Levels of persistent organic pollutants (POPs) in a coastal northern Norwegian population with high fish-liver intake.
Recent research has again raised the issue regarding the potential health effects of long term exposure to persistent organic pollutants (POPs) in the context of a risk-benefit analysis. There remains clear evidence of the beneficial effects of fish consumption on public health and in particular fatty fish with its essential fatty acids. In addition to providing fatty acids, fish fat constitutes an essential source to vitamin D for the northern Norwegian population. Norwegian Food Control Authorities have recommended that children and women of childbearing age should not consume fish liver due to the risk associated with high intake of POPs. The aim of this study was to assess the influence of fish liver intake on the levels of PCBs and chlorinated pesticides in a rural coastal community (n = 31) in northern Norway, applying a cross-sectional design. The geometric mean plasma levels of sum of PCBs (14 congeners) and p,p'-DDE was found to be 558 microg kg(-1) lipids and 179 microg kg(-1) lipids, respectively. These levels were not significantly affected by the reported intake of fish liver, when age and gender were considered. Age in particular, but also gender were significant predictors for most compounds. When merging the dataset with an urban population with considerable lower intake of fish liver, the intake of cod liver still did not significantly affect the levels of PCBs and p,p'-DDE when adjusted for age and gender. Age and gender remain the strongest predictors of plasma levels of POPs in this study whereas fish liver intake was not significantly associated with the POPs.


[Tyndalization by gamma rays. Preliminary esperiments on grape].
The analysis of rot in two grape cultivars ("Moscato bianco" and "Favorita") has shown that the most effective gamma rays dose which pasteurizes fruit pulp with little or no damages is about 180-200 Kr. if administered divided into three fractions, the irradiated sample is less affected by infections (P = 0.01) then the 100 Kr or control samples. On the opposite, no difference between various doses could be detected when gamma rays are administered all at once.


Efficient Cu-catalyzed asymmetric conjugate additions of alkylzinc reagents to aromatic and aliphatic acyclic nitroalkenes.
An efficient and highly enantioselective (up to 95% ee) Cu-catalyzed method for asymmetric conjugate addition (ACA) of alkylzinc reagents to acyclic disubstituted nitroalkenes is presented. Reactions are typically effected at ambient temperature in the presence of 2 mol % chiral dipeptide phosphine and 1 mol % (CuOTf)(2).C(6)H(6). Nitroalkenes bearing aromatic as well as aliphatic substituents readily undergo asymmetric additions. [reaction: see text]


Dietary restraint and stress-induced snacking in youth.
To determine whether dietary restraint modifies stress-induced eating in youth. Snacking was measured in boys (9.5 +/- 0.3 years) and girls (9.0 +/- 0.3 years), with and without dietary restraint, across a control day after reading children's magazines and/or coloring, and on a stress day after giving a videotaped speech, with order of conditions counterbalanced. Children were divided into four groups based on dietary restraint and changes in perceived stress: low-restraint/low-reactive (n = 9), low-restraint/high-reactive (n = 13), high-restraint/low-reactive (n = 10), and high-restraint/high-reactive (n = 8). Body composition was estimated by skinfolds. Energy intake of snack foods was influenced differently by dietary restraint and stress reactivity in the stress and control conditions (p < 0.01). After being stressed, low-restraint/low-reactive children ate fewer snacks and high-restraint/high-reactive children ate more snacks compared with the control condition. After covarying for percentage of body fat, the interactions remained (p < 0.01). Girls ate less than boys (p < 0.001), but sex did not influence eating in control and stress conditions. Dietary restraint occurs in children and may influence the effect of stress on eating. Interpersonal stress decreases snacking in low dietary restrained youth but increases snacking in high dietary restrained children, perhaps because of stress-induced disinhibition.


The usefulness of central motor conduction studies in the localization of cord involvement in cervical spondylytic myelopathy.
Cervical spondylytic myelopathy (CSM) is common. Magnetic resonance imaging (MRI), although sensitive, often reveals extensive and sometimes clinically irrelevant findings. The purpose of this study was to investigate the usefulness of central motor conduction studies in localizing the rostral level of cord involvement in 6 patients with CSM. Central motor conduction was assessed using high-voltage stimulation for the spinal roots and magnetoelectrical stimulation for the motor cortex, recording from "marker muscles" innervated by successively higher cervical cord segments. Abnormal central motor conduction affected all subjects at C8-T1, 5 subjects at C7, but none at the C5-C6 levels. The MRI showed abnormalities at multiple levels as high as C4. Our results suggest that central motor conduction studies are helpful in localizing the clinically relevant levels of spinal cord compression in CSM and correlate well with motor abnormalities on clinical examination.


Proteomic strategies in bladder cancer: From tissue to fluid and back.
We have applied protein expression profiling technologies in combination with immunohistochemistry, using fresh tissue and urine samples, to assess bladder cancer heterogeneity and prognosis as well as to generate protein markers for tumor progression and early diagnosis of the disease. Here, we review some selected lines of investigation and approaches undertaken by our laboratory, drawing on more than 15 years of experience in bladder cancer proteomics, to highlight a number of issues that may be useful for researchers entering the field. In particular, we address the identification of markers for bladder cancer progression and exemplify the potential of gel-based proteomic profiling of urine samples for the early detection of urothelial carcinomas. In addition, we provide a brief description of a novel and highly promising source of biomarkers, the tumor interstitial fluid (TIF) that perfuses the tumor microenvironment.


Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2 years.
The recently developed technique for peroral endoscopic myotomy (POEM) has been shown to be effective in several short-term studies. Longer term outcome data are largely non-existent. To systematically report clinical outcome with a minimum post-POEM follow-up of 2 years. All patients treated consecutively by POEM for achalasia at three centres were retrospectively analysed, with a minimum follow-up of 2 years. The main outcome was the rate of POEM failures (Eckardt score >3) related to follow-up time. Of 85 patients treated, five (5.9%) cases were excluded due to protocol violation or loss to follow-up; the remaining 80 patients (mean age 44.9 years, 54% men) were followed clinically for 29 months (range 24-41). Initial clinical response was observed in 77 cases (96.3%). Clinical recurrences (later failures) were seen in a further 14 cases (17.7%), accounting for a total failure rate of 21.5%. In a multivariate analysis, age and endoscopic reflux signs were independent predictors of treatment success. Of the 17 failures, eight were among the first 10 cases treated in the participating centres. Reflux-associated sequelae included one case of a severe reflux-associated stricture requiring dilatation, and two patients with minor transient Eckardt score elevations curable by proton pump inhibitor (PPI) treatment. Endoscopic signs of reflux oesophagitis, mostly Los Angeles grade A/B, were seen in 37.5% (37/72) at the 2-year control. In this multicentre retrospective analysis, a high initial success rate of POEM is followed by a mid-term recurrence rate of 18%. Reflux oesophagitis, albeit mild, is frequent and should probably be treated by regular low-dose PPI therapy. NCT 01405417 (UKE study).


Epidemiological inference for partially observed epidemics: the example of the 2001 foot and mouth epidemic in Great Britain.
This paper develops a statistical framework for a retrospective analysis for well-observed livestock epidemics during which intervention policies may conceal cases, thus potentially biasing naively derived parameter and final size estimates. We apply the methods to the 2001 foot and mouth epidemic (FMD) in Great Britain, during which a large number of farms (about 7500) were pre-emptively culled as part of the control effort without ever being diagnosed as being infected. We infer farm-level infectivity and susceptibility parameters, a distribution for the delay from infection to report, together with a time varying farm infectivity profile for farms. Hidden infections among proactively culled farms were accounted for using a data augmentation approach utilising reversible jump MCMC methods. Simulated epidemics derived using the parameter estimates obtained reproduced the 2001 epidemic well. Our analysis demonstrates that time-varying infectivity profiles fit the 2001 data better than naive assumptions of constant infectiousness. We estimate that around 210 (or 2.8%) of the farms proactively culled in the 2001 epidemic were infected. However, for the parameter estimated obtained, preliminary simulation results indicate that had contiguous culling not been applied in 2001, the epidemic might have been substantially larger.


Value of dobutamine echocardiography for the assessment of myocardial viability for revascularization.
Coronary artery disease accounts for a majority of heart failure cases in the western world. Many cardiologists believe that abnormal regional contractions in patients with coronary artery disease is equivalent to irreversibly damaged myocardium. Studies now challenge this long-held assumption. Data exist regarding the value of assessing myocardial viability in those patients with severe left ventricular dysfunction and coronary artery disease. This report discusses dobutamine echocardiography as a technique for assessing myocardial viability and for selecting patients for revascularization. (c)2001 by CHF, Inc.


Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment.
Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF.


Association between anxiety and severe quality-of-life impairment in postmenopausal women: analysis of a multicenter Latin American cross-sectional study.
To evaluate associations between anxiety and severe impairment of quality of life (QoL) in Latin American postmenopausal women. This was a secondary analysis of a multicenter cross-sectional study among postmenopausal women aged 40 to 59 from 11 Latin American countries. We evaluated anxiety (The Goldberg Depression and Anxiety Scale), and QoL (Menopause Rating Scale [MRS]), and included sociodemographic, clinical, lifestyle, and anthropometric variables in the analysis. Poisson family generalized linear models with robust standard errors were used to estimate prevalence ratios (PRs) and 95% CIs. There were two adjusted models: a statistical model that included variables associated with the outcomes in bivariate analyses, and an epidemiologic model that included potentially confounding variables from literature review. Data from 3,503 women were included; 61.9% had anxiety (Goldberg). Severe QoL impairment (total MRS score ≥17) was present in 13.7% of women, as well as severe symptoms (MRS subscales): urogenital (25.5%), psychological (18.5%), and somatic (4.5%). Anxiety was independently associated with severe QoL impairment and severe symptoms in the epidemiological (MRS total score: PR 3.6, 95% CI, 2.6-5.0; somatic: 5.1, 95% CI, 2.6-10.1; psychological: 2.8, 95% CI, 2.2-3.6; and urogenital: 1.4, 95% CI, 1.2-1.6) and the statistical model (MRS total score: PR 3.5, 95% CI, 2.6-4.9; somatic: 5.0, 95% CI, 2.5-9.9; psychological: 2.9, 95% CI, 2.2-3.7; and urogenital: 1.4; 95% CI, 1.2-1.6). In this postmenopausal Latin American sample, anxiety was independently associated with severe QoL impairment. Hence, screening for anxiety in this population is important.


MicroRNA-17 family as novel biomarkers for cancer diagnosis: a meta-analysis based on 19 articles.
Cancer remains as the leading cause of death all over the world due to the lack of efficient diagnostic techniques and therapeutic methods. Many studies have reported the potential diagnostic value of microRNA-17 (miRNA-17, miR-17) family members as biomarkers for cancer detection. However, inconsistent results were revealed from a wide range of studies. As a result of this, a meta-analysis based on 19 studies was conducted to assess the diagnostic performance of miR-17 family for cancer detection. A total of 1772 patients with certain types of cancer and 1320 healthy controls were involved in these studies. The overall diagnostic accuracy was measured by the following: sensitivity, 0.67 (95 % confidence interval (CI) 0.60-0.74); specificity, 0.83 (95 % CI 0.74-0.85); positive likelihood ratio (PLR), 3.9 (95 % CI 2.6-5.9); negative likelihood ratio (NLR), 0.40 (95 % CI 0.34-0.48); and diagnostic odds ratio (DOR), 10 (95 % CI 6-16), respectively. Additionally, the pooled area under the summary receiver operator characteristic (SROC) curve (area under the curve (AUC)) was 0.79 (95 % CI 0.75-0.82), indicating a relatively low accuracy of miR-17 family as biomarkers for cancer detection. Subgroup analysis further showed that miR-17 family had more reliable performance in cancer diagnosis for Asian than that for Caucasian. Moreover, multiple miRNAs containing miR-17, -20a/b, and -93 reflected higher diagnostic accuracy than both miR-106a/b (single miRNA) and the overall miR-17 family assay. Therefore, appropriate combinations of miR-17 family may be used as non-invasive screening biomarkers for cancer, and it is necessary to carry out a large-scale population-based study to further assess the potential diagnostic value of miR-17 family.


P wave detection in ECG signals using an extended Kalman filter: an evaluation in different arrhythmia contexts.
Monitoring atrial activity via P waves, is an important feature of the arrhythmia detection procedure. The aim of this paper is to present an algorithm for P wave detection in normal and some abnormal records by improving existing methods in the field of signal processing. In contrast to the classical approaches, which are completely blind to signal dynamics, our proposed method uses the extended Kalman filter, EKF25, to estimate the state variables of the equations modeling the dynamic of an ECG signal. This method is a modified version of the nonlinear dynamical model previously introduced for a generation of synthetic ECG signals and fiducial point extraction in normal ones. It is capable of estimating the separate types of activity of the heart with reasonable accuracy and performs well in the presence of morphological variations in the waveforms and ectopic beats. The MIT-BIH Arrhythmia and QT databases have been used to evaluate the performance of the proposed method. The results show that this method has Se = 98.38% and Pr = 96.74% in the overall records (considering normal and abnormal rhythms).


Immunohistochemical panel of antibodies in the diagnosis of brain metastases of the unknown primary.
The primary tumor of brain metastases (BM) is unknown in up to one-half of BM at the time of neurosurgery. Fifty-four consecutive unselected BM were investigated immunohistochemically using antibodies against different intermediate filaments and tumor markers. By correlating the immunohistochemical results with the location of the primary tumor, a staining pattern characteristic of the most frequent BM could be established. Subsequently, 40 cases with known primary tumor were blinded and re-evaluated based on their immunohistochemical staining pattern. Lung (20.4%), colorectum (11.1%), melanoma (7.4%), and breast (7.4%) were the most common primaries. In 14 (25.9%) cases, the primary was unknown. The characteristic immunohistochemical profiles of BM were found to be positivity of cytokeratin 7 and thyroid transcription factor-1 (TTF-1) pointing to the lung, positivity of cytokeratin 20 and negativity of cytokeratin 7 pointing to the colorectum, positivity of vimentin and protein S100 and negativity of cytokeratins (CK) pointing to a melanoma, and positivity of cytokeratin 7 and CA 15-3 with negativity of TTF-1, CA 125 and CA 19-9 pointing to the breast. These primaries comprise the majority in our series. Using the established panel of immunohistochemical markers, we were able to identify the primary in 29 out of 40 (72.5%) BM correctly. To predict the primaries of BM, a combination of antibodies against different CK, vimentin, protein S100, TTF-1, and CA 15-3 is able to point to the primary site in BM of the unknown primary.


Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin.
To study the main clinicobiologic features, response, and outcome of patients with diffuse large B-cell lymphoma (DLBCL) according to the primary site, lymph node, or different extranodal organs of the disease. We included 382 patients consecutively diagnosed with DLBCL in a single institution during a 13-year period. Morphology, immunophenotyping, proliferation index, differentiation profile, bcl-2/JH rearrangement, and clinical characteristics were analyzed according to the primary site of the lymphoma. Sites of the disease were: lymph node, 222 cases (58%); Waldeyer's ring (WR), 42 (11%); and extranodal sites, 118 (31%), including GI tract in 45 cases. Primary extranodal cases, particularly GI, showed a bcl-6 expression more frequently than nodal cases. Patients with primary WR or GI lymphomas presented with early-stage disease, no marrow infiltration, normal serum lactate dehydrogenase, and low- to low/intermediate-risk international prognostic index (IPI) more frequently than the remainder. Complete response (CR) rate was 63%, with WR and GI lymphomas having a higher CR rate (85% and 80%, respectively) than the other groups. In the whole series, 5-year overall survival (OS) was 52%. Patients with WR or GI lymphomas showed better OS (5-year OS: 77% and 68%, respectively) than patients with nodal or other extranodal sites. In the multivariate analysis, IPI, bulky disease, and beta2-microglobulin were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. In the present series, the primary site of disease was associated with particular clinicopathologic features and outcome, though the latter largely depended on other factors.


Association of polymorphic MHC microsatellites with GVHD, survival, and leukemia relapse in unrelated hematopoietic stem cell transplant donor/recipient pairs matched at five HLA loci.
In order to determine whether matching/mismatching for microsatellite polymorphism provides useful information on acute graft-vs-host disease (GVHD), survival, and leukemia relapse in hematopoietic stem cell (HSC) transplantation, we genotyped for polymorphisms at 13 microsatellite loci within the major histocompatibility complex (MHC) of 100 unrelated HSC transplant donor-recipient pairs who were matched at five classical human leukocyte antigen (HLA) loci. A high percentage of allele matching was obtained for five microsatellite loci, DQCARII (96%), MICA (93%), MIB (89%), C1-3-1 (93%), and D6S510 (97%), that are localized within 100 kb of the HLA-DR, HLA-DQ, HLA-B, HLA-C, or HLA-A locus. In contrast, the other eight microsatellites are located farther away from the HLA classical loci and have much lower percentages of allele matching [e.g. tumor necrosis factor a (TNFa) (73%), TNFd (74%), D6S273 (64%), C3-2-11 (46%), C5-3-1 (50%), C5-4-5 (63%), C5-2-7 (68%), and D6S265 (81%)]. Therefore, there were at least eight microsatellite markers with relatively high percentages of mismatches in the donor/recipient pairs with acute or chronic GVHD, poor graft survival, and leukemia relapse. However, there were no statistically significant associations between mismatched donor-recipient pairs at the 13 microsatellite loci and acute or chronic GVHD, graft survival, and leukemia relapse. Nevertheless, allele matching at the microsatellite TNFd locus near the TNFa gene was found by the Fisher's exact double-sided test to be significantly associated with decreased survival in the grade III/IV acute GVHD group. Overall, these results suggest that the matching of microsatellite polymorphisms within the HLA region, especially the ones farthest from the classical HLA loci, was not useful indicator for the outcome of HSC transplantation from unrelated donors. In this regard, the future determination of the genome-wide microsatellite genotypes in HLA-matched donor-recipient pairs, outside the MHC, may be a better possibility for identifying minor histocompatibility genes in linkage disequilibria with microsatellites as potential predictive markers for the occurrence of acute GVHD and survival rate in HSC transplantation.


Homoleptic phosphino copper(I) complexes with in vitro and in vivo dual cytotoxic and anti-angiogenic activity.
Homoleptic, tetrahedral Cu(i) complexes of the type [Cu(P)4]BF4 (1-3), where P are the phosphine ligands, 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) and 2-thia-1,3,5-triaza-phosphoaadamantane-2,2-dioxide (PTA-SO2), have been prepared. Novel complexes [Cu(DAPTA)4]BF42 and [Cu(PTA-SO2)4]BF43 have been fully characterized by means of spectroscopic methods, corroborated by XAS-EXAFS analysis of 2. In vitro cell culture experiments revealed a significant antiproliferative activity for Cu(i) compounds against several human cancer cell lines derived from solid tumors with preferential cell growth inhibition towards tumour compared to non-malignant cells. In vitro monitoring of migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs) showed an anti-angiogenic effect of copper(i) complexes at sub-cytotoxic concentrations. In vivo studies on the antitumor efficacy and ability to inhibit angiogenesis confirmed the dual cytotoxic and anti-angiogenic properties of Cu(i) derivatives.


Oscillations of polymeric microbubbles: effect of the encapsulating shell
A model for the oscillation of gas bubbles encapsulated in a thin shell has been developed. The model depends on viscous and elastic properties of the shell, described by thickness, shear modulus, and shear viscosity. This theory was used to describe an experimental ultrasound contrast agent from Nycomed, composed of air bubbles encapsulated in a polymer shell. Theoretical calculations were compared with measurements of acoustic attenuation at amplitudes where bubble oscillations are linear. A good fit between measured and calculated results was obtained. The results were used to estimate the viscoelastic properties of the shell material. The shell shear modulus was estimated to between 10.6 and 12.9 MPa, the shell viscosity was estimated to between 0.39 and 0.49 Pas. The shell thickness was 5% of the particle radius. These results imply that the particles are around 20 times more rigid than free air bubbles, and that the oscillations are heavily damped, corresponding to Q-values around 1. We conclude that the shell strongly alters the acoustic behavior of the bubbles: The stiffness and viscosity of the particles are mainly determined by the encapsulating shell, not by the air inside.


Recovery after short-term bilirubin exposure in human NT2-N neurons.
We used human NT2-N neurons to investigate delayed effects of short-term exposure to unconjugated bilirubin (UCB). Cell viability was evaluated with MTT reduction assays and nuclear morphology. A 6-h exposure to 1, 5, or 25 microM UCB and serum deprivation (SED) significantly diminished MTT reduction. 96 h after rescue of neurons with removal of UCB and re-incubation in the original serum-containing medium, delayed effects were evident as recovery (1 microM UCB), intermediate cell death (5 microM UCB), or near complete cell death (25 microM UCB). The impact of 6 h of SED alone appeared to be modest in rescued neurons. In this model, co-treatment with the specific caspase-3 inhibitor, zDEVD.FMK (100 microM), or the pancaspase inhibitor zVAD.FMK (100 microM) did not improve viability in rescued neurons exposed to 5 microM UCB, while treatment with the NMDA receptor antagonist MK-801 (1 microM) enhanced the number of undamaged nuclei (86 +/- 14% versus 50 +/- 12%, P = 0.001). MK-801 had, however, no impact on MTT reduction. In a different model with a 102-h continuous exposure to UCB and SED, we found a significant additional toxic impact of serum deprivation. Separate experiments suggested that this was a result of late caspase-mediated toxicity. We conclude that UCB-mediated effects may be reversible in this model. Blockade of excitotoxic mechanisms, but not caspase activity may prevent delayed cell death.


NMR structure of an archaeal homologue of ribonuclease P protein Rpp29.
A protein component of the Archaeoglobus fulgidus RNase P was expressed in Escherichia coli, purified, and structurally characterized using multidimensional NMR methods. The dominant structural feature of this 11 kDa protein is a sheet of six antiparallel beta-strands, wrapped around a core of conserved hydrophobic amino acids. Amide proton exchange and (15)N relaxation rate data provide evidence that the first 16 residues of the protein, located before the start of the first beta-strand, and the last 24 residues, located past the end of the last beta-strand, are relatively flexible; this contrasts with the relatively rigid and well-defined structure of the beta-sheet. Amino acid sequence comparisons among a diverse set of species indicate that the A. fulgidus protein is homologous to the human RNase P protein Rpp29, yeast RNase P protein Pop4, and a known archaeal RNase P protein from Methanobacter thermoautotrophicus; conserved hydrophobic residues indicate that the homologous protein in each of these species contains a similar beta-sheet structure. Conserved surface residues located in the loop connecting strands beta2 and beta3, the loop connecting strands beta4 and beta5, and in the flexible N- and C-terminal tails are most likely to have specific interactions with the RNA and other proteins of RNase P. The structural model of an RNase P protein component provided by the present work provides an essential step toward eventually understanding the overall architecture of this complex enzyme and the mechanism by which it performs its functions.


Use of Conductance to Detect Bacteriocin Activity.
The inhibitory activity of a bacteriocin produced by Lactobacillus delbrueckii subsp. lactis G4 (Bac+) in milk was investigated by using conductivity measurements. The bacteriocin showed an inhibitory action toward some strains belonging to L. delbrueckii subsp. bulgaricus species. A delay in detection time (δDT) of two milk cultures sensitive to bacteriocin, grown in the presence of preformed bacteriocin, was observed. An inactivation as well as a modified growth rate of the sensitive cultures due to bacteriocin activity might explain the δDT, as indicated by longer generation time (tg). Cells showed the highest sensitivity to bacteriocin during the log phase of growth that corresponded to the beginning of the acceleration of the conductance curve (DT).


Inflammatory intermediates produced by tissues encasing silicone breast prostheses.
Silicone prostheses, when implanted within the soft tissues of the breast, evoke an inflammatory reaction. In response to silicone exposure, inflammatory mediator production by individual cells has been observed in various experimental studies. In this study, inflammatory mediator production by periprosthetic tissues (whole organ) was measured. The mediator levels were correlated with both the tissue histopathology of the periprosthetic capsules and the clinical symptoms noted by each patient. Tissue surrounding breast implants removed at surgery from ten women (average age and implant duration 40 and 7 years respectively) was cultured in vitro for 24 hours. Control tissues consisting of (a) augmentation mammaplasty skin scars from eight additional patients and (b) knee synovium from seven orthopedic surgery patients with arthritis undergoing primary joint arthroplasty were similarly cultured. The mediators [interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and prostaglandin E2 (PGE2)] liberated into the culture media were measured by an enzyme linked immunosorbent assay. When compared to controls, the mediator levels of IL-6 and TNF-alpha were substantially greater, although IL-2 and PGE2 were lower. Levels varied greatly from patient to patient: in pg/ml per 10 g tissue, IL-2 ranged from 10 to over 1,000; TNF-alpha from 100 to 1,000; IL-6 from 100 to 1,000,000; and PGE2 from 100 to 10,000. The correlation between TNF-alpha and PGE2 levels was .5 between IL-6 and PGE2 was .6, and between IL-6 and TNF-alpha was .77. The correlation between TNF-alpha and IL-6 was statistically significant at a p-value less than .01. Elevated levels of TNF-alpha production were associated with an increased number of macrophages and overall tissue cellularity (p < .05). No significant relationship was observed between mediator production and clinical symptoms. We conclude that overall cellularity, specifically macrophages, in the periprosthetic capsule may lead to TNF-alpha production but that cytokine production by periprosthetic tissues alone is not a predictor of clinical symptomatology in patients with silicone breast prostheses.


Efficacy of anipamil, a phenylalkylamine calcium antagonist, in treatment of angina pectoris.
To evaluate the efficacy of anipamil, a phenylalkylamine calcium antagonist, in treatment of stable angina pectoris, we performed a randomized, double blind placebo-controlled, cross-over study. Inclusion criteria were (a) stable angina pectoris for at least 2 months, (b) an exercise test with > or = 0.1-mV horizontal or downsloping ST-segment depression limited by angina, and (c) at least 10 attacks of angina pectoris in a single-blind 3-week run-in period. Nineteen patients were randomized to enter the study. In 3-week periods, they received either anipamil 80 mg once daily (o.d.), anipamil 160 mg o.d., or placebo. At the end of each period, an exercise test was performed. The number of angina pectoris attacks was significantly reduced during treatment with anipamil 80 mg (p < 0.05) and anipamil 160 mg (p < 0.001) as compared with placebo. Glycerol nitrate consumption was significantly reduced during treatment with anipamil 80 mg (p < 0.01) and 160 mg (p < 0.001) as compared with placebo. During exercise testing, the load (W) at start of angina was significantly increased during treatment with anipamil 80 mg (p < 0.01) and 160 mg (p < 0.05) as compared with placebo. Heart rate (HR) at 0.1 mV ST-segment depression was increased during treatment with anipamil 80 mg (p < 0.001). Few adverse events were reported.


Closed treatment of femoral fractures with the fluted Sampson intramedullary rod.
A technique of closed intramedullary rodding of femur fractures using a curved fluted Sampson rod under fluoroscopic control is presented. Seventy-nine patients have been treated by this technique over the past four years. In this series there have been no cases of nonunion. There was a 6.3 per cent infection rate. There were three nerve injuries. No leg length discrepancy greater than 1 inch was encountered. We believe that the technique has been successful and has answered the demands of our young trauma population. We remain enthusiastic about its use.


Disasters, psychiatry, and psychodynamics.
The unique experience of Disaster Psychiatry Outreach, a voluntary organization devoted to providing psychiatric assistance to people affected by disasters, provides a valuable substrate for exploring the role of psychodynamics in the human experience of disaster and trauma. This article offers a theoretical framework for such an experience that takes into account personal meaning, ego psychology and defenses, and grief work and suggests how to employ this framework in the setting of a disaster by way of examples from the events of Sept. 11. A useful clinical construct for future disaster work known as the "trauma tent" is ultimately proposed, as are novel applications of psychodynamics toward the prevention and mitigation of manmade and natural disasters.


Dependence between LD50 for Rodents and LC50 for Adult Fish and Fish Embryos.
We revealed empirical dependences between common logarithm of a ratio of rat oral LD50 to LCa50 for adult fish and lgP for 50 different chemicals; and common logarithm of a ratio of the oral LD50 in rodents to LCe50 for fish embryos and lgP for 30 different chemicals. The dependences were obtained by constructing a trend line between experimental points and calculation of Pearson's R correlation coefficient as a measure of regression significance. These dependences can show the influence of substance lipophilicity on its toxicity for aquatic organisms comparing to mammals.


[Dense bone metastases and hypophosphatemic osteomalacia during the course of prostatic cancer (author's transl)].
In patient bearing an advenced prostatic carcinoma with bony metastases, a major hypophosphoremia had led to the detection of an osteomalacia. As far as we know, three observations of the same syndrome have been published previously. As a pathogenic hypothesis, we propose that this tumor secret a substance which inhibit the action of vitamine D. Hypophosphoremia could result from an hyperparathyroid due to hypocalcemia.


Forty years of malaria eradication in Sardinia. A new appraisal of a great enterprise.
The campaign against malaria in Sardinia carried out by the Ente Regionale per la Lotta Anti-Anofelica in Sardegna (ERLAAS), appears today as one of the greatest efforts against malaria since the discovery of its aetiology and mode of transmission. The disease was eradicated without achieving the eradication of the vector, Anopheles labranchiae, the main objective of the campaign. This species eradication failure had been at first attributed to the indigenous character of A. labranchiae and its long standing in the island. A more recent analysis, based on paleoclimatological information, makes virtually impossible the presence of A. labranchiae during the last (Würm) glacial period and indicates a comparatively recent introduction of the species in the island. It was the absence of A. atroparvus, with which it has usually to compete in Southern Europe, what permitted the wide distribution of A. labrianchiae in the island. Four decades after the events the concept of species eradication as an anti-malaria weapon appears as basically wrong, the results of Sardinia as well as those obtained in the Italian mainland having demonstrated that the eradication of the vector was not required for the successful eradication of the disease.


Targeting of tail-anchored proteins to yeast mitochondria in vivo.
Tail-anchored proteins are inserted into intracellular membranes via a C-terminal transmembrane domain. The topology of the protein is such that insertion must occur post-translationally, since the insertion sequence is not available for membrane insertion until after translation of the tail-anchored polypeptide is completed. Here, we show that the targeting information in one such tail-anchored protein, translocase in the outer mitochondrial membrane 22, is contained in a short region flanking the transmembrane domain. An equivalent region is sufficient to specify the localisation of Bcl2 and SNARE proteins to the secretory membranes. We discuss the targeting process for directing members of this protein family to the secretory and mitochondrial membranes in vivo.


Forecasting American health care: how we got here and where we might be going.
This article is a form of thinking about the future properly regarded as conditional forecasting. It begins by reminding readers of the enormous changes in American medicine since World War II. The second part revisits critically an earlier effort at conditional forecasting for 1995 that Paul Starr and I published in the early 1980s. Besides reviewing the prescience of our forecasts, the second part outlines the earlier trends in progress we identified and the four combinations of political and economic settings we explored. On that basis, the final part takes up the challenge of anticipating sensibly some possible medical futures in the America of the early twenty-first century, a task which excludes simple extrapolation.


A highly repetitive and transcribable sequence in the tortoise genome is probably a retroposon.
On in vitro transcription of total genomic DNA of the tortoise (Geoclemys reevessi), a discrete-sized RNA of 6.5S was obtained that represented a highly repetitive and transcribable sequence in the tortoise genome. Three sequences of the 6.5S RNA gene were sequenced, and a consensus sequence was deduced from these three sequences and one reported previously [Endoh, H & Okada, N. (1986) Proc. Natl Acad. Sci. USA 83, 251-255]. The 5' part of the gene showed close similaries to lysine (rabbit) and threonine (mouse) tRNAs (overall similarity 68-70%), so this tortoise sequence may have evolved from one of these tRNAs. The consensus sequence retained the expected CCA triplet at the 3' end of tRNA, but not at the 3' end of tDNA, supporting the idea that the tRNA-related region of the gene was generated via an RNA intermediate. The 5' and 3' flanking sequences of the four genes were found to be completely different from each other. Fingerprint analysis and S1 nuclease mapping analysis also showed that sequence boundaries of tortoise repetitive units exactly corresponded to RNA species. These results, together with data obtained by Southern blot hybridization, indicated that the 6.5S RNA genes are dispersed in the tortoise genome. Therefore, generation of the tRNA-related region of the gene and amplification of the whole unit of the gene are both RNA-mediated events. The existence of this tortoise sequence suggests that short interspersed sequences are more common in eukaryotic genomes than had previously been thought.


Characterization of CK2 holoenzyme variants with regard to crystallization.
A search for strategies was conducted in order to obtain a human protein kinase CK2 preparation which would be suitable for crystallization, despite the fact that the recombinant enzyme is abundant and can be readily purified to homogeneity. This seemingly contradiction is based on the fact that the catalytic subunit moiety of the human CK2 holoenzyme is not stable neither as a free subunit nor in the tetrameric complex. All attempts to prevent degradation failed. Hence, alternative approaches were designed in order to avoid this degradation, which was expected to hamper any crystallization efforts severely. One of the approaches chosen was the production of a chimeric holoenzyme made up from a human regulatory subunit and a catalytic subunit from Z. mays. The plant catalytic subunit, in contrast to the human counterpart is very stable and does not undergo this kind of degradation. The second strategy to tackle the problem of instability was to produce the homologous recombinant human CK2 holoenzyme and then, instead of trying to avoid degradation, attempt to accelerate degradation until all catalytic subunit material was converted to the degraded form, i.e. a 40 kDa polypeptide.


Multi-center study of noise in patients from hospitals in Spain: a questionnaire survey.
To identify the most annoying noises in the hospital environment. One hundred and ninety-three patients took part in the study. A questionnaire collected the perceptions of patients from four hospitals in Spain, with three distinct units. The most annoying noises were the repetitive ones and the most unbearable source was the people who talk loudly. The daily hours were the noisiest and the most annoying, especially when patients wanted to rest and indicated that noise was annoying for them to get to sleep. Our results demonstrate how sensitive patients are toward noise in Spain. We also suggest some strategies to reduce the noise and the harmful physiological effects of increased sound levels in order to improve the quality of life in a healthcare environment.


Prospective study of body size and risk for stroke amongst women below age 60.
The relation between obesity, particularly abdominal obesity, and risk of stroke amongst women remains unclear. In 1991-1992, a prospective study was initiated in Sweden amongst women who returned a self-administered questionnaire. Through linkage with nation-wide registries, 45,449 women, free of stroke at entry, were followed up until diagnosis of first incident stroke, death, or the end of follow-up in 2002. We estimated multivariate relative risks (RRs) with 95% confidence intervals (CIs) from Cox proportional hazards regression models. A total of 170 incident stroke cases occurred during an average of 11 years of follow-up. The RR of stroke amongst women in the highest compared with the lowest quintile was 2.4 (95% CI 1.3-4.2; P for trend 0.04) for waist-to-hip ratio, 2.5 (95% CI 1.5-4.3; P for trend 0.01) for waist-to-height ratio and 2.3 (95% CI 1.2-4.3; P for trend 0.02) for waist circumference. Adjustment for hypertension and diabetes attenuated these risk estimates. In contrast, birth weight, body mass index (BMI) at age 18, BMI at entry, weight change in adulthood and adult height were not significantly associated with risk of stroke. This study provides evidence that, in contrast to BMI, several different measures of abdominal obesity are strong predictors of stroke in women.


Transsexualism and Slater's Selective Vocabulary Test.
It has been shown elsewhere that transsexual males use a vocabulary which differs from that of normal males. This could be demonstrated by Slater's Selective Vocabulary Test. This test was administered to 56 male transsexuals and the 'd' score - a device to eliminate the influence of I.Q. - was calculated. The normal d score for males is zero and the higher the score the greater is the degree of femininity. An attempt was made to find factors which facilitate this abnormal development of the vocabulary in male transsexuals. In order to do this the cases were divided into a group of high and a group of low 'd' scores, and tested for correlations with a number of factors which seemed likely to influence the vocabulary development. No such correlations could be established.


Titanium applications in dentistry.
The ADA Council on Scientific Affairs outlines the status of titanium and titanium alloys used in dentistry and provides its recommendations concerning their use in clinical practice. Titanium and titanium alloys, based on their physical and chemical properties, appear to be especially suitable for dental implants and prostheses. For the construction of endosseous implant devices, titanium and its alloys have become well-accepted and can be considered the materials of choice. For crown and bridge prostheses, dentists can consider titanium and its alloys as viable options to more traditional noble and base metal alloys, but careful selection of processing methods and laboratory skill are necessary to ensure success.


Probabilistic model of influenza virus transmissibility at various temperature and humidity conditions.
The spread efficiency of influenza virus is significantly affected by several environmental parameters. However, neither the underlying reasons, nor the exact character and magnitude of the phenomena involved are sufficiently well understood. Here we present a probabilistic approach to the virus transmission events. For a sample ensemble, we construct a model of the infectivity as a function of the ambient conditions, and we determine its parameter values on the basis of the available experimental data.


Practice effects on the WAIS-III across 3- and 6-month intervals.
Fifty-one participants (age M = 24.6; education M = 14.4 years) were administered the Wechsler Adult Intelligence Scale - Third Edition (WAIS-III) at baseline and at an interval of either 3 or 6 months later. Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), Verbal Comprehension Index (VCI), Perceptual Organization Index (POI), and Processing Speed Index (PSI) scores improved significantly across time, whereas no significant change occurred on the Working Memory Index. Specifically, test scores increased approximately 3, 11, 6, 4, 8, and 7 points, respectively on the VIQ, PIQ, FSIQ, VCI, POI, and PSI for both groups. Notably, the degree of improvement was similar regardless of whether the inter-test interval was 3 or 6 months. These findings suggest that prior exposure to the WAIS-III yields considerable increases in test scores. Reliable change indices indicated that large confidence intervals might be expected. As such, users of the WAIS-III should interpret reevaluations across these intervals cautiously.


Effect of metergoline, a specific serotonin antagonist, on human growth hormone response to arginine and L-dopa.
In seven normal subjects the repeated oral administration of metergoline, a specific antiserotonin agent, has enhanced HGH response to arginine infusion. Following placebo administration, arginine-induced HGH release was slightly but not significantly reduced; similarly, in eight metergoline treated subjects, HGH response to oral L-Dopa was slightly but not significantly reduced. HGH response to i.v. L-Dopa was not modified by the drug. These results suggest that serotonin controls HGH response only in response to arginine, not to L-Dopa.


Intratumoural expression of TNF-R1 and EMAP-II in relation to response of patients treated with TNF-based isolated limb perfusion.
Tumour necrosis factor-alpha (TNF) has been used in the clinic for more than 10 years in an isolated limb perfusion (ILP). However, intra-tumoural expression of TNF receptor-1 (TNF-R1) and TNF-R1 upregulating factors are unknown. We determined the expression of TNF-R1, proEMAP and endothelial monocyte-activating polypeptide-II (EMAP-II) before and after ILP and evaluated this against clinical response. Tumour biopsies were taken before and after ILP of patients (n = 27) with advanced sarcoma or metastatic melanoma. Biopsies were randomly analysed by western blotting for proEMAP/EMAP-II and TNF-R1 expression. Appropriate melanoma biopsies were stained for EMAP-II, TNF-R1, CD31 and CD68. For melanomas we found that an up-regulation of EMAP-II, in contrast to proEMAP or TNF-R1, directly after ILP significantly correlated with a complete tumour response. No correlation was found for sarcoma patients. In a comparative analysis we found that the overall proEMAP and EMAP-II expression was higher in melanoma as compared to sarcoma cases and measurements in cell lines revealed high proEMAP expression by melanoma cells. We report high EMAP-II expression by endothelial cells and association with macrophages. In addition, macrophages are recruited to vessel-remnants after ILP. An upregulation of EMAP-II directly after ILP of melanoma patients correlates with and might predict a complete response to TNF-based ILP. The association of macrophages with EMAP-II expression and vascular damage suggests a role for EMAP-II in regulating the TNF-based anti-tumour effects observed with an ILP. Analysis of EMAP-II expression in melanoma biopsies should be implemented in the ILP procedure.


[Late onset of angina pectoris after coronary bypass surgery].
The repeat of angina pectoris of 598 patients with undergoing coronary bypass surgery during the years Jan. 1978 to Aug. 1987 was analyzed. The 5-year and 8-year survival rate was 88% and 84%, respectively. The 5-year and 8-year cardiac event free ratio was 91% and 83%, respectively. The 5-year and 8-year angina free ratio was 73% and 64%, respectively. The causes of repeat angina were graft occlusion in 42%, incomplete revascularization in 16%, progression of native coronary lesions in 28% and unknown in 14%, respectively. PTCR in 4 patients, PTCA in 8 patients and re-CABG in 8 patients were performed to relief from angina pectoris.


Dorsal anterior cingulate cortex integrates reinforcement history to guide voluntary behavior.
Two competing types of theory have been proposed about the function of dorsal anterior cingulate cortex (dACC): evaluative theories hold that dACC monitors ongoing behavior to detect errors or conflict, whereas response selection theories hold that dACC is directly involved in the decision making process. In particular, one response selection theory proposes that dACC utilizes reward prediction error signals carried by the midbrain dopamine system to decide which of several competing motor control systems should be given control over the motor system (Holroyd and Coles, 2002). The theory further proposes that the impact of these dopamine signals on dACC determines the amplitude of a component of the event-related brain potential called the error-related negativity (ERN). In the present study, we applied this theory to a decision making problem that requires participants to select between two response options in which an erroneous choice is not clearly defined. Rather, the reward received for a particular response evolves in relation to the individual's previous behavior. We adapted a computational model associated with the theory to simulate human performance and the ERN in the task, and tested the predictions of the model against empirical ERP data. Our results indicate that ERN amplitude reflects the subjective value attributed by each participant to their response options as derived from their recent reward history. This finding is consistent with the position that dACC integrates the recent history of reinforcements to guide voluntary choice behavior, as opposed to evaluating behaviors per se.


Differential scanning calorimetric study of the complexes of modified myosin subfragment 1 with ADP and vanadate or beryllium fluoride.
The effects of various modifications of rabbit skeletal myosin subfragment 1 on the thermal denaturation of subfragment 1 in ternary complexes with Mg-ADP and orthovanadate (V1) or beryllium fluoride (BeFx) have been studied by differential scanning calorimetry. It has been shown that specific modifications of SH1 group of Cys-707 by different sulfhydryl reagents, trinitrophenylation of Lys-83, and reductive methylation of lysine residues promote the decomposition of the S1.ADP.Vi complex and change the character of structural transitions of the subfragment 1 molecule induced by the formation of this complex, but they have much less or no influence on subfragment 1 thermal stability in the S1.ADP.BeFx complex. Thus, the differential scanning calorimetric studies on modified subfragment 1 preparations reveal a significant difference between S1.ADP.Vi and S1.ADP.BeFx complexes. It is suggested that S1.ADP.Vi and S1.ADP.BeFx complexes represent structural analogues of different transition states of the ATPase cycle, namely the intermediate states S1**.ADP.Pi and S1*.ATP, respectively. It is also proposed that during formation of the S1.ADP.Vi complex the region containing both Cys-707 and Lys-83 plays an important role in the spread of conformational changes from the active site of subfragment 1 ATPase throughout the structure of the entire subfragment 1 molecule. In such a case, the effects of reductive methylation of lysine residues on the subfragment 1 structure in the S1.ADP.Vi complex are related to the modification of Lys-83.


Electrical and thermal characterization of nanochannels between a cell and a silicon based micro-pore.
Micro and nano fabrication techniques have facilitated the production of new devices for manipulation of single cells on a chip, such as the planar micro-pore electroporation technology. To characterize this technology we have studied the seal that forms at the interface between an individual cell and the micro-pore, in which the cell normally resides, as a function of an electrical field applied across the cell and temperature. Mathematical analysis of non-electroporative electrical fields in experiments with Madin-Darby canine kidney (MDCK) cells suggests that nanoscale channels form between the exterior of the cell and the pore wall. The results indicate that the electrical currents through these channels need to be considered when using planar micro-pores in general and performing micro-pore electroporation in particular. Our results show that the size of these channels is strongly temperature dependent and the cell to pore wall distance can increase by as much as 60% when the temperature of the system is lowered from 35 to 0( composite function)C. Temperature appears to be an important factor in the use of devices for cells on a chip and our results suggest that physiological temperatures should yield better seal formation, thus improved feedback sensitivity, than the traditional use of room temperature in planar micro-pore electroporation devices.


Blockade of A(2A) adenosine receptors leads to c-fos inhibition in a rat model of brain ischemia.
Adenosine plays an important role in cerebral ischemia by acting on its own receptors, in particular the A(2A)receptor. Its activation leads to excitatory amino acid release thus contributing to the ischemic damage. Blockade by specific antagonists may protect against cytotoxic injury. Our study was aimed to investigate the effect of the blockade of A(2A)receptors, by Sch 58261, on the expression of the early gene c-fos, in a model of permanent middle cerebral artery occlusion (pMCAo), in rats. In the pMCAo model, ischemia was induced in the right hemisphere whereas the contralateral one was considered the control. In our study, we have compared pMCAo rats, pMCAo rats treated with Sch 58261 and sham operated ones.C-fos was markedly expressed in the ischemic hemispheres, whereas lower levels were detected in the contralateral ones of the ischemic animals. The lowest bands were observed in sham operated rats. After treatment with Sch 58261, a considerable reduction in c-fos expression was observed in the ischemic hemispheres, whereas a limited effect was detected in the others. Our results suggest that inhibition of immediate-early gene expression by the A(2A)receptors antagonist Sch 58261 may contribute to its neuroprotective activity.


Theoretical studies on structures and reactivities of organocuprate(I) and organocopper(III) species.
Systematic evaluation of method and basis set on the structure and energetics of organocuprate(I) and organocopper(III) species has been carried out. Various structures of organocuprate(I) and organocuprate(III) complexes were optimized with the HF, MP2, and B3LYP methods, and compared with the structures determined by X-ray crystallography (i.e., Me(2)Cu(I)(-), (CF(3))(4)Cu(III)(-)). Both the MP2 and B3LYP methods reasonably reproduce the X-ray structures while the HF method does not. Using larger basis set and incorporating the relativistic effects for Cu afford the best results. In the studies on the energetics of a Libond;Cu cluster model (Me(2)CuLi. LiCl) and Me(3)Cu model with the MP2, MP3, MP4DQ, MP4SDQ, CCSD(T), and B3LYP methods, the B3LYP method gives energetics similar to those obtained with the CCSD(T) method with much less cost, and hence, is judged to be the best practical method. The studies have shown that B3LYP method with the basis set incorporating the relativistic effective core potentials for Cu and the 6-31G* basis set for the rest is the theoretical method that is the most cost-effective for the studies of the structure and energetics of organocuprate(I) and organocopper(III) species.


Developmental expression of maf-1 messenger ribonucleic acids in rat kidney by in situ hybridization histochemistry.
maf is a family of oncogenes, originally identified from the avian oncogenic retrovirus AS42, which encodes a nuclear bZip transcription factor protein. It has been reported that maf family genes have critical roles in embryological development and cellular differentiation. In this study, the distribution of maf-1 genes, the rat homologues of mafB, was examined in rat kidneys at the embryonic stages from 13 days, gestation (E13) through E21 and then 1, 2, 4, and 8 weeks after birth by in situ hybridization with (35)S-labeled antisense riboprobes. The cellular localization was determined using double in situ hybridization. Expression of maf-1 mRNA appeared weakly on E15 and was restricted to glomerular visceral epithelial cells during the pre- and postnatal stages until 2 weeks after birth and then gradually diminished. Double in situ hybridization demonstrated that maf-1 mRNA-positive cells in glomerulus also expressed Pod-1 gene, suggesting that maf-1 mRNA was expressed in the podocyte. These findings suggest that the expression of maf-1 gene may be involved in embryological development and/or differentiation of the kidney.


Pre-attention and Working Memory in ADHD: A 25-Year Follow-Up Study.
Objective: The aim of the study was to compare the development of working memory and preliminary stages of attentional processing in individuals with ADHD over a 23- to 25-year period. Method: Individuals with ADHD (n = 19) and healthy controls (n = 26) were followed up after 13 years (T2) and 23 to 25 years (T3) after initial assessment (T1). They were reassessed with diagnostic measures and the Backward masking task (pre-attention) and the Digit span distractibility test with and without distraction conditions (working memory). Results: The ADHD group performed below the healthy controls on all time points on the Digit span distractibility test. On the distractibility condition, we found a selective decline in performance from T2 to T3 for the ADHD group. Conclusion: The results highlight that ADHD individuals continue to display working memory deficits, also in adulthood, thus creating an imperative for cognitive rehabilitation techniques to help address attention difficulties.


Conception rates following assisted reproduction in poor responder patients: a retrospective study in 300 consecutive cycles.
Poor response to ovarian stimulation for assisted reproduction treatment is a therapeutic challenge. Oocyte donation may be unacceptable to some patients, and many couples opt to continue with treatment despite low follicle numbers. Minimal data are available regarding conception rates in poor responders who elect to undergo oocyte retrieval. This study summarizes the outcome of assisted reproduction treatment in poor responders who produced four or fewer oocytes during ovarian stimulation, in order to provide better counselling to such patients in the future. Embryo transfers were performed in 208 of 300 cycles demonstrating poor ovarian response. Pregnancy rate (PR) (15.9%) was significantly higher in patients in whom four oocytes were retrieved, compared with patients in whom one or two oocytes were retrieved (2.3 and 4.3% respectively). Younger patients (< or =34 years) had significantly higher PR (19.5%) compared with older patients (> or =35 and < or =39 years, PR 7.2% and > or =40 years, PR 1.5% respectively). One hundred and twenty-six age-matched normal responders in whom three embryos were transferred had higher implantation rates (15.3%) and PR (37.3%) compared with poor responders in whom three embryos were transferred (6.6 and 16.6% respectively; P < 0.05). In this regard, patient age, number of oocytes retrieved and number of embryos available for transfer determine prognosis for the success of IVF in patients who respond to ovarian stimulation with four or fewer follicles for assisted reproduction treatment.


Prevention of bicycle-related head injuries.
Each year in the United States, bicycling accidents cause approximately 1,300 deaths and 60,000 injuries. The death and injury rates are particularly high among children. The death rate from bicycle injuries in children exceeds the death rate from accidental poisonings, falls, firearm injuries, and many major illnesses. Head trauma is the most frequent cause of death and serious injury among bicyclists. Bicycle helmets have the potential to decrease the frequency and severity of bicycle-related head injury. Unfortunately, however, most bicyclists do not use a helmet. The helmet-use rate is extremely low among children. The failure of bicyclists, particularly children, to use bicycle helmets presents an opportunity for prevention of thousands of the traumatic head injuries that occur annually in the United States. Helmet use could be encouraged by schools, community safety programs, and office-based education by physicians.


Anticoagulants for avian and reptilian blood: heparin and EDTA.
The effectiveness of EDTA (dipotassium and disodium salts) and heparin as anticoagulants for the blood of puffadders and pigeons has been investigated. In the case of the snakes all three substances produced haemolysis after variable time intervals, and increases in cell volume were observed. In the case of the pigeons, samples stored at 4 degrees C showed lower haematocrit values and haemolysed sooner than samples stored at room temperature.


Effects of dietary supplementation with cysteamine on growth hormone receptor and insulin-like growth factor system in finishing pigs.
The present study was conducted to test the hypothesis that chronic cysteamine (CS) supplementation may affect serum insulin-like growth factor (IGF)-I concentrations and growth hormone (GH) receptor (GHR), IGF-I, IGF-I receptor (IGF-IR), IGF binding protein (IGFBP)-3, and insulin receptor (IR) mRNA levels in different tissues of finishing pigs. A total of 24 finishing pigs (60.05 +/- 1.24 kg; 12 gilts and 12 barrows) were assigned randomly to one of the three dietary groups, with four pens/group (per pen: one gilt, one barrow). The pigs were fed a basal diet containing 0 (control), 70, or 140 mg/kg cysteamine feed additive (containing 28% cysteamine hydrochloride) for 47 days. The results indicated that CS supplementation (70 mg/kg) increased the average daily gain (ADG) and serum IGF-I level, upregulated mRNA levels of GHR and IGF-I (liver, stomach, muscle), IGF-IR (stomach, duodenum, muscle), and IGFBP-3 (liver) but downregulated IGFBP-3 (stomach, duodenum, muscle). CS supplementation (70 mg/kg) did not affect mRNA levels of GHR and IGF-I (duodenum), IGF-IR (liver), and IR (liver, stomach, duodenum, muscle). CS supplementation (140 mg/kg) downregulated GHR (duodenum), IGF-I, and IGF-IR mRNA (liver, stomach, duodenum, muscle) but upregulated IGFBP-3 and IR mRNA (liver, stomach, duodenum, muscle) and did not affect ADG and serum IGF-I concentration. Collectively, the results suggest that dietary CS supplementation modulates the growth rate, serum IGF-I concentrations, and the gene expression of GHR, IGF-I, IGF-IR, IGFBP-3, and IR in a dose-dependent manner. CS supplementation has tissue-specific regulation of GHR, IGF-I, IGF-IR, and IGFBP-3 mRNA levels. Moreover, the results also imply the possible physiologic role of the GH-IGF axis in mediating the dietary CS supplementation-supported growth of finishing pigs.


The Interacting Domains of PREP1 and p160 are Endowed with a Remarkable Structural Stability.
PREP1/p160 is a protein complex with relevant physiopathological roles in vivo. p160 regulates PREP1 transcriptional activity by preventing the formation of other PREP1-containing complexes, whereas PREP1 regulates p160 activity by increasing its stability. This induces the repression of the insulin-regulated glucose transporter GLUT4 dampening insulin sensitivity. In spite of the considerable amount of functional studies performed on the PREP1/p160 complex in vivo, a biochemical and structural characterization of this complex has not been so far undertaken, given the poor stability of the recombinant full-length proteins. Here, we report the design and preparation of PREP1 and p160 domains together with preliminary structural and binding studies. PREP1, residues 45-155, and p160, residues 20-160, have been expressed and purified as folded, monomeric domains. The two domains show both all-alpha secondary structures, as demonstrated by CD studies and are endowed with unusually high thermal stabilities. We have also estimated for the first time the PREP1-p160 interaction strength finding that the two recombinant domains interact with a KD ranging between about 0.3 and 1 μM. Altogether, data suggest that the selected PREP1 and p160 domains are structurally independent and that their structure is underlined by high stability and a prevailing alpha-helical organization.


Safety in pediatric sedation: practice makes perfect.


An indirect haemagglutination test for demonstration of gonococcal antibodies using gonococcal pili as antigen. I. Methodology and preliminary results.
An indirect haemagglutination (IHA) test for detection of gonococcal antibodies in human sera was established using purified pili as antigen. The majority of sera (44/51), positive in the gonococcal complement fixation test, were also positive in the IHA test with titres within the range 320-10,000. The results obtained for the following three groups of sera indicate a comparatively high speicificity of the IHA test; 1) 52 sera from children below 12 years of age were all negative, 2) 98% (184/188) of sera from blood donors were negative, 3) only sera from three adults out of 21 patients with meningococcal infections gave a positive reaction.


Liposome immunoassay (LIA) with antigen-coupled liposomes containing alkaline phosphatase.
Immunoliposomes were prepared and their immunoassay applications investigated. Liposomes were prepared from cholesterol and phospholipids including maleimidobenzoylphosphatidylethanolamine (MBPE) for conjunction with thiol-containing antigens. Alkaline phosphatase (APase) was entrapped in the liposome and BSA, the antigen, was modified by reaction with 3-(2-pyridyl-dithio)propionyl N-hydroxysuccinimide ester (SPDP) to introduce thiol groups for efficient coupling. BSA-coupled liposomes (immunoliposomes) were incubated with anti-BSA serum, complement, and then with APase substrate. The amount of coupled BSA was affected by the reaction time, the composition of the liposome and the BSA concentration in the reactant. The amount of enzyme released from immunoliposomes as a final result of the immunoreaction increased with increasing concentrations of complement and antibody. The liposome immunoassay offers a relatively rapid and simple testing procedure to quantitatively or qualitatively determine the presence or absence of antibodies, or antigenic materials for diagnostic purposes.


High percentage of dietary palm oil suppressed growth and antioxidant capacity and induced the inflammation by activation of TLR-NF-κB signaling pathway in large yellow croaker (Larimichthys crocea).
A 70-day feeding trial was conducted to investigate the effects of dietary fish oil (FO) replaced by palm oil (PO) on growth, biochemical and antioxidant response as well as inflammatory response in the liver of large yellow croaker (initial weight 15.87 ± 0.14 g). Four iso-proteic and iso-lipidic experimental diets were formulated with 0% (the control group), 33.3%, 66.7% and 100% FO replaced by PO. Fish fed the diet with 100% PO showed significantly lower growth performance than the control group. As expected, the contents of C16:0, C18:1n-9 and C18:2n-6 were increased with increasing dietary PO levels. There were remarkable increases in total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels in fish fed the diet with 100% PO compared to the control group. Moreover, dietary PO significantly increased activities of plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) in fish fed the diet with 100% PO compared to the control group. The total antioxidant capacity (T-AOC) and the activity of catalase (CAT) in plasma were significantly decreased in fish fed the diet with 100% PO compared to the control group, and meanwhile no significant differences were found in T-AOC and CAT activity in fish fed diets with no more than 66.7% PO. Fish fed the diet with 100% PO exerted significantly higher toll like receptors (TLRs) and myeloid differentiation factor (MyD88) mRNA expression levels than the control group. The IFNγ, IL-1β and TNFα mRNA expressions were increased with increasing dietary PO levels. The increase of pro-inflammatory gene expression may be due to the activation of NF-κB signaling as the ratio of nucleus p65 to total p65 protein was elevated with the increase of dietary PO levels. These results showed that relatively higher PO levels in diets suppressed the growth and antioxidant capacity as well as induced the inflammatory response by activating TLR-NF-κB signaling pathway in juvenile large yellow croaker.


Rapid induction of ovarian granulosa cell tumors by 7,12-dimethylbenz(a)anthracene in neonatally estrogenized mice.
Groups of female C3H/HeMs x 129/J F1 mice were given injections of either 20 micrograms of 17 beta-estradiol or sesame oil (vehicle) for the first 5 days after birth. Half of each group was then given gastric intubations of 20 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA) at 70, 77, and 84 days of age. The other half of each group was given sesame oil. Thus, this design yielded four experimental groups: oil + oil; 17 beta-estradiol + oil; oil + DMBA; and 17 beta-estradiol + DMBA. They were sacrificed at approximately 144 days of age (Experiment 1) or the day of palpable ovarian tumor detection or 360 days of age (Experiment 2). In Experiment 1, the total number of oocytes (follicles) per ovary in mice of the 17 beta-estradiol + oil group was maintained at the same level as mice of the oil + oil group. A significant reduction of oocytes, however, was observed in mice of the 17 beta-estradiol + DMBA group in comparison with mice of the oil + DMBA group (P less than 0.01), and neoplastic nodules of the granulosa cell type developed in the unilateral ovary in 10 of 17 mice of the 17 beta-estradiol + DMBA group. No tumors were detected in the mice of the other groups. The plasma levels of both follicle-stimulating and luteinizing hormones as determined by radioimmunoassay were significantly higher (P less than 0.01) in mice of the 17 beta-estradiol + oil group than in mice of the oil + oil group. In Experiment 2, more ovarian tumors of the granulosa cell type were detected before 360 days of age in mice of the 17 beta-estradiol + DMBA group (14 of 18) than in mice of the oil + DMBA group (5 of 15) (P less than 0.05). No tumors developed in mice of the other two groups. These results strongly indicate that an abnormal endocrine milieu caused by neonatal treatment with estrogen may induce a high frequency of transformation of some ovarian tissues and rapid growth of the ovarian tumors after DMBA treatment.


Hollow mesoporous organosilica nanoparticles: a generic intelligent framework-hybridization approach for biomedicine.
Chemical construction of molecularly organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) with silsesquioxane framework is expected to substantially improve their therapeutic performance and enhance the biological effects beneficial for biomedicine. In this work, we report on a simple, controllable, and versatile chemical homology principle to synthesize multiple-hybridized HMONs with varied functional organic groups homogeneously incorporated into the framework (up to quintuple hybridizations). As a paradigm, the hybridization of physiologically active thioether groups with triple distinctive disulfide bonds can endow HMONs with unique intrinsic reducing/acidic- and external high intensity focused ultrasound (HIFU)-responsive drug-releasing performances, improved biological effects (e.g., lowered hemolytic effect and improved histocompatibility), and enhanced ultrasonography behavior. The doxorubicin-loaded HMONs with concurrent thioether and phenylene hybridization exhibit drastically enhanced therapeutic efficiency against cancer growth and metastasis, as demonstrated both in vitro and in vivo.


Effect of kaolin and copper based products and of starter cultures on green table olive fermentation.
In the present study table olives treated in field with kaolin and copper based products against "olive-fruit fly" were fermented using two selected strains of lactic acid bacteria (LAB). The fermentation process was monitored up to 260 days from brining through physico-chemical, microbiological and sensorial analyses. Results showed a dominance of LAB and yeasts and low level of Enterobacteriaceae counts throughout the whole process both in un-treated and treated samples. When investigating the effect of the single treatments on microbial dynamics, ANOVA results highlighted that copper based products affected significantly the control sample, while the sample inoculated with LAB starters maintained high level throughout the process, guaranteeing the fermentation process. Different behavior was revealed by yeasts population, which was partially influenced by copper treatment at the beginning of the fermentation. The polyphasic approach used in the present study, which combined sensory evaluation to microbial counts and physico-chemical characteristics, let to the conclusion on the importance of starter cultures in fermentation of table olives especially those treated with "non-conventional" pesticide, which could be used to prevent olive fly damage.


Reduced auditory evoked gamma band response and cognitive processing deficits in first episode schizophrenia.
Gamma-band oscillations (e.g., the early auditory evoked gamma-band response, aeGBR) have been suggested to mediate cognitive and perceptual processes by driving the synchronization of local neuronal populations. Reduced aeGBR is a consistent finding in patients with schizophrenia and high-risk subjects, and has been proposed to represent an endophenotype for the illness. However, it is still unclear whether this reduction represents a deficit in sensory or cognitive processes, or a combination of the two. The present study investigated this question by manipulating the difficulty of an auditory reaction task in patients with first-episode schizophrenia and healthy controls. A 64-channel EEG was recorded in 23 patients with first-episode schizophrenia and 22 healthy controls during two conditions of an auditory reaction task: an easy condition that merely required low-level vigilance, and a difficult condition that placed significant demands on attention and working memory. In contrast to healthy controls, patients failed to increase aeGBR power and phase-locking in the difficult condition. In patients, aeGBR power and phase-locking indices were associated with working memory deficits. The observed results confirm the applicability of aeGBR disturbances as a stable endophenotype of schizophrenia, and suggest a cognitive, rather than sensory, deficit at their origin.


Occupational stress and burnout in radiologic technologists.
Burnout in radiologic technologists can have a direct economic impact on the radiology department in the form of absenteeism, tardiness and employee turnover. This article reports on the results of a study of stress and burnout among a sample of radiologic technologists and technologist interns in a hospital setting. Suggestions are made on how to reduce or eliminate sources of stress, thereby reducing the risk of burnout.


[Role of miR-124a methylation in patients with gastric cancer].
To investigate the DNA methylation status of the promoter region within the coding gene hsa-miR-124a in human gastric cancer tissue, and examine its association with the expression of Rb and CDK6 protein and clinicopathological factors. Methylation-specific PCR (MS-PCR) was used to detect the DNA methylation status of hsa-miR-124a in gastric cancer tissues and adjacent normal tissues from 30 patients. The expression of Rb and CDK6 protein within these tissues was examined using immunohistochemistry. The overall methylation rate of gastric cancer tissues was 73.3%, which was significantly higher than that in the adjacent tissues(10.0%, P<0.05). The overall positive rates of Rb and CDK6 protein in gastric cancer tissues were 86.7% and 80.0%, respectively. DNA methylation of hsa-miR-124a was positively correlated with the expression of Rb and CDK6 proteins. Significant associations were found between hypermethylation of hsa-miR-124a and tumor size, differentiation, lymphatic metastasis, and invasion depth(P<0.01). Hypermethylation of hsa-miR-124a is present in gastric cancer, and is associated with increased expression of CDK6 and Rb protein. These may be related to the proliferation and development of malignancy in the stomach.


Highly efficient immobilization of phospholipase A2 and its biomedical applications.
A new method for the immobilization of phospholipase A2 (PLA2) has been developed to enhance the activity retention of immobilized PLA2. When PLA2 from the venom of Agkistrodon piscivorus piscivorus was pretreated with 4-nitro-3-octanoyl-oxybenzoic acid to acylate epsilon-amino groups of two lysines (Lys-7 and Lys-10) and the resulting acylated enzyme was covalently coupled onto carbonyldiimidazole-activated cross-linked agarose beads, the immobilized acylated enzyme showed high retention of activity toward various aggregated phospholipids. Toward densely packed phospholipid bilayers, such as large unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, the immobilized acylated A. p. piscivorus PLA2 was 25-fold more active than the soluble A. p. piscivorus PLA2. The general applicability of our immobilization protocol was demonstrated by the high retention of activity achieved for the immobilized acylated PLA2 from the venom of Naja naja naja. In particular, full activity retention of the immobilized acylated A. p. piscivorus PLA2 toward phospholipids on the surface of human low density lipoproteins suggests its potential usefulness in a newly developed PLA2-based therapy for hypercholesterolemia.


SMAD-mediated modulation of YY1 activity regulates the BMP response and cardiac-specific expression of a GATA4/5/6-dependent chick Nkx2.5 enhancer.
Prior work has indicated that BMP signals act in concert with FGF8, WNT11 and WNT antagonists to induce the formation of cardiac tissue in the vertebrate embryo. In an effort to understand how these signaling pathways control the expression of key cardiac regulators, we have characterized the cis-regulatory elements of the chick tinman homolog chick Nkx2.5. We find that at least three distinct cardiac activating regions (CARs) of chick Nkx2.5 cooperate to regulate early expression in the cardiac crescent and later segmental expression in the developing heart. In this report, we focus our attention on a 3' BMP-responsive enhancer, termed CAR3, which directs robust cardiac transgene expression. By systematic mutagenesis and gel shift analysis of this enhancer, we demonstrate that GATA4/5/6, YY1 and SMAD1/4 are all necessary for BMP-mediated induction and heart-specific expression of CAR3. Adjacent YY1 and SMAD-binding sites within CAR3 constitute a minimal BMP response element, and interaction of SMAD1/4 with the N terminus of YY1 is required for BMP-mediated induction of CAR3. Our data suggest that BMP-mediated activation of this regulatory region reflects both the induction of GATA genes by BMP signals, as well as modulation of the transcriptional activity of YY1 by direct interaction of this transcription factor with BMP-activated SMADs.


[The forensic medical diagnosis of intoxication of alcohol surrogates by morphological findings].
The pathomorphology of intoxication of alcohol surrogates is described. A high frequency rate of DIC-syndrome is shown for the condition. A majority of thrombi accumulates at places with the highest concentrations of toxic substances as well as at those places, through which poisoning substances are brought out of the body, i.e. in the liver (since toxic substances are introduced perorally) and kidneys. Thrombi were detected in all internals, including the brain, in lethal intoxication. The immediate toxic effect from methanol and from higher spirits can matter in the genesis of changes, including acute swelling and chromatolysis with subsequent cell death. Exclusively cerebral or coagulopathic-cerebral types of thanatogenesis were registered in studied case of intoxication.


Noise induces partial annihilation of colliding dissipative solitons.
Partial annihilation of two counterpropagating dissipative solitons, with only one pulse surviving the collision, has been widely observed in different experimental contexts, over a large range of parameters, from hydrodynamics to chemical reactions. However, a generic picture accounting for partial annihilation is missing. Based on our results for coupled complex cubic-quintic Ginzburg-Landau equations as well as for the FitzHugh-Nagumo equation we conjecture that noise induces partial annihilation of colliding dissipative solitons in many systems.


The International Childhood Cancer Cohort Consortium (I4C): A research platform of prospective cohorts for studying the aetiology of childhood cancers.
Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples. Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.


Identification of a G protein coupled receptor induced in activated T cells.
Many genes are induced after T cell activation to make a cell competent for proliferation and ultimately, function. Many of these genes encode surface receptors for growth factors that signal a cell to proliferate. We have cloned a novel gene (clone 6H1) that codes for a member of the G protein-coupled receptor superfamily. This gene was isolated from a chicken activated T cell cDNA library by low level hybridization to mammalian IL-2 cDNA probes. The 308 amino acid open reading frame has seven hydrophobic, presumably transmembrane domains and a consensus site for interaction with G proteins. Tissue distribution studies suggest that gene expression is restricted to activated T cells. The message appears by 1 h after activation and is maintained for at least 45 h. Transcription of 6H1 is induced by a number of T cell stimuli and is inhibited by cyclosporin A, but not by cycloheximide. This is the first description of a member of this superfamily expressed specifically in activated T cells. The gene product may provide a link between T cell growth factors and G protein activation.


Influence of a low sodium diet on the renal response to amino acid infusions in humans.
In experimental animals, a high protein diet has been shown to accelerate end-stage renal disease by inducing glomerular hyperperfusion. In this study, we found that intravenous administration of amino acid, used as one component of parenteral nutrition, to normal volunteers resulted in a significant increase in renal blood flow (from 517 +/- 29 to 754 +/- 60 ml/min) and glomerular filtration rate (from 106 +/- 6 to 165 +/- 12 ml/min) without altering systemic blood pressure, renal excretion of electrolytes, plasma renin activity, or plasma aldosterone concentration, and excretory rates of prostaglandins E2 were increased (from 665 +/- 61 to 1,034 +/- 153 pg/min). These amino acid-induced renal hemodynamic effects were abolished when the volunteers received a low sodium diet (20 mEq/day) for three days before the amino acid infusions. However, the hemodynamic effects were restored when the subjects receiving low sodium diets were pretreated with captopril. Under these conditions, amino acid infusions increased renal blood flow (from 388 +/- 11 to 597 +/- 27 ml/min) and glomerular filtration rate (from 80 +/- 4 to 118 +/- 9 ml/min). Reduction of prostaglandin synthesis with indomethacin in volunteers receiving a normal sodium intake was also capable of significantly decreasing the amino acid effects on renal hemodynamics. The results indicate that the renal hemodynamic effects of amino acid infusion are strongly influenced by angiotensin II and prostaglandin formation.


The mediating role of emotional intelligence on the autonomic functioning - Psychopathy relationship.
Reduced autonomic activity is a risk factor for psychopathy, but the mechanisms underlying this association are under-researched. We hypothesize that emotional intelligence mediates this relationship. Emotional intelligence, cognitive intelligence, scores on the Psychopathy Checklist- Revised (PCL-R), skin conductance, and heart rate were assessed in 156 men from communities in Los Angeles. Emotional intelligence fully mediated the relationship between autonomic functioning and total psychopathy after controlling for cognitive intelligence for both autonomic measures. Full mediation was also found when using PCL-R factors and facets as outcome variables, with the exception of a partial mediation of the heart rate - Antisocial facet relationship. These findings are the first to document emotional intelligence as a mediator of the blunted physiological stress activity - psychopathy relationship, and are interpreted within the framework of the somatic marker and somatic aphasia theories of psychopathy. Possible implications for treatment interventions are also discussed.


Accuracy and Reproducibility Using Patient-Specific Instrumentation in Total Ankle Arthroplasty.
Implant survivorship is dependent on accuracy of implantation and successful soft tissue balancing. System instrumentation for total ankle arthroplasty implantation has a key influence on surgeon accuracy and reproducibility. The purpose of this study was to determine the accuracy and reproducibility of implant position with patient-specific guides for total ankle arthroplasty across multiple surgeons at multiple facilities. This retrospective, multicenter study included 44 patients who received a total ankle implant (INBONE II Total Ankle System; Wright Medical Technology, Memphis, TN) using PROPHECY patient-specific guides from January 2012 to December 2014. Forty-four patients with an average age of 63.0 years underwent total ankle arthroplasty using this preoperative patient-specific system. Preoperative computed tomography (CT) scans were obtained to assess coronal plane deformity, assess mechanical and anatomic alignment, and build patient-specific guides that referenced bony anatomy. The mean preoperative coronal deformity was 4.6 ± 4.6 degrees (range, 14 degrees varus to 17 degrees valgus). The first postoperative weightbearing radiographs were used to measure coronal and sagittal alignment of the implant vs the anatomic axis of the tibia. In 79.5% of patients, the postoperative implant position of the tibia corresponded to the preoperative plan of the tibia within 3 degrees of the intended target, within 4 degrees in 88.6% of patients, and within 5 degrees in 100% of patients. The tibial component coronal size was correctly predicted in 98% of cases, whereas the talar component was correctly predicted in 80% of cases. The use of patient-specific instrumentation for total ankle arthroplasty provided reliable alignment and reproducibility in the clinical situation similar to that shown in cadaveric testing. This study has shown that the preoperative patient-specific instrumentation provided for accuracy and reproducibility of ankle arthroplasty implantation in a cohort across multiple surgeons and facilities. Level III, retrospective comparative series.


Negative cross-talk between Nur77 and small heterodimer partner and its role in apoptotic cell death of hepatoma cells.
Nur77, an orphan nuclear receptor, has been implicated in apoptosis of a variety of cell types, including hepatocytes. The small heterodimer partner (SHP) binds and inhibits the function of many nuclear receptors. Here, we investigated cross-talk between Nur77 and SHP during anti-Fas antibody (CH11)-mediated apoptosis of hepatic cells. Expression of SHP decreased, whereas antisense SHP enhanced, the transcriptional activity of Nur77 in HepG2 cells. SHP and Nur77 were physically associated in vivo and colocalized in the nucleus. SHP decreased the transactivation function of the N-terminal domain of Nur77 that recruits coactivators. Nur77 and SHP competitively bound to cAMP response element-binding protein-binding protein and the expression of coactivators, such as cAMP response element-binding protein-binding protein and activating signal cointegrator-2, recovered the decreased function of Nur77 caused by SHP. Finally, SHP was differentially expressed in hepatoma cell lines in that it was not detected in the interferon-gamma (IFNgamma)/CH11-sensitive SNU354, whereas it was significantly expressed in the IFNgamma/CH11-resistant HepG2. Interestingly, a stable SNU354 cell line that expressed SHP became resistant to the IFNgamma/CH11-induced apoptosis. Together, our results suggest that SHP plays a key role in the regulation of Nur77 activation and thereby in Nur77-mediated apoptosis in the liver.


Prevalence of coronary risk factors in non-insulin dependent (type 2) diabetics.
A cross sectional study was conducted to find the prevalence of coronary risk factors in non-insulin dependent diabetic (NIDDM) patients and to compare and co-relate these risk factors in type II diabetics with and without electrocardiographic and/or symptomatic evidence of coronary heart disease (CHD). One hundred sixty-seven consecutive NIDDM patients (77 males, and 90 females) attending the diabetic clinic at Dr. RML Hospital, New Delhi were studied. Only known NIDDM cases, already on treatment and without any history of ketosis or congestive heart failure were included. Coronary risk factors comprising of age, gender, duration and treatment for diabetes, smoking, physical activity, hypertension, truncal obesity, lipids, microalbuminuria (semiquantitative) and glycemic control have been particularly ascertained in all the cases. The data was analysed using 'Epi Info version 6.0'. The mean age of patients was 53.12 year and 8.86 year was the mean duration of diabetes. 28.6% of the diabetic men were found to be currently smoking and/or consuming alcohol, 82% were involved in sedentary physical activity and 20.4% had family history of CHD. Central obesity was observed in 46.7% of the cases; more so in females. 31.74% of cases were hypertensive; more females than males had hypertension (33.8% vs 30%). Poor glycemic control (HbA1c > = 9.5%) was seen in 16.8% of the cases. In about 52.5% of the total group hypertriglyceridemia was noted. Microalbuminuria could be found in 35.93%. CHD was diagnosed in 15.57% of cases in this study. The present study revealed that high levels of serum cholesterol (p = 0.000004), LDL (p = 0.00003), HbA1c (p = 0.002), microalbuminuria (p = 0.000006) and hypertension (p = 0.00006) are significant associates of CHD in NIDDM (both the sexes). Among the female NIDDM cases, in addition BMI (p = 0.01), Waist-hip ratio (WHR) (p = 0.003) and low HDL level (p = 0.008) are important correlates of CHD. Multiple logistic regression analysis was used to allow for confounding between variables. Microalbuminuria alone entered the 'best' model for CHD prediction. Other risk factors, though significant, provided inadequate models for CHD prediction.


Evaluation of real-world preferences and performance of hearing aids fitted according to the NAL-NL1 and DSL v5 procedures in children with moderately severe to profound hearing loss.
The study aims to compare the performance of hearing aids fitted according to the NAL-NL1 and DSL v5 prescriptive procedure for children. This is a crossover four period trial. Sixteen school-aged children with moderately severe to profound hearing losses participated in the study. The children were fitted with Phonak Naida V SP hearing aids according to the two prescriptive procedures. The results showed that children performed significantly better with DSL v5 than with NAL-NL1 prescription for sentence perception in quiet. The paired-comparison judgments of speech intelligibility showed seven children significantly preferred the DSL v5 prescription while two children preferred the NAL-NL1 prescription. The average scores on functional and ratings by parents and teachers performance of children in real life were significantly better for the DSL v5 prescription. At the end of all trials, nine children preferred the DSL v5 prescription, four preferred the NAL-NL1 prescription, and two had no preference. Hearing aids fitted based on the DSL v5 procedure would seem to be more appropriate than the NAL-NL1 procedure for children with moderately severe to profound sensorineural hearing loss, at least in quiet listening environments.


Monoclonal antibody fluorescent polarisation immunoassay versus 125Iode labelled ligand radioimmunoassay for the measurement of cyclosporine concentrations in whole blood.
Monoclonal antibody fluorescent polarisation immunoassay for cyclosporine in whole blood was first evaluated. Inter- and intra-assay CVs were less than 7%. We also compared concentrations measured by 125I-RIA and FPIA in specimens obtained from kidney and bone marrow transplanted patients. FPIA correlated well with 125I-RIA (slope = 1.03, r = 0.989, n = 58) over a wide range of concentrations (44-984 ng/ml). However, an additive bias estimated by the mean difference in cyclosporine concentrations between the 2 readings (44.1 +/- 44.3 ng/ml), led to overestimation of cyclosporine concentrations measured by FPIA. The monoclonal FPIA kit is therefore a rapid and reproductive method to monitor cyclosporine concentrations in whole blood. However, FPIA and 125I-RIA are not interchangeable and the therapeutic range of cyclosporine measured by FPIA should be defined.


On the intrinsic photophysics of indigo: a time-resolved photoelectron spectroscopy study of the indigo carmine dianion.
The intrinsic photophysics of indigo has been studied using gas-phase time-resolved photoelectron imaging of the indigo carmine dianion (InC(2-)). The action spectrum reveals that the gas-phase absorption spectrum arising from the S(1) <-- S(0) transition in InC(2-) has a similar solvent shift to that of neutral indigo. Femtosecond spectroscopy shows that the S(1) state decays on a 1.4 ps timescale. Through isotopic substitution, the primary mechanism on the S(1) excited state can be assigned to an intra-molecular proton transfer, which is the same as that which has been observed in solution. However, the excited state lifetime is significantly shorter in vacuum. These similarities and differences are discussed in terms of recent theoretical investigations of the S(1) excited state of indigo.