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The University of Wollongong Graduate School of Medicine (UWGSM) opened in 2007. This is one of a new wave of medical schools to enable the more than doubling of the number of medical students graduating in the period from 2006-2014. However, this rapid expansion has exposed a relative paucity of experienced medical academics and the regional medical schools especially have found difficulty immediately attracting a full complement of academic staff. These schools have therefore sought to recruit locally and train staff who vary widely in previous experience in teaching.

Regulation of serotonin (5-HT)1A receptor expression in brain is implicated in mood disorders such as depression and anxiety. Transcriptional activity of the human 5-HT1A receptor gene was strongly repressed by a negative regulatory region containing a consensus repressor element-1 (RE-1) and two copies of the dual repressor element (DRE) identified in the rat 5-HT1A receptor gene. REST/NRSF, a silencer of neuronal genes, bound the 5-HT1A RE-1 and repressed the 5-HT1A promoter. Inactivation of RE-1 completely abolished REST-mediated repression, but resulted in only partial (15-50%) de-repression of basal 5-HT1A promoter activity. The human 5-HT1A DRE sequences bound specifically to the novel repressor Freud-1 (5'repressor element under dual repression binding protein-1) and conferred repressor activity at 5-HT1A or SV40 promoters. In 5-HT1A-negative cells [L6, human embryonic kidney (HEK) 293], the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) abolished repression mediated by both RE-1/REST and DRE/Freud-1, and induced almost complete de-repression of the 5-HT1A gene. By contrast, in 5-HT1A-expressing neuronal cells (RN46A, SN-48) TSA blocked RE-1/REST repression, but did not affect DRE/Freud-1-mediated repression. Thus in contrast to REST, Freud-1 mediates HDAC-independent repression of the 5-HT1A receptor promoter in neuronal 5-HT1A-positive cells, suggesting that HDAC recruitment might influence neuron-specific gene expression by further silencing expression in non-neuronal tissue.

This study reports, for the first time, the development of a chitosan-g-poly(N-isopropylacrylamide) (Chi-PN) biodegradable in situ gelling delivery system for ocular pilocarpine administration through intracameral injection. The number of thermo-responsive polymer segments grafted onto the chitosan via carbodiimide-mediated formation of amide linkages was greatly affected by varying the feeding amount of carboxyl-terminated poly(N-isopropylacrylamide) in the synthesis, thereby determining the phase transition temperature and enzymatic degradability of Chi-PN materials. The increase in grafting ratio facilitated temperature triggered gelation and drug encapsulation at physiological conditions. Additionally, the slow biodegradation process of delivery carriers was responsible for the delayed pilocarpine release, which allowed that the drug concentration could reach minimum therapeutic level for treating glaucoma during 42days of the study. All of the synthesized Chi-PN carriers demonstrated good ocular biocompatibility with lens epithelial cell cultures. In a rabbit model of experimental glaucoma, the intraocular pressure-lowering and miotic as well as corneal endothelial preservation responses to pilocarpine strongly depended on the drug release profiles. It is concluded that injectable biodegradable chitosan-based thermogels can be potentially utilized as intracameral biomaterials for extended release of antiglaucoma medications and improved performance of delivery carriers.

The crystal structure of penta-O-acetyl-beta-D-galactopyranose was determined with Mo K(alpha) radiation at 150 K to R = 0.029. The space group is P2(1)2(1)2(1), and the unit cell dimensions are, a = 8.348, b = 9.021 and c = 25.418 A. The ring has the usual 4C(1) shape and O-6 is in the tg position as frequently observed for sugars having the axial galacto configuration at C-4. Conformations of the acetate groups were compared with those from the literature. Nearly eclipsed, 'Z' conformations are found for the ester moieties, and the torsion angles for the sequence involving the ring hydrogen, carbon, alkoxy oxygen and carbonyl carbon for both 1 and related compounds are eclipsed-to-gauche. Orientations and conformations of the acetate substituents were modeled with both MM3 molecular mechanics and various levels of quantum mechanics theory. Higher levels of theory and more complete models provided better prediction of the experimental observations.

BACKGROUND: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism.METHOD: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression.RESULTS: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles.CONCLUSION: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons.

Hormones have been suggested to play a prominent role in the control of callus growth. In this paper, with the method of indirect enzyme-linked immunosorbent assays (ELISA), we investigated the induction effect of soundwave on the dynamic change of endogenous indole-3-acetic acid (IAA) and abscisic acid (ABA) in vitro during the differentiation process of Chrysanthemum synchronized mature Callus. These experiments showed that groups treated by optimal soundwave (1.4 kHz, 0.095 kdb) had significantly higher IAA levels and lower ABA than that of the control, which had been implicated activation of endogenous IAA and inhibition of ABA. Through the biochemical analysis, it revealed that the increased level of IAA as well as decreased levels of ABA correlated with soundwave stimulus. High rate of IAA/ABA was favorable to development of the callus and differentiation of mature callus. We conclude that soundwave contributes to endogenous hormone as well as the control of callus growth.

The blunt technique of suction-assisted lipectomy partially evolved while proving to be an efficient, albeit blind, method for the removal of lipomas. Larger or poorly encapsulated tumors were acknowledged to be at a greater risk for recurrence probably because of an unrecognized residua. Just as liposuction has enhanced body-contour surgery because of the potential for smaller and fewer scars hidden in strategically camouflaged locations, the identical advantages are possible for liposuction extraction of lipomas, with a greater assurance for their entire removal via direct visualization using a surgical endoscope.

Brain activities are often investigated through Electroencephalographic (EEG) data analysis using time-domain Independent Component Analysis (ICA). Nevertheless, the instantaneous mixing model of ICA cannot properly describe spatio-temporal dynamics, such as those related to traveling waves of neural activity. In this work, we exploit the application of the Complex ICA (cICA) to describe the underlying brain activities in time and frequency domain. In particular, we show how to effectively extract the most significant time-frequency structure of cortical activity in order to solve a compelling EEG-based pattern classification problem. The crucial step of independent component selection among frequencies is performed using an objective computational method based on template matching techniques with physiologically-plausible activations. Experimental results are obtained using on-line EEG data from the BCI Competition 2003 and are expressed in terms of confusion matrix after leave-one-out validation procedure. A comparative analysis between ICA and cICA models reveals that cICA estimation gives powerful information and allows to achieve a higher classification accuracy with respect to instantaneous ICA.

A cooperative, prospective randomized study to compare radiotherapy (50 Gy) or 2 courses of combination chemotherapy consisting of cisplatin (50 mg/m2) and vindesine (3 mg/m2) following curative resection was performed in 258 patients at 9 institutions between August 1985 and August 1987. In the two groups, no difference was present in the background factors such as sex, age, and the location and length of the tumor. Also, there was no difference of distribution of pT, pN, pM or p stage by the revised TNM classification of 1987. There was no significant difference in survival up to 5 years in the 2 groups. Concerning the side effects, the decrease in white blood cell and platelet counts was similar in the two groups, but elevation of blood urea nitrogen and creatinine concentrations was more marked in the group receiving chemotherapy than in the group with radiotherapy.

The objective of this study was to measure endometrial thickness by transvaginal ultrasonography during two regimens of hormonal replacement therapy (HRT) in postmenopausal women and to compare these data with endometrial histology. Transvaginal ultrasonographic evaluation of endometrial thickness and endometrial biopsy were performed in 80 postmenopausal women before and after 6 months of HRT (between the 24th and the 28th day of the cycle). The group was randomized so that 40 women (Group A) were treated with a continuous sequential regimen consisting of 5 micrograms/day of estradiol continuously and 5 mg/day of medrogestone from the 17th to the 28th day of the cycle; and 40 women (Group B) were given continuous administration of 50 micrograms/day estradiol and 5 mg/day medrogestone. Prior to therapy, there was no significant difference in mean endometrial thickness between the groups. After 6 months of therapy, endometrial thickness was significantly increased in comparison with basal values in both groups. The mean value was significantly higher (p < 0.001) in Group A (8.5 +/- 3.7 mm) than in Group B (3.6 +/- 1.3 mm). In Group A, endometrial thickness was < or = 4 mm in 16.7% of patients and < or = 8 mm in 69.5% of patients. In Group B, 91% of patients had an endometrium of < or = 4 mm. In both groups, the thickness of the atrophic endometrium was less than that of the other histological types of endometrium (4.1 +/- 0.3 mm for Group A and 3.5 +/- 1.2 mm for Group B). In Group A, the difference in mean endometrial thickness between the proliferative and secretory endometrium was not statistically significant. In both groups, the transvaginal ultrasonographic measurement of endometrial thickness of < or = 4 mm had a high sensitivity for detecting atrophic endometrium (83.3% for Group A and 93.7% for Group B).

Standardization of laboratory results allows for the use of common reference intervals and can be achieved via calibration of field methods with secondary reference materials. These harmonization materials should be commutable, i.e., they produce identical numerical results independent of assay principle or platform. This study assessed the commutability of a cryolyoprotectant-containing harmonization material, obtained from the Dutch Foundation for Quality Assessment in Clinical Laboratories, that is intended to harmonize measurements of enzyme activities within the Dutch project "Calibration 2000". The catalytic concentrations of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase and creatine kinase were analyzed in pooled patient sera and in the reference material in 14 laboratories. On liquid chemistry analyzers the harmonization material behaves like patient material. The enzyme activities measured in it fall on the regression lines calculated from activities measured in serum samples. For dry chemistry analyzers the activities of all enzymes measured in the harmonizator differ from the serum-based regression line. We show that this is due to the sucrose-containing cryolyoprotectant in the harmonization material. For each enzyme, correction factors were calculated that compensated for the bias and proved to be constant between reagent lots. Depending on the enzyme activity measured, application of these factors leads to 2- to 10-fold reduction of between-laboratory percentage coefficient of variation. Thus, additives to (potential) reference materials may alter their matrix in a way that interferes with analysis on certain test systems. The bias caused may be quantifiable and correctable. Establishment of correction factors leads to analytical uncertainties and costs. Therefore, matrix-based materials without additives should be selected as reference materials.

Despite a growing awareness of the need to promote equal opportunities for people with disabilities, little is known about the self-perceived employment opportunities for people with intellectual disability. This study adopted a qualitative approach to examine the issue of 'equalization of employment opportunities' with 18 young working adults with mild intellectual disability who participated in in-depth interviews. Content analysis and a constant comparative method were adopted for data analysis. Our findings revealed that having employment was regarded as being very important by all participants, and 17 participants had had both positive and negative employment experiences, which were mainly related to the workplace interpersonal relationships and the attitude of employers and co-workers. Eight participants might have experienced discrimination at work when employers and co-workers had misconceptions about people with intellectual disability. This study suggested that strategies such as equal opportunities education, natural support from employers and co-workers and disability education for the general public should be adopted to enable people with intellectual disability to have full participation in employment and social integration.

An eponymous lecture at the Australian and New Zealand Association of Neurologists Annual Scientific Meeting commemorates E. Graeme Robertson (1903-75), and some neurologists will know that particular Australian practices in clinical neurology, so far as they exist, have origins in his career. This is a historical article on the literary record of a man who had his own sense of history--an affinity with the past as well as an awareness of future generations of readers. He wrote authoritative texts on pneumoencephalography before new technology made it obsolete, and he produced a series of books on decorative architectural cast iron in Australian cities. A talent for visual interpretation seems to have drawn him to both of these topics; a common theme is contrast between light and dark, which is expatiated in images and in clear, well-written prose in his publications. We review his medical writings, including some largely forgotten principles of cerebrospinal fluid physics that he discovered when researching pneumoencephalography. We also explore his obsession with cast iron--its architectural historical significance, his techniques for photographing it, and some of the ways that it related to his life's work as a clinical neurologist.

Inflammation of the skin is the pathological base of contact dermatitis (CD), and cytokines are very important in its pathogenesis. Recently it has been shown that interferon (IFN)-ã, and the IFN-ã dependent chemokines, monokine induced by IFN-ã (MIG), IFN-ã-induced protein 10 (IP-10), and IFN-inducible T cell alpha chemoattractant (I-TAC), play an important role in CD. Allergic CD (ACD) is a T-cell-mediated disease in which expression of a distinct repertoire of chemokines results in the recruitment of effector T cells into the skin. An increased expression of MIG, IP-10 and I-TAC in the skin has been observed by many studies in ACD, but not in irritant CD. The IFN-ã dependent chemokines are produced by keratinocytes, mainly during the clinically inflammatory phase of ACD. Also chemokine (C-X-C motif) receptor (CXCR) 3, the common receptor of the three IFN-ã dependent chemokines, is upregulated in chemical-induced allergic skin responses when compared with irritant skin responses. However, other studies have shown a low level increase of IP-10 in irritant sodium dodecyl sulphate dermatitis. The above mentioned results show that although skin inflammation contact sensitizer-induced is similar to irritant-induced, the regulation of allergic inflammation-related gene MIG and IP-10, could help to discriminate skin sensitization from chemically irritation.

The role of heart-type fatty acid-binding protein (FABP3) in human physiology as an intracellular carrier of fatty acids (FAs) has been well-documented. In this study, we aimed to develop an analytical method to study real-time interaction kinetics between FABP3 immobilized on the sensor surface and unsaturated C18 FAs using surface plasmon resonance (SPR). To establish the conditions for SPR experiments, we used an FABP3-selective inhibitor 4-(2-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl)-phenoxy)-butyric acid. The affinity index thus obtained was comparable to that reported previously, further supporting the usefulness of the SPR-based approach for evaluating interactions between FABPs and hydrophobic ligands. A pseudo-first-order affinity of FABP3 to K(+) petroselinate (C18:1 Ä6 cis), K(+) elaidate (C18:1 Ä9 trans), and K(+) oleate (C18:1 Ä9 cis) was characterized by the dissociation constant (K(d)) near micromolar ranges, whereas K(+) linoleate (C18:2 Ä9,12 cis/cis) and K(+) á-linolenate (C18:3 Ä9,12,15 cis/cis/cis) showed a higher affinity to FABP3 with Kd around 1 ? 10(-6)M. Interactions between FAPB3 and C18 FAs incorporated in large unilamellar vesicles consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and FAs (5:1 molar ratio) were also analysed. Control DMPC liposomes without FA showed only marginal binding to FABP3 immobilized on a sensor chip while liposome-incorporated FA revealed significant responses in sensorgrams, demonstrating that the affinity of FAs to FABP3 could be evaluated by using the liposome-incorporated analytes. Significant affinity to FABP3 was observed for monounsaturated fatty acids (K(d) in the range of 1 ? 10(-7)M). These experiments demonstrated that highly hydrophobic compounds in a liposome-incorporated form could be subjected to SPR experiments for kinetic analysis.

Sulfonamides represent an important class of biologically active compounds. A sulfonamide possessing carbonic anhydrase (CA) inhibitory properties obtained from a pyrazole based sulfonamide, ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate (1), and its metal complexes with the Ni(II) for (2), Cu(II) for (3) and Zn(II) for (4) have been synthesized. The structures of metal complexes (2-4) were established on the basis of their elemental analysis, 1H NMR, IR, UV-Vis and MS spectral data. The inhibition of two human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes I and II, with 1 and synthesized complexes (2-4) and acetazolamide (AAZ) as a control compound was investigated in vitro by using the hydratase and esterase assays. The complexes 2, 3 and 4 showed inhibition constant in the range 0.1460-0.3930 µM for hCA-I and 0.0740-0.0980 µM for hCA-II, and they had effective more inhibitory activity on hCA-I and hCA-II than corresponding free ligand 1 and than AAZ.

Hugh Morriston Davies (1879-1965), long before anybody else, performed the first anatomic dissection lobectomy for a tumor of the lung in 1912. By replacing the hilar mass-ligation-suture technique, he was decades ahead of his time, and had his patient not died 8 days after the operation, he would have preceded Evarts Graham's first lung resection for cancer by 21 years! An all-around chest physician and surgeon in one, he had introduced chest radiography and positive-pressure intratracheal anesthesia the year before, thus making the diagnosis and operation of this lung cancer possible. He concluded that lung cancer was accessible to surgical removal on condition of an early diagnosis. By destiny a surgeon as well as a physician, Morriston Davies was probably the earliest advocate of interdisciplinary teamwork in thoracic medicine.

For nurses, the stress caused by entering a new place of employment may give rise to insecurity and a lack of confidence. Lack of confidence in one's nursing skills can affect performance and, ultimately, patient care and safety. In healthcare, growing fiscal constraints have resulted in lost resources, and support for new nursing staff is limited by both time and cost considerations. Clinical educators therefore must find innovative ways to provide education and support, including creative learning modalities that facilitate nurses' transition into a new role and work environment.

Several complex physiological processes, which include long-distance translocation in the phloem and unloading in sink tissues, govern the partitioning of sugars in economically important organs, such as peach fruit. In this study, we took advantage of a symplastic tracer, carboxyfluorescein (CF), providing evidence for an apoplastic sucrose transfer in the early (SI) and middle (SIII) phases of peach fruit development. Moreover, using a combination of in situ hybridization and laser microdissection-assisted expression analysis, three putative sucrose transporters encoding genes (PpSUT1, PpSUT2, PpSUT4) were transcriptionally analyzed to relate their expression with sucrose storage in this organ. Our study revealed that PpSUT2 and PpSUT4 are the genes predominantly expressed in fruit flesh, and the detailed analysis of their expression pattern in the different cell types enabled us to suggest a specialized role in sucrose distribution. Both PpSUTs transporters could be involved in the retrieval of sucrose lost from the symplastic continuum of the phloem and, when expressed in parenchyma cells, they could be active in the import of sucrose into sink tissues, via symport from the apoplast. An alternative hypothesis has been proposed and discussed for PpSUT4 because of its putative tonoplastic localization. Taken together, our results provide new insights into the molecular mechanisms underpinning sucrose unloading and accumulation in peach fruit.

OBJECTIVE: To explore the neuroimaging diagnosis and therapeutic efficacy of different surgical methods of gliomatosis cerebri.METHODS: 26 cases of gliomatosis cerebri at our department between September 2008 and September 2013 were retrospectively analyzed. Preoperative cranial computed tomography (CT), magnetic resonance imaging (MRI) and other multimodal imaging scans were performed. The procedures included stereotactic brain biopsy (n = 11) and large craniotomy lobotomy (n = 15). Whole brain radiotherapy and/or temozolomide therapy was performed postoperatively according to the malignancy of tumors. Follow-ups were conducted to analyze the survival differences between stereotactic brain biopsy and large craniotomy lobotomy groups.RESULTS: According to the different features of multimodal imaging, gliomatosis cerebri could be divided into two types: (1) type I(n = 19) showed a diffuse infiltrating lesion infringing multiple brain lobes or regions with central corpus callosum but without obvious enhancement; (2) type II (n = 7) appeared as sporadic or tuberous enhancement in addition to the features of type I. Pathological diagnosis: pilocytic astrocytoma (n = 2), diffuse astrocytoma (n = 13), oligodendroglial tumors (n = 3), oligoastrocytoma (n = 1), anaplastic astrocytoma (n = 5) and glioblastoma (n = 2). The degree of malignancy was a prognostic factor for postoperative survival in patients with gliomatosis cerebri. The mean survival time (MST) of large craniotomy lobotomy group (23 ± 7) was significantly longer than that of stereotactic brain biopsy group (13 ± 3) (P < 0.05).CONCLUSION: Gliomatosis cerebri is a primary brain glial tumor with diffuse infiltrative growth but retaining the general structure of central nervous system. Multimodal imaging studies plus pathological examination yield a definitive diagnosis. Comprehensive treatment of operation plus chemo- or radio-therapy can prolong postoperative MST.

The most common cause of apparent ineffectiveness or resistance to treatment with oral levothyroxine (LT(4)) is the result of noncompliance, known as pseudomalabsorption. However, an abnormality in the bioavailability of LT(4) should also be considered in patients requiring large doses of LT(4) to achieve euthyroidism. The incidence of lactose intolerance in Caucasian adult patients is 7%-20%, but the association with resistance to treatment with oral LT(4) is unusual. We report a 55-year-old woman in whom treatment LT(4) for hypothyroidism was found related to a previously undiagnosed oligo-symptomatic lactose intolerance, an unusual association. Although rare, intolerance to lactose should be considered in the differential diagnosis of gastrointestinal diseases that can cause malabsorption of LT(4). The possibility of correcting this disorder with simple dietary measures justifies its consideration.

PURPOSE: Rhegmatogenous retinal detachment (RD) has diagnostically been divided into macula-OFF or macula-ON. The aim of this study was to describe the demographics and primary outcome of patients with RD following surgery with respect to the macular status, and to determine risk factors for macular involvement.METHODS: This prospective, observational, mono-centric cohort study was conducted at the Jules-Gonin Eye Hospital, from February 2015 until March 2017. The study included 194 eligible patients with primary RD. All patients underwent surgical treatment after baseline clinical examination. The dataset was analyzed using descriptive and analytic statistics.RESULTS: A total of 52.6% (102/194) of patients presented with macula-OFF RD. Mean age was 63.9 ± 12.0 vs. 59.7 ± 11.2 years in the OFF and ON group, respectively. There were 129 men (66.5%) and 65 (33.5%) women, and there were significantly more right eyes affected [right vs. left eyes 123 (63.4%) vs. 71 (36.6%), p = 0.000]. Significantly more myopes (<-3D) presented with a macula-ON RD (p = 0.04). There were more phakic patients in the cohort (55.7%), and phakic eyes were more likely to present with macula-ON RD (p = 0.01). Multivariate modeling showed that pseudophakic lens status and eyes with axial length less than 25 mm (p = 0.06) are independent predictive factors for macula-OFF RD (p = 0.02), whereas sex and laterality were not risk factors for macular involvement.CONCLUSION: Pseudophakic lens status and axial length < 25 mm are independent predictive factors for macula-OFF RD. While pseudophakic lens status is a recognized risk factor for RD, shorter axial length has not been previously identified as a risk factor for the macula-OFF RD.

We used a fluorescence method to measure the rate constants for the elongation of pyrene-labeled actin filaments in a number of different solvents. The absolute values of the rate constants were established by electron microscopy. Using glycerol, sucrose, or ethylene glycol to vary the solution viscosity, the association rate constant (k+) was 10(7) M-1 s-1 viscosity-1 (in centipoise). Consequently, plots of 1/k+ versus viscosity are linear and extrapolate to near the origin as expected for a diffusion-limited reaction where the rate constant approaches infinity at zero viscosity. By electron microscopy, we found that this inhibitory effect of glycerol is almost entirely at the fast growing, barbed end. For the pointed end, plots of 1/k+ versus viscosity extrapolate to a maximum rate of about 10(6) M-1 s-1 at zero viscosity, so that elongation at the pointed is not limited by diffusion. In contrast to these small molecules, polyethylene glycol, dextran, and ovalbumin all cause a concentration (and therefore viscosity)-dependent increase in k+. At any given viscosity, their effects are similar to each other. For example, at 3 centipoise, k+ = 2.2 X 10(7) M-1 s-1. We presume that this is due to an excluded volume effect that causes an increase in the thermodynamic activity of the actin. If the proteins in the cytoplasmic matrix have a similar effect, the association reactions of actin in cells may be much faster than expected from experiments done in dilute buffers.

This study was conducted to investigate alterations in excretion of urea and total nitrogen after6-8 weeks of daily exercise and to establish if the capacity for amino acid oxidation in muscle is influenced by endurance training. Urea nitrogen excretion was increased in trained compared with untrained rats and nitrogen balance was less positive in trained than in untrained rats. Increased [14C]leucine oxidation with training was observed both in vivo and in vitro. The results of this study demonstrate that amino acid catabolism is increased during exercise training and that the muscle enzymes involved in leucine oxidation adapt to endurance training in a manner similar to the enzymes of carbohydrate and fat catabolism.

1. Reperfusion of hindlimbs that had previously been exposed to either 10 or 60 min global ischaemia resulted in transient washouts of uracil and uric acid in approximate proportion to the interval of ischaemia. However, changing the interval of sequential angiotensin II infusions from 10 to 60 min did not affect the magnitude of sustained uracil and uric acid release. 2. Perfused rat mesenteric artery arcade released uracil and uric acid and each was further increased approximately 2-fold by exposure to the vasoconstrictor, serotonin (6.7 microM). 3. Incubated de-endothelialized rat aorta also released purines and pyrimidines and this was increased further when subjected to increased work loads. 4. The increased rates of release of purines and pyrimidines from hindlimb, and the simpler vascular preparations of mesenteric arcade and aorta, were in proportion to the relative rates of increase in oxygen consumption under maximum vascular load. 5. It is concluded that the release of purine and pyrimidine nucleosides and their catabolites from perfused rat hindlimb occurring as a consequence of vasoconstriction is not the result of release from previously ischaemic tissue. In addition, release of purines and pyrimidines appears to be a general feature of vascular smooth muscle subjected to high workloads.

BACKGROUND: The robustness of F-test to non-normality has been studied from the 1930s through to the present day. However, this extensive body of research has yielded contradictory results, there being evidence both for and against its robustness. This study provides a systematic examination of F-test robustness to violations of normality in terms of Type I error, considering a wide variety of distributions commonly found in the health and social sciences.METHOD: We conducted a Monte Carlo simulation study involving a design with three groups and several known and unknown distributions. The manipulated variables were: Equal and unequal group sample sizes; group sample size and total sample size; coefficient of sample size variation; shape of the distribution and equal or unequal shapes of the group distributions; and pairing of group size with the degree of contamination in the distribution.RESULTS: The results showed that in terms of Type I error the F-test was robust in 100% of the cases studied, independently of the manipulated conditions.

BACKGROUND: Endometrial cells, which are shed by retrograde menstruation, may aberrantly express molecules involved in invasion and migration, leading to endometriosis. The aim of this study was to investigate the expression of the laminin gamma 2 chain (LAMC2) in the tissues of women with and without endometriosis.METHODS: Endometrial biopsy specimens were collected from healthy volunteers and from endometriosis patients. Biopsy specimens from the corresponding endometriotic lesions were also collected. The expression of laminin gamma 2 chain was evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).RESULTS: Endometrial tissue from women with or without endometriosis showed constitutive expression of LAMC2 mRNA throughout the menstrual cycle. A higher mRNA level was observed in ectopic endometrium (Ec) from women with endometriosis compared with eutopic endometrium (Eu) from women with endometriosis. Immunohistochemistry revealed a varied pattern of laminin gamma 2 chain expression, with increased epithelial expression in eutopic endometrium from women with endometriosis compared with those without endometriosis.CONCLUSIONS: The altered expression of laminin gamma 2 chain in eutopic endometrium from women with endometriosis may provide new opportunities for diagnosis and treatment.

OBJECTIVE: The objective of this study was to assess the impact of medication treatment on Medicaid costs for persons with schizophrenia.METHODS: Michigan Medicaid claims from January 1995 through September 1998 were analyzed for persons with schizophrenia diagnoses who initiated olanzapine (n = 458), risperidone (n = 481), or haloperidol (n = 252) treatment between January 1996 and September 1997. Total and component Medicaid payments were compared for the year after treatment initiation, with simultaneous adjustment for patient demographics, comorbid conditions, prior medication use, prior service use, and prior year costs.RESULTS: Significant baseline differences existed between the groups in prior medication and service use. Adherence to index medication varied between the groups (O = 60%; R = 54%; H = 37%; P < =.01 for each pairwise comparison). Average postperiod costs were US dollars 14512 per subject. After baseline adjustment, there were no significant differences in mean total cost. Excluding index medication costs, the olanzapine group's average cost was significantly lower than risperidone (-US dollars 1791, P =.002) and haloperidol (-US dollars 2080, P =.003), whereas the risperidone and haloperidol groups were not significantly different. The differences were driven by significantly lower cost for inpatient services for other medications among the olanzapine group.CONCLUSION: Total costs of schizophrenia care associated with olanzapine, risperidone, or haloperidol were similar, but component costs differed. Relative to risperidone or haloperidol, olanzapine may have a higher acquisition cost, but may decrease inpatient costs and be associated with more optimal medication use patterns. Use of risperidone may also increase pharmacy costs and be associated with greater persistence, relative to haloperidol.

As a nurse moves away from the patient's bedside, the liability exposure for malpractice decreases. However, the nurse who moves into a management position faces another kind of liability-one regarding disciplinary actions such as employee terminations.

BACKGROUND: Oxidative and nitrosative stress has suggested to be involved in the pathophysiology of cardiovascular diseases, but has unclear relationship with the risk for incident stroke.METHODS: In this nested case-control study, cases consisted of 131 participants who were free of stroke at screening and experienced incident stroke during the follow-up period. Controls were 1:1 frequency-matched for age and sex. Baseline levels of urinary creatinine-indexed biomarkers were measured using liquid chromatography-tandem mass spectrometry, including 8-iso-prostaglandin F₂á (8-iso-PGF₂á), 4-hydroxynonenal conjugate with mercapturic acid, 8-hydroxydeoxyguanosine and 8-nitroguanine.RESULTS: The levels of urinary 8-iso-PGF₂á in stroke cases were higher than in controls [median (interquartile range), 1.13 (2.23-4.36) ìg/g creatinine versus 0.71 (1.34-3.02) ìg/g creatinine, p=0.004]. After adjusting cardiovascular risk factors, the association remained that higher level of urinary 8-iso-PGF₂á entailed the greater risk for incident stroke [per 1 standard deviation increase in log-transformed value, adjusted odds ratio, 1.40; 95% confidence interval (CI), 1.06-1.85; p=0.005] with a significant increasing trend across its quartiles (p for trend=0.016). After adding urinary 8-iso-PGF₂á, the prediction model not only improved discrimination between participants with or without incident stroke (integrated discrimination improvement, 0.025; 95% CI, 0.006-0.045; p=0.005), but enhanced stroke risk stratification (net reclassification improvement, 19.8%; 95% CI, 4.6-35.1%; p=0.011). In contrast, the relationships were non-significant among the other three biomarkers.CONCLUSIONS: Our findings demonstrated that urinary 8-iso-PGF₂á could be an independent biomarker of oxidative stress for prediction of the risk for incident stroke.

We report, the application of the photoacoustic technique for monitoring the photosynthesis evolution in aquatic lirium (Eichhornia Crassipes), before and after it was exposed to ultrasonic irradiations. We obtained the disappearance of the phototobaric contribution in the PA signal measured for the irradiated samples with ultrasound of 17 kHz, and therefore of a possible damage in the centers producing the photosynthesis, due to the irradiation. These results show the utility of the ultrasonic irradiation, as well as, of the photosynthesis monitoring by means of the photoacoustic technique, for the elaboration and establishment of methodologies in the control of this aquatic plant, whose propagation causes many consequences extremely unfavorable for the environment, as well as for the diverse human activities that are developed in the bodies of water in the tropical and sub-tropical regions of the world.

Although mechanisms for chromosomal instability in tumors have been described in animal and in vitro models, little is known about these processes in man. To explore cytogenetic evolution in human tumors, chromosomal breakpoint profiles were constructed for 102 pancreatic carcinomas and 140 osteosarcomas, two tumor types characterized by extensive genomic instability. Cases with few chromosomal alterations showed a preferential clustering of breakpoints to the terminal bands, whereas tumors with many changes showed primarily interstitial and centromeric breakpoints. The terminal breakpoint frequency was negatively correlated to telomeric TTAGGG repeat length, and fluorescence in situ hybridization with telomeric TTAGGG probes consistently indicated shortened telomeres and >10% of chromosome ends lacking telomeric signals. Because telomeric dysfunction may lead to formation of unstable ring and dicentric chromosomes, mitotic figures were also evaluated. Anaphase bridges were found in all cases, and fluorescence in situ hybridization demonstrated extensive structural rearrangements of chromosomes, with terminal transferase detection showing fragmented DNA in 5-20% of interphase cells. Less than 2% of cells showed evidence of necrosis or apoptosis, and telomerase was expressed in the majority of cases. Telomeric dysfunction may thus trigger chromosomal fragmentation through persistent bridge-breakage events in pancreatic carcinomas and osteosarcomas, leading to a continuous reorganization of the tumor genome. Telomerase expression is not sufficient for completely stabilizing the chromosome complement but may be crucial for preventing complete genomic deterioration and maintaining cellular survival.

The aim of this in vitro study was to compare leakage of Enterococcus faecalis ATCC 29212 through root canals of single-rooted extracted human mandibular premolars filled with either gutta-percha/AH Plus or Resilon/Epiphany using the continuous wave of condensation technique. Test and control teeth were suspended in an experimental bacterial leakage setup for 50 days. Kaplan-Meyer curves showed a tendency of the gutta-percha/AH Plus root fillings to prevent leakage better than Resilon/Epiphany counterparts. This tendency, however, was not statistically significant (log-rank test, p = 0.141). The estimated mean time for turbidity to occur in the broth below the suspended root was 35 days (SD = 5 days) in the gutta-percha/AH Plus and 33 days (SD = 4 days) in the Resilon/Epiphany group. It was concluded that within the limitations of this study, there was no apparent advantage of using Resilon/Epiphany over gutta-percha/AH Plus.

To compare the effectiveness of a patient-completed paper-and -pencil questionnaire with the nursing interview in obtaining the admission history, 30 patients newly admitted to a Veterans Administration hospital were asked to complete a questionnaire and were given the routine nursing interview. Data were compared for accuracy and nursing time required. The nurses made significantly more errors of omission in an unstructured interview than the patient made in completing the questionnaire (p greater than .001). The nurse spent an average of 11.5 minutes on her interview while the investigator used an average of 0.9 minute to explain the reason for the questionnaire to the patient and obtain his consent to its completion. Study findings are discussed as a means of providing an accurate, systematic, recorded data base for planning nursing care.

Two mutants of Escherichia coli unable to synthesize riboflavin were grown with limiting (2 micrograms ml-1) and non-limiting (10 micrograms ml-1) concentrations of riboflavin. These riboflavin auxotrophs when grown to exponential phase with non-limiting riboflavin are more sensitive to broad spectrum near-ultraviolet light (NUV, 320-400 nm) inactivation than when they are grown with limiting riboflavin. Exponential phase cells of the riboflavin auxotrophs grown with limiting riboflavin are sensitized when irradiated in saline supplemented with riboflavin. This suggests that extracellular riboflavin is important as a NUV sensitizer when intracellular levels of riboflavin are reduced. The concentration of riboflavin in crude extracts from exponentially growing cells correlates well with the sensitivity of these mutants to NUV inactivation. The level of riboflavin supplementation has little effect on the NUV sensitivity of the parental strain.

PURPOSE: To compare the effectiveness of microwave (MW) ablation with radiofrequency (RF) ablation for treating breast tissue in a nonperfused ex vivo model of healthy bovine udder tissue.MATERIALS AND METHODS: MW ablations were performed at power outputs of 25W, 35W, and 45W using a 915-MHz frequency generator and a 2-cm active tip antenna. RF ablations were performed with a bipolar RF system with 2- and 3-cm active tip electrodes. Tissue temperatures were continuously monitored during ablation.RESULTS: The mean short-axis diameters of the coagulation zones were 1.34 ± 0.14, 1.45 ± 0.13, and 1.74 ± 0.11 cm for MW ablation at outputs of 25W, 35W, and 45W. For RF ablation, the corresponding values were 1.16 ± 0.09 and 1.26 ± 0.14 cm with electrodes having 2- and 3-cm active tips, respectively. The mean coagulation volumes were 2.27 ± 0.65, 2.85 ± 0.72, and 4.45 ± 0.47 cm(3) for MW ablation at outputs of 25W, 35W, and 45W and 1.18 ± 0.30 and 2.29 ± 0.55 cm(3) got RF ablation with 2- and 3-cm electrodes, respectively. MW ablations at 35W and 45W achieved significantly longer short-axis diameters than RF ablations (P < 0.05). The highest tissue temperature was achieved with MW ablation at 45W (P < 0.05). On histological examination, the extent of the ablation zone in MW ablations was less affected by tissue heterogeneity than that in RF ablations.CONCLUSION: MW ablation appears to be advantageous with respect to the volume of ablation and the shape of the margin of necrosis compared with RF ablation in an ex vivo bovine udder.

OBJECTIVE: To describe the methodology of a family-focused, culturally tailored program, Abriendo Caminos, for the prevention of excess weight gain in children.DESIGN: Randomized control trial with outcome assessment at pretest, posttest, and 6 months after intervention or abbreviated-attention control group.SETTING: Community setting across 5 sites (Illinois, California, Iowa, Texas, and Puerto Rico).PARTICIPANTS: Mexican American and Puerto Rican families (parent and 1 child aged 6-18 years). A sample size of 100 families (50 intervention and 50 control) per site (n = 500) will provide adequate power to detect intervention effects.INTERVENTION: Families will participate in 6 weekly, 2-hour group workshops on nutrition education through combined presentations and activities, family wellness, and physical activity.MAIN OUTCOME MEASURES: The primary outcome is prevention of excess weight gain in children; secondary outcomes include changes in child diet, specifically fruit, vegetable, and sugar-sweetened beverage consumption, and changes in parents' diets and improvement of family routines. Measures will be collected at baseline, postintervention, and 6 months after.ANALYSIS: Modeling to assess changes within and between experimental groups will be checked using standard methods including assessment of model fit, influence diagnostics, adjusted R2, and multicollinearity. Significance of effects will be examined using Type III tests.

Thearubigins are the most abundant group of phenolic pigments found in black tea, accounting for an estimated 60-70% of the solids in a typical black tea infusion. Fifty years ago the term thearubigins was first introduced and to date the chemical nature of the thearubigins remains largely unresolved, if not mysterious, despite numerous attempts made to clarify their structure. Thearubigins isolated from 15 commercial black teas have been analyzed using a strategy combining standard chemical characterization along with a series of modern complementary mass spectrometry techniques, including MALDI-TOF-MS, FTICR-MS, LC/TOF-MS and LC/MS/MS. Fifteen molecular formulas have been matched to constituents of fresh tea leaf that have survived processing and 21 to dimeric transformation products such as theasinensins, theaflavins, theaflavates, theanaphthoquinones, theacitrins and oolongtheanins, which were further confirmed by ESI MS/MS. MALDI-TOF-MS data revealed an average of 5000 additional thearubigin components in the mass range between m/z 1000 to 2100 clearly defining the molecular weight range of the thearubigin fraction. Six selected samples have for the first time been analyzed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). FT-ICR-MS data revealed the presence of a maximum of 9428 peaks in the mass range 300 to 1000 m/z and molecular formulas were assigned to 1517 of them. Data interpretation strategies developed for petrolomics studies (van Krevelen and Kendrick analyses) have for the first time been applied to black tea thearubigins and a novel interpretation protocol has been developed to refine these procedures for the investigation of complex mixtures, leading to a novel hypothesis for the formation and structure of the black tea thearubigins named oxidative cascade hypothesis.

Chelatable, mobile forms of divalent zinc, Zn(II), play essential signaling roles in mammalian biology. A complex network of zinc import and transport proteins has evolved to control zinc concentration and distribution on a subcellular level. Understanding the action of mobile zinc requires tools that can detect changes in Zn(II) concentrations at discrete cellular locales. We present here a zinc-responsive, reaction-based, targetable probe based on the diacetyled form of Zinpyr-1. The compound, (6-amidoethyl)triphenylphosphonium Zinpyr-1 diacetate (DA-ZP1-TPP), is essentially nonfluorescent in the metal-free state; however, exposure to Zn(II) triggers metal-mediated hydrolysis of the acetyl groups to afford a large, rapid, and zinc-induced fluorescence response. DA-ZP1-TPP is insensitive to intracellular esterases over a 2-h period and is impervious to proton-induced turn-on. A TPP unit is appended for targeting mitochondria, as demonstrated by live cell fluorescence imaging studies. The practical utility of DA-ZP1-TPP is demonstrated by experiments revealing that, in contrast to healthy epithelial prostate cells, tumorigenic cells are unable to accumulate mobile zinc within their mitochondria.

Plasma protein binding in seven severely burned (35% to 85% of body) patients 1 to 25 days after burn injury was examined for two drugs: diazepam (DZ), which binds mainly to serum albumin (ALB), and imipramine (IMI), which binds primarily to alpha 1-acid glycoprotein (AAG). Protein binding was determined by equilibrium dialysis, and AAG concentrations were measured by radial immunodiffusion. AAG concentrations increased from 36 to 99 mg/dl (day 1) to 221 to 268 mg/dl (days 5 to 20). The IMI free fraction values decreased from 11.2%-19.7% to 5.5%-7.8% and correlated well with AAG concentrations. IMI free fraction values were lower in burned patients (10.8% +/- 0.8%) than in healthy controls (15.3% +/- 0.7%). In contrast, DZ free fraction did not correlate with AAG or ALB concentrations. The DZ free fraction ranged from 1.5% to 8.04%, and changes in a given individual did not relate to time after injury. Free fraction of DZ was higher in the burned population (3.5% +/- 0.37%) than in healthy controls (1.25% +/- 0.05%). Basic drugs that are highly bound to AAG may show progressive, increased binding after burn injury, whereas drugs binding to ALB may decrease after burn injury. Such binding changes can alter the interpretation of total serum or plasma drug concentrations.

Recent investigations have suggested that the morphological effects of monocular deprivation can be explained by a developmental competitive interaction between the pathways from the two eyes. This study presents evidence in the tree shrew for binocular competition and for an unequal effect of such competition on the different layers of the lateral geniculate nucleus. The effects of monocular deprivation were evaluated by comparing cell size changes in the binocular and monocular segments of the lateral geniculate nucleus in three tree shrews raised with one eye sutured. In two of these animals the open eye was injected with 3H proline in order to identify accurately geniculate layers innervated by the non-deprived eye. Cell sizes in three normal animals and one monocularly enucleated animal were measured for comparison. The results show the following main effects: First, that monocular deprivation significantly changes cell size in the binocular but not the monocular segment of the geniculate nucleus. Comparisons with cell size in normal animals indicates that non-deprived cells may grow in response to deprivation. Second, that cell size in geniculate lamina 3 is not affected by monocular deprivation, suggesting that cells in this layer are morphologically or functionally secluded from competitive interactions affecting the other layers. Finally, that monocular enucleation in the adult tree shrew affects all parts of the geniculate nucleus including layer 3 and the monocular segment, demonstrating that these parts of the geniculate nucleus are responsive to lack of retinal innervation.

Clinical research informatics is the rapidly evolving sub-discipline within biomedical informatics that focuses on developing new informatics theories, tools, and solutions to accelerate the full translational continuum: basic research to clinical trials (T1), clinical trials to academic health center practice (T2), diffusion and implementation to community practice (T3), and 'real world' outcomes (T4). We present a conceptual model based on an informatics-enabled clinical research workflow, integration across heterogeneous data sources, and core informatics tools and platforms. We use this conceptual model to highlight 18 new articles in the JAMIA special issue on clinical research informatics.

Little attention has been paid to infertility in men with epilepsy and little information exists about the mechanisms by which anti-epileptic drugs affect spermatogenesis or sperm function. We report a case of a male infertility patient with asthenozoospermia during long-term treatment with anti-epileptic drugs. A 29-year-old man had continued treatment with anti-epileptic drugs under the diagnosis of epilepsy for 13 years. He and his wife had been examined and treated as an infertile couple for 3 years. The patient was found to have no motile sperm with a normal sperm count, while taking a dose of 400 mg/day of carbamazepine. On suspicion of an adverse effect of carbamazepine, he was switched to phenytoin monotherapy. One month after that, sperm motility was vastly improved (65%) and they conceived a child 5 months after that. One must be cautious in extrapolating from a case report, but these findings strongly suggest a direct effect of carbamazepine on spermatic function.

BACKGROUND: The clinical effect of thrombus aspiration in ST-elevation myocardial infarction may depend on the type of aspiration catheter and stenting technique.METHODS AND RESULTS: The multicenter, prospective, randomized, open-label trial Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE) did not demonstrate a clinical benefit of thrombus aspiration compared to percutaneous coronary intervention alone. We assessed the effect of type of aspiration device, stent type, direct stenting, and postdilatation on outcomes at 1 year. There was no difference in all-cause mortality, between the 3 most frequently used aspiration catheters (Eliminate [Terumo] 5.4%, Export [Medtronic] 5.0%, Pronto [Vascular Solutions] 4.5%) in patients randomized to thrombus aspiration. There was no difference in mortality between directly stented patients randomized to thrombus aspiration compared to patients randomized to percutaneous coronary intervention only (risk ratio 1.08, 95% CI 0.70 to 1.67, P=0.73). Similarly, there was no difference in mortality between the 2 randomized groups for patients receiving drug-eluting stents (risk ratio 0.89, 95% CI 0.63 to 1.26, P=0.50) or for those treated with postdilation (risk ratio 0.72, 95% CI 0.49 to 1.07, P=0.11). Furthermore, there was no difference in rehospitalization for myocardial infarction or stent thrombosis between the randomized arms in any of the subgroups.CONCLUSIONS: In patients with ST-elevation myocardial infarction randomized to thrombus aspiration, the type of aspiration catheter did not affect outcome. Stent type, direct stenting, or postdilation did not affect outcome irrespective of treatment with thrombus aspiration and percutaneous coronary intervention or percutaneous coronary intervention alone.CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov. Unique identifier: NCT01093404, https://clinicaltrials.gov/ct2/show/NCT01093404.

The fibroblast growth factor (FGF) family plays a key role in a multitude of physiological and pathological processes. The activities of FGFs are mediated by a family of tyrosine kinase receptors, designated FGFRs. The mechanism by which FGFs induce receptor activation is controversial. Despite their structural similarity, FGFs display distinct receptor binding characteristics and cell type specificity. Previous studies with FGF-2 identified a low affinity receptor binding site that is located within a loop connecting its 9th and 10th beta-strands. The corresponding residues in the other family members are highly variable, and it was proposed that the variability might confer on FGFs unique receptor binding characteristics. We studied the role of this loop in FGF-7 by both site-directed mutagenesis and loop replacement. Unlike the other members of the FGF family, FGF-7 recognizes only one FGFR isoform and is, therefore, ideal for studies of how the specificity in the FGF-FGFR interaction is conferred at the structural level. Point mutations in the loop of FGF-7 did not change receptor binding affinity but resulted in reduced mitogenic potency and reduced ability to induce receptor-mediated phosphorylation events. These results suggest that the loop of FGF-7 fulfills the role of low affinity binding site required for receptor activation. The observation that it is possible to uncouple FGF-7 receptor binding and biological activity favors a bivalent model for FGFR dimerization, and it may be clinically relevant to the design of FGF-7 antagonists. Reciprocal loop replacement between FGF-7 and FGF-2 had no effect on their known receptor binding affinities nor did it alter their known specificity in eliciting a mitogenic response. In conclusion, these results suggest that, despite the diversity in the loop structure of FGF-2 and FGF-7, the loop has a similar function in both growth factors.

This paper considers the role of the named nurse as a linchpin in the commissioning/providing cycle. It argues that, whatever the impact on patient care, nurses should be wary of claims that the introduction of named nursing through government policy demonstrates esteem for British nursing.

A selective reversed-phase high-performance liquid chromatographic method for the simultaneous quantification of praziquantel and its monohydroxylated metabolites in serum is described. The quantitative analysis was followed by determination of the enantiomeric ratio of praziquantel and trans-4-hydroxypraziquantel, the main metabolite of praziquantel in humans, on a cellulose tris-3,5-dimethyl-phenylcarbamate column (Chiralcel OD). Serum level data for five volunteers after oral administration of racemic praziquantel were compared with in vitro metabolism data for praziquantel, obtained with liver microsomes of different species.

Low and high-grade endometrial stromal sarcomas (ESS) can be distinguished on a morphologic basis. Low-grade ESS is composed of oval cells that resemble normal proliferative-phase endometrial stroma, while the well-known high-grade ESS is composed of round cells growing in nests separated by delicate sinusoidal vasculature. Recurrent JAZF1 rearrangements have been reported to be most frequent in low-grade stromal sarcomas (up to 60%), while YWHAE rearrangements are characteristic of high-grade ESS. Herein, we report a case of a 45-yr-old woman with stage IA typical low-grade ESS who developed multiple abdominopelvic recurrences and lung metastases 15 mo after her primary tumor was resected. The unusual morphology (without high-grade areas) as well as the aggressive behavior of the tumor prompted molecular testing which showed YWHAE rearrangement in her abdominopelvic recurrence and her primary tumor. Five years after her primary tumor was resected, she developed scalp metastases with a typical morphology of a high-grade ESS associated with t(10;17) and died of her disease. Our case highlights the potential value of molecular testing in all low-grade ESS at time of initial diagnosis to stratify patients at higher risk for developing high-grade ESS with the goal of offering closer follow-up for early detection and treatment if transformation occurs.

Dopamine is a neurotransmitter that exerts major control on important brain functions and some lines of studies suggest that dopaminergic neurotransmission may be a potential target for volatile anesthetics. In the present study, rat brain cortical slices were labeled with [(3)H]dopamine to investigate the effects of sevoflurane on the release of this neurotransmitter. [(3)H]dopamine release was significantly increased in the presence of sevoflurane (0.46 mM) and this effect was independent of extracellular or intracellular calcium. In addition, [(3)H]dopamine release evoked by sevoflurane was not affected by TTX (blocker of voltage-dependent sodium channels) or reserpine (a blocker of the vesicular monoamine transporter). These data suggest that the dopamine release induced by sevoflurane is non-vesicular, independent of exocytosis and, would be mediated by the dopamine transporter (DAT). GBR12909 and nomifensine, inhibitors of DAT, decreased the release of [(3)H]dopamine evoked by sevoflurane. The same effect was also observed when the brain cortical slices were incubated at low temperature and low extracellular sodium. Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which is known to induce dopamine release through reverse transport, decreased [(3)H]dopamine release induced by sevoflurane. In conclusion, the present study suggests that sevoflurane increases [(3)H]dopamine release in brain cortical slices that is mediated by DAT located at the plasma membrane.

OBJECTIVE: The purpose was to investigate the influence of slice thickness on multidetector computed tomography (MDCT)- and magnetic resonance (MR)-based liver volumetry.MATERIALS AND METHODS: Twenty patients who underwent liver surgery were imaged with either a 64-slice MDCT (n = 10) or a 1.5-T MR scanner (n = 10). Multidetector computed tomography and MR images were reconstructed using different slice thicknesses (2, 4, 6, and 8 mm). Total liver volumes (TLVs) were measured by 2 independent readers based on different slice thicknesses using semiautomatic software. Results were compared with TLVs based on 2-mm slices that served as standard of reference. The time to perform each volumetry was recorded.RESULTS: For MDCT volumetry, a statistical difference was seen only between TLVs based on 2-mm versus 8-mm slices (P = 0.012 and P = 0.002 for readers 1 and 2, respectively). For MR volumetry, no statistical difference was seen between TLVs of the standard of reference and TLVs based on 4-, 6-, and 8-mm slices. Regarding the time to perform volumetry, there was a significant gain of time for both readers when volumetry was performed on 6- and 8-mm MDCT slices and on 4-, 6-, and 8-mm MR slices (P < 0.0167) when compared with the standard of reference.CONCLUSIONS: The results of MDCT- and MR-based liver volumetry are dependent on slice thickness. With respect to the precision of calculated volumes and the significant gain of time, 6-mm slices are preferable for computed tomographic imaging, and 8-mm slices are preferable for MR imaging.

The stereoelectronic properties of several potent reversible monoamine oxidase B (MAO-B) inhibitors were studied with a view to develop a pharmacophore model for reversible MAO-B inhibition. This study suggested that important specific H-bond and hydrophobic interactions are required for potent and selective MAO-B inhibition. These requirements were applied in the design and synthesis of a novel reversible and selective MAO-B inhibitor, 3-methyl-8-(4,4,4-trifluoro-butoxy)indeno[1,2-c]pyridazin-5-one, that is ca. 7000 times more selective as an inhibitor for MAO-B than for MAO-A, with K(i(MAO-B)) in the low nanomolar range.

When do people express their emotions to other people and when do they choose not to do so? Emotional experience-positive or negative-often leads people to reveal their feelings to others, especially to close relationship partners. Although emotional expression has been incorporated into recent dyadic models of emotion regulation, little research has examined the specific interpersonal processes responsible for facilitating or inhibiting emotional expression. This article reports results from a pair of methodologically distinct studies examining the impact of perceived partner responsiveness (PPR) on emotional expression. The results of Study 1, a 2-week daily diary study, demonstrated that within-person variations in the perceived responsiveness of a close partner were associated with corresponding day-to-day variations in emotional expression to that partner. In Study 2, in the context of a stressful situation, we manipulated perceptions of a romantic partner's responsiveness and then measured emotion expression toward that partner. Higher levels of experimentally induced PPR causally led to greater expression of anxiety. Together, these studies identify PPR as an important interpersonal mechanism underlying emotional expression. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

MSOT has revolutionized biomedical imaging because it allows anatomical, functional, and molecular imaging of deep tissues in vivo in an entirely noninvasive, label-free, and real-time manner. This imaging modality works by pulsing light onto tissue, triggering the production of acoustic waves, which can be collected and reconstructed to provide high-resolution images of features as deep as several centimeters below the body surface. Advances in hardware and software continue to bring MSOT closer to clinical translation. Most recently, a clinical handheld MSOT system has been used to image brown fat tissue (BAT) and its metabolic activity by directly resolving the spectral signatures of hemoglobin and lipids. This opens up new possibilities for studying BAT physiology and its role in metabolic disease without the need to inject animals or humans with contrast agents. In this chapter, we overview how MSOT works and how it has been implemented in preclinical and clinical contexts. We focus on our recent work using MSOT to image BAT in resting and activated states both in mice and humans.

Porcine circovirus type 2 (PCV2) encodes two major proteins: the replication protein (Rep) and the capsid protein (Cap). Cap displays a conserved stretch of basic residues situated on the inside of the capsid, whose role is so far unknown. We used a reverse-genetics approach to investigate its function and found that mutations in these amino acids hindered Cap mRNA translation and hampered Cap/Rep co-localization, yielding unfit viruses. Intriguingly, co-transfection with a WT PCV2 of a different genotype partially rescued mutant Cap expression, showing the importance of this basic pattern for efficient translation of Cap mRNA into protein. Our results show that Cap and Rep are expressed independently of each other, and that this amino acid sequence of Cap is vital for virus propagation. This study provides a method for studying unfit PCV2 virions and offers new insights into the intracellular modus vivendi of PCV2.

We present a case of miniinvasive fetal surgery for CDH treated at 28 and 34 weeks of gestation. The first step was successfully performed at 28 weeks with Fetal Endoscopic Tracheal Occlusion with ballon. The second step was performed at 34 weeks for balloon removal. The necessity of fetal cytogenetic assessment and array CGH was carried out to exclude gene disorders that could lead to poor long-term outcome. A planned SC and optimal neonatology management were followed by a surgical operation of the newborn. Experienced interdisciplinary team successfully provide a perinatal and postnatal surgery for severe CDH. The newborn was discharged from the hospital 3 weeks after the repairing operation in a good condition.

Chiral lipidic dialkynylcarbinols (DACs), recently highlighted as antitumoral pharmacophores, have been conjugated to difluoroboron-dipyrromethene (bodipy), 7-hydroxy-coumarine, and 7-nitro-benzoxadiazole (NBD) fluorophore motifs through triazole clips. The labeled lipids preserve cytotoxic activity against HCT116 cells, and fluorescence microscopy of the stained cells showed clear signals in the intra-cellular membrane system. While the bodipy conjugate also labels lipid droplets very brightly, as expected, the coumarine and NBD probes appear as promising specific tools for the identification of the intra-cellular targets of DACs' cytotoxicity.

BACKGROUND: This study aimed to investigate the significance of circulating HER2 and MYC gene fragments quantification in the diagnosis of gastric cancer.METHODS: Levels of HER2 and MYC genes were evaluated by fluorescence in situ hybridization and real-time PCR in 81 gastric cancer tissues, and by real-time PCR in 36 gastritis tissues. Real-time PCR for HER2 and MYC products was also performed on 184 plasma samples from 81 gastric cancers, eight gastric adenomas, 63 gastritis patients, and 32 healthy individuals.RESULTS: HER2/HBB and MYC/HBB ratios in tissue and cell-free plasma from gastric cancer patients were significantly higher than those of gastritis tissue and cancer-free individuals. An optimized cut-off value of plasma target gene to HBB ratio, used to differentiate cancer patients from cancer-free individuals, was evaluated using receiver operating characteristic (ROC) curves. Values of 2.0 were calculated for HER2 [area under the ROC curve (AUC), 0.760] and 2.725 for MYC (AUC, 0.767). A combination model of HER2 and MYC provided a better differentiation condition than that for HER2 or MYC only (AUC, 0.850). HER2/HBB ratios in plasma from gastric cancer patients correlated with MYC/HBB ratios.CONCLUSIONS: Our findings suggest that the measurement of plasma HER2 and MYC gene levels could improve the screening of gastric cancer.

As an excellent model organism, zebrafish have been widely applied in many fields. The accurate identification and tracking of individuals are crucial for zebrafish shoaling behaviour analysis. However, multi-zebrafish tracking still faces many challenges. It is difficult to keep identified for a long time due to fish overlapping caused by the crossings. Here we proposed an improved Histogram of Oriented Gradient (HOG) algorithm to calculate the stable back texture feature map of zebrafish, then tracked multi-zebrafish in a fully automated fashion with low sample size, high tracking accuracy and wide applicability. The performance of the tracking algorithm was evaluated in 11 videos with different numbers and different sizes of zebrafish. In the Right-tailed hypothesis test of Wilcoxon, our method performed better than idTracker, with significant higher tracking accuracy. Throughout the video of 16 zebrafish, the training sample of each fish had only 200-500 image samples, one-fifth of the idTracker's sample size. Furthermore, we applied the tracking algorithm to analyse the depression and hypoactivity behaviour of zebrafish shoaling. We achieved correct identification of depressed zebrafish among the fish shoal based on the accurate tracking results that could not be identified by a human.

The uterine endometrium plays a critical role in regulating the estrous cycle and the establishment and maintenance of pregnancy in mammalian species. Many studies have investigated the expression and function of genes in the uterine endometrium, but the global expression pattern of genes and relationships among genes differentially expressed in the uterine endometrium during gestation in pigs remain unclear. Thus, this study investigated global gene expression profiles using microarray in pigs. Diverse transcriptome analyses including clustering, network, and differentially expressed gene (DEG) analyses were performed to detect endometrial gene expression changes during the different gestation stages. In total, 6,991 genes were found to be differentially expressed by comparing genes expressed on day (D) 12 of pregnancy with those on D15, D30, D60, D90 and D114 of pregnancy, and clustering analysis of detected DEGs distinguished 8 clusters. Furthermore, several pregnancy-related hub genes such as ALPPL2, RANBP17, NF1B, SPP1, and CST6 were discovered through network analysis. Finally, detected hub genes were technically validated by quantitative RT-PCR. These results suggest the complex network characteristics involved in uterine endometrial gene expression during pregnancy and indicate that diverse patterns of stage-specific gene expression and network connections may play a critical role in endometrial remodeling and in placental and fetal development to establish and maintenance of pregnancy in pigs.

Two patients with AIDS and progressive neurological syndromes had necropsies that identified JC virus infection of the cerebral or cerebellar cortex. The unusual presentation of progressive multifocal leukoencephalopathy with grey matter involvement and normal cerebral imaging is discussed.

To investigate the details of the pathophysiology of endogenous fungal endophthalmitis (EFE), we performed sequential histological and ophthalmoscopic examination on a rabbit model comparing immunocompromised EFE developed using a steroid with an immunocompetent one intravenously inoculated with Candida albicans. The ophthalmoscopic examination and histological analysis of the retina in both groups demonstrated that lesions appear on the equator of the eyeball and then spread toward the posterior pole. It has been speculated that, because of the unique innate vasculature system of the equator, there is a sudden, decrease of shear stress in rheologically, resulting in adhesion of yeast cells to the endothelial cells. Histological examination revealed that the degree of polymorphonuclear leukocyte (PMN) infiltration was equivalent in the two groups. However, the appearance of PMN was delayed and the number of fungi was higher in the state of hyphae and/or pseudohyphae in the steroid-treated group. Furthermore, the eyeball was found to be the second earliest organ involved in candidemia. Our results indicate that ophthalmic examination is useful to monitor the development and systemic involvement of endophthalmitis in patients with candidemia.

Endotoxins or lipopolysaccharides are the main constituents of the outer leaflet of Gram-negative bacteria membrane and play a central role in the pathogenesis of the septic shock. Polymyxin B has both antibacterial and antiendotoxin capability; indeed it is able to destroy the bacterial outer membrane and bind endotoxin neutralizing its toxic effects. Cartridges containing polymyxin B-immobilized fibers (Toraymyxin PMX-F, Toray Industries, Japan) are used in extracorporeal hemoperfusion to remove circulating endotoxin. The aim of this study is the characterization of the polymyxin B-endotoxin system at the molecular level, thus providing quantitative evaluation of the binding forces exerted in the molecular complex. Polymyxin B was interfaced with five molecular models of lipopolysaccharides differing in their structure and molecular mechanics simulations were performed at different intermolecular distances aimed at calculating the interaction energies of the complex. Binding forces were calculated by fitting interaction energies data. Results show that in the short range the polymyxin B-endotoxin complex is mediated by hydrophobic forces and in the long range the complex is driven by ionic forces only. From a mechanical standpoint, polymyxin B-endotoxin complex is characterized by maximum binding forces ranging between 1.39 nN to 3.79 nN. The knowledge of the binding force behavior at different intermolecular distances allows further investigations at higher scale level (Part II).

Chronic lymphocytic leukemia (CLL) is a progressive malignancy of mature B-cells that involves the peripheral blood (PB), lymph nodes (LNs) and bone marrow (BM). Although the majority of CLL cells are in a resting state, small populations of proliferating cells exist; however, the anatomical site of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of 'newly born' cells would be highest in the LNs. Using a deuterium oxide (2H) in vivo labeling method in which patients consumed deuterated (heavy) water (2H2O), we determined CLL cell kinetics in concurrently obtained samples from LN, PB and BM. The LN was identified as the anatomical site harboring the largest fraction of newly born cells, compared to PB and BM. In fact, the calculated birth rate in the LN reached as high a 3.3% of the clone per day. Subdivision of the bulk CLL population by flow cytometry identified the subpopulation with the CXCR4dimCD5bright phenotype as containing the highest proportion of newly born cells within each compartment, including the LN, identifying this subclonal population as an important target for novel treatment approaches.

Daily average concentrations of fine and coarse particulates, and TSP samples have been measured simultaneously at daytime and night-time periods by using Universal and PS-1 sampler in a suburban area of central Taiwan from June to August 1998. The samples were analyzed by atomic absorption spectrometry to determine the fine and coarse particulate concentrations of metallic elements (Ca, Fe, Mn, Pb, Cu, Zn and Cr). The concentration of PM2.5 and TSP showed a decreased trend for the daytime period. The fine particle concentrations were about two times as that of coarse particulate concentrations. The averaged fine particulate concentrations at daytime are higher than at night-time. Ca and Fe were mostly in the coarse particulate mode. The correlation coefficients were 0.63 and 0.69 for elements Ca and Fe in the coarse particle mode for day and night periods. Pb showed a similar distribution ratio with Mn for the fine to coarse particle ratios at both day and night period. Pb and Mn are highly correlated for the day (R = 0.78) and night period (R = 0.61) at particle size <2.5 microm. Cu and Zn were mainly in fine particles at both day and night period. Fe and Ca consist of the major parts of all the elements. Elemental Mn is the lowest among the rest of the heavy metals.

Cell surface receptors for the 86-kDa glycoprotein (gp86) of human cytomegalovirus (HCMV) were identified by using two monoclonal anti-idiotype antibodies that bear the internal image of gp86. These antibodies bound to cells permissive for HCMV infection by both ELISA and immunofluorescence assay and inhibited HCMV plaque formation in human embryonic lung (HEL) cells. Immunoblot analysis showed specific binding of both internal image anti-idiotype antibodies as well as gp86 to an HEL cell membrane protein with an approximate molecular mass of 92.5 kDa. In addition, immunoprecipitation of radiolabeled membrane and cell surface proteins from human foreskin tissue, human foreskin fibroblasts, or HEL cells showed specific binding of anti-idiotype antibody predominantly to the 92.5-kDa protein.

BACKGROUND: Allergy is diagnosed from typical symptoms, and tests are performed to incriminate the suspected precipitant. Skin prick tests (SPTs) are commonly performed, inexpensive, and give immediate results. Laboratory tests (ImmunoCAP) for serum allergen-specific IgE antibodies are usually performed more selectively. The immuno-solid phase allergen chip (ISAC) enables testing for specific IgE against multiple allergen components in a multiplex assay.METHODS: We retrospectively analysed clinic letters, case notes, and laboratory results of 118 patients attending the National Adult Allergy Service at the University Hospital of Wales who presented diagnostic difficulty, to evaluate which testing strategy (SPT, ImmunoCAP, or ISAC) was the most appropriate to use to confirm the diagnosis in these complex patients, evaluated in a "real-life" clinical service setting.RESULTS: In patients with nut allergy, the detection rates of SPTs (56%) and ISAC (65%) were lower than those of ImmunoCAP (71%). ISAC had a higher detection rate (88%) than ImmunoCAP (69%) or SPT (33%) in the diagnosis of oral allergy syndrome. ImmunoCAP test results identified all 9 patients with anaphylaxis due to wheat allergy (100%), whereas ISAC was positive in only 6 of these 9 (67%).CONCLUSIONS: In this difficult diagnostic group, the ImmunoCAP test should be the preferred single test for possible allergy to nuts, wheat, other specific foods, and anaphylaxis of any cause. In these conditions, SPT and ISAC tests give comparable results. The most useful single test for oral allergy syndrome is ISAC, and SPT should be the preferred test for latex allergy.

Orexin A belongs to the group of hypothalamic-derived peptides that are involved in a number of processes, such as regulation of energy metabolism, control of food intake and regulation of the reproductive system, by influencing the hypothalamic-pituitary-ovarian axis. Orexin A is also present in the endometrium, myometrium and placenta, which indicates that it may function as an important local regulator of the reproductive functions. The aim of this study was to explore the effects of orexin A on global gene expression in the endometrium of pigs during early gestation, on days 15 to 16 of pregnancy (implantation period). Orexin A altered the expression of 1,242 genes. In this group, 1,104 genes had a fold change greater than 1.2 (P < 0.05). In the group of genes with a fold change that was greater than 1.2, the expression of 457 genes were increased and 647 decreased because of the effects of orexin A. An analysis of the interactions between differentially expressed genes demonstrated that orexin A interacts with genes that potentially encode intracellular signalling pathways and factors regulating reproductive functions in the endometrium. The data from the present study indicate that orexin A affects a number of genes and processes in the endometrium of pregnant pigs and may be regarded as an important regulator of implantation, depending on maternal nutritional status.

Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a poor prognosis. It has histologic features that overlap with other endometrial carcinomas and is frequently misclassified. Accurate classification is crucial, however, to improve treatment options. The objectives of this study were (1) to assess diagnostic interobserver variability among 5 gynecologic pathologists for tumors originally diagnosed as CC or with a component of CC (n=44); (2) to determine the utility of immunohistochemical markers estrogen receptor and HNF-1â; and (3) to detect mutations in select genes. Clinical data and morphologic features were also recorded. Agreement among reviewers was only moderate: only 46% of the original CC remained classified as such. After reclassification, estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC), and 47% of serous carcinomas (SC). Sensitivities of HNF-1â in CC, SC, and EC were 62%, 27%, and 17%, respectively, whereas specificity for CC versus EC or SC was 78%. Mutations in PIK3CA, PIK3R1, PTEN, KRAS, and NRAS were detected in 41% of 37 cases that had adequate material for study. At least 1 mutation was identified in 33% of CC, 67% of EC, and 33% of SC. This group of patients had poor outcomes: 72% of the patients with follow-up information had died of disease. In summary, this study suggests that the current pool of CC is a heterogeneous group of tumors from the morphologic, immunophenotypic, and molecular point of views and that only a percentage of them represent true CC.

In Norway, the use of cannabis was introduced by a resourceful group of oppositional middle-class adolescents in the late 1960s. At the beginning of the 1970s there were, however, signs of a change in the recruitment of the users: youths in trouble from lower social levels gradually started to use the drug. In a prospective longitudinal study of 1311 Norwegian pupils aged 13-19, the possible links between normative and political opposition, mental health and the use of cannabis were investigated. The findings indicate that the group that experiments with cannabis, and use the drugs a few times, is still mainly characterized by a political and normative "oppositional" engagement. Heavy users of cannabis, however, also have family problems and suffer from poor mental health. Thus, the study draws attention to the importance of distinguishing between two different clusters of longitudinal predictors for adolescent cannabis use: the first consists of subcultural opposition and certain personality traits, and seems to predict the earlier stages of use. The second consists of psychosocial problems and poor mental health. From this study one may not conclude that this second cluster predicts heavy cannabis involvement. We have, however, shown that it correlates with heavy involvement, cross-sectionally.

BACKGROUND: The intake of nutrients and the nutritional status of untreated coeliac patients and coeliac patients in remission were investigated at Kuopio University Hospital.METHODS: Forty untreated and 52 coeliac patients in remission were admitted to the study. The control group included 77 persons. Four-day food records, anthropometric measurements, and blood biochemistry were examined to obtain nutrient intake and nutritional status.RESULTS: Concentrations of serum ferritin, vitamin B12, and erythrocyte folate were lower in patients with untreated coeliac disease than in those in remission. Altogether, 15-38% of the untreated patients but only 0-20% of the patients in remission had levels of haemoglobin, serum ferritin, iron, vitamin B12, or erythrocyte folate below the reference values. No difference in anthropometric measurements was found between the two groups of coeliac patients.CONCLUSIONS: Except for some subclinical abnormal values in biochemical analyses in 20-38% of coeliac patients, nutritional status was quite normal in both groups of coeliac patients.

A macromolecular-assembly of polypeptides constructs a network of anionic and cationic charges vital for recognizing and coassembling Ca(2+) and CO(3)(2-) ions to mineralize and stabilize different mineral forms of CaCO(3) with core-shell or solid morphologies in an aqueous solution.

The hydro-distilled essential oils obtained from aerial parts of the wild (w) and cultivated (c) mint timija (Mentha suaveolens subsp. timija), an endemic medicinal species of Morocco, have been analyzed by GC-MS and screened for antimicrobial activity. In total, 35 compounds representing more than 98% of the oils were identified. Menthone (39.4(w)-10.8(c)%), pulegone (62.3(c)-34.3(w)%) and isomenthone (9.3(c)-7.8(w)%) were found as the main components for the two oils. The volatiles of the wild and cultivated material differed significantly in both the percentage of the main components and antimicrobial effect. Pulegone was more dominant in cultivated mint timija (62.3%) than in wild one (34.3%), while menthone was more abundant in the wild material (39.4%). In the antimicrobial assays, both oils displayed good to excellent activity against all microorganisms tested with the oil of the cultivated form being more active.

The pathogenic mechanisms of Brucellosis used to adapt to the harsh intracellular environment of the host cell are not fully understood. The present study investigated the in vitro and in vivo characteristics of B. abortus betaine aldehyde dehydrogenase (BetB) (Gene Bank ID: 006932) using a betB deletion mutant constructed from virulent B. abortus 544. In test under stress conditions, including osmotic- and acid stress-resistance, the betB mutant had a lower osmotic-resistance than B. abortus wild-type. In addition, the betB mutant showed higher internalization rates compared to the wild-type strain; however, it also displayed replication failures in HeLa cells and RAW 264.7 macrophages. During internalization, compared to the wild-type strain, the betB mutant was more adherent to the host surface and showed enhanced phosphorylation of protein kinases, two processes that promote phagocytic activity, in host cells. During intracellular trafficking, colocalization of B. abortus-containing phagosomes with LAMP-1 was elevated in betB mutant-infected cells compared to the wild-type cells. In mice, the betB mutant was predominantly cleared from spleens compared to the wild-type strain after 2 weeks post-infection, and the vaccination test with the live betB mutant showed effective protection against challenge infection with the virulent wild-type strain. These findings suggested that the B. abortus betB gene substantially affects the phagocytic pathway in human phagocytes and in host cells in mice. Furthermore, this study highlights the potential use of the B. abortus betB mutant as a live vaccine for the control of brucellosis.

Many cells in prefrontal cortex show enhanced activity prior to movement onset in delayed or memory-guided saccade tasks. This activity is a possible neural correlate of spatial attention and working memory. The goal of this study was to determine whether delay activity is evoked when non-spatial cues such as color are used to guide saccades. Monkeys were trained on a saccade target selection task in which they were cued for either the location or color of the rewarded target. When the location of the target was specified explicitly, many cells showed visual responses and delay activity that were spatially selective. Color selective visual responses or delay activity were both rare and weak. However, for many cells, spatially selective delay activity could be evoked when color was used to specify the location of the target. These results indicate that color is capable of eliciting spatially selective activity from cells that have no overt color selectivity.

The support vector domain description is a one-class classification method that estimates the distributional support of a data set. A flexible closed boundary function is used to separate trustworthy data on the inside from outliers on the outside. A single regularization parameter determines the shape of the boundary and the proportion of observations that are regarded as outliers. Picking an appropriate amount of regularization is crucial in most applications but is, for computational reasons, commonly limited to a small collection of parameter values. This paper presents an algorithm where the solutions for all possible values of the regularization parameter are computed at roughly the same computational complexity previously required to obtain a single solution. Such a collection of solutions is known as a regularization path. Knowledge of the entire regularization path not only aids model selection, but may also provide new information about a data set. We illustrate this potential of the method in two applications; one where we establish a sensible ordering among a set of corpora callosa outlines, and one where ischemic segments of the myocardium are detected in patients with acute myocardial infarction.

Arsenic uptake by hyperaccumulator plant species depends on many different environmental factors. Soil pH is one of the most important factors due to its combined effect on both chemical and biological processes. In greenhouse experiment, the effect of pH (within the pH range 3.6 - 8.9) on As uptake as well as biomass of Pityrogramma calomelanos was evaluated. The plants were grown in mining soil containing 645.6 mg As kg(-1) for 14 weeks. Within this time, the plant biomass growth was 3.78 - 8.64 g d. wt. per plant and the removal amounted 6.3-18.4 mg As per plant. Translocation factor (ratio of As in fronds to roots) of the fern was 3.6 - 9.7, indicating its potential in phytoremediation of As contaminated soil. Influence of pH on As bioavailability was visible as the available As concentration was higher in acidic soil compared to alkaline soil. Furthermore, it was found that As accumulation by Pityrogramma calomelanos was optimum in the soil of pH 3.6. Nevertheless, the results of this study demonstrate that remediation of As-contaminated mining soils, by this fern, can be improved by changing the soil pH from 4.6 to 6.8.

Acute respiratory distress syndrome continues to have high morbidity and mortality despite more than 50 years of research. The Berlin definition in 2012 established risk stratification based on degree of hypoxemia and the use of positive end-expiratory pressure. The use of prone positioning as a treatment modality has been studied for more than 40 years, with recent studies showing an improvement in oxygenation and decreased mortality. The studies also provide evidence to support the methodology and length of treatment time. Recent guidelines include several ventilator strategies for acute respiratory distress syndrome, including prone positioning. Protocols and procedures discussed in this article ensure successful prone repositioning and prevention of complications related to the procedure itself.

One of the main environmental issues affecting coastal marine environments is the accumulation of contaminants in sediments and their potential mobility. In situ benthic chamber experiments were conducted at two tourist ports (marinas) located in the Gulf of Trieste, one in Slovenia and one in Italy. The aim was to understand if and where recycling at the sediment-water interface (SWI) may affect metal(loid)s. Short sediment cores were also collected near the chamber to investigate the solid (sediments) and dissolved phases (porewaters). Both diffusive and benthic fluxes were estimated to elucidate the release of metal(loid)s at the SWI. Total element concentrations and their labile fractions were determined in sediments to quantify their potential mobility. The total element contents were found to be two orders of magnitude higher in the Italian marina than in the Slovenian one, especially for Hg (up to 1000 mg kg-1), whereas the labile fraction was scarce or null. The opposite occurred in the Slovenian marina. Metal(loid)s in porewaters showed a clear diagenetic sequence and a close dependence upon the suboxic/anoxic conditions of sediments. The results suggest that although the sediments of the Italian marina exhibit the highest total metal(loid) concentration, these elements are scarcely remobilisable. Conversely, in the Slovenian marina, sediments seem to be comparatively more prone to release metal(loid)s at the SWI.

The adherence of resin cements to restoration as well as tooth structure is of prime importance for the longevity of cemented restorations. It was the aim of the study to investigate the effect of an acid and a base primer on (i) surface polarity of a nonprecious alloy and on (ii) adherence energy of resin cements bonded to the alloy. The beams were pretreated with a 3% acetone solution of either maleic acid or N,N-diethanol-p-toluidine, and the solvent evaporated. The polarity was determined by means of measurements of contact angles. The adherence energy was measured by means of the wedge test, according to which 2 beams were glued together with the resin cement. A wedge was introduced between the joined beams to create a fissure, and on the basis of the length of the fissure, the adherence energy was calculated. It was found that the polar component of the surface free energy of the alloy increased as a consequence of the pretreatments. The results also showed that the pretreatments gave rise to an increase in adherence energy of 11-15 J/m2, equivalent to relative increases of 22-54%. The observed increases in adherence energy may be due to an increase in polar interactions at the interface between adhesive and substrate.

Simultanagnosia is a disorder of visual attention resulting from bilateral parieto-occipital lesions. Healthy individuals look at eyes to infer people's attentional states, but simultanagnosics allocate abnormally few fixations to eyes in scenes. It is unclear why simultanagnosics fail to fixate eyes, but it might reflect that they are (a) unable to locate and fixate them, or (b) do not prioritize attentional states. We compared eye movements of simultanagnosic G.B. to those of healthy subjects viewing scenes normally or through a restricted window of vision. They described scenes and explicitly inferred attentional states of people in scenes. G.B. and subjects viewing scenes through a restricted window made few fixations on eyes when describing scenes, yet increased fixations on eyes when inferring attention. Thus G.B. understands that eyes are important for inferring attentional states and can exert top-down control to seek out and process the gaze of others when attentional states are of interest.

We employed sialidase procedures followed by lectin stainings combined with oxidizing and deacetylating agents to visualize the distribution and sequentiate sialoglycoconjugates in the bovine submandibular gland. In particular we evidenced in acinar and ductal cells the dishomogeneous presence of sialic acids acetylated in the polyhydroxy side chain (C7, C8, C9), whereas O-acetyl substituents at position C1 and/or C4 were not found. Sialoglycoderivatives were also differentiated by the occurrence of penultimate sugars; indeed the dimers sialic acid-(alpha 2----3,6)-beta-galactose and sialic acid-(alpha 2----6)-alpha-N-acetylgalactosamine were identified. Using such technique we supported further the possibility to develop methods for the identification of the positions of O-acetyl groups and the reconstruction of terminal disaccharides within surface and cytoplasm glycoconjugates. in situ the distribution of different O-acylated sialoglyco-derivatives in the bovine submandibular gland. To this purpose we employed oxydizing and deacetylating agents combined with sialidase digestion and lectin binding.

The Authors report on a case of colon carcinoma occurred in a pregnant woman. As complaints for digestive tract disfunctions are common during pregnancy, the diagnosis of the malignancy was delayed. The Authors suggest the treating physician be alert to avoid under estimation of symptomatology.

In the German health system the payment of a hospital stay is standardised. The common basis is the G-DRG System (German diagnosis-related groups) in which every stay is paid by a lump sum. Scoliosis correction in our times means pedicle screw-based multilevel double rod instrumentation or anterior plate-rod instrumentation with primary stability. The outcome of those methods has improved the results of correction and decreased the complication rate but also means high costs due to the implants. Scoliosis correction is covered by DRG I06. Due to constant efforts a general improvement took place in the assessment of DRG I06. That is the reason why the losses incurred in DRG I06C could be lowered to 38% and in I06D to 22% in 2008. For an appropriate assessment further improvements are required.

BACKGROUND: The association between asthma and obesity in children, and the effect modification of allergy on this association have not been fully established. Aims The objective of the study was to know the effect modification of the severity of asthma and of the coexistence of rhinoconjunctivitis (RC) in the relationship between obesity and asthma.METHODS: A cross-sectional study of 17 145 schoolchildren 6-7 years old from eight Spanish cities who had completed information on height and weight of the ISAAC phase III questionnaire, which also included questions about asthma and RC symptoms and on various risk factors. Body mass index (BMI) was used to define obesity according to international standards. Two different logistic regressions, using current occasional asthma (COA) and current severe asthma (CSA) as dependent variables, were made stratifying for gender and for the coexistence of RC and controlling for age, older and younger siblings, exercise, mother's education, truck traffic, cat/dog during the first year of life and smoking father or mother.RESULTS: Obesity was a risk factor of CSA without RC, both for boys (1.92, CI 95% 1.13-3.25) and for girls (2.99, CI 95% 1.68-5.32). Every BMI unit increment increased by 6.7% the risk of CSA without RC in boys and by 12.4% in girls. Obesity was not a risk factor for CSA with RC. The association between COA and obesity was weaker and the coexistence of RC did not modify it greatly.CONCLUSIONS: Obese schoolchildren are more at risk of suffering from non-allergic asthma than the non-obese subjects.

OBJECTIVE: To compare seizure induced by different epileptic drugs in ICR mice.METHODS: Male adult ICR mice were injected with pilocarpine (Pilo), kainic acid (KA) and pentylenetetrazole (PTZ) to induce status epilepticus (SE). After 2 h of SE, seizures were terminated by injection of diazepam. Mice were sacrificed and sectioned for assessment of neuronal cell death by Fluro-Jade B staining after 7 d and mossy fiber sprouting by Timm staining after 28 d, respectively. Spontaneous seizures were detected by video for 28 d.RESULTS: Pilo and KA induced typical SE in ICR mice, which was identical to those observed in rats and C57/BL6 mice. Timm staining showed evident mossy fiber sprouting in both Pilo and KA treated mice. The incidences of spontaneous seizure were 57.1% and 35.7% in Pilo and KA treated mice, respectively. Mice treated with PTZ represented kindling model. No mossy fiber sprouting and spontaneous seizures were observed. No cell death was detected in all three groups.CONCLUSION: Similar seizure pattern is observed in ICR mice as in rats and C57/BL6 mice. Both Pilo and KA model are the ideal models for chronic temporal lobe epilepsy. ICR mice can be widely used as a cheaper substitute in epilepsy research.

We treated 41 patients with transitional cell carcinoma with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy. Median patient age was 56 years. Of the patients 33 had either distant metastases or locoregional disease that could not be cured by an operation or radiation. Of these patients 30 had measurable disease and 12 responded (4 complete and 8 partial responses, response rate 40 per cent, 95 per cent confidence limits 23 to 59 per cent). Only 2 of these patients remain with an unmaintained complete response at 34 and 52 months. Of 5 patients 3 responded who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for locally advanced bladder cancer before radiation or cystectomy, and only 1 of these patients is free of disease. The remaining 3 patients were treated postoperatively because they were at high risk for recurrence and all are well. Toxicity of the regimen was severe: 41 per cent of the patients experienced neutropenic sepsis and 54 per cent required hospitalization for management of toxic complications. Three patients experienced pulmonary embolism and 1 had deep vein thrombosis. There was 1 drug-related death of sepsis. Although a patient occasionally may have long-term benefit from this chemotherapy our results suggest caution in the widespread application of this protocol.

An inhibitor of the proliferation of hepatic stellate cells (HSC) was purified from rat liver by a combination of gel filtration and ion exchange chromatography. The molecular mass of this non-arginase growth inhibitory factor (NAGIF) was determined to be 38 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration. The proliferation of HSC was inhibited by NAGIF with a 50% inhibitory dose of 5 nmol/liter. The inhibitory activity of NAGIF was not limited to HSC but also affected the growth of bovine endothelial cells and 3T6 fibroblasts. However, the growth of B16 mouse melanoma was not inhibited by NAGIF. The NH(2)-terminal sequence of NAGIF, AEPVEPWS, is identical to an internal sequence of rat Zn-alpha(2)-glycoprotein. Although the action mode of this inhibitor remains to be investigated, it seems very likely that NAGIF is involved in the negative control mechanism of HSC growth.

BACKGROUND: The efficacy of opaque contact lenses as occlusion therapy for amblyopia has been established in the literature. Prosthetic contact lenses use similar tints to improve cosmesis in scarred or deformed eyes and may be an alternative in occlusion therapy. To test this idea, we determined the degree of vision penalization elicited by prosthetic contact lenses and their effect on peripheral fusion.METHODS: We tested 19 CIBA Vision DuraSoft 3 Prosthetic soft contact lenses with varying iris prints, underprints, and opaque pupil sizes in 10 volunteers with best-corrected Snellen distance visual acuity of 20/20 or better in each eye. Snellen visual acuity and peripheral fusion using the Worth 4-Dot test at near were measured on each subject wearing each of the 19 lenses.RESULTS: Results were analyzed with 3-factor analysis of variance. Mean visual acuity through the various lenses ranged from 20/79 to 20/620. Eight lenses allowed preservation of peripheral fusion in 50% or more of the subjects tested. Iris print pattern and opaque pupil size were significant factors in determining visual acuity (p < 0.05).CONCLUSIONS: Sufficient vision penalization can be achieved to make occlusion with prosthetic contact lenses a viable therapy for amblyopia. The degree of penalization can be varied and different iris print patterns and pupil sizes, using peripheral fusion, can be preserved with some lenses. Prosthetic contact lenses can be more cosmetically appealing and more tolerable than other amblyopia treatment modalities. These factors may improve compliance in occlusion therapy.

Endothelin is a 21-residue peptide formed during incubation of isolated porcine endothelial cells. Due to its pronounced vasoconstrictor activity, endothelin has been proposed to play a role in the regulation of vascular tone. We studied the effects of synthetic endothelin (0.1-10 nM) on coronary flow, mechanical performance, myocardial oxygen uptake, and formation of purines, and outflow of 6-ketoprostaglandin F1 alpha (metabolite of prostacyclin) in rabbit hearts perfused with saline by the Langendorff method. Endothelin dose-dependently decreased the coronary flow, at 10 nM, by about 75%. Heart rate, ventricular contractility, myocardial oxygen uptake, and purine release were affected by endothelin no more than by a corresponding mechanical reduction of the coronary flow. In contrast, the diastolic relaxation appeared to be directly diminished by endothelin. The concentration of 6-ketoprostaglandin F1 alpha in the cardiac effluent was dose-dependently elevated by about 14 times by endothelin (10 nM) (p less than 0.001). A corresponding mechanical restriction of the coronary flow insignificantly affected the effluent concentration of 6-ketoprostaglandin F1 alpha. The calcium channel blocker nifedipine (1 microM) completely abolished the decrease in diastolic relaxation induced by endothelin and markedly counteracted the peptide-induced increase in effluent concentration of 6-ketoprostaglandin F1 alpha, but did not affect the vasoconstrictor activity. These data demonstrate that endothelin induces vasoconstriction and facilitates the outflow of prostacyclin in the rabbit heart. In addition, the peptide appears to affect diastolic relaxation in this organ.

This report describes the implementation and use of a maltose-inducible system for regulated gene expression in Lactococcus lactis. The system was established using Green Fluorescent Protein as reporter. The transcription of a gene of interest from the inducible promoter of pLS1RGFP plasmid vector can be easily monitored by fluorescence spectroscopy and microscopy. As an example, the lactococcal ribonuclease III was overproduced in an active form.

The subchronic toxicity of ISIS 2302 and ISIS 3082, phosphorothioate oligonucleotides with antisense activity against human and murine ICAM-1 mRNA, respectively, was investigated in CD-1 mice. ISIS 2302 is currently in clinical trials as an anti-inflammatory agent. Because of the differences in mRNA sequence targets between humans and mice, ISIS 2302 has no pharmacologic activity in mice. ISIS 3082 was specifically designed to inhibit murine ICAM-1 and was included in this study to evaluate the effects of prolonged ICAM-1 inhibition. The oligonucleotides were administered by bolus i.v. injection (via tail vein) every other day for 27 days (14 doses) at dose levels of 0, 0.8, 4, 20, and 100 mg/kg per injection ISIS 2302 or 20 mg/kg per injection ISIS 3082. The basic group size consisted of 10 male and 10 female mice, which were sacrificed 2 days after the last dose and an additional 5 mice per sex in vehicle control and 100 mg/kg ISIS 2302 dose groups, which remained on study for a 28-day treatment-free period. No treatment-related deaths occurred during this study, and there were no effects of either oligonucleotide on body weight gain or food consumption. The most common changes observed in this study included a mixed mononuclear cell infiltrate seen in a number of organs or tissues, splenomegaly, and lymphoid hyperplasia at dose levels of > or = 20 mg/kg ISIS 2302. In the group that received the highest dose level of ISIS 2302 (100 mg/kg), there were alterations in serum chemistry parameters that appeared to be related to perturbations in the liver, including 3- to 4-fold increases in aspartate and alanine aminotransferase and smaller changes in bilirubin, alkaline phosphatase, cholesterol, triglycerides, and albumin levels. Treatment-related effects on hematologic parameters were limited to the 100 mg/kg ISIS 2302 dose group and included slight monocytosis and thrombocytopenia. None of the effects observed appeared to be life threatening. Complete or partial reversal of all effects was evident in the remaining high-dose ISIS 2302 animals at the end of the 4-week recovery period. Comparison of the effects produced by the same dose level (20 mg/kg) of ISIS 2302 and ISIS 3082 did not reveal any differences that could be attributed to exaggerated pharmacology. In conclusion, treatment-related alterations were observed primarily at the 100 mg/kg dose level, including immune stimulation and hepatic alterations, which were partially reversed following a 4-week treatment-free period.

OBJECTIVE: To describe the anatomic variety of congenital cervical atresia and to explore the relationship between this disorder and pelvic endometriosis.METHODS: In a retrospective study, records were reviewed for 96 patients with a confirmed diagnosis of congenital cervical atresia treated at a center in Beijing, China, between January 1984 and October 2014. Data on demographic parameters, symptoms, anatomic features, and endometriosis were obtained and analyzed.RESULTS: Of the 96 patients, 54 (56%) had pelvic endometriosis, 23 (24%) had a uterine malformation, 75 (78%) had a vaginal malformation, and 12 (13%) had a urinary malformation. The patients with a delay from first symptoms to surgery of more than 1year had a higher incidence of endometriosis than did those with a delay of 1year or less (45/71 [63%] vs 7/23 [30%]; P=0.006), and this trend was not related to the severity of endometriosis (P=0.658). Among the 31 patients with unilateral endometrial cysts, 20 (65%) had left-sided cysts and 11 (35%) had right-sided cysts (P=0.005).CONCLUSION: More than half of patients with congenital cervical atresia had pelvic endometriosis. Early diagnosis and surgery seem to be necessary to prevent endometriosis among patients with congenital cervical atresia.

Complement C3 glomerulopathy refers to a disease process in which abnormal control of complement activation or degradation results in predominant C3 fragment deposition within the glomerulus and causes glomerular damage. Abnormal control of the complement alternative pathway is a well-established risk factor for the occurrence of C3 glomerulonephritis. It is the first reported case in Iran with multiple mutations in complement factor H, with one of these mutations we have expected in hemolytic uremic syndrome rather than C3 glomerulopathy Genetic analysis showed that the molecular abnormalities of factor H led to complement factor H malfunction that were polymorphous and not restricted to the C-terminal domains of the protein.

BACKGROUND: Although surgical studies have reported inconsistent associations between increased body mass index (BMI) and operative outcomes, the accuracy of BMI for measuring obesity has been questioned in previous epidemiologic studies. Simultaneously, BMI has known comorbidities, which may mediate the effect of BMI if included in multivariable models. We sought to examine the effect of BMI on operative outcomes after adjusting for preoperative factors.METHODS: We identified 8858 patients who underwent major thoracic, abdominal, and pelvic surgery for solid organ tumors in American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) centers from 2005 to 2007. We used multivariable analyses to assess the effect of BMI on short-term operative outcomes after controlling for covariates.RESULTS: Increased BMI was not associated with worse short-term operative outcomes in our bivariable analyses. However, patients with BMI > or = 35 had higher American Society of Anesthesiologists scores, longer operative times, and an increased number of postoperative complications (P < 0.0001). After adjusting for pre- and intraoperative factors, BMI did not predict any short-term operative outcome except for an increased total number of complications in BMI > or = 35. These results persisted after removing potential mediators from the multivariable analysis.CONCLUSIONS: In ACS NSQIP, BMI has minimal association with short-term operative outcomes after major cancer surgery. Although these findings may suggest a lack of association between obesity and cancer surgery outcomes, it confirms the previously examined limitations of BMI. Because of the rising incidence of obesity in the United States and its challenging effect on surgeon's practice, ACS NSQIP should consider exploring alternative measures of general and abdominal obesity.

Although psychosocial evaluations for implantable pain devices have been consensus recommendations since the 1990s, there is an inconsistent support regarding their ability to identify suitable pain device candidates or to predict clinical outcomes. With the emergence of evidence-based practices and the recent release of pain management guidelines emphasizing functional improvements and safety, the disparity between the recommendations for implantable pain device psychosocial evaluations and the evidence supporting them has only grown. In this special report, we describe a revised model for conducting psychosocial evaluations among implantable pain device candidates. This model includes changes to increase the evidence-basis of the psychosocial evaluations, incorporate patient-centered care standards and harmonize the evaluation structure with the most current pain management guidelines.

Accurate estimation of the liver volume may be important for the diagnosis of several pathological processes in patients and for the study of new therapies in experimental oncology. Although sonography and computed tomography (CT) have been used for this purpose in patients, the lack of spatial resolution and tissue differentiation is a source of measurement errors which, at present, makes it impossible to accept sonography and CT widely for the determination of the liver volume. In the present study, the liver volumes of seven rats were measured by magnetic resonance imaging (MRI) and an automated image analysis system before and after the animals were killed. Volume computation was carried out by adding up the individual volumes in the sequential MR sections. Adequate MR images with high contrast between the liver and surrounding structures were obtained with spin echo pulse sequence and retarded phase encoding while no contrast material was used. The mean volumes of the livers measured by MR in vivo and in cadavers were 11.91 +/- 0.40 and 11.92 +/- 0.45 ml, respectively. When compared with the actual liver volumes measured in vitro after resection, the errors of determinations in vivo and in cadavers were as small as 3.1 and 2.1%, respectively. These data indicate that MR imaging is an accurate means to determine the liver volume in vivo and that it may be potentially useful to measure small intrahepatic lesions in patients.

A case of an unusual hypertrophic gastropathy confined to the gastric antrum which presented with chronic anaemia is described. The clinical and pathological features are contrasted with Menetrier's disease and hypersecretory hypertrophic gastropathy, and a possible relation to solitary hyperplastic (regenerative) polyps is discussed.

The present work studies the characterization of the pharmacokinetic profile of paracetamol following oral administration of DUOROL tablets containing 500 mg of the active compound. Analysis is made of the influence of statistical weighting on the selection of the pharmacokinetic model chosen. In the model proposed, the uptake of the drug into the systemic circulation is described by two first-order sequential kinetic processes. The values of the first order rate constants that define the absorption process have values of 4.79 and 9.73 h-1. Validation of the absorption model proposed was performed by applying the Wagner-Nelson method, according to which values of 4.63 and 10.95 h-1 were obtained for each of the constants defining the uptake of the drug into the systemic circulation.

The interactions between HCN and reduced graphene oxides (rGO) are investigated using first-principles calculations with M06-2X functional. The results show that the adsorption of HCN on rGO is generally stronger than that on graphene, which is due to the presence of the active defect sites in rGO, such as the hydroxyl, epoxide, and carboxyl functional groups and even the carbon atom near these groups. The interaction between HCN and rGO with oxygen-containing group can result in the formation of hydrogen bonds, N · · · H and O · · · H. The adsorption of HCN on rGO depends on the type and location of oxygen-containing group in rGO. Carboxyl group on rGO is much more attractive for HCN than hydroxyl and epoxide group. The adsorption of HCN is much stronger in rGO with oxygen-containing group on the surface than that at the edge. The adsorption of HCN on rGO with carboxyl attached to vacancy on the surface is the strongest.

The phosphodiesterase 4 inhibitor cilomilast demonstrated strong inhibitory effects in a model of allergic contact dermatitis. In this study, we examined whether this inhibitory effect is at least partly due to modulation of dendritic cell function. Bone marrow-derived dendritic cells were pulsed with the sensitizer toluene-2,4-diisocyanate and administered subcutaneously to nonsensitized mice. Five days later, the mice were challenged with a low dose of toluene-2,4-diisocyanate onto the ears. In contrast to sham-treated mice, mice obtaining toluene-2,4-diisocyanate pulsed dendritic cells showed a significant increase in ear swelling. This swelling was not influenced when the dendritic cells were pre-incubated with cilomilast. When cilomilast was administered systemically simultaneously to the application of toluene-2,4-diisocyanate pulsed cells, there was an impaired allergic reaction provoked 5 days later. Additionally, a topical treatment with cilomilast resulted in a significant inhibition of skin dendritic cell migration. These results indicate that the antigen-presenting function of dendritic cells is not influenced by cilomilast but the dendritic cell T cell interaction and dendritic cell migration is modulated.