Impacts on Reticulitermes flavipes (Infraorder Isoptera: Rhinotermitidae) by Chlorantraniliprole Applied to Soil Surrounding Established Tunnels.

Soil-applied liquid termiticides are the most common control measure for subterranean termites. Characteristics unique to insecticidal chemistries such as repellency, toxicity, and time between contact and mortality, influence the interaction of termites with treated soil and overall treatment success. Two different treated-tunnel bioassays were used to evaluate the behavioral impacts and mortality of termites from treatment with chlorantraniliprole (the active ingredient in Altriset® termiticide) to existing, mature tunnels. Termites that were provided constant access to a 10-cm-long mature tunnel within soil treated with 5 or 50 ppm chlorantraniliprole were not repelled by the treatment and began exhibiting slower, uncoordinated movement, and cessation of tunneling and feeding in as little as 1 h after access. Termites provided access for 7, 14, or 21 d to previously constructed tunnels recently treated with 50 ppm chlorantraniliprole exhibited complete or near complete mortality by 28 d. The second bioassay design resembled a more typical field situation with a 40-cm-long mature tunnel and termites allowed access for a maximum of 5 min. Termites collected after just 5 min of access to the previously constructed tunnels recently treated with 50 ppm chlorantraniliprole exhibited similar symptomology within an hour followed by complete mortality at 18 d after exposure. These test designs simulate what occurs in the soil around an infested structure at the time of treatment. Results from these evaluations suggest that termites readily crawl through chlorantraniliprole-treated mature tunnels, rapidly lose ability to feed, and acquire a lethal dose from brief exposures.

Characterization and prognostic impact of ACTBL2-positive tumor-infiltrating leukocytes in epithelial ovarian cancer.

Actin beta-like 2 (ACTBL2) was recently identified as a new mediator of migration in ovarian cancer cells. Yet, its impact on tumor-infiltrating and thus migrating leukocytes (TILs) remains to date unknown. This study characterizes the subset of ACTBL2-expressing TILs in epithelial ovarian cancer (EOC) and elucidates their prognostic influence on the overall survival of EOC patients with special regard to different histological subtypes. Comprehensive immunohistochemical analyses of Tissue-Microarrays of 156 ovarian cancer patients revealed, that a tumor infiltration by ACTBL2-positive leukocytes was significantly associated with an improved overall survival (OS) (61.2 vs. 34.4 months; p = 0.006) and was identified as an independent prognostic factor (HR = 0.556; p = 0.038). This significant survival benefit was particularly evident in patients with low-grade serous carcinoma (OS: median not reached vs. 15.6 months, p < 0.001; HR = 0.058, p = 0.018). In the present cohort, ACTBL2-positive TILs were mainly composed of CD44-positive cytotoxic T-cells (CD8+) and macrophages (CD68+), as depicted by double-immunofluorescence and various immunohistochemical serial staining. Our results provide significant evidence of the prognostic impact and cellular composition of ACTBL2-expressing TILs in EOC. Complementary studies are required to analyze the underlying molecular mechanisms of ACTBL2 as a marker for activated migrating leukocytes and to further characterize its immunological impact on ovarian carcinogenesis.

Developing consistent scenarios to assess flood hazards in mountain streams.

The characterizing feature of extreme events in steep mountain streams is the multiplicity of possible tipping process patterns such as those involving sudden morphological changes due to intense local erosion, aggradation as well as clogging of critical flow sections due to wood accumulations. Resolving a substantial part of the uncertainties underlying these hydrological cause-effect chains is a major challenge for flood risk management. Our contribution is from a methodological perspective based on an expert-based methodology to unfold natural hazard process scenarios in mountain streams to retrace their probabilistic structure. As a first step we set up a convenient system representation for natural hazard process routing. In this setting, as a second step, we proceed deriving the possible and thus consistent natural hazard process patterns by means of Formative Scenario Analysis. In a last step, hazard assessment is refined by providing, through expert elicitation, the spatial probabilistic structure of individual scenario trajectories. As complement to the theory the applicability of the method is shown through embedded examples. To conclude we discuss the major advantages of the presented methodological approach for hazard assessment compared to traditional approaches, and with respect to the risk governance process.

[CARL-Controlled reperfusion of the whole body]. / CARL ­ kontrollierte Reperfusion des ganzen Körpers: Von der kardiopulmonalen Reanimation zur zielgerichteten eCPR.

BACKGROUND: The incidence and mortality of acute cardiovascular arrest have been consistently high for decades. OBJECTIVE: How to improve the currently unsatisfactory outcome after resuscitation regarding survival and neurological, especially cerebral, sequelae? MATERIAL AND METHODS: Development of a therapeutic approach to curtail ischemia/reperfusion injury in an animal model. Development of a device system optimized for resuscitation that can be used to implement controlled reperfusion of the whole body outside the hospital. RESULTS: Establishment of CARL treatment in the clinic and in the treatment of OHCA patients. Transfer of the CARL treatment and system in a clinical observational study. First case reports in which patients survived OHCA without brain damage even after ischemia times up to 2 h. CONCLUSION: CARL treatment is potentially suitable to treat patients suffering from cardiovascular arrest refractory to treatment even for prolonged periods.

[Medical services: patients' and physicians' perceptions]. / Arztliche Dienstleistung: eine Zufriedenheitsbefragung bei Patienten und niedergelassenen Arzten.

In 2007, the German health-care system was once again subject to reform. Demographic changes and a rising demand for health-care services on the one hand and technological progress with increased medical-technological possibilities on the other lead to questions about organising and financing health care. Moreover, with the German health care being a mixture of a public insurance systems and private insurances, the extent, quality and equality of access is constantly under debate. In an empirical study, 1 604 patients were asked about their satisfaction with medical services and their insurance as well as their views on the recent reform. 90 physicians were questioned about their job satisfaction and their views on the health care system and the recent reform. Patients, irrespective of their type of insurance, on average were very satisfied with the physicians' services. Privately insured patients on average were more satisfied with their insurance than publicly insured. Patients were not well informed about the reform. Physicians' job satisfaction was markedly lower, they anticipate problems with health-care provision and they judge the health-care reform as inappropriate. Thus, patients on average are very satisfied with medical services, physicians on average are not satisfied with their situation, and the health-care reform is not perceived as a great success.

[Hereditary optic atrophies]. / Les atrophies optiques héréditaires.

INTRODUCTION: Hereditary optic neuropathies, resulting from retinal ganglion cell degeneration, are a heterogeneous group of diseases ranging from asymptomatic forms to legal blindness. STATE OF KNOWLEDGE: Two most frequent phenotypes are Kjer's disease, an autosomal dominant optic atrophy caused by OPA1 gene mutations, and Leber's disease due to maternally inherited mitochondrial DNA mutations. PROSPECTS AND CONCLUSION: Both optic neuropathies usually isolated are sometimes associated with extraocular symptoms, especially neurological symptoms, thus justifying a systematic neurological evaluation and brain imaging.

Standardized amino acid digestibility in cecectomized roosters and lysine bioavailability in chicks fed distillers dried grains with solubles.

This study was conducted to compare the concentration of standardized digestible (SDD) Lys and relative bioavailable Lys in 7 sources of corn distillers dried grains with solubles (DDGS). A second objective was to evaluate 2 in vitro methods, reactive Lys and color score, to predict the concentration of SDD Lys and bioavailable Lys in DDGS. Seven sources of DDGS were fed to cecectomized roosters, and digestibility of amino acids was measured using the total excreta collection method. To measure the relative bioavailable Lys in DDGS, a standard curve (r(2) = 0.96, P < 0.01) was constructed from 9-d weight gain of young chicks fed a Lys-deficient basal diet or diets containing increasing concentrations of l-Lys-HCl. Seven additional diets were formulated by adding each of the 7 sources of DDGS to the basal diet, and total weight gain of chicks was measured. Weight gain of chicks fed each DDGS-containing diet was then compared with the standard curve to calculate the bioavailable Lys and bioavailability of Lys in each source of DDGS. All DDGS sources were analyzed for reactive Lys using the guanidination procedure, and a Hunterlab color score was used to measure the degree of lightness (L), redness (a), and yellowness (b). Results showed that the mean SDD Lys values and the mean relative bioavailability of Lys were 61.4 and 69.0%, respectively. Differences between the concentration of SDD Lys and the concentration of bio-available Lys were not observed in 5 of 7 sources of DDGS. The concentration of SDD Lys was correlated (r(2) = 0.84, P < 0.05) with the concentration of reactive Lys in DDGS. Greater Hunterlab L scores were associated with a greater (r(2) = 0.90, P < 0.05) concentration of bioavailable Lys in DDGS. In conclusion, the concentration of SDD Lys in DDGS does not overestimate the concentration of bioavailable Lys for poultry. Values for reactive Lys may be used to estimate the concentration of SDD Lys, whereas Hunterlab L may be used to estimate the concentration of bioavailable Lys in DDGS.

Cognitive changes in asymptomatic carriers of the Huntington disease mutation gene.

Huntington disease (HD) is a neurodegenerative disorder due to an excessive number of CAG repeats in the IT15 gene on chromosome 4. Studies of cognitive function in asymptomatic gene carriers have yielded contradictory results. This study compared cognitive performance in 44 subjects with the HD mutation (group of carriers) who had no clinical signs of HD and 39 at-risk individuals without HD mutation (group of non-carriers). Neuropsychological evaluation focused on global cognitive efficiency, psychomotor speed, attentional, executive and memory functions. Significant differences, with lower performances in the group of gene carriers, were detected for some measures of psychomotor speed, attention and executive functioning (all P < 0.01). More differences between groups were observed for memory measures, in particular on the California Verbal Memory Test. Complementing these observations, cognitive scores were correlated with age in the group of gene carriers, but not in the group of non-carriers. This suggests that the cognitive changes precede the appearance of the motor and psychiatric symptoms in HD and that tests proved to be sensitive to early HD deficiencies are better suited than global cognitive efficiency scales to observe them.

Arginine N-methyltransferase 1 is required for early postimplantation mouse development, but cells deficient in the enzyme are viable.

Protein arginine N-methyltransferases have been implicated in a variety of processes, including cell proliferation, signal transduction, and protein trafficking. In this study, we have characterized essentially a null mutation induced by insertion of the U3betaGeo gene trap retrovirus into the second intron of the mouse protein arginine N-methyltransferase 1 gene (Prmt1). cDNAs encoding two forms of Prmt1 were characterized, and the predicted protein sequences were found to be highly conserved among vertebrates. Expression of the Prmt1-betageo fusion gene was greatest along the midline of the neural plate and in the forming head fold from embryonic day 7.5 (E7.5) to E8.5 and in the developing central nervous system from E8.5 to E13.5. Homozygous mutant embryos failed to develop beyond E6.5, a phenotype consistent with a fundamental role in cellular metabolism. However, Prmt1 was not required for cell viability, as the protein was not detected in embryonic stem (ES) cell lines established from mutant blastocysts. Low levels of Prmt1 transcripts (approximately 1% of the wild-type level) were detected as assessed by a quantitative reverse transcription-PCR assay. Total levels of arginine N-methyltransferase activity and asymmetric N(G), N(G)-dimethylarginine were reduced by 85 and 54%, respectively, while levels of hypomethylated substrates were increased 15-fold. Prmt1 appears to be a major type I enzyme in ES cells, and in wild-type cells, most substrates of the enzyme appear to be maintained in a fully methylated state.

Large nontransplanted hepatocellular carcinoma in woodchucks: treatment with adenovirus-mediated delivery of interleukin 12/B7.1 genes.

BACKGROUND: Cytokine-based gene therapy strategies efficiently stimulate immune responses against many established transplanted tumors, leading to rejection of the tumor. In this study, we investigated the therapeutic potential of cancer immunotherapy in a clinically more relevant model, woodchucks with primary hepatocellular carcinomas induced by woodchuck hepatitis virus. METHODS: Large (2-5 cm), established intrahepatic tumors were given an injection once with 1 x 10(9) plaque-forming units of AdIL-12/B7.1, an adenovirus vector carrying genes for murine interleukin 12 and B7.1, or of AdEGFP, the control virus, and regression of the tumors was then monitored. Five animals were used in total. RESULTS: In four tumor-bearing animals, the antitumor response was assessed by autopsy and histologic analysis within 1-2 weeks after treatment. In all animals treated with AdIL-12/B7.1 therapy versus AdEGFP therapy, we observed substantial tumor regression (P =.006; two-sided unpaired Student's t test) accompanied by a massive infiltration of T lymphocytes. These tumors also contained increased levels of CD4(+) and CD8(+) T cells and interferon gamma (IFN gamma). In continuously growing tumor nodules given an injection of the control virus or in nontumoral liver, no such effects (i.e., tumor regression and increased levels of CD4(+) and CD8(+) T cells and IFN gamma) were detected. In the fifth animal, monitored for long-term antitumor efficacy by magnetic resonance imaging (MRI) after intratumoral vector administration by MRI guidance, the tumor was almost completely eliminated (> or = 95%) 7 weeks after treatment. CONCLUSION: Adenovirus vector-based immunotherapy appears to be an effective treatment of large nontransplanted (orthotopic) tumors that acquire malignant characteristics in a stepwise process, reflecting the real-world scenario of hepatocellular carcinoma in humans.

Germ-line inactivation of the murine Eck receptor tyrosine kinase by gene trap retroviral insertion.

The present study characterized a mutation in the Eck receptor tyrosine kinase gene induced by the U3betageo gene trap retrovirus. The mutation (eck(i)) was identified during an in vitro screen for proviruses that disrupt developmentally regulated genes in cultured ES cells. The germ-line eck(i) fusion gene was expressed in blastocyst and later restricted to the primitive streak, node and to regions of the hindbrain in 6.5-10.5 day embryos. This is identical to the pattern of Eck gene expression as determined by either in situ hybridization or immunostaining, suggesting that expression of the Eck promoter was not affected by provirus integration. The provirus inserted approximately 8 kb upstream of the 5' end of the published cDNA sequence, and 1.8 kb downstream of an alternatively spliced 5' exon. The eck(i) allele is essentially a null mutation since mutant mice are severely deficient for Eck protein as determined by Western blot analysis and in vitro kinase assays. Nevertheless, mice homozygous for the mutation did not exhibit any discernable phenotype. These results suggest that other members of the Eph family of receptor tyrosine kinases can functionally compensate for loss of Eck.

[Seizures and non-ketotic hyperglycemia]. / Crises epileptiques révélatrices d'une hyperglycémie sans cétose.

In patients older than 50 years, a first seizure can reveal non-ketotic hyperglycemia, regardless of any previous history of diabetes mellitus. Partial motor seizures are observed in most cases, sometimes with epilepsia partialis continua. Plasma glucose levels are usually above 20 mmol/L, and serum osmolarity is normal or slightly elevated. The absence of ketoacidosis may promote the occurrence of seizures. EEG and neuroimaging between seizures are usually normal. Treatment involves correction of the hyperglycemia with insulin treatment and rehydration.

hKChIP2 is a functional modifier of hKv4.3 potassium channels: cloning and expression of a short hKChIP2 splice variant.

OBJECTIVE: The Ca(2+) independent transient outward K(+) current (I(to1)) in the heart is responsible for the initial phase of repolarization. The hKv4.3 K(+) channel alpha-subunit contributes to the I(to1) current in many regions of the human heart. Consistently, downregulation of hKv4.3 transcripts in heart failure and atrial fibrillation is linked to reduction in I(to1) conductance. The recently cloned KChIP family of calcium sensors has been shown to modulate A-type potassium channels of the Kv4 K(+) channel subfamily. METHODS AND RESULTS: We describe the cloning and tissue distribution of hKChIP2, as well as its functional interaction with hKv4.3 after expression in Xenopus oocytes. Furthermore, we isolated a short splice variant of the hKChIP2 gene (hKCNIP2), which represents the major hKChIP2 transcript. Northern blot analyses revealed that hKChIP2 is expressed in the human heart and occurs in the adult atria and ventricles but not in the fetal heart. Upon coexpression with hKv4.3 both hKChIP2 isoforms increased the current amplitude, slowed the inactivation and increased the recovery from inactivation of hKv4.3 currents. For the first time we analyzed the influence of a KChIP protein on the voltage of half-maximal inactivation of Kv4 channels. We demonstrate that the hKChIP2 isoforms shifted the half-maximal inactivation to more positive potentials, but to a different extent. By elucidating the genomic structure, we provide important information for future analysis of the hKCNIP2 gene in candidate disorders. In the course of this work we mapped the hKCNIP2 gene to chromosome 10q24. CONCLUSIONS: Heteromeric hKv4.3/hKChIP2 currents more closely resemble native epicardial I(to1), suggesting that hKChIP2 is a true beta-subunit of human cardiac I(to1). As a result hKChIP2 might play a role in cardiac diseases, where a contribution of I(to1) has been shown.

Molecular impact of MinK on the enantiospecific block of I(Ks) by chromanols.

Slowly activating I:(Ks) (KCNQ1/MinK) channels were expressed in Xenopous: oocytes and their sensitivity to chromanols was compared to homomeric KCNQ1 channels. To elucidate the contribution of the ss-subunit MinK on chromanol block, a formerly described chromanol HMR 1556 and its enantiomer S5557 were tested for enantio-specificity in blocking I:(Ks) and KCNQ1 as shown for the single enantiomers of chromanol 293B. Both enantiomers blocked homomeric KCNQ1 channels to a lesser extent than heteromeric I:(Ks) channels. Furthermore, we expressed both WT and mutant MinK subunits to examine the involvement of particular MinK protein regions in channel block by chromanols. Through a broad variety of MinK deletion and point mutants, we could not identify amino acids or regions where sensitivity was abolished or strikingly diminished (>2.5 fold). This could indicate that MinK does not directly take part in chromanol binding but acts allosterically to facilitate drug binding to the principal subunit KCNQ1.

Comparison of plasma bismuth levels after oral dosing with basic bismuth carbonate or tripotassium dicitrato bismuthate.

In 20 healthy subjects plasma bismuth concentration was measured after single oral doses of basic bismuth carbonate or tripotassium dicitrato bismuthate. The drugs were administered in the fasted state or immediately after ingestion of a standard breakfast. After basic bismuth carbonate, plasma bismuth rose to concentrations between 0.7 and 2.6 micrograms/L in the fasted state, while after the meal the maximal level was only 1.3 micrograms/L. In contrast to these very low levels after basic bismuth carbonate, the administration of tripotassium dicitrato bismuthate was paralleled by an increase of plasma bismuth to concentrations between 15 and 232 micrograms/L with a mean peak value of 64 +/- 15.3 (S.E.M.) micrograms/L in the fasted state. Postprandial ingestion of tripotassium dicitrato bismuthate attenuated the peak concentrations to 10.9 +/- 6.3 micrograms/L. One subject, however, had a value of 120 micrograms/L. This study demonstrates that basic bismuth carbonate leads to very low plasma bismuth concentrations, which are far below the critical range that might eventually be associated with bismuth neurotoxicity. Therefore this compound can be considered potentially useful for bismuth therapy of gastrointestinal disorders.

Experimental infection of pregnant ewes with bovine viral diarrhea virus type-2 (BVDV-2): effects on the pregnancy and fetus.

The reproduction effects of bovine viral diarrhea virus type-2 (BVDV-2) infection were investigated in ewes inoculated with a non-cytopathic BVDV-2 isolate at three stages of gestation. Virus inoculation was followed by a transient viremia, accompanied by a transient and mild hyperthermia and nasal discharge in a few animals. Some ewes were sacrificed at different time-points after virus inoculation to study the kinetics of fetal infection. Infectivity and viral antigens were detected in placentomes from day 7 to 36 post-inoculation (pi) and in fetal fluids and tissues between days 10 and 28 pi. Cardiac petechial hemorrhages and hemoperitoneum accompanied by a severe fibrinous ulcerative placentitis were observed in fetuses examined at days 21, 28 and 36 pi. Inoculation of ewes at days 55-60 of gestation resulted in a prolonged virus replication in placentomes and fetal tissues; ewes that were allowed to proceed with pregnancy had 77% of abortions or fetal and perinatal deaths. Seven stillbirths, unviable and viable lambs born to these ewes were virus-positive at birth. Infectious virus was repeatedly isolated from leukocytes of two lambs up to 2 and 6 months of age, indicating they were persistently infected. Ewes inoculated at days 65-70 of gestation had 66.6% of fetal and perinatal losses. Three viable lambs born to these ewes were healthy, BVDV antibody-positive and virus-negative. A transient viral replication in placentomes and in a few fetal tissues, followed by the rise of fetal neutralizing antibodies and virus clearance was the result of inoculating ewes at days 120-125 of gestation. Lambs born to these ewes were healthy, antibody-positive and virus-negative. These results demonstrate that the biology of BVDV-2 infection in pregnant sheep is essentially similar to that of BVDV-1 in pregnant cattle and sheep. These features make this species an attractive animal model for studying the pathogenesis of congenital BVDV-2 infection.

Latent infection by bovine herpesvirus type-5 in experimentally infected rabbits: virus reactivation, shedding and recrudescence of neurological disease.

Latent infection with bovine herpesvirus type-5 (BHV-5) was established in rabbits inoculated with two South American isolates (EVI-88 and 613) by intranasal or conjunctival routes. Nine rabbits (613, 8/27; EVI-88, 1/34) developed neurological disease and died during acute infection and other three (613, n=2; EVI-88, n=1) developed a delayed neurological disease, at days 34, 41 and 56 post-inoculation (p.i.). Between days 56 and 62 p.i., the remaining rabbits were submitted to five daily administrations of dexamethasone (Dx) to reactivate the infection. Twenty-five out of 44 rabbits (56.8%) shed virus in nasal or ocular secretions after Dx treatment. Virus shedding was first detected at day two post-Dx and lasted from one to 11 days. The highest frequencies of virus reactivation were observed in rabbits inoculated conjunctivally (10/15 versus 15/29); and among rabbits infected with isolate 613 (12/16 versus 13/28). Virus reactivation upon Dx treatment was accompanied by neurological disease in nine rabbits (20.4%), resulting in six deaths (13.6%). Virus in moderate titers and mild to moderate non-suppurative inflammatory changes in the brain characterized the neurological infection. Three other rabbits showed severe neurological signs followed by death after 31 to 54 days of Dx treatment. Virus, viral nucleic acids and inflammatory changes were detected in their brains. The late-onset neurological disease, after acute infection or Dx treatment, was probably a consequence of spontaneous virus reactivation. These results demonstrate that BHV-5 does establish a latent infection in rabbits and that clinical recrudescence may occur upon reactivation.

Gerstmann-Sträussler-Scheinker disease with A117V mutation in a second French-Alsatian family.

We report a kindred of French/Alsatian origin with symptoms of Gerstmann-Sträussler-Scheinker disease over 3 generations. In the propositus, cerebellar signs and memory disturbance were the presenting features, followed by other neurological manifestations. Biopsy of the cerebral cortex showed numerous multicentric and "kuru"-type amyloid plaques that on immuno-light and electron microscopy stained with antibody to prion protein. Molecular genetic analysis revealed an A117V mutation in the open reading frame of the prion protein gene. Questions as to pathology and spread of this mutation are discussed.

Rotational dynamics of magnetic particles in suspensions.

An approach for the rotational dynamics of magnetic particles and their magnetic moments, in fluid suspensions, is developed. A possible application is to magnetic resonance in ferrofluids. Based on a generalized Lagrangian formulation for the equations of motion of the particle, we introduce its interaction with the solvent fluid via dissipative and random noise torques, as well as the interaction between the particle and its magnetic moment, treated as an independent physical entity and characterized by three generalized coordinates: its two polar angles and its modulus. In the appropriate limits, it reduces to the cases of superparamagnetic particles or nonsuperparamagnetic (blocked magnetic moments) particles. It is also indicated how the dynamic complex susceptibility may be calculated from the equations of motion, and as an example the effect of the particles inertia on the susceptibility is numerically evaluated for some arbitrary values of the parameters.

Overcoming methodological concerns in the investigation of online sexual activities.

Online Sexual Activity (OSA) is an important and growing phenomenon. Prior research in this area has been criticized on methodological grounds. This study examines the reliability of Internet research regarding online sexual activities by comparing a selected random sample to a convenience sample. Participation in the selected random sample was limited to every 1,000th visitor to the MSNBC website in June 2000. Participation in the convenience sample was available to anyone with access to the Internet during the same time period. Most differences between these samples indicated that, relative to a selected random sample, a significantly greater proportion of Internet users in the convenience sample had a heavier involvement with OSA, including online sexual difficulties. We discuss the methodological and clinical implications of this finding.