Are immigrants, ethnic and linguistic minorities over-represented in jobs with a high level of compensated risk? Results from a Montréal, Canada study using census and workers' compensation data.
Few Canadian data sources allow the examination of disparities by ethnicity, language, or immigrant status in occupational exposures or health outcomes. However, it is possible to document the mechanisms that can create disparities, such as the over-representation of population groups in high-risk jobs. We evaluated, in the Montréal context, the relationship between the social composition of jobs and their associated risk level. We used data from the 2001 Statistics Canada census and from Québec's workers' compensation board for 2000-2002 to characterize job categories defined as major industrial groups crossed with three professional categories (manual, mixed, non-manual). Immigrant, visible, and linguistic minority status variables were used to describe job composition. The frequency rate of compensated health problems and the average duration of compensation determined job risk level. The relationship between the social composition and risk level of jobs was evaluated with Kendall correlations. The proportion of immigrants and minorities was positively and significantly linked to the risk level across job categories. Many relationships were significant for women only. In analyses done within manual jobs, relationships with the frequency rate reversed and were significant, except for the relationship with the proportion of individuals with knowledge of French only, which remained positive. Immigrants, visible, and linguistic minorities in Montréal are more likely to work where there is an increased level of compensated risk. Reversed relationships within manual jobs may be explained by under-reporting and under-compensation in vulnerable populations compared to those with knowledge of the province's majority language.


Driver's Cognitive Function Estimation Using Daily Driving Data.
Driving assistance systems that support drivers by adapting to driver characteristics can provide appropriate feedback and prevent traffic accidents. Cognitive function is helpful information for such systems to assist older drivers, and automatic estimation of drivers' cognitive function enables systems to utilize this information without being burdensome to these drivers. Therefore, this study aims to estimate drivers' cognitive function from daily driving data. We focus on modeling the scores of Trail Making Test (A) and (B) as measures of cognitive function, which indicate general cognitive ability. The main challenge is learning the generalized mapping function to the cognitive status from driving behavioral features extracted from the different driving routes of each driver. To address this problem, the proposed method focuses on particular driving scenarios in which differences in cognitive function can be observed. We evaluate the performance of the proposed model and the effectiveness of driving scenario information. Experimental results show that the results of Trail Making Tests (A) and (B) can be estimated with Spearman rank correlation coefficients of r = 0.34 and 0.48, respectively. In addition, the proposed method makes it easier to analyze the relationships between driving behaviors and cognitive function by comparing driving behaviors (e.g., steering angle velocity) in specific driving scenarios (e.g., intersections).


Does psychological well-being influence oral-health-related quality of life reports in children receiving orthodontic treatment?
Although the associations between oral biologic variables such as malocclusion and oral-health-related quality of life (OHRQOL) have been explored, little research has been done to address the influence of psychological characteristics on perceived OHRQOL. The aim of this study was to assess OHRQOL outcomes in orthodontics while controlling for individual psychological characteristics. We postulated that children with better psychological well-being (PWB) would experience fewer negative OHRQOL impacts, regardless of their orthodontic treatment status. One hundred eighteen children (74 treatment and 44 on the waiting list), aged 11 to 14 years, seeking treatment at the orthodontic clinics at the University of Toronto, participated in this study. The child perception questionnaire (CPQ11-14) and the PWB subscale of the child health questionnaire were administered at baseline and follow-up. Occlusal changes were assessed by using the dental aesthetic index. A waiting-list comparison group was used to account for age-related effects. Although the treatment subjects had significantly better OHRQOL scores at follow-up, the results were significantly modified by each subject's PWB status (P <0.01). Furthermore, multivariate analysis showed that PWB contributed significantly to the variance in CPQ11-14 scores (26%). In contrast, the amount of variance explained by the treatment status alone was relatively small (9%). The results of this study support the postulated mediator role of PWB when evaluating OHRQOL outcomes in children undergoing orthodontic treatment. Children with better PWB are, in general, more likely to report better OHRQOL regardless of their orthodontic treatment status. On the other hand, children with low PWB, who did not receive orthodontic treatment, experienced worse OHRQOL compared with those who received treatment. This suggests that children with low PWB can benefit from orthodontic treatment. Nonetheless, further work, with larger samples and longer follow-ups, is needed to confirm this finding and to improve our understanding of how other psychological factors relate to patients' OHRQOL.


Nerve growth factor promotes reorganization of the axonal microtubule array at sites of axon collateral branching.
The localized debundling of the axonal microtubule array and the entry of microtubules into axonal filopodia are two defining features of collateral branching. We report that nerve growth factor (NGF), a branch-inducing signal, increases the frequency of microtubule debundling along the axon shaft of chicken embryonic sensory neurons. Sites of debundling correlate strongly with the localized targeting of microtubules into filopodia. Platinum replica electron microscopy suggests physical interactions between debundled microtubules and axonal actin filaments. However, as evidenced by depolymerization of actin filaments and inhibition of myosin II, actomyosin force generation does not promote debundling. In contrast, loss of actin filaments or inhibition of myosin II activity promotes debundling, indicating that axonal actomyosin forces suppress debundling. MAP1B is a microtubule associated protein that represses axon branching. Following treatment with NGF, microtubules penetrating filopodia during the early stages of branching exhibited lower levels of associated MAP1B. NGF increased and decreased the levels of MAP1B phosphorylated at a GSK-3β site (pMAP1B) along the axon shaft and within axonal filopodia, respectively. The levels of MAP1B and pMAP1B were not altered at sites of debundling, relative to the rest of the axon. Unlike the previously determined effects of NGF on the axonal actin cytoskeleton, the effects of NGF on microtubule debundling were not affected by inhibition of protein synthesis. Collectively, these data indicate that NGF promotes localized axonal microtubule debundling, that actomyosin forces antagonize microtubule debundling, and that NGF regulates pMAP1B in axonal filopodia during the early stages of collateral branch formation.


Peri-infarct blood-brain barrier dysfunction facilitates induction of spreading depolarization associated with epileptiform discharges.
Recent studies showed that spreading depolarizations (SDs) occurs abundantly in patients following ischemic stroke and experimental evidence suggests that SDs recruit tissue at risk into necrosis. We hypothesized that BBB opening with consequent alterations of the extracellular electrolyte composition and extravasation of albumin facilitates generation of SDs since albumin mediates an astrocyte transcriptional response with consequent disturbance of potassium and glutamate homeostasis. Here we show extravasation of Evans blue-albumin complex into the hippocampus following cortical photothrombotic stroke in the neighboring neocortex. Using extracellular field potential recordings and exposure to serum electrolytes we observed spontaneous SDs in 80% of hippocampal slices obtained from rats 24 h after cortical photothrombosis. Hippocampal exposure to albumin for 24 h through intraventricular application together with serum electrolytes lowered the threshold for the induction of SDs in most slices irrespective of the pathway of stimulation. Exposing acute slices from naive animals to albumin led also to a reduced SD threshold. In albumin-exposed slices the onset of SDs was usually associated with larger stimulus-induced accumulation of extracellular potassium, and preceded by epileptiform activity, which was also observed during the recovery phase of SDs. Application of ifenprodil (3 μM), an NMDA-receptor type 2 B antagonist, blocked stimulus dependent epileptiform discharges and generation of SDs in slices from animals treated with albumin in-vivo. We suggest that BBB opening facilitates the induction of peri-infarct SDs through impaired homeostasis of K+.


Triple antibiotic combination therapy may improve but not resolve granuloma annulare.
Granuloma annulare is a fairly common entity yet lacks reliable treatment options especially when multiple lesions or dissemination exists. A recent case series suggests that a regimen of three oral antibiotics may prove to be an effective treatment. Our objective is to evaluate the efficacy of once monthly triple antibiotic therapy for granuloma annulare. We conducted an open-label prospective study of subjects with at least five lesions of granuloma annulare who received once monthly rifampin, ofloxacin, and minocycline for 6 months. Improvement was measured with a novel objective Granuloma Annulare Severity Index (GASI) scoring system. Twenty-one subjects enrolled. Ten subjects (48%) achieved at least a 50% reduction in their GASI, including three subjects (14%) who reached 75% improvement and one subject (5%) whose skin cleared. Six subjects (29%) had no change or worsening of their granuloma annulare. Median GASI scores decreased significantly by 15 points (p < 0.01), although the clinical significance of this result is unclear. As this was a small open-label study without a control group, we cannot determine if the results simply reflect the natural course of the disease. The GASI is not a validated assessment tool. Once monthly triple antibiotic use may improve but not clear granuloma annulare over 6 months. Randomized trials may be warranted to further assess this therapy.


Myristoylated alanine-rich C kinase substrate, but not Ca2+/calmodulin-dependent protein kinase II, is the mediator in cortical granules exocytosis.
Sperm-egg fusion induces cortical granules exocytosis (CGE), a process that ensures the block to polyspermy. CGE can be induced independently by either a rise in intracellular calcium concentration or protein kinase C (PKC) activation. We have previously shown that myristoylated alanine-rich C kinase substrate (MARCKS) cross-links filamentous actin (F-actin) and regulates its reorganization. This activity is reduced either by PKC-induced MARCKS phosphorylation (PKC pathway) or by its direct binding to calmodulin (CaM; CaM pathway), both inducing MARCKS translocation, F-actin reorganization, and CGE. Currently, we examine the involvement of Ca(2)(+)/CaM-dependent protein kinase II (CaMKII) and MARCKS in promoting CGE and show that PKC pathway can compensate for lack of Ca(2)(+)/CaM pathway. Microinjecting eggs with either overexpressed protein or complementary RNA of constitutively active alphaCaMKII triggered resumption of second meiotic division, but induced CGE of an insignificant magnitude compared with CGE induced by wt alphaCaMKII. Microinjecting eggs with mutant-unphosphorylatable MARCKS reduced the intensity of 12-O-tetradecanoylphorbol 13-acetate or ionomycin-induced CGE by 50%, indicating that phosphorylation of MARCKS by novel and/or conventional PKCs (n/cPKCs) is a pivotal event associated with CGE. Moreover, we were able to demonstrate cPKCs involvement in ionomycin-induced MARCKS translocation and CGE. These results led us to propose that MARCKS, rather than CaMKII, as a key mediator of CGE.


Sexually-dimorphic alterations in cannabinoid receptor density depend upon prenatal/early postnatal history.
Recent research has demonstrated that the endogenous cannabinoid system is central to the brain's response to stress. As part of an ongoing collaboration, we sought to examine the effects of prenatal and early postnatal rearing and housing conditions on developing endocannabinoid systems. We compare brain cannabinoid receptors (CBR) in offspring of either prenatal vehicle intubated or non-treated dams (Experiment 1) or in rats derived from a vendor and shipped at weaning to a collaborating lab (Experiment 2). From postnatal day (PND) 23, all rats were either housed in isolated conditions or enriched conditions with 3 rats/cage and a variety of stimulus objects changed twice a week. All rats underwent 5days of handling as controls for a behavior study and all rats were sacrificed at approximately PND48-50 within 2hours of the last behavioral test. All brains were processed together for CB1 receptor binding using 3H CP55,940 in prefrontal cortex, striatum, amygdala and hippocampus. Conditions in the two labs were as similar as possible since the two studies were intentionally designed to be comparable and contemporary. Results show that 1) comparing offspring of non-treated dams to offspring of dams receiving daily vehicle intubations, males show decreased CB1 binding in most brain regions while females only showed alterations in the hippocampus and these were increases in the offspring of the vehicle-intubated dams. 2) When comparing offspring of non-treated dams in NY with those derived from a vendor, shipped and maintained in the collaborating lab, this latter group showed reduced CB1 binding in prefrontal cortex in males and increased binding in all four brain regions in females. Therefore, overall, both prenatal handling (intubations) and being vendor-derived, shipped and maintained in a collaborating facility reduced CB1 receptors in males and increased them in females in key limbic brain regions. Effects of environmental enrichment or isolation were minor with only the prefrontal cortex showing an increase in binding in the isolated animals that were offspring of the vehicle-intubated dams. These results support the ideas that prenatal/early postnatal conditions produce different effects in males and females and override the effects of enrichment/isolation on cannabinoid receptors. Behavioral responses to cannabinoid challenges would therefore be expected to vary depending on sex, prenatal/early postnatal history and postweaning conditions of the rats. Since exogenous cannabinoids act through the CBR, the present data may provide a molecular basis for discrepant behavioral effects reported across various labs in the literature as well as sex differences seen following stress and/or manipulation of the cannabinoid system.


Integrated Behavioral Health Implementation Patterns in Primary Care Using the Cross-Model Framework: A Latent Class Analysis.
Primary care has increasingly adopted integrated behavioral health (IBH) practices to enhance overall care. The IBH Cross-Model Framework clarifies the core processes and structures of IBH, but little is known about how practices vary in the implementation of these processes and structures. This study aimed to describe clusters of clinics using the IBH Cross-Model Framework for a large sample of primary care clinics, as well as contextual variables associated with differences in implementation. Primary care clinics (N = 102) in Minnesota reported their level of implementation across 18 different components of IBH via the site self-assessment (SSA). The components were mapped to all five principles and four of the nine structures of the IBH Cross-Model Framework. latent class analysis was used to identify unique clusters of IBH components from the SSA across the IBH Cross-Model Framework's processes and structures. Latent classes were then regressed onto context variables. A four-class model was determined to be the best fit: Low IBH (39.6%), Structural IBH (7.9%), Partial IBH (29.4%), and Strong IBH (23.1%). Partial IBH clinics were more urban than the other three classes, lower in SES risk than Structural IBH clinics, and located in smaller organizations than Strong IBH clinics. There were no differences between classes in race/ethnicity of the clinic area or practice size. Four groups of IBH implementation were identified representing unique profiles of integration. These clusters may represent patterns of community-based implementation of IBH that indicate easier and more challenging aspects of IBH implementation.


Early and late selection in partial report: evidence from degraded displays.
In studies of iconic memory using the bar-probe task, subjects see a brief display of target letters and are probed by an arrow to report one of them. According to the classic early-selection account, subjects use the probe to select material for perceptual analysis from a precategorical (iconic) memory, but according to late-selection theories, subjects first identify the letters and then use the probe to select one letter for report from the set of categorized items. Pashler (1984) based his test for the locus of selection on a manipulation of display quality in previewed displays. He presented a target for 200 msec and then added a probe, together with the target, for an additional 150 msec. Reducing the target's stimulus quality increased response latency. If the subjects identified the characters before the probe appeared and then selected an item for report, the clarity of the original array should not have affected response latency. Hence, Pashler concluded that his subjects used the probe to select from a precategorical store (early selection). Pashler's experiment did not force subjects to rely on memory of the target; hence, although his experiment documented a situation in which subjects used early selection, it did not rule out late selection in studies of information persistence. We replicated Pashler's findings and, using his logic, showed that when subjects are forced to rely on memory of the target, they select from a categorized store.


Infant feeding in diverse families; the impact of ethnicity and migration on feeding practices.
To investigate differences in infant feeding practices and styles by maternal migration status. Prospective cohort study. Maternity unit of a large hospital in Northern England PARTICIPANTS: Women recruited to the Born in Bradford longitudinal cohort study MEASUREMENTS: Breastfeeding initiation; breastfeeding at six months; breastfeeding at twelve months; timing of introduction of complementary feeding; maternal feeding style at twelve months. Migrant women were more likely to initiate breastfeeding and continue breastfeeding for longer compared to native women. Native women also introduced complementary feeding earlier than migrant women. There was evidence of feeding practices among second= generation migrants becoming increasingly more aligned with those of native women, with lower breastfeeding rates and earlier introduction of complementary feeding compared to first-generation migrants. Migrant women were more likely to adopt a 'Demanding' feeding style, with the strongest associations seen in first-generation migrants. Migration status is an important factor to consider in reference to infant feeding practices. This is particularly important in considering intergenerational changes in families with migration backgrounds and the potential of culture to impact on family practices. Interventions to maintain cultural norms around infant feeding in families with migration backgrounds would be beneficial, due to the observed higher rates of breastfeeding in first-generation migrants. Targeted interventions to improve breastfeeding in white British native women should consider the role that culture can play in encouraging positive health behaviours.


Older adults' needs and preferences for a nutrition education digital health solution: A participatory design study.
The global population is ageing rapidly and there is a need for strategies to promote health and wellbeing among older adults. Nutrition knowledge is a key predictor of dietary intake; therefore, effective educational programmes are urgently required to rectify poor dietary patterns. Digital health technologies provide a viable option for delivering nutrition education that is cost-effective and widely accessible. However, few technologies have been developed to meet the unique needs and preferences of older adults. The aim of this study was to explore technology use among older adults and qualitatively determine the content needs and design preferences for an online nutrition education resource tailored to older adult consumers in Australia. Twenty adult participants aged 55 years and older (95% female) participated in one of four 2-h participatory design workshops. In each workshop, prompted discussion questions were used to explore participants' technology use and preferences and to explore content needs and design preferences for an online nutrition education resource specific to older adults. All participants were regularly using a range of different devices (e.g., smartphones, tablets and computers) and reported being comfortable doing so. Participants wanted a website that provided general nutrition information, practical advice and recipes. To enhance engagement, they sought a personalised resource that could be adjusted to suit their needs, included up-to-date information and allowed for easy sharing with others by exporting information as a PDF. Participatory design methods generate new knowledge for designing and tailoring digital health technologies to be appropriate and useful for the target audience. Specifically, older adults seek an online resource that has large and simple fonts with clear categories, providing them with practical advice and general nutrition information that can be personalised to suit their own needs and health concerns, with the option to export and print information into a paper-based format. Older adults actively participated in the development and evaluation process to generate ideas about potential features, functionalities, uses and practicalities of an online nutrition education resource.


Immunoturbidimetric determination of C-reactive protein (CRP) and high-sensitivity CRP on heparin plasma. Comparison with serum determination.
Determination of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), markers of systemic inflammation and atherosclerosis risk, usually requires serum samples, while heparin plasma samples are routinely collected for routine chemistry. This study evaluates the use of heparin plasma samples for hs-CRP and CRP determinations using immunoturbidimetric methods on an Olympus system. As a result, analytical performance, including linearity, imprecision values, and determination from 185 clinical samples, are not affected by the type of sampling, validating the use of heparin plasma samples for CRP and hs-CRP determination with Olympus reagents.


Perceptions of faculty toward "social obligation" at an Indian medical school.
The World Health Organization has defined social accountability of medical schools as "…obligation to direct their education, research, and service activities toward addressing the priority health concerns of the community." The current study looked at the extent to which the concept was understood in an Indian medical school, exploring how faculty perceived and were involved in directing a response to the social obligation of their medical school. Seventeen semi-structured audio-recorded interviews were conducted by purposive sampling of faculty from different disciplines. Interviews were transcribed and analyzed through a collaborative thematic approach to gain insight into faculty knowledge of the "obligation triad" of responsibility, responsiveness, and accountability; enablers and barriers in implementation; and understanding stakeholder roles. Faculty were unfamiliar with the terms and were unaware of the movement towards socially accountable schools. They were, however, sensitive to their responsibilities towards students and the community. Four major themes emerged: Perceptions of social obligation, awareness of social and cultural values, the role of partnerships, and moving toward a socially accountable model. Sensitizing students towards community needs, impact of cultural and socio-economic backgrounds, importance of contextual curriculum, and stakeholder roles were some of the challenges highlighted in developing a socially accountable medical school.


Design of a 3D-printed hand prosthesis featuring articulated bio-inspired fingers.
Various upper-limb prostheses have been designed for 3D printing but only a few of them are based on bio-inspired design principles and many anatomical details are not typically incorporated even though 3D printing offers advantages that facilitate the application of such design principles. We therefore aimed to apply a bio-inspired approach to the design and fabrication of articulated fingers for a new type of 3D printed hand prosthesis that is body-powered and complies with basic user requirements. We first studied the biological structure of human fingers and their movement control mechanisms in order to devise the transmission and actuation system. A number of working principles were established and various simplifications were made to fabricate the hand prosthesis using a fused deposition modelling (FDM) 3D printer with dual material extrusion. We then evaluated the mechanical performance of the prosthetic device by measuring its ability to exert pinch forces and the energy dissipated during each operational cycle. We fabricated our prototypes using three polymeric materials including PLA, TPU, and Nylon. The total weight of the prosthesis was 92 g with a total material cost of 12 US dollars. The energy dissipated during each cycle was 0.380 Nm with a pinch force of ≈16 N corresponding to an input force of 100 N. The hand is actuated by a conventional pulling cable used in BP prostheses. It is connected to a shoulder strap at one end and to the coupling of the whiffle tree mechanism at the other end. The whiffle tree mechanism distributes the force to the four tendons, which bend all fingers simultaneously when pulled. The design described in this manuscript demonstrates several bio-inspired design features and is capable of performing different grasping patterns due to the adaptive grasping provided by the articulated fingers. The pinch force obtained is superior to other fully 3D printed body-powered hand prostheses, but still below that of conventional body powered hand prostheses. We present a 3D printed bio-inspired prosthetic hand that is body-powered and includes all of the following characteristics: adaptive grasping, articulated fingers, and minimized post-printing assembly. Additionally, the low cost and low weight make this prosthetic hand a worthy option mainly in locations where state-of-the-art prosthetic workshops are absent.


Category-specific difficulty naming with verbs in Alzheimer's disease.
We studied 20 patients with Alzheimer's disease (AD) on a picture-naming task consisting of frequency-matched pairs of nouns and verbs that were homophonic and homographic (e.g., paint). Intragroup comparisons revealed that verb naming is significantly more difficult for patients with AD than noun naming. An error analysis demonstrated that patients with AD produce significantly more semantic and descriptive errors for verbs than nouns. We correlated verb naming and noun naming with measures of grammatical comprehension, lexical retrieval, and visuoperceptual processing, but there were no selective effects for verbs compared with nouns. Differences in the mental representation of concepts underlying verbs and nouns may account, in part, for the relative difficulty naming with verbs in AD.


[The effect of hyperthyroidism on the cognition processes and the state of the glial intermediate filaments in the rat brain].
The effects of hyperthyreosis on oxidative stress, state of glial intermediate filaments and memory were investigated. We observed a significant increase in lipid peroxidation products into both hippocampus and cortex and memory worsening. The changes of GFAP polypeptides was observed in hippocampus and cortex. In group of rats with hyperthyreosis, the content of GFAP in both soluble and filamentous fractions was increased in hippocampus. This data shows, that glial cytoskeleton is reconstructed under thyroid hormone effects.


High-Throughput Synthesis and Screening of Rapidly Degrading Polyanhydride Nanoparticles.
Combinatorial techniques can accelerate the discovery and development of polymeric nanodelivery devices by pairing high-throughput synthesis with rapid materials characterization. Biodegradable polyanhydrides demonstrate tunable release, high cellular internalization, and dose sparing properties when used as nanodelivery devices. This nanoparticle platform shows promising potential for small molecule drug delivery, but the pace of understanding and rational design of these nanomedicines is limited by the low throughput of conventional characterization. This study reports the use of a high-throughput method to synthesize libraries of a newly synthesized, rapidly eroding polyanhydride copolymer based on 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and sebacic acid (SA) monomers. The high-throughput method enabled efficient screening of copolymer microstructure, revealing weak block-type and alternating architectures. The high-throughput method was adapted to synthesize nanoparticle libraries encapsulating hydrophobic model drugs. Drug release from these nanoparticles was rapid, with a majority of the payload released within 3 days. Drug release was dramatically slowed at acidic pH, which could be useful for oral drug delivery. Rhodamine B (RhoB) release kinetics generally followed patterns of polymer erosion kinetics, while Coomassie brilliant blue (CBB) released the fastest from the slowest degrading polymer chemistry and vice versa. These differences in trends between copolymer chemistry and release kinetics were hypothesized to arise from differences in mixing thermodynamics. A high-throughput method was developed to synthesize polymer-drug film libraries and characterize mixing thermodynamics by melting point depression. Rhodamine B had a negative χ for all copolymers with <30 mol % CPTEG tested, indicating a tendency toward miscibility. By contrast, CBB χ increased, eventually becoming positive near 15:85 CPTEG:SA, with increasing CPTEG content. This indicates an increasing tendency toward phase separation in CPTEG-rich copolymers. These in vitro results screening polymer-drug interactions showed good agreement with in silico predictions from Hansen solubility parameter estimation and were able to explain the observed differences in model drug release trends.


Acanthocephala from amphibians in China with the description of a new species of Pseudoacanthocephalus (Echinorhynchida).
Amphibians of 24 species were surveyed for acanthocephalans in 4 nature reserves in 2 Chinese provinces during 2004–2006. Pseudoacanthocephalus bufonis (Echinorhynchida) occurred in both nature reserves in Guangxi Province. In the Jing Xi County Provincial Nature Reserve, P. bufonis infected 36 of 62 amphibians at a mean intensity of 9.9. Less than 250 km away, at Shiwandashan National Nature Reserve, 5 of 20 amphibians were infected at a mean intensity of 6.2. Pseudoacanthocephalus bufonis was not found in either of the reserves in Guizhou Province. In the Kuan Kuoshui Nature Reserve, 9 of 28 amphibians were parasitized at a mean intensity of 2.0 by a previously undescribed species of Pseudoacanthocephalus , and no acanthocephalan occurred in a small sample of 2 toads at Dashahe Nature Reserve. The new species, Pseudoacanthocephalus reesei n. sp., differs from all others in the genus by typically having 14 longitudinal rows of 4 hooks, each of which is much longer than corresponding hooks of any other species of the genus. The length of proboscis hooks increases from the apex to the base of the proboscis, further distinguishing the new species from all but Pseudoacanthocephalus nguyenthileae .


Detecting Abnormal Brain Regions in Schizophrenia Using Structural MRI via Machine Learning.
Utilizing neuroimaging and machine learning (ML) to differentiate schizophrenia (SZ) patients from normal controls (NCs) and for detecting abnormal brain regions in schizophrenia has several benefits and can provide a reference for the clinical diagnosis of schizophrenia. In this study, structural magnetic resonance images (sMRIs) from SZ patients and NCs were used for discriminative analysis. This study proposed an ML framework based on coarse-to-fine feature selection. The proposed framework used two-sample t-tests to extract the differences between groups first, then further eliminated the nonrelevant and redundant features with recursive feature elimination (RFE), and finally utilized the support vector machine (SVM) to learn the decision models with selected gray matter (GM) and white matter (WM) features. Previous studies have tended to report differences at the group level instead of at the individual level and cannot be widely applied. The method proposed in this study extends the diagnosis to the individual level and has a higher recognition rate than previous methods. The experimental results of this study demonstrate that the proposed framework distinguishes SZ patients from NCs, with the highest classification accuracy reaching over 85%. The identified biomarkers are also consistent with previous literature findings. As a universal method, the proposed framework can be extended to diagnose other diseases.


Altered sense of agency in Gilles de la Tourette syndrome: behavioural, clinical and functional magnetic resonance imaging findings.
Current neurocognitive models of motor control postulate that accurate action monitoring is crucial for a normal experience of agency-the ability to attribute the authorship of our actions and their consequences to ourselves. Recent studies demonstrated that action monitoring is impaired in Gilles de la Tourette syndrome, a movement disorder characterized by motor and vocal tics. It follows that Tourette syndrome patients may suffer from a perturbed sense of agency, the hypothesis tested in this study. To this end, we recruited 25 Tourette syndrome patients and 25 matched healthy controls in a case-control behavioural and functional magnetic resonance imaging study. As an implicit index of the sense of agency, we measured the intentional binding phenomenon, i.e., the perceived temporal compression between voluntary movements and their external consequences. We found evidence of an impaired sense of agency in Tourette syndrome patients who, as a group, did not show a significant intentional binding. The more reduced was the individual intentional binding, the more severe were the motor symptoms. Specific differences between the two groups were also observed in terms of brain activation patterns. In the healthy controls group, the magnitude of the intentional binding was associated with the activity of a premotor-parietal-cerebellar network. This relationship was not present in the Tourette syndrome group, suggesting an altered activation of the agency brain network for self-generated acts. We conclude that the less accurate action monitoring described in Tourette syndrome also involves the assessment of the consequences of actions in the outside world. We discuss that this may lead to difficulties in distinguishing external consequences produced by their own actions from the ones caused by others in Tourette syndrome patients.


Numerical evaluation of droplet sizing based on the ratio of fluorescent and scattered light intensities (LIF/Mie technique).
The dependence of fluorescent and scattered light intensities from spherical droplets on droplet diameter was evaluated using Mie theory. The emphasis is on the evaluation of droplet sizing, based on the ratio of laser-induced fluorescence and scattered light intensities (LIF/Mie technique). A parametric study is presented, which includes the effects of scattering angle, the real part of the refractive index and the dye concentration in the liquid (determining the imaginary part of the refractive index). The assumption that the fluorescent and scattered light intensities are proportional to the volume and surface area of the droplets for accurate sizing measurements is not generally valid. More accurate sizing measurements can be performed with minimal dye concentration in the liquid and by collecting light at a scattering angle of 60° rather than the commonly used angle of 90°. Unfavorable to the sizing accuracy are oscillations of the scattered light intensity with droplet diameter that are profound at the sidescatter direction (90°) and for droplets with refractive indices around 1.4.


Physical Exercise and ACE2-Angiotensin-(1-7)-Mas Receptor Axis of the Renin Angiotensin System.
Many physiological responses of the Renin Angiotensin System (RAS) are associated with two opposite pathways: (1) a classical one formed by angiotensin-converting enzyme (ACE), Angiotensin II (Ang II) and Angiotensin type 1 (AT1) receptor, which is associated to vasoconstriction, cell proliferation, organ hypertrophy, sodium retention and aldosterone release and (2) a counter-regulatory or vasodilator pathway comprising angiotensin-converting enzyme 2 (ACE2), Angiotensin-(1-7) [Ang-(1-7)] and Mas receptor, which is involved in vasodilation, antiproliferation, anti-hypertrophy, cardioprotective and renoprotective actions. This review aimed to bring up-to-date on the interactions between physical exercise and the vasodilator axis of the RAS (ACE2-Ang-(1-7)-Mas receptor axis). We also investigated the relation of acute and chronic exercise with blood pressure regulation and components of the vasodilator axis of the RAS. We searched studies with animal models and humans in PUBMED, LILACS and IBECS. Experimental studies showed that physical training can stimulate ACE2-Ang-(1-7)-Mas receptor axis in parallel with the inhibition of ACE-Ang II-AT1 receptor pathway. However, up to now, the interaction between the counter-regulatory RAS axis and physical training is not investigated in humans. The activation of ACE2-Ang-(1-7)-Mas receptor axis may have a role in the beneficial effects of physical training in experimental models. Further studies with humans are necessary.


Tubular reabsorption delay of amino acids in the rabbit kidney.
Estimates were obtained both with a rapid-transient technique and under steady-state conditions of the average time required for filtered solutes in the intact rabbit kidney to cross tubular epithelium from tubular lumen into the peritubular inulin space. This interval, defined as the transepithelial passage time, was relatively short (about 15 s) for glucose, in agreement with earlier results in the dog. In contrast, several amino acids required an average transepithelial passage time of about 40 s. Values for aspartate could only be obtained when its large basolateral uptake was inhibited by excess succinate. The long transepithelial passage time may be due to the slow extrusion of reabsorbed amino acids across basolateral cell membranes. This hypothesis was supported by the extent of tissue accumulation of amino acids during reabsorption. Even though basolateral transfer may thus limit the linear rate of movement of filtered amino acids across the epithelium, the step determining fractional absorption from the lumen is situated at the brush border.


A Pilot Clinical Study Assessing Treatment of Canine Hip Dysplasia Using Autologous Protein Solution.
Five dogs with bilateral hip dysplasia and without osteoarthritis of other joints were enrolled in this pilot study. Objective kinetic data using a pressure sensitive mat and owner assessments using the canine brief pain inventory (CBPI) and Liverpool Osteoarthritis for Dogs (LOAD) questionnaires were obtained prior to treatment. Enrolled dogs were treated in one hip with autologous protein solution (APS) and the contralateral hip was injected with an equal volume of saline. The hip to be treated was selected using a random number generator. At exactly 28 days following treatment dogs were re-assessed using the pressure sensitive mat and the CBPI and LOAD questionnaires. No dogs were treated with any other medications or supplements throughout the study period. Assessment of the total pressure index (TPI) collected using the pressure sensitive mat showed that the hips treated with APS improved significantly more than hips treated with saline (p = 0.0005) and that the hips treated with APS bore significantly more weight than the hips treated with saline at day 28 (p < 0.05). Statistically significant improvement was noted by owners in "pain" and "function" as assessed by the CBPI as well "mobility at exercise" using the LOAD questionnaire. This pilot study provided proof of principle that APS is beneficial in treating pain and lameness in dogs affected by coxofemoral osteoarthritis.


Chemodiversity of Nepeta menthoides Boiss. & Bohse. essential oil from Iran and antimicrobial, acetylcholinesterase inhibitory and cytotoxic properties of 1,8-cineole chemotype.
The essential oil of Nepeta menthoides Boiss. & Bohse., from Iran, was analysed by GC/MS. Two types of multivariate analyses were done based on the chemical composition of the investigated sample in this study and 12 other samples reported in the literature to show the chemodiversity in essential oil composition. Antimicrobial, acetylcholinesterase inhibitory and cytotoxic activities of the essential oil and its major component were assessed. Twenty-one compounds were identified, representing 96.81% of the total oil and the major constituent was 1,8-cineole (70.06%). Multivariate analyses revealed two chemotypes, i.e. nepetalactone and 1,8-cineole. The essential oil of the sample investigated in this study which was a 1,8-cineole chemotype and 1,8-cineole showed moderate antimicrobial activity and significantly inhibited the activity of acetylcholinesterase enzyme. Cytotoxicity evaluation against three breast cancer cell lines showed a potent inhibitory activity. Further investigations are necessary to confirm the variety in several populations of N. menthoides.


Co-expression of CD133, CD44v6 and human tissue factor is associated with metastasis and poor prognosis in pancreatic carcinoma.
The metastasis-related molecules CD133, CD44v6 and human tissue factor (TF) have been shown to be associated with tumor invasion and metastasis. This study aimed to determine whether co-expression of these three molecules was associated with metastasis and overall prognosis in pancreatic carcinoma. We analyzed the expression profiles of these three molecules by immunohistochemistry and evaluated the relationship of their expression profiles with metastasis and prognosis in 109 pancreatic carcinomas. The results showed that the expression levels of CD133, CD44v6 and TF were increased in pancreatic carcinoma. Co-expression of CD133, CD44v6 and TF (tri-expression) was also detected in pancreatic carcinoma. Clinical analysis showed that individual expression of CD133, CD44v6 or TF was associated with vessel invasion, lymph node metastasis and liver metastasis, while tri-expression was associated with lymph node metastasis. Survival analysis showed that patients with co-expression of CD133 and TF or tri-expression had lower and the lowest overall survival rates, respectively. Univariate analysis showed that T-factor, lymph node metastasis, TNM stage, and individual levels or tri-expression of CD133, CD44v6 and TF were survival risk factors. Multivariate analysis showed that tri-expression of CD133, CD44v6 and TF was an independent predictor of survival. These results suggest that overexpression of CD133, CD44v6 and TF is associated with pancreatic carcinoma metastasis. Tri-expression of these three molecules may be a useful predictor for pancreatic carcinoma prognosis.


Kinetic properties of the Ca2+-accumulation system of a rat liver microsomal fraction.
1. By using Ca-EGTA buffers, the Km for Ca2+ uptake into rat liver heavy microsomes (microsomal fraction) was found to be 0.2 microM free Ca2+. 2. In the absence of oxalate, these vesicles accumulate about 20 nmol of Ca2+/mg of protein. Efflux of Ca2+ from the vesicles is much faster at pH 7.6 than at pH 6.8, but does not apparently show saturation kinetics or any stringent requirement for external ions. 3. The steady-state distribution of Ca2+ between the microsomes and the medium in the presence of ATP and the absence of oxalate is dependent on Ca2+ load. When the vesicles are loaded to 50% capacity, the external free Ca2+ concentration is 70 nM. 4. The affinity of heavy microsomes for Ca2+ is such that is seems likely that they has a dominant role in the determination of cytoplasmic free Ca2+ concentrations.


[Studies on reversing MDR of K562/A02 by ramification of curcumin hydrolyzed].
To determine the reversal effects of ramification of curcumin hydrolyzed on multidrug-resistant cell line K562/A02, and explore its reversal mechanism. After treatment with ramification of curcumin hydrolyzed, the sensitivity of K562/A02 cells to usuall chemotherapeutic drugs were determined by MTT. The expression of P-gp in K562/A02 and K562 cells was detected by immunohistochemical method. Intracellular mean fluorescence intensity (MFI) of DNR in K562 and K562/A02 cells was detected by Flow Cytometry. After treatment with the ramification of curcumin, hydrolyzed (2.5 mg x L(-1)) IC50, of usuall chemotherapeutic drugs to K562/A02 decreased. The sensitivity of K562/A02 cells increased. The expression of the P-gp in K562/A02 cells decreased (P < 0.05); MFI of the DNR in K562/A02 cells more significantly increased (P < 0.05). The expression of mdrl-mRNA decreased. The ramification of curcumin hydrolyzed have effects on the reversal multidrug-resistant of K562/A02 cells in vitro. It could enhance the sensitivity of K562/A02 cells to chemotherapeutic drugs and the mechanism might be associated with inhibiting P-gp-mediated drug efflux and increasing of intracellular concentration of chemotherapeutic drugs.


Cytogenetics in the management of T-cell acute lymphoblastic leukemia (T-ALL): Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH).
Molecular analysis is the hallmark of T-cell acute lymphoblastic leukemia (T-ALL) categorization. Several T-ALL sub-groups are well recognized based on the aberrant expression of specific transcription factors. This recently resulted in the implementation of eight provisional T-ALL entities into the novel 2022 International Consensus Classification, albeit not into the updated World Health Organization classification system. Despite this extensive molecular characterization, cytogenetic analysis remains the backbone of T-ALL diagnosis in many countries as chromosome banding analysis and fluorescence in situ hybridization are relatively inexpensive techniques to obtain results of diagnostic, prognostic and therapeutic interest. Here, we provide an overview of recurrent chromosomal abnormalities detectable in T-ALL patients and propose guidelines regarding their detection. By referring in parallel to the more general molecular classification approach, we hope to offer a diagnostic framework useful in a broad clinical genetic setting.


Viral activation of interleukin-15 (IL-15): characterization of a virus-inducible element in the IL-15 promoter region.
We identified an interferon regulatory factor motif (IRF-E) upstream of an NF-kappaB binding site in the interleukin-15 (IL-15) promoter. Since these two motifs are part of the virus-inducible enhancer region of the beta interferon promoter, we speculated that there might be similar responses of these two genes to stimuli such as viruses. To test this hypothesis, L929 cells were infected with Newcastle disease virus (NDV), which led to the induction of IL-15 mRNA and protein expression. Using IL-15 promoter-reporter deletion constructs, a virus-inducible region, encompassing IRF-E, NF-kappaB, and a 13-nucleotide sequence flanked by these two motifs, was mapped to the -295-to--243 position relative to the transcription initiation site. Using cotransfection studies, it was demonstrated that all three motifs were essential to achieve the maximum promoter activity induced by IRF-1 and NF-kappaB expression plasmids. The presence of a virus-inducible region in the IL-15 promoter suggests a role for IL-15 as a component of host antiviral defense mechanisms.


Stimulation of herpes simplex type I infection of C6 cells by trypsin-EDTA.
The nature of the refractoriness of C6 glioblastoma cells to herpes simplex virus type I (HSV-I) infection has been studied. The cells were restricted in susceptibility to HSV-I since only a small proportion of the cells could be infected by HSV-I and the virus yield per cell was low. The susceptibility to infection was increased by treating the cells with trypsin-EDTA prior to infection. The cells so treated recovered resistance to the virus when incubated at 37 degrees C, their resistance being restored to the initial level in 2 days. This restoration was inhibited by addition of cycloheximide or puromycin. Trypsin-EDTA treatment of C6 cells increased the efficiency of adsorption of HSV-I and the formation of stable cell-virus complexes from which the virus could not be dissociated by heparin.


Low incidence of left atrial delayed enhancement with MRI in patients with AF: a single-centre experience.
Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. One potential target for ablation is left atrial (LA) scar (LAS) regions that may be the substrate for re-entry within the atria, thereby sustaining AF. Identification of LAS through LA delayed gadolinium enhancement (LADE) with MRI has been proposed. We sought to evaluate LADE in patients referred for catheter ablation of AF. Prospective analysis was conducted of consecutive patients who underwent pulmonary vein antrum isolation (PVAI) ablation for AF at a single institution. Patients underwent LADE with MRI to determine LAS regions before ablation. MRI data were analysed independently in accordance with prespecified institutional protocol by two staff cardiac radiologists to whom patient outcomes were masked, and reports of LADE were documented. Where no initial consensus occurred regarding delayed enhancement (DE), a third staff cardiac radiologist independently reviewed the case and had the deciding vote. Of the 149 consecutive patients (mean (SD) age, 59 (9) years), AF was persistent in 64 (43%) and paroxysmal in 85 (57%); 45 (30%) had prior ablation. Only five patients (3%) had identifiable DE in LA walls (persistent AF, n=1; paroxysmal AF, n=4). LADE was present in two (4%) of the 45 patients with previous left PVAI. The presence of LADE was not associated with a higher recurrence rate of AF. In contrast to previous studies, the finding of DE within LA walls was uncommon and, when present, did not correlate with AF type or risk of AF recurrence. It therefore is of unclear clinical significance.


Techniques for investigation of an apparent outbreak of infections with Candida glabrata.
A cluster of Candida glabrata isolates recovered from seven patients in an intensive care unit over a 10-week period were compared with a collection of isolates from six epidemiologically distinct outpatients and a reference strain by several DNA typing methods. Restriction enzyme analysis with HinII distinguished 13 strains from the 14 sources and was the method of choice. Pulsed-field gel electrophoresis and random amplification of polymorphic DNA both detected nine types from the 14 sources; however, the results of these two methods did not always correlate. These methods demonstrated that five of the seven patients had distinguishable strains and that cross-infection was unlikely.


[The 1-hour oxycardiorespirography as routine study in the diagnosis of cardiorespiratory dysregulation in infancy--an attempt at establishing normal values].
Because of the growing demand to evaluate cardiorespiratory dysfunctions the short-time oxycardiorespirography becomes a more and more important and powerful tool in the daily clinical routine. Therefore, from about one hour lasting records we studied the distribution of MA-values (mean apnea duration), duration of the longest apnea, percentage of periodic breathing time, lowest heart rate values, lowest transcutaneous PO2 values and highest transcutaneous PCO2 values in an obstetrical optimal low-risk group of 90 infants and a obstetrical non-optimal group of 152 infants between four and ten weeks of age. Percentiles of each variable were calculated, and we suggest the 90th percentiles as new threshold values to judge these short-time recordings. In comparison to relevant data from the literature we could demonstrate that deviating threshold values have to be applied to short-time recordings in comparison to long-time recordings. In addition, the respiratory behaviour of the optimal group is compared to that of the non-optimal group of the same age. Interestingly enough, no difference in the respiratory behaviour between these groups could be demonstrated.


L-arginine for the treatment of centrally obese subjects: a pilot study.
Visceral adiposity has been linked to higher rates of cardiometabolic risk than other types of adiposity. Waist circumference (WC) is the best anthropomorphic surrogate of visceral adiposity. Reductions in central adiposity may decrease cardiovascular risk. Animal studies have demonstrated that L-arginine reduces visceral adiposity and fat mass. The primary aim of our study was to assess the efficacy of L-arginine for reducing central adiposity in nondiabetic obese subjects. Secondary aims were to assess the efficacy of L-arginine for decreasing body mass index (BMI), waist-to-hip ratio (WHR), and weight. Female subjects (n = 20) were included if they: were ≥ 18 years and ≤ 40 years of age, had a BMI of ≥ 30 and ≤ 40 kg/m(2), had a WC ≥ 89 cm. Subjects received 3 g of L-arginine three times a day for 12 weeks and were counseled on lifestyle modification. Overall, L-arginine was well tolerated with no clinically significant adverse events. Serum L-arginine levels were significantly increased from baseline at both 6 and 12 weeks (p < .05). WC (mean ± SD) decreased from 115.6 ± 12.7 cm at baseline to 109.2 ± 11.7 cm at 12 weeks (p = .0004). Weight (mean ± SD) decreased from 98.6 ± 19.7 kg at baseline to 95.7 ± 18.6 kg at 12 weeks (p = .015). Significant reductions from baseline were also observed in BMI and WHR. L-Arginine may be effective at reducing central adiposity in obese patients.


Results of endovascular repair of infrarenal aortic aneurysms using the Endurant stent graft.
Recent reports showed that the Endurant stent graft (Medtronic Cardiovascular, Santa Rosa, Calif) is safe and effective for endovascular repair of abdominal aortic aneurysms (AAAs). However, due to its relatively recent introduction, only short-term follow-up data are available. This study presents the 4-year results using this device. All clinical data, including detailed anatomic information of the first 100 consecutive patients treated with the Endurant stent graft for an infrarenal AAA in three Dutch high-volume hospitals, were prospectively collected. Computed tomography angiography was routinely performed before the procedure, ≤ 1 month, and at 1 year post-endovascular aneurysm repair. Thereafter, the imaging modality during yearly follow-up was individualized (duplex ultrasound imaging or computed tomography angiography). Patients were classified as within or outside the instructions for use (IFU) for analysis. Study end points were primary clinical success, overall and AAA-related mortality, and sac morphology changes and endoleak during follow-up. Estimates were obtained using Kaplan-Meier plots. The study included 100 consecutive patients (88 men) with a median age of 74 years (interquartile range [IQR], 67-79 years) and median AAA diameter of 58 mm (IQR, 55-65 mm), between December 2007 and March 2009. Twenty patients (20%) were treated outside the IFU (18, outside proximal neck IFU, one outside iliac IFU, and one outside both IFUs). Median follow-up was 48 months (IQR, 36-53 months), and no patients were lost. One contained rupture was observed after 1.5 months due to graft infection. No patients had graft migration. Two type Ia endoleaks, 5 type Ib endoleaks, and 15 type II endoleaks were found. Primary clinical success was 97%, 90%, 84% and 77% at 1, 2, 3, and 4 years, respectively. Primary clinical success was comparable for patients treated within or outside IFU (P = .20), although both patients outside iliac IFU needed a secondary iliac intervention. Over time, maximum aneurysm diameter decreased ≥ 5 mm, remained stable, and increased ≥ 5 mm in 58%, 32%, and 10% of the patients, respectively. All-cause mortality was 20% at 4 years, with a 3% AAA-related mortality. The 4-year follow-up data of the Endurant stent graft for AAA treatment shows its use results in a low AAA-related mortality with adequate prevention of rupture or aneurysm growth. Although patients with very challenging anatomy were treated in our series, primary clinical success rates were comparable for patients treated within and outside the IFU. However, both patients outside the iliac IFU needed a secondary iliac intervention. The knowledge of the present results may aid in improving outcomes in the future.


Optimal buffered compression and coding mode selection for MPEG-4 shape coding.
We propose an optimal buffered compression algorithm for shape coding as defined in the forthcoming MPEG-4 international standard. The MPEG-4 shape coding scheme consists of two steps: first, distortion is introduced by down and up scaling; then, context-based arithmetic encoding is applied. Since arithmetic coding is "lossless," the down up scaling step is considered as a virtual quantizer. We first formulate the buffer-constrained adaptive quantization problem for shape coding, and then propose an algorithm for the optimal solution under buffer constraints. Previously, the fact that a conversion ratio (CR) of 1/4 makes a coded image irritating to human observers for QCIF size was reported for MPEG-4 shape coding. Therefore, careful consideration for small size images such as QCIF should be given to prevent coded images from being unacceptable. To this end, a low bit rate tuned algorithm is proposed in this paper as well. Experimental results are given using an MPEG-4 shape codec.


CD4 is an important host factor for Japanese encephalitis virus entry and replication in PK-15 cells.
Japanese encephalitis virus (JEV) is a flavivirus that is spread through mosquito bites and is the leading cause of viral encephalitis in Asia. JEV can infect a variety of cell types; however, crucial receptor molecules remain unclear. The purpose of this study was to determine whether porcine CD4 protein is a receptor protein that impacts JEV entry into PK15 cells and subsequent viral replication. We confirmed the interaction between the JEV E protein and the CD4 protein through Co-IP, virus binding and internalization, antibody blocking, and overexpression and created a PK-15 cell line with CD4 gene knockdown by CRISPR/Cas9. The results show that CD4 interacts with JEV E and that CD4 knockdown cells altered virus adsorption and internalization, drastically reducing virus attachment. The level of viral transcription in CD4 antibody-blocked cells, vs. control cells, was decreased by 49.1%. Based on these results, we believe that CD4 is a receptor protein for JEVs. Furthermore, most viral receptors appear to be associated with lipid rafts, and colocalization studies demonstrate the presence of CD4 protein on lipid rafts. RT‒qPCR and WB results show that virus replication was suppressed in PK-15-CD4KD cells. The difference in viral titer between KD and WT PK-15 cells peaked at 24 h, and the viral titer in WT PK-15 cells was 5.6 × 106, whereas in PK-15-CD4KD cells, it was only 1.8 × 106, a 64% drop, demonstrating that CD4 deficiency has an effect on the process of viral replication. These findings suggest that JEV enters porcine kidney cells via lipid raft-colocalized CD4, and the proliferation process is positively correlated with CD4.


Obesity, hypertension and insulin resistance.
Being overweight or obese has become highly prevalent in Western countries and are rapidly reaching epidemic proportions in the developing world. Obesity-related disorders, such as hypertension and diabetes, are also increasing at an alarming rate. The relationship between obesity, hypertension and insulin resistance is well recognised, but the molecular mechanisms involved remain relatively poorly understood. Adipose tissue plays a key role in the pathogenesis of the metabolic syndrome. It serves as an important source of pro-inflammatory molecules, including leptin, tumour necrosis factor alpha, angiotensin II and interleukin-6, as well as anti-inflammatory molecules, such as adiponectin. Knowledge of how these adipose tissue-derived factors influence metabolic and cardiovascular disease has recently expanded. Leptin is now considered to play a key role in the elevation of sympathetic activity commonly found in obese, hypertensive patients, and decreased secretion of adiponectin appears to be an important predictor of diabetes. The ectopic storage of excess fat in skeletal muscle, liver or pancreas, due to the decreased capacity of adipose tissue to scavenge excess calories, may also play a role in the development of insulin resistance and type 2 diabetes. Overall, continuing research into the relationship between adipose-tissue biology and metabolic abnormalities may lead to a better understanding of the molecular mechanisms underlying the relationship between obesity and cardiovascular disease, and ultimately provide alternative treatments for the control of potentially life-threatening conditions.


Airway inflammation after cessation of exposure to agents causing occupational asthma.
Subjects with occupational asthma (OA) generally present asthma symptoms and airway hyperresponsiveness after cessation of exposure. We hypothesized that they are also left with airway inflammation. We assessed 133 subjects with OA at a mean interval of 8.7 years (0.5-20.8 years) after cessation of exposure by questionnaire, airway caliber, and responsiveness to methacholine. Satisfactory samples of induced sputum were obtained from 98 subjects. We defined three groups of subjects: (1) cured: normalization of the concentration of methacholine provoking a 20% decrease in FEV1 (PC20), (2) improved: increase in PC20 by 3.2-fold or more but PC20 still abnormal, and (3) not improved: no significant change in PC20. In all, 9/28 subjects (32.1%) with no improvement versus 6/56 (10.7%) subjects with partial and complete improvements had sputum eosinophils equal to or greater than 2% and 11/28 (39.3%) subjects versus 11/56 (19.6%) subjects showed sputum neutrophils equal to or greater than 61%. Levels of interleukin-8 and of the neutrophil-derived myeloperoxidase were significantly more elevated in sputum of subjects with no improvement. Those in the cured or improved groups had a significantly longer time lapse since diagnosis and a higher PC20 at the time of diagnosis. We conclude that failure to improve after cessation of exposure to an agent causing OA is associated with airway inflammation at follow-up.


Clinical evaluation of new generation oxygenators with integrated arterial line filters for cardiopulmonary bypass.
New generation oxygenators with integrated arterial line filters have been marketed to improve the efficacy of cardiopulmonary bypass (CPB). Differences in designs, materials, coating surfaces, pore size of arterial filter, and static prime exist between the oxygenators. Despite abundant preclinical data, literature lacks clinical studies. From September 2010 to March 2011, 80 consecutive patients were randomized to CPB using Terumo Capiox FX25 (40 patients, Group-T) or Sorin Synthesis (40 patients, Group-S) oxygenators. Pressure drop and gas exchange efficacy were registered during CPB. High-sensitivity C-reactive protein (hs-CRP), white blood cells (WBCs), fluid balance, activated clotting time, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, platelets (PLTs), serum albumin, and total proteins were measured perioperatively at different timepoints. Clinical outcome was recorded. Repeated measure analysis of variance and nonparametric statistics assessed between-groups and during time differences. The two groups showed similar baseline and intraoperative variables. No differences were recorded in pressure drop and gas exchange (group-P and group*time-P = N.S. for all) during CPB. Despite similar fluid balance (P = N.S. for static/dynamic priming and ΔVolume administered intraoperatively), Group-T showed higher hs-CRP (group-P = 0.034), aPTT (group-P = 0.0001), and INR (group-P= 0.05), with lower serum albumin (group-P = 0.014), total proteins (group-P = 0.0001), fibrinogen (group-P = 0.041), and PLTs (group-P = 0.021). Group-T also showed higher postoperative bleeding (group-P = 0.009) and need for transfusions (P = 0.008 for packed red cells and P = 0.0001 for fresh frozen plasma and total transfused volumes). However, clinical outcome was comparable (P = N.S. for all clinical endpoints). Both oxygenators proved effective and resulted in comparable clinical outcomes. However, Sorin Synthesis seems to reduce inflammation and better preserve the coagulative cascade and serum proteins, resulting in lower transfusions and post-CPB inflammatory response.


Thalidomide as initial therapy for early-stage myeloma.
Patients with early-stage myeloma are typically observed without therapy until symptomatic disease occurs. However, they are at high risk of progression to symptomatic myeloma, with a median time to progression of approximately 1-2 years. We report the final results of a phase II trial of thalidomide as initial therapy for early-stage multiple myeloma in an attempt to delay progression to symptomatic disease. In total, 31 patients with smoldering or indolent multiple myeloma were studied at the Mayo Clinic. Two patients were deemed ineligible because they were found to have received prior therapy for myeloma, and were excluded from analyses except for toxicity. Thalidomide was initiated at a starting dose of 200 mg/day. Patients were followed-up monthly for the first 6 months and every 3 months thereafter. Of the 29 eligible patients, 10 (34%) had a partial response to therapy with at least 50% or greater reduction in serum and urine monoclonal (M) protein. When minor responses (25-49% decrease in M protein) were included, the response rate was 66%. Three patients had progressive disease while on therapy. Kaplan-Meier estimates of progression-free survival are 80% at 1 year and 63% at 2 years. Major grade 3-4 toxicities included two patients with somnolence and one patient each with neuropathy, deep-vein thrombosis, hearing loss, weakness, sinus bradycardia, and edema. Thalidomide has significant activity in early-stage myeloma and has the potential to delay progression to symptomatic disease. This approach must be further tested in randomized trials.


openMNGlab: Data Analysis Framework for Microneurography - A Technical Report.
openMNGlab is an open-source software framework for data analysis, tailored for the specific needs of microneurography - a type of electrophysiological technique particularly important for research on peripheral neural fibers coding. Currently, openMNGlab loads data from Spike2 and Dapsys, which are two major data acquisition solutions. By building on top of the Neo software, openMNGlab can be easily extended to handle the most common electrophysiological data formats. Furthermore, it provides methods for data visualization, fiber tracking, and a modular feature database to extract features for data analysis and machine learning.


Distance sampling surveys reveal 17 million vertebrates directly killed by the 2020's wildfires in the Pantanal, Brazil.
Anthropogenic factors have significantly influenced the frequency, duration, and intensity of meteorological drought in many regions of the globe, and the increased frequency of wildfires is among the most visible consequences of human-induced climate change. Despite the fire role in determining biodiversity outcomes in different ecosystems, wildfires can cause negative impacts on wildlife. We conducted ground surveys along line transects to estimate the first-order impact of the 2020 wildfires on vertebrates in the Pantanal wetland, Brazil. We adopted the distance sampling technique to estimate the densities and the number of dead vertebrates in the 39,030 square kilometers affected by fire. Our estimates indicate that at least 16.952 million vertebrates were killed immediately by the fires in the Pantanal, demonstrating the impact of such an event in wet savanna ecosystems. The Pantanal case also reminds us that the cumulative impact of widespread burning would be catastrophic, as fire recurrence may lead to the impoverishment of ecosystems and the disruption of their functioning. To overcome this unsustainable scenario, it is necessary to establish proper biomass fuel management to avoid cumulative impacts caused by fire over biodiversity and ecosystem services.


ACC/AHA guidelines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans: the Copenhagen General Population Study.
We compared the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on prevention of atherosclerotic cardiovascular disease (ASCVD) using different risk prediction models [US Pooled Cohort Equations (US-PCE for any ASCVD) and European Systematic COronary Risk Evaluation system (European-SCORE for fatal ASCVD)] and different statin eligibility criteria. We examined 44 889 individuals aged 40-75 recruited in 2003-09 in the Copenhagen General Population Study, all free of ASCVD, diabetes, and statin use at baseline. We detected 2217 any ASCVD events and 199 fatal ASCVD events through 2014. The predicted-to-observed event ratio was 1.2 using US-PCE for any ASCVD and 5.0 using European-SCORE for fatal ASCVD. The US-PCE, but not the European-SCORE, was well-calibrated around decision thresholds for statin therapy. For a Class I recommendation, 42% of individuals qualified for statins using the ACC/AHA guidelines vs. 6% with the ESC/EAS guidelines. Using ACC/AHA- vs. ESC/EAS-defined statin eligibility led to a substantial gain in sensitivity (+62% for any ASCVD and +76% for fatal ASCVD) with a smaller loss in specificity (-35% for any ASCVD and -36% for fatal ASCVD). Similar differences between the ACC/AHA and ESC/EAS guidelines were found for men and women separately, and for Class IIa recommendations. The sensitivity and specificity of a US-PCE risk of 5% were similar to those of a European-SCORE risk of 1.4%, whereas a US-PCE risk of 7.5% was similar to a European-SCORE risk of 2.4%. The ACC/AHA guidelines were superior to the ESC/EAS guidelines for primary prevention of ASCVD, that is, for accurately assigning statin therapy to those who would benefit.


Temperature Management in the ICU.
Temperature abnormalities are recognized as a marker of human disease, and the therapeutic value of temperature is an attractive treatment target. The objective of this synthetic review is to summarize and critically appraise evidence for active temperature management in critically ill patients. We searched MEDLINE for publications relevant to body temperature management (including targeted temperature management and antipyretic therapy) in cardiac arrest, acute ischemic and hemorrhagic stroke, traumatic brain injury, and sepsis. Bibliographies of included articles were also searched to identify additional relevant studies. English-language systematic reviews, meta-analyses, randomized trials, observational studies, and nonhuman data were reviewed, with a focus on the most recent randomized control trial evidence. Data regarding study methodology, patient population, temperature management strategy, and clinical outcomes were qualitatively assessed. Temperature management is common in critically ill patients, and multiple large trials have been conducted to elucidate temperature targets, management strategies, and timing. The strongest data concerning the use of therapeutic hypothermia exist in comatose survivors of cardiac arrest, and recent trials suggest that appropriate postarrest temperature targets between 33°C and 37.5°C are reasonable. Targeted temperature management in other critical illnesses, including acute stroke, traumatic brain injury, and sepsis, has not shown benefit in large clinical trials. Likewise, trials of pharmacologic antipyretic therapy have not demonstrated improved outcomes, although national guidelines do recommend treatment of fever in patients with stroke and traumatic brain injury based on observational evidence associating fever with worse outcomes. Body temperature management in critically ill patients remains an appealing therapy for several illnesses, and additional studies are needed to clarify management strategies and therapeutic pathways.


[Ceramic cups for hip endoprostheses. 6: Cup design, inclination and antetorsion angle modify range of motion and impingement].
The present investigation focuses on total hip replacement using ceramic acetabular components. The relationship between the position of the cup and the range of motion (ROM) was investigated. A limited range of motion may cause impingement, which is defined as contact between the femoral neck and the rim of the acetabular cup. Impingement may result in wear, chipping, fracture or dislocation of the femoral head. Joint movements were simulated in a three-dimensional CAD program. The results obtained underscore the importance of correct positioning and design of the cup for achieving a ROM as close to the physiological situation as possible. With ceramic cups, the inclination angle should not be more than 45 degrees, and the antetorsion angle between 10 and 15 degrees. If the cup is too vertical, the risk of dislocation and fracture of the ceramic increases. If, on the other hand, the angle of inclination is too small, flexion and abduction will be greatly limited. The study shows that acetabular components with non-recessed ceramic inserts should not be used. Slight recession of the insert helps to avoid impingement. The ROM is reduced and the risk of impingement appreciably increased when mushroom-shaped femoral heads (XL heads) or ceramic inserts protected by a polyethylene ring are used.


Comprehensive analysis of expression, subcellular localization, and cognate pairing of SNARE proteins in oligodendrocytes.
Oligodendrocytes form the central nervous system myelin sheath by spiral wrapping of their plasma membrane around axons, necessitating a high rate of exocytic membrane addition to the growing myelin membrane. Membrane fusion is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins (SNAREs), which act by specific pairing of vesicle (R)- and target (Q)-SNAREs. To characterize oligodendroglial SNAREs and their trafficking pathways, we performed a detailed expression analysis of SNAREs in differentiating cultured oligodendrocytes and myelin and determined their subcellular localization. Expression of the plasma membrane Q-SNAREs syntaxin 3, syntaxin 4, SNAP23, and the endosomal R-SNARE VAMP3/cellubrevin increased with oligodendroglial maturation, while the expression of SNAP29 decreased. Interestingly, syntaxin 3, syntaxin 4, and VAMP7/tetanustoxin-insensitive VAMP accumulated in myelin during development, suggesting a role in myelin membrane fusion. Coimmunoprecipitation from oligodendroglial cell lysates elucidated interactions between SNAREs: for example, Golgi-localized VAMP4 associated with syntaxin 6 and SNAP29. Furthermore, we identified a cognate core complex composed of VAMP3, syntaxin 4, and SNAP23, which may mediate fusion of endosome-derived vesicles with the plasma membrane. This study provides a comprehensive analysis of SNARE proteins in oligodendrocytes and assigns defined SNAREs to putative vesicle trafficking pathways in myelinating oligodendrocytes, thus facilitating future functional analysis of distinct SNAREs in oligodendroglial membrane traffic and myelination.


A graphical representation of image quality for three-dimensional structure analysis of two-dimensional crystals.
Electron crystallography of two-dimensional (2D) crystals is a powerful approach for the analysis of membrane protein structure. Three-dimensional (3D) structures are derived by merging data from 2D crystals at varying tilt axes and tilt angles. A graphical representation was developed that incorporates the tilt geometry to display the quality of each image. Information that can be extracted from the plot includes a symbol for each image that reflects the completeness of the data for that crystal. The polar plot also includes a novel parameter that reflects the minimal variation in tilt axis to ensure overlap of data points in reciprocal space between images at the same tilt angle. The tilt geometry and image quality plot is especially useful for tracking the progress of data collection and for assessing the completeness of two data sets prior to determination of difference maps.


Effect of Illumination on Ocular Status Modifications Induced by Short-Term 3D TV Viewing.
Objectives. This study aimed to compare changes in ocular status after 3D TV viewing under three modes of illumination and thereby identify optimal illumination for 3D TV viewing. Methods. The following measures of ocular status were assessed: the accommodative response, accommodative microfluctuation, accommodative facility, relative accommodation, gradient accommodative convergence/accommodation (AC/A) ratio, phoria, and fusional vergence. The observers watched 3D television for 90 minutes through 3D shutter glasses under three illumination modes: A, complete darkness; B, back illumination (50 lx); and C, front illumination (130 lx). The ocular status of the observers was assessed both before and after the viewing. Results. After 3D TV viewing, the accommodative response and accommodative microfluctuation were significantly changed under illumination Modes A and B. The near positive fusional vergence decreased significantly after the 90-minute 3D viewing session under each illumination mode, and this effect was not significantly different among the three modes. Conclusions. Short-term 3D viewing modified the ocular status of adults. The least amount of such change occurred with front illumination, suggesting that this type of illumination is an appropriate mode for 3D shutter TV viewing.


Latitudinal variation in sexual size dimorphism of sea-run masu salmon, Oncorhynchus masou.
Sexual size dimorphism (SSD), a difference in body size between the sexes, occurs in many animal species. Although the larger sex is often considered invariable within species, patterns of selection may result in interpopulation variation or even reversal of SSD. We evaluated correlations between latitude and female body size, male body size, and relative body size (male body size/female body size) in 22 populations (ranging from 37 degrees N to 49 degrees N) of sea-run masu salmon (Oncorhynchus masou) that spawn in rivers along the Sea of Japan coast. Male size and the relative body size increased with latitude, but female size did not correlate with latitude. In addition, increase in male size with latitude was sufficient to result in a reversal of SSD, the switch-point being around 45 degrees N. We suggest that the positive correlation between latitude and male size is due to increasing operational sex ratios or sexual selection on sea-run male body size that result from sex-biased patterns of anadromy. In conclusion, our study provides the first example of predictable geographic variation in SSD shaped by apparent patterns of sexual selection.


In vitro dimerization of human RIO2 kinase.
RIO proteins form a conserved family of atypical protein kinases. RIO2 is a serine/threonine protein kinase/ATPase involved in pre-40S ribosomal maturation. Current crystal structures of archaeal and fungal Rio2 proteins report a monomeric form of the protein. Here, we describe three atomic structures of the human RIO2 kinase showing that it forms a homodimer in vitro. Upon self-association, each protomer ATP-binding pocket is partially remodelled and found in an apostate. The homodimerization is mediated by key residues previously shown to be responsible for ATP binding and catalysis. This unusual in vitro protein kinase dimer reveals an intricate mechanism where identical residues are involved in substrate binding and oligomeric state formation. We speculate that such an oligomeric state might be formed also in vivo and might function in maintaining the protein in an inactive state and could be employed during import.


Long-term hypotensive and renal effects of atrial natriuretic peptide.
The present study was designed to examine the short-term and long-term effects of increased plasma levels of atrial natriuretic peptide on the glomerular filtration rate, sodium excretion, and arterial pressure. Intravenous infusion of synthetic atrial natriuretic peptide (2 micrograms/kg/bolus, 50 ng/kg/min continuous infusion) for 45 minutes in six conscious dogs increased plasma levels of immunoreactive atrial natriuretic peptide from 69 +/- 10 to 233 +/- 14 pg/ml. Short-term increases in plasma levels of atrial natriuretic peptide increased the glomerular filtration rate from 53 +/- 15 to 82 +/- 16 ml/min and increased sodium excretion from 74.4 +/- 32.6 to 146.9 +/- 38.1 microEq/min. Mean arterial pressure decreased slightly, from 88 +/- 3 to 83 +/- 3 mm Hg, whereas no changes occurred in plasma renin activity (2.0 +/- 0.6 to 1.6 +/- 0.8 ng of angiotensin I per milliliter per hour) or plasma aldosterone concentration (6.9 +/- 2.3 to 8.1 +/- 3.9 ng/dl). To determine whether the short-term effects of atrial natriuretic peptide on the glomerular filtration rate and sodium excretion lead to a sustained reduction in mean arterial pressure, atrial natriuretic peptide (50 ng/kg/min) was infused intravenously for 5 days in six conscious dogs. Long-term infusion increased plasma levels of immunoreactive atrial natriuretic peptide from 27 +/- 5 to 292 +/- 31 pg/ml. The infusion caused only a transient increase in sodium excretion and had no significant long-term effect on the glomerular filtration rate. Mean arterial pressure decreased from 90 +/- 3 to 74 +/- 3 and 75 +/- 4 mm Hg by Days 4 and 5 of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Accelerated iterative reconstruction for positron emission tomography based on the em algorithm for maximum likelihood estimation.
The EM method that was originally developed for maximum likelihood estimation in the context of mathematical statistics may be applied to a stochastic model of positron emission tomography (PET). The result is an iterative algorithm for image reconstruction that is finding increasing use in PET, due to its attractive theoretical and practical properties. Its major disadvantage is the large amount of computation that is often required, due to the algorithm's slow rate of convergence. This paper presents an accelerated form of the EM algorithm for PET in which the changes to the image, as calculated by the standard algorithm, are multiplied at each iteration by an overrelaxation parameter. The accelerated algorithm retains two of the important practical properties of the standard algorithm, namely the selfnormalization and nonnegativity of the reconstructed images. Experimental results are presented using measured data obtained from a hexagonal detector system for PET. The likelihood function and the norm of the data residual were monitored during the iterative process. According to both of these measures, the images reconstructed at iterations 7 and 11 of the accelerated algorithm are similar to those at iterations 15 and 30 of the standard algorithm, for two different sets of data. Important theoretical properties remain to be investigated, namely the convergence of the accelerated algorithm and its performance as a maximum likelihood estimator.


Automated evaluation of goal-attainment ratings.
At the Fort Logan Mental Center in Denver, an automated system for evaluating treatment effectiveness is based on a goal-attainment approach. Patients, staff, and patients' relatives or friends specify treatment goals from a standardized list of 703 goal statements. They rate the importance of each goal at the time it is set, and later rate the degree of goal attainment. The authors describe uses of the system and emphasize its value in obtaining information during treatment that can help improve the treatment process.


A new approach for improving coronary plaque component analysis based on intravascular ultrasound images.
Virtual histology intravascular ultrasound (VH-IVUS) is a clinically available technique for atherosclerosis plaque characterization. It, however, suffers from a poor longitudinal resolution due to electrocardiogram (ECG)-gated acquisition. This article presents an effective algorithm for IVUS image-based histology to overcome this limitation. After plaque area extraction within an input IVUS image, a textural analysis procedure consisting of feature extraction and classification steps is proposed. The pixels of the extracted plaque area excluding the shadow region were classified into one of the three plaque components of fibro-fatty (FF), calcification (CA) or necrotic core (NC) tissues. The average classification accuracy for pixel and region based validations is 75% and 87% respectively. Sensitivities (specificities) were 79% (85%) for CA, 81% (90%) for FF and 52% (82%) for NC. The kappa (kappa) = 0.61 and p value = 0.02 indicate good agreement of the proposed method with VH images. Finally, the enhancement in the longitudinal resolution was evaluated by reconstructing the IVUS images between the two sequential IVUS-VH images.


Effects of environmental enrichment on repetitive behaviors in the BTBR T+tf/J mouse model of autism.
Lower order and higher order repetitive behaviors have been documented in the BTBR T+tf/J (BTBR) mouse strain, a mouse model that exhibits all three core behavioral domains that define autism. The purpose of this study was to evaluate the effectiveness of environmental enrichment for reducing repetitive behaviors in BTBR mice. Lower order behaviors were captured by assaying the time and sequence of grooming, while higher order behaviors were measured using pattern analysis of an object exploration task from digital recordings. Baseline scores were established at 7 weeks of age, followed by 30 days of housing in either a standard or enriched cage. As expected, BTBR mice spent significantly more time grooming and had a more rigid grooming sequence than control C57BL/6J mice did at baseline. After 30 days of enrichment housing, BTBR mice demonstrated a significant reduction in time spent grooming, resulting in levels that were lower than those exhibited by BTBR mice in standard housing. However, no changes were noted in the rigidity of their grooming sequence. In contrast to previous findings, there was no difference in repetitive patterns of exploration at baseline between BTBR and C57BL/6J mice in the object exploration test. Subsequently, enrichment did not significantly alter the number of repetitive patterns at posttest. Overall, the results suggest that environmental enrichment may be beneficial for reducing the time spent engaging in lower order repetitive behaviors, but may not change the overall quality of the behaviors when they do manifest.


Finesse in Nasal Tip Refinement.
Nasal tip refinement is one of the most difficult aspects of rhinoplasty surgery. In this article, the senior author (R.J.R.) presents his technique for nasal tip analysis and identifies the factors that contribute to nasal tip shape. Various techniques for nasal tip modification using both sutures and soft cartilage grafts are described to help produce optimal results.


Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β.
Protofibrils of the 42 amino acids long amyloid-β peptide are transient pre-fibrillar intermediates in the process of peptide aggregation into amyloid plaques and are thought to play a critical role in the pathology of Alzheimer's disease. Hence, there is a need for research reagents and potential diagnostic reagents for detection and imaging of such aggregates. Here we describe an in vitro selection of Affibody molecules that bind to protofibrils of Aβ42cc, which is a stable engineered mimic of wild type Aβ42 protofibrils. Several binders were identified that bind Aβ42cc protofibrils with low nanomolar affinities, and which also recognize wild type Aβ42 protofibrils. Dimeric head-to-tail fusion proteins with subnanomolar binding affinities, and very slow dissociation off-rates, were also constructed. A mapping of the chemical properties of the side chains onto the Affibody scaffold surface reveals three distinct adjacent surface areas of positively charged surface, nonpolar surface and a polar surface, which presumably match a corresponding surface epitope on the protofibrils. The results demonstrate that the engineered Aβ42cc is a suitable antigen for directed evolution of affinity reagents with specificity for wild type Aβ42 protofibrils.


The prognostic value of TP53 mutations in oesophageal adenocarcinoma: a systematic review and meta-analysis.
To clarify the prognostic role of tumour protein 53 (TP53) mutations in patients with oesophageal adenocarcinoma (OAC) as there is a need for biomarkers that assist in guiding management for patients with OAC. A systematic review was conducted using MEDLINE, Embase, PubMed and Current Contents Connect to identify studies published between January 1990 and February 2015 of oesophageal cancer populations (with OAC diagnoses >50% of cases) that measured tumoural TP53 status and reported hazard ratios (HR), or adequate data for estimation of HR for survival for TP53-defined subgroups. Risk of bias for HR estimates was assessed using prespecified criteria for the appraisal of relevant domains as defined by the Cochrane Prognosis Methods Group including adherence to Grading of Recommendations, Assessment, Development and Evaluation and REporting recommendations for tumor MARKer prognostic studies guidelines, as well as assay method used (direct TP53 mutation assessment vs immunohistochemistry) and adjustment for standard prognostic factors. A pooled HR and 95% CI were calculated using a random-effects model. Sixteen eligible studies (11 with OAC only and 5 mixed histology cohorts) including 888 patients were identified. TP53 mutations were associated with reduced survival (HR 1.48, 95% CI 1.16 to 1.90, I2=33%). A greater prognostic effect was observed in a sensitivity analysis of those studies that reported survival for OAC-only cohorts and were assessed at low risk of bias (HR 2.11, 95% CI 1.35 to 3.31, I2=0%). Patients with OAC and TP53 gene mutations have reduced overall survival compared with patients without these mutations, and this effect is independent of tumour stage.


Results of postmortem examination of psittacine birds with cardiac disease: 26 cases (1991-1995).
To characterize prevalence and type of cardiac disease evident in psittacine birds during postmortem examination. Retrospective study. 26 psittacine birds with gross and histologic evidence of cardiac disease. Records of postmortem examinations of psittacine birds necropsied during a 4-year period were reviewed. Data on gross and histologic evidence of cardiac disease were analyzed. Birds identified included those in which congestive heart failure (CHF) was considered the primary cause of death and those in which substantial cardiac disease was evident, despite a lack of postmortem findings supportive of CHF. Of 269 psittacine birds necropsied, 26 (9.7%) had evidence of cardiac disease. In 15 (58%) birds with cardiac disease, changes consistent with CHF were evident and were sufficiently severe as to be considered the cause of death. The remaining 11 birds had cardiac lesions secondary to other systemic diseases; cardiac lesions were considered to be an incidental finding in these birds, and CHF was not evident. Of the 15 birds with CHF, 10 had evidence of right ventricular or biventricular failure, whereas only 5 had evidence of left ventricular failure. Prevalence of cardiac disease in the psittacine birds reported here was similar to that seen clinically in other companion animals. The high incidence of right ventricular or biventricular heart failure in psittacine birds was similar to that for poultry in which lesions of right-sided heart failure predominate.


Improving Quality Through Nursing Participation at Bedside Rounds in a Pediatric Acute Care Unit: A Pilot Project.
Implementation of bedside rounds enhances communication and collaboration between physicians and nurses, resulting in improved clinical outcomes. Yet, the literature demonstrates that it remains difficult for nurses to attend rounds if they don't know when they are happening. This project aimed to increase nurses' presence and participation at bedside rounds in a pediatric acute care unit, enhance teamwork and collaboration, and improve quality outcomes. Nurses carried a pager so that physicians could alert them of rounds. Perception of teamwork and collaboration was assessed via surveys pre- and post-intervention as well as the annual survey evaluating RN and MD interactions from the National Database of Nursing Quality Indicators™ (NDNQI®). Other quality outcome measures included length of stay and patient satisfaction through Press Ganey™ surveys. Findings demonstrated that when nurses were notified in advance, their participation in rounds increased from 44.4 to 73%. Length of stay decreased from 2.5 days prior to the project to an average of 2.10 days during the project. Scores on inpatient satisfaction surveys increased from 82.4 to 92.2%, and nursing communication improved from 83.3 to 95.65%. Interprofessional collaboration as reflected by the inclusion of nurses at bedside rounds led to positive outcomes in patient care. Increasing nurses' presence and providing them with a role at rounds is an important step towards fostering teamwork and collaboration with physicians and enhancing team-based care in a pediatric inpatient setting. Further research measuring the impact of interprofessional collaboration in healthcare is needed.


Temperature-sensitive mutants of equine arteritis virus.
Seventeen temperature-sensitive mutants of equine arteritis virus, a nonarthropod-borne togavirus, have been isolated. 5-Fluorouracil, o-methylhydroxylamine and ethyl methanesulphonate were used as mutagens. The mutants were characterized by their ability to synthesize virus RNA and virus proteins at the permissive (35 degrees C) and restrictive temperature (40 degrees C) using autoradiography of cells labelled with 3H-uridine in the presence of actinomycin D and immunofluorescence respectively. Among the mutants, four were unable to synthesize virus RNA and virus proteins at 40 degrees C (RNA-/protein-). The other mutants were RNA-/protein+ (3); RNA +/-/protein- (2); RNA+/protein+ (6) and RNA+/protein- (1).


Clinical melanoma characteristics and survival-a single-center retrospective study between 2000 and 2010.
The aim of this study was to characterize clinical, histological, and outcome features of primary melanoma in 1329 patients managed at a single-center institution between 2000 and 2010. Parameters included age at diagnosis, sex, tumor location, histology, stage, Breslow thickness, and sentinel lymph node status among others. The mean age at diagnosis was 59.1 ± 16.7 years. Women were significantly younger than men when diagnosed (57.2 vs. 61.0 years; p < 0.001). Most melanomas (83%) were diagnosed on typically sun-exposed skin areas. Superficial spreading melanoma (39.5%) was the most frequent histological subtype. The median Breslow thickness was significantly higher for men compared to women (1.10 mm vs. 0.90 mm; p = 0.018). 38.3% of patients with positive and 12.9% of patients with negative sentinel biopsies progressed. Five-year survival analysis for a sub-cohort of 577 patients showed better 5‑year overall survival for woman compared to men (75.8% vs. 63.6%; p = 0.025). Our findings indicate differences in patient characteristics between men and women, and underscore the importance of early melanoma detection to prevent disease progression.