Combined effects of warming and acidification on accumulation and elimination dynamics of paralytic shellfish toxins in mussels Mytilus galloprovincialis.
Harmful algal blooms (HAB) have been increasing in frequency and intensity most likely due to changes on global conditions, which constitute a significant threat to wild shellfish and its commercial farming. This study evaluated the impact of increasing seawater temperature and acidification on the accumulation/elimination dynamics of HAB-toxins in shellfish. Mytilus galloprovincialis were acclimated to four environmental conditions simulating different climate change scenarios: i) current conditions, ii) warming, iii) acidification and iv) interaction of warming with acidification. Once acclimated, mussels were exposed to the paralytic shellfish toxins (PSTs) producing dinoflagellate Gymnodinium catenatum for 5 days and to non-toxic diet during the subsequent 10 days. High toxicity levels (1493 µg STX eq. kg-1) exceeding the safety limits were determined under current conditions at the end of the uptake period. Significantly lower PSP toxicity levels were registered for warming- and acidification-acclimated mussels (661 and 761 µg STX eq. kg-1). The combined effect of both warming and acidification resulted in PSP toxicity values slightly higher (856 μg STX eq. kg-1). A rapid decrease of toxicity was observed in mussels at the current conditions after shifting to a non-toxic diet, which was not noticed under the predicted climate change scenarios. Variability of each PST analogue, measured throughout the experiment, highlighted different mechanisms are associated with changes of each environmental factor, although both resulting in lower toxicity. Warming-acclimated mussels showed lower accumulation/elimination rates, while acidification-acclimated mussels showed higher capability to accumulate toxins, but also a higher elimination rate preventing high toxicity levels. As different mechanisms are triggered by warming and acidification, their combined effect not leads to a synergism of their individual effects. The present work is the first assessing the combined effect of climate change drivers on accumulation/elimination of PSTs, in mussels, indicating that warming and acidification may lead to lower toxicity values but longer toxic episodes. PSTs are responsible for the food poisoning syndrome, paralytic shellfish poisoning (PSP) in humans. This study can be considered as the first step to build models for predicting shellfish toxicity under climate change scenarios.


First-order wedge wetting revisited.
We consider a fluid adsorbed in a wedge made from walls that exhibit a first-order wetting transition and revisit the argument as to why and how the pre-filling and pre-wetting coexistence lines merge when the opening angle is increased approaching the planar geometry. We clarify the nature of the possible surface phase diagrams, pointing out the connection with complete pre-wetting, and show that the merging of the coexistence lines lead to new interfacial transitions. These occur along the side walls and are associated with the unbinding of the thin-thick interface, rather than the liquid-gas interface (meniscus), from the wedge apex. When fluctuation effects, together with the influence of dispersion forces are included, these transitions display strong non-universal critical singularities that depend on the opening angle itself. Similar phenomena are also shown to occur for adsorption near an apex tip.


Creutzfeldt-Jakob disease and vision.
This review describes a group of diseases known as the transmissible spongiform encephalopathies (TSEs), which affect animals and humans. Examination of affected brain tissue suggests that these diseases are caused by the acquisition and deposition of prion protein (PrP). Creutzfeldt-Jakob disease (CJD) is the most important form of TSE in humans with at least four different varieties of the disease. Variant CJD (vCJD), a new form of the disease found in the UK, has several features that differ from the classical forms including early age of onset, longer duration of disease, psychiatric presentation (for example, depression) and extensive florid plaque development in the brain. About 10 per cent of patients with CJD exhibit visual symptoms at disease presentation and approximately 50 per cent during the course of the disease. The most commonly reported visual symptoms include diplopia, supranuclear palsies, complex visual disturbances, homonymous visual field defects, hallucinations and cortical blindness. Saccadic and smooth pursuit movements appear to be more rarely affected. The agent causing vCJD accumulates in lymphoid tissue such as the spleen and tonsils. The cornea has lymphoid tissue in the form of corneal dendritic cells that are important in the regulation of the immune response in the anterior segment of the eye. The presence of these cells in the cornea has raised the possibility of transmission between patients via optical devices that contact the eye. Although such transmission is theoretically possible it remains highly improbable.


Risk characterization for nanotechnology.
Nanotechnology is a broad term that encompasses materials, structures, or processes that utilize engineered nanomaterials, which can be defined as materials intentionally designed to have one or more dimensions between 1 and 100 nm. Historically, risk characterization has been viewed as the final phase of a risk assessment process that integrates hazard identification, dose-response assessment, and exposure assessment. The novelty and diversity of materials, structures, and tools that are covered by above-defined "nanotechnology" raise substantial methodological issues and pose significant challenges for each of these phases of risk assessment. These issues and challenges culminate in the risk characterization phase of the risk assessment process, and this article discusses several of these key issues and approaches to developing risk characterization results and their implications for risk management decision making that are specific to nanotechnology.


Study of dissolution hydrodynamic conditions versus drug release from hypromellose matrices: the influence of agitation sequence.
In this article, the influence of agitation in descending and ascending sequences as a systematic method development process for potentially discriminating fed and fasted states and evaluation of its effects on the drug release from swelling gel-forming hydrophilic matrix tablets were investigated. Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC)) were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus at 5, 10, 15, 20, 25 and 30 dips per minute (dpm). Agitation had a profound effect on the drug release from the HPMC K100LV matrices. Drug release in pH 1.2 changed from about 40% at 5 dpm to about 80% at 30 dpm over a 60 min period alone. The matrices containing HPMC K4M, K15M and K100M however were not significantly affected by the agitation rate. The similarity factor f2 was calculated using drug release at 10 dpm as a reference. The ascending agitations of 5-30 dpm and the descending order of agitation 30-5 dpm were also evaluated. Anomalous transport was the only kinetic of release for the K4M, K15M and K100M tablet matrices. The lower viscous polymer of K100LV had some matrices exhibiting Fickian diffusion as its kinetics of release. The use of systematic change of agitation method may indicate potential fed and fasted effects on drug release from hydrophilic matrices.


Guest exchange through single crystal-single crystal transformations in a flexible hydrogen-bonded framework.
A molecular framework based on guanidinium cations and 1,2,4,5-tetra(4-sulfonatophenyl)benzene (TSPB), an aromatic tetrasulfonate with nominal 2-fold and mirror symmetry, exhibits three crystallographically unique one-dimensional channels as a consequence of molecular symmetry and complementary hydrogen bonding between the guanidinium (G) ions and the sulfonate (S) groups of TSPB. Unlike previous GS frameworks, this new topology is sufficiently flexible to permit reversible release and adsorption of guest molecules in large single crystals through a cyclic shrinkage and expansion of the channels with retention of single crystallinity, as verified by single crystal X-ray diffraction. Moreover, the G4TSPB framework permits guest exchange between various guest molecules through SCSCTs as well as exchange discrimination based on the size and character of the three different channels. The exchange of guest molecules during single crystal-single crystal transformations (SCSCT), a rare occurrence for hydrogen-bonded frameworks, is rather fast, with diffusivities of approximately 10(-6) cm(2) s(-1). Rapid diffusion in the two channels having cross sections sufficient to accommodate two guest molecules can be explained by two-way or ring diffusion, most likely vacancy assisted. Surprisingly, rapid guest exchange also is observed in a smaller channel having a cross-section that accommodates only one guest molecule, which can only be explained by guest-assisted single-file unidirectional diffusion. Several single crystals of inclusion compounds can be realized only through guest exchange in the intact framework, suggesting an approach to the synthesis of single crystalline inclusion compounds that otherwise cannot be attained through direct crystallization methods.


A biomaterial model of tumor stromal microenvironment promotes mesenchymal morphology but not epithelial to mesenchymal transition in epithelial cells.
The stromal tissue surrounding most carcinomas is comprised of an extracellular matrix densely packed with collagen-I fibers, which are often highly aligned in metastatic disease. Here we developed an in vitro model to test the effect of an aligned fibrous environment on cancer cell morphology and behavior, independent of collagen ligand presentation. We grew cells on a biomimetic surface of aligned electrospun poly-l-lactic acid (PLLA) fibers and then examined the effect of this environment on growth rate, morphology, cytoskeletal organization, biochemical and genetic markers of epithelial to mesenchymal transition (EMT), cell surface adhesion, and cell migration. We grew a phenotypically normal breast epithelial cell line (MCF10A) and an invasive breast cancer cell line (MDA-MB-231) on three different substrates: typical flat culture surface (glass or plastic), flat PLLA (glass coated with PLLA) or electrospun PLLA fibers. Cells of both types adopted a more mesenchymal morphology when grown on PLLA fibers, and this effect was exaggerated in the more metastatic-like MDA-MB-231 cells. However, neither cell type underwent the changes in gene expression indicative of EMT despite the changes in cell shape, nor did they exhibit the decreased adhesive strength or increased migration typical of metastatic cells. These results suggest that changes in cell morphology alone do not promote a more mesenchymal phenotype and consequently that the aligned fibrous environment surrounding epithelial cancers may not promote EMT solely through topographical cues.


The lunar cycle drives migration of a nocturnal bird.
Every year, billions of seasonal migrants connect continents by transporting nutrients, energy, and pathogens between distant communities and ecosystems. For animals that power their movements by endogenous energy stores, the daily energy intake rates strongly influence the speed of migration. If access to food resources varies cyclically over the season, migrants sensitive to changes in daily energy intake rates may adjust timing of migration accordingly. As an effect, individuals adjusting to a common temporal cycle are expected to approach synchrony in foraging and movement. A large-scale periodic pattern, such as the dark-light cycle of the moon, could thus synchronize migrations across animal populations. However, such cyclic effects on the temporal regulation of migration has not been considered. Here, we show the temporal influence of the lunar cycle on the movement activity and migration tactics in a visual hunting nocturnal insectivore and long-distance migrant, the European nightjar, Caprimulgus europeaus. We found that the daily foraging activity more than doubled during moonlit nights, likely driven by an increase in light-dependent fuelling opportunities. This resulted in a clear cyclicity also in the intensity of migratory movements, with occasionally up to 100% of the birds migrating simultaneously following periods of full moon. We conclude that cyclic influences on migrants can act as an important regulator of the progression of individuals and synchronize pulses of migratory populations, with possible downstream effects on associated communities and ecosystems.


Perioperative Treatment with a Prolyl Hydroxylase Inhibitor Reduces Necrosis in a Rat Ischemic Skin Flap Model.
The hypoxia-inducible factor (HIF) pathway, regulated by prolyl hydroxylase, is central to tissue adaptation to ischemia. The authors tested whether the prolyl hydroxylase inhibitor dimethyloxalylglycine reduces skin flap necrosis. Dorsal skin flaps were raised on hairless rats, with dimethyloxalylglycine delivered intraperitoneally and/or topically for 7 days before and after surgery. After 14 treatment days, percentage of flap necrosis was compared grossly and tissue perfusion compared with an in vivo imaging system. Angiogenesis was compared using immunohistochemical CD31 staining and enzyme-linked immunosorbent assay for tissue vascular endothelial growth factor. Expression levels of HIF-1α and terminal deoxynucleotidyl transferase-mediated dUDP end-labeling were compared using immunohistochemical staining. Complete blood counts and gross necropsy specimens were obtained to assess systemic toxicity. Dimethyloxalylglycine administration significantly improved postoperative flap viability, with combined topical and intraperitoneal dimethyloxalylglycine administration leading to reduced necrosis on postsurgical day 7 at 6 mg/kg/day, 12 mg/kg/day, 24 mg/kg/day, and 48 mg/kg/day versus controls (all p < 0.05). Compared with controls (unperfused, 39.9 ± 3.8 percent), dimethyloxalylglycine treatment led to a dose-dependent decrease in unperfused tissue at 6 mg/kg/day (11.4 ± 1.7 percent), 12 mg/kg/day (9.4 ± 4.2 percent), 24 mg/kg/day (4.7 ± 2.6 percent), and 48 mg/kg/day (1.4 ± 0.9 percent) (all p < 0.001). Topical dimethyloxalylglycine application alone administered at 48 mg/kg/day was sufficient to improve flap viability (p = 0.005). Dimethyloxalylglycine-treated flaps exhibited higher CD31 staining (p = 0.004), tissue vascular endothelial growth factor (p = 0.007), HIF-1α staining (p < 0.001), and reduced terminal deoxynucleotidyl transferase-mediated dUDP end-labeling staining (p = 0.045). There were no differences in hematocrit or macroscopic organ changes on gross necropsy. Topical and systemic targeting of the HIF-1 pathway may be a promising therapeutic approach to improve flap resistance to ischemia.


Obsessive-compulsive disorder and spectrum across the life span.
An obsessive-compulsive disorder (OCD) spectrum has been proposed, which includes a group of disorders that share certain features with OCD including clinical symptoms (repetitive behaviours and thoughts), neurobiology (e.g. neurotransmitters) and preferential response to anti-obsessional treatments, such as the selective serotonin reuptake inhibitors (SSRIs). Three distinct clusters have been identified within the OCD spectrum, i.e. disorders concerning preoccupations with bodily sensations or appearance, impulsive disorders, and neurologically based disorders, and these share phenotypic features. Using one example from each of these clusters, body dysmorphic disorder (BDD), pathological gambling (PG) and autism, respectively, the phenomenology, neurobiology and pharmacotherapy indicates that specific biological factors are shared by OCD and by these disorders and correlate with the severity of repetitive behaviours. Thus, in common with OCDs, in BDD there is increased activity in the limbic regions; in PG there is evidence of deficiencies in 5-HT function and receptors; and in autism there are restricted interests and repetitive behaviours which may be influenced by serotonergic mechanisms. Our findings support the notion that targeted treatments, for example using SSRIs, for the behaviours associated with these disorders are effective. Our review considers one SSRI treatment in particular, fluvoxamine, and conclusions should be drawn in light of this. Further testing of our hypothesis would be prudent to confirm its validity.


Contrasting two frameworks for ROC analysis of ordinal ratings.
Statistical evaluation of medical imaging tests used for diagnostic and prognostic purposes often employs receiver operating characteristic (ROC) curves. Two methods for ROC analysis are popular. The ordinal regression method is the standard approach used when evaluating tests with ordinal values. The direct ROC modeling method is a more recently developed approach, motivated by applications to tests with continuous values. The authors compare the methods in terms of model formulations, interpretations of estimated parameters, the ranges of scientific questions that can be addressed with them, their computational algorithms, and the efficiencies with which they use data. The authors show that a strong relationship exists between the methods by demonstrating that they fit the same models when only a single test is evaluated. The ordinal regression models are typically alternative parameterizations of the direct ROC models and vice versa. The direct method has two major advantages over the ordinal regression method: 1) estimated parameters relate directly to ROC curves, facilitating interpretations of covariate effects on ROC performance, and 2) comparisons between tests can be done directly in this framework. Comparisons can be made while accommodating covariate effects and even between tests that have values on different scales, such as between a continuous biomarker test and an ordinal valued imaging test. The ordinal regression method provides slightly more precise parameter estimates from data in our simulated data models. Although the ordinal regression method is slightly more efficient, the direct ROC modeling method has important advantages in regard to interpretation, and it offers a framework to address a broader range of scientific questions, including the facility to compare tests.


Inflammation-induced abnormalities in the subcellular localization and trafficking of the neurokinin 1 receptor in the enteric nervous system.
Activated G protein-coupled receptors traffic to endosomes and are sorted to recycling or degradative pathways. Endosomes are also a site of receptor signaling of sustained and pathophysiologically important processes, including inflammation. However, the mechanisms of endosomal sorting of receptors and the impact of disease on trafficking have not been fully defined. We examined the effects of inflammation on the subcellular distribution and trafficking of the substance P (SP) neurokinin 1 receptor (NK1R) in enteric neurons. We studied NK1R trafficking in enteric neurons of the mouse colon using immunofluorescence and confocal microscopy. The impact of inflammation was studied in IL10(-/-)-piroxicam and trinitrobenzenesulfonic acid colitis models. NK1R was localized to the plasma membrane of myenteric and submucosal neurons of the uninflamed colon. SP evoked NK1R endocytosis and recycling. Deletion of β-arrestin2, which associates with the activated NK1R, accelerated recycling. Inhibition of endothelin-converting enzyme-1 (ECE-1), which degrades endosomal SP, prevented recycling. Inflammation was associated with NK1R endocytosis in myenteric but not submucosal neurons. Whereas the NK1R in uninflamed neurons recycled within 60 min, NK1R recycling in inflamed neurons was delayed for >120 min, suggesting defective recycling machinery. Inflammation was associated with β-arrestin2 upregulation and ECE-1 downregulation, which may contribute to the defective NK1R recycling. We conclude that inflammation evokes redistribution of NK1R from the plasma membrane to endosomes of myenteric neurons through enhanced SP release and defective NK1R recycling. Defective recycling may be secondary to upregulation of β-arrestin2 and downregulation of ECE-1. Internalized NK1R may generate sustained proinflammatory signals that disrupt normal neuronal functions.


The health-enhancing efficacy of Zumba® fitness: An 8-week randomised controlled study.
The purpose of this study was to gain a holistic understanding of the efficacy of Zumba® fitness in a community-recruited cohort of overweight and physically inactive women by evaluating (i) its physiological effects on cardiovascular risk factors and inflammatory biomarkers and (ii) its mental health-enhancing effects on factors of health-related quality of life (HRQoL). Participants were randomly assigned to either engagement in one to two 1 h classes of Zumba® fitness weekly (intervention group; n = 10) or maintenance of habitual activity (control group; n = 10). Laboratory assessments were conducted pre- (week 0) and post-intervention (week 8) with anthropometric, physiological, inflammatory and HRQoL data collected. In the intervention group, maximal oxygen uptake significantly increased (P < 0.05; partial η(2) = 0.56) by 3.1 mL · kg(-1) · min(-1), per cent body fat significantly decreased (P < 0.05; partial η(2) = 0.42) by -1.2%, and interleukin-6 and white blood cell (WBC) count both significantly decreased (P < 0.01) by -0.4 pg · mL(-1) (partial η(2) = 0.96) and -2.1 × 10(9) cells · L(-1) (partial η(2) = 0.87), respectively. Large magnitude enhancements were observed in the HRQoL factors of physical functioning, general health, energy/fatigue and emotional well-being. When interpreted in a community-based physical activity and psychosocial health promotion context, our data suggest that Zumba® fitness is indeed an efficacious health-enhancing activity for adults.


A quantitative analysis of sonographic images of the salivary gland: a comparison between sonographic and sialographic findings.
We performed three quantitative analyses (particle analysis, fractional Brownian motion [fBM] model analysis, two-dimensional [2-D] fractal analysis) of the ultrasonographic (US) images of the salivary gland and evaluated whether the obtained indices correlated with the sialographic stage of Rubin-Holt. Our study included 192 patients suspected of having Sjögren's syndrome (SS). In 89 patients, sialography demonstrated abnormal findings. Based on a particle analysis, we calculated both the average size of the particles (avg-area) and the area ratio to evaluate the presence of hypoechoic areas and echogenic lines, which are characteristic of SS. According to the fBM model, we calculated the Hurst index of the original image (Hurst-ori) and the background-subtracted image (Hurst-bs) to evaluate the complexity of the pixel value distribution. We also obtained the 2-D fractal dimension (2-D-FD) to evaluate the complexity of the contour lines. We entered these indices of the parotid glands (PG) into a logistic regression analysis and evaluated which indices were useful predictors for detecting an abnormal sialographic stage. Significant differences were observed between the normal and abnormal groups in all five indices of the PG (Mann-Whitney U test) and all five indices were correlated with the Rubin-Holt stage (Spearman's Rank Correlation Test). As the Rubin-Holt stage became more severe, both the Hurst-ori and 2-D-FD became smaller. Alternatively, the Hurst-bs, avg-area, and area ratio became higher. Three indices (avg-area, area ratio and Hurst-ori) were selected as useful predictors for detecting abnormal sialographic stages. This quantitative analysis system is therefore considered to have potentially useful clinical applications for the detection of abnormal sialographic findings.


Segmentation of brain structures in presence of a space-occupying lesion.
Brain deformations induced by space-occupying lesions may result in unpredictable position and shape of functionally important brain structures. The aim of this study is to propose a method for segmentation of brain structures by deformation of a segmented brain atlas in presence of a space-occupying lesion. Our approach is based on an a priori model of lesion growth (MLG) that assumes radial expansion from a seeding point and involves three steps: first, an affine registration bringing the atlas and the patient into global correspondence; then, the seeding of a synthetic tumor into the brain atlas providing a template for the lesion; finally, the deformation of the seeded atlas, combining a method derived from optical flow principles and a model of lesion growth. The method was applied on two meningiomas inducing a pure displacement of the underlying brain structures, and segmentation accuracy of ventricles and basal ganglia was assessed. Results show that the segmented structures were consistent with the patient's anatomy and that the deformation accuracy of surrounding brain structures was highly dependent on the accurate placement of the tumor seeding point. Further improvements of the method will optimize the segmentation accuracy. Visualization of brain structures provides useful information for therapeutic consideration of space-occupying lesions, including surgical, radiosurgical, and radiotherapeutic planning, in order to increase treatment efficiency and prevent neurological damage.


Is ethnic density associated with risk of child pedestrian injury? A comparison of inter-census changes in ethnic populations and injury rates.
Research on inequalities in child pedestrian injury risk has identified some puzzling trends: although, in general, living in more affluent areas protects children from injury, this is not true for those in some minority ethnic groups. This study aimed to identify whether 'group density' effects are associated with injury risk, and whether taking these into account alters the relationship between area deprivation and injury risk. 'Group density' effects exist when ethnic minorities living in an area with a higher proportion of people from a similar ethnic group enjoy better health than those who live in areas with a lower proportion, even though areas with dense minority ethnic populations can be relatively more materially disadvantaged. This study utilised variation in minority ethnic densities in London between two census periods to identify any associations between group density and injury risk. Using police data on road traffic injury and population census data from 2001 to 2011, the numbers of 'White,' 'Asian' and 'Black' child pedestrian injuries in an area were modelled as a function of the percentage of the population in that area that are 'White,' 'Asian' and 'Black,' controlling for socio-economic disadvantage and characteristics of the road environment. There was strong evidence (p < 0.001) of a negative association between 'Black' population density and 'Black' child pedestrian injury risk [incidence (of injury) rate ratios (IRR) 0.575, 95% CI 0.515-0.642]. There was weak evidence (p = 0.083) of a negative association between 'Asian' density and 'Asian' child pedestrian injury risk (IRR 0.901, 95% CI 0.801-1.014) and no evidence (p = 0.412) of an association between 'White' density and 'White' child pedestrian injury risk (IRR 1.075, 95% CI 0.904-1.279). When group density effects are taken into account, area deprivation is associated with injury risk of all ethnic groups. Group density appears to protect 'Black' children living in London against pedestrian injury risk. These findings suggest that future research should focus on structural properties of societies to explain the relationships between minority ethnicity and risk.


Dynamic and steady state response of heart rate to orthostatic stress in normotensive and hypertensive pregnant women.
We determined the dynamic and steady state responses of heart rate (HR) to orthostatic stress (standing up) in normotensive and hypertensive pregnant women. Using a continuous recording with servo-photosphygmography, HR response to change in posture from left lateral recumbent position to standing was analysed. The subjects were divided into five groups comprising: Groups I, II and III: normotensive pregnant women in each of the three trimesters of pregnancy (total n = 77); Group IV: women with gestational proteinuric hypertension (GPH) in the third trimester (n = 16); Group V: age-matched non-pregnant normotensive controls (n = 15). The HR reacted with a typical overshoot response to this orthostatic change with HR rising to a peak and then settling to a new but higher steady state. Change in steady state HR from lying to standing (delta HR), rate of rise of HR in response to standing (i.e. the acceleration slope (HRon)), and rate of fall of HR after reaching the peak (i.e. deceleration slope (HRoff)) were evaluated from standing heart rate time curves. HRon in response to standing showed a downward trend with gestation (ANOVA, P < 0.05) in normotensive gravida. The deceleration slope (HRoff) showed a distinct gestational age-related decrease from first to third trimester in normotensive women (ANOVA, P < 0.01). The most striking observation was that the slope of HRoff for the GPH group was significantly steeper than that of normotensive women of comparable gestational age (unpaired t-test P < 0.01) and approximated to that of the non-pregnant group. The difference in HR response between normotensive women and those with GPH in the third trimester suggests it may have potential as a new marker for pre-eclampsia.


Development of Species-Specific Ah Receptor-Responsive Third Generation CALUX Cell Lines with Enhanced Responsiveness and Improved Detection Limits.
The Ah receptor (AhR)-responsive CALUX (chemically activated luciferase expression) cell bioassay is commonly used for rapid screening of samples for the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), dioxin-like compounds, and AhR agonists/antagonists. By increasing the number of AhR DNA recognition sites (dioxin responsive elements), we previously generated a novel third generation (G3) recombinant AhR-responsive mouse CALUX cell line (H1L7.5c3) with a significantly enhanced response to DLCs compared to existing AhR-CALUX cell bioassays. However, the elevated background luciferase activity of these cells and the absence of comparable G3 cell lines derived from other species have limited their utility for screening purposes. Here, we describe the development and characterization of species-specific G3 recombinant AhR-responsive CALUX cell lines (rat, human, and guinea pig) that exhibit significantly improved limit of detection and dramatically increased TCDD induction response. The low background luciferase activity, low minimal detection limit (0.1 pM TCDD) and enhanced induction response of the rat G3 cell line (H4L7.5c2) over the H1L7.5c3 mouse G3 cells, identifies them as a more optimal cell line for screening purposes. The utility of the new G3 CALUX cell lines were demonstrated by screening sediment extracts and a small chemical compound library for the presence of AhR agonists. The improved limit of detection and increased response of these new G3 CALUX cell lines will facilitate species-specific analysis of DLCs and AhR agonists in samples with low levels of contamination and/or in small sample volumes.


Differential expression of the capsaicin receptor TRPV1 and related novel receptors TRPV3, TRPV4 and TRPM8 in normal human tissues and changes in traumatic and diabetic neuropathy.
Transient receptor potential (TRP) receptors expressed by primary sensory neurons mediate thermosensitivity, and may play a role in sensory pathophysiology. We previously reported that human dorsal root ganglion (DRG) sensory neurons co-expressed TRPV1 and TRPV3, and that these were increased in injured human DRG. Related receptors TRPV4, activated by warmth and eicosanoids, and TRPM8, activated by cool and menthol, have been characterised in pre-clinical models. However, the role of TRPs in common clinical sensory neuropathies needs to be established. We have studied TRPV1, TRPV3, TRPV4, and TRPM8 in nerves (n = 14) and skin from patients with nerve injury, avulsed dorsal root ganglia (DRG) (n = 11), injured spinal nerve roots (n = 9), diabetic neuropathy skin (n = 8), non-diabetic neuropathic nerve biopsies (n = 6), their respective control tissues, and human post mortem spinal cord, using immunohistological methods. TRPV1 and TRPV3 were significantly increased in injured brachial plexus nerves, and TRPV1 in hypersensitive skin after nerve repair, whilst TRPV4 was unchanged. TRPM8 was detected in a few medium diameter DRG neurons, and was unchanged in DRG after avulsion injury, but was reduced in axons and myelin in injured nerves. In diabetic neuropathy skin, TRPV1 expressing sub- and intra-epidermal fibres were decreased, as was expression in surviving fibres. TRPV1 was also decreased in non-diabetic neuropathic nerves. Immunoreactivity for TRPV3 was detected in basal keratinocytes, with a significant decrease of TRPV3 in diabetic skin. TRPV1-immunoreactive nerves were present in injured dorsal spinal roots and dorsal horn of control spinal cord, but not in ventral roots, while TRPV3 and TRPV4 were detected in spinal cord motor neurons. The accumulation of TRPV1 and TRPV3 in peripheral nerves after injury, in spared axons, matches our previously reported changes in avulsed DRG. Reduction of TRPV1 levels in nerve fibres in diabetic neuropathy skin may result from the known decrease of nerve growth factor (NGF) levels. The role of TRPs in keratinocytes is unknown, but a relationship to changes in NGF levels, which is produced by keratinocytes, deserves investigation. TRPV1 represents a more selective therapeutic target than other TRPs for pain and hypersensitivity, particularly in post-traumatic neuropathy.


Duramycin-induced destabilization of a phosphatidylethanolamine monolayer at the air-water interface observed by vibrational sum-frequency generation spectroscopy.
Duramycin is a small tetracyclic peptide which binds specifically to ethanolamine phospholipids (PE). In this study, we used lipid monolayers consisting of 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE) and various phosphatidylcholines (PC) to investigate the effect of duramycin on the organization of lipids and its influence on surrounding water molecules, using vibrational sum-frequency generation spectroscopy in conjunction with surface pressure measurements and fluorescence microscopy. The results show that while duramycin has no effect on the PC lipid monolayers, it induces significant disorder of PE molecules and causes an increase of the PE monolayer surface pressure. Duramycin adopts a β-sheet conformation and is well-ordered at the air-water interface as well as after binding to PE. Our results are consistent with duramycin inserting into the PE monolayer via its hydrophobic end, exposing phenylalanine residues to the lipid. Binding of duramycin to PE broadens the hydrogen-bond distribution of lipid-bound water molecules, notably increasing the fraction of the less strongly hydrogen-bonded, possibly undercoordinated, water molecules. Fluorescence microscopy reveals that the interaction of duramycin with PE causes a change in the shape of the liquid-condensed domains of the PE monolayer from circular to horseshoe-like, indicating a reduction of line tension at the boundary of the two lipid phases. These results reveal that the first steps in the disruption of membrane integrity by duramycin consist of a reduction of the line tension, a decrease in the lipid order, and a weakening of the hydrogen bonding network of water around PE.


Engineering a Highly Defective Stable UiO-66 with Tunable Lewis- Brønsted Acidity: The Role of the Hemilabile Linker.
The stability of metal-organic frameworks (MOFs) typically decreases with an increasing number of defects, limiting the number of defects that can be created and limiting catalytic and other applications. Herein, we use a hemilabile (Hl) linker to create up to a maximum of six defects per cluster in UiO-66. We synthesized hemilabile UiO-66 (Hl-UiO-66) using benzene dicarboxylate (BDC) as linker and 4-sulfonatobenzoate (PSBA) as the hemilabile linker. The PSBA acts not only as a modulator to create defects but also as a coligand that enhances the stability of the resulting defective framework. Furthermore, upon a postsynthetic treatment in H2SO4, the average number of defects increases to the optimum of six missing BDC linkers per cluster (three per formula unit), leaving the Zr-nodes on average sixfold coordinated. Remarkably, the thermal stability of the materials further increases upon this treatment. Periodic density functional theory calculations confirm that the hemilabile ligands strengthen this highly defective structure by several stabilizing interactions. Finally, the catalytic activity of the obtained materials is evaluated in the acid-catalyzed isomerization of α-pinene oxide. This reaction is particularly sensitive to the Brønsted or Lewis acid sites in the catalyst. In comparison to the pristine UiO-66, which mainly possesses Brønsted acid sites, the Hl-UiO-66 and the postsynthetically treated Hl-UiO-66 structures exhibited a higher Lewis acidity and an enhanced activity and selectivity. This is further explored by CD3CN spectroscopic sorption experiments. We have shown that by tuning the number of defects in UiO-66 using PSBA as the hemilabile linker, one can achieve highly defective and stable MOFs and easily control the Brønsted to Lewis acid ratio in the materials and thus their catalytic activity and selectivity.


Programmed cell death (apoptosis) as a possible pathway to metalloproteinase activation and fetal membrane degradation in premature rupture of membranes.
Increased matrix metalloproteinase 2 expression and activity are associated with premature rupture of fetal membranes. A proapoptotic protein produced in response to deoxyribonucleic acid fragmentation, p53, can bind to the matrix metalloproteinase 2 gene promoter and cause increased gene expression. It promotes apoptosis by inducing the expression of the proapoptotic bax gene and inhibiting the antiapoptotic bcl-2 gene. This study was undertaken to investigate the expression pattern of apoptotic elements in pregnancy complications that may cause increased expression of the gene for matrix metalloproteinase 2. Amniochorial membranes were collected from the following groups of women: (1) women with premature rupture of fetal membranes, (2) women with preterm labor and intact membranes, and (3) women with term labor after vaginal delivery. Deoxyribonucleic acid fragmentation was tested with ligation-mediated polymerase chain reaction and the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyribonucleoside triphosphate end-labeling assay. Matrix metalloproteinase 2, p53, bcl-2, and bax gene expression patterns were studied with quantitative competitive polymerase chain reaction. Statistical analysis was performed with the Tukey-Kramer multiple comparison test. Quantitative competitive polymerase chain reaction documented a 10-fold increase in the expression of the gene for matrix metalloproteinase 2 in premature rupture of fetal membranes with respect to term and preterm labor. This induction coincided with an increase in the expressions of the proapoptotic genes p53 and bax and a drop in the expression of the antiapoptotic gene bcl-2. Ligation-mediated polymerase chain reaction revealed deoxyribonucleic acid fragmentation in specimens from premature rupture of fetal membranes and not in those from preterm labor or labor at term. Histochemical analysis documented fragmented deoxyribonucleic acid in chorionic and amniotic cells. This study suggests that apoptosis is associated with premature rupture of fetal membranes. Deoxyribonucleic acid fragmentation, associated with elevations in the levels of the two proapoptotic gene products evaluated (p53 and bax ) and a drop in the level of the antiapoptotic bcl-2, was seen in premature rupture of the fetal membranes. Induction of matrix metalloproteinase 2 may be a function of p53 gene expression increase in premature rupture of fetal membranes.


Responding to the health needs of women from migrant and refugee backgrounds-Models of maternity and postpartum care in high-income countries: A systematic scoping review.
Pregnant women from migrant and refugee backgrounds living in high-income countries (HIC) are at increased risk of adverse perinatal outcomes compared with women born in the host country. Women from migrant and refugee background have perinatal healthcare needs that are recognised internationally as a public health priority. The aim of this study was to identify, appraise and synthesise available evidence on the effectiveness of models of care in pregnancy or first 12 months postpartum for women from migrant and refugee backgrounds living in HIC. Care models were mapped in terms of (a) effectiveness at improving service access, (b) effectiveness at improving maternal and infant health outcomes, (c) acceptability and appropriateness from the perspective of women and (d) acceptability and appropriateness from the perspective of service providers. Using systematic scoping review methodology, qualitative, quantitative, and mixed methods research published in English 2008-2019 were included. The databases MEDLINE, Embase, Emcare, PubMed, Scopus, CINAHL, PsycINFO, Web of Science, Google Scholar, Cochrane Database of Systematic Reviews and Joanna Briggs Institute were searched between 27 February 2019 and updated 27 December 2019. Qualitative and quantitative data were analysed narratively. Seventeen studies, involving 1,499 women and 203 service providers, were included. A diverse range of interventions were identified, including bilingual/bicultural workers, group antenatal care and specialised clinics. All identified interventions were acceptable to women, and improved access, however, few provided evidence of improved perinatal outcomes. Gaps identified for future research include the use of qualitative and quantitative approaches to ascertain the experiences of women, their families, service providers and impact on perinatal outcomes. Synthesis of the included studies indicates the key elements of acceptable and accessible models, which were as follows: culturally responsive care, continuity of care, effective communication, psychosocial and practical support, support to navigate systems, flexible and accessible services.


Arthroscopic hip surgery with a microfracture procedure of the hip: clinical outcomes with two-year follow-up.
Outcome studies assessing a cohort of patients receiving microfracture in the hip have focused on second look arthroscopy and return to sport, which have shown favourable results in the absence of osteoarthritis. Few studies exist focusing on clinical outcomes after microfracture in the hip using patient reported outcome (PRO) scores. The purpose of this study is to evaluate two-year clinical outcomes of a series of patients treated with microfracture during arthroscopic hip surgery using PRO scores. During the study period, all workers' compensation (WC) and non-WC patients treated with microfracture during arthroscopic hip surgery were included. Four PRO scores, pain scores and satisfaction were used to assess clinical outcomes. Any revision surgeries or conversions to total hip arthroplasty (THA) were noted. Location of microfracture procedure, lesion size and additional variables assessed survivorship. Thirty-seven cases met the inclusion/exclusion criteria, of which 30 patients (30/37, 81%) were available for minimum two-year follow-up. Twenty-six patients were classified as survivors. Preoperative scores for patients with WC status were lower than non-WC patients and statistically significant (p<0.5) for three of the PROs. However, changes in all four PRO measurements demonstrated statistically significant improvements from preoperative to two-year follow-up for both compensation groups (p<0.05). The amount of change in PRO scores for both compensation groups was similar and not statistically significant. Two patients required THA and two patients required revision arthroscopy. Our study demonstrates statistically significant clinical improvement in PRO's after receiving microfracture during arthroscopic hip surgery at minimum two-year follow-up.


Protective Role of Tetrahydrocurcumin: an Active Polyphenolic Curcuminoid on Cadmium-InducedOxidative Damage in Rats.
In the present work, protective effect of tetrahydrocurcumin (THC) against oxidative damages in cadmium (Cd)-induced toxicity in rats was evaluated. Cd is an important environmental and industrial toxicant that affects almost all the organs, especially liver. Liver is the major organ responsible for the metabolism and the primary target for many toxic chemicals and drugs. Effect of THC, the curcumin-derived polyphenolic compound on Cd-induced oxidative stress and hepatic damage was evaluated using male albino Wistar rats. In Cd-administered rats (5 mg/kg body weight (b.w.), orally for 4 weeks), activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) were significantly increased in serum with the elevated level of bilirubin. Red blood cells (RBC), haemoglobin contents and haematocrit values were also significantly decreased in Cd-treated rats. In addition, the levels of lipid peroxidation markers like thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LHP), protein carbonyl contents (PCC) and conjugated dienes (CD) were significantly increased followed by the significant decrease in the levels of reduced glutathione (GSH), total sulphydryl groups (TSH), ascorbic acid (vitamin C) and vitamin E in liver of Cd-administered rats. Oral administration of THC (20, 40 and 80 mg/kg b.w.) followed by Cd for 4 weeks showed a significant restoration of the above changes to near normal. Histopathological changes observed in Cd intoxicated hepatic tissues were minimized on treatment with THC. This study suggests that THC at the dose of 80 mg/kg b.w. effectively subdues the Cd-induced toxicity and controls the free radical-induced liver damage in rats.


TM-wave propagation controlled by split ring resonator array.
We propose a new approach to control the propagation of electromagnetic (EM) wave with certain polarization by a split ring resonator (SRR) array. Interactions between SRR and the EM wave in the array are analyzed and it is found that the H field is always perpendicular to the SRR plane around the magnetic resonance frequency. Based on this property, a semicircular waveguide is designed to realize a 180 degrees bending with high performance. The structure of this approach is simple and feasible, providing an alternative way to construct bending waveguide with low loss.


Fitness consequences of avian personalities in a fluctuating environment.
Individual animals differ in the way they cope with challenges in their environment, comparable with variation in human personalities. The proximate basis of variation in personality traits has received considerable attention, and one general finding is that personality traits have a substantial genetic basis. This poses the question of how variation in personality is maintained in natural populations. We show that selection on a personality trait with high heritability fluctuates across years within a natural bird population. Annual adult survival was related to this personality trait (behaviour in novel environments) but the effects were always opposite for males and females, and reversed between years. The number of offspring surviving to breeding was also related to their parents' personalities, and again selection changed between years. The observed annual changes in selection pressures coincided with changes in environmental conditions (masting of beeches) that affect the competitive regimes of the birds. We expect that the observed fluctuations in environmental factors lead to fluctuations in competition for space and food, and these, in association with variations in population density, lead to a variation in selection pressure, which maintains genetic variation in personalities.


Simulating the drug discovery pipeline: a Monte Carlo approach.
The early drug discovery phase in pharmaceutical research and development marks the beginning of a long, complex and costly process of bringing a new molecular entity to market. As such, it plays a critical role in helping to maintain a robust downstream clinical development pipeline. Despite its importance, however, to our knowledge there are no published in silico models to simulate the progression of discrete virtual projects through a discovery milestone system. Multiple variables were tested and their impact on productivity metrics examined. Simulations predict that there is an optimum number of scientists for a given drug discovery portfolio, beyond which output in the form of preclinical candidates per year will remain flat. The model further predicts that the frequency of compounds to successfully pass the candidate selection milestone as a function of time will be irregular, with projects entering preclinical development in clusters marked by periods of low apparent productivity. The model may be useful as a tool to facilitate analysis of historical growth and achievement over time, help gauge current working group progress against future performance expectations, and provide the basis for dialogue regarding working group best practices and resource deployment strategies.


Identification of a novel protein from adult chicken brain that inhibits neurite outgrowth.
Glycoproteins that inhibit neurite outgrowth may guide growth cones during development by acting as a barrier and closing off inappropriate routes. Their continued expression in the adult central nervous system may be a key factor in preventing regeneration of central nervous system neurons. A glycoprotein of 55 kDa has been isolated from the detergent-insoluble membrane skeleton from adult chicken brain. Initial experiments showed that dorsal root ganglion neurons would not adhere to or extend neurites on a substratum coated with GP55. Furthermore, GP55 will act as a barrier to the advance of established growth cones in the presence of poly-L-lysine, laminin or G4. Central nervous system neurons from forebrain as well as dorsal root ganglion neurons from the peripheral nervous system are inhibited by GP55. GP55 is also effective in blocking the initial adhesion of neurons to a substratum of poly-L-lysine and, particularly, laminin. In contrast to the inhibition of neurite outgrowth, neuronal adhesion is concentration independent over the range tested. A preliminary investigation of the mechanism by which GP55 inhibits outgrowth suggests that a pertussis toxin-sensitive G protein is required. Preliminary evidence suggests that GP55 is anchored in the membrane by a glycosyl phosphatidylinositol moiety. GP55 is distinct from previously identified inhibitory proteins, based on the source and molecular mass, and is thus a new member of this rapidly expanding family.


Selective versus nonselective embolization versus no embolization in pelvic trauma: A multicenter retrospective cohort study.
Traumatic hemorrhage from pelvic fractures is a significant challenge, and angioembolization has become standard. Optimal treatment is undefined in two clinical scenarios. The first is in the presence of a negative angiogram. Can arterial embolization treat venous bleeding by decreasing the arterial pressure head? If the angiogram is positive, is nonselective embolization (NSE) or selective embolization (SE) better? The purpose of this study is to determine if embolization after a negative angiogram aids in hemorrhage control and when the angiogram is positive, which level of embolization is superior? A multicenter retrospective review was conducted including blunt trauma patients with pelvic fractures who underwent angiography. Demographic and clinical data were compiled on all subjects. NSE refers to an intervention at the level of the internal iliac artery and SE is defined as any distal intervention. Theoretical complications of pelvic embolization are those thought to arise from decreased pelvic blood flow and will be referred to as embolization-related complications. Thromboembolic complications included deep vein thrombosis or pulmonary embolism. One hundred ninety-four patients met inclusion criteria. Of the 67 patients with a negative angiogram, 26 (38.8%) were embolized. In those patients requiring transfusion, the units given in the first 24 hours were decreased in the embolization group (7.5 vs. 4.0, p = 0.054). Embolization-related complications occurred more frequently in those not embolized (11.4% vs. 6.0%, p = 0.414).One hundred forty-five patients were embolized, 99 (68.3%) NSE and 46 (31.7%) SE. There were no significant differences in mortality or transfusion requirements. There was no difference in the rate of embolization-related complications (4.1% vs. 2.1%, p = 0.352). There was a significantly increased rate of thromboembolic complications in the NSE group (12.1% vs. 0, p = 0.010). Embolization in the face of a negative angiogram may aid in hemorrhage control for those patients being actively transfused. If embolized, then selective occlusion of more distal vessels rather than of the main internal iliac artery should be performed. Therapeutic, level IV.


The Effects of Workplace Nature-Based Interventions on the Mental Health and Well-Being of Employees: A Systematic Review.
Mental health in the workplace is a societal challenge with serious economical and human costs. Most prevalent mental disorders in the workforce (e.g., depression), however, are preventable. There is widespread agreement about the favorable effects of nature exposure and consequently, nature-based interventions (NBI) in the workplace have been proposed as a cost-effective approach to promote good health among employees. The objective of the present study was to systematically review scientific evidence on the effectiveness of NBI to promote mental health and well-being among actual employees in actual workplace settings. The review was conducted and presented in accordance with the PRISMA guidelines. The literature search was performed on five databases (PubMed, Embase, CENTRAL, CINHAL, and PsycINFO), hand-searching of field-specific journals, and the reference lists of retrieved papers over the past 5 years up to November (13th, 2018). Studies were eligible for inclusion if they (i) were randomized or nonrandomized controlled trials; (ii) comprised samples of actual employees; (iii) implemented a workplace-based intervention with exposure to nature; (iv) included comparison conditions that displayed a clear contrast to NBIs; and (v) investigated the quantitative effects on mental health or well-being. No restrictions on type of employees or workplace, publication period, or language of the publication were set. Risk of bias was assessed using the Cochrane's RoB2 tool. Narrative synthesis was performed due to large heterogeneity in outcome variables. Of the 510 articles identified, 10 NBIs (nine papers) met the eligibility criteria. The outcomes were grouped in five categories: (i) mental health indices, (ii) cognitive ability, (iii) recovery and restoration, (iv) work and life satisfaction, and (v) psychophysiological indicators. Narrative synthesis indicates consistently positive effects on mental health indices and cognitive ability, while mixed results were found for the other outcome categories. Caution must be given when interpreting the current evidence in this emerging research field because of the diversity of NBIs and the overall high risk of bias in the individual studies. Although in this field often researchers have to balance scientific rigor and ecological validity, there is a need for large, well-designed and rigorously conducted trials grounded in contemporary theories.


Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma.
The broad spectrum kinase inhibitor sunitinib is a first-line therapy for advanced clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer. Unfortunately, most patients develop sunitinib resistance and progressive disease after about 1 year of treatment. In this study, we evaluated the mechanisms of resistance to sunitinib to identify the potential tactics to overcome it. Xenograft models were generated that mimicked clinical resistance to sunitinib. Higher microvessel density was found in sunitinib-resistant tumors, indicating that an escape from antiangiogenesis occurred. Notably, escape coincided with increased secretion of interleukin-8 (IL-8) from tumors into the plasma, and coadministration of an IL-8 neutralizing antibody resensitized tumors to sunitinib treatment. In patients who were refractory to sunitinib treatment, IL-8 expression was elevated in ccRCC tumors, supporting the concept that IL-8 levels might predict clinical response to sunitinib. Our results reveal IL-8 as an important contributor to sunitinib resistance in ccRCC and a candidate therapeutic target to reverse acquired or intrinsic resistance to sunitinib in this malignancy.


Computerised lung sound analysis to improve the specificity of paediatric pneumonia diagnosis in resource-poor settings: protocol and methods for an observational study.
WHO case management algorithm for paediatric pneumonia relies solely on symptoms of shortness of breath or cough and tachypnoea for treatment and has poor diagnostic specificity, tends to increase antibiotic resistance. Alternatives, including oxygen saturation measurement, chest ultrasound and chest auscultation, exist but with potential disadvantages. Electronic auscultation has potential for improved detection of paediatric pneumonia but has yet to be standardised. The authors aim to investigate the use of electronic auscultation to improve the specificity of the current WHO algorithm in developing countries. This study is designed to test the hypothesis that pulmonary pathology can be differentiated from normal using computerised lung sound analysis (CLSA). The authors will record lung sounds from 600 children aged ≤5 years, 100 each with consolidative pneumonia, diffuse interstitial pneumonia, asthma, bronchiolitis, upper respiratory infections and normal lungs at a children's hospital in Lima, Peru. The authors will compare CLSA with the WHO algorithm and other detection approaches, including physical exam findings, chest ultrasound and microbiologic testing to construct an improved algorithm for pneumonia diagnosis. This study will develop standardised methods for electronic auscultation and chest ultrasound and compare their utility for detection of pneumonia to standard approaches. Utilising signal processing techniques, the authors aim to characterise lung sounds and through machine learning, develop a classification system to distinguish pathologic sounds. Data will allow a better understanding of the benefits and limitations of novel diagnostic techniques in paediatric pneumonia.


The educational enrollment of immigrant youth: a test of the segmented-assimilation hypothesis.
An analysis of 1990 census data on the educational enrollment of 15- to 17-year-old immigrants to the United States provides partial support for predictions from both the segmented-assimilation hypothesis and the immigrant optimism hypothesis. Most immigrant adolescents, especially from Asia, are as likely as their native-born peers to be enrolled in high school, or more so. The "at-risk" immigrant youths with above-average levels of nonenrollment that are not reduced with longer exposure to American society are primarily of Hispanic Caribbean origins (from Puerto Rico, the Dominican Republic, and Cuba). Recent Mexican immigrants who arrived as teenagers have nonenrollment rates over 40%, but Mexican youths who arrived at younger ages are only somewhat less likely to be enrolled in school than are native-born Americans.


Complex Portal 2018: extended content and enhanced visualization tools for macromolecular complexes.
The Complex Portal (www.ebi.ac.uk/complexportal) is a manually curated, encyclopaedic database that collates and summarizes information on stable, macromolecular complexes of known function. It captures complex composition, topology and function and links out to a large range of domain-specific resources that hold more detailed data, such as PDB or Reactome. We have made several significant improvements since our last update, including improving compliance to the FAIR data principles by providing complex-specific, stable identifiers that include versioning. Protein complexes are now available from 20 species for download in standards-compliant formats such as PSI-XML, MI-JSON and ComplexTAB or can be accessed via an improved REST API. A component-based JS front-end framework has been implemented to drive a new website and this has allowed the use of APIs from linked services to import and visualize information such as the 3D structure of protein complexes, its role in reactions and pathways and the co-expression of complex components in the tissues of multi-cellular organisms. A first draft of the complete complexome of Saccharomyces cerevisiae is now available to browse and download.


Economic and personal factors affecting women's use of nurse-midwives in Michigan.
The proportion of American women who use a nurse-midwife rather than an obstetrician to deliver their baby is increasing. Relatively little is known, however, about the determinants of a midwife-assisted birth. Logistic regression analyses using birth-certificate data on 149,437 Michigan births in 1990 examined the characteristics associated with midwife-attended births. Women who paid for childbirth with Medicaid were 3.5 times more likely than those paying with private insurance to use a certified nurse-midwife, net of controls for maternal characteristics; this effect varied significantly by race, with Medicaid payment increasing the odds of midwife use threefold among whites and nearly fivefold among nonwhites. The effect of education on midwife use also varied by race: A college education significantly increased the likelihood of midwife use among white women (odds ratio of 2.1), but higher education decreased that probability among nonwhite women (odds ratio of 0.74). Father's education and age, were also significantly associated with the likelihood of a midwife-attended birth; the babies of college-educated fathers had higher odds of being delivered by a nurse-midwife, as did the babies of men in their 30s. The relationship between socioeconomic status and the use of midwives may not be as straightforward as previously thought. The patients of nurse-midwives are a diverse group whose socioeconomic characteristics and probable reasons for choosing a midwife over a physician vary widely.


Longterm effects of endoscopic sphincterotomy on gall bladder motility.
Some of patients with an intact gall bladder develop acute cholecystitis or have gall bladder stone formation after endoscopic sphincterotomy. Endoscopic sphincterotomy may affect gall bladder motility. To prospectively evaluate longterm effect of endoscopic sphincterotomy on gall bladder motility. Thirty two patients with an intact gall bladder (15 with and 17 without gall bladder stones) who underwent endoscopic sphincterotomy for choledocholithiasis. Gall bladder function was examined before and at from seven days to five years after sphincterotomy. Gall bladder volume, at fasting and after caerulein administration, was determined by ultrasonography. After endoscopic sphincterotomy, the enlarged orifice remained patent during a five year follow up period. One patient with gall bladder stones subsequently developed acute cholecystitis, the remaining being asymptomatic. In the patients before sphincterotomy, particularly in those with gall bladder stones, the gall bladder showed larger fasting volume and lower caerulein stimulated maximum contraction than normal controls. Throughout five years after sphincterotomy, fasting volume of the gall bladder decreased and its maximum contraction increased, regardless of gall bladder stones; significantly different from the values before sphincterotomy (p < 0.05). Endoscopic sphincterotomy decreases fasting volume of the gall bladder and increases its contraction ability for a long period. These changes may rather decrease the risk of future acute cholecystitis or gall stone formation.


Activation of nucleus accumbens μ-opioid receptors enhances the response to a glycaemic challenge.
Opioids are known to affect blood glucose levels but their exact role in the physiological control of glucose metabolism remains unclear. Although there are numerous studies investigating the peripheral effects of opioid stimulation, little is known about how central opioids control blood glucose and which brain areas are involved. One brain area possibly involved is the nucleus accumbens because, as well as being a key site for opioid effects on food intake, it has also been implicated in the control of blood glucose levels. Within the nucleus accumbens, μ-opioid receptors are most abundantly expressed. Therefore, in the present study, we investigated the role of μ-opioid receptors in the nucleus accumbens in the control of glucose metabolism. We show that infusion of the μ-opioid receptor agonist [d-Ala2 , N-MePhe4 , Gly-ol]-enkephalin (DAMGO) in the nucleus accumbens by itself does not affect blood glucose levels, but it enhances the glycaemic response after both an insulin tolerance test, as well as a glucose tolerance test. These findings indicate that the nucleus accumbens plays a role in the central effects of opioids on glucose metabolism, and highlight the possibility of nucleus accumbens μ-opioid receptors as a therapeutic target for enhancing the counter-regulatory response.


The role of obesity and weight fluctuations in the etiology of renal cell cancer: a population-based case-control study.
The causes of renal cell cancer (RCC) are poorly understood. Besides smoking, obesity remains the only risk factor that is fairly well established. The association between obesity and RCC appears stronger and more consistent in women than in men. We investigated the question of whether this apparent sex difference could be explained by repeated weight changes (weight cycling), less physical exercise, or pharmacological treatment of obesity in women. Structured face-to-face interviews were carried out with 379 (70% of all eligible) incident cases of RCC and 353 (72% of eligible) controls. The relationships between RCC and adult height, weight, and body mass index (BMI), defined as weight/height, were analyzed. Odds ratios (ORs) were estimated through logistic regression. No association was found between adult height and RCC. In men, weight and BMI appeared at most to be weakly related to risk of RCC. In women, higher adult weight and BMI (usual, highest, and lowest) and also high BMI at ages 30, 40, and 50 years were consistently associated with a significantly increased risk of RCC. Women with an usual adult BMI in the top 5% had a nearly 3-fold increased risk of RCC [OR, 2.67; 95% confidence interval (CI), 1.02-7.01]. Compared with individuals with no weight-loss periods, 2 or more such periods implied an OR of 0.96 (95% CI, 0.32-2.90) in men and 3.87 (95% CI, 1.20-12.45) in women. Physical activity at work reduced the risk of RCC in men but not women. Regular use of diet pills containing amphetamine was associated with an increased risk of RCC (OR, 4.06; 95% CI, 1.35-12.22).(ABSTRACT TRUNCATED AT 250 WORDS)


Bioactive Nanoparticles for Cancer Immunotherapy.
Currently, immunotherapy is considered to be one of the effective treatment modalities for cancer. All the developments and discoveries in this field up to the recent Nobel Prize add to the interest for research into this vast area of study. Targeting tumor environment as well as the immune system is a suitable strategy to be applied for cancer treatment. Usage of nanoparticle systems for delivery of immunotherapeutic agents to the body being widely studied and found to be a promising area of research to be considered and investigated further. Nanoparticles for immunotherapy would be one of the effective treatment options for cancer therapy in the future due to their high specificity, efficacy, ability to diagnose, imaging, and therapeutic effect. Among the many nanoparticle systems, polylactic-co-glycolic acid (PLGA) nanoparticles, liposomes, micelles, gold nanoparticles, iron oxide, dendrimers, and artificial exosomes are widely used for immunotherapy of cancer. Moreover, the combination therapy found to be the more effective way of treating the tumor. Here, we review the current trends in nanoparticle therapy and efficiency of these nanosystems in delivering antigens, adjuvants, therapeutic drugs, and other immunotherapeutic agents. This review summarizes the currently available bioactive nanoparticle systems for cancer immunotherapy.


Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria.
This article presents the revised consensus criteria for the diagnosis of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS) based on an international research workshop on frontotemporal dementia (FTD) and ALS held in London, Canada in June 2015. Since the publication of the Strong criteria, there have been considerable advances in the understanding of the neuropsychological profile of patients with ALS. Not only is the breadth and depth of neuropsychological findings broader than previously recognised - - including deficits in social cognition and language - but mixed deficits may also occur. Evidence now shows that the neuropsychological deficits in ALS are extremely heterogeneous, affecting over 50% of persons with ALS. When present, these deficits significantly and adversely impact patient survival. It is the recognition of this clinical heterogeneity in association with neuroimaging, genetic and neuropathological advances that has led to the current re-conceptualisation that neuropsychological deficits in ALS fall along a spectrum. These revised consensus criteria expand upon those of 2009 and embrace the concept of the frontotemporal spectrum disorder of ALS (ALS-FTSD).


Interrogating the Grainyhead-like 2 (Grhl2) genomic locus identifies an enhancer element that regulates palatogenesis in mouse.
The highly-conserved Grainyhead-like (Grhl) transcription factors are critical regulators of embryogenesis that regulate cellular survival, proliferation, migration and epithelial integrity, especially during the formation of the craniofacial skeleton. Family member Grhl2 is expressed throughout epithelial tissues during development, and loss of Grhl2 function leads to significant defects in neurulation, abdominal wall closure, formation of the face and fusion of the maxilla/palate. Whereas numerous downstream target genes of Grhl2 have been identified, very little is known about how this crucial developmental transcription factor itself is regulated. Here, using in silico and in utero expression analyses and functional deletion in mice, we have identified a novel 2.4 kb enhancer element (mm1286) that drives reporter gene expression in a pattern that strongly recapitulates endogenous Grhl2 in the craniofacial primordia, modulates Grhl2 expression in these tissues, and augments Grhl2-mediated closure of the secondary palate. Deletion of this genomic element, in the context of inactivation of one allele of Grhl2 (through generation of double heterozygous Grhl2+/-;mm1286+/- mice), results in a significant predisposition to palatal clefting at birth. Moreover, we found that a highly conserved 325 bp region of mm1286 is both necessary and sufficient for mediating the craniofacial-specific enhancer activity of this region, and that an extremely well-conserved 12-bp sequence within this element (CTGTCAAACAGGT) substantially determines full enhancer function. Together, these data provide valuable new insights into the upstream genomic regulatory landscape responsible for transcriptional control of Grhl2 during palatal closure.


Toward Practice Advancement in Emergency Care for Children With Autism Spectrum Disorder.
There is increasing recognition that children with autism spectrum disorder (ASD) experience challenges in busy clinical environments such as the emergency department (ED). ASD may heighten adverse responses to sensory input or transitions, which can impose greater difficulty for a child to cope with situational demands. These problems can be amplified in the ED because of its busy and unpredictable nature, wait times, and bodily care. There is little literature documenting ED-based needs of children with ASD to inform clinical guidelines. The objective was to identify stakeholder perspectives in determining clinical priorities and recommendations to guide ED service delivery for children with ASD. After qualitative interviews with children, parents, and health care providers conducted in a previous phase of this study, focus groups were convened with parents of children with ASD, ED clinicians, and ED administrators (total n = 60). Qualitative data were analyzed based on an interpretive description approach. Participants identified the ED and its delivery of care as insufficient to meet the unique needs of children with ASD. The following clinical priorities were identified: ASD-focused preparedness for ED procedures and processes, wait time management, proactive strategies for sedation and restraint, child-focused support, health care provider capacity building, post-ED follow-up resources, and transition planning to adult care. Heightened child- and family-centered care were strongly recommended.


Prediction of trace element mobility in contaminated soils by sequential extraction.
The modified three-step sequential extraction procedure proposed by the Community Bureau of Reference (or Bureau Communautaire de Reference, BCR) was used to predict trace element mobility in soils affected by an accidental spill comprising arsenopyrite- and heavy metal-enriched sludge particles and acid waste waters. The procedure was used to obtain the distribution of both the major (Al, Ca, Fe, Mg, and Mn) and trace elements (As, Bi, Cd, Cu, Pb, Tl, and Zn) in 13 soils of contrasting properties with various levels of contamination and in the sludge itself. The distributions of the major elements enabled us to confirm the main soil fractions solubilized in each of the three steps, and, in turn, to detect the presence of pyritic sludge particles by the high Fe extractability obtained in the third step. Cadmium was identified as being the most mobile of the elements, having the highest extractability in the first step, followed by Zn and Cu, Lead, Tl, Bi, and As were shown to be poorly mobile or nonmobile. In the case of some of the trace elements, the residual fractions decreased at higher levels of contamination, which was attributed to the anthropogenic contributions to the polluted samples. Comparison with soil-plant transfer factors, calculated in plants growing in the affected area, indicated that a relative sequence of trace element mobility was well predicted from data of the first step.


Weekend admissions as an independent predictor of mortality: an analysis of Scottish hospital admissions.
Weekend admissions have been shown to be associated with an increased risk of mortality compared with weekday admissions for many diagnoses. We analysed emergency department admissions within the Scottish National Health Service to investigate whether mortality is increased in case of weekend emergency department admissions. A cohort study. Scotland National Health Service (NHS) emergency departments. 5 271 327 emergency department admissions between 1999 and 2009. We included all patients admitted via emergency departments recorded in the Scottish Morbidity Records (SMR01) in NHS, Scotland for whom complete demographic data were available. Death as recorded by the General Register Office (GRO). There was a significantly increased probability of death associated with a weekend emergency admission compared with admission on a weekday (unadjusted OR 1.27, 95% CI 1.26 to 1.28, p<0.0001; adjusted for year of admission, gender, age, deprivation quintile and number of comorbidities OR 1.42, 95% CI 1.40 to 1.43, p<0.0001). Despite a general reduction in mortality over the last 11 years, there is still a significant excess mortality associated with weekend emergency admissions. Further research should be undertaken to identify the precise mechanisms underlying this effect so that measures can be put in place to reduce patient mortality.


Precipitation Fluctuations over Northern Hemisphere Land Areas Since the Mid-19th Century.
An extensive array of measurements extending back to the mid-19th century was used to investigate large-scale changes in precipitation over Northern Hemisphere land areas. Significant increases in mid-latitude precipitation and concurrent decreases in low-latitude precipitation have occurred over the last 30 to 40 years. Although these large-scale trends are consistent with general circulation model projections of precipitation changes associated with doubled concentrations of atmospheric carbon dioxide, they should be viewed as defining large-scale natural climatic variability. Additional work to refine regional variations and address potential network inhomogeneitics is needed. This study attempts to show secular precipitation fluctuations over hemispheric and continental-scale areas of the Northern Hemisphere.


Modelling the spatial and temporal variability of the SW lagoon of New Caledonia II: realistic 3D simulations compared with in situ data.
Coral reef lagoons are under the growing influence of anthropogenic activities, leading to increasing loads of nutrients and various contaminants. Modelling approaches are a useful tool for studying such a complex coastal environment. In this study, we carried out the development of a three-dimensional coupled hydrodynamical-biogeochemical model of the south-west lagoon of New Caledonia. The biogeochemical model presented in Faure et al. (2006, 2010) was dynamically coupled with a hydrodynamical model (MARS3D) in order to study the short-term variability of the ecosystem. Two simulations (in winter and summer) were then performed from measured initial conditions using realistic wind and irradiance conditions and river inputs. Examinations of the biogeochemical response to these transient meteorological conditions were presented and compared with temporal field data corresponding to the considered periods. Results highlighted the ecosystem functioning, based on the balance of hydrodynamical and biogeochemical processes. Influence of urban and terrigeneous inputs were limited to the coastal zone. The model accurately reproduced the measured Chl.a and bacterial production, highlighting the improvement made on the biogeochemical model. However, the underestimation of some variables in model outputs, in particular nutrients, led us to focus on different inputs, such as sediment inputs which were not taken into account or properly estimated. Moreover, the role of boundary waters appeared crucial and suggested a calibration effort. Last, the final aim of our modelling study will help the development of a useful tool for studying the key processes of the ecosystem of the south-west lagoon of New Caledonia, as well as the examination of the biogeochemical response under different scenarios.


Evidence-based and occupational perspective of effective interventions for older clients that remediate or support improved driving performance.
To assess the effectiveness of person-related interventions on driving ability in older adults, this literature review was completed as a part of the Evidence-Based Literature Review Project of the American Occupational Therapy Association. Nineteen articles were incorporated into the systematic review and include interventions in the following areas: visual, cognitive, and motor; educational; passengers; and medical. The results provide inconclusive evidence for the use of interventions such as the Useful Field of View training, home exercise programs, and passenger interactions. Conclusive evidence shows that older adults respond positively to programs stressing self-awareness of driving skills and that some medical interventions affect the ability to drive. Despite limitations, the studies reviewed provide useful information that deserves further exploration. Reading the literature provides therapists with knowledge that might improve client care. Learning about cutting-edge interventions and educating peers and students about evidence-based interventions may lead to safer community mobility for older adults.


Predicting an unconventional facile route to metallaanthracenes.
Metallaaromatics have attracted considerable interest from both experimentalists and theoreticians since the first prediction of metallabenzenes, in which a CH group is replaced by a transition metal fragment. In comparison with monocyclic metallabenzenes and bicyclic metallanaphthalenes, tricyclic metallaanthracenes are quite less developed. Thus, it is urgent to explore synthetic methods for this rare system. Here we report a thorough investigation on the formation of metallaanthracenes from transition metal fluorenyl complexes via density functional theory calculations. We systematically investigate how metal centres, ligands, and substituents affect such a rearrangement. Our results indicate that formation of metallaanthracenes could become thermodynamically and kinetically favourable from transition metal fluorenyl complexes by tuning suitable metal centres, ligands, and substituents, suggesting an unconventional facile way to prepare such rare tricyclic metallaaromatics for experimentalists, which is in sharp contrast to the traditional isomerisation of metallabenzenes to cyclopentadienyl complexes.


Enhanced Isotopic Ratio Outlier Analysis (IROA) Peak Detection and Identification with Ultra-High Resolution GC-Orbitrap/MS: Potential Application for Investigation of Model Organism Metabolomes.
Identifying non-annotated peaks may have a significant impact on the understanding of biological systems. In silico methodologies have focused on ESI LC/MS/MS for identifying non-annotated MS peaks. In this study, we employed in silico methodology to develop an Isotopic Ratio Outlier Analysis (IROA) workflow using enhanced mass spectrometric data acquired with the ultra-high resolution GC-Orbitrap/MS to determine the identity of non-annotated metabolites. The higher resolution of the GC-Orbitrap/MS, together with its wide dynamic range, resulted in more IROA peak pairs detected, and increased reliability of chemical formulae generation (CFG). IROA uses two different 13C-enriched carbon sources (randomized 95% 12C and 95% 13C) to produce mirror image isotopologue pairs, whose mass difference reveals the carbon chain length (n), which aids in the identification of endogenous metabolites. Accurate m/z, n, and derivatization information are obtained from our GC/MS workflow for unknown metabolite identification, and aids in silico methodologies for identifying isomeric and non-annotated metabolites. We were able to mine more mass spectral information using the same Saccharomyces cerevisiae growth protocol (Qiu et al. Anal. Chem 2016) with the ultra-high resolution GC-Orbitrap/MS, using 10% ammonia in methane as the CI reagent gas. We identified 244 IROA peaks pairs, which significantly increased IROA detection capability compared with our previous report (126 IROA peak pairs using a GC-TOF/MS machine). For 55 selected metabolites identified from matched IROA CI and EI spectra, using the GC-Orbitrap/MS vs. GC-TOF/MS, the average mass deviation for GC-Orbitrap/MS was 1.48 ppm, however, the average mass deviation was 32.2 ppm for the GC-TOF/MS machine. In summary, the higher resolution and wider dynamic range of the GC-Orbitrap/MS enabled more accurate CFG, and the coupling of accurate mass GC/MS IROA methodology with in silico fragmentation has great potential in unknown metabolite identification, with applications for characterizing model organism networks.


A practical approach to assess depression risk and to guide risk reduction strategies in later life.
Many factors have been associated with the onset and maintenance of depressive symptoms in later life, although this knowledge is yet to be translated into significant health gains for the population. This study gathered information about common modifiable and non-modifiable risk factors for depression with the aim of developing a practical probabilistic model of depression that can be used to guide risk reduction strategies. A cross-sectional study was undertaken of 20,677 community-dwelling Australians aged 60 years or over in contact with their general practitioner during the preceding 12 months. Prevalent depression (minor or major) according to the Patient Health Questionnaire (PHQ-9) assessment was the main outcome of interest. Other measured exposures included self-reported age, gender, education, loss of mother or father before age 15 years, physical or sexual abuse before age 15 years, marital status, financial stress, social support, smoking and alcohol use, physical activity, obesity, diabetes, hypertension, and prevalent cardiovascular diseases, chronic respiratory diseases and cancer. The mean age of participants was 71.7 ± 7.6 years and 57.9% were women. Depression was present in 1665 (8.0%) of our subjects. Multivariate logistic regression showed depression was independently associated with age older than 75 years, childhood adverse experiences, adverse lifestyle practices (smoking, risk alcohol use, physical inactivity), intermediate health hazards (obesity, diabetes and hypertension), comorbid medical conditions (clinical history of coronary heart disease, stroke, asthma, chronic obstructive pulmonary disease, emphysema or cancers), and social or financial strain. We stratified the exposures to build a matrix that showed that the probability of depression increased progressively with the accumulation of risk factors, from less than 3% for those with no adverse factors to more than 80% for people reporting the maximum number of risk factors. Our probabilistic matrix can be used to estimate depression risk and to guide the introduction of risk reduction strategies. Future studies should now aim to clarify whether interventions designed to mitigate the impact of risk factors can change the prevalence and incidence of depression in later life.


Optimization of apolipoprotein(a) genotyping with pulsed field gel electrophoresis.
Increased lipoprotein(a) is a risk factor for atherosclerosis, and its concentration in serum is inversely correlated with the size of the apoliprotein(a) [apo(a)] component. The size of the apo(a) gene is determined mainly by the Kringle IV size polymorphism. We have optimized and characterized pulsed field gel electrophoresis (PFGE) for apo(a) genotyping. Established PFGE protocols were adjusted. The changes included the following: (a) increased DNA yields by the use of all leukocytes for isolation from either 3 mL of fresh EDTA whole blood or 250 microL of frozen buffy coats; (b) increased efficiency of Kpn1 digestion by the inclusion of a digestion buffer wash; (c) reduction of assay time by the use of capillary blotting; (d) increased sensitivity by the use of four digoxigenin-labeled apo(a) probes; and (e) identification using a single film by the inclusion of a digoxigenin-labeled lambda marker probe in addition to apo(a) probes in the hybridization mix. In older Caucasians, 93% (buffy coats, n=468) were heterozygous for apo(a) gene size. An inverse correlation between serum lipoprotein(a) and the sum of Kringle IV alleles was found (y = -23x + 1553; r = -0.442; n = 468). Gel-to-gel variation was minimal (3%). Imprecision (SD) was one Kringle IV repeat (control sample containing eight fragments of 72-233 kb; n=34 electrophoretic runs). The practicality and sensitivity of the apo(a) genotyping technique by PFGE were improved, and accuracy and reproducibility were preserved. The optimized procedure is promising for apo(a) genotyping on frozen buffy coats from large epidemiological studies.


cIMPACT-NOW: a practical summary of diagnostic points from Round 1 updates.
cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. From 2016 to 2019 (Round 1), cIMPACT published four updates. Update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed use of the additional term NEC (Not Elsewhere Classified). Update 2 issued clarifications regarding two diagnoses: Diffuse Midline Glioma, H3 K27M-mutant and Diffuse Astrocytoma/Anaplastic Astrocytoma, IDH-mutant. Update 3 proposed molecular criteria that could be used in the setting of an IDH-wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma to infer that the tumor would behave similarly to a grade IV glioblastoma. Update 4 suggested that, in children and young adults, subtypes of IDH-wildtype/H3-wildtype diffuse gliomas may have distinct clinical features in the setting of a BRAFV600E mutation, FGFR1 alteration, other MAPK pathway alteration, or a MYB or MYBL1 rearrangement. The practical diagnostic relevance of these cIMPACT proposals is highlighted in this summary.


Arteriovenous malformation model for training and research.
To develop an arteriovenous malformation (AVM) model for teaching embolization techniques and for researching and developing new interventional devices. Open pore cellulose sponges 2 to 5 cm in diameter were coated with a watertight elastomer. One to three afferent tubes (arteries) and one large efferent tube (vein) allowed insertion of the model into a circuit of pulsatile, flowing, non-Newtonian fluid. Using fluoroscopy and angiographic imaging, five neuroradiologists practiced occluding the AVM nidus with a variety of techniques and cyanoacrylate mixtures. The model appeared and behaved like a human brain AVM. Attempts to teach liquid adhesive techniques were successful, and though they were stressful for the trainee, failure had none of the disastrous sequelae that attend training with human subjects. The AVM training and research model is of value in introducing physicians to the techniques needed for endovascular cyanoacrylate therapy: it allows users to develop skills at their own rates, and permits safe "failure-mode" learning.


Modulation of neural activity during observational learning of actions and their sequential orders.
How does the brain transform perceptual representations of others' actions into motor representations that can be used to guide behavior? Here we used functional magnetic resonance imaging to record human brain activity while subjects watched others construct multipart objects under varied task demands. We find that relative to resting baseline, passive action observation increases activity within inferior frontal and parietal cortices implicated in action encoding (mirror system) and throughout a distributed network of areas involved in motor representation, including dorsal premotor cortex, pre-supplementary motor area, cerebellum, and basal ganglia (experiments 1 and 2). Relative to passive observation, these same areas show increased activity when subjects observe with the intention to subsequently reproduce component actions using the demonstrated sequential procedures (experiment 1). Observing the same actions with the intention of reproducing component actions, but without the requirement to use the demonstrated sequential procedure, increases activity in the same regions, although to a lesser degree (experiment 2). These findings demonstrate that when attempting to learn behaviors through observation, the observers' intentions modulate responses in a widely distributed network of cortical and subcortical regions implicated previously in action encoding and/or motor representation. Among these regions, only activity within the right intraparietal sulcus predicts the accuracy with which observed procedures are subsequently performed. Successful formation of motor representations of sequential procedures through observational learning is dependent on computations implemented within this parietal region.


Cognitive functioning, depression, and HIV medication adherence in India: a randomized pilot trial.
Objective: India is home to the third-largest number of people living with HIV in the world, and no-cost antiretroviral therapy (ART) has been available across the country since 2004. However, rates of adherence to ART are often subpar in India, and interventions to increase adherence are warranted. Cognitive impairment and depression have been associated with ART non-adherence, and may also limit the impact of behavioral interventions designed to improve adherence. Studies have not evaluated the impact of cognitive impairment and depression on response to adherence interventions in India. Methods: Individuals new to ART (≤12 months prescribed) were recruited from a public hospital in Chandigarh, India. Participants (N = 80) were randomized to either a group medication adherence intervention (MAI) or an enhanced standard of care (ESOC) condition. The MAI consisted of three monthly gender-concordant group cognitive-behavioral sessions addressing HIV and ART, adherence, and HIV-related coping and social support. Participants were assessed at baseline for depression and cognitive functioning, and assessed monthly for adherence by pill count. Results: Adherence among participants receiving the MAI improved by about one day's dose over the course of the study, and no improvement was noted among those in the ESOC. Additionally, high rates of cognitive impairment (57%) and depression (25%) were identified among participants. There was no evidence that cognitive impairment moderated response to the intervention. However, while non-depressed participants benefitted from the intervention, depressed participants failed to show the same improvement. Conclusions: Results of this pilot study suggest that group behavioral interventions can be an effective strategy to promote ART adherence in this population, even among those demonstrating cognitive impairment. However, because of the negative impact of depression on adherence, future studies should continue to develop strategies to identify and treat it among people living with HIV in India.


Gait analysis using a force-measuring gangway: intrasession repeatability in healthy adults.
The goal of the present study was to determine the repeatability of gait parameters measured by a force plate gait analysis system (Leonardo Mechanograph® GW). Fifteen healthy adult participants walked at a self-selected speed on a 10 m long walkway. Vertical ground reaction forces were measured in the central 6 m of the walkway. Each participant performed three trials while walking barefoot and three trials while wearing shoes, each trial consisting of three 10 m walks. There were minimal differences between trials at each condition. All primary force, time, distance and velocity parameters had intraclass correlation coefficients above 0.90 and coefficients of variation in the order of 2% to 4%. Compared to walking barefoot, walking in shoes resulted in 14% lower maximal vertical ground reaction force, 5% longer step length and 2% higher average velocity and caused less lateral translation of the center of force. In this group of healthy adults, gait analysis with a force plate system produced repeatable intra-day results. The observation that barefoot and shod walking yield different results indicates that it is important to standardize test conditions.


A new genus of rhinebothriidean cestodes from batoid elasmobranchs, with the description of five new species and two new combinations.
Survey work of batoid elasmobranchs in the eastern Atlantic and Indo-Pacific revealed multiple species of a new genus of cestode. Stillabothrium Healy et Reyda gen. n. (Rhinebothriidea: Escherbothriidae) is unique in its possession of an even number of non-medial longitudinal septa in the posterior portion of the bothridia, resulting in a series of loculi that are longer than wide (i.e. vertically oriented) and are arranged in columns. Five new species of Stillabothrium are described, S. ashleyae Willsey et Reyda sp. n., S. davidcynthiaorum Daigler et Reyda sp. n., S. campbelli Delgado, Dedrick et Reyda sp. n., S. hyphantoseptum Herzog, Bergman et Reyda sp. n., S. jeanfortiae Forti, Aprill et Reyda sp. n., and two species are formally transferred to the genus, S. amuletum (Butler, 1987) comb. n., and S. cadenati (Euzet, 1954) comb. n., the latter of which is redescribed. The species differ in the configuration of the other bothridial septa and in proglottid anatomy. Species of Stillabothrium were found parasitising a total of 17 species of batoid elasmobranchs of the genera Dasyatis Rafinesque, Glaucostegus Bonaparte, Himantura Müller et Henle, Pastinachus Rüppell, Rhinobatos Linck and Zanobatus Garman, including several host species that are likely new to science. A phylogenetic hypothesis based on Bayesian analysis of 1 084 aligned positions of the D1-D3 region of 28S rDNA for 27 specimens representing 10 species of Stillabothrium and two outgroup species supported the monophyly of Stillabothrium. These results also supported morphologically determined species boundaries in all cases in which more than one specimen of a putative species was included in the analysis. Host specificity appears to vary across species of Stillabothrium, with the number of host species parasitised by each species of Stillabothrium ranging from one to four. The geographic distribution of species of Stillabothrium spans the eastern Hemisphere, including the eastern Atlantic (coastal Senegal) and several locations in the Indo-Pacific (coastal Vietnam, Borneo and Australia). In addition, Phyllobothrium biacetabulatum Yamaguti, 1960 is formally transferred into family Escherbothriidae, although its generic placement remains uncertain (species incertae sedis).