The identification of halogenated disinfection by-products in tap water using liquid chromatography-high resolution mass spectrometry.
In this paper, a comprehensive method for the identification of the unknown halogenated DBPs (X-DBPs, X = Cl, Br, and I) in the tap water of Wuhan, China via liquid chromatography-high resolution mass spectrometry (LC-HRMS) was developed. 123 X-DBPs were identified through the stepwise procedure, 94 of them were newly identified, and 3 of them were confirmed by standards. Most X-DBPs were aliphatic compounds and highly unsaturated and phenolic compounds, some X-DBPs contained multiple halogen atoms and rich in carboxyl groups, such as C2H2O2BrCl, C2H2O2Br2, and C2H2O2ClI. It was worth noting that the concentration of some X-DBPs had the same trend with time. Most Cl-DBPs remained stable and I-DBPs were detected occasionally by monitoring the change of concentration of these X-DPBs with the time during three consecutive months. The results demonstrate that the proposed method could provide valuable molecular formula and structure information on unknown multiple halogenated DBPs, or be used for the identification of other multiple halogenated organic compounds in different media.


Mechanism of interferon action. Kinetics of induction of the antiviral state and protein phosphorylation in mouse fibroblasts treated with natural and cloned interferons.
The induction of phosphorylation of both protein P1 and protein synthesis initiation factor eIF-2 alpha and the inhibition of virus replication were examined in mouse L929 fibroblasts treated with either natural mouse or individual cloned human interferons (IFN). Natural mouse IFN synthesized in Newcastle disease virus-induced L929 cells and two cloned human leukocyte IFN subspecies synthesized in Escherichia coli, IFN-alpha D and IFN-alpha A/D, possessed antiviral activity in L929 cells as measured by single cycle virus yield reduction with both vesicular stomatitis virus and reovirus. Natural L929 IFN and cloned IFNs, alpha D and alpha A/D, also induced the protein kinase that catalyzed the phosphorylation of endogenous ribosome-associated protein P1 and the alpha subunit of purified initiation factor eIF-2. Two other cloned human IFNs, alpha A and alpha D/A, were poor inducers of both the antiviral state and the phosphorylation of P1 and eIF-2 alpha in mouse L929 cells. The ability of individual human IFN-alpha subspecies to induce P1 and eIF-2 alpha phosphorylation in mouse L929 cells correlated with their ability to induce an antiviral state. Furthermore, the detailed kinetics of induction, in mouse L929 cells, of P1 and eIF-2 alpha phosphorylation and of the antiviral state by the heterologous cloned human IFN-alpha A/D were equivalent to the kinetics of induction by the homologous natural mouse L929 IFN. These results suggest that different subspecies of biologically active IFN induce equivalent antiviral activities and biochemical changes in mouse L929 cells, and that protein phosphorylation may play a major role in the antiviral mechanism of IFN action in mouse L929 fibroblasts.


Specific inhibition of epidermal growth factor receptor tyrosine kinase by 4-anilinoquinazolines.
Since the mitogenic action of EGF is mediated by ligand-induced autophosphorylation of the EGF receptor (EGFR), and EGFR is commonly overexpressed in solid human tumours, inhibitors of receptor tyrosine kinase activity (RTK) could prove to be effective antitumour agents. Screening of a compound library using an EGF-RTK enzyme prepared from human tumour derived A431 cells identified a series of potent (IC50 < 1 microM) enzyme inhibitors. These inhibitors are quinazolines bearing a variety of substituted anilines at the 4-position. The most potent 4-anilinoquinazolines (IC50 approximately equal to 20 nM) have small non-polar meta substituents on the aniline ring, and are competitive with ATP and non-competitive with substrate. The growth inhibitory activity of these agents was assessed in vitro using KB cells (human oral squamous tumour) grown in the absence or presence of EGF. A selected compound, 4-(3-chloroanilino)quinazoline (CAQ), inhibited EGF-stimulated growth in a concentration dependent manner and complete blockade was observed at concentrations (1-10 microM) which had no effect on basal growth. Selectivity of growth inhibition by CAQ was further exemplified in IGF1-stimulated KB cells where no effect was detected at concentrations which completely blocked EGF-stimulated growth. Similarly, CAQ blocked TGF alpha-stimulated growth in MCF-7 human breast cancer cells without affecting insulin-stimulated growth. These studies define a novel class of EGF-RTK inhibitors which are also potent and selective inhibitors of EGF-stimulated human tumour cell growth in vitro.


[Test-retest reliability of the Freiburg monosyllabic speech test].
ISO 8253-3 describes the requirements for speech tests used in audiology. One aspect is the test-retest reliability, which was here examined for the Freiburg monosyllabic speech test. Speech recognition scores were examined for 30 listeners with normal hearing ability. All 20 lists of the Freiburg monosyllabic speech test were tested at four different presentation levels. The retest was carried out 7-9 months later. The test-retest reliability of the Freiburg monosyllabic speech test in this study is between 13 percentage points for a speech recognition score of 95 %, and 24 percentage points for a speech recognition score of 39 %. The measurement accuracy can be estimated using binomial distribution. The reproducibility of the results is limited by the small number of test items (20 words) in each list. This does not fulfill the requirements for speech tests in diagnostics and rehabilitation. An improvement of the test-retest reliability can be achieved using several test lists.


Television watching, videogames, and excess of body fat in Spanish adolescents: the AVENA study.
We assessed the individual association of sedentary behaviors with the risk of overweight and excess body fat (overfat) in adolescents. A representative sample (1960 subjects, 1012 males, age 13-18.5 y) of Spanish adolescents was studied within the framework of the Alimentación y Valoración del Estado Nutricional de los Adolescentes (AVENA) study. Television (TV) watching, videogame and computer usage, doing homework, and the way students got to school, physical activity, and socioeconomic status were analyzed. Anthropometrics were measured to describe overweight (International Obesity Task Force cutoffs for body mass index) and overfat (body fat percentage >85th percentile). When all subjects were considered as an entire group, the overweight risk increased by 15.8% (P < 0.05) per increasing hour of TV watching. The overweight risks decreased by 32.5% in females, 22% per increasing year of age, and 12.5% by increasing socioeconomic status by 1 U (all Ps < 0.05). The obesity risks decreased with age by 17.8% per year in males and 27.1% in females (both Ps < 0.05). The overfat risks increased by 26.8% and 9.4% per increasing hour of TV and weekend videogame usage, respectively (both Ps < 0.05). In males, the overfat risk increased by 21.5% per increasing hour in weekend videogame usage (P < 0.05). Each hour of TV use increased the overfat risks by 22% in males and 28.3% in females (both Ps < 0.05). Time spent watching TV increased the risk of overweight and obesity in Spanish adolescents, but the effect was influenced by age, sex, and socioeconomic status. Moreover, an excess of body fat was more directly explained by the time spent watching TV and playing videogames during the weekend.


Transcriptional repression of ceramide kinase in LPS-challenged macrophages.
Ceramide kinase (CERK) produces the bioactive lipid ceramide 1-phosphate (C1P). Both CERK and C1P have been identified as mediators of cell growth and survival. Recent evidence showed that CERK is down-regulated during M1-type macrophage activation, which is known to promote cell growth arrest. However, the mechanism has not been investigated yet and, in particular, whether growth arrest might be the signal for down-regulation of CERK is currently unknown. Here, we found that LPS-mediated TLR-4 engagement reduces Cerk mRNA levels in mouse primary macrophages. Reporter gene assays in RAW264.7 macrophages showed that LPS inhibits the transcriptional activity of the Cerk proximal promoter. The G1-cell cycle blocker mimosine did not inhibit Cerk transcription, suggesting that transcriptional repression of Cerk by LPS is not a primary consequence of LPS-induced cell cycle blockade.


Vascular changes in hypertension. Therapeutic implications.
A review of the general nature of cardiovascular structural adaptation and how this per se normal process becomes of key haemodynamic importance for the development of primary hypertension, particularly with respect to the gradual elevation of systemic precapillary resistance is presented. Because of the structural 'upward resetting' of the haemodynamic equilibrium, antihypertensive therapy in reality faces a far more formidable task in chronic hypertension than merely 'normalising' a supposedly raised vascular smooth muscle activity or/and cardiac output. Rather, it must bring about sub-normal activity levels to normalise the arterial pressure level, and only when such a pressure lowering has been sustained enough to allow for structural regression towards normal dimensions is a true normalisation achieved. However, the process of structural regression takes time and is complicated by the fact that the often long duration of the high-pressure state has led to structural changes which can be quite difficult to reverse. Finally, physiological-haemodynamic reasons are discussed which direct pharmacological interferences preferentially towards the pronounced myogenic activity of the precapillary resistance vessels, which both in normo- and hypertension is by far the most dominating element behind resting smooth muscle activity in these vessels and is, moreover, especially dependent on influx of external calcium ions. As the raised precapillary resistance (by means of 'structural autoregulation') represents the key element behind the pressure rise in established hypertension, such a pharmacological interference is directed towards the proper haemodynamic site and would not directly interfere with the neurohormonal integrative control of the circulation.


Histogenesis of early preneoplastic lesions induced by N-nitrosobis(2-oxopropyl)amine in exocrine pancreas of hamsters.
The histogenesis of early putative preneoplastic lesions, arising in exocrine pancreas of Syrian hamsters after treatment with N-nitrosobis(2-oxopropyl) amine (BOP), was evaluated using electron microscopy and immunohistochemistry. Electron microscopical examination of pseudoductular lesions, present in hamster pancreas 2-4 mo after treatment with BOP, demonstrated that acinar cells forming part of these lesions frequently lose their zymogen granules. However, convincing evidence of dedifferentiation of acinar cells to proliferating ductal/ductular cells was not found. Most ductal/ductular cells of the BOP-induced pseudoductular lesions stained positively with cytokeratins specific to ductal/ductular cells. Acinar cells were all negative and, moreover, those lining the pseudoductular lesions were frequently surrounded by cytoplasmic processes of adjacent cells that stained strongly positive with the cytokeratin antibody. The present findings indicate that the early pseudoductular lesions, induced in exocrine pancreas of hamsters by BOP, originate from proliferating ductal/ductular rather than proliferating dedifferentiated acinar cells.


Overview of gastroduodenal mucosal protection.
The ability of the gastric mucosa to resist autodigestion has been recognized for over 200 years. Since these early observations, several components of gastroduodenal defense against injury from damaging luminal contents have been identified. The first line of defense is the thick layer of mucus gel into which bicarbonate is secreted by the underlying epithelial cells. The "mucus-bicarbonate" barrier sustains a pH gradient between the lumen and cell surface such that epithelial cells are maintained at pH 7 to 8, despite the presence of intraluminal acid. The epithelial cells form a second line of defense; since the pH gradient may be overwhelmed by physiologic concentrations of intraluminal acid, this mechanism may be important in maintaining mucosal integrity. The physical properties of the apical cell membrane and intercellular junctions and the presence of surface-active phospholipids on the membrane may be responsible for preventing hydrogen ions (H+) from diffusing into the mucosa by providing a physical barrier to their movement. Furthermore, epithelial cells are capable of rapid turnover and migration and may breach a defect in the epithelium within hours. The aftermath of mucosal damage may generate a further defense mechanism: a thick layer of mucus containing sloughed epithelial cells together with passive movement of bicarbonate-rich fluid from the damaged mucosa. This may prevent exposure of undamaged cell nests to acid and thus aid re-epithelialization. Finally, mucosal blood flow plays a vital role in maintaining epithelial integrity. Studies have shown that increasing or decreasing mucosal blood flow will, respectively, reduce or enhance susceptibility to damage. Although the precise physiologic control mechanisms for mucosal protection have not been defined, there is evidence that local endogenous prostaglandin metabolism may play an important role [4]. The release of neurotransmitters and hormones may also contribute to or modulate the defense mechanisms.


Doppler ultrasound compatible plastic material for use in rigid flow models.
A technique for the rapid but accurate fabrication of multiple flow phantoms with variations in vascular geometry would be desirable in the investigation of carotid atherosclerosis. This study demonstrates the feasibility and efficacy of implementing numerically controlled direct-machining of vascular geometries into Doppler ultrasound (DUS)-compatible plastic for the easy fabrication of DUS flow phantoms. Candidate plastics were tested for longitudinal speed of sound (SoS) and acoustic attenuation at the diagnostic frequency of 5 MHz. Teflon was found to have the most appropriate SoS (1376 +/- 40 m s(-1) compared with 1540 m s(-1) in soft tissue) and thus was selected to construct a carotid bifurcation flow model with moderate eccentric stenosis. The vessel geometry was machined directly into Teflon using a numerically controlled milling technique. Geometric accuracy of the phantom lumen was verified using nondestructive micro-computed tomography. Although Teflon displayed a higher attenuation coefficient than other tested materials, Doppler data acquired in the Teflon flow model indicated that sufficient signal power was delivered throughout the depth of the vessel and provided comparable velocity profiles to that obtained in the tissue-mimicking phantom. Our results indicate that Teflon provides the best combination of machinability and DUS compatibility, making it an appropriate choice for the fabrication of rigid DUS flow models using a direct-machining method.


Evaluation of oral and topical bovine colostrum compared to mesalamine in the treatment of animal model of acetic acid-induced ulcerative colitis.
Oxidative activity and inflammatory responses have been shown to play a pivotal role in the pathogenesis of ulcerative colitis (UC). Colostrum is a natural product with anti-inflammatory and antioxidative properties. UC was induced in 37 Sprague Dawley rats by administration of a 2 mL enema of 3% acetic acid (AA). The control groups received no treatment during the study, while the experimental groups received either oral or rectal administration of 100 mg/kg 5-aminosalicylic acid, or oral or rectal administration of 300 mg/kg of colostrum. Histopathological and serological analyses were performed 7 days following treatment. A significant decrease in weight was seen in all rats except for the test groups receiving colostrum (P<0.001). After treatment, the level of superoxide dismutase increased more significantly in the test groups that received colostrum (P<0.05). All test groups had a reduction in C-reactive protein and white blood cell levels. The colostrum test groups also showed a decrease in inflammation rate, ulceration, destruction, disorganization, and crypt abscess of the colonic mucosa. The findings of this study show that the administration of colostrum can improve the pathological changes of the intestinal mucosa, as well as inflammatory responses, in animal models of UC. Further studies at both preclinical and clinical levels are suggested to confirm these findings.


Resident vascular progenitor cells.
Homeostasis of the vessel wall is essential for maintaining its function, including blood pressure and patency of the lumen. In physiological conditions, the turnover rate of vascular cells, i.e. endothelial and smooth muscle cells, is low, but markedly increased in diseased situations, e.g. vascular injury after angioplasty. It is believed that mature vascular cells have an ability to proliferate to replace lost cells normally. On the other hand, recent evidence indicates stem/progenitor cells may participate in vascular repair and the formation of neointimal lesions in severely damaged vessels. It was found that all three layers of the vessels, the intima, media and adventitia, contain resident progenitor cells, including endothelial progenitor cells, mesenchymal stromal cells, Sca-1+ and CD34+ cells. Data also demonstrated that these resident progenitor cells could differentiate into a variety of cell types in response to different culture conditions. However, collective data were obtained mostly from in vitro culture assays and phenotypic marker studies. There are many unanswered questions concerning the mechanism of cell differentiation and the functional role of these cells in vascular repair and the pathogenesis of vascular disease. In the present review, we aim to summarize the data showing the presence of the resident progenitor cells, to highlight possible signal pathways orchestrating cell differentiation toward endothelial and smooth muscle cells, and to discuss the data limitations, challenges and controversial issues related to the role of progenitors. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".


Care coordination and unmet need for specialised health services among children with special healthcare needs in the USA: results from a cross-sectional analysis of the national survey of children with special healthcare needs.
To report rates of need and unmet need for specialised health services (occupational and speech therapies, durable medical equipment, home healthcare, and mobility and communication aids) from the National Survey of Children with Special Health Care Needs (CSHCN) (2009/2010) and assess the role of care coordination in having needs met. We distinguish between CSHCN with and without emotional, behavioural and developmental disorders (EBDPs) in the USA. A cross sectional cohort study of a nationally representative sample of CSHCN from the National Survey of CSHCN for 2009/2010 used logistic regression to assess the relationship between EBDPs and need and unmet need for specialised services. It also estimates the association of care coordination with unmet need for all services, for CSHCN with and without EBDPs. A nationally representative sample of CSHCN in the USA. Children ages 0-17 years of age. Across all specialised health services, rates of unmet need were at or below 25%. Need and unmet need for most services was higher among CSHCN with EBDPs than those without. For CSHCN with and without EBDPs, adequate care coordination was associated with greater probability of having needs for therapy, home health and communication aids met. Care coordination is essential to reducing barriers to a wide range of healthcare services for CSCHN. Policies requiring adequate insurance coverage for care coordination may play a critical role in ensuring access to specialised health services.


Bamboo charcoal addition enhanced the nitrogen removal of anammox granular sludge with COD: Performance, physicochemical characteristics and microbial community.
The effects of different chemical oxygen demand (COD) concentrations on the anammox granular sludge with Bamboo Charcoal (BC) addition were evaluated in UASB reactor. The results showed that the average total nitrogen (TN) removal efficiency was reduced from 85.9% to 81.4% when COD concentration was increased from 50 to 150 mg/L. However, the TN removal efficiency of BC addition reactors was dramatically 3.1%-6.4% higher than that without BC under different COD concentrations. The average diameter of granular sludge was 0.13 mm higher than that without BC. The settling velocity was increased by elevated COD concentration, while the EPS and VSS/SS were increased with BC addition. The high-throughput Miseq sequencing analyses revealed that the bacterial diversity and richness were decreased under COD addition, and the Planctomycetes related to anammox bacteria were Candidatus Brocadia and Candidatus Kuenenia. The Metagenomic sequencing indicated that the abundance of denitrification related functional genes all increased with elevated COD, while the abundance of anammox related functional genes of decreased. The functional genes related to anammox was hydrazine synthase encoding genes (hzsA, hzsB and hzsB). The average relative abundance of hzs genes in the reactor with BC addition was higher than the control at COD concentrations of 50 mg/L and 150 mg/L. The functional genes of denitrification mediated by BC were higher than those without BC throughout the operation phase. It is interesting to note that BC addition greatly enriched the related functional genes of denitrification and anammox.


Aboriginal communities need to be at the forefront of the COVID-19 vaccination campaign.
To ensure that Aboriginal and Torres Strait Islander people are vaccinated it is essential to engage, work and consult with and listen to Aboriginal and Torres Strait Islander communities.


MA-QC: Free online software for prostate MR quality control and PI-QUAL assessment.
To validate MRI Analyzer Quality Control (MA-QC), a free and open-source online software designed to facilitate MR data acquisition quality control and PI-QUAL score calculation. MA-QC is a web-based software, designed for analysing DICOM data related to MR acquisition parameters. The software allows automatic extraction of 18 technical criteria, and manual input of 12 visual criteria, to calculate the PI-QUAL score. We collected 100 prostate MRI datasets from four MR device manufacturers to test data compatibility, automatic sequence recognition, and robustness of technical criteria extraction from DICOM data. The main issue was to determine the spatial resolution in the phase and frequency directions, due to variable encoding of the DICOM datasets. Acquisition data could be extracted from all sample examinations (100%), with a median analysis speed of 15.2 ± 4.4 images per second and mean processing time of 96 [11-326] seconds per examination. MA-CQ automatically detected the optimal T2-w, DWI and DCE sequences in 71 out of 100 (71%) cases, and required manual selection of at least one sequence in 29 out of 100 (29%) cases to get the best parameters. Display of technical criteria for the 3 sequences was instantaneous. PI-QUAL score could be calculated in all cases. This software brings substantial help in the quality assessment of prostate MRI examinations, by providing fast extraction of series data and the 18 technical parameters of PI-QUAL. PI-QUAL scoring can be performed in less than two minutes, helping to focus on the visual criteria, allowing use of this software in the clinical workflow in the aim of improving overall image quality in prostate MR imaging.


Comparative study of PMS oxidation with Fenton oxidation as an advanced oxidation process for Co-EDTA decomplexation.
In nuclear industry, Co-EDTA complex is generated due to the decontamination activities of nuclear power plants (NPPs). This complex is extremely refractory to the convention methods and can escalate the mobility of Co radionuclide in the environment. Due to its hazardous impact on human and environment, the effective treatments of Co-EDTA complexes are highly recommended. In this study, for the first time, we applied both hydroxyl (OH) and sulfate radical (SO4-) based advanced oxidation processes (AOPs) namely Fenton and peroxymonosulfate (PMS) reactions for the Co-EDTA decomplexation. Both reactions exhibited higher Co-EDTA decomplexation at pH = 3, however, the PMS based reaction was found to be superior, which showed highest decomplexation efficiency (without pH adjustment) over Fenton reaction (pH = 1-13). Moreover, PMS based system was found to be more suitable than Fenton reaction, because PMS showed best Co-EDTA decomplexation efficiency without any additional catalyst dosages at the shorter reaction time. XRD data confirmed the presence of both CoO and Co(OH)2 in the precipitates after treatment. The electron spin resonance spectroscopy (ESR) analysis identified OH and SO4- in Fenton and PMS system, respectively. From this study, we believe that PMS based reaction is a superior alternative of Fenton reaction for the Co-EDTA decomplexation.


Delineating apathy profiles in Huntington's disease with the short-Lille Apathy Rating Scale.
Apathy, a prevalent feature in neurological disorders including Huntington's disease (HD), is characterized by a reduction in goal-directed behavior across cognitive, auto-activation (i.e., self-activating thoughts/behavior), and emotional domains. Nonetheless, current diagnostic criteria are incapable of distinguishing multidimensional apathy profiles. Meanwhile, the short-Lille Apathy Rating Scale (LARS-s) bears potential as an operative diagnostic tool to disentangle apathy dimensions in clinical practice. The present study thereby examines the psychometric properties and factor structure of the LARS-s to tap into apathy profiles and their underlying neural correlates in HD. Forty HD individuals were scanned and evaluated for apathy using the LARS-s, assessed for reliability and validity in HD, and the short-Problem Behavior Assessment (PBA-s). To study the dimensional structure of apathy, principal component analysis (PCA) of the LARS-s was implemented. Resulting factors were associated with gray matter volume through whole-brain voxel-based morphometry. The LARS-s demonstrated satisfactory psychometric properties, sharing convergent validity with PBA-s apathy and discriminant validity against depression. PCA resulted in three factors representative of apathy profiles across cognitive, auto-activation, and emotional domains. Anatomically, global apathy was significantly related with large-scale motor, cognitive, and limbic networks. Exploratory analyses of apathy profiles revealed correspondence between each factor and distinct cortical and subcortical nodes. The LARS-s is capable of capturing the multidimensional spectrum of apathy. At the same time, apathy profiles in HD are underpinned by functionally diverse neural networks. Such findings promote the continued study of apathy domains to pinpoint personalized therapeutic targets in neurologic disorders in addition to HD.


Sex difference analyses under scrutiny.
A survey reveals that many researchers do not use appropriate statistical analyses to evaluate sex differences in biomedical research.


Novel multiplex PCR assay using locked nucleic acid (LNA)-based universal primers for the simultaneous detection of five swine viruses.
A novel multiplex PCR assay using non-homologous oligonucleotides with locked nucleic acid (LNA) modifications as universal primers was developed and validated for the simultaneous detection of five swine viruses. The assay utilizes five virus-specific primer pairs modified at the 5' end through the addition of the universal primer sequence. In the reaction, small amounts of target templates with the 5' tail were generated and subsequently amplified through the extension of a LNA universal primer set. To validate the specificity of this assay, 27 viral target strains and 12 non-target pathogens were tested. The lower limit of detection of viral nucleic acids was 1.1-1.9 pg per reaction or 11-32 pg in a five-plex viral nucleic acid mixture. The LNA mPCR assay displayed higher analytical sensitivity and efficiency for the detection of plasmid standards compared with the conventional assay, which uses standard primers without the 5' tail. A total of 207 field samples were tested using both assays. The LNA mPCR assay provided numerically higher detection rates for all pathogens in independent samples. Moreover, the LNA mPCR assay had significantly higher detection rates in independent samples compared with the conventional assay.


Prenatal assignation of lesion levels in neural tube defects by using ultrasonography. Case report and review of the literature.
Myelomeningoceles are routinely diagnosed prenatally by using ultrasonography. Because the level of the neural defect has been shown to correlate with functional and cognitive outcome in infants with myelomeningocele, it is of prognostic importance to identify the level prenatally. The authors report on a case in which the postnatal vertebral level of the myelomeningocele was more rostral than expected based on prenatal imaging.


[Nonsteroidal anti-inflammatory drug NS398 regulates the RECK gene expression in the prostate carcinoma strain DU145].
To investigate the regulative effect of the nonsteroidal anti-inflammatory drug NS398 on the RECK gene in the prostate carcinoma strain DU145. DU145 was treated with various concentrations of NS398 for 48 hours. The mRNA level was measured by RT PCR technique and the expression of the RECK protein determined by Western blot. The mRNA level of the RECK gene was obviously higher, while the MMP9 level markedly lower in the treated group than in the control, and so was the expression of the RECK protein. NS398 induces the expression of the RECK gene, which might be the mechanism of its anti-tumor effect.


Analysis of immune-related gene expression in chicken peripheral blood mononuclear cells following Salmonella enterica serovar Enteritidis infection in vitro.
We examined mRNA expression of eight genes, TLR4, TLR5, TLR15, interleukin (IL)-1β, IL-6, transforming growth factor-β4 (TGF-β4), CXCLi2, and a macrophage inflammatory protein (MIP) family chemokine called CCLi2, in peripheral blood mononuclear cells (PBMCs) isolated from the blood of chickens after in vitro exposure to Salmonella enterica serovar Enteritidis (SE). The chickens of four Chinese native lines, Qingjiaoma, Sanhuang, Wugu, and Xueshanma, were evaluated for mRNA expression levels at 2 and 4h post-infection using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). TLR4 and TLR15 mRNA were in particular highly expressed in PBMCs of Wugu and Xueshanma chickens exposed to SE, while TLR5 was expressed less in the Sanhuang chickens than in others. Breed effect was significant (P<0.05) for IL-1β, IL-6, CXCLi2, and CCLi2 mRNA expression, all of which were expressed to a greater extent in Wugu and Xueshanma than in the other two lines. These findings demonstrate the difference of mRNA expression profiles for innate immune molecules in PBMCs infected to SE among different lines.


Predicting domain-specific outcomes using delay and probability discounting for sexual versus monetary outcomes.
Discounting, the tendency to devalue an outcome as a function of its delay or probability, is emerging as a fundamental process that underlies a broad range of impulsivity-related behaviors. Recent research suggests that people discount the value of sexual outcomes and individual differences in rate of discounting of sexual outcomes may represent an important behavioral process that underlies sexual risk behavior. However, it is not clear that discounting the value of domain-specific sexual outcomes (e.g., sexual activity) is a better predictor of sexual behaviors than is discounting for domain non-specific outcomes (e.g., money). Adult undergraduates (n=103) completed delay and probability discounting procedures in relation to money and sexual activity and a series of self-report measures concerning sexual and non-sexual outcomes. Results revealed domain-specific relationships such that (1) discounting for sexual and monetary outcomes were significantly correlated; (2) discounting for sexual activity was significantly associated with sexual excitability, but not with non-sexual outcomes; and (3) discounting for money was not related to the sexual outcomes. A consistent gender effect across measures suggests that gender may moderate the relationships between discounting and sexual and non-sexual outcomes. The relevance of these findings for domain-specific discounting is discussed.


5-HT2A receptor gene polymorphism and eating disorders.
Recent studies have reported a genetic association between the -1438 G/A polymorphism within the promoter region of the 5-HT(2A) receptor gene and eating disorders (ED), with conflicting results. To clarify the role of the -1438 G/A polymorphism in different ED categories we have analyzed the genotype and allele frequency distribution in 54 Italian patients with Binge ED (BED) compared to 132 obese non-BED subjects. No significant differences were found between obese BED and obese non-BED individuals, suggesting that this polymorphism does not genetically distinguish these two phenotypes. Moreover, the evaluation of 148 patients with anorexia nervosa and 86 patients with bulimia nervosa revealed an association of the A allele with both these disorders.


New synchrotron radiation circular dichroism end-station on DISCO beamline at SOLEIL synchrotron for biomolecular analysis.
The novel Synchrotron Radiation Circular Dichroism (SRCD) technique is becoming a new tool of investigation for the molecular structures of biomolecules, like proteins, carbohydrates or others bio-materials. Here, we describe the characteristics of a new experimental end-station for circular dichroism studies, in construction on DISCO beamline at SOLEIL synchrotron (Saint-Aubin, France). This experimental end-station will be an open facility for the community of researchers in structural biology. In order to show the kind of information accessible with this type of technique, we give an example: the conformational study of the galactose mutarotase from Escherichia coli, an enzyme involved in the galactose metabolism. This study was made using an operational SRCD station available at SRS (Daresbury Laboratory, UK).


NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus.
Brief bath application of N-methyl-D-aspartate (NMDA) to hippocampal slices produces long-term synaptic depression (LTD) in CA1 that is (1) sensitive to postnatal age, (2) saturable, (3) induced postsynaptically, (4) reversible, and (5) not associated with a change in paired pulse facilitation. Chemically induced LTD (Chem-LTD) and homosynaptic LTD are mutually occluding, suggesting a common expression mechanism. Using phosphorylation site-specific antibodies, we found that induction of chem-LTD produces a persistent dephosphorylation of the GluR1 subunit of AMPA receptors at serine 845, a cAMP-dependent protein kinase (PKA) substrate, but not at serine 831, a substrate of protein kinase C (PKC) and calcium/calmodulin-dependent protein kinase II (CaMKII). These results suggest that dephosphorylation of AMPA receptors is an expression mechanism for LTD and indicate an unexpected role of PKA in the postsynaptic modulation of excitatory synaptic transmission.


FT-IR, FT-Raman spectra, density functional computations of the vibrational spectra and molecular conformational analysis of 2,5-di-tert-butyl-hydroquinone.
The purpose of finding conformer among six different possible conformers of 2,5-di-tert-butyl-hydroquinone (DTBHQ), its equilibrium geometry and harmonic wavenumbers were calculated by the B3LYP/6-31G(d,p) method. The infrared and Raman spectra of DTBHQ were recorded in the region 400-4000 cm(-1) and 50-3500 cm(-1), respectively. In addition, the IR spectra in CCl(4) at various concentrations of DTBHQ are also recorded. The computed vibrational wavenumbers were compared with the IR and Raman experimental data. Computational calculations at B3LYP level with two different basis sets 6-31G(d,p) and 6-311++G(d,p) are also employed in the study of the possible conformer of DTBHQ. The complete assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes, calculated using VEDA 4 program. The general agreement between the observed and calculated frequencies was established.


Nitrogen exchange across the sediment-water interface after dredging: The influence of contaminated riverine suspended particulate matter.
Dredging has been widely implemented in shallow lakes to reduce internal nitrogen (N) loading. The suspended particulate matter (SPM) coming from polluted rivers usually contains high levels of N and ultimately deposits on the dredged sediment surfaces near the river mouth. To study the influence of the riverine SPM on N exchange across the sediment-water interface (SWI) after dredging, a 360-day experiment was carried out comparing un-dredged and dredged sediments from Lake Chaohu, China. Dredged treatments showed a significant increase (p < 0.01) in total N concentrations in the sediments, while the deposition of SPM had little influence on labile NH4+-N concentrations. In addition, NH4+-N concentrations in pore-water and NH4+-N fluxes were significantly lower in dredged than in un-dredged sediments, despite the deposition of SPM. The oxygen production rates and the oxygen penetration depth in the dredged sediments were both higher than those in the un-dredged sediments. The increase of Nitrospira in dredged sediments was consistent with their decreased NH4+-N concentrations and fluxes across the SWI. Therefore, the oxidizing condition, increased oxygen production/consumption rates and Nitrospira relative abundance across the SWI were believed to be correlated with the low N exchange rates in dredged sediments. Dredging for reducing internal N loading in a river mouth area is therefore feasible, although the influence of the riverine SPM should be taken into account when aiming to achieve a long-term internal N loading reduction.


Identification and bioactivity evaluation of two novel temporins from the skin secretion of the European edible frog, Pelophylax kl. esculentus.
The amphibian temporins, amongst the smallest antimicrobial peptides (AMPs), are α-helical, amphipathic, hydrophobic and cationic and are active mainly against Gram-positive bacteria but inactive or weakly active against Gram-negative bacteria. Here, we report two novel members of the temporin family, named temporin-1Ee (FLPVIAGVLSKLFamide) and temporin-1Re (FLPGLLAGLLamide), whose biosynthetic precursor structures were deduced from clones obtained from skin secretion-derived cDNA libraries of the European edible frog, Pelophylax kl. esculentus, by 'shotgun' cloning. Deduction of the molecular masses of each mature processed peptide from respective cloned cDNAs was used to locate respective molecules in reverse-phase HPLC fractions of secretion. Temporin-1Ee (MIC = 10 μM) and temporin-1Re (MIC = 60 μM) were both found to be active against Gram-positive Staphylococcus aureus, but retaining a weak haemolytic activity. To our knowledge, Single-site substitutions can dramatically change the spectrum of activity of a given temporin. Compared with temporine-1Ec, just one chemically-conservative substitution (Val8 instead of Leu8), temporin-1Ee bearing a net charge of +2 displays broad-spectrum activity with particularly high potency on the clinically relevant Gram-negative strains, Escherichia coli (MIC = 40 μM). These factors bode well for translating temporins to be potential drug candidates for the design of new and valuable anti-infective agents.


Spatially structured yeast communities: Understanding structure formation and regulation with omics tools.
Single-celled yeasts form spatially structured populations - colonies and biofilms, either alone (single-species biofilms) or in cooperation with other microorganisms (mixed-species biofilms). Within populations, yeast cells develop in a coordinated manner, interact with each other and differentiate into specialized cell subpopulations that can better adapt to changing conditions (e.g. by reprogramming metabolism during nutrient deficiency) or protect the overall population from external influences (e.g. via extracellular matrix). Various omics tools together with specialized techniques for separating differentiated cells and in situ microscopy have revealed important processes and cell interactions in these structures, which are summarized here. Nevertheless, current knowledge is still only a small part of the mosaic of complexity and diversity of the multicellular structures that yeasts form in different environments. Future challenges include the use of integrated multi-omics approaches and a greater emphasis on the analysis of differentiated cell subpopulations with specific functions.


[Bipolar disorders in oncology: Characteristics and management].
Bipolar disorders belong to the spectrum of mood disorders and represent a serious psychiatric comorbidity. Behaviors adopted by bipolar patients can foster cancer occurrence but also impact its management, especially during acute depressive or manic episode. Oncologists must adapt their protocols in order to obtain the best compliance for treatment and avoid any possible mood destabilization, with the inherent risk of suicidal attempt. Potential interactions between mood-stabilizing agents (lithium, divalproate, atypical antipsychotics, and anticonvulsivants) and oncologic treatment (chemotherapy, targeted therapy, immunotherapy, corticotherapy) will be particularly watched. To do so, a closely collaboration with the oncopsychiatrist but also with the referent or liaison psychiatry team is necessary during the patient's oncologic care. Some clinical vignettes will illustrate the modalities of care of bipolar disorders in oncology.


A new Co(2)(CO8-mediated tandem [5 + 1]/[2 + 2 + 1]-cycloaddition reaction: a one-pot synthesis of tricyclic delta-lactones from cis-epoxy ene-ynes.
In the presence of Co2(CO)8 and CO, cis-epoxyalkynes bearing a tether olefin undergo a tandem [5 + 1]/[2 + 2 + 1]-cycloaddition to give tricyclic delta-lactones efficiently in a one-pot operation. The reaction mechanism is proposed to involve a cobalt-coordinated cyclic allene species.


Systematic analysis of genes required for synapse structure and function.
Chemical synapses are complex structures that mediate rapid intercellular signalling in the nervous system. Proteomic studies suggest that several hundred proteins will be found at synaptic specializations. Here we describe a systematic screen to identify genes required for the function or development of Caenorhabditis elegans neuromuscular junctions. A total of 185 genes were identified in an RNA interference screen for decreased acetylcholine secretion; 132 of these genes had not previously been implicated in synaptic transmission. Functional profiles for these genes were determined by comparing secretion defects observed after RNA interference under a variety of conditions. Hierarchical clustering identified groups of functionally related genes, including those involved in the synaptic vesicle cycle, neuropeptide signalling and responsiveness to phorbol esters. Twenty-four genes encoded proteins that were localized to presynaptic specializations. Loss-of-function mutations in 12 genes caused defects in presynaptic structure.


Associating the mesoscale fiber organization of the tongue with local strain rate during swallowing.
The tongue is an intricately configured muscular organ that undergoes a stereotypical set of deformations during the course of normal human swallowing. In order to demonstrate quantitatively the relationship between 3D aligned lingual fiber organization and mechanics during swallowing, the tissue's myoarchitecture and strain rate were imaged before and during the propulsive phase of a 3.0ml water bolus swallow. Mesoscale fiber organization was imaged with high-resolution diffusion tensor imaging (DTI) and multi-voxel myofiber tracts generated along maximum diffusion vectors. Tissue compression/expansion was obtained via lingual pressure-gated phase-contrast (PC) MRI, a method which determines local strain rate as a function of the phase shift occurring along an applied gradient vector. The co-alignment of myofiber tract direction and the localized principal strain rate vectors was obtained by translating the strain rate tensor into the reference frame with the primary axis parallel to the maximum diffusion vector using Mohr's circle, resulting in the generation of fiber-aligned strain rate (FASR). DTI tractography displayed the complete fiber anatomy of the tongue, consisting of a core region of orthogonally aligned fibers encased within a longitudinal sheath, which merge with the externally connected styloglossus, hyoglossus, and genioglossus fibers. FASR images obtained in the mid-sagittal plane demonstrated that bolus propulsion was associated with prominent compressive strain aligned with the genioglossus muscle combined with expansive strain aligned with the verticalis and geniohyoid muscles. These data demonstrate that lingual deformation during swallowing involves complex interactions involving intrinsic and extrinsic muscles, whose contractility is directed by the alignment of mesoscale fiber tracts.


[Chemical Constituents from Przewalskia tangutica].
To study the Chemical constituents from Przewalskia tangutica. The compounds were isolated and identified from n-butanol extract of Przewalskia tangutica by various chromatographic and spectral techniques. Twelve polar compounds were isolated and identified as scopolin( 1),fabiatrin( 2),rutin( 3),queroetin-3-O-rutinoside-7-O-β-D-glucopyranoside( 4),protocatechuate( 5),vanillic acid( 6),thymine( 7),uracil( 8),cytosine( 9),adenine( 10),uridine( 11) and adenosine( 12). Compounds 3 ~ 5,8 ~ 12 are obtained from Przewalskia tangutica for the first time.


Two sides of the same coin? Empirical examination of two proposed characterizations of acute suicidal crises: Suicide crisis syndrome and acute suicidal affective disturbance.
Two proposed suicide-specific diagnoses, with accumulating research support, characterize the phenomenology of acute suicidal crises: Suicide Crisis Syndrome (SCS) and Acute Suicidal Affective Disturbance (ASAD). Despite conceptual overlap and some similar criteria, the two syndromes have never been compared empirically. The present study addressed this gap by examining SCS and ASAD utilizing a network analysis approach. A sample of 1568 community-based adults (87.6% cisgender women, 90.7% White, Mage = 25.60 years, SD = 6.59) in the United States completed an online battery of self-report measures. SCS and ASAD were first examined in individual network models, followed by a combined network to determine changes in network structure, as well as identify bridge symptoms that connected SCS and ASAD. The proposed criteria of SCS and ASAD formed sparse network structures that were largely unaffected by the influence of the other syndrome in a combined network. Social disconnection/withdrawal and manifestations of overarousal-particularly agitation, insomnia, and irritability-emerged as bridge symptoms that may connect SCS and ASAD. Our findings indicate the network structures of SCS and ASAD exhibit patterns of independence, alongside interdependence between overlapping symptom domains (i.e., social withdrawal, overarousal). Future work should examine SCS and ASAD prospectively to better understand their temporal dynamics and predictive utility in relation to imminent suicide risk.


Sample size determination for estimation of the accuracy of two conditionally independent tests in the absence of a gold standard.
We developed an Excel spreadsheet template (available at http://www.epi.ucdavis.edu/diagnostictests/) to calculate sample sizes to estimate sensitivity and specificity with desired precision in the absence of a gold standard. Calculations are predicated on the use of two conditionally independent tests for screening animals from two populations and are based on the methods of Hui and Walter(1980). Sample size calculations rely on asymptotic normality of maximum likelihood (ML) estimates of parameters. Spreadsheets for calculating standard errors for the parameter estimates and for providing ML estimates using cross-tabulated data also are included. An example of application of the methods to bovine paratuberculosis is presented.


Prognostic significance of the preoperative platelet-lymphocyte ratio in nonmetastatic renal cell carcinoma: cross-sectional study.
The prognostic significance of the platelet-lymphocyte ratio (PLR) in nonmetastatic renal cell carcinoma (RCC) is controversial, although it has been established as a prognostic factor in several cancers. The objective of our study was to evaluate the prognostic significance of the PLR in patients with nonmetastatic RCC. The authors performed a retrospective analysis of patients with nonmetastatic RCC who were operated between 2004 and 2020. Five years recurrence-free survival and metastasis-free survival were calculated. The prognostic significance of the preoperative PLR was assessed. The Kaplan-Meier method was utilized to graphically display survivor functions. Univariate and multivariate Cox's proportional hazards regression models were utilized to analyze the association between PLR and oncological outcomes. Differences were considered significant if P<0.05. Two hundred and two patients were included. The mean follow-up was 56.8±3 months. Patients with a higher PLR had larger tumors (P=0.02), higher ASA score (P=0.001), symptomatic forms (P=0.01), and more frequent tumor necrosis (P=0.02). Recurrence-free survival and metastasis-free survival rates were significantly lower in patients with high PLR than in those with low ratios (each P<0.005). Multivariate analysis identified PLR as an independent predictor of recurrence-free survival (P=0.002) and metastasis-free survival (P<0.001). A higher PLR was associated with aggressive renal cancer. In addition, the PLR was a significant prognostic factor for both recurrence-free survival and metastasis-free survival in patients with nonmetastatic RCC.


Pre-absorbed immunoproteomics: a novel method for the detection of bacterial surface proteins.
Bacterial surface proteins are often investigated as potential vaccine candidates and biomarkers of virulence. In this chapter, a novel method for identifying bacterial surface proteins is presented, which combines immunoproteomic with immunoserologic techniques. Immunoproteomics, involving the separation of proteins by two-dimensional electrophoresis (2-DE) and Western blotting, has become an increasingly popular method for identifying immunoreactive proteins. In conventional serological technique, cross-absorption is a powerful method used to minimize cross reaction during agglutination assays. The serum pre-absorption process in our method was developed from cross-absorption but modified to remove antibodies that recognized bacterial surface antigens, thereby generating pre-absorbed sera. These pre-absorbed sera were used in Western blotting after 2-DE to find bacterial surface protein antigens. This new method has been proven to be a useful tool for identifying surface proteins, and aid in the development of new vaccine subunits and disease diagnostics.


Lineage relationships of the fetal thymocyte subset that expresses the beta chain of the interleukin-2 receptor.
The beta chain (p75) of the interleukin-2 (IL-2) receptor (IL-2R) is expressed on up to 5-7% of fetal thymocytes on day 16 of gestation, declining thereafter to a minute proportion of less than 1% around birth, and of 1-2% of adult thymocytes. A significant part of fetal IL-2R beta+ thymocytes are gamma delta cells. The precursor-progeny relationships of fetal IL-2R beta+ thymocytes to the alpha beta T cell lineage have not been previously studied, nor has their position within the developmental sequence been determined. Here we show that IL-2R beta is expressed on a subset of very immature cells, along with high amounts of Pgp1 and Fc gamma RII/III, partially preceding the expression of intracellular CD3 epsilon. IL-2-R beta disappears before expression of IL-2R alpha. IL-2R beta+ cells, purified by sorting on day 15 of gestation, efficiently reconstituted fetal thymic lobes depleted of lymphoid cells by treatment with desoxyguanosine. They developed into T cell receptor (TCR) alpha beta+, TCR gamma delta+, and CD4/CD8 double- and single-positive cells in similar proportions as did sorted IL-2R alpha+ day 15 fetal thymocytes. These data suggest that IL-2R beta expression marks a short period of very early thymocyte development, perhaps immediately after entry into the thymus.


Assessment of correlations and concentrations of salivary and plasma steroids, testicular morphometry, and semen quality in different climatic conditions in goats.
The current study aimed to investigate whether steroids (testosterone, estradiol, and cortisol) in the saliva of goats reflects their concentrations in the plasma. Also, it aimed at ascertaining, for the first time, the effect of changes in climatic conditions (spring versus summer) on the aforementioned steroids, testicular volume, testicular echotexture (pixel intensity; PI, and integrated density; ID), and semen quality in goats. Saliva and plasma samples were collected from 7 male Shiba goats weekly in spring and summer for measurement of testosterone (T; ng/ml), estradiol (E2; pg/ml), and cortisol (ng/ml) using radioimmunoassay. The changes in testicular volumes (TV/ml) and echogenicity were monitored weekly using ultrasonographic assessments concomitantly with subjective evaluations of semen parameters. Results revealed a highly significant positive correlation (r = 0.72; P < 0.0001) between plasma and salivary cortisol. Mild significant positive correlation was found between salivary and plasma T levels (r = 0.31; P < 0.002). However, low non-significant negative correlation was reported between salivary and plasma E2 levels (r = -0.24; P > 0.05). Higher levels of salivary cortisol were found in summer than in the spring (3.8 ± 0.6 ng/ml versus 1.4 ± 0.3 ng/ml; P < 0.001). However, no differences in levels of T, E2, and plasma cortisol were recorded between spring and summer (P > 0.05). Values of testicular PI and ID were significantly (P < 0.001) higher in the summer (94.5 ± 4.9, 258,388 ± 13,190, respectively) than in the spring (74.0 ± 2.1, 200,922 ± 5704, respectively). Meanwhile, TV and semen parameters did not significantly differ between spring and summer. In conclusion, saliva can be considered as an alternative biological fluid for the measurement of cortisol and T, but not suitable for E2. Climatic conditions significantly impact the levels of cortisol in saliva and testicular echogenicity in goats.


Quantitative transport mapping (QTM) of the kidney with an approximate microvascular network.
Proof-of-concept study of mapping renal blood flow vector field according to the inverse solution to a mass transport model of time resolved tracer-labeled MRI data. To determine tissue perfusion according to the underlying physics of spatiotemporal tracer concentration variation, the mass transport equation is integrated over a voxel with an approximate microvascular network for fitting time-resolved tracer imaging data. The inverse solution to the voxelized transport equation provides the blood flow vector field, which is referred to as quantitative transport mapping (QTM). A numerical microvascular network modeling the kidney with computational fluid dynamics reference was used to verify the accuracy of QTM and the current Kety's method that uses a global arterial input function. Multiple post-label delay arterial spin labeling (ASL) of the kidney on seven subjects was used to assess QTM in vivo feasibility. Against the ground truth in the numerical model, the error in flow estimated by QTM (18.6%) was smaller than that in Kety's method (45.7%, 2.5-fold reduction). The in vivo kidney perfusion quantification by QTM (cortex: 443 ± 58 mL/100 g/min and medulla: 190 ± 90 mL/100 g/min) was in the range of that by Kety's method (482 ± 51 mL/100 g/min in the cortex and 242 ± 73 mL/100 g/min in the medulla), and QTM provided better flow homogeneity in the cortex region. QTM flow velocity mapping is feasible from multi-delay ASL MRI data based on inverting the transport equation. In a numerical simulation, QTM with deconvolution in space and time provided more accurate perfusion quantification than Kety's method with deconvolution in time only.


Functional characterisation of bovine interleukin 8 promoter haplotypes in vitro.
Interleukin 8 (IL-8) is a major mediator of the innate immune response and polymorphisms in this gene are associated with susceptibility to inflammatory disease in humans. The aim of this study was to characterise the promoter region of the bovine IL8 gene towards understanding its regulation and the effect of promoter polymorphisms on gene expression levels. Twenty-nine polymorphic sites were identified across a 2.1kb upstream promoter region of the IL8 gene including two insertion/deletion polymorphisms. Sequence analysis and SNP genotyping identified two distinct promoter haplotypes (IL8-h1 and IL8-h2), which were present at significantly different frequencies in two divergently selected cattle breeds - Holstein-Friesian and Norwegian Red (IL8-h1 at 48% and 80% respectively). IL8-h1 was functionally less responsive in unstimulated mammary epithelial cells and in response to stimulation with LPS or bovine TNF. Serial deletion analysis and in silico transcription-factor binding site analysis indicated that allele specific binding of the transcriptional repressor Oct-1 may account for the reduced sensitivity of IL8-h1. Our finding of genetic variation in the bovine IL8 promoter that differentially regulates its expression has significant functional implications for IL8 expression in vitro and which may impact on susceptibility to bovine infectious disease and inflammation.


A developmental study on stress-induced antinociception measured by the tail electric stimulation test.
The possible influence of weaning on the development of different neural mechanisms involved in stress-induced antinociception (SIA) was studied. Male Wistar albino rats were used for studies on adult and pre- and postweanling rats of 20 and 25 days of age, respectively. Animals were stressed by warm-water (20C) swimming for 3-min periods. Antinociception was assessed by the tail electric stimulation test. The thresholds for the motor response (tail withdrawal) (TW), vocalization during stimulus (V), and vocalization after discharge (VAD) were recorded. These responses are considered to be integrated at spinal, medulla oblongata, and diencephalon-rhinencephalon levels, respectively. In 20-day-old neonates, swimming stress only induced significant increases in the VAD thresholds that were not significantly reversed by naloxone (NAL) (1 mg/kg). Twenty-five-day-old rats showed increased threshold for the three nociceptive responses after stress, the effects on TW and V being antagonized by NAL. Adult rats subjected to stress showed increased threshold for the three responses, an effect that was antagonized by NAL in all cases. These results suggest that the weaning period might be critical for the development of the mechanisms mediating SIA. Besides, a different involvement of opioid systems throughout development, particularly in relation to the affective/emotional component of pain, is also suggested.


Dematin inhibits glioblastoma malignancy through RhoA-mediated CDKs downregulation and cytoskeleton remodeling.
Glioblastoma multiforme (GBM) is well known as a highly aggressive brain tumor subtype. Here, we show that overexpression (OE) of dematin actin-binding protein (DMTN) inhibits GBM proliferation and invasion by affecting cell cycle regulation and actin remodeling, respectively. RT-qPCR, western blotting, and immunohistochemical (IHC) staining demonstrated a significant reduction in DMTN expression in gliomas, especially in high-grade gliomas (HGG) compared with normal brains, which correlates with worse survival in HGG patients. Functional studies revealed inhibitory effects of DMTN on tumor proliferation and migratory capacities. The attenuation in tumor proliferative ability upon DMTN OE was accompanied by RhoA suppression and CDK1, CDK2, CDK4, and cyclin D1 downregulation, while RhoA rescue restored the proliferative phenotype. Meanwhile, overexpression of DMTN produced profoundly disorganized stress fibers, which led to impaired tumor invasion. Furthermore, DMTN overexpression produced substantial suppression of tumor growth upon subcutaneous and intracranial implantation in mice, and this was accompanied by significantly reduced vinculin expression and Ki67 positivity. Taken together, these findings demonstrate the role of DMTN in regulating GBM cell proliferation, actin cytoskeleton, and cell morphology and identify DMTN as a vital tumor suppressor in GBM progression.


New functional and aesthetic composite materials used as an alternative to traditional post materials for the restoration of endodontically treated teeth.
To tailor composites of polyethylene-hydroxyapatite to function as a new intracanal post for the restoration of endodontically treated teeth (ETT). Silanated hydroxyapatite (HA) and zirconium dioxide (ZrO2) filled low-density polyethylene (LDPE) composites were fabricated by a melt extrusion process and characterised using infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The flexural strength and modulus were determined in dry state and post ageing in simulated body fluid and fractured surfaces analysed by SEM. The water uptake and radiographic appearance of the experimental composites were also measured and compared with a commercially known endodontic fibre post. Data were submitted to one-way analysis of variance (ANOVA) and post hoc Tukey multiple comparison tests at a level of significance P<0.05. The LDPE/HA composites were structurally flexible and the HA content had a significant effect on the flexural strength and modulus. A univariate analysis of variance showed no significant differences in modulus and strength (P<0.05) post accelerated ageing in simulated body fluid with very low water uptake. The melting point of the LDPE/HA composites ranged between 135 and 136°C, which would facilitate removal in case of retreatment using conventional dental heating devices. The inclusion of HA reduced the damping thereby enhancing dimensional stability, whilst the addition of zirconia yielded a semi-translucent material that was sufficiently radiopaque, comparable to commercial posts, thus yielding aesthetic materials. Innovative materials for restoration of ETT were developed; offering considerable benefits over the currently available material in terms of biomechanical and thermal properties. This study provided a new option for the development of a new intracanal post made up of functional and aesthetic composites.


Supplementation Adherence and Outcomes Among Pregnant Women After Bariatric Surgery.
Most patients undergoing bariatric surgery (BS) are fertile women whose postoperative (post-op) hormonal balance and weight loss increases fertility, frequently leading to pregnancy. This study aims to analyze supplementation adherence of pregnant women after BS and perinatal outcomes. This retrospective study analyzed records from women after BS who consulted nutritionists at least twice during pregnancy. Each patient received nutritional guidance about vitamin and mineral supplementation and protein intake. Demographic data, body mass index (BMI), percentage of weight loss (%WL) at conception, maximum post-op BMI and %WL, post-op time at conception, supplementation adherence, biochemical data, possible gestational complications, and infant's birth weight were collected. Data was obtained from 23 women (mean age 33 ± 4 years). On average, patients became pregnant 43 months after surgery. The mean preoperative BMI was 40.2 kg/m2, the maximum post-op %WL was 36.6%, and the mean %WL at conception was 32.0%. No gestational intercurrence was related to biochemical data. Supplementation adherence was 34.7% for one multivitamin and 34.7% for two multivitamins; 43.5% for iron, 43.5% for omega 3, 39.1% for folic acid, 17.4% for B complex, and 60.8% for calcium. Mean infant birth weight was 3.0 kg, and it was not associated with maximum %WL, % WL at conception, and time since BS at conception. Our data indicate satisfactory adherence to post-op micronutrient supplementation and few gestational complications following BS. Moreover, child's birth weight was not associated with maximum %WL, %WL at conception, or time since BS.


Fractional flow reserve versus angiography guided percutaneous coronary intervention: An updated systematic review.
To compare outcomes of fractional flow reserve (FFR) to angiography (ANGIO) guided percutaneous coronary intervention (PCI). The results of a recent randomized controlled trial reported unfavorable effects of routine measurement of FFR, thereby questioning its validity in improving clinical outcomes. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were queried from January, 2000 through December, 2016 and studies comparing FFR and ANGIO guided PCI were included. Clinical endpoints assessed during hospitalization and at follow-up (>9 months) included: myocardial infarction (MI), major adverse cardiovascular events (MACE), target lesion revascularization (TLR), and all-cause mortality. Additional endpoints included number of PCIs performed, procedure cost, procedure time, contrast volume, and fluoroscopy time. A total of 51,350 patients (age 65 years, 73% male) were included from 11 studies. The use of FFR was associated with significantly lower likelihood of MI during hospitalization (OR 0.54, 95% CI: 0.39 to 0.75, P = 0.0003) and at follow-up (OR 0.53, 95% CI: 0.40 to 0.70, P = 0.00001). Similarly, FFR-PCI was associated with lower in-hospital MACE (OR 0.51, 95% CI: 0.37 to 0.70, P = 0.0001) and follow-up MACE (OR 0.63, 95% CI: 0.47 to 0.86, P = 0.004). In-hospital TLR was lower in the FFR-PCI group (OR 0.62, 95% CI: 0.40 to 0.97, P = 0.04), but not at follow-up (OR 0.83, 95% CI: 0.50 to 1.37, P = 0.46). There was no difference of in-hospital (OR 0.58, 95% CI: 0.31 to 1.09, P = 0.09) or follow-up all-cause mortality (OR 0.84, 95%CI: 0.59 to 1.20, P = 0.34). FFR-PCI was associated with significantly less PCI (OR 0.04, 95% CI: 0.01 to 0.15, P = 0.00001) with lower procedure cost (Mean Difference -4.27, 95% CI: -6.61 to -1.92, P = 0.0004). However, no difference in procedure time (Mean Difference 0.79, 95% CI: -2.41 to 3.99, P = 0.63), contrast use (Mean Difference -8.28, 95% CI: -24.25 to 7.68, P = 0.31) or fluoroscopy time (Mean Difference 0.38, 95% CI: -2.54 to 3.31, P = 0.80) was observed. FFR-PCI as compared to ANGIO-PCI is associated with lower in-hospital and follow-up MI and MACE rates. Although, in-hospital TLR was lower in the FFR-PCI group, this benefit was not present after 9 months. FFR-PCI group was also associated with less PCI and lower procedure costs with no effect on procedure time, contrast volume or fluoroscopy time.


[Management of urinary tract infections in children. Recommendations of the Pediatric Infectious Diseases Group of the French Pediatrics Society and the French-Language Infectious Diseases Society].
Urine dipsticks have to be used more frequently for the screening of urinary tract infections (UTI) in febrile infants and children (grade A). Confirmation of the UTI by urine culture should prefer other methods of sampling than the urine bag: sampling jet, urethral catheterization, or pubic puncture (grade A). The percentage of Escherichia coli producing extended-spectrum beta-lactamases (ESBL) in children accounts for less than 10 % in France and does not justify revising the 2007 recommendations (grade B). An increase in the use of carbapenems in first-line treatment is a major environmental hazard and exposes the patient to the risk of untreatable infections. For febrile UTI, the expert group recommended: (1) recover the results of susceptibility testing as soon as possible to quickly adapt treatment for possible resistant strains; (2) favor initial treatment with aminoglycosides (particularly amikacin) which remain active in the majority of ESBL strains for patients seen in the pediatric emergency department and/or hospital; (3) ceftriaxone (IV or IM) remains an appropriate treatment for patients seen in the emergency department or outpatient clinic because the percentage of ESBL-producing enterobacteria strains remains low; (4) use oral cefixime (grade B) in nonsevere cases and low-risk patients defined as age>3 months, general condition preserved, disease duration of fever<4 days, no associated comorbidity, and no history of urinary tract infection, uropathy, or prior antibiotic therapy in the last 3 months; (5) oral relay for parenteral treatment is guided by in vitro susceptibility testing, in an attempt to reduce the use of oral cephalosporins to limit the selection of resistant bacterial strains. The total duration of treatment recommended is usually 10 days. Except for special circumstances, there is no need to prescribe retrograde cystography or antibiotic prophylaxis after a first febrile urinary tract infection. For cystitis, the panel recommends systematic urinalysis and initial prescription before the results of the urine culture of one of the three following oral antibiotics: amoxicillin-clavulanate, cotrimoxazole, cefixime. The total duration of antibiotic treatment is 5days to tailor treatment based on clinical progression and antibiotic susceptibility.


Low linking social capital as a predictor of coronary heart disease in Sweden: a cohort study of 2.8 million people.
This study investigated the association between the recently minted concept of linking social capital and incidence of coronary heart disease (CHD). A follow-up study of 1,358,932 men and 1,446,747 women in Sweden aged 45-74 years was conducted between 1 January 1998 and 31 December 1999. Neighbourhood linking social capital was conceptualised as proportions of individuals voting in local government elections at neighbourhood level. The neighbourhood- and individual-level factors were analysed within a multilevel framework. Linking social capital was associated with CHD in both men and women beyond individual-level factors: in neighbourhoods with low linking social capital the odds ratios were 1.19 (CI = 1.14-1.24) and 1.29 (CI = 1.21-1.38) for men and women, respectively, after adjustment for age, country of birth, education, marital status, and housing tenure. The significant between-neighbourhood variance (i.e. the random intercept) showed significant differences in CHD incidence between neighbourhoods. Even in a relatively egalitarian society, as exemplified by the Swedish Welfare State, individual health is affected by differences between neighbourhoods in linking social capital. The use of linking social capital represents a novel conceptual advance in research on the association between CHD, one of the major causes of death in Western countries, and the multidimensional aspects of social capital.


Association between Interleukin-1 Polymorphisms and Susceptibility to Dental Peri-Implant Disease: A Meta-Analysis.
Interleukins (ILs), as important biochemical mediators, control the host response to inflammation and are associated with bone resorption. In the present meta-analysis, we investigated the association between IL-1 polymorphisms and susceptibility to dental peri-implant disease (PID). We searched Web of Science, Cochrane Library, Scopus, and PubMed/Medline databases for studies published until 9 September2021, without any restrictions. We calculated the crude OR and 95% confidence intervals (CI) to estimate the associations between IL-1 polymorphisms and PID risk in the five genetic models. We further performed the subgroup analysis, sensitivity analysis, meta-regression, trial sequential analysis, and calculated the publication bias. Out of 212 retrieved records, sixteen articles were used in the meta-analysis. There was no association between IL-1A (-889), IL-1B (-511), IL-1B (+3953), and IL-1RN (VNTR) polymorphisms and the risk of dental PIDs, but there was an increased risk of IL-1B (+3954) in the patients with PIDs. In addition, an association of the composite genotype of IL-1A (-889)/IL-1B (+3953) was observed with the risk of PIDs, but not for the composite genotype of IL-1A (-889)/IL-1B (+3954). The publication year, the ethnicity, sample size, and the outcome were significantly influenced pooled estimates of some genetic models. Trial sequential analysis showed the lack of sufficient sample sizes in the studies. Conclusions: Among IL-1 polymorphisms evaluated in the meta-analysis, the composite genotype of IL-1A (-889)/IL-1B (+3953) and IL-1B (+3954) were the only polymorphisms associated with the risk of PID. The T allele and CT genotype of IL-1B (+3954) polymorphism were also associated with an elevated risk of PID.


Development of a peptide mapping procedure to identify and quantify methionine oxidation in recombinant human alpha1-antitrypsin.
A peptide mapping procedure was developed to identify and quantify methionine oxidation in recombinant human alpha1-antitrypsin. Due to the protein's complex structural biochemistry, chromatographic analysis of methionine containing digest peptides was a significant challenge. However, by using a combination of mass spectrometry, protein engineering, and high-temperature reversed-phase liquid chromatography, we were able to identify methionine residues that are susceptible to oxidation by hydrogen peroxide. and quantify their reactivity. Our results show that five of the protein's 10 methionine residues are susceptible to oxidation at neutral pH, four of which are localized to the active site region.


"You can kind of just feel the power behind what someone's saying": a participatory-realist evaluation of peer support for young people coping with complex mental health and substance use challenges.
Youth peer support, as a practice that aligns youth engagement and participatory approaches, has become increasingly popular in the context of youth mental health services. However, there is a need for more evidence that describes how and why youth peer support practice might be effective. This study was designed to examine a peer support service for youth experiencing complex challenges with mental health, physical health and/or substance use to better understand key features and underlying mechanisms that lead to improved client outcomes. We applied a hybrid realist-participatory approach to explore key issues and underlying theoretical assumptions within a youth peer support approach for young people (age 14-26) experiencing complex mental health and substance use challenges. We used semi-structured interviews and focus groups with staff, including peers (N = 8), clinical service providers and administrative staff (N = 15), to develop the theories and a client survey to validate them. Our qualitative thematic analysis applied a retroductive approach that involved both inductive and deductive processes. For the client survey (N = 77), we calculated descriptive statistics to examine participant profiles and usage patterns. Pearson correlations were examined to determine relationships among concepts outlined in the program theories, including context, mechanism and outcome variables. Our analyses resulted in one over-arching context, one over-arching outcome and four program theories. Program theories were focused on mechanisms related to 1) positive identity development through identification with peers, 2) enhanced social connections, 3) observational learning and 4) enhanced autonomy and empowerment. This study serves as a unique example of a participatory-realist hybrid approach. Findings highlight possible key components of youth peer practice and shed light on the functional mechanisms that underlie successful peer practice. These key components can be examined in other settings to develop more comprehensive theories of change with respect to youth peer support and can eventually be used to develop guidelines and standards to strengthen practice. This research contributes to an expanding body of literature on youth peer support in mental health and connects peer practice with several social theories. This research begins to lay a foundation for enhanced youth peer support program design and improved outcomes for young people experiencing complex mental health and substance use challenges.


Interaction of oil and mineral fines on shorelines: review and assessment.
The interaction of fine mineral particles with stranded oil in an aqueous medium reduces the adhesion of the oil to solid surfaces, such as sediments or bedrock. The net result is the formation of stable, micron-sized, oil droplets that disperse into the water column. In turn, the increase in surface area makes the oil more available for biodegradation. This interaction, referred to as oil-mineral aggregate (OMA) formation, can explain how oiled shorelines are cleaned naturally in the absence of wave action in very sheltered coastal environments. OMA formation also plays an important role in the efficacy of shoreline treatment techniques, such as physical mixing and sediment relocation that move oiled sediments into the zone of wave action to promote the interaction between oil and mineral fines. Successful application of these shoreline treatment options has been demonstrated at two spill events (the Tampa Bay response in Florida and the Sea Empress operation in Wales) and at a controlled oil spill experiment in the field (the 1997 Svalbard ITOSS program). Sediment relocation harnesses the hydraulic action of waves so that the processes of fine-particle interaction and physical abrasion usually occur in tandem on open coasts. There has been no evidence of significant detrimental side-effects of residual oil in pelagic or benthic environments associated with the use of these treatment options to enhance rates of dispersion and oil biodegradation.


Prevention-effective adherence trajectories among transgender women indicated for PrEP in the United States: a prospective cohort study.
Adherence to pre-exposure prophylaxis (PrEP) during periods of PrEP-indication (i.e., prevention-effective adherence) is critical for preventing HIV. We sought to describe factors associated with prevention-effective adherence trajectories among transgender women (TW) to inform PrEP implementation strategies. Using data from The LITE American Cohort (n = 728), we performed group-based multi-trajectory modeling (GBMTM) to identify clusters of TW with similar trajectories of PrEP adherence and indication, and sociodemographic, biobehavioral, and structural correlates of each trajectory. We identified five trajectories: (1) consistent indication/no PrEP (15.3%), (2) initial indication/no PrEP (47.1%), (3) declining indication/discontinued PrEP (9.5%), (4) consistent indication/PrEP adherent (18.5%), and (5) increasing indication/initiated PrEP (9.6%). TW diagnosed with an STI were more likely to follow a consistent indication/no PrEP trajectory compared to consistent indication/PrEP adherent trajectory (adjusted Relative Risk Ratio [aRRR], 2.54; 95% confidence interval [CI], 1.16-5.57). TW who experienced homelessness were more likely to follow PrEP discontinuation and initiation trajectories relative to PrEP adherence (aRRR, 2.71; 95% CI, 1.10-6.70 and 2.83; 95% CI, 1.13-7.05, respectively). Over a quarter of TW followed trajectories suggestive of prevention-effective adherence, while 15% did not initiate PrEP despite consistent indication. Findings highlight missed opportunities for PrEP engagement at STI diagnosis and suggest structural interventions addressing housing instability may improve prevention-effective adherence among TW.


The F.A.S.T.E.R. trial. Focused assessment by sonography in trauma during emergency retrieval: a feasibility study.
This feasibility study aimed to establish if retrieval physicians can overcome the transport environment and obtain F.A.S.T. (focused assessment by sonography in trauma) images of suitable quality during patient retrieval in rotary wing aircraft such that diagnostic interpretation of free intra-abdominal fluid or pericardial fluid would be possible. During a 6-month trial period, one of three retrieval physicians attempted to obtain the standard four quadrant F.A.S.T. views using a portable ultrasound on patients they retrieved. Ultrasound images were obtained whilst in-flight in a rotary wing aircraft. Image adequacy was assessed by the retrieval physician and by an independent blinded physician using strict clinical criteria. Thirty-eight patients were enrolled. Thirty-six patients had a complete F.A.S.T. scan attempted whilst a further two patients had their abdominal quadrants scanned without a pericardial view being attempted. Independent blinded physician review of scans agreed with the scanning retrieval physician that images were adequate for showing the F.A.S.T. quadrants appropriately in 143 of 150 quadrants imaged and inadequate in two. Blinded physician review disagreed with scanning physician regarding adequacy of image in 5 of 150 quadrants imaged. Scanning physicians were happy with adequacy of the view in all F.A.S.T. quadrants in 34 of the 36 patients in whom a complete F.A.S.T. was performed. Blinded physician review agreed in 30 of those cases. The physicians performing the F.A.S.T. examination, all incorporate ultrasound into their daily clinical practice thereby maintaining their skill level. This is likely to contribute to the high level of view adequacy. Independent blinded image review controlled for bias regarding view adequacy. Disagreement between scanning physician and reviewing physician assessment of view adequacy in 5 of the 150 views obtained is likely to relate to the difficulties in interpreting still ultrasound images, compared to interpreting real time images at point-of-care. There were no machine limitations. This study demonstrates that it is possible for critical care retrieval physicians to obtain adequate ultrasound F.A.S.T. images on patients using a portable ultrasound machine en-route to definitive care, in a rotary wing aircraft.


Comparison of Different Carriers to Maintain a Stable Partial Nitrification Process for Low-Strength Wastewater Treatment.
Practical application of the partial nitritation-anaerobic ammonium oxidation (anammox) process has attracted increasing attention because of its low operational costs. However, the nitritation process, as a promising way to supply nitrite for anammox, is sensitive to the variations in substrate concentration and dissolved oxygen (DO) concentration. Therefore, a stable supply of nitrite becomes a real bottleneck in partial nitritation-anammox process, limiting their potential for application in mainstream wastewater treatment. In this study, five 18-L sequencing batch reactors were operated in parallel at room temperature (22°C ± 4°C) to explore the nitritation performance with different carrier materials, including sepiolite-nonwoven carrier (R1), zeolite-nonwoven carrier (R2), brucite-nonwoven carrier (R3), polyurethane carrier (R4), and nonwoven carrier (R5). The ammonia oxidation rate (AOR) in R1 reached the highest level of 0.174 g-N L-1 d-1 in phase II, which was 1.4-fold higher than the control reactor (R4). To guarantee a stable supply of nitrite for anammox process, the nitrite accumulation efficiency (NAE) was always higher than 77%, even though the free ammonia (FA) decreases to 0.08 mg-N/L, and the pH decreases to 6.8 ± 0.3. In phase V, the AOR in R1 reached 0.206 g-N L-1 d-1 after the DO content increase from 0.7 ± 0.3 mg/L to 1.7 ± 0.3 mg/L. The NAE in R1 was consistently higher than 68.6%, which was much higher than the other reactor systems (R2: 43.8%, R3: 46.6%, R4: 23.7%, R5: 22.7%). Analysis of 16S rRNA gene sequencing revealed that the relative abundance of Nitrobacter and Nitrospira in R1 was significantly lower than other reactors, indicating that the sepiolite carrier plays an important role in the inhibition of nitrite-oxidizing bacteria. These results indicate that the sepiolite nonwoven composite carrier can effectively improve the nitritation process, which is highly beneficial for the application of partial nitritation-anammox for mainstream wastewater treatment.


Pneumocele as a rare differential diagnosis in trigeminal irritation.
A case of a pneumocele concerning the maxillary sinus causing trigeminal irritation is presented. Pneumoceles are rare conditions of an abnormal dilatation of a paranasal sinus containing only air, lined by unremarkable mucosa, and associated with a bony defect. Symptoms, diagnostic findings, therapy, possible causes, and pathogenesis are discussed.


Stochastic modeling of drug resistance in cancer.
One of the main causes of failure in the treatment of cancer is the development of drug resistance by the cancer cells. Employing multi-drug therapeutic strategies is a promising way to prevent resistance and improve the chances of treatment success. We formulate and analyse a stochastic model for multi-drug resistance and investigate the dependence of treatment outcomes on the initial tumor load, mutation rates and the turnover rate of cancerous cells. We elucidate the general principles of the emergence and evolution of resistant cells inside the tumor, before and after the start of treatment. We discover that for non-mutagenic drugs, pre-existence contributes more to resistance generation than the treatment phase; this result holds for the case where all drugs are applied simultaneously, and is not applicable for sequential therapy models. The application of mathematical modelling to aspects of adjuvant chemotherapy scheduling. J. Math. Biol. 48(4), 375-422]. Also, we find that treatment success is independent on the turnover rate for one drug, and it depends strongly on it for multi-drug therapies. For low-turnover rates, increasing the number of drugs will increase the probability of successful therapy. For very high-turnover rates, increasing the number of drugs used does not significantly increase the chances of treatment success.


Analysis of transcripts homologous to acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase induced in rat liver by methylclofenapate.
Methylclofenapate is a potent peroxisome proliferating agent and liver carcinogen in rats. Animals exposed to daily oral doses (2.5 mg/kg body wt.) for a 21-day period were studied to determine the levels of mRNA homologous to peroxisomal acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme in total liver RNA. Northern blotting revealed transcripts of approximately 3.8 and 3.3 kilobases (kb), homologous to acyl-CoA oxidase and the bifunctional enzyme, respectively. Levels of these transcripts began to rise at approximately 4 h after the initial dose of the agent, and reached maximum induction (35- and 60-fold, respectively, in excess of control levels) at 2-8 days after the start of the study. The kinetics of induction for acyl-CoA oxidase mRNA resembled those of palmitoyl-CoA oxidase activity, and the induction of mRNA preceded the expression of enzyme activity, further supporting a transcriptional control model of induction of the peroxisomal enzymes. The levels of mRNA induction for the peroxisomal enzymes were higher in the present study than those reported elsewhere for single doses of peroxisome proliferating agents and probably reflect the increased tissue levels achievable in long term carcinogenesis studies.


Ultrasensitive probing of plasmonic hot electron occupancies.
Non-thermal and thermal carrier populations in plasmonic systems raised significant interest in contemporary fundamental and applied physics. Although the theoretical description predicts not only the energies but also the location of the generated carriers, the experimental justification of these theories is still lacking. Here, we demonstrate experimentally that upon the optical excitation of surface plasmon polaritons, a non-thermal electron population appears in the topmost domain of the plasmonic film directly coupled to the local fields. The applied all-optical method is based on spectroscopic ellipsometric determination of the dielectric function, allowing us to obtain in-depth information on surface plasmon induced changes of the directly related electron occupancies. The ultrahigh sensitivity of our method allows us to capture the signatures of changes induced by electron-electron scattering processes with ultrafast decay times. These experiments shed light on the build-up of plasmonic hot electron population in nanoscale media.


Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway.
Obesity has become a major public health problem of global significance. Today, aspirin remains the most commonly used medication for the treatment of pyrexia, pain, inflammation and antiplatelet. The present study aims at evaluating the possible existence of a putative p53-dependent pathway underlying the aspirin-induced inhibition of adipogenesis. Cell migration assay was identified by the ability to migrate through Transwell insert. Oil Red O staining was employed to quantify adipose accumulation. The concentration of glucose and triglyceride were measured by using assay kits. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Aspirin significantly inhibited preadipocyte migration and adipose accumulation. The p53-p21 signaling and the expression of differentiation marker glycerol-3-phosphate dehydrogenase were increased in a dose-dependent manner. It indicated that aspirin induced adipocyte differentiation through p53-p21 pathway. The oncogenic ERK 1/2 MAPK signaling was induced, whereas, the expression of adipogenic markers peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid-binding protein (A-FABP) and inflammatory factors cyclooxygenase-2 (Cox-2), tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) were inhibited. Aspirin negatively regulated the pentose phosphate pathway (PPP) by inhibiting the expression of rate-limiting enzyme glucose-6-phosphate dehydrogenase. Knockdown the expression of oncogenic ERK 1/2 MAPK by using 10 μM PD98059 significantly increased triglyceride synthesis, adipose accumulation and activated PPP, however, decreased glucose uptake. Diverted the glucose flux to PPP, rather than increased glucose uptake, was associated with adipogenesis. Down-regulated the expression of tumor suppressor p53 by 10 μM pifithrin-α (PFTα) alone had no effect on adipose accumulation. However, administration of aspirin accompanied with PFTα abolished aspirin-induced inhibition of adipogenesis. We demonstrated that aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of PPP. Blockade PPP may be a novel strategy for obesity prevention and therapy. Moreover, when use aspirin in therapeutic strategy, the p53 status should be considered.


Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study.
Most gastric cancer patients with peritoneal dissemination have been excluded from clinical studies because they usually have no measurable lesions. They also have a high risk of toxicity because of complications such as intestinal obstruction and ascites. We conducted a retrospective analysis to evaluate the efficacy and feasibility of sequential methotrexate (MTX) and 5-flurorouracil (5FU) therapy for this population. This analysis was based on 56 consecutive chemotherapy-naive patients with confirmed peritoneal dissemination of gastric cancer who were being treated with sequential MTX/5FU. The therapy comprised a weekly schedule of MTX 100 mg/m2, given as a bolus infusion 3 h prior to a bolus infusion of 5FU 600 mg/m2. Leucovorin 10mg/m2 was administered six times, every 6h, starting 24h after MTX administration. Evidence of peritoneal dissemination was confirmed by laparotomy in 16 patients, by cytologic examination of ascites in 11 patients, and by clinical imaging in 29 patients (15 with ascites, 13 with intestinal obstruction; in 10 of the 29 patients, detection was by barium enema or computed tomography [CT] scan). Neutropenia of grade 3 or worse and anemia were observed in 8 (14%) and 10 (18%) of the 56 patients, respectively. There was one treatment-related death due to neutropenic sepsis. Of the 26 patients with measurable lesions, 9 showed a response (36%). The median survival time and median time to treatment failure were 259 days and 167 days, respectively. Objective improvement of ascites was seen in 13 of 26 patients (50%), including 5 with showed complete disappearance of ascites. Seven of the 15 patients (47%) with intestinal obstruction showed resolution, and 8 of the 21 patients (38%) who needed nutritional support before the treatment were free of that support for a median duration of 220 days after the completion of the treatment. Forty-seven of the 56 patients (84%) could be treated at outpatient clinics. This regimen may be of clinical benefit for patients with peritoneal dissemination of gastric cancer.


[Technical orthopedics. Importance in an increasingly operatively oriented faculty].
The foundation of the German Society for Orthopedics in 1901 was due to a separation from the faculty of surgery because a surgical approach alone did not adequately deal with the symptoms. Orthopedists were initially considered as a fringe group. The conservative treatment approach was initially at the forefront and operative measures were a side line. The main aim was the rehabilitation of patients into a normal life as best as possible. In the conservative area treatment with orthopedic technical aids and appliances rapidly came to play an important role and a great multitude of technical appliances were developed with sometimes very different possible applications. Despite the clearly improved operative treatment approaches in orthopedics and trauma surgery, technical orthopedics still plays a substantial role even today. Healing and supportive aids and appliances are of decisive importance for the treatment of a multitude of diseases and handicaps. They stabilize and improve operative treatment results and often result in new approaches. This depends on cooperation between technicians, therapists and physicians in a team, even in the scientific field. Evidence-based studies on the effectiveness of technical aids are currently still uncommon but recently some clear evidence for effectiveness could be shown. Scientifically this is a very varied field of work. The demographic development presents new requirements which must be dealt with. Technical solutions are often very promising especially in this field. Technical orthopedics remains an important component of the specialty of orthopedics and trauma surgery and with an increasing tendency due to more recent research and development.


Intravascular ultrasound findings of stent fractures in patients with Sirolimus- and Paclitaxel-eluting stents.
We compared intravascular ultrasound (IVUS) findings of fractures of sirolimus-eluting stents (SESs) versus paclitaxel-eluting stents (PESs). IVUS findings in 6 PES fractures (all in the right coronary artery) in 6 patients from a clinical trial cohort were compared to 14 SES fractures (8 in the right coronary artery, 2 in the left anterior descending coronary artery, and 4 in the left circumflex coronary artery) in 13 patients from our institutional cohort. Comparing PES fractures to SES fractures, IVUS analysis showed (1) similar frequency of complete stent fracture (1 of 6, 17%, vs 3 of 14, 21%, p >0.99), (2) similar frequency of fracture adjacent to calcified plaque or stent metal overlap (5 of 6, 86%, vs 14 of 14, 100%, p = 0.99), (3) more frequent complete malalignment of proximal and distal fragments in PES strut fractures compared to SES fractures (5 of 6, 83%, vs 1 of 14, 7%, p = 0.002), (4) similar stent lengths (45.2 mm, 23.8 to 50.7, vs 39.3 mm, 22.6 to 73.4, p >0.99), (5) similar fracture lengths (0.5 mm, 0.4 to 0.7, vs 0.7 mm, 0.6 to 1.0, p = 0.14), and (6) larger reference external elastic membrane area (15.0 mm(2), 13.5 to 18.0, vs 10.4 mm(2), 6.8 to 13.6, p = 0.01). In conclusion, malalignment of proximal and distal stent fragments more often occurred in PES fractures compared to SES fractures; otherwise the IVUS features of PES and SES fractures were similar.