Achieving constant speed of a hydrostatic drive using controlled operation of the pump and enhancing its energy efficiency.
Novel ways of regulating the speed of a hydraulic drive through controlled operation of the pump either by loading/unloading the UPRV (unloading pressure relief valve) or by switching on/off of the prime mover driving the pump have been presented in this paper. The UPRV is used to operate the pump with a minimum load by diverting the pump delivery to the tank at low pressure. The energy efficiency of the said two methods adopted for controlling the hydro-motor speed is also compared. In this respect, the MATLAB®/Simulink model of the system is made and validated experimentally. The static and dynamic performances of the system are investigated using the validated model. The results show that the UPRV controlled system demonstrates better dynamic performance and controllability in terms of decreased fluctuations in hydro-motor speed for the small load torque demand. However, by comparing the energy efficiency of the hydraulic system for the two control strategies, it is found that with the increase in the machine torque demand, the intermittent operation of the pump unit may be more preferable with respect to the amount of energy saved for the complete duty cycle of the system.


Electron transport reactions in a cytochrome c-deficient mutant of Paracoccus denitrificans.
A mutant of Paracoccus denitrificans which is deficient in c-type cytochromes grows aerobically with generation times similar to those obtained with a wild-type strain. The aa3-type oxidase is functional in the mutant as judged by spectrophotometric assays of cytochrome c oxidation using the membrane particles and cytochrome aa3 reduction in whole cells. The cytochrome c oxidase (aa3-type) of the c-less mutant oxidizes soluble cytochrome c at rates equivalent to those obtained with the wild-type. NADH and succinate oxidase activities of the membrane preparations of the mutant and wild-type are also comparable in the absence of detergent treatment. Exogenous soluble cytochrome c can be both reduced by NADH- and succinate-linked systems and oxidized by cytochrome aa3 present in membranes of the mutant strain. Rapid overall electron transport can occur in the c-less mutant, suggesting that reactions result from collision of diffusing complexes.


Collaboration among general cardiologists, heart failure specialists, and electrophysiologists: what are the barriers?
Although ongoing research has focused on the reliability and accuracy of data derived from implanted devices, important challenges remain, among which is the development of a framework for handling the data, including delineation of responsibility for interpretation and management of the data. The barriers to a successful device-monitoring program include difficulties in data access, unfamiliarity with a new treatment approach, lack of sufficient knowledge and experience in data interpretation, and difficulty incorporating the program into the existing workflow. The dynamics of collaboration between heart failure and electrophysiology (EP) specialists may differ locally and regionally, but a common set of barriers resulting from traditional models of care constrains incorporation of device-based data into clinical practice. Active dialogue between EP and heart failure specialists that involves the sharing of experiences and practice models is an important first step to overcoming these barriers. In the future, a "virtual clinic" model of patient care can only be realized with the successful incorporation of remotely accessed device data.


Micromorphological effects and the thickness of the hybrid layer - a comparison of current adhesive systems.
the aim of this study was to evaluate the effect of dental conditioners in terms of dentin micromorphology and the thickness of the hybrid layer obtained by using the self-etching adhesive systems Adhe SE (AD), G Bond (GB), Adper Prompt L Pop (LP) and Tyrian (TY) and the etch-and-rinse Single Bond (SB). dentin sticks from 50 third human molars were obtained by first cutting dentin disks out of crowns; the disks were subsequently sectioned into sticks. The sticks were assigned to experimental groups as follows: G1: phosphoric acid 37%, Single Bond (SB); G2: Adhe SE (AD); G3: G Bond (GB); G4: Adper Prompt L-Pop (LP); G5: Tyrian SPE (TY). Half the samples served to investigate the dentin micromorphology. To this end, the proprietary conditioner of the respective adhesive system was applied to these samples, and conditioner effects were examined with SEM. The other half of the samples was hybridized and restored with composite resin to investigate the thickness of the hybrid layer, which was also evaluated with SEM. Statistical analysis was performed with ANOVA, Tukey's, and the Kruskal-Wallis tests. SEM observation showed significant differences of the hybrid layer thickness. LP presented the highest average thickness, 3.45 microm, while SB presented an average of 2.44 microm and AD an average of 1.43 microm. The averages of TY and SB did not show any statistically significant differences. The adhesive system GB presented the lowest average in hybrid layer, 0.37 microm. The micromorphological evaluation showed that the conditioners commonly removed the smear layer. all the micromorphological alterations and the hybrid layer thickness show that the adhesive systems studied performed distinct actions. Although there is no apparent correlation of the pH of the conditioners with the thickness of the hybrid layer, it is clear that more acidic conditioners promote more severe transformations in the dentin micromorphology.


Sex offender risk assessment: A reexamination of the coffee can study.
There exists a valid concern among forensic psychology scholars that measures intended for sexual offenders have plateaued in their predictive accuracy. The current study examined this concern using the "coffee can" methodology of Kroner, Mills, and Reddon (2005). The Iowa Sex Offender Risk Assessment (ISORA8), Level of Service Inventory - Revised (LSI-R), and Static-99R were used to predict various methods of detected recidivism (general, sexual, and violent recidivism) as compared to three randomly generated measures and a weighted generated measure. Independent correlation and receiver operating characteristic comparisons found that in almost all cases, generated measures outperformed established measures. Analyses indicated that the current conceptualization of risk for sexual offenders has not been thoroughly integrated into established measures. Current measures appear incomplete, but have a clear and empirically-noted ability to improve.


Coherent phonon dynamics: Br2 in solid Ar.
A long lasting coherent oscillation with a sharp frequency of f(p) = 2 THz is observed in fs pump probe spectra for B <-- X excitation of Br2 in solid argon. It exactly matches the frequency of a coherent zone boundary phonon (ZBP) of the Ar environment. The ZBPs have a vanishing group velocity v(g), thus they stay in the vicinity of the chromophore. They originate from a displacive excitation of coherent phonons (DECP) initiated in the electronic B <-- X transition, because neither f(p) nor the phase of the oscillation do depend on the B state vibrational dynamics. A model calculation shows that an expansion of the electronic density in going from the electronic ground state X to the B state kicks the Ar atoms in the Br2 vicinity. In addition, a group of Ar atoms in the (100) plane is decoupled from the intramolecular dynamics afterwards. The ZBP modulates the solvation energy of the terminal charge transfer states used in the probe transition from the B state and thus the detection sensitivity. The contrast is enhanced by probing the B state wave packet with the cutting edge of the probe window. This is in full accordance with a study for I2 : Kr.


Gender-specific changes since 1900 in the season-of-birth effect in schizophrenia.
It was hypothesised that the size of the season-of-birth effect may have decreased in tandem with the apparent decline in the incidence of schizophrenia. Through the Aberdeen Psychiatric Case Register, subjects were identified who had been diagnosed as schizophrenic and had been born between 1900 and 1969. The ratio of winter/spring to summer/autumn births was compared across the seven decades for both sexes together, for men, and for women. For the 1935 men, but not for the 1620 women, there was a highly significant increase (P = 0.0009) in season-of-birth effect. Non-seasonal factors have contributed to a declining incidence of schizophrenia in both sexes. 'Seasonal' factors to which female foetuses are more susceptible than male foetuses (such as infection or malnutrition) have also decreased in frequency, severity, or both, but this has not happened with factors affecting males, leading to an increase of their season-of-birth effect.


Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration.
Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac(V12)), at different cell densities. The results revealed for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac(V12) with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac(V12)-expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac(V12) is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac(V12) expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac(V12). The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac(V12), as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.


Cost evaluation of novel therapeutics in rheumatoid arthritis (CENTRA): a decision analysis model.
This study was performed to evaluate the potential costs of a hypothetical novel biological agent (BIO) as a therapy for rheumatoid arthritis (RA), compared with oral methotrexate (MTX) and intramuscular gold (IMG). A decision analysis model was used to compare the total costs of treating a cohort of 10,000 RA patients with each agent for 6 months. Total costs included direct costs and indirect costs. Baseline estimates were subjected to sensitivity analysis. Total costs per person were: MTX, $5,430; IMG, $6,725; BIO, $9,411. In sensitivity analysis, the primary cost drivers for MTX and IMG were the indirect costs of RA and monitoring costs. In contrast, total costs of the BIO were driven predominantly by medication costs. Sensitivity analysis showed, even when efficacy and safety were optimized, costs for the BIO still substantially exceeded those of MTX and IMG. Medication costs will be an important consideration in the development of novel BIOs for RA.


Modulation of intestinal brush border membrane chemical composition during postnatal development in rats: effect of gestational diabetes.
There was a significant increase in fucose (52%), total hexoses (16%) and hexosamine (56%) except sialic acid, which was reduced (77%) in the microvillus membrane of infants born to rat mothers made diabetic by injecting alloxan on day 3 of gestation. Expressed on the protein basis there were a significant increase in membrane, triglyceride, total cholesterol, and phospholipids content of brush border in pups from diabetic group between 5-45 days of postnatal age. Intestinal morphology in diabetic group showed, regression of tubular glands, distorted cellular organization of mucosal cells, reduction in the mucosal cell height and number of secretory goblet cells. These findings suggest that the gestational diabetes affects the sugar and lipid composition of the intestinal brush border membrane in rats during early stages of the postnatal development, which may be associated with compromised tissue functions later in life.


Detection of transmissible gastroenteritis virus in feces from pigs by reversed passive hemagglutination.
A reversed passive hemagglutination (RPHA) method was developed for the detection of transmissible gastroenteritis (TGE) virus in the fecal specimens from pigs. Ovine erythrocytes fixed with glutaraldehyde and treated with tannic acid were coated with anti-TGE virus swine antibodies, which were purified by affinity chromatographic technique linked with purified TGE virus. The RPHA test was done by the Microtiter method. Erythrocytes coated with purified specific antibodies were agglutinated by TGE virus, but not by porcine rotavirus or porcine enterovirus. The reaction was specifically inhibited by antiserum against TGE virus, confirming the specificity of the reaction. A litter of seven 3-day-old pigs was orally inoculated with TGE virus, and fecal specimens were obtained once a day and serum was obtained every 4th day. With the RPHA test, TGE virus was detected in the diarrheal feces; all of the inoculated pigs developed virus-neutralization antibody for the TGE virus. The RPHA test detected TGE virus in feces from pigs with naturally occurring diarrhea. The RPHA test detected TGE virus in 5 of 6 fecal specimens (80%), whereas the positive rate was only 50% (3/6) for the immunofluorescent staining of primary cultures of porcine kidney cells inoculated with the specimens. The advantages of the RPHA method are simplicity, high sensitivity, and rapid to do.


Catalytic asymmetric mannich-type reactions activated by ZnF2 chiral diamine in aqueous media.
Catalytic asymmetric Mannich-type reactions of an alpha-hydrazono ester with silicon enolates in aqueous media have been developed by using ZnF2 and chiral diamines as catalysts. In these reactions, both Zn2+ and a fluoride anion were necessary to achieve high yields and enantioselectivities, suggesting a double activation mechanism, in which Zn2+ activates the alpha-hydrazono ester and the fluoride anion simultaneously activates the silicon enolate. When chiral diamine ligands bearing methoxy-substituted aromatic rings were employed, the reactions in aqueous THF were markedly accelerated. Furthermore, the use of these diamines facilitated the asymmetric Mannich-type reactions in water without any organic cosolvents. It is noteworthy that either syn or anti adducts were stereospecifically obtained from (E)- or (Z)-silicon enolates, respectively. Interestingly, these reactions proceeded smoothly only in the presence of water. On the basis of several experimental results, it can be concluded that the reaction mechanism is likely to be a fluoride-catalyzed one, in which the ZnF2 chiral diamine complex is regenerated from the Me3SiF formed during the reaction.


Pancreatic Beta-Cell Proliferation Induced by Estradiol-17β is Foxo1 Dependent.
Estradiol-17β (E2) and the Foxo1 transcription factor have each been implicated in the regulation of β-cell proliferation. Interaction between Foxo1and estrogen receptor alpha (ERα), effecting cell cycle, has been demonstrated in breast cancer cells, but has not been studied thus far in β-cells. Using human islets and the INS1-E β-cell line, this study investigated the contribution of Foxo1 to E2-mediated β-cell replication. Foxo1 expression was knocked down in INS1-E cells using siRNA and Foxo1 activity was inhibited in human islets with a specific Foxo1 inhibitor (AS1842856). Cells were treated with E2 and the ERα agonist PPT and evaluated for proliferation by 3[H]-thymidine incorporation and for transcriptional activity through the estrogen response element by the luciferase assay. As Foxo1 activity is regulated by post-translational modifications, the effect of E2 on phosphorylation was also assessed. In INS1-E cells, knock down of Foxo1 abrogated the proliferative response to E2 and PPT. In human islets, inhibition of Foxo1 abrogated E2-mediated proliferation and attenuated the response to PPT. Foxo1 knock down and inhibition reduced activity through the estrogen response element by 25% (p<0.05) and 50% (p<0.01) respectively, in INS1-E cells. E2 increased Foxo1 phosphorylation in a time dependent manner in INS1-E and human islets (p<0.01, p<0.05, respectively). These findings suggest that Foxo1 is involved in E2-mediated proliferation in INS1-E cells and human islets. This may have implications vis-à-vis variations in circulating endogenous E2 concentrations in diabetes.


Novel approaches to analyse glomerular proteins from smallest scale murine and human samples using DIGE saturation labelling.
Loss of renal function is often associated with the injury of kidney glomeruli. It is therefore necessary to understand the mechanisms leading to progressive glomerular diseases; this may be addressed using proteomics. Until now, however, analysis of the glomeruli proteome using 2-DE has been technically hampered by low protein yields from scarce samples. To circumvent this problem, we developed a procedure which allows the human and mouse glomeruli proteome to be analysed. In this study, two different approaches were used to isolate mouse and human glomerular protein from kidney cortex. Mouse glomeruli were extracted by embolisation magnetic beads into the glomerular capillaries. Laser capture microdissection (LCM) was utilised to harvest glomeruli from human biopsy material. Human and murine samples were analysed using a fluorescence saturation labelling technique. Using 3 microg mouse glomerular protein a total of 2900 spots were resolved for differential proteome analysis. Moreover, it was also demonstrated for the first time that only ten glomeruli (0.5 microg) picked by LCM from a slide of a human kidney biopsy material were sufficient to visualise 900 spots. This novel strategy paves the way for future experiments aimed at investigating functional proteomics of glomerular diseases in humans and in mice.


Involvement of mitogen-activated protein kinases in the symbiosis Bradyrhizobium-Lupinus.
In plants, mitogen-activated protein kinases (MAPKs) are involved in signalling to hormones, cell cycle regulation, stresses, and plant defence responses. In this work, several MAPKs were detected by immunobloting in roots and nodules of Lupinus albus produced by inoculation with Bradyrhizobium sp. (Lupinus). In vitro kinase assays showed that inoculation of seedling roots with B. sp. (Lupinus) activates salt stress-inducible and stress-activated MAPKs after 5 min of incubation. By contrast, inoculation with dead B. sp. (Lupinus) or the heterologous bacteria Sinorhizobium meliloti did not induce salt stress-inducible and stress-activated MAPK activities. In vivo experiments showed that inoculation with B. sp. (Lupinus) induced the activation of MAPKs in roots. The maximal activation was in the region of the root tip with emerging hairs, which corresponds to the infection zone. The p38 MAPK inhibitors SB 202190 and SB 203580 blocked these kinase activities. Experiments with SB 202190 and the MAPKK inhibitor UO 126 altered the pattern of nodulation in the main root, decreasing the number and weight of nodules produced in the upper sites while increasing the nodule number in the younger lower root zone. These data suggest that MAPK inhibition blocks early events in the susceptible root zone to rhizobial infection, delaying nodulation, and support a role for MAPKs in the infection and nodulation of L. albus by B. sp. (Lupinus).


Mutations in the spike glycoprotein of human coronavirus OC43 modulate disease in BALB/c mice from encephalitis to flaccid paralysis and demyelination.
The etiology of most neurodegenerative diseases of the central nervous system remains unknown and likely involves a combination of genetic susceptibility and environmental triggering factors. Given that exposure to numerous infectious pathogens occurs during childhood, and that some viral infections can lead to neurodegeneration and demyelination, it is conceivable that some viruses may act as triggering factors in neuropathogenesis. We have previously shown that the prototype OC43 strain of the common cold-associated human respiratory coronavirus has the capacity to infect human neuronal and glial cells and does persist in human brains. Moreover, it has neuroinvasive properties in susceptible BALB/c mice, where it leads to a chronic encephalitis with accompanying disabilities. Here, we show that mutations in the viral spike glycoprotein, reproducibly acquired during viral persistence in human neural cell cultures, led to a drastically modified virus-induced neuropathology in BALB/c mice, characterized by flaccid paralysis and demyelination. Even though infection by both mutated and wild-type viruses led to neuroinflammation, the modified neuropathogenesis induced by the mutated virus was associated with increased viral spread and significantly more CD4+ and CD8+ T-lymphocyte infiltration into the central nervous system, as well as significantly increased levels of the proinflammatory cytokine interleukin (IL)-6 and the chemokine CCL2 (monocyte chemoattractant protein [MCP]-1). Moreover, recombinant virus harboring the S glycoprotein mutations retained its neurotropism, productively infecting neurons. Therefore, interaction of a human respiratory coronavirus with the central nervous system may modulate virus and host factors resulting in a modified neuropathogenesis in genetically susceptible individuals.


Bioactivity assessment of PLLA/PCL/HAP electrospun nanofibrous scaffolds for bone tissue engineering.
The purpose of this paper was to fabricate PLLA/PCL nanofibrous scaffolds containing HAP to mimic the native bone extracellular matrix for potential applications as bone tissue engineering scaffolds materials and ultimately to help the repairing of bone defects. PLLA (MW 200kDa), PCL (MW 80kDa), HAP, dichloromethane, N,N-dimethylformamide; α-MEM, FBS, trypsin-EDTA, penicillin G, streptomycin, β-sodium glycerophosphate, l-ascorbic acid, dexamethasone; CCK-8, Alkaline Phosphatase Assay Kit, Mouse Osteocalcin ELISA Kit, MC3T3-E1 cells. PLLA, PCL and HAP were dissolved in the solution of DCM and DMF to fabricate nanofibrous scaffolds through electrospinning. The morphology of the scaffolds was investigated with SEM, while the diameter of the fibers, pore size and water uptake of the scaffolds were tested, respectively. TGA was carried out to verify the percentage of HAP in the composite scaffolds fabricated with different HAP concentrations. Cell count kit-8 assay, alkaline phosphatase (ALP) assay, and osteocalcin assay were applied to observe the MC3T3-E1 cells proliferation, differentiation on the composite scaffolds. MC3T3-E1 cells were found to grow actively on the composite scaffolds based on the results of CCK-8 assay. The level of MC3T3-E1 differentiation was evaluated through the ALP activity and osteocalcin concentration, which showed higher value with HAP containing (PLLA/PCL/HAP) than that ones without (PLLA/PCL). The results demonstrated that the biocomposite PLLA/PCL/HAP nanofibrous scaffold should be a promising candidate for proliferation, differentiation and mineralization of osteoblasts, and potentially can be used for bone tissue regeneration.


Rapid screening of drug compounds in urine using a combination of microextraction by packed sorbent and rotating micropillar array electrospray ionization mass spectrometry.
Screening of drugs from urine samples can be non-selective or laborous, using either immunological, gas chromatography/mass spectrometry (GC/MS) or liquid chromatography (LC)/MS methods. Therefore, a rapid screening method for selected drugs in urine sample was developed in a proof-of-principle manner, utilizing simple and fast techniques for both sample treatment and sample analysis. Sample treament of spiked urine samples was performed with microextraction by packed sorbent (MEPS). Five different sorbent materials (C(2), C(8), C(18), M1 (cation exchanger), and Sil (pure silica)) were tested for the MEPS. The sample analysis was performed using a circular microchip with 60 micropillar electrospray ionization (μPESI) tips combined with a mass spectrometer (either a triple-quadrupole or ion-trap mass spectrometer) without any chromatographic step. The sample treatment/analysis setup was tested using three drug compounds at a concentration of 1 μM. We found that the C(2), C(8) and C(18) sorbents in combination with 96% alkaline methanol as an eluent worked the best. All compounds were easily detected and identified by MS/MS in spiked urine samples. The whole qualitative analytical procedure was rapid as the sample treatment together with the MS analysis took about 5 min per sample. A rapid screening method for selected drugs from urine samples was developed, providing adequate selectivity and sensitivity, as well as a short total analysis cycle time. This new method can provide a new alternative for screening purposes, as both the extraction and analysis steps could be totally automatized.


Biomimetic hybrid scaffold consisting of co-electrospun collagen and PLLCL for 3D cell culture.
Electrospun collagen is commonly used as a scaffold in tissue engineering applications since it mimics the content and morphology of native extracellular matrix (ECM) well. This report describes "toxic solvent free" fabrication of electrospun hybrid scaffold consisting of Collagen (Col) and Poly(l-lactide-co-ε-caprolactone) (PLLCL) for three-dimensional (3D) cell culture. Biomimetic hybrid scaffold was fabricated via co-spinning approach where simultaneous electrospinning of PLLCL and Collagen was mediated by polymer sacrificing agent Polyvinylpyrrolidone (PVP). Acidified aqueous solution of PVP was used to solubilize collagen without using toxic solvents for electrospinning, and then PVP was readily removed by rinsing in water. Mechanical characterizations, protein adsorption, as well as biodegradation analysis have been conducted to investigate feasibility of biomimetic hybrid scaffold for 3D cell culture applications. Electrospun biomimetic hybrid scaffold, which has 3D-network structure with 300-450 nm fiber diameters, was found to be maximizing cell adhesion through assisting NIH 3T3 mouse fibroblast cells. 3D cell culture studies confirmed that presence of collagen in biomimetic hybrid scaffold have created a major impact on cell proliferation compared to conventional 2D systems on long-term, also cell viability increased with the increasing amount of collagen.


mRNA cloning and expression studies of the quail homologue of HIF-2alpha.
Hypoxia inducible factors (HIF) are candidate transcriptional regulators of vascular development. Unlike HIF-1alpha - the founding member of the HIF family - which is expressed more or less ubiquitously, HIF-2alpha (also called HRF, HLF and EPAS1) is highly expressed by vascular endothelial cells and was shown to activate the transcription of endothelial cell-specific receptor tyrosine kinases (tie-2 and flk-1/VEGF receptor 2) and of vascular endothelial growth factor (VEGF). Therefore HIF-2alpha is a candidate dual regulator of vascular development. Here we describe the quail homologue of HIF-2alpha. Sequence analysis reveals that HIF-2alpha is highly conserved between birds and mammals. Like the murine HIF-2alpha, the quail molecule is highly expressed by endothelial cells but also detectable in certain epithelial cells such as in the endoderm.


Acute coronary thrombosis--the role of plaque disruption and its initiation and prevention.
A major factor invoking coronary thrombosis is disruption of an atherosclerotic plaque. Studies comparing intact and disrupted plaques have been used to define the characteristics of vulnerable plaques i.e. those at risk of disruption. The characteristics are a lipid core occupying over 50% of overall plaque volume, a thin plaque cap, a large absolute number and density of macrophages, and a reduction in the smooth muscle content of the plaque. Such vulnerable plaques make up a small proportion of all the plaques present in most individuals. Angiographic stenosis, however, does not predict vulnerability because there is no relation between core size or plaque size with stenosis. A large proportion of disruption episodes go unnoticed clinically because the thrombus does not sufficiently encroach on the lumen to cause ischaemia. These subclinical episodes, however, will invoke plaque growth. Plaque disruption is followed by a smooth muscle proliferative repair response analogous to that occurring after angioplasty. In both situations, exuberant repair leads to post event stenosis. Reconstruction of coronary lesions at autopsy shows that 70% of high grade stenosis (angiographic > 50% diameter) have had an episode of healed disruption. Such data highlight the role of plaque disruption in the generation of advanced stenotic lesions irrespective of whether an acute clinical event occurred. Any therapeutic intervention which increases plaque stability, i.e. resistance to disruption, would reduce the acute ischaemic event rate but also slow the generation of new high grade stenoses.


Efficacy of metal ions and isothiazolones in inhibiting Enterobacter cloacae BF-17 biofilm formation.
Enterobacter cloacae is a nosocomial pathogen. The E. cloacae strain BF-17, with a high capacity for biofilm formation, was screened and identified from industrially contaminated samples, carried out in our laboratory. To develop an efficient strategy to deal with biofilms, we investigated the effects of metal ions, including Na⁺, K⁺, Ca⁺, Mg⁺, Cu⁺, and Mn⁺, and 3 isothiazolones, on elimination of E. cloacae BF-17 biofilm formation by using a 0.1% crystal violet staining method. The results revealed that higher concentrations of Na⁺ or K⁺ significantly inhibited E. cloacae BF-17 biofilm development. Meanwhile, Ca²⁺ and Mn²⁺ stimulated biofilm formation at low concentration but exhibited a negative effect at high concentration. Moreover, biofilm formation decreased with increasing concentration of Mg²⁺ and Cu²⁺. The isothiazolones Kathon (14%), 1,2-benzisothiazolin-3-one (11%), and 2-methyl-4-isothiazolin-3-one (10%) stimulated initial biofilm formation but not planktonic growth at low concentrations and displayed inhibitory effects on both biofilm formation and planktonic growth at higher concentrations. Unfortunately, the 3 isothiazolones exerted negligible effects on preformed or fully mature biofilms. Our findings suggest that Na⁺, K⁺, Mg²⁺, and isothiazolones could be used to prevent and eliminate E. cloacae BF-17 biofilms.


Towards a psycho-anthropological view of religious violence.
Understanding the phenomenon of religious violence requires a theoretical approach to the task. Ideally, the theoretical framework must integrate (1) the insights of neurobiology and ethnology elucidating the roots of aggression in the organism and its manifestations in animal behaviour, (2) the expression of these in human violence, which requires careful attention to linguistic and other expressions in culture, (3) the special role of religious representations in this connection, and (4) the mechanisms, in time and place, whereby the role of religion in the maintenance of cultural order is reversed, and becomes an ally of violence. Psychological theories, like the psychoanalytic school, have a contribution to make to this end. But they also exhibit limitations. The most compelling anthropological theory to date is René Girard's, which focuses on mimetic desire, violence, its resolution through scapegoating and subsequent enactment in ritual. The sacred is seen to lie at the origins of cultural order. But it also harbours a potential for a resurgence of the violence it conceals. Other researchers have shown how certain features of modernity unwittingly fuel violence through the promulgation of stereotypical, group identities. Contemporary Islamist violence (Jihadism) offers a case-study for these theoretical axioms. The example is not peculiar or sui generis. Rather it illustrates, more widely, the nature of the sacred and its relation to history. The Islamic tradition and modern Muslim history also provide a template for an analytic understanding of religious symbols, and their degradation into symbols of a typically modern demand for recognition of ego and group orientated identities. This psychosocial configuration necessarily escapes the attention of the actors, and because of the nominal persistence of old symbols, may also escape the attention of observers. To expose and explain these discrepancies is one of the central tasks of analysis in the proposed theoretical framework.


Mifamurtide for high-grade, resectable, nonmetastatic osteosarcoma following surgical resection: a cost-effectiveness analysis.
Mifamurtide is an immune macrophage stimulant that when added to standard chemotherapy has demonstrated survival benefit for newly diagnosed osteosarcoma. The objectives of this study were to investigate the cost-effectiveness of adding mifamurtide to standard three- or four-agent chemotherapy for high-grade, resectable, nonmetastatic osteosarcoma following surgical resection and the issues of obtaining robust cost-effectiveness estimates for ultra-orphan drugs, given the shortage of data. An economic evaluation was conducted from the perspective of the UK's National Health Service as part of the manufacturer's submission to the National Institute for Health and Care Excellence. The disease process was simplified to a transition through a series of health states, modeled by using a Markov approach. Data to inform the model were derived from patient-level data of Study INT-0133, published literature, and expert opinion. The final efficacy measure was life-years gained (LYG), and utilities were used to obtain quality-adjusted life-years (QALYs). For a 60-year time frame and a discount rate of 3.5% for outcomes, patients receiving mifamurtide benefited from an average additional 1.57 years of life and 1.34 QALYs, compared with patients receiving chemotherapy alone, giving an incremental cost-effectiveness ratio (ICER) of £58,737 per LYG and £68,734 per QALY. Because treatment effects were both substantial in restoring health and sustained over a very long period, the National Institute for Health and Care Excellence changed its guidance to allow a discount of 1.5% for outcomes to be applied in these special circumstances. By using this discount factor, it was found that patients receiving mifamurtide had an average additional 2.58 years of life and 2.20 QALYs compared with patients receiving chemotherapy alone, resulting in an ICER of £35,765 per LYG and £41,933 per QALY. Mifamurtide's ICER is cost-effective compared with that of other orphan and ultra-orphan drugs, for which prices and corresponding cost-effectiveness estimates are high.


Comparison of human chorionic gonadotropin measurements by radioimmunoassay and in vitro bioassay.
A sensitive, accurate, and reproducible in vitro bioassay was developed for measuring human chorionic gonadotropin (hCG), based on testosterone production by collagenase-dispersed interstitial cells of rat testes in response to hCG. The results were compared to those obtained by established beta hCG radioimmunoassay. The assay sensitivity was 25 pg hCG-CR119/ml (65 microIU second IRP/ml). The intra-assay coefficient of variation (CV) was 8.8%, and the interassay CV was 13% and 33% in the high and low ranges of the standard curve, respectively. hCG recoveries were 89.6 +/- 3.12% (SE, n = 12). The pattern of serum bio-hCG followed established patterns of immuno-hCG, with the highest level measured during the first trimester (mean, 52,600 +/- 7,250 SE (mIU/ml, n = 11), decreasing thereafter to a mean value of 7,400 +/- 1,500 mIU/ml at term. The mean ratio of the bio/immunoactivity was consistently greater than one and did not significantly change at the various stages of pregnancy, or between normal and molar pregnancies (first trimester, 1.75 +/- 0.12 SE; midtrimester, 1.46 +/- 0.12; term, 1.50 +/- 0.09; molar, 1.55 +/- 0.2). When serum bioactive and immunoactive hCG were measured in a woman at five weeks of pregnancy, an episodic secretion of hCG was obtained by both assays.


Grow your own brain.
Jenny Straiton explores the miniature world of organoids and discusses how these small models are making big changes in the world of neurological research.


Solitary maxillary central incisor as a new finding in CHARGE association: a report of two cases.
Two cases are reported of a solitary maxillary central incisor in children with CHARGE association. The implications of the finding are discussed, along with the suggested relationship to other craniofacial disorders in which solitary central incisors have been reported.


Proposal for a Brazilian centre on alternative test methods.
Several initiatives have recently taken place in Brazil in order to foster the creation of centers dedicated to alternatives to animal testing. In 2008, Vanessa Sá-Rocha organized a meeting with Brazilian regulatory authorities and the major stakeholders in the field of testing to foster discussions on the process of funding, development, and validation of alternative methods in Brazil. Octavio Presgrave published a scientific article on "The Need for the Establishment of a Brazilian Centre for the Validation of Alternative Methods." Also in 2008, Jadir Nunes, together with Dermeval de Carvalho, prepared and presented a proposal to the Brazilian National Agency of Health Surveillance (ANVISA) for the creation of a Centre for the Validation of Alternative Methods. ECVAM and other European stakeholders have been involved in the initiatives. Furthermore, also in 2008, a new legislation has been adopted in Brazil regarding the use of animals for scientific purposes ("lei Arouca"). The legislation establishes, among other provisions, the task of monitoring and evaluating the introduction of alternative methods. However, the legislation does not provide for promotion of or information about, existing alternative methods to the larger Brazilian scientific community. In order to streamline the different activities, Chantra Eskes acted as a facilitator by establishing a new joint proposal with the current Brazilian stakeholders, aimed at setting up a Brazilian Center on Alternative Test Methods.


A de novo complex chromosomal rearrangement involving chromosomes 2, 8 and 13 in a dysmorphic case with polysyndactyly.
We report herein a case with dysmorphic features, polysyndactyly and psychomotor mental retardation, who had an apparently balanced de novo translocation between chromosomes 8 and 13 as well as a de novo insertion within chromosome 2 itself. This case is worth mentioning in the sense that it bears two de novo rearrangements with five breakpoints. The correlation between the possible disrupted genes within the given breakpoints and the phenotype of the case will be discussed.


Occurrence of polybrominated diphenyl ethers, polychlorinated biphenyls, and phthalates in freshwater fish from the Orge river (Ile-de France).
Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and phthalates were investigated from July 2009 to April 2010 in three fish species from the Orge river, which flows in a densely populated area of Ile-de-France. In two Cyprinidae (roach and chub) and one Percidae (perch), muscle contents in increasing order ranged as follows: 12-18 ng g(-1) dw for PBDEs (Σtri-hepta), 120-170 ng g(-1) dw for PCBs (Σ7), and 2,250-5,125 ng g(-1) dw for phthalates (Σ7). No variation was observed between contaminant contents and lipid levels. No biomagnification was found according to the trophic level for PBDEs and PCBs, whereas for phthalates the highest contents were found in perch. Seasonal variations were observed with the lowest PBDE and PCB contents occurring in July after spawning in roach and perch (p < 0.001). PBDE content followed a decreasing trend-gonad > liver > muscle-whatever the period. For PCBs, gonad and liver contents remained greater than that of muscle (p < 0.05). Our results indicate a preferential accumulation of halogenated compounds in gonad and liver outside the reproduction period. Bioaccumulation factors for PCBs in muscle were significantly correlated to their chlorination degree in perch (p < 0.01) and roach (p < 0.01). In roach, that correlation slope was by decreasing importance order as follows: gonad > liver > muscle. The biota-sediment accumulation factors varied from 0.1 to 29.2, from 1.6 to 4.8, and from 1 to 123.5 for PBDEs, PCBs, and phthalates, respectively. These results contribute to document the use of freshwater fish as bioindicators of river quality.


Genetics of essential tremor.
Essential tremor (ET), the cause of which remains poorly understood, is one of the most common neurological disorders. While environmental agents have been proposed to play a role, genetic factors are believed to contribute to its onset. Thus far, three gene loci (ETM1 on 3q13, ETM2 on 2p24.1 and a locus on 6p23) have been identified in patients and families with the disorder. In addition, a Ser9Gly variant in the dopamine D3 receptor gene on 3q13 has been suggested to be a risk factor. Moreover, genetically deficient animal models express a phenotype that overlaps with some clinical characteristics of the human form of the illness. Further analyses of these genetic abnormalities may lead to the identification of causative mutations and a better understanding of the molecular mechanisms in this common movement disorder.


Easy activation of two C-H bonds of an N-heterocyclic carbene N-methyl group.
The first trinuclear clusters containing NHC ligands are described; the compound [Ru3(Me2Im)(CO)11](Me2Im=1,3-dimethylimidazol-2-ylidene) is easily converted into [Ru3(mu-H)2(mu3-MeImCH)(CO)9] by a process involving the activation of two C-H bonds of a methyl group that is an example of degradation of a metal-coordinated NHC ligand under mild conditions.


Intrathecal human tetanus immunoglobulin in early tetanus.
97 patients with symptoms of early tetanus at the time of admission to hospital were treated with sedation, antibiotics, and human tetanus immune globulin (TIG). After intrathecal TIG 250 IU 3 patients out of 49 got worse but only 1 died while in a closely similar group of 48 patients in whom TIG was administered intramuscularly in dose of 1000 IU, the clinical features of the disease became severer in 15 (31%) and 10 (21%) died. The intrathecal use of TIG was devoid of side effects.


Evaluation of multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients.
1. Multi-frequency bio-impedance analysis has been used to estimate extracellular and total body water in a heterogeneous group of 43 surgical patients (23 males, 20 females). 2. Radioisotope-dilution methods were used for the measurement of extracellular and total body water. 3. Resistance and reactance were measured between wrist and ankle at frequencies from 5 kHz to 1 MHz. 4. Extracellular and total body water were estimated by multiple stepwise regression using the radioisotope values as the dependent variables. The parameters included in the regression were: resistance and reactance at each frequency, body habitus parameters, plasma albumin and plasma sodium. 5. The standard errors of the estimates between the measured and estimated values were 1.73 litres (coefficient of variation 9.6%) and 2.17 litres (coefficient of variation 6.0%) for extracellular and total body water, respectively. 6. These errors represent a useful improvement relative to those obtained from anthropometric estimates. However, the improvements relative to the use of a single frequency (50 kHz) are not clinically significant.


The control of eye movements by the cerebellar nuclei: polysynaptic projections from the fastigial, interpositus posterior and dentate nuclei to lateral rectus motoneurons in primates.
Premotor circuits driving extraocular motoneurons and downstream motor outputs of cerebellar nuclei are well known. However, there is, as yet, no unequivocal account of cerebellar output pathways controlling eye movements in primates. Using retrograde transneuronal transfer of rabies virus from the lateral rectus (LR) eye muscle, we studied polysynaptic pathways to LR motoneurons in primates. Injections were placed either into the central or distal muscle portion, to identify innervation differences of LR motoneurons supplying singly innervated (SIFs) or multiply innervated muscle fibers (MIFs). We found that SIF motoneurons receive major cerebellar 'output channels' bilaterally, while oligosynaptic cerebellar innervation of MIF motoneurons is negligible and/or more indirect. Inputs originate from the fastigial nuclei di- and trisynaptically, and from a circumscribed rostral portion of the ventrolateral interpositus posterior and from the caudal pole of the dentate nuclei trisynaptically. While disynaptic cerebellar inputs to LR motoneurons stem exclusively from the caudal fastigial region involved in saccades, pursuit and convergence (via its projections to brainstem oculomotor populations), minor trisynaptic inputs from the rostral fastigial nucleus, which contributes to gaze shifts, may reflect access to vestibular and reticular eye-head control pathways. Trisynaptic inputs to LR motoneurons from the rostral ventrolateral interpositus posterior, involved in divergence (far-response), is likely mediated by projections to the supraoculomotor area, contributing to LR motoneuron activation during divergence. Trisynaptic inputs to LR motoneurons from the caudal dentate, which also innervates disynaptically the frontal and parietal eye fields, can be explained by its superior colliculus projections, and likely target saccade-related burst neurons.


Effect of intravenous infusion of atriopeptin 3 on immediate renal allograft function.
Thirty-eight recipients of nineteen pairs of cadaveric kidneys were entered into a double-blind randomized study in which one recipient received a 12-hour intravenous infusion of Atriopeptin III (AP-3), a synthetic analogue of atrial natriuretic factor, commencing at release of the vascular clamps, and the other received a placebo infusion. In an initial dose ranging study, successive groups of six kidneys (3 pairs) were randomized to receive each of 0.0125, 0.025, 0.05 micrograms/kg/min AP-3 or placebo. Thereafter 20 kidneys (10 pairs) received 0.1 micrograms/kg/min or placebo. There was no discernable effect of AP-3 on allograft creatinine clearance or sodium excretion either when the highest dose of AP-3 was considered alone or when all doses were considered together. Averaged creatinine clearance over the period 0 to 24 hours after transplantation was 20.1 +/- 14.7 ml/min in patients receiving active treatment and 18.2 +/- 13.7 ml/min in those receiving placebo. Thus, despite the documentation of a protective effect of atrial natriuretic factor in animal models of renal ischemia, it is unlikely that intravenous infusion of AP-3 in this dose range will be of benefit in improving immediate renal allograft graft function.


Characterization of 24 microsatellite markers in 11 species of fire ants in the genus Solenopsis (Hymenoptera: Formicidae).
The social parasite ant Solenopsis daguerrei infests colonies of several mound-building fire ant species. Twenty-four microsatellite markers were isolated from a repeat-enriched genomic library of S. daguerrei. Eleven loci were polymorphic in this ant with two to six alleles per locus. Expected heterozygosity ranged from 0.0222 to 0.7940 among loci. Most microsatellites amplified successfully across the 11 Solenopsis species tested and will be useful for evolutionary genetic studies in this diverse ant group.


Five-year incidence of dental anxiety in an adult population.
The purpose of the study was to assess the incidence of dental anxiety and factors associated with onset in adults aged 18 years and over. A longitudinal mail survey of a random sample of the general population consisting of a baseline phase and a follow-up after five years. 1,422 individuals completed baseline and follow-up questionnaires concerning dental anxiety; 1,226 subjects who were not anxious at baseline were included in the analysis. A sub-sample of 747 of these subjects had also completed a psychological questionnaire at baseline. Dental anxiety was assessed using the Dental Anxiety Scale (DAS). Other measures included the Dental Belief Survey, The Iowa Dental Control Index, a scale to measure attitudes towards pain, and measures of trait anxiety and general fearfulness. Questions were also asked about dental visiting patterns and dental treatment experiences prior to baseline and between baseline and follow-up. The five-year incidence of dental anxiety in this population was 5.8%. This varied from 12.2% in those aged 18 to 24 years at baseline to 1.7% among those aged 65 years and over at baseline. Those reporting an episodic visiting pattern between baseline and follow-up and those who avoided dental care altogether were also more likely to become anxious about dental treatment. Seven variables entered a logistic regression model predicting onset: age at baseline, DAS score at baseline, fear of pain, dental visiting pattern and three variables indicating aversive dental experiences between baseline and follow-up. These were: experiencing pain during dental treatment; being treated by a dentist in a cold or uncaring manner and being frightened or worried about things the dentist did. Data from the 747 subjects completing the baseline psychological questionnaire indicated that scores on a trait anxiety index were also predictive of onset. Dental anxiety may arise during adulthood, younger adults being particularly vulnerable to onset. Both aversive conditioning experiences and pre-existing psychological states appear to be associated with the development of anxiety about dental treatment in this adult population.


Resistance exercise interventions during and following cancer treatment: a systematic review.
Findings from prior systematic reviews suggest that exercise results in meaningful improvements in many clinically relevant physiologic and quality of life (QOL) outcomes during and following cancer treatment. However, the majority of exercise-cancer studies have focused upon the benefits of aerobic exercise (AE) and knowledge of the efficacy of resistance exercise (RE) alone as a supportive care intervention for cancer patients and survivors remains limited. Consequently, the purpose of this review was to provide the first systematic evaluation of the effects of RE alone upon clinically relevant physiologic and QOL outcomes during and following cancer treatment. Literature searches were conducted to identify studies examining RE interventions in cancer patients and survivors. Data were extracted on physiologic (fitness, physical function, and body composition) and QOL (fatigue, psychological well-being, and cancer-specific and global QOL outcomes. Cohen's d effect sizes were calculated for each outcome. A total of 15 studies (6 in samples undergoing active cancer treatment and 9 in samples having completed cancer treatment) involving 1,077 participants met the inclusion criteria. Findings revealed that, on average, RE resulted in large effect-size improvements in muscular strength (d = 0.86), moderate effect-size improvements in physical function (d = 0.66), and small effect-size improvements in body composition (d = 0.28) and QOL (d = 0.25) outcomes. The effect sizes observed following RE are comparable in magnitude to the effects of exercise interventions reported in prior comprehensive reviews of the exercise-cancer literature which primarily focused upon AE. Additionally, the methodologic quality of the studies was generally strong. Taken collectively, results of this systematic review suggest that RE is a promising supportive care intervention that results in meaningful improvements in clinically relevant physiologic and QOL outcomes during and following cancer treatment.


Common vampire bat attacks on humans in a village of the Amazon region of Brazil.
Many people in Amazonian communities have reported bat bites in the last decade. Bites by vampire bats can potentially transmit rabies to humans. The objective of this study was to analyze factors associated with bat biting in one of these communities. A cross-sectional survey was conducted in a village of gold miners in the Amazonian region of Brazil (160 inhabitants). Bats were captured near people's houses and sent to a lab. Of 129 people interviewed, 41% had been attacked by a bat at least once, with 92% of the bites located on the lower limbs. A logistic regression found that adults were bitten around four times more often than children (OR = 3.75, CI 95%: 1.46-9.62, p = 0.036). Males were bitten more frequently than females (OR = 2.08, CI 95%: 0.90-4.76, p = 0.067). Nine Desmodus rotundus and three frugivorous bats were captured and tested negative for rabies. The study suggests that, in an area of gold miners, common vampire bats are more likely to attack adults and males. The control strategy for human rabies developed in this region should therefore place special emphasis on adult males. There should also be more research on how the search for gold in the Amazonian region places people and the environment at risk.


Chorismate mutase-prephenate dehydrogenase from Escherichia coli. 2. Evidence for two different active sites.
The inhibition of the bifunctional enzyme chorismate mutase-prephenate dehydrogenase by substrate analogues, by the end product, tyrosine, and by the protein modifying agent iodoacetate has been investigated. The purpose of the investigations was to determine if the two reactions catalyzed by the enzyme occur at a single active site or at two separate active sites. Evidence in support of the conclusion that the mutase and dehydrogenase reactions are catalyzed at two similar but distinct active sites comes from the following results: (1) A substrate analogue (endo-oxabicyclic diacid) that inhibits competitively the mutase reaction has no effect on the dehydrogenase reaction. (2) Malonic acid and several of its derivatives act as inhibitory analogues of chorismate in the mutase reaction and of prephenate in the dehydrogenase reaction. However, different dissociation constants for their interaction with the free enzyme are obtained from studies on the mutase and dehydrogenase reactions. (3) The kinetics of the inhibition by tyrosine of the mutase reaction in the presence of NAD differ from those of the dehydrogenase reaction. The results confirm that carboxymethylation with iodoacetate of one cysteine residue per subunit eliminates both mutase and dehydrogenase activities and show that the inactivation of the enzyme activities is due to iodoacetate functioning as an active site directed inhibitor.


Histopathology of noise deafness.
The psychophysical effects of sound stimulation at increasing intensity include adaptation, temporary threshold shift, and permanent hearing loss. The mechanisms involved in permanent loss are direct mechanical destruction, following high intensity noise exposure, and metabolic decompensation with subsequent degeneration of sensory elements, following moderate intensity noise exposure. Both these cause their own pattern of cochlear histological abnormality, while the only morphological correlate to temporary threshold shift is an increase in the number and size of liposomes, mainly in the outer hair cells after longer periods of repeated temporary threshold shift. There are critical intensity levels which determine the type and extent of damage, and for any given exposure intensity a saturation of damage is reached over time. There is great variability in acoustic cochlear damage, especially that of the delayed metabolic type, the type which results from conditions which predominate in our actual noise environment.


[Cancer epidemics and the cancer prevention and control strategies in the United States: a review study].
In the past two decades,the United States made an impressed progress in the prevention and control of cancer that the overall morbidity and mortality of cancer had shown a downward trend, while China had seen an opposite trend. Cancer, one of the major public health concerns in China, has imposed an enormous burden onthe society and individuals. Therefore,in order to scientifically formulate cancer prevention and control policies, it is essential to make a comprehensive understanding of the practical experience in the field of cancer prevention and control from the United States. This article reviews the relevant literature on cancer trends as well as the prevention and control strategies in the United States,depictsthe cancer epidemic situation in the United States in the past 30 years, and summarizes the influencing factors, strategies and intervention experiences that lead to the improvement of cancer epidemic. It highlights the policy support, surveillance and intervention adopted by the United States for the cancer prevention and control. This article is expected to provide some implications and reference for the cancer prevention and control in China.


A ubiquitous Plasmodium protein displays a unique surface labeling pattern in sporozoites.
The Plasmodium sporozoite is infective for mosquito salivary glands and vertebrate host tissues. Although it is a key developmental stage of the malaria parasite, relatively few sporozoite surface or secreted proteins have been identified and characterized. Herein, we describe the molecular and cellular characterization of a novel surface molecule that is preferentially-expressed in salivary gland sporozoites as compared to oocyst and hemolymph sporozoites. This molecule, designated the sporozoite and erythrocytic stages (SES) protein (formerly known as Pg4), exhibits a spiral surface labeling pattern that spans over a known sporozoite surface antigen, the circumsporozoite protein, with only minor co-localization. SES consists of 551 amino acids encoding a putative 63.2kDa protein that has been shown to be expressed not only on particular sporozoite stages, but also during the asexual and gametocyte stages. This novel protein also has three domains of unknown function that are conserved in at least eight Plasmodium spp. that represent human, avian, non-human primate, and rodent malarias.


Geographical Variation and Social Work Students' Job Intentions in China: A Geographic Information Systems Approach.
Social work education in China is undergoing far-reaching development. However, an important issue, low professional commitment, has been identified. Why do social work graduates-especially master's level graduates-take jobs unrelated to social work? To answer this question, it is important to take into account that the professionalization of social work is happening unevenly across China as a result of uneven social and economic development. Models used in past research do not consider the possibility that the low intention for social work jobs and its potential predictors may vary across regions. To address this problem, Geographic Information Systems software is being adopted to explore the varying degrees of social work graduates' job intention, its predictors across China, and the association between job intention and predictors at both national and regional levels. Authors of this study found substantial geographic variation in predictors of social work graduates' job intention across regions. Their findings also suggest some heterogeneity in the association between job intention and specific correlates that would be masked in the traditional nationwide model. Policymakers aiming to improve the job intention of social work graduates should consider regional variation as part of their approach.


The nursing shortage: dynamics and solutions. Solutions in a pluralistic environment.
America's education and health care environments have been intensely pluralistic since the founding of the republic. Monolithic national solutions to health problems therefore do not occur in the United States, unlike most European countries. As a result, America does not have a national health policy. The current cycle of the shortage of nurses is also complicated by deep differences of opinion among nurses, physicians, and hospitals regarding the origin of, and therefore the solution to, the problem. Despite this, I predict that by the characteristic American version of "muddling through" in health policy, the nursing shortage will be "solved," or at least resolved, by 1993.


Changes to the Editorial Team of the IJSM.
There have been some changes to the Board of Editors of the IJSM. Already this year, Prof. Donald Dengel of the University of Minnesota, USA, replaced editor Prof. Joseph Houmard, who had been with the journal since 2006 and chose to leave the team for professional reasons.Unfortunately, our Editor-in-Chief Prof. Appell Coriolano is fast approaching his retirement from academia and will also be leaving the IJSM editorial team. Hans-Joachim Appell Coriolano joined the Editorial Board of the IJSM in 1987 and accepted the position of Assistant Editor in 1989. Over the years, he gradually assumed even greater responsibility for manuscript organization and editing. He has served as Editor-in-Chief since 2006 and is regarded as a true "primus inter pares" within the editors' team. For his tremendous commitment and unwavering dedication to the IJSM for nearly 30 years, Prof. Appell Coriolano is acknowledged by his peers and Thieme Publishers as the "heart and soul" of the IJSM as it exists today. The level of scientific quality and international recognition attained by the IJSM is in large part due to his valuable contributions and scientific rigor. It is therefore with great regret that we bid him farewell, but we are sure that his guidance and spirit will continue to shape the future of this publication.


Sociological investigations of mental illness: a review.
Contemporary sociological research has expanded knowledge about how the label of mental illness affects individuals and about how patients' and psychiatrists' social characteristics affect the assessment and treatment of mental disorders. The authors review the recent sociological research dealing with the effect of extrapsychiatric factors such as social class, race, gender, marital status, and age on the development, diagnosis, and treatment of mental illness. They also examine sociological studies of the social role of the state hospital, the consequences of deinstitutionalization for chronic mentally ill patients, and the relationship of mental illness and homelessness. Studies that examine the social aspects of psychiatric practice, including the objectivity of psychiatric diagnosis, are also reviewed.


Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review.
A partial molar pregnancy almost always ends in miscarriage due to a triploid fetus. We describe a rare case of a singleton, partial molar pregnancy with a seemingly huge placenta, which continued to delivery of a live-born diploid baby. A 27-year-old primigravida suffered from severe pre-eclampsia and progressive anemia. The uterus was enormously enlarged for the gestational age. A cesarean section was performed because of deterioration of maternal status at 25 weeks' gestation, when more than 3000 mL blood spouted concurrently with the delivery of the placenta. The histological examination showed congestion in the decidua, which indicated disturbance of maternal venous return from the intervillous space. The chromosome complement of the placenta and the neonate were 69,XXX and 46,XX, respectively. We also reviewed all published cases of a singleton, partial molar pregnancy. A literature search yielded 18 cases of a singleton, diploid fetus with partial molar pregnancy. The mean gestational age at delivery was 24.5 ± 6.2 weeks, and fetuses survived outside the uterus in only four cases (22.2%). Intriguingly, previous reports numbered 10 cases with diploid placenta as well as five cases with no karyotyping of the placenta, indicating that they may have included a complete mole in a twin pregnancy or placental mesenchymal dysplasia. In conclusion, this was the first case of placentomegaly that presented manifestations of excessive abdominal distension and maternal severe anemia, and the second case of a singleton, partial molar pregnancy confirmed by chromosome analysis resulting in a diploid living baby.


A chronological framework connecting the early Upper Palaeolithic across the Central Asian piedmont.
Central Asia has delivered significant paleoanthropological discoveries in the past few years. New genetic data indicate that at least two archaic human species met and interbred with anatomically modern humans as they arrived into northern Central Asia. However, data are limited: known archaeological sites with lithic assemblages generally lack human fossils, and consequently identifying the archaeological signatures of different human groups, and the timing of their occupation, remains elusive. Reliable chronologic data from sites in the region, crucial to our understanding of the timing and duration of interactions between different human species, are rare. Here we present chronologies for two open air Middle to Upper Palaeolithic (UP) sequences from the Tien Shan piedmont in southeast Kazakhstan, Maibulak and Valikhanova, which bridge southern and northern Central Asia. The chronologies, based on both quartz optically stimulated luminescence (OSL) and polymineral post-infrared infrared luminescence (pIR-IRSL) protocols, demonstrate that technological developments at the two sites differ substantially over the ∼47-19 ka time span. Some of the innovations typically associated with the earliest UP in the Altai or other parts of northeast Asia are also present in the Tien Shan piedmont. We caution against making assumptions about the directionality of spread of these technologies until a larger, better defined database of transitional sites in the region is available. Connections between the timing of occupation of regions, living area setting and paleoenvironmental conditions, while providing hypotheses worth exploring, remain inconclusive. We cautiously suggest a trend towards increasing occupation of open air sites across the Central Asian piedmont after ∼40 ka, corresponding to more humid climatic conditions which nevertheless included pulses of dust deposition. Human occupation persisted into the Last Glacial Maximum, despite cooler, and possibly drier, conditions. Our results thus provide additional data to substantiate arguments for occupation of Central Asia.


Estrogen receptor-alpha mediates the effects of estradiol on telomerase activity in human mesenchymal stem cells.
Sex steroid hormone receptors play a central role in modulating telomerase activity, especially in cancer cells. However, information on the regulation of steroid hormone receptors and their distinct functions on telomerase activity within the mesenchymal stem cell are largely unavailable due to low telomerase activity in the cell. In this study, the effects of estrogen (E2) treatment and function of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) on telomerase activity were investigated in human mesenchymal stem cells (hMSCs). Telomerase activity and mRNA expression of the catalytic subunit of telomerase (hTERT) were upregulated by treatment of the cells with E2. The protein concentration of ERalpha was also increased by E2 treatment, and enhancement of ERalpha accumulation in the nucleus was clearly detected with immunocytochemistry. When ERalpha expression was reduced by siRNA transfection into hMSCs, the effect of E2 on the induction of hTERT expression and telomerase activity was diminished. In contrast, the transient overexpression of ERalpha increased the effect of E2 on the expression of hTERT mRNA. These findings indicate that the activation of hTERT expression and telomerase activity by E2 in hMSCs depends on ERalpha, but not on ERbeta.


Fulgides as Light-Driven Molecular Rotary Motors: Computational Design of a Prototype Compound.
A new family of light-driven molecular rotary motors utilizing the fulgide motif is proposed and its prototype molecule is studied by quantum chemical calculations and nonadiabatic molecular dynamics simulations. The new motor performs pure unidirectional axial rotation of the rotor blade with high quantum efficiency (ϕ ∼ 0.55-0.68) and ultrafast dynamics (⟨ t⟩ S1 ∼ 200-300 fs) of its successive photoisomerization steps. The photocyclization reaction typical of fulgide compounds is blocked by the design of the new motor and never occurred in the molecular dynamics simulations. The new motors can be synthesized from easily available precursors. In view of its remarkable photoisomerization ability, the new motor represents a prospective class of compounds for the use in nanosized molecular devices.


Structure of 2,4-diaminopyrimidine-theobromine alternate base pairs.
We report the structure of clusters of 2,4-diaminopyrimidine with 3,7-dimethylxanthine (theobromine) in the gas phase determined by IR-UV double resonance spectroscopy in both the near-IR and mid-IR regions in combination with ab initio computations. These clusters represent potential alternate nucleobase pairs, geometrically equivalent to guanine-cytosine. We have found the four lowest energy structures, which include the Watson-Crick base pairing motif. This Watson-Crick structure has not been observed by resonant two-photon ionization (R2PI) in the gas phase for the canonical DNA base pairs.


Koch's dilemma revisited.
Robert Koch's description of the etiologic agent of tuberculosis on 24 March 1882 made him the hero of tuberculosis research overnight. In 1890, at the 10th International Congress of Medicine in Berlin, he claimed that he had discovered a remedy for the disease. This announcement was received with great excitement by both the medical community and the public. Medical trials performed in the subsequent months failed, however, to reveal a protective effect of Koch's remedy. In contrast, the diagnostic potential of tuberculin is still used and valued nowadays. This short article discusses Koch's reasons for fighting for the success of his remedy.


[Laparoscopic treatment of a benign hepatic cyst].
We present a case of laparoscopic treatment of a symptomatic solitary hepatic cyst and the use of preoperative laparoscopic ultrasound scanning and ultrasonic scalpel.


Crystallographic and functional analyses of J-domain of JAC1 essential for chloroplast photorelocation movement in Arabidopsis thaliana.
An auxilin-like J-domain-containing protein, JAC1, is necessary for chloroplast movement in Arabidopsis thaliana, to capture photosynthetic light efficiently under weak light conditions. Here, we performed crystallographic and functional analyses of the J-domain of JAC1. The crystal structure of the J-domain is quite similar to that of bovine auxilin, and possesses a similar positively charged surface, which probably forms the interface with the Hsp70 chaperone. The mutation of the highly conserved HPD motif of the JAC1 J-domain abrogated the chloroplast photorelocation response. These results suggest that the requirement of JAC1 in chloroplast photorelocation movement is attributable to the J-domain's cochaperone activity.


Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzyme.
High blood pressure or hypertension is a condition affecting many individuals and represents a controllable risk factor for cardiovascular diseases such as coronary heart disease and stroke. A non-pharmacological approach to manage these includes the application of food components with antihypertensive activity. Milk protein-derived peptides have been exploited as natural hypotensive agents, namely the peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), already commercialized in functional foods as a potential alternative to synthetic drugs. These bioactive peptides inhibit in vitro and in vivo the Angiotensin I-converting enzyme (ACE), a protein with an important role in blood pressure regulation. In this work, we attempted to elucidate the possible mode of interaction between the peptides and ACE, including mechanisms of binding to the cofactor Zn2+, and further contrast this with the known mode of inhibition exerted by synthetic drugs (Captopril, Enalaprilat and Lisinopril). The bioactive peptide Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR), also known to inhibit the enzyme ACE but with a lower efficiency than VPP and IPP, was utilized in the docking studies for comparison. It was observed that the best docking poses obtained for VPP and IPP were located at the ACE catalytic site with very high resemblance to the drugs mode of interaction, including the coordination with Zn2+. As for ALPMHIR, the best docking poses were located in the narrow ACE channel outside the catalytic site, representing higher affinity energies and fewer resemblances with the interaction established by drugs.


Intravenous leiomyoma of the bladder in a cat.
An intravenous leiomyoma was diagnosed in a 5-year-old male cat that had a history of listlessness, dysuria, and hematuria. The cat has been clinically normal for 25 months after excision of the neoplasm.


A comparison of the effectiveness and time efficiency of traditional and photographic environmental monitoring techniques.
Photographic methods of environmental monitoring have grown in popularity and now represent one of the main ways in which habitat and biodiversity are monitored for change through time. However, efficacy and efficiency of this technique compared with traditional approaches to environmental monitoring (direct count or observation) are lacking. This study compares the results and time-efficiency of manual versus photographic monitoring of floral abundance in low-growing flowering plants in a relatively open herbfield. Specifically, we compared 1) manual flower counting of individual plants for four species, followed by data entry in the laboratory, with 2) taking photographic images of each plant and quantifying flower counts in the laboratory. Photographic monitoring underestimated flower counts by an average of 7.5%. Manual counting was more time consuming in the field, but less time consuming in post-processing than photographic monitoring. Overall, photographic monitoring took almost twice as long as manual counting (81.5% longer in duration), which was attributed to the much longer post-processing associated with photographic monitoring. This suggests that perhaps the main benefit of photographic monitoring is a permanent record of the sampling frame rather than any cost savings or enhanced data accuracy, at least in the systems investigated in this study.


Diagnostic accuracy of the Xpert® MTB/RIF cycle threshold level to predict smear positivity: a meta-analysis.
Xpert® MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, CT) correlates with the bacillary burden.OBJECTIVE To investigate the association between Xpert CT values and smear status through a systematic review and individual-level data meta-analysis. Studies on the association between CT values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated. Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off CT values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%CI 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples. Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.


Xanthogranulomatous pyelonephritis: a report of 2 cases.
Two cases of xanthogranulomatous pyelonephritis are reported in Negroes. The clinical findings are similar to those in previously reported cases. In 1 case nephrolithotomy was followed by the development of a perinephric abcess 8 months later. Late diagnosis has limited experience with more conservative management, which should be reserved for demonstrably focal disease.


Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK)
Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction. Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin (70 IU/kg body wt bolus and 15 IU.kg-1.h-1) or hirudin (0.4 mg/kg body wt bolus and 0.15 mg.kg-1.h-1) infused over 48 to 72 hours and adjusted to an activated partial thromboplastin time of 2 to 3.5 times baseline values. In a pilot phase, 1000 patients receiving front-loaded alteplase for thrombolysis were to be recruited by 93 German centers. After enrollment of 302 patients, the trial was stopped after an increased rate of intracranial bleeding was observed in the hirudin group (5 of 148, 3.4%) compared with the heparin group (0 of 154). The overall stroke rate was 3.4% in the hirudin group and 1.3% in the heparin group. Other major bleeding occurred in five versus three patients and ventricular rupture occurred in three versus one patient in the hirudin and heparin groups, respectively. There were 19 in-hospital deaths, with 13 of them from the hirudin group. Although the number of patients was too small for a definite benefit-risk assessment, at the dosage tested, hirudin in combination with front-loaded alteplase and aspirin may be associated with an increased rate of intracranial hemorrhage. Our findings are consistent with the observations of the GUSTO-II and TIMI-9 trials, where higher doses of another recombinant hirudin were used. Therefore, the therapeutic range of hirudin as an adjunct to thrombolysis may be smaller than previously thought, and reappraisal of dose finding should be considered.


Detection of copy number variation using SNP genotyping.
Genetic diversity among human genomes comes in many forms, including single nucleotide polymorphisms (SNPs) and small insertions and deletions on the order of one to several basepairs. More recently, large, >1 kb copy number changes have been identified as an important source of normal genomic variation as well as disease-causing variation. The ability to perform genome-wide discovery of large copy number variants (CNVs) has been facilitated by advances in two technologies - array comparative genomic hybridization and SNP genotyping platforms. Here, we discuss the general principles and strategies underlying CNV detection with SNP genotyping platforms, which are widely used and capable of providing both SNP and CNV genotyping information.


Institutional and policy analysis of wastewater (re)use for agriculture: case study Hyderabad, India.
Wastewater constitutes an alternative water source for the irrigation sector. To fully benefit from it, and reduce possible adverse effects on public health and the environment, we need to look at the regulation of the practice. A prerequisite for this is an institutional analysis, and the points to consider are the institutional mandates. We used the city of Hyderabad, India, as a case study. There, irrigation with wastewater is not supported or recognized, but it happens in practice. It takes place in an indirect and unplanned way. Institutions fail at enforcing regulations, and little attention is given to formalization of the practice. With this article, we aim to untangle the institutional setup, and by doing so, identify the constraints surrounding development of a formal practice. Ultimately, we aim at contributing to the discussion on the agricultural use of wastewater.


Determinants of urogenital schistosomiasis among pregnant women and its association with pregnancy outcomes, neonatal deaths and child growth.
Schistosoma haematobium is a parasitic helminth which causes urogenital pathology. The impact of urogenital schistosomiasis during pregnancy on birth outcomes and child growth is poorly understood. Risk factors for urogenital schistosomiasis were characterized among 4,437 pregnant women enrolled in a cluster-randomised community-based trial in rural Zimbabwe. Infection was defined via urine microscopy (≥1 S. haematobium egg) and urinalysis (haematuria). Associations between infection and pregnancy outcomes were assessed in case-control analyses using conditional logistic regression. The association of maternal infection with birthweight and length-for-age Z scores (LAZ) at 1 and 18 months of age were assessed using generalised estimating equations. Urogenital schistosomiasis (egg-positive and/or haematuria-positive) was detected in 26.8% of pregnant women. Risk factors significantly associated with infection were: maternal age, education, marital status and religion; household drinking water source and latrine; study region; and season. Urogenital schistosomiasis was not significantly associated with adverse pregnancy outcomes (miscarriage, stillbirth, preterm, small-for-gestational age), birthweight, neonatal death or LAZ. Including pregnant women in anti-helminthic treatment programs would benefit a large number of women in rural Zimbabwe. However, clearance of the low intensity infections that predominate in this context is unlikely to have additive benefits for pregnancy outcomes or child growth.


Detection of occult nodal metastases in patients with colorectal carcinoma.
Immunohistochemical study may be used for detecting micrometastases by their expression of tumor-associated antigens. In 48 specimens of colorectal cancer from 47 patients, 49 of 249 lymph nodes (median, five per patient; range, 2-11) examined by light microscopic study contained tumor deposits. Sections of all lymph nodes were also examined by immunohistochemical study for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression using the indirect immunoperoxidase staining method. All 49 lymph node metastases (100%) from 20 patients stained positively for CEA and 45 (92%) expressed EMA. Of the 200 lymph nodes without metastases on light microscopic examination, anti-CEA revealed a single micrometastasis in a patient staged as Dukes' B. No additional metastases were detected with anti-EMA. In this series of patients immunohistochemical study has, therefore, influenced the histologic staging in only one patient (2%) and thus does not offer a significant benefit over conventional histologic staging.


[The benign symmetrical lipomatosis (adenolipomatosis Launois-Bensaude; Madelung's fat neck)].
A case of benign symmetric lipomatosis is reported in conjunction with a review of the literature. The association with metabolic disorders such as gout and hyperlipemia, as reported by others, is fortuitous and not statistically significant. The etiology of this rare type of lipomatosis is unknown; its treatment is surgical and should be confined to cases with symptoms of compression or extremely disturbing appearance.


Steroids and nonsteroidal anti-inflammatory drugs in the postoperative regime after trabeculectomy - which provides the better outcome? A systematic review and meta-analysis.
Surgical outcome after trabeculectomy depends on maintaining a functional bleb which requires a delicate balance between incomplete wound healing to prevent fibrosis and enough wound healing to prevent hyperfiltration. Thus, controlling the inflammatory response is essential. We conducted a systematic review and meta-analysis to compare the effectiveness of different formulations of steroids (topical, systemic and depot) and nonsteroidal anti-inflammatory drugs (NSAIDs) in achieving long-term pressure control with fewer antiglaucomatous medications, preserving visual acuity and visual fields while considering surgical and postoperative complications. We used the PubMed, EMBASE and Cochrane Libraries to identify randomized controlled trials (RCTs) comparing the effect of different formulations of steroids (topical, systemic or depot) to NSAIDs. Data on prespecified outcomes from eligible references were entered into a meta-analysis using the Review Manager 5.3 program. We identified seven RCTs with a total of 342 included patients. Topical steroids were superior to placebo in controlling intraocular pressure (IOP) and reducing the risk of complications. Supplementing topical steroids with a perioperative steroid depot (subtenon or intracamerally) or systemic steroids in the early postoperative period did not provide better outcome or a change in the risk of complications. Addition of topical NSAIDs to topical steroids in patients undergoing trabeculectomy did not change the outcome or risk profile. For patients undergoing phacotrabeculectomy and topical NSAID, there was a nonsignificant trend towards better intermediate IOP control and a reduced need for antiglaucomatous medications compared to topical steroids but there was no difference in effect for patients undergoing trabeculectomy. In conclusion, there is a low level of evidence to support the clinician in deciding which postoperative regime provides a more favourable outcome because of inconsistency in the reported outcomes between studies and a low number of patients for each comparable intervention and outcome. It does seem that topical steroids are better than no anti-inflammatory treatment after glaucoma surgery, but further research is recommended.


The trigger film in nurse education.
The use of video in education is now common place. Most Colleges of Nursing and Midwifery have access to the equipment for making and/or showing their own films. Video cannot be used indiscriminately and assumed to be effective. Many educational videos are entertaining but encourage a passive audience. As a result the materials may be enjoyable but the learning achieved, disappointing. An application of video that involves the student in active learning is the trigger film. This is a short piece of film, generally only a few minutes long whose aim is to stimulate and provoke learning. It is a unique form of film possessing special characteristics. The use of the trigger film in other areas of education is documented but its application to nurse education not widely explored. A trigger film has been produced by the author and used with nursing students (RN/Dip HE) to explore professional issues. The trigger film has been found to be an excellent stimulus for discussion and particularly effective for analysis of complex issues. Evaluation by students has been overwhelmingly positive. The trigger film lends itself to exploitation within nurse education. It is particularly useful for learning within the Affective Domain (Baud & Pearson 1979). This paper will discuss the use of video in nurse education, the concept of the trigger film and the use and evaluation of the authors own film.


Apolipoprotein A-IMilano/POPC complex attenuates post-ischemic ventricular dysfunction in the isolated rabbit heart.
Irreversible myocardial injury is a potential consequence of coronary artery revascularization. Reperfusion leads to the production of oxidized products that can damage myocardium. High-density lipoproteins (HDL) are effective at removing oxidized lipids. We hypothesized that a synthetic HDL preparation, comprising recombinant apolipoprotein A-I(Milano) (apoA-I(M)) complexed with 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) (apoA-I(M)/POPC) would protect the heart from reperfusion injury. The ex vivo model consisted of rabbit hearts perfused by the Langendorff method. Hearts were equilibrated with Krebs-Henseleit buffer (10 min), pretreated with either apoA-I(M)/POPC (0.45 mg/mL) or vehicle (10 min), subjected to global ischemia (30 min) and reperfused for 60 min. ApoA-I(M)/POPC (n=7) prevented the left ventricular end-diastolic pressure elevation observed in the vehicle group (n=6) at the end of reperfusion (p<0.05). During reperfusion, coronary artery perfusion pressure increased in the controls (p<0.001), but not with apoA-I(M)/POPC. ApoA-I(M)/POPC reduced the release of creatine kinase at the end of the ischemic period (p<0.001). It also reduced cardiac left ventricle muscle lipid hydroperoxides by 46% (p<0.05). Direct comparison of the antioxidant potential indicated that recombinant apoA-I(M) was much more potent than apoA-I in attenuating low-density lipoprotein oxidation. Electron microscopy showed that apoA-I(M)/POPC prevented mitochondrial granulation, disorganization and sarcomere contraction band formation indicative of reperfusion injury. The apoA-I(M)/POPC complex thus appears to reduce reperfusion injury under global ischemic conditions, and may therefore have therapeutic application in the reduction of myocardial ischemia.


Potent antitumor activity of a tumor-specific soluble TCR/IL-2 fusion protein.
We previously have generated a single-chain T cell receptor-cytokine fusion protein (264scTCR/IL-2) comprising interleukin-2 genetically linked to a soluble HLA-A2.1-restricted TCR recognizing a peptide of human p53 protein. In this report, we show that 264scTCR/IL-2 inhibits the growth of primary tumors derived from the A375 (p53+/HLA-A2.1+) human melanoma and exhibits significantly better antitumor activity than recombinant human IL-2 alone. Moreover, treatment with 264scTCR/IL-2 results in tumor growth retardation in mice bearing large A375 tumors and other p53+/HLA-A2.1+ human tumors but does not affect tumor outgrowth of HLA-A2.1-negative tumors. This suggests that antigen targeting plays a substantial role in the efficacy of 264scTCR/IL-2 against p53+/HLA-A2+ tumors. Further, the antitumor activity of 264scTCR/IL-2 was found to be likely mediated by NK cell activation and tumor infiltration. A biologically active chimeric version of the molecule (c264scTCR/IL-2) also exhibits favorable pharmacokinetic properties required of a clinical candidate for this novel class of potent antitumor activities and targeted anticancer immunotherapeutics.


Experimental diabetes mellitus: oxidative stress and changes in lung structure.
Diabetes mellitus is an endocrine/metabolic disorder characterized by hyperglycemia. Its impact on the respiratory system is characterized by functional changes and alterations in gas exchange. The objective of this study was to evaluate the increase in oxidative stress and the potential damages to the lung structure in an experimental model of streptozotocin-induced diabetes. We conducted histological, biochemical and blood gas analyses in the lungs of diabetic rats. We concluded that the effects of experimental diabetes mellitus include oxidative stress, structural changes in the lung tissue and altered gas exchange.


Minimally invasive closure of pediatric umbilical hernias.
Pediatric umbilical hernias may close spontaneously by concentric fibrosis and scar tissue formation. Some hernias do not close. This study was developed to assess this novel minimally invasive closure (MIC), using injectable material to close the umbilical defect. Twenty-five children with umbilical hernias of 1.5 cm or less were included in the study. Deflux (Q Med, Uppsala, Sweden), a biodegradable compound of dextranomer microspheres in hyaluronic acid, was injected percutaneously in the border and preperitoneal space in 4 quadrants of the hernia defect, thereby occluding the lumen. Follow-up visits were obtained at approximately 1 week, 3 months, and 1 year. Two to twenty-four months after surgery, 21 of the 25 umbilical hernias were closed (84%). To date, there have been no complications from the injected compound substance. The average age at the time of the MIC was 6 years and 7 months, ranging from 4 months to 17 years. The average defect was more than 6.4 mm, ranging from 4 to 14 mm. Minimally invasive closure procedure with injection of dextranomer hyaluronic acid copolymer can safely be used to close umbilical hernias. The procedure closed or reduced the size of hernias in our patients immediately after surgery; and within months, 21 (84%) of 25 were closed. One defect has not closed in 1 year and will need repair. The remaining 3 defects are small and may go on to close by ongoing fibroblast ingrowth and collagen deposit. The MIC procedure may be an alternative to open repair of umbilical hernias. Increased experience and long-term follow-up will determine the true efficacy of this new technique.


The effect of pH on continuous biohydrogen production from swine wastewater supplemented with glucose.
The effect of pH on hydrogen production from liquid swine manure supplemented with glucose by a mixed culture of fermentative bacteria in an anaerobic sequencing batch reactor was evaluated in this study. At 37 +/- 1 degrees C, five pH values ranging from 4.7 to 5.9 at an increment of 0.3 were tested at a hydraulic retention time (HRT) of 16 h. The results showed that at this HRT, the optimal pH for hydrogen production was 5.0, under which the biogas comprised 33.57 +/- 5.65% of hydrogen with a production rate of 8.88 +/- 2.94 L-H(2)/day and a yield of 1.48 +/- 0.49 L-H(2)/L liquid swine manure. The highest biomass concentration, highest butyric acid to acetic acid ratio, lowest propionic acid concentration, and the best stability were all found at pH 5.0, while the highest CH(4) productivity was found at pH 5.9. For efficient hydrogen production, oxygen content should be controlled under 2%, beyond which an inverse linear relationship (R(2) = 0.986) was observed.


Acacia Ants Respond to Plant-Borne Vibrations Caused by Mammalian Browsers.
Living in the African savanna is dangerous, especially for plants. Many plants therefore engage in mutualism with ants, in which plants provide food and shelter in exchange for protection against herbivores. Ants become alarmed when the plant takes on some sort of damage. They immediately emerge from their plant shelter and aggressively defend the plant. Mammalian herbivores can have devastating effects on trees by browsing, breaking tree branches, stripping bark, and pushing over entire trees. However, mutualistic ants substantially reduce the amount of damage. To efficiently protect the tree, ants need to rapidly react together when the tree is under attack. Here, we show that the acacia ant Crematogaster mimosae defends its host tree by exploiting plant-borne vibrations caused by browsers feeding on the tree. Experiments with controlled vibrations show that ants discriminate browser-induced vibrations from those induced by wind, become alarmed, and patrol on the branches. Browser-induced vibrations serve as a long-distance alarm cue. The vibrations propagate through the whole acacia tree and trigger ants' defensive behavior, even on the other side of the tree. Furthermore, the ants make use of tropotactic directional vibration sensing to orient to the attacked part of the tree and fight back the attacker.


Molecular gene cloning and overexpression of the phytase from Debaryomyces castellii CBS 2923.
The ORF encoding the Debaryomyces castellii CBS 2923 phytase was isolated. The deduced 461-amino-acid sequence corresponded to a 51.2 kDa protein and contained the consensus motif (RHGXRXP) which is conserved among phytases. No signal sequence cleavage site was detected. Nine potential N-glycosylation sites have been predicted. The protein shared 21-69% sequence identities with various phytases of yeast or fungal origin. Heterologous expression of the D. castellii CBS 2923 phytase in the methylotrophic yeast Pichia pastoris was tested under both the P. pastoris inducible alcohol oxidase (AOX1) promoter and the constitutive glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter. Maximum production levels obtained were 476 U ml(-1), with the AOX1 expression system and 16.5 U ml(-1) with the GAP one. These productions corresponded to a 320-fold and a 10-fold overexpression of the protein, respectively as compared to the homologous production. The biochemical characteristics of the recombinant phytase were identical to those of the native enzyme.