Protein adsorption in static microsystems: effect of the surface to volume ratio.
A numerical model for the adsorption kinetics of proteins on the walls of a microchannel has been developed using the finite element method (FEM) to address the coupling with diffusion phenomena in the restricted microchannel volume. Time evolutions of the concentration of one species are given, both in solution and on the microchannel walls. The model illustrates the adsorption limitation sometimes observed when the microdimensions of these systems induce a global depletion of the bulk solution. A new non-dimensional parameter is introduced to predict the final value of the coverage of any microsystem under static adsorption. A working curve and a criteria (h/K[Gamma](max) > 10) are provided in order to choose, for given adsorption characteristics, the value of the volume-to-surface ratio (i.e. the channel height h) avoiding depletion effects on the coverage (relative coverage greater than 90% of the theoretical one). Simulations were compared with confocal microscopy measurements of IgG antibody adsorption on the walls of a PET microchannel. The fit of the model to the experimental data show that the adsorption is under apparent kinetic control.


Drug and neurotransmitter receptors in the brain.
Biochemical investigation of receptors for neurotransmitters and drugs in the brain has been one of the most active areas of molecular neuroscience during the past decade. This work has permitted fundamental insights into how binding of neurotransmitters to their receptors excites or inhibits neuronal firing or changes cellular metabolism. The recognition of receptor subtypes has suggested subtle ways for neurotransmitters to modulate neuronal functioning. Finally, the ability to measure receptor sites in simple test tube systems and to distinguish readily between agonists and antagonists has provided useful probes for drug discovery programs.


Tropical mosquito assemblages demonstrate 'textbook' annual cycles.
Annual biological rhythms are often depicted as predictably cyclic, but quantitative evaluations are few and rarely both cyclic and constant among years. In the monsoon tropics, the intense seasonality of rainfall frequently drives fluctuations in the populations of short-lived aquatic organisms. However, it is unclear how predictably assemblage composition will fluctuate because the intensity, onset and cessation of the wet season varies greatly among years. Adult mosquitoes were sampled using EVS suction traps baited with carbon dioxide around swamplands adjacent to the city of Darwin in northern Australia. Eleven sites were sampled weekly for five years, and one site weekly for 24 years, the sample of c. 1.4 million mosquitoes yielding 63 species. Mosquito abundance, species richness and diversity fluctuated seasonally, species richness being highly predictable. Ordination of assemblage composition demonstrated striking annual cycles that varied little from year to year. The mosquito assemblage was temporally structured by a succession of species peaks in abundance. Ordination provided strong visual representation of annual rhythms in assemblage composition and the means to evaluate variability among years. Because most mosquitoes breed in shallow freshwater which fluctuates with rainfall, we did not anticipate such repeatability; we conclude that mosquito assemblage composition appears adapted to predictable elements of the rainfall.


Nutritional upgrading for omnivorous carpenter ants by the endosymbiont Blochmannia.
Carpenter ants (genus Camponotus) are considered to be omnivores. Nonetheless, the genome sequence of Blochmannia floridanus, the obligate intracellular endosymbiont of Camponotus floridanus, suggests a function in nutritional upgrading of host resources by the bacterium. Thus, the strongly reduced genome of the endosymbiont retains genes for all subunits of a functional urease, as well as those for biosynthetic pathways for all but one (arginine) of the amino acids essential to the host. Nutritional upgrading by Blochmannia was tested in 90-day feeding experiments with brood-raising in worker-groups on chemically defined diets with and without essential amino acids and treated or not with antibiotics. Control groups were fed with cockroaches, honey water and Bhatkar agar. Worker-groups were provided with brood collected from the queenright mother-colonies (45 eggs and 45 first instar larvae each). Brood production did not differ significantly between groups of symbiotic workers on diets with and without essential amino acids. However, aposymbiotic worker groups raised significantly less brood on a diet lacking essential amino acids. Reduced brood production by aposymbiotic workers was compensated when those groups were provided with essential amino acids in their diet. Decrease of endosymbionts due to treatment with antibiotic was monitored by qRT-PCR and FISH after the 90-day experimental period. Urease function was confirmed by feeding experiments using 15N-labelled urea. GC-MS analysis of 15N-enrichment of free amino acids in workers revealed significant labelling of the non-essential amino acids alanine, glycine, aspartic acid, and glutamic acid, as well as of the essential amino acids methionine and phenylalanine. Our results show that endosymbiotic Blochmannia nutritionally upgrade the diet of C. floridanus hosts to provide essential amino acids, and that it may also play a role in nitrogen recycling via its functional urease. Blochmannia may confer a significant fitness advantage via nutritional upgrading by enhancing competitive ability of Camponotus with other ant species lacking such an endosymbiont. Domestication of the endosymbiont may have facilitated the evolutionary success of the genus Camponotus.


Evaluation of the Antibacterial Potential of Liquid and Vapor Phase Phenolic Essential Oil Compounds against Oral Microorganisms.
The aim of the present study was to determine the antibacterial activities of the phenolic essential oil (EO) compounds hinokitiol, carvacrol, thymol, and menthol against oral pathogens. Aggregatibacter actinomycetemcomitans, Streptococcus mutans, Methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia. coli were used in this study. The minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), bacterial growth curves, temperature and pH stabilities, and synergistic effects of the liquid and vapor EO compounds were tested. The MIC/MBC of the EO compounds, ranging from the strongest to weakest, were hinokitiol (40-60 μg/mL/40-100 μg/mL), thymol (100-200 μg/mL/200-400 μg/mL), carvacrol (200-400 μg/mL/200-600 μg/mL), and menthol (500-more than 2500 μg/mL/1000-more than 2500 μg/mL). The antibacterial activities of the four EO phenolic compound based on the agar diffusion test and bacterial growth curves showed that the four EO phenolic compounds were stable under different temperatures for 24 h, but the thymol activity decreased when the temperature was higher than 80°C. The combination of liquid carvacrol with thymol did not show any synergistic effects. The activities of the vaporous carvacrol and thymol were inhibited by the presence of water. Continual violent shaking during culture enhanced the activity of menthol. Both liquid and vaporous hinokitiol were stable at different temperatures and pH conditions. The combination of vaporous hinokitiol with zinc oxide did not show synergistic effects. These results showed that the liquid and vapor phases of hinokitiol have strong anti-oral bacteria abilities. Hinokitiol has the potential to be applied in oral health care products, dental materials, and infection controls to exert antimicrobial activity.


An atom efficient synthesis of tamoxifen.
The direct carbolithiation of diphenylacetylenes and their cross-coupling procedure taking advantage of the intermediate alkenyllithium reagents are presented. By employing our recently discovered highly active palladium nanoparticle based catalyst, we were able to couple an alkenyllithium reagent with a high (Z/E) selectivity (10 : 1) and good yield to give the breast cancer drug tamoxifen in just 2 steps from commercially available starting materials and with excellent atom economy and reaction mass efficiency.


Utilization patterns of antihyperuricemic agents following safety announcement on allopurinol and benzbromarone by Taiwan Food and Drug Administration.
The purpose of this study is to evaluate the utilization of four approved antihyperuricemic agents in Taiwan before and after two safety announcements rescinded an indication for allopurinol and added a warning on benzbromarone-induced hepatotoxicity in the year 2005. An interrupted time series design and segmented regression models were used to examine impacts of the safety announcements on the utilization of allopurinol, benzbromarone, probenecid, or sulfinpyrazone. All outpatient prescriptions of the four antihyperuricemic agents were extracted from a longitudinal cohort dataset with 1000000 individuals randomly sampled from the National Health Insurance Research Database. We examined utilization patterns of antihyperuricemic agents before and after the policy intervention (i.e., safety announcements and labeling changes of allopurinol and benzbromarone) in the year 2005. Following the safety announcements, there was a reduction in the number of allopurinol users in the first year of intervention (-95.82 users per 100000 persons, 95%CI, [-166.84, -24.80]) and a continuous reduction afterward at a rate of -53.17 per 100000 persons per year. The utilization of benzbromarone grew steadily before 2005 but decreased drastically after the intervention, with a 30.12% reduction in the number of users by the end of year 2008. There was no commensurate change in the number of probenecid or sulfinpyrazone users after the intervention. Further research is required to evaluate the direct impacts of the safety announcements on clinical outcomes, treatment costs, and patient's quality of life.


Detailed analysis of periprocedural strokes in patients undergoing intracranial stenting in Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS).
Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was halted due to the high risk of stroke or death within 30 days of enrollment in the percutaneous transluminal angioplasty and stenting arm relative to the medical arm. This analysis focuses on the patient and procedural factors that may have been associated with periprocedural cerebrovascular events in the trial. Bivariate and multivariate analyses were performed to evaluate whether patient and procedural variables were associated with cerebral ischemic or hemorrhagic events occurring within 30 days of enrollment (termed periprocedural) in the percutaneous transluminal angioplasty and stenting arm. Of 224 patients randomized to percutaneous transluminal angioplasty and stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had ischemic stroke, and 2 had cerebral infarcts with temporary signs within the periprocedural period. Ischemic events were categorized as perforator occlusions (13), embolic (4), mixed perforator and embolic (2), and delayed stent occlusion (2). Multivariate analyses showed that higher percent stenosis, lower modified Rankin score, and clopidogrel load associated with an activated clotting time above the target range were associated (P ≤ 0.05) with hemorrhagic stroke. Nonsmoking, basilar artery stenosis, diabetes, and older age were associated (P ≤ 0.05) with ischemic events. Periprocedural strokes in SAMMPRIS had multiple causes with the most common being perforator occlusion. Although risk factors for periprocedural strokes could be identified, excluding patients with these features from undergoing percutaneous transluminal angioplasty and stenting to lower the procedural risk would limit percutaneous transluminal angioplasty and stenting to a small subset of patients. Moreover, given the small number of events, the present data should be used for hypothesis generation rather than to guide patient selection in clinical practice. Clinical Trial Registration Information- URL: http://clinicaltrials.gov. Unique Identifier: NCT00576693.


Random selection algorithms for spatial and temporal sampling.
Seven BASIC programs are presented that use algorithms for selection of treatments and samples in spatial and temporal contexts. Program (1) takes a natural sequence of samples (such as logs cut from a tree trunk) and divides them into groups (equal to the number of samples divided by treatments), and then selects non-redundantly from each group a sample at random for each treatment. Program (2) matches items from different categories equally to any number of treatments in proportion to the numbers of items of each category. Program (3) selects sampling times or segment lengths of specified interval and number from within a time period or perimeter distance. These samples can be spaced apart by at least a specified amount of time or distance but otherwise are chosen at random. In program (4), a series of sample coordinates (x,y) are chosen at random from a rectangular area so that no points are closer than a specified minimum distance to any other. For each of the sample points, the Cartesian and polar coordinates are given. Program (5) generates any possible Latin square, while program (6) generates Latin cubes, and program (7) makes Graeco-Latin cubes. Examples of program use and output are presented for experiments with bark beetles (Coleoptera: Scolytidae) responding to pheromone blends and colonizing host trees.


Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia.
RNA-binding proteins of the Musashi (Msi) family are expressed in stem cell compartments and in aggressive tumors, but they have not yet been widely explored in the blood. Here we demonstrate that Msi2 is the predominant form expressed in hematopoietic stem cells (HSCs), and its knockdown leads to reduced engraftment and depletion of HSCs in vivo. Overexpression of human MSI2 in a mouse model increases HSC cell cycle progression and cooperates with the chronic myeloid leukemia-associated BCR-ABL1 oncoprotein to induce an aggressive leukemia. MSI2 is overexpressed in human myeloid leukemia cell lines, and its depletion leads to decreased proliferation and increased apoptosis. Expression levels in human myeloid leukemia directly correlate with decreased survival in patients with the disease, thereby defining MSI2 expression as a new prognostic marker and as a new target for therapy in acute myeloid leukemia (AML).


CNVs with adaptive potential in Rangifer tarandus: genome architecture and new annotated assembly.
Rangifer tarandus has experienced recent drastic population size reductions throughout its circumpolar distribution and preserving the species implies genetic diversity conservation. To facilitate genomic studies of the species populations, we improved the genome assembly by combining long read and linked read and obtained a new highly accurate and contiguous genome assembly made of 13,994 scaffolds (L90 = 131 scaffolds). Using de novo transcriptome assembly of RNA-sequencing reads and similarity with annotated human gene sequences, 17,394 robust gene models were identified. As copy number variations (CNVs) likely play a role in adaptation, we additionally investigated these variations among 20 genomes representing three caribou ecotypes (migratory, boreal and mountain). A total of 1,698 large CNVs (length > 1 kb) showing a genome distribution including hotspots were identified. 43 large CNVs were particularly distinctive of the migratory and sedentary ecotypes and included genes annotated for functions likely related to the expected adaptations. This work includes the first publicly available annotation of the caribou genome and the first assembly allowing genome architecture analyses, including the likely adaptive CNVs reported here.


Associations between a history of breast feeding, malocclusion and parafunctional habits in Puerto Rican children.
Studies relating breast-feeding, malocclusion and parafunctional habits in young children are scarce. The purpose of this study is to evaluate the associations of a history of breast-feeding, incidence of malocclusion and parafunctional habits. The dental records of a sample of 540 children aged 6 to 72 months screened for oral conditions and behavioral risk factors were evaluated for variables such as a history of breastfeeding, malocclusion and parafunctional habits. Descriptive statistics using the EPI-INFO Program and Chi-square test at the 0.05 level of probability were performed. The results showed that the mean age of the children was 28 months +/- 14. The mothers' mean age was 26.4 years +/- 6. The prevalence of breast-feeding was 34% with a mean breast-feeding time period of 3 m +/- 3.7. About 95% of the children had a history of bottle-feeding and 90% showed some evidence of malocclusion at the time of dental examination. The main malocclusion problems were space deficiency (closed contacts among incisors) (31%), open bites (6%) and crossbites (5%). A habit of thumb sucking was reported in 32% of the cases and pacifier use in 21%. there were significant differences for the following variables: mother's age and breast-feeding time period; number of children in family and breast-feeding time period; breast-feeding history and breast-feeding time with bottle use, malocclusion and thumb sucking habit; and gender and thumb-sucking habit. It is concluded that breast-feeding practices and time period are behavioral factors that contribute in the prevention of malocclusion in addition to decreasing the practice of parafunctional habits in preschool children.


Evolutionary history of hepatitis C virus genotype 5a in France, a multicenter ANRS study.
The epidemic history of HCV genotype 5a is poorly documented in France, where its prevalence is very low, except in a small central area, where it accounts for 14.2% of chronic hepatitis C cases. A Bayesian coalescent phylogenetic investigation based on the E1 envelope gene and a non-structural genomic segment (NS3/4) was carried out to trace the origin of this epidemic using a large sample of genotype 5a isolates collected throughout France. The dates of documented transmissions by blood transfusion were used to calibrate five nodes in the phylogeny. The results of the E1 gene analysis showed that the best-fitting population dynamic model was the expansion growth model under a relaxed molecular clock. The rate of nucleotide substitutions and time to the most recent common ancestors (tMRCA) of genotype 5a isolates were estimated. The divergence of all the French HCV genotype 5a strains included in this study was dated to 1939 [95% HPD: 1921-1956], and the tMRCA of isolates from central France was dated to 1954 [1942-1967], which is in agreement with epidemiological data. NS3/4 analysis provided similar estimates with strongly overlapping HPD values. Phylodynamic analyses give a plausible reconstruction of the evolutionary history of HCV genotype 5a in France, suggesting the concomitant roles of transfusion, iatrogenic route and intra-familial transmission in viral diffusion.


Changes in white matter microstructure in the developing brain--A longitudinal diffusion tensor imaging study of children from 4 to 11years of age.
The purpose of the present study was to detail the childhood developmental course of different white matter (WM) characteristics. In a longitudinal diffusion tensor imaging (DTI) study of 159 healthy children between 4 and 11years scanned twice, we used tract-based spatial statistics as well as delineation of 15 major WM tracts to characterize the regional pattern of change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD). We tested whether there were decelerations of change with increasing age globally and tract-wise, and also illustrated change along medial-to-lateral, posterior-to-anterior and inferior-to-superior gradients. We found a significant linear increase in global FA, and decrease in MD and RD over time. For mean AD, a weak decrease was observed. The developmental changes in specific WM tracts showed regional differences. Eight WM tracts showed non-linear development patterns for one or several DTI metrics, with a deceleration in change with age. Sex did not affect change in any DTI metric. Overall, greater rate of change was found in the left hemisphere. Spatially, there was a posterior-to-anterior gradient of change with greater change in frontal regions for all metrics. The current study provides a comprehensive characterization of the regional patters of change in WM microstructure across pre-adolescence childhood.


Influence of cell cycle checkpoints and p53 function on the toxicity of temozolomide in human pancreatic cancer cells.
Though an increased efficacy of carmustine and temozolomide (TMZ) has been demonstrated by inactivation of O(6)-methylguanine-DNA methyltransferase (MGMT) with O(6)-benzyl-guanine (BG) in human pancreatic tumors refractive to alkylating agents, the regulatory mechanisms have not been explored. The effects of TMZ and BG on apoptosis, cell growth, the mitotic index, cell cycle distribution, and protein expression were studied by TUNEL, cell counting, flow cytometry, and Western blot analysis, respectively. The wt-p53 human pancreatic tumor cell line Capan-2 and p53-efficient mouse embryonic fibroblasts (MEFs) were more responsive to treatment with TMZ + BG than mutant p53 Capan-1 and p53-null MEFs. S phase delay with a subsequent G2/M arrest was observed in Capans in response to BG + TMZ. The G1-to-S transition delay in Capan-2 was associated with p53-dependent apoptosis and was distinctly different from the presumed mismatch repair (MMR) killing operative during the G2/M arrest. The effect of p53 on BG + TMZ toxicity was supported by a marked change in apoptosis when p53 function was restored/inactivated. There was an early induction of MMR proteins in p53-efficient lines. p53 provokes a classic proapoptotic response by delaying G1-to-S progression, but it may also facilitate cell killing by enhancing MMR-related cell cycle arrest and cell death.


Modeling in the Time of COVID-19: Statistical and Rule-based Mesoscale Models.
We present a new technique for the rapid modeling and construction of scientifically accurate mesoscale biological models. The resulting 3D models are based on a few 2D microscopy scans and the latest knowledge available about the biological entity, represented as a set of geometric relationships. Our new visual-programming technique is based on statistical and rule-based modeling approaches that are rapid to author, fast to construct, and easy to revise. From a few 2D microscopy scans, we determine the statistical properties of various structural aspects, such as the outer membrane shape, the spatial properties, and the distribution characteristics of the macromolecular elements on the membrane. This information is utilized in the construction of the 3D model. Once all the imaging evidence is incorporated into the model, additional information can be incorporated by interactively defining the rules that spatially characterize the rest of the biological entity, such as mutual interactions among macromolecules, and their distances and orientations relative to other structures. These rules are defined through an intuitive 3D interactive visualization as a visual-programming feedback loop. We demonstrate the applicability of our approach on a use case of the modeling procedure of the SARS-CoV-2 virion ultrastructure. This atomistic model, which we present here, can steer biological research to new promising directions in our efforts to fight the spread of the virus.


Review of structured guides for deprescribing.
Avoiding inappropriate polypharmacy has become increasingly recognised as a safety imperative for older patient care. Deprescribing is an active process of reviewing all medications being used by individual patients that prompts clinicians to consider which medications have unfavourable risk-benefit trade-offs in the context of illness severity, advanced age, multi-morbidity, physical and emotional capacity, life expectancy, care goals and personal preferences. Structured guides to deprescribing include algorithms, flow charts or tables which are patient-directed and aim to guide the clinician through sequential steps in deciding which medications should be targeted for discontinuation. In this narrative review, we describe seven structured deprescribing guides whose stated purpose included the reduction of polypharmacy, their use was not restricted to a single drug or drug class and they had undergone some form of efficacy testing. There was considerable heterogeneity in guide design and content, with some guides constituting little more than a set of principles while others entail detailed processes and sub-steps which addressed multiple determinants of drug appropriateness. Evidence of effectiveness for each guide was limited in that none have been evaluated in randomised controlled trials, that pilot or feasibility studies have involved relatively small patient samples, that intra-rater and inter-rater reliabilities have not been determined and that most have been studied in hospital settings. Which is most useful to clinicians is unknown in the absence of head-to-head comparisons. While most guides have face validity, more research is needed for determining effectiveness and ease of use in routine clinical practice, especially in primary care settings.


Poisonings with Suicidal Intent Aged 0-21 Years Reported to Poison Centers 2003-12.
Few studies explore the clinical features of youth suicide by poisoning. The use of both social and clinical features of self-poisoning with suicidal intent could be helpful in enhancing existing and creating new prevention strategies. We sought to characterize self-poisonings with suicide intent in ages 0 to 21 years reported to three regional poison control centers from 2003-2012. This study was a blinded retrospective review of intentional self-poisonings by those age 21 or younger captured by the Poison Information Control Network. Age, sex, substance(s) used, medical outcome, management site, clinical effects, and therapies were described using counts and percentages and analyzed using chi-square tests. We analyzed the medical outcome ranging from no effect to death using the Wilcoxon rank-sum test. Serious medical outcome was defined as death or major outcome. We analyzed a total of 29,737 cases. The majority were females (20,945;70.5%), of whom 274 (1.3%) were pregnant. Most cases were 15-18 year olds (15,520;52.2%). Many experienced no effects (9,068;30.5%) or minor medical outcomes (8,612;29%). Males had more serious medical outcomes (p<0.0001), but females were more likely to be admitted to a critical care unit (p<0.0001). There were 17 deaths (0.06%), most in males (10;p=0.008). Of the 52 substances reported in the death cases, 12 (23.1%) were analgesics. In eight (47.1%) of the deaths, over two substances were used. Overall, drowsiness/lethargy (7,097;19.3%) and single-dose charcoal (8,815;16.3%) were frequently reported. Nearly 20% were admitted to critical care units (5,727;19.3%) and 28.7% went to psychiatric facilities (8,523). Of those admitted to hospitals (8,203), nearly 70% (5,727) required critical care units. Almost half <10 years old were evaluated and released (43;47.2%). Of the 114 reported substances for this population, 22.8% involved psychotropic medications, 15.8% analgesics, and 14% Attention Deficit-Hyperactive Disorder (ADHD) medications. Analgesics (13,539;33.6%) were the most common medication category used by all age groups. Typically only one substance (20,549;69.1%) was used. Undiagnosed ADHD may be a potential underlying cause for self-harming behaviors in the very young. Gender-specific suicide prevention strategies may be more effective at identifying those at risk than traditional measures alone. Further study into admitting practices by emergency physicians is needed to understand the difference in critical care admission rates based on gender. Once identified to be at-risk for suicidal behavior, access to analgesics and psychotropics should be monitored by care-givers especially in those between the ages of 15-18.


Prevalence of pervasive developmental disorders among children at the English Montreal School Board.
The prevalence of pervasive developmental disorders (PDDs) has increased. There has been speculation regarding a role of thimerosal-containing vaccines (TCVs) in this trend. Our objectives were to determine prevalence rates of PDDs among school-aged children, and to evaluate the impact of discontinuation of thimerosal use in 1996 in routine childhood vaccines on PDD rates. Children (n = 23 635) attending kindergarten to Grade 11 were surveyed in 71 schools from the English Montreal School Board. For children with PDD, information was obtained about their diagnostic subtype, age, sex, grade, and school. Prevalence rates were calculated for the entire school population and for each grade. Prevalence rates were also compared for children born before or after 1996. Students (n = 187; male to female ratio: 5.4:1) with PDD were identified, corresponding to a prevalence of 79.1/10 000 (95% CI 67.8 to 90.4/10 000). The prevalence was 25.4, 43.6, 9.7, and 0.4 for autistic disorder, PDD not otherwise specified, Asperger syndrome, and childhood disintegrative disorder, respectively. During the study period, there was a significant linear increase in prevalence (OR 1.17 per year; 95% CI 1.12 to 1.23). The trend in prevalence of PDDs was unrelated to the discontinuation of TCVs. Our study provides additional evidence that the PDD rate is close to 1%. We estimate that at least 11 500 Canadian children aged 2 to 5 years suffer from a PDD. The reasons for the upward trend in prevalence could not be determined with our methods. Discontinuation of thimerosal use in vaccines did not modify the risk of PDD.


Gpr126/Adgrg6 deletion in cartilage models idiopathic scoliosis and pectus excavatum in mice.
Adolescent idiopathic scoliosis (AIS) and pectus excavatum (PE) are common pediatric musculoskeletal disorders. Little is known about the tissue of origin for either condition, or about their genetic bases. Common variants near GPR126/ADGRG6 (encoding the adhesion G protein-coupled receptor 126/adhesion G protein-coupled receptor G6, hereafter referred to as GPR126) were recently shown to be associated with AIS in humans. Here, we provide genetic evidence that loss of Gpr126 in osteochondroprogenitor cells alters cartilage biology and spinal column development. Microtomographic and x-ray studies revealed several hallmarks of AIS, including postnatal onset of scoliosis without malformations of vertebral units. The mutants also displayed a dorsal-ward deflection of the sternum akin to human PE. At the cellular level, these defects were accompanied by failure of midline fusion within the developing annulus fibrosis of the intervertebral discs and increased apoptosis of chondrocytes in the ribs and vertebrae. Molecularly, we found that loss of Gpr126 upregulated the expression of Gal3st4, a gene implicated in human PE, encoding Galactose-3-O-sulfotransferase 4. Together, these data uncover Gpr126 as a genetic cause for the pathogenesis of AIS and PE in a mouse model.


Validation of third molar maturity index (I3M) for discrimination of juvenile/adult status in South Indian population.
Deliberate falsification of age was considered to be one of the main reasons for forensic age estimation of the living individuals. This posed to be a challenging task during criminal and legal proceedings, and ultimate care must be taken not to classify juveniles as adults. Third molars are the only developing teeth during late adolescence and early adulthood. Our study was designed to analyze the usefulness of the third molar maturity index (I3M) specific cut-off value (I3M < 0.08) to discriminate adults (≥18 years) and juveniles (<18 years) in South Indian children. 216 panoramic radiographs (114 females and 102 males) of living subjects aged between 14 and 21 years were analyzed. Our results demonstrated high sensitivity (83.3% and 90.2%) and specificity (98.3% and 95.1%) for females and males respectively. The positive likelihood ratios of being adult were 50.00 and 18.35 while the negative likelihood ratios were 0.17 and 0.10 in females and males respectively. The estimated posttest probability was 98.0% in females and 94.8% in males. The obtained results showed that the specific cut-off value of I3M < 0.08 may be a useful additional tool in discrimination of individuals who are around 18 years of age.


Form variation in Escherichia coli K1: determined by O-acetylation of the capsular polysaccharide.
The chemical basis for the alternating antigenic change called form variation noted for the Escherichia coli K1-capsular polysaccharide has been shown by 13C nuclear magnetic resonance to be a result of random O-acetylation of C7 and C9 carbons of the alpha-2-8-linked sialic acid homopolymer. A serologic method (antiserum agar) was developed to identify and isolate the form variants. The O-acetyl positive and O-acetyl negative K1 polysaccharides had unique biochemical and immunologic properties. The O-acetyl-positive variants resisted neuraminidase hydrolysis in contrast to the susceptibility of the O-acetyl negative variant to this enzyme. In addition, O-acetylation altered the antigenicity of the O-acetyl polysaccharides. When injected as whole organisms, O-acetyl positive organisms produced anti-K1 -antibodies in rabbits specific for this polysaccharide variant. O-acetyl negative organisms were comparatively less immunogenic; however, antibodies induced by these organisms reacted with both K1 polysaccharide variants. Burros, injected with either variant, produced antibodies reactive with both K1 polysaccharides.


Prostate cancer epidemiology.
Prostate cancer is the most common non-skin cancer among men in most western populations, and it is the second leading cause of cancer death among U.S. men. Despite its high morbidity, the etiology of prostate cancer remains largely unknown. Advancing age, race, and a family history of prostate cancer are the only established risk factors. Many putative risk factors, including androgens, diet, physical activity, sexual factors, inflammation, and obesity, have been implicated, but their roles in prostate cancer etiology remain unclear. It is estimated that as much as 42% of the risk of prostate cancer may be accounted for by genetic influences, including individual and combined effects of rare, highly penetrant genes, more common weakly penetrant genes, and genes acting in concert with each other. Numerous genetic variants in the androgen biosynthesis/metabolism, carcinogen metabolism, DNA repair, and chronic inflammation pathways, have been explored, but the results are largely inconclusive. The pathogenesis of prostate cancer likely involves interplay between environmental and genetic factors. To unravel these complex relationships, large well-designed interdisciplinary epidemiologic studies are needed. With newly available molecular tools, a new generation of large-scale multidisciplinary population-based studies is beginning to investigate gene-gene and gene-environment interactions. Results of these studies may lead to better detection, treatment, and, ultimately, prevention of prostate cancer.


Macroamylasemia with a markedly increased amylase clearance ratio in a patient with renal cell carcinoma.
We report hyperamylasemia, macroamylasemia, and a markedly increased amylase clearance/creatinine clearance ratio in a patient with renal cell carcinoma. Serum amylase activity was characterized as macroamylase by gel exclusion chromatography. Electrophoretic separation revealed an atypical band of amylase, migrating anodal to the S2 control fraction. Electrophoresis of urine revealed the presence of both S1 and S2 fractions, but not the atypical band found in serum. Quantification of the salivary- and pancreatic-type amylase fractions showed amylase in urine to be 100% salivary. Immunofixation disclosed the macroamylase to consist of an immune complex between amylase and IgA-lambda antibody. Binding-capacity studies showed that the serum immunoglobulin was present in excess and could bind 46% and 49% additional S-type amylase activity derived from saliva and the patient's urine, respectively. The amylase clearance/creatinine clearance ratio was markedly supranormal (0.134), unexpected in a patient with macroamylasemia. A biopsy specimen of the renal cell tumor was found to contain significant salivary-type amylase activity. These results suggest production of amylase by tumor tissue in the renal carcinoma and secretion of S-type amylase into the patient's urine. Evidently, macroamylase should be confirmed by gel exclusion chromatography.


Social support and mortality among older persons with diabetes.
The purpose of this study was to examine the relationship between social support and mortality among older persons with diabetes and the pathways by which social support affects diabetes survival. Using data from the Longitudinal Study of Aging cohort 2 baseline (1994) and follow-up (1997-1998 and 1999-2000 surveys), the authors identified 1431 persons aged >or=70 years with diabetes, among whom 387 deaths occurred. Social support was measured by an index with regard to participants' connection with relatives, friends, neighbors, social events, church, and senior centers. Regression analysis was used to find the pathway, and survival analysis was used to find the relationship between social support and mortality. Compared to people with a low level of social support, the risk of death is 41% lower among people with medium levels of support (hazards ratio = 0.59, 0.39-0.91) and 55% lower among those with the highest levels of support (hazards ratio = 0.45, 0.21-0.98). Eight of the 11 regression models demonstrated that the effect of social support on mortality was mediated by both physical and mental health status. Social support is strongly associated with mortality. Based on findings from this study, social support should be considered an important target for intervention to reduce mortality risk among older adults with diabetes.


Seagrass ecosystems of the Pacific Island Countries and Territories: A global bright spot.
Seagrass ecosystems exist throughout Pacific Island Countries and Territories (PICTs). Despite this area covering nearly 8% of the global ocean, information on seagrass distribution, biogeography, and status remains largely absent from the scientific literature. We confirm 16 seagrass species occur across 17 of the 22 PICTs with the highest number in Melanesia, followed by Micronesia and Polynesia respectively. The greatest diversity of seagrass occurs in Papua New Guinea (13 species), and attenuates eastward across the Pacific to two species in French Polynesia. We conservatively estimate seagrass extent to be 1446.2 km2, with the greatest extent (84%) in Melanesia. We find seagrass condition in 65% of PICTs increasing or displaying no discernible trend since records began. Marine conservation across the region overwhelmingly focuses on coral reefs, with seagrass ecosystems marginalised in conservation legislation and policy. Traditional knowledge is playing a greater role in managing local seagrass resources and these approaches are having greater success than contemporary conservation approaches. In a world where the future of seagrass ecosystems is looking progressively dire, the Pacific Islands appears as a global bright spot, where pressures remain relatively low and seagrass more resilient.


Generation and sequence characterization of a normalized cDNA library from swine ovarian follicles.
Ovulation rate is a major factor determining litter size in swine and is, therefore, a trait of economic importance to the pork industry. The dynamics of follicle development, which in turn are dictated by a balance between follicle recruitment, maturation, selection, and atresia, are a major determining factor of ovulation rate. The role of several genes expressed in the ovaries during these processes has been described, but studies utilizing large-scale genomic approaches have yet to be conducted to examine gene expression in this tissue more globally. We have developed a normalized cDNA library from swine ovarian follicles in various stages of development, ranging from 2.0 to 10.0 mm in diameter, collected from gilts from divergent genetic lines selected for high and low ovulation rates, during the 7 initial days of the follicular phase of the estrous cycle. EST sequences were obtained from 5231 distinct clones derived from this library. In total, 3479 unique sequence clusters were obtained, of which 2661 singletons (76.5%) were observed. BLASTN searches with the primary sequences from the clusters obtained resulted in 1037 sequences not matching (E <1.0(-06) any of the sequences in the nt database (29.8% novelty rate). This resource will facilitate the use of cDNA microarrays in functional genomics studies aiming at unraveling the genetic and physiological mechanisms underlying follicle maturation and ovulation rate in swine.


The efficacy of ultrasound in the evaluation of dynamic scapholunate ligamentous instability.
The accuracy of diagnostic imaging modalities that are currently used to evaluate dynamic scapholunate ligamentous instability is equivocal. Ultrasound is commonly used for a wide variety of diagnostic purposes in orthopaedics. The purpose of the present study was to determine the efficacy of ultrasound in the diagnosis of dynamic scapholunate ligamentous instability. Two groups of individuals were prospectively studied. Group A included patients with a clinical diagnosis of unilateral dynamic scapholunate ligamentous instability, and Group B included asymptomatic volunteer control subjects. Dynamic ultrasound examinations of the dorsal portion of the scapholunate ligament in both wrists of all individuals were performed by radiologists. The radiologists were blinded with regard to the group to which each person belonged as well as with regard to the affected wrist in the patients in Group A. Arthroscopic examinations of the affected wrist in all of the patients in Group A were then performed by surgeons who were blinded with regard to the results of the ultrasound examination, and the results of the arthroscopic and ultrasound examinations were compared. The ability of ultrasound to discern asymptomatic from symptomatic individuals was also determined. Over a period of 1.5 years, a total of sixty-four wrists were evaluated in fourteen patients (Group A) and eighteen normal subjects (Group B). All fourteen nonaffected wrists in Group A and all thirty-six wrists in Group B were correctly identified as normal with use of ultrasound. Of the fourteen affected wrists in Group A, thirteen were found to have scapholunate ligament laxity on the basis of arthroscopy (twelve wrists) or arthrotomy (one wrist); six of these thirteen wrists had been correctly identified as abnormal with use of ultrasound (a true-positive result), and seven had false-negative results. There was one true-negative result. The ability of ultrasound to differentiate between normal and abnormal wrists was significant (p < 0.001). For the sixty-four wrists, statistical analysis revealed that ultrasound had a sensitivity of 46.2%, a specificity of 100%, and an accuracy of 89.1%. We conclude that ultrasound has a high specificity and accuracy but a low sensitivity for the evaluation of dynamic scapholunate ligamentous instability, and we recommend its use as an adjunct to other diagnostic modalities for this purpose.


Comparison of protein patterns of Listeria monocytogenes grown in biofilm or in planktonic mode by proteomic analysis.
The proteome of a Listeria monocytogenes strain isolated from a food plant was investigated to study the differential protein pattern expressed by biofilms and planktonic bacteria. The approach used in this study was a combination of two-dimensional electrophoresis, matrix-assisted laser desorption ionization-time of flight and database searches for the protein identification. Thirty-one proteins varied significantly between the two growth conditions. Twenty-two and nine proteins were up- and down-regulated respectively and nine proteins were successfully identified. The variations of the protein patterns indicated that the biofilm development is probably controlled by specific regulation of protein expression involved at various levels of cellular physiology.


Relationship between androgen levels and blood pressure in young women with polycystic ovary syndrome.
The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age- and body mass index-adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: >or=19%) in women with PCOS increased the risk of elevated blood pressure (SBP >or=130 mm Hg and/or DBP >or=85 mm Hg) with an odds ratio of 3.817 (P=0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia.


The Ribavirin Pregnancy Registry: Findings after 5 years of enrollment, 2003-2009.
Ribavirin, with interferons or pegylated interferons, is used to treat chronic hepatitis C. Ribavirin is contraindicated in pregnancy (FDA Pregnancy Category X) and in men whose partners may become pregnant. In 2003, the Ribavirin Pregnancy Registry was established to monitor pregnancy exposures to ribavirin and to evaluate the potential human teratogenicity of prenatal exposure. This voluntary registry enrolls pregnant women who have been exposed to ribavirin during pregnancy or during the six months prior to conception either directly, by taking ribavirin, or indirectly through sexual contact with a man taking ribavirin. Women are followed until delivery; live born infants are followed for one year. The Registry aims to enroll 131 live births following direct (maternal) exposure to ribavirin and 131 live births following indirect (male) exposures. After more than five years of operation, the Registry has enrolled 49 live births with direct exposure and 69 live births following indirect exposure. Six outcomes with birth defects have been reported. All were among live born infants: torticollis (2), hypospadias (1), polydactyly and a neonatal tooth (1), glucose-6-phosphate dehydrogenase deficiency (1), ventricular septal defect and cyst of 4th ventricle of the brain (1). Three received direct exposures ([6.1% (95% CI: 1.2, 16.9)], three were exposed indirectly [4.3% (95% CI: 0.9, 12.2)]. Although current enrollment is far short of the required sample size, preliminary findings have not detected a signal indicating human teratogenicity for ribavirin. However, findings must be interpreted with caution concerning direct or indirect prenatal ribavirin exposures.


RT-PCR detection of the expression of the polymerase gene of a novel reptilian herpesvirus in tumor tissues of green turtles with fibropapilloma.
An alpha-herpesvirus has recently been associated with green turtle fibropapilloma (FP). To further understand the etiological role of this newfound green turtle herpesvirus (GTHV) in the pathogenesis of FP, expression of GTHV polymerase ( pol) gene was determined in tumors and normal-appearing nontumor tissues and organs from five green turtles suffering multiple fibropapillomas, using reverse transcription-polymerase chain reaction (RT-PCR). Amplification of RNA prepared from tumor tissues evidenced the substantial expression of GTHV DNA pol gene in all specimens tested (15/15). However, GTHV pol gene expression in normal-appearing tissues and organs of affected animals was limited (4/45), and GTHV mRNA was detected only in periorbital tissue (1/2), gall bladder (2/5) and lung (1/5) by nested RT-PCR. By contrast, RT-PCR evaluation of RNA isolated from non-tumored turtles revealed undetectable expression of this herpesvirus gene. cDNA sequence analysis revealed that GTHV gene sequences were identical in different tumors. Our data represent the first evidence of the replication of this putative turtle herpesvirus in affected green turtles and fibropapilloma tissues are always active sites of GTHV mRNA synthesis. These findings extend and substantiate the pathogenic association of GTHV with FP.


Sleep ability mediates individual differences in the vulnerability to sleep loss: evidence from a PER3 polymorphism.
Sleep deprivation is highly prevalent in our 24/7 society with harmful consequences on daytime functioning on the individual level. Genetically determined, trait-like vulnerability contributes to prominent inter-individual variability in the behavioral responses to sleep loss and adverse circadian phase. We aimed at investigating the effects of differential sleep pressure levels (high vs low) on the circadian modulation of neurobehavioral performance, sleepiness correlates, and nap sleep in individuals genotyped for a polymorphism in the clock gene PERIOD3. Fourteen homozygous long (PER3(5/5)) and 15 homozygous short (PER3(4/4)) allele carriers underwent both a 40-h sleep deprivation and multiple nap protocol under controlled laboratory conditions. We compared genotypes regarding subjective and ocular correlates of sleepiness, unintentional sleep episodes as well as psychomotor vigilance during both protocols. Nap sleep was monitored by polysomnography and visually scored according to standard criteria. The detrimental effects of high sleep pressure on sleepiness correlates and psychomotor vigilance were more pronounced in PER3(5/5) than PER3(4/4) carriers. Under low sleep pressure, both groups showed similar circadian time courses. Concomitantly, nap sleep efficiency and subjective sleep quality across all naps tended to be higher in the more vulnerable PER3(5/5) carriers. In addition, PER3-dependent sleep-loss-related attentional lapses were mediated by sleep efficiency across the circadian cycle. Our data corroborate a greater detrimental impact of sleep deprivation in PER3(5/5) compared to PER3(4/4) carriers. They further suggest that the group with greater attentional performance impairment due to sleep deprivation (PER3(5/5) carriers) is superior at initiating sleep over the 24-h cycle. This higher sleep ability may mirror a faster sleep pressure build-up between the multiple sleep opportunities and thus a greater flexibility in sleep initiation. Finally, our data show that this higher nap sleep efficiency is positively related to attentional failures under sleep loss conditions and might thus be used as a marker for inter-individual vulnerability to elevated sleep pressure.


Omega-3 fatty acids reduce obesity-induced tumor progression independent of GPR120 in a mouse model of postmenopausal breast cancer.
Obesity and inflammation are both risk factors for a variety of cancers, including breast cancer in postmenopausal women. Intake of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) decreases the risk of breast cancer, and also reduces obesity-associated inflammation and insulin resistance, but whether the two effects are related is currently unknown. We tested this hypothesis in a postmenopausal breast cancer model using ovariectomized, immune-competent female mice orthotopically injected with Py230 mammary tumor cells. Obesity, whether triggered genetically or by high-fat diet (HFD) feeding, increased inflammation in the mammary fat pad and promoted mammary tumorigenesis. The presence of tumor cells in the mammary fat pad further enhanced the local inflammatory milieu. Tumor necrosis factor-alpha (TNF-α) was the most highly upregulated cytokine in the obese mammary fat pad, and we observed that TNF-α dose-dependently stimulated Py230 cell growth in vitro. An ω-3 PUFA-enriched HFD (referred to as fish oil diet, FOD) reduced inflammation in the obese mammary fat pad in the absence of tumor cells and inhibited Py230 tumor growth in vivo. Although some anti-inflammatory effects of ω-3 PUFAs were previously shown to be mediated by the G-protein-coupled receptor 120 (GPR120), the FOD reduced Py230 tumor burden in GPR120-deficient mice to a similar degree as observed in wild-type mice, indicating that the effect of FOD to reduce tumor growth does not require GPR120 in the host mouse. Instead, in vitro studies demonstrated that ω-3 PUFAs act directly on tumor cells to activate c-Jun N-terminal kinase, inhibit proliferation and induce apoptosis. Our results show that obesity promotes mammary tumor progression in this model of postmenopausal breast cancer and that ω-3 PUFAs, independent of GPR120, inhibit mammary tumor progression in obese mice.


Biohybrid robot powered by an antagonistic pair of skeletal muscle tissues.
Biohybrid robots are attracting attention as promising candidates to enhance robot applicability to studies on biological designs and in vitro construction of biological dynamic systems. Rapid progress in biohybrid robots with skeletal muscle tissues formed on a flexible substrate has enabled various types of locomotion powered by muscle tissue. However, it has been difficult to achieve high levels of both large and long-term actuations of the skeletal muscle tissues because of their spontaneous shrinkage through the course of the tissue culture. To overcome this limitation, we adapted the concept of biological systems and developed a biohybrid robot actuated by an antagonistic pair of skeletal muscle tissues. Our robot achieved large actuation (~90° of rotation of a joint) by selective contractions of the skeletal muscle tissues and a long lifetime (~1 week) by balancing tensions of the antagonistic tissues to prevent the spontaneous shrinkage. As a demonstration, we showed that our biohybrid robots allowed a pick-and-place manipulation of objects. This research may provide a platform to exceed the limitations of design in conventional biohybrid robots and replicate various lifelike movements.


Inter-rater reliability of the Chedoke Arm and Hand Activity Inventory.
The Chedoke Arm and Hand Activity Inventory (CAHAI) is an assessment of upper limb function designed for use in the stroke population. The CAHAI has strong reliability and validity in this population; however, it is unknown whether this measure can be used with other clinical populations such as acquired brain injury (ABI). The purpose of this study was to estimate the inter-rater reliability of the CAHAI when used with persons with ABI. The research design was an observational parameter estimation study. The administration of the CAHAI was videotaped for 6 persons with ABI. To estimate inter-rater reliability each video was assessed independently by 6 clinicians yielding a total of 36 assessments. A Latin square design was used to balance the order raters evaluated the videos. Shrout and Fleiss Type 2,1 intra class correlation coefficients (ICC) and standard error of measurement (SEM) were calculated to estimate inter-rater reliability of the CAHAI. Inter-rater reliability was high ICC = 0.96 (95% CL: 0.88, 0.99) and the SEM was 3.35 (95% CL: 2.63, 4.63) CAHAI points. These results suggest that the CAHAI, although designed for use in the stroke population, can be used reliably in the ABI population.


Community health workers improve contact tracing among immigrants with tuberculosis in Barcelona.
The important increase in immigration during recent years has changed the epidemiology and control strategies for tuberculosis (TB) in many places. This study evaluates the effectiveness of intervention with community health workers (CHW) to improve contact tracing among immigrants. The study included all TB cases detected by the Barcelona TB Program from 2000 to 2005 and compared a period without CHW intervention (2000-2002) to a period with CHW intervention (2003-2005). The influence on contact tracing of sex, age, hospital of diagnosis, district of residence, birthplace, HIV, homeless and CHW intervention was analysed by logistic regression. Odds ratio (OR) and 95% confidence intervals (CI) were calculated. 960 foreign born TB cases were detected, 388 in the intervention period. Contact tracing was performed on 65,7% of 201 smear-positive cases during the pre-intervention period compared to 81.6% of 152 smear-positive TB cases during the intervention period (p < 0.001). Risk factors associated with incomplete contact tracing of smear-positive index cases included being diagnosed in two hospitals without contact tracing TB unit (OR = 3.5; CI:1.4-8.9) and (OR = 4.6; CI:1.6-13.5) respectively, birth place in India-Pakistan (OR = 4.4; CI:1.9-10.3) or North Africa (OR = 4.3; CI:1.8-10.5), having an unknown residence (OR = 5.4; CI:1.6-18.0), being HIV-infected (OR = 6.1; CI:2.5-14.8) or homeless (OR = 3.3; CI:1.3-8.2), and the absence of CHW intervention (OR = 2.4; CI:1.3-4.3). The effectiveness of contact tracing for TB control in areas with high immigration can be improved by incorporating CHWs who act as translators, cultural mediators and facilitators who accompany cases and contacts through treatment and follow-up.


Comparative analysis of element concentrations and translocation in three wetland congener plants: Typha domingensis, Typha latifolia and Typha angustifolia.
This study analyzed the concentrations and distributions of Al, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb and Zn in three different cattail species growing spontaneously in a natural wetland subject to municipal wastewater and metal contamination. The cattail species included Typha domingensis, T. latifolia and T. angustifolia. Results showed that all Typha species have similar element concentrations in roots, rhizomes and leaves, and similar element mobility from sediments to roots and from roots to leaves. This study corroborated three patterns of Typha species growing in metal contaminated environments: high tolerance to toxic conditions, bulk element concentrations in roots, and restricted element translocation from roots to leaves. This study showed that three different Typha species respond similarly to metal inputs under the same polluting field conditions. Given their similar metal content and similar biomass size, our results suggest that T. domingensis, T. latifolia and T. angustifolia may have comparable capacity of phytoremediation. High element uptake and large biomass make Typha species some of the best species for phytoremediation of metal contaminated environments.


Posterior correction and fusion surgery using pedicle-screw constructs for Lenke type 5C adolescent idiopathic scoliosis: a preliminary report.
A retrospective case series. To assess whether a short fusion strategy is applicable when treating adolescent idiopathic scoliosis with Lenke type 5C curve by posterior correction and fusion surgery using pedicle-screw constructs. Previous studies have discussed the selection of the lower instrumented vertebra to best preserve motion segments and obtain coronal balance. However, reports evaluating the selection of the upper instrumented vertebra when treating Lenke type 5C curves are not available. We evaluated 29 patients who were treated surgically for adolescent idiopathic scoliosis with Lenke type 5C curve (mean age, 16.8 ± 4.7 yr; range, 10-29 yr). The mean follow-up period was 28.0 ± 6.3 months (range, 24-48 mo). We compared radiographical parameters and clinical outcomes between patients with an upper instrumented vertebra at the end vertebra (EV) (n = 10) and those treated by short fusion (S group), with a upper instrumented vertebra 1-level caudal to the EV (n = 19 patients). In the EV group, a preoperative mean Cobb angle of 50°± 15° was corrected to 8°± 7°, which was maintained at the final follow-up (7°± 1°). In the S group, a mean preoperative Cobb angle of 47°± 4° was corrected to 8°± 5°, but this increased significantly to 12°± 7° at final follow-up (P = 0.033). The mean correction rate at final follow-up was significantly lower in the S group (72%) than in the EV group (86%) (P = 0.027). Coronal and sagittal balance, thoracic kyphosis, lumbar lordosis, L4 tilt, and clinical outcomes evaluated by Scoliosis Research Society patient questionnaire-22 were equivalent between the 2 groups. Scoliosis Research Society patient questionnaire-22 scores and radiographical parameters other than the correction rate were equivalent between the 2 groups. A short fusion strategy, in which the upper instrumented vertebra is 1-level caudal to the upper EV, is applicable to posterior correction and fusion surgery with pedicle-screw constructs for Lenke type 5C curves.


A white paper on nematode comparative genomics.
In response to the new opportunities for genome sequencing and comparative genomics, the Society of Nematology (SON) formed a committee to develop a white paper in support of the broad scientific needs associated with this phylum and interests of SON members. Although genome sequencing is expensive, the data generated are unique in biological systems in that genomes have the potential to be complete (every base of the genome can be accounted for), accurate (the data are digital and not subject to stochastic variation), and permanent (once obtained, the genome of a species does not need to be experimentally re-sampled). The availability of complete, accurate, and permanent genome sequences from diverse nematode species will underpin future studies into the biology and evolution of this phylum and the ecological associations (particularly parasitic) nematodes have with other organisms. We anticipate that upwards of 100 nematode genomes will be solved to varying levels of completion in the coming decade and suggest biological and practical considerations to guide the selection of the most informative taxa for sequencing.


Carotid Webs and Recurrent Ischemic Strokes in the Era of CT Angiography.
Carotid webs may cause recurrent ischemic stroke. We describe the prevalence, demographics, clinical presentation, imaging features, histopathology, and stroke risk associated with this under-recognized lesion. A carotid web was defined on CTA as a thin intraluminal filling defect along the posterior wall of the carotid bulb just beyond the carotid bifurcation on oblique sagittal section CTA that was seen as a septum on axial CTA. Using a prospective case series from April 2013 to April 2014, we describe the demographics, spectrum of imaging features on CTA, and histopathology of these carotid webs. From a retrospective analysis of patients at our center from May 2012 to April 2013 who had a baseline head and neck CTA followed by a brain MR imaging within 1-2 days of the CTA, we determine the period prevalence of carotid webs and the prevalence of ipsilateral stroke on imaging. In the prospective series, the mean age was 50 years (range, 41-55 years); 5/7 patients were women. Recurrent stroke was seen in 5/7 (71.4%) patients with the carotid web; time to recurrence ranged from 1 to 97 months. Histopathology suggested a high probability of fibromuscular dysplasia. In the retrospective series, carotid webs were seen in 7/576 patients for a hospital-based-period prevalence of 1.2% (95% CI, 0.4%-2.5%). Two of these 7 patients had acute stroke in the vascular territory of the carotid web. A carotid web may contribute to recurrent ischemic stroke in patients with no other determined stroke mechanism. Intimal variant fibromuscular dysplasia is the pathologic diagnosis in most cases. The prevalence of carotid web is low, while the optimal management strategy remains unknown.


Genomic analysis of C-type lectins.
Many biological effects of complex carbohydrates are mediated by lectins that contain discrete carbohydrate-recognition domains. At least seven structurally distinct families of carbohydrate-recognition domains are found in lectins that are involved in intracellular trafficking, cell adhesion, cell-cell signalling, glycoprotein turnover and innate immunity. Genome-wide analysis of potential carbohydrate-binding domains is now possible. Two classes of intracellular lectins involved in glycoprotein trafficking are present in yeast, model invertebrates and vertebrates, and two other classes are present in vertebrates only. At the cell surface, calcium-dependent (C-type) lectins and galectins are found in model invertebrates and vertebrates, but not in yeast; immunoglobulin superfamily (I-type) lectins are only found in vertebrates. The evolutionary appearance of different classes of sugar-binding protein modules parallels a development towards more complex oligosaccharides that provide increased opportunities for specific recognition phenomena. An overall picture of the lectins present in humans can now be proposed. Based on our knowledge of the structures of several of the C-type carbohydrate-recognition domains, it is possible to suggest ligand-binding activity that may be associated with novel C-type lectin-like domains identified in a systematic screen of the human genome. Further analysis of the sequences of proteins containing these domains can be used as a basis for proposing potential biological functions.


Effects of hyposmotic shock on ion fluxes in isolated trout hepatocytes.
Isolated trout hepatocytes exposed to hypotonic Hank's medium (isotonicity x 0.70) swelled to 1.17 times the control volume after 3 min; by 15 min the cell volume had returned to normal. The ouabain-insensitive K+ uptake increased, indicating an immediate rise in K+ membrane permeability. As indicated by analysis of cellular contents, the regulatory volume decrease (RVD) was ensured by a release of intracellular K+. Na+ was not implicated in this mechanism. This potassium permeability induced by hypotonic shock was transient (maximum at 6 min), insensitive to blocking agents of voltage- and Ca2+-dependent K+ channels, and chloride-dependent. This result, together with a time-course of Cl- uptake similar to that of K+, suggests a K+/Cl- cotransport mechanism. This cotransport is inhibited by high furosemide concentrations (10(-3) mol l-1) but not by bumetanide (10(-4) mol l-1) or piretanide (10(-4) mol l-1).


(Un)awareness of unilateral spatial neglect: a quantitative evaluation of performance in visuo-spatial tasks.
Right-brain-damaged patients with unilateral spatial neglect are usually unaware (anosognosic) about their spatial deficits. However, in the scientific literature there is a lack of systematic and quantitative evaluation of this kind of unawareness, despite the negative impact of anosognosia on rehabilitation programs. This study investigated anosognosia for neglect-related impairments at different clinical tasks, by means of a quantitative assessment. Patients were tested in two different conditions (before and after execution of each task), in order to evaluate changes in the level of awareness of neglect-related behaviours triggered by task execution. Twenty-nine right-brain-damaged patients (17 with left spatial neglect) and 27 neurologically unimpaired controls entered the study. Anosognosia for spatial deficits is not pervasive, with different tasks evoking different degrees of awareness about neglect symptoms. Indeed, patients showed a largely preserved awareness about their performance in complex visuo-motor spatial and reading tasks; conversely, they were impaired in evaluating their spatial difficulties in line bisection and drawing from memory, showing over-estimation of their performance. The selectivity of the patients' unawareness of specific manifestations of spatial neglect is further supported by their preserved awareness of performance at a linguistic task, and by the absence of anosognosia for hemiplegia. This evidence indicates that discrete processes are involved in the aware monitoring of cognitive and motor performance, which can be selectively compromised by brain damage. Awareness of spatial difficulties is supported by a number of distinct components, and influenced by the specific skills required to perform a given task.


Efficient interfacial charge transfer through plasmon sensitized Ag@Bi2O3 hierarchical photoanodes for photoelectrocatalytic degradation of chlorinated phenols.
The present work demonstrates an extremely proficient and robust study of efficient interfacial charge transfer through plasmonic Ag decorated Bi2O3 hierarchical photoanodes for the photoelectrochemical treatment of chlorinated phenols. Unique 2D flake-like Bi2O3 hierarchical nanostructures were grown onto a fluorine-doped tin oxide (FTO) substrate by a simple chemical bath deposition method using triethanolamine as complexing agent. The formation of Bi2O3 on FTO was governed by the decomposition of a nucleated bismuth-hydroxyl complex (Bi2O1-x(OH)x) and modification to the electrode was carried out by the deposition of Ag via a chemical reduction method using hydrazine hydrate. Both the fabricated electrodes were well characterized for their photo- and electro-optical properties. Efficient charge separation was observed due to the surface plasmon resonance phenomenon of silver nanoparticles with the favorable intrinsic properties of Bi2O3 under application of a small electric bias of 1 V preventing the recombination of charge carriers and thereby increasing the rate of photoelectrocatalytic degradation of the chlorinated phenols. PEC degradation using the Ag@Bi2O3 photoelectrode followed the trend 4-CP < 2,4-DCP < 2,4,6-TCP < P-CP due to efficient attack at the chlorinated positions by reactive oxygen species with increasing chlorine substitution and also due to the absence of an expected chain reaction of the generated chlorine radicals (Cl˙) during the PEC reaction. The PEC activity of Ag@Bi2O3 was 1.5 times higher than a Bi2O3 nanoflake electrode for 4-CP over 2 h. The fabricated Ag@Bi2O3 proved to be an efficient photoelectrode with synergistic solar-induced photoactivity. A detailed mechanistic study in the presence of scavengers suggests degradation by produced hydroxyl radical species. Thus, physical insights into the degradation of chlorinated phenols were obtained.


Comparison of trends in habitat and resource selection by the Spanish Festoon, Zerynthia rumina, and the whole butterfly community in a semiarid Mediterranean ecosystem.
Butterfly community and single species based approaches were taken to establish conservation priorities within a nature reserve in Central Spain. In this study, patch type (sclerophyllous, halophilous, or disturbed), potential herbaceous nectar availability, potential woody plant nectar availability, total nectar availability, and two approximations to plant diversity (herbaceous and woody plant diversity) were evaluated as variables that account for adult butterfly density. Butterfly communities in the reserve, which consist mostly of generalist species, were denser in relatively wet areas dominated by halophilous vegetation. Diversity did not significantly vary between ecologically different transects. Total nectar availability correlated with higher butterfly densities within both undisturbed and disturbed areas, which could be primarily explained by the lack of water typical of semiarid Mediterranean climates, where fresh, nectariferous vegetation is scarce. Woody plants were also found to be important sources of nectar and shelter. In the dryer sclerophyllous sites, adult butterfly density was best explained by herbaceous plant diversity, suggesting better quality of available resources. The endangered specialist Zerynthia rumina (L.) (Lepidoptera: Papilionidae) was only present at the sclerophyllous sites. Its density was very low in all sampled transects, excluding one relatively isolated transect with high larval hostplant density. In contrast to the community-based approach, density of Z. rumina adults is better explained by the density of its larval hostplant than by nectar availability, a trend previously described for other sedentary species. Management strategies for protecting insect-rich areas should consider the specific ecological requirements of endangered species.


Relationships between Mucosal Antibodies, Non-Typeable Haemophilus influenzae (NTHi) Infection and Airway Inflammation in COPD.
Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD. Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls. BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls. NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve-29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation. When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM. We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway. Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients. This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi.


Paradoxical effect of diphenyleneiodonium in inducing DNA damage and apoptosis.
Diphenyleneiodonium (DPI) is often used as a molecular tool in unravelling redox-sensitive cellular events involving NADPH oxidase. However, to better understand unexpected actions of DPI, it was ascertained if DPI affects cellular DNA. DPI induced single-strand breaks in DNA of HCT-116 cells, although this only slightly increased GADD153 expression. Nevertheless, after sustaining DNA damage, the DPI-treated cells subsequently had features characteristic of apoptosis, such as translocated membrane phospholipid and nuclei containing condensed chromatin. Paradoxically, DPI attenuated the DNA damage and overall ROS production caused by sodium deoxycholate (DOC), although DPI did not inhibit DOC-induced generation of mitochondrial [image omitted] . Furthermore, DPI prevented the occurrence of apoptosis caused by DOC. However, other known chemical inhibitors of NADPH oxidase did not produce the same results as DPI in negating the effects of DOC. Collectively, these disparate findings suggest that DPI can act not in accord with conventional wisdom depending on the experimental conditions.


Loss of density-dependence and incomplete control by dominant breeders in a territorial species with density outbreaks.
A territory as a prerequisite for breeding limits the maximum number of breeders in a given area, and thus lowers the proportion of breeders if population size increases. However, some territorially breeding animals can have dramatic density fluctuations and little is known about the change from density-dependent processes to density-independence of breeding during a population increase or an outbreak. We suggest that territoriality, breeding suppression and its break-down can be understood with an incomplete-control model, developed for social breeders and social suppression. We studied density dependence in an arvicoline species, the bank vole, known as a territorial breeder with cyclic and non-cyclic density fluctuations and periodically high densities in different parts of its range. Our long-term data base from 38 experimental populations in large enclosures in boreal grassland confirms that breeding rates are density-regulated at moderate densities, probably by social suppression of subordinate potential breeders. We conducted an experiment, were we doubled and tripled this moderate density under otherwise the same conditions and measured space use, mortality, reproduction and faecal stress hormone levels (FGM) of adult females. We found that mortality did not differ among the densities, but the regulation of the breeding rate broke down: at double and triple densities all females were breeding, while at the low density the breeding rate was regulated as observed before. Spatial overlap among females increased with density, while a minimum territory size was maintained. Mean stress hormone levels were higher in double and triple densities than at moderate density. At low and moderate densities, breeding suppression by the dominant breeders, But above a density-threshold (similar to a competition point), the dominance of breeders could not be sustained (incomplete control). In our experiment, this point was reached after territories could not shrink any further, while the number of intruders continued to increase with increasing density. Probably suppression becomes too costly for the dominants, and increasing number of other breeders reduces the effectiveness of threats. In wild populations, crossing this threshold would allow for a rapid density increase or population outbreaks, enabling territorial species to escape density-dependency.


Drug ReposER: a web server for predicting similar amino acid arrangements to known drug binding interfaces for potential drug repositioning.
A common drug repositioning strategy is the re-application of an existing drug to address alternative targets. A crucial aspect to enable such repurposing is that the drug's binding site on the original target is similar to that on the alternative target. Based on the assumption that proteins with similar binding sites may bind to similar drugs, the 3D substructure similarity data can be used to identify similar sites in other proteins that are not known targets. The Drug ReposER (DRug REPOSitioning Exploration Resource) web server is designed to identify potential targets for drug repurposing based on sub-structural similarity to the binding interfaces of known drug binding sites. The application has pre-computed amino acid arrangements from protein structures in the Protein Data Bank that are similar to the 3D arrangements of known drug binding sites thus allowing users to explore them as alternative targets. Users can annotate new structures for sites that are similarly arranged to the residues found in known drug binding interfaces. The search results are presented as mappings of matched sidechain superpositions. The results of the searches can be visualized using an integrated NGL viewer. The Drug ReposER server has no access restrictions and is available at http://mfrlab.org/drugreposer/.


Antimicrobial activity, toxicity and accumulated hard-tissue debris (AHTD) removal efficacy of several chelating agents.
To evaluate the antimicrobial, toxicity and cleaning effectiveness of ethylenediaminetetraacetic acid (EDTA) and maleic acid (MA) alone and combined with cetrimide (CTR). Cytotoxic and genotoxic effects were assessed on Chinese hamster cells V79 using the MTT, clonogenic and micronucleus assays, respectively. The bacterial inhibitory and bactericidal concentrations (MIC and MBC, respectively) were determined on a strain of Enterococcus faecalis. Antimicrobial tests were performed on a biofilm model after treatment with the chelating agents by using a biofilm eradication concentration (MBEC) and confocal laser scanning microscope (CLSM) assays. Quantification of cell biomass and percentage of live and dead cells in the biomass were assessed for each group. The percentage reduction of accumulated hard-tissue debris (AHTD) after root canal preparation and final irrigation protocols was evaluated by micro-CT. Statistical tests of one-way analysis of variance (anova), Bonferroni test, Kruskal-Wallis test, Dunn's multiple comparison test and Wilcoxon matched-pairs signed-rank tests were used. Cetrimide alone as well as in combination with EDTA and MA at dilutions of 1/10 and 1/100 was significantly more toxic as compared to untreated controls (P < 0.001). All tested mixtures were nontoxic at a dilution of 1/1000. EDTA retained a weak inhibitory and bactericidal effect against planktonic cells, whilst MA inhibited cells growth and killed 99.9% of the cells when diluted. CTR revealed the most prominent effect, being inhibitory and bactericidal, also when diluted. Cetrimide alone or combined with EDTA was able to remove, respectively, 40% (P < 0.01) and 60% (P < 0.001) of the entire biomass after 1 min. Conversely, MA alone and in combination with CTR did not have a significant effect on biomass reduction. After final irrigation, the AHTD volume was significantly decreased in all groups (P < 0.05). EDTA + CTR and MA + CTR were associated with a significant reduction in the percentage of AHTD on the entire root canal compared to the same solutions without surfactant. 7% MA was less cytotoxic in comparison with 17% EDTA. The addition of cetrimide to EDTA and MA removed accumulated hard-tissue debris effectively from the canal walls and increased their antimicrobial activity when compared to the same solutions without detergents.


Identification of protein C in sera of the frogs, Rana nigromaculata and Rana brevipoda.
When sera from the frogs, Rana (R.) nigromaculata and Rana (R.) brevipoda, were run on starch-gel electrophoresis (SGE), several bands were seen in an electrophoretic pattern of proteins. This pattern on SGE appeared the same at stages XIV, XV and XXI, and in the adult frog, R. niguromaculata. However, the pattern at stage X was different. A protein, designated "protein C", did not appear clearly at this stage, but afterwards. This protein was the second richest among serum proteins of mature frogs. Protein C (Mr = 180 kD, when estimated by SDS-PAGE) was obtained after SGE and then subjected to an NH2-terminal sequence analysis. Sequences of protein C from R. nigromaculata and R. brevipoda were NH2-TDPMYVIFIPQTLXE for the first 15 amino acids and NH2-TDPHYVIFKG for the first 10 amino acids, respectively. Homology search of GenBank sequences indicated no significant similarity with any known proteins. The results suggest that protein C is a new protein, and that it may play an important role(s) in the serum after stage X in these species.


[Nine cases of sporadic acute hepatitis E in Korea].
Hepatitis E virus is an enterically transmitted virus that causes endemic cases of acute hepatitis in many countries in Africa, and Southeast and Central Asia. Sporadic cases of acute hepatitis E also have been reported in developed countries. In non-endemic areas, most of the sporadic cases of hepatitis E are introduced from the endemic areas. Until now, only three cases of acute hepatitis E have been reported in Korea. Recently, we experienced nine cases of acute hepatitis, in which serologic studies showed positive of IgM anti-HEV. We report these as cases of acute hepatitis E. These cases suggest that HEV infection occurs sporadically in Korea and should be considered as a cause of cryptogenic acute hepatitis.


Managing conflicting ethical concerns in modern small animal practice-A comparative study of veterinarian's decision ethics in Austria, Denmark and the UK.
Small animal veterinarians frequently have to manage conflicting interests. Beside the key consideration of the patient's interests, small animal veterinarians are often challenged to consider not only client's emotional needs, but also their own personal aspirations to provide quality patient care and to make a good living as a professional. Further, veterinarians have an interest in continuous professional development and the use of the newest treatments, which may influence their decision-making process. Based on published work, we hypothesize the existence of four decision ethics orientations that veterinarians can use to manage potentially conflicting concerns. These are: the patient-focused, the client-empathetic, the client-devolved and the development-oriented decision ethics orientations. We surveyed small animal veterinarians in Austria, Denmark, and the UK using a questionnaire (N = 648), and successfully identified the four decision ethics orientations in all three countries. The patient-focused and client-empathetic decision ethics orientations are salient in all countries, whereas Danish and UK veterinarians are slightly more client-empathetic and client-devolved compared to their Austrian colleagues. Across countries our findings show that experienced and older veterinarians tend to be more client-empathetic. Younger and less experienced professionals are more development-oriented compared to their older and more experienced colleagues. In contrast to other studies investigating ethical issues in small animal practice, we found no evidence that gender plays a decisive role in the tendency towards any decision ethics orientation. We also show that veterinarians with a higher client-empathetic orientation and development-orientation more often discuss the possibility of health insurance with clients who do not have it. The present study provides a first empirical insight into how veterinarians manage challenging expectations and ethical concerns as part of decision making in modern small animal practice.


Poly(A) signals and transcriptional pause sites combine to prevent interference between RNA polymerase II promoters.
Transcriptional termination by RNA polymerase II at the 3' end of genes encoding poly(A)+ mRNAs is thought to require two distinct cis-active elements: a functional poly(A) signal and a downstream transcriptional pause site. An important requirement for efficient termination is to prevent transcriptional interference of downstream-located promoters. We have therefore investigated whether these two elements, individually or in combination, can prevent transcriptional interference of RNA polymerase II-activated promoters. For this purpose, we constructed an expression plasmid containing two tandem retroviral long terminal repeats (LTRs) derived from HIV-1. When transfected into HeLa cells, this construct resulted in transcriptional interference of the LTR promoters. Using this assay, we were able to show that a single poly(A) signal was able to protect an otherwise occluded promoter. This effect depended on the RNA-processing strength of the poly(A) signal. Furthermore, transcriptional pause sites provided adequate protection against promoter occlusion even when tested alone. Finally, a combined element consisting of a poly(A) signal followed by a pause site was more efficient in promoter protection than either element on its own. These results indicate that an interference-blocking element can take various forms: a poly(A) signal, a transcriptional pause site or a combination of both.


Antioxidant and hypolipidemic activity of Kumbhajatu in hypercholesterolemic rats.
To study the efficacy of Kumbhajatu in reducing the cholesterol levels and as an antioxidant in hypercholesterolemic rats. Hypercholesterolemia was induced in normal rats by including 2% w/w cholesterol, 1% w/w sodium cholate and 2.5% w/w coconut oil in the normal diet. Powdered form of Kumbhajatu was administered as feed supplement at 250 and 500 mg/kg dose levels to the hypercholesterolemic rats. Plasma lipid profile, hepatic superoxide dismutase (SOD) activity, catalase activity, reduced glutathione and extent of lipid peroxidation in the form of malondialdehyde were estimated using standard methods. Feed supplementation with 250 and 500 mg/kg of Kumbhajatu resulted in a significant decline in plasma lipid profiles. The feed supplementation increased the concentration of catalase, SOD, glutathione and HDL-c significantly in both the experimental groups (250 and 500 mg/kg). On the other hand, the concentration of malondialdehyde, cholesterol, triglycerides, LDL-c and VLDL in these groups (250 and 500 mg/kg) were decreased significantly. The present study demonstrates that addition of Kumbhajatu powder at 250 and 500 mg/kg level as a feed supplement reduces the plasma lipid levels and also decreases lipid peroxidation.


Evaluation of factors influencing liver function test in on-pump coronary artery bypass graft surgery.
Liver dysfunction during on-pump coronary artery bypass graft surgery (CABG) is a rare complication but is associated with significant morbidity and mortality. The ability to identify high-risk patients may be helpful in planning appropriate management strategies. We aimed to evaluate the factors influencing liver function tests during on-pump CABG. In 146 patients scheduled for on-pump CABG, the liver function test was done preoperatively and on the first postoperative day. Some preoperative and intraoperative risk factors were checked and then the postoperative liver function tests were compared with the preoperative ones. Probable relationships between these changes and the preoperative and intraoperative risk factors were studied. A medical history of diabetes had a significant relationship with the changes in direct bilirubin. Preoperative central venous pressure had a significant relationship with the changes in aspartate aminotransferase and alanine aminotransferase. Use of intra-aortic balloon pump and duration of aortic cross-clamp were significantly related to the changes in the liver function tests except for alanine aminotransferase and alkaline phosphatase. It seems that the techniques for the reduction of cardiopulmonary bypass and aortic cross-clamp duration may be useful to protect liver function. We recommend that a larger population of patients be studied to confirm these findings.


Pharmacy care perspectives on problems with HIV antiretroviral therapy in Sweden.
This study has three main objectives (1) to identify the major problems or difficulties pharmacy staff in Sweden experience regarding pharmacy care of patients receiving antiretroviral therapy, (2) to identify the perceptions of pharmacy staff regarding what are patient-related concerns with antiretroviral therapy and (3) to compare the extent to which pharmacy staff awareness matches patient perceptions regarding what are the major problems or difficulties associated with antiretroviral therapy. A problem detection study (PDS) containing two questionnaires was conducted: one to be completed by pharmacy staff and another to be completed by both pharmacy staff and patients. In the latter survey, staff were asked about what they thought that patients would have responded. Staff and patient responses were then matched and compared with one another. The pharmacy staff expressed their need for continuous education so as to assist the patients with their complex regimens. The staff were aware that patients were worried about therapy failure and viral resistance, medication-related problems and negative attitudes from the public. The staff however were less aware of the extent to which patients worried about not having their HIV infection under control. The staff also valued written patient information to a much higher extent than the patients. The pharmacy staff' awareness of the major problems HIV patients are experiencing seems incomplete and may lead to lack of concordance between the patients and pharmacy staff. This in turn may lead to non-adherence and poor therapy outcomes. Pharmacy staff should be encouraged to improve and systematically assess patient issues regarding antiretroviral therapy. Through assessing patient needs and concerns, the pharmacists can better identify patient needs and thus better tailor their educational and behavioural interventions to improve therapy outcomes.


Management Strategies and Outcomes for VHL-related Craniospinal Hemangioblastomas.
Hemangioblastomas are rare and benign tumors accounting for less than 2% of all central nervous system (CNS) tumors. The vast majority of hemangioblastomas occur sporadically, whereas a small number of cases, especially in younger patients, are associated with Von Hippel-Lindau (VHL) syndrome. It is thought that loss of tumor suppressor function of the VHL gene results in stabilization of hypoxia-inducible factor alpha with downstream activation of cellular proliferative and angiogenic genes that promote tumorigenesis. VHL-related hemangioblastomas predominantly occur in the cerebellum and spine. Lesions are often diagnosed on contrast-enhanced craniospinal MRIs, and the diagnosis of VHL occurs through assessment for germline VHL mutations. Surgical resection remains the primary treatment modality for symptomatic or worrisome lesions, with excellent local control rates and neurological outcomes. Stereotactic radiotherapy can be employed in patients who are deemed high risk for surgery, have multiple lesions, or have non-resectable lesions. Given the tendency for development of either new or multiple lesions, close radiographic surveillance is often recommended for asymptomatic lesions.


International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. IV. Comparability of apolipoprotein B values by use of International Reference Material.
We performed temporal and thermal stability studies on SP3-07, a liquid-stabilized reference material for apolipoprotein (apo) B, selected during the previous phase of the International Federation of Clinical Chemistry project on standardization of apolipoprotein measurements. Results indicate that SP3-07 stored at -70 degrees C has the long-term stability required for a reference material. We assigned an accuracy-based apo B value of 1.22 g/L to SP3-07, using a nephelometric method that was calibrated with freshly isolated low-density lipoprotein for which the apo B mass value was determined by a standardized sodium dodecyl sulfate-Lowry procedure. Using a common protocol, the study participants transferred the assigned mass value from SP3-07 to the individual calibrators of the analytical systems and measured the apo B concentration of 20 fresh-frozen samples obtained from individual donors and covering a clinically relevant range of apo B values. The among-laboratory CV on these samples, analyzed by 25 analytical systems, ranged from 3.1% to 6.7%. These results demonstrate the lack of matrix effects of SP3-07 and its ability to provide accurate and comparable apo B values in a variety of immunochemical methods. On the basis of the outcome of these studies, the World Health Organization has endorsed SP3-07 as the International Reference Material for Apolipoprotein B.


EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay.
EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization.


Regulation of cell surface GABA(B) receptors: contribution to synaptic plasticity in neurological diseases.
γ-Amino butyric acid (GABA(B)) receptors are heterodimeric G protein-coupled receptors expressed throughout the central nervous system in virtually all neurons. They control the excitability of neurons via activation of different downstream effector systems in pre- and postsynaptic neurons and as such regulate all major brain functions including synaptic plasticity, neuronal network activity, and neuronal development. Accordingly, GABA(B) receptors have been implicated in a variety of neurological disorders and thus are regarded as promising drug targets. A key factor determining the extent of GABA(B) receptor-mediated inhibition is the level of receptors at the cell surface available for signaling. There is increasing evidence that cell surface expression of functional GABA(B) receptors is affected in neurological diseases. This diminishes inhibitory control of neuronal excitation and may contribute to the disease state. Here, we discuss recent findings on mechanisms involved in regulating cell surface expression of GABA(B) receptors in addiction, neuropathic pain, and brain ischemia.