The challenge of distinguishing figure from ground: reaction to Gelso's work on the real relationship.
The motives of the beginning psychotherapist for choosing his or her orientation are an underresearched issue in psychotherapy training. This study focuses on the role of personality-based factors, specifically the epistemological preferences of the therapist that Kolb (1984) has termed "learning style" (LS). The aim of the present study was to explore possible associations between psychology students' developing LSs and their choice of psychotherapeutic orientation (psychodynamic [PDT] vs. cognitive-behavioural [CBT]). Students in a psychologist's program (N = 175) took the Learning Style Inventory in their third semester and, before their formal choice, in their seventh semester. Besides a common trend toward radicalization or purification of their LS, the average PDT student tended to stick to the "feel and watch" style from the third semester to the seventh, whereas the CBT student tended to move toward "think and do." A cluster analysis revealed that the average movement among the CBT students was the result of the forces in two different subgroups, one toward "think" (and, more weakly, "watch"), the other toward "do" (and, more weakly, "feel").


Tumor necrosis factor induces the loss of sphingosine kinase-1 by a cathepsin B-dependent mechanism.
Sphingosine kinase-1 (SK1) has emerged as a key component of cytokine responses, including roles in apoptosis, yet the specific mechanisms by which cytokines regulate SK1 in the apoptotic responses have not been studied. In this study, we show that prolonged treatment of MCF-7 cells with tumor necrosis factor (TNF) induces a dose- and time-dependent decrease in SK1 protein. Inhibition of the upstream caspase 8 by IETD significantly rescued TNF effects on SK1, yet the caspase 7 inhibitor DEVD failed to have any effect, suggesting that the decline in SK1 occurs downstream of the initiator caspase but upstream of the effector caspase. In addition to caspase activation, TNF caused disruption of lysosomes with relocation of the cysteine protease cathepsin B into the cytosol. Down-regulation of cathepsin B using small interfering RNA significantly restored SK1 levels following exposure to TNF, suggesting that SK1 loss was dependent on cathepsin B activity. The regulation of SK1 by the lysosomal protease was further supported by the colocalization of SK1 with the lysosome and cathepsin B in cells and the loss of the colocalization following exposure to TNF. The ability of cathepsin B to regulate SK1 was further corroborated by an in vitro approach where recombinant cathepsin B cleaved SK1 at multiple sites to produce several cleavage fragments. Therefore, these studies show that SK1 down-regulation by TNF is dependent on the "lysosomal pathway" of apoptosis and specifically on cathepsin B, which functions as an SK1 protease in cells.


Inosine : a naturally occurring cardiotonic agent.
For many years, Inosine was considered to be a simple metabolite of adenosine which was devoid of any cardiovascular effects. This theoretical ineffectiveness can be explained in the light of recent studies by the use of inadequate doses. In fact, higher doses of inosine, a non-toxic nucleoside, have demonstrated, experimentally, a cardiovascular activity and the pharmacological profile of this naturally occurring substance has been defined. Like adenosine, inosine is a potent coronary vasodilator. The vasodilatation induced by inosine is only partly due to increased metabolic demands. Inosine has a direct action on coronary artery relaxation independent of the inotropic effect. It alters the balance between oxygen supply and demand which is reflected by an intramyocardial redistribution of oxygen in favour of the sub-endocardial zones. Inosine acts on the coronary circulation like a "regulator of myocardial nutrition", unlike adenosine, which can be thought of as a "coronary vasoregulator". This dissociation between the two nucleosides is apparently due to different vascular sites of action. The positive inotropic action of inosine, which has been demonstrated in both healthy and pathological myocardium in all of the experimental animal species studied, is not due to stimulation of the cardiac beta-adrenergic receptors, as beta-blockers do not antagonize the positive inotropic effect of inosine. This increase in myocardial contractile dynamics is evident in infarcted as well as healthy areas of myocardium. The inotropic and coronary vasodilator effects of inosine are not associated with any modification of the chronotropic function. Inosine is not arrhythmogenic, even at high doses. Furthermore, it does not affect atrioventricular conduction. It has been demonstrated that inosine is capable of antagonizing ouabain induced arrhythmias. Various clinical studies confirm the positive inotropic action of inosine, without any alteration in the post-load, the pre-load or the heart rate. The positive inotropic action of inosine can therefore be considered to be selective. Together with these haemodynamic effects, it has been shown that the addition of inosine to cardioplegic solutions improves the functional recovery of the myocardium, by increasing the quantity of energy-rich phosphates. Similar beneficial results have been obtained in renal transplantation, both experimentally and in clinical studies. The mechanism of action of inosine remains unknown. Are the haemodynamic effects of this compound due to its metabolic effects? Are there specific myocardial purinergic receptors? (ABSTRACT TRUNCATED AT 400 WORDS)


Alterations in brain activation during working memory processing associated with breast cancer and treatment: a prospective functional magnetic resonance imaging study.
To prospectively examine alterations in working memory (WM) -associated brain activation related to breast cancer and treatment by using functional magnetic resonance imaging. Patients treated with chemotherapy (CTx+; n = 16) or without chemotherapy (CTx-; n = 12) and healthy controls (n = 15) were scanned during an n-back task at baseline (after surgery but before radiation, chemotherapy, and/or antiestrogen treatment), 1 month after completion of chemotherapy (M1), and 1 year later (Y1), or at yoked intervals for CTx- and controls. SPM5 was used for all image analyses, which included cross-sectional between-group and group-by-time interaction and longitudinal within-group analyses, all using a statistical threshold of 0.001. At baseline, patients with cancer showed increased bifrontal and decreased left parietal activation compared with controls. At M1, both cancer groups showed decreased frontal hyperactivation compared with controls, with increased hyperactivation at Y1. These cross-sectional findings were confirmed by group-by-time interaction analyses, which showed frontal activation decreases from baseline to M1 in patients compared with controls. Within-group analyses showed different patterns of longitudinal activation change by treatment group (CTx+ or CTx-), with prominent alterations in the frontal lobes bilaterally. Significant frontal lobe hyperactivation to support WM was found in patients with breast cancer. Superimposed on this background, patients showed decreased frontal activation at M1, with partial return to the previously abnormal baseline at Y1. These functional changes correspond to frontal lobe regions where we previously reported structural changes in this cohort and provide prospective, longitudinal data that further elucidate mechanisms underlying cognitive effects related to breast cancer and its treatment.


Form follows function: Nuclear morphology as a quantifiable predictor of cellular senescence.
Enlarged or irregularly shaped nuclei are frequently observed in tissue cells undergoing senescence. However, it remained unclear whether this peculiar morphology is a cause or a consequence of senescence and how informative it is in distinguishing between proliferative and senescent cells. Recent research reveals that nuclear morphology can act as a predictive biomarker of senescence, suggesting an active role for the nucleus in driving senescence phenotypes. By employing deep learning algorithms to analyze nuclear morphology, accurate classification of cells as proliferative or senescent is achievable across various cell types and species both in vitro and in vivo. This quantitative imaging-based approach can be employed to establish links between senescence burden and clinical data, aiding in the understanding of age-related diseases, as well as assisting in disease prognosis and treatment response.


[Thermoregulating devices for artificial circulation apparatus with thermoelectric elements].
The increase of the absolute capacity of temperature control devices used in extracorporeal blood circulation apparatus has necessitated the intensification of heat exchange and, as a consequence, the work of heat exchangers under anisothermal conditions. This concerns mainly thermoelectric temperature control devices. Calculations in the process of their design and, to a greater extent, the optimization of their parameters under the conditions of anisothermality in the soldered joints become far more complicated. The numerical analysis of such thermoelectric device with anisothermal soldered joints has demonstrated the possibility of its analytical optimization by assuming it to be a thermoelectric device working under the average effective values of temperature and the coefficients of electrical characteristics. The results thus obtained allow to considerably decrease labor consumption in designing the above-mentioned devices.


The relationship of oxygen delivery to absolute haemoglobin oxygenation and mitochondrial cytochrome oxidase redox state in the adult brain: a near-infrared spectroscopy study.
Near-infrared spectroscopy was used to determine the effect of changes in the rate of oxygen delivery to the adult rat brain on the absolute concentrations of oxyhaemoglobin, deoxyhaemoglobin and the redox state of the CuA centre in mitochondrial cytochrome oxidase. The cytochrome oxidase detection algorithm was determined to be robust to large changes in haemoglobin oxygenation and concentration. By assuming complete haemoglobin deoxygenation and CuA reduction following mechanical ventilation on 100% N2O, the absolute concentration of oxyhaemoglobin (35 microM), deoxyhaemoglobin (27 microM) and the redox state of CuA (82% oxidized) were calculated in the normal adult brain. The mean arterial blood pressure was decreased by exsanguination. When the pressure reached 100 mmHg, haemoglobin oxygenation started to fall, but the total haemoglobin concentration and oxidized CuA levels only fell when cerebral blood volume autoregulation mechanisms failed at 50 mmHg. Haemoglobin oxygenation fell linearly with decreases in the rate of oxygen delivery to the brain, but the oxidized CuA concentration did not start to fall until this rate was 50% of normal. The results suggest that the brain maintains more than adequate oxygen delivery to mitochondria and that near-infrared spectroscopy may be a good measure of oxygen insufficiency in vivo.


Primary esophageal carcinoma in the era of highly active antiretroviral therapy.
As human immunodeficiency virus (HIV)-infected individuals are living longer, non-AIDS-defining cancers are becoming increasingly recognized. Primary esophageal tumors in people living with HIV have seldom been reported. We sought to document patient, virologic, and tumor characteristics and clinical outcomes in this patient group. International physicians involved in the care of AIDS-defining and non-AIDS-defining cancers accrued cases of primary esophageal malignant neoplasms in HIV-infected individuals. Patient demographics, HIV status, cancer risk factors, esophageal tumor characteristics, treatment, and outcomes were analyzed. A total of 19 patients with primary adenocarcinoma and/or squamous cell carcinoma of the esophagus were identified. The median age was 48 years (range, 35-69 years) and the median CD4 lymphocyte count measured 376 cells/microL (range, 42 to >1000 cells/microL) (to convert to x10(9)/L, multiply by 0.001). The majority of patients were men with a history of smoking or considerable alcohol consumption. Prior esophageal disease (reflux, peptic ulcers, and achalasia) was reported in almost half of all patients. Seven patients (37%) underwent surgical resection, 11 (58%) received fluorouracil-based chemotherapy, and 7 (37%) underwent radiotherapy; survival correlated with stage at cancer presentation. While the majority of patients died, only 5 deaths (26%) were attributed to progression of esophageal carcinoma. Primary esophageal carcinoma is another non-AIDS-defining cancer associated with moderate immunosuppression and lifestyle habits including tobacco and alcohol use. The biological behavior, treatment, and outcome of HIV-related esophageal cancer appear similar to the general population with this disease; the same screening and risk moderation strategies are likely to apply.


Annual circulating testosterone levels in captive and free-ranging male armadillos (Dasypus novemcincuts).
Mean circulating concentrations and seasonal changes in plasma testosterone over 3 years were similar in free-ranging and captive male armadillos. The highest concentrations were seen in the summer months, i.e. at the time of maximum breeding, but the relatiely high values at other times and the inability of ACTH to restore dexamethasone-suppressed testosterone concentrations confirms that testicular function continues throughout the year. There was a gradual rise in plasma testosterone to adult levels from the 5th to the 9th month of life in captive-born males, indicating that sexual maturity is reached within the first year of life and that captivity is not deleterious to Leydig cell function.


Purification and characterization of three forms of microsomal cytochrome P-450 in liver from 3-methylcholanthrene-treated guinea pigs.
One molecular form of cytochrome P-450IIA from liver microsomes of guinea pigs treated with 3-methylcholanthrene was purified to a specific content of 17.4 nmoles/mg of protein. The difference spectrum of reduced hemoprotein-carbon monoxide complex of this cytochrome exhibits an absorption maximum at 448 nm. The absolute absorption spectrum of the oxidized form of this hemoprotein suggests a high-spin state of heme iron. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the purified protein shows a single band of polypeptide stained with Coomassie brilliant blue at the position corresponding to Mr 54,000. On the other hand, the other two forms of cytochrome P-450, cytochrome P-450I and P-450IIB, were also separated and purified to specific contents of 8.7 and 5.2 nmoles/mg of protein, respectively. Both cytochrome P-450I and P-450IIB exhibit absorption maxima at 450 nm in the difference spectrum of reduced hemoprotein-carbon monoxide complex, and a low-spin state of ferric iron in the heme. The spectrophotometrical property of cytochrome P-450I and P-450IIB was clearly different from that of cytochrome P-450IIA. Molecular activities of a reconstituted aryl hydrocarbon hydroxylase (EC 126.96.36.199) containing, respectively, cytochrome P-450I, P-450IIA, and P-450IIB were 0.224, 0.250, and 0.395 (moles per minute per mole of cytochrome P-450), and were estimated to be one-tenth that of cytochrome P-448 induced in rat liver by 3-methylcholanthrene, indicating the presence of the low inducibility by 3-methylcholanthrene of aryl hydrocarbon hydroxylase in liver microsomes of guinea pigs.


Loss of dynein-2 intermediate chain Wdr34 results in defects in retrograde ciliary protein trafficking and Hedgehog signaling in the mouse.
The Wdr34 gene encodes an intermediate chain of cytoplasmic dynein 2, the motor for retrograde intraflagellar transport (IFT) in primary cilia. Although mutations in human WDR34 have recently been reported, the association of WDR34 function with Hedgehog (Hh) signaling has not been established, and actual cilia defects in the WDR34 mutant cells have also not been completely characterized. In the present study, we show that Wdr34 mutant mice die in midgestation and exhibit open brain and polydactyly phenotypes. Several Hh-dependent ventral neural cell types are not specified in the mutant neural tube. The expression of the direct Hh targets, Gli1 and Patched 1, is inhibited, while the expression of limb patterning genes that are normally inhibited by the Gli3 repressor is anteriorly expanded in mutant limbs. Comparison of cilia phenotype and function among wild type, Dnchc2 (dynein 2 heavy chain), and Wdr34 mutant cells demonstrates that cilia in both Dnchc2 and Wdr34 mutant cells are stumpy. Several ciliary proteins examined abnormally accumulate in the cilia of both mutant cells. Consistent with its function, overexpressed Wdr34 is occasionally localized to cilia, and Wdr34 is required for the ciliary localization of dynein 2 light intermediate chain Lic3. More interestingly, we show that both Dnchc2 and Wdr34 act between Smo and Gli2/Gli3 in the Hh pathway. Therefore, like Dnchc2, Wdr34 is required for ciliogenesis, retrograde ciliary protein trafficking, and the regulation of Gli2/Gli3 activators and repressors. Furthermore, both Wdr34 and Dnchc2 promote microtubule growth, a novel dynein 2 function in a non-cilia structure.


Construction of swine-specific CpG motif enriched plasmid and the study of its immunostimulatory effects both in vitro and in vivo.
A swine-specific CpG motif enriched plasmid (pUC18-CpG) was constructed in this study. Its immunostimulant property was tested in vitro via lymphocyte transformation assay using swine peripheral blood mononuclear cells (PBMCs). The recombinant plasmid showed higher Stimulation Index (SI) compared to the positive control (LPS). In a following animal experiment, pUC18-CpG was co-administered with a commercial swine FMD killed vaccine. Animals in the pUC18-CpG adjuvanted groups showed much higher antibody titers during the vaccination period.


Numerical survey of some bacterial taxa.
Focht, D. D. (Iowa State University, Ames), and W. R. Lockhart. Numerical survey of some bacterial taxa. J. Bacteriol. 90:1314-1319. 1965.-A numerical analysis was made of 77 properties of each of 43 bacterial strains, representing 25 genera from 8 families in the orders Eubacteriales and Pseudomonadales. Four major groups were found, related to one another at approximately the same level of similarity: (1) a large cluster containing the subgroups (1a) Athiorhodaceae-Spirillaceae, (1b) Xanthomonas, and (1c) "inactive" Micrococcaceae-Achromobacteraceae; (2) a cluster containing the "active" Micrococcaceae and Lactobacillaceae; (3) the enterobacteria; and (4) Aeromonas. There was a sharp distinction between the branches of groups 1a, 1c, and 2. The composition of groups was essentially the same whether or not fermentation of carbohydrates (28 characters) was included in the analysis. Several individual strains, notably, Bacillus subtilis, Leuconostoc mesenteroides, Pseudomonas aeruginosa, and Erwinia amylovora, were related to none of the groups, and others (two species of Proteus, Flavobacterium devorans, and Lactobacillus casei) showed only minimal quantitative relationships with their groups. These results suggest that there may be significant variation in levels of similarity within microbial groups presently accorded equivalent taxonomic rank, and that some present distinctions among taxa, particularly at the generic level, cannot be confirmed on the basis of overall similarity.


Time-dependent ARMA modeling of genomic sequences.
Over the past decade, many investigators have used sophisticated time series tools for the analysis of genomic sequences. Specifically, the correlation of the nucleotide chain has been studied by examining the properties of the power spectrum. The main limitation of the power spectrum is that it is restricted to stationary time series. However, it has been observed over the past decade that genomic sequences exhibit non-stationary statistical behavior. Standard statistical tests have been used to verify that the genomic sequences are indeed not stationary. More recent analysis of genomic data has relied on time-varying power spectral methods to capture the statistical characteristics of genomic sequences. Techniques such as the evolutionary spectrum and evolutionary periodogram have been successful in extracting the time-varying correlation structure. The main difficulty in using time-varying spectral methods is that they are extremely unstable. Large deviations in the correlation structure results from very minor perturbations in the genomic data and experimental procedure. A fundamental new approach is needed in order to provide a stable platform for the non-stationary statistical analysis of genomic sequences. In this paper, we propose to model non-stationary genomic sequences by a time-dependent autoregressive moving average (TD-ARMA) process. The model is based on a classical ARMA process whose coefficients are allowed to vary with time. A series expansion of the time-varying coefficients is used to form a generalized Yule-Walker-type system of equations. A recursive least-squares algorithm is subsequently used to estimate the time-dependent coefficients of the model. The non-stationary parameters estimated are used as a basis for statistical inference and biophysical interpretation of genomic data. In particular, we rely on the TD-ARMA model of genomic sequences to investigate the statistical properties and differentiate between coding and non-coding regions in the nucleotide chain. Specifically, we define a quantitative measure of randomness to assess how far a process deviates from white noise. Our simulation results on various gene sequences show that both the coding and non-coding regions are non-random. However, coding sequences are "whiter" than non-coding sequences as attested by a higher index of randomness. We demonstrate that the proposed TD-ARMA model can be used to provide a stable time series tool for the analysis of non-stationary genomic sequences. The estimated time-varying coefficients are used to define an index of randomness, in order to assess the statistical correlations in coding and non-coding DNA sequences. It turns out that the statistical differences between coding and non-coding sequences are more subtle than previously thought using stationary analysis tools: Both coding and non-coding sequences exhibit statistical correlations, with the coding regions being "whiter" than the non-coding regions. These results corroborate the evolutionary periodogram analysis of genomic sequences and revoke the stationary analysis' conclusion that coding DNA behaves like random sequences.


Rigorous evaluation of genetic and epigenetic effects on clinical laboratory measurements using Japanese monozygotic twins.
The investigation of environmental effects on clinical measurements using individual samples is challenging because their genetic and environmental factors are different. However, using monozygotic twins (MZ) makes it possible to investigate the influence of environmental factors as they have the same genetic factors within pairs because the difference in the clinical traits within the MZ mostly reflect the influence of environmental factors. We hypothesized that the within-pair differences in the traits that are strongly affected by genetic factors become larger after genetic risk score (GRS) correction. Using 278 Japanese MZ pairs, we compared the change in within-pair differences in each of the 45 normalized clinical measurements before and after GRS correction, and we also attempted to correct for the effects of genetic factors to identify Cytosine-phosphodiester-Guanine (CpG) sites in DNA sequences with epigenetic effects that are regulated by genetic factors. Five traits were classified into the high heritability group, which was strongly affected by genetic factors. CpG sites could be classified into three groups: regulated only by environmental factors, regulated by environmental factors masked by genetic factors, and regulated only by genetic factors. Our method has the potential to identify trait-related methylation sites that have not yet been discovered.


Development of PrimeTime-Real-Time PCR for Species Identification of Soybean Cyst Nematode (Heterodera glycines Ichinohe, 1952) in North Carolina.
Soybean cyst nematode (SCN) is an obligate, sedentary parasite that is a major pathogen of soybean and accounts for an estimated 1 billion dollars in production losses annually in the United States of America. This paper describes the development of a real-time PCR method for rapid, sensitive, species-specific and accurate identification of SCN alone or on mixed populations with other nematodes in North Carolina. The 83-bp DNA fragment of PrimeTime-real-time PCR was designed based on a 477-bp-SCN-SCAR marker previously proved to be SCN-specific. A total of 44 populations including cyst forming nematodes (Heterodera glycines, H. fici, H. schachtii, H. trifolii, Cactodera weissi, Globodera tabacum, Meloidodera floridensis and other unidentified cyst nematodes) and non-cyst forming nematodes (Ditylenchus dipsaci, Meloidogyne incognita and Xiphinema chambersi) were tested in this study, all SCN populations are tested positive and non-SCN populations negative. This assay for the detection and identification has been successfully applied for testing a single SCN cyst, a 2(nd)-stage-SCN juvenile, a single SCN egg, up to ten SCN cysts, a 10-fold dilution of a single 2(nd)-stage-SCN juvenile and 20-fold dilution of one SCN cyst. The assay is not SCN-race specific. It gave an accurate positive result when SCN is mixed with other cyst species. Also, nematode universal primers/probes for real-time PCR amplification as a nematode endogenous control to detect the presence of 18S ribosomal RNA (rRNA) gene were employed in this assay, so that a SCN-negative sample can be tested to exclude false negative. This method will be very useful for a broad range of research programs as well as the regulatory response and management of SCN in North Carolina and other region of the southeastern U.S.A.


Evaluation of the success rate of nonsurgical single visit retreatment.
Advantages of endodontic treatments over tooth extraction have increased the demands for these treatments. Success rate of these treatments is generally lower than the primary root canal therapies. Recently, single visit treatments have gained more popularity. But, the influence of completing retreatment in a single appointment on success of the treatment is still a controversy. The aim of this study was evaluating the most common causes of failures and determining the success rate of completing retreatments in single appointment. Hundred and twenty four patients who had single appointment retreatment within past 4 years in postgraduate ward of Shahid Beheshti Dental School were selected and clinical and radiographic examinations were carried out. The data were analyzed by SPSS using Chi-square and Exact Fisher tests. Success rate and uncertain cases were shown to be 50.7% and 34.2%, respectively and failure rate was 15.1%. Presence of periradicular lesion or history of swelling prior to retreatment had significant effect on the success of single visit retreatments (p<0.001). Another important finding of the study was that the success rate of retreatments was significantly higher in cases referred for restorative purposes compared with retreatments for nonrestorative purposes (p<0.001). The overall success rate of single appointment retreatments is up to 84.9% which is considerably higher in cases referred for restorative purposes. So based on the results of this study single appointment retreatment of symptom less teeth is recommended.


Exacerbation of coagulopathy with concurrent bone marrow necrosis, hepatic and renal dysfunction secondary to all-trans retinoic acid therapy for acute promyelocytic leukemia.
A 22-year-old female presented with acute promyelocytic leukemia (APL). Treatment with all-trans retinoic acid (ATRA) resulted in a severe exacerbation of the coagulopathy 5 days after its introduction. This was complicated by bone marrow necrosis, parenchymal liver damage and acute tubular necrosis. Temporary cessation of the drug and subsequent dose reduction was effective in controlling the coagulopathy.


Serologic detection of Angiostrongylus vasorum infection in dogs.
Angiostrongylus vasorum, French Heartworm, is a metastrongylid nematode infecting the pulmonary arteries and right heart of wild and domestic canids in various regions of the world. Infection in dogs can result in fatal cardiopulmonary disease. A single endemic focus of A. vasorum in North America occurs in the southeastern portion of Newfoundland, Canada. Dogs are currently diagnosed by detection of first-stage larvae shed in feces using the Baermann technique or fecal flotation. However, these procedures may lack sensitivity due to intermittent fecal larval shedding. The potential for using detection of circulating worm antigen for diagnosis was investigated by developing a sandwich-ELISA using rabbit anti-whole adult worm antiserum. This test detected circulating antigen in sera from 22/24 Baermann positive dogs naturally infected with A. vasorum. Negative results (0/52) were obtained from sera collected from Baermann negative dogs from outside of the endemic region, and from sera (0/30) from dogs from non-endemic regions that were infected with Crenosoma vulpis, the fox lung worm. Receiver operating curve analysis gave a specificity of 100% and a sensitivity of 92% for the sandwich-ELISA at an optical density cut-off of 0.19. Subsequently, 239 dogs from Newfoundland displaying clinical signs of cardiopulmonary disease, were examined using both the Baermann fecal examination and the sandwich-ELISA. Larvae were detected in 10% (24/239) of these dogs by fecal examination, whereas the sandwich-ELISA detected circulating antigen of A. vasorum in serum from 18.8% (45/239) of the dogs. This suggests that fecal diagnostics may have missed approximately half of the A. vasorum infected dogs, and that the sandwich-ELISA may be a useful tool in the diagnosis of this parasite.


Stochastic, stage-specific mechanisms account for the variegation of a human globin transgene.
The random insertion of transgenes into the genomic DNA of mice usually leads to widely variable levels of expression in individual founder lines. To study the mechanisms that cause variegation, we designed a transgene that we expected to variegate, which consisted of a beta-globin locus control region 5' HS-2 linked in tandem to a tagged human beta-globin gene (into which a Lac-Z cassette had been inserted). All tested founder lines exhibited red blood cell-specific expression, but levels of expression varied >1000-fold from the lowest to the highest expressing line. Most of the variation in levels of expression appeared to reflect differences in the percentage of cells in the peripheral blood that expressed the transgene, which ranged from 0.3% in the lowest expressing line to 88% in the highest; the level of transgene expression per cell varied no more than 10-fold from the lowest to the highest expressing line. These differences in expression levels could not be explained by the location of transgene integration, by an effect of beta-galactosidase on red blood cell survival, by the half life of the beta-galactosidase enzyme or by the age of the animals. The progeny of all early erythroid progenitors (BFU-E colony-forming cells) exhibited the same propensity to variegate in methylcellulose-based cultures, suggesting that the decision to variegate occurs after the BFU-E stage of erythroid differentiation. Collectively, these data suggest that variegation in levels of transgene expression are due to local, integration site-dependent phenomena that alter the probability that a transgene will be expressed in an appropriate cell; however, these local effects have a minimal impact on the transgene's activity in the cells that initiate transcription.


A Comparative Study of Insect Succession on Rabbit Carrion in Three Different Microhabitats.
Insect succession on three rabbit carcasses placed 110.49 cm above ground in winter in Riyadh City, Saudi Arabia was examined in three different microhabitats: dry, semi-submerged, and submerged in tap water. The complete decomposition of the carcasses took 20 d and included five stages. In total 715 insects collected from carrion in different microhabitats were identified morphological, followed by the partial sequence confirmation of their 16S rRNA mitochondrial genes. Results showed that the insect species found and species richness differed among microhabitats. Carrion placed in the dry microhabitat showed the highest species richness and colonized by 400 insect specimens belonging to 16 species. Carrion placed in the semi-submerged microhabitat contained 271 insect specimens belonging to 12 species, showing a relatively low species richness. Lastly, the submerged microhabitat showed the lowest species richness, as the carrion placed in it attracted only 44 insects belonging to 9 species.


Inherited primary hypothyroidism in mice.
A new autosomal recessive mutation that causes hypothyroidism has been identified in mice. The gene, herein named hypothyroid (hyt), has been mapped on chromosome 12 approximately 30 units from the centromere. The mutants are characterized by retarded growth, infertility, mild anemia, elevated serum cholesterol, very low to undetectable serum thyroxine, and elevated serum thyroid-stimulating hormone. Thyroid glands are in the normal location but are reduced in size and hypoplastic. Mutant mice respond to thyroid hormone therapy by improved growth and fertility. These findings suggest that the hyt mutant gene results in primary hypothyroidism unresponsive to thyroid-stimulating hormone.


The Multidimension of Malnutrition among School Children in a Rural Area, South Africa: A Mixed Methods Approach.
To address childhood malnutrition, the use of multifaceted methodologies, such as mixed methods research, is required to inform effective and contextual interventions. However, this remains limited in studying malnutrition among school children in a South African context, notwithstanding its persistence. We adopted a convergent parallel mixed methods design to best understand the magnitude of malnutrition through multilevel influences in a rural area. A quantitative survey determined the magnitude of malnutrition and associated factors among school children and their mothers (n = 508), parallel to a qualitative study, which explored mothers' insights into the influences of child growth and nutrition in interviews using seven focus group discussions. Mixed methods integration was achieved through convergence of the quantitative constructs developed from measured variables for malnutrition and related factors with ten emergent qualitative themes using a joint display analysis to compare the findings and generate meta-inferences. Qualitative themes on food unavailability and affordability, poor feeding beliefs and practices, and decision to purchase foods were consistent with the quantified poor socio-demographic status of mothers. Furthermore, the qualitative data explained the high prevalence of undernutrition among children but did not corroborate the high estimated households' food security in the quantitative survey. The misperceptions of mothers on child growth agreed with limited food knowledge as well as lack of knowledge on child growth gathered during the survey. Moreover, mothers believed that their children were growing well despite the high presence of childhood undernutrition. Mothers further overrated the effectiveness of school feeding programmes in providing healthy food to children as compared to their household food. They reported high incidence of food allergies, diarrhea, and vomiting caused by food consumed at school which resulted in children not eating certain foods. This might have impacted on the nutritional status of children since mothers depended on the school feeding program to provide food for their children. The ambiguity of cultural influences in relation to child growth was evident and substantiated during qualitative interview. Mixed methods integration offered a better understanding of malnutrition from empirical findings on interrelated factors at child, maternal, household, and school levels. This study points to a need for multilevel, informed, and contextual multidimensional interventions to contribute towards addressing childhood malnutrition in South Africa.


Complement pathway is frequently altered in endometriosis and endometriosis-associated ovarian cancer.
Mechanisms of immune dysregulation associated with advanced tumors are relatively well understood. Much less is known about the role of immune effectors against cancer precursor lesions. Endometrioid and clear-cell ovarian tumors partly derive from endometriosis, a commonly diagnosed chronic inflammatory disease. We performed here a comprehensive immune gene expression analysis of pelvic inflammation in endometriosis and endometriosis-associated ovarian cancer (EAOC). RNA was extracted from 120 paraffin tissue blocks comprising of normal endometrium (n = 32), benign endometriosis (n = 30), atypical endometriosis (n = 15), and EAOC (n = 43). Serous tumors (n = 15) were included as nonendometriosis-associated controls. The immune microenvironment was profiled using Nanostring and the nCounter GX Human Immunology Kit, comprising probes for a total of 511 immune genes. One third of the patients with endometriosis revealed a tumor-like inflammation profile, suggesting that cancer-like immune signatures may develop earlier, in patients classified as clinically benign. Gene expression analyses revealed the complement pathway as most prominently involved in both endometriosis and EAOC. Complement proteins are abundantly present in epithelial cells in both benign and malignant lesions. Mechanistic studies in ovarian surface epithelial cells from mice with conditional (Cre-loxP) mutations show intrinsic production of complement in epithelia and demonstrate an early link between Kras- and Pten-driven pathways and complement upregulation. Downregulation of complement in these cells interferes with cell proliferation. These findings reveal new characteristics of inflammation in precursor lesions and point to previously unknown roles of complement in endometriosis and EAOC.


Fibroblast response to a controlled nanoenvironment produced by colloidal lithography.
It is thought that by understanding how cells respond to topography, that better tissue engineering may be achievable. An important consideration in the cellular environment is topography. The effects of microtopography have been well documented, but the effects of nanotopography are less well known. Previously, methods of nanofabrication have been costly and time-consuming, but research by engineers, physicists, and chemists is starting to allow the production of nanostructures using low-cost techniques. In this report, nanotopography is specifically considered. Controlled patterns of 160 nm high nanocolumns were produced for in vitro cell culture using colloidal lithography. By studying cell adhesion with time and cytoskeletal (actin, tubulin, and vimentin) maturity, insight has been gained as to how fibroblasts adhere to these nanofeatures.


Brain receptors and zopiclone.
Zopiclone (ZPC; RP 27,267), which is chemically unrelated to benzodiazepines (BZD), was found to have a similar pharmacological profile and to possess in man hypnotic activity similar to that of some BZD such as nitrazepam. It was, therefore, interesting to study the interaction of ZPC with rat brain receptors and specially with the so-called 'BZD receptors'. ZPC possesses in three rat brain regions a high affinity for BZD receptors: its Ki values measured against [3H]-flunitrazepam are 24 nM in the cerebral cortex, 31 nM in the cerebellum, and 36 nM in the hippocampus. No other brain receptors such as gamma-aminobutyric acid receptor, dopamine receptor, serotonin and noradrenergic receptors are reached by ZPC. Moreover, ZPC seems to bind only to brain BZD receptors and, contrarily to some BZD such as flunitrazepam, it does not reach the peripheral renal BZD-binding sites. The synthesis of [3H]-ZPC has permitted a more in-depth study of the interaction of ZPC with brain receptors. The high affinity of ZPC has been confirmed by equilibrium-binding studies (KD = 13 +/- 4 nM in rat hippocampus) and the study of the modulating effect of gamma-aminobutyric acid and barbiturates on ZPC binding has revealed some differences between ZPC and BZD. It could, therefore, be postulated that ZPC might bind in rat brain to sites which do not correspond exactly to BZD sites.


Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis.
A critical outcome of periodontal disease is degradation of the collagenous periodontal ligament that connects teeth to bone in the dental arch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. One family of enzymes, known as the matrix metalloproteinases (MMPs), has been implicated in the degradation of the periodontal ligament. MMPs, which are also suspected to play a role in many other physiologic and pathologic remodeling processes, can be secreted by epithelial cells surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are secreted as inactive zymogens which may be activated by limited proteolysis, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or accelerate degradation of the collegenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs and bacterial proteinase. In this article, we demonstrate that a proteinase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these MMPs is demonstrated to result from initial hydrolysis within their propeptide. Also, for MMP-1 and MMP-9, the P. gingivalis proteinase cleaves the MMP propeptide following a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathogen Porphyromonas gingivalis that involves activation of host-degradative enzymes.


Anomalous right coronary artery from the left coronary sinus with an interarterial course: is it really dangerous?
Anomalous origin of the right or left coronary artery from the contralateral sinus of Valsalva is often asymptomatic, but many patients, particularly young ones, present with sudden death or myocardial ischemia without symptoms. The mechanism of sudden death in this entity is unclear and has not been fully evaluated. These anomalies are rare, and many cardiologists and radiologists are unfamiliar with them. Surgical repair is recommended, especially with anomalous origin of the left coronary artery (LCA). However, there is controversy concerning the treatment of anomalous right coronary artery (RCA) with interarterial course due to its relatively high incidence and the fact that it leads to few, if any, clinical problems.


Efficient message passing for cascade size distributions.
How big is the risk that a few initial failures of networked nodes amplify to large cascades that endanger the functioning of the system? Common answers refer to the average final cascade size. Two analytic approaches allow its computation: (a) (heterogeneous) mean field approximation and (b) belief propagation. The former applies to (infinitely) large locally tree-like networks, while the latter is exact on finite trees. Yet, cascade sizes can have broad and multi-modal distributions that are not well represented by their average. Full distribution information is essential to identify likely events and to estimate the tail risk, i.e. the probability of extreme events. We therefore present an efficient message passing algorithm that calculates the cascade size distribution in finite networks. It is exact on finite trees and for a large class of cascade processes. An approximate version applies to any network structure and performs well on locally tree-like networks, as we show with several examples.


Influence of the formulation on the tolerance profile of nanoparticle-bound doxorubicin in healthy rats: focus on cardio- and testicular toxicity.
A toxicological study of doxorubicin bound to poly(butyl cyanoacrylate) or human serum albumin nanoparticles coated with polysorbate 80 was performed in healthy rats. The doxorubicin formulations were injected at a therapeutic dose regimen (3 x 1.5 mg/kg with a 72 h interval), and the animals were followed up for 15 or 30 days. The overall result of this study suggests that the surfactant-coated nanoparticle formulations of doxorubicin have favorable toxicological profiles. Specifically, these formulations display a considerably reduced cardio- and testicular toxicity, as compared to a free drug.


Tyrosine hydroxylase expression in hypothalamic cells: analysis of the roles of adenosine 3',5'-monophosphate- and Ca2+/calmodulin-dependent protein kinases in the action of pituitary cytotropic factor.
We investigated the involvement of second messenger systems in the control by pituitary cytotropic factor (CTF) of tyrosine hydroxylase (TH) expression in primary cultures of hypothalamic cells. Forskolin, an activator of adenylyl cyclase, as well as Sp-cAMP[S] [(Sp)-cyclic adenosine 3',5'-monophosphothioate], a cAMP agonist, and theophylline, an inhibitor of phosphodiesterase activity, stimulate the secretion of dihydroxyphenylalanine (DOPA) and dopamine (DA), suggesting a role for cAMP-dependent protein kinase in the secretion of catecholamines by hypothalamic dopaminergic cells. When cells were cultured with either CTF or forskolin for 14 days, a progressive increase in the secretion of DOPA and DA was observed throughout the period of incubation. At the end of the 2-week culture period, the amount of TH in the cells, determined by immunoblot analysis, was appreciably increased compared to controls. When the cells were analyzed immunocytochemically for TH, the TH-positive cells that had been incubated with CTF or forskolin for 2 weeks were found to have neurites that appeared larger than those of TH-positive cells in the controls. The diameters of the perikarya of TH-positive cells in cultures incubated with CTF also appeared larger than the controls. After incubation of hypothalamic cells with CTF for 96 h, the amount of TH mRNA in the cultures was significantly increased. When membranes isolated from PC12 cells were incubated for 10 min with 50 microM forskolin, the specific activity of adenylyl cyclase was increased 20-fold; CTF had no effect on adenylyl cyclase activity of PC12 cell membranes. Yet, CTF significantly (P less than 0.001) stimulated the secretion of DOPA and DA by PC12 cells. When hypothalamic cells were incubated with both forskolin and CTF, using doses of each that stimulated maximal secretion, the secretion of DOPA and DA was equal to sum of the secretions with each stimulant alone. These additive actions of forskolin and CTF and the failure of CTF to activate adenylyl cyclase in membranes of PC12 cells suggest that forskolin and CTF stimulate catecholamine secretion by hypothalamic dopaminergic cells through different mechanisms, perhaps through different protein kinases. When hypothalamic cells were incubated with CTF and W-7 [N-(6-aminohexyl)5-chloro-1-naphthalenesulfonamide], an inhibitor of calmodulin, the secretion of DOPA was significantly (P less than 0.001) less than that in cultures that were not incubated with W-7. The findings of this study suggest that TH expression in hypothalamic dopaminergic cells is controlled by redundant protein kinases, including cAMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase.


Dehydroepiandrosterone treatment in the aging male--what should the urologist know?
Dehydroepiandrosterone (DHEA) has attracted considerable attention as a means against the decrements of aging. This review will summarize clinical studies evaluating DHEA as a treatment option for age-related conditions and diseases. Literature search of PubMed documented publications and abstracts from meetings. The collected data indicate that DHEA supplementation to counteract its gradual decrease over age is beneficiary. Positive effects on the cardiovascular system, body composition, BMD, the skin, the CNS, and the immune system have been reported. Improvement of sexual function by DHEA has been demonstrated. Although long-term clinical trials (applying the standards of evidence-based methods) are not available at present, the consistency of the data and the extensive practical experience may justify the use of DHEA in aging men given the rules of classical endocrinology are thoroughly followed including diagnosis based on clinical picture and biochemical evidence, compliance to periodic evaluations, and individual dose adjustment to maintain serum concentrations in the physiological range of young males. Being one among other important hormonal factors, DHEA can delay and correct age-related disorders only to a certain degree.


Childhood ecology influences salivary testosterone, pubertal age and stature of Bangladeshi UK migrant men.
Male reproductive investment is energetically costly, and measures of human reproductive steroid hormones (testosterone), developmental tempo (pubertal timing) and growth (stature) correlate with local ecologies at the population level. It is unclear whether male reproductive investment in later life is 'set' during childhood development, mediated through adulthood, or varies by ethnicity. Applying a life-course model to Bangladeshi migrants to the United Kingdom, here we investigate plasticity in human male reproductive function resulting from childhood developmental conditions. We hypothesized that childhood ecology shapes adult trade-offs between reproductive investment and/or other fitness-related traits. We predicted correspondence between these traits and developmental timing of exposure to ecological constraints (Bangladesh) or conditions of surplus (United Kingdom). We compared: Bangladesh sedentees (n = 107); Bangladeshi men who migrated in childhood to the United Kingdom (n = 59); migrants who arrived in adulthood (n = 75); second-generation UK-born and raised children of Bangladeshi migrants (n = 56); and UK-born ethnic Europeans (n = 62). Migration before puberty predicted higher testosterone and an earlier recalled pubertal age compared with Bangladeshi sedentees or adult migrants, with more pronounced differences in men who arrived before the age of eight. Second-generation Bangladeshis were taller, with higher testosterone than sedentees and adult migrants, and higher waking testosterone than Europeans. Age-related testosterone profiles varied by group, declining in UK migrants, increasing in sedentees, and having no significant relationship within UK-born groups. We conclude that male reproductive function apparently remains plastic late into childhood, is independent of Bengali or European ethnicity, and shapes physiological trade-offs later in life.


Changes in myocardial iron content following administration of intravenous iron (Myocardial-IRON): Study design.
Treatment with intravenous ferric carboxymaltose (FCM) has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure and iron deficiency. However, the underlying mechanisms for these beneficial effects remain undetermined. The aim of this study is to quantify cardiac magnetic resonance changes in myocardial iron content after administration of intravenous FCM in patients with heart failure and iron deficiency and contrast them with parameters of heart failure severity. This is a multicenter, double-blind, randomized study. Fifty patients with stable symptomatic heart failure, left ventricular ejection fraction <50%, and iron deficiency will be randomly assigned 1:1 to receive intravenous FCM or placebo. Intramyocardial iron will be evaluated by T2* and T1 mapping cardiac magnetic resonance sequences before and at 7 and 30 days after FCM. After 30 days, patients assigned to placebo will receive intravenous FCM in case of persistent iron deficiency. The main endpoint will be changes from baseline in myocardial iron content at 7 and 30 days. Secondary endpoints will include the correlation of these changes with left ventricular ejection fraction, functional capacity, quality of life, and cardiac biomarkers. The results of this study will add important knowledge about the effects of intravenous FCM on myocardial tissue and cardiac function. We hypothesize that short-term (7 and 30 days) myocardial iron content changes after intravenous FCM, evaluated by cardiac magnetic resonance, will correlate with simultaneous changes in parameters of heart failure severity. The study is registered at http://www.clinicaltrials.gov (NCT03398681).


Molecular biology and regulation of methane monooxygenase.
Methanotrophs are ubiquitous in the environment and play an important role in mitigating global warming due to methane. They are also potentially interesting for industrial applications such as production of bulk chemicals or bioremediation. The first step in the oxidation of methane is the conversion to methanol by methane monooxygenase, the key enzyme, which exists in two forms: the cytoplasmic, soluble methane monooxygenase (sMMO) and the membrane-bound, particulate methane monooxygenase (pMMO). This paper reviews the biochemistry and molecular biology of both forms of MMO. In the past few years there have been many exciting new findings. sMMO components have been expressed in heterologous and homologous hosts. The pMMO has been purified and biochemically studied in some detail and the genes encoding the pMMO have been sequenced. Copper ions have been shown to play a key role in regulating the expression of both MMO enzyme complexes. We also present a model for copper regulation based on results from Northern analysis, primer-extensions and new sequence data, and raise a number of unanswered questions for future studies.


Clinical pharmacology of proton pump inhibitors: what the practising physician needs to know.
Proton pump inhibitors (PPIs) [omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole] are widely utilised for the treatment of gastro-oesophageal reflux disease, as well as other acid-related disorders. All PPIs suppress gastric acid secretion by blocking the gastric acid pump, H(+)/K(+)-adenosine triphosphatase (ATPase), but the physicochemical properties of these drugs result in variations in the degree of acid suppression, as well as the speed of onset of acid inhibition. Such differences may impact on the clinical performance of PPIs, and this manuscript discusses data that may help clinicians choose between the available PPIs for specific clinical situations and indications. The characteristics of PPIs that have been developed subsequent to omeprazole offer several advantages over this prototype PPI, particularly with respect to the onset of acid suppression and reduced potential for inter-individual pharmacokinetic variation and drug interactions. Newer agents inhibit H(+)/K(+)-ATPase more rapidly than omeprazole and emerging clinical data support potential clinical benefits resulting from this pharmacological property. Although key pharmacokinetic parameters (time to maximum plasma concentration and elimination half-life) do not differ significantly among PPIs, differences in the hepatic metabolism of these drugs can produce inter-patient variability in acid suppression, in the potential for pharmacokinetic drug interactions and, quite possibly, in clinical efficacy. All PPIs undergo significant hepatic metabolism. Because there is no direct toxicity from PPIs, there is minimal risk from the administration of any of them - even to patients with significant renal or hepatic impairment. However, there are significant genetic polymorphisms for one of the cytochrome P450 (CYP) isoenzymes involved in PPI metabolism (CYP2C19), and this polymorphism has been shown to substantially increase plasma levels of omeprazole, lansoprazole and pantoprazole, but not those of rabeprazole. Hepatic metabolism is also a key determinant of the potential for a given drug to be involved in clinically significant pharmacokinetic drug interactions. Omeprazole has the highest risk for such interactions among PPIs, and rabeprazole and pantoprazole appear to have the lowest risk.Thus, whereas all PPIs have been shown to be generally effective and safely used for the treatment of acid-mediated disorders, there are chemical, pharmacodynamic and pharmacokinetic differences among these drugs that may make certain ones more, or less, suitable for treating different patient subgroups. Of course, the absolute magnitude of risk from any PPI in terms of drug-drug interactions is probably low - excepting interactions occurring as class effects related to acid suppression (e.g. increased digoxin absorption or inability to absorb ketoconazole).


Three-dimensional tertiary structure of yeast phenylalanine transfer RNA.
The 3-angstrom electron density map of crystalline yeast phenylalanine transfer RNA has provided us with a complete three-dimensional model which defines the positions of all of the nucleotide residues in the moleclule. The overall features of the molecule are virtually the same as those seen at a resolution of 4 angstroms except that many additional details of tertiary structure are now visualized. Ten types of hydrogen bonding are identified which define the specificity of tertiary interactions. The molecule is also stabilized by considerable stacking of the planar purines and pyrimidines. This tertiary structure explains, in a simple and direct fashion, chemical modification studies of transfer RNA. Since most of the tertiary interactions involve nucleotides which are common to all transfer RNA 's, it is likely that this three-dimensional structure provides a basic pattern of folding which may help to clarify the three-dimensional structure of all transfer RNA's.


Ionic mechanism of dopaminergic and muscarinic auto- and heteroreceptor activation in superfused striatal slices: role of extracellular chloride.
The Cl dependency of agonist-induced ionic mechanisms involved in the receptor-mediated modulation of electrically stimulated release of dopamine (DA) and acetylcholine (ACh) was examined in superfused rabbit striatal slices prelabeled with [3H] DA (3,4-[8-3H]dihydroxyphenylethylamine) and [14C]choline ([ methyl-14C]choline Cl). Cl- was substituted in the superfusion medium to varying degrees with the impermeant anions isethionate, methanesulfonate or gluconate. The sodium concentration was held constant. Apomorphine (30 nM), a DA receptor agonist, inhibited the stimulation-evoked (1 Hz, 2 min) release of both DA and ACh in Krebs-Ringer-bicarbonate medium (KRB; 125.4 mM Cl-). The inhibitory effects of the agonist were not altered significantly in media containing 66.4 mM Cl-. In 7.4 mM Cl- medium (isethionate replacement), apomorphine-induced inhibition of DA release was reduced (40% inhibition vs. 67% inhibition in KRB). Similarly, apomorphine inhibition of ACh release was lowered from 38% in KRB to 25% in 7.4 mM Cl-. The muscarinic receptor agonist carbachol (10 microM) inhibited the stimulation-evoked release of ACh while enhancing the evoked release of DA in normal Cl- (125.4 mM) medium. Inhibition of ACh release was not altered in 66.4 mM Cl- media but was increased in 7.4 mM Cl- (63% inhibition in low Cl- vs. 50% in KRB). The enhancing effects of carbachol on stimulated DA release were potentiated in 66.4 mM Cl- (88% enhancement vs. 57% in KRB), whereas no change in the agonist effect was observed in the lower Cl- medium (7.4 mM Cl-).(ABSTRACT TRUNCATED AT 250 WORDS)


Safety and tolerability of controlled-release oxycodone on postoperative pain in patients submitted to the oncologic head and neck surgery.
To evaluate the safety and tolerability of controlled-release oxycodone in the treatment of postoperative pain of head and neck oncologic resections. We conducted a prospective, observational and open study, with 83 patients with moderate to severe pain after head and neck oncological operations. All patients received general anesthesia with propofol, fentanyl and sevoflurane. Postoperatively, should they have moderate or severe pain, we began controlled-release oxycodone 20 mg 12/12 b.i.d on the first day and 10 mg b.i.d. on the second. We assessed the frequency and intensity of adverse effects, the intensity of postoperative pain by a verbal numeric scale and the use of rescue analgesia from 12 hours after administration of the drug and between 7 and 13 days after the last oxycodone dose. The most common adverse events were nausea, vomiting, dizziness, pruritus, insomnia, constipation and urinary retention, most mild. No serious adverse events occurred. In less than 12 hours after the use of oxycodone, there was a significant decrease in the intensity of postoperative pain, which remained until the end of the study. The rescue medication was requested at a higher frequency when the opioid dose was reduced, or after its suspension. Controlled release oxycodone showed to be safe and well tolerated and caused a significant decrease in post-operative pain.


Identification of adiponectin as a novel hemopoietic stem cell growth factor.
The hemopoietic microenvironment consists of a diverse repertoire of cells capable of providing signals that influence hemopoietic stem cell function. Although the role of osteoblasts and vascular endothelial cells has recently been characterized, the function of the most abundant cell type in the bone marrow, the adipocyte, is less defined. Given the emergence of a growing number of adipokines, it is possible that these factors may also play a role in regulating hematopoiesis. Here, we investigated the role of adiponectin, a secreted molecule derived from adipocytes, in hemopoietic stem cell (HSC) function. We show that adiponectin is expressed by components of the HSC niche and its receptors AdipoR1 and AdipoR2 are expressed by HSCs. At a functional level, adiponectin influences HSCs by increasing their proliferation, while retaining the cells in a functionally immature state as determined by in vitro and in vivo assays. We also demonstrate that adiponectin signaling is required for optimal HSC proliferation both in vitro and in long term hemopoietic reconstitution in vivo. Finally we show that adiponectin stimulation activates p38 MAPK, and that inhibition of this pathway abrogates adiponectin's proliferative effect on HSCs. These studies collectively identify adiponectin as a novel regulator of HSC function and suggest that it acts through a p38 dependent pathway.


Approach and avoidance strength during goal attainment: regulatory focus and the "goal looms larger" effect.
Three studies tested the hypothesis that regulatory focus, both as a chronic person variable and as a manipulated situational variable, differentially affects the strength of participants' approach and avoidance strategic motivations as they get closer to the goal. In 2 studies, flexion and extension arm pressure were used as on-line measures of approach and avoidance intensity, respectively. As predicted, the approach gradient was steeper for participants with a promotion focus on aspirations and gains than for participants with a prevention focus on responsibilities and nonlosses, whereas the reverse was true for the avoidance gradient. In a third study, the same pattern of results was found on a persistence measure of motivational strength. Participants with a promotion focus worked longer on anagrams closer to the goal when they were approach means for goal attainment than when they were avoidance means, whereas the reverse was true for participants with a prevention focus.


Molecular mechanics of elastic and bendable caffeine co-crystals.
Complementing recent experimental results, here we report a computational study of remarkably flexible, elastically bendable caffeine cocrystals (cocrystal solvate 1), formed from caffeine (CAF), 4-chloro-3-nitrobenzoic acid (CNB), and methanol, and compare with its unsolvated brittle form, 1 (dry). We show that 1 is able to maintain stable cocrystal structures at temperatures between 100 K and 400 K. The tensile and compressive Young's modulus of 1 are close to ~10 GPa. The ultimate strength is more than 600 MPa in tensile and 400 MPa in compressive at temperature of 100 K. The simulation results of the structural and mechanical properties of 1 are in good agreement with our previous experimental work. Notably, before the ultimate tensile stress, the stress-to-strain curves of 1 show linear behavior, but 1 (dry) show nonlinear behavior. This study might explain the remarkable elasticity of 1 and is relevant to the design of high-performance organic materials with excellent self-healing or efficient stress dissipating properties.


Cardiac structure discontinuities revealed by ex-vivo microstructural characterization. A focus on the basal inferoseptal left ventricle region.
While the microstructure of the left ventricle (LV) has been largely described, only a few studies investigated the right ventricular insertion point (RVIP). It was accepted that the aggregate cardiomyocytes organization was much more complex due to the intersection of the ventricular cavities but a precise structural characterization in the human heart was lacking even if clinical phenotypes related to right ventricular wall stress or arrhythmia were observed in this region. MRI-derived anatomical imaging (150 µm3) and diffusion tensor imaging (600 µm3) were performed in large mammalian whole hearts (human: N = 5, sheep: N = 5). Fractional anisotropy, aggregate cardiomyocytes orientations and tractography were compared within both species. Aggregate cardiomyocytes orientation on one ex-vivo sheep whole heart was then computed using structure tensor imaging (STI) from 21 µm isotropic acquisition acquired with micro computed tomography (MicroCT) imaging. Macroscopic and histological examination were performed. Lastly, experimental cardiomyocytes orientation distribution was then compared to the usual rule-based model using electrophysiological (EP) modeling. Electrical activity was modeled with the monodomain formulation. The RVIP at the level of the inferior ventricular septum presented a unique arrangement of aggregate cardiomyocytes. An abrupt, mid-myocardial change in cardiomyocytes orientation was observed, delimiting a triangle-shaped region, present in both sheep and human hearts. FA's histogram distribution (mean ± std: 0.29 ± 0.06) of the identified region as well as the main dimension (22.2 mm ± 5.6 mm) was found homogeneous across samples and species. Averaged volume is 0.34 cm3 ± 0.15 cm3. Both local activation time (LAT) and morphology of pseudo-ECGs were strongly impacted with delayed LAT and change in peak-to-peak amplitude in the simulated wedge model. The study was the first to describe the 3D cardiomyocytes architecture of the basal inferoseptal left ventricle region in human hearts and identify the presence of a well-organized aggregate cardiomyocytes arrangement and cardiac structural discontinuities. The results might offer a better appreciation of clinical phenotypes like RVIP-late gadolinium enhancement or uncommon idiopathic ventricular arrhythmias (VA) originating from this region.


Mechanisms of regulation of glycogen synthesis and degradation.
The control of glycogen metabolism is discussed in terms of four principles which have emerged from molecular analysis of these systems; namely, separate enzymes for synthesis and degradation, covalent controls, noncovalent controls, and the cascade concept. The extension of some of these principles into other areas, including the control of inotropic action, is considered. Finally, how these controls function in the living cell physiologically is considered in two specific examples.


A comparison of the bronchodilator and vasopressor effects of exercise levels of adrenaline in man.
1. Plasma adrenaline was measured at rest and on exercise in six normal, non-atopic subjects. The exercise test produced a minimum tachycardia of 158 beats/min and a mean plasma adrenaline level of 1.89 nmol/l. 2. On a separate occasion, two doses of L-adrenaline (0.025 micrograms min-1 kg-1 and 0.05 micrograms min-1 kg-1) were infused in the same subjects at rest to produce two mean plasma levels similar to those found on exercise. 3. Significant bronchodilation and elevation of plasma glucose occurred with both infusion doses when compared with placebo. 4. Neither infusion caused a significant change in heart rate and only the higher dose caused a small but significant rise in systolic and fall in diastolic blood pressure. 5. Our results suggest that adrenaline as a hormone, at the levels found on exercise, is capable of causing bronchodilation and glycogenolysis in normal subjects. Its contribution to the cardiovascular response to exercise appears to be slight and suggests that its role in cardiovascular physiology may also be marginal.


Defining body-weight reduction as a humane endpoint: a critical appraisal.
In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct animal experiments in multiple research facilities, and assessed whether 20% body-weight reduction is a valid humane endpoint criterion in rodents. In most experiments (restraint stress, distinct models for epilepsy, pancreatic resection, liver resection, caloric restrictive feeding and a mouse model for Dravet syndrome) the animals lost less than 20% of their original body weight. In a glioma model, a fast deterioration in body weight of less than 20% was observed as a reliable predictor for clinical deterioration. In contrast, after induction of chronic diabetes or acute colitis some animals lost more than 20% of their body weight without exhibiting major signs of distress. In these two animal models an exclusive application of the 20% weight loss criterion for euthanasia might therefore result in an unnecessary loss of animals. However, we also confirmed that this criterion can be a valid parameter for defining the humane endpoint in other animal models, especially when it is combined with additional criteria for evaluating distress. In conclusion, our findings strongly suggest that experiment and model specific considerations are necessary for the rational integration of the parameter 'weight loss' in severity assessment schemes and humane endpoint criteria. A flexible implementation tailored to the experiment or intervention by scientists and authorities is therefore highly recommended.


Molecular studies on bromovirus capsid protein. VII. Selective packaging on BMV RNA4 by specific N-terminal arginine residuals.
An arginine-rich RNA-binding motif (ARM) found at the N-proximal region of Brome mosaic virus (BMV) coat protein (CP) adopts alpha-helical conformation and shares homology with CPs of plant and insect RNA viruses, HIV-Rev and Tat proteins, bacterial antiterminators, and ribosomal splicing factors. The ARM of BMV CP, consisting of amino acids 9 through 21 with six arginine residues, is essential for RNA binding and subsequent packaging. In this study analysis of the alpha-helical contents of wild-type and mutant peptides by circular dichroism spectra identified protein determinants required for such conformation. Electrophoretic mobility-shift assays between viral RNA and BMV CP peptides with either proline or alanine substitutions revealed that the interaction is nonspecific. Expression in vivo of mature full-length BMV CP subunits, having the same substitutions for each arginine within the ARM, derived from biologically active clones was found to be competent to assemble into infectious virions and cause visible symptom phenotypes in whole plants. However, analysis of virion progeny RNA profiles of CP variants and subsequent in vitro reassembly assays between mutant CP and four BMV RNAs unveiled the ability of arginine residues at positions 10, 13, or 14 of the ARM to confer selective packaging of BMV RNA4. Thus, BMV CP contains determinants that specifically interact with RNA4 to ensure selective packaging.


Very-Low-Dose Decitabine Is Effective in Treating Intermediate- or High-Risk Myelodysplastic Syndrome.
Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months, 10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and 3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%. Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed among all courses. The median cost of each course was USD 5,300, 3,000, 2,900, and 2,000, respectively. Multivariate analysis identified bone marrow blast cells ≥10% and a Charlson comorbidity index ≥1 as 2 independent factors for efficacy. In conclusion, very-low-dose decitabine showed relatively good efficacy, good tolerance, and low medical cost in the treatment of intermediate- or high-risk MDS. Elderly patients with more than 1 complication or patients with a higher proportion of blast cells may be the most suitable candidates for this regimen.


Linear plasmids of Borrelia burgdorferi have a telomeric structure and sequence similar to those of a eukaryotic virus.
Spirochetes of the genus Borrelia have double-stranded linear plasmids with covalently closed ends. The physical nature of the terminal connections was determined for the 16-kb linear plasmid of the B31 strain of the Lyme disease agent Borrelia burgdorferi. Native telomeric fragments representing the left and right ends of this plasmid were isolated and subjected to Maxam-Gilbert sequence analysis. At the plasmid ends the two DNA strands formed an uninterrupted, perfectly palindromic, AT-rich sequence. This Borrelia linear plasmid consisted of a continuous polynucleotide chain that is fully base paired except for short single-stranded hairpin loops at each end. The left and right telomeres of the 16-kb plasmid were identical for 16 of the first 19 nucleotide positions and constituted an inverted terminal repeat with respect to each other. The left telomere of the 49-kb plasmid of strain B31 was identical to the corresponding telomere of the 16-kb plasmid. Different-sized plasmids of other strains of B. burgdorferi also contained sequences homologous to the left end of the 16-kb plasmid. When the borrelia telomeres were compared with telomeric sequences of other linear double-stranded DNA replicons, sequence similarities were noted with poxviruses and particularly with the iridovirus agent of African swine fever. The latter virus and a Borrelia sp. share the same tick vector. These findings suggest that the novel linear plasmids of Borrelia originated through a horizontal genetic transfer across kingdoms.


Oxidation of citronellal to citronellic acid by molecular oxygen using supported gold catalysts.
The oxidation of citronellal to citronellic acid was studied using molecular oxygen as oxidant and gold-containing supported catalysts under aqueous conditions. The reactions were carried out at 60-90 degrees C, with 200 Nml min(-1) O2 and at pH values from 9 to 12. The alumina- or titania-supported catalysts were synthesized according to the deposition-precipitation procedure using urea or NaOH. Mechanistic studies have revealed that radical-initiated reactions lead to undesired by-products especially at pH <9, that is, the C=C bond is attacked and a diol is primarily formed probably via an epoxide intermediate. This side reaction can be suppressed to a large extent by increasing the pH to 12 and by raising the catalyst/oxygen ratio. Furthermore, detailed studies on the influence of reaction time, pH value, reactant concentration and amount of catalyst show that citronellic acid can be obtained in over 90% yield with total conversion of citronellal at pH 12 and a temperature of 80 degrees C.


Association of selenium status and blood glutathione concentrations in blacks and whites.
Selenium deficiency has been linked with increased cancer risk and, in some studies, selenium supplementation was protective against certain cancers. Previous studies have suggested that selenium chemoprevention may involve reduced oxidative stress through enhanced glutathione (GSH). Our objectives were to examine the relationships between selenium and GSH in the blood and the modifying effects of race and sex in free-living adults and individuals supplemented with selenium. Plasma selenium concentrations and free and bound GSH concentrations and γ-glutamyl cysteine ligase (GCL) activity in the blood were measured in 336 healthy adults (161 Blacks, 175 Whites). Plasma selenium and blood GSH were also measured in 36 healthy men from our previously conducted placebo-controlled trial of selenium-enriched yeast (247 μg/day for 9 mo). In free-living adults, selenium concentrations were associated with increased blood GSH concentration and GCL activity (P < 0.05). Further, selenium was significantly higher in Whites than in Blacks (P < 0.01). After 9 mo of supplementation, plasma selenium increased 114% in Whites and 50% in Blacks (P < 0.05), and blood GSH increased 35% in Whites (P < 0.05) but was unchanged in Blacks. These results indicate a direct association between selenium and GSH in the blood of both free-living and selenium-supplemented individuals, with race being an important modifying factor.


Surgical Attitudes And Preferences Regarding Choice Of Anaesthesia Amongst Orthopaedic Surgeons.
Regional anaesthesia is choice of anaesthesia for orthopaedic surgery due to lower side effects such as nausea, vomiting, postoperative pain and early mobilization. Despite of this, some orthopaedic patients refuse this modality. This study was conducted to interrogate the surgeons about their choice of anaesthesia in order to gain some insights into the concerns of surgeons and to change their minds and choose a safer mode of anaesthesia. The aim of the study was to assess the surgeons' fears and their perception about regional anaesthesia. After institutional approval, thirty surgeons from three different tertiary care hospitals were interviewed. They were asked questions as per the questionnaire to choose choice of anaesthesia for their patients. After regional anaesthesia, 27.6% of respondents were concerned about paralysis and neurological disorders, 34.5% about seeing and hearing whatever is happening in theatre, 17.2% about perioperative pain, 24.1% about backache and 24.1% about delayed discharge. The most important reason to change their mind was the reassurance that the complications are not as frequently as they thought their patient would receive after a block. Due to the lack of information on regional anaesthesia and the risks of general anaesthesia, orthopaedic surgeons' fears and conceptions about regional anaesthesia are distorted. Anaesthesiologists should be aware of the concerns of the surgeons as well as the patients and should be willing to discuss the concerns with them and suggest the safest way to receive anaesthesia with evidence-based data.


[Alveolar bone thickness in A point area : how to avoid periodontal failures in front of upper incisors].
Studies on orthodontic-periodontics relationships are numerous but few have benefited from the contribution of new 3D imaging techniques that emphasize iatrogenic effects that orthodontics may have on the periodontium. Periodontal risk in terms of fenestration, bone dehiscences next maxillary incisors are real during or after orthodontic treatment. The accurate assessment of the initial situation in terms of bone quantity in this dental arch anterior segment is thus very important. Our study aimed to evaluate the reliability of conventional lateral cephalograms to quantify alveolar bone thickness in relation to the maxillary incisors by comparing it with data from CT scans. The second objective was to identify an at risk patient profile by assessing possible correlations between this thickness and dysmorphia components. The results revealed a half of assessment error in the estimation of bone thickness and increased risk in case of hyperdivergence typology, Class III skeletal relationships and dento-alveolar protrusion. Finally, in view of these data, we discussed the clinical procedures to avoid such periodontal failures in this anterior segment of the dental arch.


[Pathogenesis and management of hemorrhage and thrombosis in plasma cell dyscrasias].
Unexpectedly high rates of venous thromboembolic events (VTE) induced by highly effective immune modulating drugs thalidomide and lenalidomide for treatment of multiple myeloma have focused attention on the incidence and underlying pathophysiology of VTE in patients with plasma cell dyscrasias, and on thromboprophylaxis approaches. While bleeding complications are relatively uncommon in the patients with lymphoproliferative disorders, acquired von Willebrand syndrome, typically occurring in the patients with monoclonal gammopathy of unknown significance, and acquired coagulopathies associated with primary amyloidosis can present with haemorrhagic complications and both are challenges to the management. This review highlights these important haemostasis-related complications of plasma cell dyscrasias and provides an overview of other uncommon bleeding and thrombotic events that can affect diagnosis and therapeutic management of clonal plasma cell disorders. Due to the infrequency of most these haemostasis complications, available information is typically based on retrospective cases or series analysis.


Prediction of BRCA Mutations Using the BRCAPRO Model in Clinic-Based African American, Hispanic, and Other Minority Families in the United States.
BRCAPRO, a BRCA mutation carrier prediction model, was developed on the basis of studies in individuals of Ashkenazi Jewish and European ancestry. We evaluated the performance of the BRCAPRO model among clinic-based minority families. We also assessed the clinical utility of mutation status of probands (the first individual tested in a family) in the recommendation of BRCA mutation testing for other at-risk family members. A total of 292 minority families with at least one member who was tested for BRCA mutations were identified through the Breast Cancer Family Registry and the University of Chicago. Using the BRCAPRO model, the predicted likelihood of carrying BRCA mutations was generated. Area under the receiver operating characteristic curves (AUCs) were calculated. There were 104 African American, 130 Hispanic, 37 Asian-American, and 21 other minority families. The AUC was 0.748 (95% CI, 0.672 to 0.823) for all minorities combined. There was a statistically nonsignificant trend for BRCAPRO to perform better in Hispanic families than in other minority families. After taking into account the mutation status of probands, BRCAPRO performance in additional tested family members was improved: the AUC increased from 0.760 to 0.902. The findings support the use of BRCAPRO in pretest BRCA mutation prediction among minority families in clinical settings, but there is room for improvement in ethnic groups other than Hispanics. Knowledge of the mutation status of the proband provides additional predictive value, which may guide genetic counselors in recommending BRCA testing of additional relatives when a proband has tested negative.


A phase-field model for the evaporation of thin film mixtures.
The performance of solution-processed solar cells strongly depends on the geometrical structure and roughness of the photovoltaic layers formed during film drying. During the drying process, the interplay of crystallization and liquid-liquid demixing leads to structure formation on the nano- and microscale and to the final rough film. In order to better understand how the film structure can be improved by process engineering, we aim at theoretically investigating these systems by means of phase-field simulations. We introduce an evaporation model based on the Cahn-Hilliard equation for the evolution of the fluid concentrations coupled to the Allen-Cahn equation for the liquid-vapour phase transformation. We demonstrate its ability to match the experimentally measured drying kinetics and study the impact of the parameters of our model. Furthermore, the evaporation of solvent blends and solvent-vapour annealing are investigated. The dry film roughness emerges naturally from our set of equations, as illustrated through preliminary simulations of spinodal decomposition and film drying on structured substrates.


Therapeutic Strategies in the Management of Nonresorbable Membrane and Titanium Mesh Exposures Following Alveolar Bone Augmentation: A Systematic Scoping Review.
The exposure of nonresorbable membranes following alveolar bone augmentation is one of the most frequently occurring complications. This review aimed to investigate the treatments that can be adopted to manage the exposure of polytetrafluoroethylene-based membranes (PTFE-ms) and titanium meshes (TMs) and their outcomes. Two independent reviewers electronically and manually searched the EMBASE, PubMed/MEDLINE, Scopus, and Cochrane bibliographic databases to retrieve pertinent articles available between January 2000 and March 2021. Only human studies describing the type of treatment and the soft tissue outcome following exposure of PTFE-ms or TMs were included. Overall, 11 articles in the PTFE-ms group and 24 in the TM group were included for data analysis. Results indicated that, in both groups, two distinct therapeutic strategies are mostly applied in case of exposure, namely, pharmacologic and mechanical treatments. Other options have been identified seldomly. Statistically significant evidence of an association between the type of barrier membrane and the exposure rate (28.7% vs 38.5% for TMs and PTFE-ms, respectively; P = .019) and between the type of exposed device and the treatment outcome in terms of removal rate following therapy (11.9% and 44.4% for TMs and PTFE-ms, respectively; P < .001) was noted. In both groups, chlorhexidine applications and meticulous plaque control may lead to improved healing conditions after exposure. Surgical removal of the exposed portion can be considered to promote secondary intention healing. The beneficial effects of systemic antibiotics could not be demonstrated in the management of the exposure but should be evaluated in case of graft infection.


A computational framework for gene regulatory network inference that combines multiple methods and datasets.
Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective. This paper presents a new method for network inference, which uses multi-objective optimisation (MOO) to integrate multiple inference methods and experiments. We illustrate the potential of the methodology by combining ODE and correlation-based network inference procedures as well as time course and gene inactivation experiments. Here we show that our methodology is effective for a wide spectrum of data sets and method integration strategies. The approach we present in this paper is flexible and can be used in any scenario that benefits from integration of multiple sources of information and modelling procedures in the inference process. Moreover, the application of this method to two case studies representative of bacteria and vertebrate systems has shown potential in identifying key regulators of important biological processes.


A push-pull CORF model of a simple cell with antiphase inhibition improves SNR and contour detection.
We propose a computational model of a simple cell with push-pull inhibition, a property that is observed in many real simple cells. It is based on an existing model called Combination of Receptive Fields or CORF for brevity. A CORF model uses as afferent inputs the responses of model LGN cells with appropriately aligned center-surround receptive fields, and combines their output with a weighted geometric mean. The output of the proposed model simple cell with push-pull inhibition, which we call push-pull CORF, is computed as the response of a CORF model cell that is selective for a stimulus with preferred orientation and preferred contrast minus a fraction of the response of a CORF model cell that responds to the same stimulus but of opposite contrast. We demonstrate that the proposed push-pull CORF model improves signal-to-noise ratio (SNR) and achieves further properties that are observed in real simple cells, namely separability of spatial frequency and orientation as well as contrast-dependent changes in spatial frequency tuning. We also demonstrate the effectiveness of the proposed push-pull CORF model in contour detection, which is believed to be the primary biological role of simple cells. We use the RuG (40 images) and Berkeley (500 images) benchmark data sets of images with natural scenes and show that the proposed model outperforms, with very high statistical significance, the basic CORF model without inhibition, Gabor-based models with isotropic surround inhibition, and the Canny edge detector. The push-pull CORF model that we propose is a contribution to a better understanding of how visual information is processed in the brain as it provides the ability to reproduce a wider range of properties exhibited by real simple cells. As a result of push-pull inhibition a CORF model exhibits an improved SNR, which is the reason for a more effective contour detection.


Adopting the Concept of 'Ba' and the 'SECI' Model in Developing Person-Centered Practices in Child and Adolescent Mental Health Services.
The concept of knowledge is divided into explicit and tacit knowledge; explicit knowledge refers to the knowledge that can be articulated, written and stored, while tacit knowledge refers to personal experiences, values, beliefs and emotions of an individual. By Nonaka's theory, explicit and tacit knowledge do not lie separately but interact together by interactions and relationships between human beings. Thus, the SECI model is based on the assumption that knowledge is created through the social interaction of tacit and explicit knowledge; known as knowledge conversion. The SECI model is based upon four modes of knowledge conversion; socialization, externalization, combination and internalization. 'Ba' is considered to be a shared platform for knowledge creation. 'Ba' is a shared space, be it physical, mental or a combination of both that serves as a foundation of knowledge creation. Ba involves sharing of tacit knowledge i.e. emotions, feelings, experiences and mental images. It also involves the formation of a collective relationship which is open to the sharing of practices, values, processes and culture. This concept focuses mainly on the individual as a person who holds the knowledge rather than just on the knowledge itself. It aims to create a common space to bring people together where they can dialogue to share and create knowledge. As in the relationships formed in person-centered practices, relationships formed in Ba are based on not just the sharing of objective knowledge but also on sharing values, beliefs, and emotions. It also reflects the formation of a person-centered environment as a basis for person-centered research where healthful relationships with the participants are formed. Furthermore, Ba will aid in creating a sense of connectiveness and dialogue, thus focusing on the idea that the development of new practices is done with others rather than to others. In this article we will discuss how these Eastern concepts can be adapted and used to develop person-centered practices within child and adolescent mental health services, specifically related to rehabilitation and recovery. The concepts of personhood will be discussed, followed by a reflection on current practices adopted when working with children and adolescents.


Case-control study on renal cell cancer and occupational exposure to trichloroethylene. Part II: Epidemiological aspects.
To test the effect of the exposure to trichloroethylene (TCE) on renal cell cancer (RCC) risk, a case-control study was performed in the Arve Valley (France), a geographic area with a high frequency and a high degree of such exposure. Cases and controls were selected from various sources: local general practitioners and urologists practicing in the area and physicians (urologists and oncologists) from other hospitals of the region who might treat patients from this area. Blinded telephone interviews with cases and controls were administered by a single trained interviewer using occupational and medical questionnaires. The analysis concerned 86 cases and 316 controls matched for age and gender. Three approaches were developed to assess the link between TCE exposure and RCC: exposure to TCE for at least one job period (minimum 1 year), cumulative dose (number of p.p.m. of TCE per job period multiplied by the number of years in the job period) and the effect of exposure to peaks. Multivariate analysis was performed taking into account potential confounding factors. Allowing for tobacco smoking and Body Mass Index, a significantly 2-fold increased risk was identified for high cumulative doses: odds ratio (OR)=2.16 (1.02-4.60). A dose-response relationship was identified, as was a peak effect; the adjusted OR for highest class of exposure-plus-peak being 2.73 (1.06-7.07). After adjusting for exposure to cutting fluids the ORs, although still high, were not significant because of lack of power. This study suggests an association between exposures to high levels of TCE and increased risk of RCC. Further epidemiological studies are necessary to analyze the effect of lower levels of exposure.


Initial Experience Using Intraoperative Magnetic Resonance Imaging During a Trans-Sulcal Tubular Retractor Approach for the Resection of Deep-Seated Brain Tumors: A Case Series.
Treatment of deep-seated subcortical intrinsic brain tumors remains challenging and may be improved with trans-sulcal tubular brain retraction techniques coupled with intraoperative magnetic resonance imaging (iMRI). To conduct a preliminary assessment of feasibility and efficacy of iMRI in tubular retractor-guided resections of intrinsic brain tumors. Assessment of this technique and impact upon outcomes were assessed in a preliminary series of brain tumor patients from 2 centers. Ten patients underwent resection with a tubular retractor system and iMRI. Mean age was 53.2 ± 9.0 yr (range: 37-61 yr, 80% male). Lesions included 6 gliomas (3 glioblastomas, 1 recurrent anaplastic astrocytoma, and 2 low-grade gliomas) and 4 brain metastases (1 renal cell, 1 breast, 1 lung, and 1 melanoma). Mean maximal tumor diameter was 2.9 ± 0.95 cm (range 1.2-4.3 cm). The iMRI demonstrated subtotal resection (STR) in 6 of 10 cases (60%); additional resection was performed in 5 of 6 cases (83%), reducing STR rate to 2 of 10 cases (20%), with both having tumor encroaching on eloquent structures. Seven patients (70%) were stable or improved neurologically immediately postoperatively. Three patients (30%) had new postoperative neurological deficits, 2 of which were transient. Average hospital length of stay was 3.4 ± 2.0 d (range: 1-7 d). Combining iMRI with tubular brain retraction techniques is feasible and may improve the extent of resection of deep-seated intrinsic brain tumors that are incompletely visualized with the smaller surgical exposure of tubular retractors.