Chronic Histological Outcomes of Indirect Traumatic Optic Neuropathy in Adolescent Mice: Persistent Degeneration and Temporally Regulated Glial Responses.
Injury to the optic nerve, termed, traumatic optic neuropathy (TON) is a known comorbidity of traumatic brain injury (TBI) and is now known to cause chronic and progressive retinal thinning up to 35 years after injury. Although animal models of TBI have described the presence of optic nerve degeneration and research exploring acute mechanisms is underway, few studies in humans or animals have examined chronic TON pathophysiology outside the retina. We used a closed-head weight-drop model of TBI/TON in 6-week-old male C57BL/6 mice. Mice were euthanized 7-, 14-, 30-, 90-, and 150-days post-injury (DPI) to assess histological changes in the visual system of the brain spanning a total of 12 regions. We show chronic elevation of FluoroJade-C, indicative of neurodegeneration, throughout the time course. Intriguingly, FJ-C staining revealed a bimodal distribution of mice indicating the possibility of subpopulations that may be more or less susceptible to injury outcomes. Additionally, we show that microglia and astrocytes react to optic nerve damage in both temporally and regionally different ways. Despite these differences, astrogliosis and microglial changes were alleviated between 14-30 DPI in all regions examined, perhaps indicating a potentially critical period for intervention/recovery that may determine chronic outcomes.


Changes in acetabular orientation during total hip arthroplasty.
The aims of this study were to determine the change in pelvic sagittal alignment before, during, and after total hip arthroplasty (THA) undertaken with the patient in the lateral decubitus position, and to determine the impact of these changes on acetabular component position. We retrospectively compared the radiological pelvic ratio among 91 patients undergoing THA. In total, 41 patients (46%) were female. The mean age was 61.6 years (sd 10.7) and the mean body mass index (BMI) was 20.0 kg/m2 (sd 5.5). Anteroposterior radiographs were obtained: in the standing position preoperatively and at six weeks postoperatively; in the lateral decubitus position after trial reduction intraoperatively; and in the supine position in the post-anaesthesia care unit. Pelvic ratio was defined as the ratio between the vertical distance from the inferior aspect of the sacroiliac (SI) joints to the superior pubic symphysis and the horizontal distance between the inferior aspect of the SI joints. Changes in the apparent component position based on changes in pelvic ratio were determined, with a change of > 5° considered clinically significant. Analyses were performed using Wilcoxon's signed-rank test, with p < 0.05 considered significant. Intraoperatively, in the lateral decubitus position, the pelvic ratio increased (anterior tilt) in 69.4% of cases, did not change significantly in 20.4%, and decreased (posterior tilt) in 10.2% of cases. When six-week postoperative radiographs were compared with preoperative radiographs, the pelvic ratio decreased in 44.9% of cases, did not change significantly in 42.3%, and increased in 12.8% of cases. This change in alignment correlated with a change in acetabular component version of > 5° in 79.6% of cases intraoperatively and 57.7% of cases at six weeks postoperatively. Changes in pelvic sagittal pelvic position occur throughout THA that, if unaccounted for, introduce errors in acetabular component placement. The use of intraoperative imaging may help the appropriate placement of the acetabular component. Cite this article: Bone Joint J 2019;101-B(6 Supple B):45-50.


Synephrine as a Specific Marker for Orange Consumption.
To validate the suitability of synephrine, known to be a highly abundant alkaloid in oranges, as a dietary biomarker for orange consumption, a highly sensitive and robust stable isotope dilution analysis (SIDA) as well as an ECHO method, using the analyte itself as a pseudointernal standard injected into the analysis run to provide an "echo peak" of the analyte, was developed to quantitate synephrine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in citrus juices and human urine before and after the ingestion of orange juice. A citrus juice screening revealed high synephrine concentrations of 150-420 nmol/mL in orange (n = 11) and tangerine (n = 2) juices, whereas 20-100 times lower levels were found in juice from grapefruit (n = 14), lemon (n = 5), pomelo (n = 2), and lime (n = 4). Application of the SIDA to quantitate synephrine in sulfatase/glucuronidase-treated urine samples (n = 10) after orange juice consumption showed an increase of synephrine from trace levels (0.1 ± 0.1 nmol/mL) in the 2-day washout phase to a maximum concentration of 8.9 (±5.5) nmol/mL found 4 h after ingestion of orange juice. Whereas proline betaine was recently reported as a dietary biomarker indicating the ingestion of any citrus product and Chinese artichoke, synephrine can be used a reliable additional biomarker with high specificity for orange and tangerine.


Comparing effectiveness of prognostic tests in idiopathic pulmonary fibrosis.
Introduction: Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive fibrotic interstitial lung disease often resulting in death over several years. Prediction of disease course or survival remains of keen interest for clinicians and patients though a commonly used test or tool remain elusive. Areas covered: We undertook a comprehensive review of the published literature highlighting prognostic indicators and predictors of survival in IPF. Baseline and longitudinal clinical, functional, histopathologic, and radiologic findings have been extensively studied as prognostic predictors, both individually and in composite models. Recent approaches include automated quantifiable radiologic scoring, circulating biomarkers, and genetic polymorphisms or abnormalities. This review highlights individual and composite predictors and their relative utility in clinical practice and research studies. Expert opinion: There is a growing body of knowledge highlighting readily available individual and composite predictors of outcome, though none have come to the forefront for common clinical use. Recent advances include quantitative imaging analysis, circulating serologic markers, and genetic testing, which may be more standardized and less prone to lead-time bias or related complications and comorbidities.


The primate as a model for the human temperature-sensing system: 2. Area of skin receiving thermal stimulation (spatial summation).
The thermal sensitivities of three humans and one monkey were measured using the "yes-no" paradigm based on the Theory of Signal Detection. The aim was to evaluate the monkey's thermal-sensing system as a model for that of humans. Three of the principal variables of human thermal sensations--the temperature to which the skin was adapted, the rate of temperature change, and the site of application of the thermal stimuli--were held constant. The other three variables--area of stimulation, intensity, and direction of the temperature change--were varied systematically. All four subjects displayed spatial summation for both warming and cooling. Isodetectability curves (d'e = 1) to small temperature changes, both for humans and for the monkey, could reasonably be fitted by the function I = kappa A-b, where I is stimulus intensity, A is the area of stimulation, and b is the rate at which spatial summation occurred. The rate of summation, b, to warming stimuli for the humans ranged from 0.60 to 1.14, while that for the monkey was 0.14. The rate of summation to cooling stimuli for the humans ranged from 0.50 to 0.87, while that for the monkey was 0.43. The main species difference was that summation on the monkey palm all but ceased for both warming and cooling stimuli applied to areas larger than 4 cm2. Data from the human subjects did not demonstrate an upper limit of spatial summation. However, there was an indication that the human subjects would show a ceiling for spatial summation near the largest area tested in this study. Thus, when considering the spatial extent of a thermal stimulus and its influence upon thermal sensations, it may be more appropriate to compare areas relative to body size, rather than absolute values.


Expression of a defense-related 3-hydroxy-3-methylglutaryl CoA reductase gene in response to parasitization by Orobanche spp.
Orobanche spp. are angiosperms that live parasitically on the roots of other plants, and are capable of significantly reducing the yield and quality of their crop hosts. We have demonstrated that parasitization by Orobanche induces expression of hmg2, a defense-related isogene of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) in tobacco. Transgenic tobacco plants expressing a construct containing 2.3 kb of the tomato hmg2 gene promoter fused to the beta-glucuronidase (GUS) reporter gene were parasitized by O. aegyptiaca. Expression of the hmg2:GUS construct was detected within 1 day following penetration of the host root by the O. aegyptiaca radicle and was localized to the region immediately around the site of parasite invasion. This expression continued and intensified over the course of O. aegyptiaca development. In addition, the hmg2:GUS expression was induced by secondary parasitization, where secondary roots of O. aegyptiaca contacted the host root at a distance from the primary attachment site. This GUS expression was specific to plants containing the hmg2:GUS construct, and was not observed in control plants transformed with a construct of the cauliflower mosaic virus 35S promoter fused to the GUS gene. These results indicate that Orobanche parasitization initiates rapid and sustained induction of a defense-related gene in the host root.


[New approaches to the treatment of a ligature fistulas].
Original method of treatment of a ligature fistulas was proposed, using the ligature taking out via fistular passway or doing the cutaneous cutting under continuous ultrasonographic control. The efficacy and safety of the method, comparing with existing methods (probing "blindly" and excision of the fistula), was estimated. Original method owes advantage of possibility to visualize the ligatures and instruments on all stages of the intervention, small need in anesthesia, good medical-statistical indices. The method proposed constitute a clinically beneficial intervention and more effective one.


3D Printed Cardiac Models as an Adjunct to Traditional Teaching of Anatomy in Congenital Heart Disease-A Randomised Controlled Study.
Three-dimensional (3D) printed cardiac models are increasingly being used for medical education, simulation and training, communication, surgical planning and research. Given the complexities of congenital cardiac anatomy, 3D printing is well suited as an adjunct to traditional teaching methods. This study aims to explore the influence of 3D printed cardiac models as a teaching aid for nurses and paediatric trainees. We hypothesise that using 3D models as an adjunct to didactic teaching methods improves knowledge and confidence levels of participants, regardless of their cardiology experience. A prospective randomised study was performed recruiting paediatric nurses and doctors at a tertiary paediatric hospital. All participants undertook traditional congenital cardiac teaching describing normal cardiac anatomy and seven congenital lesions of increasing complexity (atrial septal defect, ventricular septal defect, vascular ring, partial anomalous pulmonary venous return, tetralogy of Fallot, transposition of the great arteries, and double outlet right ventricle). The intervention group received an additional recorded demonstration while handling 3D printed models of a normal heart and the same lesions. Pre- and post-intervention assessments were completed using a subjective Likert-scale questionnaire and objective multiple-choice examination. A total of 73 health practitioners (30 cardiac nurses and 43 paediatric trainees) were included. Subjective knowledge and confidence levels substantially improved in the intervention group (both p<0.001), with no differences observed in the control group. Greater improvement in both subjective and objective post-test scores was observed in the intervention group. A pronounced difference between pre- and post-teaching objective examination scores was found in both groups (p=0.002), with larger improvements observed in the intervention group. The mean score in the intervention group after teaching increased by 4.27 (21.4% improvement), as opposed to 2.28 (11.4% improvement) in the control group. There was no difference in pre-test score or post-test improvement based on previous cardiology experience. Three-dimensional (3D) printed cardiac models, when used as an adjunct to traditional teaching methods, substantially improve knowledge and confidence levels of health professionals on a range of congenital cardiac lesions. These models enhance the learners' educational experience and understanding of cardiac anatomy by overcoming the limitation of two-dimensional representations of 3D structures.


Culture medium, gas atmosphere and MAPK inhibition affect regulation of RNA-binding protein targets during mouse preimplantation development.
During oogenesis, mammalian oocytes accumulate maternal mRNAs that support the embryo until embryonic genome activation. RNA-binding proteins (RBP) may regulate the stability and turnover of maternal and embryonic mRNAs. We hypothesised that varying embryo culture conditions, such as culture medium, oxygen tension and MAPK inhibition, affects regulation of RBPs and their targets during preimplantation development. STAU1, ELAVL1, KHSRP and ZFP36 proteins and mRNAs were detected throughout mouse preimplantation development, whereas Elavl2 mRNA decreased after the two-cell stage. Potential target mRNAs of RBP regulation, Gclc, Slc2a1 and Slc7a1 were detected during mouse preimplantation development. Gclc mRNA was significantly elevated in embryos cultured in Whitten's medium compared with embryos cultured in KSOMaa, and Gclc mRNA was elevated under high-oxygen conditions. Inhibition of the p38 MAPK pathway reduced Slc7a1 mRNA expression while inhibition of ERK increased Slc2a1 mRNA expression. The half-lives of the potential RBP mRNA targets are not regulated in parallel; Slc2a1 mRNA displayed the longest half-life. Our results indicate that mRNAs and proteins encoding five RBPs are present during preimplantation development and more importantly, demonstrate that expression of RBP target mRNAs are regulated by culture medium, gas atmosphere and MAPK pathways.


A blue luminescent MOF as a rapid turn-off/turn-on detector for H2O, O2 and CH2Cl2, MeCN: ∞³[Ce(Im)3ImH]·ImH.
The blue emitting luminescent MOF ∞³[Ce(Im)3ImH]·ImH forms a 3D-framework with Kagomé net topology. The framework exhibits an intense blue luminescence which can be retained upon activation of the MOF with the formula ∞³[Ce(Im)3ImH]. The luminescence is metal-based due to parity-allowed 5d-4f-transitions. Time-dependent investigations of the interaction with liquid and gas analytes show that the MOF – by utilising 5d-4f-transitions of Ce(3+) – can be used as a high-speed "turn-off" detector for water and oxygen in dry air. Other protic or polar solvents, like methanol, acetone or pyridine, which also show a "turn-off"-effect can be distinguished from water-detection either on a time scale (ranging up to 250,000 : 1) or a shift of the chromaticity, the latter being pronounced for MeOH. The fast time-dependent decrease of the luminescence intensity for water arises from an extremely fast hydrolysis and is irreversible. Polar aprotic molecules like dichloromethane and acetonitrile can also result in a "turn-on"-effect of the luminescence intensity due to their behaviour as additional sensitizers for Ce(3+)-emission. We conclude that the cerium-MOF can be utilised in gas and liquid sensing applications as a detector material for water and oxygen in dry air. The luminescence is intense with good quantum yield between 55% (as-synthesised) and 36% (activated). This implies that only milligram amounts of the material are needed to detect the analyte species and is especially useful, as the MOF can be directly used as-synthesised for water detection in applications for which an irreversible signal change is desired, e.g. preventing a signal change upon unwanted re-drying.


Apolipoprotein secretion and lipid synthesis: regulation by fatty acids in newborn swine intestinal epithelial cells.
The IPEC-1 newborn swine intestinal epithelial cell line was used to determine the effects of the uptake of various fatty acids on the secretion of apolipoprotein (apo) B and apo A-I, as well as triglyceride and phospholipid. Long-chain saturated fatty acids were taken up and stimulated triglyceride synthesis, and palmitic (16:0) and stearic (18:0) acids also stimulated phospholipid synthesis. However, these fatty acids did not enhance triglyceride, phospholipid, or apo B or apo A-I secretion. Oleic acid (18:1) was the most effective of all fatty acids tested in stimulating triglyceride synthesis and the secretion of triglyceride, phospholipid, and apo B. Linoleic (18:2) and linolenic (18:3) acids were no more effective than long-chain saturated fatty acids in stimulating these processes. With saturated fatty acids, apo A-I followed the same secretory pattern as apo B. However, among the unsaturated fatty acids, oleic acid was the least effective and linolenic acid was the most effective in stimulating apo A-I secretion. Basolateral secretion of lipid and apolipoproteins by differentiated IPEC-1 cells is differentially regulated by apical exposure to fatty acids.


Risk factors for functional status decline in community-living elderly people: a systematic literature review.
To lay the groundwork for devising, improving and implementing strategies to prevent or delay the onset of disability in the elderly, we conducted a systematic literature review of longitudinal studies published between 1985 and 1997 that reported statistical associations between individual base-line risk factors and subsequent functional status in community-living older persons. Functional status decline was defined as disability or physical function limitation. We used MEDLINE, PSYCINFO, SOCA, EMBASE, bibliographies and expert consultation to select the articles, 78 of which met the selection criteria. Risk factors were categorized into 14 domains and coded by two independent abstractors. Based on the methodological quality of the statistical analyses between risk factors and functional outcomes (e.g. control for base-line functional status, control for confounding, attrition rate), the strength of evidence was derived for each risk factor. The association of functional decline with medical findings was also analyzed. The highest strength of evidence for an increased risk in functional status decline was found for (alphabetical order) cognitive impairment, depression, disease burden (comorbidity), increased and decreased body mass index, lower extremity functional limitation, low frequency of social contacts, low level of physical activity, no alcohol use compared to moderate use, poor self-perceived health, smoking and vision impairment. The review revealed that some risk factors (e.g. nutrition, physical environment) have been neglected in past research. This review will help investigators set priorities for future research of the Disablement Process, plan health and social services for elderly persons and develop more cost-effective programs for preventing disability among them.


Immuno-isolation of a plasma membrane fraction from the Fao cell.
A plasma membrane was immuno-isolated from a post-nuclear supernatant of a cultured rat hepatocyte, the Fao cell, using a cellulose immuno-adsorbent and antibodies raised against a variety of endogenous antigens of hepatocytes: 5'-nucleotidase, a plasma membrane fraction and the whole Fao cell. The antibodies which recognize antigens on the cell surface were selected from the total serum by first binding the antiserum to suspension cells. Alternatively, the plasma membrane and Fao antisera were affinity purified on a column prepared from a Triton X-114 extract of a plasma membrane fraction. The immuno-isolation was most efficient when carried out with either the plasma membrane or the Fao anti-serum. When alkaline phosphodiesterase I or 5'-nucleotidase was used as the plasma membrane marker, 40-60% of the plasma membrane of the post-nuclear supernatant was isolated representing a maximum 34-fold increase in the specific activity of the enzymes in the bound material. Using the NaB-[3H]4-labelled glycoproteins of the plasma membrane or the IgG bound to the plasma membrane as alternative markers, an 80% isolate of the plasma membrane of the post-nuclear supernatant was achieved, resulting in an estimated 40-fold purification. The non-specific binding was low despite the use of a post-nuclear supernatant as the input fraction. The characterization of the bound materials suggested that the whole plasma membrane was immuno-isolated and not a particular domain.


Efficacy of Feed Additive Containing Bentonite and Enzymatically Hydrolyzed Yeast on Intestinal Health and Growth of Newly Weaned Pigs under Chronic Dietary Challenges of Fumonisin and Aflatoxin.
This study aimed to investigate the efficacy of a feed additive containing bentonite and enzymatically hydrolyzed yeast on the intestinal health and growth of newly weaned pigs under chronic dietary exposure to fumonisin and aflatoxin. Newly weaned pigs were randomly allotted to one of four possible treatments: a control diet of conventional corn; a diet of corn contaminated with fumonisin and aflatoxin; a diet of mycotoxin-contaminated corn with 0.2% of feed additive; and a diet of mycotoxin contaminated corn with 0.4% of feed additive. We observed lower average weight gain and average daily feed intake in pigs that were fed only mycotoxin-contaminated corn compared to the control group. Feed additive supplementation linearly increased both average weight gain and feed intake, as well as tumor necrosis factor-alpha. In the jejunum, there was an observed decrease in immunoglobulin A and an increase in claudin-1. Additionally, feed additive supplementation increased the villus height to crypt depth ratio compared to the control. In conclusion, feed additives containing bentonite and enzymatically hydrolyzed yeast could mitigate the detrimental effects of mycotoxins on the growth performance of newly weaned pigs by improving intestinal integrity and positively modulating immune response.


Re-thinking performance assessment for primary care: Opinion of the expert panel on effective ways of investing in health.
In 2017, the European Commission (EC) identified as a policy priority the performance assessment of primary care systems, which relates to a country's primary care structure, services delivery and outcomes. The EC requested its Expert Panel on Effective Ways of Investing in Health (Expert Panel) to provide an opinion on ways for improving performance assessment of primary care. To provide an overview of domains and dimensions to be taken into consideration in assessing primary care and specific indicators to be collected and analysed to improve understanding of primary care performance. A sub-group of the Expert Panel performed a literature review. The opinion was drafted, improved and approved through working-group discussions, consultations with the EC, the Expert Group on Health Systems Performance Assessment, and a public hearing. Drawing on the main characteristics of primary care, we propose essential elements of a primary care performance assessment system based on specific indicators. We identified ten domains with accompanying dimensions for which comparative key indicators and descriptive indicators are proposed: (1) universal and accessible care, (2) integrated, (3) person-centred, (4) comprehensive and community-oriented care, (5) provided by a team accountable for addressing a vast majority of personal health needs, (6) sustained partnership with patients and informal caregivers, (7) coordination, (8) continuity of care, (9) primary care organization, and (10) human resources. The identified characteristics and criteria for development of a primary care performance assessment system provides a starting point for strengthening the coherence of assessment frameworks across countries and exchanging best practices.


Designing of self-deploying origami structures using geometrically misaligned crease patterns.
Usually, origami-based morphing structures are designed on the premise of 'rigid folding', i.e. the facets and fold lines of origami can be replaced with rigid panels and ideal hinges, respectively. From a structural mechanics viewpoint, some rigid-foldable origami models are overconstrained and have negative degrees of freedom (d.f.). In these cases, the singularity in crease patterns guarantees their rigid foldability. This study presents a new method for designing self-deploying origami using the geometrically misaligned creases. In this method, some facets are replaced by 'holes' such that the systems become a 1-d.f. mechanism. These perforated origami models can be folded and unfolded similar to rigid-foldable (without misalignment) models because of their d.f. focusing on the removed facets, the holes will deform according to the motion of the frame of the remaining parts. In the proposed method, these holes are filled with elastic parts and store elastic energy for self-deployment. First, a new extended rigid-folding simulation technique is proposed to estimate the deformation of the holes. Next, the proposed method is applied on arbitrary-size quadrilateral mesh origami. Finally, by using the finite-element method, the authors conduct numerical simulations and confirm the deployment capabilities of the models.


Anoxybacillus tengchongensis sp. nov. and Anoxybacillus eryuanensis sp. nov., facultatively anaerobic, alkalitolerant bacteria from hot springs.
Two novel thermophilic, spore-forming bacterial strains, T-11(T) and E-112(T), were isolated from hot springs in Tengchong and Eryuan counties of Yunnan province in south-west China. The strains were Gram-stain-positive rods, occurring singly or in chains. Growth of strain T-11(T) was observed between 30 and 75 °C (optimum 50 °C) and at pH 7-11 (optimum pH 8.5), while the temperature range for strain E-112(T) was 35-70 °C (optimum 55 °C) and the pH range was 7.0-11.0 (optimum pH 8.0). The DNA G+C contents of strains T-11(T) and E-112(T) were 41.1 and 42.6 mol%, respectively. On the basis of 16S rRNA gene sequence similarity, the two strains were shown to be related most closely to Anoxybacillus species. The chemotaxonomic characteristics [predominant isoprenoid quinone menaquinone 7 (MK-7); major fatty acids iso-C(15 : 0) and iso-C(17 : 0)] also supported the affiliation of strains T-11(T) and E-112(T) to the genus Anoxybacillus. The results of DNA-DNA hybridization and physiological and biochemical tests allowed genotypic and phenotypic differentiation of strains T-11(T) and E-112(T) from Anoxybacillus species with validly published names. Strains T-11(T) and E-112(T) therefore represent two novel species, for which the names Anoxybacillus tengchongensis sp. nov. (type strain T-11(T) =CCTCC AB209237(T) =KCTC 13721(T)) and Anoxybacillus eryuanensis sp. nov. (type strain E-112(T) =CCTCC AB209236(T) =KCTC 13720(T)) are proposed.


An adaptable pentaloop defines a robust neomycin-B RNA aptamer with conditional ligand-bound structures.
Aptamers can be highly specific for their targets, which implies precise molecular recognition between aptamer and target. However, as small polymers, their structures are more subject to environmental conditions than the more constrained longer RNAs such as those that constitute the ribosome. To understand the balance between structural and environmental factors in establishing ligand specificity of aptamers, we examined the RNA aptamer (NEO1A) previously reported as specific for neomycin-B. We show that NEO1A can recognize other aminoglycosides with similar affinities as for neomycin-B and its aminoglycoside specificity is strongly influenced by ionic strength and buffer composition. NMR and 2-aminopurine (2AP) fluorescence studies of the aptamer identified a flexible pentaloop and a stable binding pocket. Consistent with a well-structured binding pocket, docking analysis results correlated with experimental measures of the binding energy for most ligands. Steady state fluorescence studies of 2AP-substituted aptamers confirmed that A16 moves to a more solvent accessible position upon ligand binding while A14 moves to a less solvent accessible position, which is most likely a base stack. Analysis of binding affinities of NEO1A sequence variants showed that the base in position 16 interacts differently with each ligand and the interaction is a function of the buffer constituents. Our results show that the pentaloop provides NEO1A with the ability to adapt to external influences on its structure, with the critical base at position 16 adjusting to incorporate each ligand into a stable pocket by hydrophobic interactions and/or hydrogen bonds depending on the ligand and the ionic environment.


Mimicking Microbial Rhodopsin Isomerization in a Single Crystal.
Bacteriorhodopsin represents the simplest, and possibly most abundant, phototropic system requiring only a retinal-bound transmembrane protein to convert photons of light to an energy-generating proton gradient. The creation and interrogation of a microbial rhodopsin mimic, based on an orthogonal protein system, would illuminate the design elements required to generate new photoactive proteins with novel function. We describe a microbial rhodopsin mimic, created using a small soluble protein as a template, that specifically photoisomerizes all- trans to 13- cis retinal followed by thermal relaxation to the all- trans isomer, mimicking the bacteriorhodopsin photocycle, in a single crystal. The key element for selective isomerization is a tuned steric interaction between the chromophore and protein, similar to that seen in the microbial rhodopsins. It is further demonstrated that a single mutation converts the system to a protein photoswitch without chromophore photoisomerization or conformational change.


Direct and vicarious victimization at school and at home as risk factors for suicidal cognition among Italian adolescents.
Suicidal cognition is defined here as the combination of thinking about committing suicide and engaging in self-harm and is considered to indicate maladjustment following an extreme internalized reaction to negative life events. Victimization at home and at school might lead some youth to suicidal cognition. The present study aimed to examine cross-sectional predictors of suicidal cognition focusing on the unique influence of 'direct victimization' at school by peers and at home by parents, over and above that of vicarious victimization (i.e. exposure to domestic violence). Participants were 998 adolescents randomly recruited from high schools in Italy who had to fill in a cross-sectional survey measuring different dimensions associated with suicidal cognition. Thoughts about committing suicide and self-harming in the previous 6 months were reported by almost a fourth of the whole sample, with girls having these thoughts more frequently than boys. A high prevalence rate was reported also for direct victimization at school (over half of the sample), and at home (a third of the sample) and for vicarious victimization at home (reported by a fifth of the entire sample). Multiple hierarchical regressions showed that a significant proportion of the total variance of suicidal cognition was explained by gender and age, meaning that older girls are more at risk of suicidal cognition than boys; relational victimization at school is also a risk factor. Direct victimization at home by the father for boys and by the father and the mother for girls significantly predicted suicidal cognition after controlling for exposure to domestic violence.


Rapid mask prototyping for microfluidics.
With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.


Highly Conductive Transparent and Flexible Electrodes Including Double-Stacked Thin Metal Films for Transparent Flexible Electronics.
To keep pace with the era of transparent and deformable electronics, electrode functions should be improved. In this paper, an innovative structure is suggested to overcome the trade-off between optical and electrical properties that commonly arises with transparent electrodes. The structure of double-stacked metal films showed high conductivity (<3 Ω/sq) and high transparency (∼90%) simultaneously. A proper space between two metal films led to high transmittance by an optical phenomenon. The principle of parallel connection allowed the electrode to have high conductivity. In situ fabrication was possible because the only materials composing the electrode were silver and WO3, which can be deposited by thermal evaporation. The electrode was flexible enough to withstand 10 000 bending cycles with a 1 mm bending radius. Furthermore, a few μm scale patterning of the electrode was easily implemented by using photolithography, which is widely employed industrially for patterning. Flexible organic light-emitting diodes and a transparent flexible thin-film transistor were successfully fabricated with the proposed electrode. Various practical applications of this electrode to new transparent flexible electronics are expected.


Aerodynamic performance of flapping wing with alula under different kinematics of complex flapping motion.
The flight of birds is a remarkable feat, and their remarkable ability to fly derives from complex multi-degree-of-freedom flapping motions and small-scale feather structures that have evolved over millions of years. One of these feather structures is the alula, which can enhance the birds' flight performance at low speeds and large angles of attack. Previous studies on the alula have focused on the steady state. This undoubtedly ignores the unsteady effect caused by complex flapping motion, which is also the most important characteristic of avian flight. Therefore, this paper carries out a study on the effect of different motion modes and motion parameters on the aerodynamic mechanism of the alula. Previous studies found the dominate effect in the lift enhancement is influenced by Reynolds number, stall condition and geometric parameters. After coupling complex flapping motion, aerodynamic characteristics of the flapping wing are greatly influenced by different motion patterns and parameters. For pure plunge motion, both the slot effect and the vortex generator effect of the alula dominate the lift enhancement; while for plunge-twist and plunge-sweep motion, the vortex generator dominates more. At a low plunge amplitude, a low twist amplitude and a low sweep amplitude, the deflection of the alula has a good lift enhancement compared with the baseline wing. Increasing these amplitudes attenuates both the slot effect and the vortex generator effect. The alula can enhance the lift by 10.4% at the plunge amplitude of 25 deg (for pure plunge motion), by 7.9% at the plunge amplitude of 25 deg and twist amplitude of 10 deg (for plunge-twist motion), by 3.3% at the plunge amplitude of 25 deg and sweep amplitude of 15 deg (for plunge-sweep motion). Meanwhile, at a large sweep phase angle, the alula has a better lift enhancement. Increasing the phase angle enhances the vortex generator effect of the alula, and it has an optimal lift enhancement effect of 11% at the phase angle of 180 deg.


[Creutzfeldt-Jakob disease; one year later].
During the last year the knowledge of the transmission of prion diseases has increased. New diagnostic methods were developed: investigation of cerebrospinal fluid for the 14-3-3 protein and tonsillar biopsy to detect protease resistant prion protein. Indirect evidence of a causal relation between new variant Creutzfeldt-Jakob disease (nvCJ) and bovine spongiform encephalopathy (BSE) is accumulating, although epidemiological data do not indicate that the incidence of CJ is increasing.


Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility.
The potential use of nanomaterials in medicine offers opportunities for novel therapeutic approaches to treating complex disorders. For that reason, a new branch of science, named nanotoxicology, which aims to study the dangerous effects of nanomaterials on human health and on the environment, has recently emerged. However, the toxicity and risk associated with nanomaterials are unclear or not completely understood. The development of an adequate experimental strategy for assessing the toxicity of nanomaterials may include a rapid/express method that will reliably, quickly, and cheaply make an initial assessment. One possibility is the characterization of the hemocompatibility of nanomaterials, which includes their hemolytic activity as a marker. In this review, we consider various factors affecting the hemolytic activity of nanomaterials and draw the reader's attention to the fact that the formation of a protein corona around a nanoparticle can significantly change its interaction with the red cell. This leads us to suggest that the nanomaterial hemolytic activity in the buffer does not reflect the situation in the blood plasma. As a recommendation, we propose studying the hemocompatibility of nanomaterials under more physiologically relevant conditions, in the presence of plasma proteins in the medium and under mechanical stress.


Entertainment-Education Narrative Versus Nonnarrative Interventions to Educate and Motivate Latinas to Engage in Mammography Screening.
The evidence is limited comparing the effects of entertainment-education (E-E) narrative versus nonnarrative interventions to educate and motivate Latinas to engage in mammography screening. This study compared an E-E narrative intervention to two nonnarrative interventions' effects among Latinas on breast cancer knowledge and motivation, as measured by changes in self-efficacy, behavioral norms, and behavioral intentions to engage in mammography screening. A sample of 141 Spanish-speaking Latinas was randomly assigned to one of three arms: an E-E narrative video, a nonnarrative educational video, and printed educational materials. Using a repeated measures design, the influence of the E-E narrative on pretest to posttest measures was assessed and compared to the influence of the other two interventions. The E-E narrative and nonnarrative interventions significantly increased Latinas' breast cancer knowledge, mammography self-efficacy, and behavioral norms from pretest to posttest. However, the E-E narrative participants' pretest to posttest difference in mammography self-efficacy was significantly higher when compared to the difference of the other two interventions. The effect of the E-E narrative intervention on self-efficacy and behavioral norms was moderated by the participants' absorption in the story and identification with the story characters. E-E narrative and nonnarrative interventions significantly educated and motivated Latinas to engage in mammography screening. The effects on mammography self-efficacy, an important precursor to behavior change, can be more strongly influenced by E-E narratives. Although E-E narrative and nonnarrative interventions were effective, the need still exists to assess if they can ultimately influence lifesaving breast cancer screening behaviors.


Cross-cultural adaptation of the Brazilian-Portuguese version of the Cumberland Ankle Instability Tool (CAIT).
To develop and psychometrically test a Brazilian-Portuguese version of the Cumberland Ankle Instability Tool (CAIT), the only questionnaire that provides a numeric measure for functional ankle instability. The CAIT was translated and adapted into Brazilian-Portuguese according to the Guidelines for the process of cross-cultural adaptation of self report measures. The Brazilian-Portuguese version of the CAIT was tested for internal consistency, test-retest reliability, ceiling and floor effects and responsiveness in 131 participants. Participants were recruited from the general community in Brazil (N = 101, community group) and from those seeking treatment for an ankle sprain from 2 clinics in Brazil (N = 30, treatment group). The Brazilian-Portuguese version of the CAIT had high internal consistency (Cronbach alpha = 0.86 for right ankles and 0.88 for left ankles), reliability (ICC = 0.95, 95% CI 0.93-0.97); and good responsiveness (ES = 0.75, 95% CI 0.49-1.00). No ceiling or floor effects were observed. The Brazilian-Portuguese version of the CAIT is as reliable as the English version of the questionnaire, has high internal consistency and good responsiveness. It thus provides the first tool that can be used to assess functional ankle instability by clinicians and researchers working among Brazilian-Portuguese speakers.


The ethical basis of psychiatric research: conceptual issues and empirical findings.
The study objective was to clarify the ethical basis of psychiatric research by outlining conceptual issues and empirical findings related to the ethics of human experimentation. A systematic review of scholarly and empirical literature covering three decades was performed. The ethics of human research has come to be understood in relation to the principles of respect for persons, beneficence, justice, and the ideal of informed consent. Subjects who cannot fully participate in informed-consent processes are especially vulnerable to exploitation. Current dilemmas stem from insufficient attention to the vulnerabilities of mentally ill research participants, problems in applying ethical concepts and guidelines to psychiatric research, and claims of research misconduct. Empirical studies indicate that (1) psychiatric symptoms significantly affect informed consent, (2) psychiatric patients may possess certain strengths with respect to research involvement, (3) proxy decision-making is problematic, (4) informed consent is also difficult to attain with the medically ill and others, (5) patients are motivated to participate in research by the hope of personal benefit, (6) ethical aspects of research are poorly documented, and (7) institutional review processes may not be adequate to protect vulnerable subjects. Psychiatric research can be performed ethically, according to standards set throughout the biomedical and behavioral sciences, so long as researchers and institutions are respectful of special ethical issues in human experimentation and strive to include vulnerable study participants fully in research decisions. However, many gaps in the empirical literature exist regarding the specific nature and implementation of ethics principles in psychiatric research. Efforts to advance both science and ethics, including the study of ethical dimensions of human research itself, are essential for the future of psychiatry.


Sex of muscle stem cells does not influence potency for cardiac cell therapy.
We have previously shown that populations of skeletal muscle-derived stem cells (MDSCs) exhibit sex-based differences for skeletal muscle and bone repair, with female cells demonstrating superior engrafting abilities to males in skeletal muscle while male cells differentiating more robustly toward the osteogenic and chondrogenic lineages. In this study, we tested the hypothesis that the therapeutic capacity of MDSCs transplanted into myocardium is influenced by sex of donor MDSCs or recipient. Male and female MDSCs isolated from the skeletal muscle of 3-week-old mice were transplanted into recipient male or female dystrophin-deficient (mdx) hearts or into the hearts of male SCID mice following acute myocardial infarction. In the mdx model, no difference was seen in engraftment or blood vessel formation based on donor cell or recipient sex. In the infarction model, MDSC-transplanted hearts showed higher postinfarction angiogenesis, less myocardial scar formation, and improved cardiac function compared to vehicle controls. However, sex of donor MDSCs had no significant effects on engraftment, angiogenesis, and cardiac function. VEGF expression, a potent angiogenic factor, was similar between male and female MDSCs. Our results suggest that donor MDSC or recipient sex has no significant effect on the efficiency of MDSC-triggered myocardial engraftment or regeneration following cardiac injury. The ability of the MDSCs to improve cardiac regeneration and repair through promotion of angiogenesis without differentiation into the cardiac lineage may have contributed to the lack of sex difference observed in these models.


Chondritic xenon in the Earth's mantle.
Noble gas isotopes are powerful tracers of the origins of planetary volatiles, and the accretion and evolution of the Earth. The compositions of magmatic gases provide insights into the evolution of the Earth's mantle and atmosphere. Despite recent analytical progress in the study of planetary materials and mantle-derived gases, the possible dual origin of the planetary gases in the mantle and the atmosphere remains unconstrained. Evidence relating to the relationship between the volatiles within our planet and the potential cosmochemical end-members is scarce. Here we show, using high-precision analysis of magmatic gas from the Eifel volcanic area (in Germany), that the light xenon isotopes identify a chondritic primordial component that differs from the precursor of atmospheric xenon. This is consistent with an asteroidal origin for the volatiles in the Earth's mantle, and indicates that the volatiles in the atmosphere and mantle originated from distinct cosmochemical sources. Furthermore, our data are consistent with the origin of Eifel magmatism being a deep mantle plume. The corresponding mantle source has been isolated from the convective mantle since about 4.45 billion years ago, in agreement with models that predict the early isolation of mantle domains. Xenon isotope systematics support a clear distinction between mid-ocean-ridge and continental or oceanic plume sources, with chemical heterogeneities dating back to the Earth's accretion. The deep reservoir now sampled by the Eifel gas had a lower volatile/refractory (iodine/plutonium) composition than the shallower mantle sampled by mid-ocean-ridge volcanism, highlighting the increasing contribution of volatile-rich material during the first tens of millions of years of terrestrial accretion.


Differences in Proprioception Between Young and Middle-Aged Adults With and Without Chronic Low Back Pain.
Introduction: While young adults with chronic low back pain (CLBP) exhibit impaired lumbar proprioception, it remains unclear if the same phenomenon is observed in middle-aged adults with CLBP. Objectives: This study aimed to investigate whether young or middle-aged adults with CLBP displayed different proprioception ability as compared to age-matched asymptomatic controls. Methods: Sixty-four young adults with [median age:34 [interquartile range (IQR): 29-37] years] and without [median age:29 (IQR; 23-34) years] CLBP, and 87 middle-aged adults with [median age:53 (IQR: 49-58) years] and without [median age: 54 (IQR: 45-64) years] CLBP underwent postural sway tests on a force-plate with (unstable surface) and without a foam (stable surface), while bilateral L5/S1 multifidi and triceps-surae were vibrated separately. An individual's proprioception reweighting ability was estimated by relative proprioceptive reweighting (RPW). Higher RPW values indicate less reliance on lumbar multifidus proprioceptive signals for balance. Participants also underwent lumbar repositioning tests in sitting to determine repositioning errors in reproducing target lumbar flexion/extension positions. Results: Young adults with CLBP demonstrated significantly higher median RPW values than age-matched asymptomatic controls for maintaining standing balance [stable surface: CLBP: 0.9 (IQR: 0.7-0.9), asymptomatic: 0.7 (IQR: 0.6-0.8), p < 0.05; unstable surface: CLBP: 0.6 (IQR: 0.4-0.8), asymptomatic: 0.5 (IQR: 0.3-0.7), p < 0.05]. No significant differences in repositioning error were noted between young or middle-aged adults with and without CLBP (p > 0.05). RPW values were unrelated to repositioning errors in all groups (p > 0.05). Conclusion: Young adults with CLBP, and middle-aged adults with and without CLBP had inferior proprioceptive reweighting capability. This finding may indicate potential age-related deterioration in central and peripheral processing of lumbar proprioceptive signals. Future studies should use advanced imaging and/or electroencephalogram to determine mechanisms underlying changes in proprioceptive reweighting in middle-aged adults.


Increase in docetaxel-resistance of ovarian carcinoma-derived RMG-1 cells with enhanced expression of Lewis Y antigen.
Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (Le(Y)) antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of Le(Y). We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-Le(Y) antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of Le(Y) were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance.


Cardiac Abnormalities in Type 1 Facioscapulohumeral Muscular Dystrophy.
We conducted a retrospective study to characterize the cardiac complications in patients with genetically confirmed type 1 facioscapulohumeral dystrophy. We reviewed baseline cardiac investigations, including electrocardiogram, Holter electrocardiogram and echocardiogram, as well as cardiac complications that occurred during follow-up in 56 adult patients (37 men, mean duration of disease: 20 years). Baseline evaluation revealed minor cardiac anomalies in 23 patients including incomplete right bundle branch block (iRBBB) in 13 patients (23%). Over a mean follow-up period of 7.2 years, there was no cardiac death, no patient developed cardiomyopathy, and 28 patients (50%) experienced cardiac anomalies. Among these patients, 3 had one or more major events (heart failure and/or atrial fibrillation). The remaining 25 patients presented minor cardiac anomalies of which iRBBB was the most frequent (25%). Cardiac anomalies identified during the follow-up of patients with type 1 facioscapulohumeral dystrophy are mainly minor anomalies, dominated by the iRBBB.


Protective effects of selenium, zinc, or their combination on cadmium-induced oxidative stress in rat kidney.
The present study was conducted to investigate whether the combined treatment with Se and Zn offers more beneficial effects than that provided by either of them alone in reversing Cd-induced oxidative stress in the kidney of rat. For this purpose, 30 adult male Wistar albino rats, equally divided into control and four treated groups, received either 200 ppm Cd (as CdCl(2)), 200 ppm Cd + 500 ppm Zn (as ZnCl(2)), 200 ppm Cd + 0.1 ppm Se (as Na(2)SeO(3)), or 200 ppm Cd + 500 ppm Zn + 0.1 ppm Se in their drinking water for 35 days. The results showed that Cd treatment decreased significantly the catalase (CAT) and glutathione peroxidase (GSH-Px) activities, whereas the superoxide dismutase (SOD) activity and the renal levels of lipid peroxidation (as malondialdehyde, MDA) were increased compared to control rats. The treatment of Cd-exposed rats with Se alone had no significant effect on the Cd-induced increase in the MDA concentrations but increased significantly the CAT activities and reversed Cd-induced increase in SOD activity. It also partially prevented Cd-induced decrease in GSH-Px activity. The treatment of Cd-exposed animals with Zn alone increased significantly the CAT activity and partially protected against Cd-induced increase in the MDA concentrations, whereas it had no significant effect on the Cd-induced increase in SOD activity and decrease in GSH-Px activity. The combined treatment of Cd-exposed animals with Se and Zn was more effective than that with either of them alone in reversing Cd-induced decrease in CAT and GSH-Px activities and Cd-induced increase in MDA concentrations. Results demonstrated beneficial effects of combined Se and Zn treatment in Cd-induced oxidative stress in kidney and suggest that Se and Zn can have a synergistic role against Cd toxicity.


Fitness of Salmonella enterica serovar Thompson in the cilantro phyllosphere.
The epiphytic fitness of Salmonella enterica was assessed on cilantro plants by using a strain of S. enterica serovar Thompson that was linked to an outbreak resulting from cilantro. Salmonella serovar Thompson had the ability to colonize the surface of cilantro leaves, where it was detected by confocal laser scanning microscopy (CLSM) at high densities on the veins and in natural lesions. The population sizes of two common colonizers of plant surfaces, Pantoea agglomerans and Pseudomonas chlororaphis, were 10-fold higher than that of the human pathogen on cilantro incubated at 22 degrees C. However, Salmonella serovar Thompson achieved significantly higher population levels and accounted for a higher proportion of the total culturable bacterial flora on cilantro leaves when the plants were incubated at warm temperatures, such as 30 degrees C, after inoculation, indicating that the higher growth rates exhibited by Salmonella serovar Thompson at warm temperatures may increase the competitiveness of this organism in the phyllosphere. The tolerance of Salmonella serovar Thompson to dry conditions on plants at 60% relative humidity was at least equal to that of P. agglomerans and P. chlororaphis. Moreover, after exposure to low humidity on cilantro, Salmonella serovar Thompson recovered under high humidity to achieve its maximum population size in the cilantro phyllosphere. Visualization by CLSM of green fluorescent protein-tagged Salmonella serovar Thompson and dsRed-tagged P. agglomerans inoculated onto cilantro revealed that the human pathogen and the bacterial epiphyte formed large heterogeneous aggregates on the leaf surface. Our studies support the hypothesis that preharvest contamination of crops by S. enterica plays a role in outbreaks linked to fresh fruits and vegetables.


Heterocyclic aromatic amines and their contribution to the bacterial mutagenicity of the particulate phase of cigarette smoke.
Heterocyclic aromatic amines (HAAs) rank among the strongest known mutagens. Approximately 30 HAAs have been found in cooked foods (broiled, fried, and grilled) and several HAAs have been characterized as animal carcinogens. Nine HAAs have also been reported to be constituents of cigarette smoke (CS) raising concerns that HAAs might contribute significantly to the known carcinogenicity of CS. As HAAs are found predominantly in the total particulate matter (TPM) of CS, an improved method for the quantification of HAAs in TPM is reported allowing detection and quantification of 8 HAAs in a single run. The mutagenic potency of these HAAs and that of TPM from the reference cigarette 2R4F was determined in the Salmonella Reverse Mutation Assay (Ames assay) with tester strain TA98 and a metabolic activation system. The 8 HAAs, when applied together in the Ames assay, showed a clear sub-additive response. Likewise, the combination of HAAs and TPM, if at all, gave rise to a slight sub-additive response. In both cases, however, the sub-additive response in the Ames assay was observed at HAA doses that are far above the amounts found in CS. The contribution of the individual HAAs to the total mutagenic activity of TPM was calculated and experimentally confirmed to be approximately 1% of the total mutagenic activity. Thus, HAAs do not contribute significantly to the bacterial in vitro mutagenicity of CS TPM.


Studies on J-chain biosynthesis in tumours producing immunoglobulins in NZB mice.
Investigation of biosynthesis of J chain in plasmacytomas induced in NZB mice revealed that this protein was not only synthesized in the cells that produce polymer immunoglobulin A but also in those that produce immunoglobulin G monomer. It was also found that protein similar to J chain of BALB/c-mice was associated with polymer immunoglobulin A but not with immunoglobulin G of NZB mouse myeloma proteins.


Electrochemical immunosensor array using a 96-well screen-printed microplate for aflatoxin B1 detection.
A novel analytical immunosensor array, based on a microtiter plate coupled to a multichannel electrochemical detection (MED) system using the intermittent pulse amperometry (IPA) technique, is proposed for the detection of aflatoxin B1 (AFB1). In the present work, the electrochemical behaviour and electroanalytical performance of the thick-film carbon sensors (also designated as screen-printed electrodes) incorporated in the multichannel electrochemical plate were first evaluated. Then the 96-well screen-printed microplate was modified in accord with a competitive indirect enzyme-linked immunoassay (ELISA) format for aflatoxin B1 detection. The measurements were performed using both spectrophotometric and electrochemical procedures and the results of the calibration curves, detection limit (LOD), sensitivity and reproducibility of the respective assay systems were evaluated. The immunoassay was then applied for analysis of corn samples spiked with AFB1 before and after the extraction treatment, in order to study the extraction efficiency and the matrix effect, respectively. These studies have shown that using this system, AFB1 can be measured at a level of 30 pg/mL and with a working range between 0.05 and 2 ng/mL. Good recoveries (103+/-8%) were obtained, demonstrating the suitability of the proposed assay for accurate determination of the AFB1 concentration in corn samples. The specificity of the assay was assessed by studying the cross-reactivity of PAb relative to AFB1. The results indicated that the PAb could readily distinguish AFB1 from other aflatoxins, with the exception for AFG1.


Changes in biochemical markers of pain perception and stress response after spinal manipulation.
Controlled, repeated-measures, single-blind randomized study. To determine the effect of cervical or thoracic manipulation on neurotensin, oxytocin, orexin A, and cortisol levels. Previous studies have researched the effect of spinal manipulation on pain modulation and/or range of movement. However, there is little knowledge of the biochemical process that supports the antinociceptive effect of spinal manipulation. Thirty asymptomatic subjects were randomly divided into 3 groups: cervical manipulation (n = 10), thoracic manipulation (n = 10), and nonmanipulation (control) (n = 10). Blood samples were extracted before, immediately after, and 2 hours after each intervention. Neurotensin, oxytocin, and orexin A were determined in plasma using enzyme-linked immuno assay. Cortisol was measured by microparticulate enzyme immuno assay in serum samples. Immediately after the intervention, significantly higher values of neurotensin (P<.05) and oxytocin (P<.001) levels were observed with both cervical and thoracic manipulation, whereas cortisol concentration was increased only in the cervical manipulation group (P<.05). No changes were detected for orexin A levels. Two hours after the intervention, no significant differences were observed in between-group analysis. The mechanical stimulus provided by spinal manipulation triggers an increase in neurotensin, oxytocin, and cortisol blood levels. Data suggest that the initial capability of the tissues to tolerate mechanical deformation affects the capacity of these tissues to produce an induction of neuropeptide expression. J


Osteopathy and Mental Health: An Embodied, Predictive, and Interoceptive Framework.
Globally, mental and musculoskeletal disorders present with high prevalence, disease burden, and comorbidity. In order to improve the quality of care for patients with persistent physical and comorbid mental health conditions, person-centered care approaches addressing psychosocial factors are currently advocated. Central to successful person-centered care is a multidisciplinary collaboration between mental health and musculoskeletal specialists underpinned by a robust therapeutic alliance. Such a collaborative approach might be found in osteopathy, which is typically utilized to treat patients with musculoskeletal disorders but may arguably also benefit mental health outcomes. However, research and practice exploring the reputed effect of osteopathy on patients with mental health problems lack a robust framework. In this hypothesis and theory article, we build upon research from embodied cognition, predictive coding, interoception, and osteopathy to propose an embodied, predictive and interoceptive framework that underpins osteopathic person-centered care for individuals with persistent physical and comorbid mental health problems. Based on the premise that, for example, chronic pain and comorbid depression are underlined by overly precise predictions or imprecise sensory information, we hypothesize that osteopathic treatment may generate strong interoceptive prediction errors that update the generative model underpinning the experience of pain and depression. Thus, physical and mental symptoms may be reduced through active and perceptual inference. We discuss how these theoretical perspectives can inform future research into osteopathy and mental health to reduce the burden of comorbid psychological factors in patients with persistent physical symptoms and support person-centered multidisciplinary care in mental health.


Parallelization of Molecular Docking: A Review.
Molecular docking, as one of the widely used virtual screening methods, aims to predict the binding-conformations of small molecule ligands to the appropriate target binding site. Because of the computational complexity and the arrival of the big data era, molecular docking requests High- Performance Computing (HPC) to improve its performance and accuracy. We discuss, in detail, the advances in accelerating molecular docking software in parallel, based on the different common HPC platforms, respectively. Not only the existing suitable programs have been optimized and ported to HPC platforms, but also many novel parallel algorithms have been designed and implemented. This review focuses on the techniques and methods adopted in parallelizing docking software. Where appropriate, we refer readers to exemplary case studies.


Vitamin C and sugar levels as simple markers for discriminating Spanish honey sources.
In this work, 7 Spanish honeys with different botanical origins were studied. The honey origins were rosemary, chestnut, lavender, echium, thyme, multifloral, and honeydew. The chemical compounds determined were ascorbic acid (vitamin C), hydroxymethylfurfural, and major sugar contents (glucose and fructose). The physicochemical parameters, pH, conductivity, moisture, free acidity, and color, were also measured. Vitamin C is an important antioxidant in food, and the possibility to use it as discriminate parameter among different honeys was studied. The determination of vitamin C in honey samples was carried out by 2 different methods, volumetric and chromatographic comparing the results by both statistically. Vitamin C content was higher in thyme honeys than in the other types; however a wide dispersion in the values was found. Through a linear discriminant analysis (LDA), conductivity, glucose, fructose, and vitamin C content were the most important discriminant parameters. Vitamin C content in different honey sources has been determined by a simple and rapid chromatographic method (less than 3 min) in honeys from 6 botanical origins. The results together with glucose and fructose content and some physicochemical parameters have been studied in order to discriminate the botanical origin of honeys and in the future certified their quality. A statistical LDA was applied to the data, and differentiation of honey sources was possible with very good agreement. The vitamin C content found in thymus honeys was significantly higher than in other types. This fact makes vitamin C a special marker for thymus honeys that have a higher antioxidant effect than the others giving it special properties. The identification of honey sources is essential for beekeepers in order to certify honeys for consumers.


Verbal communication in MR environments: effect of MR system acoustic noise on speech understanding.
To assess the masking effect of magnetic resonance (MR)-related acoustic noise and the effect of passive hearing protection on speech understanding. Acoustic recordings were made at 1.5 T at patient and operator (interventionalist in the MR suite) locations for relevant pulse sequences. In an audiologic laboratory, speech-to-noise ratios (STNRs) were determined, defined as the difference between the absolute sound pressure levels of MR noise and speech. The recorded noise of the MR sequences was played simultaneously with the recorded sentences at various intensities, and 15 healthy volunteers (seven women, eight men; median age, 27 years) repeated these sentences as accurately as possible. The STNR that corresponded with a 50% correct repetition was used as the measure for speech intelligibility. In addition, the effect of passive hearing protection on speech intelligibility was tested by using an earplug model. Overall, speech understanding was reduced more at operator than at patient location. Most problematic were fast gradient-recalled-echo train and spiral k-space sequences. As the absolute sound pressure level of these sequences was approximately 100 dB at patient location, the vocal effort needed to attain 50% intelligibility was shouting (>77 dB). At operator location, less effort was required because of the lower sound pressure levels of the MR noise. Fast spoiled gradient-recalled-echo and echo-planar imaging sequences showed relatively favorable results with raised voice at operator location and loud speaking at patient location. The use of hearing protection slightly improved STNR. At 1.5 T, the level of MR noise requires that large vocal effort is used, at the operator and especially at the patient location. Depending on the specific MR sequence used, loud speaking or shouting is needed to achieve adequate bidirectional communication with the patient. The wearing of earplugs improves speech intelligibility.


A clinical overview of bone marrow edema.
Bone marrow edema (BME) is a descriptive term which identifies a specific magnetic resonance imaging (MRI) pattern that can be observed in a number of clinical entities, which are often characterized by pain as their main symptom, but show significant differences in terms of histopathological findings, causal mechanisms and prognosis. Bone marrow lesions in the subchondral bone of subjects with knee osteoarthritis (OA) seem to be associated with pain and progression of cartilage damage over time. Some histopathological studies of advanced OA have shown a prevalent fibrosis and bone marrow necrosis. BME of the subchondral bone in rheumatoid arthritis is associated with an infiltrate of inflammatory cells and osteoclasts and has a predictive value of further development of erosions. In spondyloarthritis, BME of the sacroiliac joints identifies an active sacroiliitis and is associated with histological inflammation and radiographic progression, whereas the relationship between BME lesions of the spine and syndesmophyte development is still controversial. BME syndromes (BMES), such as transient osteoporosis of the hip, regional migratory osteoporosis, and transient post-traumatic BMES, are characterized by a BME pattern on MRI and a self-limiting course. The potential evolution of BMES toward osteonecrosis is still controversial.


Towards Greener and More Sustainable Synthesis of MXenes: A Review.
The unique properties of MXenes have been deemed to be of significant interest in various emerging applications. However, MXenes provide a major drawback involving environmentally harmful and toxic substances for its general fabrication in large-scale production and employing a high-temperature solid-state reaction followed by selective etching. Meanwhile, how MXenes are synthesized is essential in directing their end uses. Therefore, making strategic approaches to synthesize greener, safer, more sustainable, and more environmentally friendly MXenes is imperative to commercialize at a competitive price. With increasing reports of green synthesis that promote advanced technologies and non-toxic agents, it is critical to compile, summarize, and synthesize the latest development of the green-related technology of MXenes. We review the recent progress of greener, safer, and more sustainable MXene synthesis with a focus on the fundamental synthetic process, the mechanism, and the general advantages, and the emphasis on the MXene properties inherited from such green synthesis techniques. The emerging use of the so-called green MXenes in energy conversion and storage, environmental remediation, and biomedical applications is presented. Finally, the remaining challenges and prospects of greener MXene synthesis are discussed.


High gene flow in polar cod (Boreogadus saida) from West-Svalbard and the Eurasian Basin.
The current and projected environmental change of the Arctic Ocean contrasts sharply with the limited knowledge of its genetic biodiversity. Polar cod Boreogadus saida (Lepechin, 1774) is an abundant circumpolar marine fish and ecological key species. The central role of polar cod in the Arctic marine food web warrants a better understanding of its population structure and connectivity. In this study, the genetic population structure of 171 juveniles, collected from several fjords off West-Svalbard (Billefjorden, Hornsund and Kongsfjorden), the northern Sophia Basin and the Eurasian Basin of the Arctic Ocean, was analysed using nine DNA microsatellite loci. Genetic analyses indicated moderate to high genetic diversity, but absence of spatial population structure and isolation-by-distance, suggesting ongoing gene flow between the studied sampling regions. High levels of connectivity may be key for polar cod to maintain populations across wide spatial scales. The adaptive capacity of the species will be increasingly important to face challenges such as habitat fragmentation, ocean warming and changes in prey composition. In view of a limited understanding of the population dynamics and evolution of polar cod, a valuable next step to predict future developments should be an integrated biological evaluation, including population genomics, a life-history approach, and habitat and biophysical dispersal modelling.


Is hypothermia a benefit? Von Willebrand factor in pediatric cardiopulmonary bypass.
The use of cardiopulmonary bypass (CPB) is associated with the risk of development of postpump syndrome. Thrombocyte activation leads to microembolism, endothelial damage and necrosis with release of various substances, such as the von Willebrand factor (vWf). High levels of vWf increase the risk of postoperative complications and mortality. Our objective was to find a correlation between CPB and plasma levels of vWf in pediatric patients operated on for congenital heart defects. Twenty patients with congenital heart defects (ventricular septal defect, atrial septal defect/partial anomalous pulmonary vein drainage, Bland White Garland syndrome) were operated on with the use of CPB. The arterial blood was sampled after induction of anesthesia, 5 minutes after commencing CPB, 1 hour and 3 hours after surgery. The plasma levels of vWf were measured and compared to selected clinical findings. There was no early mortality. There were no significant differences in CPB and aortic cross clamp times when compared in patients with various defects. vWf plasma levels were significantly elevated in all patients 1 hour and 3 hours after surgery. We found no correlation between vWf levels and type of defect, CPB duration, aortic cross clamp as well as reperfusion time. However, we were able to demonstrate that the observed elevation of vWf levels was almost 4-fold higher in patients cooled down to lower temperatures (15 patients; mean rectal value 27.64+/-0.7 degrees C) than in 5 patients (mean rectal temperature 30.74+/-1.56 degrees C) where only slight elevation was found. There were no differences in the postoperative course of these patients. All patients were discharged from hospital 10+/-3 days after operation (mean value 9 days). vWf plasma levels are significantly elevated after pediatric hypothermic CPB. It seems that the augmentation of vWf values could be independently associated with rate of hypothermia.


Development of MPS1 Inhibitors: Recent Advances and Perspectives.
Monopolar spindle kinase 1 (MPS1) plays a pivotal role as a dual-specificity kinase governing spindle assembly checkpoint activation and sister chromatid separation in mitosis. Its overexpression has been observed in various human malignancies. MPS1 reduces spindle assembly checkpoint sensitivity, allowing tumor cells with a high degree of aneuploidy to complete mitosis and survive. Thus, MPS1 has emerged as a promising candidate for cancer therapy. Despite the identification of numerous MPS1 inhibitors, only five have advanced to clinical trials with none securing FDA approval for cancer treatment. In this perspective, we provide a concise overview of the structural and functional characteristics of MPS1 by highlighting its relevance to cancer. Additionally, we explore the structure-activity relationships, selectivity, and pharmacokinetics of MPS1 inhibitors featuring diverse scaffolds. Moreover, we review the reported work on enhancing MPS1 inhibitor selectivity, offering valuable insights into the discovery of novel, highly potent small-molecule MPS1 inhibitors.


Hospital antibiotic stewardship.
Antibiotic stewardship is designed to optimize antimicrobial therapy administered to hospitalized patients, to ensure cost-effective therapy and improve patients' outcome while containing bacterial resistance. Current data on the development of effective programmes, including guidelines for their implementation, have demonstrated some efficacy and controversies are reviewed. Guidelines have been recently issued for the development and implementation of active antibiotic stewardship programmes in hospitals. A multidisciplinary team including at least an infectious disease physician and a clinical pharmacist is required. Multiple strategies are available, including prospective audit with feedback to the provider, education and antimicrobial restriction. Interventions have shown a positive effect on optimization of antimicrobial use, reduced costs and bacterial resistance, but studies showing improvement in patient outcomes are sparse. Results of studies may be confounded by several factors, mainly due to their before-after design and lack of control for cointerventions. Combined with an effective infection control programme, antibiotic stewardship can help contain antimicrobial resistance. Studies demonstrating improvement of patients' outcomes are needed to increase acceptance by a broader audience of physicians. A proactive strategy of prospective auditing with direct counsels and feedback to the prescriber, ensuring systematic reassessment of ongoing therapy, appears most useful.


Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis.
To study the density and morphologic characteristics of epithelial dendritic cells, as correlated to subbasal corneal nerve alterations in acute infectious keratitis (IK) by in vivo confocal microscopy (IVCM). IVCM of the central cornea was performed prospectively in 53 eyes with acute bacterial (n = 23), fungal (n = 13), and Acanthamoeba (n = 17) keratitis, and in 20 normal eyes, by using laser in vivo confocal microscopy. Density and morphology of dendritic-shaped cells (DCs) of the central cornea, corneal nerve density, nerve numbers, branching, and tortuosity were assessed and correlated. It should be noted that due to the "in vivo" nature of the study, the exact identity of these DCs cannot be specified, as they could be monocytes or tissue macrophages, but most likely dendritic cells. IVCM revealed the presence of central corneal DCs in all patients and controls. The mean DC density was significantly higher in patients with bacterial (441.1 ± 320.5 cells/mm(2); P < 0.0001), fungal (608.9 ± 812.5 cells/mm(2); P < 0.0001), and Acanthamoeba keratitis (1000.2 ± 1090.3 cells/mm(2); P < 0.0001) compared with controls (49.3 ± 39.6 cells/mm(2)). DCs had an increased size and dendrites in patients with IK. Corneal nerves were significantly reduced in eyes with IK compared with controls across all subgroups, including nerve density (674.2 ± 976.1 vs. 3913.9 ± 507.4 μm/frame), total nerve numbers (2.7 ± 3.9 vs. 20.2 ± 3.3), main trunks (1.5 ± 2.2 vs. 6.9 ± 1.1), and branching (1.2 ± 2.0 vs. 13.5 ± 3.1; P < 0.0001). A strong association between the diminishment of corneal nerves and the increase of DC density was observed (r = -0.44; P < 0.0005). IVCM reveals an increased density and morphologic changes of central epithelial DCs in infectious keratitis. There is a strong and significant correlation between the increase in DC numbers and the decreased subbasal corneal nerves, suggesting a potential interaction between the immune and nervous system in the cornea.


Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock: a randomized controlled efficacy trial.
Severe, uncompensated, traumatic hemorrhagic shock causes significant morbidity and mortality, but resuscitation with an oxygen-carrying fluid might improve patient outcomes. To determine if the infusion of up to 1000 mL of diaspirin cross-linked hemoglobin (DCLHb) during the initial hospital resuscitation could reduce 28-day mortality in traumatic hemorrhagic shock patients. Multicenter, randomized, controlled, single-blinded efficacy trial conducted between February 1997 and January 1998 at 18 US trauma centers selected for their high volume of critically injured trauma patients, but 1 did not enroll patients. A total of 112 patients with traumatic hemorrhagic shock and unstable vital signs or a critical base deficit, who had a mean (SD) patient age of 39 (20) years. Of the infused patients, 79% were male and 56% were white. An exception to informed consent was used when necessary. All patients were to be infused with 500 mL of DCLHb or saline solution. Critically ill patients who still met entry criteria could have received up to an additional 500 mL during the 1-hour infusion period. Twenty-eight day mortality, 28-day morbidity, 48-hour mortality, and 24-hour lactate levels. Of the 112 patients, 98 (88%) were infused with DCLHb or saline solution. At 28 days, 24 (46%) of the 52 patients infused with DCLHb died, and 8 (17%) of the 46 patients infused with the saline solution died (P = .003). At 48 hours, 20 (38%) of the 52 patients infused with DCLHb died and 7 (15%) of the 46 patients infused with the saline solution died (P = .01). The 28-day morbidity rate, as measured by the multiple organ dysfunction score, was 72% higher in the DCLHb group (P = .03). There was no difference in adverse event rates or the 24-hour lactate levels. Mortality was higher for patients treated with DCLHb. Although further analysis should investigate whether the mortality difference was solely due to a direct treatment effect or to other factors, DCLHb does not appear to be an effective resuscitation fluid.


Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent.
Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified. This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect. Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies. The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl (p=0.026) and 40 mg/100 µl (p=0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl (p=0.000) and 300 µl/100 µl (p=0.030). The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.


Cost-effective restoration and conservation planning in Green and Blue Infrastructure designs. A case study on the Intercontinental Biosphere Reserve of the Mediterranean: Andalusia (Spain) - Morocco.
Green and Blue Infrastructure (GBI) is a network designed and planned to deliver a wide range of ecosystem services and to protect biodiversity. Existing GBI designs lacked a systematic method to allocate restoration zones. This study proposes a novel approach for systematically selecting cost-effective areas for restoration on the basis of biodiversity, ecosystem services, and ecosystem condition to give an optimal spatial design of GBI. The approach was tested at a regional scale, in a transboundary setting encompassing the Intercontinental Biosphere Reserve of the Mediterranean in Andalusia (Spain) - Morocco (IBRM), across three aquatic ecosystems: freshwater, coastal and marine. We applied Marxan with Zones to stakeholder-defined scenarios of GBI in the IBRM. Specifically, we aimed to identify management zones within the GBl that addressed different conservation, restoration and exploitation objectives. Although almost all conservation targets were achieved, our results highlighted that the proportion of conservation features (i.e., biodiversity, ecosystem services) that would be compromised in the GBl, and the proportion of provisioning services that would be lost due to conservation (i.e., incidental representation) are potentially large, indicating that the probability of conflicts between conservation and exploitation goals in the area is high. The implementation of restoration zones improved connectivity across the GBI, and also achieved European and global policy targets. Our approach may help guide future applications of GBI to implement the flexible conservation management that aquatic environments require, considering many areas at different spatial scales, across multiple ecosystems, and in transboundary contexts.


Naturally Acquired Antibody Responses to Plasmodium vivax and Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) C-Terminal 19 kDa Domains in an Area of Unstable Malaria Transmission in Southeast Asia.
Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies.


[Psychosocial correlates of drug abuse and dependence among young Mexicans].
to test that drug abuse and dependence would be greater among those who have: higher depression, a family with dysfunctional cohesion and adaptability, greater exposure to stressful situations; maladaptive coping strategies. a case-control study design was used, with three controls matched to each case by on age, sex, and neighborhood of residence. The sample included 218 cases and 677 controls. cases of drug abuse and dependence were estimated to have higher odds of elevated depression symptoms, as well as high psychosocial stress from maladaptive school adjustment, compared to controls. Cases of drug dependence had higher odds to maladaptive family cohesion and adaptation, as well as higher odds of exposure to high-impact stress related to family separations, as well as family communication problems. findings indicate that drug abuse and dependence are significantly related to maladaptative adjustment indicators, family disfunctionality and affective disorders.


Hydrocephalus in patients with vestibular schwannoma.
Hydrocephalus (HC) is common in patients with vestibular schwannoma (VS). This can be managed with a cerebrospinal fluid (CSF) diversion procedure prior to VS resection or with VS resection, keeping CSF diversion in reserve unless required postoperatively. No clear consensus exists as to which approach is superior. This study identifies factors predictive of the development of HC, and analyses outcomes for those managed with primary CSF resection versus tumour resection. Single-centre retrospective cohort study of 204 consecutive adult patients with a unilateral VS from May 2009 to June 2021. Data was collected on patient and tumour demographics, management, and outcome. 204 patients, with a mean age at presentation of 59.5 (21-83), with 50% female, and a mean follow-up of 7.5 years (1.8-13.9) were included. 119 were managed conservatively, 36 with stereotactic radiosurgery only, and 49 with surgery. 30 (15%) patients had radiological HC, of which 23 (77%) were obstructive, and 7 (23%) were communicating. Maximum intracranial tumour diameter and Koos grade were higher in patients with HC. Of the patients with HC the majority (20, 67%) were managed initially with CSF diversion, with 12 patients undergoing subsequent tumour resection, and three patients avoiding primary resection. Nine (30%) were managed with primary surgical resection, of whom three required subsequent CSF diversion. Complication rates and Modified Rankin Scale (MRS) were comparable or lower in the CSF diversion group (8%, MRS ≤2 = 83%), versus the primary resection group (67%, MRS ≤2 = 67%), and the primary surgical resection without HC group (25%, MRS ≤2 = 86%). CSF diversion prior to tumour resection is a safe and acceptable strategy compared to primary VS resection, with improved outcomes and reduced surgical complications. Randomized studies and national databases are needed to determine the long-term outcomes of patients treated with CSF diversion versus primary resection.


Hemangiomas of infancy.
Hemangiomas of infancy are unique, benign, pediatric tumors of endothelial cells characterized by an initial phase of rapid proliferation, followed by slow involution, often leading to complete regression. Although most of these tumors are small and innocuous, some may be may be life- or function-threatening, or have associated structural congenital anomalies. Uncertainties regarding their diagnosis or management often prompt referral to a dermatologist. The pathogenesis of hemangiomas of infancy is not well understood, but recent findings suggest a unique vascular phenotype with dysregulated vascular homeostasis. This article reviews new information regarding the pathogenesis of these tumors and highlights the more worrisome presentations, including syndromic hemangiomas, that are likely to be problematic. In addition, management strategies and treatment options are discussed. (J Am Acad Dermatol 2003;48:477-93.) At the completion of this learning activity, participants should be able to describe the clinical features of hemangiomas of infancy and potential complications as well as to understand the strengths and limitations of various treatment options.


Relevance feedback for CBIR: a new approach based on probabilistic feature weighting with positive and negative examples.
In content-based image retrieval, understanding the user's needs is a challenging task that requires integrating him in the process of retrieval. Relevance feedback (RF) has proven to be an effective tool for taking the user's judgement into account. In this paper, we present a new RF framework based on a feature selection algorithm that nicely combines the advantages of a probabilistic formulation with those of using both the positive example (PE) and the negative example (NE). Through interaction with the user, our algorithm learns the importance he assigns to image features, and then applies the results obtained to define similarity measures that correspond better to his judgement. The use of the NE allows images undesired by the user to be discarded, thereby improving retrieval accuracy. As for the probabilistic formulation of the problem, it presents a multitude of advantages and opens the door to more modeling possibilities that achieve a good feature selection. It makes it possible to cluster the query data into classes, choose the probability law that best models each class, model missing data, and support queries with multiple PE and/or NE classes. The basic principle of our algorithm is to assign more importance to features with a high likelihood and those which distinguish well between PE classes and NE classes. The proposed algorithm was validated separately and in image retrieval context, and the experiments show that it performs a good feature selection and contributes to improving retrieval effectiveness.


Reconstitution of higher plant chloroplast chaperonin 60 tetradecamers active in protein folding.
Unlike the GroEL homologs of eubacteria and mitochondria, oligomer preparations of the higher plant chloroplast chaperonin 60 (cpn60) consist of roughly equal amounts of two divergent subunits, alpha and beta. The functional significance of these isoforms, their structural organization into tetradecamers, and their interactions with the unique binary chloroplast chaperonin 10 (cpn10) have not been elucidated. Toward this goal, we have cloned the alpha and beta subunits of the ch-cpn60 of pea (Pisum sativum), expressed them individually in Escherichia coli, and subjected the purified monomers to in vitro reconstitution experiments. In the absence of other factors, neither subunit (alone or in combination) spontaneously assembles into a higher order structure. However, in the presence of MgATP, the beta subunits form tetradecamers in a cooperative reaction that is potentiated by cpn10. In contrast, alpha subunits only assemble in the presence of beta subunits. Although beta and alpha/beta 14-mers are indistinguishable by electron microscopy and can both assist protein folding, their specificities for cpn10 are entirely different. Similar to the authentic chloroplast protein, the reconstituted alpha/beta 14-mers are functionally compatible with bacterial, mitochondrial, and chloroplast cpn10. In contrast, the folding reaction mediated by the reconstituted beta 14-mers is only efficient with mitochondrial cpn10. The ability to reconstitute two types of functional oligomer in vitro provides a unique tool, which will allow us to investigate the mechanism of this unusual chaperonin system.


Late graft loss after intestinal transplantation in an adult patient as a result of necrotizing enterocolitis.
A 50-year-old recipient of an intestinal and coecal graft with sudden onset of abdominal distention and pain, lack of bowel movements, and vomiting after closure of the diagnostic ostomy 7 months after transplantation is reported. A plain abdominal radiograph revealed pneumatosis intestinalis. An angiography excluded obstruction of large vessels, however, with absent microcirculation of the intestine. Upper gastrointestinal endoscopy showed extensive ulcerative enteritis with several spontaneous perforations. The patient underwent exploration demonstrating a nonviable intestine. The entire necrotic intestine was removed. Vascular thrombosis was excluded. Clinical data, and macroscopic and histologic features of the intestinal graft were diagnostic for necrotizing enterocolitis (NEC). Though there has been evidence for the occurrence of NEC not only in premature infants but even in older infants, children and adolescents, the presented case is, to our knowledge, the first report of NEC as etiology of late graft loss after intestinal transplantation in an adult recipient.


The effectiveness of mass vaccination on Marek's disease virus (MDV) outbreaks and detection within a broiler barn: a modeling study.
Marek's disease virus (MDV), a poultry pathogen, has been increasing in virulence since the mid twentieth century. Since multiple vaccines have been developed and widely implemented, losses due to MDV have decreased. However, vaccine failure has occurred in the past and vaccine breakthroughs remain a problem. Failure of disease control with current vaccines would have significant economic and welfare consequences. Nevertheless, the epidemiology of the disease during a farm outbreak is not well understood. Here we present a mathematical model to predict the effectiveness of vaccines to reduce the outbreak probability and disease burden within a barn. We find that the chance of an outbreak within a barn increases with the virulence of an MDV strain, and is significantly reduced when the flock is vaccinated, especially when there the contaminant strain is of low virulence. With low quantities of contaminated dust, there is nearly a 100% effectiveness of vaccines to reduce MDV outbreaks. However, the vaccine effectiveness drops to zero with an increased amount of contamination with a middle virulence MDV strain. We predict that the larger the barn, and the more virulent the MDV strain is, the more virus is produced by the time the flock is slaughtered. With the low-to-moderate virulence of the strains studied here, the number of deaths due to MDV is very low compared to all-cause mortality regardless of the vaccination status of the birds. However, the cumulative MD incidence can reach 100% for unvaccinated cohorts, and 35% for vaccinated cohorts. These results suggest that death due to MDV is an insufficient metric to assess the prevalence of MDV broiler barns regardless of vaccine status, such that active surveillance is required to successfully assess the probability of MDV outbreaks, and to limit transmission of MDV between successive cohorts of broiler chickens.