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.

[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.

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.

Exigência de treonina digestível para codornas de corte no período de 15 a 35 dias de idade / Digestible threonine requirements for quail meat from 15 to 35 days of age

Estimou-se a exigência de treonina digestível (ThrD) para codornas de corte (Coturnix coturnix sp.) em fase de crescimento no período de 15 a 35 dias de idade. Foram utilizadas 1020 codornas com 15 dias de idade, não sexadas, distribuídas em um delineamento experimental inteiramente ao acaso, com seis porcentagens de adição de treonina digestível - 0,93; 1,00; 1,07; 1,14; 1,21 e 1,28% na dieta - , cinco repetições e 34 codornas por unidade experimental. Não houve efeito sobre o desempenho, o rendimento e a composição química da carcaça e sobre o balanço de nitrogênio com o aumento da porcentagem de treonina digestível na dieta. Houve aumento linear no consumo de treonina e no custo da ração por quilograma de peso vivo ganho com o aumento da porcentagem de treonina digestível. Concluiu-se que o melhor nível de treonina digestível avaliado foi suficiente para atender as exigências de codornas de corte, no período de 15 a 35 dias de idade.

The digestible threonine (DThr) requirements for meat quails (Coturnix coturnix sp) during growing phase from 15 to 35 days of age were estimated, using 1,020 quails with 15 days of age, of both sexes, distributed in a completely randomized design, with six levels of digestible threonine - 0.93; 1.00; 1.07; 1.14; 1.21 and 1.28% in diet, five replications and 34 quails per experimental unit. There was no effect on performance variables, carcass yield and chemical composition and nitrogen balance with the studied increase in digestible threonine levels. There was a linear increase in threonine intake andfeed cost per kilogram of body weight gain with increasing levels of digestible threonine. It was concluded that the best level of threonine evaluated was sufficient to meet the requirements of meat quails, in the period from 15 to 35.

Avaliação de probiótico na alimentação de poedeiras comerciais no segundo ciclo de postura / Evaluation of probiotics in feed for laying hens in the second cycle stance

Avaliou-se o efeito da inclusão de probiótico sobre o desempenho e a qualidade dos ovos de poedeiras semipesadas no segundo ciclo de postura. Foram utilizadas 450 aves com 69 semanas de idade, distribuídas aleatoriamente em um delineamento inteiramente ao acaso, em cinco tratamentos, seis repetições e 15 aves por unidade experimental. A ração experimental foi à base de milho e farelo de soja e suplementada com probiótico composto por Lactobacillus acidophilus, Streptococcus faecium e Bifidobacterium bifidum. O experimento teve a duração de 16 semanas e foi dividido em quatro períodos de 28 dias cada, nos quais as aves receberam cinco rações experimentais contendo diferentes porcentagens de inclusão de probiótico, 0; 0,05; 0,10; 0,15 e 0,20%. Não foi observado efeito (P>0,05) da inclusão de probiótico sobre o desempenho e a qualidade dos ovos de galinhas poedeiras no segundo ciclo de postura. A inclusão de 0,10% de probiótico influenciou negativamente a gravidade específica dos ovos. A utilização de probiótico para galinhas no segundo ciclo de postura não interfere na produção e na qualidade dos ovos.

Evaluating the effect of the inclusion of probiotic on the performance and egg quality of laying hens in the second laying cycle, 450 birds were used at 69 weeks of age, distributed in a completely randomized design, in five treatments, six replicates and 15 poultries per experimental unit. The experimental diets were based on corn and soybean meal and supplemented with increasing levels of probiotic consisting of Lactobacillus acidophilus, Streptococcus faecium, and Bifidobacterium bifidum. The experiment lasted 16 weeks, divided into four periods of 28 days each, in which the birds were fed five experimental diets containing different percentages of probiotic inclusion, 0; 0.05; 0.10; 0.15 and 0.20%, in the period from 69 to 85 weeks of age. There was no effect (P> 0.05) of the inclusion of probiotic on performance and egg quality of laying hens in the second laying cycle. The inclusion of 0.10% of probiotic negatively influenced the specific gravity of eggs. The probiotic used for laying hens in the second cycle does not interfere in production and egg quality.

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.

[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.

[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.

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.

Exon deletion in the non-catalytic domain of eIF2Bepsilon due to a splice site mutation leads to infantile forms of CACH/VWM with severe decrease of eIF2B GEF activity.

The CACH/VWM syndrome is an autosomal recessive leukodystrophy characterized by a broad spectrum of clinical presentations and by diffuse cavitary degeneration of the white matter on MRI. Mutations responsible for this disorder are missense or frameshift mutations occurring in the five genes (EIF2B1-5) that encode the translation eukaryotic initiation factor eIF2B. We found that a patient with infantile CACH/VWM carries a mutation in the acceptor splice site of EIF2B5 exon 6. In lymphoblastoid cells of the patient, we detected an abnormal EIF2B5 transcript in which exon 6 was absent, however, the predicted protein product lacking part of the non-catalytic domain encoded by exon 6 was not detected. The eIF2B GEF activity was severely decreased. These data support the importance of the non-catalytic domain of the eIF2Bepsilon subunit in the eIF2B complex formation and activity.

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.

[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.

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.

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.

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.

Neoadjuvant chemotherapy for unresectable ovarian carcinoma: a French multicenter study.

BACKGROUND: Initial debulking surgery followed by chemotherapy is the current treatment for International Federation of Gynecology and Obstetrics Stage IIIC/IV ovarian carcinoma but has a limited efficacy when optimal cytoreduction is not achieved at the end of the surgical procedure. An alternative treatment for these patients could be neoadjuvant chemotherapy. The purpose of this retrospective study was to report the results of neoadjuvant chemotherapy in operable patients (no medical contraindication to surgery) presenting with primary unresectable tumors. METHODS: Between January 1996 and March 1999, operable patients presenting with Stage IIIC or IV ovarian carcinoma underwent, in six French gynecologic oncology departments, surgical staging to evaluate tumor resectability. When the tumor was deemed unresectable by standard surgery, the patient received three to six cycles of platinum-based neoadjuvant chemotherapy according to the response and the center's usual protocol. Patients were surgically explored after completion of neoadjuvant chemotherapy when the tumor did not progress during treatment. Debulking was performed during this secondary surgery when a response to chemotherapy was observed. RESULTS: Fifty-four patients were treated by neoadjuvant chemotherapy. The first surgical staging procedure was laparoscopy in 33 patients (61%) and laparotomy in 21 patients (39%). The median number of neoadjuvant chemotherapy cycles was 4 (range, 0-6). Forty-three patients (80%) responded to neoadjuvant chemotherapy and then tumors were debulked. Optimal cytoreduction was obtained in 39 patients (91% of the patients who underwent debulking) and with standard surgery in 32 patients (82%). For patients whose tumors were optimally debulked, blood transfusions were administered to 17 patients (43%), median intensive care unit stay was 0 days (range, 0-7 days), and median postoperative hospital stay was 10 days (range, 4-62 days). Median overall survival for the total series was 22 months. Survival was better for patients debulked after neoadjuvant chemotherapy compared with patients with nondebulked tumors (P < 0.001). CONCLUSIONS: Neoadjuvant chemotherapy for primary unresectable ovarian carcinoma leads to the selection of a subset of patients sensitive to chemotherapy in whom optimal cytoreduction can be achieved after chemotherapy by standard surgery in a high proportion of cases. Conversely, aggressive surgery can be avoided in patients with initial chemoresistance, in whom the prognosis is known to be poor regardless of treatment.

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.