biological samples by liquid chromatography/mass spectrometry results in datasets too large to evaluate manually. Fortunately, a variety of software programs are now available to automate the data analysis. Selection of the appropriate processing solution is dependent upon experimental design. Most metabolomic studies a decade ago had a relatively simple experimental design in which the intensities of compounds were compared between only two sample groups. More recently, however, increasingly sophisticated applications have been pursued. Examples include comparing compound intensities between multiple sample groups and unbiasedly tracking the fate of specific isotopic labels. The latter types of applications have necessitated the development of new software programs, which have introduced additional functionalities that facilitate data analysis. The objective of this review is to provide an overview of the freely available bioinformatic solutions that are either based upon or are compatible with the algorithms in XCMS, which we broadly refer to here as the 'XCMS family' of software. These include CAMERA, credentialing, Warpgroup, metaXCMS, X(13)CMS, and XCMS Online. Together, these informatic technologies can accommodate most cutting-edge metabolomic applications and offer unique advantages when compared to the original XCMS program.


The effects of lavender oil inhalation on emotional states, autonomic nervous system, and brain electrical activity.
Investigate the effects of lavender oil on the central nervous system, autonomic nervous system, and mood responses in humans after inhalation. Twenty healthy volunteers participated in the experiments. The present study assessed autonomic parameters such as blood pressure, heart rate, respiratory rate, and skin temperature to determine the arousal level of the autonomic nervous system. In addition, subjects were asked to estimate their mood responses such as feeling pleasant or unpleasant, uncomfortable, sensuality, relaxation, or refreshing in order to assess subjective behavioral arousal. Finally, electroencephalogram (EEG) was recorded from 31 electrodes on the scalp according to the international 10 to 20 system, and EEG power spectra were calculated by Fast Fourier Transform (FFT). Data was analyzed by comparing the effects of lavender oil on physiological and mood states with sweet almond oil. These assessments were measured before and after using paired t-test statistical procedure. The results revealed that lavender oil caused significant decreases of blood pressure, heart rate, and skin temperature, which indicated a decrease of autonomic arousal. In terms of mood responses, the subjects in the lavender oil group categorized themselves as more active, fresher relaxed than subjects just inhaling base oil. Compared with base oil, lavender oil increased the power of theta (4-8 Hz) and alpha (8-13 Hz) brain activities. The topographic map showed obviously more scattering power in alpha range waves particularly in bilateral temporal and central area. The findings provided evidence the relaxing effect of inhaling lavender oil.


Blood pressure re-screening for healthy adults: what is the best measure and interval?
Blood pressure (BP) screening is important to identify those at risk of cardiovascular disease, but there has been little data on the appropriate interval of screening. We aimed to evaluate the optimal interval and the best measure for BP re-screening by estimating the long-term, true change variance ('signal') and short-term, within-person variance ('noise'). Study design was a cohort study from 2005 to 2008. Target population was Japanese healthy adults not taking antihypertensive medication at baseline, in a teaching hospital. We measured annually the systolic BP (SBP) and the diastolic BP (DBP), and calculated the pulse pressure (PP) and the mean arterial pressure (MAP). A total of 15,055 individuals (51% male) with a mean age of 49 years had annual check-ups. Short-term coefficient of variation was lowest for MAP at 5.2%, followed by SBP (5.7%) and DBP (5.8%), and highest for PP (12%). After 3 years, the 'signal' of true BP changes of only SBP and MAP equaled the 'noise' of BP measurement; however, it was larger for those with higher initial BPs. SBP or MAP appears to be a better screening measure. The optimal interval should be 3 years or more, with SBP<130 mm Hg and 2 years for those with SBP ≥ 130 mm Hg.