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Background: Production of the versatile bulk chemical 1,2-propanediol and the potential biofuel 1-propanol is still dependent on petroleum, but some approaches to establish bio-based production from renewable feed stocks and to avoid toxic intermediates have been described. The biotechnological workhorse Corynebacterium glutamicum has also been shown to be able to overproduce 1,2-propanediol by metabolic engineering. Additionally, C. glutamicum has previously been engineered for production of the biofuels ethanol and isobutanol but not for 1-propanol., Results: In this study, the improved production of 1,2-propanediol by C. glutamicum is presented. The product yield of a C. glutamicum strain expressing the heterologous genes gldA and mgsA from Escherichia coli that encode methylglyoxal synthase gene and glycerol dehydrogenase, respectively, was improved by additional expression of alcohol dehydrogenase gene yqhD from E. coli leading to a yield of 0.131 mol/mol glucose. Deletion of the endogenous genes hdpA and ldh encoding dihydroxyacetone phosphate phosphatase and lactate dehydrogenase, respectively, prevented formation of glycerol and lactate as by-products and improved the yield to 0.343 mol/mol glucose. To construct a 1-propanol producer, the operon ppdABC from Klebsiella oxytoca encoding diol dehydratase was expressed in the improved 1,2-propanediol producing strain ending up with 12 mM 1-propanol and up to 60 mM unconverted 1,2-propanediol. Thus, B12-dependent diol dehydratase activity may be limiting 1-propanol production., Conclusions: Production of 1,2-propanediol by C. glutamicum was improved by metabolic engineering targeting endogenous enzymes. Furthermore, to the best of our knowledge, production of 1-propanol by recombinant C. glutamicum was demonstrated for the first time.

For synthetic biology applications, a robust structural basis is required, which can be constructed either from scratch or in a top-down approach starting from any existing organism. In this study, we initiated the top-down construction of a chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the relevant gene set to maintain its fast growth on defined medium. We evaluated each native gene for its essentiality considering expression levels, phylogenetic conservation, and knockout data. Based on this classification, we determined 41 gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36 deletions were successful and 10 genome-reduced strains showed impaired growth rates, indicating that genes were hit, which are relevant to maintain biological fitness at wild-type level. In contrast, 26 deleted clusters were found to include exclusively irrelevant genes for growth on defined medium. A combinatory deletion of all irrelevant gene clusters would, in a prophage-free strain, decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp. Finally, five combinatory deletions of irrelevant gene clusters were investigated. The study introduces the novel concept of relevant genes and demonstrates general strategies to construct a chassis suitable for biotechnological application., (© 2014 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial-NoDerivs Licence, which permits use and distribution in any medium, provided the original work is properly cited, the use is non- commercial and no modifications or adaptations are made.)

This article describes the development and validation of the theoretically grounded Emergency Medical Services Role Identity Scale (EMS-RIS), which measures four domains of EMS role identity. The EMS-RIS was developed using a mixed methods approach. Key informants informed item development and the scale was validated using a representative probability sample of EMS personnel. Factor analyses revealed a conceptually consistent, four-factor solution with sound psychometric properties as well as evidence of convergent and discriminant validities. Social workers work with EMS professionals in crisis settings and as their counselors when they are distressed. The EMS-RIS provides useful information for the assessment of and intervention with distressed EMS professionals, as well as how role identity may influence occupational stress.

Purpose: This study was designed to determine if first-year radiology resident attendance at the ACR AMCLC over a period of 3 years from 2009 to 2011 led to increased resident knowledge regarding the ACR and Minnesota Radiological Society (MRS), and whether resident involvement in the conference would influence their decisions to participate in the ACR and state radiological societies in the future., Methods: All first-year radiology residents from the University of Minnesota and the Mayo Clinic residency programs were invited to attend the ACR AMCLC from 2009 to 2011. Local radiology and radiation oncology groups provided funding for travel and hotel expenses, and both residency programs granted residents one day off from clinical duties to travel. Preconference and postconference questionnaires were used to assess residents' knowledge of the general structure and function of the ACR and MRS. Postconference questionnaires were also used to assess residents' satisfaction with the conference and determine their likelihood of joining the ACR and MRS in the future., Results: A total of 46 residents from the residency programs attended the conference over this time period. Residents' knowledge regarding the ACR and MRS increased after the conference, with improved performance on postconference objective and subjective responses. The number of issues residents identified as important to radiology increased after the conference. The vast majority of residents had a very positive experience at the conference and were "highly likely" or "likely" to join the ACR and MRS in the future., Conclusions: Results from the first 3 years of this ongoing study indicate that attending the ACR AMCLC has been an overwhelmingly positive experience for first-year radiology residents from the University of Minnesota and the Mayo Clinic programs. Residents' knowledge regarding the ACR and MRS increased nearly 2-fold following the conference. Future state radiological society and ACR membership rates among the participants in our study could potentially be higher than the current national average. Furthermore, we believe the residents' experiences at the conference play an important role in their development as more connected, informed, and politically active radiologists in the future., (Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

High-throughput screening, based on subcellular imaging, has become a powerful tool in lead discovery. Through the generation of high-quality images, not only the specific target signal can be analyzed but also phenotypic changes of the whole cell are recorded. Yet analysis strategies for the exploration of high-content screening results, in a manner that is independent from predefined control phenotypes, are largely missing. The approach presented here is based on a well-established modeling technique, self-organizing maps (SOMs), which uses multiparametric results to group treatments that create similar morphological effects. This report describes a novel visualization of the SOM clustering by using an image of the cells from each node, with the most representative cell highlighted to deploy the phenotype described by each node. The approach has the potential to identify both expected hits and novel cellular phenotypes. Moreover, different chemotypes, which cause the same phenotypic effects, are identified, thus facilitating "scaffold hopping."

Introduction: During a medical emergency, the American public often relies on the expertise of emergency medical technicians (EMTs). These professionals face a number of occupational hazards, and the literature suggests that EMTs are at a greater risk of developing physical and mental stress-related disorders. The purpose of this paper is to systematically examine gaps in the extant literature and to present a theoretically driven conceptual model to serve as a basis for future intervention and research efforts., Methods: A systematic review of the literature was conducted utilizing relevant databases (e.g., PsychInfo, Medline). All empirical articles regarding emergency medical responders were reviewed, but given the limited research available, relevant theoretical and conceptual literature on the constructs of interest in other, related populations also were included. Based on this extensive review, a modification of the stress process model is suggested to explain the relationships among occupational stress exposure, post-traumatic stress disorder (PTSD), and high-risk alcohol and other drug use., Results: Exposure to traumatic events was reported to be between 80% and 100% among EMTs, and rates of PTSD are >20%. High-risk alcohol and drug use rates among other emergency response professionals were reported to be as high as 40%. The proposed model suggests direct linkages between occupationally related stress exposure, including chronic and critical incident stress, PTSD, and high-risk alcohol and other drug use. Social support and personal resources (e.g., coping, locus of control) are proposed to have mediating and moderating influences on the three main constructs, and cohesion is introduced as an important, idiosyncratic influence in this population. The moderating influences of gender, age, ethnicity, marital status, and socioeconomic status, level of training, and years of service are included in the proposed model., Conclusions: High-risk alcohol and other drug use and post-traumatic symptomatology pose substantial risks for EMTs, and consequently, for the patients they serve. It is imperative that researchers develop and test a theoretically grounded model of risk and protective factors that will guide intervention development and future study. The model suggested in this paper, based on a comprehensive literature review and development of theory, represents a critical first step in the intervention research process.

Locomotor sensitization induced by the dopamine agonist quinpirole can be potentiated by co-treatment with the synthetic kappa opioid agonist U69593. The identification of salvinorin A, an active component of the psychotropic sage Salvia divinorum, as a structurally different agonist of kappa-opioid receptors raised the question of whether this compound would similarly potentiate sensitization to quinpirole. Rats were co-treated with 0.5 mg/kg quinpirole and either salvinorin A (0.04, 0.4 or 2.0 mg/kg) or U69593 (0.3 mg/kg). Control groups were co-treated with vehicle and saline, vehicle and quinpirole (0.5 mg/kg), or saline and salvinorin A (0.4 mg/kg). Rats were injected biweekly for a total of 10 injections and locomotor activity measured after each treatment. Results showed that the highest dose of salvinorin A potentiated sensitization to quinpirole as did U69593, the middle salvinorin A dose had no effect on quinpirole sensitization, and the lowest dose of salvinorin A attenuated sensitization to quinpirole. These findings indicate that structural differences between salvinorin A and U69593 do not affect the potentiation of quinpirole sensitization. Moreover, the opposite effects of high and low salvinorin A doses suggest that salvinorin A can produce bidirectional modulation of sensitization to dopamine agonists.

Although several thermal lattice Boltzmann models have been proposed, this method has not yet been shown to be able to describe nonisothermal fully compressible flows in a satisfactory manner, mostly due to the presence of important deviations from the advection-diffusion macroscopic equations and also due to numerical instabilities. In this context, this paper presents a linear stability analysis for some lattice Boltzmann models that were recently derived as discrete forms of the continuous Boltzmann equation [P. C. Philippi, L. A. Hegele, Jr., L. O. E. dos Santos, and R. Surmas, Phys. Rev. E 63, 056702 (2006)], in order to investigate the sources of instability and to find, for each model, the upper and lower limits for the macroscopic variables, between which it is possible to ensure a stable behavior. The results for two-dimensional (2D) lattices with 9, 17, 25, and 37 velocities indicate that increasing the order of approximation of the lattice Boltzmann equation enhances stability. Results are also presented for an athermal 2D nine-velocity model, the accuracy of which has been improved with respect to the standard D2Q9 model, by adding third-order terms in the lattice Boltzmann equation.

Time-resolved (TR) fluorescence resonance energy transfer (FRET) is a widely accepted technology for high throughput screening (HTS), being able to detect and quantify the interactions of specific biomolecules in a homogeneous format. TR-FRET has several advantages for HTS applications that reduce assay artifacts such as compound interference. However, in some cases artifacts due to compound autofluorescence, color quenching, or signal stability are still observed. This report presents strategies addressing these issues by several means. One recommendation is the recording and visualization of differences in the donor/acceptor fluorescence, which allows the identification of compound artifacts. Another suggestion is to adjust the time delay, between excitation and recording of the fluorescence, in order to reduce compound interference. Furthermore, configuring the assay to allow the TR-FRET measurement to be taken at different time points, creating a reaction time course, allows background correction for each sample. Finally, the optimization of the FRET pair, to ensure assay signal stability under screening conditions, can improve the assay quality. This report presents examples of how these simple steps can be applied to enhance the quality of TR-FRET screening campaigns.

Background: Genital ulcer disease (GUD) is commonly caused by pathogens for which suitable therapies exist, but clinical and laboratory diagnoses may be problematic. This collaborative project was undertaken to address the need for a rapid, economical, and sensitive approach to the detection and diagnosis of GUD using noninvasive techniques to sample genital ulcers., Methods: The genital ulcer disease multiplex polymerase chain reaction (GUMP) was developed as an inhouse nucleic acid amplification technique targeting serious causes of GUD, namely, herpes simplex viruses (HSVs), H. ducreyi, Treponema pallidum, and Klebsiella species. In addition, the GUMP assay included an endogenous internal control. Amplification products from GUMP were detected by enzyme linked amplicon hybridization assay (ELAHA)., Results: GUMP-ELAHA was sensitive and specific in detecting a target microbe in 34.3% of specimens, including 1 detection of HSV-1, three detections of HSV-2, and 18 detections of T. pallidum. No H. ducreyi has been detected in Australia since 1998, and none was detected here. No Calymmatobacterium (Klebsiella) granulomatis was detected in the study, but there were 3 detections during ongoing diagnostic use of GUMP-ELAHA in 2004 and 2005. The presence of C. granulomatis was confirmed by restriction enzyme digestion and nucleotide sequencing of the 16S rRNA gene for phylogenetic analysis., Conclusions: GUMP-ELAHA permitted comprehensive detection of common and rare causes of GUD and incorporated noninvasive sampling techniques. Data obtained by using GUMP-ELAHA will aid specific treatment of GUD and better define the prevalence of each microbe among at-risk populations with a view to the eradication of chancroid and donovanosis in Australia.

Salvia divinorum is a widespread hallucinogenic herb traditionally employed for divination, as well as a medicament for several disorders including disturbances of gastrointestinal motility. In the present study we evaluated the effect of a standardized extract from the leaves of S. divinorum (SDE) on enteric cholinergic transmission in the guinea-pig ileum. SDE reduced electrically evoked contractions without modifying the contractions elicited by exogenous acetylcholine, thus suggesting a prejunctional site of action. The inhibitory effect of SDE on twitch response was abolished by the opioid receptor antagonist naloxone and by the kappa-opioid antagonist nor-binaltorphimine, but not by naltrindole (a delta-opioid receptor antagonist), CTOP (a mu-opioid receptor antagonist), thioperamide (a H(3) receptor antagonist), yohimbine (an alpha(2)-receptor antagonist), methysergide (a 5-hydroxytryptamine receptor antagonist), N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase) or apamin (a blocker of Ca(2+)-activated K(+) channels). Salvinorin A, the main active ingredient of S. divinorum, inhibited in a nor-binaltorphimine- and naloxone-sensitive manner electrically induced contractions. It is concluded that SDE depressed enteric cholinergic transmission likely through activation of kappa-opioid receptors and this may provide the pharmacological basis underlying its traditional antidiarrhoeal use. Salvinorin A might be the chemical ingredient responsible for this activity.

Scedosporium prolificans is a saprophytic fungus responsible for an increasing number of infections among immunocompromised hosts. Historically, disseminated infection with this organism has resulted in death. We report on a pediatric patient who developed overwhelming S. prolificans sepsis after induction chemotherapy for acute lymphoblastic leukemia. She is well 18 months after the diagnosis of fungal sepsis and continues to receive chemotherapy for leukemia, which remains in remission.

It is argued that medical science requires a classificatory system that (a) puts functions in the taxonomic center and (b) does justice ontologically to the difference between the processes which are the realizations of functions and the objects which are their bearers. We propose formulae for constructing such a system and describe some of its benefits. The arguments are general enough to be of interest to all the life sciences.

Salvinorin A, TRK-820 (17-cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido]morphinan hydrochloride), and 3FLB (diethyl 2,4-di-[3-fluorophenyl]-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane-9-one-1,5-dicarboxylate) are structurally distinctly different from U50,488H [(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate], the prototypic selective kappa agonist. Here, we investigated their in vitro pharmacological activities on receptors expressed in Chinese hamster ovary cells and in vivo antiscratch and antinociceptive activities in mice. All three compounds showed high selectivity for the kappa opioid receptor (KOR) over the mu opioid receptor (MOR) and delta opioid receptor (DOR) and nociceptin or orphanin FQ receptors. In the guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding assay, all three were full agonists on the KOR. The rank order of affinity and potency for the KOR was TRK-820 >> U50,488H approximately salvinorin A >> 3FLB. TRK-820 acted as a partial agonist on MOR and DOR, whereas salvinorin A and 3FLB showed no activities on these receptors. Salvinorin A, TRK-820, and 3FLB caused internalization of the human KOR in a dose-dependent manner. Interestingly, although salvinorin A and U50,488H had similar potencies in stimulating [(35)S]GTPgammaS binding, salvinorin A was about 40-fold less potent than U50,488H in promoting internalization. Following 4-h incubation, all three compounds induced down-regulation of the human KOR, with salvinorin A causing a lower extent of down-regulation. Although TRK-820 was potent and efficacious against compound 48/80-induced scratching, salvinorin A showed low and inconsistent effects, and 3FLB was inactive. In addition, salvinorin A and 3FLB were not active in the acetic acid abdominal constriction test. The discrepancy between in vitro and in vivo results may be due to in vivo metabolism of salvinorin A and 3FLB and possibly to their effects on other pharmacological targets.

A series of dinickel(II) complexes with the 24-membered macrocyclic hexaazadithiophenol ligand H(2)L(Me) was prepared and examined. The doubly deprotonated form (L(Me))(2-) forms complexes of the type [(L(Me))Ni2II(mu-L')](n+) with a bioctahedral N(3)Ni(II)(mu-SR)(2)(mu-L')Ni(II)N(3) core and an overall calixarene-like structure. The bridging coordination site L' is accessible for a wide range of exogenous coligands. In this study L'=NO(3)(-), NO(2)(-), N(3)(-), N(2)H(4), pyrazolate (pz), pyridazine (pydz), phthalazine (phtz), and benzoate (OBz). Crystallographic studies reveal that each substrate binds in a distinct fashion to the [(L(Me))Ni(2)](2+) portion: NO(2)(-), N(2)H(4), pz, pydz, and phtz form mu(1,2)-bridges, whereas NO(3)(-), N(3)(-), and OBz(-) are mu(1,3)-bridging. These distinctive binding motifs and the fact that some of the coligands adopt unusual conformations is discussed in terms of complementary host-guest interactions and the size and form of the binding pocket of the [(L(Me))Ni(2)](2+) fragment. UV/Vis and electrochemical studies reveal that the solid-state structures are retained in the solution state. The relative stabilities of the complexes indicate that the [(L(Me))Ni(2)](2+) fragment binds anionic coligands preferentially over neutral ones and strong-field ligands over weak-field ligands. Secondary van der Waals interactions also contribute to the stability of the complexes. Intramolecular ferromagnetic exchange interactions are present in the nitrito-, pyridazine-, and the benzoato-bridged complexes where J=+6.7, +3.5, and +5.8 cm(-1) (H=-2 JS(1)S(2), S(1)=S(2)=1) as indicated by magnetic susceptibility data taken from 300 to 2 K. In contrast, the azido bridge in [(L(Me))Ni(2)(mu(1,3)-N(3))](+) results in an antiferromagnetic exchange interaction J=-46.7 cm(-1). An explanation for this difference is qualitatively discussed in terms of bonding differences.

Objective: Elevated cerebrospinal fluid (CSF) lactate concentrations in neurotrauma and sub-arachnoid haemorrhage are associated with a poor prognosis. However, in blood-stained CSF, elevated lactate levels may arise from red cell metabolism, even without ischaemia, potentially reducing specificity. This study was undertaken to quantify the erythrocyte contribution to CSF lactate measurements, with and without, exposure to room air., Methods: Blood was added to CSF to achieve three different red cell concentrations. The CSF was then exposed at 37 degrees C to either room air or 5% CO2 and 95% oxygen. Vancomycin and gentamycin were added to inhibit bacterial growth. Lactate concentrations and red cell concentrations were measured prior to the addition of blood and 10 minutes, 6 hours and 24 hours later. CSF without the addition of blood was used as a control., Results: In the control specimens there were no increases in CSF lactate concentrations over time, either in air or CO2, whereas all specimens with blood added demonstrated significant increases in lactate at 6 and 24 hours (P < 0.01). The lactate increases in both air and CO2 were correlated directly with red cell counts (R2 = 0.62 to 0.87). At all red cell concentrations, the mean lactate increase was greater in air., Conclusions: Red cells in CSF cause significant increases in lactate concentrations, more so when exposed to air. This should be considered when interpreting lactate in blood stained CSF. Blood-stained CSF specimens for lactate assay should be collected directly from an external ventricular drain rather than a reservoir bag.

Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that Salvinorin A potently and selectively inhibited (3)H-bremazocine binding to cloned kappa opioid receptors. Salvinorin A had no significant activity against a battery of 50 receptors, transporters, and ion channels and showed a distinctive profile compared with the prototypic hallucinogen lysergic acid diethylamide. Functional studies demonstrated that Salvinorin A is a potent kappa opioid agonist at cloned kappa opioid receptors expressed in human embryonic kidney-293 cells and at native kappa opioid receptors expressed in guinea pig brain. Importantly, Salvinorin A had no actions at the 5-HT(2A) serotonin receptor, the principal molecular target responsible for the actions of classical hallucinogens. Salvinorin A thus represents, to our knowledge, the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist. Because Salvinorin A is a psychotomimetic selective for kappa opioid receptors, kappa opioid-selective antagonists may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that kappa opioid receptors play a prominent role in the modulation of human perception.

The coordinatively unsaturated dinickel(II) complex [(L2)Ni2](BPh4)2 (2), where (L2)2- represents the dianionic form of the 'N4S2' ligand N,N'-bis(2-thio-3-aminomethyl-5-tert-butylbenzyl)propane-1,3-diamine), has been investigated with respect to its ability to function as a building block for the preparation of polynuclear nickel complexes with a high-spin ground state. Treatment of 2 with pyridazine (pydz) followed by addition of two equivalents of NH4SCN afforded the dinuclear mupyridazine complex [(L2)Ni2(mu-pydz)(NCS)2] (4). The reaction of 2 with pyridazine and NaN3 in a 1:1:1 molar ratio gave the tetranuclear nickel(II) complex [[(L2)Ni2(mu-pydz)(N3)]2](BPh4)2 (5). Both complexes have been characterized by X-ray crystallography and variable-temperature magnetic susceptibility studies. In complex 4 two fac(SCN)N2Ni(II) units are linked by two thiophenolate sulfur atoms and a mu-pydz ligand to give a (SCN)N2Ni(mu-S)2(mu-pydz)NiN2(NCS) core structure with a pseudoconfacial bioctahedral geometry. The two NCS- groups occupy opposite coordination sites, each is in a cis position to the pydz bridge. Analyses of the susceptibility data indicate the presence of an intramolecular ferromagnetic exchange interaction between the two Ni(II) (S = 1) ions. Complex 5 is composed of two binuclear [(L2)Ni2(mu-pydz)]2+ subunits which are linked by two azide ions to give a rectangular array of four six-coordinate Ni(II) ions. The binuclear [(L2)Ni2(mu-pydz)]2+ fragments in 4 and 5 are isostructural. Analyses of the susceptibility data of 5 reveal ferromagnetic exchange interactions between the Ni(II) ions of the binuclear subunit as well as for the mu(1,3)N3-bridged Ni(II) ions. Thus, compound 4 has an S = 2 ground state, whereas in 5 it is S = 4.

At an antenatal clinic at a Melbourne obstetric hospital, 308 women were questioned about a known past history of infection with varicella zoster virus (VZV), human parvovirus B19 and Toxoplasma gondii. Immunoglobulin G (IgG) concentrations were determined for the 3 infectious agents and a recalled history of infection was compared with the presence of specific antibody. Exactly 66% of women recalled being infected with chickenpox (VZV) and 94% showed serological evidence of past exposure. Although 64% of women had parvovirus specific IgG, only one gave a definite history of past parvovirus infection. None of the 23% of women with evidence of previous exposure to Toxoplasma gondii recalled a past infection. The proportion of antenatal women at risk in this study was used to estimate the potential burden of disease from congenital infections in Australia and to examine implications for management of pregnancies complicated by these 3 infections.

The age-specific immunity to human parvovirus infection was estimated in Victoria, Australia using prospectively collected samples from the Royal Children's Hospital, the Royal Women's Hospital and the Australian Red Cross Blood Service and from sera stored at the Victorian Infectious Diseases Reference Laboratory (VIDRL). All testing was performed at VIDRL using a commercial enzyme-linked immunosorbent assay (Biotrin). Of the 824 sera tested, 28% of those drawn from people aged 0-9 years contained protective antibodies to human parvovirus. This rose to 51% in the next decade of life. There was then a slow rise to about 78% immunity over 50 years of age. An analysis of all requests for parvovirus serology at VIDRL from 1992 to 1998 suggested that parvovirus tended to occur in 4-year cycles, with 2 epidemic years followed by 2 endemic years. A review of published reports of parvovirus immunity suggested that parvovirus infection may be more common, with a correspondingly higher proportion of the community immune, in temperate as opposed to tropical countries.

This article proposes role identity theory as a means of integrating the diverse frameworks and findings that populate the social support literature, and it highlights the importance of the friendship role on life satisfaction for aging adults. A sample of 800 preretirement-age working men and women were surveyed as part of a longitudinal study, Roles and Self: Factors in Development and Retirement. The results include differences in social support by gender, no significant influence of structural support variables, and the significant effect of the role of friendship on respondents' life satisfaction. Hierarchical regression analysis showed that commitment to the role of friend is significant in predicting life satisfaction when controlling for background variables, and friendship identity meanings emerged as the strongest predictor--stronger than income or marital status--when predicting well-being. Integration of theory with current and previous research, implications for practice, and directions for future research are discussed.

An important step toward our main goal of a completely computer-based maxillofacial surgical planning system is the availability of tools for the surgeon to define bone segments from skull and jaw bones. We have developed an easy-to-handle user interface that employs visual and force-feedback devices to define subvolumes of a patient's volume dataset. This interface is a main component of our maxillofacial surgical planning tool MeVisTo-Jaw [1]. The defined subvolumes together with their spatial arrangements lead to an operation plan.

A coordinatively unsaturated dinuclear Ni(II) complex of the tridentate ligand 2,6-di(aminomethyl)-4-tert-butyl-thiophenol (HL) has been synthesized and investigated in the context of ligand binding and oxidation state changes. The starting complex [L(2)Ni(2)][BPh(4)](2) (1) is readily prepared from NaL, NiCl(2).6H(2)O, and NaBPh(4) in methanol. Compound 1.CH(3)CN.CH(3)OH crystallizes from an acetonitrile/methanol mixed-solvent system in monoclinic space group P2(1)/n with a = 21.940(4) Å, b = 13.901(3) Å, c = 23.918(5) Å, beta = 110.00(3) degrees, and Z = 4. The structure consists of dinuclear [L(2)Ni(2)](2+) cations with two distorted planar cis-N(2)S(2)Ni coordination units joined by the thiophenolate sulfur atoms. The molecule has idealized C(2)(v)() symmetry. Complex 1 readily adds another 1 equiv of HL to afford the pale green complex [L(3)Ni(2)]Cl (2). The dinuclear structure and its formulation as a 3:2 complex (six-coordinate Ni ions) is derived from UV spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction of its oxidation product, [L(3)Ni(2)](2+). The dication was prepared by chemical oxidation of 2 with iodine in DMF and isolated as the dark brown BPh(4)(-) salt, [L(3)Ni(2)][BPh(4)](2).CH(3)OH (3), which crystallizes in monoclinic space group P2(1)/c with a = 23.678(5) Å, b = 20.090(4) Å, c = 16.797(3) Å, beta = 106.16(3) degrees, and Z = 4. Complex 3 is the first structurally characterized example that features a bioctahedral N(3)Ni(&mgr;(2)-SR)(3)NiN(3) core. Distortions from D(3)(h)() symmetry suggest that 3 is a trapped-valence Ni(II)Ni(III) compound. The Ni-S and Ni-N bond lengths vary from 2.2975(9) to 2.4486(12) Å and from 2.027(3) to 2.120(3) Å, respectively. On the CV time scale complex 2 undergoes two reversible electron-transfer reactions at E(1/2) = -0.02 and +0.44 V vs SCE, affording 3 and the transient dark green trication [L(3)Ni(2)](3+) (tau(1/2) approximately 15 min at 295 K), respectively. While 2 is EPR silent, the EPR spectrum of a powdered sample of 3 reveals g( perpendicular) = 4.0 and g( parallel) = 2.09 at 77 K, consistent with an S = (3)/(2) spin state of the mixed-valent Ni(II)Ni(III) complex.

Objective: To determine the prevalence of markers of past hepatitis B infection among participants in Australian Rules football, to estimate the potential exposure of Australians to hepatitis B virus (HBV) in contact sport., Design and Setting: A point prevalence survey for antibody to hepatitis B surface antigen (anti-HBs) and core antigen (anti-HBc), supported by a questionnaire used to determine the history of risk and exposure, in South Australian National Football League (SANFL) players supervised at club level by general practitioners and sports medicine specialists., Participants: Of 245 players from seven clubs, 49 were excluded from the study because they had been previously vaccinated. Of 196 eligible participants, 117 submitted blood samples and, of these, 85 returned questionnaires., Results: One player was positive for anti-HBc (a prevalence rate of 0.85%). This individual and three anti-HBc-negative players were positive for anti-HBs in the absence of a history of vaccination. We could not ascertain whether these additional three players had been previously infected, or vaccinated without this fact having been recorded on the questionnaires. No single behavioural factor correlated with positive anti-HBs results., Conclusions: The prevalence of markers of past hepatitis B infection in SANFL football players was no different to that in blood donors of the same age group from the same city. There was no evidence for any additional HBV transmission due to participation in football over that in the blood donor population. Vaccination of footballers and people engaged in similar sports is of benefit in conferring protection on the individual, but would be unlikely to make a significant public health impact on community rates of HBV infection.

Strongyloides stercoralis infections frequently present with eosinophilia and abdominal pain. Since the gastrointestinal symptoms are non-specific, only 15 percent of these patients are correctly considered to have an infectious enteritis or intestinal parasite. In fact, the initial diagnosis is peptic ulcer disease in most patients. The clinical course may be indolent, or patients may develop a sudden catastrophic illness, particularly following the administration of corticosteroids.

1. The inhibitory effects of aspirin on platelet function in vitro have been shown to be both time (over 3 h) and concentration (1-10 mumol/l) dependent. 2. To determine if these effects occurred in vivo, four volunteers received intravenous infusions on four occasions, to give constant plasma aspirin concentrations of 0, 1, 2 and 4 mumol/l over 3 h. Infusions were performed at intervals of at least 2 weeks. 3. Before and during the infusions, blood was taken for assay of aspirin concentrations, and measurements of platelet aggregation in response to collagen, adenosine 5'-pyrophosphate and arachidonate. Thromboxane generation after stimulated platelet aggregation and whole-blood coagulation was also measured. 4. At each aspirin concentration, both platelet aggregation and thromboxane generation in response to collagen and arachidonate were inhibited progressively over the 3 h infusion period. Greatest inhibition was seen during the 4 mumol/l infusion, which produced maximal or near-maximal inhibition by the third hour. 5. Thromboxane generated during whole-blood coagulation was similarly inhibited in both a time- and concentration-dependent manner throughout all aspirin infusions. 6. The progressive nature of the inhibition of platelet function with these low aspirin concentrations may be due to either slow aspirin transport across the platelet membrane or delayed interaction with cyclo-oxygenase.

The chloroplast isoprenoid synthesis of very young leaves is supplied by the plastidic CO(2) --> pyruvate --> acetyl-coenzyme A (C(3) --> C(2)) metabolism (D Schulze-Siebert, G Schultz [1987] Plant Physiol 84: 1233-1237) and occurs via the plastidic mevalonate pathway. The plastidic C(3) --> C(2) metabolism and/or plastidic mevalonate pathway of barley (Hordeum vulgare L.) seedlings changes from maximal activity at the leaf base (containing developing chloroplasts with incomplete thylakoid stacking but a considerable rate of photosynthetic CO(2)-fixation) almost to ineffectivity at the leaf tip (containing mature chloroplasts with maximal photosynthetic activity). The ability to import isopentenyl diphosphate from the extraplastidic space gradually increases to substitute for the loss of endogenous intermediate supply for chloroplast isoprenoid synthesis (change from autonomic to division-of-labor stage). Fatty acid synthesis from NaH(14)CO(3) decreases in the same manner as shown for leaf sections and chloroplasts isolated from these. Evidence has been obtained for a drastic decrease of pyruvate decarboxylase-dehydrogenase activity during chloroplast development compared with other anabolic chloroplast pathways (synthesis of aromatic amino acid and branched chain amino acids). The noncompetition of pyruvate and acetate in isotopic dilution studies indicates that both a pyruvate-derived and an acetate-derived compound are simultaneously needed to form introductory intermediates of the mevalonate pathway, presumably acetoacetyl-coenzyme A.

A high-performance liquid chromatographic assay for the determination of endogenous plasma and urine concentrations of N1-methylnicotinamide was developed. N1-Methylnicotinamide and N1-ethylnicotinamide (internal standard) are reacted with acetophenone in a strong base at 0 degree C, formic acid is added, and the reaction mixture is heated in a boiling water bath, resulting in the formation of fluorescent derivatives. These derivatives were chromatographed on a C18 reverse-phase column using a mobile phase of acetonitrile-triethylamine and 0.01 M heptanesulfonic acid adjusted to pH 3.2. Fluorescent detection was achieved using 366-nm excitation and 418-nm emission filters. Precision and accuracy were generally greater than 90%, interfering peaks did not cochromatograph, and the limit of quantification was 2 ng/ml in plasma using a 0.2-ml sample. The method was used to examine the concentrations of endogenous N1-methylnicotinamide in the plasma of 36 subjects with various pathology. The mean concentration was 18 ng/ml and the range was 6.2 to 116.7 ng/ml. The assay represents a marked improvement on previous methods and is suitable for routine clinical monitoring.

1. The effect of dipyridamole on platelet function was measured in twelve normal subjects given 150 or 200 mg tablets as single and multiple doses, and in six subjects given single doses of 25, 50 and 100 mg and multiple doses of 50 mg 8 hourly. 2. Platelet aggregation was measured in response to ADP and collagen. In the subjects given 150/200 mg, the platelets were assayed for content of cyclic AMP and for formation of thromboxane after addition of collagen. The responses to ADP and collagen and the cyclic AMP content were assessed in both the presence and absence of added PGE1. The pharmacokinetics of dipyridamole were studied in all subjects. 3. One hour after 150/200 mg single doses of dipyridamole there was significant inhibition of platelet aggregation in response to both collagen and ADP. There was no detectable effect on aggregation at other time points or with lower doses of dipyridamole. The addition of PGE1 to platelets prior to testing did not enhance the effect of dipyridamole on platelet aggregation. 4. In multiple doses, dipyridamole (150/200 mg twice daily for 11 days) had no detectable effect on platelet aggregation. 5. Dipyridamole did not have any effect on platelet cyclic AMP content, whether or not PGE1 was added prior to assay. 6. Dipyridamole did not affect platelet thromboxane formation. 7. Plasma dipyridamole concentrations were maximal 1-2 h after ingestion, at the same time that inhibition of platelet aggregation was detected. The concentrations declined in a biexponential fashion, with a terminal half life of 24.1 +/- 1.9 h (mean +/- s.e. mean). In six of the 17 subjects, the mean steady state plasma concentration was less than 75% of the value predicted from the single dose data.

Our aims were (1) to determine the effect of six commercially available aspirin (ASA) preparations on in vitro platelet aggregation, and (2) to relate changes in platelet function to ASA kinetics. Each of six subjects took a single dose of one of the following preparations--600 mg Asproclear, 600 mg Bufferin, 600 mg Bi-prin, 600 mg compressed ASA, 650 mg Ecotrin, or 650 mg S.R.A.--in random order every 3 wk. Venous blood was drawn before and at 2, 4, 6, and 24 hr after ASA dosage to measure platelet aggregation in response to collagen and adenosine diphosphate and, at more frequent intervals, to characterize ASA kinetics. Asproclear, Bufferin, Bi-prin, and compressed ASA yielded peak plasma ASA levels of 28 to 56 mumol/l (5 to 10 mg/l) within 15 to 60 min and peak salicylic acid (SA) levels of 72 to 290 mumol/l (10 to 40 mg/l) within 2 hr. Ecotrin and S.R.A. yielded plasma SA levels of 14 to 87 mumol/l (2-12 mg/l) within 4 to 24 hr and no measurable ASA at any time after dosing. Platelet aggregation was inhibited to an equal extent by all preparations. The time course for this inhibition was the same for all preparations but Ecotrin (which led to a more delayed effect). There was significant recovery of collagen-induced platelet aggregation at 24 hr with all preparations but Ecotrin. With Ecotrin and S.R.A. there was inhibition of platelet aggregation in the absence of measurable circulating ASA. We postulate that this was due to acetylation of cyclooxygenase in the portal circulation and that inhibition of peripheral cyclooxygenase may be spared.

The diploid respiratory-deficient strain of yeast D4-RDII was used to assay PAH and urethane as well as some oxygenated derivatives of PAH and the (aliphatic) epoxide hydrolase inhibitor TCPO for convertogenic (mutagenic) activity. As a positive control, the convertogenic ultimate rat liver carcinogen NOAcAAF was used. PAH and urethane were found inactive as convertogens, TCPO was weakly active, whereas oxygenated electrophilic derivatives of PAH, such as K-region oxides, were found strong convertogens. For comparison, some convertogenic key compounds were assayed for their tumor-initiating activity in mouse skin in the standardized system using TPA as a promotor. PAH were stronger initiators than all oxygenated derivatives of PAH tested. TCPO alone exhibited very weak, if any, initiating activity. It was unable to modify initiation to any significant extent, if administered 5 min prior to administration of an initiator. In the absence of correlation between convertogenic and initiating activity the question of the chemical nature of "ultimate initiators" of mouse skin carcinogenesis awaits further investigation.

Carefully isolated intact spinach chloroplasts virtually free of contamination of other organelles effectively form beta-carotene from NaH(14)CO(3) or [U-(14)C]-3-phosphoglycerate (PGA) under photosynthetic conditions. The photosynthate pool formed in chloroplasts from 1 to 2 millimolar [U-(14)C]-3-PGA or 3 to 6 millimolar NaH(14)CO(3) was fully sufficient to supply beta-carotene synthesis with intermediates for about 1 hour at maximal rates of about 20 nanomoles (14)C incorporated per milligram chlorophyll per hour. Fatty acid synthesis remains, under these circumstances, in linear dependence to substrate concentrations with far lower activity. Isotopic dilution of the beta-carotene synthesis by adding unlabeled glyceraldehyde 3-phosphate, dihydroxyacetone-P, 3-PGA, 2-PGA, phosphoenolpyruvate, pyruvate, respectively, may be interpreted as a direct substrate flow from photosynthetically fixed CO(2) to isopentenyl pyrophosphate synthesizing system. Unlabeled acetate did not dilute beta-carotene synthesis. Fatty acid synthesis acted similarly with unlabeled substrates; but it also was diluted by unlabeled acetate. These results indicate a tight linkage of photosynthetic carbon fixation and plastid isoprenoid synthesis.

A new method for trace analysis of gases, based on the pulsed photoacoustic Raman spectroscopy (PARS) technique, is described. The method has been applied to the analysis of mixtures of CH(4) in N(2), CO(2) in N(2), and N(2)O in N(2) at concentrations near 1 ppm. The apparatus used is described in some detail. Means of improving the method's sensitivity as well as sensitivity-limiting processes are evaluated. The analytical capabilities of this technique are compared with both direct (IR) absorption and other Raman techniques such as CARS and stimulated Raman gain spectroscopy (SRGS).

A probable carbon flow from the Calvin cycle to branched chain amino acids and lipids via phosphoenolpyruvate (PEP) and pyruvate was examined in spinach (Spinacia oleracea) chloroplasts. The interpendence of metabolic pathways in and outside chloroplasts as well as product and feedback inhibition were studied. It was shown that alanine, aromatic, and small amounts of branched chain amino acids were formed from bicarbonate in purified intact chloroplasts. Addition of PEP only favored formation of aromatic amino acids. Mechanisms of regulation remained unclear. Concentrations of PEP and pyruvate within the chloroplast impermeable space during photosynthetic carbon fixation were 15 times higher than in the reaction medium. A direct carbon flow to pyruvate was identified (0.1 micromoles per milligram chlorophyll per hour). Pyruvate was taken up by intact chloroplasts slowly, leading to the formation of lysine, alanine, valine, and leucine plus isoleucine (approximate ratios, 100-500:60-100:40-100:2-10). The K(m) for the formation of valine and leucine plus isoleucine was estimated to be 0.1 millimolar. Ten micromolar glutamate optimized the transamination reaction regardless of whether bicarbonate or pyruvate was being applied. Alanine and valine formation was enhanced by the addition of acetate to the reaction mixture. The enhancement probably resulted from an inhibition of pyruvate dehydrogenase by acetyl-S-coenzyme A formed from acetate, and resulting accumulation of hydroxyethylthiamine diphosphate and pyruvate. High concentrations of valine and isoleucine inhibited their own and each others synthesis and enhanced alanine formation. When pyruvate was applied, only amino acids were formed; when complemented with bicarbonate, fatty acids were formed as well. This is probably the result of a requirement of acetyl-S-coenzyme A-carboxylase for bicarbonate.

The genetic activity of cyclophosphamide (Cy) was tested in the host-mediated assay (injection of yeasts into the peritoneal cavity of rats) modified by the use of probenecid (Pro) (Benemid) to block the renal tubular excretion of the genetically active metabolites. The genetic test system used was the induction of mitotic gene conversion in two unliked loci of a diploid strain of Saccharomyces cerevisiae. By this method the genetic effect of By was doubled in comparison with the case of administering Cy alone. Compared with the animals which received only Pro, increases of conversion frequencies of 20 times in the ade2 locus and of 15 times in the trp5 locus were found.

The pharmacokinetics of low-dose aspirin and the resulting salicylic acid were studied in 6 healthy volunteers. Each received a single 50-mg dose of (1) oral modified release capsules, (2) oral solution and (3) intravenous solution. The volunteers also received 50 mg modified release capsules daily for 6 days to determine the effect on collagen, ADP and arachidonate induced platelet aggregation and thromboxane production, and to compare the pharmacokinetics after repeated dosing with the parameters obtained after the single dose. The formulation and route of administration profoundly influenced several pharmacokinetic parameters for aspirin: the maximum concentration (Cmax, ng.ml-1) was 221 and 191 after modified release for single and chronic dosing respectively, 1323 after the oral solution and 6000 after intravenous injection; the time to achieve this maximum concentration (tmax, h) was 3.42 and 3.02 after modified release for single and chronic dosing respectively, and 0.29 after the oral solution; the area under the plasma drug concentration versus time curve (AUC, microgram.h.ml-1) was 0.38 and 0.27 after modified release single and chronic dosing respectively, 0.68 after the oral solution and 1.57 after intravenous injection. The elimination of aspirin after the two solutions was at least biphasic. The terminal phase rate constant ranged from 1.52 h-1 after intravenous injection to 1.88 h-1 after the oral modified release form. The absorption of the oral forms of aspirin was complete as reflected by the total recovery of the doses as salicylic acid in urine.(ABSTRACT TRUNCATED AT 250 WORDS)