Narcissism and birth order.
The purpose of this investigation was to clarify the relationship between birth-order position and the development of narcissism, while refining research and theory. The relationship between birth-order status and narcissism was examined with a sample of 79 undergraduate students (55 women and 24 men). These subjects were placed in one of the four following birth-order categories of firstborn, second-born, last-born, and only children. These categories were chosen given their significance in Adlerian theory. Each subject completed the Narcissistic Personality Inventory and a demographic inventory. Based on psychodynamic theory, it was hypothesized that firstborn children were expected to score highest, but statistical significance was not found for an association between narcissism and birth order. Further research is urged to investigate personality theory as it relates to parenting style and birth order.


Coffee Consumption Reduces Gout Risk Independently of Serum Uric Acid Levels: Mendelian Randomization Analyses Across Ancestry Populations.
The effects of coffee consumption on serum uric acid (SUA) levels and gout risk are controversial. There have hitherto been no reports based on Mendelian randomization (MR) analysis of its effects that consider pleiotropy. Here, we evaluated the effects of coffee consumption across ancestry populations, taking pleiotropy into account. We performed the first MR analyses for coffee consumption on SUA levels and gout, considering pleiotropy. We used the following summary statistics of genome-wide association studies from a Japanese population: habitual coffee consumption (152,634 subjects), gout (3053 cases and 4554 controls), and SUA levels (121,745 subjects). In addition to fixed-effect inverse variance weighted (IVW) meta-analysis, we performed a robust evaluation of heterogeneity and removed several instruments for reasons of possible pleiotropy. Previous European datasets were also reevaluated while heterogeneity was considered. Habitual coffee consumption was significantly and inversely associated with gout (odds ratio [OR] = 0.29, 95% confidence interval [95% CI]: 0.16-0.51, P = 1.9 × 10-5 ) in random-effect IVW (Phet = 5.5 × 10-19 ). Excluding pleiotropic instruments, the protective effect on gout was confirmed in fixed-effect IVW analysis (OR = 0.75, 95% CI: 0.58-0.97, P = 0.026) without heterogeneity (Phet = 0.39). However, we observed no significance in the previous European datasets when heterogeneity was considered. Associations were not observed between coffee consumption and SUA levels in either ancestry in MR analyses that considered pleiotropy. Multivariable MR analysis showed that increased coffee consumption significantly reduced gout risk, even after adjusting for SUA levels (OR = 0.50, 95% CI: 0.31-0.81, P = 0.0046). With pleiotropy taken into account, our MR analyses revealed that coffee consumption can causally reduce gout risk, and that it may reduce gout risk independently of SUA levels.


Ectopic bone formation is enhanced in senescent animals implanted with embryonic cells.
Ectopic bone formation induced by the subcutaneous implantation of demineralized bone matrix (DBM) is very significantly reduced in older Fischer 344 rats. Cells originating from calvaria of 20-day-old embryo donors were introduced into cylinders of DBM sealed at the ends with a Millipore filter or collagen sponges prior to subcutaneous implantation. Cells within the chambers had access to vascular channels that could penetrate through the interstices of the DBM. After four weeks of implantation in 26-month-old rats, the cylinders were full of bone. This bone was assessed by histologic techniques, by calcium and bone gamma-carboxyglutamic acid (gla) protein (BGP) concentrations, and by alkaline phosphatase activity. Cylinders to which no cells were added produced no bone. Bone marrow cells enclosed in similar cylinders or injected weekly at the implantation site also enhanced new bone formation but to a much lesser extent. Embryonic muscle cells formed large amounts of cartilage and less bone. Fibroblasts were inactive in this system. Prior treatment of the DBM with trypsin inhibited the myoblast response but not that of calvaria cells.


Increased insulin sensitivity and distorted mitochondrial adaptations during muscle unloading.
We aimed to further investigate mitochondrial adaptations to muscle disuse and the consequent metabolic disorders. Male rats were submitted to hindlimb unloading (HU) for three weeks. Interestingly, HU increased insulin sensitivity index (ISI) and decreased blood level of triglyceride and insulin. In skeletal muscle, HU decreased expression of pyruvate dehydrogenase kinase 4 (PDK4) and its protein level in mitochondria. HU decreased mtDNA content and mitochondrial biogenesis biomarkers. Dynamin-related protein (Drp1) in mitochondria and Mfn2 mRNA level were decreased significantly by HU. Our findings provide more extensive insight into mitochondrial adaptations to muscle disuse, involving the shift of fuel utilization towards glucose, the decreased mitochondrial biogenesis and the distorted mitochondrial dynamics.


The effect of nifedipine on ischemia-induced changes in the biochemical properties of isolated sarcolemmal vesicles and the ultrastructure of myocardium.
To investigate whether slow Ca2+ channel blockers protect against development of changes in properties of the sarcolemma and in the tissue ultrastructure during myocardial ischemia, nifedipine was administered prior to occlusion (up to 3 hours) of the left anterior descending coronary artery in anesthetized pigs. Intravenous doses which reduced arterial blood pressure by 20-25%, had no effect on the time-dependent reduction of Ca2+-calmodulin and cyclic AMP-dependent 32P incorporation into sarcolemmal phospholamban-like protein. Nifedipine blocked the reduction in the activity of sarcolemmal 5'-nucleotidase. Nifedipine had no significant effect on the long-chain fatty acylcarnitine accumulation in sarcolemma. A marked delay in the appearance of ultrastructural indicators of irreversible tissue injury in subepicardial myocardium was observed, when nifedipine was infused. Particularly the reduced appearance of electron-dense bodies in mitochondria suggested a reducing effect of nifedipine on cellular net gain of Ca2+. Apparently, ischemia-induced loss of the ability of the proteinkinases to incorporate phosphate into sarcolemmal phospholamban-like protein is not a process secondary to Ca2+ overload of the myocardium. The involvement of accumulation of long-chain fatty acylcarnitine within the sarcolemma may also be excluded. The membrane defect as indicated by a change in phosphorylation-mediated control of Ca2+ transport may itself be associated with the development of ischemia (-reperfusion)-induced Ca2+ overload.


One-step facile preparation of carbon dots with high fluorescence quantum yield and application in rapid latent fingerprint detection.
The development of luminescent materials greatly affects the development of fluorescence imaging technology. The preparation of carbon dots (CDs) with high photoluminescence quantum yield (PLQY) in the solid-state is challenging due to excessive resonance energy transfer (RET) and direct π-π interactions. In this study, we synthesized carbon dots that exhibit green fluorescence (GCDs) with absolute PLQYs up to 35.65% in one step by a microwave-assisted method. In the solid-state, the absolute PLQY reached 19.25%. Then, the GCDs were mixed with soluble starch in appropriate proportions, which improved the adsorption and dispersion of the GCDs and greatly reduced the cost of the fingerprint powder, and increased the absolute PLQY of the fingerprint powder to 41.75%. Finally, we prepared GCDs for preliminary fabrication of luminescent films, and the GCD-starch powder was successfully applied to high-quality latent fingerprint (LFP) imaging. The related properties of GCDs and the LFP detection performance of fingerprint detection powders prepared by GCDs were studied in detail. The results showed that the LFP system developed with GCDs-starch powder visualized LFPs with high definition and contrast under different conditions, and GCDs had potential for application in light-emitting devices. This study developed a new type of solid-state luminescent CDs and demonstrated that these GCDs have great application potential for LFP detection. This study may also provide inspiration for other applications based on efficient solid-state fluorescence.


Genetics and personalized medicine in antidepressant treatment.
Antidepressant medication is a major cornerstone in treatment of mood and anxiety disorders. Numerous substances are available on the market; however, only 60% of treated patients show sufficient response to medication and side effects are common. Lengthy trials are not uncommon until the optimized drug and dose is found and unfortunately, no valid predictors to match the 'right' drug to the 'right' patient exist nowadays. Genetic factors are thought to be involved as evidenced by numerous pharmacogenetic studies. This comprehensive review summarizes the most interesting findings and discusses clinical implications of pharmacogenetic results. We reviewed available literature on pharmacogenetics of antidepressant response and side effects until summer 2011 using the PubMed database. Promising findings exist for several variants in candidate genes involved in the pharmacokinetics or pharmacodynamics of antidepressants. These include association findings in the serotonin transporter gene (5-HTT), serotonin receptor genes, a gene coding an efflux pump in the blood-brain-barrier (ABCB1), and genes involved in the HPA axis. Promising candidate genes increasing risk for side effects include some of the genes associated with treatment response and cytochrome P450 genes. A high number of studies on pharmacogenetics of antidepressants have been published during the past decades. However, contradictory results still limit clinical use of these findings. Future studies should include functional analyses and consider gene-gene and gene-environment interactions. This will aid in facilitating a future use of pharmacogenetics in clinical practice, likely leading to improved patient care.


Pharmacokinetic evaluation of Chalcone derivatives with antimalarial activity in New Zealand White Rabbits.
Malaria is a major global health concern with the urgent need for new treatment alternatives due to the alarming increase of drug-resistant Plasmodium strains. Chalcones and its derivatives are important pharmacophores showing antimalarial activity. Determination of the pharmacokinetic variables at the preliminary step of drug development for any drug candidates is an essential component of in vivo antimalarial efficacy tests. Substandard pharmacokinetic variables are often responsible for insufficient therapeutic effect. Therefore, three chalcone derivatives, 1, 2, and 3, having antimalarial potency were studied further for potential therapeutic efficacy. In vivo pharmacokinetic studies of these three derivatives were performed on New Zealand White rabbits. The three derivatives were administered intra-peritoneally or orally at effective dose concentration and blood samples at different time points were collected. The determination of drug concentration was done through reverse phase-high performance liquid chromatography. The peak plasma concentration of derivative 1, 2, and 3 were 1.96 ± 0.46 µg/mL (intraperitoneal route), 69.89 ± 5.49 µg/mL (oral route), and 3.74 ± 1.64 µg/mL (oral route). The results indicate a very low bioavailability of these derivatives. The present study gives a benchmark to advance the investigation of more derivatives in order to revamp the pharmacokinetic variables while maintaining both potency and metabolic constancy.


Power of Words: Influence of Preexercise Information on Hypoalgesia after Exercise-Randomized Controlled Trial.
Exercise increases pressure pain thresholds (PPT) in pain-free individuals, known as exercise-induced hypoalgesia (EIH). Positive preexercise information can elicit higher EIH responses, but the effect of positive versus negative preexercise information on EIH is unknown. The primary aim of this randomized controlled trial was to compare EIH at the exercising thigh muscle after an isometric squat exercise between individuals receiving positive versus negative preexercise information about the effect of exercise on pain. Secondary aims were to compare EIH at nonexercising muscles between groups, and to investigate the relationship between participants' expectations and EIH. Eighty-three participants were randomly assigned to brief positive (n = 28), neutral (n = 28) or negative (n = 27) verbal information. The neutral information group was included in the study as a reference group. Pressure pain thresholds at the thigh and trapezius muscles were assessed before and after the intervention (i.e., preexercise information+squat exercise). Expectations of pain relief were assessed using a numerical rating scale (-10 [most negative] to 10 [most positive]). Change in quadriceps and trapezius PPT after the squat exercise showed a large difference between the positive and negative information groups (quadriceps, 102 kPa; 95% confidence interval, 55-150; effect size, 1.2; trapezius, 41 kPa; 95% confidence interval, 16-65; effect size:, 0.9). The positive information group had a 22% increase in quadriceps PPT whereas the negative information group had a 4% decrease. A positive correlation was found between expectations and increase in PPT. Negative preexercise information caused hyperalgesia after the wall squat exercise, whereas positive or neutral preexercise information caused hypoalgesia. Positive preexercise information did not change the magnitude of EIH compared with neutral information.


Surface Area of Patellar Facets: Inferential Statistics in the Iraqi Population.
Background. The patella is the largest sesamoid bone in the body; its three-dimensional complexity necessitates biomechanical perfection. Numerous pathologies occur at the patellofemoral unit which may end in degenerative changes. This study aims to test the presence of statistical correlation between the surface areas of patellar facets and other patellar morphometric parameters. Materials and Methods. Forty dry human patellae were studied. The morphometry of each patella was measured using a digital Vernier Caliper, electronic balance, and image analyses software known as ImageJ. The patellar facetal surface area was correlated with patellar weight, height, width, and thickness. Results. Inferential statistics proved the existence of linear correlation of total facetal surface area and patellar weight, height, width, and thickness. The correlation was strongest for surface area versus patellar weight. The lateral facetal area was found persistently larger than the medial facetal area, the p value was found to be <0.001 (one-tailed t-test) for right patellae, and another significant p value of < 0.001 (one-tailed t-test) was found for left patellae. Conclusion. These data are vital for the restoration of the normal biomechanics of the patellofemoral unit; these are to be consulted during knee surgeries and implant designs and can be of an indispensable anthropometric, interethnic, and biometric value.


Inter-Rater Agreement for Diagnosing Adenomyosis Using Magnetic Resonance Imaging and Transvaginal Ultrasonography.
Our aim was to compare the inter-rater agreement about transvaginal ultrasonography (TVS) with magnetic resonance imaging (MRI) with regard to diagnosing adenomyosis and for assessing various predefined imaging features of adenomyosis, in the same set of women. The study cohort included 51 women, prospectively, consecutively recruited based on a clinical suspicion of adenomyosis. MRIs and TVS videoclips and 3D volumes were retrospectively assessed by four experienced radiologists and five experienced sonographers, respectively. Each rater subjectively evaluated the presence or absence of adenomyosis, as well as imaging features suggestive of adenomyosis. Fleiss kappa (κ) was used to reflect inter-rater agreement for categorical data, and the intraclass correlation coefficient (ICC) was used to reflect the reliability of quantitative data. Agreement between raters for diagnosing adenomyosis was higher for TVS than for MRI (κ = 0.42 vs. 0.28). MRI had a higher inter-rater agreement in assessing wall asymmetry, irregular junctional zone (JZ), and the presence of myometrial cysts, while TVU had a better agreement for assessing globular shape. MRI showed a moderate to good reliability for measuring the JZ (ICC = 0.57-0.82). For TVS, the JZ was unmeasurable in >50% of cases, and the remaining cases had low reliability (ICC = -0.31-0.08). We found that inter-rater agreement for diagnosing adenomyosis was higher for TVS than for MRI, despite the fact that MRI showed a higher inter-rater agreement in most specific features. Measurements of JZ in the coronal plane with 3D TVS were unreliable and thus unlikely to be useful for diagnosing adenomyosis.


Asymmetric Arylative Dearomatization of β-Naphthols Catalyzed by a Chiral Phosphoric Acid.
An enantioselective arylative dearomatization reaction of β-naphthols with quinone monoimides has been developed for the first time using a chiral phosphoric acid as the catalyst, the desired enantioenriched cyclohexadienones were prepared with excellent yields and enantioselectivities by a domino Michael addition and aromatization process (up to 99 % yield, up to 98 % ee). This process is operationally simple and readily scaled up, as well as a broad substrate scope which includes 1-substituted-2-naphthols with/without 3-substituents. Furthermore, this organocatalytic procedure allows the lowering of catalyst loading to 0.5 mol % without considerable loss in reactivity and enantioselectivity.


Microbiota and pelvic inflammatory disease.
Female genital tract microbiota play a crucial role in maintaining health. Disequilibrium of the microbiota has been associated with increased risk of pelvic infections. In recent years, culture-independent molecular techniques have expanded understanding of the composition of genital microbiota and the dynamic nature of the microbiota. There is evidence that upper genital tract may not be sterile and may harbor microflora in the physiologic state. The isolation of bacterial vaginosis-associated organisms in women with genital infections establishes a link between pelvic infections and abnormal vaginal flora. With the understanding of the composition of the microbiota in healthy and diseased states, the next logical step is to identify the function of the newly identified microbes. This knowledge will further expand our understanding of the causation of pelvic infections, which may lead to more effective prevention and treatment strategies.


Guillain-Barré syndrome.
Individuals with Guillain-Barré syndrome (GBS) have sudden-onset polyneuropathy. This is characterised by muscle weakness, which occurs because of damage to the peripheral nervous system.


Identification and Characterization of a Trillin Rhamnosyltransferase From Dioscorea zingiberensis.
Dioscorea zingiberensis accumulates abundant steroidal saponins, such as dioscin, which is the principal bioactive ingredient displaying a wide range of pharmacological activities. Diosgenin is the aglycone of dioscin, and recently, genes encoding cytochrome P450 enzymes in the late steps of diosgenin biosynthesis have been isolated. Diosgenin was successfully synthesized in the cholesterol-producing yeasts. From diosgenin to dioscin, one glucose and two rhamnose groups need to be added. Although genes encoding UDP-glucosyltransferases converting diosgenin to trillin were isolated, genes encoding UDP-rhamnosyltransferases involved in dioscin biosynthesis remain unknown. In this study, we isolated the cDNA encoding the trillin rhamnosyltransferase (designated DzGT1) from D. zingiberensis. Heterologous expression of DzGT1 in Escherichia coli cells showed that the gene product exhibits an enzyme activity that glycosylates the trillin to form prosapogenin A of dioscin (PSA). The transcript level of DzGT1 is in accord with PSA accumulation in different organs of D. zingiberensis. Integration of the biochemical, metabolic, and transcriptional data supported the function of DzGT1 in dioscin biosynthesis. The identification and characterization of DzGT1 will help understand the metabolism of steroidal saponins in D. zingiberensis and provide candidate UDP-rhamnosyltransferase for efficient production of PSA, dioscin, and relevant steroidal saponins in microbial hosts.


A rare patient with a false median cleft lip associated with multiple congenital anomalies.
A girl manifesting a false median cleft lip associated with hypertelorism, anophthalmos, hydranencephaly with holoprosencephaly, and osteogenesis imperfecta, among other disorders, survived and was fed mainly milk products up to the age of 11. Then, surgical closure of the false median cleft lip was undertaken to improve the face aesthetically and to make the child more acceptable to society at large. The patient's median cerebrofacial dysgenesis with other anomalies was unique, compared with disorders reported in the literature. The embryological distinction between a false and true median cleft lip is also discussed.


Spectrotemporal characterization of photoluminescent silicon nanocrystals and their energy transfer to dyes.
Silicon nanocrystals (SiNCs) are a promising material for applications in bioanalysis and imaging. Compared to other types of semiconductor nanocrystals, the development and characterization of energy transfer (ET) configurations with SiNCs has been far more limited, resulting in an equally limited understanding of this process and its SiNC-specific nuances. Here, we present a systematic and detailed study of ET between SiNCs and dyes. A combination of spectroelectrophoresis and time-gated and time-resolved photoluminescence measurements were used to characterize the photophysical properties of ensembles of SiNCs and gain insight into how these properties varied as a function of nanocrystal size. ET between SiNC donors and a series of non-fluorescent Black Hole Quencher (BHQ) dyes and fluorescent sulfo-Cyanine 5.5 dye acceptors was evaluated in terms of spectral properties, wavelength-resolved efficiencies, trends with spectral overlap integral, and differences between two methods of BHQ association with the SiNCs. The overall results were consistent with a Förster resonance energy transfer (FRET) mechanism where the polydispersity of the SiNCs had a significant impact on the observed ET: the choice of wavelength and timing parameters were important, and ensemble measurements represented an average of heterogeneous ET behaviors. Prospective advantages and disadvantages of SiNCs as ET donors are discussed. This study serves as a foundation for the continued and optimized development of ET configurations with SiNCs.


Priority oral health research identification for clinical decision-making.
The Cochrane Library is a core resource for clinical decision-making globally, by clinicians, guideline developers, healthcare providers and patients.The publication of Cochrane Library systematic reviews concerning oral health conditions has grown exponentially to over 215 individual titles (as of 20 June 2015) during the past 20 years.Consequently, maintaining updates of the most clinically important reviews to provide up-to-date and accurate sources of evidence for decision-making has become a pressing concern for the editorial group behind their production, Cochrane Oral Health Group.To identify priority research required by oral health decision-makers, the Cochrane OHG embarked on a consultation process across eight defined areas of dentistry (periodontology, operative (including endodontics) and prosthodontics, paediatric dentistry, dental public health, oral and maxillofacial surgery, oral medicine, orthodontics, cleft lip and/or palate) with existing authors (by email), with members of the public (by online survey), and established internationally clinically expert panels for each area of defined area of dentistry to discuss and ratify (by teleconference) a core portfolio of priority evidence to be produced and maintained on the Cochrane Library.The resulting portfolio of priority research encompasses 81 existing titles to be maintained, and an additional 15 new systematic reviews to be developed by the Cochrane OHG in due course.The Cochrane OHG has actively responded to the outcomes of this prioritisation process by allocating resources to primarily supporting the maintenance of identified priority evidence for the Cochrane Library.


Effects of feedborne fusarium mycotoxins on brain regional neurochemistry of turkeys.
An experiment was conducted to investigate the effects of feeding grains naturally contaminated with Fusarium mycotoxins on brain regional neurochemistry of turkeys. The possible preventative effect of a poly-meric glucomannan mycotoxin adsorbent (GMA) was also determined. Forty-five 1-d-old male turkey poults were fed wheat-, corn-, and soybean meal-based diets up to wk 6, formulated with control grains, contaminated grains, or contaminated grains + 0.2% GMA. Deoxynivalenol was the major contaminant, and the concentrations were 2.2 and 3.3 mg/kg of feed during starter and grower phases, respectively. Concentrations of brain monoamine neurotransmitters and metabolites were measured in discrete regions of the brain including the pons, hypothalamus, and cortex by HPLC with electrochemical detection. Neurotransmitters and metabolites analyzed included norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA). The concentration of 5-HIAA and the 5-HIAA:5-HT-ratio were significantly decreased in pons after feeding contaminated grains. Dietary supplementation with GMA prevented these effects. In the pons, a significant positive correlation (r = 0.52, P < 0.05) was observed between the concentration of 5-HT and BW gain after feeding contaminated diets. The feeding of contaminated diet had no significant effects on the concentrations of neurotransmitters and metabolites in hypothalamus and cortex. It was concluded that consumption of grains naturally contaminated with Fusarium mycotoxins adversely altered the pons serotonergic system of turkeys. Supplementation with GMA partially inhibited these effects.


[Imbalanced T cell-specific transcription factors T-bet and GATA-3 contributes to type 2 T helper cell polarization in asthmatic patients].
To identify the T helper cell predominant differentiation in asthmatic patients and to explore the modulation of T cell-specific transcription factors T-bet/GATA-3. Thirty-two asthmatic patients were enrolled, among whom 18 were atopic defined by positive antigen skin test and 12 were children. Lymphocytes were isolated from peripheral blood and incubated with PHA (100 microg/ml) at 37 degrees C for 48 hours. INF-gamma and IL-4 concentrations in the supernatant were detected by ELISA. The T-bet and GATA-3 mRNA expression levels in lymphocytes were assayed by reverse transcription-polymerase chain reaction (RT-PCR) while the ratio of CCR3+ and CCR5+ cells in lymphocytes was counted by flow cytometry (FCM) after direct immunofluorescence staining. IL-4 concentration in the lymphocyte supernatant of the asthmatic group was (118 +/- 25) microg/L, which was significantly elevated compared to that of the healthy control group (75 +/- 12) microg/L (P < 0.01). When subgroups of asthmatic patients were compared, the results showed that atopic subjects had a higher IL-4 level than non-atopic subjects [(126 +/- 23) microg/L vs (107 +/- 26) microg/L, P < 0.01], but no significant difference was demonstrated between adults and children [(118 +/- 25) micro g/L vs (121 +/- 25) microg/L, P > 0.05]. Significantly lower concentration of INF-gamma in the asthmatic group was detected as compared to the control [(651 +/- 85) microg/L vs (1 179 +/- 332) microg/L, P < 0.001]. The concentration of INF-gamma was higher in atopic subjects than in non-atopic subjects [(618 +/- 89) micro g/L vs (680 +/- 83) microg/L, P < 0.01], but no difference was found between adults and children. The percentage of CCR3+ cells in lymphocytes was (9.4 +/- 5.8)% in the asthmatic group and (4.9 +/- 2.3)% in the control (P < 0.05), while the percentages of CCR5+ cells was (6 +/- 7)% and (13 +/- 7)%, respectively (P < 0.05). RT-PCR revealed that T-bet mRNA expression levels were as follows: 0.13 +/- 0.03 in the asthmatic group and 0.18 +/- 0.04 in the control (P < 0.01); 0.120 +/- 0.030 in atopic subjects and 0.140 +/- 0.010 in the non-atopic subjects (P < 0.05); 0.120 +/- 0.020 in children and 0.130 +/- 0.020 in adults (P > 0.05). The levels of GATA-3 mRNA expression were 0.43 +/- 0.07 in asthma and 0.29 +/- 0.09 in the control (P < 0.01), however, no differences were found between atopic and non-atopic, children and adults (0.50 +/- 0.12 vs 0.40 +/- 0.10, 0.44 +/- 0.09 vs 0.43 +/- 0.07, respectively, P > 0.05). A positive correlation was found between concentration of INF-gamma and T-bet mRNA level (r=0.663, P < 0.01), while no correlation with GATA-3 mRNA expression was found. The concentration of IL-4 was negatively correlated with T-bet mRNA level (r=-0.250, P < 0.05) and positively with GATA-3 mRNA level (r=0.72, P < 0.01). It was interesting that a closer relationship existed between the ratio of T-bet to GATA-3 and the ratio of INF-gamma to IL-4 (r=0.873, P < 0.01). In asthma there is a tendency of Th2 polarization with over-production of Th2-like cytokines in which T-bet deficiency may be a key factor. T-bet might direct T cells to Th1 differentiation while GATA-3 orientated Th2 maturation. Considering the fact that committed Th2 cells underwent re-differentiation induced by T-bet, this novel Th1-specific transcription factor is a fascinating target gene for modifying to restore the Th1 and Th2 balance.


Numerical discrimination in Drosophila melanogaster.
Sensitivity to numbers is a crucial cognitive ability. The lack of experimental models amenable to systematic genetic and neural manipulation has precluded discovering neural circuits required for numerical cognition. Here, we demonstrate that Drosophila flies spontaneously prefer sets containing larger numbers of objects. This preference is determined by the ratio between the two numerical quantities tested, a characteristic signature of numerical cognition across species. Individual flies maintained their numerical choice over consecutive days. Using a numerical visual conditioning paradigm, we found that flies are capable of associating sucrose with numerical quantities and can be trained to reverse their spontaneous preference for large quantities. Finally, we show that silencing lobula columnar neurons (LC11) reduces the preference for more objects, thus identifying a neuronal substrate for numerical cognition in invertebrates. This discovery paves the way for the systematic analysis of the behavioral and neural mechanisms underlying the evolutionary conserved sensitivity to numerosity.


Sex-biased oviposition by a nursery pollinator on a gynodioecious host plant: Implications for breeding system evolution and evolution of mutualism.
Dioecy, a breeding system where individual plants are exclusively male or female, has evolved repeatedly. Extensive theory describes when dioecy should arise from hermaphroditism, frequently through gynodioecy, where females and hermaphrodites coexist, and when gynodioecy should be stable. Both pollinators and herbivores often prefer the pollen-bearing sex, with sex-specific fitness effects that can affect breeding system evolution. Nursery pollination, where adult insects pollinate flowers but their larvae feed on plant reproductive tissues, is a model for understanding mutualism evolution but could also yield insights into plant breeding system evolution. We studied a recently established nursery pollination interaction between native Hadena ectypa moths and introduced gynodioecious Silene vulgaris plants in North America to assess whether oviposition was biased toward females or hermaphrodites, which traits were associated with oviposition, and the effect of oviposition on host plant fitness. Oviposition was hermaphrodite-biased and associated with deeper flowers and more stems. Sexual dimorphism in flower depth, a trait also associated with oviposition on the native host plant (Silene stellata), explained the hermaphrodite bias. Egg-receiving plants experienced more fruit predation than plants that received no eggs, but relatively few fruits were lost, and egg receipt did not significantly alter total fruit production at the plant level. Oviposition did not enhance pollination; egg-receiving flowers usually failed to expand and produce seeds. Together, our results suggest that H. ectypa oviposition does not exert a large fitness cost on host plants, sex-biased interactions can emerge from preferences developed on a hermaphroditic host species, and new nursery pollination interactions can arise as negative or neutral rather than as mutualistic for the plant.


More money, fewer lives: the cost effectiveness of welfare reform in the United States.
We evaluated the economic benefits of Temporary Assistance to Needy Families (TANF) relative to the previous program, Aid to Families with Dependent Children (AFDC). We used pooled mortality hazard ratios from 2 randomized controlled trials-Connecticut Jobs First and the Florida Transition Program, which had follow-up from the early and mid-1990s through December 2011-and previous estimates of health and economic benefits of TANF and AFDC. We entered them into a Markov model to evaluate TANF's economic benefits relative to AFDC and weigh them against the potential health threats of TANF. Over the working life of the average cash assistance recipient, AFDC would cost approximately $28000 more than TANF from the societal perspective. However, it would also bring 0.44 additional years of life. The incremental cost effectiveness of AFDC would be approximately $64000 per life-year saved relative to TANF. AFDC may provide more value as a health investment than TANF. Additional attention given to the neediest US families denied cash assistance could improve the value of TANF.


Immunohistochemical detection of epithelial membrane antigen in normal perineurial cells and perineurioma.
The use of epithelial membrane antigen (EMA) as an immunohistochemical marker for normal and neoplastic perineurial cells is described. Normal perineurial cells react strongly for this antigen, which is also expressed by the cells of perineurioma. Instead, neurofibromas and schwannomas only show some peripheral or entrapped layers of EMA-positive cells. In traumatic and Morton's neuromas, bundles of neural fibers are wrapped in layers of EMA-positive perineurial cells. Neurothekeoma and granular cell tumor show no EMA reactivity. The detection of an epithelial marker in perineurial cells is in agreement with the concept of a "perineural epithelium" and seems to support a common embryologic origin for the perineurial cell and the equally EMA-positive arachnoidal cap cell. The availability of an immunohistochemical marker for the perineurial cell provides an easy and convenient tool for the evaluation of the participation of this cell in a variety of pathologic processes.


Epilepsy or stereotypy? Diagnostic issues in learning disabilities.
Approximately 0.8% of people in the general population have epilepsy. Within this group are specific sub-populations who co-present with other additional conditions, learning disability being one such example. Epilepsy rates are the highest of all in this subgroup, between 21% and 50% and positively correlated with degree of learning disability. In addition, in the more severe categories, problems frequently arise when attempting to differentiate epileptic events from other phenomenon, such as stereotyped behaviours and involuntary movements. The individual is unable to communicate changes in consciousness and perception and observers often find it difficult to detect such changes, particularly with regard to the partial epilepsies. Intensive monitoring using EEG and video equipment can often prove valuable in such a situation in assisting carers to recognize epileptic episodes and respond accordingly.


Sappanin-type homoisoflavonoids from Scilla nervosa inhibits acetylcholinesterase enzyme: a combined in silico and in vitro approach.
Alzheimer's disease is among the major health challenges that currently attract the attention of health care givers and drug discovery and development experts worldwide. This study investigated the acetylcholinesterase inhibitory activity of sappanin-type homisoflavonoids isolated from the inter-bulb surface of Scilla nervosa. Molecular docking, molecular dynamics simulation, ADMET and in vitro studies were performed to identify the hit molecules, understand their binding mode and interaction, druggability and establish their inhibitory potentials against acetylcholinesterase enzyme. The hit compounds 5, 2, 1 and 4 were identified as the hit molecules through the molecular docking. The molecular dynamics simulation and MM-PBSA analysis showed the hit homoisoflavonoids established stability and good binding affinity against the acetylcholinesterase enzyme. Also, 5 elicited the best inhibitory activity followed by 2, 1 and 4 in the in vitro experiment. Furthermore, the selected homoisoflavonoids exhibit interesting drug likeness and pharmacokinetic properties as drug candidate. The results suggest further investigations towards the development of the phytochemicals as possible acetylcholinesterase inhibitors.Communicated by Ramaswamy H. Sarma.


Clinicoradiologicial aspects of secretory carcinoma breast: A rare pediatric breast malignancy.
Secretory carcinoma (juvenile carcinoma) is one of the very rare breast malignancy reported to be prevalent in pediatric age group. We report imaging and clinicopathological features of secretory carcinoma breast with distant and axillary metastasis, in an 11-year-old girl, who presented with a painful lump in right breast. Ultrasound revealed a well-defined, partially microlobulated hypoechoic mass with skin and pectoralis muscle involvement and a suspicious morphology right axillary lymph node. Color Doppler revealed increased vascularity in both the breast mass and suspicious axillary node. Magnetic resonance imaging helped in better evaluation of pectoralis muscle involvement. Computed tomography (CT) neck, chest, and abdomen revealed multiple fibronodular opacities in bilateral lung fields. 18 Flouro-Deoxy-Glucose Positron Emission Tomography (FDG PET-CT) showed a hypermetabolic retroareolar breast mass with multiple hypermetabolic bilateral lung nodules suggesting lung metastasis. The histopathology confirmed the diagnosis of secretory carcinoma. The patient was offered chemotherapy for 2 years and put on follow-up since then.


Community-acquired methicillin-resistant Staphylococcus aureus, Finland.
Methicillin-resistant Staphylococcus aureus (MRSA) is no longer only hospital acquired. MRSA is defined as community acquired if the MRSA-positive specimen was obtained outside hospital settings or within 2 days of hospital admission, and if it was from a person who had not been hospitalized within 2 years before the date of MRSA isolation. To estimate the proportion of community-acquired MRSA, we analyzed previous hospitalizations for all MRSA-positive persons in Finland from 1997 to 1999 by using data from the National Hospital Discharge Register. Of 526 MRSA-positive persons, 21% had community-acquired MRSA. Three MRSA strains identified by phage typing, pulsed-field gel electrophoresis, and ribotyping were associated with community acquisition. None of the strains were multiresistant, and all showed an mec hypervariable region hybridization pattern A (HVR type A). None of the epidemic multiresistant hospital strains were prevalent in nonhospitalized persons. Our population-based data suggest that community-acquired MRSA may also arise de novo, through horizontal acquisition of the mecA gene.


Dose-dependent inhibition of cold air-induced bronchoconstriction by atropine.
We undertook a study to demonstrate whether inhalation of atropine could inhibit cold air-induced bronchoconstriction in a dose-dependent fashion. In seven subjects with asthma we assessed the effects of placebo and of various doses of inhaled atropine (0.13-2.08 mg) on a base-line specific airway resistance (sRaw) and on the increase in sRaw produced by 5 min of voluntary eucapnic hyperventilation with subfreezing air at -17 degrees C. We also assessed the effect of the lowest doses of atropine on the increase in sRaw produced by five breaths of 1.0% metacholine. Atropine in doses of 0.13 or 0.26 mg caused a maximal reduction in base-line sRaw and completely inhibited the effect of 1.0% methacholine on sRaw, but it did not inhibit the bronchomotor response to cold air. Higher doses of atropine did inhibit the effect of cold air on sRaw in a dose-dependent fashion. The dose of atropine required to inhibit this effect of cold air varied with the increase in sRaw produced by cold air after placebo. These results suggest that cold air causes bronchoconstriction through vagal pathways and that higher doses of antimuscarinic agents are required to inhibit vagally mediated bronchoconstriction than those required to reduce base-line airway tone or to inhibit the effects of a large dose of an inhaled muscarinic agonist.


Patterned-wettability-induced alteration of electro-osmosis over charge-modulated surfaces in narrow confinements.
In the present study, we focus on alterations in flow physics as a consequence of interactions between patterned-wettability gradients on microfluidic substrates with modulated surface charge distributions, giving rise to an intricate electrohydrodynamic coupling over small scales. We demonstrate that by exploiting such intricate coupling, it may be possible to pattern vortices occurring in the fluidic confinement by exploiting an interplay between the Navier slip and electro-osmotic transport. Our studies do reveal that the resultant flow structure originating out of the spatially periodic variations in the surface charge and surface wettability may depend critically on several independently tunable controlling parameters, such as the amplitudes and frequencies of the respective patterning functions, the phase shift between the two, an asymmetry factor, and the channel height to Debye length ratio. We show that judicious choices with regard to the combinations of these parameters may result in significant augmentations in the corresponding mixing efficiency without any appreciable compromise in the net microfluidic throughput. Furthermore, our studies reveal an optimum patterning frequency, which results in the most efficient microfluidic mixing within the constraints of achieving a desired volumetric flow rate. Our results also demonstrate that the net flow rate is maximized when the surface wettability variation functions and surface charge-density functions are in phase, whereas mixing is best facilitated when they are in opposite phase. In practice, therefore, one may select an intermediate value of the phase angle depending on the extent of compromise necessary between flow rate and mixing characteristics, yielding far-ranging scientific and technological advances toward an improved design of miniaturized fluidic devices of practical relevance.


Maternal identification: a description of the process in real time.
This research, using the method of microanalysis, explores the to-and-fro activity of the self- and object representational world of mothers as they observe their children. Under examination is a "moment" usually lasting not more than 5-20 seconds that was selected by the mother as outstanding to her during the time she was observing her child. A microanalytic interview technique was developed in which the mother is asked about everything she experienced about "the moment," including what she was feeling, imagining, doing, perceiving, and remembering. At brief intervals she was asked to indicate on a scale where--on herself or her child--her experience was centered. These data were organized in terms of tracking the locus of the mother's perspective: from dwelling in her own mind (self-representation) to inhabiting that of her child (object representation). Results indicate that these representational shifts occurred frequently, usually every one to three seconds, and that there were significant individual differences among the mothers.


Measurement Invariance of the Short Home Attachment Scale: A Cross-Cultural Study.
The home environment is a particularly significant part of life that is supposed to satisfy inhabitants' needs, form their identity, and contribute to psychological wellbeing. The construct of home attachment is especially relevant for students as a most mobile social group. This study is devoted to the validation of the Short Home Attachment Scale (SHAS) in a student sample from five countries (Armenia, India, Indonesia, Russia, and Ukraine). A total of 1,349 (17-26 years; Mage = 19.82, SDage = 2.14; 78% females) university students participated in the study and filled in the 14 items of HAS. In order to avoid redundant items with high error covariances damaging the model, a new scale-the SHAS was developed by eliminating seven items. The shortened scale has satisfactory structure validity in terms of model fit in all countries except Indonesia; internal reliability values were acceptable in all countries. Measurement invariance across countries was tested with Multi-Group Confirmatory Factor Analysis (MG CFA) and Alignment Analysis. MG CFA confirmed both configurational and metric invariance. The invariance of item factor loadings, as well as item intercepts, was also confirmed by the Alignment Analysis. The mean scores varied across cultures, with the highest in India and the lowest in Russia. The final version of SHAS is a valid, reliable tool that may be recommended for use in cross-cultural research. However, the SHAS factor structure robustness in the Indonesian population should be investigated thoroughly.


Complete and remarkable reversal of chemoselectivity in [4 + 2] cycloadditions involving electron-poor indoles as dienophiles. Diels-Alder versus hetero-Diels-Alder processes.
The reaction between indole-3-carboxaldehyde 1a or indole-3-glyoxalate 1b and 2,3-dimethylbutadiene under thermal activation leads exclusively to the Diels-Alder cycloadducts resulting from the participation of the indole 2,3-carbon-carbon double bond. The concomitant use of zinc chloride and high pressure (16 kbar) induces the primary cycloadduct to react further, and biscycloadducts 11 and 12 are now isolated in high yields, the result of two consecutive [4 + 2] processes on, first, the indole 2,3 C=C bond and, second, the 3-carbonyl unit. The possibility of using two different dienes in a tandem, sequential process is demonstrated by the preparation of tetracycle 13. Interactions between the carbonyl dienophile and Danishefsky diene yield exclusively yet another type of product, namely the gamma-dihydropyranones arising from the sequential [4 + 2] heterocycloaddition, hydrolysis of the silyl enol ether, and loss of methanol. Isolation of the Mukaiyama-type adduct 16 indicates that a stepwise mechanism may be involved, at least under zinc chloride catalysis. N,N-Disubstituted indole-3-glyoxamides undergo the expected, usual Diels-Alder process, with the 2,3 C=C bond acting as dienophile, and cycloadducts of the type 3 are obtained in high yields, regardless of the mode of activation. Remarkably, however, N-monosubstituted indole-3-glyoxamides react almost exclusively as heterodienophiles, the 3-carbonyl unit being now the preferred site of reactivity, and gamma-dihydropyranones of the type 6 are isolated in yields ranging from 72 to 92%. Conformational analysis of the Diels-Alder adducts based on both (1)H NMR spectrometry and X-ray diffraction data indicates that the newly created cyclohexene and cyclohexanone rings adopt a pseudoboat conformation.


Persistent dyspnea and leg edema.
This case illustrates a complexity of confounding and overlapping symptoms that can masquerade as another diagnosis. A 56-year-old African American man with persistent dyspnea and leg edema was hospitalized three times in a period of 6 months. The patient was treated for asthma, chronic obstructive pulmonary disease, and congestive heart failure. Hypertension and peptic ulcer disease were treated also. Complete clinical improvement was not observed. A careful review of his last admission and current admission clinical presentation and laboratory evaluation revealed a systemic manifestation and laboratory findings consistent with atypical systemic lupus erythematosus.


The effect of adrenergic and cholinergic antagonists on central histaminergic stimulation of pituitary-adrenocortical response under stress in rats.
A possible interaction of central histaminergic receptors with adrenergic and cholinergic muscarinic neurons in increasing the pituitary-adrenocortical response under stress, assessed indirectly from the corticosterone concentration in blood serum, was investigated in conscious rats. All the drugs were administered intracerebroventriculary, the antagonists 15 to 30 min prior to the agonists. The histamine-induced increase in serum corticosterone levels of stressed rats was considerably antagonized by prazosin, phenoxybenzamine, phentolamine and yohimbine, alpha 1 and alpha 2-adrenergic antagonists. These antagonists abolished or significantly attenuated the corticosterone response to 2-pyridylethylamine (PEA), an H1-receptor agonist, and to dimaprit and 4-methylhistamine(4-MeHA), H2-receptor agonists. Propranolol, a beta-adrenergic blocker, did not substantially change the corticosterone response induced by histamine or histamine H1- and H2-receptor agonists. Similarly, atropine was ineffective in blocking the increase in serum corticosterone responses induced by either histamine or PEA and dimaprit in stressed rats. These results suggest that both alpha 1- and alpha 2-adrenergic receptors, but not beta-adrenergic and cholinergic muscarinic receptors interact with central H1 and H2 histaminergic stimulation of the increased pituitary-adrenocortical response in stressed rats.


Transient quadriceps paresis following cocaine use.
A 31-year-old man presented with bilateral thigh muscle paralysis several hours after intranasal cocaine use. His blood results showed a creatine kinase (CK) level of 3447 u/L and a normal renal function. He made a marked recovery in just 2 h following the intravenous normal saline 0.9%, and was able to walk. He was discharged home the next day.


VEGFR-1 and VEGFR-2: two non-identical twins with a unique physiognomy.
Angiogenesis involves endothelial cell differentiation, proliferation, migration and cord formation, which lead to tubulogenesis to form vessels. One group of growth factor receptors implicated in angiogenesis is the VEGFR family of receptor tyrosine kinases. VEGFR-1 and VEGFR-2 are closely related receptor tyrosine kinases and have both common and specific ligands. VEGFR-1 is a kinase-impaired RTK whereas VEGFR-2 is a highly active kinase. Despite their differential kinase activation potentials, both VEGFR-1 and VEGFR-2 are required for normal development and angiogenesis. VEGFR-1 regulates angiogenesis by mechanisms that involve ligand-trapping, receptor homo- and heterodimerization. VEGFR-2 stimulates variety of signaling pathways and broad biological responses in vitro. The mechanisms that govern VEGFR-2 activation, its ability to recruit signaling proteins and to undergo downregulation are highly regulated by its carboxyl terminus. This review highlights recent insights into the mechanism of activation of VEGFR-1 and VEGFR-2, and focuses on the signaling pathways employed by VEGFR-1 and VEGFR-2 that regulate angiogenesis.


Evaluation of Syncope in Older Adults.
The older adult patient with syncope is one of the most challenging evaluations for the emergency physician. It requires clinical skill, patience, and knowledge of specific older adult issues. It demands care in the identification of necessary resources, such as medication review, and potential linkage with several multidisciplinary follow-up services. Excellent syncope care likely requires reaching out to ensure institutional resources are aligned with emergency department patient needs, thus asking emergency physicians to stretch their administrative talents. This is likely best done as preset protocols prior to individual patient encounters. Emergency physicians evaluate elders with syncope every day and should rise to the challenge to do it well.


Effects of X irradiation on angiogenesis.
We have evaluated the effect of X irradiation on the mesenchymal tissue growth (blood capillaries and stromal cells) in an angiogenesis system in the mouse. This was accomplished by implanting a polyvinyl alcohol sponge disc in the subcutis of the thorax, and quantifying the extent of growth reduction of capillaries and stromal cells following graded doses of X rays. The sponge disc contained a centrally located pellet impregnated with 20 micrograms of epidermal growth factor and coated with a thin film of slow-releasing compound. Total growth of vessels and fibroblasts was determined by morphometric analysis of histologic sections. The incorporation of [3H]TdR was measured during a 24-h period. A dose-response relationship was observed when X irradiation was given on Day 11 after implantation, with the disc removed on Day 20. A single dose of 15 Gy reduced both the rate of incorporation of [3H]TdR and the total growth area. These and previous observations point to endothelial cells as important targets of ionizing radiation in the stroma, especially during the period of active proliferation of these cells, induced by growth factors.


Evanescent imaging with induced polarization by using a solid immersion lens.
Image contrast enhancement, high lateral resolution, and height information are obtained with induced polarization evanescent imaging using a solid immersion lens. Experiments are conducted by imaging features on a patterned Si substrate. Imaging theory is used to predict optimum orientation of high-spatial-frequency samples, and a topographical image is derived from the induced polarization image through a calibration procedure. A numerical aperture of 1.5 is used in the experiment. Height accuracy of +/-2 nm is demonstrated with a known sample.


Quantification of glutamate, glutamine, and other metabolites in in vivo proton NMR spectroscopy.
A reliable quantification of in vivo 1H MRS spectra is hampered by extensive line overlap, by intensity distortions due to the water suppressing pulse sequence and complex modulation patterns of J-coupled spins, and by deviations between the experimental and model lineshapes in computer fitting programs. By correcting the experimental lineshape, using a suitable pulse sequence, and incorporating prior knowledge about the spin systems and the intensity distortions, a sufficient quantification is possible. If reliable T2 values are available absolute concentrations can be determined.


Sexual Dimorphism and the Origins of Human Spinal Health.
Recent observations indicate that the cross-sectional area (CSA) of vertebral bodies is on average 10% smaller in healthy newborn girls than in newborn boys, a striking difference that increases during infancy and puberty and is greatest by the time of sexual and skeletal maturity. The smaller CSA of female vertebrae is associated with greater spinal flexibility and could represent the human adaptation to fetal load in bipedal posture. Unfortunately, it also imparts a mechanical disadvantage that increases stress within the vertebrae for all physical activities. This review summarizes the potential endocrine, genetic, and environmental determinants of vertebral cross-sectional growth and current knowledge of the association between the small female vertebrae and greater risk for a broad array of spinal conditions across the lifespan.


Participation of leukotriene D4 and tumor necrosis factor on lipopolysaccharide-induced airway hyperresponsiveness in guinea pigs.
In guinea pigs, a marked increase in airway responsiveness to acetylcholine (Ach) was observed at 2 h after lipopolysaccharide (LPS) inhalation. To examine the mediators responsible for the airway hyperresponsiveness, the changes of peptide-leukotrienes (LTs), tumor necrosis factor (TNF), interleukin-1 (IL-1), histamine and 5-hydroxytryptamine (5-HT) levels in bronchoalveolar lavage fluid (BALF) were measured. Airway responsiveness to Ach reached a peak 2 h after LPS inhalation. The influx of neutrophil into BALF increased gradually and reached a peak 24 h after LPS inhalation. After the inhalation of LPS, LTD4 and TNF contents in BALF increased within the first 2 h after LPS inhalation. However, other mediators were not detected or increased 6 h after LPS inhalation. Aeroinhalation of LTD4 and murine recombinant TNF-alpha caused airway hyperresponsiveness in guinea pigs. In addition, a LTD4 antagonist, BAYx7195, and an inhibitor of TNF, pentoxifylline, inhibited the LPS-induced airway hyperresponsiveness. These results suggest that LTs and/or TNF play an important role in the onset of airway hyperresponsiveness in guinea pigs.


Metabotropic glutamate receptor-mediated signaling in neuroglia.
Metabotropic glutamate (mGlu) receptors are G-protein-coupled receptors, which include eight subtypes that have been classified into three groups (I-III) based upon sequence homology, signal transduction mechanism and pharmacological profile. Although most studied with regard to neuronal function and modulation, mGlu receptors are also expressed by neuroglia-including astrocytes, microglia and oligodendrocytes. Activation of mGlu receptors on neuroglia under both physiologic and pathophysiologic conditions mediates numerous actions that are essential for intrinsic glial cell function, as well as for glial-neuronal interactions. Astrocyte mGlu receptors play important physiological roles in regulating neurotransmission and maintaining neuronal homeostasis. However, mGlu receptors on astrocytes and microglia also serve to modulate cell death and neurological function in a variety of pathophysiological conditions such as acute and chronic neurodegenerative disorders. The latter effects are complex and bi-directional, depending on which mGlu receptor sub-types are activated.


Gastric and duodenal mucosal ornithine decarboxylase and damage after corticosterone.
We recently found that stress increases gastric and duodenal ornithine decarboxylase (ODC) activity and damages both tissues. The current study investigated whether corticosterone induces ODC activity in gastric and duodenal mucosa in rats and compared plasma corticosterone levels after stress and treatment with corticosterone to determine whether this hormone mediated the effects of stress on the mucosa. Rats were fasted 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for 6 h. Stress markedly increased plasma corticosterone levels; the increase was 10.5 times control and lasted the duration of stress. The maximum increase was observed 1 h after a single injection of corticosterone (5 mg/kg sc) and represented 11.1 times control values. By 6 h, plasma corticosterone had returned to normal levels. A single injection of corticosterone had no effect on the gastric mucosa, but duodenal ODC was increased significantly from 4 to 8 h after injection, peaking at 6 h. Histological examination revealed no damage in either tissue. Administration of corticosterone three times daily for 3 days dramatically elevated ODC activity and produced significant microscopic damage. The surface epithelium of the stomach was disrupted, with many surface cells shed, and most villi were absent from the duodenal mucosa. Corticosterone also markedly decreased DNA and RNA content of both tissues. Inhibition of ODC with DL-alpha-difluoromethylornithine additionally decreased DNA, RNA, and protein content, exacerbating the damage.(ABSTRACT TRUNCATED AT 250 WORDS)


[Successful multi-step management of developmental heart defects after intrauterine diagnosis].
At 28th week of gestation a conotruncal malformation with ventricular septal defect was diagnosed by fetal echocardiography. Postnatal echocardiographic and angiocardiographic examinations confirmed the diagnosis of conotruncal malformation (pulmonary atresia, ventricular septal defect, patent ductus arteriosus, aortopulmonary collateral arteries). The unifocalization (age: 11 months) and total correction with aortic homograft (age: 7 years) were performed. To our knowledge our case is the first whose intrauterine diagnosis of complex congenital heart disease was confirmed after delivery and had successful two-stage surgical management.


Use of an advanced formulation of beta-tricalcium phosphate as a bone extender in interbody lumbar fusion.
Despite numerous advances in the development of bone graft substitutes over the past 20 years, iliac crest autograft remains the gold standard for lumbar spinal fusion. However, donor site morbidity associated with the harvesting of iliac crest autograft remains problematic. Acute and chronic pain, prolonged operative time, bleeding, infection, deformity, and nerve and vascular injury still produce significant postoperative morbidity, even in the presence of careful surgical technique. Although allograft circumvents donor site morbidity, the growing number of spinal fusions performed in the United States and worldwide is creating a shortage of cadaver bone acceptable for use. Additionally, the extensive processing and storage of allograft is expensive. Synthetic materials, such as beta-tricalcium phosphate (beta-TCP), have been developed as alternatives to both autograft and allograft. A novel formulation of ultraporous beta-TCP (Vitoss, Orthovita, Malvern, Pa) offers interconnected microporosity, providing it with good wicking and hydrophilic properties. These properties allow the migration of nutrients, growth factors, and osteogenic cells into the ultraporous beta-TCP scaffold, thereby promoting new bone growth and concurrent scaffold resorption. This study presents a retrospective review of 7 patients who underwent anterior (ALIF) or posterior (PLIF) interbody fusion at 12 levels with a 3- to 6-month follow-up. At the patients' last radiographic examination, all 12 levels were solidly fused with interbody grafting material consisting only of allograft plus a combination of ultraporous beta-TCP and venous blood as an extender. Additionally, all 7 patients had segmental pedicle-screw fixation.


Case Report: Low-Frequency Repetitive Transcranial Magnetic Stimulation to Dorsolateral Prefrontal Cortex and Auditory Cortex in a Patient With Tinnitus and Depression.
Repetitive transcranial magnetic stimulation (rTMS) has been widely used as a promising therapy for tinnitus. However, the exact target and stimulation sequence of rTMS that is most effective for treating tinnitus remains unclear. Here, we report a case of a 62-year-old man with treatment-refractory tinnitus and depression whose symptoms markedly improved after undergoing low-frequency rTMS over the right-side dorsolateral prefrontal cortex and left auditory cortex area. Our report indicates that low-frequency rTMS treatment that stimulates multiple brain regions sequentially is feasible and may clinically benefit patients with tinnitus and depression.


Microembolus detection in four patients with Fabry's disease: further support for a primarily microangiopathic origin of early cerebrovascular symptoms.
Fabry's disease is a sex-linked recessive storage disorder leading to cerebrovascular symptoms in many cases. Whether the primary origin of cerebrovascular symptoms in these patients is due to autochthonous thrombosis of small vessels or embolic infarction from large vessels is under debate. Microembolic signals (MES) indicative of an active embolic source can be recorded by transcranial Doppler sonography. We report four patients (34, 44, 62 and 66 years old) with Fabry's disease from one kindred in whom we carried out microembolus detection recordings to disclose active embolic sources. Three of the patients had had transient focal neurological deficits. Two patients had angina pectoris and one had exercise dyspnea, but no patient had clear evidence of disease of the large coronary vessels or brain-supplying arteries. No MES were found in 1-hour recordings in any patients, supporting the hypothesis that early cerebrovascular symptoms arise from small vessel occlusion and not from embolic sources as an indicator of disease of large brain-supplying arteries or cardiac embolism.


Comparison of Serum Apolipoprotein Levels of Diabetic Children and Healthy Children with or without Diabetic Parents.
Introduction. The association of diabetes and atherosclerosis with disorders of lipids and lipoproteins, notably high apolipoprotein B (apoB) and low apolipoprotein A1(apoA1) is well established. Because of the beginning of the atherosclerosis' process from early life, in this study, the plasma levels of apoA1 and apoB were compared in diabetic children with type I diabetes mellitus(DM), healthy children with diabetic parents (HDPs),and healthy children with nondiabetic parents (HNDPs). Methods. This case-control study was conducted among 90 children aged 9-18 years. Serum levels of apoA and apoB were compared among 30 diabetic children (DM), 30 healthy children with diabetic parents (HDPs), and 30 healthy children with nondiabetic parents (HNDP). Results. The mean serum apoA1 was higher in DM (153 ± 69 mg/dL) followed by HNDPs (138 ± 58 mg/dL) and HDPs (128 ± 56 mg/dl), but the difference was not statistically significant. The mean apoB value in HNDPs was significantly lower than DM and HDPs (90 ± 21 mg/dL versus 127 ± 47 and 128 ± 38 mg/dL, P < 0.05, respectively). The mean apoB levels in DM (127 ± 47 mg/dl) and HDP (128 ± 38 mg/dL) were not statistically significantly different (P > 0.05). Conclusions. Diabetic children and healthy children with diabetic parent(s) are at higher risk of dyslipidemia and atherosclerosis. Thus for primordial and primary prevention of atherosclerosis, we suggest screening these children for low plasma apoA1 and high plasma apoB levels.


Oviedomycin, an unusual angucyclinone encoded by genes of the oleandomycin-producer Streptomyces antibioticus ATCC11891.
Our investigations on the discovery of novel natural metabolites using type II polyketide synthase gene probes (actI/III) yielded an unusual angucyclinone, oviedomycin (2), when applied to the oleandomycin (1) producer Streptomyces antibioticus ATCC11891. The novel natural product was produced using S. albus R(-)M(-) as a host strain, into which a cosmid containing the oviedomycin gene cluster was transformed. Its structure was elucidated by NMR spectroscopy and mass spectrometry.


Protection of renal ischemia injury using combination gene silencing of complement 3 and caspase 3 genes.
Ischemia/reperfusion (I/R) injury occurs in clinical kidney transplantation, which results in graft dysfunction and rejection. It has been documented that I/R injury is associated with complement activation and renal cell apoptosis. The purpose of this study was to develop a strategy to prevent I/R injury using small interfering RNA (siRNA) that target complement 3 (C3) and caspase 3 genes. siRNA-expression vectors were constructed to target C3 and caspase 3 genes. Gene silencing efficacy was assessed using real-time polymerase chain reaction. In vivo gene silencing was performed by hydrodynamic injection with C3 and caspase 3 siRNA. Renal I/R injury was induced through clamping the renal vein and artery for 25 min. I/R injury was evaluated using kidney histopathology, blood urea nitrogen (BUN), serum levels of creatinine, and survival. Effective gene silencing was first confirmed in vitro. Notably upregulated expression of C3 and caspase 3 genes was observed from 2 to 48 hr after I/R injury, which were effectively and specifically inhibited by C3 and caspase 3 siRNA. In comparison with control mice, serum levels of creatinine and BUN were also significantly decreased in C3 and caspase 3 siRNA-treated mice. Furthermore, the therapeutic effect of siRNA was assessed in a severe, lethal I/R injury experiment, in which siRNA treatment significantly reduced mortality. Tissue histopathology showed an overall reduction in injury area in siRNA-treated mice. This is the first demonstration that renal I/R injury can be prevented through silencing the complement gene and apoptosis gene, highlighting the potential for siRNA-based clinical therapy.


Formation of the prohead core of bacteriophage T4 in vivo.
Formation of the prohead core of bacteriophage T4 was not dependent on shell assembly. In mutant infections, where the production or assembly of active shell protein was not possible, naked core structures were formed. The particles were generally attached to the bacterial inner membrane and possessed defined prolate dimensions. The intracellular yield varied between 15 and 71% of a corresponding prohead yield and was dependent on the temperature of incubation. The products of genes 21 and 22 were found to be essential for in vivo core formation, whereas those of genes 20, 23, 24, 31, and 40, as well as the internal proteins I to III, were dispensable.


Costs and benefits of laparoscopic cholecystectomy: abdominal wall lifting vs. pneumoperitoneum procedure.
Gasless laparoscopic surgery using the abdominal wall lifting (AWL) method was first developed in Japan and has been used in various surgical fields. The AWL method allows the use of conventional reusable surgical instruments. The purpose of this study was to compare the cost-effectiveness of laparoscopic cholecystectomy (LSC) using the AWL method in relation to that using pneumoperitoneum (P) method. Retrospective analysis of 431 LSC procedures between 1991 and 2004 was performed. The two surgical groups consisted of consecutively operated patients with a diagnosis of cholecystolithiasis or gallbladder polyps. One group consisted of 224 LSC procedures performed using the P method from 1992 to 1998 and the other group comprised 207 LSC performed using the AWL method from 1998 to 2004. All instruments used in the P method were disposable, whereas trocars, scissors, dissectors, graspers and L-hook electrodes (excluding clips) used in the AWL method were reusable. Hospital expenses, length of hospital admission and complication rates were analyzed. Mean hospital cost per case for LSC using the AWL method (dollars 6743) was 7% less expensive than that using the P method (dolars 7215). Costs of operative equipment contributed to the difference (mean dollars 912 per case) in total cost. Conversion to open cholecystectomy occurred in 6 cases (2.9%) using the AWL method and 7 cases (3.1%) using the P method. There were no significant differences in length of hospital admission or complication rates between the two groups. LSC using AWL method was less expensive than that using P method. This is mainly due to the use of reusable instruments in the AWL method. If LSC is performed using the AWL method instead of using disposable equipment, considerable savings can be achieved without compromising patient safety.


[Application study of vertebral column metastasis tumor with embedment of ¹²⁵I by CT guide].
To discuss the method, safety and effect of embedding ¹²⁵I to Brachytherapy vertebral column metastasis tumor by CT guided. 31 cases of vertebral column metastasis tumor were treated with percutaneous embedding ¹²⁵I by CT guided. They were observed the preoperative size and contour of lesions and were planed the activity and dosage of ¹²⁵I , the PD (prescribed dose) was 110-140 Gy, and the particle activity was 26.0-29.6 Mbq. CT scanning and therapeutic effect analysis were immediately carried out after operations. We also made CT scanning regularly to analyze the effect. 31 cases of vertebral column metastasis tumor were respectively re-examed of CT in 2, 4, 6 and 12 months after operation. We surveyed the local rate, evaluate the easement of pain and observed the tumor. The local response rate of 19 cases with paravertebral mass was 19/19, 19/19, 18/19, 17/19 cases in turn. The probability of odynolysis 31 cases after 2, 4, 6 months therapy was 96.8% (30/31) , 96.8% (30/31) , 90.3% (28/31) , 71.0% (22/31) in turn. 9.68% of 31 cases that was happened significant ossification in the devastated vertebral body. 12 cases appeared skin pigmentation without myelodiastasis or cutaneous ulcer. The method to treat the vertebral column metastasis tumor of embedding ¹²⁵I by CT guided was simple, reliable and safety.


[Early microsurgical treatment of upper obstetrical brachial plexus injury].
To search for the operation timing and methods for obstetrical brachial plexus injury (OBPI). Thirty-two children with upper OBPI were treated by microsurgical procedure from October 1997 to April 2001. The average age of patients was 10 months, ranged from 3 months to 24 months; of them, 19 were below 6 months while 13 were over 6 months. Surgical procedure included neurolysis(n = 12), coaptation after resection of the neuroma without function (n = 7), phrenic nerve transfer to anterior cord of upper trunk or musculocutaneous nerve (n = 7) and intercostal nerves transfer to musculocutaneous nerve(n = 6). The children underwent operation with microsurgical technique and 7/0 or 9/0 nylon was used for nerve suture. Thirty cases were followed up for 21 months postoperatively; the excellent and good rate was 76.7% (23/30). The results of the children under 6 months were better than those over 6 months. The microsurgical operation might be considered at the age of 3-6 month infants who had shown little or no improvement in elbow flexion. Neurolysis and nerve coaptation are superior to neurotization. The appropriate procedure should be selected according to the findings of exploration.


Subtype-specific patterns of molecular mutations in acute myeloid leukemia.
Acute myeloid leukemia (AML) can be grouped into morphologically or genetically defined subtypes. Today, the AML phenotype-genotype associations, that is, FAB/WHO (French-American-British/World Health Organization) definitions and recurrent molecular mutations, are not fully understood. Therefore, we evaluated the impact of molecular mutations on the AML differentiation stage by molecular profiling of 4373 adult de novo AML patients in 7 cytomorphological subtypes. We investigated mutations in 20 genes, including myeloid transcription factors (CEBPA, RUNX1), tumor suppressors (TP53, WT1), DNA modifiers (DNMT3A, IDH1/2, TET2), chromatin modifiers (ASXL1, MLL), signal transduction genes (FLT3, KRAS, NRAS) and NPM1. The most frequently mutated genes per cytomorphological subtype were RUNX1 in M0 (43%), NPM1 in M1 (42%), DNMT3A in M2 (26%), NPM1 in M4 (57%), M5a (49%) and M5b (70%) and TP53 in M6 (36%). Although some gene mutations were frequent in several cytomorphological subtypes, a series of associations of co-occurring mutations with distinct phenotypes were identified for molecularly defined subcohorts. FLT3, NPM1 and WT1 mutations were associated with an immature phenotype in myeloblastic AML, whereas other combinations involving ASXL1, RUNX1, MLL-PTD, CEBPA or KRAS were more frequent in myeloblastic AML with maturation. Within the NPM1 mutated subcohort, ASXL1 mutations were significantly associated with a monoblastic differentiation and DNMT3A mutations with a monocytic phenotype.


A Predictive Model for the Decarboxylation of Silver Benzoate Complexes Relevant to Decarboxylative Coupling Reactions.
Decarboxylative coupling reactions offer an attractive route to generate functionalized arenes from simple and readily available carboxylic acid coupling partners, yet they are underutilized due to limitations in the scope of carboxylic acid coupling partner. Here we report that the field effect parameter (F) has a substantial influence on the rate of decarboxylation of well-defined silver benzoate complexes. This finding provides the opportunity to surpass current substrate limitations associated with decarboxylation and to enable widespread utilization of decarboxylative coupling reactions.


Functional analysis of NtMPK2 uncovers its positive role in response to Pseudomonas syringae pv. tomato DC3000 in tobacco.
Mitogen-activated protein kinase cascades are highly conserved signaling modules downstream of receptors/sensors and play pivotal roles in signaling plant defense against pathogen attack. Extensive studies on Arabidopsis MPK4 have implicated that the MAP kinase is involved in multilayered plant defense pathways. In this study, we identified tobacco NtMPK2 as an ortholog of AtMPK4. Transgenic tobacco overexpressing NtMPK2 markedly enhances resistance to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) virulent and avirulent strains. Transcriptome analysis of NtMPK2-dependent genes shows that possibly the basal resistance system is activated by NtMPK2 overexpression. In addition to NtMPK2-mediated resistance, multiple pathways are involved in response to the avirulent bacteria based on analysis of Pst-responding genes, including SA and ET pathways. Notably, it is possible that biosynthesis of antibacterial compounds is responsible for inhibition of Pst DC3000 avirulent strain when programmed cell death processes in the host. Our results uncover that NtMPK2 positively regulate tobacco defense response to Pst DC3000 and improve our understanding of plant molecular defense mechanism.


Establishing a national resource: a health informatics collection to maintain the legacy of health informatics development.
This case study report of the establishment of a national repository of multi-media materials describes the creation process, the challenges faced in putting it into operation and the opportunities for the future. The initial resource has been incorporated under standard library and knowledge management practices. A collaborative action research method was used with active experts in the domain to determine the requirements and priorities for further development. The National Health Informatics Collection (NatHIC) is now accessible and the further issues are being addressed by inclusion in future University and NHS strategic plans. Ultimately the Collection will link with other facilities that contribute to the description and maintenance of effective informatics in support of health globally. The issues raised about the National Health Informatics Collection as established in the UK have resonance with the challenges of capturing the overall historic development of an emerging discipline in any country.


Na,K-ATPases of the lens epithelium and fiber cell: formation of catalytic cycle intermediates and Na+: K+ exchange.
Previous studies suggest that an alpha 2-related isoform of the catalytic subunit is predominant in the lens fiber cells. The alpha 1 isoform is predominant in the lens epithelium (Garner, Horwitz and Enomoto, 1992). Data are presented to show that strophanthidin-sensitive K+ transport is sustained by both of these lens Na,K-ATPases. The K50 for strophanthidin inhibition of K+ transport was 1.4 +/- 0.5 x 10(-6) M for the alpha 1 isoform of the epithelium, 1.3 +/- 0.6 x 10(-7) M for the alpha 2-related isoform of the lens fiber cells. Na+ accumulation in cultured bovine lenses was strophanthidin sensitive. The K50 values for strophanthidin-sensitive Na+ accumulation were similar to those obtained for K+ transport. ARP turnover by the lens fiber cell Na,K-ATPase (1700 +/- 600 min-1) was lower than ATP turnover by the lens epithelium Na,K-ATPase (8000 +/0 1000 min-1). Both lens Na,K-ATPases form the (ouabain + Mg(2+) + phosphate)-dependent phosphoenzyme. Both lens Na,K-ATPases form the (ATP + Na(+) + Mg2+)-dependent phosphorylated intermediate. K+ does not effectively dephosphorylate the Na,K-ATPase of the lens fibers. K+ does cause dephosphorylation of the Na,K-ATPase of the lens epithelium. Interaction of the Na,K-ATPase with Mg2+ would appear to cause the monovalent cation insensitivity. The lens fiber cell Na,K-ATPase, like the lens epithelium Na,K-ATPase occludes two K+ ions. However, between the two major Na,K-ATPases of the lens, there would appear to be differences in the ATP dissolution of the K-occluded state.


The value of ultrasound elastography combined with multi-parameters in the diagnosis of BI-RADS 4 breast lesions.
Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%) in the global cancer statistics 2020. To evaluate the diagnostic value of ultrasound elastography combined with multi-parameters in differentiating category 4 benign and malignant lesions in the breast imaging reporting and data system (BI-RADS). This study retrospectively analyzed 206 patients (213 breast lesions) who visited the Department of Breast Surgery and underwent a breast core needle biopsy in the Department of Ultrasound in Peking University First hospital from April to December 2019. The shear wave velocity (SWV) values were collected at the following locations by virtual touch tissue imaging quantification (VTIQ): breast lesion interior, breast lesion margin, surrounding glands, and surrounding fat. Simultaneously, the strain ratio (SR) of breast lesions to glands and the area ratio (AR) of breast lesions were collected under strain elastography and a two-dimensional ultrasound mode. Univariate analysis found that the SWV value, measured by ultrasound elastography parameters, and the AR between the elasticity and the two-dimensional ultrasound breast lesions showed statistical differences when differentiating benign and malignant lesions (p< 0.05). Binary logistic regression analysis found that the SWV values of the lesion interior and the surrounding glands were statistically significant. The joint predictors were calculated and analyzed by Receiver Operating Characteristic (ROC), and it was found that the joint predictors and the SWV values of the lesion interior have great diagnostic value. The cut-off value, sensitivity and specificity of the joint predictor and the SWV value of the lesion interior were > 3.65, 88.35% and 76.36% and > 5.55 m/s, 79.61% and 82.73%, respectively. Ultrasound elastography combined with multi-parameters has good diagnostic value in differentiating BI-RADS 4 breast lesions.


Parvovirus B19-induced acute bilateral carpal tunnel syndrome in twin girls.
We describe 2 cases of 6-year-old twin girls presenting with acute carpal tunnel syndrome (CTS) associated with human parvovirus B19 (HPV-B19) infection, as evidenced by serological data and detection of HPV-B19 DNA in blood with use of polymerase chain reaction (PCR). To our knowledge, this is the first time that HPV-B19 infection has been suggested as the causal agent of simultaneous acute bilateral CTS in twins, thus presenting the possibility that similar immunologic responses can be observed in twins during viral infections.


3D interactive surgical visualization system using mobile spatial information acquisition and autostereoscopic display.
Three-dimensional (3D) visualization of preoperative and intraoperative medical information becomes more and more important in minimally invasive surgery. We develop a 3D interactive surgical visualization system using mobile spatial information acquisition and autostereoscopic display for surgeons to observe surgical target intuitively. The spatial information of regions of interest (ROIs) is captured by the mobile device and transferred to a server for further image processing. Triangular patches of intraoperative data with texture are calculated with a dimension-reduced triangulation algorithm and a projection-weighted mapping algorithm. A point cloud selection-based warm-start iterative closest point (ICP) algorithm is also developed for fusion of the reconstructed 3D intraoperative image and the preoperative image. The fusion images are rendered for 3D autostereoscopic display using integral videography (IV) technology. Moreover, 3D visualization of medical image corresponding to observer's viewing direction is updated automatically using mutual information registration method. Experimental results show that the spatial position error between the IV-based 3D autostereoscopic fusion image and the actual object was 0.38±0.92mm (n=5). The system can be utilized in telemedicine, operating education, surgical planning, navigation, etc. to acquire spatial information conveniently and display surgical information intuitively.


Identification of encapsulated and non-encapsulated Yersinia pestis by immunofluorescence tests using polyclonal and monoclonal antibodies.
Rabbit polyclonal hyperimmune antibodies to Yersinia pestis, and a mouse monoclonal antibody against the capsular antigen fraction 1 (F1) were compared in immunofluorescence (IF) tests. Fluorescent antibody conjugates were prepared from polyclonal antisera to four F1 positive Y. pestis strains; the conjugated antibody to strain A1122 gave the strongest IF staining of F1 positive and F1 negative Y. pestis strains. Indirect assays were rejected in favour of direct assays utilizing polyclonal and monoclonal reagents because the increased background staining reduced the effective contrast of bacterial visualisation. Polyclonal conjugates gave fairly homogeneous staining of Y. pestis bacterial populations, but in monoclonal assays a skew distribution of fluorescence intensity was observed, the majority of bacteria being poorly stained. The proportion of cells stained well by the monoclonal sufficed for easy identification of Y. pestis of the F1 positive phenotype however, and staining was not affected by washing the bacteria or treating them with formaldehyde. Y. pestis strains of the F1 positive genotype reacted with the monoclonal if bacteria were grown at 37 degrees C but not if the growth temperature was reduced to 25 degrees C thus preventing capsule production. The polyclonal conjugate reacted with bacteria of these strains that had been grown at either temperature. Strains of F1 negative genotype grown at either temperature reacted with the polyclonal conjugate but not with the monoclonal. Cross reactions between the polyclonal reagents and Y. enterocolitica biovar 2, serovar O 8 could not be removed by selective absorption; however, the monoclonal antibody gave no cross reaction. The F1 phenotypic status of bacterial preparations was verified by ELISA measurement of the fraction 1 antigen concentration. Antigen levels for F1 positive and F1 negative phenotypes differed by about three logs for suspensions of Y. pestis harvested from solid media. The polyclonal and monoclonal direct IF tests applied to spleen and blood smears of laboratory mice infected with Y. pestis were able to differentiate between lethal infection with an F1 positive strain carrying all four classical virulence determinants, an F1 positive vaccine strain, and an F1 negative strain.


Endothelial cell tropism is a determinant of H5N1 pathogenesis in mammalian species.
The cellular and molecular mechanisms underpinning the unusually high virulence of highly pathogenic avian influenza H5N1 viruses in mammalian species remains unknown. Here, we investigated if the cell tropism of H5N1 virus is a determinant of enhanced virulence in mammalian species. We engineered H5N1 viruses with restricted cell tropism through the exploitation of cell type-specific microRNA expression by incorporating microRNA target sites into the viral genome. Restriction of H5N1 replication in endothelial cells via miR-126 ameliorated disease symptoms, prevented systemic viral spread and limited mortality, despite showing similar levels of peak viral replication in the lungs as compared to control virus-infected mice. Similarly, restriction of H5N1 replication in endothelial cells resulted in ameliorated disease symptoms and decreased viral spread in ferrets. Our studies demonstrate that H5N1 infection of endothelial cells results in excessive production of cytokines and reduces endothelial barrier integrity in the lungs, which culminates in vascular leakage and viral pneumonia. Importantly, our studies suggest a need for a combinational therapy that targets viral components, suppresses host immune responses, and improves endothelial barrier integrity for the treatment of highly pathogenic H5N1 virus infections.


Role of mitochondrial Ca2+ uniporter in remifentanil-induced postoperative allodynia.
Opioid-induced hyperalgesia (OIH) and allodynia is a well-known phenomenon and refers to the pain sensitization in patients after prolonged opioid exposure. OIH limits the use of opioids in pain control, but the underlying mechanisms are not fully clear. This study investigated the role of mitochondrial Ca2+ uniporter (MCU) in remifentanil (a commonly used opioid analgesic)-induced allodynia. Using a rat model of OIH, we found that incision- and remifentanil-induced mechanical allodynia were remarkably attenuated by pretreatment with Ru360, a specific MCU antagonist, suggesting a critical role of MCU in both incision- and opioid-induced allodynia. In addition, imaging studies with Rhod-2 (a mitochondrial Ca2+ dye) in spinal tissues demonstrated increased mitochondrial Ca2+ level in response to incision and remifentanil infusion, which was attenuated by Ru360. Western blot and immunohistochemistry showed that pNR [phosphorylated N-methyl-D-aspartate (NMDA) receptor] and pERK (phosphorylated extracellular signal-regulated kinase) are increased during both incision-induced hyperalgesia and remifentanil-induced hyperalgesia, and again the increases in pNR and pERK were remarkably attenuated by Ru360. Together, our data demonstrate that MCU plays a critical role in remifentanil-induced postoperative mechanical allodynia, with NMDA receptor and ERK as possible downstream effectors. Our findings provide novel mechanisms for remifentanil-induced mechanical allodynia and encourage future studies to examine the mitochondrial Ca2+ uniporter as a potential therapeutic target for prevention of OIH.


Hippocampal-Cortical Encoding Activity Predicts the Precision of Episodic Memory.
Our recollections of past experiences can vary in both the number of specific event details accessible from memory and the precision with which such details are reconstructed. Prior neuroimaging evidence suggests the success and precision of episodic recollection to rely on distinct neural substrates during memory retrieval. In contrast, the specific encoding mechanisms supporting later memory precision, and whether they differ from those underlying successful memory formation in general, are currently unknown. Here, we combined continuous measures of memory retrieval with model-based analyses of behavioral and neuroimaging data to tease apart the encoding correlates of successful memory formation and mnemonic precision. In the MRI scanner, participants encoded object-scene displays and later reconstructed features of studied objects using a continuous scale. We observed overlapping encoding activity in inferior prefrontal and posterior perceptual regions to predict both which object features were later remembered versus forgotten and the precision with which they were reconstructed from memory. In contrast, hippocampal encoding activity significantly predicted the precision, but not overall success, of subsequent memory retrieval. The current results align with theoretical accounts proposing the hippocampus to be critical for representation of high-fidelity associative information and suggest a contribution of shared cortical encoding mechanisms to the formation of both accessible and precise memory representations.


Effect of melittin on the apical membrane Na+ and Cl- conductances of frog cornea epithelium.
The transepithelial conductance increased with 10(-6) M melittin on the tear side of the frog cornea. This effect was attributed to the opening of an apical membrane Na+ conductance. However, the potency of the venom at this concentration (apical membrane fractional resistance (fRo) decreased to near zero) masked this and other effects. With 3 x 10(-7) M on the tear side, the effects were finite (fRo > 0) and reversible. With fRo > 0, the effects of melittin could be readily studied on the transport parameters of Na+, Cl-, and K+. Epithelial cells of intact bullfrog corneas were impaled with microelectrodes using an in vitro preparation. Under short-circuit current (Isc) conditions, 20 min after melittin Isc increased by 3.1 from 8.2 microA/cm2., fRo decreased by 18 from 51%; the intracellular potential, Vo, depolarized by 19.4 from -56.5 mV; and the transepithelial conductance, gv increased by 0.57 from 0.29 mS/cm2. Tenfold decreases in tear Na+ or Cl- concentrations changed the transport parameters consistent with the formation of a Na+ conductance and an increase in the apical membrane Cl- conductance by the venom. These conclusions were further supported by the minimal effect of melittin in Cl(-)-fre and, particularly, in Na(+)-free solutions. Changes in K+ concentration had no effect on transport parameters. These findings indicate that the effect of melittin at this low concentration is upon a Na+ channel protein and not due to nonspecific conductances.


Prediction of whole blood selenium levels in patients on long-term parenteral nutrition.
In an attempt to define clinical variables which might predict the whole blood selenium level prior to supplementation, whole blood selenium levels were determined in 21 home parenteral nutrition patients who were not receiving selenium supplementation. These levels were examined for possible correlations by single and multivariant analysis with the following clinical parameters: age at initiation of home parenteral nutrition, months of home parenteral nutrition received, hematocrit, albumin, estimated length of remaining small bowel, kilocalories per kilogram actual body weight infused per day, grams protein per kilogram actual body weight infused per day, and multiple of ideal body weight. Of all the combinations of variables examined, the best correlation obtained was between whole blood selenium levels and the total kilocalories per kilogram body weight per day delivered intravenously (r = -0.89, p less than 0.001). A statistically significant correlation (r = -0.67, p less than 0.01) was also observed between selenium levels and the grams protein per kilogram actual body weight infused per day. However, inclusion of this or additional variables did not increase the predictive value of the equation describing whole blood selenium levels as a function of the calories delivered. The implication of this study is that patients requiring more intensive nutritional support develop lower selenium levels during the course of treatment. Despite these correlations, no single clinical parameter or combination of parameters, however, was of sufficient predictive value to preclude laboratory determination of whole blood selenium values in deciding which patients might benefit from selenium supplementation.


Nurses' attitudes toward the advantages of master's degree preparation in nursing.
The first objective of this study was to measure attitudes and opinions regarding master's degree preparation in nursing. The second objective was to identify important characteristics of graduate nursing education programs. The researcher developed Educational Attitude Questionnaire was mailed to a random sample of members of the Association of Rehabilitation Nurses and the Oncology Nursing Society. Five hundred twenty-four completed questionnaires were used for data analysis. Study findings revealed the bachelor's prepared nurses surveyed held a generally positive attitude toward graduate education in nursing. Fifty percent of the subjects indicated an intention to obtain a masters degree in nursing. For the majority of subjects the characteristics of graduate programs considered most important included faculty with high academic standards who offer challenging specialty area programs on a flexible time schedule.


Relative Age Effects and Self-Organized Sport Practices Among Adults.
Purpose: Given that previous research on relative age effects (RAEs) has only focused on organized sport, the aim of this exploratory study was to examine whether this phenomenon also existed among self-organized practitioners. In relation to that, a second aim was to know whether self-organized sport practices could be favored by late-born practitioners as a result of a strategic adaptation. Method(s): Representative sub-samples of 474 soccer players, 363 basketball players, 2,536 swimmers, 1,788 strength training practitioners, 1,873 pétanque players, 973 table tennis players and 2,136 runners were analyzed. Results: The results did not show any significant RAEs, including in sport practices that are sensitive to this phenomenon such as soccer or basketball. The results did not show any significant overrepresentation of late-born people either. Conclusion: This study suggests that self-organized sport practices are not impacted by the RAEs. This finding is interesting because self-organized sport practice is the most important one in numbers.


Diffuse Large B-Cell Lymphoma of the Trachea in a Child With Symptoms of Bronchial Asthma.
Tracheal tumors are rare in children and manifest symptoms of airway obstruction. A 14-year-old boy with a 5-month history of dyspnea and wheezing was referred to our hospital. Although he had been initially diagnosed with bronchial asthma, computed tomography revealed tracheal tumors. Histologic examination showed only necrotic tissue. Thereafter, the systemic steroid treatment for bronchial asthma was tapered off. A second computed tomography scan revealed new lesions in the pancreas and lung. Biopsy of the pancreatic lesion revealed a diffuse large B-cell lymphoma. The patient was administered standard chemotherapy, following which he went into complete remission.