Detection of human influence on twentieth-century precipitation trends.
Human influence on climate has been detected in surface air temperature, sea level pressure, free atmospheric temperature, tropopause height and ocean heat content. Human-induced changes have not, however, previously been detected in precipitation at the global scale, partly because changes in precipitation in different regions cancel each other out and thereby reduce the strength of the global average signal. Models suggest that anthropogenic forcing should have caused a small increase in global mean precipitation and a latitudinal redistribution of precipitation, increasing precipitation at high latitudes, decreasing precipitation at sub-tropical latitudes, and possibly changing the distribution of precipitation within the tropics by shifting the position of the Intertropical Convergence Zone. Here we compare observed changes in land precipitation during the twentieth century averaged over latitudinal bands with changes simulated by fourteen climate models. We show that anthropogenic forcing has had a detectable influence on observed changes in average precipitation within latitudinal bands, and that these changes cannot be explained by internal climate variability or natural forcing. We estimate that anthropogenic forcing contributed significantly to observed increases in precipitation in the Northern Hemisphere mid-latitudes, drying in the Northern Hemisphere subtropics and tropics, and moistening in the Southern Hemisphere subtropics and deep tropics. The observed changes, which are larger than estimated from model simulations, may have already had significant effects on ecosystems, agriculture and human health in regions that are sensitive to changes in precipitation, such as the Sahel.


An improved long-range corrected hybrid exchange-correlation functional including a short-range Gaussian attenuation (LCgau-BOP).
A new hybrid exchange-correlation functional is presented based on the long-range correction (LC) scheme [H. Iikura et al., J. Chem. Phys. 115, 3540 (2001); Tawada et al., J. Chem. Phys. 120, 8425 (2004)], named LCgau-BOP. The key feature is the use of a two-parameter Gaussian correction to the Coulomb attenuation, which allows a more flexible description of exact exchange at short-range interelectronic separations. The new partitioning preserves 100% exact exchange in the long range, which is known to be important for the success of the LC scheme, with an asymptotic attenuation described by a standard error function with a parameter of 0.42. The LCgau partitioning was optimized for the reproduction of atomization energies over the G2 set and reaction barrier heights over Database/3, and produced results which are superior to B3LYP, CAM-BLYP, and the best LC functionals we are aware of. The results highlight the importance of including a substantial portion of exact exchange in the short range. Using the same parameters, the new functional was tested for the reproduction of geometries, as well as valence, Rydberg and charge-transfer excitations which are known challenges for conventional density functional theory. Our conclusion is that LCgau-BOP can provide a consistently more accurate description of thermochemistries, chemical reactions, and excitation energies than other existing long-range corrected functionals.


How to do (or not to do) ... Designing a discrete choice experiment for application in a low-income country.
Understanding the preferences of patients and health professionals is useful for health policy and planning. Discrete choice experiments (DCEs) are a quantitative technique for eliciting preferences that can be used in the absence of revealed preference data. The method involves asking individuals to state their preference over hypothetical alternative scenarios, goods or services. Each alternative is described by several attributes and the responses are used to determine whether preferences are significantly influenced by the attributes and also their relative importance. DCEs are widely used in high-income contexts and are increasingly being applied in low- and middle-income countries to consider a range of policy concerns. This paper aims to provide an introduction to DCEs for policy-makers and researchers with little knowledge of the technique. We outline the stages involved in undertaking a DCE, with an emphasis on the design considerations applicable in a low-income setting.


Role of magnetic resonance enterography in the management of Crohn disease.
To assess the impact of magnetic resonance enterography (MRE) on therapeutic decision making for patients with Crohn disease. Retrospective study. Tertiary care medical center. One hundred twenty patients who had either a history of or high suspicion for Crohn disease with onset of new symptoms underwent MRE over 18 months at our institution. All patients with Crohn disease were classified according to the Montreal system. Magnetic resonance enterography and medical vs surgical therapy. Changes in management after MRE findings. Magnetic resonance enterography demonstrated active Crohn disease in 57.5% of patients, chronic changes of Crohn disease without active inflammation (eg, stricture, fistula, or abscess) in 12.5% of cases, and no evidence of Crohn disease in 30% of cases. After MRE, 37 (31%) had no change in medical therapy, 64 (53%) had additional medical management for active inflammation, and 19 (16%) underwent an operation for complicated Crohn disease or medical intractability. In all surgical patients, the intraoperative findings were consistent with the MRE diagnosis. The mean (SD) MRE score was 1.6 (0.5) for patients who had no change in their treatment plans, 5.8 (1) for patients who underwent surgery, and 8 (0.4) for patients who had their drug regimen changed (P < .001). The MRE score independently correlated with need for intervention (P = .001). Magnetic resonance enterography shows promising ability to characterize the presence of active Crohn disease as well as chronic complications (eg, differentiate between stricture due to edema vs fibrotic scarring). Magnetic resonance enterography is fast becoming a useful adjunct in the management algorithm of patients with Crohn disease.


Assessment of affinity constants by rapid solid phase detection of equilibrium binding in a flow system.
We present a method for the determination of affinity constants based on equilibrium binding between an analyte and an antibody in liquid phase by a heterogeneous phase detection scheme. Equilibrium concentration of free antibody binding sites was probed kinetically by direct optical detection of specific binding to an immobilised analyte derivative. The additional binding signal due to dissociation of the analyte-antibody complex during detection was minimised by the use of fast flow-through conditions. The concentration of free antibody binding sites was titrated by adding increasing analyte concentrations. The affinity constant was derived from the titration curve by a non-linear least square fit of a model function. The affinity of monoclonal triazine antibodies to several s-triazine pesticides and a relevant metabolite was investigated. Kinetic determination of equilibrium concentration of free binding sites was carried out by reflectometric interference spectroscopy (RIfS) using flow injection analysis. The capabilities of the model were investigated using different analyte-antibody pairs and various antibody concentrations. Both bivalent IgG and monovalent Fab fragments were used to compare different binding models. The applied model corresponds well to the titration curves for affinity constants of 10(7) M(-1) and higher. For lower affinity constants significant deviations due to dissociation of the analyte-antibody complex during detection were observed.


[Cloning of mitomycin C resistance gene from Streptoverticillium caespitosum ATCC27422 and studying its function].
Streptoverticillium caespitosum is the major producer of anti-cancer drug mitomycin. It demonstrated that there exists a strong restriction system for the transformation of foreign DNA in this strain. Using the blocked mutant S-6 which is sensitive to mitomycin C (MC) and does not produce mitomycin as a recepient and plasmid pIJ699 as vector, the gene library of the strain ATCC27422 was constructed. A clone of mitomycin C resistance gene(mcr) was obtained by screening from this library. The mitomycin C resistance gene cloned on the 6.2 kb fragment of plasmid pLX5 could be expressed in the Strptonmyces lividans TK54. It was the first time to introduce successfully the plasmid pLX5 into the wild type strain ATCC27422 by electroporation technique. And the transformant's resistance to mitomycin C has risen greatly: the MIC has gone up from 200 micrograms/ml to more than 1000 micrograms/ml. The result of fermentation showed that the yield of mitomycin of ATCC27422 harboring plasmid pLX5 was more than the wild strain ATCC27422's. It suggested that there is some relationship between the level of the resistance to mitomycin C and its biosynthesis.


Alcohol consumption among drivers subject to the Swiss license restriction of zero tolerance when driving.
The restriction of zero tolerance when driving (ZTD) imposed on drivers in Switzerland means that they may drink no alcohol at all before driving and basically consume only moderate amounts of alcohol at any other time. The Institute of Traffic Medicine in Zurich has recently started to confirm this moderate alcohol consumption by analyzing hair samples for ethyl glucuronide (EtG), a metabolite of ethanol. On the basis of the EtG results, this article looks at the alcohol consumption of drivers subject to ZTD restrictions and determines what recommendations can be made in relation to traffic safety. In particular, the behavior of people with alcohol dependence, who are known to have a reduced ability to control their drinking, is looked at in detail. Data from all 250 persons with ZTD restrictions, assessed at our Institute in 2010, were evaluated retrospectively. These drivers included 220 men and 30 women, all aged between 21 and 75 (mean age 41 ± 12 years). At the time of the expert review, 26 (10.4%) had no record of driving under the influence (DUI), 121 (48.4%) had one DUI offense, and the rest had 2 or more drunk driving offenses. The length of time for which ZTD is imposed is determined on an individual basis, depending on the history of use and course of events. EtG hair analysis of all 250 drivers with ZTD restrictions provided the following results: EtG assay was not performed in 16 cases (6%); 126 drivers (50%) did not have any detectable EtG (corresponding to total abstinence); 93 (37%) had an EtG concentration within the limits of social drinking; and the EtG concentration indicated excessive alcohol use by 15 people (6%). EtG was found to be in the range of excessive alcohol consumption in 3 (8%) of the drivers diagnosed as alcohol dependent. It was seen that the majority of those drivers who had previously abstained totally from alcohol continued to do so. None of the drivers with ZTD restrictions committed any drunk driving offenses in 2010. Imposing a ZTD restriction on individuals with moderate alcohol consumption or those with previous alcohol problems who have been stable for some time and now drink little or no alcohol is worthwhile. In addition, total abstinence from alcohol should be made a license restriction for those with serious alcohol dependence, due to the poor long-term prognosis.


Myocardial salvage efficacy of the thromboxane receptor antagonist ifetroban in ferrets and dogs.
The effects of the thromboxane A2 (TXA2)/prostaglandin endoperoxide (TP) receptor antagonist ifetroban (BMS-180291) on infarct size (IS) resulting from coronary occlusion/reperfusion was determined in anesthetized dogs and ferrets. In dogs, ifetroban (1 + 1 mg/kg/h, intravenously, i.v.) or vehicle administration was initiated 10 min before left circumflex coronary artery (LCX) occlusion. In ferrets, the left anterior descending coronary artery (LAD) was occluded; after 75 min, a continuous infusion of ifetroban (0.3 + 0.3 mg/kg/h i.v.) or vehicle was started. After 90-min ischemia in both species, the LCX or LAD occlusion was released; reperfusion was continued for 5 h, at which time IS was determined. Regional myocardial blood flow (RMBF) before and during occlusion and during reperfusion were measured with radioactive microspheres. Ifetroban significantly decreased the extent of infarction to 39 +/- 5% of the area at risk (AAR) from 64 +/- 5% in dogs and to 15 +/- 2% of the left ventricle as compared with a control of 22 +/- 2% in ferrets. The protective effect of ifetroban in both species occurred with no increase in collateral BF or treatment-related alterations in peripheral hemodynamic status. Ifetroban, at the doses that reduced IS in ferrets, inhibited 99% of platelet TP receptors throughout the experiment, as measured by inhibition of the ex vivo platelet shape change response to U-46,619, a TP receptor agonist. Thus, doses of ifetroban causing profound TP receptor blockade also salvaged jeopardized myocardium in dogs and ferrets without changing collateral BF or peripheral hemodynamics.


Establishment, characterization and viral susceptibility of a new cell line derived from goldfish, Carassius auratus (L.), tail fin.
A continuous cell line [goldfish tail fin (GFTF)] derived from a goldfish tail fin, Carassius auratus, was established and characterized. GFTF cells predominantly consist of fibroblast-like cells that were maintained and subcultured more than 50 times over a period of 15 months. Cells grew at temperatures between 15 and 37°C, with an optimum temperature of 25°C. The growth rate of GFTF cells increased proportionally with the foetal bovine serum (FBS) concentration (5-20%), with optimum growth at 20% FBS. The chromosome numbers were 88-112, with a modal peak of 104 chromosomes. Five known fish viruses were tested to determine susceptibility. Results demonstrated that GFTF is susceptible to snakehead rhabdovirus, spring viraemia of carp virus and channel catfish virus (CCV). In addition, GFTF demonstrated a higher sensitivity to, and increased viral production of, CCV than that observed in the control cell line, channel catfish ovary cells. This suggests that GFTF cells would be useful as a diagnostic tool for viral diseases in this fish species, as well as for the isolation and study of goldfish viruses in the future. Furthermore, these cells were transfected with pEGFP-N1 vector DNA and some fluorescent signals were observed, suggesting that GFTF cells could be a useful tool for transgenic and genetic manipulation studies.


Electro-wetting of a nanoscale water droplet on a polar solid surface in electric fields.
Molecular dynamics simulations were applied to study the wetting properties of nanoscale droplets on a polar silica solid substrate subjected to constant and alternative electric fields with various field frequencies. Results show that the external applied electric fields have significant effects on the wetting of the nanoscale droplet on a polar solid substrate. The droplet spreads asymmetrically under the effect of the external applied field, and this asymmetry culminates to the maximum when the electric field equals to 0.45 V nm-1. For an electric field of 1.0 V nm-1, the dynamic electro-wetting process undergoes two stages even with a symmetric equilibrium spreading state. The stage A-B transition happens suddenly when molecules on the leading edge drop onto the solid surface due to the strong attraction of the solid substrate. Furthermore, under the alternative electric field with a different GHz frequency range, it was observed that the spreading asymmetry was weakened by increasing the field frequency and the nanoscale water droplet shape changes very slightly above a threshold frequency. Accompanied by the shape variation of water droplets, the molecular dipole orientations of water molecules experience a remarkable change from a random disordered distribution to an ordered profile because of the realignment of water molecules induced by electric fields. In addition, the polar solid surface has significant effects on the rearrangement of water molecules compared with a single droplet. Thus, the electro-wetting behaviors of water droplets on a silica solid surface are determined by the competing intermolecular forces among water, solid and the electric field.


Pathogenesis of segmental glomerular changes at the tubular origin, as in the glomerular tip lesion.
Segmental abnormalities at the glomerulo-tubular junction, or tip changes, are a common and early feature in several experimental and human renal disorders. Scanning and transmission electron microscopic study of an experimental model, Lewis rats given anti-glomerular basement membrane antibodies, showed that at 5 days there were monocytes/macrophages in glomerular capillary loops next to the tubular origin, with abnormalities of visceral epithelium, including prolapse of groups of these cells into the tubular origin. At 12 days, there was contact and adhesion between glomerular capillary loops and Bowman's capsule. Transmission electron microscopic study of human renal biopsies showed that the human tip changes resembled the later lesions seen in rats, with intracapillary foam cells confirmed by immunohistological study to be monocytes/macrophages. These findings show that abnormalities of the glomerular tuft precede adhesion to Bowman's capsule and that the earliest changes recognized by light microscopy in human renal biopsies are relatively late in their natural history, meaning at least several days old. Prolapse of visceral epithelial cells into the tubular origin may explain the characteristic site of tip changes.


The managed-care perspective for improving quality.
The role of managed-care organizations (MCOs) is to determine the existence of a benefit and how it is to be covered. Clinical guidelines and evidence-based medicine are critical parts of those decisions, and help drive much of the medical policies of MCOs. The goal is to identify and support medically appropriate and cost-effective interventions, and not cover treatments that do not have those characteristics. This will become increasingly important as more payers move to defined contribution plans, which place added responsibility for care decisions on the medical care consumer. Improving quality, creating consistency, and establishing the credibility of MCOs and their guidelines are imperative for integrating evidence-based medicine into coverage decisions. The ultimate outcome sought by MCOs and payers is improvement of the health of the populations they serve.


Trends in trace element determinations in blood, serum, and urine of the Dutch population, and the role of neutron activation analysis.
A critical review on the quality of literature data on trace elements in human blood, serum, and urine of inhabitants in the Netherlands has shown that many of the currently available data have been established 15-20 years ago. Only in a few publications are quality indicators mentioned, which should be considered typical--and minimal--for studies resulting at reference values. The use of neutron activation analysis for determination of trace elements in human body fluids was restricted to a few studies in the 1970s. However, although it is frequently assumed that the sensitivity of NAA might be insufficient, it is demonstrated that modern, large, well-type Ge detectors may serve well for the determination of trace elements in human body fluids via radiochemical NAA, for example.


Comparison of fat-saturated T2-weighted and contrast-enhanced fat-saturated T1-weighted sequences in MR imaging of sacroiliac joints in diagnosing active sacroiliitis.
To compare fat-saturated T2-weighted (FST2W) with contrast-enhanced fat-saturated T1-weighted (cFST1W) pulse sequences in magnetic resonance (MR) imaging of sacroiliac joints in diagnosis of active sacroiliitis associated with axial spondyloarthropathies. MR examinations of 147 adult patients suspected for sacroiliitis were retrospectively analyzed. Signs of active inflammation, bone marrow edema/osteitis, capsulitis, enthesitis, and synovitis were noted both on FST2W and cFST1W images. Diagnosis of active sacroiliitis was made according to the Assessment in SpondyloArthritis international Society (ASAS) definition. Sixty three patients were diagnosed as having active sacroiliitis based on both FST2W images showing bone marrow edema and cFST1W images showing osteitis. All areas with osteitis seen on cFST1W images were also noted as having bone marrow edema on FST2W images while FST2W images revealed 4 additional areas of active bone marrow changes. Qualitative and quantitative analyses also revealed that FST2W images were superior in showing active bone marrow lesions, the hallmark of active sacroiliitis, while cFST1W images helped detecting enthesitis and/or capsulitis and were necessary for detecting synovitis. Although cFST1W images help detecting enthesitis and/or capsulitis and are necessary for detecting synovitis, FST2W sequence is superior in detecting active bone marrow lesions and therefore more valuable in diagnosing active sacroiliitis associated with axial spondyloarthropathies based on ASAS criteria.


Characteristics of patients with chronic obstructive pulmonary disease choosing rehabilitation.
To identify and compare objective and self-perceived characteristics of patients with chronic obstructive pulmonary disease, who do and do not choose rehabilitation. The study comprised 205 consecutive patients with mild to very severe chronic obstructive pulmonary disease. They chose either inpatient rehabilitation (n = 161) or ordinary outpatient consultations (n = 44). Disease severity was assessed with spirometric tests, health-related quality of life was assessed with the St George's Respiratory Questionnaire, and mental status was measured using the Hospital Anxiety and Depression Scale. Socio-demographic and social characteristics, and co-morbidity variables were available. Patients in the rehabilitation group had a lower level of overall health-related quality of life (63.8 vs 47.6, p = 0.000) and a higher prevalence of anxiety (34.6% vs 13.6%, p = 0.007) than the outpatients. The outpatients received more psychological support from spouse/partner than patients in the rehabilitation group (70.5% vs 49.1%, p = 0.012). There were no differences in disease severity and co-morbidity. The decision to choose rehabilitation may be determined by impaired health-related quality of life, psychological distress and lack of psychological support from a significant other. Our findings suggest that patients with chronic obstructive pulmonary disease are conscious of their overall health status and the necessary treatment to maintain or improve it.


SiRNA drug delivery by biodegradable polymeric nanoparticles.
RNA interference (RNAi) is an emerging technology in which the introduction of double-stranded RNA (dsRNA) into a diverse range of organisms and cell types causes degradation of the complementary mRNA. It offers a broad spectrum of applications in both biological and medical research. Small interference RNA (siRNA) was recently explored for its therapeutical potential. However, the drug delivery of siRNA oligos is very novel and is in great need of future research. To this end, a biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticle drug carrier system was prepared to load siRNA oligos with desired physicochemical properties. The nanoparticles were characterized by scanning electron microscopy and laser diffraction particle sizer. The delivery of siRNA into the targeted 293T cells was observed using fluorescent-labeled double-stranded Cy3-oligos. The model siRNA oligos, si-GFP-RNA, were also successfully loaded into PLGA nanoparticles and delivered in 293T cells. The gene silencing effect and the inhibition of GFP expression were investigated using fluorescent microscopy. Both positive and negative controls were used to compare with the new siRNA nanoparticle delivery system. It was found that nanoparticles offered both effective delivery of siRNA and prominent GFP gene silencing effect. Compared to conventional carrier systems, the new biodegradable polymeric nanoparticle system may also offer improved formulation stability, which is practically beneficial and may be used in the future clinical studies of siRNA therapeutics.


[Perinatal variables and association with very low birthweight newborns in a Brazilian public university hospital].
To investigate the association of perinatal variables with the birth of very low birth weight (VLBW) preterm newborns. It was a retrospective study of the medical records of infants born after spontaneous preterm labor with admission to a neonatal intensive care unit. Preterm infants were divided into two groups: very low birth weight (VLBW) group (weight <1,500 g) and low birth weight (LBW) group (weight ≥1,500 g and <2,500 g). Prenatal variables such as maternal complications during pregnancy and childbirth/postpartum, and fetal/neonatal complications were investigated. Statistical analysis was performed using the Fisher exact test or χ2 test, with calculation of relative risk (RR), and the Student t test for comparison of group means, with the level of significance set at p≤0.05. Hemorrhagic comorbidities (p=0.006; RR=1.2) and hypertension (p=0.04; RR=1.5), surgical delivery (p=0.001; RR=0.5), gestational age <33 weeks (p< 0.001; RR=16.7) and Apgar score at 1st and 5th minute (p=0.006; RR=1.6; p=0.01; RR=1.9) were associated with the occurrence of VLBW. Infants with VLBW had a significant association with the occurrence of metabolic comorbidities (p=0.01; RR=1.8), neurological (p=0.01; RR=1.7) and infectious diseases (p=0.001; RR=1.9), hospitalization >4 weeks (p=0.02; RR=1.8) and early neonatal death (p=0.0001; RR=2.9). Factors such as hypertension and bleeding comorbidities during delivery and management of gestational age of less than 33 weeks were associated with the birth of VLBW newborns. This group of infants also showed higher RR for the occurrence of early neonatal death.


Evaluation of the ability of glass-ionomer cement to bond to glass-ionomer cement.
This study investigated the cohesive bond strengths of glass-ionomer cement at three setting and etching intervals and compared these bonds to the shear strength of the material itself. Bonded cylinders were created and then sheared using the Instron Universal Testing Machine. Analysis of bond values of glass ionomer added to glass ionomer indicate bond variability and low cohesive bond strength of the material. Bond values of unbonded glass-ionomer material indicate that the material itself is stronger than bonds established between bonded samples.


Suicidal ideation and associated factors among in-school adolescents in Zambia.
A cross sectional study was conducted to estimate the prevalence and correlates of suicidal ideation among in-school adolescents in Zambia. Backward logistic regression analysis was conducted to assess the association between relevant predictor variables and suicidal ideation within the last 12 months. A total of 1970 in-school adolescents who participated in the Zambia Global School-Based Health Survey in 2004 responded to the question on suicidal ideation. Overall, 54.0% were males, 40.8% were current drinkers, and 35.9% ever smoked marijuana (cannabis). Altogether 31.3% reported suicidal ideation in the past 12 months (males = 31.1%; females = 31.4%). Being male (OR = 1.05; 95%CI 1.03, 1.05): being <14 years old (OR = 1.21; 95%CI 1.19, 1.23), having been drunk (OR = 1.28; 95%CI 1.27, 1.29). worried (OR= 1.05; 95%CI 1.04, 1.06), sad or hopeless in the past 12 months (OR = 1.02; 95%CI 1.01, 1.03) and ever used marijuana (OR = 1.18; 95%CI 1.17, 1.19) were positively associated with suicidal ideation. Loneliness appeared to be protective (OR = 0.92; 95%CI 0.91, 0.92). All the results, except for ever smoked marijuana and ever been drunk, may have been biased due to non-response to the question on suicidal ideation. A series of cross sectional studies should be conducted to monitor changes in behavioural factors among others ever smoked marijuana and ever been drunk in order to broaden our understanding of factors that may be causing adolescents to seriously consider committing suicide.


Impacts of conventional coronary risk factors, diabetes and hypertension, on coronary atherosclerosis during statin therapy: subanalysis of the TRUTH study.
Patients with diabetes mellitus (DM) and hypertension (HT) are at a high risk of coronary artery disease. However, the mechanisms underlying this have not been well characterized. The purpose of the present study was to evaluate the impacts of DM and HT on coronary atherosclerosis during statin therapy. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated in the TRUTH study using virtual histology intravascular ultrasound. Analyzable intravascular ultrasound data were obtained from 119 patients who were divided into four subgroups, namely, group A: DM (+), HT (+); group B: DM (+), HT (-); group C: DM (-), HT (+); and group D: DM (-), HT (-). The pattern of arterial remodeling, extent of coronary atherosclerosis, and plaque composition were compared among the four subgroups. Atheroma volume decreased significantly in group D (-3.9%, P=0.01), whereas it tended to increase in group A (1.0%, P=0.77). A significant difference in the mean percent change of atheroma volume was observed between groups A and D (1.0 vs. -3.9%, P=0.03). Furthermore, the frequency of progression in atheroma volume was significantly higher in group A (60, 33, 45, and 24% in groups A, B, C, and D, respectively; P=0.03). No significant differences in the changes in the four plaque components among the four subgroups were observed. A combination of DM and HT attenuates the degree of regression of coronary atherosclerosis, but does not influence changes in plaque composition during statin therapy.


CMTM5 induces apoptosis of pancreatic cancer cells and has synergistic effects with TNF-alpha.
Our previous data show that CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) is a potential tumor suppressor gene, but its function in pancreatic cancer is unknown. Herein we first report that CMTM5 is also absent in pancreatic cancer cell lines with promoter methylation. Compared with normal pancreatic tissues, CMTM5 is significantly decreased in cancer tissues. Restoration of CMTM5-v1 not only induces MIA PaCa-2 cell apoptosis with activation of caspase 3, 8 and 9, but also has synergistic effects with TNF-alpha. Thus, CMTM5 may play a role in the pancreatic cancer.


Synthesis of secondary metabolites by Cladosporium resinae (NRL-6437) under different growth media and chemical inducers and their pharmaceutical activity.
The role of different growth media and chemical enhancer on synthesis of secondary metabolites Cladosporium resinae (NRL-6437) was investigated for their in vitro biological activities. Cladosporium resinae (NRL-6437) were grown in various nutrient media (Czapeak-dox Broth (CB), Czapeak Yeast-extract Broth (CYB), Yeast Extract Sucrose (YES), Potato Dextrose Broth (PDB) and Czapeak-dox (supplemented with glucose and starch) Broth (CGSB) for the production of metabolites. Two chemical epigenetic modifiers (suberoyl-anilide hydroxamic acid (SAHA) and 5-azacytidine (5-AZA) were also used for the expression of silent genes for secondary metabolite production. Our results indicated that among different media, Czapeak yeast extract broth produced more secondary metabolites. Application of 15mM of both modifiers was effective for the expressions of silent genes resulting in an increased metabolites production. Secondary metabolites extracted in ethyl acetate and fractionized in n-Hexane were also tested for their biological activity. The secondary metabolites revealed varying degrees of growth inhibitions of the tested organisms. Similarly, these metabolites were also active against brine shrimps and Lemna.


Paraneoplastic scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia: a report of 10 cases.
Systemic plasma cell dyscrasias have diverse manifestations in the skin and include an inflammatory paraneoplastic process. We encountered cases of scleroderma and eosinophilic fasciitis in the setting of an underlying plasma cell dyscrasia. Ten cases of scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia were encountered. The biopsies were stained for Transforming growth factor (Transforming growth factor) beta, IgG4, kappa, and lambda. Patients presented with a sclerodermoid reaction represented by eosinophilic fasciitis (5 cases), morphea (3 cases), and systemic scleroderma (2 cases). The mean age of presentation was 70 years with a striking female predominance (4:1). Acral accentuation was noted in 8 cases. In 6 of the cases, the cutaneous sclerosis antedated (4 cases) by weeks to 2 years or occurred concurrently (2 cases) with the initial diagnosis of the plasma cell. The biopsies showed changes typical of eosinophilic fasciitis and/or scleroderma. In 5 cases, light chain-restricted plasma cells were present on the biopsy. There was staining of the plasma cells for Transforming growth factor beta in 3 out of 5 cases tested. In any older patient presenting with a sudden onset of eosinophilic fasciitis or scleroderma especially with acral accentuation, investigations should be conducted in regards to an underlying plasma cell dyscrasia.


State commitment to home and community-based services: effects on independent living for older unmarried women.
This study examines the impact of state variation in commitment to the provision of home and community-based services on the living arrangement outcomes of older unmarried females with functionallimitations. We combine data from the 1990 U.S. Census of Population (PUMS) with state-level information on long-term care home and community- based service expenditures, nursing home bed availability, and Medicaid nursing home costs from a special report that compares state variation in long-term care systems. Using multilevel logistic regression modeling techniques, we find that the risk of institutionalization compared to community living arrangements is reduced as spending for home and community-based services at the state level increases. We discuss these findings in light of policy changes during the 1990s.


Immunocytochemistry and in situ hybridisation of epidermal growth factor receptor and relation to prognostic factors in breast cancer.
The breast tumour distribution of epidermal growth factor receptor (EGFR) was studied in 193 patients with primary breast cancer by immunocytochemistry on frozen sections. EGFR was correlated (P = 0.0009) with growth fraction assessed by Ki-67, and negatively correlated with oestrogen receptor (ER, P = 0.0001) and progesterone receptor (PR, P = 0.0001) status. In 47 patients, in-situ hybridisation for EGFR mRNA showed good agreement with the immunocytochemically assessed EGFR protein. There were, however, several tumours in which EGFR mRNA could be detected in the absence of EGFR protein and there were differences between the ER and PR status of those tumours in which translation of EGFR mRNA was not seen. The cause of these differences is unclear, but these findings may represent a clue as to the differential control of breast cancer cell receptors.


An event-related potential study of older children with an early history of failure to thrive.
Elementary and junior high school children (n = 13), who were diagnosed with nonorganic failure to thrive (FTT) as infants and toddlers, were compared with a normal control group (n = 14) on visual event-related potentials (ERPs) elicited during a primed lexical decision task. Positive stimuli were real words that were identical to the priming stimuli; negative stimuli were nonpronounceable letter strings. Although the groups did not differ in word-list reading level, the former FTT group had slower reaction (decision) times and did not show ERP evidence of priming in the N400 epoch. Anterior sites yielded better separation of the real words and letter strings than posterior sites. A late anterior component between 500 msec to 650 msec poststimulus onset showed the largest condition effect for both groups. The control group had a larger negative going late anterior component to words than the FTT group. The combined reaction time and ERP findings point to less automatized word recognition in the FTT group.


An In Vitro Comparative Evaluation of Shear Bond Strengths of Veneering Porcelain and Different Core Materials.
The aim of the present study was to evaluate and compare the bond strengths of different core structures to veneering porcelain. Sixty specimens were divided into 4 groups of 15 each. Specimen fabrication was done according to the International Organization for Standardization (ISO) specifications 9693:1999. Group 1 comprised core structure made of cast alloy, group 2 from sintered metal, group 3 from milled zirconia and group 4 milled zirconia without liner at the interface. The shear bond strengths were recorded and the values obtained were statistically examined. Highest values were recorded in group 3 and there were significant differences between groups 1 and 3 while groups 3 and 4 were not statistically different. This led us to imply that zirconia as a core structure provided maximum strengths and laser sintered metal came second. The results also pointed out that the role of the zirconia liner is not that crucial to attaining adequate strength. The present study concluded that zirconia and laser sintered metal are excellent core materials and feasible alternatives to cast alloy. We also concluded from our study that a zirconia liner did not affect the bond strength significantly and is not absolutely essential. This study helps us to understand the role of materials used as core structures in enhancing the shear bond strength to veneer porcelains and also clarifies the role of a zirconia liner in the process.


Vinyl polysiloxane impression material in removable prosthodontics. Part 1: edentulous impressions.
Recent advances in impression materials and stock edentulous impression trays have resulted in simplified approaches to impression making in removable prosthodontics. Once considered an absolute necessity, it is now possible to avoid the need for custom impression trays. In an effort to achieve reliable master casts in a single appointment, new and innovative procedures are now available. This article, the first in a 3-part series, will review historical information, basic concepts, materials considerations, and philosophic approaches to impression making in complete-denture therapy. A modem technique using readily available impression materials will be described and illustrated so readers can consider the benefits of incorporation into their daily management of edentulous patients.


The differential effect of prostaglandin E2 on transforming growth factor-beta and insulin-induced collagen formation in lung fibroblasts.
We examined the effect of prostaglandin (PG) E2 on transforming growth factor-beta (TGF-beta) and insulin-stimulated collagen formation in lung fibroblast cultures. TGF-beta increased type I collagen production 2-3-fold as determined by the densitometric analysis of autoradiograms from polyacrylamide gels and by measuring the amount of nondialyzable hydroxyproline. This was associated with a 5-6-fold increase in alpha 1(I) mRNA levels. PGE2 at 10(-7) M strongly inhibited type I collagen formation in TGF-beta-stimulated cultures by 60-70%. PGE2 blocked collagen formation in TGF-beta-stimulated cultures by decreasing levels of alpha 1(I) gene expression. PGE2 inhibited alpha 1(I) gene expression in part through inhibition of transcription. In contrast, insulin increased type I collagen production 2-fold and was associated with a 30-40% increase in alpha 1(I) mRNA. Although PGE2 also decreased alpha 1(I) mRNA levels in insulin-treated cultures, PGE2 had no effect on collagen formation. Taken together, these results demonstrate that collagen formation may proceed through two distinct pathways. These two pathways are distinguishable by their sensitivity to PGE2 treatment and their relationship to increases in collagen mRNAs.


Alkylpyridiniums. 2. Isolation and quantification in roasted and ground coffees.
Recent model studies on trigonelline decomposition have identified nonvolatile alkylpyridiniums as major reaction products under certain physicochemical conditions. The quaternary base 1-methylpyridinium was isolated from roasted and ground coffee and purified by ion exchange and thin-layer chromatography. The compound was characterized by nuclear magnetic resonance spectroscopy ((1)H, (13)C) and mass spectrometry techniques. A liquid chromatography-electrospray ionization tandem mass spectrometry method was developed to quantify the alkaloid in coffee by isotope dilution mass spectrometry. The formation of alkylpyridiniums is positively correlated to the roasting degree in arabica coffee, and highest levels of 1-methylpyridinium, reaching up to 0.25% on a per weight basis, were found in dark roasted coffee beans. Analyses of coffee extracts also showed the presence of dimethylpyridinium, at concentrations ranging from 5 to 25 mg/kg. This is the first report on the isolation and quantification of alkylpyridiniums in coffee. These compounds, described here in detail for the first time, may have an impact on the flavor/aroma profile of coffee directly (e.g., bitterness), or indirectly as precursors, and potentially open new avenues in the flavor/aroma modulation of coffee.


Effect of pharmacist intervention on blood conservation therapy in total knee arthroplasty: A retrospective, observational study.
Total knee arthroplasty (TKA) is associated with blood loss and an increased risk of transfusion. Guidelines for antifibrinolytic drug tranexamic acid (TXA) treatment in TKA patients are available. We evaluated the effects of anticoagulant pharmacist intervention on perioperative blood conservation treatment in TKA patients. In a retrospective, observational experimental study, patients admitted for TKA were allocated into the control or pharmacist intervention group. In the intervention phase, multiple interventions of TXA treatment based on guidelines were implemented. The primary endpoint was blood loss. Other outcome included postoperative haemoglobin and haematocrit levels, allogeneic blood transfusion, cost savings and safety. A total of 177 patients were included (88 and 89 in the control and intervention group, respectively). In the intervention group, 24.72% orders of TXA dosage, 20.22% orders of drug choice, 26.97% orders of TXA timing and 30.34% orders of TXA administration manner were adjusted. Eighty-nine (100%) patients received blood conservation therapy compared with 21 (23.86%) patients in the control group (P < 0.001). Total blood loss was 1133.31 ± 627.08 mL in the control group compared with 604.34 ± 459.09 mL in the intervention group (P < 0.001). Postoperative drops in haemoglobin and haematocrit in the control group were greater than in the intervention group (P < 0.001). The rate of allogeneic blood transfusion was 40.91% in the control group compared with 21.35% in the intervention group (P = 0.01). Pharmacist intervention was conducted to cost savings resulting from reduced transfusion, but with comparable safety profile. Anticoagulant pharmacist intervention on blood conservation treatment of TKA patients leads to favourable clinical and economic outcome.


Screen-printed amperometric biosensors for the rapid measurement of L- and D-amino acids.
Screen-printed three-electrode amperometric sensors incorporating L- and/or D-amino acid oxidase for the general purpose measurement of L- or D-amino acids is described. The working electrode incorporates rhodinized carbon, to facilitate hydrogen peroxide oxidation at a decreased operating potential, and immobilized enzyme. The devices responded to all 20 common L-amino acids and all of the D-amino acids examined, the exceptions being L- and D-proline. Linear response profiles were observed for L-leucine, L-glycine and L-phenylalanine with limits of detection of 0.47, 0.15 and 0.20 mM respectively. The devices were reproducible and exhibited stability over a 56 d test period. The biosensor compares favourably with a standard photometric amino acid test and was used to monitor milk ageing effects. The assay is cheap, simple to perform and rapid, requiring only buffer-electrolyte and a small sample volume.


Inhibitor development in previously untreated patients with severe haemophilia A: a nationwide multicentre study in Finland.
Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL(-1) ). We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2-13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.


Effect of selenium supplementation on lipid peroxidation, antioxidant enzymes, and lactate levels in rats immediately after acute swimming exercise.
The present study aims to evaluate the effect of selenium supplementation on lipid peroxidation and lactate levels in rats subjected to acute swimming exercise. Thirty-two adult male rats of Sprague-Dawley type were divided into four groups. Group 1, control; group 2, selenium-supplemented; group 3, swimming control; group 4, selenium-supplemented swimming group. The animals in groups 2 and 4 were supplemented with (i.p.) 6 mg/kg/day sodium selenite for 4 weeks. The blood samples taken from the animals by decapitation method were analyzed in terms of erythrocyte-reduced glutathione (GSH), serum glutathione peroxidase (GPx) and superoxide dismutase (SOD), and plasma malondialdehyde (MDA) and lactate using the colorimetric method, and serum selenium values using an atomic emission device. In the study, the highest MDA and lactate values were found in group 3, while the highest GSH, GPx and SOD values were obtained in group 4 (p < 0,001). Group 2 had the highest and group 3 had the lowest selenium levels (p < 0,001). Results of the study indicate that the increase in free radical production and lactate levels due to acute swimming exercise in rats might be offset by selenium supplementation. Selenium supplementation may be important in that it supports the antioxidant system in physical activity.


Complete genome sequence of the entomopathogenic and metabolically versatile soil bacterium Pseudomonas entomophila.
Pseudomonas entomophila is an entomopathogenic bacterium that, upon ingestion, kills Drosophila melanogaster as well as insects from different orders. The complete sequence of the 5.9-Mb genome was determined and compared to the sequenced genomes of four Pseudomonas species. P. entomophila possesses most of the catabolic genes of the closely related strain P. putida KT2440, revealing its metabolically versatile properties and its soil lifestyle. Several features that probably contribute to its entomopathogenic properties were disclosed. Unexpectedly for an animal pathogen, P. entomophila is devoid of a type III secretion system and associated toxins but rather relies on a number of potential virulence factors such as insecticidal toxins, proteases, putative hemolysins, hydrogen cyanide and novel secondary metabolites to infect and kill insects. Genome-wide random mutagenesis revealed the major role of the two-component system GacS/GacA that regulates most of the potential virulence factors identified.


Early argon laser photocoagulation of presumed histoplasma maculopathy.
In this study, 66 patients with presumed ocular histplasmic maculopathy and in whom the edge of the neovascular membrane was at least 200 micron from the center of the fovea were selected for treatment with argon laser photocoagulation. They were divided into three groups depending on the time elapsed between the beginning of symptoms and treatment with argon laser photocoagulation. The size of the neovascular membrane, the distance from the center of the fovea, and the presence of hemorrhage in the foveal area were also noted. We found that the most important prognostic factor for best final visual acuity was the interval of time between onset of symptoms and treatment. The study showed that 73.3% (22 of 30) of patients with symptoms of short duration (four weeks or less) compared with 17.6% of those with symptoms of long duration (16 weeks or more) retained 6/15 (20/50) or better final visual acuity following argon laser photocoagulation treatment.


Mapping polypeptide hormone genes in the mouse: somatostatin, glucagon, calcitonin, and parathyroid hormone.
Mouse-Chinese hamster hybrids segregating mouse chromosomes were analyzed by Southern hybridization techniques to map the genes for somatostatin (Smst), glucagon (Gcg), calcitonin (Calc), and parathyroid hormone (Pth). The mouse gene for somatostatin, detected on a 20-kb EcoRI fragment, is located on mouse chromosome 16. Glucagon cDNA hybridized to a 14-kb EcoRI fragment residing on chromosome 2. Calcitonin and parathyroid hormone genes, detected on 7.8-kb HindIII and 6.0-kb BamHI fragments, respectively, were on mouse chromosome 7. The calcitonin and parathyroid hormone genes appear to be part of a larger linkage group which has been conserved in mouse and man.


Vascular pseudoinvasion in a solitary Peutz-Jeghers polyp in the ileum.
A Peutz-Jeghers polyp (PJP) is a hamartomatous lesion characterized by arborescent smooth muscle bundles covered with mucosa native to the site of involvement. PJPs in the small intestine may represent misplacement of non-neoplastic epithelium into the submucosa, muscularis propria and subserosa. Although epithelial misplacement in PJPs is a well-documented phenomenon, pseudoinvasion even into the vascular space in PJPs has not previously been reported. We report a case of a 22-year-old Japanese woman with a solitary PJP in the ileum. The ileal PJP in this patient showed epithelial herniation even into the vascular space. All the herniated epithelium, including the epithelial components invaginated into the vascular space, demonstrated features of pseudoinvasion, that is, presence of normal small intestinal type mucosa accompanied by the lamina propria, absence of any stromal desmoplastic reaction, and retention of the basal-luminal gradient. Pathologists must be aware of the possibility of vascular pseudoinvasion in small intestinal PJPs to avoid overdiagnosis of carcinoma and resulting unnecessary major surgery.


Partnering to Establish and Study Simulation in International Nursing Education.
The purpose of this article was to describe an international partnership to establish and study simulation in India. A pilot study was performed to determine interrater reliability among faculty new to simulation when evaluating nursing student competency performance. Interrater reliability was below the ideal agreement level. Findings in this study underscore the need to obtain baseline interrater reliability data before integrating competency evaluation into a simulation program.


[Effect of collagenase on neuromuscular transmission in the frog].
Modification of synaptic function was estimated through the action of 0.1% solution of collagenase on neuromuscular junction in frog. Electrophysiological experiments revealed a decrease of the e.p.p. quantum content on single nerve stimulation with collagenase. The latter or the product of its splitting modify the action zones of mediator secretion. The demyelination action of collagenase on nerve is discussed.


Mitosis-specific monoclonal antibodies block cleavage in amphibian embryos.
By microinjecting monoclonal antibodies that bind specifically to mitotic and meiotic cells of a variety of species, we studied the biological activity of antigens recognized by these antibodies. The antibodies recognize a family of phosphoprotein antigens that are found throughout the cytoplasm of mitotic cells and particularly at microtubule organizing centers, including centrosomes and kinetochores. Their binding is dependent on phosphorylation of the polypeptides. Immunoglobulins were introduced into Xenopus laevis and Rana pipiens oocytes or cleaving embryos using glass micropipettes. The ability of the antibody-injected oocytes to undergo mitosis or meiosis was compared with those injected with control mouse immunoglobulins. The antibodies failed to block chromosome condensation and germinal vesicle breakdown in progesterone-treated oocytes. However, functional mitotic spindles were not assembled in cleavage stage frog embryos injected with antibodies. In vitro, the binding of the antibodies to the antigens inhibited the dephosphorylation of the antigens by alkaline phosphatase. The antibody binding to the activated microtubule organizing centers (MTOC) seems to block not only the nucleation of microtubules and the organization of the mitotic spindle, but also the dephosphorylation of proteins associated with the MTOC that normally occurs at the mitosis-G1 transition.


Promoter-directed expression of recombinant fire-fly luciferase in the salivary glands of Hermes-transformed Aedes aegypti.
Molecular genetic analyses of biological properties characteristic of insect vectors of disease, such as hematophagy and competence for pathogens, require the ability to isolate and characterize genes involved in these processes. We have been working to develop molecular approaches for studying the promoter function of genes that are expressed specifically in the adult salivary glands of the yellow fever mosquito, Aedes aegypti. Genomic DNA fragments containing cis-acting promoter elements from the Maltase-like I (MalI) and Apyrase (Apy) genes were cloned so as to direct the expression of the reporter gene, luciferase (luc). The function of the promoters was assayed transiently in cultured insect cells and by germ-line transformation of Ae. aegypti. MalI and Apy DNA fragments consisting of at least 650 nucleotides (nt) of DNA immediately adjacent to the 5'-end of the initiation codon of the mosquito genes directed constitutive expression of the luc reporter gene in cultured cells. When introduced into Ae. aegypti chromosomes, approximately 1.5 kilobases (kb) of each promoter were able to direct the predicted developmental-, sex- and tissue-specific expression of the reporter gene in patterns identical to those determined for the respective endogenous genes.


VEGF at the neurovascular interface: therapeutic implications for motor neuron disease.
VEGF was discovered almost 25 years ago, and its angiogenic activity has been extensively studied ever since. Accumulating evidence indicates, however, that VEGF also has direct effects on neuronal cells. VEGF exerts neuroprotective effects on various cultured neurons of the central nervous system. In vivo, VEGF controls the correct migration of facial branchiomotor neurons in the developing hindbrain and stimulates the proliferation of neural stem cells in enriched environments and after cerebral ischemia. Transgenic mice expressing reduced levels of VEGF develop late-onset motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis (ALS), whereas reduced levels of VEGF have been implicated in a polyglutamine-induced model of motor neuron degeneration. Recent data further reveal that intracerebroventricular delivery of recombinant VEGF protein delays disease onset and prolongs survival of ALS rats, whereas intramuscular administration of a VEGF-expressing lentiviral vector increases the life expectancy of ALS mice by as much as 30%. Deciphering the precise role of VEGF at the neurovascular interface promises to uncover new insights into the development and pathology of the nervous system, helpful to design novel strategies to treat (motor) neurodegenerative disorders.


[Thalamic infarcts--clinical aspects, neuropsychological findings, prognosis].
Results of clinical investigations and CCT of 23 patients with thalamic infarctions were evaluated retrospectively. Nineteen patients underwent a clinical and 15 a neuropsychological examination one to 5 years after their stroke. Regarding the affected vascular territory, the patients were divided into the following subgroups: paramedian infarctions (posterior thalamo-subthalamic arteries, 13 patients, among them 5 bilateral infarcts); anterolateral infarcts (tuberothalamic arteries, 5 patients); posterolateral infarcts (thalamo-geniculate arteries, 5 patients). The leading symptoms of paramedian thalamic infarcts were disturbance of consciousness, amnesia and vertical gaze palsy. The patients with anterolateral thalamic infarctions became acutely confused and disorientated, whereas those with posterolateral infarcts suffered from focal neurological deficits in the first place. Five patients with leftsided thalamic infarctions of varying localization were aphasic. Two patients died within the observation period. A slight hemiparesis was detected in two patients and a vertical gaze palsy in 4, respectively, by the neurological reexamination one to 5 years after the stroke, whereas the clinical findings in 11 patients were completely normal. However 5 patients had a chronic psychosyndrome. The neuropsychological examination showed in some cases disorders of visual retention and verbal function as well as deficits in concentration. Neither the character nor the degree of the neuropsychological deficits did depend on the affected vascular territory but on the existence of further cerebral infarcts on CT-scan.


Gasification treatment of poplar biomass produced in a contaminated area restored using plant assisted bioremediation.
Remediation of polluted soils using phytoremediation techniques is an effective strategy. However, the use of the biomass from these soils for energy purposes may raise efficiency and pollution emission problems and there is currently little research on this issue. In this work, the main results of a fluidized-bed gasification treatment conducted on poplar biomass pruning residues from a multi-contaminated area are presented. The samples were collected from an experimental site in which a plant-assisted bioremediation (PABR) technology has been applied since 2013 to reduce the soil heavy metal (HM) and polychlorinated biphenyl (PCB) contents. The main goal of this study was to identify the specific treatment necessary, in addition to conventional tar reforming, for trapping possible residues of HMs and PCBs in ashes during the gasification process. In our study, we demonstrate that gasification of contaminated biomass coming from PABR (where contaminant residues are concentrated mainly in the roots and are insignificant in the shoots) produces syngas whose characteristics are similar to those obtained using non-contaminated biomass. The results showed that contaminant concentrations in the prunings were negligible; the total amount of PCBs was 1.63 ng/g, while HMs ranged from 0.01 to 0.70 mg/kg, except for Cu and Zn (∼20 mg/kg). Furthermore, the presence in the biomass of Ca and traces of other metals showed a possible catalytic effect with an improvement in the tar conversion in the gasifier leading to a reduction of 5-10% in tar content. The overall results suggest that a specific treatment for pollutant capture is necessary only when the roots, the part of the plants where these contaminants are concentrated, are sampled and used for the gasification process. Although energy from biomass produced on a contaminated site is currently considered waste and involves disposal costs, this paper shows that the poplar biomass grown on a multi-contaminated soil can be used for energy purposes without any impact on the environment.


Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury.
Necrosis and apoptosis differentially contribute to myocardial injury. Determination of the contribution of these processes in ischemia-reperfusion injury would allow for the preservation of myocardial tissue. Necrosis and apoptosis were investigated in Langendorff-perfused rabbit hearts (n = 47) subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25 (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion. Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9 cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD). The contribution of apoptosis was determined separately (n = 42) using irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed pressure (LVPDP) and systolic shortening (SS) were significantly decreased and infarct size and TUNEL-positive cells were significantly increased (P < 0.05 vs. Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD, and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of caspase-3 and -9 activity significantly decreased (P < 0.05) infarct size at GI-25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from a significant increase in both necrosis and apoptosis (P < 0.05 vs. Control group) evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic proapoptotic activation is evident early during ischemia but does not significantly contribute to infarct size before GI-25. The contribution of necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than that of apoptosis. Apoptosis is significantly decreased by caspase inhibition during early reperfusion, but this protection does not improve immediate postischemic functional recovery.


Rap G protein signal in normal and disordered lymphohematopoiesis.
Rap proteins (Rap1, Rap2a, b, c) are small molecular weight GTPases of the Ras family. Rap G proteins mediate diverse cellular events such as cell adhesion, proliferation, and gene activation through various signaling pathways. Activation of Rap signal is regulated tightly by several specific regulatory proteins including guanine nucleotide exchange factors and GTPase-activating proteins. Beyond cell biological studies, increasing attempts have been made in the past decade to define the roles of Rap signal in specific functions of normal tissue systems as well as in cancer. In the immune and hematopoietic systems, Rap signal plays crucial roles in the development and function of essentially all lineages of lymphocytes and hematopoietic cells, and importantly, deregulated Rap signal may lead to unique pathological conditions depending on the affected cell types, including various types of leukemia and autoimmunity. The phenotypical studies have unveiled novel, even unexpected functional aspects of Rap signal in cells from a variety of tissues, providing potentially important clues for controlling human diseases, including malignancy.


Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes.
Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of "insulin provision" versus "insulin sensitization" among patients with CAD remains unclear. To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD.


In vivo electrophysiology of dopamine-denervated striatum: focus on the nitric oxide/cGMP signaling pathway.
Within the striatum, the gaseous neurotransmitter nitric oxide (NO) is produced by a subclass of interneurons containing the neuronal NO synthase (nNOS). NO promotes the second messenger cGMP through the activation of the soluble guanyl cyclase (sGC) and plays a crucial role in the integration of glutamate (GLU) and DA transmission. The aim of this study was to characterize the impact of 6-hydroxyDA (6-OHDA) lesion of the rat nigrostriatal pathway on NO/cGMP system. In vivo extracellular single units recordings were performed under urethane anesthesia to avoid any potentially misleading contributions of cortically-driven changes on endogenous NO. Hence, no electrical extrastriatal stimulation was performed and great attention was paid to the effects of 3-morpholinosydnonimine (SIN-1, a NO donor), N(G)-nitro-L-arginine methyl ester (L-NAME, a nonselective NOS inhibitor) and Zaprinast (a PDE inhibitor) delivered by iontophoresis upon the main striatal phenotypes. The latter were operationally distinguished in silent medium spiny-like neurons (MSN), with negligible spontaneous activity but displaying glutamate-induced firing discharge at rest and spontaneously active neurons (SAN), representing to a large extent nonprojecting interneurons. SANs were excited by SIN-1 and Zaprinast while MSNs showed a clear inhibition during local iontophoretic application of SIN-1 and Zaprinast. In 6-OHDA animals, SIN-1-induced excitation in SANs was significantly increased (on the contrary, the inhibitory effect of L-NAME was less effective). Interestingly, in DA-denervated animals, a subclass of MSNs (40%) displayed a peculiar excitatory response to SIN-1. These findings support the notion of an inhibitory modulatory role exerted by endogenous NO on control striatal projection cells. In addition, these findings suggest a functional cross-talk between NO, spontaneously active interneurons, and projection neurons that becomes critical in the parkinsonian state.


[Effects of flutropium bromide, a new antiasthma drug, on mediator release from mast cells and actions of mediators].
The effects of flutropium bromide (Ba598Br), a new antiasthma drug possessing the quarternary ammonium structure of atropine derivatives, on mediator release from mast cells and on actions of leukotriene (LT) D4 and serotonin were investigated. Flutropium bromide (3 and 10 mg/kg, i.v.) showed an inhibitory action on the 48 hr homologous PCA in guinea pigs. Atropine showed no inhibitory effect. Flutropium bromide also inhibited the release of histamine from isolated rat mast cells stimulated by antigen, although the inhibitory action was weaker than that of disodium cromoglycate. Atropine also had no inhibitory action in this case. Flutropium bromide and atropine showed no antagonistic action against LTD4-induced contraction of isolated tracheal smooth muscle of guinea pigs. Inhalation of flutropium bromide (0.3%) also showed no antagonistic action against serotonin-induced bronchoconstriction in dogs. From the above results, it is indicated that flutropium bromide has a weak mast cell stabilizing action, but no antagonistic action against LTD4 and serotonin.


Circulating sperm-agglutinating antibodies in azoospermic men with congenital bilateral absence of the vasa deferentia.
Congenital bilateral absence of the vasa deferentia has been found to be the cause for azoospermia in 101 patients who have been examined in our urologic practice since 1956. This represents approximately 2% of the 5112 patients seen during that time because of problems relating to infertility. Of these 101 men, 29 have had their sera tested for the presence of circulating sperm-agglutinating antibodies. The Shulman15 modification of the macroscopic gelatin sperm-agglutination test of Kibrick et al6 was used. None of these patients had had testicular biopsy. Significantly high titers (1:32 or greater) of antibodies were found in 18 (62.1%) men, low titers (1:16 or less) in five (17.2%), and no antibodies in six (20.7%).


Clinical applications of real-time PCR for diagnosis and treatment of human cytomegalovirus infection in children.
There are many methods of detecting human cytomegalovirus (HCMV) infection. So far, the quantitative polymerase chain reaction (PCR) has been very useful not only in aiding in the diagnosis of HCMV but also in determining the severity and predicting HCMV infection. However, it is time-consuming and labor intensive. Real-time PCR (RT-PCR) is an exception, for it allows rapid quantification of HCMV DNA load. Our group used this method for detecting and monitoring HCMV and compared it with the diagnostic criterion recommended by the Pediatric Branch of Chinese Medical Association, in 45 children suspected of having HCMV infection. The response to two types of antiviral treatment on HCMV DNA load was also monitored in HCMV hepatitis cases. RT-PCR was positive in 30 cases while the diagnostic criterion, which includes enzyme-linked immunosorbent assay (ELISA) and/or conventional PCR, was positive in 32 cases. The decrease in the HCMV DNA load was achieved earlier in the modified treatment group compared with the conventional treatment group. A 10(3) copies/ml of HCMV DNA load of is a useful cut-off value in predicting patients who will have symptoms of the disease. RT-PCR can be used not only in detecting HCMV but also in monitoring response to antiviral treatment and risk of having symptoms of the disease.


Image-guided sinus surgery: practical considerations.
The availability and use of image-guidance systems for sinus surgery will probably continue to increase in the years ahead. Surgeons who use this technology must do so with an appreciation of its potential benefits, as well as its possible pitfalls.


Conformational analysis of the single-stranded ribonucleic acid A-A-C-C. A one-dimensional and two-dimensional proton NMR study at 500 MHz.
Proton NMR studies at 300 MHz and 500 MHz are reported on the ribotetranucleotide A-A-C-C. The complete 1H-NMR spectral assignment at 20 degrees C is given. Two-dimensional NMR was used to elucidate spin multiplets in 'crowded' regions. Nuclear Overhauser enhancement (NOE) experiments made an unambiguous spectral assignment possible and yielded information on interproton distances. The N/S equilibrium of the riboses and the rotamer populations around some backbone torsion angles are presented. A large preference for N-type ribose and gamma+ and beta t backbone torsions is observed, in particular in the central A-C unit of A-A-C-C. Information on distances between protons of different nucleotide units, obtained from NOE experiments, constitutes a probe of base-base stacking. It is concluded that A-A-C-C offers a good model for RNA single-strand conformation.


Structural validity and reliability of the Positive and Negative Affect Schedule (PANAS): evidence from a large Brazilian community sample.
Positive and negative affect are the two psychobiological-dispositional dimensions reflecting proneness to positive and negative activation that influence the extent to which individuals experience life events as joyful or as distressful. The Positive and Negative Affect Schedule (PANAS) is a structured questionnaire that provides independent indexes of positive and negative affect. This study aimed to validate a Brazilian interview-version of the PANAS by means of factor and internal consistency analysis. A representative community sample of 3,728 individuals residing in the cities of São Paulo and Rio de Janeiro, Brazil, voluntarily completed the PANAS. Exploratory structural equation model analysis was based on maximum likelihood estimation and reliability was calculated via Cronbach's alpha coefficient. Our results provide support for the hypothesis that the PANAS reliably measures two distinct dimensions of positive and negative affect. The structure and reliability of the Brazilian version of the PANAS are consistent with those of its original version. Taken together, these results attest the validity of the Brazilian adaptation of the instrument.


Effects of neurogenic bladder dysfunction in utero seen in neonates with myelodysplasia.
Twenty neonates with myelodysplasia were prospectively evaluated during the first month of life with urodynamic studies, contrast voiding cystourethrograms (VCUG) and renal ultrasound scans. Ten of 20 infants had abnormal VCUGs--6 with vesicoureteric reflux (VUR) and 4 with bladder trabeculation alone. Only 2/20 neonates had abnormal ultrasounds--both with hydroureteronephrosis secondary to VUR. Elevated leak point pressure (LPP) and/or detrusor sphincter dyssynergia (DSD) were present in 10/20 infants--6 with elevated LPP and DSD, 3 with elevated LPP alone and 1 with DSD alone. Eight of 10 neonates with DSD or elevated LPP had abnormal VCUGs--4 with VUR and 4 with bladder trabeculation alone. Conversely, 8/10 neonates without DSD or elevated LPP had normal VCUGs. Contrast VCUG performed shortly after birth, therefore, is essential for the discovery of bladder trabeculation and reflux. There is a strong correlation between an abnormal VCUG and the presence of DSD and elevated LPP, suggesting that neurogenic bladder dysfunction in utero can lead to these structural abnormalities.


Development and immunogenicity of recombinant Mycoplasma gallisepticum vaccine strain ts-11 expressing chicken IFN-gamma.
Mycoplasma gallisepticum (MG) is a poultry pathogen that causes respiratory disease and loss of egg production worldwide. A live attenuated vaccine, ts-11, has been used for the control of MG in several countries. To improve the functionality of the vaccine and investigate its potential as a delivery vector for host immune molecules and foreign antigens, we have developed ts-11 as a vector to express and secrete chicken IFN-gamma (ts-11 C3) using a transposon-based delivery vector. Following administration of ts-11 C3 in chickens by eye drop, up to 2 weeks post-vaccination, neither significant systemic IFN-gamma expression nor an antibody response as determined by the rapid serum agglutination (RSA) could be detected, while moderate RSA scores were detected in birds vaccinated with ts-11. However, the MG-specific IFN-gamma response in spleen cultures was significantly enhanced in ts-11 C3 vaccinated chickens and, more interestingly, significant heterophil infiltration was detected in the tracheal epithelium in ts-11 C3 vaccinated birds, but not in ts-11 vaccinated birds. These results indicate that the IFN-gamma expressed by ts-11 C3 enhanced host cellular immunity rather than humoral immunity and may also have stimulated mucosal heterophil infiltration. These results also suggest that ts-11 is a promising vector for protective antigens of other chicken respiratory pathogens.


Docetaxel in the management of ovarian cancer.
Standard first-line treatment for Stage IC-IV ovarian cancer is currently a platinum agent or a combination of a platinum agent with a taxane. The use of a taxane compound in addition to single-agent platinum is increasingly preferred to platinum alone. In countries such as the UK, the taxane paclitaxel has been approved by the government for first-line use. However, it has yet to receive US Food and Drug Administration approval in the USA for use in this context. Typically, in countries such as the UK, patients with advanced ovarian cancer receive a combination of paclitaxel and carboplatin first line, both drugs given 3-weekly by intravenous infusion. Subsequent trials have demonstrated that the second-generation taxane docetaxel can be used as a substitute for paclitaxel; sharing many of its actions but with a different toxicity profile. However, docetaxel has not yet received approval for standard use. Here, the clinical development of docetaxel and its present and future place in the management of ovarian cancer is discussed.


Effects of non-steroidal anti-inflammatory drugs on demineralized bone-induced bone formation.
The inhibitory effect of some non-steroidal anti-inflammatory drugs (NSAIDs) on bone resorption is well documented. To explore the effect of NSAIDs on bone formation, we investigated the time course and dose/response characteristics of treatment with various non-steroidal anti-inflammatory drugs (NSAIDs) on ectopic bone formation induced by demineralized bone matrix (DBM) in the rat model. Using biochemical assays, both inhibitory and stimulatory effects on bone formation were found in rats treated with NSAIDs prior to DBM implantation depending on the type and amount of drug administered. There appears to be an enhancement of bone formation for acetaminophen (50 mg/kg), acetylsalicylic acid (50 mg/kg), and ibuprofen (50 mg/kg). Indomethacin (4 mg/kg) and piroxicam (4 mg/kg) had inhibitory effects. Flurbiprofen, on the other hand, did not appear to affect bone formation significantly. In contrast, there was no effect of NSAIDs on bone formation in rats treated with the drugs after implantation of the DBM. It appears that the time course of the drug administration is critical, suggesting that early events in bone formation may be modulated by arachidonic acid metabolites.


[Systemic and regional hemodynamics during audiogenic convulsions in rats genetically epilepsy-prone].
Changes in systemic and regional hemodynamic during sound-induced convulsions were measured with microsphere technique in genetically epilepsy-prone rats of Krushinsky-Molodkina (KM-rats) strain. Blood pressure increased from 103 till 178 mm Hg and cardiac index rose from 27.3 till 49.3 ml/min/100 g b. w. during convulsions. Blood flow was increased in the brain and in the heart by 140-700%, whereas in most of internal organs it was decreased by 40-94%.


[Experimental study on the quality of projective picture material].
This paper empirically evaluates a series of photographs that have been used successfully by J.E. Meyer in a recent contribution. Nine photographs we selected which significantly arouse emotional reactions in patients. They are intended to find a wider field of application and to stimulate the discussion on projective methods.


Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography.
Electrical impedance tomography measures changes in lung impedance, which are mainly related to changes in lung volume. We used electrical impedance tomography to investigate the effects of high-flow nasal cannula (HFNC) and body position on global and regional end-expiratory lung impedance variation (ΔEELI). Prospective study with 20 healthy adults. Two periods were defined: the first in supine position and the second in prone position. Each period was divided into 3 phases. In the first and the third phases the subjects were breathing ambient air, and in the second HFNC was implemented. Four regions of interest were defined: 2 ventral and 2 dorsal. For each respiratory cycle, global and regional ΔEELI were measured by electrical impedance tomography and were expressed as a function of the tidal variation of the first stable respiratory cycle (units). HFNC increased global EELI by 1.26 units (95% CI 1.20-1.31, P < .001) in supine position, and by 0.87 units (95% CI 0.82-0.91, P < .001) in prone position. The distribution of ΔEELI was homogeneous in prone position, with no difference between ventral and dorsal lung regions (-0.01 units, 95% CI -0.01 to 0, P = .18), while in supine position a significant difference was found (0.22 units, 95% CI 0.21-0.23, P < .001) with increased EELI in ventral areas. HFNC increased global EELI in our population, regardless of body position, suggesting an increase in functional residual capacity. Prone positioning was related to a more homogeneous distribution of ΔEELI, while in supine position ΔEELI was higher in the ventral lung regions.


Impact of elevated CO2 on grain nutrient concentration varies with crops and soils - A long-term FACE study.
The impact of elevated CO2 (eCO2) on grain nutrient concentration is becoming a global concern in terms of future human nutrition. Previous research has shown that eCO2 can alter the availability and uptake of nutrients in crops. However, the interactive effects of long-term eCO2 and soil types on the concentrations of nutrients in grain are poorly understood. By understanding such effects, we are able to develop management practices that maintain grain nutritional quality while improving crop yield in response to future climatic conditions. We conducted a seven-year experiment of free air CO2 enrichment (FACE) with a rotation of wheat, field pea and canola grown in a Chromosol (Luvisol), Vertosol (Vertisol) and Calcarosol (Calcic Xerosol) under ambient CO2 (aCO2) (390 ± 10 μmol mol-1) or eCO2 (550 ± 30 μmol mol-1). The concentration and amount of five macro- and four micro-nutrients in grain over the seven years were determined. Compared to aCO2, the concentrations of N, P and Zn decreased by 6%, 5% and 10% under eCO2, respectively, irrespective of soil, crop and year. A greater decrease in N concentration was found in canola and wheat compared to field pea. The reduction in P and Mg concentration of canola was significant in Chromosol, but not in the Vertosol nor Calcarosol soils. The concentrations of K, Fe, Mn and Cu were not affected by eCO2 in any crop grown in the soils tested. Furthermore, eCO2 significantly decreased soil labile N and P and exchangeable Mg and Cu due to greater nutrient uptake, which was in part ascribed to the decreased nutrient accumulation in crop grains. It appears that eCO2 lowers the nutritional quality (nutrient concentration) in grains of non-legume crops, and that the extent of this decrease was greater in relatively fertile than infertile soils.


Paracrine interactions of mammalian adipose tissue.
Adipose tissue develops in and/or around most lymphoid tissues in mammals and birds. Early reports of this widespread association and hypotheses for its functional basis were long ignored in the planning of in vitro studies and the interpretation of in vivo results. Biochemical studies on rodent tissues reveal many site-specific properties of adipocytes anatomically associated with lymph nodes and omental milky spots that equip them to interact locally with lymphoid cells. The paracrine interactions are strongest for the most readily activated lymph nodes and are modulated by dietary lipids. Perinodal adipocytes contribute less than those in the large nodeless depots to whole-body lipid supplies during fasting. Observations on wild animals show that perinodal adipose tissue is selectively conserved even in starvation but does not enlarge greatly in natural obesity. Such paracrine provisioning of peripheral immune responses improves their efficiency and emancipates activated lymphocytes from competition with other tissues for blood-borne nutrients. The relationship is found in extant protherians and metatherians, so it almost certainly arose early in the evolution of mammals, possibly as part of the metabolic reorganisation associated with homeothermy, viviparity, and lactation. Prolonged disruption to paracrine interactions between lymphoid and adipose tissue may contribute to the HIV-associated adipose redistribution syndrome, causing selective hypertrophy of the mesentery, omentum, and other adipose depots that contain much activated lymphoid tissue. Skeletal and cardiac muscle may also have paracrine relationships with anatomically associated adipose tissue, but interactions between contiguous tissues have not been demonstrated directly.


Chronic kidney disease and cardiovascular complications.
Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias and sudden cardiac death represent main causes of morbidity and mortality in patients with chronic kidney disease (CKD). Pathogenesis includes close linkage between heart and kidneys and involves traditional and non-traditional cardiovascular risk factors. According to a well-established classification of cardiorenal syndrome, cardiovascular involvement in CKD is known as "type-4 cardiorenal syndrome" (chronic renocardiac). The following review makes an overview about epidemiology, pathophysiology, diagnosis and treatment of cardiovascular complications in CKD patients.


Immunogenicity, safety, and memory of different schedules of Neisseria meningitidis A/C-diphtheria toxoid conjugate vaccine in infants in Niger.
We studied one to four doses of meningococcal polysaccharides A and C conjugated to diphtheria toxoid (Men D) versus A/C polysaccharide (Men PS) vaccine in 618 infants in Niger. Men PS at 24 months permitted evaluating memory. Two Men D doses (at 3 and 9 months) induced higher serum bactericidal activity (SBA) than other regimens. SBA titers after Men PS at 24 months were higher in those given Men D in infancy versus Men PS. While responses were lower for serogroup C, hyporesponsiveness was not evident. Men D was well-tolerated. A single Men D dose in infancy appeared to induce memory.


The effect of a combination of zindoxifene and cisplatin on Dunning R3327-G prostatic carcinomas of the rat.
Endocrine therapy of hormone-dependent prostatic carcinomas can be very effective at the beginning. However, tumour growth eventually resumes possibly because of the presence of androgen-independent cell clones. Addition of a cytotoxic agent to the hormonally active drug at an early stage could possibly delay progression of disease. Therefore, we studied the effects of hormonal and cytostatic treatment in a rat prostate carcinoma model: freshly transplanted Dunning R3327-G prostatic tumours of the rat were treated with the partial antioestrogen zindoxifene and cisplatin alone and in combination. In addition we tested a 2-phenylindole-linked platinum complex 3-PtCl2, which contains both effective functions. This particular complex had only a weak non-significant inhibitory effect on tumour growth. Comparing monotherapies with zindoxifene or cisplatin at various dose levels with the corresponding combinations, it became evident that the latter treatment was significantly more effective than the use of single agents. A very low dose of 0.4 mg cisplatin together with 2 mg/kg zindoxifene inhibited tumours by 91%, which was close to the effects of castration or diethylstilbestrol (1 mg). The analyses of accessory sex organs revealed much weaker oestrogenic side-effects than those observed with diethylstilbestrol at an equivalent dose. These results demonstrated that it is possible to increase the efficacy of hormonal therapy of prostatic carcinomas by concomitant administration of cisplatin and reduce side-effects of oestrogenic drugs.


Longing for existential recognition: a qualitative study of everyday concerns for people with somatoform disorders.
Patients with somatoform disorders could be vulnerable to stressors and have difficulties coping with stress. The aim was to explore what the patients experience as stressful and how they resolve stress in everyday life. A cross-sectional retrospective design using 24 semi-structured individual life history interviews. Data-analysis was based on grounded theory. A major concern in patients was a longing for existential recognition. This influenced the patients' self-confidence, stress appraisals, symptom perceptions, and coping attitudes. Generally, patients had difficulties with self-confidence and self-recognition of bodily sensations, feelings, vulnerability, and needs, which negatively framed their attempts to obtain recognition in social interactions. Experiences of recognition appeared in three different modalities: 1) "existential misrecognition" covered the experience of being met with distrust and disrespect, 2) "uncertain existential recognition" covered experiences of unclear communication and a perception of not being totally recognized, and 3) "successful existential recognition" covered experiences of total respect and understanding. "Misrecognition" and "uncertain recognition" related to decreased self-confidence, avoidant coping behaviours, increased stress, and symptom appraisal; whereas "successful recognition" related to higher self-confidence, active coping behaviours, decreased stress, and symptom appraisal. Different modalities of existential recognition influenced self-identity and social identity affecting patients' daily stress and symptom appraisals, self-confidence, self-recognition, and coping attitudes. Clinically it seems crucial to improve the patients' ability to communicate concerns, feelings, and needs in social interactions. Better communicative skills and more active coping could reduce the harm the patients experienced by not being recognized and increase the healing potential of successful recognition.


Comparative randomized study on the efficaciousness of treatment of BOO due to BPH in patients with prostate up to 100 gr by endoscopic gyrus prostate resection versus open prostatectomy. Preliminary data.
With the advent of medical management and minimally techniques for benign prostate hypeplasia (BPH), invasive surgical procedures such open prostatectomy (OPSU) have become less common, although selected patients may still benefit from open prostatectomy. Aim of this study was to evaluate efficacy and safety of Bipolar TURP (Gyrus electro surgical system) versus standard open prostatectomy in patients with lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO) with markedly enlarged glands refractory to medical therapy. From January 2003 to January 2004, 140 patients affected by mild-severe LUTS, secondary to BOO from BPH, refractory to medical therapy, with markedly enlarged glands, were randomized in two groups (1:1), and subjected to open prostatectomy (OPSU) carried out with traditional method (Bracci Thechnique) versus transurethral resection of the prostate (TURP) utilizing the bipolar methodology. Preoperative work-up included IPSS, IIEF-5 and Qol questionnaires. All patients were submitted to uroflowmetry, transrectal ultrasound (TRUS), measurament of postvoidal residual urine and PSA determination. IPSS, IIEF-5 and Qol, uroflowmetry, TRUS, measurement of post-voidal residual urine, PSA determination and number of reoperations were evaluated at 1, 3, 6, 12, 18, 24, 30 and 36 months. Operative time, resected tissue weight and perioperative complications were also registered. Total post-operative catheter time, total postoperative hospital stay, haemoglobin loss were recorded in the 2 groups. Comparative data on IPSS symptom score, IIEF-5 and Qol, PSA, peak urinary flow rates and post-void residual urine volume in the 2 groups were similar but showed a significative improvement with respect to baseline value. Postoperative haemoglobin levels, postoperative catheterization, hospital stay and 3-yr overall surgical re-treatment-free rate were significantly better in the Bipolar group. In the treatment of LUTS due to bladder outlet obstruction (BOO) with markedly enlarged glands refractory to medical therapy, Bipolar TURP has a comparable outcome to open prostatectomy at short and medium term according to both subjective and objective outcome measures.


[Synthesis of Circular DNA Templates with T4 RNA Ligase for Rolling Circle Amplification].
Currently, isothermal methods of nucleic acid amplification have been well established; in particular, rolling circle amplification is of great interest. In this approach, circular ssDNA molecules have been used as a target that can be obtained by the intramolecular template-dependent ligation of an oligonucleotide C-probe. Here, a new method of synthesizing small circular DNA molecules via the cyclization of ssDNA based on T4 RNA ligase has been proposed. Circular ssDNA is further used as the template for the rolling circle amplification. The maximum yield of the cyclization products was observed in the presence of 5-10% polyethylene glycol 4000, and the optimum DNA length for the cyclization constituted 50 nucleotides. This highly sensitive method was shown to detect less than 10^(2) circular DNA molecules. The method reliability was proved based on artificially destroyed dsDNA, which suggests its implementation for analyzing any significantly fragmented dsDNA.


Asymmetric dimethylarginine concentration and early recurrence of atrial fibrillation after electrical cardioversion.
The purpose of this study was to determine whether high asymmetric dimethylarginine (ADMA) levels could predict early recurrence of atrial fibrillation (AF) after successful electrical cardioversion (CV). Seventy patients with persistent AF, but without known heart disease, who underwent elective electrical CV were enrolled. Blood samples for ADMA determination were drawn from all patients just before the CV. The study population comprised 64 patients (men 73%, age 62.56 +/- 7.72 years, duration of AF 6.00 +/- 1.90 months) in whom sinus rhythm was restored. After 1-month follow-up, 30 (47%) patients had recurrence of AF. The median ADMA concentration was significantly higher in patients with AF recurrence (1.93 micromol/L vs 1.43 micromol/L; P = 0.001). AF recurrence was associated with higher pre-CV ADMA levels (odds ratio [OR]= 4.20; 95% confidence interval [CI], 1.44-12.22; P = 0.001). On multivariate analysis, ADMA was the only independent predictor of arrhythmia recurrence (OR = 4.19; 95%CI, 1.12-15.77; P = 0.034). Our data suggest that high levels of ADMA are associated with an increased risk of AF recurrence within 1 month after electrical CV, supporting the hypothesis that ADMA might participate in the process of atrial remodeling.


Fully automatic exposed and in-syringe dynamic single-drop microextraction with online agitation for the determination of polycyclic musks in surface waters of the Pearl River Estuary and South China Sea.
An automatic exposed and in-syringe dynamic single-drop microextraction method (SDME) for the determination of five polycyclic musks in natural waters was developed using gas chromatography with mass spectrometry. Online agitation was first introduced to the automatic SDME with a magnetic mixer fixed to the bottom of the sample tray of the autosampler. A high enrichment factor (110 ∼182) for the target analytes could be achieved after several parameters that affected the microextraction were optimized. The recoveries were between 84.9 and 119.5%, while the limit of detection ranged from 3.4 to 11 ng/L with relative standard deviation < 11.1% for the polycyclic musks. This new SDME mode is fully automatic with great convenience, high enrichment and good reproducibility, and no human intervention. The proposed method was, therefore, successfully applied to determine the polycyclic musks in 31 surface sea waters that were collected from the Pearl River Estuary and the South China Sea. Most polycyclic musks could be detected with the total concentrations ranging from 58.9 to 528.5 ng/L. By using spatial interpolation method of ordinary kriging, the most contaminated area was found near the cities of Dongguan and Guangzhou with local discharge via the major rivers.