Circular RNA BMI1 Serves as a Potential Target for Diagnosis and Treatment in Esophageal Cancer.
Previous studies have confirmed that BMI1 is elevated in esophageal cancer, which is a potential therapeutic target for esophageal cancer. However, the clinical significance of circular RNA BMI1 (circ-BMI1) in esophageal cancer is not yet clear. Herein, we revealed the clinical implication of circ-BMI1 in esophageal cancer, and provided a theoretical basis for molecular diagnosis and potential targeted therapy of esophageal cancer. Firstly, 10 fresh paired esophageal cancer tissues and paracancer tissues, 49 esophageal cancer serum samples and 28 healthy control serum samples were involved in our study. Differential expression and clinical significance of circ-BMI1 in esophageal cancer patients and healthy controls were evaluated by quantitative Real-time RT-PCR (RT-qPCR). Secondly, effects of circ-BMI1 differential expression on biological function of esophageal cancer cell line Eca109 were analyzed. Effects of circ-BMI1 on cell proliferation, migration and colony forming ability were evaluated by CCK-8, wound healing, and colony-forming assay. Cell apoptosis, drug sensitivity tests were also be conducted. Finally, influence of Eca109 cells differentially expressed by circ-BMI1 on tumorigenicity in nude mice was studied. Expression of circ-BMI1 in serum and tissues of esophageal cancer patients was significantly decreased compared to controls (P < 0.001 and P = 0.003, respectively). Area under the receiver operating characteristic curve (ROC) was 0.726. Cell proliferation, migration and colony forming ability of circBMI1-Eca109 cells were obviously decreased than that of NC-Eca109 cells (P < 0.05). circBMI1-Eca109 cells were more sensitive to 5-fluorouracil and cisplatin, and tumor volume of nude mice in circBMI1-Eca109 group was smaller (P < 0.05). The study indicated that expression of circ-BMI1 was significantly down-regulated in esophageal cancer. Overexpression of circ-BMI1 inhibited proliferation, migration, colony formation of Eca109 cells, and tumor growth of Eca109 cells in nude mice. circ-BMI1 may be a potential target for diagnosis and treatment in esophageal cancer.


Building self-ordered tubular macro- and mesoporous nitridated titania from gas bubbles towards high-performance lithium-ion batteries.
Robust well-defined tubular structural materials based on macro- and mesoporous nitridated titania (TMMN-TiO2) were obtained by a simple solution-phase approach in ammonia solution. In this approach, the gas bubbles derived from ammonia solution play the role of templates that direct the ordered growth in the form of a tubular structure. The results demonstrated that the volume ratio of ammonia to water can be favorable for the formation of TMMN-TiO2, which are characterized by FESEM and FTIR. What is more, ammonia was used not only as the template but also as the nitrogen source. Interestingly, it was found that the TiO2 nanocrystals building blocks were assembled into an interconnected mesoporous skeleton and built in ordered tubular macroporous channels. This unique architecture provides many important features that are required for high-performance anodes, such as fast ion transport, high conductivity, and structure stability, thus enabling an electrode with outstanding lithium storage performance. For example, such an electrode delivers 112 mA h g(-1) capacity at 5100 mA g(-1) (30 C) even after 1200 cycles.


Physiological investigations of a tobacco mutant with o(2)-resistant photosynthesis and enhanced catalase activity.
Experiments are described further indicating that O(2)-resistant photosynthesis observed in a tobacco (Nicotiana tabacum) mutant with enhanced catalase activity is associated with decreased photorespiration under conditions of high photorespiration relative to net photosynthesis. The effects on net photosynthesis of (a) increasing O(2) concentrations from 1% to 42% at low CO(2) (250 microliters CO(2) per liter), and (b) of increasing O(2) concentrations from 21% to 42% at high CO(2) (500 microliters CO(2) per liter) were investigated in M(6) progeny of mutant and wild-type leaf discs. The mutant displayed a progressive increase in net photosynthesis relative to wild type with increasing O(2) and the faster rate at 42% O(2) was completely reversed on returning to 21% O(2). The photosynthetic rate by the mutant was similar to wild type in 21% and 42% O(2) at 500 microliters CO(2) per liter, and a faster rate by the mutant was restored on returning to 250 microliters CO(2) per liter. The results are consistent with a lowered release of photorespiratory CO(2) by the mutant because greater catalase activity inhibits the chemical decarboxylation of alpha-keto acids by peroxisomal H(2)O(2). Higher catalase activity was observed in the tip and middle regions of expanding leaves than in the basal area. On successive selfing of mutant plants with enhanced catalase activity, the percent of plants with this phenotype increased from 60% in M(4) progeny to 85% in M(6) progeny. An increase was also observed in the percent of plants with especially high catalase activity (averaging 1.54 times wild type) on successive selfings suggesting that homozygosity for enhanced catalase activity was being approached.


Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
Malaria is still considered as the major parasitic disease and the development of artemisinin resistance does not improve this alarming situation. Based on the recent identification of relevant malaria targets in the artemisinin resistance context, novel drug combinations were evaluated against artemisinin-sensitive and artemisinin-resistant Plasmodium falciparum parasites. Corresponding hybrid molecules were also synthesized and evaluated for comparison with combinations and individual pharmacophores (e.g. atovaquone, mefloquine or triclosan). Combinations and hybrids showed remarkable antimalarial activity (IC50 = 0.6 to 1.1 nM for the best compounds), strong selectivity, and didn't present any cross-resistance with artemisinin. Moreover, the combination triclosan + atovaquone showed high activity against artemisinin-resistant parasites at the quiescent stage but the corresponding hybrid lost this pharmacological property. This result is essential since only few molecules active against quiescent artemisinin-resistant parasites are reported. Our promising results highlight the potential of these combinations and paves the way for pharmacomodulation work on the best hybrids.


Long-term clinical experience with guanfacine.
Efficacy of guanfacine was studied in 20 hypertensive patients and 20 patients with diabetes mellitus and hypertension in a 12-month follow-up. Besides routine biochemical parameters, glycaemia, platelet aggregation and the parameters of serotonergic and adrenergic activity (5-hydroxyindoleacetic acid and vanilmandelic acid urinary excretion) were investigated. Blood pressure was well controlled and no changes in glucose levels occurred in either of the study groups. The decrease in the urinary excretion of vanilmandelic and 5-hydroxyindoleacetic acid was more marked in hypertensive patients with normal glucose tolerance. These data suggest that activity of both adrenergic and serotonergic systems may be more impaired in diabetes. Further, changes in the serotonergic system are not caused only by antiserotonergic drugs. Finally, guanfacine was shown to be an effective and suitable drug for the long-term treatment of hypertension, particularly in patients with diabetes mellitus II.


Influence of iloprost and various prostaglandin derivatives on mouse skin allograft survival, HLA-DR antigen expression and eicosanoid metabolism by human leukocytes.
Treatment of mice bearing allogeneic tail skin grafts with iloprost, a stabilized prostacyclin derivative, as well as dexamethasone prolonged graft survival. Nalador and flunoprost, stabilized prostaglandin E analogues, had similar but weaker effects. The thromboxane agonist U 46619 had no effect on graft rejection. An incubation of human monocytes with iloprost or prostaglandin E2 led to a dose-dependent reduction of HLA-DR antigen expression by these cells. Furthermore, a suppressive effect of these prostaglandin derivatives on the calcium ionophore stimulated release of arachidonic acid metabolites by human polymorphonuclear leukocytes has been shown, which demonstrates an antiinflammatory action of these drugs. Additionally, the eicosanoids were determined in the tail skin after complete allograft rejection. The importance of thromboxane for the rejection of skin grafts has not been confirmed. These data, along with the known antiaggregatory and antiischemic cytoprotective effects of iloprost, suggest that this newly developed drug may be all the more important in clinical organ transplantation.


Faraday-like Screening by Two-Dimensional Nanomaterials: A Scale-Dependent Tunable Effect.
The modulation of electric fields by mono- or few-layer two-dimensional (2D) nanomaterials embodies a major challenge through vast technological areas, including 2D nanoscale electronics, ultrathin cable shielding, and nanostructured battery and supercapacitor electrodes. By a quantum-mechanical analysis of Faraday-like electrostatic screening due to diverse 2D nanolayers we demonstrate that electric field screening is triggered by charge response nonlocality. The effective screening factor is not only influenced by average polarizability but further exhibits nontrivial scalings with respect to surface distance: while ideal 2D metallic systems cause complete Faraday-cage screening, semimetallic graphene yields a finite, roughly scale-independent field reduction factor. Conversely, screening by finite-gap MoS2 appears most effective in the vicinity of the surfaces, gradually vanishing in the long-distance limit because of the intrinsic finiteness of the charge-response length scale. The variability of screening effects and of their scaling laws with respect to accessible physical parameters opens novel pathways for experimental modulation of electric fields, ionic interactions, and adsorption of charged or polar moieties.


Levels of analysis in etiological research on schizophrenia.
Etiological research spanning domains of inquiry as diverse as social psychology and molecular genetics has identified a number of potential factors that likely contribute to the development and clinical manifestation of schizophrenia. In this article, we first highlight the challenges inherent in developing cogent etiological models that represent both the diversity of suspected causal influences and their mechanisms of action. Then, using our own research program as a heuristic context, we present a general analytical framework for identifying and integrating multiple types of etiologic factors across different levels of analysis in the prediction of schizophrenia. In recognition of the myriad complexities of multifactorial causation, we argue that a multilevel causal perspective is required for the development and advancement of a fully nuanced theory of schizophrenia etiology and pathophysiology.


Discovery of undefined protein cross-linking chemistry: a comprehensive methodology utilizing 18O-labeling and mass spectrometry.
Characterization of protein cross-linking, particularly without prior knowledge of the chemical nature and site of cross-linking, poses a significant challenge, because of their intrinsic structural complexity and the lack of a comprehensive analytical approach. Toward this end, we have developed a generally applicable workflow-XChem-Finder-that involves four stages: (1) detection of cross-linked peptides via (18)O-labeling at C-termini; (2) determination of the putative partial sequences of each cross-linked peptide pair using a fragment ion mass database search against known protein sequences coupled with a de novo sequence tag search; (3) extension to full sequences based on protease specificity, the unique combination of mass, and other constraints; and (4) deduction of cross-linking chemistry and site. The mass difference between the sum of two putative full-length peptides and the cross-linked peptide provides the formulas (elemental composition analysis) for the functional groups involved in each cross-linking. Combined with sequence restraint from MS/MS data, plausible cross-linking chemistry and site were inferred, and ultimately confirmed, by matching with all data. Applying our approach to a stressed IgG2 antibody, 10 cross-linked peptides were discovered and found to be connected via thioethers originating from disulfides at locations that had not been previously recognized. Furthermore, once the cross-link chemistry was revealed, a targeted cross-link search yielded 4 additional cross-linked peptides that all contain the C-terminus of the light chain.


New example of a non-heme mononuclear iron(IV) oxo complex. Spectroscopic data and oxidation activity.
The green complex S=1 [(TPEN)FeO]2+ [TPEN=N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine] has been obtained by treating the [(TPEN)Fe]2+ precursor with meta-chloroperoxybenzoic acid (m-CPBA). This high-valent complex belongs to the emerging family of synthetic models of Fe(IV)=O intermediates invoked during the catalytic cycle of biological systems. This complex exhibits spectroscopic characteristics that are similar to those of other models reported recently with a similar amine/pyridine environment. Thanks to its relative stability, vibrational data in solution have been obtained by Fourier transform infrared. A comparison of the Fe=O and Fe=(18)O wavenumbers reveals that the Fe-oxo vibration is not a pure one. The ability of the green complex to oxidize small organic molecules has been studied. Mixtures of oxygenated products derived from two- or four-electron oxidations are obtained. The reactivity of this [FeO]2+ complex is then not straightforward, and different mechanisms may be involved.


Bayesian tests of extra-Binomial variability.
A simple model for extra-Binomial variability is the Beta-Binomial. A complication in testing the Binomial against the Beta-Binomial alternative is that the Binomial lies on the boundary of the Beta-Binomial, which forces modifications to the usual asymptotic arguments. In this paper, we propose a Bayesian test using a pair of approximate Bayes factors, one for the case in which the maximum likelihood estimator (MLE) of the extra-Binomial variability is zero and one for the case in which it is positive. These approximate Bayes factors are easy to compute. We evaluate the operating characteristics of the Bayes factors and find them to be more powerful than the likelihood ratio test. We then apply the method to three data sets, including one in which the issue is whether a logistic regression intercept should be considered a random effect. In each case, our approximate Bayes factors are close to the exact Bayes factors, which may also be computed with additional effort.


Approximation scheme for master equations: Variational approach to multivariate case.
We study an approximation scheme based on a second quantization method for a chemical master equation. Small systems, such as cells, could not be studied by the traditional rate equation approach because fluctuation effects are very large in such small systems. Although a Fokker-Planck equation obtained by the system size expansion includes the fluctuation effects, it needs large computational costs for complicated chemical reaction systems. In addition, discrete characteristics of the original master equation are neglected in the system size expansion scheme. It has been shown that the use of the second quantization description and a variational method achieves tremendous reduction in the dimensionality of the master equation approximately, without loss of the discrete characteristics. Here, we propose a new scheme for the choice of variational functions, which is applicable to multivariate cases. It is revealed that the new scheme gives better numerical results than old ones and the computational cost increases only slightly.


Robot-Assisted Laparoscopic Removal of a Large Primary Retroperitoneal Mature Cystic Teratoma in an Adult.
Mature teratomas are unique and generally benign neoplasms. They are derived from embryonic tissues and typically located within the gonadal region. Primary retroperitoneal teratomas are uncommon in adults and often challenging to treat, given their location and size. Here, we offer a rare case of a large primary retroperitoneal mature cystic teratoma, detected on abdominal ultrasound during the work-up of abdominal bloating and nausea and treated with robot-assisted laparoscopic excision in a 58-year-old male. In this report, we sought to describe the evaluation, treatment, and follow-up of this condition, as well as review the associated literature.


Increased carbon monoxide excretion in Bolivian squirrel monkeys with fasting hyperbilirubinemia.
Pulmonary carbon monoxide (CO) excretion rates (VeCO) were 50% greater, on average, in Bolivian squirrel monkeys (BoSMs) which exhibit a unique fasting hyperbilirubinemia (FH), than in fasted control Brazilian squirrel monkeys (BrSMs). Since the catabolism of heme produces equimolar amounts of CO and bilirubin, the increased VeCOs are consistent with concurrent increases in endogenous bilirubin production rates. Tin-protoporphyrin, a competitive inhibitor of heme oxygenase, significantly decreased both the VeCO and serum bilirubin level in fasted BoSMs. Overproduction of bilirubin may be responsible in part for the marked FH in BoSMs.


Rupture resolution in cognitive analytic therapy for adolescents with borderline personality disorder.
Ruptures are potential change events in therapy that might result in positive or negative consequences for the therapeutic alliance and outcome. Alliance ruptures and premature drop-out are common with clients diagnosed with borderline personality disorder, limiting treatment effectiveness. To test a nine stage model of rupture resolution in cognitive analytic therapy (CAT) with adolescents. The validation phase of task analysis was employed to test the rupture resolution model and to relate handling of ruptures to outcome using quantitative and qualitative analysis of transcripts. Eighteen ruptures and resolution attempts were intensively examined across three good and two poor outcome sessions, as rated by clients. The number of model stages employed by therapists was related to outcome. Sessions evaluated as poor or good by clients could be distinguished according to the extent to which therapists used model stages. Treatment outcome was significantly associated with number of model stages included by therapists. Competent resolution of ruptures in CAT is dependent on therapists' inclusion of stages of the model, providing validation for the model, and demonstrating that effective rupture resolution might be related to treatment outcome. Ruptures and their resolution are likely to be key events in psychotherapy process.


Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1.
RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development. RasGRP1 is important in some cancers and autoimmune diseases but, in contrast to SOS, its regulatory mechanisms are poorly understood. Activating signals lead to the membrane recruitment of RasGRP1 and Ras engagement, but it is unclear how interactions between RasGRP1 and Ras are suppressed in the absence of such signals. We present a crystal structure of a fragment of RasGRP1 in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface of RasGRP1 is hidden within a dimerization interface that may be stabilized by the C-terminal oligomerization domain. NMR data demonstrate that calcium binding to the regulatory module generates substantial conformational changes that are incompatible with the inactive assembly. These features allow RasGRP1 to be maintained in an inactive state that is poised for activation by calcium and membrane-localization signals. DOI:http://dx.doi.org/10.7554/eLife.00813.001.


Association between Left Atrial Deformation and Brain Involvement in Patients with Anderson-Fabry Disease at Diagnosis.
Anderson-Fabry disease (AFD) can induce both central nervous system white matter lesions (WMLs) and cardiac abnormalities including left atrial (LA) dysfunction. We sought to evaluate the possible interrelations of LA structure and function impairment with the presence of WMLs in AFD patients. Methods 22 AFD patients and 22 controls, matched for age and sex, underwent an echo-Doppler exam including quantification of peak atrial longitudinal strain (PALS). AFD patients underwent also a 3-T brain magnetic resonance imaging with a visual quantification of WMLs by Fazekas' score (FS) on 3D FLAIR images. Results AFD patients had significantly higher left ventricular (LV) mass index (LVMi) and relative wall thickness, and lower PALS compared to controls. Among AFD patients, 9 showed a FS = 0, and 13 a FS > 1. AFD patients with FS ≥ 1 showed lower PALS (29.4 ± 6.7 vs. 37.2 ± 3.9%, p = 0.003) than those with FS = 0, without difference in LA volume index and LVMi. In AFD patients, FS was inversely related to PALS (r = -0.49, p < 0.0001), even after adjusting for LVMi (r = -0.43, p < 0.05). Conclusions In the absence of significant alterations in LA size, AFD patients had lower PALS compared to controls. The inverse association between PALS and presence of WMLs indicates a possible parallel early involvement of heart and brain.


Immediate effect of standing and sit-to-stand training on postural vertical for backward disequilibrium following stroke: a case report.
Effects of therapeutic interventions backward disequilibrium following stroke are scarcely reported. To clarify the effects of standing and sit-to-stand/stand-to-sit training aimed at postural deviation in the anterior direction for backward disequilibrium and posterior deviation of subjective postural vertical. The participant presented with backward disequilibrium and pontine hemorrhage-associated sensory impairment of the extremities. Physical therapy included standing and sit-to-stand/stand-to-sit training, expected to bias the center of gravity in the anterior direction. We measured subjective postural vertical on the sagittal plane to assess vertical perception. Backward disequilibrium was evaluated using the Backward Disequilibrium Scale. Walking ability was assessed using the functional ambulation category. These outcomes were assessed before and at 3 days post-intervention. Neurological findings were unchanged between pre- and post-intervention. Post-intervention, in subjective postural vertical, tilt direction modulated from -6.1° to 1.3°, variability changed from 5.9° to 3.3°, and Backward Disequilibrium Scale score improved from 7 to 1 point. Functional ambulation category changed from 2 to 3. Standing and sit-to-stand/stand-to-sit training aimed at shifting center of gravity and subjective postural vertical in the anterior direction appeared to improve backward disequilibrium and correct tilt to the anterior direction for this participant. Long-term effects of the training for this participant were not determined.


Spatial congruence in language and species richness but not threat in the world's top linguistic hotspot.
Languages share key evolutionary properties with biological species, and global-level spatial congruence in richness and threat is documented between languages and several taxonomic groups. However, there is little understanding of the functional connection between diversification or extinction in languages and species, or the relationship between linguistic and species richness across different spatial scales. New Guinea is the world's most linguistically rich region and contains extremely high biological diversity. We demonstrate significant positive relationships between language and mammal richness in New Guinea across multiple spatial scales, revealing a likely functional relationship over scales at which infra-island diversification may occur. However, correlations are driven by spatial congruence between low levels of language and species richness. Regional biocultural richness may have showed closer congruence before New Guinea's linguistic landscape was altered by Holocene demographic events. In contrast to global studies, we demonstrate a significant negative correlation across New Guinea between areas with high levels of threatened languages and threatened mammals, indicating that landscape-scale threats differ between these groups. Spatial resource prioritization to conserve biodiversity may not benefit threatened languages, and conservation policy must adopt a multi-faceted approach to protect biocultural diversity as a whole.


Metabolism of H-Gibberellin A(1) and H-Gibberellin A(4) by Phaseolus coccineus Seedlings.
[(3)H]-Gibberellin A(1) (GA(1)) and (3)H-GA(4) were applied separately to Phaseolus coccineus seedlings grown under red light. (3)H-GA(1) was converted to a compound with gas-liquid radiochromatography retention times identical to those of GA(8). (3)H-GA(4) underwent conversion to at least three metabolites, none of which corresponded to GA(1-38). The rate of metabolism of (3)H-GA(4) was significantly higher than that of (3)H-GA(1).


[Migratory movements in Central and Eastern Europe from the early 1950s till the late 1980s].
"The major aim of the present paper is to disclose the magnitude of immigration from Central-Eastern Europe, to selected European and overseas countries of immigration and the changes those flows underwent over the period 1950-1989. The analysis focuses on the late 1980s.... It follows from the analysis that there were no regular and uniform trends, and the intensity of immigration depended on [the] political cycle in particular countries of Central-Eastern Europe...." (SUMMARY IN ENG)


Molecular characterization of serogrouping and virulence genes of Malaysian Vibrio cholerae isolated from different sources.
A pair of primers targeting the hlyA gene for Vibrio cholerae which could distinguish the classical from El Tor biotypes was designed and combined with other specific primers for ompW, rfb complex, and virulence genes such as ctxA, toxR, and tcpI in a multiplex PCR (m-PCR) assay. This m-PCR correctly identified 39 V. cholerae from clinical, water and seafood samples. The efficiency of this multiplex PCR (m-PCR) was compared with conventional biochemical and serogrouping methods. One O139 and 25 O1 V. cholerae strains including 10 environmental strains harbored all virulence-associated genes except 1 clinical strain which only had toxR and hlyA genes. Thirteen environmental strains were classified as non-O1/non-O139 and had the toxR and hlyA genes only. The detection limit of m-PCR was 7 x 10(4) cfu/ml. The m-PCR test was reliable and rapid and reduced the identification time to 4 h.


Virulence and prodigiosin antibiotic biosynthesis in Serratia are regulated pleiotropically by the GGDEF/EAL domain protein, PigX.
Gram-negative bacteria of the genus Serratia are opportunistic human, plant, and insect pathogens. Serratia sp. strain ATCC 39006 secretes pectinases and cellulases and produces the secondary metabolites carbapenem and prodigiosin. Mutation of a gene (pigX) resulted in an extremely pleiotropic phenotype: prodigiosin antibiotic biosynthesis, plant virulence, and pectinase production were all elevated. PigX controlled secondary metabolism by repressing the transcription of the target prodigiosin biosynthetic operon (pigA-pigO). The transcriptional start site of pigX was determined, and pigX expression occurred in parallel with Pig production. Detailed quantitative intracellular proteome analyses enabled the identification of numerous downstream targets of PigX, including OpgG, mutation of which reduced the production of the plant cell wall-degrading enzymes and virulence. The highly pleiotropic PigX regulator contains GGDEF and EAL domains with noncanonical motifs and is predicted to be membrane associated. Genetic evidence suggests that PigX might function as a cyclic dimeric GMP phosphodiesterase. This is the first characterization of a GGDEF and EAL domain protein in Serratia and the first example of the regulation of antibiotic production by a GGDEF/EAL domain protein.


Reproducibility of metabolomic profiles among men and women in 2 large cohort studies.
Rigorous studies are necessary to demonstrate suitability of metabolomics platforms to profile metabolites in archived plasma within epidemiologic studies of human disease, for which attenuation of effect estimates due to measurement error is a key concern. Using a liquid chromatography-tandem mass spectrometry platform, we quantified 257 metabolites from archived plasma to evaluate metabolite interassay reproducibility, reproducibility with delayed processing, and within-person reproducibility over time. Interassay reproducibility was assessed with CVs from 60 duplicate plasma samples donated by participants in the Nurses' Health Study and Health Professionals Follow-up Study, and 20 QC pool plasma replicates. Metabolite reproducibility over a 24- to 48-h processing delay (n = 48 samples) and within-person reproducibility over 1-2 years (n = 80 samples) were assessed using Spearman and intraclass correlation coefficients (ICCs). CVs were <20% for 92% of metabolites and generally were similar by plasma anticoagulant type (heparin or EDTA) and fasting time. Approximately 75% of metabolites were reproducible over delays in processing of blood samples (Spearman correlation or ICC ≥ 0.75, comparing immediate and 24-h delayed processing). Carbohydrates and purine/pyrimidine derivatives were most adversely affected by the processing delay. Ninety percent of metabolites were reproducible over 1-2 years within individuals (Spearman correlation or ICC ≥ 0.4). For potential use in epidemiologic studies, the majority of plasma metabolites had low CVs and were reproducible over a 24-h processing delay and within individuals over 1-2 years. Certain metabolites, such as carbohydrates and purine/pyrimidine derivatives, may be challenging to evaluate if samples have delayed processing.


Complete Response to Trastuzumab-Based Chemotherapy in a Patient with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Salivary Duct Carcinoma ex Pleomorphic Adenoma.
Carcinoma ex pleomorphic adenoma (CXPA) of the salivary glands has often a salivary duct carcinoma (SDC) component, which resembles ductal carcinoma of the breast and frequently overexpresses human epidermal growth factor receptor-2 (HER2). We report a case of metastatic CXPA with SDC component who was treated with trastuzumab-based chemotherapy and has had a durable complete response. A 74-year-old man was diagnosed with CXPA of the right parotid gland. The resected tumor was histologically diagnosed as CXPA with a predominant SDC component that showed strong positivity for HER2 protein and HER2 gene amplification. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with paclitaxel and trastuzumab was initiated. A complete response was confirmed after 7 treatment cycles, and no evidence of disease progression has been observed after 13 months of initiation of therapy. This report suggests a potential utility of trastuzumab-based chemotherapy for HER2-positive CXPA.


Cellulolytic activity of moulds. III. Enzymatic hydrolysis of cellulose by cellulase preparation from Aspergillus terreus F-413.
The strain Aspergillus terreus F-413 was used to obtain cellulolytic enzymes; it was cultivated on cellucotton by the submerged method in a 101 fermenter. The crude enzymatic preparation obtained from the post-culture liquid, containing small amounts of other enzymes besides active cellulases, was used for hydrolysis of several kinds of cellulose. The highest saccharification percentage was obtained with cellucotton and filter paper, while the lowest with lignocellulosic materials such as straw and sawdust. It was shown that cellulose pretreatment, both mechanical (grinding in a ball mill) and chemical (with alkali) distinctly increased the yield of enzymatic hydrolysis. In the obtained hydrolyzates the presence of glucose as the main product of cellulose decomposition was found.


Timing of inpatient rehabilitation initiation in stroke patients: factors influencing early admission.
[Purpose] Early admission to inpatient rehabilitation is critical for reducing post-stroke disability. Assessing admission timing and other trends in inpatient rehabilitation are essential for improving health outcomes. This study is the first to evaluate the timing of admission of stroke patients to inpatient rehabilitation in Turkey. [Subjects and Methods] We retrospectively analyzed acute stroke survivors who were admitted to the inpatient rehabilitation program in the Ministry of Health, Ankara Physical Medicine and Rehabilitation Training and Research Hospital between January 2009 and December 2010. [Results] The mean onset of inpatient rehabilitation was 9.8 ± 6.7 weeks post-stroke in the entire cohort. Occurrence of ischemic stroke and undergoing acute stroke care at a teaching hospital were most strongly associated with early admission. These results did not change after multivariate analysis. [Conclusion] Turkish stroke survivors begin inpatient rehabilitation later than patients in other countries. The type of stroke and type of hospital in which the patient undergoes acute stroke treatment affects early admission.


Endofacial competitive inhibition of the glucose transporter 1 activity by gossypol.
Gossypol is a natural disesquiterpene that blocks the activity of the mammalian facilitative hexose transporter GLUT1. In human HL-60 cells, which express GLUT1, Chinese hamster ovary cells overexpressing GLUT1, and human erythrocytes, gossypol inhibited hexose transport in a concentration-dependent fashion, indicating that blocking of GLUT1 activity is independent of cellular context. With the exception of red blood cells, the inhibition of cellular transport was instantaneous. Gossypol effect was specific for the GLUT1 transporter since it did not alter the uptake of nicotinamide by human erythrocytes. Gossypol affects the glucose-displaceable binding of cytochalasin B to GLUT1 in human erythrocyte ghost in a mixed noncompetitive way, with a K(i) value of 20 microM. Likewise, GLUT1 fluorescence was quenched approximately 80% by gossypol, while Stern-Volmer plots for quenching by iodide displayed increased slopes by gossypol addition. These effects on protein fluorescence were saturable and unaffected by the presence of D-glucose. Gossypol did not alter the affinity of D-glucose for the external substrate site on GLUT1. Kinetic analysis of transport revealed that gossypol behaves as a noncompetitive inhibitor of zero-trans (substrate outside but not inside) transport, but it acts as a competitive inhibitor of equilibrium-exchange (substrate inside and outside) transport, which is consistent with interaction at the endofacial surface, but not at the exofacial surface of the transporter. Thus, gossypol behaves as a quasi-competitive inhibitor of GLUT1 transport activity by binding to a site accessible through the internal face of the transporter, but it does not, in fact, compete with cytochalasin B binding. Our observations suggest that some effects of gossypol on cellular physiology may be related to its ability to disrupt the normal hexose flux through GLUT1, a transporter expressed in almost every kind of mammalian cell and responsible for the basal uptake of glucose.


Computerized evaluation of skin stiffening in scleroderma.
Modern non-invasive biometrological methods have proven to be helpful in monitoring some skin disorders. The present study was designed to evaluate the mechanical properties of skin in systemic scleroderma. The Cutometer SM 474 was used to measure the rheological properties of the skin in 33 patients suffering from scleroderma. The most prominent abnormality consisted in a marked reduction in skin extensibility. Changes occurring in time objectivate the evolution of the disease. Measuring the mechanical properties of skin in patients with scleroderma may be useful in monitoring the disease and its treatment.


Moving on: autism and movement disturbance.
Many authors have reported on the presence of movement disturbance symptoms in some individuals with autism. Typically, these symptoms have been seen as peripheral to autism or as belonging to a co-occurring syndrome. Some have dismissed these symptoms as having no apparent impact on the presence of behaviors defined as the core characteristics of autism. In this article we considered the relation between symptoms of movement disturbance and symptoms of autism and included our speculative and exploratory analyses of shared symptoms. The analyses point out the difficulties posed by current definitions of autism. We proposed that symptoms of movement disturbance can affect a person's experience of life and how he or she may be perceived by others.


Automated formation of multicomponent-encapuslating vesosomes using continuous flow microcentrifugation.
Vesosomes - hierarchical assemblies consisting of membrane-bound vesicles of various scales - are potentially powerful models of cellular compartmentalization. Current methods of vesosome fabrication are labor intensive, and offer little control over the size and uniformity of the final product. In this article, we report the development of an automated vesosome formation platform using a microfluidic device and a continuous flow microcentrifuge. In the microfluidic device, water-in-oil droplets containing nanoscale vesicles in the water phase were formed using T-junction geometry, in which a lipid monolayer is formed at the oil/water interface. These water-in-oil droplets were then immediately transferred to the continuous flow microcentrifuge. When a water-in-oil droplet passed through a second lipid monolayer formed in the continuous flow microcentrifuge, a bilayer-encapsulated vesosome was created, which contained all of the contents of the aqueous phase encapsulated within the vesosome. Encapsulation of nanoscale liposomes within the outer vesosome membrane was confirmed by fluorescence microscopy. Laser diffraction analysis showed that the vesosomes we fabricated were uniform (coefficient of variation of 0.029). The yield of the continuous flow microcentrifuge is high, with over 60% of impinging water droplets being converted to vesosomes. Our system provides a fully automatable route for the generation of vesosomes encapsulating arbitrary contents. The method employed in this work is simple and can be readily applied to a variety of systems, providing a facile platform for fabricating multicomponent carriers and model cells.


Early cerebral activities of the environmental estrogen bisphenol A appear to act via the somatostatin receptor subtype sst(2).
Recently, considerable interest has been aroused by the specific actions of bisphenol A (BPA). The present investigation represents a first study dealing with the interaction of BPA with the biologically more active somatostatin receptor subtype (sst(2)) in the rat limbic circuit. After treating pregnant female Sprague-Dawley rats with two doses (400 microg/kg/day; 40 microg/kg/day) of BPA, the binding activity of the above receptor subtype was evaluated in some limbic regions of the offspring. The higher dose proved to be the more effective one, as demonstrated by the elevated affinity of sst(2) with its specific radioligand, [(125)I]-Tyr(0)somatostatin-14. The most dramatic effects of BPA on sst(2) levels occurred at the low-affinity states of such a subtype in some telencephalic limbic areas of postnatal rats (10 days of age; postnatal day [PND] 10). These included lower (p < 0.05) sst(2) levels in the gyrus dentate of the hippocampus and basomedial nucleus of the amygdala; significantly higher (p < 0.01) levels were observed only for the high-affinity states of the periventricular nucleus of the hypothalamus. A similar trend was maintained in PND 23 rats with the exception of much lower levels of the high-affinity sst(2) receptor subtype in the amygdala nucleus and ventromedial hypothalamic nucleus. However, greater changes produced by this environmental estrogen were reported when the binding activity of sst(2) was checked in the presence of the two more important selective agonists (zolpidem and Ro 15-4513) specific for the alpha-containing Gamma-aminobutyric acid (GABA) type A receptor complex. In this case, an even greater potentiating effect (p < 0.001) was mainly obtained for the low-affinity sst(2) receptor subtype in PND 10 animals, with the exception of the high-affinity type in the ventromedial hypothalamic nucleus and gyrus dentate. These results support the contention that an sst(2) subtype alpha-containing GABA type A receptor system might represent an important neuromediating station capable of promoting estrogenlike mechanisms of BPA, especially during the early developmental phases.


Anticancer effects of the organosilicon multidrug resistance modulator SILA 421.
1,3-dimethyl-1,3-bis(4-fluorophenyl)-1,3-bis{3-[1(4-butylpiperazinyl)]-propyl}-disiloxan-tetrahydrochlorid (SILA 421) is a compound that was developed as modulator of the ABC cassette transporter P-glycoprotein. Furthermore, it exerted antimicrobial toxicity, vascular effects, downregulation of chaperone induction and plasmid curing in bacterial cells. Here, this drug was found to possess cytotoxic activity against a panel of human cancer cell lines that do not overexpress P-gp, with 50% inhibitory concentrations ranging between 1.75±0.38 μM for GLC14 small cell lung cancer and 34.00±4.75 μM for PC-3 prostate cancer cells. HL-60 leukemia and MDA-MB-435 breast cancer cells exhibited cell cycle arrest and apoptotic cell death in response to SILA 421. Assessment of global gene expression of SILA 421-treated HL-60 cells was employed to identify cellular pathways affected by the compound and revealed disturbance of DNA replication, transcription and production of apparently misfolded proteins. Endoplasmatic reticulum stress and downregulation of cell cycle, cellular repair mechanisms and growth factor-related signaling cascades eventually resulted in induction of apoptosis in this cell line. In addition to the well established P-gp inhibitory effect of SILA compounds, reversal of resistance to taxanes, which had been reported for SILA 421 and the related molecule SILA 409, may be linked to downregulation of gene expression of kinesins. Interference with DNA replication and transcription seems to be the common denominator of antimicrobial activity and plasmid curing, as well as anticancer toxicity in human cell lines. Thus, in consideration of the full range of putative cellular targets found in the present work, the application of these SILA compounds for treatment of tumors should be further evaluated.


Monitoring of home safety issues in children on enteral feeds with inherited metabolic disorders.
To assess the safety aspects of carers' enteral feeding technique when home enteral tube feeding children with inherited metabolic disorders (IMD). 40 patients (median age, 5.1 years; range, 0.3-13.6 years) with IMD requiring pump tube feeding were recruited. 12 patients had glycogen storage disease, 11 organic acidemias, 8 fatty acid oxidation disorders, 4 urea cycle disorders, and 5 had other conditions. 50% of the patients were fed by gastrostomy and 50% nasogastric tube. A questionnaire and practical assessment of feeding process was completed with carers by a dietician and nurse in the child's home. Areas investigated included carer hygiene, feed preparation, tube care, tube changing, use of feeding pumps and equipment, and storage of enteral feeding equipment. The main issues identified were poor hygiene practices (78% unclean work surfaces; 25% no hand washing); inaccurate ingredient measuring (40%); irregular checking of tube position (40%); inadequate tube flushing (50%); poor knowledge of how to clear tube blockages (80%); incorrect priming of pump sets (50%); incorrect position of child for night feeding (63%); untrained secondary carers (43%); and poor knowledge of pump alarms, battery life, and charging time. Children commonly slept in parent's room as a safety precaution (58%). Long term follow-up of children with IMD on home enteral tube feeding suggests that regular updates on knowledge and technique for carers may be necessary to reduce risk.


Metastasis in colorectal cancer: what makes the tumor aggressive?
While local control of colorectal cancer can usually be obtained, distant spread is frequent and nearly always results in incurable disease and death. Therefore, the critical determinant of aggressiveness of colorectal cancers is the ability to disseminate widely. While the molecular biology of colorectal carcinogenesis is comparatively well understood, the mechanisms important in metastasis remain relatively cryptic. Conceptually, metastasis is a multistep process with a number of potential therapeutic targets. Critical steps include angiogenesis, local invasion, embolization to distant sites, and extravasation. Identification of high risk tumors may allow more judicious use of effective, but nonselective, cytotoxic adjuvant therapy. Specific inhibitors of particular steps of metastasis are already in various stages of testing.


A 1 MHz BW 34.2 fJ/step Continuous Time Delta Sigma Modulator With an Integrated Mixer for Cardiac Ultrasound.
Fully digitized 2D ultrasound transducer arrays require one ADC per channel with a beamforming architecture consuming low power. We give design considerations for per-channel digitization and beamforming, and present the design and measurements of a continuous time delta-sigma modulator (CTDSM) for cardiac ultrasound applications. By integrating a mixer into the modulator frontend, the phase and frequency of the input signal can be shifted, thereby enabling both improved conversion efficiency and narrowband beamforming. To minimize the power consumption, we propose an optimization methodology using a simulated annealing framework combined with a C++ simulator solving linear electrical networks. The 3rd order single-bit feedback type modulator, implemented in a 65 nm CMOS process, achieves an SNR/SNDR of 67.8/67.4 dB across 1 MHz bandwidth consuming 131 [Formula: see text] of power. The achieved figure of merit of 34.2 fJ/step is comparable with state-of-the-art feedforward type multi-bit designs. We further demonstrate the influence to the dynamic range when performing dynamic receive beamforming on recorded delta-sigma modulated bit-stream sequences.


A new butenolide with antifungal activity from solid co-cultivation of Irpex lacteus and Nigrospora oryzae.
A new antifungal butenolide irperide (1) along with five known compounds were isolated from the co-culture of endophyte Irpex lacteus and pathogenic Nigrospora oryzae. The structure of 1, including the absolute configuration, was elucidated by analysis of NMR, HR-ESI-MS data and ECD spectra. Compounds 1, 4 and 6 exhibited significant antifungal activity against Aspergillus fumigatus, with MIC values of 1, 2 and 1 μg/mL, respectively.


"On demand" posterior tibial artery perforator flaps: a versatile surgical procedure for reconstruction of soft tissue defects of the leg after tumor excision.
Relatively small soft-tissue defects of the lower leg following tumor excision are usually treated, especially in older patients, by split-thickness skin grafting. On specific sites where periosteum or paratenon is exposed, as well as when a skin graft is best avoided for cosmetic reasons, an excellent alternative option is the use of posterior tibial artery perforator flaps.Such flaps are designed and elevated "on demand," ie, according to the defect location and on whichever perforator is best found suited to supply the flap and allow adequate transposition.However, operative time is longer, and the surgeon needs to be judicious in dissection, as well as versatile in choosing the best flap design after identifying a suitable perforator.Between 2003 and 2008, 24 patients underwent this procedure, with uniformly successful result except for 2 partial flap necrosis.The advantages of posterior tibial artery perforator flaps are a quick and usually safe procedure, which provides good contour with excellent color, texture, and thickness match, with long-term stability of the reconstruction at the expense of minimal donor-site morbidity.


SPINK3 modulates mouse sperm physiology through the reduction of nitric oxide level independently of its trypsin inhibitory activity.
Serine protease inhibitor Kazal-type (SPINK3)/P12/PSTI-II is a small secretory protein from mouse seminal vesicle which contains a KAZAL domain and shows calcium (Ca(2+))-transport inhibitory (caltrin) activity. This molecule was obtained as a recombinant protein and its effect on capacitated sperm cells was examined. SPINK3 inhibited trypsin activity in vitro while the fusion protein GST-SPINK3 had no effect on this enzyme activity. The inactive GST-SPINK3 significantly reduced the percentage of spermatozoa positively stained for nitric oxide (NO) with the specific probe DAF-FM DA and NO concentration measured by Griess method in capacitated mouse sperm; the same effect was observed when sperm were capacitated under low Ca(2+) concentration, using either intracellular (BAPTA-AM) or extracellular Ca(2+) (EDTA) chelators. The percentage of sperm showing spontaneous and progesterone-induced acrosomal reaction was significantly lower in the presence of GST-SPINK3 compared to untreated capacitated spermatozoa. Interestingly, this decrease was overcome by the exogenous addition of the NO donors, sodium nitroprusside (SNP), and S-nitrosoglutathione (GSNO). Phosphorylation of sperm proteins in tyrosine residues was partially affected by GST-SPINK3, however, only GSNO was able to reverse this effect. Sperm progressive motility was not significantly diminished by GST-SPINK3 or BAPTA-AM but enhanced by the addition of SNP. This is the first report that demonstrates that SPINK3 modulates sperm physiology through a downstream reduction of endogenous NO concentration and independently of SPINK3 trypsin inhibitory activity.


Bacillus subtilis division protein DivIVA - screen for stable oligomer state conditions.
The cell division protein DivIVA is predicted to be a coiled-coil, tropomyosin-like protein, that self-associates both in vivo and in vitro into oligomers of up to 10-12 monomers. A simple and quick screen for conditions supporting the stable oligomer structure has been developed revealing that DivIVA forms a homogeneous oligomer in the presence of PEGs (PEG 4 K or PEG 8K and PEG 1K).


Isolation and characterization of acid-tolerant, thermophilic bacteria for effective fermentation of biomass-derived sugars to lactic acid.
Biomass-derived sugars, such as glucose, xylose, and other minor sugars, can be readily fermented to fuel ethanol and commodity chemicals by the appropriate microbes. Due to the differences in the optimum conditions for the activity of the fungal cellulases that are required for depolymerization of cellulose to fermentable sugars and the growth and fermentation characteristics of the current industrial microbes, simultaneous saccharification and fermentation (SSF) of cellulose is envisioned at conditions that are not optimal for the fungal cellulase activity, leading to a higher-than-required cost of cellulase in SSF. We have isolated bacterial strains that grew and fermented both glucose and xylose, major components of cellulose and hemicellulose, respectively, to l(+)-lactic acid at 50 degrees C and pH 5.0, conditions that are also optimal for fungal cellulase activity. Xylose was metabolized by these new isolates through the pentose-phosphate pathway. As expected for the metabolism of xylose by the pentose-phosphate pathway, [(13)C]lactate accounted for more than 90% of the total (13)C-labeled products from [(13)C]xylose. Based on fatty acid profile and 16S rRNA sequence, these isolates cluster with Bacillus coagulans, although the B. coagulans type strain, ATCC 7050, failed to utilize xylose as a carbon source. These new B. coagulans isolates have the potential to reduce the cost of SSF by minimizing the amount of fungal cellulases, a significant cost component in the use of biomass as a renewable resource, for the production of fuels and chemicals.


Intraocular radiation blocking.
Iodine-based liquid radiographic contrast agents were placed in normal and tumor-bearing (Greene strain) rabbit eyes to evaluate their ability to block iodine-125 radiation. This experiment required the procedures of tumor implantation, vitrectomy, air-fluid exchange, and 125I plaque and thermoluminescent dosimetry (TLD) chip implantation. The authors quantified the amount of radiation attenuation provided by intraocularly placed contrast agents with in vivo dosimetry. After intraocular insertion of a blocking agent or sham blocker (saline) insertion, episcleral 125I plaques were placed across the eye from episcleral TLD dosimeters. This showed that radiation attenuation occurred after blocker insertion compared with the saline controls. Then computed tomographic imaging techniques were used to describe the relatively rapid transit time of the aqueous-based iohexol compared with the slow transit time of the oil-like iophendylate. Lastly, seven nontumor-bearing eyes were primarily examined for blocking agent-related ocular toxicity. Although it was noted that iophendylate induced intraocular inflammation and retinal degeneration, all iohexol-treated eyes were similar to the control eyes at 7 and 31 days of follow-up. Although our study suggests that intraocular radiopaque materials can be used to shield normal ocular structures during 125I plaque irradiation, a mechanism to keep these materials from exiting the eye must be devised before clinical application.


Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles.
DNA double-strand breaks (DSBs) are the main factor behind carbon-ion radiation therapy (CIRT)-induced cell death. Nuclear interactions along the beam path between the primary carbon ions and targets result in nuclear fragmentation of carbon ions and recoiled particles. These secondary particles travel further distances past the Bragg peak to the tail region, leading to unwanted biological effects that may result in cytotoxicity in critical organs and secondary induced tumors following CIRT. Here, we confirmed that the density of the DSB distributions increases as the cell survival decreases at the Bragg peak and demonstrated that by visualizing DSBs, the various LET fragmentation ions and recoiled particles produced differences in their biological effects in the post-Bragg peak tail regions. This suggests that the density of the DSBs within the high-LET track structures, rather than only their presence, is important for inducing cell death. These results are essential for CIRT treatment planning to limit the amount of healthy cell damage and reducing both the late effect and the secondary tumor-associated risk.


The effects of epidermal growth factor and the state of confluence on enzymatic activities of cultured rat liver epithelial cells.
In cultured normal rat liver epithelial cells, the specific activity and/or isozyme expression of NADH-diaphorase (NADH-D), pyruvate kinase (PK), glucose-6 phosphate dehydrogenase (G6PD), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (AP) were markedly dependent on the growth state of the cultures. Proliferating, preconfluent cells had higher specific activities of PK, NADH-D, and G6PD but lower activities of GGT and AP than did the more stationary confluent cells. Addition of epidermal growth factor [EGF] to the media of proliferating cells enhanced the specific activities of PK, NADH-D, G6PD, GGT, and lactate dehydrogenase (LDH) of these cells, but the specific activity of AP was markedly depressed. The increase in activity of PK and GGT by EGF appeared to involve new protein synthesis, whereas the effect of EGF on AP appeared to involve the EGF-directed suppression of the synthesis of a form of AP that is produced exclusively by cells in confluent cultures. Furthermore, the preconfluent cells were more responsive to the action of EGF on AP than were confluent cells, i.e., the EGF-mediated decrease in AP activity was seen at lower concentration in preconfluent than in confluent cells. Paradoxically, confluent cells exhibited a two-to threefold higher capacity to bind [125 I]EGF because of an increase in surface receptor number. The results of this study indicate that enzymatic or other biochemical studies performed on cultured cells must take into account the growth-state of the cultures. EGF can modulate enzyme activity in growing and nongrowing cells; one effect of EGF is to maintain higher activity of glycolytic enzymes, suggesting that EGF or EGF-like factors may contribute to the high rate of glycolysis in certain neoplasms.


Neutrophil to high-density lipoprotein cholesterol ratio predicts adverse cardiovascular outcomes in subjects with pre-diabetes: a large cohort study from China.
This study aimed to examine whether the neutrophil to high-density lipoprotein cholesterol ratio (NHR) can predict cardiovascular outcomes in normoglycemic individuals with elevated fasting glucose levels. A total of 130,801 participants with normal blood glucose levels were enrolled in the Kailuan study. Participants were categorized according to NHR quartiles and further divided into normal glucose regulation (NGR) and pre-diabetes (pre-DM) subgroups. The follow-up endpoint was major adverse cardiovascular events (CVE), including stroke and myocardial infarction. Over a median of 12.53 (8.95-13.08) years of follow-up, subjects with NHR levels in the highest quartile experienced more CVE than those with NHR levels in the lowest quartile. Multivariate Cox analyses showed that continuous changes in NHR (hazard ratio, 1.21; 95% confidence interval [CI], 1.15-1.28) and the highest quartile of NHR (hazard ratio, 1.30; 95% CI, 1.21-1.39) were independent predictors of CVE (all P < 0.001). Furthermore, when participants were categorized by both NHR quartile and glucose metabolism status, the NHR level in the highest quartile plus pre-DM group was associated with a 1.60-fold (95% CI, 1.38-1.86; P < 0.001] higher risk of CVE than that in the lowest quartile plus normoglycemic group. Significantly, the addition of NHR only, presence of pre-DM only, or combination of NHR and pre-DM to the prediction algorithm, including traditional risk factors, improved the C-statistic by 0.19, 0.05, and 0.23 (all P < 0.001). Elevated NHR or fasting blood glucose level were independently associated with a higher risk of CVE among normoglycemic individuals. Moreover, pre-DM participants with high NHR levels tended to have worse prognosis, suggesting that NHR could provide greater risk stratification value than traditional risk factors for subjects with pre-DM.


Ponderal index of the newborn: effect of smoking on the index of the small-for-gestational-age infant.
The ponderal index (PI) is evaluated in the context of its distribution within a given population. Low PI (<10th percentile for gestational age) has been extensively studied but not much is known about the distribution and factors associated with a high (>90th percentile) PI among small-for-gestational-age (SGA) infants. This retrospective study of singleton live first births from 1990 to 2007 in a Midwestern city explores factors associated with a high PI, particularly among SGA infants. Independent variables included exposures (none, smoke, hypertension) and maternal and infant demographic characteristics. There were 45,453 births, 28 to 42 weeks' gestational age, 55% Whites and 51% male. Mean PI increased with gestational age and was highest among Hispanics and lower among SGA infants. High PI was present in 11% of appropriate-for-gestational-age and 4% of SGA infants. Among SGA infants, odds ratios (ORs) of high PI were higher for smoke exposure (1.21; 95% confidence interval 0.97, 1.87) and lower for males (0.66; 0.47, 0.93). In conclusion, the distribution of PI varies by exposures and of high PI by race/ethnicity/gender. SGA infants with high PI have relative surplus of mass, and ostensibly, adiposity, for their frame. There is a need to use PI in exploring and defining previously observed associations between SGA and adult-onset obesity/metabolic syndrome.


[Plasmodium vivax malaria in the Brazilian Amazon: some aspects of its epidemiology, clinical spectrum and naturally induced immune responses].
Malaria was a nationwide problem in Brazil in the 1940's. However during the late fifties a national and successful campaign gained strength in the country decreasing malaria to its lowest level by 1960, when only 36,9 thousand cases were registered. Although the Malaria Eradication Program of the Ministry of Health in Brazil succeeded by the late 60's in freeing the majority of the country from malaria transmission, it was unable to contain the rapid spread of the disease in the Amazon Basin. In the 1970's the Amazon region witnessed a huge transformation. Colonization programs sponsored by the government, mining exploration, massive migration and the construction of roads and dams brought a new reality for which the area was not prepared. The last data available show that in 2007, the Amazon registered around 450 thousand cases, 99.9% of the national cases. P. vivax has been reported as representing around 80% of all malaria cases. P. vivax is thought to cause little mortality but like P. falciparum, P. vivax accounts for vast amounts of morbidity and for huge burdens on the prosperity of endemic communities. However, in the last few years a pattern of unusual clinical complications with fatal cases associated with it have been reported in Brazil and is a matter of tremendous concern in the Brazilian community of malariologists. In addition, the emergence of P. vivax strains resistant to chloroquine and primaquine in some reports needs to be further investigated. In contrast, asymptomatic infections by P. falciparum and P. vivax were detected in epidemiological studies in the states of Rondonia and Amazonas. Seropidemiological studies investigating the type of immune responses elicited in naturally exposed populations to several malaria vaccine candidates in Brazilian populations have also been providing important information on whether immune responses specific to those antigens are generated in natural infections and their immunogenic potential as vaccine candidates. In fact ultimate test of a malaria vaccine will be determined in field trials under natural conditions of parasite exposure.


Caudal Epidural Steroid Injections in Postlaminectomy Patients: Comparison of Ultrasonography and Fluoroscopy.
To compare the results of ultrasound and fluoroscopy guided caudal epidural steroid injections in postlaminectomy patients. Thirty postlaminectomy patients were randomly divided into two groups, Group I (n=15) received ultrasound-guided and Group II (n=15) received fluoroscopy-guided caudal epidural local anesthetic and steroid injection. Time of block for each patient was recorded. The patients" visual analogue scale (VAS), Oswestry Disability Index (ODI), and satisfaction with the therapy during the 3-month follow-up were evaluated. The caudal block performed with both methods resulted in similar improvement in low back pain and functions. Time of block was shorter in Group I than in Group II (6.06 ±0.88 minutes versus 11.2±1.14 minutes). Caudal epidural steroid injection is an effective analgesic method for postlaminectomy patients. Ultrasound-guided caudal block can be as effective as fluoroscopy-guided block and even more comfortable.


The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study.
Accurate estimates of the risk of transfusion-transmitted infectious disease are essential for monitoring the safety of the blood supply and evaluating the potential effect of new screening tests. We estimated the risk of transmitting the human Immuno-deficiency virus (HIV), the human T-cell lymphotropic virus (HTLV), the hepatitis C virus (HCV), and the hepatitis B virus (HBV) from screened blood units donated during the window period following a recent, undetected infection. Using data on 586,507 persons who each donated blood more than once between 1991 and 1993 at five blood centers (for a total of 2,318,356 allogeneic blood donations), we calculated the incidence rates of seroconversion among those whose donations passed all the screening tests used. We adjusted these rates for the estimated duration of the infectious window period for each virus. We then estimated the further reductions in risk that would result from the use of new and more sensitive viral-antigen or nucleic acid screening tests. Among donors whose units passed all screening tests, the risks of giving blood during an infectious window period were estimated as follows: for HIV, 1 in 493,000 (95 percent confidence interval, 202,000 to 2,778,000); for HTLV, 1 in 641,000 (256,000 to 2,000,000); for HCV, 1 in 103,000 (28,000 to 288,000); and for HBV, 1 in 63,000 (31,000 to 147,000). HBV and HCV accounted for 88 percent of the aggregate risk of 1 in 34,000. New screening tests that shorten the window periods for the four viruses should reduce the risks by 27 to 72 percent. The risk of transmitting HIV, HTLV, HCV, or HBV infection by the transfusion of screened blood is very small, and new screening tests will reduce the risk even further.


Long-term protection of HPV test in women at risk of cervical cancer.
To evaluate the 9-year incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cumulative adherence to perform a next test in a cohort of women aged 40+ years with no cervical screening cytology within a window of 5 years (underscreened women), after baseline cervical cytology and HPV tests. In Catalonia, Spain, co-testing with cytology and HPV test has been recommended in the Public Health system since 2006 for underscreened women. In 2007, 1,594 women with underscreened criteria were identified and followed through medical records form Pathological Department. 9-year cumulative incidence of histologically confirmed CIN2+ and cumulative adherence to perform a next test were estimated using Kaplan-Meier statistics. Follow-up was available for 1,009 women (63.3%) resulting in 23 women with. CIN2+ (2.3%). Of them, 4 women (17%) had both tests negative at baseline (3CIN2 and 1CIN3) with cumulative incidence of CIN2+ of 0.4% (95% CI: 0.1-1.4) at 5-years and 1.3% (95% CI: 0.4-3.7) at 9-years. During the first year, the prevalence among women with both tests positive was 27.0% (95% CI: 13.0-50.6) for CIN2+. Lost to follow-up was higher among women with both tests negative compared to those with both positive tests (38.7% vs 4.2%, p-value <0.001). 40.5% of the women HPV-/cyto- had a re-screening test during the 4 years following the baseline, increasing until 53.5% during the 6 years of follow-up. HPV detection shows a high longitudinal predictive value at 9-year to identify women at risk to develop CIN2+. The data validate a safe extension of the 3-year screening intervals (current screening interval) to 5-year intervals in underscreened women that had negative HPV result at baseline. It is necessary to establish mechanisms to ensure screening participation and adequate follow-up for these women.


A comparative study on conformation and ligand binding of the neuronal uncoupling proteins.
Mitochondrial uncoupling proteins of the nervous system (UCPs 2, 4, and 5) have potential roles in the function and protection of the central nervous system (CNS). In the absence of structural information, conformations of the hexahistidine-tagged versions of all five human UCPs in liposomes were investigated for the first time, using far- and near-UV CD and fluorescence spectroscopy. Highly pure UCPs 1-5 were reconstituted in detergents and stable small unilamellar vesicles, appropriate for spectroscopic studies. All UCPs formed dominantly helical conformations in negatively charged phospholipid vesicles (palmitoyloleoylphosphatidylcholine/palmitoyloleoylphosphatidylglycerol, 7:3 molar ratio). UCPs 2 and 5 exhibited comparable helical conformations with possible association in lipid bilayers, whereas UCP4 had a different helical profile that can be related to its less associated form. Interaction of reconstituted UCPs with GDP and GTP, inhibitors of the prototypic UCP1, was detected by near-UV CD and fluorescence spectroscopy, utilizing the sensitivity of these techniques to microenvironments around Trp residues close to the nucleotide binding site. Binding of UCP4 to purine nucleotides was also different from other UCPs. Binding of fatty acids, activators of proton transport in UCPs, to UCPs could not be unambiguously detected, implying a nonbinding conformation/orientation of the proteoliposomes. Interaction of CoA with UCPs was comparable to nucleotide binding, suggesting a possible binding of this molecule at the nucleotide binding site. Despite dissimilar primary sequences, neuronal UCPs share common structural and functional properties with UCPs 1 and 3, supporting a common physiological role in addition to their specific roles in the CNS.


Late patency of long saphenous vein bypass grafts to the anterior and posterior cerebral circulation.
To evaluate the late results and the natural history of long saphenous vein bypass grafts (SVGs) between the extracranial and intracranial circulation, the authors retrospectively analyzed 202 consecutive SVGs performed at the Mayo Clinic from 1979 to 1992. The distal anastomosis was to the vertebrobasilar system in 98 patients and to the carotid artery system in 103 patients. Surgical indications were advanced cerebroocclusive disease in 63% (127 cases), giant aneurysm in 37% (74 cases), and neoplasm in one patient. In 125 patent SVGs follow-up information was obtained for longer than 1 year and in 23 patent SVGs it was over 10 years (maximum 13 years, median 6.5 years). Most of the graft failures (76%) occurred during the 1st year after surgery, with 42% of all graft failures found during the first 24 hours after operation. Late graft attrition occurred in only 10 patients (8%). Cumulative patency at 1 year was 86% +/- 3%, at 5 years 82% +/- 4%, and at 13 years 73% +/- 19%. Neurological worsening at the time of occlusion developed in 72% of patients with early occlusion, whereas 80% of patients with late graft occlusion had no new neurological symptoms. Long-term patency of SVGs for cerebral revascularization appears to be excellent, with an average failure rate of 1% to 1.5% per year following the 1st year after surgery. To minimize early graft thrombosis, meticulous attention must be paid to technical detail.


Distal hereditary motor neuropathy type II (distal HMN II): mapping of a locus to chromosome 12q24.
The distal hereditary motor neuropathy (distal HMN) or the spinal form of Charcot-Marie-Tooth (CMT) disease is an exclusively motor disorder of the peripheral nervous system. The disorder clinically resembles the hereditary motor and sensory neuropathies (HMSN) type I and type II or CMT type 1 and type 2. Distal HMN might also be related to the spinal muscular atrophies (SMA) since, in both disorders, the lower motor neurons are affected. Electrophysiological and neuropathological examinations of peripheral nerves show the absence of sensory involvement. We performed a genome search in an extended Belgian family with autosomal dominant distal HMN type II. Significant linkage was obtained with markers located at chromosome 12q24, and the gene for distal HMN II was assigned to the 13 cM interval between D12S86 and D12S340.


[Multidisciplinary therapy for peritoneal dissemination using peritonectomy].
An aggressive approach to peritoneal dissemination involves peritonectomy procedures combined with preoperative intraperitoneal chemotherapy, intraoperative chemo-hyperthermia, and postoperative systemic chemotherapy. We have been performing multimodal therapy consisting of peritonectomy plus perioperative chemotherapy for the treatment of patients with peritoneal dissemination. Fifty-seven patients with established peritoneal dissemination from gastric cancer (n = 32), colon cancer (n = 17), ovarian cancer (n = 7), and mesothelioma (n = 1) have been treated with peritonectomy and intraoperative chemo-hyperthermia. Five-year survival rates of patients with gastric and colon cancer were 18% and 38%, respectively. Among various clinical factors, complete tumor resection was the most significant prognostic factor, and the prognosis of patients who underwent complete cytoreduction was significantly better than those who received incomplete cytoreduction. A multimodal therapy consisting of perioperative chemotherapy and peritonectomy with complete cytoreduction may be the most powerful method to treat patients with established peritoneal dissemination.


Platelet microbicidal protein 1: structural themes of a multifunctional antimicrobial peptide.
Mammalian platelets release platelet microbicidal proteins (PMPs) as components of their antimicrobial armamentarium. The present studies defined the structure of PMP-1 and examined its structure-activity relationships. Amino acid sequencing and mass spectroscopy demonstrated that distinct N-terminal polymorphism variants of PMP-1 isolated from nonstimulated or thrombin-stimulated platelets arise from a single PMP-1 propeptide. Sequence data (NH(2)-[S]D(1)DPKE(5)SEGDL(10)HCVCV(15)KTTSL(20) . . .) enabled cloning of PMP-1 from bone marrow and characterization of its full-length cDNA. PMP-1 is translated as a 106-amino-acid precursor and is processed to yield 73-residue (8,053 Da) and 72-residue (7,951-Da) variants. Searches with the BLAST program and sequence alignments demonstrated the homology of PMP-1 to members of the mammalian platelet factor 4 (PF-4) family of proteins. On the basis of phylogenetic relatedness, congruent sequence motifs, and predicted three-dimensional structures, PMP-1 shares the greatest homology with human PF-4 (hPF-4). By integration of its structural and antimicrobial properties, these results establish the identity of PMP-1 as a novel rabbit analogue of the microbicidal chemokine (kinocidin) hPF-4. These findings advance the hypothesis that stimuli in the setting of infection prompt platelets to release PF-4-class or related kinocidins, which have structures consistent with their likely multiple roles that bridge molecular and cellular mechanisms of antimicrobial host defense.


Erythropoietin rescues primary rat cortical neurons from pyroptosis and apoptosis via Erk1/2-Nrf2/Bach1 signal pathway.
The most commonly used inhalation anesthetics, sevoflurane, is reported to be a risk for development of learning disability. Erythropoietin (EPO) administration might be involved an effective therapy for sevoflurane neurotoxicity. EPO-EPO receptor-extracellular signal-related kinases 1/2 (Erk1/2) signal pathway plays a pivotal role in the neuroprotective effect. Nuclear factor erythroid 2-related factor (Nrf2)/BTB and CNC homology 1 (Bach1) ratio altering by Erk1/2 could ameliorate oxidative stress occurred in human macrophages. Primary cortical neuron cultures exposed to sevoflurane were assessed for cleaved caspase-1, cleaved caspase-3, Nrf2, Bach1, total Erk1/2, and phosphorylated Erk1/2 with the following: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT); propidium iodide uptake (PI); lactate dehydrogenase (LDH); malondialdehyde (MDA); superoxide dismutase (SOD); Real-time PCR; and Western blot. We found that sevoflurane exposure increased cell pyroptosis, apoptosis, injury, and MDA (n=9, P<0.05), but decreased cell viability (n=9, P<0.05) and down-regulated SOD (n=9, P<0.05), while EPO partially rescued the neurotoxicity induced by sevoflurane (n=9, P<0.05), as well as increase the expression of Nrf2 mRNA and Nrf2/Bach1 ratio (n=9, P<0.05). Inhibition of Erk1/2 phosphorylation via PD98059 reversed the protective effect of EPO (n=9, P<0.05). Thus, protection of EPO markedly attenuated pyroptosis and apoptosis of neurons exposed to sevoflurane via Erk1/2-Nrf2/Bach1 signal pathway.


Cell Surface Interactions between Bean Leaf Cells and Colletotrichum lindemuthianum: Cytochemical Aspects of Pectin Breakdown and Fungal Endopolygalacturonase Accumulation.
After a brief period of biotrophic growth, the anthracnose fungus Colletotrichum lindemuthianum (Sacc. et Mgn.) Bri et Cav. develops extensively in bean leaf cells, causing severe wall alterations and death of the host protoplast. Aplysia gonad lectin, a polygalacturonic acid-binding agglutinin, was complexed to gold and used to study the extent of pectin breakdown during the necrotrophic phase of the infection process. In view of its specific binding properties for the endopolygalacturonase produced by C. lindemuthianum, a polygalacturonase-inhibiting protein isolated from bean cell walls was successfully tagged with gold particles and used for localizing the sites of enzyme accumulation in infected host tissues. The basal level of endopolygalacturonase produced by C. lindemuthianum grown in culture was found to increase severalfold when the fungus developed in host plant tissues. The enzyme was able to diffuse freely in the host cell wall, causing drastic degradation of the pectic material of primary walls and middle lamella matrices. The enzymatic alteration of plant cell walls was accompanied by the release of pectic fragments and by the accumulation of pectic molecules at specific sites, such as intercellular spaces and aggregated cytoplasm of infected host cells. The occurrence of pectic molecules at those sites where fungal growth is likely to be restricted is discussed in relation to their origin and their implication in the plant's defense system.


How well does reflectance pulse oximetry reflect intrapartum fetal acidosis?
The purpose of this study was to determine the sensitivity and specificity for acidosis of intrapartum fetal oxygen saturation measured by reflectance pulse oximetry. Intrapartum fetal oxygen saturation values per labor stage were correlated with umbilical artery pH, base excess and PCO(2) by regression analysis. Receiver operating characteristic curve analysis was performed with the use of historic umbilical arterial cutoff values; a fetal oxygen saturation cutoff range with optimal sensitivity and specificity was calculated. Mean fetal oxygen saturation was 42.8%, over the mean 132 minutes of 107 recordings. Overall areas under the sensitivity and specificity curves were 0.77 for pH and PCO(2), decreasing sharply toward birth; all areas for base excess were poor (approximately 0.5). Depending on stage and umbilical artery parameter, fetal oxygen saturation cutoffs were 33% to 36%, with sensitivities of 0.67 to 0.8 and specificities of 0.62 to 0.90. Fetal oxygen saturation sensitivities and specificities for acidosis do not yet justify the supplementation of cardiotocography with routine reflectance pulse oximetry.


Synthesis and Thermal Decomposition of Heavy Tetrylenes Bearing N-Aminocarbazolyl Substituents.
The synthesis of the N-aminocarbazole R-NH2 (2) is reported. Subsequent reaction with bis[bis(trimethylsilyl)amido]tetrylenes E[N(SiMe3 )2 ]2 (E=Ge, Sn, or Pb) allowed the isolation of formal hydrazidotetrylene derivatives, R-N(H)EN(SiMe3 )2 (3) that includes the first example of a hydrazidoplumbylene to date. Thermal decomposition of these compounds resulted in the elimination of "NH" and afforded the tetrylenes R-EN(SiMe3 )2 (4).


The microsomal ethanol oxidizing system and its interaction with other drugs, carcinogens, and vitamins.
The interaction of ethanol with the oxidative drug-metabolizing enzymes present in liver microsomes results in a number of clinically significant side effects in the alcoholic. Following chronic ethanol consumption, the activity of the microsomal ethanol oxidizing system (MEOS) increases. This enhancement of MEOS activity is primarily due to the induction of a unique microsomal cytochrome P-450 isozyme, which has a high capacity for ethanol oxidation, as shown in reconstituted systems. Normally present in liver microsomes at low levels, this form of cytochrome P-450 increases dramatically after chronic ethanol intake in many species, including baboons. The in-vivo role of cytochrome P-450 in hepatic ethanol oxidation, especially following chronic ethanol consumption, has been conclusively demonstrated in deer-mice lacking liver ADH. Induction of microsomal cytochrome P-450 by ethanol is associated with the enhanced oxidation of other drugs as well, resulting in metabolic tolerance to these agents. There is also increased cytochrome P-450-dependent activation of known hepatotoxins such as carbon tetrachloride and acetaminophen, which may explain the greater susceptibility of alcoholics to the toxicity of industrial solvents and commonplace analgesics. In addition, the ethanol-inducible form of cytochrome P-450 has the highest capacity of all known P-450 isozymes for the activation of dimethylnitrosamine, a potent (and ubiquitous) carcinogen. Moreover, cytochrome P-450-catalyzed oxidation of retinol is accelerated in liver microsomes, which may contribute to the hepatic vitamin A depletion seen in alcoholics. In contrast to chronic ethanol consumption, acute ethanol intake inhibits the metabolism of other drugs via competition for shared microsomal oxidation pathways. Thus, the interplay between ethanol and liver microsomes has a profound impact on the way heavy drinkers respond to drugs, solvents, vitamins, and carcinogens.


Wettability Improvement in Oil-Water Separation by Nano-Pillar ZnO Texturing.
The nanostructure-based surface texturing can be used to improve the materials wettability. Regarding oil−water separation, designing a surface with special wettability is as an important approach to improve the separation efficiency. Herein, a ZnO nanostructure was prepared by a two-step process for sol−gel process and crystal growth from the liquid phase to achieve both a superhydrophobicity in oil and a superoleophobic property in water. It is found that the filter material with nanostructures presented an excellent wettability. ZnO-coated stainless-steel metal fiber felt had a static underwater oil contact angle of 151.4° ± 0.8° and an underoil water contact angle of 152.7° ± 0.6°. Furthermore, to achieve water/oil separation, the emulsified impurities in both water-in-oil and oil-in-water emulsion were effectively intercepted. Our filter materials with a small pore (~5 μm diameter) could separate diverse water-in-oil and oil-in-water emulsions with a high efficiency (>98%). Finally, the efficacy of filtering quantity on separation performance was also investigated. Our preliminary results showed that the filtration flux decreased with the collection of emulsified impurities. However, the filtration flux could restore after cleaning and drying, suggesting the recyclable nature of our method. Our nanostructured filter material is a promising candidate for both water-in-oil and oil-in-water separation in industry.


Chemoenzymatic synthesis of homochiral (R)- and (S)-karahanaenol from (R)-limonene.
Terpinolene oxide, a monoterpene belonging to the p-menthane group, is easily derived from naturally abundant (R)-limonene. It was isomerized with montmorillonite clay catalyst to karahanaenone (2,2, 5-trimethylcyclohept-4-en-1-one) by ring enlargement. The enantiomers of the corresponding alcohol, karahanaenol (2,2, 5-trimethylcyclohept-4-en-1- ol), known for their individual organoleptic properties, were resolved through Pseudomonas cepacia lipase mediated enantiospecific alcoholysis of its acetate derivative.


Preparation and Characterization of Antibacterial Cellulose/Chitosan Nanofiltration Membranes.
Abstract: Presently, most nanofiltration membranes are prepared with non-biodegradable petrochemical materials. This process is harmful to the ecosystem and consumes a large amount of non-renewable energy. In this study, biodegradable and biocompatible antibacterial cellulose/chitosan nanofiltration membranes (BC/CS-NFMs) were fabricated and characterized for their mechanical strength, antimicrobial activity, salt and dye filtration performance, and polyethylene glycol (PEG) retention using Thermal gravimetric analysis (TGA), Field emission scanning electron microscopy(FE-SEM), Fourier transform infrared spectroscopy(FT-IR), and X-ray diffraction (XRD). The BC/CS-NFMs were obtained by the hydrolysis and carboxymethylation of dense cellulose/chitosan membranes (BC/CSMs). The tensile strength of the BC/CS-NFMs decreased as the chitosan content increased. In addition, the thermal stability and antibacterial ability of the BC/CS-NFMs improved. The pore size is less than 1 nm, and a spongy, layered structure is observed in the cross-sectional FE-SEM images. FT-IR analysis shows that a part of the hydroxyl in cellulose transforms to carboxymethyl during the hydrolysis and carboxymethylation of the BC/CSMs. No obvious changes can be observed in the cellulose and chitosan after the blend membrane formation from the XRD measurements. Based on the experimental results on the permeation and rejection of BC/CS-NFMs, different proportions of cellulose and chitosan nanofiltration membranes almost did not affect the water flux and rejection rate. The BC/CS-NFMs showed better water flux and a higher rejection rate in aqueous dye-salt solutions.


The management of extensive penile fibrosis: a new technique of 'minimal scar-tissue excision'.
To evaluate the results of excising minimal scar tissue in patients undergoing insertion of a penile prosthesis for extensive corporal fibrosis. Twelve patients (mean age 58 years, range 44-73) with extensive corporal fibrosis who underwent the insertion of a penile prosthesis were evaluated. Eleven patients had a defect of varying extent after the insertion of the penile prosthesis, and a polytetrafluoroethylene graft was used to cover the area. All 12 patients tolerated the procedure well and currently have a functioning penile implant. Minimal excision of scar tissue provided better results and fewer complications when compared to other studies which used extensive excision.


[Endonasal plasmocytoma: diagnosis and management].
Plasmocytomas are either medullary (disseminated form) or extramedullary with or without bone infiltration (located form). Plasmocytoma is not a common tumor but extramedullary forms mostly occur in the upper respiratory tract without specific manifestations. The aim of this study is to discuss the management (diagnostic and therapeutic) and the follow-up of extramedullary nasal plasmocytoma. We report a case of a 71-year-old patient with unilateral nasal obstruction manifestation. Endonasal biopsy concluded plasma cell tumor without extension on CT scan. Treatment consisted of external nasal surgery and radiotherapy. Diagnosis of solitary extramedullary plasmocytoma can only be confirmed when the presence of systemic disease is excluded by performing clinical, biological (marrow bone biopsy) and radiological investigations. The treatment should be based on surgery with complementary radiotherapy if there is a skull base erosion. Long term follow-up is necessary because of the high risk of diffuse marrow involvement (multiple myeloma) which may occur after a long delay.


Targeting of liposomes to hepatocytes.
We began our investigations about 15 years ago with the concept that it should be possible to deliver drugs or enzymes intracellularly into lysosomes for diseases associated with lysosomal enzymes (e.g., sphingolipidosis). The results have been very gratifying. It now has been possible to extend our in vitro studies on the kinetics of lectin-liposome interaction to the targeting of glycolipid liposomes to specific liver cell types in vivo by simply varying the sugar residue on the surface of liposome. Nevertheless, much remains to be done to ascertain the stability of the external enzyme and the expression of its activity after the delivery into the lysosomes.


Caenorhabditis elegans MAI-1 protein, which is similar to mitochondrial ATPase inhibitor (IF1), can inhibit yeast F0F1-ATPase but cannot be transported to yeast mitochondria.
In Caenorhabditis elegans, two proteins that are similar to mitochondrial ATPase inhibitor protein (IF(1)) have been found and named MAI-1 and MAI-2. In this study, we overexpressed and purified both the proteins and examined their properties. Circular dichroism spectra indicated that both the MAI-1 and MAI-2 predominantly consisted of beta- and random structure, and in contrast to mammalian IF(1), alpha-helixes were barely detected. Both MAI-1 and MAI-2 could inhibit yeast F(0)F(1)-ATPase, but the inhibition by MAI-1 was pH-independent. MAI-2-GFP fusion protein was transported to yeast mitochondria, but MAI-1-GFP was not. These results indicate that the MAI-2 is (C. elegans) IF(1). MAI-1 seems to be a cytosolic protein and may regulate cytosolic ATPase(s).


Simeon Solomon and the biblical construction of marginal identity in Victorian England.
During the formative stages of his sexual development (1855-1860), the Pre-Raphaelite artist Simeon Solomon (1840-1905) appropriated the authority of the Bible to explore, camouflage, and ultimately, legitimize his own homoerotic yearnings. Using Plummer and Troiden's four-stage constructionist model of Gay Identity Acquisition to provide an interpretive framework for six of the artist's early Old Testament drawings, this paper charts Solomon's development from awareness, to crisis, to acceptance. Solomon's use of biblical subjects to express his inner states reflects his construction of a socially marginal homosexual identity, an act which allowed him to overcome the despair and the isolation engendered by his peripheral standing in Victorian society.


Redox regulation of thyroid-transcription factors, Pax-8 and TTF-1, is involved in their increased DNA-binding activities by thyrotropin in rat thyroid FRTL-5 cells.
Thyroid-enriched transcription factors, Pax-8 and TTF-1, are involved in the thyroid-specific expression of thyroglobulin (TG) gene. Here we demonstrate redox regulation of both factors in vitro and in vivo. When analyzed by electrophoretic mobility shift assay (EMSA), oxidation with diamide abolished the DNA binding of Pax-8. Subsequent reduction with dithiothreitol (DTT) restored the binding. Thioredoxin (TRX), a cellular reducing catalyst, restored the binding more efficiently than DTT. When TTF-1 was oxidized with diamide, its binding was decreased and the TTF-1-DNA complex migrated faster on EMSA. DTT reversed these effects. These observations indicate that reduction is required for full DNA binding of Pax-8 and TTF-1 in vitro. We then examined whether TSH modulates their binding through redox regulation. Whole cell extracts were prepared from FRTL-5 cells at intervals after TSH treatment without reducing agents and subjected to EMSA. Pax-8 and TTF-1 binding activities were gradually increased during the initial 6 h after TSH. This increase was due to reduction of the factors, since treatment of the extracts with DTT masked the increase by enhancing their binding activities. These results suggest that TSH up-regulates the binding of Pax-8 and TTF-1, at least in part, by reducing the preexisting, oxidized forms in FRTL-5 cells. Northern analysis showed that the increase in TRX mRNA level by TSH in FRTL-5 cells was associated with the increase in the binding activities. Cotransfection of luciferase-reporter plasmid driven by TG promoter with Pax-8- and TRX-expressing plasmids into a heterologous cells revealed that TRX up-regulated the Pax8-mediated TG promoter activity. Taken together, the present study suggests that the redox regulation of Pax-8 and TTF-1 by TSH, probably through TRX, modulates the TG gene expression.


Stability of Ca2+-, Cd2+-, and Cu2+-illite complexes.
In this study, using ion selective electrode techniques, we investigated the influence of pH on metal-ion, Ca2+, Cd2+, and Cu2+, adsorption by Fithian illite. The results showed that Fithian illite exhibited at least two types of metal-ion adsorption sites, high and low strength with the strength of metal-ion-illite surface complexes following the order of Cu2+ > Cd2+ > Ca2+ (strongest to weakest acids) at any of the pH values tested. The ability of metal-ions to form complexes with illite surfaces was affected by type of metal-ions and pH, especially for low metal-ion affinity sites. These sites formed stronger metal-ion complexes at high pH than at low pH, which implicated clay edge sites and indicated that H+ competed with metal-ions for available complexation sites. The data also showed that illite functional groups forming the strongest metal-ion complex did not appear to be pH-sensitive, which implicated wedge siloxane cavities or extremely low pKa clay-edge OH functional groups, but the total number of such sites were very small. The magnitude of the metal-ion-illite stability constants, as metal-ion solution concentration approached zero, on a log-scale, varied from 3.52 to 4.21 for Ca2+, 4.38 to 5.18 for Cd2+, and from 5.23 to 5.83 for Cu2+. These constants were approximately an order of magnitude smaller than those representing illite with sorbed humic fractions. The above results along with the results from our previous studies imply that metal-ion mobility and bioavailability would be affected by soil mineral surface properties, which would be significantly influenced by sorption of humic substances.


Relations between personality changes and cerebrospinal fluid biomarkers of Alzheimer's disease pathology.
Specific changes in personality profiles may represent early non-cognitive symptoms of Alzheimer's disease (AD). Evaluating the subject's personality changes may add significant clinical information, as well as help to better understand the interaction between personality change, cognitive decline, and cerebral pathology. With this study we aimed to describe the relationship between personality changes and cerebrospinal fluid (CSF) markers of AD pathology at early clinical stages of the disease. One hundred and ten subjects, of whom 66 cognitively impaired patients (57 with mild cognitive impairment (MCI), and 9 with mild dementia) and 44 healthy controls, had neuropsychological examination as well as lumbar puncture to determine concentrations of CSF biomarkers of AD pathology (amyloid beta1-42 (Aβ1-42), phosphorylated tau (ptau-181), and total-tau (tau)). The Revised NEO Personality Inventory (NEO-PI-R) was administered twice, once to evaluate subjects' current personality and once to assess personality traits retrospectively 5 years before evaluation. Subjects with an AD CSF biomarker profile showed significant increase in neuroticism and decrease in conscientiousness over time as compared to non-AD CSF biomarker group. In regression analysis controlling for global cognition as measured by the MMSE score, increasing neuroticism and decreasing extraversion, openness to experience and conscientiousness were associated with lower Aβ1-42 concentrations but not with tau and ptau-181 concentrations. Our findings suggest that early and specific changes in personality are associated with cerebral AD pathology. Concentrations of CSF biomarkers, additionally to severity of the cognitive impairment, significantly contribute in predicting specific personality changes.


Content analysis of reminiscences of elderly women.
The content of reminiscences of 21 cognitively intact elderly women registered in an adult daycare program was examined. Content analysis of transcripts from a semistructured interview was used to discover categories of reminiscence meaning. The interpretations made about past experiences were grouped under two categories: (a) validating reminiscences that involved confirming or verifying that one had lived a fruitful life; and (b) lamenting reminiscences that involved negative interpretations of past events. Validating themes were: positive self-appraisals, choices, social connections, joys, and past to present comparisons. Lamenting themes were: regrets, difficulties, and lacking choice.


The growth and development of Echinococcus granulosus of sheep origin in dogs and foxes in Britain.
Four separate experiments were carried out by dosing dogs (Beagles and Border collies) and red foxes with protoscoleces obtained from hydatid cysts in sheep from mid-Wales. The dogs and foxes were killed at intervals over a period from 34-180 days after infection and the intestines were examined for Echinococcus granulosus. Border collie dogs were efficient hosts in that large numbers of worms developed, with gravid segments present by 55 days after infection; but Beagle dogs were poor hosts in that only small numbers of immature worms developed. Foxes were poor hosts in that few or no worms developed, but gravid segments were seen in three of 29 foxes. The worms showed morphological features similar to the 'sheep' rather than the 'horse' strain.


Ent-Kaurene Biosynthesis in Extracts of Helianthus annuus L. Seedlings.
Kaurene synthetase B activity (conversion of copalyl pyrophosphate to ent-kaurene) is readily detectable in crude cell-free extracts of 3- to 4-day old dark-grown sunflower (Helianthus annuus cv. Mammoth) seedlings, whereas little or no kaurene synthetase AB activity (conversion of geranylgeranyl pyrophosphate to ent-kaurene) can be found in these extracts under comparable assay conditions. A low amount of AB activity is evident only if an extensively dialyzed extract is used in low concentrations as the enzyme source. One factor which may contribute to the low apparent levels of AB activity is the presence of inhibitory factors in the crude sunflower extract since these extracts can be shown to act as a potent inhibitor of Marah macrocarpus endosperm kaurene synthetase AB activity. Heat treatment (100 degrees C) or dialysis of the sunflower extract reduces the amount of its inhibitory activity. Also, it was observed that low concentrations of extensively dialyzed sunflower extracts act to stimulate M. macrocarpus AB activity. There is no evidence for the presence of an inhibitory factor for M. macrocarpus kaurene synthetase B activity in sunflower extracts. However, there does appear to be present in the crude preparation of sunflower extract a dialyzable factor(s) that impedes its own B activity. There is little information to date on the nature of these inhibitory and stimulatory factors for kaurene synthetase activity or their possible roles in physiological regulation. The possible presence of such factors should be considered, however, when attempting to evaluate kaurene synthetase activities in extracts of vegetative plants.