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Purpose: Percutaneous hepatic perfusion with melphalan (M-PHP) is a minimally invasive therapy with proven efficacy in patients with uveal melanoma (UM) liver metastases. M-PHP is associated with a short hospital admission time and limited systemic side effects. In this study, we assessed quality of life (QoL) in UM patients treated with M-PHP. Materials and Methods: A prospective, single-center study including 24 patients treated with M-PHP for UM metastases to the liver. QoL questionnaires were collected at baseline, on day 2/3 after M-PHP, and on day 7 and day 21 after M-PHP, according to study protocol. The results were scored according to EORTC-QLQ C30 global health status (GHS), functional scales, and symptom scales. The difference in scores at baseline and subsequent time points was analyzed with the Wilcoxon signed-rank test and multiple testing Bonferroni correction. Adverse events (AE) were registered up to 30 days after M-PHP according to CTCAE v5.0. Results: Twenty-four patients (14 males; median age 63.0 years) completed 96 questionnaires. Most scores on all scales declined on day 2/3 after M-PHP. On day 21 after M-PHP, 12 out of 15 scores returned to baseline, including median GHS scores. Three variables were significantly worse on day 21 compared to baseline: fatigue (6–33; p = 0.002), physical functioning (100 vs 86.7; p = 0.003), and role functioning (100 vs 66.7; p = 0.001). Grade 3/4 AEs consisted mainly of hematological complications, such as leukopenia and thrombopenia. Conclusion: M-PHP causes fatigue and a decline in physical and role functioning in the 1st weeks after treatment, but GHS returns to baseline levels within 21 days. Level of Evidence 3: Cohort study. [ABSTRACT FROM AUTHOR]

One of the core questions of quantum physics is how to reconcile the unitary evolution of quantum states, which is information-preserving and time-reversible, with evolution following the second law of thermodynamics, which, in general, is neither. The resolution to this paradox is to recognize that global unitary evolution of a multi-partite quantum state causes the state of local subsystems to evolve towards maximum-entropy states. In this work, we experimentally demonstrate this effect in linear quantum optics by simultaneously showing the convergence of local quantum states to a generalized Gibbs ensemble constituting a maximum-entropy state under precisely controlled conditions, while introducing an efficient certification method to demonstrate that the state retains global purity. Our quantum states are manipulated by a programmable integrated quantum photonic processor, which simulates arbitrary non-interacting Hamiltonians, demonstrating the universality of this phenomenon. Our results show the potential of photonic devices for quantum simulations involving non-Gaussian states. The emergence of relaxation in unitarily evolving systems can be seen as a paradox, but not once the distinction between local and global dynamics is considered. Here, the authors use photons in an integrated optical interferometer to show that, for a system evolving unitarily on a global level, single-mode measurements converge to those of a thermal state. [ABSTRACT FROM AUTHOR]

Purpose: To define a safe treatment dose of ipilimumab (IPI) and nivolumab (NIVO) when applied in combination with percutaneous hepatic perfusion with melphalan (M-PHP) in metastatic uveal melanoma (mUM) patients (NCT04283890), primary objective was defining a safe treatment dose of IPI/NIVO plus M-PHP. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAEv4.03). Secondary objective was response rate, PFS and OS. Materials and Methods: Patients between 18–75 years with confirmed measurable hepatic mUM according to RECIST 1.1 and WHO performance score 0–1 were included. Intravenous IPI was applied at 1 mg/kg while NIVO dose was increased from 1 mg/kg in cohort 1 to 3 mg/kg in cohort 2. Transarterial melphalan dose for M-PHP was 3 mg/kg (maximum of 220 mg) in both cohorts. Treatment duration was 12 weeks, consisting of four 3-weekly courses IPI/NIVO and two 6-weekly M-PHPs. Results: Seven patients were included with a median age of 63.6 years (range 50–74). Both dose levels were well tolerated without dose-limiting toxicities or deaths. Grade III/IV adverse events (AE) were observed in 2/3 patients in cohort 1 and in 3/4 patients in cohort 2, including Systemic Inflammatory Response Syndrome (SIRS), febrile neutropenia and cholecystitis. Grade I/II immune-related AEs occurred in all patients, including myositis, hypothyroidism, hepatitis and dermatitis. There were no dose-limiting toxicities. The safe IPI/NIVO dose was defined as IPI 1 mg/kg and NIVO 3 mg/kg. There was 1 complete response, 5 partial responses and 1 stable disease (3 ongoing responses with a median FU of 29.1 months). Conclusion: Combining M-PHP with IPI/NIVO was safe in this small cohort of patients with mUM at a dose of IPI 1 mg/kg and NIVO 3 mg/kg. [ABSTRACT FROM AUTHOR]

Background: The mean incidence of ovarian metastases (OM) in patients with colorectal cancer (CRC) is 3.4%. The 5-year survival of these patients, even when operated with curative intent, is remarkably low. The lifetime risk of ovarian cancer is approximately 1.3%. Prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries and fallopian tubes) could reduce the number of CRC patients that develop OM after removal of the primary tumor, as well as preventing the occurrence of primary ovarian cancer. Recently, the care pathway for CRC has been changed in several hospitals in line with the updated Dutch guideline. The possibility of PSO is now discussed with postmenopausal CRC patients in these hospitals. The aims of the current study are firstly to estimate the incidence of OM and primary ovarian cancer in postmenopausal patients with CRC, and secondly to evaluate the effect of PSO in these patients.Methods: An information bulletin and decision guide on this topic was implemented in several Dutch hospitals in 2020. Post-decision outcomes will be collected prospectively. The study population consists of postmenopausal (≥ 60 years of age) patients that are operated with curative intent for CRC. Based on their own preference, patients will be divided into two groups: those who choose to undergo PSO and those who do not. The main study parameters are the reduction in incidence of ovarian malignancies (metastatic or primary) following PSO, and the number needed to treat (NNT) by PSO to prevent one case of ovarian malignancy.Discussion: This will be the first study to evaluate the effect of PSO in postmenopausal CRC patients that is facilitated by an altered CRC care pathway. The results of this study are expected to provide relevant information on whether PSO adds significant value to postmenopausal patients with CRC.Trial Registration: International Clinical Trials Registry Platform, NL7870. Registered on 2019 July 12. URL of trial registry record: https://trialsearch.who.int/Trial2.aspx?TrialID=NL7870 .Protocol Version: 1.0, date 2021 June 8. [ABSTRACT FROM AUTHOR]

Background and purpose: Previous studies indicated that approximately 3.4% of female colorectal cancer (CRC) patients are at increased risk of developing ovarian metastases (OM). It has been suggested that young women more frequently develop this form of metastatic disease. Methods: This study evaluated, in 6 Dutch hospitals, the proportion of young women with CRC who developed OM. Results: In a cohort of 200 young (age ≤ 55) women with CRC, the proportion of patients diagnosed with synchronous or metachronous OM was calculated. This study revealed that 5% (n = 10) of young female CRC patients developed ovarian metastases resulting in a 5-year overall survival rate of approximately 40%. Furthermore, six patients had concurrent peritoneal metastases, five patients had bilateral ovarian metastases, and five patients had synchronous metastases, while the median time of the occurrence of metachronous metastases (n = 5) was 19 months. Conclusion: This retrospective multicenter cohort study indicates that 5% of young women with CRC either present with or develop OM. This result appears to be clinically relevant and demonstrates the need for improved surveillance for young women diagnosed with CRC. [ABSTRACT FROM AUTHOR]

Background and purpose: Women with colorectal cancer (CRC) are at risk not only of developing ovarian metastases, but also of developing a primary ovarian malignancy. Several earlier studies have in fact shown a link between the development of primary ovarian cancer and CRC. The purpose of this study was therefore to determine the risk of developing a primary ovarian cancer in women with prior CRC compared to the general population. Methods: Data from the Netherlands Cancer Registry were used. All women diagnosed with invasive CRC between 1989 and 2017 were included. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10,000 person-years were calculated. Results: During the study period, 410 (0.3%) CRC patients were diagnosed with primary ovarian cancer. Women with CRC had a 20% increased risk of developing ovarian cancer compared to the general population (SIR = 1.2, 95% CI: 1.1–1.3). The AER of ovarian cancer was 0.9 per 10,000 person-years. The risk was especially increased within the first year of a CRC diagnosis (SIR = 3.3, 95% CI: 2.8–3.8) and in women aged ≤ 55 years (SIR = 2.0, 95% CI: 1.6–2.6). Conclusion: This study found a slightly increased risk of primary ovarian cancer in women diagnosed with CRC compared to the general population. However, this may be partly attributable to surveillance or detection bias. Nevertheless, our findings could be helpful for patient counseling, as CRC patients do not currently receive information concerning the increased risk of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response. We hypothesize that combining M-PHP with ICI will lead to enhanced antigen presentation and increased immunomodulatory effect, improving control of both hepatic and extrahepatic disease.Methods: Open-label, single-center, phase Ib/randomized phase II trial, evaluating the safety and efficacy of the combination of M-PHP with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) in patients with unresectable hepatic metastases of UM in first-line treatment, with or without the limited extrahepatic disease. The primary objective is to determine the safety, toxicity, and efficacy of the combination regimen, defined by maximum tolerated dose (MTD) and progression-free survival (PFS) at 1 year. Secondary objectives include overall survival (OS) and overall response rate (ORR). A maximum of 88 patients will be treated in phase I and phase II combined. Baseline characteristics will be described with descriptive statistics (t-test, chi-square test). To study the association between risk factors and toxicity, a logistic regression model will be applied. PFS and OS will be summarized using Kaplan-Meier curves.Discussion: This is the first trial to evaluate this treatment combination by establishing the maximum tolerated dose and evaluating the efficacy of the combination treatment. M-PHP has shown to be a safe and effective treatment for UM patients with liver metastases and became the standard treatment option in our center. The combination of ICI with M-PHP is investigated in the currently described trial which might lead to a better treatment response both in and outside the liver.Trial Registration: This trial was registered in the US National Library of Medicine with identifier NCT04283890 . Registered as per February 2020 - Retrospectively registered. EudraCT registration number: 2018-004248-49. Local MREC registration number: NL60508.058.19. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Quality of Life Analysis of Patients Treated with Percutaneous Hepatic Perfusion for Uveal Melanoma Liver Metastases" published in the journal CardioVascular & Interventional Radiology. The correction addresses an error in the second affiliation of the corresponding author, Thaïs Tong. The correct affiliation is the Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands. The original article has been corrected. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Purpose: Temporary balloon occlusion of the inferior vena cava to lower cardiac output is a relatively infrequently used technique to induce controlled systemic hypotension. In this technical note, we describe the feasibility, reliability, and safety of partial occlusion of right atrial inflow and the effect on systemic blood pressure during the deployment of a thoracic stentgraft.Materials and Methods: Twenty consecutive patients undergoing thoracic endovascular aortic repair, with proximal landing in zone 0-3 of the thoracic aorta, were prospectively included. Right atrial inflow occlusion was performed with a compliant occlusion balloon.Results: Median time to reach a mean arterial pressure of 50 mmHg was 43 s. Median recovery time of blood pressure was 42 s.Conclusion: Partial right atrial inflow occlusion with an occlusion balloon is feasible with reliable results and without procedure-related complications. [ABSTRACT FROM AUTHOR]

For chemistry an accurate description of bond weakening and breaking is vital. The great advantage of density matrix functionals, as opposed to density functionals, is their ability to describe such processes since they naturally cover both nondynamical and dynamical correlation. This is obvious in the Löwdin-Shull functional, the exact natural orbital functional for two-electron systems. We present in this paper extensions of this functional for the breaking of a single electron pair bond in N-electron molecules, using LiH, BeH+, and Li2 molecules as prototypes. Attention is given to the proper formulation of the functional in terms of not just J and K integrals but also the two-electron L integrals (K integrals with a different distribution of the complex conjugation of the orbitals), which is crucial for the calculation of response functions. Accurate energy curves are obtained with extended Löwdin-Shull functionals along the complete dissociation coordinate using full CI calculations as benchmark. [ABSTRACT FROM AUTHOR]

Aims: With rising rates of mental health disorders being reported globally, it is imperative that we investigate economical and accessible ways to increase relaxation and reduce stress. While there is a plethora of anecdotal evidence as to the positive effects of domestic crafts on mental wellbeing, there is little empirical research in this area. As such, we aimed to explore perceived links between crochet and wellbeing.Methods: An online survey was developed and piloted, based on an existing tool that explored knitting and wellbeing. The final survey was promoted through social media, over a 6-week period, resulting in valid responses from 8391 individuals.Results: Most respondents were female (99.1%), aged between 41 and 60 years (49.5%) and living in 87 different countries. Many respondents reported crocheting for between 1 and 5 years (42.6%). The three most frequent reasons reported for crocheting were: to be creative (82.1%), to relax (78.5%) and for a sense of accomplishment (75.2%). Respondents reported that crochet made them feel calmer (89.5%), happier (82%) and more useful (74.7%). There was a significant improvement in reported scores for mood before crocheting (M = 4.19, SD = 1.07) and mood after crocheting (M = 5.78, SD = 0.82); z = -69.86, p < .001, r = -0.56. Content analysis of free-text responses identified five major themes: (1) health benefits, (2) process of crochet, (3) personal connection, (4) crochet as contribution and (5) online crochet communities.Conclusion: The data suggests that crochet offers positive benefits for personal wellbeing with many respondents actively using crochet to manage mental health conditions and life events such as grief, chronic illness and pain. Crochet is a relatively low-cost, portable activity that can be easily learnt and seems to convey all of the positive benefits provided by knitting. This research suggests that crochet can play a role in promoting positive wellbeing in the general population, adding to the social prescribing evidence base. [ABSTRACT FROM AUTHOR]

Time dependent density matrix functional theory in its adiabatic linear response formulation delivers exact excitation energies ?a and oscillator strengths fa for two-electron systems if extended to the so-called phase including natural orbital (PINO) theory. The Löwdin-Shull expression for the energy of two-electron systems in terms of the natural orbitals and their phases affords in this case an exact phase-including natural orbital functional (PILS), which is non-primitive (contains other than just J and K integrals). In this paper, the extension of the PILS functional to N-electron systems is investigated. With the example of an elementary primitive NO functional (BBC1) it is shown that current density matrix functional theory ground state functionals, which were designed to produce decent approximations to the total energy, fail to deliver a qualitatively correct structure of the (inverse) response function, due to essential deficiencies in the reconstruction of the two-body reduced density matrix (2RDM). We now deduce essential features of an N-electron functional from a wavefunction Ansatz: The extension of the two-electron Löwdin-Shull wavefunction to the N-electron case informs about the phase information. In this paper, applications of this extended Löwdin-Shull (ELS) functional are considered for the simplest case, ELS(1): one (dissociating) two-electron bond in the field of occupied (including core) orbitals. ELS(1) produces high quality ωα(R) curves along the bond dissociation coordinate R for the molecules LiH, Li2, and BH with the two outer valence electrons correlated. All of these results indicate that response properties are much more sensitive to deficiencies in the reconstruction of the 2RDM than the ground state energy, since derivatives of the functional with respect to both the NOs and the occupation numbers need to be accurate. [ABSTRACT FROM AUTHOR]

An argon plasma jet was sustained in open air and characterized for its chemical composition. The optically characterized plasma jet was used to treat industrial wastewater containing mixed textile dyes and heavy metals. Since plasma jet produces UV-radiations, the photocatalytic TiO2 was used to enhance plasma treatment efficiency especially for degradation of dyes. Mixed anatase and rutile phases of TiO2 (5.2–8.5 nm) were produced through surfactant assisted sol–gel approach. The emission spectrum confirmed the presence of excited argon, OH, excited nitrogen, excited oxygen, ozone and nitric oxide in the plasma jet. The spectral lines of excited Ar, NO, O3, OH−, N2, N 2 + , O, O 2 + and O+ species were observed at wavelength of 695–740 nm, 254.3 nm, 307.9 nm, 302–310 nm, 330–380 nm, 390–415 nm, 715.6 nm, 500–600 nm and 400–500 nm. These reactive species decompose the organic pollutants and separate the heavy metals from the water samples. The conductivity of plasma exposed water samples increased while pH and hardness decreased. The atomic absorption spectrophotometry analysis confirmed the presence of heavy metals in the samples, which were effectively removed through plasma treatment. Finally, the effect of plasma treatment on Staphylococcus aureus strains was more pronounced than Escherichia coli strains. [ABSTRACT FROM AUTHOR]

Objective: The aim of this nationwide study was to provide insight in the incidence, risk factors, treatment, and survival of patients with ovarian metastases from colorectal cancer (CRC). Methods: Data from the Netherlands Cancer Registry were used. All newly diagnosed female CRC patients between 2008 and 2016 were included. Treatment was categorized as follows: cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC); resection of the primary tumor; palliative treatment; and no treatment. Overall survival (OS) was investigated using Kaplan-Meier and multivariable Cox regression analyses. Results: Of 53,883 female CRC patients, 11,343 (21.1%) had metastases at time of diagnosis. Among them, 471 (4.2%) had ovarian metastases. Within latter group, 27.2% received CRS-HIPEC; 38.4% underwent resection of the primary tumor; 25.3% received palliative treatment; and 9.1% received no treatment. Median OS of all patients with ovarian metastases was 17.5 months. In patients receiving CRS-HIPEC, OS was significantly longer than in patients undergoing resection only (median OS 34.1 vs. 17.5 months, adjusted HR 0.44 [0.33–0.66]). Five-year OS was 28.5% for patients having underwent CRS-HIPEC, 11.0% for patients having underwent resection of the primary tumor, 1.2% for patients having underwent palliative treatment, and 0.0% for patients without treatment. Conclusions: Synchronous ovarian metastases are diagnosed in 4.2% of female colorectal patients presenting with metastatic disease. Risk factors are young age, T4/N+ tumor and histology of signet ring cell carcinoma. Median OS of the entire cohort was 17.5 months, ranging from 3.1 months in patients without treatment to 34.1 months in patients undergoing CRS-HIPEC. [ABSTRACT FROM AUTHOR]

Ferrite nanoparticles are interesting materials owing to their unique physical and chemical properties. The metal-doped ferrites have well-defined structures and magnetic response, such as high permeability for a specific frequency range. In this study, copper-substituted nickel ferrite (Ni1−xCuxFe2O4) nanoparticles with a compositional range of 0 ≤ x ≤ 0.3 were synthesised through a co-precipitation technique. Metal chlorides were used as precursors and NaOH as a precipitating agent for the growth of ferrite nanoparticles. To minimise the internal stresses and maximise the magnetic response, ferrite nanoparticles were annealed in a furnace at 700°C for 6 h. The structural and magnetic response of Ni1−xCuxFe2O4 ferrite with different values of x were investigated using Scanning Electron Microscopy (SEM), Fourier Transform Infrared spectroscopy (FT-IR), Vibrating Sample Magnetometer (VSM) and X-ray Diffraction (XRD) techniques. XRD analysis confirmed the formation of cubic spinel structure of single phase for all the compositions. The lattice constant decreased with increase in the value of x. FT-IR study showed two main metal oxygen bonds in the range 500–700 cm−1 confirming the formation of a single-phase cubic inverse structure of Cu-substituted Ni ferrite. VSM results revealed the formation of ferrimagnetic nanoparticles. The optical and magnetic response of the ferrite nanoparticles changed with Cu content. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the value of single-energy metal artifact reduction (SEMAR) algorithm on image quality in patients after complex endovascular aortic repair (EVAR) with fenestrated and branched devices.Methods: Routine follow-up computed tomography angiography (CTA) examinations were performed between February 2016 and May 2017 in 18 patients who underwent a complex EVAR procedure at our institution. Objective analysis was performed by measuring the standard deviation (SD) of attenuation (Hounsfield Units), and the contrast-to-noise ratio (CNR) in regions of interests in the stented visceral arteries. Subjective analysis of the degree of artifacts and stent visualization was performed independently by two interventional radiologists, blinded to the image reconstruction.Results: The SD of attenuation was significantly lower in all target visceral arteries (p < .001), the celiac artery (p = .002), the superior mesenteric artery (SMA; p = .043), and renal arteries (p < .001) in the CT images with SEMAR reconstruction. The CNR significantly increased in all SEMAR-reconstructed target visceral arteries (overall: p < .001, celiac artery: p = .009; SMA: p = .003; renal arteries: p < .001). The reviewers rated a significantly lower artifact degree in all target vessels (overall: p < .001, celiac artery: p = .001; SMA: p = .008; renal arteries: p < .001) and a significantly improved visualization of the stent patency in all target vessels (overall: p < .001, celiac artery: p = .031; SMA: p = .047; renal arteries: p < .001) in the SEMAR images. Overall preference of both reviewers was in favor of the SEMAR reconstruction in 15/18 cases (83%).Conclusion: Reconstruction with SEMAR algorithm significantly improves CTA image quality in patients after complex EVAR.Level Of Evidence: Level 4, Case series. [ABSTRACT FROM AUTHOR]

The red imported fire ant, Solenopsis invicta (Buren), left most of its natural enemies behind in South America when it arrived in Mobile, AL, in the 1930s and spread rapidly throughout the southeastern United States, reaching population levels up to 10 times those found in South America. The large population densities and propensity for disturbed habitats led to direct conflict with human activities. Bait control methods were first developed for fire ants in the early 1960s and little has changed in the subsequent decades, despite the drawback that the bait carrier rapidly breaks down when wet. The southeast United States is wet; thus, bait labels have various guidance-restricting applications based on potential wet conditions. Here we compare a hydrophobic fire ant bait to the equivalent standard bait formulation and demonstrate in a paired-mound field experiment under natural wet conditions in Florida (heavy dew on ground), a significant advantage for the hydrophobic bait. An effective hydrophobic ant bait would extend the utility of current bait insecticides to wet conditions and also fill an important gap in our ability to control invasive pest ant species that thrive in wet tropical and subtropical habitats, e.g., Wasmannia auropunctata (Roger), the little fire ant. [ABSTRACT FROM AUTHOR]

The development of new functional foods requires technologies for incorporating health-promoting ingredients into food without reducing their bioavailability or functionality. In many cases, microencapsulation can provide the necessary protection for these compounds, but in all cases bioavailability should be carefully studied. The present paper gives an overview of the application of various microencapsulation technologies to nutritionally-important compounds, i.e. vitamins, n-3 polyunsaturated fatty acids, Ca, Fe and antioxidants. It also gives a view on future technologies and trends in microencapsulation technology for nutritional applications. [ABSTRACT FROM AUTHOR]

Almost all functionals that are currently used in density matrix functional theory have been created by some a priori ansatz that generates approximations to the second-order reduced density matrix (2RDM). In this paper, a more consistent approach is used: we analyze the 2RDMs (in the natural orbital basis) of rather accurate multi-reference configuration interaction expansions for several small molecules (CH4, NH3, H2O, FH, and N2) and use the knowledge gained to generate new functionals. The analysis shows that a geminal-like structure is present in the 2RDMs, even though no geminal theory has been applied from the onset. It is also shown that the leading non-geminal dynamical correlation contributions are generated by a specific set of double excitations. The corresponding determinants give rise to non-JKL (non Coulomb/Exchange like) multipole-multipole dispersive attractive terms between geminals. Due to the proximity of the geminals, these dispersion terms are large and cannot be omitted, proving pure JKL functionals to be essentially deficient. A second correction emerges from the observation that the “normal” geminal-like exchange between geminals breaks down when one breaks multiple bonds. This problem can be fixed by doubling the exchange between bond broken geminals, effectively restoring the often physically correct high-spin configurations on the bond broken fragments. Both of these corrections have been added to the commonly used antisymmetrized product of strongly orthogonal geminals functional. The resulting non-JKL functional Extended Löwdin-Shull Dynamical-Multibond is capable of reproducing complete active space self-consistent field curves, in which one active orbital is used for each valence electron. [ABSTRACT FROM AUTHOR]

Background Histologic and molecular subtyping have become increasingly important as predictors of treatment benefit in lung cancer. The objective of the present study was to determine whether current diagnostic approaches provide adequate tissue to allow for individualized treatment decisions. Methods Our retrospective cohort study of new lung cancer patients seen at an academic centre between July 2007 and June 2008 collected baseline demographic and diagnostic information, including mode of diagnosis, type of diagnostic material, and pathology diagnosis. Results Of the 431 study patients, 20% had stage I or II non-small-cell lung cancer (NSCLC), 24% stage III disease, and 39% stage IV NSCLC. Three quarters of the small-cell lung cancer (SCLC) cases were extensive stage. Diagnostically, 18% of patients had SCLC; 30%, adenocarcinoma; 27%, squamous-cell cancer; 2%, large-cell carcinoma; 1%, bronchoalveolar carcinoma; 1%, mixed histology; 18%, NSCLC not otherwise specified; 4%, other; and 2%, no pathology diagnosis. Surgical pathology material was available in 80% of cases, and cytology material alone in 20%. Surgical pathology material was more common in patients with early-stage than with advanced disease (89% for stages I and II vs. 74% for stages III and IV, p < 0.0001). The pathology report included ambiguous terms in 24% of cases: "consistent" (12%), "suspicious" (3%), "favour" (2%), "suggestive" (2%), "likely" (1%), "compatible" with malignancy (1%), "at least" (1%), "atypical" (0.5%), and "no pathology" (1.5%). Conclusions Current diagnostic approaches in most lung cancer patients appear adequate, but complete histopathologic identification is missing in nearly 20% of cases, and some uncertainty as to the final diagnosis is expressed in 24% of pathology reports. Some improvement in diagnostic sampling and pathology reporting are required to allow for implementation of current treatment approaches. [ABSTRACT FROM AUTHOR]

In order to determine the reliability of the Cobb angle measurement as it is used in the clinical management of scoliosis, a methodological survey was carried out. In the measurement of a Cobb angle two phases can be distinguished: (a) the production of a spinal radiograph and (b) the measurement of the angle itself. In respect of the first phase, the variation in production of the radiographs was calculated on Cobb angle measurements made by one investigator on serial radiographs of patients who underwent spinal fusion for scoliosis and therefore had a fixed spinal curvature. For the second phase, the accuracy of Cobb angle measurement was investigated by comparing measurements on the same radiographs of 46 scoliosis patients obtained by three investigators, namely two orthopaedic surgeons and an orthopaedic fellow who was assigned to a school screening project. Results were expressed as a Spearman correlation coefficient and a standard deviation of the differences. The Spearman correlation coefficient was 0.98 for the repeated radiographs (production variation) and also 0.98 for the repeated measurements on one radiograph (interobserver measurement variation). The standard deviation of the differences in Cobb angle for the repeated radiographs amounted to 3.2 degrees and for the repeated measurements on one radiograph it was 2.0 degrees. Although there is a good reproducibility of the Cobb angle measurement between different investigators, the variation in production of a spinal radiograph is an important source of error. This should be taken into account when making decisions in scoliosis management. [ABSTRACT FROM AUTHOR]

The Netherlands has well-organized school health services, and children are assessed on a regular basis for scoliosis among other disturbances and pathologies. The purpose of this study was to assess the benefits of an annual screening programme for scoliosis in the Netherlands. Three cohorts of 10,000 children sampled at 10, 12 and 14 years of age, respectively, were followed for 3 years. Children with a positive bending sign were referred to a second screening stage, in which external asymmetry was quantified. Children diagnosed via the programme (group 1) were compared with those children who had been referred for treatment independently of the screening (group 2). The total number of children in these groups combined was then compared with the number that would have been expected on the basis of accepted prevalence figures for idiopathic scoliosis given in current literature. Over 30,000 children were screened. Although the programme established a total of 57 cases of definite scoliosis (0.18%), the 34 cases (0.11%) already known, mainly detected by previous school health checks, were more severe regarding the risk of progression and treatment. The annual screening programme did not detect a single case that needed surgery. These figures provide the basis on which to decide for or against adopting an annual screening programme for scoliosis; the decision is a socio-political one. Based on this study, we expect all scoliotic patients needing treatment should be detected in time if periodic health checks will be maintained biennially. On medical grounds, it is our view, that screening for scoliosis should not be performed in the Netherlands annually. [ABSTRACT FROM AUTHOR]

Several studies advocate quantification of the bending test or performing surface topography to reduce the referral rate and to increase the specificity of the bending test in screening for scoliosis. Within the framework of a school screening project all children with a positive bending test were reexamined with measurement of rib hump height, angle of trunk rotation and moiré topography. In the period 1983-1986, out of three cohorts of 10,000 children of 10, 12 and 14 years of age, 3,069 were reexamined, of whom 1931 again tested positive (63%). The value of the three techniques in terms of sensitivity and specificity within the reexamined group was evaluated with regard to the Cobb angle on a spinal radiograph, which was made in 671 cases. A reduction in referrals of 37% was found. No significant difference in the ability to detect scoliosis was found between the three techniques mentioned. It is concluded that measurement techniques are valuable in school screening programmes. In particular, if instead of a single cut-off value, a range within which the examination should be repeated is chosen, high sensitivity and high specificity can be combined. Angle of trunk rotation measurement seems to be the easiest method of screening. [ABSTRACT FROM AUTHOR]

The presented contribution deals with the material properties of chain-extended polylactide. In the course of this study, two different functional additives were used, namely an epoxidized and a maleated styrene-acrylic copolymer. Both additives were compounded together with polylactide using a conventional twin-screw extruder, and were then injection moulded to standardized testing specimens. The main focus of the investigation is on structural changes as well as the mechanical performance, e.g. crack propagation and arresting mechanisms that are affected by reactive chain extension. The first section of the experimental part consists of results regarding modifications achieved on the macromolecular level. Based on size exclusion chromatography and DSC-OIT experiments, different structural changes and their influence on the material behaviour are presented. Subsequently, a comprehensive analysis of the quasi-static tests and the impact strength of notched and unnotched specimens was performed, and correlated with the following fatigue experiments. A discussion concerning morphological aspects and finally a correlation to the fracture surface topography after fatigue test completes the experimental part. [ABSTRACT FROM AUTHOR]

Heartwood samples from Juniperus virginiana L. were extracted with liquid carbon dioxide, and the bioactivity of carbon dioxide-derived cedarwood oil (CWO) toward several species of ants and cedrol toward ticks was determined. Repellency was tested for ants, and toxicity was tested for ticks. Ants in an outdoor bioassay were significantly repelled by the presence of CWO on a pole leading to a sugar-water solution. Similarly, CWO was a significant repellent barrier to red imported fire ants and prevented them from finding a typical food source. Black-legged tick nymphs exhibited dosage-dependent mortality when exposed to cedrol and at the highest dosage (i.e., 6.3 mg/ml) tested, the cedrol killed 100% of the ticks. These repellency and toxicity results together demonstrate a clear potential for the use of CWO as a pest control agent. [ABSTRACT FROM AUTHOR]

A number of consequences of the presence of the exchange–correlation hole potential in the Kohn–Sham potential are elucidated. One consequence is that the HOMO–LUMO orbital energy difference in the KS-DFT model (the KS gap) is not “underestimated” or even “wrong”, but that it is physically expected to be an approximation to the excitation energy if electrons and holes are close, and numerically proves to be so rather accurately. It is physically not an approximation to the difference between ionization energy and electron affinity I−A (fundamental gap or chemical hardness) and also numerically differs considerably from this quantity. The KS virtual orbitals do not possess the notorious diffuseness of the Hartree–Fock virtual orbitals, they often describe excited states much more closely as simple orbital transitions. The Hartree–Fock model does yield an approximation to I−A as the HOMO–LUMO orbital energy difference (in Koopmans' frozen orbital approximation), if the anion is bound, which is often not the case. We stress the spurious nature of HF LUMOs if the orbital energy is positive. One may prefer Hartree–Fock, or mix Hartree–Fock and (approximate) KS operators to obtain a HOMO–LUMO gap as a Koopmans' approximation to I−A (in cases where A exists). That is a different one-electron model, which exists in its own right. But it is not an “improvement” of the KS model, it necessarily deteriorates the (approximate) excitation energy property of the KS gap in molecules, and deteriorates the good shape of the KS virtual orbitals. [ABSTRACT FROM AUTHOR]

Background:After treatment with cisplatin-based chemotherapy for testicular cancer (TC), patients have higher prevalence of cardiovascular complications after long-term follow up. Little is known about acute cardiovascular effects of cisplatin-based chemotherapy. The aim of this study was to explore acute effects of chemotherapy on cardiac function in patients treated for TC.Methods:Fourteen TC patients (age 34.6±12.3 years) were studied before and 3 months after start with cisplatin-based chemotherapy. Cardiac function was assessed with magnetic resonance imaging. Fasting glucose and insulin levels were measured and insulin sensitivity, reflected by the quantitative insulin sensitivity index (Quicki index), was calculated.Results:Left ventricular (LV) end-diastolic volume and LV stroke volume (SV) significantly decreased from 192±27 to 175±26 ml (P<0.05) and 109±18 to 95±16 ml (P<0.05), respectively. The ratio of early and atrial filling velocities across the mitral valve, a parameter of diastolic heart function, decreased after chemotherapy from 1.87±0.43 to 1.64±0.45 (P<0.01). Metabolic parameters were unfavourably changed, reflected by a decreased Quicki index, which reduced from 0.39±0.05 to 0.36±0.05 (P<0.05).Conclusion:Chemotherapy for TC induces acute alterations in diastolic heart function, paralleled by unfavourable metabolic changes. Therefore, early after chemotherapy, metabolic treatment may be indicated to possibly reduce long-term cardiovascular complications. [ABSTRACT FROM AUTHOR]

Objective: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures and thiazolidinediones (TZDs) increase this risk. TZDs stimulate the expression of sclerostin, a negative regulator of bone formation, in vitro. Abnormal sclerostin production may, therefore, be involved in the pathogenesis of increased bone fragility in patients with T2DM treated with TZDs. Methods: We measured serum sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in 71 men with T2DM treated with either pioglitazone (PIO) (30 mg once daily) or metformin (MET) (1000 mg twice daily). Baseline values of sclerostin and P1NP were compared with those of 30 healthy male controls. Results: Compared with healthy controls, patients with T2DM had significantly higher serum sclerostin levels (59.9 vs 45.2 pg/ml, P<0.001) but similar serum P1NP levels (33.6 vs 36.0 ng/ml, P=0.39). After 24 weeks of treatment, serum sclerostin levels increased by 11% in PIO-treated patients and decreased by 1.8% in MET-treated patients (P=0.018). Changes in serum sclerostin were significantly correlated with changes in serum CTX in all patients (r=0.36, P=0.002) and in PIO-treated patients (r=0.39, P=0.020), but not in MET-treated patients (r=0.17, P=0.31). Conclusions: Men with T2DM have higher serum sclerostin levels than healthy controls, and these levels further increase after treatment with PIO, which is also associated with increased serum CTX. These findings suggest that increased sclerostin production may be involved in the pathogenesis of increased skeletal fragility in patients with T2DM in general and may specifically contribute to the detrimental effect of TZDs on bone. [ABSTRACT FROM AUTHOR]

To investigate in type-1 diabetes mellitus (DM1) patients the role of hypertension and of DM1 itself on aortic stiffness by using magnetic resonance imaging (MRI). Consecutive patients from the diabetes and hypertension outpatient clinic and healthy volunteers were included in our study. Subjects were divided into four groups: 32 healthy volunteers (mean age: 54.5 ± 6.8 years), 20 DM1 patients (mean age: 48.3 ± 5.9 years), 31 hypertensive patients (mean age: 59.9 ± 7.2 years) and 28 patients with both DM1 and hypertension (mean age: 50.1 ± 6.2 years). Aortic stiffness was measured by means of pulse wave velocity (PWV) using velocity-encoded MRI. Analysis of variance (ANOVA), uni- and multivariable regression models and the Bonferroni-test for multiple testing, were used for statistical analyses. Mean aortic PWV was 5.7 ± 1.2 m/s in healthy volunteers, 5.9 ± 1.2 m/s in DM1 patients without hypertension, 7.3 ± 1.2 m/s in hypertensive patients and 7.3 ± 1.3 m/s in patients with both DM1 and hypertension. Compared to healthy control subjects, aortic PWV was significantly higher in patients with hypertension (P < 0.001) and in patients with both DM1 and hypertension (P < 0.001), whereas aortic PWV was not increased in patients having DM1 alone. Furthermore, aortic PWV was significantly higher in DM1 patients with hypertension than in patients with DM1 alone (P = 0.002). These findings remained after adjustment for confounding factors. Hypertension has a predominant contributive effect on aortic stiffness in DM1 patients whereas the direct diabetic effect on aortic stiffness is small. [ABSTRACT FROM AUTHOR]

To investigate in type-1 diabetes mellitus (DM1) patients the role of hypertension and of DM1 itself on aortic stiffness by using magnetic resonance imaging (MRI). Consecutive patients from the diabetes and hypertension outpatient clinic and healthy volunteers were included in our study. Subjects were divided into four groups: 32 healthy volunteers (mean age: 54.5 ± 6.8 years), 20 DM1 patients (mean age: 48.3 ± 5.9 years), 31 hypertensive patients (mean age: 59.9 ± 7.2 years) and 28 patients with both DM1 and hypertension (mean age: 50.1 ± 6.2 years). Aortic stiffness was measured by means of pulse wave velocity (PWV) using velocity-encoded MRI. Analysis of variance (ANOVA), uni- and multivariable regression models and the Bonferroni-test for multiple testing, were used for statistical analyses. Mean aortic PWV was 5.7 ± 1.2 m/s in healthy volunteers, 5.9 ± 1.2 m/s in DM1 patients without hypertension, 7.3 ± 1.2 m/s in hypertensive patients and 7.3 ± 1.3 m/s in patients with both DM1 and hypertension. Compared to healthy control subjects, aortic PWV was significantly higher in patients with hypertension ( P < 0.001) and in patients with both DM1 and hypertension ( P < 0.001), whereas aortic PWV was not increased in patients having DM1 alone. Furthermore, aortic PWV was significantly higher in DM1 patients with hypertension than in patients with DM1 alone ( P = 0.002). These findings remained after adjustment for confounding factors. Hypertension has a predominant contributive effect on aortic stiffness in DM1 patients whereas the direct diabetic effect on aortic stiffness is small. [ABSTRACT FROM AUTHOR]

Nestmate recognition is a ubiquitous phenomenon in social insects as a means to prevent entry of undesired individuals aiming at exploiting the rich nest resources. The recognition cues in ants were shown in a few cases to be cuticular hydrocarbons, although there are a quite number of correlated associations. In the present study we modified the cuticular profiles of workers Camponotus fellah hydrocarbons with cuticular washes from a closely related, yet undescribed species, Camponotus sp. Although these sympatric species are morphologically indistinguishable, cuticular washes of C. sp. contain 9,13-dimethylpentacosane and 11,15-dimethylheptacosane that are either absent or occur as traces in C. fellah. In addition, C. sp. contains significantly greater amounts of 3-methylpentacosane than C. fellah workers. The cuticle modification was done solventless in a manner that minimized disruption to the cuticular structure of the ant being modified. Judging from the 3 focal compounds, such treatment added between 20 and 30% of the original amounts present in C. sp. to the treated C. fellah workers. This addition changed consistently the cuticular hydrocarbon profile of the treated ant. Dyadic assays between C. fellah and their nestmates treated with C. sp. cuticular rinses revealed a significantly higher level of aggression compared to non-treated nestmates. There was no aggression between nestmates of C. sp. These results demonstrate that in heterospecific interactions between the two Camponotus species there is a correlation between cuticular hydrocarbons and a nestmate recognition response, albeit not as high as the response of C. fellah to of C. sp. workers. This is consistent with the hypothesis that cuticular hydrocarbons may play a role in nestmate recognition. [ABSTRACT FROM AUTHOR]

Neuropeptide hormones produced by neurosecretory cells in the central or peripheral nervous systems regulate various physiological and behavioral events during insect development and reproduction. PBAN/Pyrokinin is a major neuropeptide family, characterized by a 5-amino-acid C-terminal sequence, FXPRLamide. This family of peptides has been implicated in regulating various physiological functions including, pheromone biosynthesis, muscle contraction, diapause induction or termination, melanization, and puparium formation in different insect species. In the present study, we report a new member of the PBAN family from the red imported fire ant, Solenopsis invicta, Soi-PBAN, composed of 26-AA (GSGEDLSYGDAYEVDEDDHPLFVPRL). Three additional peptides were deduced from Soi-PBAN cDNA: 15-AA (TSQDIASGMWFGPRL), 8-AA (QPQFTPRL) and 9-AA (LPWIPSPRL), that correspond to diapause hormone (DH), β-neuropeptide (NP), and γ-NP, which are found in many lepidopteran moths. Five peptides, DH, α, β, γ NPs, and PBAN are encoded from PBAN genes of lepidopteran moths, but in the fire ant the α-NP is missing. Each of the four synthetic peptides from the fire ant Soi-PBAN cDNA showed significant pheromonotropic activity in a moth model, indicating that these peptides are cross-reactive. Soi-β-NP induced the highest amount of pheromone production of the four peptides evaluated. The Soi-DH homologue had the lowest pheromonotropic activity, but was still significantly greater than control values. When the deduced amino acid sequences (entire ORF domains) from Soi-PBAN cDNA were compared with other known sequences, the fire ant was most similar to the honey bee, but phylogenetically distant from moth and beetle species. Soi-PBAN (26-AA) unlike the other three peptides shows a low degree of sequence identity with honeybee PBAN (33-AA). Based on the amino acid sequences encoded from insect PBAN genes identified to date, neuropeptide diversity is correlated with the taxonomic or phylogenetic classification of Insecta. From the present study we report the first neuropeptide identified and characterized from the central nervous system of Formicidae. [ABSTRACT FROM AUTHOR]

The oviposition process of the red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae), is described as a succession of four events forming one egg-laying cycle. Each time an egg is laid, the vulva opens and the sting is fully extended. When the vulva closes, the egg is forced to the base of the sting, whereupon the sting is usually retracted across the egg. This phenomenon has been consistently observed for queens from monogynous and polygynous S. invicta colonies. Zero to four eggs can be laid for each opening of the vulva. Multiple egg deposition is more frequent for monogyne queens, and it generally follows an oviposition cycle in which no egg is laid. The egg-laying cycles were evenly distributed during the observation periods, regardless of the total number of eggs laid, thereby suggesting that oviposition is a continuous process in S. invicta. [ABSTRACT FROM AUTHOR]

Cardiovascular molecular imaging is a rapidly evolving field of research, aiming to image and quantify molecular and cellular targets in vivo. MR imaging has some inherent properties that make it very suitable for cardiovascular molecular imaging. Until now, only a limited number of studies have been published on cardiovascular molecular imaging using MR imaging. In the current review, MR techniques that have already shown potential are discussed. Metabolic MR imaging can be performed by 31P-MR spectroscopy, 23Na MR spectroscopy and 1H-MR spectroscopy; some examples are shown. Furthermore, a concise overview is given of several aspecific and specific contrast agents for cardiovascular molecular MR imaging, such as gadolinium-based contrast agents, iron oxide MR contrast agents and fibrin-targeted MR contrast agents. We expect that in the next decade currently promising MR molecular imaging agents will be introduced into the clinical arena to guide diagnosis and therapy of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Queens of the red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae), release a primer pheromone that inhibits dealation (wing removal) of nestmate female alates by presumably suppressing endogenous concentrations of juvenile hormone (JH). Alates cast their wings once separated from the queen; however, the point of initiating dealation varies upon conditions. Alates are stimulated to shed their wings after several days of the death or removal of the queen, whereas newly mated alates dealate within 1 h after the mating flight. We found no single premating behavior or combination of behaviors associated with the nuptial flight that induces dealation rates comparable with that of newly mated queens. Copulation by itself or in conjunction with other behavioral signals and environmental prompts seems to be critical in causing rapid dealation in newly inseminated alates. In addition, colonies containing alates treated with precosene would not initiate mating flights nor could they be induced to fly. We suggest that precosene treatment affects the corpora allata (CA), but CA products other than juvenile hormone (JH) or in combination with JH are responsible for rapid dealation after mating. Dealation in the two contexts, within the colony and after mating flights, seems to occur via separate mechanisms. [ABSTRACT FROM AUTHOR]

This paper uses data envelopment analysis (DEA) to assess the operational effectiveness of the UK Coastguard (Maritime Rescue) coordination centres over the period 1995-1998. Based on the development of a performance measurement framework that is considerably more realistic and complex than the one apparently used by the Government, the main grounds for the latter's decision—confirmed in 1999—to close the Oban, Pentland and Tyne Tees coordination centres are called into question. The paper aims to contribute to the relevant academic literature in two ways: (1) by using formal analysis methods to measure the operational performance of a vital government-supplied service where such methods have not been applied before; and (2) by demonstrating how the results of suitable regression models can be used to inform the specification of appropriate DEA models, particularly with respect to the incorporation of relevant environmental factors. [ABSTRACT FROM AUTHOR]

This paper combines the use of (binary) logistic regression and stochastic frontier analysis to assess the operational effectiveness of the UK coastguard (Maritime Rescue) coordination centres over the period 1995-1998. In particular, the rationale for the Government's decision-confirmed in 1999-to close a number of coordination centres is scrutinized. We conclude that the regression models developed in this paper represent a performance measurement framework that is considerably more realistic and complex than the one apparently used by the UK Government. Furthermore, we have found that the coordination centres selected for closure were not necessarily the ones that were least effective in their primary purpose that is, to save lives, In a related paper, we demonstrate how the regression models developed here can be used to inform the application of data envelopment analysis to this case. [ABSTRACT FROM AUTHOR]

Systematic risk assessment and training courses have been suggested as interventions to deal with patient violence in psychiatric institutions. A dual centre prospective feasibility study was conducted on two Swiss psychiatric admission wards to test the hypothesis that such interventions will reduce the frequency and severity of violent events and coercion. A systematic aggression risk assessment, in combination with a standardized training course in aggression management was administered and the frequency and severity of aggressive incidents and the frequency of coercive measures were registered. The incidence rates of aggressive incidents and attacks showed no significant reduction from the baseline through risk prediction and staff training, but the drop in coercive measures was highly significant. A 'ward effect' was detected with one ward showing a decline in attacks with unchanged incidence rates of coercion and the other ward showing the opposite. The severity of the incidents remained unchanged whilst the subjective severity declined after the training course. We conclude that a systematic risk assessment and a training course may assist in reducing the incidence rate of coercive measures on psychiatric acute admission wards. Further testing of the interventions is necessary to measure the effect of the training alone and to counteract 'ward effects'. [ABSTRACT FROM AUTHOR]

Background: Colonic mucosa has a high turnover rate. At the end of their lifespan, colonocytes become senescent and die. Histological studies indicate that senescent colonocytes are shed (exfoliated) into the fecal stream in rats, but phagocytosed by mucosal macrophages in humans. We study whether quantification of host DNA in feces can be used as a non-invasive marker for this differential disposal of colonocytes. Methods: Selective primers and probes for the rat and human β-globin genes were designed and used in real-time PCR reactions. Results: Host DNA was quantitatively extracted and detected in fecal samples of both species. Feces of rats fed a humanized diet contained approximately 100 μg rat DNA per g freeze-dried feces. In human feces, however, only 5 out of 12 samples contained detectable, though very low (less than 0.35 μg/g), levels of host DNA. This about 300-fold difference could not be attributed to differences in DNase activities in the fecal stream. Conclusion: Our results indicate that there is considerable luminal shedding of senescent colonocytes in rats, whereas mucosal phagocytosis is the main route of colonocyte disposal in humans. Thus, real-time PCR of host DNA in feces can be applied as a non-invasive method for studying the differential exfoliation of colonocytes. [ABSTRACT FROM AUTHOR]

Background: We have shown recently that rapid fermentable fructo-oligosaccharides (FOS) decreased resistance of rats towards salmonella. It is not known whether inulin (which is fermented more gradually) has similar effects or whether buffering nutrients can counteract the adverse effects of rapid fermentation. Aims: To compare the effects of dietary inulin and FOS on resistance of rats to Salmonella enterica serovar Enteritidis and to determine whether calcium phosphate counteracts the effects of fermentation. Methods: Male Wistar rats (n = 8 per group) were fed a human "Western style diet". Diets with 60 g/kg cellulose (control), FOS, or inulin had either a low (30 mmol/kg) or high (100 mmol/kg) calcium concentration. After an adaptation period of two weeks, animals were orally infected with 2 x 109 colony forming units of Salmonella enterica serovar Enteritidis. Colonisation of salmonella was determined by quantification of salmonella in caecal contents. Translocation of salmonella was quantified by analysis of urinary nitric oxide metabolites in time. Results: Inulin and FOS decreased intestinal pH and increased faecai lactobacilli and enterobacteria. Moreover, both prebiotics increased the cytotoxicity of faecal water and faecal mucin excretion. Both prebiotics increased colonisation of salmonella in caecal contents and enhanced translocation of salmonella. Dietary calcium phosphate counteracted most of the adverse effects of inulin and FOS. Conclusions: Both inulin and FOS impair resistance to intestinal infections in rats. This impairment is partially prevented by dietary calcium phosphate. The results of the present study await verification in other controlled animal and human studies. [ABSTRACT FROM AUTHOR]

The Dietary Supplement Health and Education Act (DSHEA 1994) provides for the use of label statements on dietary supplements. In the 'Dietary Supplement Strategy: The Ten Year Plan' (Jan 2000) and 'Better Health Information for Consumers Initiative,' (Dec. 2002) the FDA placed emphasis on improving consumer labeling information and strengthening enforcement of DSHEA rules. The purpose of this research project was to (1) gain insight into consumer's awareness and understanding of nutritional claims on dietary supplements using focus groups and (2) evaluate industry's compliance with selected labeling requirements by conducting product surveillance at retail establishments. Thirty four individuals (17 men and 17 women) participated in the focus groups. Slightly more women 88% than men 76% indicated that they were familiar with nutritional claims on dietary supplements. While most consumers remain skeptical about the efficacy of dietary supplements and truthfulness of corresponding labeling, it does not preclude their use. The use of a scientific ranking system, similar to what's proposed for qualified health claims, for structural/function claims would provide a standard for claim substantiation and for consumers to judge their credibility. Five hundred thirty-five supplement products, manufactured and/or distributed by 238 companies, were evaluated for their compliance to selected labeling requirements. The majority (83%) of products screened, had labeling consistent with recent regulations. Having no or incomplete disclaimer with a structural/functional claim was the most common issue, occurring in 65% of the noncompliant products. The proportion of compliant and noncompliant products was not significantly different between retail categories. [ABSTRACT FROM AUTHOR]

BACKGROUND: and aims: It is frequently assumed that dietary non-digestible carbohydrates improve host resistance to intestinal infections by stimulating the protective gut microflora. However, compelling scientific evidence from in vivo infection studies is lacking. Therefore, we studied the effect of several non-digestible carbohydrates on the resistance of rats to Salmonella enteritidis infection. METHODS: Rats (n=8 per group) were fed "humanised" purified diets containing 4% lactulose, fructo-oligosaccharides (FOS), resistant starch, wheat fibre, or cellulose. After an adaptation period of 2 weeks the animals were orally infected with S enteritidis. Supplement induced changes in faecal biochemical and microbiological parameters were studied before infection. Colonisation of salmonella was determined by studying the faecal excretion of this pathogen and translocation by analysis of urinary nitric oxide metabolites over time and classical organ cultures. Intestinal mucosal myeloperoxidase activity was determined to quantify intestinal inflammation after infection. RESULTS: Despite stimulation of intestinal lactobacilli and bifidobacteria and inhibition of salmonella colonisation, FOS and lactulose significantly enhanced translocation of this pathogen. These supplements also increased cytotoxicity of faecal water and faecal mucin excretion, which may reflect mucosal irritation. In addition, caecal and colonic, but not ileal, mucosal myeloperoxidase activity was increased in infected rats fed FOS and lactulose. In contrast, cellulose, wheat fibre, and resistant starch did not affect the resistance to salmonella. CONCLUSIONS: In contrast to most expectations, FOS and lactulose impair the resistance of rats to intestinal salmonella infection. Obviously, stimulation of the endogenous lactobacilli and bifidobacteria is no guarantee of improved host defence against intestinal infections. [ABSTRACT FROM AUTHOR]

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (n NOS), bovine recombinant endothelial (e NOS), and murine recombinant immunologic (i NOS). Cytosolic NOS activity was determined by measuring the conversion of [3H]arginine to [3H]citrulline in vitro. Rat n NOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For n NOS, enzyme activity was inhibited by approximately 50% with 0.33 ± 0.06 μgg of this venom extract, and over 95% inhibition of the three isoforms, n NOS, e NOS, and i NOS, was found with doses of 60 μg in 60-μl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A (cis-2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for n NOS and e NOS were over 95% inhibited with 1000 μM of isosolenopsin A, whereas the activity of i NOS was inhibited by only about 20% at the same concentration. The IC50 for each of three NOS isoforms was approximately 18 ± 3.9 μM for n NOS, 156 ± 10 μM for e NOS, and >1000 μM for i NOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine (Ki= 19 ± 2 μM). The potency of isosolenopsin A as an inhibitor of n NOS compares favorably with the inhibitory potency of widely used n NOS inhibitors. Inhibition of NOS isoforms by isosolenopsin A and structurally similar compounds may have toxicological significance with respect to adverse reactions to fire ant stings. [ABSTRACT FROM PUBLISHER]

Massive, multiple fire ant, Solenopsis invicta , stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (nNOS), bovine recombinant endothelial (eNOS), and murine recombinant immunologic (iNOS). Cytosolic NOS activity was determined by measuring the conversion of [ 3 H]arginine to [ 3 H]citrulline in vitro. Rat nNOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For nNOS, enzyme activity was inhibited by approximately 50% with 0.33 ± 0.06 μg of this venom extract, and over 95% inhibition of the three isoforms, nNOS, eNOS, and iNOS, was found with doses of 60 μg in 60-μl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A ( cis -2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for nNOS and eNOS were over 95% inhibited with 1000 μM of isosolenopsin A, whereas the activity of iNOS was inhibited by only about 20% at the same concentration. The IC 50 for each of three NOS isoforms was approximately 18 ± 3.9 μM for nNOS, 156 ± 10 μM for eNOS, and >1000 μM for iNOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine ( K i = 19 ± 2 μM). The potency of isosolenopsin A as an inhibitor of nNOS compares... [ABSTRACT FROM AUTHOR]

The response of copper metabolism to dietary copper challenge was investigated in jaundiced rats with elevated plasma concentrations of conjugated bilirubin as a result of impaired canicular transport of bilirubin glucuronides. Control and jaundiced rats were fed purified diets with either normal (64 µmol Cu/kg) or high (640 µmol Cu/kg) concentration of added copper. Copper loading produced a greater increase in hepatic copper concentrations in the jaundiced than in control rats. The greater dietary-copper-induced increase in hepatic copper in the jaundiced rats can be explained by the observed smaller rise in biliary copper excretion and a greater efficiency of dietary copper absorption. In individual rats, there was a positive relationship between hepatic copper concentrations and biliary copper concentrations. It is suggested that not the transport of copper from liver cells to bile but that from plasma to bile is diminished in the jaundiced rats. The elevated plasma copper concentrations in the jaundiced rats may support this suggestion. [ABSTRACT FROM AUTHOR]