Distribution and expression of type VI collagen and elastic fibers in human rotator cuff tendon tears.
There is increasing evidence for a progressive extracellular matrix change in rotator cuff disease progression. Directly surrounding the cell is the pericellular matrix, where assembly of matrix aggregates typically occurs making it critical in the response of tendon cells to pathological conditions. Studies in animal models have identified type VI collagen, fibrillin-1 and elastin to be located in the pericellular matrix of tendon and contribute in maintaining the structural and biomechanical integrity of tendon. However, there have been no reports on the localization of these proteins in human tendon biopsies. This study aimed to characterize the distribution of these ECM components in human rotator cuffs and gain greater insight into the relationship of pathology to tear size by analyzing the distribution and expression profiles of these ECM components. Confocal microscopy confirmed the localization of these structural molecules in the pericellular matrix of the human rotator cuff. Tendon degeneration led to an increased visibility of these components with a significant disorganization in the distribution of type VI collagen. At the genetic level, an increase in tear size was linked to an increased transcription of type VI collagen and fibrillin-1 with no significant alteration in the elastin levels. This is the first study to confirm the localization of type VI collagen, elastin and fibrillin-1 in the pericellular region of human supraspinatus tendon and assesses the effect of tendon degeneration on these structures, thus providing a useful insight into the composition of human rotator cuff tears which can be instrumental in predicting disease prognosis.


Estimating animal population density using passive acoustics.
Reliable estimation of the size or density of wild animal populations is very important for effective wildlife management, conservation and ecology. Currently, the most widely used methods for obtaining such estimates involve either sighting animals from transect lines or some form of capture-recapture on marked or uniquely identifiable individuals. However, many species are difficult to sight, and cannot be easily marked or recaptured. Some of these species produce readily identifiable sounds, providing an opportunity to use passive acoustic data to estimate animal density. In addition, even for species for which other visually based methods are feasible, passive acoustic methods offer the potential for greater detection ranges in some environments (e.g. underwater or in dense forest), and hence potentially better precision. Automated data collection means that surveys can take place at times and in places where it would be too expensive or dangerous to send human observers. Here, we present an overview of animal density estimation using passive acoustic data, a relatively new and fast-developing field. We review the types of data and methodological approaches currently available to researchers and we provide a framework for acoustics-based density estimation, illustrated with examples from real-world case studies. We mention moving sensor platforms (e.g. towed acoustics), but then focus on methods involving sensors at fixed locations, particularly hydrophones to survey marine mammals, as acoustic-based density estimation research to date has been concentrated in this area. Primary among these are methods based on distance sampling and spatially explicit capture-recapture. The methods are also applicable to other aquatic and terrestrial sound-producing taxa. We conclude that, despite being in its infancy, density estimation based on passive acoustic data likely will become an important method for surveying a number of diverse taxa, such as sea mammals, fish, birds, amphibians, and insects, especially in situations where inferences are required over long periods of time. There is considerable work ahead, with several potentially fruitful research areas, including the development of (i) hardware and software for data acquisition, (ii) efficient, calibrated, automated detection and classification systems, and (iii) statistical approaches optimized for this application. Further, survey design will need to be developed, and research is needed on the acoustic behaviour of target species. Fundamental research on vocalization rates and group sizes, and the relation between these and other factors such as season or behaviour state, is critical. Evaluation of the methods under known density scenarios will be important for empirically validating the approaches presented here.


The significance of autophagy in colorectal cancer pathogenesis and implications for therapy.
Colorectal cancer (CRC) is one of the most common cancers in developed countries with poor survival outcome in advanced stages of the disease due to its resistance to chemotherapy and other forms of treatment. New and alternative approaches are needed to overcome the tumour cells' capacity for survival and to drive the tumour towards cell death. Autophagy is a mechanism involved in the elimination of damaged cellular components through lysosomal degradation and is capable of inducing programmed cell death. The process has recently gained much interest in understanding the pathogenesis of CRC and its potential for treatment of the disease due to its role in host protection and anticancer activity. This review describes and illustrates the fundamental mechanisms of autophagy, its importance as a prognostic marker and the current approaches to harness its protective and anticancer activity in CRC therapy.


The Effects of Human Beta-Defensins on Skin Cells in vitro.
Defensins are antimicrobial peptides that exert immunomodulatory and chemotactic functions. Based on these properties and their high expression levels in the skin, they are likely to affect skin inflammation, infection, and wound healing. This may lead to therapeutic applications in (burn) wound healing. We aimed to investigate the effects of human β-defensins (hBDs) on keratinocytes and fibroblasts, 2 major skin cell types involved in skin regeneration. Monolayer keratinocyte and fibroblast cultures were exposed to recombinant hBDs, and we overexpressed hBD2 and hBD3 in keratinocytes of reconstructed epidermal equivalents by lentiviral transduction. The effects were measured by immunohistochemistry, quantitative real-time PCR, and migration assays. Kinome analyses were performed on cultured keratinocytes to investigate the signal transduction events elicited by hBD stimulation. We found that hBD3 induced the expression of cytokines and chemokines in keratinocytes, which was not observed in fibroblasts. hBD2, however, stimulated cell migration only in fibroblasts, which was not found for hBD3. Both defensins are likely to exert receptor-mediated effects in keratinocytes, as witnessed by changes in protein kinase activation following stimulation by hBD2 and hBD3. Kinome analysis suggested that protein kinase C activation was a common event for both defensins. We observed, however, considerable differences in keratinocyte responses between stimulation by exogenous recombinant defensins and endogenous defensins expressed following lentiviral transduction. Defensins exert modest biological effects on skin cells that are potentially beneficial in wound healing, but many questions regarding the biological mechanisms of action and relevance for the in vivo situation are still remaining.


A meta-ethnography of patients' experiences of chronic pelvic pain: struggling to construct chronic pelvic pain as 'real'.
To review systematically and integrate the findings of qualitative research to increase our understanding of patients' experiences of chronic pelvic pain. Chronic pelvic pain is a prevalent pain condition with a high disease burden for men and women. Its multifactorial nature makes it challenging for clinicians and patients. Synthesis of qualitative research using meta-ethnography. Five electronic bibliographic databases from inception until March 2014 supplemented by citation tracking. Of 488 papers retrieved, 32 met the review aim. Central to meta-ethnography is identifying 'concepts' and developing a conceptual model through constant comparison. Concepts are the primary data of meta-ethnography. Two team members read each paper to identify and collaboratively describe the concepts. We next compared concepts across studies and organized them into categories with shared meaning. Finally, we developed a conceptual model, or line of argument, to explain the conceptual categories. Our findings incorporate the following categories into a conceptual model: relentless and overwhelming pain; threat to self; unpredictability, struggle to construct pain as normal or pathological; a culture of secrecy; validation by diagnosis; ambiguous experience of health care; elevation of experiential knowledge and embodiment of knowledge through a community. The innovation of our model is to demonstrate, for the first time, the central struggle to construct 'pathological' vs. 'normal' chronic pelvic pain, a struggle that is exacerbated by a culture of secrecy. More research is needed to explore men's experience and to compare this with women's experience.


Changing environments and genetic variation: natural variation in inbreeding does not compromise short-term physiological responses.
Selfing plant lineages are surprisingly widespread and successful in a broad range of environments, despite showing reduced genetic diversity, which is predicted to reduce their long-term evolutionary potential. However, appropriate short-term plastic responses to new environmental conditions might not require high levels of standing genetic variation. In this study, we tested whether mating system variation among populations, and associated changes in genetic variability, affected short-term responses to environmental challenges. We compared relative fitness and metabolome profiles of naturally outbreeding (genetically diverse) and inbreeding (genetically depauperate) populations of a perennial plant, Arabidopsis lyrata, under constant growth chamber conditions and an outdoor common garden environment outside its native range. We found no effect of inbreeding on survival, flowering phenology or short-term physiological responses. Specifically, naturally occurring inbreeding had no significant effects on the plasticity of metabolome profiles, using either multivariate approaches or analysis of variation in individual metabolites, with inbreeding populations showing similar physiological responses to outbreeding populations over time in both growing environments. We conclude that low genetic diversity in naturally inbred populations may not always compromise fitness or short-term physiological capacity to respond to environmental change, which could help to explain the global success of selfing mating strategies.


Comparisons of the Rayleigh and K-distribution models using in vivo breast and liver tissue.
There is a strong interest in finding out which statistical model is the most appropriate for describing the envelope of the backscattered ultrasonic echoes from different types of tissues. The Rayleigh model is commonly employed, but this requires conditions, such as the presence of large number of randomly located scatterers with fairly uniform cross-sections, that are not always met. However, our research indicates that a model based on the K-distribution may provide a better fit to empirical data over a range of scattering conditions than the standard Rayleigh model. In this study, we looked at the K-distribution as a descriptor of the backscattered envelope of the breast and liver tissues (in vivo). By examining data from various tissue regions, a goodness-of-fit test (a least squares error method) was used to determine whether a Rayleigh or K-distribution model is more appropriate. From a large group of patients and volunteer scans (a total of 72 subjects), the fit between the K-distribution and the data is shown to have a much smaller error than the Rayleigh model.


Determination of the intracellular state of soluble macromolecules by gel filtration in vivo in the cytoplasm of amphibian oocytes.
A method to examine the diffusible state and the sizes of major cytoplasmic proteins in a living cell is described. Small (40-300 microns) commercially available gel filtration beads of a broad range of Mr exclusion limits were microsurgically implanted into the cytoplasm of oocytes of the frog, Xenopus laevis, usually after metabolic labeling of oocyte proteins with [35S]methionine. After equilibration in vivo for several hours, the appearance of the implanted cells, notably the bead-cytoplasm boundary, was examined by light and electron microscopy of sections and found to be unaffected. After incubation the beads were isolated, briefly rinsed, and their protein contents examined by one- or two-dimensional gel electrophoresis. We show that diffusible proteins can be identified by their inclusion in the pores of the gel filtration beads used and that their approximate sizes can be estimated from the size exclusion values of the specific materials used. The application of this method to important cell biological questions is demonstrated by showing that several "karyophobic proteins," i.e., proteins of the cytosolic fraction which accumulate in the cytoplasm in vivo, are indeed diffusible in the living oocyte and appear with sizes similar to those determined in vitro. This indicates that the nucleo-cytoplasmic distribution of certain diffusible proteins is governed, in addition to size exclusion at nuclear pore complexes and karyophilic "signals," by other, as yet unknown forces. Some possible applications of this method of gel filtration in vivo are discussed.


Effect of SDF-1/CXCR4 axis on the migration of transplanted bone mesenchymal stem cells mobilized by erythropoietin toward lesion sites following spinal cord injury.
Accumulating evidence has indicated that the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis plays a crucial role in the recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) into lesion sites in animal models. The aim of this study was to investigate the effects of the SDF-1/CXCR4 axis on the migration of transplanted BMSCs mobilized by erythropoietin (EPO) toward the lesion site following spinal cord injury (SCI). A model of SCI was established in rats using the modified Allen's test. In the EPO group, EPO was administered at a distance of 2 mm cranially and then 2 mm caudally from the site of injury. In the BMSC group, 10 µl of BMSC suspension was administered in the same manner. In the BMSC + EPO group, both BMSCs and EPO were administered as described above. In the BMSC + EPO + AMD3100 group, in addition to the injection of BMSCs and EPO, AMD3100 (a chemokine receptor antagonist) was administered. The Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale and a grid walk test were used to estimate the neurological recovery following SCI. Enzyme-linked immunosorbent assay (ELISA) was performed to assess the tumor necrosis factor-α (TNF-α) and SDF-1 expression levels. An immunofluorescence assay was performed to identify the distribution of the BMSCs in the injured spinal cord. A Transwell migration assay was performed to examine BMSC migration. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to detect the apoptotic index (AI). Western blot analysis was performed to measure the expression levels of erythropoietin receptor (EPOR) and CXCR4. Significant improvements in locomotor function were detected in the BMSC + EPO group compared with the BMSC group (P<0.05). GFP-labeled BMSCs were observed and were located at the lesion sites. Additionally, EPO significantly decreased the TNF-α levels and increased the SDF-1 levels in the injured spinal cord (P<0.05).The AI in the BMSC + EPO group was significantly lower compared with that in the other groups (P<0.05). Furthermore, EPO significantly upregulated the protein expression of CXCR4 in the BMSCs and promoted the migration of the BMSCs, whereas these effects were markedly inhibited when the BMSCs were co-transplanted with AMD3100. The findings of the present study confirm that EPO mobilizes BMSCs to the lesion site following SCI and enhances the anti-apoptotic effects of the BMSCs by upregulating the expression of SDF-1/CXCR4 axis.


Probing the ability of the coat and vertex protein of the membrane-containing bacteriophage PRD1 to display a meningococcal epitope.
Bacteriophage PRD1 is an icosahedral dsDNA virus with a diameter of 740 A and an outer protein shell composed of 720 copies of major coat protein P3. Spike complexes at the vertices are composed of a pentameric base (protein P31) and a spike structure (proteins P5 and P2) where the N-terminal region of the trimeric P5 is associated with the base and the C-terminal region of P5 is associated with receptor-binding protein P2. The functionality of proteins P3 and P5 was investigated using insertions and deletions. It was observed that P3 did not tolerate changes whereas P5 tolerated changes much more freely. These properties support the hypothesis that viruses have core structures and functions, which remain stable over time, as well as other elements, responsible for host interactions, which are evolutionally more fluid. The insertional probe used was the apex of exposed loop 4 of group B meningococcal outer membrane protein PorA, a medically important subunit vaccine candidate. It was demonstrated that the epitope could be displayed on the virus surface as part of spike protein P5.


Genome to Phenome: Improving Animal Health, Production, and Well-Being - A New USDA Blueprint for Animal Genome Research 2018-2027.
In 2008, a consortium led by the Agricultural Research Service (ARS) and the National Institute for Food and Agriculture (NIFA) published the "Blueprint for USDA Efforts in Agricultural Animal Genomics 2008-2017," which served as a guiding document for research and funding in animal genomics. In the decade that followed, many of the goals set forth in the blueprint were accomplished. However, several other goals require further research. In addition, new topics not covered in the original blueprint, which are the result of emerging technologies, require exploration. To develop a new, updated blueprint, ARS and NIFA, along with scientists in the animal genomics field, convened a workshop titled "Genome to Phenome: A USDA Blueprint for Improving Animal Production" in November 2017, and these discussions were used to develop new goals for the next decade. Like the previous blueprint, these goals are grouped into the broad categories "Science to Practice," "Discovery Science," and "Infrastructure." New goals for characterizing the microbiome, enhancing the use of gene editing and other biotechnologies, and preserving genetic diversity are included in the new blueprint, along with updated goals within many genome research topics described in the previous blueprint. The updated blueprint that follows describes the vision, current state of the art, the research needed to advance the field, expected deliverables, and partnerships needed for each animal genomics research topic. Accomplishment of the goals described in the blueprint will significantly increase the ability to meet the demands for animal products by an increasing world population within the next decade.


Enhanced precipitation variability decreases grass- and increases shrub-productivity.
Although projections of precipitation change indicate increases in variability, most studies of impacts of climate change on ecosystems focused on effects of changes in amount of precipitation, overlooking precipitation variability effects, especially at the interannual scale. Here, we present results from a 6-y field experiment, where we applied sequences of wet and dry years, increasing interannual precipitation coefficient of variation while maintaining a precipitation amount constant. Increased precipitation variability significantly reduced ecosystem primary production. Dominant plant-functional types showed opposite responses: perennial-grass productivity decreased by 81%, whereas shrub productivity increased by 67%. This pattern was explained by different nonlinear responses to precipitation. Grass productivity presented a saturating response to precipitation where dry years had a larger negative effect than the positive effects of wet years. In contrast, shrubs showed an increasing response to precipitation that resulted in an increase in average productivity with increasing precipitation variability. In addition, the effects of precipitation variation increased through time. We argue that the differential responses of grasses and shrubs to precipitation variability and the amplification of this phenomenon through time result from contrasting root distributions of grasses and shrubs and competitive interactions among plant types, confirmed by structural equation analysis. Under drought conditions, grasses reduce their abundance and their ability to absorb water that then is transferred to deep soil layers that are exclusively explored by shrubs. Our work addresses an understudied dimension of climate change that might lead to widespread shrub encroachment reducing the provisioning of ecosystem services to society.


MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2.
Pilocytic astrocytoma (PA) is a World Health Organization grade I glioma that occurs most commonly in children and young adults. Specific genetic alterations have been described in PA, but the pathogenesis remains poorly understood. We studied microRNA (miRNA) alterations in a large cohort of patients with PA. A total of 43 PA, including 35 sporadic grade I PA, 4 neurofibromatosis-1 (NF1)-associated PA, and 4 PA with pilomyxoid features, as well as 5 nonneoplastic brain controls were examined. BRAF fusion status was assessed in most cases. RNA was examined using the Agilent Human miRNA Microarray V3 platform. Expression of miRNA subsets was validated using quantitative real-time PCR (qRT-PCR) with Taqman probes. Validation of predicted protein targets was performed on tissue microarrays with the use of immunohistochemistry. We identified a subset of miRNAs that were differentially expressed in pediatric PAs versus normal brain tissue: 13 miRNAs were underexpressed, and 20 miRNAs were overexpressed in tumors. Differences were validated by qRT-PCR in a subset, with mean fold change in tumor versus brain of -17 (miR-124), -15 (miR-129), and 19.8 (miR-21). Searching for predicted protein targets in Targetscan, we identified a number of known and putative oncogenes that were predicted targets of miRNA sets relatively underexpressed in PA. Predicted targets with increased expression at the mRNA and/or protein level in PA included PBX3, METAP2, and NFIB. A unique miRNA profile exists in PA, compared with brain tissue. These miRNAs and their targets may play a role in the pathogenesis of PA.


Outcome measures in randomized-controlled trials of neuropathic pain conditions: a systematic review of systematic reviews and recommendations for practice.
Neuropathic pain (NeP) is a prevalent, disabling, multidimensional condition with significant morbidity; however, there appears to be a variable approach in the use of outcome measures in NeP trials. A search of systematic reviews of interventional randomized-controlled trials for NeP was undertaken to investigate the range and types of outcome measures used to determine treatment effects. Keywords and MESH searches were conducted in 5 electronic databases from inception to January 31, 2012. Full-text English-language reviews based on various acute and chronic NeP conditions were included. Two independent reviewers screened papers for inclusion, extracted data, and assessed the quality of reviews. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to critically appraise the reviews. A total of 46 studies were identified: the majority of reviews (n=28/46, 61%) scored well on the PRISMA (PRISMA scores of 20-27/27). Change in levels or intensity of pain were used by the majority of studies as the primary outcome measure in intervention studies (n=40/46 studies, 87%). Few studies used a functional outcome measure as either a primary or secondary outcome measure (n=7/46, 15% of studies). These results demonstrate that measures of pain are predominantly used in trials of NeP conditions and highlight the scant usage of functional outcome measures. The lack of standardization for the diagnostic criteria in NeP trials is also an issue that needs to be considered for future research and guideline development.


6-Shogaol enhances renal carcinoma Caki cells to TRAIL-induced apoptosis through reactive oxygen species-mediated cytochrome c release and down-regulation of c-FLIP(L) expression.
6-Shogaol, a potent bioactive compound in ginger (Zingiber officinale Roscoe), has been reported for anti-inflammatory and anti-cancer activity. In this study, we investigated the effect of 6-shogaol to enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The combined treatment with 6-shogaol and TRAIL markedly induces apoptosis in various cancer cells (renal carcinoma Caki cells, breast carcinoma MDA-MB-231 cells and glioma U118MG cells), but not in normal mesangial cells and normal mouse kidney cells. 6-Shogaol reduced the mitochondrial membrane potential (MMP) and released cytochrome c from mitochondria to cytosol via Bax activation. Furthermore, we found that 6-shogaol induced down-regulation of c-FLIP(L) expression at the post-translational levels and the overexpression of c-FLIP(L) markedly inhibited 6-shogaol plus TRAIL-induced apoptosis. Moreover, 6-shogaol increased reactive oxygen species (ROS) production in Caki cells. Pretreatment with ROS scavengers attenuated 6-shogaol plus TRAIL-induced apoptosis through inhibition of MMP reduction and down-regulation of c-FLIP(L) expression. In addition, 6-gingerol, another phenolic alkanone isolated from ginger, did not enhance TRAIL-induced apoptosis and down-regulate c-FLIP(L) expression. Taken together, our results demonstrated that 6-shogaol enhances TRAIL-mediated apoptosis in renal carcinoma Caki cells via ROS-mediated cytochrome c release and down-regulation of c-FLIP(L) expression.


[Eggs and reproductive organs of female Angiostrongylus costaricensis are more intensely recognized by human sera from acute phase in abdominal angiostrongyliasis].
Angiostrongylus costaricensisis is an intra-arterial nematode of rodents. Man may become accidentally infected through ingestion of contaminated food or water. Our objective was to describe the parasite structures recognized by human antibodies in serum samples from acute and convalescent phases of abdominal angiostrongyliasis. An indirect immunofluorescent method was employed to study reactivity on whole eggs and sections of female worms and first stage larvae (L1). L1 were also studied before and after sonication. Fluorescence, always higher with acute phase sera, was detected on the surface of whole eggs and in L1 fragments and was neither present on whole L1 nor on their sections. An inespecific reactivity was seen on the cuticular border of the general cavity and reproductive organs. The data indicate the latter as a main source of antigenicity.


Medication use and predictors of sexual activity in men and women with CVD.
To examine the influence of cardiac and noncardiac medications on sexual activity by drug classification and generation of the drug, among men and women with cardiovascular disease. This study was a subanalysis (n = 224) of survey data from a cross-sectional sample of 336 cardiac patients. Self-reported medications were categorized by generic drug name, classification, and subclass and/or generation of the drug. Sexual activity was the presence or absence of current sexual activity in the last 2 months. Patients taking generation one beta blockers, particularly men; diuretics as a class; and loop diuretics, were significantly less likely to be sexually active, with diuretics negatively influencing sexual activity in women, but not men. Certain antidepressant medications positively influenced sexual function, particularly for women. Nearly 20% of the variances in sexual activity were explained by younger age, fewer number of medications, higher education, and having a sexual partner. A new finding meriting further study was that loop diuretics negatively impacted sexual activity, particularly for women; and further studies of women overall are clearly needed. Advance practice nurses play an important role in evaluating medications, proactively choosing drugs within a class or subclass less likely to cause sexual problems, and in promoting sexual quality of life of cardiac patients.


Encoded exposure to tobacco use in social media predicts subsequent smoking behavior.
Assessing the potential link between smoking behavior and exposure to mass media depictions of smoking on social networking Web sites. A representative longitudinal panel of 200 young adults in Connecticut. Telephone surveys were conducted by using computer assisted telephone interviewing technology and electronic dialing for random digit dialing and listed samples. Connecticut residents aged 18 to 24 years. To measure encoded exposure, respondents were asked whether or not they had smoked a cigarette in the past 30 days and about how often they had seen tobacco use on television, in movies, and in social media content. Respondents were also asked about cigarette use in the past 30 days, and a series of additional questions that have been shown to be predictive of tobacco use. Logistic regression was used to test for our main prediction that reported exposure to social media tobacco depictions at time 1 would influence time 2 smoking behavior. Encoded exposure to social media tobacco depictions (B = .47, p < .05) was a significant predictor of time 2 smoking, even after controlling for all the aforementioned predictors. Our results suggest that social media depictions of tobacco use predict future smoking tendency, over and above the influence of TV and movie depictions of smoking. This is the first known study to specifically assess the role of social media in informing tobacco behavior.


Relationship of education to the racial gap in neonatal and postneonatal mortality.
To examine the impact of education on race differences in neonatal and postneonatal mortality. Data were from North Carolina's Linked Birth and Infant Death File for 1988 through 1993. The study population included 169,601 African American births and 400,359 European American births, with 2606 and 3060 deaths, respectively. Multiple logistic regression was used to assess the effects of race and education on neonatal and postneonatal mortality, adjusting for sociodemographic, lifestyle, and medical risk factors. Risks of death were higher for African Americans than for European Americans, more so in the neonatal than in the postneonatal period. Odds ratios (with 95% confidence intervals in parentheses) comparing African Americans to European Americans were as follows: neonatal deaths, 2.2 (1.9-2.5), 2.3 (2.1-2.6), and 2.8 (2.5-3.2) for less than 12, 12, and more than 12 years of education; and postneonatal deaths, 1.3 (1.1-1.6), 1.5 (1.3-1.7), and 2.1 (1.7-2.6), respectively. The biggest gap was for deaths in the first day of life, with odds ratios ranging from 2.8 to 3.6. Education had no impact on neonatal mortality in either race. Medical factors were more influential in the neonatal than in the postneonatal period, whereas environmental and social factors appeared to play a greater role in the postneonatal period. Racial differences in neonatal death are increasing and may be related to inequities in the provision of health care. The racial gap in the postneonatal period, although declining, has not disappeared and may be more related to environmental, social, and economic factors.


Interrater Reliability of Osteopathic Sacral Palpatory Diagnostic Tests Among Osteopathy Students.
Somatic dysfunctions are a key element of osteopathic practice. The evaluation of somatic dysfunctions is achieved by assessment of the TART (tissue texture abnormality, asymmetry, restriction of motion, tenderness) parameters. The reliability of a diagnostic method is the crux of successful treatment. Interrater reliability of osteopathic palpatory diagnostic tests have been studied on different anatomical areas, but there are no studies on the evaluation of all of the TART parameters on the sacrum. To evaluate the interrater reliability of osteopathic sacral palpatory diagnostic tests. The hypothesis was that 3 trained osteopathy students at the end of their curriculum could achieve at least moderate agreement on osteopathic sacral palpatory diagnostic tests. Three students from the Centre pour l'Étude, la Recherche et la Diffusion Ostéopathiques school in Rome, Italy, at the end of their curriculum participated as raters and received consensus training. Eligible subjects among students of the same school were recruited on a voluntary basis to be tested. All of the raters tested the sacrum by evaluating the TART parameters on every subject for 3 minutes. Raters were blinded to the other raters' findings. Interrater reliability was evaluated using Fleiss κ statistics. Fifty-two subjects (20 women) were enrolled in the study. Mean (SD) age was 25.9 (7.03) years; height, 1.73 (0.09) ms; weight, 68.73 (14.2) kg; and body mass index, 22.66 (3.58). Agreement was fair for tissue texture abnormality (κ=0.28), asymmetry (κ=0.29), restriction of motion (κ=0.32), and tenderness (κ=0.34); agreement was slight for landmark position (κ=0.06) and diagnosis of somatic dysfunction (κ=0.17). Results showed a level of agreement ranging from slight to fair in the assessment of the TART parameters among raters, who were in their last year of osteopathy school. The tenderness parameter was the most reliable. Our findings are consistent with other interrater reliability studies carried out in different body regions, contributing to show an overall heterogeneous level of diagnostic reliability in osteopathy.


Reinvestigating an enigmatic Late Cretaceous monocot: morphology, taxonomy, and biogeography of Viracarpon.
Angiosperm-dominated floras of the Late Cretaceous are essential for understanding the evolutionary, ecological, and geographic radiation of flowering plants. The Late Cretaceous-early Paleogene Deccan Intertrappean Beds of India contain angiosperm-dominated plant fossil assemblages known from multiple localities in central India. Numerous monocots have been documented from these assemblages, providing a window into an important but poorly understood time in their diversification. One component of the Deccan monocot diversity is the genus Viracarpon, known from anatomically preserved infructescences. Viracarpon was first collected over a century ago and has been the subject of numerous studies. However, resolution of its three-dimensional (3D) morphology and anatomy, as well as its taxonomic affinities, has remained elusive. In this study we investigated the morphology and taxonomy of genus Viracarpon, combining traditional paleobotanical techniques and X-ray micro-computed tomography (μCT). Re-examination of type and figured specimens, 3D reconstructions of fruits, and characterization of structures in multiple planes of section using μCT data allowed us to resolve conflicting interpretations of fruit morphology and identify additional characters useful in refining potential taxonomic affinities. Among the four Viracarpon species previously recognized, we consider two to be valid (Viracarponhexaspermum and Viracarponelongatum), and the other two to be synonyms of these. Furthermore, we found that permineralized infructescences of Coahuilocarpon phytolaccoides from the late Campanian of Mexico correspond closely in morphology to V. hexaspermum. We argue that Viracarpon and Coahuilocarpon are congeneric and provide the new combination, Viracarpon phytolaccoides (Cevallos-Ferriz, Estrada-Ruiz & Perez-Hernandez) Matsunaga, S.Y. Smith, & Manchester comb. nov. The significant geographic disjunction between these two occurrences indicates that the genus Viracarpon was widespread and may be present in other Late Cretaceous assemblages. Viracarpon exhibits character combinations not present in any extant taxa and its affinities remain unresolved, possibly representing an extinct member of Alismatales. The character mosaic observed in Viracarpon and the broad distribution of the genus provide new data relevant to understanding early monocot evolution and suggest that the (thus far) largely invisible Late Cretaceous monocot diversification was characterized by enigmatic and/or stem taxa.


Harmonised collection of data in youth mental health: Towards large datasets.
The current international trend is to create large datasets with existing data and/or deposit newly collected data into repositories accessible to the scientific community. These practices lead to more efficient data sharing, better detection of small effects, modelling of confounders, establishment of sample generalizability and identification of differences between any given disorders. In Australia, to facilitate such data-sharing and collaborative opportunities, the Neurobiology in Youth Mental Health Partnership was created. This initiative brings together specialised researchers from around Australia to work towards a better understanding of the cross-diagnostic neurobiology of youth mental health and the translation of this knowledge into clinical practice. One of the mandates of the partnership was to develop a protocol for harmonised prospective collection of data across research centres in the field of youth mental health in order to create large datasets. Four key research modalities were identified: clinical assessments, brain imaging, neurocognitive assessment and collection of blood samples. This paper presents the consensus set of assessments/data collection that has been selected by experts in each domain. The use of this core set of data will facilitate the pooling of psychopathological and neurobiological data into large datasets allowing researchers to tackle important questions requiring very large numbers. The aspiration of this transdiagnostic approach is a better understanding of the mechanisms underlying mental illnesses.


Exploring the differences in general practitioner and health care specialist utilization according to education, occupation, income and social networks across Europe: findings from the European social survey (2014) special module on the social determinants of health.
Low socioeconomic position (SEP) tends to be linked to higher use of general practitioners (GPs), while the use of health care specialists is more common in higher SEPs. Despite extensive literature in this area, previous studies have, however, only studied health care use by income or education. The aim of this study is, therefore, to examine inequalities in GP and health care specialist use by four social markers that may be linked to health care utilization (educational level, occupational status, level of financial strain and size and frequency of social networks) across 20 European countries and Israel. Logistic regression models were employed using data from the seventh round of the European Social Survey; this study focused upon people aged 25–75 years, across 21 countries. Health care utilization was measured according to self-reported use of GP or specialist care within 12 months. Analyses tested four social markers: income (financial strain), occupational status, education and social networks. We observed a cross-national tendency that countries with higher or equal probability of GP utilization by lower SEP groups had a more consistent probability of specialist use among high SEP groups. Moreover, countries with inequalities in GP use in favour of high SEP groups had comparable levels of inequalities in specialist care utilization. This was the case for three social markers (education, occupational class and social networks), while the pattern was less pronounced for income (financial strain). There are significant inequalities associated with GP and specialist health care use across Europe—with higher SEP groups more likely to use health care specialists, compared with lower SEP groups. In the context of health care specialist use, education and occupation appear to be particularly important factors.


The Role of Pleiotropy in the Evolutionary Maintenance of Positive Niche Construction.
Organisms often modify their environments to their advantage through a process of niche construction. Environments that are improved through positive niche construction can be viewed as a public good. If free riders appear that do not contribute to the shared resource and therefore do not incur any associated costs, the constructed niche may become degraded, resulting in a tragedy of the commons and the extinction of niche constructors. Niche construction can persist if free riders are excluded, for example, if niche constructors monopolize the resource they produce to a sufficient degree. We suggest, however, that the problem of free riders remains because it is possible that nonniche constructors with an enhanced ability to access the resource appear and invade a population of constructors. Using mathematical models we show that positive niche construction can be maintained if it is inextricably linked to a mechanism that makes free riding costly, such as a trait that confers a benefit to only niche constructors. We discuss this finding in terms of genetic interactions and illustrate the principle with a two-locus model. We conclude that positive niche construction can both evolve and be maintained when it has other beneficial effects via pleiotropy. This situation may apply generally to the evolutionary maintenance of cooperation.


Intraocular Pressure, Glaucoma, and Dietary Caffeine Consumption: A Gene-Diet Interaction Study from the UK Biobank.
We examined the association of habitual caffeine intake with intraocular pressure (IOP) and glaucoma and whether genetic predisposition to higher IOP modified these associations. We also assessed whether genetic predisposition to higher coffee consumption was related to IOP. Cross-sectional study in the UK Biobank. We included 121 374 participants (baseline ages, 39-73 years) with data on coffee and tea intake (collected 2006-2010) and corneal-compensated IOP measurements in 2009. In a subset of 77 906 participants with up to 5 web-based 24-hour-recall food frequency questionnaires (2009-2012), we evaluated total caffeine intake. We also assessed the same relationships with glaucoma (9286 cases and 189 763 controls). We evaluated multivariable-adjusted associations with IOP using linear regression and with glaucoma using logistic regression. For both outcomes, we examined gene-diet interactions using a polygenic risk score (PRS) that combined the effects of 111 genetic variants associated with IOP. We also performed Mendelian randomization using 8 genetic variants associated with coffee intake to assess potential causal effects of coffee consumption on IOP. Intraocular pressure and glaucoma. Mendelian randomization analysis did not support a causal effect of coffee drinking on IOP (P > 0.1). Greater caffeine intake was associated weakly with lower IOP: the highest (≥232 mg/day) versus lowest (<87 mg/day) caffeine consumption was associated with a 0.10-mmHg lower IOP (Ptrend = 0.01). However, the IOP PRS modified this association: among those in the highest IOP PRS quartile, consuming > 480 mg/day versus < 80 mg/day was associated with a 0.35-mmHg higher IOP (Pinteraction = 0.01). The relationship between caffeine intake and glaucoma was null (P ≥ 0.1). However, the IOP PRS also modified this relationship: compared with those in the lowest IOP PRS quartile consuming no caffeine, those in the highest IOP PRS quartile consuming ≥ 321 mg/day showed a 3.90-fold higher glaucoma prevalence (Pinteraction = 0.0003). Habitual caffeine consumption was associated weakly with lower IOP, and the association between caffeine consumption and glaucoma was null. However, among participants with the strongest genetic predisposition to elevated IOP, greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence.


Late hepatic artery thrombosis after orthotopic liver transplantation.
Late hepatic artery thrombosis (HAT) is a rare complication after orthotopic liver transplantation (OLT), conventionally described as occurring more than 30 days after surgery. Only a few reports document its course. In a consecutive series of 634 OLTs (704 grafts), 11 patients (1.7%) had late HAT, diagnosed a median of 6 months (range, 1.8 to 79 months) after OLT. Clinical variables were compared with those of 415 patients without HAT who had a complete database and follow-up, including cytomegalovirus (CMV) surveillance. At presentation, 11 patients had fever, 4 patients had jaundice. Hepatic abscesses were present in 6 patients (3 patients with biliary leak), 4 patients had biliary tree necrosis (2 patients with biliary leak), and 1 patient had no biliary complications. Five patients (45%) underwent accessory hepatic artery anastomosis versus 73 patients (17%) without HAT (P <.05). Five patients (45%) with late HAT had CMV infection versus 14% without HAT (P <.05). Two episodes of late HAT (11 and 79 months) occurred in patients who underwent re-OLT for early HAT (3.9%). Re-OLT was performed in 8 patients a median of 11 days (range, 3 to 37 days) after diagnosis (preceded by intravenous antibiotics and percutaneous drainage). The other 3 patients underwent partial hepatectomy (1 patient), external percutaneous drainage as unfit for surgery (1 patient), and antibiotic therapy only (1 patient). Death occurred in 4 patients who underwent re-OLT (50%) because of septicemia at 11, 23, and 60 days after re-OLT and 17 days after a third OLT. There was one late death (30 months) after partial hepatectomy (hepatitis C recurrence) and one death 6 months after long-term biliary drainage because of sepsis. The 5 survivors have good health with normal liver function test results at a median 52 months (range, 6 to 57 months). In conclusion, late HAT presents with fever caused by hepatic abscesses or biliary leak associated with biliary ischemia and necrosis. CMV infection and accessory hepatic artery anastomosis are risk factors for late HAT in our cohort. Early intervention followed by re-OLT can salvage patients.


Issues in the development and implementation of clinical pathways.
Issues related to the development and implementation of clinical pathways require thoughtful planning, collaborative teamwork, and an understanding of the evolutionary nature of this work. Creating an understanding of the purpose behind the development of these guidelines often is only the first issue to be considered. Other common issues include physician involvement, documentation, pathway development, variance data analysis and feedback, and integration with outcomes management activities. Successfully addressing these issues is an ongoing component of a clinical pathway program.


Effect of the administration of recombinant hirudin and/or tissue-plasminogen activator (t-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits.
We evaluated the effect of r-hirudin and/or tissue-plasminogen activator (t-PA) in a model of DIC in rabbits induced by i.v. infusion of 100 micrograms/kg/h/6 h endotoxin. Rabbits were treated with saline (endotoxin control group), r-hirudin at 0.3 mg/kg/h/6 h, t-PA at 0.3 mg/kg for 90 min and r-hirudin plus t-PA at the doses described above. The best results were achieved when r-hirudin and t-PA were infused together. This treatment reduced the consumption of platelets and protein C and attenuated the increase of PAI-1 more efficiently than r-hirudin or t-PA alone. r-Hirudin plus t-PA also resulted in the lowest formation of fibrin deposits in the kidneys. Finally, mortality at 24 h dropped from 70% in the endotoxin control group to 40%, 10% and 0% in the t-PA, r-hirudin and r-hirudin plus t-PA groups respectively. None of the t-PA-infused rabbits which had died by 24 h showed macroscopic signs of haemorrhage. r-Hirudin alone was better than t-PA alone, as was shown by fibrin deposits and mortality. We conclude that r-hirudin and t-PA given simultaneously were more efficient than either given alone in this model of DIC. Effective thrombin inhibition, which could influence other pathophysiological mechanisms apart from coagulation, together with the improvement in fibrinolysis, would explain these results.


An International Position Statement on the Management of Frailty in Diabetes Mellitus: Summary of Recommendations 2017.
The International Position Statement provides the opportunity to summarise all existing clinical trial and best practice evidence for older people with frailty and diabetes. It is the first document of its kind and is intended to support clinical decisions that will enhance safety in management and promote high quality care. The Review Group sought evidence from a wide range of studies that provide sufficient confidence (in the absence of grading) for the basis of each recommendation. This was supported by a given rationale and key references for our recommendations in each section, all of which have been reviewed by leading international experts. Searches for any relevant clinical evidence were generally limited to English language citations over the previous 15 years. The following databases were examined: Embase, Medline/PubMed, Cochrane Trials Register, Cinahl, and Science Citation. Hand searching of 16 key major peer-reviewed journals was undertaken by two reviewers (AJS and AA) and these included Lancet, Diabetes, Diabetologia, Diabetes Care, British Medical Journal, New England Journal of Medicine, Journal of the American Medical Association, Journal of Frailty and Aging, Journal of the American Medical Directors Association, and Journals of Gerontology - Series A Biological Sciences and Medical Sciences. Two scientific supporting statements have been provided that relate to the area of frailty and diabetes; this is accompanied by evidence-based decisions in 9 clinical domains. The Summary has been supported by diagrammatic figures and a table relating to the inter-relations between frailty and diabetes, a frailty assessment pathway, an exercise-based programme of intervention, a glucose-lowering algorithm with a description of available therapies. We have provided an up to date evidence-based approach to practical decision-making for older adults with frailty and diabetes. This Summary document includes a user-friendly set of recommendations that should be considered for implementation in primary, community-based and secondary care settings.


Evidence Supports No Relationship between Obstructive Sleep Apnea and Premolar Extraction: An Electronic Health Records Review.
A controversy exists concerning the relationship, if any, between obstructive sleep apnea (OSA) and the anatomical position of the anterior teeth. Specifically, there has been speculation that extraction orthodontics and retraction of the anterior teeth contributes to OSA by crowding the tongue and decreasing airway space. This retrospective study utilized electronic medical and dental health records to examine the association between missing premolars and OSA. The sample (n = 5,584) was obtained from the electronic medical and dental health records of HealthPartners in Minnesota. Half of the subjects (n = 2,792) had one missing premolar in each quadrant. The other half had no missing premolars. Cases and controls were paired in a 1:1 match on age range, gender, and body mass index (BMI) range. The outcome was the presence or absence of a diagnosis of OSA confirmed by polysomnography. Of the subjects without missing premolars, 267 (9.56%) had received a diagnosis of OSA. Of the subjects with four missing premolars, 299 (10.71%) had received a diagnosis of OSA. The prevalence of OSA was not significantly different between the groups (OR = 1.14, p = 0.144). The absence of four premolars (one from each quadrant), and therefore a presumed indicator of past "extraction orthodontic treatment," is not supported as a significant factor in the cause of OSA.


LPXTG protein InlJ, a newly identified internalin involved in Listeria monocytogenes virulence.
Listeria monocytogenes expresses surface proteins covalently anchored to the peptidoglycan by sortase enzymes. Inactivation of srtA attenuates Listeria virulence in mice (H. Bierne, S. K. Mazmanian, M. Trost, M. G. Pucciarelli, G. Liu, P. Dehoux, L. Jansch, F. Garcia-del Portillo, O. Schneewind, and P. Cossart, Mol. Microbiol. 43:869-881, 2002). We show here that an srtA mutant is more attenuated than an internalin mutant in orally infected guinea pigs and transgenic mice expressing human E-cadherin (hEcad mice), indicating the involvement of other SrtA substrates, LPXTG proteins, in food-borne listeriosis. Data recently generated with a listerial DNA macroarray identified two LPXTG protein-encoding genes present in the genomes of L. monocytogenes strains and absent from all other Listeria species, inlI (lmo0333) and inlJ (lmo2821). They also revealed two other LPXTG protein-encoding genes, ORF29 and ORF2568, present only in a subclass of L. monocytogenes serovars, including the epidemic serovar 4b. We report here that an inlJ deletion mutant, in contrast to inlI and ORF29 mutants, is significantly attenuated in virulence after intravenous infection of mice or oral inoculation of hEcad mice. Interestingly, a DeltaORF2568 strain showed a slight increase in virulence. inlJ encodes a leucine-rich repeat (LRR) protein that is structurally related to the listerial invasion factor internalin. However, the consensus sequence of the InlJ LRR defines a novel subfamily of cysteine-containing LRRs in bacteria. In conclusion, this postgenomic approach identified InlJ as a new virulence factor among the proteins belonging to the internalin family in L. monocytogenes.


2016 White Paper on recent issues in bioanalysis: focus on biomarker assay validation (BAV): (Part 2 - Hybrid LBA/LCMS and input from regulatory agencies).
The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it is specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecules involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This White Paper is published in 3 parts due to length. This part (Part 2) discusses the recommendations for Hybrid LBA/LCMS and regulatory inputs from major global health authorities. Parts 1 (small molecule bioanalysis using LCMS) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) have been published in the Bioanalysis journal, issues 22 and 23, respectively.


Polycyclic aromatic hydrocarbon (PAH) and oxygenated PAH (OPAH) air-water exchange during the deepwater horizon oil spill.
Passive sampling devices were used to measure air vapor and water dissolved phase concentrations of 33 polycyclic aromatic hydrocarbons (PAHs) and 22 oxygenated PAHs (OPAHs) at four Gulf of Mexico coastal sites prior to, during, and after shoreline oiling from the Deepwater Horizon oil spill (DWH). Measurements were taken at each site over a 13 month period, and flux across the water-air boundary was determined. This is the first report of vapor phase and flux of both PAHs and OPAHs during the DWH. Vapor phase sum PAH and OPAH concentrations ranged between 1 and 24 ng/m(3) and 0.3 and 27 ng/m(3), respectively. PAH and OPAH concentrations in air exhibited different spatial and temporal trends than in water, and air-water flux of 13 individual PAHs were strongly associated with the DWH incident. The largest PAH volatilizations occurred at the sites in Alabama and Mississippi in the summer, each nominally 10,000 ng/m(2)/day. Acenaphthene was the PAH with the highest observed volatilization rate of 6800 ng/m(2)/day in September 2010. This work represents additional evidence of the DWH incident contributing to air contamination, and provides one of the first quantitative air-water chemical flux determinations with passive sampling technology.


Eight Weeks of a High Dose of Curcumin Supplementation May Attenuate Performance Decrements Following Muscle-Damaging Exercise.
It is known that unaccustomed exercise-especially when it has an eccentric component-causes muscle damage and subsequent performance decrements. Attenuating muscle damage may improve performance and recovery, allowing for improved training quality and adaptations. Therefore, the current study sought to examine the effect of two doses of curcumin supplementation on performance decrements following downhill running. Sixty-three physically active men and women (21 ± 2 y; 70.0 ± 13.7 kg; 169.3 ± 15.2 cm; 25.6 ± 14.3 body mass index (BMI), 32 women, 31 men) were randomly assigned to ingest 250 mg of CurcuWIN® (50 mg of curcuminoids), 1000 mg of CurcuWIN® (200 mg of curcuminoids), or a corn starch placebo (PLA) for eight weeks in a double-blind, randomized, placebo-controlled parallel design. At the end of the supplementation period, subjects completed a downhill running protocol intended to induce muscle damage. Muscle function using isokinetic dynamometry and perceived soreness was assessed prior to and at 1 h, 24 h, 48 h, and 72 h post-downhill run. Isokinetic peak extension torque did not change in the 200-mg dose, while significant reductions occurred in the PLA and 50-mg groups through the first 24 h of recovery. Isokinetic peak flexion torque and power both decreased in the 50-mg group, while no change was observed in the PLA or 200-mg groups. All the groups experienced no changes in isokinetic extension power and isometric average peak torque. Soreness was significantly increased in all the groups compared to the baseline. Non-significant improvements in total soreness were observed for the 200-mg group, but these changes failed to reach statistical significance. When compared to changes observed against PLA, a 200-mg dose of curcumin attenuated reductions in some but not all observed changes in performance and soreness after completion of a downhill running bout. Additionally, a 50-mg dose appears to offer no advantage to changes observed in the PLA and 200-mg groups.


The effects of low frequency noise on mental performance and annoyance.
Low frequency noise (LFN) as background noise in urban and work environments is emitted from many artificial sources such as road vehicles, aircraft, and air movement machinery including wind turbines, compressors, and ventilation or air conditioning units. In addition to objective effects, LFN could also cause noise annoyance and influence mental performance; however, there are no homogenous findings regarding this issue. The purpose of this research was to study the effects of LFN on mental performance and annoyance, as well as to consider the role of extraversion and neuroticism on the issue. This study was conducted on 90 students of Iran University of Medical Sciences (54 males and 36 females). The mean age of the students was 23.46 years (SD = 1.97). Personality traits and noise annoyance were measured by using Eysenck Personality Inventory and a 12-scale self-reported questionnaire, respectively. Stroop and Cognitrone computerized tests measured mental performance of participants each exposed to 50 and 70 dBA of LFN and silence. LFNs were produced by Cool Edit Pro 2.1 software. There was no significant difference between mental performance parameters under 50 and 70 dBA of LFN, whereas there were significant differences between most mental performance parameters in quiet and under LFN (50 and 70 dBA). This research showed that LFN, compared to silence, increased the accuracy and the test performance speed (p < 0.01). There was no association between LFN and noise annoyance (p > 0.01). Introverts conducted the tests faster than extraverts (p < 0.05). This research showed that neuroticism does not influence mental performance. It seems that LFN has increased arousal level of participants, and extraversion has a considerable impact on mental performance.


Isolation and characterization of bacteria resistant to metallic copper surfaces.
Metallic copper alloys have recently attracted attention as a new antimicrobial weapon for areas where surface hygiene is paramount. Currently it is not understood on a molecular level how metallic copper kills microbes, but previous studies have demonstrated that a wide variety of bacteria, including Escherichia coli, Staphylococcus aureus, and Clostridium difficile, are inactivated within minutes or a few hours of exposure. In this study, we show that bacteria isolated from copper alloy coins comprise strains that are especially resistant against the toxic properties exerted by dry metallic copper surfaces. The most resistant of 294 isolates were Gram-positive staphylococci and micrococci, Kocuria palustris, and Brachybacterium conglomeratum but also included the proteobacterial species Sphingomonas panni and Pseudomonas oleovorans. Cells of some of these bacterial strains survived on copper surfaces for 48 h or more. Remarkably, when these dry-surface-resistant strains were exposed to moist copper surfaces, resistance levels were close to those of control strains and MICs for copper ions were at or below control strain levels. This suggests that mechanisms conferring resistance against dry metallic copper surfaces in these newly isolated bacterial strains are different from well-characterized copper ion detoxification systems. Furthermore, staphylococci on coins did not exhibit increased levels of resistance to antibiotics, arguing against coselection with copper surface resistance traits.


Thrombotic obstruction of the central venous catheter in patients undergoing hematopoietic stem cell transplantation.
This is an integrative literature review with the aim of summarizing the prevention measures and treatment of thrombotic obstruction of long-term semi-implanted central venous catheters, in patients undergoing hematopoietic stem cell transplantation. The sample consisted of seven studies, being two randomized controlled clinical trials, three cohort studies and two case series. Regarding the prevention measures, one single study demonstrated effectiveness, which was a cohort study on the oral use of warfarin. In relation to the treatment measures, three studies evidenced effectiveness, one highlighted the efficacy of streptokinase or urokinase, one demonstrated the benefit of using low-molecular-weight heparin and the other treated the obstruction with heparin or urokinase. Catheter patency research shows a restricted evolution that does not follow the evolution of transplantations, mainly regarding nursing care.


Preparation of size tunable giant vesicles from cross-linked dextran(ethylene glycol) hydrogels.
We present a novel chemically cross-linked dextran-poly(ethylene glycol) hydrogel substrate for the preparation of dense vesicle suspensions under physiological ionic strength conditions. These vesicles can be easily diluted for individual study. Modulating the degree of cross-linking within the hydrogel network results in tuning of the vesicle size distribution.


Folate and vitamin B12: friendly or enemy nutrients for the elderly.
In the UK vitamin B12 deficiency occurs in approximately 20% of adults aged >65 years. This incidence is significantly higher than that among the general population. The reported incidence invariably depends on the criteria of deficiency used, and in fact estimates rise to 24% and 46% among free-living and institutionalised elderly respectively when methylmalonic acid is used as a marker of vitamin B12 status. The incidence of, and the criteria for diagnosis of, deficiency have drawn much attention recently in the wake of the implementation of folic acid fortification of flour in the USA. This fortification strategy has proved to be extremely successful in increasing folic acid intakes pre-conceptually and thereby reducing the incidence of neural-tube defects among babies born in the USA since 1998. However, in successfully delivering additional folic acid to pregnant women fortification also increases the consumption of folic acid of everyone who consumes products containing flour, including the elderly. It is argued that consuming additional folic acid (as 'synthetic' pteroylglutamic acid) from fortified foods increases the risk of 'masking' megaloblastic anaemia caused by vitamin B12 deficiency. Thus, a number of issues arise for discussion. Are clinicians forced to rely on megaloblastic anaemia as the only sign of possible vitamin B12 deficiency? Is serum vitamin B12 alone adequate to confirm vitamin B12 deficiency or should other diagnostic markers be used routinely in clinical practice? Is the level of intake of folic acid among the elderly (post-fortification) likely to be so high as to cure or 'mask' the anaemia associated with vitamin B12 deficiency?


Inferring Aberrant Signal Transduction Pathways in Ovarian Cancer from TCGA Data.
This paper concerns a new method for identifying aberrant signal transduction pathways (STPs) in cancer using case/control gene expression-level datasets, and applying that method and an existing method to an ovarian carcinoma dataset. Both methods identify STPs that are plausibly linked to all cancers based on current knowledge. Thus, the paper is most appropriate for the cancer informatics community. Our hypothesis is that STPs that are altered in tumorous tissue can be identified by applying a new Bayesian network (BN)-based method (causal analysis of STP aberration (CASA)) and an existing method (signaling pathway impact analysis (SPIA)) to the cancer genome atlas (TCGA) gene expression-level datasets. To test this hypothesis, we analyzed 20 cancer-related STPs and 6 randomly chosen STPs using the 591 cases in the TCGA ovarian carcinoma dataset, and the 102 controls in all 5 TCGA cancer datasets. We identified all the genes related to each of the 26 pathways, and developed separate gene expression datasets for each pathway. The results of the two methods were highly correlated. Furthermore, many of the STPs that ranked highest according to both methods are plausibly linked to all cancers based on current knowledge. Finally, CASA ranked the cancer-related STPs over the randomly selected STPs at a significance level below 0.05 (P = 0.047), but SPIA did not (P = 0.083).


Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer's disease.
We have developed an in vitro model in which isolated senile plaque (SP) cores are presented to rat microglial cells in culture. Microglia rapidly phagocytosed, broke apart, and cleared SP cores. However, when cocultured with astrocytes, microglial phagocytosis was markedly suppressed, allowing the SPs to persist. Suppression of phagocytosis by astrocytes appears to be a general phenomena since microglia in the presence of astrocytes showed reduced capacity to phagocytose latex beads as well. The astrocyte effect on microglia is related in part to a diffusible factor(s) since astrocyte- but not fibroblast-conditioned media also reduced phagocytosis. These results suggest that while microglia have the capacity to phagocytose and remove SPs, astrocytes which lie in close association to microglia may help prevent the efficient clearance of SP material allowing them to persist in Alzheimer's disease.


Factors associated with psychotherapy longevity among HIV-positive patients.
Mental health concerns are salient to many HIV-positive individuals, yet, there are also numerous challenges with regard to access and retention in care. The present study sought to investigate factors that are associated with longevity in outpatient psychological care for HIV-positive patients. We aimed to better understand what factors (e.g., race, gender, age, history of mental health service utilization) are associated with the length of participation in psychotherapy in our clinic. This is an archival study consisting of chart review of our clinical documentation related to the psychological services provided in our clinic from January 2005 through December 2007. Eligible charts included all HIV-positive individuals seeking psychotherapy in the Department of Psychiatry and Health Behavior at the Medical College of Georgia (n = 87 records; 33.3% female; 52.9% ethnic minority, 57% sexual minority, middle-aged (42.0 years +/- 9.6 years). Results indicated that the presence of cohabitating social support distinguished between those who continued or terminated after the intake session, with social support being associated with continuation after intake. Furthermore, shorter distance from clinic, history of previous psychotherapy, concurrent pharmacotherapy, comorbid personality disorder diagnosis, and having an ethnic minority provider were associated with greater longevity in treatment. As a result of modest sample size relative to the number of predictor variables, analyses utilized multiple bivariate analyses and thus, results must be considered preliminary and should be replicated in a larger investigation. However, treatment providers may utilize these initial findings to improve retention in care and to improve the quality of mental health care provided to HIV-positive outpatients.


Large-diameter graft-stent (Advanta V12) implantation in various locations: early results.
Transcatheter stent placement carries the risk of cardiovascular aneurysm or rupture. Covered stent implantation reduces these risks. The recently marketed Advanta V12 large-diameter-covered stent is pre-mounted and requires 9 (8)-11 Fr delivery systems. The aim was to report on the early results of the treatment of various cardiovascular obstructions by the implantation of a new polytetrafluoroethylene-covered stent (V12). Graft stents on balloons with a diameter (12, 14, 16 millimetres) sufficient to anchor the stent in various obstructions (congenital aortic coarctation, n = 5; obstruction after ascending aorta repair, n = 2; pulmonary arteries, n = 5; inferior caval vein, n = 1; atretic superior caval vein, n = 1; pulmonary vein obstruction, n = 1; and right ventricular outflow tract, n = 1) were implanted using the smallest available delivery system. Secondary dilation with larger-diameter balloons was performed when the residual pressure was gradient, the stent-vessel wall relationship or stent re-coiling due to different reasons needed a re-intervention by pure ballooning or second stent placement. All 16 patients aged 5-46 years underwent V12 implantation. The variability of the treated lesions and the need for additional interventions were responsible for large ranges in fluoroscopy time between 7.3 to 48.2 minutes (median 17.3). Considering the additional procedures, the V12 stent achieved the desired result in all cases. There were no major complications. At short-term median follow-up of 2 months, all patients are alive and well with no evidence of stent failing. These initial results show that the covered Advanta V12 large-diameter stent is safe and effective in the immediate treatment of various cardiovascular obstructions. Long-term follow-up is required.


A behavioral comparison of male and female adults with high functioning autism spectrum conditions.
Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males.


Automated workflow-based exploitation of pathway databases provides new insights into genetic associations of metabolite profiles.
Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) that associate with clinical phenotypes, but these SNPs usually explain just a small part of the heritability and have relatively modest effect sizes. In contrast, SNPs that associate with metabolite levels generally explain a higher percentage of the genetic variation and demonstrate larger effect sizes. Still, the discovery of SNPs associated with metabolite levels is challenging since testing all metabolites measured in typical metabolomics studies with all SNPs comes with a severe multiple testing penalty. We have developed an automated workflow approach that utilizes prior knowledge of biochemical pathways present in databases like KEGG and BioCyc to generate a smaller SNP set relevant to the metabolite. This paper explores the opportunities and challenges in the analysis of GWAS of metabolomic phenotypes and provides novel insights into the genetic basis of metabolic variation through the re-analysis of published GWAS datasets. Re-analysis of the published GWAS dataset from Illig et al. (Nature Genetics, 2010) using a pathway-based workflow (http://www.myexperiment.org/packs/319.html), confirmed previously identified hits and identified a new locus of human metabolic individuality, associating Aldehyde dehydrogenase family1 L1 (ALDH1L1) with serine/glycine ratios in blood. Replication in an independent GWAS dataset of phospholipids (Demirkan et al., PLoS Genetics, 2012) identified two novel loci supported by additional literature evidence: GPAM (Glycerol-3 phosphate acyltransferase) and CBS (Cystathionine beta-synthase). In addition, the workflow approach provided novel insight into the affected pathways and relevance of some of these gene-metabolite pairs in disease development and progression. We demonstrate the utility of automated exploitation of background knowledge present in pathway databases for the analysis of GWAS datasets of metabolomic phenotypes. We report novel loci and potential biochemical mechanisms that contribute to our understanding of the genetic basis of metabolic variation and its relationship to disease development and progression.


Mitochondrial retrograde signaling inhibits the survival during prolong S/G2 arrest in Saccharomyces cerevisiae.
Cell senescence is dependent on the arrest in cell cycle. Here we studied the role of mitochondrial retrograde response signaling in yeast cell survival under a prolonged arrest. We have found that, unlike G1, long-term arrest in mitosis or S phase results in a loss of colony-forming abilities. Consistent with previous observations, loss of mitochondrial DNA significantly increased the survival of arrested cells. We found that this was because the loss increases the duration of G1 phase. Unexpectedly, retrograde signaling, which is typically triggered by a variety of mitochondrial dysfunctions, was found to be a negative regulator of the survival after the release from S-phase arrest induced by the telomere replication defect. Deletion of retrograde response genes decreased the arrest-induced death in such cells, whereas deletion of negative regulator of retrograde signaling MKS1 had the opposite effect. We provide evidence that these effects are due to alleviation of the strength of the S-phase arrest.


Variation of ion polarizability from vacuum to hydration: insights from Hirshfeld partitioning.
The results of iterative Hirshfeld partitioning on the polarizability of monovalent anions (F(-), Cl(-), and Br(-)) and Na(+) in water clusters ranging from n = 0 to n = 25 are presented. In each case, the ions reach a limiting intrinsic polarizability in the fully hydrated state. For F(-), Cl(-), and Br(-) using B3LYP/aug-cc-pVDZ, the intrinsic polarizabilities in the condensed-phase limit are 47.2 +/- 0.7%, 47.2 +/- 0.3%, and 54.2 +/- 0.4% of their gas-phase value at the corresponding level of theory. The extent of this scaling depends on the basis set (we also consider B3LYP/aug-cc-pVTZ), but intrinsic polarizabilities are generally within 35-55% of the gas-phase value. The sodium cation is the least polarizable in the condensed-phase limit. The average intrinsic polarizability of water in these clusters decreases with the size of the cluster, which is consistent with earlier Hirshfeld analysis of intrinsic polarizabilities of pure water (Krishtal, A.; Senet, P.; Yang, M.; van Alsenoy, C. J. Chem. Phys. 2006, 125, 034312). Further analysis demonstrates that water molecules near ions in sufficiently large clusters (n = 25) have intrinsic polarizabilities similar to those of water molecules fully coordinated in a pure aqueous cluster. The observed binodal distribution of the water intrinsic polarizability within the cluster is attributed to polarizability differences between interior and exterior water molecules. This observation is in qualitative agreement with arguments based on Pauli's exclusion principle that suggest a reduced polarizability for condensed-phase water relative to the vacuum value.


Quantitative assessment of cerebral connectivity deficiency and cognitive impairment in children with prenatal alcohol exposure.
It is common knowledge that alcohol consumption during pregnancy would cause cognitive impairment in children. However, recent works suggested that the risk of drinking during pregnancy may have been exaggerated. It is critical to determine whether and up to which amount the consumption of alcohol will affect the cognitive development of children. We evaluate time-varying functional connectivity using magnetoencephalogram data from somatosensory evoked response experiments for 19 teenage subjects with prenatal alcohol exposure and 21 healthy control teenage subjects using a new time-varying connectivity approach, combining renormalised partial directed coherence with state space modeling. Children exposed to alcohol prenatally are at risk of developing a Fetal Alcohol Spectrum Disorder (FASD) characterized by cerebral connectivity deficiency and impaired cognitive abilities. Through a comparison study of teenage subjects exposed to alcohol prenatally with healthy control subjects, we establish that the inter-hemispheric connectivity is deficient for the former, which may lead to disruption in the cortical inter-hemispheric connectivity and deficits in higher order cognitive functions as measured by an IQ test, for example. We provide quantitative evidence that the disruption is correlated with cognitive deficits. These findings could lead to a novel, highly sensitive biomarker for FASD and support a recommendation of no safe amount of alcohol consumption during pregnancy.


Experimental herbivore exclusion, shrub introduction, and carbon sequestration in alpine plant communities.
Shrub cover in arctic and alpine ecosystems has increased in recent decades, and is predicted to further increase with climate change. Changes in shrub abundance may alter ecosystem carbon (C) sequestration and storage, with potential positive feedback on global C cycling. Small and large herbivores may reduce shrub expansion and thereby counteract the positive feedback on C cycling, but herbivore pressures have also changed in the alpine-arctic tundra; the increased shrub cover together with changes in herbivore pressure is leading to unpredictable changes in carbon sequestration and storage. In this study we investigate the importance of herbivory and shrub introduction for carbon sequestration in the short term. We measured standing biomass and daytime mid-growing season carbon fluxes in plots in a full factorial design where we excluded small and large mammalian herbivores and introduced Salix by planting Salix transplants. We used three study sites: one Empetrum-dominated heath, one herb- and cryptogam-dominated meadow, and one Salix-dominated shrub community in the low-alpine zone of the Dovre Mountains, Central Norway. After 2 years, significant treatment effects were recorded in the heath community, but not in the meadow and shrub communities. In the heath community cessation of herbivory increased standing biomass due to increased biomass of dwarf shrubs. Cessation of herbivory also reduced biomass of bryophytes and ecosystem respiration (ER). Except for an increase in biomass of deciduous shrubs caused by the Salix introduction, the only effect of Salix introduction was an increase in biomass of graminoids in the heath. Our short-term study demonstrated that herbivore exclusion had small but still significant effects on heath vegetation, whereas such effects were not apparent in the herb-and cryptogam-dominated meadow and the Salix-dominated shrub community. Following the treatments over more years is needed to estimate the long-term effects on community structure and the consequences for C sequestration in the three plant communities. Such data are important for predicting the impact of shrub expansion on C budgets from alpine regions.


In situ synthesis of zeolitic imidazolate frameworks/carbon nanotube composites with enhanced CO₂ adsorption.
A series of ZIF-8 and hydroxyl-functionalized carbon nanotube (CNT) composites were successfully synthesized by the solvothermal method. The obtained ZIF-8/CNT composites were characterized by XRD, SEM, TGA and N2 adsorption at 77 K. The contents of ZIF-8 and CNTs in the composites were calculated from thermal analysis data. CO2 and N2 adsorption at 273 K on the composites was also investigated and compared. The ZIF-8 particles in the composites exhibit similar crystal structures and morphology to those of pure ZIF-8, but display enhanced thermal stability. The surface areas and pore volumes of the ZIF-8/CNT composites are higher than the values calculated for hypothetical physical mixtures, and the synergetic effect between ZIF-8 and CNTs can be proposed. This phenomenon demonstrates that the incorporation of CNTs into ZIF-8 can facilitate the nucleation and crystallization of ZIF-8. As a result, the composites with an optimal CNT content (3.63 wt%) show improved CO2 adsorption capacity and higher relative selectivity for CO2/N2 compared with pure ZIF-8.


Influence of cartilage on reactivity and on the effectiveness of verapamil in guinea pig isolated airway smooth muscle.
The authors have examined the effects of cartilage removal on smooth muscle reactivity and the action of verapamil in guinea pig trachealis. In preparations devoid of cartilage, smooth muscle reactivity to both histamine and KCl was reduced. Reactivity to methacholine was unaffected by cartilage removal. In the absence of cartilage, verapamil had a greater depressant effect on the maximum responses to histamine and methacholine than in intact tissues. Similarly, verapamil was more potent against histamine- and methacholine-induced responses in the absence of cartilage where a greater shift to the right was seen in the concentration-response curves when compared with cartilage-containing controls. The spasmolytic action of verapamil on methacholine-induced responses was greater in the absence of cartilage and was greater than its antispasmogenic activity against methacholine (whether or not cartilage was present). Thus, cartilage removal reduces muscle reactivity and increases the potency of verapamil in guinea pig trachealis.


Surface-modified nanoparticles enhance transurothelial penetration and delivery of survivin siRNA in treating bladder cancer.
Penetration of the bladder permeability barrier (BPB) is a major challenge when treating bladder diseases via intravesical delivery. To increase transurothelial migration and tissue and tumor cell uptake, poly(lactic-co-glycolic acid; PLGA) nanoparticles (NP) were modified by addition of a low molecular weight (2.5 or 20 kDa) positively charged mucoadhesive polysaccharide, chitosan, to the NP surface. In designing these NPs, we balanced the adhesive properties of chitosan with the release and bioactivity of the siRNA. Chitosan-functionalized NPs demonstrated increased binding to and uptake in intravesically instilled mouse bladders and human ureter at 10 times the level of unmodified NPs. Furthermore, we extended the bioactivity of survivin siRNA in vitro for up to 9 days and demonstrated a decrease in proliferation when using chitosan-modified NPs relative to unmodified NPs. In addition, treatment of xenograft tumors with chitosan-modified NPs that encapsulate survivin siRNA (NP-siSUR-CH2.5) resulted in a 65% reduction in tumor volume and a 75% decrease in survivin expression relative to tumors treated with blank chitosan NPs (NP-Bk-CH2.5). Our low molecular weight chitosan delivery system has the capacity to transport large amounts of siRNA across the urothelium and/or to the tumor site, thus increasing therapeutic response.


Nano-SQUIDs with controllable weak links created via current-induced atom migration.
As the most sensitive magnetic field sensor, the superconducting quantum interference device (SQUID) became an essential component in many applications due to its unmatched performance. Through recently achieved miniaturization, using state-of-the-art fabrication methods, this fascinating device extended its functionality and became an important tool in nanomaterial characterization. Here, we present an accessible and yet powerful technique of targeted atom displacement in order to reduce the size of the weak links of a DC nano-SQUID beyond the limits of conventional lithography. The controllability of our protocol allows us to characterize in situ the full superconducting response after each electromigration step. From this in-depth analysis, we reveal an asymmetric evolution of the weak links at cryogenic temperatures. A comparison with time resolved scanning electron microscopy images of the atom migration process at room temperature confirms the peculiar asymmetric evolution of the parallel constrictions. Moreover, we observe that when electromigration has sufficiently reduced the junction's cross section, superconducting phase coherence is attained in the dissipative state, where magnetic flux readout from voltage becomes possible.


SUMOylation of the lens epithelium-derived growth factor/p75 attenuates its transcriptional activity on the heat shock protein 27 promoter.
Lens epithelium-derived growth factor (LEDGF) proteins p75 and p52 are transcriptional coactivators that connect sequence-specific activators to the basal transcription machinery. We have found that these proteins are posttranslationally modified by SUMO (small ubiquitin-like modifier)-1 and SUMO-3. Three SUMOylation sites, K75, K250, and K254, were mapped on the shared N-terminal region of these molecules, while a fourth site, K364, was identified in the C-terminal part exclusive of LEDGF/p75. The N-terminal SUMO targets are located in evolutionarily conserved charge-rich regions that lack resemblance to the described consensus SUMOylation motif, whereas the C-terminal SUMO target is solvent exposed and situated in a typical consensus motif. SUMOylation did not affect the cellular localization of LEDGF proteins and was not necessary for their chromatin-binding ability, nor did it affect this activity. However, lysine to arginine mutations of the identified SUMO acceptor sites drastically inhibited LEDGF SUMOylation, extended the half-life of LEDGF/p75, and significantly increased its transcriptional activity on the heat shock protein 27 promoter, indicating a negative effect of SUMOylation on the transcriptional activity of LEDGF/p75. Considering that SUMOylation is known to negatively affect the transcriptional activity of all transcription factors known to transactivate heat shock protein 27 expression, these findings support the paradigm establishing SUMOylation as a global neutralizer of cellular processes upregulated upon cellular stress.


A new hydrostatic anti-G suit vs. a pneumatic anti-G system: preliminary comparison.
A newly developed hydrostatic anti-G suit is now commercially available. The suit is said to offer a high level of protection against +Gz acceleration. However, past experience shows that it is difficult to produce a hydrostatic suit with effective high-G protection. Careful testing is, therefore, needed to verify its efficacy. The G-protective properties of the hydrostatic anti-G suit (Libelle; L) were compared with those of a pneumatic anti-G ensemble (AGE-39) used in the Swedish JAS 39 Cripen aircraft. Three pilots were studied during vertical (+Gz) acceleration in a centrifuge using the following: 1) the L-suit with varied straining maneuvers; 2) the AGE-39 in combination with full anti-G straining maneuvers (AGSM) throughout each high-G exposure (full maneuver; FM); and 3) the AGE-39 in combination with AGSM during the initial part of each high-G exposure (reduced maneuver; RM). G-intensity tolerance was established during exposures to rapid onset rate (ROR) profiles with G-plateau levels ranging from +6.0 to +9.0 Gz. G-endurance was studied during simulated aerial combat maneuvers (SACM) consisting of 10 cycles of 5.5 to 7.5 G. All three pilots tolerated 9.0 G with the pneumatic system both in the RM and FM conditions; their tolerances averaged 6.3 G (range 6.0 to 7.0 G) for the L suit. Thus, during the ROR exposures only the 6.0 G profile was completed by all subjects in all three conditions. At this G-load both muscle straining (as indicated by electromyographic activity in thigh and abdomen) and heart rate were higher in the L than in the RM condition. Mean arterial pressure at eye level was higher in the FM than in the L and RM conditions. Only one subject was able to complete the SACM profile in the L condition. In the RM condition all subjects completed the SACM profile and in the FM condition two subjects completed the SACM. Whether the AGE-39 was used in combination with maximal AGSM throughout the duration of each high-G exposure or with AGSM only during the initial part of the high-G exposure, G-intensity tolerance was 9.0 G. While wearing the L-suit, G-tolerance was 6.3 G. Thus, under the conditions tested, the G-protection afforded by the L-suit is not adequate for use in a 9-G aircraft.


Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells.
We have used the nested polymerase chain reaction (PCR) combined with fluorescence-activated cell sorting to define sites of latency of human cytomegalovirus (HCMV) in the peripheral blood of healthy subjects. Peripheral blood mononuclear (PBM) cells were separated into T cell or non-T cell populations and monocytes, and were then analysed by PCR for the presence of HCMV DNA. In five of six seropositive subjects, HCMV was found predominantly in the non-T cell population. Further analysis suggested that the virus was present in adherent cells and CD14+ cells. In three of nine seronegative subjects we could demonstrate HCMV DNA, which we do not believe was due to contamination, reproducibly by PCR. In one of these seronegative subjects, HCMV DNA was present predominantly in the non-T cell fraction of PBM cells. No HCMV DNA was detectable in the remaining six seronegative subjects. We conclude that, within the PBM cells of normal asymptomatic seropositive and some seronegative subjects, HCMV is present predominantly in the monocyte fraction. In addition, the detection of HCMV sequences in seronegative subjects may indicate that infection with HCMV is more widespread than conventional seroepidemiology suggests.


Complex spatial filtering with binary masks.
Usually a hologram is produced by means of an interference experiment. Here, however, we let a computer- guided plotter draw the hologram. The plot, which has to be minified and recorded on film, contains no grey, only binary transmittance values. Our binary holograms yield reconstructed images of a quality equal to that of images obtained from usual holograms of comparable dimensions. When a Fourier hologram is inserted into the Fraunhofer plane of a coherent image forming system, it acts as a special type of a spatial filter, a so-called optical matched filter. Our binary matched filter is suitable for optical character recognition, the same as the usual optical matched filter introduced by Vander Lugt.


Heightened resistance of the neonatal brain to ischemia-reperfusion involves a lack of mitochondrial damage in the nerve terminal.
Mitochondria are known targets of ischemia-reperfusion injury in adult brain. Although neonates are more resistant to ischemic episodes, the mechanisms accounting for this are not yet fully understood. The aim of this study therefore was to determine whether a difference in post-ischemic mitochondrial function may play a role in the heightened recovery of the neonatal brain following ischemia-reperfusion. We have therefore compared the effects of an in vitro model of ischemia on the enzymes of the mitochondrial respiratory chain in isolated nerve terminals (synaptosomes) from neonatal and adult rats. Ischemia caused a significant, reversible decrease in mitochondrial Complex I activity in both adult and neonatal preparations. In neonatal preparations alone, ischemia also led to a significant decrease in mitochondrial Complexes II-III activity. Following 30 min of reperfusion mitochondrial Complexes II-III and IV exhibited decreased activity in synaptosomes from adult, but not neonatal rats. These data suggest a difference in the susceptibility of adult as compared to neonatal nerve terminal mitochondria to ischemia-reperfusion. These data show for the first time that nerve terminal mitochondria from immature animals remain undamaged following a period of ischemia and reperfusion, in contrast to nerve terminal mitochondria from the adult brain. This adds to the growing body of evidence that mitochondrial function plays a key role in neuronal death following cerebral ischemia reperfusion.


Real-time control strategy for simultaneous nitrogen and phosphorus removal using aerobic granular sludge.
To achieve stable and simultaneous removal of nitrogen and phosphorus using aerobic granular sludge in a sequencing batch reactor, a real-time control strategy was established, where time derivatives of electric conductivity (EC) and pH were monitored to facilitate the determinations of ends of phosphate release, nitrification and denitrification as well as corresponding optimum time-lengths of anaerobic, oxic, and anoxic phases in treatment cycles. Although biomass concentration in a reactor drastically fluctuated at the startup period because of very short sludge settling time for the formation of aerobic granular sludge, cycle length for proper treatment was automatically adjusted in this control system. Even when characteristics of influent wastewater markedly fluctuated, stable nitrogen and phosphorus removal was successfully attained both before and at pseudo-steady-state. Effluent concentrations of NH4-N, NOx-N and PO4-P were always lower than 0.3 mg/L. On the other hand, when time lengths of the anaerobic/oxic/anoxic phases were fixed, stable nitrogen and phosphorus removal was not accomplished. Therefore, it is clear that the designed control system is very effective to obtain stable treatment performance in simultaneous nitrogen and phosphorus removal by aerobic granular sludge.


Living ring-opening homo- and copolymerisation of ε-caprolactone and L-lactide by cyclic β-ketiminato aluminium complexes.
A series of novel aluminium complexes containing cyclic β-ketiminato ligands of type Me2Al{O-[(ArN=CHC4H4(C6H4))]} (3a, Ar = 2,6-(i)Pr2C6H3; 3b, Ar = C6H5; 3c, Ar = C6F5) have been prepared in high yields. These complexes were identified by (1)H, (13)C NMR spectroscopy and elemental analysis. X-ray structural analyses for 3a-c revealed that these complexes have a distorted tetrahedral geometry around Al, and both bond distances and bond angles were considerably influenced by the ligand structure. These complexes were tested as catalyst precursors for ring-opening polymerisation of ε-caprolactone (ε-CL) and L-lactide (L-LA) in the presence of 2-propanol as an initiator. Complex 3a could polymerize ε-CL in a controlled manner with high efficiency. Based on the living characteristics, the preparation of well-defined block copolymers PCL-b-PLLA via sequential addition of monomers was performed by 3a. Note that complex 3c exhibited rather high catalytic activity for the ROP of L-LA with narrow molecular weight distribution. The monomer conversion reached completion only in 4 h when the L-LA/Al molar ratio was 100 at 80 °C. PLLA-b-PCL copolymers were thus easily produced by 3c.