A comparative study of four independent methods to measure LDL particle concentration.
Low-density lipoprotein particle concentration (LDL-P) is generally more predictive of clinical cardiovascular endpoints than LDL cholesterol (LDL-C). Few studies have directly compared multiple LDL-P methods, particularly with ultracentrifugation. Examine comparability and precision of 4 LDL-P methods. We divided serum from 48 subjects into blinded triplicates and measured LDL-P in 3 separate laboratories by 4 methods: ultracentrifugation (reference method), a novel electrophoretic method, and nuclear magnetic resonance spectroscopy (NMR) by 2 independent methods: a 400 MHz Vantera(®) instrument supplied by Liposcience (LS-NMR) and operated at ARUP Laboratories, and a 600 MHz Bruker instrument (ASCEND 600) operated at Health Diagnostic Laboratory (HD-NMR). Of the 4 methods, ultracentrifugation was the most precise and LS-NMR the least; the latter had a significantly greater CV (p < 0.0001) as compared with all 3 of the other methods, although all CVs were clinically acceptable. The electrophoretic method showed similar precision to ultracentrifugation, while HD-NMR was intermediate. The HD-NMR had the slope closest to 1 (0.90, 95% CI 0.71 to 1.09) and the intercept closest to 0 (-48, -353 to 256) compared to the ultracentrifugation method in Deming regression models. While the two NMR methods correlated well (r = 0.95) with each other and had a slope equivalent to 1 (1.08, 0.98 to 1.19), their intercept in Deming regression excluded 0 (194, 53 to 335) indicating a vertical shift between the two methods. This LDL-P method comparison may prove useful for future research and clinical applications.


Brain-Derived neurotrophic factor Val66Met induces female-specific changes in impulsive behaviour and alcohol self-administration in mice.
Substance use disorders are a debilitating neuropsychiatric condition, however it remains unclear why some individuals are at greater risk of substance use disorders than others and what genetic factors determine such individual differences. Impulsivity appears a promising candidate endophenotype to bridge the gap between genetic risk and addiction. Brain-derived neurotrophic factor (BDNF), and in particular the BDNFVal66Met polymorphism, has been suggested to be involved in both impulsivity and substance use disorders, however results so far have been inconsistent. To investigate the role of BDNF, and more specifically the BDNFVal66Met polymorphism, in both impulsivity and operant alcohol self-administration using the same animal model. Separate cohorts of humanized Val66Met transgenic mice were assessed for either trait impulsivity in the 5-choice serial reaction time (5-CSRT) touchscreen task, or propensity towards obtaining ethanol in an operant paradigm. It was found that female hBDNFVal/Val mice exhibited both greater impulsivity compared to hBDNFMet/Met mice of the same sex as shown by a higher number of premature responses at one of three increased inter-trial intervals tested in the 5-CSRT task, and a greater propensity toward stable ethanol self-administration relative to male mice of the same genotype in the operant paradigm. By contrast, male mice showed no difference between genotypes in impulsivity or stable ethanol self-administration. The hBDNFMet/Met genotype appears to sex-specifically alter aspects of both impulsive behaviour and addiction propensity. These results suggest that impulse behaviour may be a possible predictor of addiction risk.


Distribution of the existence forms of condensable particulate matter during condensation: The surface collection and the space suspension forms.
Condensable particulate matter (CPM), as an air pollutant that has received wide attention in recent years, has a high emission concentration compared to filterable particulate matter (FPM), yet there is not a well-developed removal method. Air pollution control devices (APCDs) with a condensation process have a certain effect on CPM removal, which inspired us to study the condensation behavior of CPM. During the condensation process, the condensed CPM may exist in two final forms: one was collected by the cold surface that caused the condensation; the other was converted to fine particles and suspended in the space of the flue. In a sense, the surface collection form can reflect the removal of CPM, while the CPM in the space suspension form should be further separated with the aim of removal. In this work, we adopted a CPM sampling system based on EPA Method 202 to reveal the distribution of the condensation behavior of CPM. In this sampling system, the CPM collected by all the cooling surfaces, including the cooling coil and impingers, can be counted as the surface collection form, while those collected by the terminal CPM filter can be regarded as the space suspension form. It was found that about 75 % of CPM was collected by the cooling surfaces, which suggested that CPM preferred to be in the surface collection form than the space suspension form. This preference characteristic also could be observed in the inorganic (CPMi) and organic components of the CPM (CPMo). Among the CPMi, almost all NH4+ and SO42- condensed in the form of surface collection. The preference characteristics in CPM's (and its components') condensation behavior are similar under every temperature reduction condition. In this work, the interference of CPM measurement error was resolved by the statistical method of ANOVA.


The Influence of Rocker Bar Ankle Foot Orthosis on Gait in Patients with Chronic Hemiplegia.
This study aimed to evaluate the effect of rocker bar ankle foot orthosis (RAFO) on the spatiotemporal characteristics of gait in chronic hemiplegic patients compared with the effect of solid ankle foot orthosis (SAFO). Following ethical approval, 18 patients with chronic hemiplegia, at least 6 months post stroke, were investigated in barefoot condition, with SAFO and RAFO in random sequences. Their spatiotemporal characteristics were examined by 2 force platforms and a Vicon motion analysis system. There were significant changes in spatiotemporal outcome measures between barefoot condition and using SAFO and RAFO (P < .05). Compared with SAFO, RAFO resulted in significantly more step length, faster gait velocity, and less preswing time (P < .05), although no significant differences were seen regarding step width and cadence (P > .05). Furthermore, RAFO led to significant increases in hip extension and knee flexion at toe-off, whereas SAFO did not change these parameters (P < .05). Findings of the present study showed that RAFO further improves gait abilities in chronic hemiplegic patients compared with SAFO, which could be due to the positive effect of added rocker bar on push-off function during the late stance phase of gait.


Dietary alpha-linolenic acid/linoleic acid ratios modulate intestinal immunity, tight junctions, anti-oxidant status and mRNA levels of NF-κB p65, MLCK and Nrf2 in juvenile grass carp (Ctenopharyngodon idella).
This study was conducted to investigate the effects of dietary alpha-linolenic acid/linoleic acid (ALA/LNA) ratios on the immune response, tight junctions, antioxidant status and immune-related signaling molecules mRNA levels in the intestine of juvenile grass carp (Ctenopharyngodon idella). A total of 1260 juvenile grass carp with an average initial weight of 8.78 ± 0.03 g were fed diets with different ALA/LNA ratios (0.01, 0.34, 0.68, 1.03, 1.41, 1.76 and 2.15) for 60 days. Results indicated that ALA/LNA ratio of 1.03 significantly increased acid phosphatase, lysozyme activities and complement C3 contents, promoted interleukin 10, transforming growth factor β1 and κB inhibitor α mRNA abundance, whereas suppressed pro-inflammatory cytokines (interleukin 1β, interleukin 8, tumor necrosis factor α and interferon γ2) and signal molecules (IκB kinase β, IκB kinase γ and nuclear factor κB p65) mRNA levels in the intestine (P < 0.05), suggesting that optimal dietary ALA/LNA ratio improved intestinal immune response of juvenile fish. Additionally, ALA/LNA ratio of 1.03 significantly promoted Claudin-3, Claudin-b, Claudin-c, Occludin and ZO-1 gene transcription, whereas reduced Claudin-15a and myosin light-chain kinase mRNA levels in the intestine, suggesting that appropriate dietary ALA/LNA ratio strengthened tight junctions in the intestine of juvenile fish. Meanwhile, ALA/LNA ratio of 1.03 noticeably elevated glutathione contents, copper/zinc superoxide dismutase, glutathione peroxidase, glutathione S-transferase and glutathione reductase activities and mRNA levels, as well as signaling molecule nuclear factor erythoid 2-related factor 2 gene transcriptional abundance in the intestine, suggesting that proper ratio of dietary ALA/LNA ameliorate the intestinal antioxidant status of juvenile fish. Based on the quadratic regression analysis of the complement C3 content in the distal intestine and malondialdehyde content in the whole intestine, optimal ALA/LNA ratio for maximum growth of juvenile grass carp (8.78-72.00 g) were estimated to be 1.13 and 1.12, respectively.


Establishing the validity and reliability of a pediatric pain knowledge and attitudes questionnaire.
Children continue to experience unrelieved pain during hospitalization, despite the evidence to guide nurses' pain management practices being readily available. Nurses' knowledge and attitudes have been identified as a possible reason for suboptimal pain management. This study examines the validity and reliability of an existing questionnaire to validate it for use in the population of interest. Initial testing demonstrated low reliability and validity. Modifications to the questionnaire were made on the basis of these results and the feedback provided by experts in pediatric pain management. Subsequent testing demonstrated good validity and reliability, suggesting that the questionnaire is appropriate for measuring nurses' knowledge and attitudes in relation to pediatric pain management.


Observations on the interaction of calcium and hydrogen ions on ATP hydrolysis by the contractile elements of cardiac muscle.
The ability of cardiac myosin, actomyosin, and myofibrils to hydrolyze ATP has been studied at varying hydrogen and calcium ion concentrations. The ATPase activity of dog cardiac myofibrils was measured over the pH range of 6.5-7.4, as the calcium ion concentration was varied from 0-1.5 X 10(-4) M. The ATPase of these myofibrils, and of rabbit cardiac myosin and actomyosin was also measured in the absence of ionic calcium over the pH range 6-9. The Km of MgATP of cardiac myofibrils was studied over the pH range 6.5-7.4. In the absence of calcium ions, myofibrillar, myosin, and actomyosin ATPase activities are maximal at pH 8.0. At any given calcium ion concentration, the myofibrillar ATPase is depressed by lowering pH. The results suggest that the influence of hydrogen ions on the ability of myofibrils to hydrolyze ATP is complex, and may not only be the result of a simple competition between hydrogen and calcium ions for binding sites on troponin.


The cognitive modulation of pain: hypnosis- and placebo-induced analgesia.
Nowadays, there is compelling evidence that there is a poor relationship between the incoming sensory input and the resulting pain sensation. Signals coming from the peripheral nervous system undergo a complex modulation by cognitive, affective, and motivational processes when they enter the central nervous system. Placebo- and hypnosis-induced analgesia form two extreme examples of how cognitive processes may influence the pain sensation. With the advent of modern brain imaging techniques, researchers have started to disentangle the brain mechanisms involved in these forms of cognitive modulation of pain. These studies have shown that the prefrontal and anterior cingulate cortices form important structures in a descending pathway that modulates incoming sensory input, likely via activation of the endogenous pain modulatory structures in the midbrain periaqueductal gray. Although little is known about the receptor systems involved in hypnosis-induced analgesia, studies of the placebo response suggest that the opiodergic and dopaminergic systems play an important role in the mediation of the placebo response.


Color Doppler imaging of the retrobulbar circulation in age-related macular degeneration.
The aim of this study was to assess hemodynamic changes in the retrobulbar circulation in patients with age-related macular degeneration (ARMD). Color Doppler imaging was used to calculate blood flow velocities and vascular resistance of the central retinal artery, short posterior ciliary artery and ophthalmic artery in patients with ARMD and in control patients. The average peak systolic velocity was significantly lower in the central retinal artery (p < 0.001), posterior ciliary artery (p < 0.001) and ophthalmic artery (p < 0.01) of the patients with ARMD than in control. End-diastolic blood flow velocities in the retrobulbar arteries of ARMD patients were also significantly lower (p < 0.001) than controls. Gosling's pulsatility index was significantly higher in the ophthalmic artery (p < 0.01) and posterior ciliary artery (p < 0.001) of eyes with ARMD. In addition, the resistivity index was significantly higher in all retrobulbar arteries (p < 0.001) of these patients. The hemodynamic abnormalities in the retrobulbar circulation suggest that vascular impairment may play a role in the pathogenesis of ARMD.


Population-Based Impact of Rurality and Neighborhood-Level Socioeconomic Disadvantage on Pediatric Cancer Mortality in Washington State.
Childhood cancer-related mortality differs by socioeconomic factors, but the impact of residential location, including rurality and neighborhood-level socioeconomic disadvantage, is not well-characterized. This retrospective cohort study linked Washington State cancer registry data (1992-2013) to state birth (1974-2013) and death records (1992-2013) to identify residents <20 years diagnosed with cancer (n = 4,306). Census-based rural-urban commuting area codes and Area Deprivation Index (ADI) defined rural residence and neighborhood socioeconomic disadvantage at time of cancer diagnosis, respectively. Neighborhoods in the highest state ADI quintile were classified as the most disadvantaged. Kaplan-Meier estimates and Cox hazards models, adjusted for key characteristics, were used to compare mortality by rural and ADI classification. Five-year overall survival for children from non-rural low ADI neighborhoods (referent) was 80.9%±0.8%, versus 66.4%±2.9% from non-rural high ADI neighborhoods, 69.4%±3.8% from rural low ADI neighborhoods, and 66.9%±3.8% from rural high ADI neighborhoods (P < 0.01 for each comparison versus referent). Compared with the referent group, children from comparator neighborhoods had a greater mortality risk: Rural low ADI [hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.12-2.02], rural high ADI (HR, 1.53; 95% CI, 1.16-2.01), and non-rural high ADI (HR, 1.64; 95% CI, 1.32-2.04). Associations of ADI and rurality with mortality varied in sub-analyses by cancer type. Children with cancer living in rural and/or socioeconomically disadvantaged neighborhoods at diagnosis experienced greater mortality relative to those without either factor. Future investigation is needed to examine how rurality and poverty potentially impact healthcare utilization and health-related outcomes in pediatric oncology.


Causal attribution and coping with parental dominance and deprecation in youth with mild intellectual disability.
Although interactions among parents and Youth with Mild Intellectual Disability (MID) may be stressful at times, most studies focus on the effects of stressful interactions on the parents. This study considers the Youth's perspective - particularly their beliefs about the reason for the parent's actions as well as how they would respond in the situation. The RA-PD test (American Psychologist, 28, 2015, 107) was administered to 151 transition age youth with MID in Poland. The test includes vignettes that describe common situations in which the parent engages in Domination or Deprecation. The participants coping responses, based on a multi-axial approach developed by Hobfoll (Stress, culture, and community. The psychology and philosophy of stress, 1998, Springer, New York, NY), and attributions toward the parental figure in the scenarios, based on Kelley (American Psychologist, 28, 2015, 107), were coded by judges. Correlations between causal attribution and coping response showed a consistent pattern where positive attributions were associated with prosocial coping and negative attributions were significantly related to antisocial coping. The implications for improving coping, especially for Youth with aggressive and passive tendencies, are discussed.


Evaluation of startle response and prepulse inhibition based on changes in the range of vertical pressure force of the feet on the ground: a preliminary study.
The aim of the study was to evaluate the possibility of estimating a startle response and sensorimotor gating based on changes in the range of vertical pressure force of the feet on the ground during a dynamometric examination. The study encompassed 13 healthy and physically fit men (age: 23.3 ± 2.0 years; height: 178.0 ± 6.1 cm; and weight: 76.1 ± 9.0 kg). The inhibitory mechanisms of startle reflex were used as the measure of sensorimotor gating. It was triggered by a strong acoustic stimulus (106 dB SPL, 40 ms), which was preceded by a similar, weaker signal (80 dB SPL, 20 ms). Startle reflex was evaluated using a piezoelectric force platform. The results of the conducted study show that the range of vertical pressure force of the feet caused by the reaction to a strong acoustic stimulus is significantly smaller when this stimulus is preceded by a signal of lower intensity (prepulse). Such assessment is only possible with the participants' eyes open. The generalized startle response of a person may be estimated using a force platform, based on changes in the range of vertical pressure force of the feet on the ground, which are caused by unexpected acoustic stimuli. There is a strong indication that using a force platform to evaluate sensorimotor gating could be used as an alternative to electromyographic examinations.


Effects of dopamine beta-hydroxylase genotype and disulfiram inhibition on catecholamine homeostasis in mice.
Dopamine beta-hydroxylase (DBH) converts dopamine (DA) to norepinephrine (NE), thus playing a critical role in catecholamine metabolism. We examined the effects of Dbh gene dosage and the DBH inhibitor disulfiram in mice with zero, one, or two null Dbh alleles (+/+, +/-, and-/- mice). DBH protein levels in adrenal and prefrontal cortex (PFC) and adrenal DBH activity were proportional to number of wild-type alleles. Adrenal DA was slightly increased in+/- mice and markedly increased (80-fold) in -/- mice compared to wild-type animals. While adrenal NE and epinephrine (EPI) were undetectable in -/- mice, adrenal concentrations of NE and EPI were similar in +/+ and +/- mice, suggesting that the increase in DA maintains the normal rate of beta-hydroxylation in Dbh +/- mice. Disulfiram had little effect on adrenal catecholamine levels, regardless of genotype or dose. NE was absent in the PFC of -/- mice, but only slightly reduced in +/- animals compared to wild-type animals. PFC DA was increased twofold in +/- mice and fivefold in -/- mice, and the NE to DA ratio was reduced ( approximately 35%) in +/- mice, compared to wild-type mice. Disulfiram significantly decreased PFC NE and increased DA in +/+ and +/- animals, with the disulfiram and genotype effects on the PFC NE to DA ratio apparently additive. The data reveal potentially important and apparently additive effects of Dbh genotype and disulfiram administration on PFC catecholamine metabolism. These effects may have implications for genetic control of DBH activity in humans and for understanding therapeutic effects of disulfiram.


Detection of circulating immune complexes in hepatitis by means of a new method employing 125i-antibody. circulating immune complexes in hepatitis.
A new RIA method for the detection of circulating immune complexes and antibodies arising in the course of viral hepatitis is described. It involves the use of 125I-labeled antibodies and foresees the possibility of employing immune complex-coated polypropylene tubes. This simple and sensitive procedure takes into account the possibility that the immune complexes may be absorbed by the surface of polypropylene tubes during the period in which the serum remains there.


Stabilization of scleral collagen by glycerol aldehyde cross-linking.
The paper aims at the evaluation of prospects for using glyceraldehyde as a cross-linking agent for the scleral tissue. Stability parameters (denaturation temperature, Young's modulus, ultimate tensile stress, proteolytic resistance) and analytical parameter (fluorescence intensity) were determined during the glycation process of isolated rabbit sclera. The analysis of fluorescence spectral characteristic provided information about some glycation products. The glyceraldehyde treatment was resulted in a significant increase in thermal stability, proteolytic resistance and improvement of biomechanical characteristics (Young's modulus, ultimate tensile stress). Unique properties of the reaction between scleral collagen and glyceraldehyde are observed at short cross-linking times. The appearance of intermediate collagen fraction with lowest thermal and proteolytic stability was detected.


Efficient Gene Targeting in Maize Using Inducible CRISPR-Cas9 and Marker-free Donor Template.
CRISPR-Cas9 is a powerful tool for generating targeted mutations and genomic deletions. However, precise gene insertion or sequence replacement remains a major hurdle before application of CRISPR-Cas9 technology is fully realized in plant breeding. Here, we report high-frequency, selectable marker-free intra-genomic gene targeting (GT) in maize. Heat shock-inducible Cas9 was used for generating targeted double-strand breaks and simultaneous mobilization of the donor template from pre-integrated T-DNA. The construct was designed such that release of the donor template and subsequent DNA repair activated expression of the selectable marker gene within the donor locus. This approach generated up to 4.7% targeted insertion of the donor sequence into the target locus in T0 plants, with up to 86% detected donor template release and 99% mutation rate being observed at the donor loci and the genomic target site, respectively. Unlike previous in planta or intra-genomic homologous recombination reports in which the original chimeric GT plants required extensive progeny screening in the next generation to identify non-chimeric GT individuals, our method provides non-chimeric heritable GT in one generation.


Enzyme-labeled type III bacterial Fc receptors. A versatile tracer for immunoassay.
The type III bacterial Fc receptor isolated form a group C streptococcus has been conjugated to alkaline phosphatase and used as a tracer in a variety of direct and indirect immunoassays. These immunoassays have utilized specific antibodies prepared in species whose immunoglobulins are poorly reactive with the type I Fc receptor, staphylococcal protein A. The value of the type III Fc receptor as a tracer for immunoassays utilizing antibodies produced in sheep and goats is documented.


Perceptions of two different alcohol use behaviours in pregnancy: an application of the prototype/willingness model.
This study explored whether exposure to either an 'ambiguous consumption' prototype (no amount of alcohol specified) or a 'small consumption' prototype ('small' amount of alcohol specified) had an impact on prototype perceptions of, and willingness to use, small amounts of alcohol during pregnancy. Participants were 140 women living in the UK, aged 20-45 years old, of whom 92% had previously been, or intended to become, pregnant. Participants completed measures to assess how favourably they viewed alcohol use in pregnancy, how similar they felt to those who would use alcohol in pregnancy and how responsible they perceived those who would use alcohol in pregnancy to be. Participant's own willingness to use small amounts of alcohol during pregnancy was also assessed. Having at least one child was positively correlated with being willing to accept an alcoholic drink while pregnant for those exposed to the 'ambiguous consumption' prototype only. Although perceptions of favourability, similarity and responsibility were consistently higher for those exposed to a 'small consumption' condition, there were no differences in willingness to drink according to exposure. This research suggests that women's perceptions of those who drink alcohol while pregnant differ according to the amount of alcohol that they perceive as typical. This may have implications for how alcohol use in pregnancy is portrayed in public health messaging, particularly regarding the level of acceptance that may be associated with low to moderate alcohol use.


Cardiac status of children infected with human immunodeficiency virus who are receiving long-term combination antiretroviral therapy: results from the Adolescent Master Protocol of the Multicenter Pediatric HIV/AIDS Cohort Study.
Prior to contemporary antiretroviral therapies (ARTs), children infected with human immunodeficiency virus (HIV) were more likely to have heart failure. This study suggests that highly active ART (HAART) does not appear to impair heart function. To determine the cardiac effects of prolonged exposure to HAART on HIV-infected children. In the National Institutes of Health-funded Pediatric HIV/AIDS Cohort Study's Adolescent Master Protocol (AMP), we used linear regression models to compare echocardiographic measures. A total of 14 US pediatric HIV clinics. Perinatally HIV-infected children receiving HAART (n = 325), HIV-exposed but uninfected children (n = 189), and HIV-infected (mostly HAART-unexposed) historical pediatric controls from the National Institutes of Health-funded Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2-HIV) Study (n = 70). EXPOSURE Long-term HAART. Echocardiographic measures of left ventricular (LV) function and structure. The 325 AMP HIV-infected children had lower viral loads, higher CD4 counts, and longer durations of ART than did the 70 HIV-infected children from the P2C2-HIV Study (all P < .001). The z scores for LV fractional shortening (a measure of cardiac function) were significantly lower among HIV-infected children from the P2C2-HIV Study than among the AMP HIV-infected group or the 189 AMP HIV-exposed but uninfected controls (P < .05). For HIV-infected children, a lower nadir CD4 percentage and a higher current viral load were associated with significantly lower cardiac function (LV contractility and LV fractional shortening z scores; all P = .001) and an increased LV end-systolic dimension z score (all P < .03). In an interaction analysis by HIV-infected cohort, the HIV-infected children from the P2C2-HIV Study with a longer ART exposure or a lower nadir CD4 percentage had lower mean LV fractional shortening z scores, whereas the mean z scores were relatively constant among AMP HIV-infected children (P < .05 for all interactions). Long-term HAART appears to be cardioprotective for HIV-infected children and adolescents.


Strain differentiation of dermatophytes.
As molecular-based investigations begin to uncover the large degree of genetic variation that can exist within dermatophyte species, and population-based studies reveal exceedingly high rates of endemicity for these organisms, species typing has become inadequate to gain insight into these pathogens and the nature of the infections that they cause. This review examines studies that have applied strain typing strategies to explore intra-specific genetic diversity among the dermatophytes in attempts to address a number of relevant clinico-epidemiologic questions about these common fungal pathogens.


Mitogen-activated protein kinases as key players in osmotic stress signaling.
Osmotic stress arises from the difference between intracellular and extracellular osmolality. It induces cell swelling or shrinkage as a consequence of water influx or efflux, which threatens cellular activities. Mitogen-activated protein kinases (MAPKs) play central roles in signaling pathways in osmotic stress responses, including the regulation of intracellular levels of inorganic ions and organic osmolytes. The present review summarizes the cellular osmotic stress response and the function and regulation of the vertebrate MAPK signaling pathways involved. We also describe recent findings regarding apoptosis signal-regulating kinase 3 (ASK3), a MAP3K member, to demonstrate its regulatory effects on signaling molecules beyond MAPKs. MAPKs are rapidly activated by osmotic stress and have diverse roles, such as cell volume regulation, gene expression, and cell survival/death. There is significant cell type specificity in the function and regulation of MAPKs. Based on its activity change during osmotic stress and its regulation of the WNK1-SPAK/OSR1 pathway, ASK3 is expected to play important roles in osmosensing mechanisms and cellular functions related to osmoregulation. MAPKs are essential for various cellular responses to osmotic stress; thus, the identification of the upstream regulators of MAPK pathways will provide valuable clues regarding the cellular osmosensing mechanism, which remains elusive in mammals. The elucidation of in vivo MAPK functions is also important because osmotic stress in physiological and pathophysiological conditions often results from changes in the intracellular osmolality. These studies potentially contribute to the establishment of therapeutic strategies against diseases that accompany osmotic perturbation.


Molecular identification of four phenotypes of human Demodex mites (Acari: Demodicidae) based on mitochondrial 16S rDNA.
Classification of Demodex mites has long depended on hosts and morphological characteristics. However, the fact that two species coexist in the same host and phenotype is easily influenced by environment causes difficulty and indeterminacy in traditional classification. Genotype, which directly reflects the molecular structure characteristics, is relatively stable. In this study, species identification of four phenotypes of human Demodex mites was conducted. Mites were morphologically classified into four phenotypes: long- and short-bodied Demodex folliculorum with finger-like terminus and Demodex brevis with finger- or cone-like terminus. The mitochondrial 16S ribosomal DNA (rDNA) fragment of individual mite was amplified, cloned, sequenced, and aligned. Sequence divergences, genetic distances, transition/transversion rates, and phylogenetic trees were analyzed. The results demonstrated that the 16S rDNA sequence of three phenotypes with finger-like terminus was 337 bp, and that of phenotype with cone-like terminus was 342 bp. The divergences, genetic distances, and transition/transversion rates among the three phenotypes with finger-like terminus were 0.0-2.7%, 0.000-0.029, and 5.0-7/0 (5/1-7/0), respectively, indicating an intraspecific variation. Yet, those between these three phenotypes and the one with cone-like terminus were 21.6-22.8%, 2.510-2.589, and 0.47-0.59 (22/47-27/46), respectively, suggesting an interspecific variation. The five phylogenetic trees showed that the three phenotypes with finger-like terminus clustered into one branch, while the phenotype with cone-like terminus clustered into another. In conclusion, terminus is a major morphological characteristic for the identification of human Demodex species. The three phenotypes with finger-like terminus belong to D. folliculorum, while the phenotype with cone-like terminus belongs to D. brevis. Molecular identification can verify and replenish morphological identification.


TUNEL analysis of DNA fragmentation in mouse unfertilized oocytes: the effect of microorganisms within human follicular fluid collected during IVF cycles.
Recently we reported the presence of bacteria within follicular fluid. Previous studies have reported that DNA fragmentation in human spermatozoa after in vivo or in vitro incubation with bacteria results in early embryo demise and a reduced rate of ongoing pregnancy, but the effect of bacteria on oocytes is unknown. This study examined the DNA within mouse oocytes after 12 hours' incubation within human follicular fluids (n=5), which were collected from women undergoing in vitro fertilization (IVF) treatment. Each follicular fluid sample was cultured to detect the presence of bacteria. Terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) was used to label DNA fragmentation in ovulated, non-fertilized mouse oocytes following in vitro incubation in human follicular fluid. The bacteria Streptococcus anginosus and Peptoniphilus spp., Lactobacillus gasseri (low-dose), L. gasseri (high-dose), Enterococcus faecalis, or Propionibacterium acnes were detected within the follicular fluids. The most severe DNA fragmentation was observed in oocytes incubated in the follicular fluids containing P. acnes or L. gasseri (high-dose). No DNA fragmentation was observed in the mouse oocytes incubated in the follicular fluid containing low-dose L. gasseri or E. faecalis. Low human oocyte fertilization rates (<29%) were associated with extensive fragmentation in mouse oocytes (80-100%). Bacteria colonizing human follicular fluid in vivo may cause DNA fragmentation in mouse oocytes following 12h of in vitro incubation. Follicular fluid bacteria may result in poor quality oocytes and/or embryos, leading to poor IVF outcomes.


Sex differences in prolactin secretion in parental male and female rats.
The present series of experiments report the behavioral and endocrine responses of male and female rats to rat young. In the first experiment, the behavioral responses of intact male and ovariectomized female rats to foster young were measured. While both of these groups exhibited most components of parental behavior after four to six days of exposure to rat young, males failed to build good nests and to crouch over the young. In addition significantly more males killed young than did ovariectomized females. In the second experiment, treatment of male and virgin female rats with a 21-day hormone regimen of estradiol and progesterone stimulated an equally rapid onset of parental behavior in both sexes. Latencies to exhibit parental responses were approx. two days for both males and females. Pup killing was virtually eliminated in males by hormone treatment. Although the behavioral responses of hormone-primed males and females were similar, their prolactin responses to the presentation of rat young differed. Pup presentation stimulated an increase in plasma prolactin content in hormone-primed parental virgin females similar, but not identical, to that found in lactating control rats, while plasma prolactin levels in hormone-primed parental males did not rise in response to the presentation of young. These data indicate that a sex difference in neuroendocrine, but not behavioral, responsiveness to young exists between parental males and females.


Evaluation of the uncertainty associated with the off line HPLC-GC(FID) determination of 4-desmethyl sterols in vegetable oils.
This paper discusses the estimation of the uncertainty of the chromatographic determination of 4-desmethyl sterols in vegetable oils, combining the off line HPLC fractionation of the analytes, from the unsaponifiable fraction of the samples, with their determination as TMS derivatives by GC(FID), using the data obtained from a single internal calibration (one surrogate) at one level and "bottom up" approach. The methodology used, makes possible to identify the main uncertainty contributions, find their origins, and reduce them. The final results show that the main contributions to the relative overall uncertainty are those closely related with the chemical aspects of the method, i.e. those related to derivatization reaction and quantification of the analytes, although others aspects, such as the addition of a mass of surrogate, are not negligible.


Reasoning, problem-solving, and visual learning as candidate endophenotypes for first-episode, drug-naïve obsessive-compulsive disorder in the Han Chinese population.
Obsessive-compulsive disorder (OCD) is a mental disease with obsessions and compulsions as its main symptom dimensions. In recent years, endophenotype (intermediate phenotype) method has been used to study OCD. This study aimed to evaluate the cognitive function for patients with OCD and search for possible endophenotype. This study utilized a comparison control group design with 64 OCD patients, 49 healthy siblings (HS) of the patients, and 53 healthy controls. Several projects were selected to evaluate patients' cognition functions, such as reasoning, problem-solving, attention/vigilance, visual learning, speed of processing, and verbal learning. Results suggested that the patients with OCD and their HS have cognitive deficits in reasoning, problem-solving, trail making test, and visual learning. Significant differences were observed among the three groups of subjects in verbal learning. No significant difference was observed in attention/vigilance among the three groups. Our results suggest that reasoning, problem-solving, and visual learning may be candidate endophenotypes for the early diagnosis of prodrome Han Chinese patients with OCD.


Comparison of higher order aberrations in eyes with aspherical or spherical intraocular lenses.
To compare ocular, internal, corneal aberrations, and contrast sensitivity in patients implanted with aspheric or spherical intraocular lenses (IOLs). Total, corneal, and internal aberrations were measured using ray-tracing technology in 23 eyes implanted with aspheric (Tecnis ZA9003) IOLs, and in 25 eyes implanted with spherical (AcrySof SA60AT) IOLs. Spherical aberration (SA), coma, trefoil, and RMS of higher order aberrations (HOAs) were analysed for 4.0 and 6.0 mm optical zones. Best-corrected visual acuities (BCVAs), contrast sensitivity under photopic and mesopic conditions, and modulation transfer function (MTF) were evaluated to compare visual performances. The mean internal SA was -0.06/-0.35 microm in the aspheric IOL group and 0.04/0.17 microm in the spherical IOL group (at 4 mm/6 mm pupil). Total SA was near to zero in the aspheric IOL group, and was 0.11+/-0.034/0.48+/-0.13 microm in the spherical IOL group. The internal Z(3)(-1) and total Z(3)(-1) were more negative in the spherical IOL group. The internal Z(3)(-3) was more negative in the aspheric IOL group. The two groups were similar in terms of other Zernike values and RMS of HOA. There were no differences in BCVA between groups. The aspheric IOL group showed better contrast sensitivity at 3-6 cpd in photopic and 1.5-6 cpd in mesopic conditions. The MTF curve was better for the aspheric IOL group at 5-10 cpd. The aspheric IOL with a negative SA reduced total SA by compensating for positive corneal SA. These effects resulted in improved contrast sensitivity.


Dual subcellular localization of the 3 beta-hydroxysteroid dehydrogenase isomerase: characterization of the mitochondrial enzyme in the bovine adrenal cortex.
The enzyme 3 beta-hydroxysteroid dehydrogenase isomerase (3 beta-HSD/I) is an essential step in the biosynthesis of steroid such as progesterone, mineralo- and gluco-corticoids, estrogens and androgens in steroidogenic tissues. It is considered to be mainly localized in microsomes; however, 3 beta-HSD/I activity has also been described to be associated with mitochondrial preparations. In this study, we examined the subcellular distribution of 3 beta-HSD/I in bovine adrenocortical tissue and we characterized the catalytic properties of the enzyme present in the various cell compartments. About 30% of the total 3 beta-HSD/I activity was found to remain tightly associated with the purified mitochondrial pellet. The 3 beta-HSD/I and 3-ketoreductase activities were found in microsomes as well as in mitochondria. The 3 beta-HSD/I associated with the mitochondrial fraction did not require addition of exogenous NAD+. When the pyridine nucleotide was reduced following addition of substrates of the tricarboxylic acids cycle, the mitochondrial 3 beta-HSD/I activity decreased, suggesting that the enzyme utilizes NAD+ available from the matrix space. By contrast, the microsomal enzyme was inactive in the absence of exogenous NAD+. Submitochondrial fractionation disclosed that 3 beta-HSD/I was associated (i) with the inner membrane and (ii) with a particulate fraction sedimenting in a density gradient between inner and outer membranes. This fraction was characterized as contact sites between the two membranes. 3 beta-HSD/I specific activity was much higher in this fraction than in the inner mitochondrial membrane. Altogether, these observations suggest that these mitochondrial intermembrane contact sites may represent a special organization of functional significance, facilitating both the access of cholesterol to the inner membrane where cytochrome P-450scc is located and the rapid transformation of its product, pregnenolone, to progesterone, through 3 beta-HSD/I activity.


Cycle-related LHRH responsiveness of superfused pituitary cells in a Phenol red free medium.
Anterior pituitary cell cultures are frequently used in studying the control of gonadotropin secretion. Historically, many (if not most) of these studies have been performed in the presence of Phenol red as a pH indicator. Phenol red preparations, because of their potential estrogenic activity, may have influenced the results of previous studies defining the relative luteinizing hormone releasing hormone responsiveness of rat anterior pituitary-cells derived from various stages of the estrous cycle. We therefore felt it of interest to investigate this possibility by repeating our previous cycle-related superfusion studies [(1988) Life Sci. 42, 61-72] in the absence of these Phenol red preparations. Comparisons of data obtained in the presence or absence of Phenol red revealed cells derived from late proestrous (19.00) and cultured in the absence of Phenol red continued to evidence the highest LH responsiveness. However, diestrous 1 08.00 cells cultured in the absence of Phenol red were lower in responsiveness than previously observed in the presence of the substance and the responsiveness of proestrous 08.00 and 15.00 in the presence was lower in comparison to the same stages in the absence of Phenol red. The results suggest that Phenol red preparations are capable of modulating LHRH responsiveness in superfusion and that the effect is more pronounced at certain cycle stages than at others.


Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange.
Elk-1 is a member of the TCF subfamily of Ets proteins. TCFs interact with SRF at serum response elements (SREs) of immediate early genes (IEGs), such as c-fos and Egr-1, thereby mediating IEG induction upon extracellular stimulation. We previously generated an Elk-1 null allele (Elk1-137) in murine embryonic stem (ES) cells by homologous recombination. In Elk1-137, the Elk-1 gene was replaced by a Hygromycin B phosphotransferase - Thymidine Kinase (HygTk) fusion gene, flanked by two nonidentical Flp recombinase recognition (FRT) sites (Cesari et al., [2004] Mol Cell Biol, in press) to allow for the subsequent generation of alternative alleles of interest by recombinase-mediated cassette exchange (RMCE). Elk1-deficient mice derived from Elk-1((137/0)) ES cells are viable and do not reveal strong phenotypical abnormalities, apart from male sterility. However, the Elk-1 locus contains the Tk cassette, which has previously been related to this defect. Therefore, in our first experiment involving the technique of Flp RMCE we chose to remove the HygTk cassette in Elk-1((137/0)) ES cells and to generate Elk-1((RMCE16/0)) and Elk-1((RMCE16/RMCE16)) mice. In so doing, we provide evidence that the sterility of Elk1((137/0)) mice was not due to the absence of Elk-1 but rather the presence of HygTk. This is the first report of mice derived from ES cells which were subjected to Flp RMCE and thus proves that RMCE is a powerful tool for the genetic engineering of previously tagged loci in the mouse genome.


Antibody recognition of epitopes on wild-type and mutant beta-(1-->4)-galactosyltransferase-1.
The epitopes present on beta-(1-->4)-galactosyltransferase-1 (beta 4Gal-T1) have been explored using a panel of monoclonal antibodies (mAbs) raised against the soluble form of the human enzyme. Reactivity of the antibodies with site-specific and truncated mutants of human beta 4Gal-T1 suggests the presence of a major immunogenic epitope cluster consisting of four epitopes within the stem region and mapping between amino acids 42 and 115. The catalytic activity of the enzyme is increased in the presence of stem region-specific antibody. Two of the epitopes were further localized to a region between amino acids 42 and 77, sequences which are not shared with the recently cloned beta 4Gal-T2 and beta 4Gal-T3 enzymes. An epitope located close to or within the catalytic domain is also identified, and the mAb to this region binds synergistically with antibodies to the stem region.


¹H, ¹³C, ¹⁵N backbone and side chain NMR resonance assignments of BPSL1050 from Burkholderia pseudomallei.
BPSL1050 is a 13.9 kDa protein produced by the Gram-negative bacterium Burkholderia pseudomallei, the etiological agent of melioidosis. Immunodetection assays against sera patients using protein microarray suggest BPSL1050 involvement in melioidosis. Herein we report its backbone and side chains NMR assignment.


Core design principles for nurturing organization-level selection.
Dynamic relationships between individuals and groups have been a focus for evolutionary theorists and modelers for decades. Among evolutionists, selfish gene theory promotes reductionist approaches while multilevel selection theory encourages a context-sensitive approach that appreciates that individuals and groups can both matter. Among economists, a comparable contrast is found wherein the reductionist shareholder primacy theory most associated with Nobel laureate Milton Friedman is very different from the context-sensitive focus on managing common resources that Nobel laureate Elinor Ostrom pioneered. In this article, we examine whether the core design principles that Ostrom advanced can cultivate selection at supra-individual levels across different domains. We show that Ostrom's design principles that were forged in the context of managing natural resources are associated with positive outcomes for human social groups across a variety of functional domains.


The influence of resin infiltration system on enamel microhardness and surface roughness: An in vitro study.
To investigate the effect of a resin infiltrant on the surface microhardness and roughness of healthy enamel and, as a subsidiary aim, to compare it with a fissure sealant. Twenty freshly extracted premolars were used. Sound enamel surfaces were treated with a resin infiltrant (Icon) or fissure sealant (Seal-Rite). The average roughness (R a, μm) of the specimens was measured with a profilometer (Surtronic 10 Tylor Hobson). Surface hardness was determined by utilizing Vicker's surface hardness (VHN) with a Micromet II Microhardness tester. Each specimen acted as its own control. Data were analyzed with 2-way analysis of variance (ANOVA), and mean values were compared with independent t-test. All analyses were performed with the SPSS program version 16 (USA). Differences with a P-value of ⩽0.05 were considered statistically significant. Comparison of enamel surfaces before and after application of resin infiltrant revealed no significant differences in surface hardness; however, enamel surfaces treated by infiltrant showed significantly higher VHN (244.0 ± 79.8) values than those treated with fissure sealant (37.5 ± 14.2). Surface roughness did not differ before and after application of either material to sound enamel. Enamel surfaces treated with fissure sealant (5.3 ± 1.4) were significantly smoother than those treated with infiltrant (6.9 ± 2.0). Within the limitations of the study, the results showed that enamels treated with the resin infiltrant showed approximately the same microhardness and surface roughness as sound enamel, indicating that this material might be suitable for the treatment of enamel subsurface lesions.


Maternal Nanos regulates zygotic gene expression in germline progenitors of Drosophila melanogaster.
Maternal Nanos (Nos) protein is required for germline development in Drosophila embryos. Here we show that Nos regulates zygotic gene expression in the germline progenitors, or pole cells. In order to probe the gene expression in pole cells, we screened ten enhancer-trap lines which showed beta-gal expression in pole cells. All of these enhancer-trap markers were fully activated in pole cells after their migration to the embryonic gonads. In the pole cells lacking Nos, the expression of nine out of ten enhancer-trap markers was affected. Among nine markers, five (Type-A) were prematurely expressed in the pole cells during the course of their migration. The expression of other four markers (Type-B) initiated correctly after pole-cell migration, but their expression was significantly reduced. Thus, we conclude that the maternal Nos plays a dual role in zygotic gene regulation in pole cells: to define the stages of expression for Type-A markers, and to enhance expression for Type-B markers. Contrary to our results, "Heller and Steinmann-Zwicky (1998)" have recently reported that no premature expression of Type-A markers occurs in the pole cells of embryos derived from nos mutant females. This discrepancy is due to the difference in the nos mutant alleles used for these analyses. We used the much stronger allele, nosBN.


Anti-HLA antibodies in kidney transplanted patients.
Anti-human leukocyte antibodies (HLA) play a central role in graft survival, particularly in kidney transplantation. The presence of preformed donor specific anti-HLA antibodies is always excluded before transplantation by performing crossmatches using current and historic recipient serum samples. Several recent studies have observed a correlation between HLA antibodies and graft rejection. It has been suggested that these antibodies should be monitored routinely after kidney transplant to predict graft failure. Here in report the results of a study of on serum samples from 111 kidney transplant recipients that were monitored for anti-HLA antibodies using flow cytometry. Anti-HLA antibodies were only detected in four pre-immunized patients and showed the same HLA specificity that was present before the transplantation (in two cases against previous graft antigens). Furthermore, only two patients with functioning grafts developed anti-HLA antibodies, at 1 month and 1 year after the transplantation. However, they were not donor specific, but probably related to posttransplant transfusions. In our study, none of the patients who suffered an adverse event during the first year (including two with histologically documented acute rejection) developed anti-HLA antibodies. These results are probably related to the use of mycophenolate mofetil, which may reduce the incidence of HLA antibodies. We cannot exclude the possibility that antibodies produced by some patients may not be detectable because they are attached to the graft.


Pulmonary anaphylaxis and the kallikrein-kinin system.
The kallikrein-kinin system has been thought to participate in the pathogenesis of anaphylaxis. Kallikrein, released from lungs, has been postulated to contribute to cardiovascular collapse. Further to test the hypothesis, we examined for the occurrence of a kallikrein-like enzyme in guinea pig lungs and examined for release of such an enzyme by isolated, perfused lungs of guinea pig sensitized to and challenged with egg albumin. In addition, we treated guinea pigs with the bradykinin potentiating agents, BPP9a and SQ 14,225. In parallel experiments, we examined for effects of non-steroidal anti-inflammatory agents on the supposition that prostaglandin-related substances may mediate or modulate actions of kinins during anaphylaxis. A plasma kallikrein-like enzyme was found in lung homogenates and occurred in concentrations greater than that of plasma itself. Similarly, a store of kininogen occurs in lungs. However, using a sensitive radioassay for kallikrein-like enzymes, we were unable to confirm that antigenic challenge of sensitized lungs causes the release of enzyme into pulmonary venous effluent. Further, we were unable to modify the acute course of anaphylaxis by pretreatment of guinea pigs with bradykinin potentiating agents. However, indomethacin and aspirin at 20-40 mg/kg were found to greatly increase the severity of pulmonary anaphylaxis in terms of increased resistance to ventilation and increased numbers of lung hemorrhages. Paradoxically, aspirin or sodium salicylate at 80-100 mg/kg prevents the characteristic rise of insufflation pressure and the formation of lung hemorrhages.


Novel approaches for treatment of endometrial carcinoma.
Endometrial cancer (EC) is common malignancy in women and its incidence is slowly on the rise. Accurate surgical staging, with aggressive cytoreduction when indicated, remains the most critical step in the treatment. Careful pathological evaluation and/or molecular risk stratification guides for proper systemic adjuvant radiotherapy ± chemotherapy. Recurrent and metastatic EC has dismal prognosis and palliative therapies (chemotherapy, hormonal therapy or radiation) forms the backbone of treatment. There is an unmet need of newer therapies to improve survival in such cases. A number of tyrosine kinase inhibitors are currently under evaluation. Recent data on therapeutic targeting of HER2 positive serous EC is exciting. Data on check point inhibitors particularly based on biomarker select population has raised hope for potentially effective treatment for women with high risk endometrial cancer .


The use of equine chondrogenic-induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double-blinded, placebo-controlled proof-of-concept study.
There is a need to improve therapies for osteoarthritis in horses. To assess the efficacy of equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma as a novel therapy for osteoarthritis in horses. Randomised, double-blinded, placebo-controlled experiment. In 12 healthy horses, osteoarthritis was induced in the metacarpophalangeal joint using an osteochondral fragment-groove model. Five weeks after surgery, horses were randomly assigned to either an intra-articular injection with chondrogenic-induced mesenchymal stem cells + equine allogeneic plasma (= intervention) or with 0.9% saline solution (= control). From surgery until the study end, horses underwent a weekly joint and lameness assessment. Synovial fluid was collected for cytology and biomarker analysis before surgery and at Weeks 5, 5 + 1d, 7, 9 and 11. At Week 11, horses were subjected to euthanasia, and the metacarpophalangeal joints were evaluated macroscopically and histologically. No serious adverse events or suspected adverse drug reactions occurred during the study. A significant improvement in visual and objective lameness was seen with the intervention compared with the control. Synovial fluid displayed a significantly higher viscosity and a significantly lower glycosaminoglycan concentration in the intervention group. Other biomarkers or cytology parameters were not significantly different between the treatment groups. Significantly less wear lines and synovial hyperaemia were present in the intervention group. The amount of cartilage oligomeric matrix protein, collagen type II and glycosaminoglycans were significantly higher in the articular cartilage of the intervention group. This study assessed the short-term effect of the intervention on a limited number of horses, using an osteoarthritis model. This study also included multiple statistical tests, increasing the risk of type 1 error. Equine allogeneic chondrogenic-induced mesenchymal stem cells combined with equine allogeneic plasma may be a promising treatment for osteoarthritis in horses. The Summary is available in Spanish - see Supporting Information.


Left-handers' sensitivity to hand usage: theoretical note on saliency in the self-concept.
Etaugh and Brausam (1978) reported that left-handers were more sensitive than right-handers to hand usage by figures in a picture. Their interpretation emphasizes particular social experiences of left-handers. We propose a theoretically broader explanation--that there are general tendencies to characterize the self in terms of characteristics that are distinctive relative to others and to note in others those qualities salient in the self-concept.


How different data sources and definitions of neighbourhood influence the association between food outlet availability and body mass index: a cross-sectional study.
Inconsistencies in methodologies continue to inhibit understanding of the impact of the environment on body mass index (BMI). To estimate the effect of these differences, we assessed the impact of using different definitions of neighbourhood and data sets on associations between food outlet availability within the environment and BMI. Previous research has not extended this to show any differences in the strength of associations between food outlet availability and BMI across both different definitions of neighbourhood and data sets. Descriptive statistics showed differences in the number of food outlets, particularly other food retail outlets between different data sets and definitions of neighbourhood. Despite these differences, our key finding was that across both different definitions of neighbourhood and data sets, there was very little difference in size of associations between food outlets and BMI. Researchers should consider and transparently report the impact of methodological choices such as the definition of neighbourhood and acknowledge any differences in associations between the food environment and BMI.


Effects of cyclooxygenase-1/cyclooxygenase-2 inhibition on leukocyte/endothelial cell interactions in the rat mesentery.
Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase activity and cause gastrointestinal damage in part by promoting leukocyte accumulation in the mucosa. Our aim was to evaluate the effects of selective blockade of the isoenzymes cyclooxygenase-1 and cyclooxygenase-2 on leukocyte adhesion in vivo. Leukocyte/endothelial cell interactions were examined in rat mesenteric venules before and after treatment with indomethacin, SC-560 (5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole, cyclooxygenase-1 inhibitor), DFP (5,5-dimethyl-3-(2-propoxy)-4-(4-methanesulfonyl)-2(5H)-furanone, cyclooxygenase-2 inhibitor), or SC-560 plus DFP (20 mg/kg, i.v. each). Indomethacin increased leukocyte-rolling flux, reduced rolling velocity and elicited significant leukocyte adhesion. Neither SC-560 nor DFP induced these effects although their co-administration reproduced the indomethacin response. Indomethacin and SC-560, but not DFP, abolished cyclooxygenase-1 activity in blood. Plasma from indomethacin- or DFP-, but not from SC-560-treated rats abolished cyclooxygenase-2 activity in activated A549 cells. Specific blockade of cyclooxygenase-1 or cyclooxygenase-2 does not induce any inflammatory event in the rat mesentery and the inflammatory response observed with non-selective NSAIDs seems to be due to the inhibition of both isoenzymes.


The Redelberger antigen Rba.
A new low frequency antigen, Rba, has been found in three blood donors. Studies on their families show that the antigen is inherited as a Mendelian autosomal dominant character. Rba segregates independently from ABO, MNSs P1, Rh, Kell, Duffy, Kidd, ACP1 and PGM1. Anti-Rba is not common in sera containing multiple antibodies ot low frequency antigens.


Visual marking and change blindness: moving occluders and transient masks neutralize shape changes to ignored objects.
Visual search efficiency improves by presenting (previewing) one set of distractors before the target and remaining distractor items (D. G. Watson & G. W. Humphreys, 1997). Previous work has shown that this preview benefit is abolished if the old items change their shape when the new items are added (e.g., D. G. Watson & G. W. Humphreys, 2002). Here we present 5 experiments that examined whether such object changes are still effective in recapturing attention if the changes occur while the previewed objects are occluded or masked. Overall, the findings suggest that masking transients are effective in preventing both object changes and the presentation of new objects from capturing attention in time-based visual search conditions. The findings are discussed in relation to theories of change blindness, new object capture, and the ecological properties of time-based visual selection.


Association of interleukin-6 circulating levels with coronary artery disease: a meta-analysis implementing mendelian randomization approach.
We aim to investigate whether the association between circulating interleukin 6 (IL-6) levels and the risk for coronary artery disease (CAD) is robust and perhaps even causal by a meta-analysis implementing mendelian randomization approach with IL-6 gene G-174C polymorphism as an instrument. Data were available from 19 articles encompassing 9417 CAD patients and 15982 controls. A random effects model was applied irrespectively of between-study heterogeneity, and publication bias was examined using a funnel plot and the corresponding statistics. Overall, comparison of IL-6 gene alleles -174C with -174G had 4% increased risk for CAD (95% confidence interval [95% CI]: 0.97-1.10; P=0.285), accompanying marginal heterogeneity (I(2)=38.3%; P=0.033). This association was potentiated in dominant model as odds ratio (OR) reached 1.08 (95% CI: 0.96-1.22; P=0.204) and heterogeneity was significant (I(2)=58.4%; P<0.0005). Subgroup analysis by ethnicity indicated that carriers of -174C allele were associated with a 12% increased risk for CAD in prospective studies involving White populations (OR=1.12; 95% CI: 0.95-1.33; P=0.184), whereas the association in East Asians was remarkably reversed with 37-46% reduced risk. Relative to -174GG homozygotes, carriers of -174C allele had an overall 0.24 pg/ml high circulating IL-6 levels (P=0.047). The predicted OR for 1 pg/ml elevation in IL-6 levels was 1.60 (95% CI: 1.44-1.72; P<0.01) in prospective studies involving White populations. Publication biases were absent for all comparisons (P>0.1). Our findings provided strong evidence on the causal association of circulating IL-6 levels with the development of CAD in White populations.


Characterization of fecal branched-chain fatty acid profiles and their associations with fecal microbiota in diarrheic and healthy dairy calves.
Branched-chain fatty acids (BCFA) have recently been reported to play a role in human gut health during early life. However, little information is available on the fecal BCFA profiles in young ruminants and whether they are associated with the development of neonatal calf diarrhea. The objectives of this study were to (1) characterize BCFA profiles in feces collected from young calves, (2) compare the fecal BCFA composition between diarrheic and nondiarrheic dairy calves, and (3) explore the potential relationships between BCFA and microbiota in the feces. A total of 32 male Holstein dairy calves (13 ± 3 d old) with the same diet management were grouped as diarrheic (n = 16) or healthy (n = 16) based on fecal score (determined by liquid fecal consistency with some solid particles); diarrhea cases were defined as fecal score ≥2 for at least 2 d. Fecal samples were collected on the seventh day after calf arrival, and the fecal BCFA and microbial profiles were assessed using gas chromatograph and amplicon sequencing, respectively. In total, 7 BCFA were detected in the feces of all dairy calves; however, the concentrations of fecal BCFA differed between diarrheic and nondiarrheic calves. Specifically, the concentrations of iso-C16:0, iso-C17:0, anteiso-C17:0, and total even-chain BCFA were significantly higher in the feces of diarrheic calves. When the associations between BCFA and bacteria were studied, the relative abundance of Eggerthella was positively correlated with the concentrations of iso-C16:0 (ρ = 0.67), iso-17:0 (ρ = 0.77), anteiso-C17:0 (ρ = 0.73), and iso-C18:0 (ρ = 0.65), whereas the relative abundance of Subdoligranulum was positively correlated with the concentrations of iso-C14:0 (ρ = 0.62), iso-C15:0 (ρ = 0.78), and anteiso-C15:0 (ρ = 0.63). Use of random forest algorithm showed that BCFA such as anteiso-C15:0, iso-C16:0, iso-C17:0, iso-C18:0, and total even-chain BCFA could be used as biomarkers to differentiate diarrheic calves from healthy ones. Our findings generated fundamental knowledge on the potential roles of BCFA in neonatal calf gut health. Follow-up studies with larger animal populations are warranted to validate the feasibility of using BCFA as indicators of health status in neonatal calves.


A Rare Case of Vocal Cord Aspergillosis.
Primary aspergillosis of larynx is very rare. Till now only 28 cases of isolated laryngeal aspergillosis are documented in the English literature. In the field of otorhinolaryngology, aspergillosis most frequently affects external auditory canal or nasal sinuses and larynx is usually secondarily involved. It usually affects the patients with immunocompromised state and usually presents with hoarseness of voice. Laryngeal lesions usually mimics malignancy, so accurate diagnosis with direct laryngoscopy and biopsy is needed for further management. As these lesions responds very well to antifungal therapy, early diagnosis and starting antifungal therapy is important. Here we are presenting a case report of 67 years old male with aspergillosis of vocal folds without any immunodeficiency.


[General research modalities with traditional remedies of plant origin with a view to their introduction into pharmacotherapy].
The literature had suggested some schemes of tests and procedures to be employed in the scientific investigations and pharmaceutical evaluation of the traditional plant remedies. The present paper is intended to be a critical review.


Large Epicardial Hematoma After Percutaneous Coronary Intervention: Multimodality Imaging.
Epicardial hematoma can manifest immediately or within a few minutes to hours after coronary intervention. Review of angiogram after the diagnosis of hematoma, in our case, showed deep distal positioning of a non-polymer jacketed wire, which is the most likely cause of the adverse outcome. Multimodality imaging is critical for diagnosis and management of such cases.


Real-time PCR detection and quantification of elephantid DNA: species identification for highly processed samples associated with the ivory trade.
The ivory industry is the single most serious threat to global elephant populations. A highly sensitive, species-specific real-time PCR assay has been developed to detect and quantify African elephant (Loxodonta africana), Asian elephant (Elephas maximus) and Woolly Mammoth (Mammuthus primigenius) mitochondrial DNA from highly processed samples involved in the international ivory trade. This assay is especially useful for highly processed samples where there are no distinguishing morphological features to identify the species of origin. Using species-specific Taqman(®) probes targeting a region of the mitochondrial cytochrome b gene, we developed an assay that can be used to positively identify samples containing elephant or Woolly mammoth DNA faster and more cost-effectively than traditional sequencing methods. Furthermore, this assay provides a diagnostic result based on probe hybridization that eliminates ambiguities associated with traditional DNA sequence protocols involving low template DNA. The real-time method is highly sensitive, producing accurate and reproducible results in samples with as few as 100 copies of template DNA. This protocol can be applied to the enforcement of the Convention on the International Trade of Endangered Species (CITES), when positive identification of species from illegally traded products is required by conservation officers in wildlife forensic cases.


The consistent application of hydrogen peroxide controls biofilm growth and removes Vermamoeba vermiformis from multi-kingdom in-vitro dental unit water biofilms.
The water systems inside a dental unit are known to be contaminated with a multi-kingdom biofilm encompassing bacteria, fungi, viruses and protozoa. Aerosolization of these micro-organisms can potentially create a health hazard for both dental staff and the patient. Very little is known on the efficacy of dental unit disinfection products against amoeba. In this study we have examined the effect of four different treatment regimens, with the hydrogen peroxide (H2O2) containing product Oxygenal, on an in-vitro multi-kingdom dental unit water system (DUWS) biofilm. The treatment efficacy was assessed in time using heterotrophic plate counts, the bacterial 16S rDNA, fungal 18S rDNA gene load and the number of genomic units for Legionella spp. the amoeba Vermamoeba vermiformis. The results indicated that a daily treatment of the DUWS with a low dose H2O2 (0.02% for 5 h), combined with a weekly shock dose (0.25% H2O2, 30 min) is necessary to reduce the heterotrophic plate count of a severely contaminated DUWS (>106 CFU.mL-1) to below 100 CFU.mL-1. A daily treatment with a low dose hydrogen peroxide alone, is sufficient for the statistically significant reduction of the total amount of bacterial 16S rDNA gene, Legionella spp. and Vermamoeba vermiformis load (p < 0.005). Also shown is that even though hydrogen peroxide does not kill the trophozoite nor the cysts of V. vermiformis, it does however result in the detachment of the trophozoite form of this amoeba from the DUWS biofilm and hereby ultimately removing the amoeba from the system.


Purification and reconstitution of an intestinal Na(+)-dependent neutral L-alpha-amino acid transporter.
Using an improved reconstitution method, we have purified an Na(+)-dependent neutral L-alpha-amino acid transporter from rabbit small intestine to apparent homogeneity. The preparation solubilized with octaethylene glycol dodecyl ether (C12E8) was purified by successive chromatographies on DEAE-Toyopearl and lentil lectin-Sepharose 4B columns. The transport activity was assayed by reconstitution of the protein into liposomes. The specific activity of the final preparation was 1364-fold that of brush border membrane vesicles. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the active fractions gave one band of 90 kDa. Kinetic analysis using proteoliposomes reconstituted with the purified fraction showed that alanine transport was mediated by high affinity system with Kt value of 0.19 mM and Jmax value of 2.8 nmol/mg protein/s. Analysis of the amino acid composition of the purified transporter revealed that the transporter is very hydrophobic protein. From its specific activities for transport of individual amino acids this transporter was concluded to possess broad specificity for neutral L-alpha-amino acids. Furthermore, inhibition study of other amino acids allowed us to identify this transport pathway as the intestinal system B.


Pharmacokinetics and efficacy of pirmenol hydrochloride in the treatment of ventricular dysrhythmia.
Pirmenol hydrochloride (CI-845), a new antiarrhythmic agent available for both oral and intravenous administration, was given to seven patients with chronic ventricular dysrhythmia in an open-label fashion. After intravenous infusion of 150 mg over 30 min, the mean (+/- SD) peak plasma concentration achieved was 2.14 +/- 0.75 microgram/ml. The terminal elimination half-life, the volume of the central compartment, and the total body clearance averaged 6.5 h, 0.70 +/- 0.36 L/kg, and 3.0 +/- 2.6 ml/min/kg, respectively. After a single 150-mg oral dose, the peak plasma concentration of 1.3 +/- 0.55 microgram/ml was achieved 1 to 3 h after dosing. The mean apparent elimination half-life was 7.6 h. An estimated absorption lag time ranging from 14 to 37 min was observed in all but one patient. The mean absolute bioavailability for the oral dose was 87%. Dysrhythmia data were available in six patients. Complete (100%) suppression of ventricular ectopic beats occurred in four patients for 1/2 to 15 h after intravenous infusion, and in three patients for 7 to 25 h after oral dose. This suppression occurred with a plasma pirmenol level as low as 0.4 microgram/ml. No significant side effects were observed.


Resource use by an introduced and native carrion flies.
The carrion fly Chrysomya rufifacies has recently been introduced to North America. Larvae of this species are facultative predators on other carrion larvae, and are known to reduce populations of the New World fly Cochliomyia macellaria in the laboratory and in certain field situations. In order to identify conditions under which native taxa might avoid interaction with the invader, we examined broad patterns of resource use by capturing postfeeding larvae as they left a carcass. The Calliphorinae were least similar to C. rufifacies since they were able to exploit smaller carrion, showed a peak in density during cold weather while C. rufifacies numbers were low, and occurred much earlier than the invader during succession within a carcass. Phormia regina also was most abundant during cold weather. The Sarcophagidae were able to exploit smaller carcasses than the invader but are likely to encounter it in larger carcasses. C. macellaria was the species most similar to C. rufifacies in carrion use, and probably is reduced in number by the invader wherever they coexist. In contrast to all other taxa, C. rufifacies exited a carcass alone, suggesting that other larvae of the same age were attacked. Manipulation of a conspicuous predator, the ant Solenopsis invicta, revealed a negative effect on numbers of P. regina and C. macellaria.


Arm strength training improves activities of daily living and occupational performance in patients with COPD.
Arm strength training may improve functional performance for patients with chronic obstructive pulmonary disease (COPD). This trial investigated the effects of arm strength training on arm exercise capacity, activities of daily living (ADL) and occupational performance in patients with COPD. These was a randomized controlled trial in an outpatient clinic. Forty-two stable patients with COPD were randomly assigned into treatment and control groups. The treatment group underwent an 8-week (23 sessions) arm strength training programme. Both groups completed daily breathing exercises at home. Tests included hand grip strength, arm ergometer test, the Glittre-ADL and ADL Simulation tests and measures included the Milliken ADL Scale (MAS) and the Canadian Occupational Performance Measure (COPM). Statistically significant increases were detected in hand grip strength and %hand grip strength values, peak arm ergometer workload and the number of ADL simulation test cycles for the treatment group (P < 0.05). Significant decreases were also found in dyspnea and arm fatigue perception during arm ergometer test, and heart rate and dyspnea perception during Glittre-ADL test in the treatment group (P < 0.05). The treatment group also showed significant increases in MAS-house cleaning and laundry and MAS-other activities integrated scores and COPM-performance and satisfaction scores (P < 0.05). Arm strength training increases peripheral muscle strength, arm exercise capacity, ADL performance and patients' ADL performance satisfaction. Training decreases dyspnea and arm fatigue perception during supported arm exercises, and dyspnea perception during ADL. Arm strength training is a reliable and feasible treatment for COPD patients.


Kainic acid and penicillin: differential effects on excitatory and inhibitory interactions in the CA1 region of the hippocampal slice.
The effects of kainic acid (KA, 0.05-1.0 microM), and penicillin (PN, 3.4 mM) were studied in the CA1 region of rat hippocampal slices. Three components of the overall input/output function were taken: (1) the amplitude of the presynaptic compound action potential (prevolley) vs stimulation current applied to Schaffer collaterals, (2) the magnitude of the focally recorded synaptic potential (population EPSP) vs prevolley amplitude; and (3) the amplitude of the focally recorded population spike vs population EPSP magnitude. Recurrent inhibition was measured using the antidromic-orthodromic paired pulse method. KA caused a significant and reversible enhancement of all 3 component input/output functions while having no effect on paired pulse inhibition. PN caused a left shift in the EPSP-population spike relationship and decreased or abolished paired pulse inhibition; the other two measures of excitability were not changed. These results suggest that PN and KA differ fundamentally in the mechanisms by which they produce seizures: PN by removing inhibition while not affecting neuronal excitability per se; KA by exerting a generalized excitatory effect on neural membranes and on synaptic function while leaving recurrent inhibition unchanged.


Physiological responses to hyposmotic stress in the supralittoral amphipod Talitrus saltator (Crustacea: Amphipoda).
We investigated the effect of hyposmotic stress upon osmotic capacity (OC), heart rate (HR) and heart rate variability (HRV) of an Atlantic population of the sandhopper Talitrus saltator. Strictly consecutive monitoring of cardiac activity and measurement of OC was achieved by employing a non-invasive infrared technique to monitor heart activity and direct cardiac puncture to collect the haemolymph. Body mass (range 60-160 mg) had no effect on mean HR nor the mean HRV in adult individuals of both sexes. Both OC and HR, but not HRV, were influenced by the interaction between osmotic stress and exposure time. In addition, OC and HR were coupled within a moderate range of osmotic stress, beyond which this association breaks down, and bradycardia and a positive correlation between HR and HRV occur. A possible rise in metabolic cost, indicated by HR increase, was described for hyper-osmotic regulation. This is the first assessment of the relationship OC and HR in a non-decapod crustacean, and the results indicate that, in sandhoppers, the disruptions of cardiac activity may lead to impairment in maintaining an efficient haemolymph osmotic regulation.


Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening.
Glutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals.


Degradable collagen/sodium alginate/polyvinyl butyral high barrier coating with water/oil-resistant in a facile and effective approach.
Degradable bio-based materials have been widely considered as functional coatings, however, it is a great challenge to fabricate biodegradable coatings with high barrier, water- and oil- resistance. In this work, such coatings were fabricated by using collagen fibers (CF), sodium alginate (SA), and polyvinyl butyral (PVB). CF and SA were mixed evenly and coated on Ca2+ pretreated filter paper. It was mainly due to the electrostatic adsorption between collagen fibers and sodium alginate, and the crosslinking between the adsorption products and Ca2+. By coating PVB solution, the barrier performance was further improved. Notably, the composite exhibited excellent water vapor resistance (48 g/m2·24 h), water resistance (31 g/m2), oil resistance (kit rating: 12/12) and good mechanical properties. This degradable, environmentally friendly, and simple composite paper method has excellent barrier properties, mechanical properties and fluorine-free properties, and will have many applications in the food and packaging fields.


Sex differences in susceptibility to development of contact hypersensitivity to dinitrochlorobenzene (DNCB).
We have investigated the differences between the sexes in the development of contact sensitivity induced by dinitrochlorobenzene (DNCB). Ten male and 12 female subjects were sensitized with DNCB (30 micrograms applied on a 1 cm patch test disc) and challenged 1 month later with doses of 8.8, 12.5, 17.7 and 25 micrograms. The responses were measured after 48 h as increase in skinfold thickness with Harpenden callipers. Females showed a larger response at all challenge doses studied, and the slope of the log-dose response curve was significantly steeper in females. We conclude that there are significant differences in delayed type hypersensitivity between males and females.


Randomized comparison of a 90 uF capacitor three-electrode defibrillation system with a 125 uF two-electrode defibrillation system.
A variety of factors, including the number of defibrillation electrodes and shocking capacitance, may influence the defibrillation efficacy of an implantable defibrillator system. Therefore, the purpose of this study was to compare the defibrillation energy requirement using a 125 uF two-electrode defibrillation system and a 90 uF three-electrode defibrillation system. The defibrillation energy requirements measured with both systems were compared in 26 consecutive patients. The two-electrode system used a single transvenous lead with two defibrillation coils in conjunction with a biphasic waveform from a 125 uF capacitor. The three-electrode system used the same transvenous lead, utilized a pectoral implantable defibrillator generator shell as a third electrode, and delivered the identical biphasic waveform from a 90 uF capacitor. The two-electrode system was associated with a higher defibrillation energy requirement (10.8 +/- 5.5 J) than was the three-electrode system (8.9 +/- 6.7 J, p < 0.05), however, the leading edge voltage was not significantly different between systems (361 +/- 103 V vs. 397 +/- 123 V, P = 0.07). The two-electrode system also had a higher shocking resistance (49.0 +/- 9.0 ohms vs. 41.4 +/- 7.3 ohms, p < 0.001) and a lower peak current (7.7 +/- 2.6 A vs. 10.1 +/- 3.7 A, p < 0.001) than the three-electrode system. A three-electrode defibrillation system that utilizes a dual coil transvenous lead and a subcutaneous pectoral electrode with lower capacitance is associated with a lower defibrillation energy requirement than is a dual coil defibrillation system with higher capacitance. This finding suggests that the utilization of a pectoral generator as a defibrillation electrode in conjunction with smaller capacitors is a more effective defibrillation system and may allow for additional miniaturization of implantable defibrillators.


Influence of group A streptococcal acid glycoprotein on expression of major virulence factors and internalization by epithelial cells.
A single transposon insertion upstream to the open-reading-frame identified as the streptococcal acid glycoprotein (sagp) gene rendered a Tn916 isolate of Streptococcus pyogenes with elevated susceptibility to internalization by the epithelial cells. The role of SAGP in S. pyogenes internalization was further studied using isogenic mutant containing an in-frame deletion within the sagp gene. The sagp mutant displayed slower growth-rate and showed 5-fold higher internalization efficiency than the parent strain. Transcription of sagp at the logarithmic phase, but not at the stationary phase of the growth was repressed by csrR, the global regulator gene. At the same time, mutation of the sagp gene partially decreased the transcription of hasA, a gene that is required for capsule synthesis. The mutation had no effect on transcription of the emm3 gene, encoding for the M protein. The most striking effect of the sagp mutation was a down-regulation of the streptococcal pyrogenic exotoxin B (SpeB) at both translational and transcriptional level. Treatment of the SAGP mutant cells with the exogenous mSpeB (mature protease) only partially reduced their susceptibility to internalization. The exogenous mSpeB was more effective in reducing the internalization efficiency of a speB mutant and brought it to the level observed for the parent strain. In overall, results show that CsrR, directly or indirectly, affects the expression of SAGP, and that the SAGP modulates expression of not only SpeB, but also other genes that facilitate S. pyogenes internalization.


Causal effects of maternal exposure to PM2.5 during pregnancy on depression symptoms in adolescence: Identifying vulnerable windows and subpopulations in a national cohort study.
Few studies have examined the causal relationship between chronic exposure to air pollutants during pregnancy and depression in adolescent offspring. In addition, it has not been investigated whether exposure is most harmful to adolescents in certain populations and at certain stages of pregnancy. A total of 1975 adolescents from 1632 families from the China Family Panel Study, a representative national longitudinal cohort, were included in this study. We used high-resolution satellite retrieval data to assess the PM2.5 exposure of mothers during pregnancy. Specifically, we employed a two-stage instrumental variable model (IV-2SLS) within the counterfactual causal inference framework, and selected and validated appropriate instruments, thereby mitigating potentially biased results arising from bi-direction between dependent and independent variables. This approach allowed us to explore the causal relationship between maternal PM2.5 exposure during pregnancy and adolescent depression symptoms. The endogeneity of air pollution during pregnancy and the need for a causal model were suggested by the results of the model comparisons. Using the IV-2SLS model, we found that maternal exposure to PM2.5 during pregnancy exacerbates depressive symptoms in the offspring during adolescence (β = 0.2, 95% CI: 0.05-0.34). We also found that exposure during the first trimester may cause greater harm. Adolescents with low household income, being male, irregular exercise habits, living in rural areas, and having mothers with poorer mental status may be more vulnerable. The findings suggest that maternal exposure to PM2.5 during pregnancy may have a negative impact on the depression symptoms of offspring in adolescence and that more attention should be paid to vulnerable populations and the window of vulnerability.


A new correlation belief function in Dempster-Shafer evidence theory and its application in classification.
Uncertain information processing is a key problem in classification. Dempster-Shafer evidence theory (D-S evidence theory) is widely used in uncertain information modelling and fusion. For uncertain information fusion, the Dempster's combination rule in D-S evidence theory has limitation in some cases that it may cause counterintuitive fusion results. In this paper, a new correlation belief function is proposed to address this problem. The proposed method transfers the belief from a certain proposition to other related propositions to avoid the loss of information while doing information fusion, which can effectively solve the problem of conflict management in D-S evidence theory. The experimental results of classification on the UCI dataset show that the proposed method not only assigns a higher belief to the correct propositions than other methods, but also expresses the conflict among the data apparently. The robustness and superiority of the proposed method in classification are verified through experiments on different datasets with varying proportion of training set.


Activation of invariant NKT cells exacerbates experimental visceral leishmaniasis.
We report that natural killer T (NKT) cells play only a minor physiological role in protection from Leishmania donovani infection in C57BL/6 mice. Furthermore, attempts at therapeutic activation of invariant NKT (iNKT) cells with alpha-galactosylceramide (alpha-GalCer) during L. donovani infection exacerbated, rather than ameliorated, experimental visceral leishmaniasis. The inability of alpha-GalCer to promote anti-parasitic immunity did not result from inefficient antigen presentation caused by infection because alpha-GalCer-loaded bone marrow-derived dendritic cells were also unable to improve disease resolution. The immune-dampening affect of alpha-GalCer correlated with a bias towards increased IL-4 production by iNKT cells following alpha-GalCer stimulation in infected mice compared to naïve controls. However, studies in IL-4-deficient mice, and IL-4 neutralisation in cytokine-sufficient mice revealed that alpha-GalCer-induced IL-4 production during infection had only a minor role in impaired parasite control. Analysis of liver cell composition following alpha-GalCer stimulation during an established L. donovani infection revealed important differences, predominantly a decrease in IFNgamma+ CD8+ T cells, compared with control-treated mice. Our data clearly illustrate the double-edged sword of NKT cell-based therapy, showing that in some circumstances, such as when sub-clinical or chronic infections exist, iNKT cell activation can have adverse outcomes.


Acceptable noise level: repeatability with Danish and non-semantic speech materials for adults with normal hearing.
The acceptable noise level (ANL) is used to quantify the amount of background noise that subjects can accept while listening to speech, and is suggested for prediction of individual hearing-aid use. The aim of this study was to assess the repeatability of the ANL measured in normal-hearing subjects using running Danish and non-semantic speech materials as stimuli and modulated speech-spectrum and multi-talker babble noises as competing stimuli. ANL was measured in both ears at two test sessions separated by a period ranging from 12 to 77 days. At each session the measurements at the first and the second ear were separated in time by 15-30 minutes. Bland-Altman plots and calculation of the coefficient of repeatability (CR) were used to estimate the repeatability. Thirty nine normal-hearing subjects. The ANL CR was 6.0-8.9 dB for repeated tests separated by about 15-30 minutes and 7.2-10.2 dB for repeated tests separated by 12 days or more. The ANL test has poor repeatability when assessed with Danish and non-semantic speech materials on normal-hearing subjects. The same CR among hearing-impaired subjects would imply too poor repeatability to predict individual patterns of future hearing-aid use.


Cell polarity: the ups and downs of the Par6/aPKC complex.
A signaling complex in which atypical protein kinase C associates with a regulatory protein, Par6, plays an essential role in establishing cell polarity. Recent studies in organisms ranging from worms to mammals have highlighted some of the conserved mechanisms by which the assembly, localization and activity of this complex are regulated. Recent work is also beginning to unravel how this complex acts in concert with additional molecular complexes to establish and maintain polarity.


Corticosteroids lead to short-term improvement in cerebral amyloid angiopathy-related inflammation.
Cerebral amyloid angiopathy - related inflammation (CAA-ri) is an uncommon manifestation of CAA. Single-center, retrospective review of all charts with ICD-code I68.0 (CAA) from 2/2/2016-1/1/2020. Of 152 CAA cases, 13 (8.6%) were consistent with CAA-ri. Corticosteroid-treatment led to short-term reduction in modified Rankin Scale scores (2.6 ± 1.4 vs. 1.6 ± 1.5; p = 0.01) and T2/FLAIR lesion volume (78.1 ± 52.2 cm3 vs. 30 ± 30.9 cm3, p < 0.01) as well as short-term improvement in post-treatment Clinical Global Impression - Global Change scores compared to pre-treatment scores (clinical: 6 ± 1 vs. 2.6 ± 1.3, p = 0.03; radiological: 4.6 ± 1.9 vs. 1.2 ± 0.4, p = 0.03). Corticosteroid-treatment leads to clinical and radiological short-term improvement (class IV evidence).


Development of an on-site rapid real-time polymerase chain reaction system and the characterization of suitable DNA polymerases for TaqMan probe technology.
On-site quantitative analyses of microorganisms (including viruses) by the polymerase chain reaction (PCR) system are significantly influencing medical and biological research. We have developed a remarkably rapid and portable real-time PCR system that is based on microfluidic approaches. Real-time PCR using TaqMan probes consists of a complex reaction. Therefore, in a rapid real-time PCR, the optimum DNA polymerase must be estimated by using actual real-time PCR conditions. In this study, we compared the performance of three DNA polymerases in actual PCR conditions using our rapid real-time PCR system. Although KAPA2G Fast HS DNA Polymerase has the highest enzymatic activity among them, SpeedSTAR HS DNA Polymerase exhibited better performance to rapidly increase the fluorescence signal in an actual real-time PCR using TaqMan probes. Furthermore, we achieved rapid detection of Escherichia coli in 7 min by using SpeedSTAR HS DNA Polymerase with the same sensitivity as that of a conventional thermal cycler.


Pulmonary Manifestations of Systemic Vasculitis in Children.
Vasculitides are defined according to the vessel size involved, and they tend to affect certain organ systems. Pulmonary involvement is rare in the common childhood vasculitides, such as Kawasaki disease, IgA vasculitis (Henoch Schonlein purpura). On the other hand, lung involvement is common in a rare pediatric vasculitis, granulomatosis with polyangiitis (GPA) (Wegener granulomatosis), where respiratory system findings are common. A criterion in the Ankara 2008 classification criteria for GPA is the presence of nodules, cavities, or fixed infiltrates. The adult data suggest that rituximab may be an alternative to cyclophosphamide in induction treatment.


The comparative efficacy of four broad spectrum anthelmintics against some experimentally induced trichostrongylid infections in sheep and goats.
A controlled slaughter trial was undertaken to compare the efficacies of oxfendazole (5 mg/kg), morantel citrate (10 mg/kg), levamisole (8 mg/kg) and ivermectin (0.2 mg/kg) against experimentally induced infections of adult Haemonchus contortus, Ostertagia spp., Trichostrongylus colubriformis and Cooperiacurticei in sheep and goats. Ivermectin and oxfendazole achieved similar levels of efficacy in both hosts against all four worm genera as did levamisole and mortantel against H. contortus and C. curticei. Against Ostertagia spp. and T. colubriformis, however, the latter two drugs were less effective in goats than sheep. Neither the numbers of Ostertagia spp. removed from goats by levamisole (81% reduction) nor the numbers of T. colubriformis removed from goats by morantel (56% reduction) were statistically significant (P>0.05).


Vimentin plays an important role in the promotion of breast cancer cell migration and invasion by leucine aminopeptidase 3.
Breast cancer is a common type of cancer in females. Our previous studies indicated that leucine aminopeptidase 3 (LAP3) promotes migration and invasion of breast cancer cells. Vimentin is a mesenchymal marker, and its upregulation represents the promotion of epithelial-mesenchymal transition. In this study, we found that LAP3 and vimentin were highly expressed in breast cancer tissues, and the overexpression of LAP3 in breast cancer cells promoted the expression of vimentin. Western blot analysis indicated that the overexpression of LAP3 upregulated the phosphorylation of Erk1/2. MEK inhibitor PD98059 downregulated the expression of vimentin, matrix metalloproteinase-2/9 (MMP-2/9), and fascin through the inhibition of Erk1/2 activity. We hypothesized that LAP3 promoted tumor migration and invasion by upregulating vimentin. The knockdown of vimentin resulted in the inhibited migration and invasion of MDA-MB-231 and MDA-MB-468 cells. The expression of MMP-2/9 and fascin could also be downregulated. In conclusion, vimentin might play an important role in the promotion of breast cancer metastasis by LAP3.