Unveiling the neuromorphological space.
This article proposes the concept of neuromorphological space as the multidimensional space defined by a set of measurements of the morphology of a representative set of almost 6000 biological neurons available from the NeuroMorpho database. For the first time, we analyze such a large database in order to find the general distribution of the geometrical features. We resort to McGhee's biological shape space concept in order to formalize our analysis, allowing for comparison between the geometrically possible tree-like shapes, obtained by using a simple reference model, and real neuronal shapes. Two optimal types of projections, namely, principal component analysis and canonical analysis, are used in order to visualize the originally 20-D neuron distribution into 2-D morphological spaces. These projections allow the most important features to be identified. A data density analysis is also performed in the original 20-D feature space in order to corroborate the clustering structure. Several interesting results are reported, including the fact that real neurons occupy only a small region within the geometrically possible space and that two principal variables are enough to account for about half of the overall data variability. Most of the measurements have been found to be important in representing the morphological variability of the real neurons.


Fine needle aspiration cytology of a lipoblastoma.
A lipoblastoma, an uncommon tumor of childhood that can be mistaken for a liposarcoma, was preoperatively diagnosed by fine needle aspiration cytology. The characteristic features on the cytologic smears were the presence of immature fat cells in the form of spindle-shaped cells, stellate cells and vacuolated lipoblasts along with lipocytes. The cytologic diagnosis was confirmed by histologic study of the excised tumor.


Decontamination of Gutta-percha Cones employed in Endodontics.
The gutta-percha cones used in endodontic treatment are produced in aseptic conditions and their composition includes zinc oxide, which is responsible for antibacterial activity. However, there is the possibility of microbial contamination by manipulation, aerosol or during storage. Although several chemical agents have been tested for their decontamination, there is no consensus on the best disinfection protocol to be used. The aim of this study was to evaluate the decontamination of gutta-percha cones contaminated with the bacteria Enterococcus faecalis, by using chlorhexidine digluconate (CHX) and sodium hypochlorite (NaClO) at different concentrations for short exposure times. For this purpose, gutta-percha cones (size 40) were selected at random from a sealed box and immersed for 1 min in a microbial suspension. Then they were immersed in specific Petri dishes for different groups containing: CHX 2%, NaClO 1% or NaClO 2.5% for 30 s or 1 min, and subsequently placed in tubes containing BHI broth. After incubating the tubes for 48 h, it was observed that 1% and 2.5% NaClO and 2% CHX were effective for decontaminating the cones at those exposure time intervals. Microbial growth was detected in one of the replicates of the group with CHX applied for 30 s. To prevent the possibility of failures at this stage, the exposure time of gutta-percha cones to the decontaminating agent should not be reduced.


Sustained release of acetaminophen from heterogeneous matrix tablets: influence of polymer ratio, polymer loading, and co-active on drug release.
The aim of this research was to investigate the effect of pseudoephedrine (PE), polymer ratio, and polymer loading on the release of acetaminophen (APAP) from hydroxypropyl methyl cellulose (HPMC)/polyvinylpyrrolidone (PVP) matrices. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and PVP were compressed into tablets at varying compression forces ranging from 2000 to 6000 Ib. In vitro drug release from the matrix tablets was determined and the results correlated with those of tablet water uptake and erosion studies. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP (P < 0.05, F = 3.10). Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45, and at high total polymer loading (> or = 9.6%). Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.45. At pH 1.16, a decline in the percentage of APAP released occurred after 18 hours. This was due to the hydrolysis of APAP to p-aminophenol. The drug dissolution data showed good fit to the Korsmeyer and Peppas model, and the values of the release exponents ranged from 0.20 to 0.62, indicating a complex drug release pattern. Tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation controlled mechanism. Overall, the results of this study indicated that PE, as a co-active in the formulation, modified the matrix, and hence retarded APAP release.


Rapid axonal transport in primate optic nerve. Distribution of pressure-induced interruption.
Six primate eyes were studied after four hours of elevated intraocular pressure. Tissue specimens from the region of the lamina cribrosa were examined in cross section by transmission electron microscopy. Interruption in fast orthograde and retrograde axonal transport was identified in individual axons by noting accumulation of membraneous microorganelles, such as mitochondria and microvesicles within axon cylinders. Although organelle accumulation varied from bundle to bundle, involvement of individual axons was diffuse across the extent of a specific axon bundle. This observation contradicts the apparent association of axonal transport block with crosswise-oriented trabecular beams at the level of the lamina cribrosa as seen in tissue specimens examined in longitudinal section. It also fails to support the notion that blocked axonal transport with elevated pressure is produced by kinking of axons at the lamina.


Thermal Conductance in Cross-linked Polymers: Effects of Non-Bonding Interactions.
Weak interchain interactions have been considered to be a bottleneck for heat transfer in polymers, while covalent bonds are believed to give a high thermal conductivity to polymer chains. For this reason, cross-linkers have been explored as a means to enhance polymer thermal conductivity; however, results have been inconsistent. Some studies show an enhancement in the thermal conductivity for polymers upon cross-linking, while others show the opposite trend. In this work we study the mechanisms of heat transfer in cross-linked polymers in order to understand the reasons for these discrepancies, in particular examining the relative contributions of covalent (referred to here as "bonding") and nonbonding (e.g., van der Waals and electrostatic) interactions. Our results indicate cross-linkers enhance thermal conductivity primarily when they are short in length and thereby bring polymer chains closer to each other, leading to increased interchain heat transfer by enhanced nonbonding interactions between the chains (nonbonding interactions being highly dependent on interchain distance). This suggests that enhanced nonbonding interactions, rather than thermal pathways through cross-linker covalent bonds, are the primary transport mechanism by which thermal conductivity is increased. We further illustrate this by showing that energy from THz acoustic waves travels significantly faster in polymers when nonbonding interactions are included versus when only covalent interactions are present. These results help to explain prior studies that measure differing trends in thermal conductivity for polymers upon cross-linking with various species.


Characterization of the insulin receptor kinase from human erythrocytes.
The insulin receptor from human erythrocytes was studied for receptor-associated tyrosine kinase activity. Receptor phosphorylation was performed by incubation of the receptor with [gamma-32P]ATP and Mn2+ in the presence or absence of insulin, and the phosphorylated receptor was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In Triton X-100-solubilized, and partially purified, receptor preparations, insulin stimulated the phosphorylation of a 95,000 dalton protein in a dose-dependent fashion. Immunoprecipitation with antiinsulin receptor antibodies indicates that this 95,000 dalton protein corresponds to the beta-subunit of the insulin receptor. Phosphoaminoacid analysis revealed that 32P incorporation occurred predominantly on tyrosine residues of the beta-subunit. In addition, the insulin receptor kinase catalyzed the phosphorylation of Histone H2b. Dose response curves for insulin-stimulated phosphorylation of the beta-subunit and Histone H2b were sigmoidal. Both half-maximal effects were observed at 3 X 10(-9) M insulin with maximal effects at 10(-6) M. When insulin binding was examined under the same conditions as phosphorylation, the dose-response curves for receptor occupancy and the kinase activation were nearly superimposable, indicating few or no spare receptors for this response to insulin. Insulin-stimulated receptor phosphorylation was diminished by treatment with N-ethylmaleimide, indicating that the receptor possesses sulfhydryl groups, which are important for its enzyme activity. This study demonstrates that insulin receptor kinase from human erythrocytes shares characteristics which are similar to those found in other classical insulin target cells and tissues.


Improving the CHARMM force field for polyunsaturated fatty acid chains.
CHARMM36 (C36) is the most up-to-date pairwise additive all-atom lipid force field and is able to accurately represent bilayer properties of saturated and monounsaturated lipid molecules in the natural constant particle, pressure, and temperature (NPT) ensemble. However, molecular dynamics (MD) simulations on 1-stearoyl-2-docosahexaenoyl-sn-glycerco-3-phosphocholine (SDPC) bilayers of the polyunsaturated fatty acid (PUFA) chains result in inaccuracies of the surface area per lipid (SA), deuterium order parameters (S(CD)), and X-ray form factors. Therefore, in this study, high-level quantum mechanical calculations are used to improve the dihedral potential of neighboring double bonds, and the corresponding force field is referred to as C36p. The SA for SDPC at 303 K increases from 63.2 ± 0.2 (C36) to 70.8 ± 0.2 (C36p) Å(2) and agrees favorably with X-ray diffraction results at 297 K. The resulting S(CD) are in excellent agreement with experimental values of both the sn-1 and sn-2 chains. Calculated NMR (13)C relaxation times and X-ray form factors from MD simulations of SDPC bilayers also agree with experiments. MD simulations of 1,2-diarachidonyl-phosphatidylcholine (DAPC) bilayers are used to further validate our force field parameters on a lipid with both chains containing PUFAs. As expected, the thickness of DAPC bilayers is reduced, and the SA is increased compared to the SDPC bilayers. This update in the PUFA force field should allow for accurate MD simulations of PUFA-containing bilayers in the NPT ensemble.


Positional nystagmus of horizontal canalolithiasis.
Vertical and torsional components occur from the horizontal semicircular canal, and the response to ampullopetal flow is greater than that to ampullofugal flow in every component. To clarify whether positional nystagmus of horizontal canalolithiasis contains vertical and torsional components, and to quantify the asymmetry of nystagmus. Twenty patients with transient direction-changing geotropic positional nystagmus were examined, and we performed three-dimensional video-oculography and measured the maximum slow-phase velocity (MSV) of three components. Positional nystagmus was not purely horizontal. Fifteen (75%) patients revealed a vertical component and 19 (95%) patients had a torsional component. The mean value of MSV of the horizontal component in the affected-ear-down position was 51.5°/s and that in the healthy-ear-down position was 19.1°/s. The mean value of MSV of the vertical component in the affected-ear-down position was 8.7°/s and that in the healthy-ear-down position was 3.0°/s. The mean value of MSV of the torsional component in the affected-ear-down position was 12.8°/s and that in the healthy-ear-down position was 6.5°/s. For every component, MSV in the affected-ear-down position was significantly greater than that in the healthy-ear-down position (p < 0.01).


[Total synthesis of schizandrin, the main active ingredient isolated from the Chinese herbal medicine fructus schizandrae].
In this paper, schizandrin(9), the main active ingredient isolated from Schisandra chinensis, was synthesized from gallic acid by a new route. This route consists of only nine steps, including reductive-coupling reaction of compound(5) and dehydryoxylatic reaction of compound(6) to give compounds(7Z, 7E). By hydroboration, compound (8) was obtained from compound(7Z). With the presence of thallium trifluoroacetate (TTFA) and 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) compound (9) is obtained from compound (8) by intramolecular nonphenolic oxidative coupling. These compounds were identified by elemental analysis, MS, UV, IR and NMR spectra.


Sodium chloride supplementation of all plant protein broiler diets.
Male broiler chicks were fed all plant protein diets with soybean meal or a mixture of soybean and canola meals as the source of supplementary protein from 0 to 4 weeks of age. Supplementation of the diets with .25% sodium chloride did not meet the requirements of the chicks for maximum growth. Growth was accelerated when the dietary sodium chloride concentration was increased to .50 and 1.00%.


Finite-size effects on order reconstruction around nematic defects.
By use of the Landau-de Gennes phenomenological theory, we study the texture of a nematic liquid crystal confined within a hybrid cell. Precisely, we consider cylindrically symmetric solutions containing topological defects dictated by appropriate boundary conditions. We focus our attention on cells whose dimensions are comparable with the biaxial correlation length xi(b) . For such severe confinements the order reconstruction (OR) configuration could be stable. Its structural details reflect the balance among boundary-enforced frustration, elastic penalties, and finite-size effects. In particular, we analyze the interplay between finite-size effects and topological defects. We show that defects are always pinned to the negatively (planar) uniaxial sheet of the OR structure. The presence of a ring defect can dramatically increase the critical threshold below which the OR structure is stable.


The Dose-Response Relationship Between Training Load and Aerobic Fitness in Academy Rugby Union Players.
To identify the dose-response relationship between measures of training load (TL) and changes in aerobic fitness in academy rugby union players. Training data from 10 academy rugby union players were collected during a 6-wk in-season period. Participants completed a lactate-threshold test that was used to assess VO2max, velocity at VO2max, velocity at 2 mmol/L (lactate threshold), and velocity at 4 mmol/L (onset of lactate accumulation; vOBLA) as measures of aerobic fitness. Internal-TL measures calculated were Banister training impulse (bTRIMP), Edwards TRIMP, Lucia TRIMP, individualized TRIMP (iTRIMP), and session RPE (sRPE). External-TL measures calculated were total distance, PlayerLoad™, high-speed distance >15 km/h, very-high-speed distance >18 km/h, and individualized high-speed distance based on each player's vOBLA. A second-order-regression (quadratic) analysis found that bTRIMP (R2 = .78, P = .005) explained 78% of the variance and iTRIMP (R2 = .55, P = .063) explained 55% of the variance in changes in VO2max. All other HR-based internal-TL measures and sRPE explained less than 40% of variance with fitness changes. External TL explained less than 42% of variance with fitness changes. In rugby players, bTRIMP and iTRIMP display a curvilinear dose-response relationship with changes in maximal aerobic fitness.


Role of methylation in vernalization and photoperiod pathway: a potential flowering regulator?
Recognized as a pivotal developmental transition, flowering marks the continuation of a plant's life cycle. Vernalization and photoperiod are two major flowering pathways orchestrating numerous florigenic signals. Methylation, including histone, DNA and RNA methylation, is one of the recent foci in plant development. Considerable studies reveal that methylation seems to show an increasing potential regulatory role in plant flowering via altering relevant gene expression without altering the genetic basis. However, little has been reviewed about whether and how methylation acts on vernalization- and photoperiod-induced flowering before and after FLOWERING LOCUS C (FLC) reactivation, what role RNA methylation plays in vernalization- and photoperiod-induced flowering, how methylation participates simultaneously in both vernalization- and photoperiod-induced flowering, the heritability of methylation memory under the vernalization/photoperiod pathway, and whether and how methylation replaces vernalization/photoinduction to regulate flowering. Our review provides insight about the crosstalk among the genetic control of the flowering gene network, methylation (methyltransferases/demethylases) and external signals (cold, light, sRNA and phytohormones) in vernalization and photoperiod pathways. The existing evidence that RNA methylation may play a potential regulatory role in vernalization- and photoperiod-induced flowering has been gathered and represented for the first time. This review speculates about and discusses the possibility of substituting methylation for vernalization and photoinduction to promote flowering. Current evidence is utilized to discuss the possibility of future methylation reagents becoming flowering regulators at the molecular level.


Effects of whole body vibration on dorsal root ganglion neurons. Changes in neuronal nuclei.
This blinded, histomorphometric analysis compared neuronal nuclei from lumbar dorsal root ganglia from three groups of rabbits: normal controls, immobilized controls, and an experimental group exposed to daily, whole body vibration. To identify ultrastructural changes in dorsal root ganglion neurons consistent with, and capable of producing, neuropeptide changes previously documented in vibration-exposed animals. Normal adult rabbits were exposed to modulated whole body vibration at a frequency and amplitude previously shown to produce changes in dorsal root ganglion neuropeptides. Lumbar ganglia from control and vibrated rabbits were fixed, stained, and studied under transmission electron microscopy. One-thousand-two-hundred cells were sampled, and 190 appropriately sectioned cells were analyzed. Epidemiologic studies have suggested a strong correlation between vibration and back pain. Previous studies have shown that short-term exposure to whole body vibration alters the normal neuropeptide profile seen in dorsal root ganglion neurons. Nuclear clefting was increased 39% in vibrated nuclei relative to controls, and nuclear pores were increased 46% in areas of clefting compared with adjacent nonclefted segments and controls (P < .001). Mitochondria, rough endoplasmic reticulum, and free ribosomes crowded the cleft spaces of vibrated cells, and the normal perinuclear clear space was lost. Mitochondrial and lysosomal volumes were significantly increased in vibrated cells. These ultrastructural changes, generated by a physiologically valid vibration stimulus, provide an anatomic link between the clinical observation of increased back pain and the biochemical alterations involving pain-related neuropeptides.


Dopaminergic modulation of adenylate cyclase stimulation by vasoactive intestinal peptide in anterior pituitary.
The activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 18.104.22.168] by vasoactive intestinal peptide (VIP) was used as a model to investigate the molecular mechanisms triggered by the occupancy of dopamine recognition sites in rat anterior pituitary. Dopamine failed to change the basal enzyme activity, but it inhibited the stimulation of adenylate cyclase elicited by VIP. Apomorphine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene, and 2-bromo-alpha-ergocryptine mimicked the effect of dopamine, whereas (-)-sulpiride and and classical neuroleptics antagonized it. Dopamine failed to modulate the activation of pituitary adenylate cyclase by prostaglandin E1, which does not increase prolactin secretion. From these results we infer that stimulation of D-2 (dopamine) receptors may affect pituitary secretion by inhibiting the activation of anterior pituitary adenylate cyclase by VIP or other secretagogues.


Human brucellosis in Kenya.
The serology, epidemiologic features and clinical presentation of 39 patients suffering from Brucellosis in Kenya are described. The prevalent species was Brucella melitensis. There was a striking preference in the localisation of the infection for the spine and the hip joint. The disease runs a protracted course. Phenomena due to hypersensitivity and neuropsychiatric disorders are discussed. Advice regarding specific treatment is given.


Fluorine-18 click radiosynthesis and preclinical evaluation of a new 18F-labeled folic acid derivative.
The folate receptor (FR) is highly expressed on most epithelial cancer cells, while normal cells show only restricted expression of FR. As a result, the FR is an ideal target for receptor-based molecular imaging and therapy of cancer and has become a promising target in oncology. To date, several folate-based chemotherapeutics and imaging probes such as radiopharmaceuticals for single photon emission computed tomography (SPECT) have been developed. However, an (18)F-labeled folic acid derivative suitable for positron emission tomography (PET) imaging that can be routinely applied is still lacking. In this study, a new fluorinated and radiofluorinated folic acid derivative, (18/19)F-click folate, was synthesized using click chemistry. In a convenient and very efficient two-step radiosynthesis, the isolated (18)F-click folate was obtained in good radiochemical yields of 25-35% with a specific activity of 160+/-70 GBq/micromol after <or=90 min synthesis time. The new compound was pharmacologically evaluated in vitro and in vivo. The affinity of the non-radioactive (19)F-click folate to the FR was determined in displacement studies with FR expressing KB tumor cells using (3)H-folic acid. In these in vitro binding studies, a nanomolar affinity with a K(i) of 9.76+/-3.13 nM was found for (19)F-click folate. The (18)F-labeled click folate derivative was then applied for in vivo PET studies and ex vivo biodistribution experiments using nude mice bearing KB tumor xenografts. The post mortem dissection experiments showed a high specific uptake of (18)F-click folate derivative in FR-expressing tissues. Uptake in KB tumor xenografts and kidneys (FR-positive tissue) amounted to 3.13%ID/g (94% specific blockade) and 16.53%ID/g (75% specific blockade), respectively. PET imaging using (18)F-click folate permitted a visualization of KB tumors, and blockade studies confirmed the specific accumulation of the radiotracer in vivo. However, strong hepatobiliary excretion of the new tracer led to elevated accumulation of radioactivity in the abdominal region. In conclusion, the click chemistry approach is convenient to accomplish and provided high radiochemical yields of (18)F-click folate. The new tracer showed good in vitro but limited in vivo properties. Ultimately, the (18)F-click folate emphasizes the potential of (18)F-labeled folates for receptor-based tumor PET imaging.


A Protracted Course of COVID19 Infection in a Metastatic Breast Cancer Patient During CDK4/6 Inhibitor Therapy.
We describe the first case report of a patient with COVID19 infection and metastatic breast cancer, while on systemic therapy with a CDK4/6 inhibitor. The patient had unique disease course, characterized with delayed symptomatology. The case highlights novel findings and stress careful and extended follow-up during COVID19 infection in patients taking biologic therapies affecting the immune system.


Medical Registry Data Collection Efficiency: A Crossover Study Comparing Web-Based Electronic Data Capture and a Standard Spreadsheet.
Electronic medical records and electronic data capture (EDC) have changed data collection in clinical and translational research. However, spreadsheet programs, such as Microsoft Excel, are still used as data repository to record and organize patient data for research. The objective of this study is to assess the efficiency of EDC as against a standard spreadsheet in regards to time to collect data and data accuracy, measured in number of errors after adjudication. This was a crossover study comparing the time to collect data in minutes between EDC and a spreadsheet. The EDC tool used was Research Electronic Data Capture (REDCap), whereas the spreadsheet was Microsoft Excel. The data collected was part of a registry of patients who underwent coronary computed tomography angiography in the emergency setting. Two data collectors with the same experience went over the same patients and collected relevant data on a case report form identical to the one used in our Emergency Department (ED) registry. Data collection tool was switched after the patient that represented half the cohort. For this, the patient cohort was exactly 30 days of our ED coronary Computed Tomography Angiography registry and the point of crossover was determined beforehand to be 15 days. We measured the number of patients admitted, and time to collect data. Accuracy was defined as absence of blank fields and errors, and was assessed by comparing data between data collectors and counting every time the data differed. Statistical analysis was made using paired t -test. The study included 61 patients (122 observations) and 55 variables. The crossover occurred after the 30th patient. Mean time to collect data using EDC in minutes was 6.2±2.3, whereas using Excel was 8.0±2.0 (P <.001), a difference of 1.8 minutes between both means (22%). The cohort was evenly distributed with 3 admissions in the first half of the crossover and 4 in the second half. We saw 2 (<0.1%) continuous variable typos in the spreadsheet that a single data collector made. There were no blank fields. The data collection tools showed no differences in accuracy of data on comparison. Data collection for our registry with an EDC tool was faster than using a spreadsheet, which in turn allowed more efficient follow-up of cases.


Selective targeting of angiogenic tumor vasculature by vascular endothelial-cadherin antibody inhibits tumor growth without affecting vascular permeability.
Vascular endothelial-cadherin (VE-cadherin) is an endothelial cell-specific adhesion molecule that is localized exclusively at cell-cell contacts referred to as adherens junctions. VE-cadherin-mediated adhesion is crucial for proper assembly of vascular structures during angiogenesis as well as for maintenance of a normal vascular integrity. We have shown previously that a monoclonal antibody (BV13) to VE-cadherin not only inhibits the formation of vascular tubes during tumor angiogenesis but also disrupts adherens junctions of normal vasculature with a concomitant increase in vascular permeability. The goal of the current studies was to block VE-cadherin function during angiogenesis without disrupting existing junctions on normal endothelium. Using in vitro screening assays to test for functional blocking of adherens junction formation and in vivo assays to detect antibody effects on vascular permeability in normal tissues, we have identified a novel blocking antibody (E4G10) that inhibits VE-cadherin function during angiogenesis but does not disrupt existing adherens junctions on normal vasculature. E4G10 inhibited formation of vascular tubes in vivo in the Matrigel plug and corneal micropocket assays. E4G10 also inhibited tumor growth in three models of mouse and human tumors via an antiangiogenic mechanism. Examination of normal mouse and tumor tissues showed that E4G10 bound to endothelial cells in a subset of tumor vasculature but not to normal vasculature. Bromodeoxyuridine labeling experiments showed that E4G10 specifically targeted a subset of tumor endothelium that is undergoing active cell proliferation, which likely reflects the activated, angiogenic endothelium. These findings indicate that VE-cadherin can be selectively targeted during states of pathological angiogenesis, despite its ubiquitous distribution throughout the entire vasculature. Our data also suggest that antibody E4G10 recognizes VE-cadherin epitopes that are only accessible on endothelial cells forming new adherens junctions, such as in angiogenic tumor vasculature.


Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.
Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD.


Boltzmann equation and hydrodynamic fluctuations.
We apply the method of invariant manifolds to derive equations of generalized hydrodynamics from the linearized Boltzmann equation and determine exact transport coefficients, obeying Green-Kubo formulas. Numerical calculations are performed in the special case of Maxwell molecules. We investigate, through the comparison with experimental data and former approaches, the spectrum of density fluctuations and address the regime of finite Knudsen numbers and finite frequencies hydrodynamics.


Differential expression of dentin matrix protein 1, type I collagen and osteocalcin genes in rat developing mandibular bone.
The expression of dentin matrix protein 1 (Dmp1) mRNA has been compared with that of type I collagen and osteocalcin mRNAs during bone formation in the rat mandible, using in situ hybridization. At embryonic day 15 (E15), type I collagen and osteocalcin mRNAs were expressed by the majority of newly-differentiated osteoblasts attached to unmineralized bone matrices, whereas Dmp1 mRNA expression was confined to only a few osteoblasts. Expression of these genes increased as the number of osteoblasts increased in specimens from E16 to E18. At E20, expression of Dmp1, type I collagen and osteocalcin was also observed in osteocytes. Dmp1 expression continued in osteocytes as they matured up to the 90-day-old specimens, whereas type I collagen and osteocalcin expression in osteocytes almost disappeared at 30 days of postnatal life. In contrast, osteoblasts continued to express type I collagen and osteocalcin in 90-day-old rats, but transiently expressed Dmp1 mRNA, which was seen in the minority of osteoblasts at 14 days of postnatal life. These data show that the developmental expression patterns of Dmp1 in osteogenic differentiation differ from those of type I collagen and osteocalcin, and Dmp1 appears to be expressed by osteocytes throughout ossification in the skeleton. These observations indicate that Dmp1 may serve unique biological functions in osteocyte and bone metabolism.


Vascular endothelium and blood flow.
Major advances have been made over the last decade towards the elucidation of the molecular mechanisms involved in the endothelium-dependent regulation of vascular tone and blood flow. While the primary endothelium-derived vasodilator autacoid is nitric oxide, it is clear that epoxyeicosatrienoic acids and other endothelium-derived hyperpolarising factors, as well as endothelin-1 and reactive oxygen species, play a significant role in the regulation of vascular tone and gene expression. This review is intended as an overview of the signalling mechanisms that link haemodynamic stimuli (such as shear stress and cyclic stretch) and endothelial cell perturbation to the activation of enzymes generating vasoactive autacoids.


Splenic Injury and ERCP: A Possible Risk for Patients with Advanced Chronic Pancreatitis.
Splenic injury is a rare but potentially life-threatening complication of endoscopy, with very few cases of endoscopic retrograde cholangiopancreatography (ERCP)-induced injury reported in the literature. Here we report a patient with chronic alcoholic pancreatitis who was diagnosed with a sub-capsular splenic laceration nearly 6 days after an ERCP. Clinicians should be alerted to the potential post-procedure complications associated with ERCP, particularly as this procedure is being utilized more frequently for the management of patients with complex hepatobiliary and pancreatic conditions.


Examining life-course influences on chronic disease: the Ribeirão Preto and São Luís birth cohort studies (Brazil).
More than any other low- and middle-income country, Brazil has the longest research tradition of establishing, maintaining and exploiting birth cohort studies. This research pedigree is highlighted in the present issue of the Brazilian Journal of Medical and Biological Research, which contains a series of twelve papers from the Ribeirão Preto and São Luis birth cohort studies from the Southeast and Northeast of Brazil, respectively. The topics covered in this raft of reports vary and include predictors of perinatal health and maternal risk factors, early life determinants of cardiovascular risk factors in childhood and adolescence, use of health services, and a description of dietary characteristics of young adults, amongst other topics. There is also a guide to the background, objectives, sampling and protocols employed across these studies, which, together with similar pieces published in past issues of the Brazilian Journal, serve as a very useful starting point, particularly for potential collaborators. In the fervent hope that further follow-up of these cohorts will take place--we provide our own justification for cohort maintenance and extension in this issue--future data collection could include: genetic material, atherosclerosis, ascertained, for instance, by intima-media thickness, and IQ testing in children--scores from which are emerging as potentially important predictors of adult health outcomes up to six decades later.


The Efficacy of Intraoperative Passive Language Mapping for Glioma Surgery: A Case Report.
Background: Recently, electrocorticographic (ECoG) studies have emphasized the importance of gamma band-based functional mapping in the presurgical localization of the eloquent cortex. Passive functional mapping using ECoG signals provides a reliable method for identifying receptive language areas without many of the risks and limitations associated with electrical cortical stimulation. We report a surgical case of left temporal malignant glioma with intraoperative passive language mapping. Case Description: A 78-year-old woman was diagnosed with left temporal glioma with inspection of her language difficulty. MRI showed a left temporal tumor measuring 74.6 × 50.0 × 51.5 mm in size. Real-time CortiQ-based mapping using high-gamma activity by word-listening and story-listening tasks was performed. Significant listening task-evoked high gamma activities were detected in 5 channels in the superior temporal gyrus and one channel in the middle temporal gyrus. The tumor was grossly removed except for the region corresponding to listening task-evoked high gamma activities. Postoperatively, the patient's symptoms of language comprehension difficulty improved, and no new neurological deficits were observed. Conclusion: Intraoperative passive language mapping was successfully performed, and the patient's language function was well-preserved. Intraoperative passive language mapping, which is applicable in a short time and under general anesthesia, can be an important tool for detecting language areas.


Effect of fluensulfone on different functional genes of root-knot nematode Meloidogyne incognita.
Meloidogyne incognita is an obligate plant-parasitic nematode causing serious damage to agricultural crops. Major constraints in nematode management arose due to the limited availability of non-fumigant nematicides in conjunction with the considerable ill effects of fumigants on human and non-target organisms. Recently, fluensulfone has been reported to be an effective non-fumigant nematicide against plant-parasitic nematodes and the model nematode Caenorhabditis elegans. The nematicidal efficacy varies according to its concentration at the time of application, exposure timing, nematode species variability, and even across subpopulations within the same species. It interferes with the key physiological processes of nematodes, like motility, behavior, chemosensation, stylet thrusting, infectivity, metabolism, lipid consumption, tissue integrity, oviposition, egg hatching, and survival. However, the molecular basis of these multivariate physiological anomalies is still largely unknown. Quantitative real-time PCR was carried out to understand the acute transcriptional perturbation of 30 functional genes associated with key physiological and life processes in a M. incognita population, following exposure of 10, 50, and 100 ppm of fluensulfone for 5 and 10 hr. The chemical treatment resulted in significant downregulation of all the neuropeptidergic genes, with concomitant repression of majority of genes related to chemosensation, esophageal gland secretion, parasitism, fatty acid metabolism, and G-protein coupled receptors. Collectively, the parasitism genes were found to be perturbed at highest magnitude, followed by the GPCRs and neuropeptidergic genes. These results establish the wide ranging effect of fluensulfone on various metabolic and physiological pathways of nematode.


Oligosaccharides of Polygonatum Cyrtonema Hua ameliorates dextran sulfate sodium-induced colitis and regulates the gut microbiota.
Ulcerative colitis (UC) is one common chronic inflammatory bowel disease that causes severe side effects, and expensive treatment limits effective and sustained treatment of UC. Fructooligosaccharide was isolated from Polygonatum Cyrtonema Hua (PFOS) and exhibits anti-inflammatory effects. Therefore, we are curious whether PFOS could be used for the treatment of UC. PFOS was introduced via intragastric gavage to C57BL/6 J mice exposed to acute colitis induced by DSS. The results showed that doses of PFOS at 2 and 5 mg/kg/day alleviated the DSS-induced histopathological damage and improved intestinal barrier function. qPCR analysis revealed that PFOS exerted a significant downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and upregulation of antioxidant genes, including superoxide dismutase1 (SOD1), glutathion peroxidase2 (GPX2), and nuclear factor erythroid 2 related factor2 (Nrf2). Furthermore, PFOS suppressed the DSS-induced disruption of the mucosal barrier by downregulating MMP13. Moreover, using 16 S rRNA gene-based microbiota analysis, PFOS could selectively enhance the growth of probiotics, including Bifidobacterium, Alloprevofella, and Alistipes. Our findings indicated that PFOS attenuated DSS-induced colitis in mice, suggesting that PFOS might be used as an efficacious supplement for reducing inflammatory bowel disease.


Candida periprosthetic infection of the hip: a systematic review of surgical treatments and clinical outcomes.
To produce a systematic analysis of types of treatment and outcomes of Candida hip periprosthetic joint infections and their correlation with specific pathogen species. During June 2018, a literature search of candida periprosthetic hip infection in PubMed, Scopus and Embase databases was performed according to the PRISMA (Preferred Reporting Item for Systematic Reviews and Meta-Analyses) guideline. Reviewers used Oxford level of evidence (LoE) and methodological index for non-randomised studies (MINORS) score. Modal distribution of surgical, pharmacological treatment and outcome along with the correlation between types of treatment and outcomes was calculated through the chi-square test. Seventy-nine cases were collected through 35 articles, identifying 81 pathogens. Candida albicans was the most common pathogen. Analysis of LoE reveals 26 LoE 5 (74.29%) and nine LoE 4 (26.71%). From nine LoE 4, ten patients (20.41%) underwent one-stage revision, 22 patients (44.90%) two-stage revision, 11 patients (22.45%) resection arthroplasty and six patients (12.24%) debridement with prosthesis retention. Global success was obtained in 31 cases (63.27%). Modal distribution revealed a preference for two-stage revision (22/49) and fluconazole as medical therapy (36/49). A significant difference was found between one-stage revision and resection arthroplasty (p = 0.031) or debridement (p = 0.003) and between two-stage revision and debridement (p = 0.013). No differences were found between Candida spp. in terms of the outcomes (p = 0.736). Methodological index showed a poor MINOR score. Analysis of the literature suggests better clinical outcome with one- or two-stage revision than with resection arthroplasty or debridement, but the level of evidence is low.


Dietary modification and moderate antioxidant supplementation differentially affect serum carotenoids, antioxidant levels and markers of oxidative stress in older humans.
Oxidative stress is thought to be a factor in the progression of chronic diseases, and even the aging process itself. We examined the effect of two moderate vitamin, mineral and phytochemical supplements and a dietary intervention on markers of oxidative stress and antioxidant status in older humans. Subjects (n = 60, 65-85 y old) were enrolled in a 5-wk, double-blind, placebo-controlled study. The subjects were randomly assigned to a group with one of four interventions: antioxidant supplement capsule, antioxidant supplement tablet, high carotenoid diet or placebo. Postintervention serum levels of some of the supplemented carotenoids and alpha-tocopherol were higher in all treated groups compared with the placebo group and with preintervention levels within groups. Markers of oxidative stress or antioxidant capacity were not significantly different from preintervention levels, although the diet and supplement capsule groups had lower levels of some of those markers than the placebo group postintervention. The results suggest that both moderate antioxidant supplementation and a diet high in carotenoids elevate serum carotenoids and antioxidant levels in an older adult population, although with different specific effects.


[Right optic perineuritis and myelitis 6 years following left optic perineuritis in anti-myelin oligodendrocyte glycoprotein-associated disorder: a case report].
We report a patient with myelin oligodendrocyte glycoprotein (MOG) antibody positivity who manifested myelitis with right optic perineuritis (OPN) 6 years following left OPN. A 45-year-old man treated 6 years previously for left OPN developed ascending numbness in both legs, urinary dysfunctions, and constipation. Neurologic examination disclosed bilateral hypesthesia extending downward over the chest from the T8 level. No motor weakness was evident. Visual field testing showed dense peripheral constriction with intact central vision on the right and a smaller superior scotoma on the left. Visual acuity and funduscopic findings were normal. Results of routine serologic investigations and autoimmune antibody titers, including those of anti-aquaporin 4 antibody, were within normal limits, except that both serum and cerebrospinal fluid were positive for anti-MOG antibody. MRI displayed a longitudinal cord lesion extending from T2 to T9, as well as optic nerve sheath enhancement characteristic of OPN. The patient was diagnosed with myelitis in addition to OPN, both resulting from MOG antibody-associated demyelination. Patients with myelitis, require careful assessment of visual acuity and visual fields to detect possible accompanying OPN and ON. We suspect that OPN in some other patients may likewise be caused by anti-MOG antibody.


Proteomic analysis of plasma from children with sickle cell anemia and silent cerebral infarction.
Silent cerebral infarction is the most common neurological abnormality in children with sickle cell anemia, affecting 30-40% of 14 year olds. There are no known biomarkers to identify children with silent cerebral infarcts, and the pathological basis is also unknown. We used an unbiased proteomic discovery approach to identify plasma proteins differing in concentration between children with and without silent cerebral infarcts. Clinical parameters and plasma samples were analysed from 51 children (mean age 11.8 years, range 6-18) with sickle cell anemia (HbSS). A total of 19 children had silent cerebral infarcts and 32 normal MRI; the children with silent infarcts had lower HbF levels (8.6 vs 16.1%, P=0.049) and higher systolic blood pressures (115 vs 108.6, P=0.027). Plasma proteomic analysis showed 13 proteins increased more than 1.3 fold in the SCI patients, including proteins involved in hypercoagulability (α2-antiplasmin, fibrinogen-γ chain, thrombospondin-4), inflammation (α2-macroglobulin, complement C1s and C3), and atherosclerosis (apolipoprotein B-100). Higher levels of gelsolin and retinol-binding protein 4 were also found in the population with silent infarcts, both of which have been linked to stroke. We investigated the genetic basis of these differences by studying 359 adults with sickle cell disease (199 with silent cerebral infarcts, 160 normal MRIs), who had previously undergone a genome-wide genotyping array. None of the genes coding for the differentially expressed proteins were significantly associated with silent infarction. Our study suggests that silent cerebral infarcts in sickle cell anemia may be associated with higher systolic blood pressure, lower HbF levels, hypercoagulability, inflammation and atherosclerotic lipoproteins.


Perylenetetracarboxylic diimide derivatives linked with spirobifluorene.
A series of perylenetetracarboxylic diimide (PDI) compounds linked with spirobifluorene have been prepared. The orthogonal configuration of the PDI subunits efficiently hindered their molecular aggregation in solution. Energy transfer from a 1,7-diphenoxyl group substituted PDI (PO-PDI) to a 1,7-dipyrrolidinyl group substituted PDI (PY-PDI) occurred with a large efficiency when PO-PDI was selectively excited, despite the orthogonal orientation of the two units. This observation was in direct conflict with predictions derived from the Förster theory. More interestingly, this efficient energy transfer also occurred in the solid state.


A New Wavelet Denoising Method for Experimental Time-Domain Signals: Pulsed Dipolar Electron Spin Resonance.
We adapt a new wavelet-transform-based method of denoising experimental signals to pulse-dipolar electron-spin resonance spectroscopy (PDS). We show that signal averaging times of the time-domain signals can be reduced by as much as 2 orders of magnitude, while retaining the fidelity of the underlying signals, in comparison with noiseless reference signals. We have achieved excellent signal recovery when the initial noisy signal has an SNR ≳ 3. This approach is robust and is expected to be applicable to other time-domain spectroscopies. In PDS, these time-domain signals representing the dipolar interaction between two electron spin labels are converted into their distance distribution functions P(r), usually by regularization methods such as Tikhonov regularization. The significant improvements achieved by using denoised signals for this regularization are described. We show that they yield P(r)'s with more accurate detail and yield clearer separations of respective distances, which is especially important when the P(r)'s are complex. Also, longer distance P(r)'s, requiring longer dipolar evolution times, become accessible after denoising. In comparison to standard wavelet denoising approaches, it is clearly shown that the new method (WavPDS) is superior.


Reduced multimodal integration of memory features following continuous theta burst stimulation of angular gyrus.
Lesions of the angular gyrus (AnG) region of human parietal cortex do not cause amnesia, but appear to be associated with reduction in the ability to consciously experience the reliving of previous events. We used continuous theta burst stimulation to test the hypothesis that the cognitive mechanism implicated in this memory deficit might be the integration of retrieved sensory event features into a coherent multimodal memory representation. Healthy volunteers received stimulation to AnG or a vertex control site after studying stimuli that each comprised a visual object embedded in a scene, with the name of the object presented auditorily. Participants were then asked to make memory judgments about the studied stimuli that involved recollection of single event features (visual or auditory), or required integration of event features within the same modality, or across modalities. Participants' ability to retrieve context features from across multiple modalities was significantly reduced after AnG stimulation compared to stimulation of the vertex. This effect was observed only for the integration of cross-modal context features but not for integration of features within the same modality, and could not be accounted for by task difficulty as performance was matched across integration conditions following vertex stimulation. These results support the hypothesis that AnG is necessary for the multimodal integration of distributed cortical episodic features into a unified conscious representation that enables the experience of remembering.


Hamiltonian chaos in a model alveolus.
In the pulmonary acinus, the airflow Reynolds number is usually much less than unity and hence the flow might be expected to be reversible. However, this does not appear to be the case as a significant portion of the fine particles that reach the acinus remains there after exhalation. We believe that this irreversibility is at large a result of chaotic mixing in the alveoli of the acinar airways. To test this hypothesis, we solved numerically the equations for incompressible, pulsatile, flow in a rigid alveolated duct and tracked numerous fluid particles over many breathing cycles. The resulting Poincare sections exhibit chains of islands on which particles travel. In the region between these chains of islands, some particles move chaotically. The presence of chaos is supported by the results of an estimate of the maximal Lyapunov exponent. It is shown that the streamfunction equation for this flow may be written in the form of a Hamiltonian system and that an expansion of this equation captures all the essential features of the Poincare sections. Elements of Kolmogorov-Arnol'd-Moser theory, the Poincare-Birkhoff fixed-point theorem, and associated Hamiltonian dynamics theory are then employed to confirm the existence of chaos in the flow in a rigid alveolated duct.


Making Waves: Modeling bioturbation in soils - are we burrowing in the right direction?
The burrowing, feeding and foraging activities of terrestrial and benthic organisms induce displacements of soil and sediment materials, leading to a profound mixing of these media. Such particle movements, called "sediment reworking" in aquatic environments and "bioturbation" in soils, have been thoroughly studied and modeled in sediments, where they affect organic matter mineralization and contaminant fluxes. In comparison, studies characterizing the translocation, by soil burrowers, of mineral particles, organic matter and adsorbed contaminants are paradoxically fewer. Nevertheless, models borrowed from aquatic ecology are used to predict the impact of bioturbation on organic matter turnover and contaminant transport in the soil. However, these models are based on hypotheses that have not been tested with adequate observations in soils, and may not necessarily reflect the actual impact of soil burrowers on particle translocation. This paper aims to (i) highlight the possible shortcomings linked to the current use of sediment reworking models for soils, (ii) identify how recent progresses in aquatic ecology could help to circumvent these limitations, and (iii) propose key steps to ensure that soil bioturbation models are built on solid foundations: more accurate models of organic matter turnover, soil evolution and contaminant transport in the soil are at stake.


Malignant ovarian germ cell tumours in gonadal Y chromosome mosaicism.
Previous studies have shown that two partially overlapping mechanisms are responsible for the development of malignant ovarian germ cell tumours (MOGCT): either spontaneous mutations, mostly in KIT gene, or the presence of Y chromosome material, in dysgenetic gonads. While unilateral oophorectomy and preservation of fertility is favourable in most cases, presence of whole or part of Y chromosome in dysgenetic ovaries is associated with a risk of bilateral germ cell tumour development. The aim of this study was to evaluate the frequency of Y chromosome material in these tumours. A total of 47 cases with histopathologic diagnosis of malignant germ cell tumour were selected in a period of 9 years. A relative quantitative PCR (RQ-PCR) method was designed and validated to detect testis-specific protein Y-encoded (TSPY) gene on Y chromosome. After DNA extraction, TSPY gene was sought as a surrogate of Y chromosome. Significant amounts of TSPY gene were found in seven cases, two of which had gonadoblastoma and one had cytogenetic proof of Y chromosome presence. Some MOGCTs develop on the background of gonadal mosaicism and gonadal dysgenesis. Bilateral oophorectomy may be indicated in patients with these disorders because they are at risk of developing an MOGCT on the contralateral gonad. Moreover, this chromosomal abnormality is hardly found by routine methods, and the abnormality is more easily sought in MOGCT cells by means of RQ-PCR.


[Safety awareness of anticancer drug handling among Japanese nurses].
The purpose of this study was to investigate Japanese nurses' awareness of the adverse effects of occupational exposure to anticancer drugs and safe handling, as well as their associations. A self-rating questionnaire was mailed to 939 nurses in 107 university hospitals, 13 cancer-special hospitals, and 193 general hospitals with over 300 beds and at least five or more clinics in Japan. A total of 571 female nurses responded to the questionnaire. About 40% of the nurses were not at all aware of the potential adverse effects of occupational exposure to anticancer drugs. Eighty-eight percent of the nurses prepared anticancer drugs in the hospital wards; in most cases, nurses, not doctors or pharmacists, transported and administered such drugs to cancer patients. Regarding safety, 39% of the nurses took protective countermeasures against anticancer drugs; 15% paid special attention to the handling environment; 10% had guidelines for the handling of anticancer drugs; and, only 7% took countermeasures with body fluids or linen handling of cancer patients. Although 82% of the nurses were concerned about the potential health effects of occupational exposure, 75% or over did not know whether the exposure might affect their future health or progeny. Awareness of adverse effects was significantly related with precaution in anticancer drug handling, for which 95% of the nurses stated a desire for special education and training. Approximately 60% of Japanese nurses are aware of the risk of occupational exposure to anticancer drugs, but this might be an overestimate because of the sampling bias. Since only small numbers of nurses take sufficient safety precaution, programs for education and training for safe handling of anticancer drugs are crucial.


Phenethyl Isothiocyanate Suppresses the Proinflammatory Cytokines in Human Glioblastoma Cells through the PI3K/Akt/NF-κB Signaling Pathway In Vitro.
Phenethyl isothiocyanate (PEITC), extracted from cruciferous vegetables, showed anticancer activity in many human cancer cells. Our previous studies disclosed the anticancer activity of PEITC in human glioblastoma multiforme (GBM) 8401 cells, including suppressing the cell proliferation, inducing apoptotic cell death, and suppressing cell migration and invasion. Furthermore, PEITC also inhibited the growth of xenograft tumors of human glioblastoma cells. We are the first to investigate PEITC effects on the receptor tyrosine kinase (RTK) signaling pathway and the effects of proinflammatory cytokines on glioblastoma. The cell viability was analyzed by flow cytometric assay. The protein levels and mRNA expressions of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay (ELISA) reader and real-time polymerase chain reaction (PCR) analysis, respectively. Furthermore, nuclear factor-kappa B- (NF-κB-) associated proteins were evaluated by western blotting. NF-κB expression and nuclear translocation were confirmed by confocal laser microscopy. NF-κB binding to the DNA was examined by electrophoretic mobility shift assay (EMSA). Our results indicated that PEITC decreased the cell viability and inhibited the protein levels and expressions of IL-1β, IL-6, and TNF-α genes at the transcriptional level in GBM 8401 cells. PEITC inhibited the binding of NF-κB on promoter site of DNA in GBM 8401 cells. PEITC also altered the protein expressions of protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and NF-κB signaling pathways. The inflammatory responses in human glioblastoma cells may be suppressed by PEITC through the phosphoinositide 3-kinase (PI3K)/Akt/NF-κB signaling pathway. Thus, PEITC may have the potential to be an anti-inflammatory agent for human glioblastoma in the future.


Effectiveness of simulation-based learning on student nurses' self-efficacy and performance while learning fundamental nursing skills.
It was noted worldwide while learning fundamental skills and facing skills assessments, nursing students seemed to experience low confidence and high anxiety levels. Could simulation-based learning help to enhance students' self-efficacy and performance? Its effectiveness is mostly unidentified. This study was conducted to provide a shared experience to give nurse educators confidence and an insight into how simulation-based teaching can fit into nursing skills learning. A pilot study was completed with 50 second-year undergraduate nursing students, and the main study included 98 students where a pretest-posttest design was adopted. Data were gathered through four questionnaires and a performance assessment under scrutinized controls such as previous experiences, lecturers' teaching skills, duration of teaching, procedure of skills performance assessment and the inter-rater reliability. The results showed that simulation-based learning significantly improved students' self-efficacy regarding skills learning and the skills performance that nurse educators wish students to acquire. However, technology anxiety, examiners' critical attitudes towards students' performance and their unpredicted verbal and non-verbal expressions, have been found as possible confounding factors. The simulation-based learning proved to have a powerful positive effect on students' achievement outcomes. Nursing skills learning is one area that can benefit greatly from this kind of teaching and learning method.


Radioimmunoassay of ganirelix in plasma or serum.
A procedure for the radioimmunoassay (RIA) of ganirelix in plasma or serum at concentrations as low as 0.050 ng/ml is described. Antiserum was produced by coupling the N-terminus glycyl analog of ganirelix to BSA by a carbodiimide reaction and immunizing rabbits with this conjugate. The antiserum did not crossreact with LHRH or with various ganirelix peptide fragments. For RIA, 125I labeled ganirelix was used as the tracer and a double antibody procedure was used to separate the free and bound fractions. No purification of the analyte was required prior to RIA. Accuracy of the method was assessed by adding known quantities of ganirelix to ganirelix-free plasma and determining the ratio of measured to added analyte. Linear regression analysis for the concentration range 0.050-50.0 ng/ml yielded a regression equation of y = 0.97x + 0.18, r = 0.999, where x is the amount added and y is the amount measured. Additional validation was obtained from an in vivo study in which [3H]-ganirelix was administered to monkeys and plasma clearance profiles were determined by RIA and an HPLC-radiochemical method. The results were in agreement within experimental error of the two methods. Linear regression analysis of the comparative data gave the equation y = 0.92x + 33.7, r = 0.980, where x is the amount measured by RIA and y is the amount measured by HPLC-radiochemical analysis.


Antimicrobial resistance pattern of Neisseria gonorrhoeae isolates from peripheral health centres and STD clinic attendees of a tertiary care centre in India.
The aim of the study was to compare the antimicrobial resistance pattern of Neisseria gonorrhoeae isolates from urban and rural peripheral health centres and from sexually transmitted disease (STD) clinic attendees. Antimicrobial susceptibility testing of 191 N. gonorrhoeae isolates (165 isolates from STD clinic attendees and 26 from peripheral health centres) was carried out in Delhi, India, using the calibrated dichotomous sensitivity technique for penicillin, tetracycline, ceftriaxone, ciprofloxacin, spectinomycin and nalidixic acid, and minimum inhibitory concentrations were determined using E-test. Penicillin-resistant, ciprofloxacin-resistant, penicillinase-producing N. gonorrhoeae and tetracycline-resistant N. gonorrhoeae strains were higher in STD clinic attendees than in peripheral health centres, probably because of less antibiotic pressure in the peripheral areas. High-level resistance to ciprofloxacin and multiresistant strains were also higher in STD clinic attendees. The present study emphasizes the importance of surveillance of antimicrobial resistance of N. gonorrhoeae in different population subgroups in order to monitor the spread of multiresistant strains and to update the national treatment recommendations.


The influence of a fish oil dietary supplement on immunogenic keratitis.
Fish lipids contain large amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid. These fatty acids are known to have an influence on prostaglandin (PG) and leukotriene (LT) synthesis. We studied the effect of a fish oil dietary supplement on an immune-complex-induced keratitis of the rabbit eye and compared it with the effect of a sunflower seed oil dietary supplement, rich in linoleic acid. Immune complex keratitis induced by intrastromal injection of human serum albumin (HSA) was characterized by leukocyte infiltrate, neovascularization, and corneal edema. Animals given a fish oil diet showed significantly less leukocyte infiltrate, neovascularization, and corneal edema, compared to those given a sunflower seed oil diet.


Numerical evaluation of the effect of electronically steering a phased array transducer: axially post-focal shifting.
HIFU has been emerging as an effective and safe modality for the treatment of solid tumours and cancers. The focus shifting range of phased array HIFU transducer is an important safety concern because of the presence of grating lobe in the pre-focal region. However, previous studies were only based on linear acoustic wave model. The nonlinear wave propagation from a 256-element phased array through multiple layered media was simulated using the angular spectrum approach (ASA) in marching fractional steps with the consideration of diffraction, attenuation and non-linearity effects by a second-order operator splitting scheme. The distribution of acoustic intensities, temperature elevations, lesion sizes and grating lobe levels were calculated at various axially post-focal shifting distances and driving frequencies. Axially shifting HIFU focus leads to significant increase of the acoustic intensity at the grating lobe, but decrease at the main lobe. The influences on the acoustic field, thermal field and lesion sizes are determined by the shifting distance and driving frequency, and variations can be fit monotonically and linearly. Prediction accuracies by simple regression models are satisfactory. Irreversible tissue coagulation could be generated by the grating lobe at certain conditions. The established nonlinear wave propagation algorithm allows the accurate description of HIFU field and consequently the evaluation of grating lobe and steerability of focus. The influence of focus shifting may be predicted simply. The treatment planning of phased array HIFU ablation could be optimised by setting the appropriate exposure and focus scanning schemes.


Quantum chemical study of the structure and thermochemistry of the five-membered nitrogen-containing heterocycles and their anions and radicals.
The nitrogen-containing heterocycles are of interest as high-energy-density materials for use as propellants and explosives, while the pyrolysis of these compounds is also important in understanding the evolution of unwanted NO and NO2 (NOx) from organic fuels such as coal and biomass. We have used ab initio and density functional methods to study the molecular structures and thermochemical properties of the five-membered nitrogen-containing heterocycles and their anions and radicals corresponding to respective heterolytic and homolytic loss of a hydrogen atom from either a nitrogen or carbon site. Many of these thermochemical properties have not previously been measured, especially for the heterocycles containing three and four nitrogen atoms. Using the theoretical methods CBS-APNO, G3, and G3B3, we calculate enthalpies of formation of 26.5, 42.4, 31.9, 63.7, 46.8, 81.0, and 79.0 kcal mol-1 for pyrrole, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, 1H-tetrazole, and 2H-tetrazole. A correlation is developed between the number of nitrogen atoms in a heterocycle and its enthalpy, and we extrapolate this relationship to predict the enthalpy of formation of pentazole. N-H BDEs in the heterocycles typically increase with the number of nitrogen atoms in the molecule, while C-H BDEs are similar in all of the studied heterocycles, at around 120 kcal mol-1. In all cases the N-H BDEs are weaker than the C-H BDEs, suggesting abstraction of the N-H hydrogen atom is more likely. Deprotonation enthalpies and free energies reveal that the N-H protons become more acidic with increasing number of nitrogen atoms in the heterocycle. C-H protons are less acidic than N-H protons by ca. 49 kcal mol-1, or ca. 35 kcal mol-1 when adjacent to the NH group. Trends in N-H and C-H acidities can be qualitatively explained by electrostatic effects and electron affinities. From its use as a reference species in our calculations, we identify that the experimental enthalpy of pyrimidine (1,3-diazine) may be in error by ca. 1-3 kcal mol-1, and we recommend an enthalpy of formation of 44.8 +/- 1.0 kcal mol-1.


Clean photodecomposition of 1-methyl-4-phenyl-1H-tetrazole-5(4H)-thiones to carbodiimides proceeds via a biradical.
The photochemistry of 1-methyl-4-phenyl-1H-tetrazole-5(4H)-thione (1a) and 1-(3-methoxyphenyl)-4-methyl-1H-tetrazole-5(4H)-thione (1b) was studied in acetonitrile at 254 and 300 nm, which involves expulsion of dinitrogen and sulfur to form the respective carbodiimides 5a,b as sole photoproducts. Photolysis of the title compounds in the presence of 1,4-cyclohexadiene trap led to the formation of respective thioureas, providing strong evidence for the intermediacy of a 1,3-biradical formed by the loss of dinitrogen. In contrast, a trapping experiment with cyclohexene provided no evidence to support an alternative pathway of photodecomposition involving initial desulfurization followed by loss of dinitrogen via the intermediacy of a carbene. Triplet sensitization and triplet quenching studies argue against the involvement of a triplet excited state. While the quantum yields for the formation of the carbodiimides 5a,b were modest and showed little change on going from a C(6)H(5) (1a) to mOMeC(6)H(4) (1b) substituent on the tetrazolethione ring, the highly clean photodecomposition of these compounds to a photostable end product makes them promising lead structures for industrial, agricultural, and medicinal applications.


Methyl Salicylate Enhances Flavonoid Biosynthesis in Tea Leaves by Stimulating the Phenylpropanoid Pathway.
The phytohormone salicylic acid (SA) is a secondary metabolite that regulates plant growth, development and responses to stress. However, the role of SA in the biosynthesis of flavonoids (a large class of secondary metabolites) in tea (Camellia sinensis L.) remains largely unknown. Here, we show that exogenous methyl salicylate (MeSA, the methyl ester of SA) increased flavonoid concentration in tea leaves in a dose-dependent manner. While a moderate concentration of MeSA (1 mM) resulted in the highest increase in flavonoid concentration, a high concentration of MeSA (5 mM) decreased flavonoid concentration in tea leaves. A time-course of flavonoid concentration following 1 mM MeSA application showed that flavonoid concentration peaked at 2 days after treatment and then gradually declined, reaching a concentration lower than that of control after 6 days. Consistent with the time course of flavonoid concentration, MeSA enhanced the activity of phenylalanine ammonia-lyase (PAL, a key enzyme for the biosynthesis of flavonoids) as early as 12 h after the treatment, which peaked after 1 day and then gradually declined upto 6 days. qRT-PCR analysis of the genes involved in flavonoid biosynthesis revealed that exogenous MeSA upregulated the expression of genes such as CsPAL, CsC4H, Cs4CL, CsCHS, CsCHI, CsF3H, CsDFR, CsANS and CsUFGT in tea leaves. These results suggest a role for MeSA in modulating the flavonoid biosynthesis in green tea leaves, which might have potential implications in manipulating the tea quality and stress tolerance in tea plants.


Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy.
Post-translational modifications of host or viral proteins are key strategies exploited by viruses to support virus replication and counteract host immune response. SUMOylation is a post-translational modification process mediated by a family of ubiquitin-like proteins called small ubiquitin-like modifier (SUMO) proteins. Multiple sequence alignment of 78 representative flaviviruses showed that most (72/78, 92.3%) have a putative SUMO-interacting motif (SIM) at their non-structural 5 (NS5) protein's N-terminal domain. The putative SIM was highly conserved among 414 pre-epidemic and epidemic Zika virus (ZIKV) strains, with all of them having a putative SIM core amino acid sequence of VIDL (327/414, 79.0%) or VVDL (87/414, 21.0%). Molecular docking predicted that the hydrophobic SIM core residues bind to the β2 strand of the SUMO-1 protein, and the acidic residues flanking the core strengthen the binding through interactions with the basic surface of the SUMO protein. The SUMO inhibitor 2-D08 significantly reduced replication of flaviviruses and protected cells against ZIKV-induced cytopathic effects in vitro. A SIM-mutated ZIKV NS5 failed to efficiently suppress type I interferon signaling. Overall, these findings may suggest SUMO modification of the viral NS5 protein to be an evolutionarily conserved post-translational modification process among flaviviruses to enhance virus replication and suppress host antiviral response.


One Gene, Many Facets: Multiple Immune Pathway Dysregulation in SOCS1 Haploinsufficiency.
Inborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that SOCS1 haploinsufficiency has a pleiotropic effect in humans. We sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of SOCS1 haploinsufficiency. We assessed impacts of reduced SOCS1 expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells. SOCS1 haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in SOCS1 haploinsufficiency patients. SOCS1 haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for SOCS1 haploinsufficient patients.


Oxidation of salicylates by stimulated granulocytes: evidence that these drugs act as free radical scavengers in biological systems.
Although salicylates have been used for centuries as treatment of inflammatory diseases, the mechanism of action of these drugs is still not clear. Aspirin (acetylsalicylic acid) and other nonsteroidal anti-inflammatory drugs (NSAID) inhibit prostaglandin biosynthesis, a property that appears to explain part of their anti-inflammatory activity. However, this mechanism does not appear to explain the anti-inflammatory properties of salicylic acid, which is a major metabolite of ASA in vivo. Results of prior studies in our laboratory have established that benzoic acid, the parent compound of the salicylate group of drugs, is decarboxylated and hydroxylated by the hydroxyl free radical (OH.) produced by stimulated granulocytes. These observations suggested that salicylates might be similarly metabolized by granulocytes. If so, the capacity of salicylates to rapidly react with OH. might relate directly to their known anti-inflammatory properties. Preliminary experiments established that salicylic acid and aspirin were decarboxylated by the hydroxyl free radical generated by the enzyme system xanthine-xanthine oxidase. We then studied the metabolism of salicylates by human granulocytes. Unstimulated granulocyte suspensions did not oxidize ASA or salicylic acid. However, suspensions stimulated by opsonized zymosan particles rapidly oxidized both substrates in pharmacological concentrations. The rate of oxidation of salicylic acid was 16-fold higher than benzoic acid, whereas the rate of oxidation of ASA was four-fold higher. The reaction was oxygen dependent and could be inhibited by known hydroxyl scavengers, particularly dimethylthiourea. The reaction could also be inhibited by superoxide dismutase and azide, indicating that O-2 and heme or an iron-dependent enzyme were required for the reaction. The reaction was not impaired by compounds known to react with the HOCL and the chloramines generated by stimulated PMN. Furthermore, salicylic acid in high concentrations did not impair the HMPS pathway, the production of O-2 or the production of H2O2 by granulocytes. These data provide evidence that salicylates are rapidly oxidized by the hydroxyl free radical produced by granulocytes and not O-2, H2O2, or HOCL. This capacity of salicylates to react rapidly and selectively react with OH. may directly relate to their anti-inflammatory properties. In addition, results of our experiments indicate that stimulated granulocytes acquire the capacity to metabolize these drugs. Therefore, several metabolites of salicylates may be produced at a site of inflammation, all of which may have altered biological activity compared with the parent compound.


Enantioselective Bioaccumulation, Tissue Distribution, and Toxic Effects of Myclobutanil Enantiomers in Pelophylax nigromaculatus Tadpole.
Research on the enantioselective behavior of chiral pesticides on amphibians has received growing attention, because amphibians are experiencing a population decline and amphibian metamorphosis shares many similarities with human fetal development. In this study, the enantioselective behavior of myclobutanil on Pelophylax nigromaculatus tadpole was studied. The antioxidant enzyme (SOD, GST) activities and malondialdehyde (MDA) content were investigated to assess the different toxic effects when tadpoles were exposed to myclobutanil enantiomers for 96 h. In the chronic exposure experiment, the bioaccumulation concentration of (-)-myclobutanil in tadpoles is significantly higher than that of (+)-myclobutanil, and the concentration of myclobutanil in tadpole intestine and liver was higher compared with other tissues. During the elimination experiment, about 95% of myclobutanil in tadpoles was eliminated within only 24 h. On the basis of these data, the enantiomeric differences should be taken into consideration in the risk assessment of myclobutanil.


Toxic effects of adriamycin on the ganglia of the peripherial nervous system: a neuropathological study.
Rats were injected intravenously with 10 mg/kg of adriamycin (doxorubicin). All the treated animals developed severe posterior limb ataxia on days 11 and 12 following the injection. Mild ataxia of the forelimbs was noted later. The animals were killed between days 10 and 50. Light microscopy revealed changes in ganglion cells of the peripheral nervous system with sparing of neurons in the central nervous system. In the spinal, paravertebral and trigeminal ganglia, necrosis of neurons was followed by mild lymphocytic infiltration, and ultimate loss of ganglion cells, and a marked proliferation of nerve sheath cells. Electron microscopic study revealed increased numbers of neurofilaments and the presence of membrane-bound cisterns in the affected dorsal root ganglion cell bodies. It is concluded that adriamycin, an important anticancer therapeutic agent, has neurotoxic properties and that it selectively damages the ganglia of the peripheral nervous system.


Is diffusion anomalous in two-dimensional Yukawa liquids?
There have recently been many predictions of "superdiffusion" in two-dimensional strongly coupled Yukawa systems, both by computer simulations and in dusty plasma experiments, with substantially varying diffusion exponents. Here we show that the results crucially depend on the strength of dissipation and the time instant of the measurement. For sufficiently large friction even subdiffusion is possible. However, there are strong indications that, in the long-time limit, anomalous diffusion vanishes and the system returns to normal diffusion, for dissipative as well as for frictionless systems.


Decreasing incidence of critical limb ischemia after intra-aortic balloon pump counterpulsation.
The authors investigated the incidence of critical limb ischemia (CLI) in 187 patients with intra-aortic balloon pump (IABP) support during a 6-year study period and determined risk factors and long-term outcome (median 5 years) after discharge from a cardiac intensive care unit. Cardiogenic shock following acute myocardial infarction was the predominant cause of IABP support. CLI occurred in 10% of the patients after IABP implantation. Nevertheless, in light of the overall high mortality in this patient population, CLI seems not a primary concern. Furthermore, its incidence significantly decreased during recent years. Duration of IABP support was a significant predictor for CLI.


Glossing over cryptic species: Descriptions of four new species of Glossodoris and three new species of Doriprismatica (Nudibranchia: Chromodorididae).
Advances in molecular systematics have led to a rapid increase in the identification of cryptic and pseudocryptic species in organisms exhibiting diverse and complex coloration with complicated taxonomic histories. A recent molecular phylogenetic analysis of nudibranchs in the genus Glossodoris (Mollusca: Gastropoda: Heterobranchia: Chromodorididae) and related genera identifies multiple cryptic and pseudocryptic species complexes, one within Glossodoris pallida and three within Glossodoris cincta, and support for three new species of Doriprismatica. Morphological analyses of color pattern, radular structure, buccal mass, and reproductive system support these identifications. Descriptions for Glossodoris buko sp. nov., Glossodoris bonwanga sp. nov., Glossodoris andersonae sp. nov., Glossodoris acosti sp. nov., and what will retain the name Glossodoris sp. cf. cincta are provided here, in addition to descriptions for new species Doriprismatica balut sp. nov., Doriprismatica rossi sp. nov., and Doriprismatica marinae sp. nov.. Glossodoris pallida and G. buko exhibit extreme differences in radular structure in addition to a clear biogeographic split in range. Glossodoris bonwanga, G. andersonae, G. acosti and G. sp. cf. cincta, share morphological and geographic differences but these are not as pronounced as in G. pallida and G. buko. More detailed study of the G. cincta complex is necessary to resolve some remaining systematic challenges. Doriprismatica balut is clearly distinct from all other congeners based on molecular and morphological characters. In contrast, D. rossi and D. marinae are not strongly divergent genetically, but have major morphological divergences that clearly distinguish them.


Challenges in pig artificial insemination.
Semen extended in a liquid state, together with conventional artificial insemination (AI), is the sole sperm technology used by the pig industry. Sperm technologies known for many years, such as cryopreservation, and others developed during recent years, such as sperm sexing, have not yet been integrated into commercial use. Moreover, there has recently been an explosion of new technologies, such as sperm mediated gene transfer or encapsulated spermatozoa which need additional supportive techniques before they can be economically applied to pig breeding. The speed with which the aforementioned sperm technologies are accepted and utilized by the pig industry depends on the availability of efficient insemination procedures. Therefore, AI is entering a new dimension where it will be converted into a tool for the efficient application of current and new sperm technologies. Some new insemination procedures have been recently developed. This review examines the suitability of available insemination procedures for the efficient application of current, emergent and future sperm technology to the pig industry.


[Criteral for assessing quantitative disability in expert determination of functional physical disorders. Review of the literature].
The assessment of individuals with somatoform disorders seeking payments or compensation is a major challenge for psychiatrists, insurers and the social welfare system. It is difficult to examine these disorders objectively and to quantify the impairment people experience in their work or private life. In order to develop more rational criteria for the assessment of these patients, we first reviewed the relevant literature and extracted the criteria mentioned by the respective authors. We then grouped these criteria in clinically plausible dimensions in order to develop a list of parameters that could help psychiatric experts to analyse the impairment more objectively and to help institutions in evaluating the assessments.


Budget impact analysis of liposomal amphotericin B and amphotericin B lipid complex in the treatment of invasive fungal infections in the United States.
Liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) are both indicated for treating invasive fungal infections (IFIs) caused by Aspergillus, Candida and Cryptococcus spp. among patients who are refractory to or intolerant of conventional amphotericin B (CAB). Prior studies have suggested similar efficacies but differences in adverse event (AE) profiles between L-AMB and ABLC. Our objective was to conduct a cost-minimisation and budget impact analysis for the treatment of IFIs with L-AMB and ABLC in a US hospital setting. A Microsoft® Excel-based budget impact model was developed to estimate the costs associated with using L-AMB and ABLC for the treatment of adult patients with Aspergillus, Candida and Cryptococcus spp. infections, who are refractory to or intolerant of CAB, during a hospital stay. The model was built from a hospital perspective, and included drug costs of L-AMB and ABLC, and costs for treating drug-related AEs (i.e. nephrotoxicity with/without dialysis, infusion-related reactions, anaphylaxis, hypomagnesaemia and hypokalaemia). Average sales price was used as the drug cost estimate in the base-case analyses. The treatment duration and rates of AEs for L-AMB and ABLC were mainly obtained from a retrospective study of these two drugs in the target population using the Cerner Health Facts data. Treatment costs of AEs were obtained from the publicly available sources. The budget impact ($US, year 2011 values) was evaluated for a hypothetical hospital with 100 administrations where L-AMB and ABLC are used for the treatment of the target population by changing the market share of L-AMB and ABLC from 32/68% to an anticipated market share of 60/40% in the base-case analysis. Sensitivity analyses were conducted by varying drug costs, rates of AEs, costs of AEs and anticipated market shares of L-AMB and ABLC. The estimated per-patient cost per hospital episode associated with L-AMB and ABLC use were $US14,563 and $US16,748, respectively. Cost of AEs accounted for 68.7% of the costs for L-AMB and 85.4% for ABLC. In a hypothetical hospital with 100 annual admissions of patients using these two drugs for IFIs, changing the market shares from 32/68% for L-AMB and ABLC, respectively, to 60/40% yielded a 3.8% cost reduction, which corresponded to an absolute cost savings of $US61,191. Sensitivity analyses indicated that the results were robust to changes in input parameter values in most cases. This study suggests that hospitals can realize cost savings by substituting L-AMB for ABLC in the treatment of IFIs. The cost savings are driven by the lower rates of AEs associated with L-AMB use compared with ABLC.


The use of corticosteroids in croup: a survey.
The use of corticosteroids to treat laryngotracheobronchitis (croup) is controversial. Although some evidence supports the efficacy of treating hospitalized patients with croup, there is no published information on the use of corticosteroids in the outpatient population. We sought to determine what the current practice in the use of corticosteroids to treat croup was in our community. One hundred thirty-eight questionnaires were mailed to pediatricians and family practitioners in our geographic region. One hundred twelve surveys were completed and returned. The majority of responding physicians used corticosteroids to treat both inpatients and outpatients with croup at least some of the time. A significantly greater percentage used them to treat hospitalized patients (93%) compared with nonhospitalized patients (68%). The drug used by the majority of respondents was dexamethasone (87% in treating inpatients, 56% in treating outpatients). The initial dosage, cumulative dosage, number of doses, and route of administration varied greatly among the respondents. This survey demonstrates that most physicians in our area are using corticosteroids to treat both hospitalized and non-hospitalized patients with croup. However, the form of drug used, dosing regimen, and route of administration are highly variable. This survey highlights the need for clinical studies to assess the efficacy of using corticosteroids to treat outpatients with croup and to determine how best to use them.


In the world but not of it: managing the conflict between Christian and institution.
Christian physicians, nurses and other health care workers must manage a daily conflict of conscience between their Christian faith and predominantly secular health care institutions. This essay examines various efforts for managing these conflicts: a turn towards social justice or a seeking of holiness. Seeking social justice, however, is theologically empty. Traditionally, the Christian requirement that we be "in this world but not of it" requires a journey along a narrow path to holiness. Christian medical morality must, therefore, be understood within this light. However, just as there cannot be generic health care, but rather health care for a particular person's needs and problems there cannot be generic holiness, but only a holiness grounded in worshiping God rightly. In so worshiping the Christian will be assisted in negotiating the inescapable and perilous vocation of being in the world but not of it.


Allergic angina following wasp sting: Kounis syndrome.
Kounis syndrome is defined as an acute coronary syndrome triggered by the release of inflammatory mediators following an allergic insult characterized by acute onset of breathlessness, palpitations, diaphoresis and chest tightness (Gázquez V, Dalmau G, Gaig P, Gómez C, Navarro S, Mercé J. Kounis syndrome: report of 5 cases. J Investig Allergol Clin Immunol 2010;20:162-5). We report a 20-year-male patient who presented with acute myocardial infarction following a wasp sting at our institute. ECG showed non-ST-elevation myocardial infarction. Symptoms settled with hydrocortisone and adrenaline. Coronary angiogram revealed normal epicardial coronaries.


Paramagnetic and Superparamagnetic Inorganic Nanoparticles for T1-Weighted Magnetic Resonance Imaging.
Magnetic resonance imaging (MRI) has become a promising technique in the early diagnosis of cancers, especially the application of contrast agents can further enhance the detection limit. Compared with the dark signal in "negative" contrast agents (T2), "positive" contrast agents (T1) with bright signal are more desirable for high-resolution imaging. However, the clinically used gadolinium complexes have short circulation time and the risk of nephrogenic system fibrosis. Therefore, to overcome the disadvantage of T2 agents and traditional T1 agents, it is very interesting to develop nano-scaled T1-weighted MRI contrast agents with safer and more precise imaging performance. The present review systematically summarized the recent progress of paramagnetic and superparamagnetic inorganic nanoparticles as T1-weighted MRI contrast agents, including gadolinium oxide nanoparticles, gadoliniumbased upconversion nanoparticles, manganese oxide nanoparticles, and ultra-small iron oxide nanoparticles. Moreover, we also described their applications in multi-modal imaging and visualized theranostics.


Isolation and characterization of a polymerized prion protein.
A polymerized form of recombinant mouse prion protein (mPrP) domain 23-231 [mPrP-(23-231)], designated mPrP-z, was generated at acidic pH (pH 2-5) in the presence of selected concentrations of denaturant (2 M guanidinium chloride or 5 M urea). This isoform of mPrP is stable in acidic solution after removal of denaturant. It can be isolated and purified using reversed-phase HPLC or size-exclusion HPLC. mPrP-z bears structural properties that partially resemble those of scrapie prion. Unlike the native mPrP-(23-231) (mPrP-N), mPrP-z exhibits a high content of beta-sheet structure, as shown by CD spectroscopy, and exists as an oligomer with an approximate molecular mass of 340000 Da, as measured by light scattering. However, similarly to mPrP-N, mPrP-z contains the intact disulphide bond and is sensitive to digestion by proteinase K.


Comparative evaluation of the nutrient and COD removal performances of various sequentially operated biofilm reactors.
In this paper, the performances of Fixed Bed (FXB), Fluidized Bed (FLB), and Hybrid (HYB, i.e. fluidized bed followed by fixed) operational conditions of biofilm reactors were investigated. The COD (chemical oxygen demand), TN (total nitrogen) and TP (total phosphorus) were taken as performance-indicator parameters. For that purpose, a pilot experimental setup allowing FXB, FLB and HYB operations in a single reactor was run under varying COD (between 500 to 2000 mg COD l(-1)), TN (between 25 to 100 mg l(-1)) and TP (between 5 to 20 mg l(-1)) influent concentrations. The system was operated as sequentially batch (SBR) and a filtering process was added at the end of each operational phase in order to achieve liquid-solid separation. Results indicated that FXB and FLB are two upper and lower cases, and HYB plays a role between them and respond as a best alternative. For example, for the lower influent concentrations (around 500 mg l(-1)), 84% of COD was removed to final averages of 78 +/- 15.4 mg l(-1); simultaneously, TN reduced to 18.55 +/- 3.48 mg l(-1) (corresponding to 31% TN removal) and 60% of TP was treated to final averages of 1.92 +/- 0.2 mg l(-1) in the HYB operation. When the influent concentrations were increased to 1000 mg l(-1) , COD removal efficiency of the HYB reactor was reduced to 73% (COD reduced from 1005.3 +/- 6.13 mg l(-1) to 270.57 +/- 13.18 mg l(-1)) and, due to incomplete organic matter degradation and oxygen deficiency, 40% of TN was removed to final averages of 34.03 +/- 5.04 mg l(-1) and 56% of TP treated to final averages of 3.98 +/- 0.28 mg l(-1). Performance of the HYB reactor was decreased when influent concentration increased to 2000 mg COD l(-1).


Artificial nighttime light changes aphid-parasitoid population dynamics.
Artificial light at night (ALAN) is recognized as a widespread and increasingly important anthropogenic environmental pressure on wild species and their interactions. Understanding of how these impacts translate into changes in population dynamics of communities with multiple trophic levels is, however, severely lacking. In an outdoor mesocosm experiment we tested the effect of ALAN on the population dynamics of a plant-aphid-parasitoid community with one plant species, three aphid species and their specialist parasitoids. The light treatment reduced the abundance of two aphid species by 20% over five generations, most likely as a consequence of bottom-up effects, with reductions in bean plant biomass being observed. For the aphid Megoura viciae this effect was reversed under autumn conditions with the light treatment promoting continuous reproduction through asexuals. All three parasitoid species were negatively affected by the light treatment, through reduced host numbers and we discuss induced possible behavioural changes. These results suggest that, in addition to direct impacts on species behaviour, the impacts of ALAN can cascade through food webs with potentially far reaching effects on the wider ecosystem.


Flow cytometric analysis of DNA in bone and soft-tissue tumors using nuclear suspensions.
Ninety-four bone and soft tissue tumors were analyzed for their DNA content using flow cytometry (FCM). A simple, rapid method for preparing isolated nuclear suspensions was used. Tissues, minced in a hypotonic solution containing detergent and propidium iodide as a fluorescent probe for DNA, provided in most instances high nuclear yields from only 0.02 to 0.03 g of solid tumor. Whereas all nonneoplastic samples had a diploid DNA content, various degrees of abnormal DNA distributions were detected in 90% of the neoplastic samples and were present in benign as well as malignant tumors. Our findings demonstrate that FCM DNA analysis is practical in most musculoskeletal tumors and support the observations of others that abnormal DNA content may serve as a general neoplastic marker in these tumors.


Preservation of left ventricular function during coronary artery bypass graft surgery.
Effects of hypothermic potassium cardioplegia on left ventricular performance and myocardial damage were assessed in 35 patients undergoing coronary artery bypass surgery. Hemodynamic data and enzymatic evidence of left ventricular ischemic damage were examined and compared in the immediate postoperative period. Left ventricular stroke work index showed a significant depression during the first hour with gradual recovery and a significant increase after 24 h. Myocardial specific isoenzyme creatine kinase (CK-MB) showed a very good nonlinear relationship with stroke work index within the whole range, whereas lactate dehydrogenase isoenzyme (LDH-I) had no relationship with the stroke work index. There was a high incidence of transient postoperative arrhythmias and electrical activity took a long time to stabilize. Left ventricular ultrastructure was generally well preserved. The results of this study demonstrate adequate structural and functional preservation of left ventricle by hypothermic potassium cardioplegia.