A proposal for dose-adjustment of dabigatran etexilate in atrial fibrillation guided by thrombin time.
Dabigatran is an oral anticoagulant that is increasingly used for atrial fibrillation (AF). Presently, many authorities state that routine laboratory coagulation monitoring is not required. However, data have recently been published demonstrating that higher trough plasma dabigatran concentrations are associated with lower thromboembolic and higher haemorrhagic event rates. Using these data, we simulate a range of AF patients with varying risks for these events and derive a target range of trough plasma dabigatran concentrations (30-130 μg l(-1) ). Finally, we propose that a conventional screening coagulation assay, the thrombin time (TT), can be used to discern whether or not patients are within this range of dabigatran concentrations.


Cladocerans of Alona affinis group (Cladocera: Anomopoda: Chydoridae) from North America.
Cladocera of Alona affinis group from North America preserved in the collection of Professor D. G. Frey were investigated. A new subspecies of Alona ossiani Sinev, 1998 is described. Alona ossiani herricki ssp. nov. differs from the nominative subspecies in presence of 2-3 marginal denticles on postanal angle of male postabdomen, no differences between subspecies were revealed in the female morphology. An obscure taxon Alona lepida Birge,1892 was shown to be a valid species of affinis-group and is redescribed. A. lepida shares characteristic features of the group, but differs from all other species in the body shape, by postabdominal claw with basal spine almost parallel to the claw itself, and by IDL seta 1 being not claw-like. Morphology, relationships and distribution of studied taxa are discussed.


Direct effect of dsRNA mimetics on cancer cells induces endogenous IFN-β production capable of improving dendritic cell function.
Viral double-stranded RNA (dsRNA) mimetics have been explored in cancer immunotherapy to promote antitumoral immune response. Polyinosine-polycytidylic acid (poly I:C) and polyadenylic-polyuridylic acid (poly A:U) are synthetic analogs of viral dsRNA and strong inducers of type I interferon (IFN). We describe here a novel effect of dsRNA analogs on cancer cells: besides their potential to induce cancer cell apoptosis through an IFN-β autocrine loop, dsRNA-elicited IFN-β production improves dendritic cell (DC) functionality. Human A549 lung and DU145 prostate carcinoma cells significantly responded to poly I:C stimulation, producing IFN-β at levels that were capable of activating STAT1 and enhancing CXCL10, CD40, and CD86 expression on human monocyte-derived DCs. IFN-β produced by poly I:C-activated human cancer cells increased the capacity of monocyte-derived DCs to stimulate IFN-γ production in an allogeneic stimulatory culture in vitro. When melanoma murine B16 cells were stimulated in vitro with poly A:U and then inoculated into TLR3(-/-) mice, smaller tumors were elicited. This tumor growth inhibition was abrogated in IFNAR1(-/-) mice. Thus, dsRNA compounds are effective adjuvants not only because they activate DCs and promote strong adaptive immunity, but also because they can directly act on cancer cells to induce endogenous IFN-β production and contribute to the antitumoral response.


Multivariate Analysis of Risk Factors in the Development of a Lower-Pitched Voice After Thyroidectomy.
Thyroid surgeons frequently encounter outpatients with mobile vocal cords complaining of lower-pitched voices following thyroidectomy. This study investigated the clinical and pathological parameters affecting voice pitch following thyroid surgery. We analyzed the data of 393 patients with mobile vocal cords and who also underwent thyroid surgery. Speaking fundamental frequency (SFF) and fundamental frequency (F0) were compared before and after surgery. Approximately 26.7% of patients had significantly lowered SFFs (ΔSFF ≥ 12 Hz), and 30.2% exhibited significantly lower sustained vowel F0s (ΔF0 ≥ 12 Hz) following thyroid surgery. On multivariate analysis, only gender: female remained a significant predictor of a clinically significant change in SFF following thyroid surgery ( P < .001). Gender: female and extent of surgery: total remained significant predictors of a clinically significant change in F0 after surgery ( P = .006 and P = .007, respectively). Appreciable proportions of patients experience lower-pitched voice and related vocal symptoms early after thyroid surgery. Such problems develop more frequently in females who underwent total thyroidectomy.


Cyclin E1 in Murine and Human Liver Cancer: A Promising Target for Therapeutic Intervention during Tumour Progression.
Cyclin E1 (CCNE1) is a regulatory subunit of Cyclin-dependent kinase 2 (CDK2) and is thought to control the transition of quiescent cells into cell cycle progression. Recently, we identified CCNE1 and CDK2 as key factors for the initiation of hepatocellular carcinoma (HCC). In the present study, we dissected the contributions of CCNE1 and CDK2 for HCC progression in mice and patients. Therefore, we generated genetically modified mice allowing inducible deletion of Ccne1 or Cdk2. After initiation of HCC, using the hepatocarcinogen diethylnitrosamine (DEN), we deleted Ccne1 or Cdk2 and subsequently analysed HCC progression. The relevance of CCNE1 or CDK2 for human HCC progression was investigated by in silico database analysis. Interventional deletion of Ccne1, but not of Cdk2, substantially reduced the HCC burden in mice. Ccne1-deficient HCCs were characterised by attenuated proliferation, impaired DNA damage response and downregulation of markers for stemness and microinvasion. Additionally, the tumour microenvironment of Ccne1-deficient mice showed a reduction in immune mediators, myeloid cells and cancer-associated fibroblasts. In sharp contrast, Cdk2 was dispensable for HCC progression in mice. In agreement with our mouse data, CCNE1 was overexpressed in HCC patients independent of risk factors, and associated with reduced disease-free survival, a common signature for enhanced chromosomal instability, proliferation, dedifferentiation and invasion. However, CDK2 lacked diagnostic or prognostic value in HCC patients. In summary, CCNE1 drives HCC progression in a CDK2-independent manner in mice and man. Therefore, interventional inactivation of CCNE1 represents a promising strategy the treatment of liver cancer.


Postmortem blood concentrations of R- and S-enantiomers of methadone and EDDP in drug users: influence of co-medication and p-glycoprotein genotype.
We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S-enantiomers (Wilcoxon's test, p < 0.001). The samples were divided into four groups according to other drugs detected (methadone only, methadone and strong analgesics, methadone and benzodiazepines, or methadone and other drugs). There was no significant difference in any of the R-methadone/total methadone ratios among the four groups. The median R/S ratio was 1.38, which tends to be higher than that reported for the plasma of living subjects. In addition, we investigated whether small nucleotide polymorphisms in the MDR1 gene that encode the drug transporter P-glycoprotein were associated with the concentrations of R- and S-methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. No significant association was detected.


Synaptic vesicle protein synaptoporin is differently expressed by subpopulations of mouse hippocampal neurons.
In the hippocampus, the synaptic vesicle protein synaptoporin (SPO) has been reported to be exclusively enriched in the granule cell axons, the mossy fibers. In this study, we show that in adult rats and mice SPO immunoreactivity (IR) is also detectable in strata oriens, radiatum, and lacunosum-moleculare of CA1-CA3, as well as perisomatically in the hippocampus proper and fascia dentata. In situ hybridization confirmed that SPO mRNA was present in granule cells and CA3 pyramidal cells but not in CA1 pyramidal cells. Importantly, cells scattered throughout the hippocampal layers resembling the distribution of interneurons were found to synthesize high amounts of SPO mRNA, too. Thus, these findings indicate that SPO expression in the hippocampus was underestimated until now. Moreover, double-labeling immunohistochemistry and confocal microscopy revealed selective colocalization of SPO and glutamate decarboxylase (GAD 65), a marker for gamma-aminobutyric acid (GABA)ergic terminals. To identify SPO expressing interneurons, in situ hybridization was combined with immunocytochemistry against parvalbumin (PV), calbindin (CB), calretinin (CR), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP). We found that SPO transcripts were differentially expressed by various interneuron subpopulations in the hippocampus of C57Bl/6 mice (PV 44.2%, CB 46.3%, CR 19.3%, CCK 38.6%, VIP 59.9%). Immunoelectron microscopy for SPO labeled synaptic vesicle profiles in distinct symmetric and asymmetric synapses. In conclusion, our data demonstrate that hippocampal principal cells and interneurons display a variety of synaptic vesicles that are likely to contribute to the functional characteristics of their output synapses.


Cytokines and the immune response.
Cytokines participate in many physiological processes including the regulation of immune and inflammatory responses. These effector molecules are produced transiently and locally controlling the amplitude and duration of the response. A variety of experiments has shown that excessive or insufficient production may significantly contribute to the pathophysiology of a range of diseases. Particularly cytokines released by CD4+ T cells at the onset of an immune response are thought to be decisive for pathological or physiological consequences. The meeting in Budapest was focussed on cytokines known to contribute to the pathophysiology of autoimmune diseases, infectious diseases and allograft rejection (e.g., IL-1, IL-4, IL-6, IL-10, IL-12, TNF-alpha and IFN-alpha, -beta, -gamma). A central role for IFN-gamma in autoimmunity was suggested by blocking experiments in vivo using monoclonal antibodies and soluble forms of the IFN-gamma receptor (IFN-gamma SR). These agents ameliorated disease development in a variety of experimental autoimmune diseases in rodents. In a mouse model for the human disease Myasthenia gravis, IFN-alpha was found to reduce both the incidence and progression of the disease. Treatment of R. aurantiacus-infected mice with anti-IL-4 monoclonal antibodies (mAbs) was reported to interfere with the regression of granulomas in spleen and liver, most likely through inadequate IL-4-mediated suppression of IFN-gamma production. In addition, it was shown that mice with disrupted IFN-gamma R genes died rapidly after infection with the BCG strain of M. bovis, whereas normal mice survived the infection. IL-12 was found to be the main inductor of IFN-gamma during the lethal Shwartzman reaction. TNF-alpha was identified as the principal cause of mortality after the second injection with LPS. In a variety of studies examining the role of cytokines in the pathogenesis of AIDS, much attention was given to the in vitro effects of HIV-1 and/or the HIV-1 viral membrane protein gp120 on triggering cytokine production by peripheral blood leukocytes (PBLs) and purified monocytes/macrophages (Mø) originating from healthy donors. Gp120 as a sole agent significantly suppressed IFN-gamma production by mitogen-stimulated PBLs and induced the production of IFN-alpha in cultures of normal human peripheral blood mononuclear cells (PBMCs). In a human macrophage cell line, TNF-alpha exerted a stimulatory effect on viral replication and programmed cell death induced by HIV-1 which was potentiated by the simultaneous incubation with IFN-gamma. Upon transfection of human PBLs and CD4+ T cells with a retroviral vector encoding human IFN-beta, a notable reduction in reverse transcriptase activity after HIV-1 challenge was observed. Gp120 was also found to induce both IL-6 and TNF-alpha expression and to induce morphological changes reminiscent for apoptosis in primary astrocytes and in a re-aggregated human brain cell model, suggesting a role for these cytokines in the neuropathology of AIDS dementia. Moreover, data were presented indicating that cytokine-induced expression of cell adhesion molecules (e.g., ICAM-1) in HIV-1 infected U 937 cells leads to high level incorporation of this molecule in the membrane of the viral progeny which may play a role in the attachment of such virions to CD4-negative cells.


Assessing adolescents who threaten homicide in schools.
Psychoanalytic and psychiatric perspectives on children who threaten to kill others are reviewed in the context of the need for an interdisciplinary approach to the problem. Converging technologies derived from a psychoanalytically informed social systems model are compared to law enforcement approaches, psychoanalytic understanding of the individual dynamics of the child, and empirical research on conduct disordered adolescents. The interdisciplinary orientation of a broadly trained community psychoanalyst allows a unique contribution when trying to distinguish adolescents who make a threat from those who pose a threat. Case vignettes are used to illustrate the hypotheses.


Prevalence of problem behavior in Dutch children aged 2-3.
The present study provides prevalence data on behavioral and emotional problems in Dutch preschool children from the general population. The Child Behavior Checklist for ages 2-3 (3) was completed by parents of 421 children aged 2-3 living in the Dutch province of Zuid-Holland. Mean 3-week test-retest reliability of the instrument was .79 (pearson correlation) and the mean interparent agreement was .47. The CBCL/2-3 scores correlated positively and significantly (mean r of .65) with the BCL, an instrument designed to measure behavior problems, and not substantially (mean r of -.06) with the MCDI, an instrument to assess the child's level of general development. For each of the 99 problem items the prevalence rates were presented graphically for boys and girls in 6-months age-groups. The prevalence rates of individual problem items ranged from 1% to 80%. Sixteen percent of the items was scored for more than half of the sample, indicating that the behavior covered in these items may be quite common in young preschool children. In this sample 7.8% of the children were estimated to have a behavior problem, which compares well to the rates found in other studies. No age, sex, or SES differences in total problem scores were found. Almost all significant age, sex, and SES differences found for individual items were small. Age differences found for individual problem items probably reflect the growing self-other differentiation in 2-3-year-olds. Analysis of sex differences revealed that boys were rated to be more aggressive and oppositional and as having more developmental problems, and that girls were rated to have more sleep problems. SES differences were found for items which reflect hyperactive, undercontrolled, dependent, and depressed behaviors. Comparison of problem scores for referred and nonreferred preschool children indicated higher scores for referred children on 72 of the 99 problem items. The largest differences were found for the items Doesn't get along with other children, Wants a lot of attention, and Can't concentrate. Based on the total problem score 70 percent of the children could be correctly classified as referred or non-referred. A large percentage of children, however, was incorrectly classified based on the total problem score alone.


The retinoic acid signaling pathway regulates anterior/posterior patterning in the nerve cord and pharynx of amphioxus, a chordate lacking neural crest.
Amphioxus, the closest living invertebrate relative of the vertebrates, has a notochord, segmental axial musculature, pharyngeal gill slits and dorsal hollow nerve cord, but lacks neural crest. In amphioxus, as in vertebrates, exogenous retinoic acid (RA) posteriorizes the embryo. The mouth and gill slits never form, AmphiPax1, which is normally downregulated where gill slits form, remains upregulated and AmphiHox1 expression shifts anteriorly in the nerve cord. To dissect the role of RA signaling in patterning chordate embryos, we have cloned the single retinoic acid receptor (AmphiRAR), retinoid X receptor (AmphiRXR) and an orphan receptor (AmphiTR2/4) from amphioxus. AmphiTR2/4 inhibits AmphiRAR-AmphiRXR-mediated transactivation in the presence of RA by competing for DR5 or IR7 retinoic acid response elements (RAREs). The 5' untranslated region of AmphiTR2/4 contains an IR7 element, suggesting possible auto- and RA-regulation. The patterns of AmphiTR2/4 and AmphiRAR expression during embryogenesis are largely complementary: AmphiTR2/4 is strongly expressed in the cerebral vesicle (homologous to the diencephalon plus anterior midbrain), while AmphiRAR expression is high in the equivalent of the hindbrain and spinal cord. Similarly, while AmphiTR2/4 is expressed most strongly in the anterior and posterior thirds of the endoderm, the highest AmphiRAR expression is in the middle third. Expression of AmphiRAR is upregulated by exogenous RA and completely downregulated by the RA antagonist BMS009. Moreover, BMS009 expands the pharynx posteriorly; the first three gill slit primordia are elongated and shifted posteriorly, but do not penetrate, and additional, non-penetrating gill slit primordia are induced. Thus, in an organism without neural crest, initiation and penetration of gill slits appear to be separate events mediated by distinct levels of RA signaling in the pharyngeal endoderm. Although these compounds have little effect on levels of AmphiTR2/4 expression, RA shifts pharyngeal expression of AmphiTR2/4 anteriorly, while BMS009 extends it posteriorly. Collectively, our results suggest a model for anteroposterior patterning of the amphioxus nerve cord and pharynx, which is probably applicable to vertebrates as well, in which a low anterior level of AmphiRAR (caused, at least in part, by competitive inhibition by AmphiTR2/4) is necessary for patterning the forebrain and formation of gill slits, the posterior extent of both being set by a sharp increase in the level of AmphiRAR. Supplemental data available on-line


Impacts of Proppant Flowback on Fracture Conductivity in Different Fracturing Fluids and Flowback Conditions.
Multistage hydraulic fracturing is used in horizontal wells to increase the production of tight oil. Fracturing fluids are used in hydraulic fracturing to ensure proppants are suspended, but fluid residuals can cause formation damage and reduce rock permeability; meanwhile, fracture conductivity can be further reduced due to the flowback of proppants during the early stage of production. In this study, steel plates and hydraulically fractured reservoir rocks are tested in a modified API cell to understand the impacts of flowback rate, fracturing fluid, and closure stress on proppant flowback and fracture conductivity. When the closure stress increased from 21 to 30 MPa, retained permeability decreased by slickwater from 35.71 to 29.84% in steel plates; during the flowback, more than 47% of proppants flowed back, and the fracture conductivity increased by 10 times under 21 MPa, which shows the limitation of the API method on the study of proppant flowback. When shale plates are used, the critical flow rate that prevents the proppant flowback was found to be 5.5 × 10-4-1.6 × 10-3 m/s for the 30/50 mesh sands (around 55-340 m3/d for a typical horizontal well), and the retained permeability decreased from 23.33 to 22.86% due to an increase of closure stress from 21 to 30 MPa. Results of this study can guide the optimizing of the flowback scheme in the field that minimizes the proppant flowback in different fracturing fluids.


Effects of modulation wave shape on modulation frequency discrimination with electrical hearing.
Amplitude modulations of pulsitile stimulation can be used to convey pitch information to cochlear implant users. One variable in designing cochlear implant speech processors is the choice of modulation waveform used to convey pitch information. Modulation frequency discrimination thresholds were measured for 100 Hz modulations with four waveforms (sine, sawtooth, a sharpened sawtooth, and square). Just-noticeable differences (JNDs) were similar for all but the square waveform, which often produced larger JNDs. The results suggest that a sine, sawtooth, and sharpened sawtooth waveforms are likely to provide similar pitch discrimination within a speech processing strategy.


Weight-corrected islet counts are predictive of outcome in the canine intrahepatic islet autograft model.
A combination of high-concentration collagenase digestion and density-gradient purification of canine pancreatic tissue made it possible to obtain relatively pure islets which could be quantified and the outcome of intrahepatic autotransplantation correlated with weight-corrected islet counts in the transplanted tissue. Of eleven dogs, seven achieved durable euglycaemia within 24 hours. All of these animals received islet doses of greater than 4,380 per kilogram of body weight. The remaining four animals became progressively hyperglycaemic necessitating sacrifice within one week; they all received islet doses of less than 4,380 per kilogram (p = 0.042). This model is therefore satisfactory for the investigation of preservation injury to islets and of allotransplantation because it identifies prospectively the transplants which ought to succeed, giving evidence for or against additional immune or ischaemic resistance to graft function.


Peripheral Blood CD64 Levels Decrease in Crohn's Disease following Granulocyte and Monocyte Adsorptive Apheresis.
Granulocyte and monocyte adsorptive apheresis (GMA) is reportedly useful as induction therapy for Crohn's disease (CD). However, the effects of GMA on CD64 have not been well characterized. We report here our assessment of CD64 expression on neutrophils before and after treatment with GMA in two patients with CD. The severity of CD was assessed with the CD activity index (CDAI). The duration of each GMA session was 60 min at a flow rate of 30 ml/min as per protocol. CD64 expression on neutrophils was measured by analyzing whole blood with a FACScan flow cytometer. In case 1, CD64 levels after each session of GMA tended to decrease compared to pretreatment levels, whereas in case 2, CD64 levels dropped significantly after treatment. The CDAI decreased after GMA in both cases 1 and 2. A significant correlation was noted between CDAI scores and CD64 levels in both cases. In conclusion, GMA reduced blood CD64 levels, which would be an important factor for the decrease of CDAI scores.


Directions of the relationship between substance use and depressive symptoms from adolescence to young adulthood.
Both substance use and depression are common in adolescence and often comorbid. Past research has produced conflicting results on whether there is a temporal relationship and if so, in which direction it operates and how it may vary by sex. The purpose of this paper is to explore the longitudinal, potentially bidirectional, relationships between high-frequency substance use and depressive symptoms from adolescence into young adulthood for males and females. Using data from the National Longitudinal Study of Adolescent to Adult Health we investigated longitudinal associations between high frequency substance use (alcohol, cigarettes, and marijuana) and depressive symptoms. The linear mixed effects models were stratified by sex and used a lagged measure of the dependent variable to test temporal relationships. A random intercept was used for respondent ID. Increases in depressive symptoms were significantly associated with a later increase of about a half day in marijuana use frequency for males and nearly a two day increase in smoking frequency for females. Conversely, increases in smoking frequency were significantly associated with approximately a 0.6-point increase for females and 0.4-point increase for males in depressive symptoms at a later wave. Results indicate a bidirectional relationship between smoking and depressive symptoms for females. For males, there was evidence supporting self-medication with marijuana and for smoking being associated with later increases in depressive symptoms. Results inform how substance use and depression screening, prevention and treatment efforts should be paired and targeted for males and females.


[The methods of evaluation of aggregative activity of blood corpuscles in norm and in patients with ischemic stroke.]
The article presents comparative evaluation of aggregative activity of blood corpuscles in norm and in patients with ischemic stroke derived using flow cytofluorometry and light microscopy. It is noted that in patients with stroke in peripheral blood absolute content of leukocyte thrombocyte and erythrocyte thrombocyte aggregates is drastically increased as compared with healthy examined persons. Besides, more the number of aggregates is formed during the first day of onset of disease more the severe cerebral stroke progresses.


Catalytic enantioselective allylation of ketones with novel chiral bis-titanium(IV) catalyst.
Our recently designed chiral bis-titanium(IV) catalyst can be successfully utilized for the catalytic enantioselective allylation of ketones with tetraallyltin. The high asymmetric induction is achievable in the case of aromatic ketones.


Polycystic liver and kidney diseases.
There have been remarkable advances in research on polycystic liver and kidney diseases recently, covering cloning of new genes, refining disease classifications, and advances in understanding more about the molecular pathology of these diseases. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary disease affecting kidneys. It affects 1/400 to 1/1000 live births and accounts for 5% of the end stage renal disease in the United States and Europe, and is caused by gene defects in the PKD1 or PKD2 genes. Compared to ADPKD, polycystic liver disease (PCLD) is a milder disease and does not lower life expectancy. Both diseases are usually adult-onset diseases. Defects in genes, which code the hepatocystin and SEC63 proteins, have just recently been found to cause PCLD. It now seems that ADPKD is caused by malfunction of the primary cilia, a cell organ sensing fluid movement, and that PCLD is a sequel from defects in protein processing. Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes. All ARPKD patients have a gene defect in a gene called PKHD1, the protein product of which localizes to primary cilia. We summarize the present clinical and molecular knowledge of these diseases in this review.


Ecological and evolutionary consequences of metabolic rate plasticity in response to environmental change.
Basal or standard metabolic rate reflects the minimum amount of energy required to maintain body processes, while the maximum metabolic rate sets the ceiling for aerobic work. There is typically up to three-fold intraspecific variation in both minimal and maximal rates of metabolism, even after controlling for size, sex and age; these differences are consistent over time within a given context, but both minimal and maximal metabolic rates are plastic and can vary in response to changing environments. Here we explore the causes of intraspecific and phenotypic variation at the organ, tissue and mitochondrial levels. We highlight the growing evidence that individuals differ predictably in the flexibility of their metabolic rates and in the extent to which they can suppress minimal metabolism when food is limiting but increase the capacity for aerobic metabolism when a high work rate is beneficial. It is unclear why this intraspecific variation in metabolic flexibility persists-possibly because of trade-offs with the flexibility of other traits-but it has consequences for the ability of populations to respond to a changing world. It is clear that metabolic rates are targets of selection, but more research is needed on the fitness consequences of rates of metabolism and their plasticity at different life stages, especially in natural conditions. This article is part of the theme issue 'The role of plasticity in phenotypic adaptation to rapid environmental change'.


A compressed sensing based approach for subtyping of leukemia from gene expression data.
With the development of genomic techniques, the demand for new methods that can handle high-throughput genome-wide data effectively is becoming stronger than ever before. Compressed sensing (CS) is an emerging approach in statistics and signal processing. With the CS theory, a signal can be uniquely reconstructed or approximated from its sparse representations, which can therefore better distinguish different types of signals. However, the application of CS approach to genome-wide data analysis has been rarely investigated. We propose a novel CS-based approach for genomic data classification and test its performance in the subtyping of leukemia through gene expression analysis. The detection of subtypes of cancers such as leukemia according to different genetic markups is significant, which holds promise for the individualization of therapies and improvement of treatments. In our work, four statistical features were employed to select significant genes for the classification. With our selected genes out of 7,129 ones, the proposed CS method achieved a classification accuracy of 97.4% when evaluated with the cross validation and 94.3% when evaluated with another independent data set. The robustness of the method to noise was also tested, giving good performance. Therefore, this work demonstrates that the CS method can effectively detect subtypes of leukemia, implying improved accuracy of diagnosis of leukemia.


TiCl4-promoted Baylis-Hillman reaction: mechanistic rationale toward product distribution and stereoselectivity.
The mechanism of TiCl(4)-promoted Baylis-Hillman reaction between methyl vinyl ketone (MVK) and acetaldehyde, in the absence of any base, is studied using the mPW1K density functional theory. The study focuses on several mechanistic intricacies as well as selectivity issues at each step of the reaction. The minimum energy pathway for this reaction involves three major steps such as a chloride transfer resulting in a chloro-enolate, titanium-mediated aldol reaction, and elimination of HCl or HOTiCl(3). Both s-cis and s-trans conformers of MVK are considered along with various modes of chloride transfer involving different complexes between TiCl(4), aldehyde, and MVK. Chloride transfer is found to be kinetically more favored for s-cis-MVK than for s-trans-MVK. The diastereoselectivity in the next step, i.e., Ti-mediated aldol reaction between the enolate and aldehyde, is found to be dependent on the geometry of the enolate, wherein anti and syn BH products are predicted for Z and E enolates, respectively. An interesting secondary orbital interaction between the oxygen atoms of the enolate and aldehyde moieties in the transition states for the C-C bond formation is identified as one of the contributing factors toward the predicted diastereoselectivity in the formation of the alpha-chloromethyl aldol product (P2). It has earlier been reported that under different experimental conditions, any of the three products such as (i) a normal BH product (P1), (ii) 2-(chloromethyl)vinyl ketones (P3), and (iii) alpha-chloro methyl aldol could be generated (Scheme 1 ). The present study offers valuable insights toward rationalizing the observed product distribution as well as diastereoselectivity in TiCl(4)-promoted BH reaction under base-free conditions. The computed energetics indicate that when MVK is employed as the Michael acceptor, the formation of 2-(choromethyl)vinyl ketone is the preferred product rather than the corresponding normal BH product, consistent with the known experimental reports.


Impairment of BMIPP accumulation at junction of ventricular septum and left and right ventricular free walls in hypertrophic cardiomyopathy.
Myocardial scintigraphy using 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) reveals a high incidence of reduced accumulation of the tracer in patients with hypertrophic cardiomyopathy (HCM). This defect is thought to reflect impairment of myocardial fatty acid metabolism. In this study, the distribution of BMIPP defects was characterized and correlated with the clinical features of patients with HCM. Thirty patients with asymmetric septal hypertrophy (ASH) were examined. Regional BMIPP accumulation was evaluated. Each region was normalized to the accumulation in the nonhypertrophic lateral region, which was represented as 100% on each bull's-eye map. The corresponding thallium accumulation for, each region was then used to correct for the partial-volume effect. BMIPP accumulation was significantly less in the septal portion of the anterior wall (As), the septal portion of the posterior wall (Ps) and the apex than in the lateral segments. BMIPP defects were significantly more frequent in the As, Ps and apical segments (20.0%, 20.0% and 33.3%, respectively) and were present in the As or Ps segments in 8 patients (27%). The patients with BMIPP defects in the As or Ps segments had a more frequent family history of HCM or sudden death and severe cardiac dysfunction. BMIPP defects occur predominantly in the As and Ps segments in some patients with ASH, which is often associated with severe cardiac dysfunction. The distribution of BMIPP defects may contribute to the classification of HCM and the assessment of its severity.


Changes in plasma cyclic AMP and cyclic GMP during spontaneous labor and labor induced by oxytocin, prostaglandin F2 alpha and prostaglandin E2.
To investigate the response of cyclic nucleotides to the oxytocic agents administered for induction of labor, plasma concentrations of cyclic AMP (cAMP) and cyclic GMP (cGMP) were determined by radioimmunoassay during spontaneous labor and labor induced by oxytocin (OT), prostaglandin F2 alpha (PGF2 alpha), or PGE2 (PGE2). Subjects were 7 Japanese women in each labor group. Plasma cAMP levels significantly rose at the time of crowning of the fetal head in all 4 groups. They did not increase until that time in the 3 labor groups (spontaneous, OT-induced, and PGF2 alpha-induced labor groups). In the PGE2-induced labor group, plasma cAMP levels were significantly higher at labor onset (mean +/- SEM = 16.5 +/- 1.3 pg/ml) when compared to the pretreatment values (13.7 +/- 1.0 pg/ml), and increased thereafter gradually toward the time of crowning of the head (26.3 +/- 2.0 pg/ml). Plasma cGMP levels in the OT-induced group significantly rose after the onset of labor and remained at a high level until expulsion of the fetus. Plasma cGMP levels in the other groups did not change significantly throughout labor. These results suggest that cAMP may be involved in the labor process induced by PGE2, and that cGMP may be in that induced by OT.


Dietary sodium, calcium, and potassium, and blood pressure.
The cross-sectional association of systolic blood pressure with dietary sodium, calcium, and potassium, as estimated from dietary histories, was investigated by multiple regression analysis of data gathered in the Netherlands in the early 1950s in a general health examination of 2,291 middle-aged civil servants and spouses of civil servants. A statistically significant negative trend with systolic blood pressure was seen for calcium intake in both males and females, even after adjustments for covariates. For sodium and potassium intake, the observed negative trends were not significant after multivariate analyses. In addition, no consistent associations were found between diastolic blood pressure and the micronutrients after multivariate analyses, except for a significant negative association with calcium intake in females. In this study population, blood pressure was a strong independent risk factor of total mortality: 15- and 25-year mortality was about twice as high for hypertensives (greater than or equal to 160 mmHg) as for normotensives (less than 160 mmHg). These findings support the conclusion in recent epidemiologic studies that higher intakes of calcium are associated with lower systolic blood pressure, and they extend the evidence to an earlier time period.


Implication of mitochondrial dysfunction and cell death in cold preservation--warm reperfusion-induced hepatocyte injury.
Cold ischemia--warm reperfusion (CI/WR) injury of liver transplantation involves hepatocyte cell death, the nature and underlying mechanisms of which remain unclear. Isolated hepatocytes and isolated perfused livers were used to determine the prevalence of necrosis and apoptosis as well as mitochondrial dysfunction. In isolated cells, propidium iodide and Hoechst 33342 staining showed a cold-storage, time-dependent increase in necrosis, whereas apoptosis was minimal even after 48 h of hypothermia. Nonetheless, a progressive loss of mitochondrial membrane potential was observed. Translocation of mitochondrial cytochrome c toward microsomes occurred within 24 h of CI/WR, with cytochrome c reaching the cytosol later. Mitochondria isolated from whole livers subjected to CI/WR also display reduced metabolic parameters and increased susceptibility to swelling. These events are associated with increased activity of major initiator (caspase 9) and effector (caspase 3) caspases. The results demonstrate that CI/WR induces mitochondrial dysfunction in isolated cells and in the whole organ; only in the latter is that sufficient to trigger the classical mitochondrial pathway of apoptosis. Our study also provides evidence for the involvement of endoplasmic reticulum stress in CI/WR hepatocyte injury. Combined protection of mitochondria and endoplasmic reticulum may thus represent an innovative therapeutic avenue to enhance liver graft viability and functional integrity.


Predominance of L-dopa in fetal plasma and the amniotic fluid during late gestation in the rat.
The purpose of this study was to reevaluate catecholamine distribution in fetal and maternal compartments during late gestation in the rat. Fetal and maternal plasma and amniotic fluid were collected from anesthetized rats on consecutive days from day 17 to day 22, the day of parturition. The fluid was analyzed for dihydroxyphenylalanine (L-dopa), dopamine, norepinephrine, and epinephrine by radioenzymatic assays. Amniotic fluid volume was determined by a direct weighing method. L-Dopa concentrations constituted approximately 50% of total fetal plasma catecholamines and were significantly higher in fetal than in maternal circulation. Dopamine concentrations in fetal plasma were tenfold lower than those of L-dopa but were also significantly higher in fetal than in maternal plasma; norepinephrine levels were similar in both. Maternal plasma epinephrine levels remained relatively constant, whereas fetal epinephrine levels increased fiftyfold from day 17 to day 22. L-Dopa concentrations in the amniotic fluid were tenfold higher than those of dopamine, and the concentrations of both increased markedly during the last 2 days of gestation. However, this apparent rise could be attributed to the concomitant fivefold reduction in the amniotic fluid volume observed at this time. It is concluded that L-dopa is the predominant catecholamine in both the fetal plasma and the amniotic fluid during late gestation in the rat. At the present time, neither the source nor the possible physiologic functions of L-dopa during fetal life are known.


Micro-Lens-Based Matching for Scene Recovery in Lenslet Cameras.
Since a light-field camera is able to capture more information than a traditional camera, a lot of methods, such as depth estimation, image super-resolution, and view synthesis, are explored for recovering scene information. In this paper, we propose a novel framework for scene recovery based on lenslet-based light-field camera images. Instead of using traditional matching terms, we design a new micro-lens-based matching term to calculate structure information and recover several kinds of scene information simultaneously. On the one hand, inherent information in micro-lens images is selected to complement details in sub-aperture images. On the other hand, sub-aperture images are used to expand micro-lens images and synthesize new view images. A new micro-lens-based consistency metric is introduced for the matching term to handle occlusions in depth estimation and image reconstruction. The newly appeared and newly occluded areas in synthesized views are analyzed and recovered based on information from surrounding points. Experimental results show that the proposed depth estimation method outperforms state-of-the-art methods on both synthetic and lenslet-based light-field images, especially in low-texture and occlusion regions. Furthermore, the super-resolution and view synthesis methods are able to acquire view images with more details and less aliasing artifacts.


The docking protein Cas links tyrosine phosphorylation signaling to elongation of cerebellar granule cell axons.
Crk-associated substrate (Cas) is a tyrosine-phosphorylated docking protein that is indispensable for the regulation of the actin cytoskeletal organization and cell migration in fibroblasts. The function of Cas in neurons, however, is poorly understood. Here we report that Cas is dominantly enriched in the brain, especially the cerebellum, of postnatal mice. During cerebellar development, Cas is highly tyrosine phosphorylated and is concentrated in the neurites and growth cones of granule cells. Cas coimmunoprecipitates with Src family protein tyrosine kinases, Crk, and cell adhesion molecules and colocalizes with these proteins in granule cells. The axon extension of granule cells is inhibited by either RNA interference knockdown of Cas or overexpression of the Cas mutant lacking the YDxP motifs, which are tyrosine phosphorylated and thereby interact with Crk. These findings demonstrate that Cas acts as a key scaffold that links the proteins associated with tyrosine phosphorylation signaling pathways to the granule cell axon elongation.


Modeling the arrangement of particles in natural swelling-clay porous media using three-dimensional packing of elliptic disks.
Swelling clay minerals play a key role in the control of water and pollutant migration in natural media such as soils. Moreover, swelling clay particles' orientational properties in porous media have significant implications for the directional dependence of fluid transfer. Herein we investigate the ability to mimic the organization of particles in natural swelling-clay porous media using a three-dimensional sequential particle deposition procedure [D. Coelho, J.-F. Thovert, and P. M. Adler, Phys. Rev. E 55, 1959 (1997)]. The algorithm considered is first used to simulate disk packings. Porosities of disk packings fall onto a single master curve when plotted against the orientational scalar order parameter value. This relation is used to validate the algorithm used in comparison with existing ones. The ellipticity degree of the particles is shown to have a negligible effect on the packing porosity for ratios ℓ(a)/ℓ(b) less than 1.5, whereas a significant increase in porosity is obtained for higher values. The effect of the distribution of the geometrical parameters (size, aspect ratio, and ellipticity degree) of particles on the final packing properties is also investigated. Finally, the algorithm is used to simulate particle packings for three size fractions of natural swelling-clay mineral powders. Calculated data regarding the distribution of the geometrical parameters and orientation of particles in porous media are successfully compared with experimental data obtained for the same samples. The results indicate that the obtained virtual porous media can be considered representative of natural samples and can be used to extract properties difficult to obtain experimentally, such as the anisotropic features of pore and solid phases in a system.


Ultrasound diagnosis of C-cell carcinoma of the thyroid.
Ultrasound screening in 9 and 21 members, respectively, of two families affected by familial C-cell carcinoma, as well as sonographic findings in 6 patients with sporadic medullary carcinoma of the thyroid (MCT), are reported. Unilateral and bilateral tumor nodules were identified by sonography in 12 of a total of 13 patients with MCT (n = 9) or local tumor recurrence following thyroidectomy (n = 4); one carcinoma, 3 X 6 mm in diameter, was missed. Nine of the 12 (75%) were clinically occult, nonpalpable C-cell carcinomas. The smallest occult MCT correctly diagnosed by ultrasound had a diameter of 4 mm. A positive correlation was found between the sonographically determined tumor mass (number/size of nodules/metastases) and the plasma calcitonin level. Pheochromocytomas were diagnosed by ultrasound as part of a multiple endocrine neoplasia (MEN IIa) in two patients with MCT. The echomorphologic findings of the intrathyroid C-cell carcinomas and their metastases display characteristic but nonspecific features. Sonographic findings on these tumors should therefore not be interpreted without consideration of plasma calcitonin assays.


Demographic and socioeconomic characteristics of Korean Americans in the United States in 1980.
"Based on the analysis of 1980 [U.S. Census] Public-Use Microdata Samples, this article demonstrates that the Korean immigrant stream, particularly men, has been very selective even before the 1965 reform.... Despite the educational superiority and somewhat positive occupational position, Korean men in the U.S. are seriously disadvantaged in income regardless of nativity status. Korean Americans are not as successful as whites in translating their education into occupation and income; they are better educated for the same job, but experience a lower income return to the same education and the same occupation."


Kinds of mutations induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the hprt gene of Chinese hamster ovary cells.
The kinds of mutations induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the protein coding region of the hprt gene of Chinese hamster ovary (CHO) cells were determined by direct sequencing of polymerase chain reaction (PCR)-amplified cDNA. Primary mutations were found in 15 of 19 of the mutants: 11 were G:C-->T:A transversions, two were A:T-->T:A transversions and two were deletions of single G:C base pairs (-1 frameshifts). The remaining four mutants had large alterations in the cDNA that were explained by mRNA splicing errors. A group of control mutants had more diverse hprt cDNA alterations than MX-induced mutants. Transversions yielding an A:T base pair were the predominant type of MX-induced mutations, in agreement with previous findings in bacteria. This specificity may be explained by the 'A rule', that DNA polymerases preferentially insert adenine nucleotides opposite non-instructional lesions.


Modulation of GABA transmission by diazoxide and cromakalim in the globus pallidus: implications for the treatment of Parkinson's disease.
An ATP-sensitive potassium channel (KATP) is known to modulate insulin release from pancreatic beta cells. It has been proposed that potassium channels related to KATP in the nervous system might similarly modulate neurotransmitter release. We have therefore investigated the effects of KATP opening agents on GABA release in the globus pallidus. Diazoxide and cromakalim decreased the K(+)-evoked release of [3H]GABA from pallidal slices. The maximum inhibition observed for diazoxide (59%) and cromakalim (66%) was achieved at a concentration of 100 microM. The effects of both cromakalim and diazoxide were significantly antagonized by the concurrent application of the sulfonylurea glibenclamide (100 microM). Intrapallidal injections of diazoxide in the reserpine-treated rat model of Parkinson's disease reduced akinesia in a dose-dependent manner. These data suggest that manipulation of neuronal potassium channels with pharmacological properties similar to KATP may prove useful in the treatment of Parkinson's disease.


The Waterloo-Stanford Group C (WSGC) scale of hypnotic susceptibility: normative and comparative data.
The Waterloo-Stanford Group C (WSGC) hypnotic susceptibility scale was developed as a substitute for the individually administered Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C). A first investigation with WSGC reports normative data on 259 subjects, and the results indicate that it is comparable in most important respects to the norms of SHSS:C. A second investigation directly compared WSGC and SHSS:C in a counterbalanced design on 65 subjects, and the two scales correlated .85. It is argued that, when used as a follow-up to the Harvard Group Scale of Hypnotic Susceptibility, Form A, WSGC provides a valid criterion of hypnotic ability.


[Medication a complement to other forms of pain management in osteoarthritis].
Osteoarthritis of the peripheral joints is a common cause of joint pain and joint stiffness. There is still no treatment that effectively can inhibit the structural changes of osteoarthritis, i.e. osteophytes, cartilage thinning and subchondral sclerosis. The main goal of treating patients with osteoarthritis is thus to relieve symptoms and to restore function. Pharmacological treatment with NSAIDs is often, used. However, there is good evidence for the effectiveness of both other pharmacological treatments (i.e. paracetamol) and non-pharmacological treatments like training, patient education and sometimes local treatment of affected joints. When using pharmacological treatment, a standardised evaluation is recommended. There are studies suggesting a "disease modifying effect" of some compounds, but their role in modern osteoarthritis therapy remains to be established.


Placental transfer and milk secretion of gadodiamide injection in rats.
The disposition of gadodiamide (CAS 122795-43-1) injection (Omniscan), a nonionic paramagnetic contrast-enhancing medium developed for magnetic resonance imaging, was characterized in the pregnant and lactating rat. After a single intravenous dose of 0.3 mmol/kg 14C-labeled gadodiamide to rats on day 18 of gestation, the maximum levels of radioactivity in the fetus were attained at 5 min, and were approximately 170 times lower than those in the maternal plasma. The AUC ratio of fetal to maternal blood was less than 0.1. Moreover, the distribution percentage of radioactivity in the fetus were on the average 0.01% of the administered dose up to 4 h, and trace amounts of radioactivity were present in fetal tissues at 24 h after dosing. Whole body autoradiography showed that the smallest amounts of radioactivity were present in the fetus, whereas the highest concentrations of radioactivity were noted in the fetal membrane and the kidney at 24 h after dosing. These results indicate that exposure of the developing rat fetus to gadodiamide after maternal drug administration is quantitatively small. The radioactivity levels in the milk increased with time, reaching a maximum 1 h after dosing, and gradually decreased to levels below detection limits over 8 h. A comparison of the AUCs of milk and plasma showed the comparatively small amounts of the drug excreted into milk.


Characteristics of falls in 70 year olds in Jerusalem.
Falling is a serious and common problem among the elderly and may result in injury and functional deterioration. The characteristics and risk factors for falling were studied in a cross-sectional study of a cohort of 70-year-old community-dwelling Jewish elderly in Jerusalem. The cohort was found to be representative of the total 70-year-old population of Jerusalem by virtue of having similar hospitalization and mortality rates. Around 28.2% of the cohort reported falling during the past year. Women were more likely than men to have fallen during the past year (39 vs. 19%; P < 0.001). Falls occurred mainly outside of the home, resulting in fractures in 8.4% of persons who fell, all of them women. A female gender, low visual efficiency, poor self-reported general health status, low serum hemoglobin levels, and low lymphocyte counts were associated with a higher incidence of falls. There was no relationship between the pattern of pharmaceutic drug use or utilization of health care services and the risk of falling. We conclude that among the younger elderly, characteristics of falls and risk factors may be different from those in the older elderly.


Measuring physical activity self-regulation strategies in older adults.
Theoretically, self-regulatory strategies (e.g., goal setting, self-monitoring) are an important influence of behavior change, but very little research has examined the relationship between self-regulation and physical activity (PA) behavior. Petosa's (1993) 43-item PA self-regulation scale (PASR-43) affords the opportunity for studying this construct in the context of PA; however the PASR-43 has not been tested for structural aspects of validity. Therefore, this study examines the structural validity of the PASR-43 in older adults. The structural validity of the PASR-43 was tested in a large sample of older adults from North and South Carolina and Ohio (N = 460) using maximum likelihood estimation and confirmatory factor analysis in AMOS 5.0. The original 6-factor model for the PASR-43 scale did not represent an acceptable fit to the data (chi2 = 4732.25, df = 845, P < .0001, RMSEA = 0.10, NNFI = 0.67, CFI = 0.71). Based on a post hoc specification search, iterative model modifications resulted in a 12-item PA self-regulation scale (PASR-12) that represented an excellent fit to the data (chi2 = 70.75, df = 39, P = .001, RMSEA = 0.04, NNFI = 0.98, CFI = 0.99). The PASR-12 provides a concise and valid measure of PA self-regulation for use with older adults. Future studies should cross-validate the PASR-12 and examine invariance across time and between age, ethnic, gender, and geographical groups.


New approach for atomic force microscopy of membrane proteins. The imaging of cholera toxin.
We demonstrate that supported synthetic phospholipid bilayers, which are stabilized by lateral cross-linking in both leaflets, can be used for specimen preparation for atomic force microscopy of purified membrane proteins with high stability and excellent reproducibility under water or low-salt buffer. A bilayer containing 1,2-dipentacosa-10,12-diynoyl-phosphatidylcholine and 20 mol % ganglioside (GM1) was transferred onto the surface of mica from a Langmuir trough. Cholera toxin, both the B-subunit and the complete molecular randomly bound to the gangliosides, were imaged by atomic force microscopy in solution with a resolution of better than 2 nm. The pentameric structure of the B-subunit oligomers was well resolved. This result indicates that, with this preparation procedure, other membrane proteins may be studied at intermediate to high resolution under physiologically relevant conditions without the need for crystallization.


Fate of gram-positive bacteria in reconditioned, pork-processing plant water.
This study investigated the responses of Enterococcus faecium (ATCC 19433), Staphylococcus aureus (196E), and Listeria monocytogenes Scott A in water from a local meat-processing plant. Each bacterium was added to a starting count of 3 log10 CFU/ml and held from 5 to 28 degrees C. At intervals (0, 2, 7, 14, and 21 days), aliquots were plated on appropriate selective agars. In contrast to the gram-negative bacteria studied previously and which grew, the three gram-positive bacteria survived with some slight increase in number in only nonchlorinated, reconditioned water, either filtered (0.22 microm pore size) or nonfiltered. The presence of chlorine in either potable or reconditioned water contributed to the rapid decline in viable counts for all three bacteria. These results further emphasize the importance of residual chlorine in preventing the growth of these gram-positive bacteria in potable and reconditioned waters.


Expert systems for medical applications.
Expert systems, also known as intelligent knowledge based systems (IKBS), are computer programs which act as decision-support systems. They are currently being applied to a number of medical domains, most notably diagnosis and treatment planning. Their function is to assist the medical practitioner by giving ready access to the levels of skill shown by experts in a particular field. Much research effort has been expended but few systems have reached routine medical use. This paper presents a tutorial introduction to expert systems in medicine, explaining the basis of the technology, its current limitations and its prospective uses.


[No rearrangement of the breakpoint cluster region in two juvenile chronic myeloid leukemia].
We performed cytogenetic studies and breakpoint cluster region (bcr) rearrangement analysis in two cases of juvenile chronic myeloid leukemia (JCML) which is special type of chronic myeloid leukemia (CML). Case 1 (8-month-old male) and case 2 (3-month-old female) showed clinical and hematologic manifestations similar to CML. Each of case 1 and 2 had normal karyotype and no bcr rearrangement. These findings suggest that JCML is a different heterogeneous disorder from that of adult CML.


Design of a modified uniform redundant-array mask for portable gamma cameras.
Uniform redundant-array masks have been reported as good lenses to form the image of gamma sources, with the correlation between the mask-aperture matrix and the shadows projected on a static position-sensitive detector. We present a modified uniform redundant-array configuration suitable for portable and small-size gamma cameras; its ability to reconstruct the image of several sources is analyzed. We have carried out a Montecarlo simulation of the gamma interactions in the mask, defining the expected response of the correlation process and comparing it with that achieved with the usual uniform redundant-array configurations.


Multiple-filter approach to phase retrieval from modulus data.
A new approach is given for the problem of reconstruction of phase from modulus data. A set of Wiener-filter functions is formed that multiply, in turn, displaced versions of the modulus data (in frequency space) such that the sum is a minimum L(2)-error norm solution for the object. The modulus data are permitted to contain both noise and signal (object) components. The required statistics are power spectra of the signal and noise, and correlations between modulus data at given frequencies and complex object spectral values at adjacent frequencies. In a numerical simulation, a 3 x 3 filter array is used to reconstruct any member of an object class consisting of 16 pictures of space shuttles in various combinations. The 16 pictures are used as a learning set to form the required power spectra and correlations mentioned above. Reconstructions are formed in the presence of data noise, data gaps, and filter-construction noise, in varying amounts. Results are encouraging in that the space shuttle images are always recognizable.


The gamma delta T cell repertoire in Graves' disease and multinodular goitre.
gamma delta T cells are a subset of T cells with unknown function, and restriction of the gamma delta T cell receptor (TCR) repertoire has been described in rheumatoid arthritis and multiple sclerosis. Elevated numbers of gamma delta T cells have been reported in the peripheral blood and thyroids of patients with Graves' disease. We have carried out flow cytometric analysis on peripheral blood mononuclear cells (PBMC) and intrathyroidal lymphocytes (ITL) from 12 patients with Graves' disease and nine patients with multinodular goitre (MNG), a thyroid disease of unknown etiology. There was no significant difference between the proportion of gamma delta T cells in the PBMC of Graves' and MNG patients, nor between the PBMC and ITL populations in either patient group. We have also carried out polymerase chain reaction amplification on RNA prepared from matched PBMC, ITL and the activated (CD25+) subset of ITL using six TCR V delta-family specific primers. Although there were differences in the amounts of each V delta transcript amplified from PBMC and ITL, there was no difference between the two patient groups. No consistent differences were therefore found between the gamma delta T cell populations in Graves' and MNG patients, arguing against the direct involvement of this T cell subset in the pathogenesis of Graves' disease.


[Cloning and immunological characteristics of canine IL-18 cDNA].
To clone the canine IL-18 cDNA and to explore the immunological effectiveness of canine IL-18 as an adjuvant of genetic vaccine. Canine leukocytes were separated from peripheral blood stimulated with ConA for 5-12 h. The full length cDNA of canine IL-18 was amplified by RT-PCR using leukocyte mRNA as a template. IL-18 cDNA was cloned into pMD18-T. Sequencing result showed that the full length cDNA was 582 bp, encoding 193 amino acids, which was identical with that published. The eukaryotic expression vector pIIL18 was constructed. Dogs were inoculated in mixture form of pIGneo and pIIL18. Canine IL-18 cDNA was successfully cloned and eukaryotic expression vector pIIL18 was constructed. The immunological assay result showed that the anti-rabies virus-specific antibody level of the group immunized with mixture of pIIL18 and pIGneo was obviously lower than that of the group immunized with pIGneo alone, but the level of cellular immunity of the former was higher than the latter. Canine IL-18 can enhance cellular immunity but at the same time suppress humoral immunity, which lays the foundation for IL-18 as an adjuvant of genetic vaccine.


Primary fibro sarcoma of the heart.
Primary malignant heart tumors represent rare entities where fibro sarcoma represents about 3% of all. Introducing the patient: A 15 years old patient with cardiac insufficiency (heart failure) symptoms, such as weakness, cyanosis, palpitations and breathing difficulties; enlargement of upper mediastinum and pleural effusion. Through echocardiography a pericardial effusion and intracavitary thrombus in atrium was diagnosed. With computed tomography is diagnosed a tumoral mass in right atrium which is also spread in the right ventricle of the heart. Tumor is completely removed; pat histology result showed primary fibro sarcoma of the heart. At that time no metastasis was found. Conclusion. Primary malignant heart tumors may manifest like cardiac insufficiency or like systemic diseases. Fibrosarcomas are rare and have bad prognosis. On average patients can live around six months after initial symptoms appeared and diagnosis of the tumor was done. In the case of cardiac insufficiency with differential diagnosis we should also think of heart tumors, which could certainly be proved for or eliminated by echocardiography.


The distribution and density of airway vasoactive intestinal polypeptide (VIP) binding sites in cystic fibrosis and asthma.
The densities of airway binding sites for Vasoactive intestinal polypeptide (VIP) were determined using 125I-labelled VIP (IVIP) and the technique of autoradiography applied to cryostat sections. Tissue studied included: grossly normal airway tissue taken from lungs resected for bronchial carcinoma (Ca; n = 11) and lungs removed at transplant from patients with cystic fibrosis (CF; n = 7). Lung tissue obtained at post-mortem in cases of fatal asthma (n = 3) or lobes resected for bronchiectasis (n = 3) were taken as further disease controls. In the Ca controls there was dense IVIP labelling, of alveolar wall, blood vessels, airway epithelium, submucosal glands, and bronchial smooth muscle: labelling of bronchiolar smooth muscle was sparse. In comparison with the Ca controls, IVIP labelling of all tissue structures in CF, with the exception of bronchial smooth muscle, was reduced (P <0.01). The most striking reductions were associated with airway epithelium and alveolar wall. These reductions showed a similar trend in bronchiectasis but did not achieve statistical significance. There was no such change in lung tissue obtained from the cases of fatal asthma where labelling of bronchial smooth muscle and all other structures was similar to that of the Ca controls. It is likely that the reduction of VIP binding sites in CF is secondary to infection and inflammation.


A systematic analysis of college substance use policies.
College substance use policies provide guidelines for student behavior and influence campus culture. Although they are the primary environmental strategy to address campus substance use, policies have not been systematically compared and studied. We constructed a systematic review method to examine the accessibility, comprehensiveness, enforcement procedures, and clarity of college substance use policies. We developed an objective evaluation scheme for each of these 4 dimensions and then applied it to documented substance use policies from a sample of colleges and universities (N = 24). Policies were found to vary considerably but tended to specify compliance with local laws and emphasize student health and well-being. The next stage of campus policy review should examine actual implementation, evaluate potential differentiating factors among institutions, and assess the influence of policy on campus climate and student outcomes.


In vivo assay of nitrate reductase in cotton leaf discs: effect of oxygen and ammonium.
Factors affecting nitrate reduction by leaf discs of cotton (Gossypium hirsutum L.) were investigated. When incubated in 30 mm nitrate, discs reduced nitrate much more slowly under air or O(2) than under N(2). Inhibition by O(2) did not occur at nitrate levels of 100 mm or greater. Treatment with arsenate had little effect under N(2) but stimulated nitrate reduction under air. Similarly, ammonium inhibited nitrate reduction, with the inhibition being partially relieved by arsenate. Uptake of nitrate was unaffected by ammonium. The NAD/NADH ratio increased in response to both oxygen and ammonium. The effects of these treatments on nitrate reduction can be explained by competition with nitrate for NADH generated by glycolysis.


The modified water swallowing test score is the best predictor of postoperative pneumonia following extubation in cardiovascular surgery: A retrospective cohort study.
No guidelines have been established for the evaluation of swallowing function following extubation. The factors of bedside swallowing evaluations (BSEs) that are associated with the development of pneumonia have not been fully elucidated. This study aimed to retrospectively investigate the most appropriate measurements of BSEs for predicting pneumonia.The study subjects were 97 adults who underwent BSEs following cardiovascular surgery. Patients were divided into the pneumonia onset group (n = 21) and the non-onset group (n = 76). Patient characteristics, intraoperative characteristics, complications, BSE results, and postoperative progress were compared between the groups. BSEs were composed of consciousness level, modified water swallowing test (MWST) score, repetitive saliva swallowing test score, speech intelligibility score, and risk of dysphagia in the cardiac surgery score. Univariate and multivariate analyses with the BSE as the independent variable and pneumonia onset as the dependent variable were also performed to identify factors that predict pneumonia. For factors that became significant in univariate analysis, the incidence of pneumonia was shown using the Kaplan-Meier curve.No significant differences were found in patient characteristics, intraoperative characteristics, and complications between the 2 groups. The postoperative progress was significantly different between the 2 groups, the pneumonia-onset group had a significantly longer time until the start of oral intake and a significantly lower median value of Food Intake Level Scale at the time of discharge. According to univariate and multivariate analyses, MWST score was a significant factor for predicting the onset of pneumonia even after adjusting for patient characteristics and surgical factors, and the incidence of pneumonia increased approximately 3 times when the MWST score was 3 points or less.The MWST score after extubation in cardiovascular surgery was the strongest predictor of postoperative pneumonia in BSEs. Furthermore, the incidence of pneumonia increased approximately 3 times when the MWST score was 3 points or less. Predicting cases with a high risk of developing pneumonia allows nurses and attending physicians to monitor the progress carefully and take aggressive preventive measures.


A New Fluorescence Detection Method for Tryptophan- and Tyrosine-Derived Allelopathic Compounds in Barley and Lupin.
Barley (Hordeum vulgare) is one of the most widely cultivated crops for feedstock and beer production, whereas lupins (Lupinus spp.) are grown as fodder and their seeds are a source of protein. Both species produce the allelopathic alkaloids gramine and hordenine. These plant-specialized metabolites may be of economic interest for crop protection, depending on their tissue distribution. However, in high concentrations they pose a health risk to humans and animals that feed on them. This study was carried out to develop and validate a new method for monitoring these alkaloids and their related metabolites using fluorescence detection. Separation was performed on an HSS T3 column using slightly acidified water-acetonitrile eluents. Calibration plots expressed linearity over the range 0.09-100 pmol/µL for gramine. The accuracy and precision ranged from 97.8 to 123.4%, <7% RSD. The method was successfully applied in a study of the natural range of abundance of gramine, hordenine and their related metabolites, AMI, tryptophan and tyramine, in 22 barley accessions and 10 lupin species. This method provides accurate and highly sensitive chromatographic separation and detection of tryptophan- and tyrosine-derived allelochemicals and is an accessible alternative to LC-MS techniques for routine screening.


Real-time medical applications and telecommunications.
Telecommunications play an important role in telemedicine. Many forms of telecommunication services based on different telecommunication technologies are developed for various needs. The paper deals with complex real-time applications which demand high telecommunication requirements. At the beginning, medical applications are categorised and real-time applications qualified as multimedia applications. Requirements for multimedia elements are listed separately. Later on, short introduction of related telecommunication protocols is given. Real-time medical applications can show their ability in case of guaranteed quality of services delivered by telecommunication network as it is explained in the end.


Uterine papillary serous carcinoma after radiation therapy for carcinoma of the cervix.
This article describes the clinicopathologic features of six cases of uterine papillary serous carcinoma (UPSC), which developed several years after radiation therapy (RT) for cervical carcinoma. The possible etiologic role of radiation is discussed, and the literature on endometrial carcinomas developing after RT is reviewed.


On-line prediction of ferrous ion concentration in goethite process based on self-adjusting structure RBF neural network.
Outlet ferrous ion concentration is an essential indicator to manipulate the goethite process in the zinc hydrometallurgy plant. However, it cannot be measured on-line, which leads to the delay of this feedback information. In this study, a self-adjusting structure radial basis function neural network (SAS-RBFNN) is developed to predict the outlet ferrous ion concentration on-line. First, a supervised cluster algorithm is proposed to initialize the RBFNN. Then, the network structure is adjusted by the developed self-adjusting structure mechanism. This mechanism can merge or divide the hidden neurons according to the distance of the clusters to achieve the adaptability of the RBFNN. Finally, the connection weights are determined by the gradient-based algorithm. The convergence of the SAS-RBFNN is analyzed by the Lyapunov criterion. A simulation for a benchmark problem shows the effectiveness of the proposed network. The SAS-RBFNN is then applied to predict the outlet ferrous ion concentration in the goethite process. The results demonstrate that this network can provide a more accurate prediction than the mathematical model, even under the fluctuating production condition.


Imaging of cerebral vasculitis.
In young patients, vasculitic stenoses of cerebral blood vessels are an important cause of cerebral ischaemia. Diagnosis may prove very difficult. The diagnostic process is usually initiated by the detection of brain lesions consistent with cerebral vasculitis. Multiple infarcts of various ages in more than one vascular territory are thought to be suggestive of a vascular inflammatory disease. The next step in the imaging of patients with suspected vasculitis is the search for an underlying vascular stenosis. Today, magnetic resonance angiography is the principal modality for the investigation of patients thought to have intracranial stenoses. At 1.5 T, only large brain arteries can be imaged with a high diagnostic accuracy. Intraarterial DSA remains an indispensable tool for the investigation of medium and small brain artery stenoses. However, contrast-enhanced magnetic resonance imaging may be able to demonstrate wall thickening and contrast uptake in large cerebral arteries, obviating biopsy in patients with basal vasculitis.


Total knee arthroplasty with subvastus approach in patient with chronic post-traumatic patellar dislocation.
Chronic lateral dislocation of the patella is a rare condition and acquired causes are usually secondary to knee trauma. The neglected chronic dislocation leads to progressive genu valgum and external tibial torsion deformities with subsequent gonarthrosis, which becomes painful and debilitating. There is no consensus regarding treatment of these patients, but total knee arthroplasty (TKA) is a useful therapy in cases of painful symptomatic gonarthrosis. Few reports have shown that subvastus approach and lateral release may be a valid option for TKA, since it allows the correction of valgus deformity and patellar tracking without interrupting vascular blood supply of patella. This article reports a case of TKA and extensor mechanism realignment without patellar resurfacing in a patient with genu valgum and chronic post-traumatic patellar dislocation with satisfactory results after two years of follow-up.


Exploring the Effect of Assisted Repeated Reading on Incidental Vocabulary Learning and Vocabulary Learning Self-Efficacy in an EFL Context.
The purpose of the current study was to investigate the effect of two types of repeated reading (i.e., assisted and unassisted) on incidental vocabulary learning of Iranian English as a Foreign Language (EFL) learners. In so doing, a sample of 45 intermediate EFL students from two intact classes of a language institute were selected as the participants. The two classes were randomly assigned to an unassisted group (N = 21) who were required to just read and an assisted group (N = 24) who were asked to read and listen to 24 short texts several times. The assisted group employed their smartphones to listen to the audio files of the short stories. The data were gathered via a researcher-made vocabulary test and vocabulary learning self-efficacy scale. The results of ANCOVA revealed that although both types of repeated reading contributed to enhancing vocabulary learning of the participants, assisted repeated reading led to significantly greater EFL vocabulary gains. Additionally, the findings revealed that both assisted and unassisted repeated reading improved vocabulary learning self-efficacy of the participants and there was not a significant difference between the two types of interventions. The findings of the present study have implications for EFL researchers and practitioners.


Cigarette Purchasing Patterns, Readiness to Quit, and Quit Attempts Among Homeless Smokers.
Cigarette purchasing patterns may be linked with greater readiness to make a quit attempt and more quit attempts among domiciled samples. However, little is known about the cigarette purchasing patterns of homeless smokers or their potential relations to quitting intention and behaviors. This study redressed this gap among a convenience sample of homeless adult smokers from a large shelter in Dallas, Texas. Participants (N = 207; Mage = 43; 71.5% male) smoked ≥100 cigarettes over the lifetime and endorsed current daily smoking. Variables assessed included cigarette dependence (time to first cigarette of the day), monthly income, quantity of cigarettes most recently purchased, average money spent on cigarettes weekly, readiness/motivation to quit smoking, and the number intentional quit attempts lasting ≥24h in the past year. Regression analyses were conducted to characterize associations of cigarette purchasing patterns with readiness to quit and quit attempts controlling for sex, age, cigarette dependence, and income. Most participants purchased cigarettes by the pack (61.4%), and more than half the sample spent ≤$20 on cigarettes per week. Results indicated that spending less money per week on cigarettes was associated with greater readiness to quit (P = .016), even when controlling for income, cigarette dependence, and other covariates. Stratified analyses indicated that this association was significant only for homeless smokers reporting no regular monthly income. Homeless daily smokers with no reported income who spend little money on cigarettes may make particularly apt targets for cessation interventions due to potential associations with quitting motivation. Adults who are homeless smoke at greater rates and quit at lower rates than domiciled adults, leading to significant smoking-related health disparities among this group. Findings suggest that cigarette purchasing patterns are linked with readiness to quit smoking among smokers who are homeless. Results elucidate one of the myriad factors that contribute to tobacco-related disparities among this group and findings may have implications for cessation interventions in homeless shelters and other contexts where resources are limited.


Hinge keratoplasty.
A simple trephination technique is described that allows the surgeon to be prepared to handle an expulsive hemorrhage before it occurs. After trephination is performed, the host button is excised except for a 1 clock hour width of tissue. This hinge allows the attached button to fold over the corneal rim away from the surgical field. There is no interference with subsequent intraocular procedures. Should expulsive hemorrhage develop, the attached button can be immediately flipped into place and the wound quickly sewn closed.


Characteristics and treatment outcomes of tuberculosis cases by risk groups, Japan, 2007-2010.
We studied the characteristics and treatment outcomes of the following risk groups for tuberculosis (TB): those with HIV and diabetes mellitus (DM), contact cases, the homeless, foreigners, health care workers (HCW) and the elderly. A descriptive cross-sectional study was conducted by analysing the Japanese tuberculosis surveillance data of all cases registered between 2007 and 2010 (n = 96 689). The annual proportion of TB cases by risk group was stable over the study period, although there was a slight but significant increase observed for foreigners and elderly cases. Homeless and elderly TB cases had the highest DM co-morbidity (16.6% and 15.3%). HIV co-infection was low in all TB cases (0.2%) yet highest in foreigners (1.3%). HIV status of 45% of TB cases was unknown. The proportion of multi drug resistant (MDR) TB was similar among all risk groups (0.0-0.9%) except foreigners, at 3.4%. Males in most risk groups had higher mortality than females; the mortality of all TB cases in all age groups for both males and females were 3.6-24 times higher than the general population. Reasons for the high proportion of "HIV status unknown" should be investigated and improved. Contact tracing among foreign cases with MDR-TB should be a priority. Homeless persons should be screened for DM together with TB. Programs to enhance health and nutrition status may benefit tuberculosis prevention among the elderly. Tuberculosis screening and TB education are important for HCW.


Public palliative care: review of key developments and implementation issues.
This review identifies and briefly describes palliative care programmes that are integrated into the national or regional health care plans of various countries. The uneven development of palliative care in clear favour of developed countries, together with the menace that the growing epidemics of cancer and HIV/AIDS represent to the developing world, have heightened interest in promoting integration of palliative care into public health care strategies. Several successful examples exist in Asia, Africa, Europe, Australia and North America, which may serve as sources of expertise for new initiatives. Success in making palliative care a public discipline that is fully integrated into a country's health care system requires considerable effort in terms of advocacy and lobbying. International support from and networking with experienced individuals who are involved in more mature programmes is crucial to changing attitudes and transforming ideas into action, and strategic and sustainable plans.


Identification of the enzymatic mechanism of nitroglycerin bioactivation.
Nitroglycerin (glyceryl trinitrate, GTN), originally manufactured by Alfred Nobel, has been used to treat angina and heart failure for over 130 years. However, the molecular mechanism of GTN biotransformation has remained a mystery and it is not well understood why "tolerance" (i.e., loss of clinical efficacy) manifests over time. Here we purify a nitrate reductase that specifically catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from GTN, leading to production of cGMP and relaxation of vascular smooth muscle both in vitro and in vivo, and we identify it as mitochondrial aldehyde dehydrogenase (mtALDH). We also show that mtALDH is inhibited in blood vessels made tolerant by GTN. These results demonstrate that the biotransformation of GTN occurs predominantly in mitochondria through a novel reductase action of mtALDH and suggest that nitrite is an obligate intermediate in generation of NO bioactivity. The data also indicate that attenuated biotransformation of GTN by mtALDH underlies the induction of nitrate tolerance. More generally, our studies provide new insights into subcellular processing of NO metabolites and suggest new approaches to generating NO bioactivity and overcoming nitrate tolerance.


Amygdala-cortical collaboration in reward learning and decision making.
Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. These mental simulations are informed by stored memories of the associative relationships that exist within an environment. In this review, I discuss recent investigations of the function of circuitry between the basolateral amygdala (BLA) and lateral (lOFC) and medial (mOFC) orbitofrontal cortex in the learning and use of associative reward memories. I draw conclusions from data collected using sophisticated behavioral approaches to diagnose the content of appetitive memory in combination with modern circuit dissection tools. I propose that, via their direct bidirectional connections, the BLA and OFC collaborate to help us encode detailed, outcome-specific, state-dependent reward memories and to use those memories to enable the predictions and inferences that support adaptive decision making. Whereas lOFC→BLA projections mediate the encoding of outcome-specific reward memories, mOFC→BLA projections regulate the ability to use these memories to inform reward pursuit decisions. BLA projections to lOFC and mOFC both contribute to using reward memories to guide decision making. The BLA→lOFC pathway mediates the ability to represent the identity of a specific predicted reward and the BLA→mOFC pathway facilitates understanding of the value of predicted events. Thus, I outline a neuronal circuit architecture for reward learning and decision making and provide new testable hypotheses as well as implications for both adaptive and maladaptive decision making.


Oxidative Stress and Antioxidant Defense in Endometriosis and Its Malignant Transformation.
The aim of this study was to investigate the role of redox status in endometriosis and its malignant transformation. A search was conducted between 1990 and 2014 through the English language literature (online MEDLINE PubMed database) using the keywords endometriosis combined with malignant transformation, oxidative stress, and antioxidant defense. In benign endometriosis, autoxidation and Fenton reaction of hemoglobin from the ferrous Fe(2+) (oxyhemoglobin) state to the ferric Fe(3+) (methemoglobin) state lead to production of excess reactive oxygen species (ROS) such as O2(-) and (∙)OH. Hemoglobin, heme, and iron derivatives in endometriotic cysts cause distortion in the homeostatic redox balance. Excess oxidative stress could trigger DNA damage and cell death. In contrast, endometriosis-associated ovarian cancer (EAOC) might be associated with an effective antioxidant defense, including heme oxygenases, cytochrome P450 family, and glutathione transferase family. The pattern of redox balance supports that enhanced antioxidants may be involved in the pathogenesis of malignant transformation. In conclusion, oxidant/antioxidant balance function is a double-edged sword, promoting cell death or carcinogenesis. Upregulation of antioxidant functions in endometriotic cyst may result in restoration of cell survival and subsequent malignant transformation.


Synthesis and photoelectrochemical performance of chalcogenopyrylium monomethine dyes bearing phosphonate/phosphonic acid substituents.
Chalcogenopyrylium monomethine dyes were prepared via condensation of a 4-methylchalcogenopyrylium compound with a chalcogenopyran-4-one bearing a 4-(diethoxyphosphoryl)phenyl substituent (or the phosphonic acid derivative). The dyes have absorbance maxima of 603-697 nm in the window where the solar spectrum is most intense. The dyes formed H-aggregates on TiO2, increasing the light-harvesting efficiency of the dyes. Shortcircuit photocurrent action spectra were acquired to evaluate the influence of dye structure on the photoelectrochemical performance.


Anti-Thyroperoxidase Antibody Levels >500 IU/ml Indicate a Moderately Increased Risk for Developing Hypothyroidism in Autoimmune Thyroiditis.
Autoimmune Thyroiditis (AIT) is the most common autoimmune disease, which is characterized by cellular and humoral immunity leading to thyroid destruction. The impact of the humoral immunity on the risk to develop hypothyroidism has not exactly been defined yet. The aim of the present study was to investigate the association between thyroid antibody levels and the risk for developing hypothyroidism. In this retrospective study, 335 untreated AIT patients were enrolled. Anti-thyroperoxidase (TPO) antibodies, anti-thyroglobulin (Tg) antibodies (Abs), and the TSH level were measured. Patients with TPO-Ab levels>500 IU/ml showed a moderately increased risk of having elevated TSH levels [p=0.0023; relative risk (95% confidence interval): 1.343 (1.108-1.627)] compared to those below this threshold. AIT patients with TPO- or Tg-Abs<100 IU/ml and between 100-500 IU/ml had no significantly different TSH levels. Presence of Tg-Abs alone or in combination with TPO-Abs did not help to increase the sensitivity to identify patients at risk. Long term follow-up of AIT patients with high TPO-Abs level (>500 IU/ml) showed an increase of TSH levels (mean: 0.5 mIU/l; range: 2.52±2.73 to 3.02±3.05 mIU/l; p=0.0420). Still, these patients remained euthyroid. Our data indicate largely elevated levels of TPO-Abs being associated with a moderately increased risk of developing hypothyroidism.


Toothbrushing frequency in relation to family size and bedtimes in English schoolchildren.
Data from a survey of 3727 14-yr-old children from 31 secondary schools in England in 1984-85 were analysed to obtain information about toothbrushing frequency, social group, number of siblings, and time of going to bed. Subjects completed a questionnaire, anonymously, in class. One third of respondents cleaned their teeth once or less per day. Toothbrushing frequency was found to increase significantly with improvement in social status in males (P less than 0.05), while a similar non-significant trend was found in females. Toothbrushing frequency decreased significantly as the number of siblings increased (P less than 0.01) and a trend towards decreasing brushing frequency as bedtimes became later was observed. These findings indicate that family factors do influence toothbrushing practice in adolescents. These factors need to be understood more thoroughly if toothbrushing habits in school-age children are to be improved.


Different patterns of insulin resistance in relatives of type 1 diabetic patients with retinopathy or nephropathy: the Genesis France-Belgium Study.
Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes. The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes. The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA(1c) (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy. Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy.


Surface-enhanced Raman scattering investigation of the adsorption of 2-mercaptobenzoxazole on smooth copper surfaces doped with silver colloidal nanoparticles.
The adsorption of 2-mercaptobenzoxazole on copper has been investigated by means of surface-enhanced Raman scattering (SERS) by doping smooth copper surfaces with silver colloidal nanoparticles. The metal surfaces have been characterized by means of atomic force microscopy measurements. The compound adsorbs on the Cu/Ag surfaces in its ionized thiolic form, adopting a tilted orientation with respect to the metal surface. The anion is chemisorbed through the sulfur and nitrogen atoms on the smooth copper surface, and the silver colloidal nanoparticles only enhance the Raman signal due to the electromagnetic mechanism. SERS data have been interpreted with the help of DFT calculations on models of the ligand bound to copper adclusters.


Identification of a gene cluster of biosynthetic genes of rubradirin substructures in S. achromogenes var. rubradiris NRRL3061.
Rubradirin, an ansamycin antibiotic has been purified from Streptomyces achromogenes var. rubradiris NRRL3061. It consists of four distinct structural moieties, rubransarol, 3-amino-4-hydroxy-coumarin, dihydroxydipicolinic acid, and 2,6-dideoxynitrosugar (DNS). Polymerase chain reaction (PCR) primers were designed based on consensus sequences of dTDP-D-glucose 4,6-dehydratase, one of enzymes involved in the biosynthesis of 2,6-dideoxysugar. A PCR product was obtained from S. achromogenes var. rubradiris. Hybridization of the PCR product to a cosmid library constructed from S. achromogenes genomic DNA has led to the identification of three unlinked regions of DNA. One of three kinds of cosmid clones contains homologues of dTDP-D-glucose 4,6-dehydratase, 3-amino-5-hydroxybenzoic acid (AHBA) synthase, and eryA genes. The size of the gene homologous to eryA is 30 kb, and the AHBA synthase gene homologue resides between the eryA homologous genes. A gene cluster of rubransarol and 2,6-dideoxynitrosugar is around 50 kb. Sequencing of the PCR product from the AHBA synthase gene homologue isolated from S. achromogenes revealed 85% amino acid sequence homology (73/86) with the AHBA synthase from a rifamycin-producer. dTDP-D-glucose 4,6-dehydratase gene homologue was subcloned from one of the isolated cosmid clones and sequenced. It showed 65% homology (43/66) with dTDP-D-glucose 4,6-dehydratase from a streptomycin-producer.


Prion Protein PRNP: A New Player in Innate Immunity? The Aβ Connection.
The prion protein PRNP has been centrally implicated in the transmissible spongiform encephalopathies (TSEs), but its normal physiological role remains obscure. We highlight emerging evidence that PRNP displays antimicrobial activity, inhibiting the replication of multiple viruses, and also interacts directly with Alzheimer's disease (AD) amyloid-β (Aβ) peptide whose own antimicrobial role is now increasingly secure. PRNP and Aβ share share membrane-penetrating, nucleic acid binding, and antiviral properties with classical antimicrobial peptides such as LL-37. We discuss findings that binding of abnormal nucleic acids to PRNP leads to oligomerization of the protein, and suggest that this may be an entrapment and sequestration process that contributes to its antimicrobial activity. Some antimicrobial peptides are known to be exploited by infectious agents, and we cover evidence that PRNP is usurped by herpes simplex virus (HSV-1) that has evolved a virus-encoded 'anti-PRNP'.unction. These findings suggest that PRNP, like LL-37 and Aβ, is likely to be a component of the innate immune system, with implications for the pathoetiology of both AD and TSE.


[Hemophilia patient education: teaching and assessment of 10 programs].
A group of health professionals and patients conducted a pedagogical assessment of Therapeutic Patient Education (TPE) in haemophilia in France, focused on 2 main subjects: "the objectives and aims of TPE programs" and "the health professionals' ability to lead and contribute to TPE programs" (3). The use of a research laboratory and a participatory methodology allowed for identifying the assessment's challenges and contributed to its smooth running. TPE is starting to be integrated with medical care for patients, and a multidisciplinary approach better meets patients' educational needs. Two prerequisites for improving the pedagogical quality of these programs are self-reported patient needs and coordination of the TPE activities. The parties involved in this study are now better prepared to meet the ARS (4) TPE program specifications in haemophilia, and, importantly, are better prepared to undergo the assessment that takes place every 4 years.


A Case of Dural Herniation of the Cauda Equina Caused by Enlarged Spinal Subdural Extra-arachnoid Hygroma Following Lumbar Microsurgical Decompression: Case Report.
We experienced a rare case of transdural herniation of cauda equina caused by increased pressure with spinal subdural extra-arachnoid hygroma (SSEH) following lumbar microsurgical decompression. A 68-year-old woman presented with complaints of right leg pain and intermittent claudication. By the diagnosis of L2/3 lumbar spinal stenosis, microsurgical decompression was performed. The surgery was successful with no issues arising such as damage to the dura mater. Lumbar magnetic resonance imaging (MRI) performed 8 days after the surgery confirmed asymptomatic SSEH on the ventral side of the cauda equina. However, posterior cervical pain and lower back pain developed 32 days after the surgery. Lumbar MRI demonstrated that SSEH had markedly increased and advanced from the lumbar spine to the cranium, compressing the spinal cord posteriorly. In addition, herniation of the cauda equina was confirmed in the dura. An emergency surgery was performed. The herniated cauda equina was fully positioned in the dural sac, and the arachnoid membrane with accumulation of spinal fluid on the ventral side was fenestrated. Immediately after the surgery, the patient's symptoms disappeared. Sufficient caution is required regarding the possibility of SSEH associated with spinal failed back surgery syndrome as it can become excessively enlarged, leading to a poor prognosis.


Scanner conformity in CT densitometry of the lungs.
To quantify inter- and intrascanner conformity in computed tomographic (CT) densitometry of the lungs. With six scanners from four manufacturers, a lung densitometry protocol with several variations was applied for performance comparison. Phantoms included water, air, and a humanoid thorax phantom equipped with a dog lung and exchangeable pseudolungs of polyethylene foam. All scanners produced acceptable CT numbers (Hounsfield units) for water, but some not for air. An incorrect calibration of air density affected all CT numbers at lung densities, but the error was easily correctable. Some systems were more sensitive to object size than others were. Sensitivity of CT numbers to section thickness, reconstruction filter, zoom factor, and table height was small, except for two scanners in relation to section thickness. After correction for poor air calibration, scanner conformity was acceptable when the reproducibility of lung densitometry in clinical practice was set as a reference.